key: cord- -fsx s authors: balocco, carla title: hospital ventilation simulation for the study of potential exposure to contaminants date: - - journal: build simul doi: . /s - - - sha: doc_id: cord_uid: fsx s airflow and ventilation are particularly important in healthcare rooms for controlling thermo-hygrometric conditions, providing anaesthetic gas removal, diluting airborne bacterial contamination and minimizing bacteria transfer airborne. an actual hospitalization room was the investigate case study. transient simulations with computational fluid dynamics (cfd), based on the finite element method (fem) were performed to investigate the efficiency of the existing heating, ventilation and air-conditioning (hvac) plant with a variable air volume (vav) primary air system. solid modelling of the room, taking into account thermo-physical properties of building materials, architectural features (e.g., window and wall orientation) and furnishing (e.g., beds, tables and lamps) arrangement of the room, inlet turbulence high induction air diffuser, the return air diffusers and two patients lying on two parallel beds was carried out. multiphysics modelling was used: a thermo-fluidynamic model (convection-conduction and incompressible navier-stokes) was combined with a convection-diffusion model. three d models were elaborated considering different conditions/events of the patients (i.e., the first was considered coughing and/or the second breathing). a particle tracing and diffusion model, connected to cough events, was developed to simulate the dispersal of bacteria-carrying droplets in the isolation room equipped with the existing ventilation system. an analysis of the region of droplet fallout and the dilution time of bacteria diffusion of coughed gas in the isolation room was performed. the analysis of transient simulation results concerning particle path and distance, and then particle tracing combined with their concentration, provided evidence of the formation of zones that should be checked by microclimatic and contaminant control. the present study highlights the fact that the cfd-fem application is useful for understanding the efficiency, adequacy and reliability of the ventilation system, but also provides important suggestions for controlling air quality, patients’ comfort and energy consumption in a hospital. an effective ventilation is recognized as a very important factor in the control of infections, for human comfort and also for energy recovery and system reliability solutions in operating theatres and isolation rooms in hospitals (galson and guisbond ; li et al. ; méndez et al. ; dascalaki et al. ; lim et al. ) . it has been shown that an efficient heating, ventilation and air-conditioning (hvac) installations can control the air quality and aseptic conditions, safe and suitable indoor thermal conditions for medical staff and surgeons, and patients (balaras et al. ). hvac operating for hospitals and their particular sectors has been investigated to guarantee the optimal airflow pattern inside isolation rooms for infective and in particular immune suppressed patients, so that clean air from the air-supply vents may carry the air across infectious sources, and then flow through the exhaust vents completely (soper ) . design of air ventilation systems has been greatly assisted by computer simulations based on computational fluid dynamics (cfd) modelling (chow and yang ) . cfd can predict air velocities, temperatures and contaminant concentrations throughout the room for a range of plant design changes. this information has been interpreted in terms of indoor air quality indices, and then compared against health criteria and also thermal comfort indices to assess patient comfort (rygielsky and uden ; walker et al. ; soper ; tunga et al. ). cfd modelling provides useful indications on the supply diffuser locations and types, flow and ventilation rates, exhaust air vent locations, air filter efficiency, distribution of heat loads in the room, arrangement of furniture, and other obstacles to air movement (jiang et al. ; qian et al. ) . the work of jiang et al. ( ) is crucial to derive useful suggestions on the minimum ventilation rate, corresponding to the dilution level for preventing airborne infection. many authors have included a review of cfd techniques, including patankar ( ) , chen and srebric ( ) , and jiang et al. ( ) providing basic support for cfd simulations for studying the ventilation system performances for isolation rooms. the airflow patterns in isolation rooms are governed by the positions, configurations and specified velocities/pressures of the air-supply and exhaust vents of the ventilation system. several works have highlighted how the indoor air quality of an isolation room can be guaranteed by efficient air-conditioning and ventilation system design, in controlling temperature, humidity, pressure and air quality (farnsworth et al. ; martini et al. ) . recent findings, reported in the literature, allowed switching on from operating rooms to isolation room which have similarities. memarzadeh and manning ( ) used computational fluid dynamics analysis to show that when the design is appropriate, laminar flow conditions are the best choice among a large comparison of flows and ventilation systems in order to control the risk of contaminant deposition in an operating room surgical site. they found that a low velocity ( to fpm), vertically directed, unidirectional downward airflow over the operation room table with return air (exhaust) ducts at various heights achieved optimal removal of airborne particulates (memarzadeh and manning ) . comparison of performances (number of airborne particles, microbial contamination, kinetics of decontamination, rate of mixing and an index of functionality) of three types of airflow systems: laminar (unidirectional) flow, stabilised flow and turbulent flow, in the operating theatre in a french hospital, has shown that during operations, the laminar flow is the single airflow system to reach the class b (talon et al. ) . in a recent study, brandt et al. ( ) analysed hospitals in germany and concluded there may be little benefit from vertical laminar airflow (laf) for preventing surgical site infections in surgical procedures. both the authors and many researchers have pointed that, although with conspicuous statistics, this was not a randomised, controlled, blind study. other researchers have also pointed out that this investigation lacked details of the design of hvac in operating rooms and of a number of preoperative care processes such as in participating facilities, skin preparation, timing of preoperative antibiotic prophylaxis, etc. (brandt et al. ) . the present article investigates the airflow patterns, distribution and velocity, and the particulate dispersion inside an existing typical hospitalization room equipped with an hvac, with variable air volume (vav) primary air system, combined with a ceiling radiant panel, for immunesuppressed patients, never modelled before. the present study is inspired by widespread awareness the importance of hvac systems in resource allocation on the frontlines of public health preparedness (soper ; tang et al. ) and response to infectious disease. transient simulations, applied to a three-dimensional model of the room, considering most typical positions of two patients, investigated the airflow patterns associated with different cough conditions, in order to develop an understanding of the effects of these arrangements on the regions of droplet fallout. to study particles and/or control of virus dispersion in the isolation room, the door at first was considered closed, as often as practical so that the airflow can be kept stable, then in the last simulation it was considered open. for this study, results obtained in a recent work (balocco and liò ) were used, improving fluid-dynamic, thermal and diffusion modelling. the numerical simulations were performed to analyse diffusion of particles that emitted from a patient entering the breathing zone or reaching the body surface of another patient. for this reason a particle tracing and diffusion model, connected to cough events, was also defined. transient simulations of the patients coughing conditions were performed over seconds. the simulations were performed with the help of a commercial software (comsol ) to solve simultaneously coupled partial differential equations resulting from the fluid-dynamic, thermal and mass transfer (conduction, convection and diffusion). in recent years many works have focused on computational models using fluid dynamics approaches to investigate airflow patterns and the related spreading of infection in isolation rooms for different ventilation systems muia et al. ; méndez et al. ) . the main attention of these papers has been the evaluation of the effects of supply and return air diffuser location and negative pressure in isolation rooms for patients with highly infectious diseases (tunga et al. ; walker et al. ). the hvac design is fundamental to maintain negative pressure within isolation rooms and to protect health of workers, patients and visitors. this is also necessary to control patient risk from airborne diseases (rygielski and uden ) . door opening causes the dispersion of air out of the isolation room. an isolation room held at negative pressure to reduce aerosol escape and a high air-change rate to allow rapid removal of aerosols can eliminate transmission of infectious aerosols to those outside the room. tunga et al. ( ) found that an air velocity above . m/s via a doorway effectively prevents the spread of airborne contaminants out of the isolation room with an open door (méndez et al. ; rygielski and uden ) . techniques such as aerosol particle tracer sampling and computational fluid dynamics can be applied to study the performance of ventilation systems during coughing episodes. hvac switch on-off impact on virus and bacteria load has been widely investigated recently (rygielski and uden ; soper ; stanley et al. ; talon et al. ) . it is very frequent for visitors or nurses to stand next or lean on a reclining patient or an upright sitting patient (münch et al. ; kao and yang ) . a breathing zone in these studies refers to the roughly cm area around the patient's face. the work, presented in the present article, started from the consideration that badly designed and/or incorrectly operating ventilation arrangements in isolation rooms could put patients at risk from airborne diseases. starting from critic analysis of literature results and experimental evidence, the present article provides a multiphysics approach to investigate the condition that particles emitted from patients coughing can have a very high probability of interacting with the patient's breathing and vice versa. all the practical difficulties, mainly depending from long time legal permissions, and low cooperation of the technicians of the hospital plants, for realizing experimental measurements (no spot test) in the isolation room e.g., particle image velocimetry (piv); see gupta et al. ; vanschiver et al. ), also without patients, made these collected literature results and experimental evidence very important to validate the cfd-fem simulation. in particular, referring to the steady sate condition, concerning the air distribution and the assessment of the ventilation effectiveness, a good agreement between simulation results and literature can be deduced. in the present work a simple model concerning droplet dispersion that can carry viruses, due to coughing and sneezing, was defined and incorporated in the cfd-fem transient simulations based on multiphysics approach. virus dispersal in a hospital mainly depends on perturbation of intensity and direction caused by people moving or doors opening. starting from literature ) the effects of the airflow patterns associated with different cough conditions and the ventilation assessments on microbial growth in supply air ducts were analysed. the coughing events that cause droplet transmission have been modelled in several sophisticated ways (cunningham ; yu and diu ; marianne et al. ; batchelor ; tellier ) but they were not incorporated in a cfd intensive simulation. several studies show that a close cough is unlikely to cause infection, whereas a close, unprotected, horizontally directed sneeze may be potent enough to cause droplet transmission (yu and diu ; marianne et al. ; tellier ; stanley et al. ). referring to the literature (diekmann and heesterbeek ; tang et al. ; walker et al. ) large droplets were considered with a diameter larger than μm, small ones, if the diameter is less than μm, and nucleus droplets when less than μm. therefore, coughing and sneezing produce droplets in a size range from less than to up to μm. in the present study particles of μm, which are contagious at to meters distance, were considered. particles with this dimension remain in the air up to seconds when performing a trajectory of . m as reported by yu and diu ( ) and diekmann and heesterbeek ( ) . particles larger than μm have a remarkably lower permanence in the air and are rarely inhaled by the patients. moreover, particles of the size of . μm evaporate very quickly (marianne et al. ; diekmann and heesterbeek ; tellier ). the cunningham slip correction (c c ) which is a correction to the drag coefficient, used to predict the drag force between a fluid and a particle moving through this fluid (cunningham ; marianne et al. ; tellier ) was used in the proposed model. when the particle diameters become small (less than μm in the air) the fluid can no longer be considered continuous: the drag coefficient on each particle must be divided by the cunningham correction factor. the correction factor is greater than , which means that the effective particle drag coefficient goes down. this reduction in particle drag is the "particle slip" (cunningham ; marianne et al. ; batchelor ) : where λ is the mean free path and d p is the particle diameter. the free mean path of a particle, such as a molecule, is the average distance the particle travels between collisions with other moving particles. if a particle is much smaller than the mean free path, missed collisions are much more likely. for particle-droplets of μm, in the air at atmospheric standard pressure, the mean free path of the air molecules is . μm and the corresponding cunningham factor is . . in the present paper the following conditions were taken into account: the negative pressure of the isolation room provides the airflow performance that effectively controls the mean free path and dispersion of particles with respect to the atmospheric standard pressure; the droplets are initially larger and the evaporation will reduce their dimension; the droplets contain glycol-proteins, lipid-proteins and lipid-glycids constituents of the mucous and also viral particles; these molecules are often very long, some of them reaching nm (cunningham ; marianne et al. ) ; they are sparsely distributed on the droplet surface increasing the collision of the droplets with the air molecules; the presence of glycol and lipid-proteins can increase the local viscosity of the droplets rather than that of pure water. these conditions generate a reduction of the cunningham factor, towards its lower boundary, which is . therefore in all the simulations a value of cunningham factor, equal to , was used. after several exploratory analyses, the droplet turned out to be subjected to two forces: the force of gravity and the drag force of air resistance (cunningham ; batchelor ) . at low speed (v) and relatively low reynolds number the air resistance ( f ) for a droplet of mass (m) is mainly proportional to the viscosity of the medium (η) and to the linear size of the droplet, and is given by the linear term. so the vertical component of the settling velocity is derived from where ρ is the density of the particle (kg/m ), d p the particle diameter (m), g the gravity acceleration (m/s ), η the air viscosity (pa·s) and c c the cunningham factor. the horizontal component of the velocity can be derived from ( ) that is the linear term of the drag force of the air resistance (b is a coefficient that depends on particle diameter and nature of the medium) which gives where ( n·s/m (cunningham ; batchelor ) . the initial concentration value is due to the liquid phase and the corresponding density is kg/dm ; the velocity which represents the mass transport equation solution was introduced into the software cfd-fem simulation (comsol ) as initial condition. the diffusion coefficient of the contaminant was considered to be zero ( . ) − ⋅ assuming that the bio-aerosols, in the form of aerosol, are immiscible with the air (cunningham ; batchelor ) . the progressive dilution of the biological effluent concentration is connected to the mass transport mechanism due to the ventilation plant. an expression that provides the cough velocity function f c (τ ) during time τ (in seconds) taking into account both the horizontal and vertical components expressed in eqs. ( ) and ( ), was carried out: at the initial instant τ = , it is equal to m/s. for mass transport with diffusion (mol/(m ·s)) the following expression was defined using all the real data, a full-scale isolation room present in four hospitals in italy (in pistoia, prato, massa and lucca, tuscany) was modelled. it represents the typical isolation room equipped with a typical hvac system for hospitalization in italian hospitals. the d model of the room is provided in fig. . in italy health care facility design should follow regulations as in (uni ; ashrae ; uni en ) that suggest m /h of volumetric flow rate of outside air being introduced for hospitalization rooms (with m /h for pediatrics) and m /h of air exchange rate for isolation rooms. for air exchange rate different values are imposed: hospitalization rooms m /h (in particular m /h pediatrics), immune suppressed patients m /h of inlet airflow rate and m /h of extraction; infectious patients m /h of inlet airflow rate and m /h of extraction. the isolation room is equipped with a vav and reliable central control system to sense the pressure differential between the patient room and surroundings and adjust fan operation to maintain desired pressure differential. this is a typical hvac primary air system designed for hospitalization infected patients and provides m /h of inlet air and m /h of extraction air (uni ; uni en ) . the room is ventilated by a commercial "turbulence" high induction air diffuser (ceiling diffuser) located in the centre of the ceiling and in the middle area between the two beds, indicated by a (fig. ) . in particular its data sheets call the inlet high induction air diffuser "turbulence" because it is composed of radial distribution of fins that are differently oriented and inclined. the exhaust air is expelled by three return air diffusers located on the ceiling, the door of the toilet and the one adjacent to the corridor. these air vents are respectively indicated by capital letters b, c, d (fig. ) . the scheme of the constant pressures inside the room was calculated referring to these data and the air diffuser dimensions. for the air inlet, the ceiling return air and door return air, the dimensions (transversal section), set constant total pressure and airflow rates respectively as follows: . m , pa and m /h; . m , pa and m /h; . m , pa and m /h; . m , pa and m /h. the exhaust vents of the ventilation system were set at an outlet pressure value in order to maintain the negative pressure within the room as imposed for infectious patients (uni ; uni en ) . a three dimensional model of the isolation room was produced using a cad data base. the inlet high induction air diffuser was solid-modelled by commercial design software (solidworks ) gradually changing its geometry considering tilt and directionality of its fins. at the same time testing simulation results were obtained by cfd-fem simulations (comsol ). this supply air diffuser spreads in all directions and its modelling is complicated. referring to literature (huo et al. ) useful suggestions provided by the method for describing the supply air diffuser boundary conditions were taken into account for the cfd simulation, using the diffuser characteristic jet equations. this allowed comparison of the real data provided by the company on the air inlet velocity and its downward flow from the ceiling with those obtained by first basic simulations (fig. ) . the heads of the two patients, lying on two parallel beds, were modelled using solid geometry to take into account their different positions. in particular three outflow head surfaces were modelled and used to simulate the inlet surface of the bio-aerosols (mouth) related to the different position of each patient. the head surfaces of the patients were also considered two heat sources (latent and sensible). the two bedheadboard lamps, the safety lamps on the ceiling, external opaque wall and the french-window were also modelled. architectural features and thermo-physical properties of different opaque and transparent components of the room were taken into account. three models/scenarios which differ in the direction of coughing and breathing for the same position of the two patients, described by the "supine position" that is when the patients lie on their backs facing the ceiling, were considered. according to studies and experimental results in the literature (memarzadeh and manning ; talon et al. ; brandt et al. ) , laminar airflow condition was assumed in the present work, because air velocity is at low values as imposed (uni ; ashrae ; uni en ) , with low values of reynolds number (< ). this means that large convective vortices may occur, within which an airflow of a "laminar type" is still present, because it is connected to the fluid layers slipping. as a matter of fact, one of the most important simulation issues is the use of turbulent versus laminar flow modelling approaches. high velocity vertical laminar airflow (laf) ( to feet per minute, or fpm) has been typical and used in many hospitals for decades in the us, uk, and europe. the use of unidirectional laminar flow ventilation is today a valid system used for patient isolation and bacterial control. time dependent simulations based on incompressible navier-stokes, convection and diffusion and convection and conduction model for the three scenarios with the aim of investigating the temporal patterns of the ventilation flow and the particles tracing and diffusion in the conditions of coughing and breathing of the two patients, were carried out. comsol multhiphysics code was used (comsol ). see (verdier ; van schijndel ) for a comparison of comsol with respect to other currently used cfd software. the transient simulations with thermal and fluid-dynamic coupled models were preceded by a long enough run without cough/sneeze events. the sneeze and/or cough events were considered at the beginning of the transient simulation. then for all the transient simulations, considering the "supine position" three events (coughing and/or breathing) were investigated: the first event (model_ ) concerns the first patient coughing three times when the second is breathing; the second event (model_ ) concerns the first patient coughing three times when immediately after the second coughs twice, the third (model_ ) concerns both patients coughing, at the same time, three times. for all these models the door was kept closed, so that particle diffusion would be influenced by ventilation airflow patterns alone. the "impulse" functions (volumetric and mass flow due to coughing) for the simulation of coughing events were repeated over time, with a time interval as "peak-to-peak" equal to seconds. in model_ , the time phase displacement between coughing events of the two patients was taken as seconds. these conditions remain throughout the entire simulation of seconds when the ventilation system operating and the coughing/breathing events happen. each simulation considers the results of both the ventilation system in standard operating conditions and the effect of the coughing/breathing events. they were performed with a long enough run ( seconds) for the cough/sneeze events combined with the stationary model of ventilation considering a single and/or repeated sneeze and/or cough event at the beginning of the simulation, with an inlet velocity at the initial instant due to the cough of m/s, which is the maximum experimentally determined connected to the transient flow due to the impulse that has a length of about one second (phillips et al. ). the inlet/outlet breathe velocity was considered constant . m/s. thermal boundary conditions due to sensible and latent heat released by the head surface of the two patients, sensible heat of the two bed-headboard lamps and safety lamps on the ceiling, and then thermal conditions of the external opaque wall and the french-window were taken into account. the thermal conditions that are strictly connected to the indoor airflow displacement and buoyancy thermal effects, in particular due to the plant system solution (the hvac-vav plant combined with radiant panel in the ceiling) and variation of temperature and heat flows related to climatic stresses and external building thermo-physics, were taken into account. the (full) input data, sub-domains settings, boundary conditions and basic equations used for all the time dependent simulations, combining the incompressible navier-stokes, convection-conduction (appendix eq. (a )) and convection-diffusion models (appendix eq. (a )) on the non-isothermal airflow (appendix eq. (a )), are provided in the appendix. for indoor climatic conditions, a uniform internal air temperature of ℃ and % of relative humidity were assumed, as provided by the plant and suggested (uni ; ashrae ; uni en ) . external climatic data were set at the external design conditions of ℃ air temperature and % relative humidity. the simulations started with the incompressible navier-stokes application mode, under laminar flow conditions and then the turbulence k-ε model was activated. the software automatically reformulates the equations with the exception that additional boundary conditions for the turbulence model needed to be specified: e.g., the eddy viscosity automatically replaces the molecular viscosity (batchelor ; comsol ). simulation results were used to calculate the mean air velocity value of the central inlet air diffuser, that is . m/s according to the technical data provided by the company. therefore even with reduced surface diffusion, the airflow is laminar and produces the airflow adherence to the ceiling (it guarantees the "coanda effect") and its slow fall down. the airflow modelling based on cfd with fem, solves the fundamental conservation equations for mass momentum and energy in the form of the navier-stokes equations. the airflow modelling without taking into account the coughing events, provided low reynolds numbers ( − ) that suggested using the incompressible navier-stokes model (that uses the boussinesq approximation) which was combined with convection-diffusion and convection-conduction models. the boussinesq approximation is a way to treat some simple cases of buoyant flows without having to use a compressible formulation of the navier-stokes equations. this approximation assumes that variations in density have no effect on the flow field, except that they give rise to buoyant forces. the air density was then taken to be a reference value, ρ , except in the body force term, which was set to where g is the gravity vector. first extensive transient simulations were performed employing coarse and normal and fine mesh, checking the mesh quality to obtain solutions with acceptable accuracy. then grid independence analysis, that is a very important issue in this type of modelling, was performed. in conducting cfd analysis it is important to undertake a grid refinement process by gradually reducing the grid spacing (cell size) used in the analysis to examine the effect of the reduced cell size on the predicted outcome. it is usual to find that, as the cell size is reduced, the results converge. thus, further reducing the cell size has virtually no effect on the results produced and the result is known as grid-independent result. results obtained from grid dependent solutions may prove to be costly, in that engineering design decisions can be made using potentially faulty information. in order to quantify the influence of the mesh quality and resolution on results, the reference numerical model was gradually solved by varying the number of constituent elements of the computational grid: different simulations were performed under the same physical reference settings on domains and boundary conditions referring to the all parameters value of model_ . the check on grid quality was conducted by monitoring the spatial distribution of thermo-physical parameters and the relative differences between the results, by varying the degree of the mesh fitting and defining higher mesh resolution and quality. seven cases (Ⅰ− Ⅶ), corresponding to higher mesh density, were considered. table shows the number of mesh elements (all tetrahedral), percentage of mesh element increase, degrees of freedom solved, system solver used for the simulations, computational time and ram needed. increase in the number of elements leading to negligible differences in the solutions was also checked. the mesh density was selected to combine solution accuracy with reduction of computational time needed for convergence: a good mesh quality was obtained by degrees of freedom with tetrahedral elements for a non-structured grid. this is consistent with most recent similar studies that use meshes with a number of degrees of freedom usually ranging from to ). these numbers are of the same order of magnitude as the present study but with an important difference: studies in the literature do not take into account simulation of hvac system performance based on multiphysics approach (heat and mass transfer combined with diffusion and fluid-dynamics model). numerical integration used is the implicit backward euler method with backward differentiation formulae (bdf) multistep which guaranteed the quality and robustness of the solution: this method allowed by automatic choices the time step on each iteration with checks and controls on the tolerance imposed on the error and stability regions. the stopconvergence criterion was chosen − ⋅ with independence of the results to the mesh density less than % compared to the reference mesh. the direct system solver "umfpack" of unsymmetrical multi-frontal was used (comsol ). the influence of the mesh degree quality and resolution on the simulation results was checked calculating the value of velocity, pressure and temperature at a barycentric point in the room. table shows the relative differences of these variables, calculated by taking as a reference and normalization value for each parameter, the one achieved by the finer mesh (mesh case Ⅶ). this means, e.g., for the velocity v: due to computational time and complexity, the optimization as good practice in cfd, all simulations to study ventilation and airflow displacement were carried out disregarding the coughing and breathing of the patients. then transient simulations considering the ventilation system operating and the seconds long coughing/breathing events of the two patients were performed. figure shows the velocity field with a slice representation at the height of m (nearest to the beds, fig. (a) and m (fig. (b) ). their comparison shows that the hvac plant does not produce important vertical air vortices but stagnation zones between the two beds and the ceiling. the ventilation and air diffusion pattern inside the room with no coughing and breathing events of the patients, are provided in fig. . this result agrees with the literature results by phillips et al. ( ) , for a steady state scenario. analysing fig. , it appears that the higher particle concentration remains in the zone of the emission sources (the fig. velocity field at m (nearest to the beds; (a)) and m (b) height from the floor provided by the only air ventilation system operating-slice representation fig. the velocity field with wide convective vortices due to the combined effect of the ventilation with the temperature gradient breathing zone) at about cm, as shown in the literature (rygielski and uden ; stanley et al. ; talon et al. ) , whereas the streamlines of the velocity field rise to the ceiling with wide convective vortices due to the combined effect of the ventilation with the temperature gradient. the airflow field is minimally influenced by patients sensible heat transfer and the fact that the temperature difference throughout the room is small. the flow field and velocity distribution induced by the high turbulence air inlet diffuser, combined with the air return diffusers, produce wide recirculation zones near the wall and small partial stagnation areas near the ceiling and between the two beds (fig. ) . variable directions of the airflow, due to the high turbulence air inlet diffuser, provide its widespread and homogeneous distribution (the so called "coanda effect") on the ceiling and then its progressive drop down. the mean air velocity value of the central diffuser, calculated by obtained results, is . m/s, therefore even with reduced surface diffusion, the airflow is laminar in adherence to the ceiling. comparing fig. and fig. , it can be seen that the airflow field is minimally influenced by the patient heads and lamps and the temperature difference throughout the air volume in the room is . ℃. the mean indoor air temperature value is almost identical to the supply air temperature of ℃, except in areas close to the patients and to the radiant panel on the ceiling (fig. ) . vertical temperature variation at the occupant zone is lower than ℃ and this provides uniformity in temperature distribution in the zone between the two beds, according to iso ( ) . this result could be due to high rate level of ventilation. the downward airflow from the inlet air diffuser pushes air from the ceiling downward towards the return air outlet diffusers. both the velocity and temperature field are similar in the three scenarios (models_ , , ), all of which have "laminar" streams with wide convective vortices. obstacles and heat transfer (from patient heads, lighting and the ceiling radiant panel) but also the building components (windows and external walls) interaction with solar radiation and the external air temperature value, interact with the main airflow pattern. buoyancy driven airflow around the patient heads raises particles above lighting, the wall behind and in the particular zone between the beds. it can be found that the position of the two bed-headboard lamps has a remarkable effect on airborne particle dispersion fig. temperature field-at m height (a), slice-detail (b) on the wall (c), and the whole room (d) (fig. ) . the particle concentrations (point sources were assumed for the present study) in various parts of the room are very sensitive to the location of the particle sources as highlighted by chow and yang ( ) . particle tracing and diffusion suggest that in the room there is a formation of a zone, albeit a limited one, that should be checked by a microclimatic and contaminant control between the two beds and around the ceiling surface. in particular, model_ and model_ provide the most critical conditions in the isolation room, due to bio-aerosol concentration: the temporal and spatial dynamics of coughing of the two patients produces an increase in bio-aerosol residual concentration. the analysis of the residual concentration highlights the presence of important levels of bio-aerosol in the vicinity of the upper zone of the two beds, of the wall adjacent to them and the surfaces of the bed-headboard lamps. bio-aerosol concentration, over − seconds, achieves high values and then decreases with time because of the continuous dilution provided by the airflow inlet. during transient airflow displacement ( − seconds) a local stagnation zone of higher bio-aerosol concentration is produced between the two beds and small recirculation flows are generated near the patients, due to lower displacement efficiency of the plant. the particle tracing results show that particles arrive at more than meters distance from the coughing patient and also show their impact on the wall, ceiling and, in particular, bed-board lamps. the contrast of the particle tracing results highlights − μm during time due to coughing ( fig. (a) at seconds, and (b) at seconds). these trajectories (fig. ) refer to these particles whose positions at the initial instant overlap with the surface of the mouth of the coughing patient. to better investigate the ventilation system performances, a new model that takes into account open door condition was simulated. starting from the model_ concerning both patients coughing three times at the same time (in particular from to seconds during transient simulation), the door was opened and simulation was performed from to seconds under this condition. the wall adjacent to the corridor and its open door were considered separated for imposing different sub-domain settings and boundary conditions. the boundary condition for the wall with the open door was assumed to be of "fluid adhesion" (no-slip boundary condition) and the constraint condition for the opening was taken at the same pressure difference as the air return diffuser located on the closed door. the door opening causes a remarkable airflow to the adjacent zone (fig. ) as well as particle diffusion in the corridor even if bio-aerosol residual concentration remains higher in the zone of the wall opposite to the patients bed (fig. ) as reported from experimental results by phillips et al. ( ) . the simulation results showed that the position of an air inlet ceiling diffuser and of the exhaust vents is critical: the location on the centre of the ceiling of the high induction air supply diffuser, combined with the placement of the air return diffusers produces effects on the airflow pattern and causes the arrive of some particles at the door, according to the fundamental work of kao and yang ( ) . the placement of the air return diffuser in particular immediately over the patient bed would result in better removal of airborne particles as also reported from the experimental results by kim and augenbroe ( ) and kao and yang ( ) . meanwhile the airflows in regions of the room, away from the supply vent, have lower velocity values and variable direction due to recirculation effects near the air return diffusers and the radiant panel on the ceiling. the region of droplet fallout is wide, even when the door is open, because positioning in the centre of the ceiling of the high induction air supply vent. this study provides useful indications for controlling dispersion and concentration zones of droplet nuclei. it can provide important recommendations for disease control and careful design and optimization of ventilation in the studied isolation room obtaining significant reduction of energy consumption in the hospital where it is located. results can provide useful indications on the selection of the best type and position of the high inlet air diffuser in order to minimize the intermixing between supply air and the air in the room. this is crucial because in italy it is very difficult to carry out experimental measurements and/or monitoring campaigns inside hospitals, especially in isolation rooms, because there are very strict sanitary regulations mainly depending on long time legal permissions and complicated procedures. the main problem, highlighted by the sanitary regulations, concerns experimental measurements with the presence of patients in isolation rooms. the obtained results provide a mean air velocity at the patients' beds, within the recommended threshold value of less than . m/s and its accordance with literature results (chow and yang ; tunga et al. ), but most importantly, indicate the risk contagious zones. results show the best position for the room studied, of the extract air diffuser that should be at low levels (close to the floor and between and behind the head of two patients). the residual bio-aerosol concentration (under closed and open door conditions) provides an indication for the best protection distance between the beds for controlling patient but also medical staff and visitor infection. this study highlights the fact that contaminant removal efficiency, in particular in the zone between the two beds, would appear to be more appropriate: it is not possible with the existent ventilation system to control the particles released during coughing events to prevent them from reaching the breathing zone. results comparison highlights how the present ventilation system can not control particle diffusion and residual concentration when the door is open. this agrees with some literature results (kao and yang ; kim and augenbroe ; phillips et al. ) . it would appear that for severe and acute contagions, an anteroom should be necessary to protect the patient and/or occupants/workers in the hospital. the cfd-fem simulation approach, reproducing real cases, is a valid method for determining the efficiency of the ventilation system, is rather inexpensive (in particular it can also be applied for using open software) and could be used (after threshold evaluation assessed through tests and data fitting on the particular conditions) for routine evaluation of effectiveness in normal plant activity. this approach can be also a valid tool for proper ventilation design in order to reduce energy consumption due to operation modes of the vav ventilation system. the method, that was applied to an isolation room, could equally be extended to other targets such as: operating theatres, wards, reception areas and admission wards, public transport. time scaling coefficient sub-domain settings equation used for the incompressible navier-stokes model: and starting with the momentum balance in terms of stresses, the generalized equations in terms of transport properties and velocity gradients are the boundary settings used are provided for the convection-conduction model a) − f), convection-diffusion model e) − g) and then for the incompressible navier-stokes model h) − k): a) "insulation" for all the internal walls and doors, the two beds, ceiling, floor, the two bed-headboard lamps and the lighting on the ceiling. b) "heat flux" for the external wall and the french-window taking into account for the convective coefficient and the external air temperature a constant value w/(m ·℃) and ℃, respectively. c) "temperature" for the radiant panel on the ceiling, at the fixed value of ℃ as suggested (ashrae ). d) "temperature" for the inlet air diffuser, assuming the constant value of the air inlet of ℃. e) "insulation symmetry" linked to all the walls and doors, the two beds, the ceiling, floor and all the lighting. f) "convective flux" for all the air return diffuser and also for the air inlet diffuser. g) at the "supine position" of the patients, the boundary condition associated with the mouth of the patient breathing was "convective flux"; the boundary condition associated with the mouth of the patient coughing was "inward flux" linked to the "cough function". h) "no-slip" for the all walls and doors, the two beds, the ceiling and floor. i) "pressure-no viscous stress" with a boundary type "outlet" for the air return diffuser b, located in the ceiling, for the air return diffuser c, located in the door of the toilet and for the air return diffuser d, located in the door adjacent to the corridor (fig. ). j) "velocity" with a boundary type "inlet-normal inflow velocity" for the air inlet diffuser a, located in the centre of the ceiling (fig. ). k) the boundary type and boundary condition associated with the mouth of the patient breathing were respectively "outlet" and "velocity-normal outflow"; the boundary type and boundary condition associated with the mouth of the patient coughing, were respectively "inlet" and "velocity-normal inflow" that is the velocity value provided by the cough function. input data used were as follows: a) the thermal conductivity, density, viscosity conductivity and specific heat of the air were considered constant. b) the density, molecular mass ( • − kg/mol) and diffusion coefficient of the water ( • − m /s) were considered constant. c) the inlet velocity at the initial instant of transient simulation, due to coughing event was considered constant ( m/s). d) the inlet/outlet breathe velocity was considered constant ( . m/s). e) the inlet air temperature form the central air diffuser was taken at ℃ as provided by the plant design. f) the mean ambient temperature and relative humidity were fixed to the values provided by the plant at ℃ and %, respectively. g) the sensible and latent loads due to "rest and sat" activity, taking into account the clothes and the ambient air temperature of ℃, are w and w, respectively, as usually suggested for the standard body area of . m (from dubois formula (galson and guisbond ) ). then taking into account the mean body conductivity and the head volume, the specific dissipation heat and total power of the head were evaluated. h) the pressure scheme inside the room was calculated referring to the hvac-vav primary air system and to the air diffuser dimensions indicated in the plant system project. i) taking into account the thermo-physical properties of the different constituent layers, the equivalent thermal transmittance of the external wall and french-window were evaluated and considered constant (external wall . w/(m ·k); french-window . w/(m ·k)). j) specific dissipating heat and power for the two bedheadboard lamps were calculated taking into account their lighting parameters (compact fluorescent, k colour temperature, w absorbed power, lm lighting flux). k) safety lighting on the ceiling was considered a barrier to the air displacement. ashrae handbook: hvac applications, si edition hvac and indoor thermal conditions in hospital operating rooms assessing ventilation system performance in an isolation room an introduction to fluid dynamics operating room ventilation with laminar airflow shows no protective effect on the surgical site infection rate in orthopedic and abdominal surgery simplified diffuser boundary conditions for numerical room airflow model: final report of rp- refrigerating and air-conditioning engineers performance of ventilation system in a non-standard operating room on the velocity of steady fall of spherical particles through fluid medium indoor environmental quality in hellenic hospital operating rooms mathematical epidemiology of infectious diseases development of a method for bacteria and virus recovery from heating, ventilation, and air conditioning (hvac) filters hospital sepsis control and tb transmission flow dynamics and characterization of a cough a systematic approach to describe the air terminal device in cfd simulation for room air distribution analysis moderate thermal environments-determination of the pmv and ppd indices and specification of the conditions for thermal comfort using large eddy simulation to study airflows in and around buildings investigating a safe ventilation rate for the prevention of indoor sars transmission: an attempt based on a simulation approach virus diffusion in isolation rooms ventilation operation in hospital isolation room: a multi-criterion assessment considering organizational behaviour the effect of airconditioning parameters and deposition dust on microbial growth in supply air ducts role of ventilation in airborne transmission of infectious agents in the built environment-a multidisciplinary systematic review the predictions of infection risk of indoor airborne transmission of diseases in high-rise hospitals: tracer gas simulation peptides of human bronchial mucus glycoproteins. size determination by electron microscopy and by biosynthetic experiments methodology developed for the energy-productive diagnosis and evaluation in health buildings comparison of operating room ventilation systems in the protection of the surgical site optimization of a hospital room by means of cfd for more efficient ventilation numerical modelling of exhaled droplet nuclei dispersion and mixing in indoor environments flow of microorganisms in a hospital stair-shaft. full-scale measurements and mathematical model numerical heat transfer and fluid flow isolation room ventilation. design case studies particle removal efficiency of the portable hepa air cleaner in simulated hospital ward creating comfort. nine considerations for selecting the right hospital hvac system pandemic ready. hvac systems for worst-case scenarios background culturable bacteria aerosol in two large public buildings using hvac filters as long term, passive, high-volume air samplers performances of different types of airflow system in operating theatre factors involved in the aerosol transmission of infection and control of ventilation in healthcare premises review of aerosol transmission of influenza a virus an experimental study on ventilation efficiency of isolation room air-conditioning systems for thermal comfort in buildings. general, classification and requirements. offer, order and supply specifications ventilation for non-residential buildings-performance requirements for ventilation and room-conditioning systems integrated modelling of dynamic heat, air and moisture processes in buildings and systems using simulink and comsol particle image velocimetry of human cough benchmark of femlab, fluent and ansys hospital and community acquired infection and the built environment-design and testing of infection control rooms total and regional deposition of inhaled aerosols in humans how many airborne particles emitted from a nurse will reach the breathing zone/body surface of the patient in iso class- single-bed hospital protective environments? a numerical analysis the sub-domain settings and boundary conditions, used for all the time dependent simulations, combining the incompressible navier-stokes, convection-conduction and convection-diffusion models on the non-isothermal airflow, are provided in this appendix. the equations used by cfd-fem transient simulation are as follows:sub-domain settings equation used for convection-conduction model:where ρ density (kg/m ) c p the specific heat capacity at constant pressure (j/(kg·k)) t absolute temperature ( key: cord- - cargkwy authors: nazaroff, william w title: indoor bioaerosol dynamics date: - - journal: indoor air doi: . /ina. sha: doc_id: cord_uid: cargkwy inhaling indoor air is the primary means by which humans are exposed to bioaerosols. considering bacteria, fungi, and viruses, this study reviews the dynamic processes that govern indoor concentrations and fates of biological particulate material. bioaerosol behavior is strongly coupled to particle size; this study emphasizes the range . – μm in aerodynamic diameter. the principle of material balance allows concentrations to be determined from knowledge of important source and removal processes. sources reviewed here include outdoor air introduced by air exchange plus indoor emission from occupants, occupant activities, and moldy materials. important mechanisms that remove bioaerosols from indoor air include air exchange, deposition onto indoor surfaces, and active filtration. the review summarizes knowledge about size‐dependent particle deposition in different regions of the respiratory tract, techniques for measuring indoor bioaerosols, and evidence for diseases caused by airborne exposure to bioaerosols. future research challenges and opportunities are highlighted. in our daily lives, we humans move through a sea of microbial life that is seldom perceived except in the context of potential disease and decay (feazel et al., ) . it is by now well established that most humans spend most of their time indoors. furthermore, it is also well known that the indoor environments occupied by humans contain abundant material of microbial origin. however, we have gained until now only partial understanding of the complexity and richness of the indoor microbiome and its significance for human well-being. while acknowledging the limitations, in this article, i seek to summarize what is known or what can reasonably be inferred about an important subtopic of the microbiology of the built environment. the title 'indoor bioaerosol dynamics' is meant to imply that we seek a mechanistic, quantitative description of the processes and outcomes regarding the microbiology of the built environment, centering on what is, was, or will be airborne. there are many reasons to be interested in the microbiology of the built environment. the context for this study derives from three primary concerns. first, exposure to bioaerosol material can cause or can contribute to many important diseases. second, adverse respiratory symptoms correlate well with indicators of indoor dampness (fisk et al., ) . it is a reasonable hypothesis, although not yet well established, that the underlying cause of these associations is microbial. third, the microbiology of spaces we occupy may influence the human microbiome in ways that could confer health benefits. evidence for this last point is admittedly thin. there is growing evidence that people influence the microbiology of the spaces they inhabit (e.g., lax et al., ) . emerging evidence also indicates that some aspects of the human microbiome are important for health (grice and segre, ) . we further know that aspects of our personal microbiome can be influenced by individual factors such as diet and illness. so, it is not a large stretch to imagine that elements of our personal microbiome that matter for health might in fact be influenced by attributes of the spaces we inhabit, including their microbiology generally and their bioaerosol aspects specifically. hanski et al. ( ) reported evidence supporting an analogous suggestion: 'rapidly declining biodiversity may be a contributing factor to . . . the rapidly increasing prevalence of allergies and other chronic inflammatory diseases among urban populations. . .. ' following the introduction, the study is organized into two main sections. in 'framing the issues,' i define a framework for considering indoor bioaerosol dynamics. that section also defines the scope and limitations of this study. it presents some empirical evidence about indoor bioaerosols to help establish a context for studying dynamics. the section outlines the use of a material balance as a first-principles method for linking process to outcome for indoor bioaerosols. the size of particles is described as a primary variable of concern. regional deposition of bioaerosol particles in the respiratory tract is described as a process linking concentrations and exposure to dose. opportunities and limitations for progress in understanding indoor bioaerosol dynamics are strongly influenced by measurement technology, so some of the key measurement methods are summarized. evidence regarding infectious disease transmission by airborne routes is also assembled. the second primary section ('dynamic processes') summarizes available information on many important processes that affect the concentrations and fates of indoor bioaerosol particles. this section begins by reviewing the state of knowledge regarding building air exchange, an important removal mechanism for indoor bioaerosols and also a means by which outdoor bioaerosol particles are brought indoors. then, the article proceeds to discuss several additional processes that can affect indoor bioaerosol levels: deposition onto room surfaces, bioaerosol intrusion from outdoor air, indoor emission sources, and other factors, including bioaerosol control, airborne growth and decay, and indoor transport and mixing. in the conclusion, important challenges facing further studies are described along with several opportunities for near-term progress advancing knowledge about indoor bioaerosol dynamics. such progress is fundamental to efforts to better understand how the microbiome of indoor environments interacts with human health and well-being. framing the issues scope, limitations, and approach bioaerosols are usually defined as aerosols or particulate matter of microbial, plant or animal origin. . .. bioaerosols . . . may consist of pathogenic or nonpathogenic live or dead bacteria and fungi, viruses, high molecular weight . . . allergens, bacterial endotoxins, mycotoxins, peptidoglycans, b( ? )-glucans, pollen, plant fibers, etc.- douwes et al. ( ) 'bioaerosol' is a contraction of 'biological aerosol', and 'aerosol' refers to a suspension of particles in a gas. the exact boundary for what should be included or excluded in the term 'bioaerosol' is challenging to define. for the purposes of this study, the central focus will be defined more narrowly. all microbes are included: viruses, bacteria, and fungi. also included are microbe-associated chemicals such as endotoxins and mycotoxins. however, although they are part of bioaerosols, this article shall not explicitly address either pollen or pet-or pest-associated allergens such as cat dander or fecal pellets of dust-mites. this review also emphasizes the human-bioaerosol nexus in indoor environments. the indoor environments to be considered are those ordinarily and commonly occupied by humans: residences, offices, schools, and other settings that are occupied a high proportion of the time, or in which occupant density is high. not included are industrial environments that have high associated occupational exposure potential, such as those associated with food systems. much of the literature concerning microbiology in indoor environments focuses on dust as the sampled matrix (rintala et al., ) . favoring this approach is that dust reflects a longer term average condition in the environment, whereas bioaerosols are more dynamically variable and therefore more challenging to sample in a manner that is representative of time-averaged conditions. the primary counterargument is that the relationship between dust and human exposure is much less clear than is the relationship between bioaerosol particles and inhalation exposure. notwithstanding its prominence in the literature, the microbiological composition of indoor dust is not a primary focus of this study. the overall approach employed in this review is to adapt and apply concepts from indoor aerosol science (e.g., as described in nazaroff, ) . in particular, material balance is utilized as a core principle. particle size is a primary determinant of indoor bioaerosol behavior. we seek a mechanistic understanding because it provides a powerful basis for extrapolating from limited empirical evidence. we also seek to develop quantitative insight, because knowledge of the scale of processes and outcomes is essential as a basis for separating the important from the trivial. some prior scholarly reviews cover similar topics (burge, ; douwes et al., ; gregory, ; spendlove and fannin, ) . however, none of these earlier reviews is as strongly grounded in indoor aerosol science as the present article. to provide context for the process-oriented discussion to follow, it is instructive to consider some of the important empirical evidence concerning indoor bioaerosols. in the summaries to follow, i highlight several field-sampling studies whose results provide important clues about bioaerosol concentrations, associated particle-size distributions, and potential influencing factors. the largest published survey of indoor bioaerosol levels involved more than fungi samples measured indoors and outdoors in~ buildings in the united states (shelton et al., ) . the analysis was culture based, so the results reflect number concentrations of viable airborne spores. little information was reported on the sampling protocol; however, it seems likely that the measurements were based on short-term sample collection. also, little information was reported about the buildings in which these measurements were taken. the cumulative probability distribution functions ( figure ) show that the data are well fit by lognormal distributions. the geometric mean outdoor concentration ( cfu/m ) is about higher than the geometric mean indoor concentration ( cfu/ m ). the indoor levels show considerably broader range of concentration than do the outdoor levels (gsd of . compared to . ). these data support an important general finding that 'in the majority of cases, indoor fungal aerosols are controlled by outdoor concentrations' (burge, ) . note that the ratio of geometric mean concentrations, . , lies well within the range . - . predicted by riley et al. ( ) to apply as the fraction of coarse-mode ( . - lm) particles that would be found in indoor air when outdoor air was the sole source. culture-based analyses measure only a small portion of bioaerosols. figure presents data from a personal monitoring study of elementary school teachers in finland (toivola et al., ) . for each of the subjects, air was sampled through filters throughout two -h periods using personal sampling pumps. particles were extracted from the filters and analyzed for both fungi and bacteria, using culture-based methods and also using microscope-assisted visual counting. a key point is that the total number concentrations of fungal spores and bacterial cells determined microscopically were a few orders of magnitude higher than the corresponding number concentrations of colony forming units, as determined by culture-based assessment. if (shelton et al., ) . in all, indoor and outdoor samples were collected during indoor air quality investigations although it is common for fungi concentrations to be higher in outdoor air than indoors, in occupied spaces the reverse is commonly true for bacteria (bartlett et al., ; fox et al., ; hospodsky et al., ) . figure (chen and hildemann, a) illustrates this point. the plotted results are geometric mean concentrations based on filter samples of - h duration collected inside and outside of ten occupied residences in california. summing across all particle sizes, the gm level of endotoxin (associated with gramnegative bacteria) was about % higher indoors than outside, whereas the gm level of ( - )-b-d-glucans (a marker of fungi) in outdoor air was almost twice the corresponding indoor level. an important point is that human occupancy and activities are major factors influencing indoor microbiology. humans are important primary sources of certain bacteria and viruses. even for fungi, for which humans do not appear to be a major primary source, human activities play an important role, for example, in shedding particulate matter from our clothing or in suspending settled dust that can contain materials of fungal origin. figure illustrates this point using samples collected in the same ten houses as discussed in connection with figure . in this case, only indoor air samples are considered. the ten houses are divided into two equal-sized groups, sorted according to degree of occupancy (chen and hildemann, b) . occupancy is used here as a surrogate measure of the intensity of human activity. across all measures displayed in the figure-that is, airborne concentrations of particulate matter, protein, endotoxin, and glucans -the geometric mean level in the high activity homes was considerably higher than in the low activity homes. measurement of airborne viruses in indoor environments has lagged behind measurement of bacteria and fungi. the recent development of quantitative polymerase chain reaction (qpcr) and other dnabased measurement technologies has facilitated studies that measure pathogenic viruses in indoor air. data from one study targeting the influenza a virus are presented in figure . during the flu season, sizeresolved particle samples were collected on filters in three different environment types: a day care center, a health center, and (three) airplanes. in all, samples were collected by means of sampling at a rate of l/min for periods of - h. eight of these samples ( %) contained influenza a virus, with concentrations ranging from to genomes per m , and a substantial proportion of the detected virus was associated with fine particles (< . lm) that can remain airborne for extended periods and that can also penetrate and deposit deeply in the respiratory tract when inhaled. a fundamental principle that is usefully applied in quantitative, mechanistic studies of indoor environmental quality is material balance: stuff is conserved. on a time-averaged basis, the sum of the rates of supply of a bioaerosol component to the indoor air must balance the sum of the rates of removal. this quantitative balance provides a basis for connecting rates of processes to concentrations of bioaerosol components. figure presents schematic representations of indoor environments that can be used to formulate material balance equations. consider a residential space ( figure a ). in this representation, three processes can add bioaerosol material to the indoor air: (i) natural ventilation through designed openings (at rate q n c o ); (ii) infiltration through leaks in the building envelope (p q l c o ); and (iii) direct indoor emissions (e). (to the extent that tracked-in microbes contribute to the indoor bioaerosol load, this process would be included in the direct indoor emission term, e.) three processes can remove bioaerosol material: (i) ventilation airflow out of the building ([q n + q l ] c); (ii) filtration in the recirculating airflow (g r q r c); and (iii) deposition onto room surfaces (bvc). some important observations should be made about equation ( ). first, the symbol '~' is used instead of an equal sign because the expression is only approximately true. among the considerations that limit its strict applicability are that some of the parameters on the right-hand side are time dependent. if applied over short time intervals, one must also be concerned that accumulation, that is, the increase or decrease in the amount of bioaerosol in the indoor space, is not incorporated in equation ( ). also, on a time-averaged basis, the equation is only approximately correct because it does not account for the possibility that time-varying parameters may correlate in such a way that the average of the product is not the same as the product of the averages. a second key point is that some of the processes exhibit strong dependence on particle size. this aspect is addressed in detail in subsequent sections of the study. a third feature of this equation is that it implicitly assumes that the indoor space can be represented as well mixed. that is not always the case. finally, the equation is specific to the particular schematic representation of the indoor environment depicted in figure a . this configuration accommodates some common conditions in residences, such as air exchange by a combination of natural ventilation schematic representation of indoor environments for quantitatively relating influencing processes to resulting concentrations of bioaerosol parameters: (a) residence; (b) commercial building. symbols (associated units) are as follows: c o -outdoor concentration of bioaerosol parameter (quantity/m ); cindoor concentration of bioaerosol parameter (quantity/m ); v -interior volume (m ); q n -natural ventilation rate (m /h); q l -ventilation rate associated with infiltration (m /h); q r -recirculation airflow rate (m /h); q m -mechanical ventilation supply flow rate (m /h); p-penetration efficiency of bioaerosol parameter associated with infiltration (-); g r -single-pass filtration plus deposition efficiency in recirculating airflow (-); g m -single-pass filtration plus deposition efficiency in mechanical ventilation supply flow (-); b-rate coefficient for deposition on indoor surfaces (h À ); and e-emission rate from indoor sources (quantity/h) (yang et al., ) . in all, eight of sixteen samples collected ( of in a health center, of in a day care center, and of in an airplane) tested positive for influenza a. abbreviation: gcn = genome copy number (q n ) and infiltration (q l ), and the potential presence of a central air distribution system (with flow rate q r ) for heating and cooling. on the other hand, the schematic and the resulting equation would need to be modified to accommodate mechanical ventilation. for a commercial building space, the schematic representation in figure b is more common, with mechanical ventilation (q m ) and no natural ventilation. the appropriate material balance in this case is presented in equation ( ). similar caveats as in equation ( ) apply. particle size most indoor airborne microbial material is found on particles in the diameter range . - lm. this range of diameters corresponds to six orders of magnitude in particle mass. in part because of the large range, size is a major determinant of indoor airborne particle behavior (nazaroff, ) . the behavior of larger particles is strongly influenced by their mass. gravitational settling and inertial impaction are important deposition mechanisms. the smaller particles in this size range follow airstreams more closely. transport mechanisms leading to the departure of smaller particles from air streamlines include brownian motion. generally, the efficiency of filtration, the likelihood of deposition somewhere in the respiratory tract, and the rate of deposition onto indoor surfaces are all considerably smaller for particles with diameters in the range . - lm as compared with particles with diameters in the range - lm. whole microbial agents vary widely in size and mainly follow this pattern: viruses are much smaller than bacterial cells or endospores, which are smaller than fungal spores. for example, the influenza a virion is~ . lm in size (noda, ) . the cells of staphylococcus aureus, a common opportunistic pathogenic species, have diameters of~ lm (http://textbookofbacteriology.net/staph.html). common indoor fungal spores have been measured to have aerodynamic diameters of~ . lm (cladosporium cladosporioides), . lm (aspergillus fumigatus), and~ . lm (penicillium melinii) (reponen et al., ) . spores of other species such as alternaria alternata and epicoccum nigrum are considerably larger (mcginnis, ) . bioaerosol particles can be larger or smaller than the size of whole microbial agents. for example, bacteria have been observed to occur in clusters or attached to other material such as fragments of human skin (davies and noble, ) . fungal fragments have also been measured in indoor air (g orny et al., ) . based on samples of outdoor air, yamamoto et al. ( ) found that the geometric mean size of fungal dna associated with particular taxa was considerably larger than individual cultured spores. theoretical and experimental evidence support an expectation that microbial airborne particles behave similarly to abiotic particles of the same aerodynamic size. consequently, powerful tools and theories from aerosol mechanics can be applied to study indoor bioaerosols. for bioaerosol particles, arguably the most important exposure pathway is inhalation followed by deposition in the respiratory tract. the probability of deposition varies with particle size, with lung morphology, and with breathing characteristics. figure , which is based on semi-empirical modeling originally developed for radiological protection (yeh et al., ) , illustrates some of these features. in these model calculations, the respiratory tract is divided into three zones: the head region (nopl), the tracheobronchial or conducting airways (tb), and the pulmonary or gas-exchange region (p). the information presented in this figure reflects two dominant characteristics of the system. first, the three regions of the respiratory tract are exposed to bioaerosol particles sequentially. for the largest particles considered, the high deposition effi- fractional particle deposition in different regions of the respiratory tract in relation to particle size. the results are from the ncrp/itri semi-empirical model (yeh et al., ) . particle density is assumed to be g/cm . the results assume nose breathing, tidal volume of . l, breathing frequency of / min, and a functional residual capacity of l. in each frame, the deposition fraction is referenced to particle concentrations in the inhaled air. total deposition fraction in the respiratory tract for a given particle size would be obtained by summing results for the three regions ciency in the head protects the distal airways from exposure. second, two different mechanism classes control particle deposition. the behavior of the larger particles is dominated by their inertia. larger particles have a higher mass-to-drag ratio, and so the larger the particle, the more efficient the deposition. however, for submicron particles, inertial processes are relatively unimportant. for the smallest particles in this figure, brownian diffusion is the dominant transport mechanism. this is a slow process, important only in the smallest airways: deposition efficiency of . - lm particles is small in the head region, yet substantial in the pulmonary region. similarly, the deposition efficiency increases with decreasing particle size when brownian diffusion dominates. worth noting is that the combination of these effects leads to two important modes of particle deposition in the pulmonary region. not only are the smallest particles deposited with reasonable efficiency, but there is also an important mode that peaks in efficiency at about lm in diameter, a size that is important for bacterial and fungal bioaerosol particles. measure what is measurable, and make measurable what is not so.-galileo galilei many important aspects of indoor bioaerosols must be determined by experiment rather than from theory. experimental capabilities are intrinsically linked to technologies available for measurement. while many methods have been developed for mea-suring bioaerosol attributes, the availability of suitable methods remains an important constraint on research progress. table provides a summary of many methods that have been used for bioaerosol sampling and analysis. (see also the reviews by henningson and ahlberg, and verreault et al., ) . the most widely applied methods have been culture based. these are subject to the limitations noted in connection with figure . culture-based methods offer the virtues of being relatively inexpensive, well developed, quantitative, and taxon specific. disadvantages include that only viable organisms are measured and only a subset of airborne organisms is culturable. a commonly employed method of direct impaction onto an agar substrate utilizes a short sampling period, which provides only a snapshot of the viable organism concentration at the time of sampling. relating these results to longer term exposure conditions is challenging because of the high degree of temporal variability, for example, associated with occupancy and occupant activities. effective bioaerosol sampling and analysis for studies of indoor environmental conditions must address two key challenges: specificity and temporality. no method is well suited to address both of these challenges well. the nature and significance of these issues varies according to the specific concern. in studies of airborne infection, specificity is essential. pathogenic strains may be closely related to nonpathogenic organisms of the same species. some of the chemical analytes that can be used in bioaerosol studies are of interest because of their direct potential for adverse health consequences. examples include endotoxin and ( ? )-b-d-glucans. other analytes, such as ergosterol or muramic acid, are not of direct health concern, but rather can be valuable as quantitative indicators of broad bioaerosol categories. dynamic processes can influence indoor bioaerosol concentrations by an order of magnitude or more over time scales that are as short as minutes. consequently, it is important to have measurement tools that permit sampling and analysis with high time resolution. there are no methods for bioaerosol sampling and analysis that are suitable for routine research application, that are highly specific, and that exhibit good time resolution. because of these limitations, process-oriented studies that are discussed in the next section have largely used abiotic particles as surrogates. the recent advent of real-time fluorescence-based instruments enhances capabilities for studying dynamic behavior of bioaerosols. these instruments offer excellent time and size resolution, but typically provide no biological specificity, even at the level of differentiating between bacteria and fungi. diseases associated with bioaerosol exposure . . .there is a growing body of data in support of the conclusion that air transmission within enclosed spaces plays an important role in the communication of many bacterial and viral diseases, especially those of the respiratory tract.- robertson ( ) there are two noteworthy points to make about the quote from robertson: (i) it was published more than years ago and (ii) the role of airborne routes in the transmission of disease remains controversial today for many infectious agents. table provides a list of many diseases for which there is published evidence indicating that airborne exposure indoors makes a meaningful contribution to the occurrence or spread of disease. this section summarizes evidence concerning the dynamic processes that influence indoor bioaerosol levels. the emphasis is on those processes depicted schematically in figure . building air exchange is the replacement of indoor air with outdoor air. air exchange is needed to limit the accumulation of carbon dioxide and other bioeffluents from human occupants. it is also used to limit the concentrations of pollutants emitted from inanimate indoor sources. when outdoor air is uncontaminated, then increasing the air exchange rate consistently improves indoor air quality. however, when climate conditions are not comfortable, then the air exchange rate is limited to avoid excessive energy use. in many circumstances, outdoor air is polluted to levels that exceed health-based standards. in these cases, by introducing pollutants from outdoor air, air exchange can be an important contributor to indoor pollution. building air exchange may be divided into three modes: infiltration refers to the uncontrolled leakage of air through the building envelope; natural ventilation occurs through windows and other designed openings; and fans induce mechanical ventilation. buildings generally leak, so infiltration is regularly a contributor to air exchange. although practices vary and are changing with time, it is common in the united states for air exchange in single-family dwellings to occur by a combination of natural ventilation plus infiltration. mechanical ventilation plus infiltration is common in commercial buildings. the air exchange rate (aer) is an important metric for characterizing air quality aspects of buildings. this measure is the volume-normalized flow rate of air from the building to outdoors. as depicted in figure , the aer would be (q n +q l )/v for the residential sche- matic (i) and (q m +q l )/v for the commercial schematic (ii). figure presents a summary of aer data from two large studies conducted in the united states. the measurements in residences ( figure a) show a median in the approximate range of . - per hour. considering individual households, most of the data lie within a range that spans about an order of magnitude, from . to per hour. the base study of~ commercial buildings (figure b) shows a similar central tendency and a somewhat larger range, especially at the high end of the distribution. each of these data sets conforms reasonably well to a lognormal distribution. the aer sets a time scale for one of the main removal processes for impurities in indoor air. an aer of . - per hour means that any airborne species removed primarily by air exchange will have a characteristic residence time of one to two hours in the building air. across the aerodynamic diameter range of . - lm, particle deposition onto room surfaces is an important fate. in equations ( ) and ( ), the deposition loss rate is parameterized by a size-dependent rate constant, b. the importance of deposition as a removal mechanism for airborne bioaerosol particles can be explored by comparing b to the air exchange rate. figure presents some data on size-dependent particle loss rates by means of deposition to room surfaces. these data show that, for particles in the size range . - lm, the deposition loss rate coefficient is~ . - . per hour, a value that is comparable to the lower end of range of air exchange rates discussed in the previous subsection. under low air exchange conditions, deposition of these submicron particles is competitive with air exchange as a removal process, but in indoor for each house, one or two measurements of air exchange rate were taken over a few-day period using perfluorocarbon tracers. analysis is based on treating each house as a single unit; in cases where two aer measurements were taken, the results were averaged. yamamoto et al. ( ) have also published an analysis of these data. fig. particle deposition loss rate coefficient (b) measured in a -m room as a function of particle diameter. three of four experiments were conducted with four small fans operating to induce different degrees of air motion. as noted in the key, the mean measured speed in the room with the fans on ranged between . and . cm/s. the room was furnished with carpeting, chairs, table, bookcase, and curtains. source: thatcher et al. ( ) spaces with high air exchange rates, deposition of these smaller particles is less important than air exchange. for larger particles, in the range - lm in diameter, the deposition loss rate coefficient is much higher, in the range - per hour. for these larger particles, deposition is an important mechanism influencing the fate of bioaerosols even for buildings with relatively high air exchange rates. the data in figure also illustrate that enhanced air movement increases the rate of particle deposition, at least over the range of conditions studied (up to air speeds of about cm/s). the effect of such air movement is to more rapidly deliver particles to surfaces to which they deposit. these air speeds are too low to cause particles to be resuspended from surfaces onto which they had previously deposited. most of the particle loss reflected in figure is attributable to gravitational settling onto upward facing surfaces. however, some deposition also occurs to vertical and even downward facing surfaces. figure shows results from a study that measured particle deposition to chamber walls under stirred conditions. the deposition velocity, plotted on the vertical axis of the figure, multiplied by the airborne concentration yields the deposition flux. so, for example, if we consider as a typical indoor air value for viable fungal spores of cfu/m (figure ) and assume they are associated with -lm particles for which the deposition velocity is mm/h (= . m/h), then the resulting deposition flux to vertical walls would be . = . cfu/m /h. this process would represent a small contribution to the total loss rate of fungi from indoor air, but could be an important step in the process of fungal colonization of walls. such colonization would also require sufficient quality and quantity of nutrients, appropriate surface ph, and sufficient water activity in the substrate (pasanen et al., ) . bioaerosol sources: outdoor air . . .the atmosphere is thronged with travellers: microbes using the wind, speaking teleologically, as a convenient transport from one place to another. travellers mostly performing quite short journeys.- gregory ( ) it is worthwhile to differentiate among the sources that contribute to indoor bioaerosols. such differentiation can improve the basis for understanding concentrations, exposures, and influencing factors. it also serves as a basis for engineering interventions to alter exposures. among the major categories that can contribute to indoor bioaerosols is air exchange-induced supply from outdoor air. from equations ( ) and ( ), the rate of supply of bioaerosol material from outdoors is represented either by the term (q n + pq l )c o (for the residential schematic, figure a ) or by the term [( Àg m ) q m + pq l ]c o (for the commercial building schematic, figure b ). we have discussed the various air exchange flow rates and-to an extent-the outdoor bioaerosol concentration, c o . the new terms to address here are the fractional penetration of bioaerosols along with infiltration flow, p, and the efficiency of bioaerosol particle removal in the mechanical ventilation supply flow, g m . an important point is that both of these efficiency terms are expected to exhibit significant particle-size dependence. consequently, the relationship between outdoor bioaerosol concentrations and the source of indoor bioaerosols can vary with particle size. the main principles that govern p and g m are well understood. however, evaluation of proper values of these parameters for any particular building remains a challenge because uncontrolled and unknown details of construction and operation can influence the outcomes. consider particle penetration through leakage paths. as air flows into a building through a leak in the envelope, particles suspended in that airstream may contact a surface bounding the leak, adhere, and be lost from the airstream. the penetration factor, p, represents that portion of particles in the outside air that make it through the leaks to enter the indoor environment. large particles may deposit because of gravitational settling or inertial impaction. small particles may deposit because of brownian motion. figure presents the results of model calculations showing how the fig. deposition velocity (v d ) measured to the vertical wall of a -m chamber as a function of particle diameter (d p ) (lai and nazaroff, ) . the deposition velocity is linked to the loss rate coefficient as follows: b w = v d s w /v, where b w is the contribution to the total loss rate coefficient attributable to deposition on the walls (h À ), s w is the wall area, and v is the room volume. the model equations are linear regressions to the log-transformed data, utilizing three measured points (v d ) and six measured points (v d ), respectively penetration factor varies with particle size for idealized crack geometry. different parameter values are assumed for the indoor-outdoor pressure drop ( or pa) and the height of the crack ( . , . , and . mm). an important message from this figure is that cracks must be quite fine for any meaningful attenuation of the airborne particles during infiltration. specifically, penetration is essentially complete across the full diameter range . - lm for any crack whose minimum dimension exceeds~ mm (given a pa or higher pressure drop and assuming that the flow channel through the crack is no longer than cm). the distribution of leak dimensions in any real building is not known. however, it seems likely that a normal case would feature most of the infiltrating air flowing through cracks larger than mm in minimum dimension. hence, there is an expectation that p~ for bioaerosol particles. in the case of a mechanically ventilated building, a second important parameter is the efficiency of a particle filter in the flow path connecting outdoor air to the air supply registers. figure illustrates two important points about filter efficiency. first, it is highly variable with filter quality, ranging from low for filters with a merv rating to high for merv or merv filters. second, filter efficiency can vary markedly with particle size. across the range that is pertinent for bioaerosols, the filtration efficiency tends to be higher for larger particles than for smaller particles. a mechanically ventilated building with a high mechanical ventilation to infiltration flow rate ratio (q m /q l ≫ ) and a high-efficiency filter ( Àg m ( ) can provide a high degree of protection of the indoor environment from outdoor bioaerosols. in mechanical ventilation systems, some bioaerosol deposition can occur on surfaces other than the filters, including ducts and heat-exchanger fins. evidence suggests that such deposition is size dependent and much higher for the larger bioaerosol particles than for the smaller ones (sippola and nazaroff, ; waring and siegel, ) . this deposition process might contribute to meaningful rates of removal from airstreams in some circumstances. however, a more significant concern is the risk of fouling and the degradation of system hygiene. an important and challenging feature of indoor bioaerosol dynamics is characterizing indoor emission sources. from a systematic research perspective, a core advantage of source characterization is that it is likely to provide more generalizable information than would phenomenological studies of concentrations or other outcome variables. the information sought in source characterization would include these factors for any particular bioaerosol analyte: the quantity emitted per time, the size distribution of particles with which the emitted analyte is associated, and the important parameters that influence the emission rate. depending on the particular source, experiments to investigate emissions might suitably be conducted in a bench-scale laboratory apparatus, in a room scale chamber, or through controlled field monitoring. there are many potential indoor sources of bioaerosols. research that characterizes emissions is still in a relatively early stage of development, with limited specified minimum single-pass particle removal efficiency of fibrous filters used in ventilation systems as a function of particle size (three shading styles) and merv rating (horizontal axis). source: azimi and stephens ( ) quantitative information available for most sources. in the following paragraphs, several studies that have investigated indoor bioaerosol sources are highlighted. primary goals include indicating the breadth of source types that have been investigated and providing entry points into the literature for those interested in deeper study. among the merits of quantifying emissions from interior sources are these. first, such quantification allows for the assessment of the relative importance of indoor vs. outdoor sources as contributors to the indoor burden. examine the numerators of equations ( ) and ( ), and note that in each case, there is a term that is proportional to the outdoor concentration and a term (e) that reflects indoor emissions. if, for a particular bioaerosol component of concern, the indoor emissions term is small compared to the outdoor source, then we can safely focus our attention on the outdoor environment transported via air exchange as the dominant contributor to indoor levels. conversely, if the indoor emission source greatly exceeds the term associated with the outdoor level, then we can focus on indoor emissions and scale down our attention to the outdoor air as a significant contributor. second, if the indoor emissions are well-characterized, then (provided we have adequate additional information about the indoor environment) we can estimate the contribution of the indoor emissions to airborne concentrations. equations ( ) and ( ) illustrate the relationship, and the additional required information is that needed to quantify the appropriate denominator. human occupants. adult man carries microbes associated with his epidermis and microbes in his alimentary tract. . . . the cells in his body are a distinct numerical minority of the total being that we call man. if we abandon anthropomorphism for the microbic view, we must admire the efficiency of these microbes in using man as a vehicle to further their own cause. -luckey ( ) in the context of better understanding and controlling airborne infection, bioaerosol emissions from humans have been a topic of concern since at least the s. for example, duguid ( ) experimentally assessed the size distribution of particles and droplets emitted by sneezing, coughing, and talking. the likelihood that such particles would contain bacteria was estimated based on their prevalence in respiratory fluids. duguid and wallace ( ) experimentally investigated the 'bacterial contamination of air produced by liberation of dust from the skin and personal clothing during bodily movement'. using culture-based analysis methods, they found that dust particles carrying bacteria were liberated at a rate of about per minute from a 'person making slight movements' and that marching liberated culturable bacteria about more intensely. bernard et al. ( ) observed that the shedding of airborne bacteria from humans was markedly elevated during a period - min after showering. the application of lanolin or alcohol to the skin reduced the effect, as did wearing a tightly woven fabric. hall et al. ( ) did not find this showering effect to occur. however, they did observe that 'men dispersed many more bacteria than women' and that the emissions rate could be considerably lowered through the application of skin lotion. they also noted that friction between skin and clothing appeared to be an important factor inducing the release. a second mechanism by which human activities may contribute to bioaerosol loading is through resuspension of biological particles that had previously settled on flooring or on other upward facing surfaces . using a mechanical stepping apparatus that mimicked walking combined with artificially seeded flooring materials, tian et al. ( ) found that the fractional resuspension of abiotic particles was À and~ À per step for particles with diameters - lm and - lm, respectively. goebes et al. ( ) documented that foot traffic contributes to measureable concentrations of airborne aspergillus; resuspension from flooring was demonstrated to be an important mechanism. a few recent studies have aimed to quantify sizeresolved biological particle emission rates associated with human occupants using modern analytical methods. qian et al. ( ) studied a university classroom with bioaerosol sampling using a cascade impactor followed by quantitative pcr applied with universal bacterial and fungal primers. by applying material balance to the indoor and outdoor data under room-occupied and unoccupied conditions, they inferred the per-occupant effective emission rates of bacteria and fungi. for example, the bacterial emission rates were determined to average million genome copy numbers per hour per occupant. particle size conformed reasonably well to a lognormal distribution with a geometric mean aerodynamic diameter of . lm and a geometric standard deviation of . . bhangar et al. ( ) used realtime particle detection to quantify size-resolved emissions of fluorescent biological aerosol particles also in a university classroom. they concluded that the modal size was in the range - lm and that the average emission rates were . million particles per person per hour during the main portion of lecture classes plus . million particles per person emitted during transitions between classes. advanced analytical methods and ongoing concerns about the spread of infectious respiratory diseases have motivated a renewed effort to study bioaerosol release from the nose and mouth. fennelly et al. ( ) measured the size distribution of coughgenerated particles containing culturable mycobacte-rium tuberculosis emitted from patients with pulmonary tuberculosis. stelzer-braid et al. ( ) collected respiratory emissions from subjects while breathing, talking, and coughing. they detected one or more of nine respiratory viruses in of subjects who had symptoms of upper respiratory tract infections and only in four among asymptomatic subjects. gralton et al. ( ) conducted an analogous study that focused on breathing and coughing, included children among the subjects, and investigated the size distribution of the emitted particles and droplets. they concluded that 'individuals with symptomatic respiratory viral infections produce both large and small particles carrying viral rna on coughing and breathing'. overall, human occupants are important contributors to the bioaerosol burden of indoor environments. they shed bacteria along with their skin; they emit viruses from their respiratory tract; and they resuspend particulate material that contains biological agents from floors and other surfaces that they contact. moldy materials. a second potentially important emission source category for indoor bioaerosols is moldy building materials. dampness and mold is common in buildings. for example, spengler et al. ( ) reported that half of surveyed households in us and canadian cities had a dampness-related condition (water damage, water in basement, and/or mold or mildew). several laboratory studies have investigated emissions of bioaerosols from moldy materials. for example, g orny et al. ( ) characterized the release of fungal spores-aspergillus versicolor, cladosporium cladosporioides, and penicillium melinii-from ceiling tiles in relation to the air speed above the surface and the vibration of the contaminated material. seo et al. ( ) investigated the release of ( ? )-b-d-glucan from moldy ceiling tiles and gypsum board. in many buildings, moisture intrusion or condensation occurs in wall cavities or in other hidden spaces that may be coupled by airflow pathways to the occupied building interior. muise et al. ( ) demonstrated experimentally that mold spores could penetrate effectively through wall service outlets. that finding is consistent with expectations (see figure ) as most fungal spores are smaller than lm in diameter and as cracks and gaps between a wall cavity and the indoor space would commonly be larger than mm in minimum dimension. housekeeping and hygiene. a third bioaerosol source category that is potentially important indoors is related to housekeeping and hygiene. several examples are briefly mentioned here. davies and noble ( ) demonstrated that bedmaking increased the airborne concentrations of skin scales and bacteria. wouters et al. ( ) reported increased levels of microbial markers in house dust in homes in which household organic waste was separately stored indoors. floor dust or settled dust can be richly microbial (rintala et al., ) , and this can serve as a bioaerosol source through resuspension . in a laboratory study, substantial bacteria and mold emission rates were observed from the operation of household vacuum cleaners (veillette et al., ) . this finding is not a surprising: vacuum cleaner use was already demonstrated to be a potent short-term generator of airborne particulate matter, both in the exhaust air (because of incomplete filtration) and through mechanical agitation of the floor (corsi et al., ; knibbs et al., ) . the net effect of vacuuming on indoor bioaerosol levels is not clear, however, as presumably vacuum cleaner use would also reduce the floor load of microbes available for later resuspension. indoor surfaces that are frequently moist can harbor microbial growth; examples related to household hygiene include shower curtains (kelley et al., ) and sink drains . bollin et al. ( ) showed that showerheads and hot-water faucet use could produce aerosols containing legionella pneumophila. thomson et al. ( ) found non-tuberculous mycobacteria (ntm) in shower aerosols in homes of patients with pulmonary disease caused by ntm, a finding broadly consistent with evidence from feazel et al. ( ) of enhanced ntm prevalence in showerhead biofilms. toilet flushing can produce aerosol droplets, and as fecal material is rich in microbes, the toilet is a potentially important source of indoor bioaerosols, especially in connection with diarrheal diseases (johnson et al., ) . bioaerosol exposure control. let us acknowledge that the goal should not be to make indoor environments sterile. at the same time, elevated levels of airborne pathogens are to be avoided, as are excessive levels of many bioaerosol attributes. and in certain circumstances, we should be particularly concerned about protecting vulnerable people from even ordinary bioaerosol exposure, such as individuals who are immunocompromised. how can bioaerosol control be achieved? conceptually, in the context of the material balance described earlier, there are two broad options: (i) reduce sources and/or (ii) increase removal rates. equations ( ) and ( ) provide a basis for quantitatively estimating the benefit of a control measure. among the options for source control are to keep indoor environments dry, to maintain good hygienic conditions in ventilation systems, to apply effective filtration on mechanical supply ventilation, and to use masks in the event of respiratory illness. regarding removal processes, the primary control alternatives are three, which appear in the denominator of equations ( ) and ( ): (i) increase the outdoor air ventilation rate (typically either q n or q m ); (ii) use recirculating air filtration (i.e., introduce or enhance g r q r , where g r is the filtration efficiency, as illustrated in figure , and q r is the recirculating flow rate through the filter; or (iii) enhance the rate of deposition or degradation of the bioaerosol attribute (thereby increasing b). miller-leiden et al. ( ) explored the effectiveness of in-room recirculating filtration for controlling the transmission of tuberculosis. cheng et al. ( ) have evaluated the use of portable air cleaners for reducing indoor concentrations of fungal spores. ultraviolet germicidal irradiation can be applied to reduce the infectivity of air without actively removing the bioaerosol particles (reed, ) . the control measures described in the preceding paragraphs all aim to reduce the airborne concentration of the bioaerosol agent, denoted c in equations ( ) and ( ). a complementary approach is to provide susceptible individuals with personal protective equipment, which-if performed well-can reduce the inhalation intake by an order of magnitude or more for a given airborne concentration. nicas ( ) presents an illustrative example for the case of respiratory protection of healthcare workers against mycobacterium tuberculosis bacilli. airborne growth and decay. the embodiment of the material balance principle in equations ( ) and ( ) does not account for microbial reproduction or for any other bioaerosol growth process during the period of suspension in the indoor air. there is some evidence supporting the possibility of airborne microbial life in the atmosphere, as reviewed by womack et al. ( ) . however, indoors, where the airborne residence time is limited to about a few hours or less, such processes have not been demonstrated and seem unlikely to be important. infectious agent viability may decay at a significant rate when airborne (weber and stilianakis, ) . incorporating the effects of such processes into model equations can be achieved through the decay parameter, b, in equations ( ) and ( ). transport and mixing. throughout this study, it has been assumed that an indoor environment can be represented as a well-mixed space. at the level of an individual room, the size of a typical bedroom or private office, that description is often but not always reasonable. an entire residence, or a large building, might be appropriately represented as a network of well-mixed rooms or zones, interconnected by airflow paths (feustel, ) . for some situations, the well-mixed conceptualization is inappropriate. for example, while much of mechanical ventilation practice uses air diffusers designed to promote rapid mixing, other concepts aim to deliberately exploit incomplete mixing as a basis to improve efficiency. such methods include displacement ventilation (novoselac and srebric, ) and personalized ventilation (melikov, ) . understanding how sources relate to concentrations in the breathing zone of occupants in cases like these cannot be accurately accomplished using a well-mixed analysis framework; instead, more sophisticated methods are required, such as approaches based on computational fluid dynamics (chen, ). experimentally, investigations in such conditions require methods that can accommodate spatially varying contaminant concentrations (bjørn and nielsen, ; brohus and nielsen, ) . although study of the normal human lung microbiome is still in its early stages, the bulk of published evidence demonstrates that phylogenetically diverse microbial communities in the lungs of healthy humans can be detected using high throughput sequencing. -beck et al. ( ) in a recent review, grice and segre ( ) articulate important ways in which microorganisms modulate human health: 'the human microbiome is a source of genetic diversity, a modifier of disease, an essential component of immunity, and a functional entity that influences metabolism and modulates drug interactions'. they then summarize what has recently been learned about the microbiology of the human gastrointestinal tract, the oral cavity, the reproductive tract, and the skin. however, they do not comment on the microbiology of the respiratory tract. beck et al. ( ) , in their review, note that, 'although the lungs were classically believed to be sterile, recently published investigations have identified microbial communities in the lungs of healthy humans'. lax et al. ( ) document that the microbes found in a home are distinctively related to the people who live in that home and that 'after a house move, the microbial community in the new house rapidly converged on the microbial community of the occupants' former house, suggesting rapid colonization by the family's microbiota'. what is not yet clear, but seems plausible, is whether aspects of the human microbiome are strongly influenced by microbiological and other conditions in inhabited indoor spaces. indoor bioaerosol behavior might play an important role in these stories. almost certainly, the most important exposures of the human lung to environmental microorganisms occur via inhalation of bioaerosols. furthermore, most of the air that is inhaled by humans is indoor air. bioaerosols also are important vectors transporting microorganisms from outdoors to indoors and from one indoor surface to another. it is feasible that airborne transport to and deposition on the human envelope influences skin microbiota . relative to the complexity and importance of the subject of indoor bioaerosol dynamics, our understanding is not yet mature. one might anticipate fundamental paradigm shifts to occur as our knowledge grows. our ability to ask and answer incisive questions should improve. although the gap between what we know and what we would like to know is quite large, our current knowledge is substantial. for example, in considering the dynamic behavior of airborne biological particles in buildings, indoor aerosol science provides a good starting point. mechanistically, bioaerosol particles behave like their abiotic counterparts. particle size is a primordial determinant of behavior, and bioaerosol particles are mainly found in the aerodynamic diameter range . - lm. aerosol science has developed powerful tools and theories regarding emission processes, airborne behavior, and fate. much of the understanding developed from aerosol science can be applied to indoor bioaerosol dynamics. as we proceed in studying the microbiology of the indoor environment, we should maintain a central focus on people. human occupants are a major source of indoor bacteria. our activities influence the emissions and fate of other bioaerosols as well. the outcomes of primary concern are centered on human health and welfare. technological advances enable the acquisition and analysis of microbial data of phenomenal richness. as we conduct research with the new tools, it is important that we not lose sight of the knowledge gained by prior generations of scholars. public health engineering studies conducted in the s through s, for example, on the theme of infection control in healthcare settings, contain particularly important insights that remain relevant to our current research agendas. the diversity and complexity of the system will continue to pose great challenges for studies of indoor bioaerosol dynamics, especially in efforts to link microbiological abundance to exposure and to health outcomes. the measurement limitations continue to be daunting. dust is an attractive sampling medium of questionable exposure relevance. culture-based analysis methods have limited scope. microscopic methods, dna-based analysis, and methods using chemical markers are best suited for making time-integrated measurements with sampling periods of hours. these methods are not well suited for studying dynamic processes. the fluorescent particle-sampling and analysis methods have the advantage of offering excellent time and particle-size resolution. however, these methods lack specificity. in recent years, we have seen benefits from efforts to fuse concepts and approaches from the indoor environmental sciences with the rapidly developing techniques and evolving knowledge of microbial ecology. we can anticipate continuing opportunities from cooperation between scholars from these domains. as we gain empirical knowledge, it will be important to seek generalizable understanding from the specifics of particular investigations. we will never measure everything! research that focuses on processes and that is framed in the context of well-established mechanistic knowledge can be a valuable way to proceed. in this review, the principle of material balance has served to structure a relationship between bioaerosol processes and indoor concentrations, an important intermediate outcome. further studies can be fruitfully pursued to better understand each of the input parameters that appear in the material balance equations. research could also be undertaken to test the accuracy of and to refine as necessary the model equations themselves. benefits would especially be anticipated from studies to better characterize and quantify indoor bioaerosol emission sources and the influencing factors. this particular process has especially large influence on outcomes, it is difficult to characterize without direct experimental measurement, and it is subject to enormous variability. the ultimate goal for improving knowledge about indoor bioaerosol dynamics is to contribute to a stronger knowledge base for the design, construction, operation, and maintenance of healthful buildings. this review has focused on the natural science and engineering aspects of the theme. this review has not addressed the complementary and comparably complex theme of how human health is influenced by bioaerosol exposure. because we are at an early stage of understanding both themes and because of their complementarity, progress toward the ultimate goal would benefit from the development of synergistic interactions between the respective research communities. that is a challenging proposition for several reasons, including largely independent educational tracks and funding agencies that-at least in the united states -do not embrace the nexus between the built environment and health. the first steps to overcoming any challenge are recognizing its importance and making a commitment to the attempt. perhaps the recent efforts to improve knowledge about the indoor microbiome and about the relationship between the human microbiome and health are establishing fertile ground for future synergistic efforts to better understand the relationship between the indoor microbiome and health. singapore-berkeley building efficiency and sustainability in the tropics (sinberbest) program. bears has been established by the university of california, berkeley, as a center for intellectual excellence in research and education in singapore. thanks to naomichi yamamoto, jordan peccia, and two anonymous reviewers for constructive comments and suggestions that contributed to improvements in the final article. the diversity and distribution of fungi on residential surfaces hvac filtration for controlling infectious airborne disease transmission in indoor environments: predicting risk reductions and operational costs evaluation and determinants of airborne bacterial concentrations in school 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study of airborne microbial communities evidence of airborne transmission of the severe acute respiratory syndrome virus partial support for this work was provided by a grant from the alfred p. sloan foundation in support of the berkeley indoor microbial ecology research consortium (bimerc). additional support was provided by the republic of singapore's national research foundation through a grant to the berkeley education alliance for research in singapore (bears) for the key: cord- -psnec qp authors: mbareche, hamza; veillette, marc; pilote, jonathan; létourneau, valérie; duchaine, caroline title: bioaerosols play a major role in the nasopharyngeal microbiota content in agricultural environment date: - - journal: int j environ res public health doi: . /ijerph sha: doc_id: cord_uid: psnec qp background: bioaerosols are a major concern for public health and sampling for exposure assessment purposes is challenging. the nasopharyngeal region could be a potent carrier of long-term bioaerosol exposure agents. this study aimed to evaluate the correlation between nasopharyngeal bacterial flora of swine workers and the swine barns bioaerosol biodiversity. methods: air samples from eight swine barns as well as nasopharyngeal swabs from pig workers (n = ) and from a non-exposed control group (n = ) were sequenced using s rrna gene high-throughput sequencing. wastewater treatment plants were used as the industrial, low-dust, non-agricultural environment control to validate the microbial link between the bioaerosol content (air) and the nasopharynxes of workers. results: a multivariate analysis showed air samples and nasopharyngeal flora of pig workers cluster together, compared to the non-exposed control group. the significance was confirmed with the permanova statistical test (p-value of . ). unlike the farm environment, nasopharynx samples from wastewater workers did not cluster with air samples from wastewater treatment plants. the difference in the microbial community of nasopharynx of swine workers and a control group suggest that swine workers are carriers of germs found in bioaerosols. conclusion: nasopharynx sampling and microbiota could be used as a proxy of air sampling for exposure assessment studies or for the determination of exposure markers in highly contaminated agricultural environments. the microbial flora of aerosols, referred to as bioaerosols, consists of a combination of viable and non-viable microorganisms (e.g., bacteria, fungi and viruses) and derived compounds of biological origin (e.g., animal and plant debris, endotoxins, exotoxins, and other microbial metabolites) [ ] [ ] [ ] . bioaerosols are ubiquitous in indoor and outdoor environments and are generated from various natural and/or anthropogenic sources. composed of particles ranging in size from a few nanometers to µm in diameter, bioaerosols remain suspended in the air for long periods of time and may travel many kilometers depending on the size of the particle [ , [ ] [ ] [ ] [ ] [ ] . therefore, the dispersal of bioaerosols may impact the air quality of extensive areas that are far from the source and can create public health issues, due to the presence of highly diverse and dynamic microbial communities. beyond affecting the time that particles remain suspended and the distances they travel, particle size plays a role in human diseases, as it dictates which pathway the particle follows in the respiratory tract after inhalation [ ] . for example, particles with a size of µm to µm tend to get deposited in the upper airways, while larger particles may remain in the nasal cavity [ , ] . bioaerosols can be a transmission vector for infectious diseases and are responsible for a variety of health problems, principally through inhalation [ , [ ] [ ] [ ] [ ] . human exposure to bioaerosols is associated with a wide variety of acute and chronic diseases ranging from allergies, asthma, rhinitis, sinusitis and bronchitis, mostly due to occupational exposure [ , [ ] [ ] [ ] [ ] . however, health risks from bioaerosols also exist just from living in close proximity to an intensive source of airborne biological particles [ , ] . additionally, other health problems linked to bioaerosols include fatigue, headache, mucous membrane irritation syndrome, nasal congestion, sore throat, and irritation of the nose and eyes [ , , ] . the industrial environment is the main source of occupational health issues, due to the presence of raw organic materials, the prevalence of operations releasing harmful bioaerosols (e.g., mechanical operations such as wood planning, straw chopping, animal bedding, hay handling, and compost pile turning) and the eventual large amounts of bioaerosols present in confined spaces. for example, biowaste facilities are characterized by notable concentrations of bioaerosols, due to the intense microbial activity involved in waste degradation and the activities performed by workers [ ] [ ] [ ] [ ] . wastewater treatment plants (wwtps) represent another environment where workers are subject to bioaerosol exposure, due to the steps required for the treatment of discharged municipal and industrial effluents [ , ] . intensive animal farming practices in confined buildings that hold a large number of animals (e.g., pigs, poultry, cattle) are also associated with extreme exposure to airborne microbes. the variety of possible sources (e.g., animals, feces, feed, litter) present at farms leads to the emission of complex mixtures of biological particles [ ] [ ] [ ] [ ] [ ] [ ] . moreover, the dynamic nature of the microbial composition makes health risk evaluation complicated for farm workers and nearby residents [ , ] . environmental hygienists continue to insist that insufficient exposure assessments are a primary reason for the absence of bioaerosol exposure limits and strategies to mitigate risk [ , ] . there are several challenges and limitations to measuring bioaerosol exposure. the type of sampler, time and duration of sampling, meteorological conditions [ ] , and geographical positions all affect bioaerosol sampling efficiency, making it difficult to compare studies and limiting collaboration efforts in bioaerosol exposure studies. an added challenge in terms of measuring microbial diversity is that culture-dependent analytical approaches recuperate the cultural/viable portion of bioaerosols exclusively. in contrast, high-throughput sequencing (hts) methods are associated with a more in-depth characterization of the microbial content of a sample [ , , [ ] [ ] [ ] [ ] . to overcome the aforementioned challenges, the scientific community that studies aerosols has identified the need to explore new alternatives and complementary approaches for assessing bioaerosol exposure, such as identifying markers that can help classify environments based on human health risks [ ] [ ] [ ] . the upper respiratory tract, which includes the nasal cavity and the nasopharynx and is a primary pathway for inhaled air, is an important niche for transient environmental bacteria and for colonization. previous studies have already used nasopharynx or nasal cavity samples to look for specific microorganisms, using culture-based approaches [ , ] , or revealed the presence of bacterial resistance genes, using molecular biology approaches [ ] . recently, an hts approach was used on samples from the anterior and posterior cavity of the nose to study the bacterial diversity of individuals [ ] . however, because the microflora in the nasal cavity is dynamic and fluctuant [ ] , a region like the nasopharynx may represent a more long-term reservoir of inhaled bioaerosols. to the best of our knowledge, no study has ever used a s rrna amplicon-based hts approach to investigate the microbial diversity of nasopharyngeal flora, in order to assess occupational exposure. microbiome studies that use upper respiratory tract tissue and focus on specific pathologies (such as asthma, chronic obstructive pulmonary disease and chronic rhinosinusitis) may underestimate the effect of occupational exposure on the microbiomes of the subjects examined in those studies. we hypothesis that the microbiome of patients with respiratory disease is most likely affected by exposure to their work environment in addition to disease, rather than to disease alone. this study aims to contribute to the development of a new alternative method for assessing bioaerosol exposure, by linking the nasopharyngeal flora of pig farm workers to the bioaerosol microbial composition of their occupational environment, and to explore the role of bioaerosols in the nasopharyngeal microbial content. the s rrna amplicon-based hts approach was used to determine bacterial diversity, while qpcr was used to evaluate the presence of human pathogenic agents and bacterial resistance genes in bioaerosols and in nasopharyngeal samples from pig workers. additionally, wwtps were used as the industrial, low-dust, non-agricultural environment control to validate the microbial link between the bioaerosol content (air) and the nasopharynxes of workers. although the experiment focused on pig farmers and the buildings that they work in, the results may have implications for a wider population of agricultural workers. consequently, nasopharynx samples could be used as proxies for air samples in exposure assessment studies and for the determination of exposure markers in agricultural settings. in addition, the study advocates for the need of systematic bioaerosol exposure study when evaluating the nasopharyngeal microbiota. air samples were collected from eight confined pig buildings in eastern canada during fall/winter . inside each farm building, a sampling site was designated based on worker activities and bioaerosol exposure. the buildings visited were mechanically ventilated and contained between - pigs each weighing between - kg. there were no obvious signs of illness affecting the animals. air samples were collected from eight wwtps in the province of quebec, located in eastern canada, the during summer and winter seasons. summer visits occurred between september and july , and winter visits occurred between february and march . four sampling sites were chosen depending on the wastewater treatment process (screening, de-gritting/degreasing, settling tank, and bio-filtration), workers' daily tasks, and the level of confinement of the space. a liquid cyclonic impactor coriolis µ biological air sampler (bertin corp., rockville, md, usa) was used for collecting air samples. the samplers were set at l/min for min ( m of air per sample), placed within - m of the bioaerosol source and away from any turbulent air flow (e.g., away from building exhaust fans). fifteen milliliters of a phosphate buffer saline (pbs) solution ( . m, ph . , lonza, walkersville, md, usa) were used as the collecting solution. nasopharyngeal samples were taken from controls (university students and staff never exposed to animal farms), pig farmers and wwtp workers between the fall of and spring . all controls, pig farmers, and wwtp workers were non-smokers and none were taking antibiotics. the protocol was approved by the ethics committee of the institut universitaire de cardiologie et de pneumologie de québec (cer ). nasopharyngeal samples were collected by a nurse using swabs (puritan ® hydraflock ® collection devices, guilford, ma, usa) with a dry secure transport system. briefly, a swab was inserted into the nose until a resistance was felt and then turned a few times before it was removed. samples were transported to the laboratory at • c. from the ml collecting solution of the coriolis µ biological air sampler (bertin corp.), a . ml aliquot was centrifuged for min at , × g (j. pilote protocol = ml aliquot, min, , × g). the supernatant was discarded and the pellets were kept at − • c until dna extraction. likewise, the tips of the swabs were cut and vortexed thoroughly in ml pbs (lonza) and discarded. suspensions were then centrifuged for min at , × g, the supernatants were discarded and the pellets were stored at − • c until dna extraction. total genomic dna from air and nasopharyngeal samples was extracted with a powerlyser ® powersoil isolation dna kit (mo bio laboratories, carlsbad, ca, usa) following the manufacturer's instructions. dna samples were stored at − • c until subsequent analyses. the amplification of targeted genes, equimolar pooling, and sequencing were performed at the plateforme d'analyses génomiques (ibis, université laval, québec, qc, canada). the s rrna v -v region was amplified using the sequence-specific regions described in comeau et al. using a two-step dual-indexed pcr approach, specifically designed for illumina ® instruments, san diego, ca, usa [ ] . the gene-specific sequence was first fused to the illumina ® truseq sequencing primers and pcr was carried out in a total volume of µl containing × q buffer (neb, ipswish, ma, usa), . µm of each primer, µm of each of the dntps, u of q high-fidelity dna polymerase (neb) and µl of template dna. pcr thermoprotocol began with an initial denaturation at • c for s followed by cycles of denaturation at • c for s, annealing at • c for s, extension at • c for s and a final extension at • c for min. the pcr reaction was purified using the axygen pcr cleanup kit (axygen ® , waltham, ma, usa). the quality of the purified pcr product was checked on a % agarose gel. a fifty to -fold dilution of the purified product was used as a template for a second round of pcr in order to add barcodes (dual-indexed) and for missing sequences required for illumina sequencing. the thermoprotocol for the second pcr was identical to the first one but with cycles. pcr reactions were purified again in the same way as above, checked for quality on a dna bioanalyzer chip (agilent ® , santa clara, ca, usa) and then quantified spectrophotometrically with the nanodrop ® (thermo fisher scientific, waltham, ma, usa). barcoded amplicons were pooled in equimolar concentrations for sequencing on the illumina ® miseq machine. the oligonucleotide sequences that were used for pcr amplification are presented in table . briefly, after de-multiplexing the raw fastq files, the reads generated from the paired end sequencing were combined using the make.contigs script from mothur [ ] . quality filtering was also performed with mothur, using the screen.seqs script to discard homopolymers, reads with ambiguous sequences, and reads with suspiciously short lengths. similar sequences were gathered together in order to reduce the computational burden, and the number of copies of the same sequence was displayed to monitor the abundance of each sequence. this de-replication step was performed with vsearch [ ] . the sequences were then aligned with the bacterial reference silva core alignment using the qiime script align_seqs.py [ ] . operational taxonomic units (otus), with a % similarity cut-off, were clustered using the uparse method implemented in vsearch. uchime was used to identify and remove the chimeric sequences [ ] . qiime was used to assign taxonomy to otus based on the silva database reference training dataset for taxonomic assignment and to generate an otu table. a metadata-mapping file was produced that includes information about air and nasopharyngeal samples. the microbial diversity analyses, including statistical analyses, conducted in this study, were achieved using qiime plugins in version . . as described in qiime scripts (http://qiime.org/scripts/). the names of the scripts used are mentioned in the results section of each analysis. pcr was performed with cfx- and cfx- touch™ real-time pcr detection systems (bio-rad laboratories, mississauga, on, canada) to evaluate the presence of six human pathogens (clostridium difficile, listeria monocytogenes, mycobacterium avium, salmonella spp., staphylococcus aureus, and methicillin-resistant staphylococcus aureus (mrsa)), and antibiotic and metal resistance genes (cephalosporin, colistin, zinc). the pcr mixture contained µl of dna template, - nm for each primer, - nm probe and µl of × iq™ supermix or iq™ sybr ® green supermix (bio-rad laboratories) in a µl reaction mixture. the results were analyzed using bio-rad cfx manager software, version . (bio-rad laboratories). positive control and standard curves ranging from × to one copy of the targeted genes were used for each protocol using genomic dna or synthetic genes as templates (integrated dna technologies, coralville, ia, usa). negative controls were included in the plates as ntc (non-template controls). all primers and probes were purchased from integrated dna technologies. the primers, probes, hybridization temperatures, amplicon sizes and original references for all targeted genes are listed in pilote et al. [ ] . for alpha diversity measures, the normality was verified using the d'agostino and pearson omnibus normality test. the assumption of data normality was not fulfilled. non-parametric mann-whitney u tests (two-tailed) were performed to highlight that there are significant differences in diversity measures between the groups of samples. a p-value ≤ . was considered statistically significant. all of the results were analyzed using the software graphpad prism . (graphpad software, inc., san diego, ca, usa). to determine the statistical significance of the variation in the observed microbial community composition with multivariate analyses (pcoa), a permanova test was performed on the unweighted unifrac matrix. the compare_categories.py qiime script was used to generate the statistical results. because permanova is a non-parametric test, significance is determined through permutations. in this case, permutations were used. a p-value ≤ . was considered to be statistically significant. detailed information about the performance of the test is presented in the multivariate section of the results. the non-parametric mann-whitney u test was used to ascertain whether or not differences in otu abundances were statistically significant between the controls and pig farmers. to test otu differential abundance, the null hypothesis was that the populations that the two groups of samples were collected from have equal means. the range of p-values obtained for the most differentially abundant otus between the control samples and the pig farmer samples are presented in the differential abundance section of the results. this study used both positive and negative controls. the negative controls include unused swabs that underwent the same extraction protocol as the swabs collected from the subjects of this study. a pcr amplification targeting the s rrna genes allowed us to confirm the very low biomass of the negative controls compared to the nasopharyngeal swabs from the pig workers and non-exposed controls. for this reason, negative controls did not pass the next step of illumina hts. additional negative controls consisted of outdoor air samples that were taken outside the pig buildings sampled in this study. these samples showed enough concentration of bacterial biomass with the pcr amplification. thus, outdoor negative controls were sequenced. however, the number of reads and subsequent otu clustering was low compared to the indoor air samples. during the rarefaction step, the negative controls were not included in the analyses due to a low number of sequences. the goal is to have a number of sequences per sample deep enough to cover most of the bacterial diversity. positive controls consisted of a mock community containing equal concentrations of bacteria purchased from atcc ( strain even mix genomic material atcc ® msa- tm ). sequencing of the mock community showed a taxonomic profile resembling the expected microbial community, but with different relative abundances. in total, air samples from pig buildings, nasopharynx samples from farmers and nasopharynx samples from the non-exposed control group resulted in , , sequences (air samples = , ; farmers = , , , controls = , , ). following quality filtering and the discarding of singletons, , , unique sequences clustered into otus. representing the non-agricultural control environment (wwtps), , , sequences came from air samples ( , ) and nasopharynx samples ( , , ) from plant workers. after quality filtering and the removal of singletons, , unique sequences clustered into otus. a rarefaction analysis was performed to validate the sequencing depth and to confirm the effective sampling of the microbial diversity using the alpha_rarefaction.py qiime script. the lowest-depth sample parameter was used for the rarefaction analyses, allowing equal numbers of sequences for all samples. therefore, the samples with a sequencing depth lower than the reference sample were excluded from the analyses. the higher the sequencing depth, the more likely that the full diversity coverage is attained. the sequencing depth was , sequences for all the groups of samples: the air samples from pig buildings, the nasopharyngeal samples of pig farmers and non-exposed controls. the points shown in figure were calculated as follows: ten values from to , analyzed sequences were randomly selected. for each of these values, the corresponding number of otus observed, was noted for all of the samples. then, the average number of otus observed, plus or minus one standard deviation, were calculated for each of the ten values. the samples were divided into three groups: air from pig buildings, pig farmers and non-exposed controls. the slope of the curves shows sufficient sequencing depth and good bacterial coverage in all samples. moreover, pig farmers and air samples showed the highest average number of otus compared to non-exposed controls. four indexes were used to measure alpha diversity using the alpha_diversity.py script: chao richness estimator (the higher the number of otus in a sample, the higher the value of the chao index). for a more detailed explanation about richness estimate calculation, please refer to http://chao.stat.nthu.edu.tw/wordpress/paper/ .pdf. in shannon and simpson diversity measures, richness is combined with abundance to obtain an evenness measure. simpson values are bounded between and , where represents the most diverse case. shannon values are bounded between and , where represent the highest diversity) and phylogenetic diversity (pd) whole tree (quantitative measure of phylogenetic diversity; the higher the value, the higher the diversity; no limit value). the nasopharynx samples from pig farmers consistently showed the highest richness estimates and diversity measure values, whereas non-exposed controls displayed the lowest values (figure a-d) . the difference between the two groups of samples was significant (chao p = . ; shannon p = . ; simpson p = . ; pd whole tree p = . ). the richness estimates and diversity measures in the air samples were nearly as high as the pig farmer nasopharynx samples, although the measures from the pig farmer samples were statistically higher (chao p = . ; shannon p = . ; simpson p = . ; pd whole tree p = . ). the difference between the air samples from pig buildings and non-exposed controls (nasopharynx) was significant as well (chao p = . ; shannon p = . ; simpson p = . ; pd whole tree p = . ). four indexes were used to measure alpha diversity using the alpha_diversity.py script: chao richness estimator (the higher the number of otus in a sample, the higher the value of the chao index). for a more detailed explanation about richness estimate calculation, please refer to http://chao.stat.nthu.edu.tw/wordpress/paper/ .pdf. in shannon and simpson diversity measures, richness is combined with abundance to obtain an evenness measure. simpson values are bounded between and , where represents the most diverse case. shannon values are bounded between and , where represent the highest diversity) and phylogenetic diversity (pd) whole tree (quantitative measure of phylogenetic diversity; the higher the value, the higher the diversity; no limit value). the nasopharynx samples from pig farmers consistently showed the highest richness estimates and diversity measure values, whereas non-exposed controls displayed the lowest values (figure a-d) . the difference between the two groups of samples was significant (chao p = . ; shannon p = . ; simpson p = . ; pd whole tree p = . ). the richness estimates and diversity measures in the air samples were nearly as high as the pig farmer nasopharynx samples, although the measures from the pig farmer samples were statistically higher (chao p = . ; shannon p = . ; simpson p = . ; pd whole tree p = . ). the difference between the air samples from pig buildings and non-exposed controls (nasopharynx) was significant as well (chao p = . ; shannon p = . ; simpson p = . ; pd whole tree p = . ). an ecological analysis was conducted to reveal the variation in the community composition between the three sample groups (nasopharynx of pig farmers and non-exposed controls and air from pig farms). the weighted unifrac distance metric was used to calculate the pairwise distances between samples using the beta_diversity.py script. the distance matrix was then transformed into coordinates using the principal_coordinates.py script and inter-samples distances were represented in a two-dimensional ( d) space using ordination. the samples closer to one another were more similar than those ordinated further apart. the principal coordinate analysis (pcoa) was used to visualize bacterial community variation (make_ d_plots.py). figure a shows the two principal coordinate axes capturing a total of . % of the variation observed. a distinct clustering of pig farmers, nonexposed controls, and air samples from pig buildings is also illustrated in that figure. the profiles of pig farmers were more similar to the profiles of air samples than to the profiles of non-exposed controls. the distinct clustering was confirmed by the per-mutational multivariate analyses of variance (permanova p = . ). the same statistical test was used to confirm the non-significant clustering of air and pig farmer (nasopharynx) samples, as the test showed a non-significant difference (permanova p = . ). interestingly, air samples from the pig buildings seemed to display less dispersion amongst its individuals than the farmers and non-exposed groups, indicating a more homogenous bacterial community structure. we used a phylogram that displays sample clustering, using the unweighted pair group method, with arithmetic mean to confirm the sample clustering observed with the pcoa analyses ( figure b ). an ecological analysis was conducted to reveal the variation in the community composition between the three sample groups (nasopharynx of pig farmers and non-exposed controls and air from pig farms). the weighted unifrac distance metric was used to calculate the pairwise distances between samples using the beta_diversity.py script. the distance matrix was then transformed into coordinates using the principal_coordinates.py script and inter-samples distances were represented in a two-dimensional ( d) space using ordination. the samples closer to one another were more similar than those ordinated further apart. the principal coordinate analysis (pcoa) was used to visualize bacterial community variation (make_ d_plots.py). figure a shows the two principal coordinate axes capturing a total of . % of the variation observed. a distinct clustering of pig farmers, non-exposed controls, and air samples from pig buildings is also illustrated in that figure. the profiles of pig farmers were more similar to the profiles of air samples than to the profiles of non-exposed controls. the distinct clustering was confirmed by the per-mutational multivariate analyses of variance (permanova p = . ). the same statistical test was used to confirm the non-significant clustering of air and pig farmer (nasopharynx) samples, as the test showed a non-significant difference (permanova p = . ). interestingly, air samples from the pig buildings seemed to display less dispersion amongst its individuals than the farmers and non-exposed groups, indicating a more homogenous bacterial community structure. we used a phylogram that displays sample clustering, using the unweighted pair group method, with arithmetic mean to confirm the sample clustering observed with the pcoa analyses ( figure b) . the clustering (air from pig buildings and pig farmers together, versus the non-exposed controls) was statistically significant as confirmed by the permanova test (p-value = . ). given the observed difference in the number of bacterial otus, evenness, and evolutionary distance (alpha diversity) and in the bacterial community composition (beta diversity) in samples of the nasopharyngeal flora of farmers and non-exposed individuals and bioaerosols, collected in pig buildings, the next step was to reveal the taxonomic profiles of the three groups. figure shows the taxonomic distribution of the bacterial phyla across the three groups of samples. overall, actinobacteria, proteobacteria, bacteriotedes, and firmicutes dominated the three profiles, representing more than % of the taxonomic abundance. however, major differences distinguished the pig farmer samples from the non-exposed controls. in the latter, actinobacteria and proteobacteria were the most abundant phyla (relative abundances of %, and %, respectively). however, in farmers, firmicutes and bacteriotedes were the most dominant phyla with relative abundances of %, and %, respectively. consistent with the previous analyses, air samples from pig farms had different relative abundances values, but comparable profiles (with the same conclusions) to the nasopharyngeal flora of farmers, with a dominance of firmicutes ( %), followed by bacteriotedes ( %). actinobacteria, and proteobacteria had a relative abundance of less than % in bioaerosol samples. notably, spirochaetes, tenericutes, and verrumicrobia were detected only in farmers and the air from pig buildings. the clustering (air from pig buildings and pig farmers together, versus the non-exposed controls) was statistically significant as confirmed by the permanova test (p-value = . ). given the observed difference in the number of bacterial otus, evenness, and evolutionary distance (alpha diversity) and in the bacterial community composition (beta diversity) in samples of the nasopharyngeal flora of farmers and non-exposed individuals and bioaerosols, collected in pig buildings, the next step was to reveal the taxonomic profiles of the three groups. figure shows the taxonomic distribution of the bacterial phyla across the three groups of samples. overall, actinobacteria, proteobacteria, bacteriotedes, and firmicutes dominated the three profiles, representing more than % of the taxonomic abundance. however, major differences distinguished the pig farmer samples from the non-exposed controls. in the latter, actinobacteria and proteobacteria were the most abundant phyla (relative abundances of %, and %, respectively). however, in farmers, firmicutes and bacteriotedes were the most dominant phyla with relative abundances of %, and %, respectively. consistent with the previous analyses, air samples from pig farms had different relative abundances values, but comparable profiles (with the same conclusions) to the nasopharyngeal flora of farmers, with a dominance of firmicutes ( %), followed by bacteriotedes ( %). actinobacteria, and proteobacteria had a relative abundance of less than % in bioaerosol samples. notably, spirochaetes, tenericutes, and verrumicrobia were detected only in farmers and the air from pig buildings. the relative abundance of taxa was more thoroughly analyzed by examining the most abundant bacterial classes across the three groups of samples ( figure ). similar to the phyla profiles, the class profiles showed notable differences between non-exposed controls and farmers/air from pig buildings. in the former, actinobacteria ( %), saprospirae ( %), bacilli ( %), gammaproteobacteria ( %) and betaproteobacteria ( %) represented more than % of the taxonomic profile. however, the profile from farmers was more evenly distributed. clostridia had the highest relative abundance ( %) followed by saprospirae ( %), bacilli ( %) and actinobacteria ( %). unlike the non-exposed control group, gammaproteobacteria and betaproteobacteria represented less than % of the profile, whereas bacteroidia represented % of the relative abundance. in the non-exposed control group, bacteroidia represented . % of the taxonomic profile. in air samples, clostridia, bacilli and bacteroidia dominated the profile representing more than % of the relative abundance, thus confirming the previous observations about the similarity between the flora from pig farmers and air samples. interestingly, the presence of coriobacteria, erysipelotrichi, spichaetes, mollicutes, sphyngobacteria, epsilonproteobacteria, and verruco- was exclusive to samples from the nasopharynx of pig farmers and sampled bioaerosols. the relative abundance of taxa was more thoroughly analyzed by examining the most abundant bacterial classes across the three groups of samples ( figure ). similar to the phyla profiles, the class profiles showed notable differences between non-exposed controls and farmers/air from pig buildings. in the former, actinobacteria ( %), saprospirae ( %), bacilli ( %), gammaproteobacteria ( %) and betaproteobacteria ( %) represented more than % of the taxonomic profile. however, the profile from farmers was more evenly distributed. clostridia had the highest relative abundance ( %) followed by saprospirae ( %), bacilli ( %) and actinobacteria ( %). unlike the non-exposed control group, gammaproteobacteria and betaproteobacteria represented less than % of the profile, whereas bacteroidia represented % of the relative abundance. in the non-exposed control group, bacteroidia represented . % of the taxonomic profile. in air samples, clostridia, bacilli and bacteroidia dominated the profile representing more than % of the relative abundance, thus confirming the previous observations about the similarity between the flora from pig farmers and air samples. interestingly, the presence of coriobacteria, erysipelotrichi, spichaetes, mollicutes, sphyngobacteria, epsilonproteobacteria, and verruco- was exclusive to samples from the nasopharynx of pig farmers and sampled bioaerosols. a non-parametric mann-whitney u test, was used to analyze count data and determine the species most significantly associated with farming. the test compares otu frequencies in groups of samples and ascertains if there are statistically different otu abundances between the two groups of samples. the mann-whitney u test uses absolute data counts rather than relative abundances. more specifically, the output of the test contains the test statistic, the p-value corrected for multiple comparisons, and a mean count for each otu in the given sample group. this test was used following instructions from the group_significance.py qiime script. the thirty taxa (identified to the species or genera) with the greatest significant differences in counts between samples from pig farmers and non-exposed controls are presented in figure . however, to better visualize and emphasize the most striking cases of differential abundance, the list is not exhaustive. the complete results output of differential abundance is presented in additional file (supplementary material). it represents the results of the mann-whitney u test to determine the statistical differential abundance of taxa in nasopharynx of workers and non-exposed controls. the test was applied to sequences using qiime script (group_significance.py) with the mann-whitney u test option. the taxonomy represent bacteria from the nasopharynx samples. notably, some taxa were identified only to class or family, as those were the highest levels of identification possible using the silva database. p-values were corrected for multiple comparisons using the bonferroni correction. values ranged from . to . for the differentially abundant taxa, from pig farmer samples, and from . to . for the differentially abundant taxa, from non-exposed controls. the most notable imbalance was observed for the class clostridia with a mean count of more than sequences in pig farmer samples and less figure . taxonomic profile showing the relative abundance of each bacterial class across nasopharyngeal flora samples from pig farmers, non-exposed controls and air samples from pig buildings. taxa written in bold type were specific to farmers and air from pig buildings. a non-parametric mann-whitney u test, was used to analyze count data and determine the species most significantly associated with farming. the test compares otu frequencies in groups of samples and ascertains if there are statistically different otu abundances between the two groups of samples. the mann-whitney u test uses absolute data counts rather than relative abundances. more specifically, the output of the test contains the test statistic, the p-value corrected for multiple comparisons, and a mean count for each otu in the given sample group. this test was used following instructions from the group_significance.py qiime script. the thirty taxa (identified to the species or genera) with the greatest significant differences in counts between samples from pig farmers and non-exposed controls are presented in figure . however, to better visualize and emphasize the most striking cases of differential abundance, the list is not exhaustive. the complete results output of differential abundance is presented in additional file (supplementary materials). it represents the results of the mann-whitney u test to determine the statistical differential abundance of taxa in nasopharynx of workers and non-exposed controls. the test was applied to sequences using qiime script (group_significance.py) with the mann-whitney u test option. the taxonomy represent bacteria from the nasopharynx samples. notably, some taxa were identified only to class or family, as those were the highest levels of identification possible using the silva database. p-values were corrected for multiple comparisons using the bonferroni correction. values ranged from . to . for the differentially abundant taxa, from pig farmer samples, and from . to . for the differentially abundant taxa, from non-exposed controls. the most notable imbalance was observed for the class clostridia with a mean count of more than sequences in pig farmer samples and less than sequences in the non-exposed controls. staphylococcus epidermis was present with a mean count of sequences in non-exposed individuals and less than sequences in pig farmers. other important examples related to human health include, the greater differential abundance of haemophilus influenzae in non-exposed controls ( sequences in non-exposed control samples vs. in samples from pig farmers), and the differential abundance of klebsiella in samples from pig farmers ( sequences in pig farmer samples vs. in non-exposed controls). than sequences in the non-exposed controls. staphylococcus epidermis was present with a mean count of sequences in non-exposed individuals and less than sequences in pig farmers. other important examples related to human health include, the greater differential abundance of haemophilus influenzae in non-exposed controls ( sequences in non-exposed control samples vs. in samples from pig farmers), and the differential abundance of klebsiella in samples from pig farmers ( sequences in pig farmer samples vs. in non-exposed controls). figure . taxa identified to highest possible taxonomic level with statistically significant differential abundances across pig farmers and non-exposed controls. from the bottom to the top: the first taxa were the most abundant in samples from farmers and the last were more abundant in nonexposed controls. the taxa written in bold type affect human health. a non-agricultural low-dust control environment (wwtps) was used as a control to validate the link between the microbial composition of nasopharyngeal flora of exposed workers and that of bioaerosols released in the workplace. the nasopharynx samples of the non-exposed controls figure . taxa identified to highest possible taxonomic level with statistically significant differential abundances across pig farmers and non-exposed controls. from the bottom to the top: the first taxa were the most abundant in samples from farmers and the last were more abundant in non-exposed controls. the taxa written in bold type affect human health. a non-agricultural low-dust control environment (wwtps) was used as a control to validate the link between the microbial composition of nasopharyngeal flora of exposed workers and that of bioaerosols released in the workplace. the nasopharynx samples of the non-exposed controls (subjects not previously exposed to any animal farm) were again used for comparison with the nasopharynx samples from wastewater workers and air samples from wwtps. the distances between the groups of samples were compared and visualized using the pcoa approach. similar to the pig farm environment, the pairwise distances were calculated using the weighted unifrac distance metric. figure shows the two principal coordinate axes capturing a total of . % of the variation observed. unlike the farm environment, the nasopharynx samples from wastewater workers did not cluster with air samples from wwtps. in fact, nasopharyngeal flora of wastewater workers and non-exposed controls had similar microbial compositions. the difference between air and nasopharynx samples (controls and wastewater workers) was statistically significant (permanova p = . ). as shown in figure , the difference between non-exposed controls and wastewater workers was not significant (permanova p = . ). (subjects not previously exposed to any animal farm) were again used for comparison with the nasopharynx samples from wastewater workers and air samples from wwtps. the distances between the groups of samples were compared and visualized using the pcoa approach. similar to the pig farm environment, the pairwise distances were calculated using the weighted unifrac distance metric. figure shows the two principal coordinate axes capturing a total of . % of the variation observed. unlike the farm environment, the nasopharynx samples from wastewater workers did not cluster with air samples from wwtps. in fact, nasopharyngeal flora of wastewater workers and non-exposed controls had similar microbial compositions. the difference between air and nasopharynx samples (controls and wastewater workers) was statistically significant (permanova p = . ). as shown in figure , the difference between non-exposed controls and wastewater workers was not significant (permanova p = . ). principal coordinate analysis plot. the plot shows the distances for the microbiota of three groups of samples: nasopharynx samples from wastewater workers and from non-exposed controls and bioaerosols from wastewater treatment plants (wwtps). the pairwise distances were calculated using the weighted unifrac distance metric. the presence of human pathogens was investigated in the nasopharynx of pig farmers. as noted in table , all of the pathogens were more frequently detected in the pig farmer nasopharynx samples, compared to non-exposed controls, with the exception of salmonella spp. striking examples include, mrsa and clostridium difficile, which were present in the nasopharyngeal flora of %, and % of pig farmers, respectively. they were found in %, and % of the non-exposed controls, respectively. principal coordinate analysis plot. the plot shows the distances for the microbiota of three groups of samples: nasopharynx samples from wastewater workers and from non-exposed controls and bioaerosols from wastewater treatment plants (wwtps). the pairwise distances were calculated using the weighted unifrac distance metric. the presence of human pathogens was investigated in the nasopharynx of pig farmers. as noted in table , all of the pathogens were more frequently detected in the pig farmer nasopharynx samples, compared to non-exposed controls, with the exception of salmonella spp. striking examples include, mrsa and clostridium difficile, which were present in the nasopharyngeal flora of %, and % of pig farmers, respectively. they were found in %, and % of the non-exposed controls, respectively. listeria monocytogenes was detected in % of non-exposed controls and in % of pig worker samples. mycobacterium avium was not detected in the nasopharynx samples of either group. likewise, antibiotic and zinc resistance genes were present at a higher frequency among pig farmers compared to non-exposed controls. moreover, cephalosporin, and colistin resistance genes were exclusively detected in the nasopharyngeal flora of pig farmers. table . human pathogens and antibiotic and zinc resistance genes in the nasopharyngeal flora of pig workers compared to non-exposed controls. given the many potential microbial sources, animal farmers inhale a variety of aerosolized bacteria that impact their health [ , , ] . in this study, the bacterial populations in bioaerosols from pig buildings were compared to those of the nasopharyngeal flora of farmers using bioinformatics tools to determine if nasopharynx sampling could be used as a proxy for air sampling in exposure assessment studies. systemic microbial ecology analyses led to unequivocal results with identical conclusions throughout the analyses. the alpha diversity of bacterial species in the air from pig buildings and the nasopharyngeal flora of farmers were not statistically different. the evaluation of species diversity was introduced by whittaker and defined as the number of species and their proportional abundance within one sampling site [ ] . there are different ways to measure alpha diversity and an extensive list of indexes has been presented by magurran and mcgill [ ] . in addition to the usual chao richness estimates and shannon/simpson diversity measures [ ] [ ] [ ] [ ] , pd whole tree was also used to analyze the alpha diversity in samples in this study. pd stands for phylogenetic diversity and is defined as the minimum length of all phylogenetic branches required to span a given set of taxa on the phylogenetic tree [ ] . all four of the alpha diversity measures revealed greater bacterial richness and diversity in the nasopharyngeal samples from pig farmers compared to non-exposed individuals. the observed similarity between bioaerosols from pig buildings and the nasopharyngeal flora from farmers is indicative of occupational exposure and, consequently, a transient presence and/or possible colonization of the upper respiratory tract regions by environmental bacteria. these findings are even more interesting given that the majority of pig farmers recruited for this study do not work in the eight pig buildings selected for air analysis. this suggests that airborne bacteria associated with pig buildings can take over the microbiota in farmers' nasopharynxes. the establishment of this "new" microbial community could represent a microbial signature for the nasopharynx of pig farmers. also, a higher prevalence of viruses in the nasopharynxes of farmers compared to the non-exposed control group could play a role in the increased alpha-diversity [ ] . beta diversity analyses revealed that long-term exposure, such as occupational exposure to bioaerosols in the air of pig buildings, appeared to modify the nasopharyngeal microbiota of farmers. common approaches to evaluating changes in the community composition (beta diversity) rely on the creation of a (dis)similarity matrix to calculate the distance between samples. dis(similarity) matrices may be calculated using different methods depending on the type of dataset, analyses, and the objectives of the study, as some metrics are more suitable than others [ ] [ ] [ ] [ ] . the unifrac distance metric was used as efficacy was proven with s rrna bacterial genes [ ] . in addition, pcoa coupled with permanova offers a robust statistical significance of sample grouping using distance matrices. this non-parametric multivariate analysis of variance separates the distance matrix into sources of variation to describe the robustness and significance of a variable in explaining the variations observed between samples. it is based on the anova experimental design but analyzes the variance and determines the significance by permutations, as it is a non-parametric test [ ] . whereas, anova/manova assumes normal distributions and a euclidean distance, permanova can be used with any distance measure. the two analyses led to the same conclusions for this study. therefore their usefulness when used together as a tool to visualize and evaluate sample clustering was confirmed. the distinct clusters formed between the combination of pig farmers, and the air from pig buildings, and non-exposed individuals, is clearly linked to a strong divergence in the nasopharyngeal microbiota of farmers compared to other non-exposed individuals. mechanical deposition of < µm diameter inhaled particles on nasopharyngeal surfaces by inertial impaction [ ] , represents a continuous source of environmental bacteria to the nasopharynx. this continuous source of bacterial exposure may therefore be responsible for the establishment of a reservoir of bacteria reflecting long-term exposure (e.g., occupational exposure). a thorough understanding of the established bacterial community may then lead to a better evaluation of the risks associated with an environment. for example, domestic animals share some of their microbiota with their human cohabitants, supposedly through frequent and direct contact [ , ] . song et al., ( ) mention that airborne microbiota plays an important role in microbial transfer to the human upper respiratory tract. ten thousand litres of air are inhaled daily and the bioaerosols in the air may have an effect on the human nasal microbial community [ ] . finally, as different farm animals are associated with different microbiota, the normal nasopharyngeal flora of farmers may be differently disturbed. in other words, farmers working with different animals may have a different disturbances of their natural nasopharyngeal flora. therefore, the microbial fingerprint of the nasopharynx may be directly linked to a specific type of farming environment and the potential long-term health effects on farmers. the high abundance of firmicutes and bacteriotedes in pig buildings has been shown [ ] [ ] [ ] . interestingly, the results of this study are consistent with the literature, but with the added information indicating that, these same phyla colonize the nasopharynxes of farmers. more particularly, other studies have previously shown clostridia to be the most abundant class of bacteria in bioaerosols from pig buildings [ ] . this study not only confirmed the abundance of clostridia in air samples, but also that this class was the dominant class found in nasopharynx samples, while it was practically absent in non-exposed individuals. clostridium spp., identified as differentially abundant in the farmer nasopharyngeal samples in the present study, comprise potentially pathogenic species [ ] . specifically, clostridium butyricum, also differentially abundant in samples from farmers, has been identified as an emerging pathogen by public health authorities. some c. butyricum pathogenic strains were associated with the occurrence of necrotizing enterocolitis, a bowel disease [ ] . in addition, prevotella spp., which was strikingly more abundant in nasopharynx samples, is a well-known agent involved in upper respiratory tract infections [ ] [ ] [ ] . moraxella is another genus identified by the differential abundance analyses as being predominant in the nasopharynxes of farmers. like for other taxa identified in this study, strains of moraxella spp. were previously detected as airborne bacteria in pig buildings [ ] . the rate of colonization of moraxella spp. in healthy adult populations is around % [ ] . species of this genus are opportunistic pathogens responsible for upper and lower respiratory tract infections [ ] . taxa identified exclusively in nasopharyngeal samples and air samples from pig buildings could be candidates for new markers to assess exposure to bioaerosols in pig farming environments. although, actinobacteria are most abundant in the non-exposed controls, no pathogen was identified in the most abundant taxa presented in figure (except haemophilus influenza). an example of the most abundant actinobacteria in non-exposed control is micrococcus luteus that was differentially more abundant in controls compared to farmers. another example of firmicutes is staphylococcus epidermis that was more abundant in the controls compared to the farmers. the respiratory health of farmers has been of great interest for testing the hygiene hypothesis that stipulates that exposure to microbes from intensive farming during early life could be beneficial to health in adulthood [ , ] . however, the acceptance of the hygiene hypothesis is not unanimous in the scientific community [ ] . in this study, taxa identified as differentially abundant among farmers could hypothetically play a role in the prevention of allergy and the development of atopic diseases. indeed, some bacteria identified through this investigation (e.g., pedobacter, pelomonas, and megasphaera) have been linked to healthy respiratory conditions [ ] . a recent study, conducted by kraemer and colleagues, also found a distinct clustering between samples from the nasal cavities of pig farmers and air samples from their workplace, when compared to the nasal cavities of non-exposed individuals [ ] . moreover, samples from the nasal cavities of cow farmers clustered separately from pig worker samples and air samples from pig buildings [ ] . although the nasal cavity is a more transient environment for environmental bacteria than the nasopharynx, it confirms the hypothesis of a microbial fingerprint specific to the farming environment. it supports the idea of creating a worldwide database, that lists potential markers specific to certain environments, and to the nasopharynxes of the people working in them. this database could represent an important asset for associating bioaerosol exposure with health problems [ ] . the lack of a correlation between the nasopharynx of wastewater workers and bioaerosols from wwtps could be explained by the nature and duration of exposure. workers wear personal protective devices (e.g., masks) at certain working sites (e.g., biofiltration), which may affect the establishment of a 'new' environmental microflora. supporting this idea, the most abundant bacteria, shared by non-exposed controls and wastewater workers, are naturally occurring skin bacteria like propionibacterium, corynebacterium, staphylococcus, streptococcus, and cutibacterium. these taxa were not present (relative abundance less than %) in air samples from wwtps (data not shown). farmers do not usually wear respiratory protection and, moreover, they often live in the farming environment (e.g., in a house located near farms) and are consequently continuously exposed to the microbes generated from farming activities (occupational and residential exposures). therefore, the exposure that farmers are subjected to is more likely to modify their natural nasopharyngeal flora. the agricultural/non-agricultural hypothesis presented in this work regarding the nasopharyngeal flora of exposed workers should be validated in other agricultural and industrial environments. recent studies of the microbiome of the upper respiratory tract may have underestimated the influence of occupational exposure when considering the effect of a particular disease on the natural flora of upper respiratory tract tissue [ ] [ ] [ ] . the fact that the work environment may affect the natural flora of an exposed person on a long-term scale is a crucial consideration when he/she becomes a patient whose upper respiratory tract microbiota is the target of the disease. the results obtained in this work emphasize the importance of considering the environment of the nasopharyngeal flora of exposed workers, who are or could become patients suffering from chronic respiratory diseases. in the same way that recent advances in methods for identifying microbes has helped implicate the upper respiratory tract microbiome in inflammatory respiratory diseases, evaluating bioaerosol exposure can help us support the roles of resident microbes in both healthy and diseased tissues. specific human pathogens and antibiotic and zinc resistance genes were detected in the nasopharynxes of pig farm workers as well as in bioaerosols of pig buildings [ ] . for bacterial diversity analyses, the qpcr approach supports the use of the nasopharynx as an alternative to air sampling. the presence of zinc and antibiotic resistance genes, in the nasopharynxes of farmers, is explained by the use of zinc and antibiotics in animal farming (for therapeutic or sub-therapeutic use, such as for growth promotion) and implies possible human health risks. extensive use of zinc in pig feed is responsible for the proliferation of zinc-resistant bacterial communities at farms [ ] . cephalosporin is a commonly used antimicrobial drug in human infections and the spread of its resistance constitutes part of the antibiotic resistance crisis [ ] . finally, the mcr- gene was found in the nasopharynxes of half of the pig farmers in this study, although the use of colistin is extremely regulated in north america and limited to multi-drug resistant microbes [ ] . future studies should include detailed health information on the sampled individuals to investigate the nasopharynx microbiota associated with certain occupational health problems. additionally, a longitudinal study of the bacterial diversity, in the nasopharynxes of farmers and in bioaerosols from pig buildings, could unveil a long-term variation in microbial content. finally, information about the diet of exposed human (or animal) and antibiotic use could be added to the analyses as important factors influencing the microbiota. this is the first study to link the nasopharyngeal flora of exposed humans with the source of the exposure in an agricultural setting, using bacterial diversity analyses and the detection of specific pathogens and resistance genes. the results suggest that workers are carriers of bioaerosol-associated bacteria and that nasopharynx sampling could be used as a proxy for air sampling in exposure assessment studies. furthermore, pig farmers are also carriers of specific human pathogens and resistance genes 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open access article distributed under the terms and conditions of the creative commons attribution (cc by) license key: cord- -jzhuq te authors: hui, david s. c. title: noninvasive mechanical ventilation: models to assess air and particle dispersion date: - - journal: noninvasive ventilation in high-risk infections and mass casualty events doi: . / - - - - _ sha: doc_id: cord_uid: jzhuq te respiratory failure is a major complication of viral infections such as severe acute respiratory syndrome (sars) [ ], avian influenza h n infection [ ], and the pandemic influenza (h n ) infection [ ]. the course may progress rapidly to acute respiratory distress syndrome (ards) and multi-organ failure, requiring intensive care. noninvasive ventilation (niv) may play a supportive role in patients with severe viral pneumonia and early ards/acute lung injury. it can act as a bridge to invasive mechanical ventilation, although it is contraindicated in critically ill patients with hemodynamic instability and multi-organ dysfunction syndrome [ ]. transmission of some of these viral infections can convert from droplets to airborne during respiratory therapy. particles generated during tidal breathing [ ] , niv may disperse potentially infected aerosols, especially when patients cough and sneeze frequently, contributing to nosocomial transmission of infl uenza. pulmonary tuberculosis (tb) is well known to spread by the airborne route. a recent study showed that a small number of patients with pulmonary tb ( %) produced culturable cough aerosols [ ] . thus, it is important to examine the exhaled air directions and dispersion distances during application of niv to patients with respiratory failure via commonly used face masks. the data can improve our understanding of and knowledge about infection control. such knowledge can facilitate the development of preventive measures to reduce the risk of nosocomial transmission during application of niv to high-risk patients with respiratory infections. as there is no reliable, safe marker that can be introduced into human lungs for experimental purposes, the laser smoke visualization method and the human patient simulator (hps) model have been adopted as the method for studying exhaled air dispersion during application of various types of respiratory therapy in hospital medical wards, including the negative-pressure isolation room [ - ] . the hps represents a -kg adult man sitting on a °-inclined hospital bed ( fig. . ) . the hps contains a realistic airway and is programmed to remove oxygen and inject carbon dioxide into the system according to a preset respiratory exchange ratio and oxygen consumption. the lung compliance can also be changed to simulate different degrees of lung injury during chest infection. by varying the oxygen consumption ( , , and ml/min) and lung compliance ( , , and ml/cmh o), these sets of values produce a range of tidal volumes, respiratory rates, and peak inspiratory fl ow similar to those of patients with minimal (essentially normal lung function), moderate, or severe lung injury, respectively. for example, lung compliance is set at ml/cm h o and oxygen consumption at ml/min to mimic mild lung injury. tidal volume and respiratory rate are regulated so a respiratory exchange ratio of . is maintained during measurements. typically, this is achieved with a tidal volume of ml and a respiratory rate of breaths/min [ - ] . lung compliance and airway resistance also responds in a realistic manner to relevant respiratory challenges. the hps produces an airfl ow pattern that is close to the in vivo situation. it has been applied in previous studies to simulate human respiration [ - ] . deliberate leakage from the exhalation ports of the mirage mask (resmed, bella vista, nsw, australia) [ ] , comfortfull , and image masks (respironics, murrysville, pa, usa) [ ] fi rmly attached to a high-fi delity hps (hps . ; medical education technologies, sarasota, fl, usa) has been evaluated. niv was applied using a bilevel positive airway pressure device (vpap iii st; resmed) via each mask. the inspiratory positive airway pressure (ipap) was initially set at cmh o and gradually increased to cmh o. the expiratory positive airway pressure (epap) was maintained at cmh o throughout the study [ , ] . visualization of airfl ow around each niv face mask was facilitated by marking the air with smoke particles produced by a m- smoke generator (n ; ds electronics, sydney, australia), as in our previous studies [ - ] . the oil-based smoke particles, measuring less than μm in diameter, are known to follow the airfl ow pattern precisely with negligible slip [ ] . the smoke was introduced continuously to the right main bronchus of the hps. it mixed with alveolar gas and then was exhaled through the airway. sections through the leakage jet plume were then revealed by a thin, green laser light sheet ( nm wavelength, continuous-wave a laser beam located on the right side of the bed lateral to the human patient simulator illuminates the exhaled air particles leaking from the exhalation ports of the face mask in the coronal plane. a camera was positioned along the sagittal plane at the end of the bed to capture lateral dispersion of exhaled air illuminated by the laser device. positions of the camera and the laser device would be exchanged when the exhaled air dispersion from the face mask is examined along the sagittal plane mode) created by a diode-pumped solid-state laser (oem ugh- mw; lambda pro technologies, shanghai, china) with custom cylindrical optics to generate a two-dimensional laser light sheet [ - ] . the light sheet was initially positioned in the median sagittal plane of the hps and subsequently shifted to paramedian sagittal planes. this allowed us to investigate the regions directly above and lateral to the mask and the patient [ - ] . all leakage jet plume images revealed by the laser light sheet were captured by a high-defi nition video camera-sony high-defi nition digital video camcorder (hdr-sr e; sony, tokyo, japan); clearvid complementary metal oxide semiconductor sensor (sony) with a carl zeiss vario-sonnar t* lens (carl zeiss, jena, germany)-with optical resolution of , × , pixels per video frame. the normalized smoke concentration in the plume was estimated from the light intensity scattered by the smoke particles [ - ]. the normalized smoke concentration in the mask leakage air was estimated from the light scattered by the particles. the analysis was based on scattered light intensity being proportional to the particle concentration under the special conditions of constant-intensity laser light sheet illumination and monodispersion of small (submicron) particles [ ] . in short, the thin laser light sheet of near-constant intensity illuminated the smoke particle markers in the mask airfl ow leakage. smoke particles scattered laser light perpendicular to the light sheet. the pictures were then collected and integrated by the video camera element and lens [ - ]. a motion video of at least breathing cycles for each niv setting was captured and individual frames extracted as gray-scale bitmaps for intensity analysis. frames were extracted at time points starting from the beginning of each inspiration to generate an ensemble average for the corresponding instant of the respiratory cycle [ - ] . the time at which the normalized concentration contours spread over the widest region from the niv mask was chosen for the ensemble average to estimate the greatest dispersion distance. this was found to be approximately at the mid-respiratory cycle [ , ] . all gray-scale frames were read into a program specifi cally developed for these studies [ - ] (mathcad . ; mathsoft, cambridge, ma, usa) [ ] along with the background intensity images obtained with the laser switched off. the background intensity image was subtracted from each frame, pixel by pixel, to remove any stray background light. the pixel intensity values were averaged over all frames to determine the average intensity. the resulting image was the total intensity of light scattered perpendicular to the light sheet by the smoke particles. it was directly proportional to the smoke concentration under the conditions mentioned above. the image was normalized against the highest intensity found within the leakage jet plume to generate normalized particle concentration contours [ - ] . as the smoke particles marked air that originated from the hps's airways before leaking from the mask, the concentration contours effectively represent the probability of encountering air around the patient that has come from within the mask and the patient's respiratory system. the normalized concentration contours are made up of data collected from at least breaths. a contour value of indicates a region that consists entirely of air exhaled by the patient, where there is a high chance of exposure to the exhaled air, such as at the mask exhaust vents. a value near indicates no measurable air leakage in the region and a small chance of exposure to the exhaled air [ - ]. the results are presented with reference to the median sagittal plane. with the resmed mirage mask, a jet plume of air escaped through the exhaust holes to a distance of approximately . m radially during application of ipap cmh o, with some leakage from the nasal bridge. the leakage jet probability was highest about - mm lateral to the sagittal plane of the hps. without nasal bridge leakage, the plume jet from the exhaust holes increased to a . m radius circle, and exposure probability was highest about . m above the patient. when ipap was increased to cmh o, the vertical plume extended to about . m above the patient and the mask, with some horizontal spread along the ward roof [ ]. with the comfortfull mask, a vertical, cone-shaped plume leaked out from the mask exhalation diffuser and propagated well above and almost perpendicular to the patient at an ipap and an epap of and cmh o, respectively. the maximum dispersion distance of smoke particles-defi ned as the boundary with a region encountering < % normalized concentration of exhaled air (light blue contour smoke concentration scale)-was . m, whereas that of a high concentration (containing > % normalized concentration of exhaled air, red zone, and above) was . m. there was no signifi cant room contamination by exhaled air (as refl ected by the blue background in the isolation room) other than the exhalation jet plume [ ] . when the ipap was increased from to cmh o, the maximum exhaled dispersion distance of low-concentration exhaled air was similar at . m, but that of high-concentration exhaled air increased to . m, with contamination of the isolation room. also, there was some exhaled air concentration outside the exhalation jet plume. when ipap was increased to cmh o, the dispersion distance of lowconcentration exhaled air was . m, whereas that of high-concentration exhaled air increased to . m along the median sagittal plane. more background contamination of the isolation room by smoke particles was noted at higher ipaps owing to interaction between the downstream ceiling-mounted ventilation vent and the upstream exhaled air from the hps (images at left in fig. . ) [ ]. the image mask required an additional exhalation device (whisper swivel) to prevent carbon dioxide rebreathing. the exhaled air leakage was much more diffuse than that with the comfortfull mask because of the downstream leakage of d.s.c. hui exhaled air through the whisper swivel exhalation port. at an ipap of cmh o, the maximum dispersion distance of a low concentration in exhaled air (light blue zone on the smoke concentration scale) was . m toward the end of the bed, whereas that of a medium concentration (containing > % of the normalized concentration of exhaled air, green zone, and above) was about . m along the median sagittal plane. as the ipap was increased from to cmh o, the exhaled air with a medium concentration increased to . m toward the end of the bed along the median sagittal plane of the hps [ ] . when the ipap was increased to cmh o, the exhaled air with a low concentration dispersed diffusely to fi ll up most of the isolation room (i.e., beyond . m, as captured by the camera), whereas that with a medium concentration, occupying wider air space, was noted to spread . m toward the end of the bed, with accumulation of a high concentration of exhaled air (red zone on scale) within . m from the center of the mask, along the median sagittal plane of the hps (images on the right in fig. . ) [ ] . there is no reliable, safe marker that can be introduced into human lungs for experimental purposes. hence, the maximum distribution of exhaled air, marked by very fi ne smoke particles, from the hps during application of niv using three face masks was examined by the laser smoke visualization method on a high-fi delity hps model. the studies showed that the maximum distances of exhaled air particle dispersion from patients undergoing niv with the resmed ultra mirage mask was . m along the exhalation port [ ] . in contrast, the dispersion distances of a low, normalized concentration of exhaled air through the comfortfull mask exhalation diffuser increased from . to . m at a direction perpendicular to the head of the hps along the sagittal plane when ipap was increased from to cmh o. there was also more background contamination of the isolation room at the higher ipap [ ] . even when a low ipap of cmh o was applied to the hps via the image mask connected to the whisper swivel exhalation port, the exhaled air leaked far more diffusely than from the comfortfull mask, dispersing a low normalized concentration of . m along the median sagittal plane of the hps. the higher ipap resulted in wider spread of a higher normalized concentration of smoke around the hps in the isolation room with negative pressure [ ] . simonds et al. [ ] applied the laser visualization method to assess droplet dispersion during application of niv in humans with an optical particle sizer (aerotrak ; tsi instruments, high wycombe, uk) and showed niv as a droplet-(not aerosol-) generating procedure, producing droplets measuring > μm. most of them fell onto local surfaces within m of the patient. noninvasive ventilation is an effective treatment for patients with respiratory failure due to copd, acute cardiogenic pulmonary edema, or pneumonia in immunocompromised patients. however, evidence supporting its use in patients with pneumonia is limited. niv was applied to patients with severe pneumonia caused by a pandemic infl uenza (h n ) infection with a success rate of about %. although there were no reported nosocomial infections [ ] , there is a potential risk of applying niv to patients hospitalized with viral pneumonia on a crowded medical ward with inadequate air changes [ ] . in this regard, deliberate leakage via the exhalation ports may generate droplet nuclei and disperse infective aerosols through evaporation of water content of respiratory droplets, resulting in a superspreading event. nonetheless, niv was applied using a single circuit to treat patients effectively with respiratory failure due to sars in hospitals with good infection control measures (including installation of powerful exhaust fans to improve the room air change rate and good protective personal equipment at a level against airborne infection). there were no nosocomial infections among the health care workers involved [ , ] . in contrast, a case-control study involving patients in medical wards of hospitals in guangzhou and hong kong identifi ed the need for oxygen therapy and use of niv as independent risk factors for superspread of nosocomial sars outbreaks [ ] . similarly, a systematic review has shown a strong association between ventilation, air movement in buildings, and airborne transmission of infectious diseases such as measles, tuberculosis, chickenpox, infl uenza, smallpox, and sars [ ] . these studies of infection with the hps model [ , ] and in humans [ ] have important clinical implications for preventing future nosocomial outbreaks of sars and other highly infectious conditions such as pandemic infl uenza when niv is provided. niv should be applied in patients with severe community acquired pneumonia only if there is adequate protection for health care workers because of the potential risk of transmission via deliberate or accidental mask interface leakage and fl ow compensation causing dispersion of a contaminated aerosol [ , ] . pressure necrosis may develop in the skin around the nasal bridge if the niv mask is applied tightly for a prolonged period of time. many patients loosen the mask strap to relieve discomfort. air leakage from the nasal bridge is defi nitely a potential means of transmitting viral infections. fitting a mask carefully is important for successful, safe application of niv. addition of a viral/bacterial fi lter to the breathing system of niv, between the mask and the exhalation port, or using a dual-circuit niv via full face mask or helmet without heated humidifi cation may reduce the risk of nosocomial transmission of a viral infection [ , ] . in view of the observation that higher ventilator pressures result in wider dispersion of exhaled air and more air leakage [ , ] , it is advisable to start niv with a low ipap ( - cmh o) and increase it gradually as necessary. the whisper swivel is an effi cient exhalation device to prevent carbon dioxide rebreathing, but it would not be advisable to use such an exhalation port in patients with febrile respiratory illness of unknown etiology. this is especially true in the setting of an infl uenza pandemic with the high potential of human-to-human transmission for fear of causing a major outbreak of nosocomial infections. it is also important to avoid the use of high ipap, which could lead to wider distribution of exhaled air and substantial room contamination [ ] . there are some limitations regarding the use of smoke particles as markers for exhaled air. the inertia and weight of large droplets in an air-droplet two-phase fl ow would certainly cause them to have less horizontal dispersion than occurs with the continuous air carrier phase during which the particles travel with increased inertia and drag. however, evaporation of the water content of some respiratory droplets during coughing or sneezing when exposed to niv may produce droplet nuclei suspended in air, whereas the large droplets fall to the ground in a trajectory pathway [ - ] . as smoke particles mark the continuous air phase, the data contours described refer to exhaled air. the results would therefore represent the "upper bound" estimates for dispersion of the droplets-which would be expected to follow a shorter trajectory than an air jet due to gravitational effects-but not fully refl ect the risk of large-droplet transmission [ - ] . in summary, the laser visualization technique using smoke particles as a marker in the hps model is a feasible means of assessing exhaled air dispersion during application of niv and other modes of respiratory therapy [ - ] . substantial exposure to exhaled air occurs within m of patients undergoing niv in an isolation room with negative pressure via the comfortfull mask and the image mask connected to the whisper swivel exhalation port. it must be noted that there is far more extensive leakage and room contamination with the image mask, especially at higher ipaps [ ] . health care workers should take adequate precautions for infection control. they especially must pay attention to environmental air changes when providing niv support to patients with severe pneumonia of unknown etiology complicated by respiratory failure . a major outbreak of severe acute respiratory syndrome in hong kong review of clinical symptoms and spectrum in humans with infl uenza a/h n infection clinical management of pandemic (h n ) infection infl uenza a/h n infection: other treatment options and issues transmission of severe acute respiratory syndrome during intubation and mechanical ventilation why did outbreaks of severe acute respiratory syndrome occur in some hospital wards but not in others? possible role of aerosol transmission in a hospital outbreak of infl uenza infl uenza virus in human exhaled breath: an observational study variability of infectious aerosols produced during coughing by patients with pulmonary tuberculosis non-invasive positive pressure ventilation: an experimental model to assess air and particle dispersion exhaled air dispersion distances during application of noninvasive ventilation via different respironics face masks exhaled air dispersion during oxygen delivery via a simple oxygen mask exhaled air and aerosolized droplet dispersion during application of a jet nebulizer breathing pattern and workload during automatic tube compensation, pressure support and t-piece trials in weaning patients patient simulation for training basic and advanced clinical skills a model for educational simulation of infant cardiovascular physiology an audible indication of exhalation increases delivered tidal volume during bag valve mask ventilation of a patient simulator fluid dynamics of multiphase systems mathcad . for windows, users guide evaluation of droplet dispersion during non-invasive ventilation, oxygen therapy, nebuliser treatment and chest physiotherapy in clinical practice: implications for management of pandemic infl uenza and other airborne infections early non-invasive ventilation treatment for severe infl uenza pneumonia effectiveness of noninvasive positive pressure ventilation in the treatment of acute respiratory failure in severe acute respiratory syndrome noninvasive positive pressure ventilation treatment for acute respiratory failure in sars role of ventilation in airborne transmission of infectious agents in the built environment-a multidisciplinary systematic review on the role of non-invasive ventilation (niv) to treat patients during the h n infl uenza pandemic. ers and esicm guideline • the laser visualization technique using smoke particles as markers in the hps model is a feasible means of assessing exhaled air dispersion during application of niv and other modes of respiratory therapy. • substantial exposure to exhaled air occurs within m of patients undergoing niv even in an isolation room with negative pressure. • during application of niv, it is advisable to choose face masks with predictable exhaled air directions and distances through the exhalation port without addition of the whisper swivel device. • it is important to avoid using high inspiratory pressures and any face mask that requires connection to the whisper swivel exhalation port as they would lead to wider distribution of exhaled air and substantial room contamination. key: cord- -fne p h authors: wu, yan; niu, jianlei; liu, xiaoping title: air infiltration induced inter-unit dispersion and infectious risk assessment in a high-rise residential building date: - - journal: build simul doi: . /s - - - sha: doc_id: cord_uid: fne p h identifying possible airborne transmission routes and assessing the associated infectious risks are essential for implementing effective control measures. this study focuses on the infiltration-induced inter-unit pollutant dispersion in a high-rise residential (hrr) building. the outdoor wind pressure distribution on the building facades was obtained from the wind tunnel experiments. and the inter-household infiltration and tracer gas transmission were simulated using multi-zone model. the risk levels along building height and under different wind directions were examined, and influence of component leakage area was analysed. it is found that, the cross-infection risk can be over % because of the low air infiltration rate below . ach, which is significantly higher than the risk of % obtained in our previous on-site measurement with air change rate over ach. as the air infiltration rate increases along building height, cross-infection risk is generally higher on the lower floors. the effect of wind direction on inter-unit dispersion level is significant, and the presence of a contaminant source in the windward side results in the highest cross-infection risks in other adjacent units on the same floor. properly improving internal components tightness and increasing air change via external components are beneficial to the control of internal inter-unit transmission induced by infiltration. however, this approach may increase the cross-infection via the external transmission, and effective control measures should be further explored considering multiple transmission routes. airborne transmission is responsible for the spread of various respiratory infectious diseases, such as tuberculosis, measles, influenza, smallpox, and sars (riley ; riley et al. ; nicas et al. ; li et al. ). studies after the outbreak of sars in attributed the vertical spread of the virus in the re-entrance space of high-rise buildings to the buoyancy-dominant natural ventilation (yu et al. ; li et al. ; wang et al. a; cheng et al. ) . the airborne transmission can trigger a large scale outbreak of an infectious disease due to the rapid spread of pathogens along the airflow (wu and niu ) . identifying the possible airborne transmission routes related to air movement and assessing the associated infectious risks are essential for implementing effective control measures. the inter-unit cross-contamination in high-rise residential (hrr) buildings has been a concern as a typical airborne transmission mode ever since the sars outbreak in in hong kong. ventilation airflows in hrr buildings involve single-sided ventilation, cross-ventilation and air infiltration. the external transmission induced by the re-entry of single-sided natural ventilation has been comprehensively investigated. niu and tung ( ) verified and quantified the vertical upward transmission under buoyancy effects. in such a transmission route, air expelled from the open window of the lower floor re-enters the windows of upper floors. gao et al. ( gao et al. ( , ) and liu et al. ( liu et al. ( , further studied the characteristics of inter-unit dispersion induced by single-sided natural ventilation and the cross-contamination around a hrr building using cfd modeling approach and wind tunnel experiments. the re-entry ratio can be over % and the infectious risk can be . %. mak ( , ) systematically evaluated and improved the cfd methods for simulating the single-sided natural ventilation and inter-unit dispersion, especially in predicting of coupled indoor and outdoor airflow and dispersion, and it was found that not only vertically upward, but also vertically downward and horizontal transmission can occur under wind effects along the façade. the effect of mechanical exhausts to prevent inter-unit transmission induced by single-sided natural ventilation was also evaluated . another internal inter-unit pollutant transmission route driven by air infiltration and cross-ventilation were investigated in our previous on-site measurements . the measurements were carried out in three horizontal adjacent units on the same floor. the air change rate contributed by thermal effect was estimated in the range of %- % and the mean was %. it seems that wind effect is more dominant. the horizontal inter-unit dispersion induced by air infiltration exhibits higher risk than the cross-ventilation because of the low air change rate. the cross-infection risk through this internal air infiltration route assessed using the wells-riley model can reach % , which is higher than the risk of . % via the external vertical spread route through single-sided open windows (gao et al. ) . however, the measurements were conducted in an old leaky building with high air infiltration rate over ach, which may significantly favor the dilution of pathogens and under-estimate the infectious risk. for energy conserving reasons, the recommended value of air leakage in residential buildings is under . - . ach in the ashrae handbook (ashrae ) . the risk assessment of this internal transmission route under lower air infiltration rate should be further studied. the experimentation is a widely used technique for studying air infiltration, and two common experimental methods are fan pressurization and tracer gas techniques. the former is used to measure the air tightness of the building envelope, while the latter is employed to measure the air infiltration. the multi-zone modeling is another efficient approach that is used in many studies for calculating air infiltration and contaminant transport (li et al. (li et al. , emmerich ; wang et al. b; parker et al. ). this method simplifies airflow and contaminant-related phenomenon with a few assumptions, which considers each zone as a single node with uniform air conditions. the multi-zone method assumes that the inflow momentum effect in each zone is disregarded. the temperature and contaminant concentration in each zone is supposed to be uniform, and the distribution of pressure is hydrostatic. air resistance in each zone is neglected while the contaminant transport is considered instantaneously. given these assumptions, the multi-zone method is unsuitable for describing wind pressure around buildings, and simulating indoor airflow with momentum effects or contaminant gradients. however, it has good performance in solving problems related to entire-building or long-term dynamic simulations and modeling building air infiltrations. considering the difficulties to capture the wide range of air-leakage scenarios with measurements, the multi-zone modeling method was used in the present study to reproduce the internal transmission route induced by air infiltration, and to assess the infectious risks under more appropriate air leakage levels. the air infiltration through cracks under wind effect is focused on. the pollutant dispersion characteristics between horizontal adjacent units were examined in a hrr building. the risk levels of cross-infection were assessed along building height and under different wind directions. moreover, the effects of air airtightness on air infiltration and cross-infection were investigated. a major issue in analyzing air infiltration driven by outdoor wind is the accurate solving of the interaction between outdoor wind flow and indoor airflow (ramponi and blocken ) . figure shows the diagram of the coupled and decoupled approaches. the coupled approach directly solves the outdoor and indoor airflow. while the decoupled approach solves outdoor and indoor flow field separately. the outdoor wind flow is studied first with sealed building assumption and then the indoor airflow is solved based on wind pressure distributions on building façades obtained from the outdoor study. the coupled approach is difficult to employ when the differences in length scale are substantial or when flow behavior problems exist (nore et al. ) . the decoupled approach is simplified compared to the coupled approach, but it is only efficient for certain phenomena. many studies have verified the applicability of the decoupled approach (seifert et al. ; kobayashi et al. kobayashi et al. , . this approach fig. diagram of coupled and decoupled approaches (ramponi and blocken ) is unsuitable when flow has large openings, specifically when the wall porosities are larger than % (karava et al. (karava et al. , (karava et al. , . and, the approach is impractical when the area of windward openings is significantly smaller than that of the leeward openings (sandberg ) . moreover, the approach cannot be applied when the velocity pressure on the retardation section is larger than the static pressure (sandberg ). in the present study, the decoupled approach is applicable for analyzing air infiltration flow with small cracks and wall porosity. thus, the decoupled approach was employed. the outdoor airflow patterns around an isolated building and the pressure distributions on building façades were studied using wind tunnel experiments in our previous study (liu et al. ; liu ) . the wind tunnel experiments aimed at investigating the cross-contamination around hrr building caused by wind effect. two sets of experiments were carried out with different building models and wind speeds. in set , a : scaled -story building model without open windows was used, and the experiments were conducted in the high-speed section of the clp power wind/wave tunnel in the hong kong university of science and technology. in set , a : scaled -story building model with open windows was employed, and the experiments were performed in the low-speed section of the wind tunnel. wind parameters were measured using gobra probe. surface pressures were measured simultaneously by pressure taps (diameter of . mm), which were connected to -channel electronic pressure scanners manufactured by pressure system inc. pressure taps were set up in each floor. the incoming wind velocity profile was described using the power law. and the turbulence intensity profile in the wind tunnel test was defined based on the terrain category in australian/new zealand standard (standard ) , since that the longitudinal turbulence intensity profile at different terrain conditions are only provided in japan, eccs (the european convention for constructional steelwork) and australia. the detailed experiment configuration are introduced in our previous study (liu ) . the wind pressure distributions on the high-rise sealed building of set were utilized as the boundary conditions in the present study for calculating indoor air infiltration in contam. the normalized pressure coefficients on the building envelopes were used to define the pressure conditions of open windows in contam. the experiment configuration and approaching wind profiles of set is shown in fig. . indoor air infiltration and inter-unit contaminant transmission were simulated using the multi-zone model, which assumes the uniform distributions of wind pressure, momentum effects, and contaminant concentration in a zone. a multizone computer program contam . was used (walton and dols ) , which has been employed in many research of indoor air quality and contaminant transport (standard ; temenos et al. ; jomehzadeh et al. ) . in this program, air infiltration is calculated based on the power law relationship between the flow and pressure difference across a crack in the building envelope as follows: where q is the volumetric flow rate (m /s), Δp is the pressure drop (pa), c is the flow coefficient and n is the flow exponent. a variation of the power law equation is related to the orifice fig. configuration of the wind tunnel experiment and approaching wind profiles in our previous study (liu ) (u is the mean velocity, and ti (= u/u) the turbulence intensity, and u is the square root of the mean squared fluctuating velocity. x-axial scales can be used for both u and ti) equation: where c d is the discharge coefficient, and a is the component leakage area (m ). the pressure drop and component leakage data are required using this program in calculating the infiltration rate. the pressure data on the building envelopes were obtained from the wind tunnel experiments mentioned above. the leakage areas of components were specified on the basis of the best estimate values in the ashraela library in contam . (walton and dols ) . infection probability p i was calculated using the wells-riley model to estimate the infectious risk of diseases. here, c is the number of infection cases, s is the number of susceptibles. in the calculation, the infector number i in the index unit is , the quanta generation rate q is quanta per hour, the pulmonary ventilation rate p of a person is . m /h, and the exposure time t is h. the values of the parameters were the same as those in our previous study (gao et al. ; ) about the external dispersion for the comparison between two transmission routes. the calculated infectious risks are relative values rather than absolute values. cross-infection risks for receptor units without a source can be calculated using the following equation: where c i and c s are the equilibrium tracer gas concentrations of unit i and the source unit (flat ), respectively. to reproduce the horizontal pollutant dispersion induced by air infiltration, a single-floor model (fig. ) with nine zones was constructed. the model includes eight units and one lift lobby, which is the same to a typical floor of the cross-type building model in the wind tunnel experiments. the full-scale building was modeled in contam. the vertical transmission via lift shaft or other vertical paths was not included to concentrating on the horizontal route as verified in our previous on-site measurements . each unit has three windows that connect the unit to the ambient environment and a door that links the unit to the lift lobby. all windows and doors are closed, but air leakage can easily occur, which are considered as the main airflow paths. a pollutant source is set in flat , which releases tracer gas co with a constant rate of g/h. co was used to simulating the diffusion of the gaseous pollutant or fine particles, which exhibit higher pathogenicity than coarse particles. fine particles less than . μm disperse similar to gaseous pollutants despite deposition and gravitational effects (gao et al. ). particles with a size of . - . μm can completely penetrate through building envelopes when the cracks are larger than mm and the pressure difference is higher than pa (liu and nazaroff ) . however, tung et al. ( ) experimentally demonstrated that %- % of particles with a size range of . - . μm can be trapped by the building shell. particle deposition onto indoor surfaces can also limit the spread (lai and nazaroff ) . therefore, the cross-infectious risk determined using gaseous pollutants may be over-estimated. besides, considering the low contribution of thermal effect in the airflow and dispersion in our previous on-site measurements , the thermal effect was neglected in the present study. four cases on the th, th, nd and th floor were calculated to study the characteristics of inter-unit dispersion along building height. three cases with wind directions of °, ° and ° were simulated in studying the effect of wind direction. in these cases, the multi-zone models, component leakage data, and tracer gas sources were fixed. the window leakage areas were set to cm /item and the door leakage area was set to cm /item. the reference parameters of airflow paths, namely, reference pressure drop and discharge coefficient c d , were set to pa and , respectively. only the pressure boundary conditions were varied for different cases. to study the effects of window or door airtightness on air infiltration and dispersion, cases with different window and door leakage areas were examined. in these cases, all the multi-zone models, tracer gas sources and pressure boundary conditions are fixed, except the window and door leakage data. the wind directions for four different floor cases are all °, which means that flats , , , and are on the windward side and the other units are on the leeward side. the pressure coefficient distributions on building façades of different floors are shown in fig. . the pressure coefficient is defined as: where p ref is the atmospheric pressure, u ref is the incoming wind velocity at the building height. similar pressure distribution characteristics on different floors are obtained. the distributions present to be asymmetry. the pressure coefficients on the building façades of the windward side are positive, whereas those on the lateral and leeward sides are negative. high floors generally exhibit large absolute pressure coefficients. however, the pressure coefficients on some façades of the th floor are lower than that of the nd floor, which can be caused by the separation flow near the roof of the building. furthermore, the differences in pressure coefficients between various floors are larger on the windward side than those in the leeward side. figure compares the infiltration rate of the units on different floors. the air infiltration rate is directly proportional to the pressure difference based on the orifice equation. the infiltration rates of flats and on the windward side are the largest among the studied units, whereas the infiltration rates of flats and on the leeward side are the smallest. the infiltration rate reduces gradually from upstream side to downstream side, which can be achieved on all floors. the infiltration rates are nearly symmetrical in the left and right units. this result can be explained by the symmetrical pressure boundary condition. the maximum air infiltration rate is . , which is consistent with the recommended value of air leakage under . - . ach reported in the ashrae handbook. the air infiltration rate on the windward side significantly increases along building height. and this increase rate slows down along building height. the results of the nd and th floors are similar. such similarity may be influenced by the separation flow near the roof. the largest infiltration rates for the lower floor ( th floor), middle floor ( th floor), and higher floors ( nd and th floors) are . , . , and . h − , respectively. the difference can reach %, and the difference in the air infiltration rates of various floors on the leeward side are smaller than that of windward side. figure shows the mass fraction of air from flat to other units, which is used to quantify the internal transmission rate of tracer gas. the mass fractions of air in the leeward units that originate from source unit (flat ) are higher than those in the windward units. the mass fractions are below % in the windward units and above % in the leeward units. the highest mass fraction can reach %. this value is significantly higher than % in our previous on-site measurements ). the differences in mass fractions among units in the same floor can be more than five times. in the leeward side (flats and ) , the mass fraction elevates along building height. on the contrary, the mass fraction reduces slightly along building height in the lateral and windward side. the infectious risks on different floors are shown in fig. , which was calculated using the wells-riley model. the infectious risk in the index unit is above %. in receptor units, leeward units with low air infiltration rates and high mass fractions exhibit high cross-infection probabilities, which are approximately %. it is substantially higher than the risks of % in the measurements in our previous study ). this result can be attributed to the high air tightness of windows, which dramatically restricts the dilution of pollutants to outdoor space. lower floor exhibits larger infectious risk than that of higher floor because of the low air infiltration rate, especially in the index and lateral units. air infiltration and contaminant transmission were calculated under three different wind directions, namely, °, °, and °. the tracer gas sources for all cases are located in flat . the pressure boundary conditions of the th floor under three wind directions are extracted from the wind tunnel experiments and presented in fig. . when the wind direction changes clockwise, the maximum value of pressure coefficient also moves clockwise. the windward façades exhibit the highest pressure coefficients, while the leeward and lateral façades show the lowest and middle pressure coefficients, respectively. however, the pressure coefficient distributions are not simply rotate with wind direction because of the non-centro symmetric building configuration in the wind tunnel experiments. figure shows the infiltration rate of each unit for cases with various wind directions. units in the windward side exhibit the maximum infiltration rate in all wind directions. for wind direction of °, the infiltration rates in flats and are the largest among all units. for wind direction °, the infiltration rate of flat is the largest. for wind direction of °, the infiltration rate of flat is the largest. when the wind direction changes from ° to °, the maximum infiltration rate decreases slightly. the value is . for the wind direction of °, while . for the wind directions of ° and °. the air infiltration rates of the leeward units increase when wind direction changes. accordingly, the difference of infiltration rates among all units decreases. figure shows the mass fraction of air in each unit from the source unit under different wind directions. given the fixed tracer gas source in flat , the effect of wind direction on the exposure levels of other units is significant. when the wind direction is °, the maximum mass fraction is % in the leeward unit (flat ). however, the value is just below % when the wind direction changes to °. moreover, tracer gas cannot be detected in other units when the angle of wind direction further increases to °. the low mass fractions for the ° and ° wind direction cases may be under-estimated because of the limitation that ignoring the re-entry through the outdoor space. wind direction can significantly affect inter-unit contaminant transmission. the inter-unit dispersion induced by air infiltration suffers most seriously when the contaminant source is in the windward side. the infectious risks under different wind directions are presented in fig. . when the wind direction is ° and the index unit is in the windward side, the cross-infection risks in units on the leeward side are high with infectious possibilities near %. when the wind direction is °, the risks in other horizontal adjacent units are significantly reduced to %. ignoring re-entry through the outdoor space, the crossinfection risk is minimal when the wind direction is °. the infectious risk in the index unit is also significantly affected by wind direction. when the index unit is in lateral sides, the infectious risk is significantly higher than that in the windward side. compared with the effect of different floor in the previous section, the influence of the wind direction is more significant. to investigate the effect of air tightness on inter-unit pollutant dispersion and cross-infection, cases with different leakage data of windows and doors (representing external airflow path and internal airflow path, respectively) were calculated. the door leakage areas are fixed at cm /item in cases with window leakage change. similarly, the window leakage areas remain at cm /item in cases with door leakage change. figure presents the relationship between leakage area and air infiltration rate. the infiltration rate is proportional to both window and door leakage areas within the scope of the present study. however, the curve of the infiltration rate against window leakage area is significantly steeper. increasing the window leakage area to cm /item or increasing the door leakage area to cm /item has the same total leakage area of cm , but the infiltration rate of the former case is much higher than that of the latter one. thus, the effect of window tightness on air infiltration rate is more significant than that of door tightness. figure indicates the effects of window or door tightness on indoor contaminant level. for the source unit (flat ), both increasing external window and internal door leakage areas can help remove the contaminant. for other receptor units, large external window leakage area can help reduce tracer gas concentration, but large internal door leakage area may lead to high contaminant level. the reason is that large external window leakage area causes advantageous air change with outdoor space. large internal door leakage area may results in disadvantageous air change with the contaminated lift lobby. but, when the door leakage increases further, the effect may differ. the influence of external window tightness on indoor contaminant level is higher than internal door tightness, which is similar to its effect on air infiltration rate. the effects of window or door tightness on mass fraction and infectious risk are shown in fig. and fig. . enlarging the leakage in the external window reduces the mass fraction, while increasing the leakage in the internal door elevates mass fraction. the effects of window or door tightness on infectious risk are exactly the same as that on tracer gas concentration. cross-infection risk can be significantly reduced by increasing the leakage of external window. enlarging door leakage can increase cross-infection risk. and, while the air tightness is better, its effects on cross-infection risk is higher. the internal inter-unit pollutant dispersion induced by air infiltration was investigated in a hrr building. the pressure coefficients distributions on building façades were obtained from wind tunnel experiments, and the indoor air infiltration and contaminant transmission were calculated using the multi-zone method. the results show that the predicted air infiltration rate is below . ach, which is consistent with the recommended value of air leakage under . - . ach for conserving energy in the ashrae handbook. the assessed cross-infection risk can be over % because of the low air infiltration rate, which is significantly higher than the risk of % obtained in our previous on-site measurement. the inter-unit dispersion induced by air infiltration must not be overlooked. air infiltration rates increase along building height. this increase is minimal on the leeward side but significant on the windward side. cross-infection risk between horizontal adjacent units is generally higher on lower floors. the location of the tracer gas source in a unit in relation to the wind direction is determinant on the exposure levels of other units. the presence of a contaminant source in the windward side results in the highest cross-contaminant level to other horizontal adjacent units. enlarging external leakage can increase the air change with outdoor fresh air and dilute indoor contaminant, while enlarging internal leakage may enhance inter-unit dispersion. practically, in the residential building design, internal windows that have potential leakages should be avoided. and the airtightness of individual entrance doors and other doors to public spaces, such as corridors, staircases, and elevators, should be improved. these strategies are also beneficial for the fire control in hhr buildings and meet the privacy requirements for modern living. as far as public health and occupants behaviors are concerned, proper opening external windows should be encouraged, in particular in conjunction with the proper use of mechanical exhausts provided in the bathroom and kitchens. however, these approaches may increase the cross-infection via external routes, such as singlesided natural ventilation. effective control measures should be further explored considering multiple transmission routes. a study of interunit dispersion around multistory buildings with single-sided ventilation under different wind directions large eddy simulation of wind-induced interunit dispersion around multistory buildings ashrae handbook-hvac applications wind-induced natural ventilation of re-entrant bays in a high-rise building validation of multizone iaq modeling of residential-scale buildings: a review the airborne transmission of infection between flats in high-rise residential buildings: tracer gas simulation the airborne transmission of infection between flats in high-rise residential buildings: particle simulation effects of window or door tightness on the infectious risk (left: window leakage change situation, right: door leakage change situation) a review on windcatcher for passive cooling and natural ventilation in buildings, part : indoor air quality and thermal comfort assessment impact of internal pressure coefficients on wind-driven ventilation analysis wind-induced natural ventilation analysis airflow assessment in cross-ventilated buildings with operable façade elements stream tube based analysis of problems in prediction of cross-ventilation rate experimental investigation and cfd analysis of cross-ventilated flow through single room detached house model modeling indoor particle deposition from turbulent flow onto smooth surfaces prediction of natural ventilation in buildings with large openings multi-zone modeling of probable sars virus transmission by airflow between flats in block e role of ventilation in airborne transmission of infectious agents in the built environment-a multidisciplinary systematic review particle penetration through building cracks experimental and numerical investigation of air crosscontamination around typical high-rise residential building in hong kong investigation of indoor air pollutant dispersion and cross-contamination around a typical high-rise residential building: wind tunnel tests local characteristics of cross-unit contamination around high-rise building due to wind effect: mean concentration and infection risk assessment toward understanding the risk of secondary airborne infection: emission of respirable pathogens on-site quantification of re-entry ratio of ventilation exhausts in multi-family residential buildings and implications on cfd simulation of windinduced airflow in narrow ventilated facade cavities: coupled and decoupled simulations and modelling limitations implementing state-space methods for multizone contaminant transport cfd simulation of cross-ventilation for a generic isolated building: impact of computational parameters airborne spread of measles in a suburban elementary school airborne infection an alternative view on the theory of crossventilation calculation of wind-driven cross ventilation in buildings with large openings as/nzs modelling of indoor air quality of greek apartments using contam (w) software a methodology to investigate the particulate penetration coefficient through building shell nistir , contam . user guide and program documentation assessment of pollutant dispersion in the re-entrance space of a high-rise residential building, using wind tunnel simulations using cfd capabilities of contam . for simulating airflow and contaminant transport in and around buildings assessment of mechanical exhaust in preventing vertical cross-household infections associated with single-sided ventilation numerical study of inter-building dispersion in residential environments: prediction methods evaluation and infectious risk assessment on-site measurement of tracer gas transmission between horizontal adjacent flats in residential building and cross-infection risk assessment evidence of airborne transmission of the severe acute respiratory syndrome virus the research is financially funded by health and medical research fund, hong kong sar government, with the project reference no. . key: cord- -erbftqgh authors: lau, stephen s.y. title: physical environment of tall residential buildings: the case of hong kong date: - - journal: high-rise living in asian cities doi: . / - - - - _ sha: doc_id: cord_uid: erbftqgh increasing urban populations, scarcity of urban land, depletion in resources and severe impact of urban development on sustainability are critical contemporary issues. such issues have vast implications on the desirability of compact, high-rise high-dense built forms. yet, the environmental quality and social acceptance of these forms remain barely studied. this chapter reviews some of the critical environmental implications posed by the closely packed high-rise building and high urban densities. to the physical form, urban morphology would also study social forms, which are expressed in the physical layout of a city, and conversely, how physical form produces or reproduces various social forms. urban morphology is at times considered as the study of urban fabric, as a means of discerning the underlying structure of the built landscape. this approach challenges the common perception of unplanned environments as chaotic or vaguely organic through an understanding of the structures and processes embedded in urbanization. it is widely accepted that there is a close relationship between shape, size, density and uses of a city and the sustainability of that city. however, this chapter is limited to the characteristics of a high-rise, high-density compact urban environment: hong kong and its environmental implications. it is said that urban intensification creates frequent walking trips and better accessibility to facilities (masnavi, ) . in a compact city the reduction in car ownership, vehicular trips and increase of pedestrian and transit use alleviate the environmental consequences associated with the automobile. compact city has many advantages such as conservation of countryside, reduced need to travel by car and thereby reduction in fuel and pollution, support for public transport, walking and cycling, better access to services, more efficient utility and infrastructure provisions, and revitalization and regeneration of urban areas (burton, ) . in contrast to compact city, dispersed cities suffer from inefficient transport management and long commuting trips, which lead to a high dependency on automobile high energy consumption and pollution (newman & kenworthy, ) . although high density combined with mixed use allows for high accessibility to a majority of users, the mixing and co-location of incompatible uses such as housing, community, recreational and public spaces near commercial, industrial and transport can have consequences on the physical quality of the living environment. greater intensification has implications on urban green space. even though a valuable contributor to urban quality, urban greenery provision is often reduced under pressure from other land use development. research claims that compact city suffers from a perceived lack of greenery, open spaces and parks which provision is seen to be better in low-density environment (masnavi, ) . however, urban sprawl results in unsustainable levels of resource use and inequitable lifestyles (williams, burton, & jenks, ) . in comparison with urban sprawl, the compact city is a dominant model for sustainability (jenks, ) . yet, evidence on the impact of higher and lower densities on sustainability, the impact of centralized decentralized city form on sustainability are lacking. review of some city forms indicates both advantages as well as disadvantages in sustainability. for example, forms that reduce travel and are fuel-efficient may be harmful to the environment and have social inequities. they may be locally beneficial but not city-wise beneficial (williams et al., ) . the effects of urban density on the total energy demand of a city are complex and at times conflicting (givoni, ) . compactness of land use patterns will bring benefits to energy distribution and transport system design, but crowded conditions may create congestion and undesirable local microclimate (hui, ) . the compact city challenges are mainly associated with environmental quality and social acceptability (williams et al., ) . a multiple intensive land use development in hong kong is formed by an intensification of land use through mixing residential and other uses at higher densities at selected urban locations, together with an efficient transport and pedestrian network (lau & coorey, ; lau, ghiridharan, & ganesan, ) . hong kong is one of the asian cities that have evolved as a compact urban form. situated at the south-eastern tip of china, hong kong is ideally positioned at the centre of rapidly developing east asia. with a total area of , km , it covers hong kong island ( . km ), the kowloon peninsula just opposite ( . km ), and the more rural section of hong kong new territories and outlying islands ( . km ). the central part of both hong kong island and kowloon are hilly rising to a height of , m. only . % of hong kong land is built up, concentrating on the triangular tip of kowloon and the coastal strip of northern hong kong island. the total population in hong kong is , , with the median age rising from in to in (census and statistics department, ) . the median monthly household income is hk$ , . a population growth rate of approximately million is observed in every years in the last decade and the population forecast for , is million (fung, ) . although the total population density is , persons per km , urban areas hold a staggering population density of over , persons per km where certain districts rank among the most densely populated places in the world. the density of public housing reaches at least , residents per ha, which is twice the density of the most crowded residential areas in mainland china (xue, manuel, & chung, ) . high-density in a land limited country like hong kong is the norm. cities often respond to development pressure by setting targets for increased urban densities, and the establishment of high-rise cityscape and compact urban settings is unavoidable (hui, ) . a chronological classification of tall building types in hong kong can be observed. the typology includes the verandah type from the s, the cantilevered living quarters type from the - s, the rectangular mass type from the s, and the podium type from the s onwards. among the rectangular mass type and podium type buildings, several shapes of building forms are observed such as the rectangular, "y" shape, clusters and crucifix shapes. when observing the pattern of development at a district scale, two significant variations in development is observed, namely, the clusters of multiple intensive land use developments around the mass transit nodes and the linear multiple intensive land use development alongside main roads and streets in the older parts of hong kong. the cluster of a high-density multiple intensive land use (milu) development is mainly observed along (under) the three main rail lines of mass transit railway, namely, the airport railway, urban lines and tseung kwan o lines. they are three-dimensional distribution of density and land uses integrated by three parallel ( ), and wikipedia ( ) commuting levels, namely, the mass transit rail (mtr), kowloon-canton railway, subways below ground, buses, taxis, light rail transit and tramways on ground and walkways above ground which are then vertically connected via ramps, stairways, elevators and escalators. such developments are built above or connected in close proximity to mass transit railway and other public transport modes. as seen in fig. . , when several milu nodes are developed in close proximity, an interdependency is formed among these developments where land use functions and services are shared, thus creating primary, secondary and tertiary interdependent zones (lau et al., ) . plot ratios, also known as floor area ratios, of up to for commercial uses and up to for residential uses have led to buildings of up to storeys built above - level podiums. the podium levels incorporate the secondary supporting functions such as commercial, recreational, government, institutional and community (gic) land uses while the primary residential, office or hotels/serviced apartments are located above as seen in fig. . . four major types of milu developments can be discerned according to its mix of land use types: . the primary use being office and/or hotel/serviced apartments with supporting secondary commercial, gic and transport uses; . primary use being residential supported by secondary commercial, gic and transport uses; . primary use being both residential and office supported by secondary commercial, gic and transport uses; . primary uses being office, residential, hotel/serviced apartments and secondary commercial, gic and transport uses. lau and coorey ( ) these development clusters are defined as primary milu nodes (lau et al., ) . table . illustrates some examples of the four types of primary milu developments that are commonly seen in hong kong. in hong kong where the buildable land resources are scarce due to hilly terrain and scarcity of usable land, tall buildings serve as an optimal option to maximise development potentials and best returns. reduction in travel time due to intensification of mixed land uses contributes to efficiency and economic viability of the city (wu, ) . the concept of home-work-play gives the residents efficiency, convenience and savings in time. tall buildings also provide a heuristic device to meet the housing demands for the increasing population. additionally, the mixed use nature of developments creates places that are active and lively for longer duration of time, providing safe neighbourhoods and additional time for use of urban spaces for its residents. rich, vibrant urban spaces are created within neighbourhoods. urban intensification and compactness also provides savings in infrastructure and services, and high penetration of infrastructure and services for all residents. for example, it results in an overall reduction in energy use and traffic fumes (wu, ) . high-rise building rather than urban sprawl reduces the use of woodlands and forest areas for development, saving valuable land resources for future use and recreation purposes. in hong kong such country parks and woodlands can be easily accessed. yet, there are some consequences associated with tall residential built forms arising from the very high population and extreme density. both social and environmental implications are prevalent in such conditions. this chapter is specifically focused on the environmental implications and various measures and solutions that may mitigate the environmental consequences of tall residential buildings taking hong kong as a case study. high-density living in hong kong is strongly linked with significant air, water and noise pollution. drastic environmental implications such as living in busy urban centres with high air and noise pollution, poor lighting and ventilation in individual housing units, urban heat island and wind tunnel effects are observed in hong kong's high-rise building developments. one of the problems related to mixed land use developments at very high intensities is the incompatibility of uses. this problem is particularly apparent in the old built-up areas because of a lack of comprehensive planning in the past (fung, ) . examples include those residential developments that face environmental nuisance due to its location adjacent to industrial areas. another example is where highways pass through residential areas, posing the threat of noise and air pollution. probably due to poor ventilation and lighting conditions, as high as % of all electricity used in hong kong is for lighting and space conditioning (wu, ) . air conditioning accounts for one-third of the total power consumption of hong kong each year and costs hk$ billion (ching, ) . high space conditioning further aggravates the outdoor climate conditions creating a vicious cycle of environmental pollution such as urban heat island. table . outlines the positive and negative effects of high density on city's energy demand as identified by hui ( ) . current air pollution levels in hong kong are high due to the high intensity of emissions from industry and traffic as well as a lack of proper environmental planning in the past. the number of motor vehicles is increasing due to population growth and demands. many areas in hong kong are topographically confined by hills and the air pollution dispersion in these areas is inhibited (hong kong use of solar energy -roof and exposed areas for collection of solar energy are limited planning department, a). hong kong has been facing two air pollution issues: local street-level pollution caused by motor vehicles; and regional smog problem caused by motor vehicles, industry and power plants both in hong kong and in the pearl river delta. street level pollution is mainly caused by the large number of motor vehicles in highly dense urban areas. the emissions are trapped in between the very tall buildings along the streets. the tall stacks of building towers create urban walls that are barriers to wind circulation and vistas in the city. further, it causes wind tunnel effects and unsafe environments at street levels. walking at street levels in compact cities is no longer safe for the pedestrian. the high flow of vehicular traffic damages the quality of the street environment, with their high noise and air pollutants. therefore, whether within enclosed spaces or outside in the public areas and streets, the quality of the living environment is being damaged, affecting the overall quality of life. furthermore, since , there has been an increasing concern on the "wall effect" caused by uniform high-rise developments, which adversely impact air circulation. a survey carried out by the environmental group, green sense revealed that of housing estates surveyed have a "wall-like" design (yueng, ) . the survey found the estates of tai kok tsui and tseung kwan o as the best examples of this kind of design. in may , citing concern over developments in west kowloon, and near tai wai yuen long railway stations, some legislators called for a law to stop developers from constructing tall buildings which adversely affect air flow in densely populated areas, but the bid failed (wong, ) . more recently, in december , a protest against "wall-effect" for a dozen of current and planned constructions was held at central government offices (ng, ) . these protesters were also concerned about the development plans for nam cheong and yueng long stations. tall buildings also pose threats to public safety and health in terms of easy spread of disease and viruses, fire risks and domestic accidents. adequate ventilation and building maintenance are therefore an important issue for high-rise buildings in order to avoid the spread of disease and accidents associated with dilapidated structures (wu, ) . study on residents' satisfactions and aspirations of high-rise living in hong kong shows that better view, less noise, better air quality are the major reasons for people to opt for high-rise living (lau, ) . the higher selling prices for apartments on higher floors are also attributed to better views, less noise and better environmental quality. this trend may seem to suggest that residents who choose living on higher floors are seeking an escape from the environmental problems since living on higher floors allows one to be further way from the city surface. but, opting for taller buildings alone may not be a solution to the problem. there exists a strong pressure from people to improve air quality and environment. the government has acknowledged this requirement and taken measures to improve the environment. for example, it has implemented vehicle emission and fuel standards, cleaner alternatives to diesel, emission inspection and enforcements such as controlling smoky vehicles, etc. and promoting vehicle maintenance and ecodriving. in his - policy address, the chief executive of hong kong has emphasized the importance of addressing these issues in order to secure sustainable development for future generations. he has outlined some of the measures, to reduce air pollution, we have formulated the pearl river delta (prd) regional air quality management plan. this plan, prepared in partnership with the guangdong provincial government, aims to achieve specific emissions reduction targets by . we have now set up a -station air quality monitoring network in the prd. based on the data collected, the prd regional air quality index is released everyday on the internet to keep the public informed of the actual regional air quality. the data collected will also help us assess the effectiveness of our pollution reduction measures . . . in hong kong, we have imposed emission caps on power plants at castle peak, black point and lamma island. these emission caps will be progressively tightened to meet the emission reduction targets. (chief executive, . in , particulates and nitrogen oxides levels on the street have dropped by and % respectively since . the number of smoky vehicles on the road has also reduced by about % (environmental protection department, ) . increased use of mass transport and reduction in private car and taxi could help to reduce the air pollution levels caused by vehicular traffic. in addition to policy measures, urban design measures are suggested for improving air ventilation (chinese university of hong kong, ; hong kong planning department, b) . recent study identifies the following urban design issues as a means to a better quality and comfortable urban environment: lack of breezeways air paths; tall and bulky buildings closely packed causing undesirable wind breaks to urban fabric; uniform building heights resulting in wind skimming over the top of buildings and not being re-routed into the fabric; tight narrow streets not aligned with prevailing wind with tall buildings resulting in urban canyons; lack of urban permeability-with few open spaces, minimal gaps between buildings, excessive podium structures reducing air volumes at ground levels; large building blocks forming wind barriers; projections from buildings and obstructions on narrow streets and general lack of soft landscaping, shading and greenery as contributing to poor air ventilation and environmental quality in high-rise, compact built areas (chinese university of hong kong, ; hong kong planning department, b) . for better urban air ventilation breezeways in the forms of roads, open spaces, and low-rise building corridors are suggested to allow air penetration to inner parts of urbanized areas. breezeways, roads, main streets and avenues should be aligned either parallel or • to the prevailing wind directions. open spaces must be linked and aligned to form unobstructed wind corridors with low-rise structures alongside them. space between buildings must be maximized, especially in large sites with dense developments. the longer frontages of blocks may be aligned parallel to wind corridors, and non-built areas and setbacks may be introduced to further allow for good wind penetration. to maximise the penetration of sea breezes and land breeze water front sites may take special precautions to avoid blockages in wind paths (chinese university of hong kong, ) . street patterns, building heights, open spaces, density, and landscape will determine the air ventilation, solar radiation, day lighting and air temperature in compact high-rise built forms having implications on indoor and outdoor environmental quality. to illustrate, reference is made to the natural ventilation study conducted for a proposed luxury residential development in shenzhen, china. an assessment of air flow, solar energy and daylighting is done using computer based simulation tools such as airpak (usa), ecotect (uk) and radiance (usa) (lau & li, ) . table . shows the airflow study and wind velocities within the compact high dense residential site. all three graphs in table . show high age of air, indicating low ventilation and increased stagnated air. in the surrounding areas of the high-rise towers the age of air reduces when elevation height increases from to m, indicating better ventilation and cleaner air in the upper floors. the low age of air is also spread in larger proportions when the elevation height increases. as seen in the graphs, both low-and high-rise buildings form a wall that is oriented perpendicular to the prevailing wind patterns. this creates a barrier to the southeast winds and creates stagnant air in the leeward sides of the buildings. ideally, these built forms must be oriented parallel to the prevailing wind direction to ensure better ventilation and cleaner air. lower age of air and better ventilation is observed surrounding the smaller fragmented in the three diagrams above concentrated areas denote higher wind velocities. the short arrow strokes indicate low and long arrow strokes indicate high velocities. the red, yellow, green and blue strokes denote wind velocity in descending order building shapes and footprints. the areas surrounding larger blocks show high age of air and comparatively poor ventilation. in all three graphs, the row of high-rise building further away from the wind direction have a higher age of air spread in larger compositions compared to the row of buildings closer to the wind direction. observations confirm that the block size, orientations, building heights and distance from wind source affect the age of air, ventilation and air quality surrounding those buildings especially on the leeward side. the analysis can be further substantiated by the qualitative data gathered among occupants in high-rise living in hong kong (lau, ) . the general conceptions of occupants are that the apartments in higher floors are preferred due to better quality of environment -such quality can be specifically referred to as the air quality and reduced noise levels. the wind velocity graphs further confirm the observations made on the age of air distributions at varying heights. lower wind velocities are observed at low height levels. low wind velocities are also observed in the leeward sides of high-rise buildings, causing high age of air, poor ventilation and air quality in those areas. also, when the distance from wind source increases, the velocities decrease indicating the higher age of air surrounding built forms further away from the wind source. in order to enhance the wind environment in hong kong, an air ventilation issue has been included in the hong kong planning standards and guidelines. a set of qualitative guidelines and a framework for carrying out air ventilation assessment have been formulated on the basis of the air ventilation assessment study recommendations. the guidelines incorporated in the hong kong planning standards and guidelines are to strengthen the urban design guidelines for better air ventilation. the guidelines were developed according to the results of "feasibility study for establishment of air ventilation assessment system" (the ava study) was conducted and completed in . in addition to the guidelines, a technical guide for air ventilation assessment (ava) has been issued by the planning department of hong kong ( ) . ava can be used to compare the air ventilation impacts of different design options and to identify the potential problem areas for design improvements. this technical guide specifies three steps in conducting ava, i.e. expert evaluation, initial study and detailed study. the expert evaluation is a qualitative assessment based on the guidelines provided in hong kong planning standards and guidelines, while the initial study will refine the expert evaluation and the detailed study will conclude the ava. the ava technical guide recommends using wind tunnel as the tool for carrying out both initial and detailed study. however, the use of computational fluid dynamic (cfd) will be permitted in the initial study (hong kong planning department, ) . the examples of using cfd simulation in ava study are presented in table . . this study highlighted the air ventilation benefits of raising the podium level of residential buildings. the table shows the comparison of mountain and valley breezes for base case and proposed designs. according to the mountain/valley breeze simulations, we can find that the mountain can create local winds that vary from day to night if there is no background wind, which can also increase the air flow around the buildings in the mid-level. during the daytime, the air near the mountain surface can be heated up and higher than the free air far away at the same height due to the solar radiation. thus the warm air moves up along the slopes. while during the night-time, as the mountain surfaces cool down, the cold breezes can be formed and flow down the slopes. the proposed new podium can enhance the air flow through the building. it can be imagined that the building region can benefit from the mountain breezes by bringing the cooled air at night-time on hot days. the thermal environment can be improved and energy can be saved (li & yang, ) . the air ventilation and daylight penetration into individual housing units play an important role in high-rise residential building designs. many factors determine the daylight quality within housing units. study done by the students of the final year bachelor of arts in architectural studies, department of architecture university of hong kong ( kong ( / reveals several factors that determine the daylight quality within housing units. table . illustrates the types of building footprints found in high-rise residential buildings in hong kong and the evaluation of the lighting quality within a selected individual housing unit. a qualitative appraisal of the lighting quality in individual rooms of the housing unit is done by its occupant. this is combined with a quantitative -daylight simulation for the residential units showing the distribution of lighting within the spaces. the distribution of lighting quality significantly varied across the building types and spaces/rooms within the individual units. lack of sufficient lighting and ventilation in the kitchen and washrooms were a common observation. obstructions to light due to windows being covered for better privacy and furniture layout were also observed as barriers to daylighting within the spaces. some spaces have no windows at all and may be for the purpose of storage. but due to the lack of sufficient living space such spaces are also used for habitation. on most occasions, occupants use artificial lighting in such spaces even during day-time. small window sizes and fixed glazing were also commonly noted as causes for poor light and ventilation. further, it can be observed that most kitchen and toilet spaces in high-rise buildings are ventilated via "re-entrant light wells". these are equivalent to a light well with the main purpose of bringing in light and ventilation . residents most often use the window opening into re-entrants for drying clothes, etc. the inlet and outlet water pipes to kitchen and toilets are located along the re-entrant spaces. the mechanical ventilation outlets are also located along these re-entrants that act as a shaft for bringing in fresh air as well as outlets for foul air from toilets and kitchen. the building shapes play a major role in determining the re-entrant shapes (see table . for building shapes and re-entrant shapes). most often, the reentrants are too narrow and inadequate for bringing in light and ventilation. wider, more open re-entrant shapes are needed for sufficient light and ventilation. the size, number and positioning of windows, the floor area of space, windowfloor area ratio, the shape of the room and depth of space from window, internal reflectance of materials and finishes, the building footprint shape, external obstructions, building orientation, obstructions caused by neighbouring towers and distance between towers, external barriers to wind and daylight such as hills and internal furniture layouts all affect the quality of ventilation and daylighting within residential units in high-rise towers (final year bachelor of arts in architectural studies students, students, / . a common issue is windows placed within the visibility range from neighbouring blocks cause lack of privacy. as a result, most windows are kept closed and covered using opaque materials such as shades, curtains, etc. blocking light and ventilation into the housing units. tables . and . illustrate the case studies and respective daylight analyses. uneven day light distribution in several spaces within the block is caused due to window sizes and numbers, the floor area, window-floor area ratio, the location of windows, shape of building foot print, interior furniture layout and distance between blocks and block layout, contextual barriers such as hills, obstructions from other buildings also determine the lighting quality and ventilating inside housing units of high rise blocks. windows facing neighbouring blocks are being constantly kept closed due to lack of privacy, thereby does not serve the purpose of brining in light and ventilation table . day light study of high rise housing. sources: chan ( ), cheung ( , kei ( ), wong ( in addition, investigated the effect of relaxation of room height as a means for improving daylight conditions. the study investigated the relaxation of room heights from , to , mm and sustainable design features of proposed residential building located at mid-levels, hong kong. when window size remains the same and the room height is increased the day light within the room is improved but not a very significant improvement is seen. but when window size and room height is increased there is a significant increase in the daylight quality within the room. also graph shows that in room with higher room height and larger window size the day light factor shows significant increase the simulations were carried out based on the parameters: date dec (winter solstice), time : am, sky condition: overcast sky, design sky , lux. this analysis is regarded as the worst-case scenario for daylight calculation. three cases are presented in table . . the study revealed that an increase in room height has some effect on improving the daylight quality within a room. in addition, the increase of window height can make a significant contribution to the daylight quality within the room. outdoor living space of high-rise residential buildings is equally important. adequate provision of open space, greenery, vistas and visual corridors is a critical issue in the light of high land prices and the general lack of space between and around tall buildings. open spaces and landscaping on podiums are design measures taken to improve resident perceptions of open spaces, views and greenery. open spaces located close to highways, roadways, and transport nodes create poor environmental quality due to noise, dust and smoke emissions. in other words, it can be argued that even if open spaces are provided within residential blocks or outside in close proximity to homes, if its quality does not meet the demands and satisfaction of its users, such open spaces may not be efficiently utilised. podium open spaces and sky gardens create a barrier from traffic and pollution at road levels. yet, being surrounded by high-rise buildings these spaces have a tendency to trap pollutants due to a lack of cross ventilation and high building mass. the lack of green cover, trees and hard landscaping may contribute to poor micro climatic conditions in the outdoor spaces of high-rise developments (tan & fwa, ; wilmers, wilmers, / . but, people are forced to use these open spaces despite its poor environmental quality. study by davies ( ) has shown that the most popular form of recreation among hong kong residents is the use of passive local open spaces. it is observed that the majority of users of such open spaces are elderly, low income groups whose accessibility to district open spaces and country parks may be limited. study of open space satisfaction among occupants of high-rise public residential estates in hong kong by coorey ( ) shows that satisfaction of open space is primarily dependent on the physical qualities as opposed to its social qualities. the physical qualities such as climatic comfort, maintenance, facilities and provisions were identified as having important implications on their overall satisfaction. the study involved questionnaire interviews conducted in high-density public housing estates in hong kong. respondents evaluated the physical and social quality of open space and their levels of satisfaction in open spaces including those on podiums and ground level in the six high-rise developments. a comparison of open spaces located within public housing of varying density showed that occupants in higher density developments considered the physical qualities of open space such as climatic comfort, provision for open space and maintenance as having higher impact on their overall open space satisfaction. respondents living in the lower density cases tend to consider the social qualities such as safety, crowding, privacy and interaction to have a higher implication on their open space satisfaction (coorey, ) . the study highlighted the importance of environmental quality for optimum satisfaction of open spaces located within high-rise residential developments. it further highlighted that open space satisfaction among occupants living in higher density cases was significantly influenced by its environmental quality as opposed to its social qualities. such open spaces play a critical role in the lives of residents living in high-rise buildings as they are their only means of escape from the otherwise built up urban setting. additionally, its importance for the elderly and low-income groups, specifically draws on the need for optimizing the environmental quality of open spaces in high-rise developments. an increase in respondents' satisfaction with climatic comfort in open space is shown when the number of trees, the proportion of greenery is higher and the sky view factor is low due to taller buildings adjacent to smaller narrower open spaces (coorey, ) . noise pollution is a common environmental quality issue associated with mixed use and high connectivity with transport networks. taller buildings with residences in the higher floors are preferred due to less noise in the higher floors (lau, ) . also, elevated walkways and podiums serve as design principles for segregating pedestrian routes from noise and pollutant sources at street and ground levels. the podiums act as buffers from noise at ground level. the building clusters in hong kong are well integrated through elevated walkways subways and podiums that induce people to walk through buildings rather than being exposed to the fumes and noise of vehicular traffic at road levels. study of external noise measurements in the surrounding areas of an arts performing school showed that high traffic noise reflectance was caused by the façade effect and canyon effect due to high-rise built forms running parallel to the roadways (lau, ) . measurements were taken alongside two roadways on opposite sides of the arts school. one roadway has high-rise buildings located alongside it while low-rise buildings frame the roadway on the opposite side. higher noise levels are observed from the roadway with high-rise buildings. the facades of high-rise built form act as reflectors for noise sources from vehicular traffic. the taller building forms create a canyon effect causing higher noise levels. it can be suggested that the building facades, orientations with the noise sources and its noise reflectance and absorption values must be manipulated. this can be done by orientating the buildings so that it does not obstruct and reflect noise. instead, it disseminates the noise and avoids a canyon effect. the materials of the facades should be of less reflectance and higher absorption values. in addition, trees and shrubs can be introduced as noise screens alongside roadways. zoning at planning stage must be done with an awareness of the noise sources and noise reflectors in the surrounding context. habitable spaces can be buffered by elevating the units above the noise source levels. soft landscaping features such as water fountains can be used to mask and create distraction from traffic noise. although tall residential buildings have many social and environmental implications, hong kong's topography and continuous increase in population have propelled the planning and design of hong kong's built form clearly in the direction of tall buildings. but how tall and how to design such tall building is the question of concern. the general policy and regulations provoke taller buildings. but the regulations and attention of hong kong designers are turned towards more sensitive design measures that will balance the demand for taller buildings with more sensitive, sustainable and liveable design features. the critical implications for building tall are mainly associated with poor air quality, lack of wind ventilation in a macro context of a high-rise city as well as the micro context within the residential units or apartments. poor daylighting quality within tall buildings is a pressing issue for tall buildings. the lack of open space and the poor environmental quality in such open space is another issue that impacts the quantity and quality of open space among highrise occupants. the noise levels due to reflectance from high-rise towers caused by façade and canyon effects are also a challenge for zoning, orientations and design. such issues bring about specific criteria for zoning, planning and design in tall building contexts. this chapter highlighted some of the design issues and possibilities. the compact city: just or just compact? a preliminary analysis unpublished bachelor of arts in architectural studies final year projectwork unpublished bachelor of arts in architectural studies final year projectwork - policy address by chief executive. hong kong: hong kong sar government. last accessed feasibility study for establishment of air ventilation assessment system-executive summary. hong kong: department of architecture sustainable development of tall buildings in hong kong. paper presented at the tall buildings: from engineering to sustainability unpublished bachelor of arts in architectural studies final year projectwork design of open spaces in high density zones: case study of public housing estates in hong kong study of leisure habits and recreation preferences and review of chapter four of the hong kong planning standards and guidelines. final report, planning department final year bachelor of arts in architectural studies students -department of architecture university of hong kong planning for high density development in hong kong. hong kong: the planning department of hong kong climate consideration in building and urban design ifc, kornhill, telford, union square images in google earth milunet: multi functional intensive land use -principle, practices, projects, policies -towards sustainable area development. harbiforum foundation daylight analysis: residential buildings in hong kong outbreak of severe acute respiratory syndrome (sars) at amoy gardens, kowloon bay, hong kong -main findings of the investigations. department of health air quality in hong kong mtr properties. hong kong mass transit railway corporation, hong kong. last accessed technical guide for air ventilation assessment for developments in hong kong. hong kong planning department, hong kong. last accessed planning department annual report hong kong planning standards and guidelines. hong kong planning department low energy building design in high density urban cities sustainable urban form in developing countries daylight analysis: residential buildings in hong kong a survey on residents' responses to high rise living in hong kong. centre for architecture and urban design for china and hong kong traffic noise measurement for the school of performing arts sustainable building design: residential development reconsidering daylighting design parameters for tall buildings in densely built city hong kong: milu and how it is perceived policies for implementing multiple intensive land use in hong kong environmental performance analysis: proposed luxury residential development in shenzhen ventilation study of residential development at il & extension, magazine gap road, mid-levels the compact city in practice: the new millennium and the new urban paradigm is there a role for physical planners technical guide for air ventilation assessment (ava) for developments in hong kong. planning department of hong kong, hong kong. last accessed influence of pavement materials on the thermal environment of outdoor spaces achieving sustainable urban form effects of vegetation on urban climate and buildings daylight analysis: residential buildings in hong kong. unpublished bachelor of arts final year projectwork call for law against 'wall effect' fails, south china morning post policies and planning of tall buildings in hong kong. paper presented at the tall buildings: from engineering to sustainability public space in the old derelict city area -a case study of mong kok, hong kong asia's walled city' leaves -residents longing for air, the standard key: cord- - ujnmxhx authors: rufino de sousa, nuno; shen, lei; silcott, david; call, charles j; rothfuchs, antonio gigliotti title: operative and technical modifications to the coriolis(®) µ air sampler that improve sample recovery and biosafety during microbiological air sampling date: - - journal: ann work expo health doi: . /annweh/wxaa sha: doc_id: cord_uid: ujnmxhx detecting infectious aerosols is central for gauging and countering airborne threats. in this regard, the coriolis(®) µ cyclonic air sampler is a practical, commercial collector that can be used with various analysis methods to monitor pathogens in air. however, information on how to operate this unit under optimal sampling and biosafety conditions is limited. we investigated coriolis performance in aerosol dispersal experiments with polystyrene microspheres and bacillus globigii spores. we report inconsistent sample recovery from the collector cone due to loss of material when sampling continuously for more than min. introducing a new collector cone every min improved this shortcoming. moreover, we found that several surfaces on the device become contaminated during sampling. adapting a high efficiency particulate air-filter system to the coriolis prevented contamination without altering collection efficiency or tactical deployment. a coriolis modified with these operative and technical improvements was used to collect aerosols carrying microspheres released inside a biosafety level- laboratory during simulations of microbiological spills and aerosol dispersals. in summary, we provide operative and technical solutions to the coriolis that optimize microbiological air sampling and improve biosafety. mycobacterium tuberculosis, measles virus, influenza virus, severe acute respiratory syndrome coronavirus- , and other highly contagious human pathogens transmit through air either by aerosols or droplets (riley et al., ; bloch et al., ; remington et al., ; fennelly et al., ; yang et al., ; cowling et al., ; patterson et al., ; meselson, ) . these airborne pathogens pose a heavy burden on society by incurring severe clinical outcomes including death. airborne microbes are of particular concern in enclosed and crowded environments, where occupants are readily exposed to respired air and thus at risk of inhaling infectious bioaerosols carrying viruses, bacteria, or fungi. this is well-recognized during infection with m. tuberculosis where congregate settings such as prisons, homeless shelters, slums, and refugee camps are recognized hotspots of transmission (who, ) . the ability to monitor pathogens in air is an important investment for gauging and controlling infectious disease in society. microbiological air-sampling tools coupled to analytical methods enable detection of pathogens in air and as such improve our position to investigate the transmission of airborne pathogens and to counter airborne threats through capacitybuilding, infection control measures (mubareka et al., ) . in particular, there is an outstanding need to monitor pathogens in air in critical infrastructure such as government buildings, hospitals, mass transit, and airports, during manufacturing in clean rooms and 'ready-to-eat' food preparation, to name but a few. there is also a growing interest in detection of infectious bioaerosols for point-of-care diagnostics (fung and mykhaylova, ) . most air samplers operate by filtration, electrostatic precipitation, or inertial/gravitational collection (fronczek and yoon, ; sharma ghimire et al., ) . inertial/gravitational-type samplers include impactors, impingers, and cyclones and are heavily used for microbiological air-sampling purposes. the coriolis ® µ (bertin instruments, montigny-le-bretonneux, france) is a state-of-the-art, high-volume cyclone sampler that collects airborne particles into liquid. the cyclonic sampling mechanism is based on the principle of a liquid-scrubber aerosol collector with tangential impingement into liquid (decker et al., ) . briefly, the unit pulls air into a collector cone containing buffer to form a vortex that traps particles through centrifugal force onto the inner walls of the collector cone, separating particles from the air and concentrating them in the collection buffer. a diagram of the principle is available in the bertin user manual ( - -du -f eng) and in original reports (carvalho et al., ; gómez-domenech et al., ) . the coriolis has tactical capacity and produces a sample that is amenable to different analytical methods. it is gaining ground as a tool for microbiological air sampling where it has been successfully used to detect toxins or microbial contaminants in the food industry (verreault et al., ; viegas et al., viegas et al., , ahmed et al., ; chang et al., ) , fungus and pollen in outdoor and indoor air (carvalho et al., ; gómez-domenech et al., ; chang et al., ) and airborne pathogens in healthcare facilities (choukri et al., ; bellanger et al., ; le gal et al., ; montagna et al., ; alsved et al., ; montagna et al., ) . in the above studies the coriolis was used mainly in conjunction with culture and nucleic acid amplification methods, although microscopy and in some cases spoligotyping and sequencing were also performed. in addition, flow cytometry, solid-phase cytometry, and immunoassays have been employed to detect aerosolized microbes or their simulants collected on the coriolis (langer et al., ; le goff et al., ; rufino de sousa et al., ) . the coriolis has also been used to detect airborne traces of the explosive trinitrotoluene through an electrochemical assay (caygill et al., ) . liquid loss during air sampling is known to occur with traditional impingers (willeke et al., ; han and mainelis, ) and has also been reported for the coriolis (carvalho et al., ; chang et al., ) . during impingement, liquid loss may be coupled to the escape and reaerosolization of material from the collection media (grinshpun et al., ; riemenschneider et al., ; han and mainelis, ) . this raises similar concerns for the coriolis. indeed, unintentional reaerosolization of a microorganism during sampling may contaminate sampler parts and expose the operator to a pathogen threat. despite its increasing use in different microbiological air-sampling applications, investigation on actual coriolis performance and biosafety concerns during operation have not been thoroughly addressed. herein we have evaluated the coriolis in a series of aerosol collection experiments with microspheres and bacterial spores under controlled laboratory conditions. we report on a sampling protocol to maximize sample recovery from the unit and a high efficiency particulate air (hepa)-filter adaptation to reduce unintentional contamination of device parts which occurs as a consequence of reaerosolization of collected material during sampling. we demonstrate the use of the modified coriolis in the detection of aerosols generated during a simulated laboratory spill and aerosol dispersal. lyophilized endospores of bacillus atrophaeus var. globigii (bg) (from ecbc pine bluff arsenal laboratories, us army, originally given to d. silcott) were resuspended in sterile deionized (di) water. quantification of bg colony-forming units (cfus) in stocks and aerosol samples was determined by culture on luria-bertani (lb) miller agar (sigma-aldrich) for day at °c. stock solutions of bg were diluted to × cfus ml − and stored at °c until further use. stock solutions of µm, yellow-green ( / ) fluorescent, polystyrene fluospheres™ (thermofisher) were also prepared in di water at × beads ml − , stored at °c and protected from light until further use. a coriolis ® µ cyclonic air sampler (bertin instruments, montigny-le-bretonneux, france) ( fig. a ) was used to collect aerosolized microparticles in controlled, aerosol dispersal experiments. a bespoke solution for integrating a hepa-filter system to the coriolis was conceived and assembled as illustrated ( fig. b) with necessary filter component, stainless-steel metal tubing, and other fittings ( supplementary fig. s , available at annals of work exposures and health online edition) (all mcmaster-carr, elmhurst, il, usa). the tube fitting that connects the air intake headpiece to the hepa filter is similar in area to the commercial tubing supplied by bertin instruments. air-flow measurements were made on the coriolis with a tsi mass flow meter (tsi, shoreview, mn, usa) connected to the blower inlet of the coriolis using thinwall latex tubing, stretched such that a tight seal was obtained on both the air-flow meter and the coriolis inlet. measurements were made at the manufacturer-specified flow rate setting of l air min − . the flow rate measured was l air min − without a collector cone (fig. a) connected to the device. with a collector cone loaded with ml connected to the coriolis the flow rate measured was l air min − . with the hepa filter attached to the unit and loaded with a collector cone containing ml, the flow rate at the inlet was l air min − . contained aerosol dispersal experiments were performed inside a large, airtight, flexible polyvinyl chloride enclosure mounted on a metal-support frame (solo containment, uk). the enclosure measures cm (l) × cm (w) × cm (h) with an inner volume of . m (rufino de sousa et al., ). it was assembled and kept inside a biosafety level (bsl)- laboratory. particles were purged from the chamber before the start of experiments by drawing air into the enclosure through a hepa filter using an attix industrial-grade vaccuum cleaner (nilfisk, sweden). fluospheres or bg were aerosolized into the chamber using a -jet baustein atomizing module (blam) nebulizer (ch technologies, westwood, nj, usa) operated in multipass mode and producing quasi-monodisperse aerosols with a particlesize diameter range of . - . µm. aerosolization was performed for min. previous tests established a steady concentration of particles in the enclosure min after completing the aerosolization cycle on the blam (fig. c) and (data not shown); air sampling was therefore routinely initiated min after finishing the aerosolization cycle. in certain experiments, a lighthouse handheld particle counter (lighthouse worldwide solutions, medford, or, usa) or an ibac fluorescent particle counter (flir systems, orlando, fl, usa) was used to measure the decay of aerosolized fluospheres inside the enclosure. the coriolis was placed on a table cm away from the blam aerosol port with the collector part of the unit approximately cm from the ground. as per the manufacturer's recommendation, the collector cones were filled with ml di water and kept sealed. after completion of the aerosolization cycle, a collector cone was unsealed, loaded onto the coriolis and the sampler operated at the manufacturer-designated flow rate of l air min − . collection on the coriolis was performed using the same cone for the entire sampling duration and referred to as standard sampling. in this setting an injection port was used to manually replenish the collector cone back to ml of di water after every min of sampling. alternatively, a new collector cone containing ml of di water was replaced after every min of sampling, referred to as cumulative sampling. at the end of experiments, collector cones were placed in a pass box where the surface of the cones were disinfected with % ethanol before being removed from the chamber. the entire chamber was then decontaminated with % hydrogen peroxide vapor using a bq- unit (bioquell, uk). before starting this procedure, the removable metal piping was disassembled from the body of the coriolis and the coriolis operated in decontamination mode. metal piping was cleaned in mild detergent and autoclaved. laboratory spill and aerosol dispersal simulations were performed inside a suite of the bsl- facility at biomedicum, karolinska institutet, solna, sweden. the suite dimensions measure cm (l) × cm (w) × cm (h). the facility operates at approximately - air-changes-per-hour (ach) depending on the number of microbiological safety cabinets in simultaneous use. safety cabinets in the suite were inactive during our experiments, lowering forced ventilation parameters to about ach. our experiments were done before the bsl- was opened to users and pathogens introduced to the facility. for spill simulations, the coriolis was placed approximately cm from the planned spill site and rested either on top of a working bench ( cm from the ground) or just above the ground ( cm). a large microbiological spill was simulated by tumbling a container carrying . l of fluospheres ( × beads ml − in di water, × beads in total) from the same working bench resting the coriolis. for aerosol dispersal experiments, the coriolis was placed on the working bench cm from the ground. the coriolis was located cm in front of the blam, which was supported on a tripod cm from the ground. the blam was loaded with fluospheres ( × beads ml − ). aerosolization was performed for min, releasing a maximum of × figure . clearance of aerosolized microspheres from air during coriolis sampling. (a-c) fluospheres ( µm, × ) were aerosolized inside the aerosol chamber. coriolis was turned on or left off (dashed line) and particle counters used to record microspheres in the air. (a) fluorescent particle counts recorded on an ibac sensor with coriolis on. particle counts recorded on a lighthouse particle counter with coriolis on (b) and at steady state with coriolis off (c). microspheres into the room. in both simulations, air sampling was performed on the coriolis with accompanying hepa-filter modification (fig. b) for h using the cumulative sampling method described above. researchers donned full-body tyvek ® labo overalls, m ® ffp d respirators, safety goggles, and nitrile gloves (all vwr), providing all-around contact protection from aerosol exposure. at the end of experiments, working surfaces were cleaned with mild detergent and the entire bsl- suite was decontaminated with % hydrogen peroxide vapor using a bq- unit. at the end of a collection cycle on the coriolis, the aerosol chamber was purged from airborne particles as described above. the coriolis was then swabbed using sterile cotton swabs (vwr) at the designated points p -p in fig. c ,d. sample was extracted from swabs by breaking the cotton-end of the swab into a sterile microcentrifuge tube. . ml phosphate buffered saline- . % tween- was added to the tube, the tube was sealed, incubated at room temperature for min and vortexed for min. the cotton-end of the swab was then aseptically removed from the tube using a pair of sterile tweezers and the sample plated on lb agar for quantification of bg cfus. the particle clearance rate for aerosolized fluospheres in the aerosol chamber was obtained by dividing the inner volume of the chamber ( l) by the amount of time needed to reach a -log reduction of the starting material of fluospheres aerosolized in the chamber (i.e. . % clearance). the amount of time needed to reach a -log reduction was calculated by fitting a onephase decay curve to the particle counts measured in the chamber over time using designated particle counters (ibac sensor and lighthouse particle counter). the particle clearance rate for the coriolis was expressed in l air min − . fluospheres collected on the coriolis were quantified on a flow cytometer using countbright™ absolute counting beads (thermofisher). briefly, a defined number of countbright beads were added to ml of sample, samples were acquired on a facs calibur (bd biosciences) and analyzed on flowjo (bd biosciences). the number of fluospheres in the sample was calculated with countbright™ beads according to the instructions of the manufacturer (thermofisher). the significance of differences in data group means was analyzed using student's t test or analysis of variance where appropriate, with a cutoff of p < . . rapid decay of aerosolized particles from air during coriolis sampling a robust air sampler must be able to effectively collect particles from air while also generating a sample that is amenable to downstream analysis. for the coriolis (fig. a) , we investigated particle collection indirectly by measuring the unit's particle clearance rate, i.e. the rate at which the coriolis removes airborne particles from air. fluorescent polystyrene ( µm) fluospheres were aerosolized in the aerosol chamber in the presence of the coriolis and airborne particles measured in real time with an ibac sensor and a lighthouse particle counter, respectively. when the coriolis was turned on the number of airborne particles recorded in the chamber began to steadily decay and decreased about . orders of magnitude in h ( fig. a,b) . on the contrary, particle decay was not observed when the coriolis was left off (fig. c) . with this information the effective clearance rate for the aerosolized microspheres was calculated to approximately l air min − . this number was reached with the help of either particle counter. additional sizediscriminating particle analysis with the lighthouse particle counter showed that the coriolis struggled with particles smaller than . µm (fig. b ), in line with technical specifications reported by the manufacturer (bertin instruments). a cumulative sampling method that improves sample recovery during coriolis air sampling we aerosolized fluospheres in the aerosol chamber and investigated their collection on the coriolis over time to see if this process could be improved. collection was performed every min for a total of h. the sample volume on the collector cone was manually replenished to ml every min as recommended by the manufacturer. indeed, although the coriolis is reported by the manufacturer to be able to collect material for up to h, we found that sample recovery was inconsistent after min of sampling (fig. a) . we hypothesized that the collected material might be escaping the collector cone over time as a consequence of cyclonic sampling. hence, we modified the sampling procedure by replacing the collector cone after every -min cycle with a new one; analyzing each cone individually and cumulatively adding the quantification obtained from each time point to the detection curve. at the end of the -h sampling interval we found that this cumulative sampling protocol lead to a % improvement of collection compared with the standard, manufacturer-recommended sampling with manual liquid replenishment (fig. a) . analysis of material recovered from individual time points during cumulative sampling showed that approximately % of the fluospheres recovered during the -h sampling interval were collected within the first min (fig. b) . still, an appreciable amount of microspheres were collected by the coriolis during the remaining min of sampling. overall, our observations suggest that the cumulative sampling protocol may be especially useful for long-term sampling applications. given that sample recovery decreased with increasing sampling time, we asked whether sampled material redistributed to other parts of the coriolis during operation. to investigate this, we decided to swab various surfaces of the coriolis after air sampling to see if any parts other than the collector cone became positive after collection. we chose to aerosolize bg spores, the anthrax simulant, since we have successfully extracted bg by surface swabs in the past (rufino de sousa et al., ). thus, we aerosolized bg spores in the chamber and used the coriolis to collect bg bioaerosols. we then investigated regrowth of bg from different parts of the coriolis, more specifically, the collector cone and parts p -p according to the schematics in fig. c . we found that many surfaces on the device exposed to air flow were contaminated with bg. substantial regrowth of bg was obtained from the headpiece inlet (p ) where air enters the device (fig. a ). bacilli were also readily detected at the initial tubing after the collector cone (p ) and importantly, at the air outlet (p ) (fig. a) , suggesting that bacteria may become deposited on the unit's fan as well. this raises overall concerns regarding user safety, deposition of contaminants on the fan over time and the validity of samples analyzed on the unit. in an attempt to improve device function and tactical deployment, we tailored and adapted a hepa-filter system to the coriolis (fig. b,d and supplementary fig. s , available at annals of work exposures and health online) and repeated bg aerosol sampling. the hepa filter significantly reduced bg contamination from the piping (p -p ) going into the body of the coriolis (fig. a) . spiking the collector cone with bg confirmed that at least part of this contamination originated from reaerosolization of bacilli in the collector cone, as the pattern of bg deposition on the coriolis was similar (fig. a) or with the hepa-filter adaptation (fig. b) . surface swabs were obtained from positions p -p on the coriolis (fig. c,d) . regrowth of bg from surface swabs and the collector cone was quantified on lb agar and graphed as total number of cfus. (b) bg spores ( × cfus) were loaded directly into the collector cone, the coriolis was turned on for h and bg regrowth investigated as in (a). (c and d) fluospheres ( µm, × ) were aerosolized inside the aerosol chamber. coriolis with the hepa modification was turned on (dashed line) while particle counters were used to record airborne microspheres in the air. (c) fluorescent particle counts recorded on an ibac sensor. (d) particle counts recorded on a lighthouse particle counter. data from five experimental repeats shown. dots represent individual measurements. bar graphs depict average of cfus obtained. error bars show standard error of the mean. * denotes statistically significant differences between coriolis with and without the hepa-filter modification. after aerosol dispersal (fig. a) and spiking (fig. b) . reducing buffer volume on the collector cone from to ml produced the same result (data not shown), suggesting that reaerosolization was independent of the buffer volume in the cone. importantly, there was no bacillary regrowth from the air outlet (p ) of the hepa-modified coriolis when the collector cone was spiked with bg (fig. b) , indicating that the fan was protected from contamination in the presence of the hepa filter. bg could be detected on the outlet (p ) of the hepa-modified unit after aerosol sampling (fig. a) . since the hepa filter prevents access to the outlet (p ) during spiking, detection here must be due to the high concentration of bg aerosols inside the chamber, promoting deposition of bacilli onto the outside surface of the outlet, rather than a contamination coming from inside the unit. lastly, introducing the hepa filter did not negatively impact on the effective clearance rate of the coriolis (fig. c,d) . we used the coriolis with the above operative and technical modifications to investigate aerosols generated during simulated microbiological accidents in a laboratory work place. we simulated spills and aerosol dispersals in a functional bsl- infrastructure before it was opened to users. to simulate a large microbiological spill, we dropped a container with . l of di water carrying a total of × ( µm) fluospheres over the edge of a designated working surface in the bsl- . a particle counter was used to record particle dispersal from the spill. airborne fluospheres where collected on the coriolis and quantified by flow cytometry. the impaction of liquid on the ground was accompanied by a detectable peak of . , . , and µm particles close to the ground (fig. a) . to our surprise, the number of particles generated by this large liquid impaction was only marginally above baseline-particle counts in the room. levels returned to steady state about min after the spill and were altogether undetectable when measured at the height of the working bench from which the spill was generated (fig. a) . despite the generation of few airborne particles from this simulation, it was nevertheless possible to use the coriolis in conjunction with flow cytometry to detect fluospheres aerosolized from the spill (fig. b ). next, we tested coriolis sampling during aerosol dispersal of the same amount of fluospheres but on a blam aerosol generator. a similar peak with albeit much higher particle counts was observed concomitant with the aerosolization of these microspheres on the blam (fig. a) . in line, significant numbers of fluospheres were detected by coriolis air sampling (fig. b ) and followed the general decay of particles in the bsl- suite due to forced ventilation. when central ventilation in the suite was intentionally turned off and the experiment repeated, airborne particle counts were increased further and remained elevated for the duration of the experiment without returning to baseline (fig. c) . consistent with elevated and steady detection of particles in the room when central ventilation was inactivated, the coriolis collected an elevated, steady number of fluospheres in the air (fig. d) . overall, these spill and aerosol dispersal experiments reinforce the capacity of the coriolis to enable detection of aerosolized microparticles from settings where these particles are present in not only high but also low amounts. the first line in protective measures against microbiological airborne threats is the ability to detect the pathogen in air, as it enables the mounting of adequate countermeasures in the next step, such as treatment, containment, or disinfection, which greatly limits human exposure, prevents illness, and save lives. this requires air-sampling tools that can be used in conjunction with analysis methods to rapidly detect microbes in air. in this regard, portable, tactical collectors are particularly useful in infection control as they can be widely distributed throughout society for air surveillance and research purposes. the coriolis ® µ is a commercially available, fieldable solution for air sampling that uses cyclonic technology to collect airborne particles directly into ml buffer. our study presents operative and technical modifications to the coriolis to circumvent caveats during sampling and to improve its deployment. building on the increasing number of applications for this sampler, we reveal its suitability in collecting aerosols generated through simulated spills or experimental aerosolization in a bsl- laboratory. information on pathogen quanta in aerosols or droplets is incomplete even for pathogens that undisputedly transmit through air. efficient air-sampling tools coupled to sensitive analysis methods are needed to bridge this gap. quantification of m. tuberculosis in bioaerosols suggests that patients with active tuberculosis expectorate a low number of culturable bacilli (fennelly et al., (fennelly et al., , patterson et al., ) . pathogen load in air is thus assumed to be limited for m. tuberculosis. this may not be true for other airborne pathogens, but for air-sampling purposes, low pathogen load is generally assumed. successful detection of low pathogen numbers may require both continuous monitoring and collecting a large volume of air. the cumulative sampling protocol for the coriolis improves sample recovery especially during prolonged collection and may thus be useful in this setting. replacing collector cones instead of replenishing liquid to an existing cone does not impact significantly on the overall workload for manual sampling. sample collection time needs to be the same regardless of protocol. cumulative sampling generates more collector cones for analysis, which could increase handling time and analysis cost depending on the method but is an acceptable trade-off for improving detection and reducing cross-contamination. the coriolis is a high-volume, portable sampler that delivers a liquid sample compatible with culture and many other analysis methods. unlike the agi and skc biosampler impingers which also collect into liquid, the coriolis does not require a pump and operates at a much higher flow rate. the advantages of the coriolis are weighed against its high cost of purchase, energy consumption, and noise during operation. several studies have used the coriolis together with impingers or impactors. the comparative data generated have for the most part revealed concordance in detection between the coriolis and other collectors (carvalho et al., ; gómez-domenech et al., ; bellanger et al., ; langer et al., ; ahmed et al., ; chang et al., ) . these studies did not formally investigate particle collection efficiency (ladhani et al., ; kim et al., ) . indeed, useful, bona fide metrics for the latter are difficult to obtain. important previous work figure . aerosol release inside a bsl- laboratory. fluospheres ( µm, × ) were aerosolized inside a bsl- suite in the presence (a and b) or absence of forced ventilation (c and d). a lighthouse particle counter was used to record airborne particles in the room. coriolis air sampling was done with a hepa-modified unit using the cumulative sampling method. has circumvented this by measuring relative sampling efficiency against the skc biosampler. several different air samplers were benchmarked in this way and the coriolis performed well against the other devices in sampling several aerosol-test agents including bg and fluorescent microspheres (dybwad et al., ) . in our investigation of coriolis performance, we evaluated the rate at which airborne microparticles were removed from the air during active sampling and report an effective clearance rate of approximately l air min − . this is the rate at which the coriolis clears µm particles from air and not a direct measure of particle collection on the device. still, this value could be used to estimate operation time in a given volume. coriolis collection greatly suffered from the harsh nature of cyclonic sampling as we observed sample loss and reaerosolization from the collector cone. both could contribute to misleading analysis results. reaerosolization was responsible at least in part for disseminating collected particles to various other parts of the sampler. this could lead to cross-contamination of samples and also inadvertently expose the user to pathogens during microbiological air sampling. introduction of a cumulative sampling protocol and a hepa-filter adaptation to the device improved these shortcomings. the metal fittings are robust and tolerate routine autoclaving and disinfection while the hepa filter is amiable to hydrogen peroxide favor decontamination. we estimate the loading capacity of the filter to be approximately g of dust. under normal, intermittent use in laboratory environments, even at the highest flow rate of operation the risk of excessive particle buildup on the filter media would be very low. out of an abundance of caution we recommend replacing the hepa filter once per year and opening the filter casing under containment conditions or after first completing decontamination with e.g. hydrogen peroxide vapor. we have recently used the hepa-modified coriolis with the cumulative sampling protocol in our aerosol chamber to investigate the performance of a portable electrostatic air sampler for tuberculosis (rufino de sousa et al., ) . a similar hepa-modified coriolis has also been used in a clinical, experimental setting to quantify m. tuberculosis from human bioaerosols (patterson et al., ) . in the current study, we provide a thorough presentation of these technical and operational improvements to the coriolis and supply details for assembly of the hepa filter so that others can benefit from this adaptation. the hepa-modified coriolis operates otherwise like the standard, commercially available unit. we observed a small increase in coriolis particle clearance rate upon mounting the hepa filter. this is probably due to the hepa filter trapping airborne particles that would otherwise be subject to continuous recirculation through the device during operation. despite biosafety and other regulatory precautions in place, the research laboratory remains an indoor environment where infections are acquired, albeit unintentionally, due to accidental exposure (sulkin and pike, ; pike et al., ; pike, ) . we thought it interesting to employ the coriolis with improvements in the assessment of simulated incidents in the laboratory coupled to microbiological exposure. here, collectors such as the coriolis may bring important insight on exposure that may impact on future biosafety regulations and recommendations. in this context, following a substantial microbiological spill, it is generally recommended by biosafety delegates that personnel should vacate the room for - min due to the risk of exposure to aerosols (who, ) . cleaning and decontamination procedures are consequently delayed although robust experimental support for this risk assessment is missing. using the coriolis and particle counters, we show that a simulated spill with a large, concentrated volume of microspheres does not generate a significant number of aerosol particles in the environment. because few airborne particles were generated in the spill, it might not have been a preferred simulation to study coriolis performance. nonetheless, it gave insight into an important and common biosafety issue related to microbiological exposure in the laboratory work environment. our data thus suggest that infection control measures can be applied immediately after a large microbiological spill since the risk of aerosol dissemination and exposure to the user in this condition is negligible. it is unclear to what degree dust particulates from a surface could be reaerosolized during a spill to potentiate airborne particles and microbial exposure. bacillus anthracis spores have been reported to be reaerosolized from contaminated office surfaces under conditions of low personnel activity (weis et al., ) . a review of historical data on tuberculosis transmission highlights the risk of dust-borne m. tuberculosis in spreading the infection (martinez et al., ) . a premise for our recommendation of immediate decontamination is therefore that it be performed on laboratory surfaces that are otherwise kept clean and accumulation of dust minimized. in the unique setting of our bsl- infrastructure with forced ventilation, we also used the coriolis to investigate detection of aerosols carrying microspheres aerosolized on a blam, a collison-type nebulizer. collison nebulizers are readily used to experimentally infect laboratory animals through the aerosol route (may, ; roy and pitt, ) . this experiment thus simulates a potential incident in an animal bsl- or aerobiology laboratory with ensuing infectious bioaerosol dispersal. even though forced ventilation returned particle counts in the room to background levels within min after the simulated incident, microspheres could be detected with the aid of the coriolis up to h after aerosol release. in the absence of forced ventilation, particle numbers remained high and elevated for the entire duration of the experiment. these experiments reveal the importance of ventilation in limiting transmission of infectious bioaerosols. they also indicate that the risk of exposure remains for at least h after a bona fine aerosolization, even in the presence of forced ventilation. thus, our simulations show that an accident with an aerosol generator introduces a much higher risk for occupational exposure compared with a large ( . l) microbiological spill. the field of aerobiology has been hampered by the lack of tactical (fieldable) units for microbiological air sampling. units such as the coriolis are helping to fill this gap by providing a useful tool for the study and quantification of infectious bioaerosols. our simple operative and technical modifications to the coriolis should add to its biosafe deployment and promote continued investigation on human transmission and exposure to airborne pathogens. supplementary data are available at annals of work exposures and health online. this work was funded by the bill and melinda gates foundation (grant number opp ), karolinska innovations ab, and karolinska institutet, all to a.g.r. the funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. air samplings in a campylobacter jejuni positive laying hen flock sources of airborne norovirus in 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indoors at a health centre, a day-care centre and on aeroplanes we thank roland möllby (karolinska institutet, sweden) and wayne bryden (zeteo tech, usa) for suggestions and critical reading of this manuscript. we would also like to thank sören hartmann and per-erik björk (karolinska institutet) and erik ekstedt (akademiska hus ab, stockholm, sweden) for technical assistance. flow cytometry was performed at the biomedicum flow cytometry core facility (bfc), department of microbiology, tumor and cell biology, biomedicum, karolinska institutet. the authors declare no conflict of interest. key: cord- -pzwlxtd authors: pal, subrata title: the lung and its transplantation and artificial replacement date: - - journal: design of artificial human joints & organs doi: . / - - - - _ sha: doc_id: cord_uid: pzwlxtd the human thoracic cavity houses a pair of lungs, the left lung and the right lung. the left lung is slightly smaller (since the heart is placed a bit to the left in the body) and has two lobes, and the right lung is bigger, with three lobes. they are spongy and elastic organs that are broad at the bottom and taper at the top. they consist of air sacs, the alveoli. many alveoli group together and open into a common space. from this space arise the alveolar ducts, which join together to form bronchioles. the bronchioles connect them to the respiratory tract. the lungs also have blood vessels, the branches of the pulmonary artery and veins (fig. . ). apart from the lungs, several associated organs and structures together form the respiratory system. the respiratory system is closely linked with the circulatory system, as the transport of the gases takes place through blood. the lung and its transplantation and artificial replacement the respiratory system starts with the nose, which covers the nasal cavity. the nasal cavity opens to the atmosphere through the openings called the nostrils. the nasal cavity is divided into two portions by a cartilagenous septum and is lined by fine hairs that filter the dust particles from the air. the nasal cavity is separated from the mouth by hard and soft palates that form its floor. it opens into the region called the pharynx (fig. . ) . the pharynx is a common passage to both food and air. this allows more air whenever required and also allows passage of air in case the nose is blocked. the pharynx continues into the glottis. the glottis is the narrow opening into the larynx. it is guarded by a flap of tissue called the epiglottis. several folds of elastic connective tissue are embedded into the posterior end of the glottis. they are called the vocal cords. these extend into the larynx. the larynx is also called the voice box. the vocal cords stretch across the larynx and vibrate when the air passes through them. this vibration produces various sounds. the coordinated movement of the lips, cheeks, tongue, and jaws produce specific sounds that result in speech. speech is an ability that only humans are gifted with, the larynx is held open with the help of cartilages. the "adam's apple" is a prominent cartilage of the larynx. the larynx continues as the trachea after the cords. the trachea is also called the windpipe. the trachea is held open with the help of c-shaped cartilagenous rings. the open ends of the rings are located toward the esophagus, also known as the foodpipe. the trachea is situated in front of the esophagus. the cartilages keep the larynx and trachea from collapsing even when there is no air in them. the trachea then branch into two main branches called bronchi. each bronchus is also supported by the cartilagenous rings. the bronchus then branches into several bronchioles. the bronchioles progressively lose the cartilages as they become narrower. the bronchioles end as fine tubules called the alveolar ducts ( fig. . ) . each alveolar duct opens into an alveolar sac. an alveolar sac is the extended region into which a group of alveoli or air sacs open. each alveolus is a saclike structure lined by a single layer of epithelial cells. it is bound on the outside by a network of capillaries. all the alveoli on one side are enclosed by the membrane called the pleural membrane and constitute a lung. the pulmonary artery from the heart containing impure blood enters the lungs and branches into minute capillaries that surround the alveoli. these capillaries then join together to form the pulmonary vein, which carries the purified blood back to the heart. the common composition of atmospheric air that we breathe in is nitrogen- %, oxygen- %, carbon dioxide- . - . %, hydrogentraces and noble gases in traces. thus, the air naturally contains nearly times more oxygen than carbon dioxide. this oxygen-rich air is taken in by the nostrils. in the nasal cavity, it is filtered by the fine hairs in the nose. the cavity also has a rich supply of blood vessels that keep the air warm. this air then enters the pharynx, then the larynx, and then into the trachea. the trachea and the bronchi are lined with ciliated epithelial cells and secretory cells (goblet cells). the secretory cells secrete mucus, which moistens the air as it passes through the respiratory tract, and also trap any fine particles of dust or bacteria that have escaped the hairs of the nasal cavity. the cilia beat with an upward motion such that the foreign particles along with the mucus is sent to the base of the buccal cavity, from where it may be either swallowed or coughed out ( fig. . ). the air from the bronchus then enters the bronchioles and then the alveoli. the alveoli form the respiratory surface in humans. the capillaries lining the alveoli have blood that has a low concentration of oxygen. so the oxygen from the air easily diffuses into the blood through the thin barrier of the alveolus wall. similarly, since the concentration of carbon dioxide is quite high in the blood, the gas easily diffuses out into the alveolar space. from here, the air-which has a comparatively higher concentration of carbon dioxide than the air that entered it-leaves the lungs (fig. . ). the human lung is a very important and strong organ that has to withstand a strong and continuous assault stemming from a wide range of environmental conditions and the lifestyle in our modern world, which cause a multitude of diseases and conditions, as outlined here: • lung transplantation is a surgical procedure to totally or partially replace a patient's diseased lung with a donor's lung. while lung transplants carry certain associated risks, they can also extend life expectancy and enhance the quality of life for end-stage pulmonary patients. lung transplantation is the therapeutic measure of last resort for patients with end-stage lung disease who have exhausted all other available treatments without improvement. a variety of conditions may make such surgery necessary. as of , the most common reasons for lung transplantation in the united states were the following [ ] : % from chronic obstructive pulmonary disease (copd), including emphysema % from idiopathic pulmonary fibrosis % from cystic fibrosis % from idiopathic (formerly known as "primary") pulmonary hypertension % from alpha -antitrypsin deficiency % due to replacing previously transplanted lungs that have failed after a period % from other causes. a lobe transplant is a surgery in which part of a living donor's lung is removed and used to replace part of a recipient's diseased lung. this procedure usually involves the donation of lobes from two different people, thus replacing a single lung in the recipient. donors who have been properly screened should be able to maintain a normal quality of life despite the reduction in lung volume. many patients can be helped by the transplantation of a single healthy lung. the donated lung typically comes from a donor who has been pronounced brain-dead. certain patients may require both lungs to be replaced. this is especially the case for people with cystic fibrosis, due to the bacterial colonization commonly found within such patients' lungs; if only one lung were transplanted, bacteria in the native lung could potentially infect the newly transplanted organ. some respiratory patients may also have severe cardiac disease that itself would necessitate a heart transplant. these patients can be treated by a surgery in which both lungs and the heart are replaced by organs from a donor or donors. first performed in , this type of transplant typically involves the transplantation of a heart and lungs into a recipient. prior to operating on the recipient, the transplant surgeon inspects the donor lung(s) for signs of damage or disease. if the lung or lungs are approved, then the recipient is connected to an intervenous line and various monitoring equipment, including pulse oximetry. the patient will be given general anesthesia, and a machine ventilator will breathe for the patient. the donors are usually road accident victims whose organs can be transplanted within - h of death. there are a large number of patients who are waiting for such transplantation from donors. potkey of vamc cleveland, ohio ( ), recently developed one model of artificial lungs. he indicated more than million americans are living with chronic lung disease; it is responsible for nearly , deaths every year in the united states alone [ ] . acute respiratory distress syndrome has a mortality rate of % and affects . lakh americans each year [ ] . many patients waiting for lung transplants die while on the waiting list. to help combat these problems, artificial lungs have been developed with the goal of replacing or supplementing the respiratory function of the lung. artificial lungs mimic the function of real lungs, adding oxygen to, and removing carbon dioxide from, the blood. in all cases, however, the performance of artificial lungs is still significantly lower than that of natural lungs. the human lung is a remarkable organ, providing a maximum gas exchange rate for both o and co of - l/min [ ] . on the other hand, current artificial lungs are only capable of a maximum gas exchange rate of . - . l/min, limiting their use to the short-term respiratory support for patients at rest. this insufficiency is due to the smaller surface area, smaller surface-area-to-volume ratio, and greater membrane thickness of artificial lungs compared to the human lung [ ] . recent advances in the micromachining of silicone elastomer (pdms) have made possible the creation of a new highly efficient artificial lung (fig. . ) with feature sizes similar to or better than those of the human lung. such a micromachined artificial lung would have an improved gas exchange performance compared to its conventional counterparts, potentially resulting in increased clinical use. silicone has been used as the membrane material in some commercially available artificial lungs due to its biocompatibility, durability, stability, and high permeability to oxygen and carbon dioxide. however, these devices have limited gas-exchange capability mainly due to the membrane's thickness (> μm). a significant advantage of silicone membranes is that blood plasma leakage does not occur as it does in microporous hollow fiber oxygenators [ ] . in fact, hollow fiber oxygenators are sometimes coated with a thin layer of silicone in order to reduce plasma leakage and increase the device lifetime. due to these advantages, silicone was utilized as the membrane material in this study (fig. . ) . lung, artificial: basic principles and current applications new design for a pumping artificial lung development of a total artificial lung . describe the structure and function of natural lungs. what conditions in a patient create the requirement for an artificial lung? . describe how to develop an artificial lung. indicate the volume of blood and oxygen and other gases to be handled. develop a schematic diagram for an artificial lung. key: cord- - srun l authors: xu, zhonglin; zhou, bin title: design points for negative pressure isolation ward date: - - journal: dynamic isolation technologies in negative pressure isolation wards doi: . / - - - - _ sha: doc_id: cord_uid: srun l according to “law of the people’s republic of china on the prevention and control of infectious diseases” issued on december st in , infectious diseases can be classified as the first class, the second class and the third class. diseases, it must be approved, published and implemented by the state council after the epidemic incidence is reported immediately by the health administrative department of the state council. now more attention has been paid on the ebola virus. . isolation ward can be classified as the infectious isolation ward and the protective isolation ward (the isolation ward for curing the mental disease is not included in this book). the infectious isolation ward is also termed as the negative pressure isolation ward. it is mainly used for prevention of the airborne disease from infecting both the environment outside the ward and the people except for the patient. these diseases include the tuberculosis, the chickenpox, the pneumonia, sars, the hemorrhagic fever virus, etc. this book focuses on the negative pressure isolation ward only. some infected patients may also need protection, such as tuberculosis patients. in occasions when there is no infectious patient inside, the isolation ward can be used as the ordinary ward. this has been clearly specified in the standard of some nations, such as the aia standard in u.s.a. "when there is no need for isolation, the isolation ward can be used as the ordinary nursing room or can be divided into individual isolation wards." "when there is not patients with airborne diseases, the isolation ward can be used for patients without infectious diseases" [ ] . . the infectious strength of the disease on patient inside the infectious isolation ward can be classified as four levels which can be referred in chap. . the function of the isolation ward is as follows: ( ) the isolation ward should play the role of isolation. isolate the ward from the ambient environment, and isolate the patient from the medical personnel. ( ) the isolation ward should play the role of safety. to guarantee the safety of the environment outside the ward. to guarantee the safety of the medical personnel inside the ward. it could also be classified as four levels according to the required pressure difference, such as the australian standard which is shown in table . [ ] . the distance between the isolation ward and the surrounding buildings especially the dormitories and the public buildings should be m at least [ ] . this has been pointed out for the site selection of the infectious diseases hospital in the national standard gb - "code for design of infectious diseases hospital". since the isolation ward is the main component of hospital, this principle should be followed naturally. the concept of the minimum distance m was first proposed by author, which was adopted by the national standard gb - "architectural and technical code for biosafety laboratories". this is aimed in terms of the risk of the exhaust air from the biosafety laboratories. when the microbes with highly pathogenic and the safety of the exhaust air are concerned, the isolation ward should not be an exceptional. . in the general hospital, it is better if the isolation ward can be placed alone. otherwise it should be set at one edge of the building as possible. if should form a zone and placed at the leeward wind side in the most annual wind direction in this area. when there are two most wind directions in this area, the isolation ward should be placed at the opposite direction facing the wind direction with the least frequency. . for the ward are consisting of multiple isolation wards, the clean area, the potentially polluted area and the polluted area should be strictly distinguished. in general, the ward itself (including its bathroom) and the area for activity of patients are the polluted area. the public corridor is the potentially polluted area. the primary changing room, the preparatory room and the offices for the medical personnel area the clean area. . if there is enough space for setting double corridors, the patient should enter into the ward through the back corridor and the back door. in this case, the back corridor should be classified as the polluted area. the relative pressure inside the back corridor is positive. the net width of the corridor should be not less than . m. when there is relative height difference in the corridor, the barrier-free cohesion edge should be used, and the antiskid measures should be taken. the medical personnel should enter into the ward through the front corridor which should be classified as the potentially polluted area. only the region outside the exit of this corridor could be classified as the clean area. figure . shows the renovated sars ward in a hospital in shanghai, where the scheme with two corridors was adopted [ ] . in the figure, the semi-clean area can be considered as the potentially polluted area. while the semi-polluted area can also be considered as the polluted area, where the pressure is slightly higher than that in the ward. besides, buffer rooms should be set at two edges of this corridor. as shown in fig. . , it is better if there is also the buffer room at the back door of the ward. in this case, it is unnecessary to set the buffer room at two edges of the exterior corridor which can be classified as the potentially polluted area. . in the national standard gb - "code for design of infectious diseases hospital", more than two passageways should be set for the ward in the hospital where the number of the sickbeds is more than , and two passageways are required to be set for the ward in the hospital where the number of the sickbeds is less than . the detailed information is given in if the ward is placed in other buildings, the passageway must be set independently, which could be disinfected in a closed space. . according to the different transmission routes of the infectious diseases, the ward and the outpatient room (or the emergency room) in the hospital are set. the ward with infectious disease by airborne transmission must be set independently, which is shown in table . . in the local standard db / - "essential construction requirements of negative pressure isolation ward" was issued in beijing (which is shortened as "essential requirements"), it is required that the maximum number of occupants is three. while in standards from germany and u.s.a., it is required that the maximum number of occupants in each ward is two, and for the renovated ward the corresponding value is four. table . shows the data on the area of the ward by "essential requirements" and standard from u.s.a. in hospitals from the netherlands, the width of the sickbed is m, and the minimum distance between sickbeds is . m. in u.s.a., the distance between sickbed is required . m. ( ) it is set inside the isolated region, which is the pathway for the infected patient and the ambulance. if it must be set at the same side with the passageway for the cleaning suppliers because of the space limit, the distance between them must be clearly specified for avoiding confusion infectious ward for digestive tract when the pathogen (such as typhoid fever, bacillary dysentery, cholera) contaminates the food, the drinking water or the dishes, the susceptible is infected during intaking of food isolation measures were taken according to the feature of the disease. individual bathroom must be set inside every ward (or treatment room). the waste is disinfected and sterilized, and then discharged into the drainage system of the hospital infectious ward for respiratory tract for the pathogen such as measles, diphtheria and tuberculosis, they are likely to be inhaled by the susceptible once they are suspended in the air, which will cause the infection clean area, potentially polluted area and polluted area are strictly distinguished. organized air distribution is required for the airflow in the ward. the pressure in the clean area should be larger than that in the potentially polluted area. the pressure of the potentially polluted area should be higher than that in the polluted area. the negative pressure is kept inside the ward, so that the polluted air cannot disperse towards outside. it is better that the treatment room should be set independently, which is located at the bottom infectious ward (or treatment room) for entomophily when bloodsucking arthropods such as mosquito, human louse, rat flea, sandfly and chigger mite bite the susceptible, the infection by the pathogen will occur. malaria, epidemic typhoid fever, endemic typhoid fever, kala-azar and tsutsugamushi disease will be induced respectively attention should be paid on killing the mosquito and defaunate in the ward (or treatment room). insect screen should be installed at the door and the window locations. blacklight trap can be used to kill the mosquito and the fly at the window location, which can prevent the disease transmission through the mosquito and the fly infectious ward (or treatment room) for other diseases (blood source) pathogens such as malaria, hepatitis b, hepatitis c and hiv virus exist in the blood or the body fluid of the carrier or the patient. transmission occurs during the application of the blood product, the delivery process or the sexual intercourse process the hand-washing apparatus should be set in the passageway of the medical personnel for each ward (or treatment room). responsive switch should be used. disinfection and hand-washing should be carried out when the medical personnel walk in and out of the ward (or treatment room) special ward (or treatment room) it is aimed to treat the sudden and the fulminating infectious disease such as sars it should be set independently. clean area, potentially polluted area and polluted area are strictly distinguished. buffer room should be placed between different areas. organized air distribution is required for the airflow in the ward. the negative pressure is kept inside the ward. the polluted air can be discharged outside after it is disinfected in short, the space inside the ward should be spacious enough to place equipments such as the bedside x-ray machine and the breathing machine. therefore, the values of the distances are larger than that in the ordinary ward. according to "essential requirements", the net height of the ward should not be less than . m. . except for the isolation, the intensive care unit, the office for doctor, the office for nurse, the nurse station, the disposal room, the treatment room, the duty room, the base for bed and cloth, the canteen preparation room and the room for boiling water should also be placed inside the ward area. when the number of the wards is large, x-ray room should be set. when there is the teaching task, the demonstration classroom should be set. . the bathroom should be annexed in the isolation ward, which includes the closet bowel flushed with sterilized water, the shower, the washbasin with inductive tap. door should not be placed for other bathrooms outside of the ward. instead, the open labyrinth-style inlet can be adopted. . the canteen preparation room in each ward area should distinguish the clean room from the polluted room. the delivery window is set between them. if the disposable tableware is used, the canteen preparation room can be set inside the clean area, and no isolation is needed. . if needed, biosafety cabinet should be set for testing of special specimens, which is operated inside the class biosafety laboratory. . the autopsy room for the infected patients especially those with the severe acute respiratory syndrome (sars) should be designed according to class biosafety laboratory. according to the japanese standard, the anatomy station should be placed inside the unidirectional flow unit. . delivery window should be placed on the wall of the corridor adjacent to the isolation ward, which is used for deliver the medicine and the food. according to the nation standard jg/t - "pass box", the classification of the delivery window is shown in table . . the delivery window set between the isolation ward and the polluted area should be type b or c . figure . shows the basic appearance of the delivery window. . air shower should not be placed along the passage of people flow. air curtain should not be used at the gate in the ward area. basic a it is installed on the partition wall of the ward, which is used for delivery of goods. two doors are inter-locked. it has the basic function of isolation for air from rooms in two sides of the partition wall with function of air cleaning b self-purification system composed of fan and hepa filter is included, which has the function of air cleaning for aerosol inside the delivery window b it includes the air supply system and the air exhaust system containing hepa filters, which has the function of removing aerosol inside the delivery window and aerosol exhausted out of the delivery window b it has the function of air shower. the particles on the surface of the delivered goods inside the unit are cleaned by high speed clean airflow injected through the nozzles with function of disinfection c uv-light tube is installed in the passage of the delivery window. the microbes on the surface of the wall and the delivered goods, and the air through the passage should be disinfected if needed c inlet and outlet of the sterilization gas are set on the wall of the delivery window. the interior surface of the delivery window can be disinfected by the disinfection apparatus outside the delivery window when it is connected with the inlet and outlet of the sterilization gas if needed negative pressure d under the operational condition, the negative pressure with certain value can be maintained inside the delivery window air-tight e there is no visible gas leakage e when the pressure in the passage reaches − pa, the decay rate of the negative pressure within min is less than pa . the ordinary vertical hinged door or the upper suspended sliding door can be used between the isolation ward and the buffer room. the vertical hinged door is suitable to be set between the buffer room and the corridor. in both cases, the wooden door should not be used. . when it is possible, the advantage is more obvious if the sliding door is adopted between the isolation ward and the buffer room. in this case, the velocity of the induced turbulence by the sliding door is the minimum, compared with that of the vertical hinged door. therefore, the sliding door is recommended for the entrance of the isolation ward in related standards in japan. this is also recommended in aia standard in u.s.a. and it is also pointed out that the sliding slot should not be set on the floor for this kind of the sliding door. therefore the upper suspected sliding door should be used, which is the same as that of the clean operating room. of course, whether the sliding door can be set depends on the space of the buffer room. the gap of the vertical hinged door is small, so it should be used between the buffer room and the corridor, which is suggested in japanese standard. . it is not necessary to use the air-tight door and the air-tight inter-lock door for the doors of the isolation ward and the buffer room. the requirement can be met when the ordinary door is used. but the wooden door should not be used. . except for the safety door and the door towards the entrance hall which open outwardly, other doors should open towards the side with larger pressure. . door should not be placed for other bathrooms outside of the ward. instead, the open labyrinth-style inlet used in the airport terminal building can be adopted. . buffer room is placed outside of the isolation ward. positive pressure is maintained in the buffer room relative the isolation ward, while negative pressure or zero pressure is kept in buffer room relative to the outside of the buffer room. this kind is called three-room-one-buffer, or two-area-one-buffer, which is shown in fig. . . the isolation ward is the polluted area, while the area outside of the corridor is the clean area. it is understandable that these provisional measures were specified. but during the east asia rainy season (or meiyu season) and the hot summer in the southern region where the humidity is extremely large, the propagation of pathogenic microbes indoors cannot be prevented in hospitals by natural ventilation alone. in this case, the microbial contamination may still occur. if the temperature and the humidity indoors are very high, the patient will generate heat and sweat, which will increase the bacterial generation rate. when the medical personnel wear the insulation garment, the protective cloth, the mask and eyeglasses, sweating will occur soon after the work. sometimes febrile disease may even appear. especially in the isolation ward for sars, the working environment will be worsened if the problem of hvac and environmental control is not solved. this will influence the physical and mental health of the medical personnel. in june of , the who representative office in china wrote to ministry of health of china. different opinion was proposed. natural ventilation by window opening is not allowed in the isolation ward for sars. the hvac system should be operated continuously. exhaust air fan should be installed on the exterior window or the exterior wall, so that negative pressure is maintained indoors. however, the "hospital infection control guidance for severe acute respiratory syndrome (sars)" issued by who pointed out that when there is no independent air exhaust system in hvac system, the air conditioning system can be turned off, and ventilation can be provided by window opening. but windows are prohibited to be open towards the public space. in fact, air conditioning system is not prohibited in related foreign standards. and circulation air can be adopted conditionally. in "guidelines for preventing the transmission of mycobacterium tuberculosis in health-care facilities" issued by cdc from u.s.a. in , it was emphasized that for the known airborne infectious droplet nuclei, the general exhaust system can be adopted. meanwhile, it was pointed out that it was inevitable to adopt the scheme of recirculation air. when hepa filter is used, air can be re-circulated. three kinds of air distribution were proposed, which would be introduced in the next section. it was also pointed out in "the guideline of design and management for air-conditioning system of hospital" by healthcare engineering association of japan that the fan unit with hepa filter can be installed in the isolation ward. in march st of , novel idea for central air conditioning system appeared in "code for hygiene of central air-conditioning ventilation system in public places" published by ministry of health of china. it was specified that when the epidemic of airborne disease occurs in the local area, the central air conditioning system can be operated continuously only when the following requirements are satisfied. it can be used when the full fresh air scheme is used. it can also be used when the air cleaning device with disinfection function is installed and its performance is guaranteed to be effective. it can also be used when independent ventilation is accessible to each room when the hvac system scheme by the combination of the fan coil unit and the outdoor air is adopted. however, this solution is obviously not enough. it should be pointed out that for the isolation ward with infectious disease, except for the full fresh air system, air can be circulated only when hepa filter is installed (at the return air grille). of course, no matter whether full fresh air system is used, exhaust air must pass through hepa filter. for the infectious diseases hospital and isolation ward, the above idea is also applicable. but different cleaning air conditioner system should be set for the clean area, the potentially polluted area and the polluted area, respectively. . the air-circulation system is only suitable for the single ward with infectious disease. or circulation of indoor air is adopted for the ward receiving multiple people with the same kind of disease. when heating and cooling are provided by fan coil unit, another independent or public outdoor air supply system should be set. in this case, it is suitable to switch to or adopt the full fresh air system for one or more wards. . the air change rate in the isolation ward should be - h − . the flow rate of outdoor air per person should not be less than m /h. in other auxiliary rooms, the air change rate should be - h − . . although there is no requirement on the air cleanliness level in the isolation ward, air filtration device with low pressure drop and efficiency larger than the high and medium efficiency air filter shown in table . ( ), ( ) must be installed at the air supply opening. hepa filter should be installed for the supplied air into the buffer room where the air change rate is ! h − . . the safely demountable leakage-free high efficiency negative pressure air exhaust device sealed with dynamic air current can be used in the isolation ward and its bathroom. . the outlet of the air exhaust pipeline should be linked towards outdoors. the check valve and the rain droplet prevention measures should be used. the end of the air exhaust pipeline should be above the roof by more than m. it should be far away from the air intake opening on the wall by more than m, and it should be located in the downstream of the air intake opening. when the distance between them is less than m, the retaining fence should be set. . the cleaning air conditioning system should be operated for h continuously. the air velocity of the supplied air in the daytime should not be less than . m/s. while in the evening, the flow rate is under the low gear station, and the velocity of the supplied air should not be larger than . m/s. the air supply and air exhaust should be inter-locked. the air exhaust system should be turned on at first and closed later. . in the ordinary time, the cleaning air conditioning system can provide normal pressure status in the isolation ward, when the non-infectious patients are received. but the pressure conversion scheme is not allowed in the infectious isolation ward and the protective isolation ward. this has also been specified in the related standards in japan and u.s.a. . in the isolation ward where cleaning air conditioning system and air circulation system with hepa filter are used, indoor air cleaning device should not be used again to disturb the original air distribution. . air cleaning device must be installed at the entrance of the outdoor air. according to national standard gb - "code for design of general hospital", two-stage air filters including the coarse and fine filters should be installed at least for the entrance of the outdoor air, when the annual concentration of respirable particulate matter pm in the atmosphere does not exceed . mg/m . when it exceeds . mg/m , the high and medium efficiency air filter should be added. in european standard en , it is also specified that when the outdoor air is clean, two-stage air filters such as f + f should be set for the outdoor air pipeline. it is also specified in iso that g + f should be set for outdoor air. it is better to set f + f . it is very good to set f + f . . according to gb - "code for design of general hospital", for the return air grille in the hvac system in the auxiliary room for isolation ward area, air filters with initial pressure drop less than pa, the one-pass penetration for microbes not larger than % and the one-pass arrestance for particles not larger than % should be installed. . the air distribution scheme with upper-supply and lower-return should be adopted in negative pressure isolation ward. the total trend of airflow should be consistent with the settlement direction of particles. the airflow inside the negative pressure ward and its ward area should be directional, which flows from the clean area towards the polluted area. . according to the simulated and experimental results in chap. , the primary and secondary air supply outlets as shown in fig. . should be chosen for the negative pressure isolation ward. the primary air supply outlet is set on the ceiling above where the medical personnel usually stand near the sickbed. the distance from the head of the sickbed should not be larger than . m. the length should not be less than . m. the secondary air supply outlet should be set on the ceiling above the end of the sickbed. the distance from the end of the sickbed should not be larger than . m. the length should not be less than . m. . the ratio of the areas between the primary and the secondary air supply outlets should be between : and : . the velocity of supplied air should not be less than . m/s. for the ward with multiple beds, it is not allowed that one bed is located at the leeward side of another ward. figure . shows an example where infection occurred in practice. airflow from natural ventilation or mechanical ventilation moves from one side of the room (at the window side) towards the door side (or the bathroom). this results in infection at the leeward side. . when the temperature inside the ward is higher than that in the buffer room, the air return (or exhaust) openings inside the buffer room should be placed on the ceiling above the door connecting the ward. air supply outlet should be placed on the ceiling at the opposite side relative to the air return (or exhaust) openings. they are not necessarily symmetric. based on the analysis on the function of temperature difference in chap. , when the door of the ward is open under this condition, the convection of air with air out above and air entrance down will appear. the air return opening above the door of the buffer room can remove the pollutant from the airflow leaving the ward immediately, which is shown in fig. . . . if the temperature inside the buffer room is higher than that in the ward, the air distribution with the upper-supply and lower-return scheme can be adopted inside the buffer room. this is because when the door of the ward is open, the polluted air will penetrate into the buffer room from the lower part of the door. . determination of pressure difference and differential pressure flow rate . . pressure difference "essential construction requirements of negative pressure isolation wards", the distribution of the pressure difference of the isolation wards can be set as shown in fig. . . the relative pressure between the ward and the buffer room, as well as that between the buffer room and the interior corridor, should not be less than pa. the sequence for the extent of negative pressure is the bathroom, the negative pressure isolation ward, the buffer room, and the interior corridor. for the ordinary negative pressure isolation ward, at least one buffer room should be set outside the ward based on the actual condition. . for the buffer room between the corridor inside or in front of the potentially polluted area and the clean area, its pressure relative to both this corridor and outdoor should be positive. the relative positive pressure between the buffer room and the region connecting the ambient should not be less than pa. . because the ward and its bathroom are polluted areas and there is usually exhaust air system in the bathroom, the air must flow from the ward towards the bathroom. from the viewpoint of principle of dynamic isolation with dynamic current, the value of pressure difference between the ward and the bathroom was not given in db / - . instead, it was required for the directional airflow from the ward towards the bathroom. by adjusting the exhaust air volume, the degree of negative pressure in the bathroom should be higher than that in the ward. upward shutter can be set above the door of the bathroom. . for the isolation ward with extreme high risk, two negative pressure buffer rooms can be set in series at the gate of the ward. in japanese standard, this suggestion has been proposed. the gradient of the pressure difference is: ward--← buffer room ( )-← buffer room ( )-← interior corridor ! ←buffer room ( )(+ or −)-$clean area (+ or ). when it is not convenient to calculate the pressure difference or when the value of the pressure difference has not been obtained, the value of air change rate is usually used to obtain the differential pressure flow rate in engineering. it is also pointed out in cdc from u.s.a. that since the pressure difference is too small, the flow rate of the exhaust air from the room can also be used to determine the pressure difference in the room. this means when the flow rate of the exhaust air is less than m /h, the requirement for the negative pressure is satisfied. based on the data in table . , for the ward where the door of the room is not air-tight, this flow rate of the exhaust air is equivalent to the pressure difference with value slightly more than pa indoors. if the pressure difference with value not less than pa as analyzed before, the corresponding flow rate of exhaust air should reach m /h. therefore, the suggested flow rate of exhaust air should not be less than m /h. the corresponding flow rate of exhaust air for the pressure difference pa should be m /h. however, it is still a pure theoretical value with m /h. when the differential pressure flow rate Δq is determined, the practical problem should also be considered. figure . shows the negative pressure room with supplied air and exhaust air. in the ventilation system of the room there could be fan and the adjusting valve, or fan and the constant air volume valve. there are positive and negative deviations of the flow rate for the fan and the constant air volume valve. for example, the deviation of the trox valve can reach ± %, which has no relationship with the pressure. the deviation of the venturi valve can reach ± %. in situ adjusting test shows that because the area of the ward is not large, when the ward is very air-tight, the fluctuation of extreme flow rate in the ward will influence the variation of its pressure [ ] . one most unfavorable condition in the negative pressure room is that positive deviation Δq appears on the supply fan or the constant volume valve. this means fig. . schematic of the negative pressure room with supplied air and exhaust air system the actual flow rate of the supplied air is larger than the designed or rated flow. the other most unfavorable condition in the negative pressure room is that negative deviation Δq appears on the exhaust fan or the constant volume valve. this means the actual flow rate of the exhaust air is smaller than the designed or rated flow. the aforementioned situations can be expressed with three conditions shown in figs. . , . and . . for condition one, we know: in this case, both the flow rate and the pressure difference can be adjusted normally, which is not affected. for condition two, we know: in this case, the flow rate of the exhaust air is obviously not enough. the negative pressure cannot meet the requirement, which needs further adjustment. for condition two, we know: in this case, the actual flow rate of the exhaust air is smaller than that of the supplied air. slight positive pressure appears in the ward, which needs further adjustment. therefore, for the negative pressure ward, the designed differential pressure flow rate of exhaust air is not only the difference of the flow rates between the exhaust air and the supplied air, but also the deviation of the fan or the adjusting valve. this means the differential pressure flow rate of the exhaust air should be larger than the summation of the leakage air flow rate and the absolute value of the positive and negative deviation for the flow rate of fan and adjusting valve. this means: now the easily appearance of the problem can be better explained for the air-tight room. when the room is too air-tight, the leakage flow rate is very small. in this case, the difference of the flow rate between the exhaust air and the supplied air is very small. if the value of this difference is smaller than the summation of the absolute value of the positive and negative deviation for the flow rate, it is difficult to adjust the pressure difference inside the room. the pressure always fluctuates, or slight positive pressure appears. therefore, the real differential pressure flow rate should be the summation of the above differential pressure flow rate value m /h and the absolute value of the positive and negative deviation for the flow rates for supplied and exhaust air. in this case, it may be ! m /h. . compared with the atmospheric pressure, the relative pressure inside each room is marked in the frame as shown in fig. . . fig. . expression of absolute pressure difference . compared with the pressure in the adjacent room, the direction of the pressure difference is expressed with the arrow at the gate connecting two rooms. the value of the pressure difference is marked beside the arrow or at the end of the arrow. take the above figure as an example, fig. . can be obtained. in fig. . , the value "− pa" means the pressure difference between the room where the arrow starts and the room where the arrow points to is − pa. the value "+ pa" means the pressure difference between the room where the tail of the arrow starts and the room where the arrow points to is + pa. therefore, both the value of the pressure difference and the location cannot be confused. it is shown in figs. . and . that these two kinds of expression methods are different. . in terms of the pressure difference itself, it is aimed to prevent the leakage from adjacent room or the outward leakage towards adjacent room. because the room studied is connected with the adjacent room, the pressure difference between them is meaningful. however, it has no practical implication to discuss the leakage towards the ambient air through the envelope or the inward leakage from the ambient air towards indoors. the biosafety laboratory with high class level is an exceptional. in the layout shown in fig. . , it is required that: the absolute value of negative pressure in room a Δp ao ¥ pa. the absolute value of negative pressure in corridor b Δp bo ¥ pa. figure . shows another example. the differential pressure gauge only set on the partition wall between the isolation ward and the polluted corridor, which shows the relative pressure difference between them. inspection shows that there is no differential pressure gauge between the isolation ward and the buffer room, but the actual pressure difference is . in this case, even though the pressure difference between the isolation ward and the polluted corridor meets the requirement, there is no pressure difference between the isolation ward and the buffer room. the buffer room and the isolation ward is combined to be one unit. the function of buffer loses, so the buffer room only exists as a name. . it has been mentioned before that it is difficult to control with the absolute pressure during the actual adjusting process. if one side of the differential pressure sensor connects indoors while the other connects outdoors as shown in fig. . , the sampled pressure difference is unstable because of the wind direction and wind magnitude of the atmosphere. it may be positive or negative, large or small. in fact, during the process of system design, the flow rate by negative pressure or positive pressure is calculated based on the relative pressure difference. figure . should be expressed as fig. where Δp ,n is the absolute pressure difference at room n. the value of n is the sequence number of the room n along the passage from outdoors towards indoors. Δp n is the magnitude of the relative pressure difference between room n and room (n − ). Δp n− is the magnitude of the relative pressure difference between room (n − ) and room (n − ), and so on. next we will take the plane layout of a negative pressure room in an animal health company as an example, which is shown in fig. . . except for the treatment room for abandoned embryo which forms one passage itself, there are three routes for connecting the ambient with the inoculation chamber which needs the highest requirement. these routes are expressed with dashed lines. (a) the left route can be simplified as fig. . . we obtain the middle route can be simplified as fig. . . we obtain the right route can be simplified as fig. . . we obtain it is shown that when anyone route is chosen among the left, middle and right routes, the absolute pressure differences for the inoculation chamber obtained with relative pressure difference are the same. this is the same as the in situ measured absolute pressure difference. similarly the absolute pressure difference in the treatment room for abandoned embryo can be obtained: it is known from fig. . that even though the relative pressure in the inoculation chamber compared with that in the post hatching room is "+ pa", the absolute pressure difference is still: this means because the relative pressure difference in the post hatching room close to the inoculation chamber is − pa, although the relative difference between the inoculation chamber and the post hatching room reaches + pa, the condition of negative pressure compared with atmospheric pressure can still not be changed. to determine whether the relative pressure in a room compared with atmospheric pressure is negative or not, calculation with various adjacent rooms connecting outdoors should be performed. . differential pressure gauges should be set at the view height on each exterior wall of the region where the pressure difference is required. since the indoor cooling load is dealt with the fan coil unit, the capacity of the outdoor air handling unit reduces. because the bacterial removal efficiency of the hepa filter on the return air grille reaches more than . %, one bacterium can penetrate through only when the indoor bacterial concentration reaches millions per cubic meter. in common situation, indoor bacterial concentration cannot reach such high value. therefore, the return air is quite clean. the problem for deposition and accumulation of dust and bacteria on fan coil unit is not a concern. therefore, air filters with performance lower than sub-hepa filter can be installed for the supplied air, such as the low-resistance and high and medium efficiency air filter, or even fine filter. the unit with static pressure between and pa should be selected. the problem of condensation should be paid attention to. the system is shown in fig. . . condensation water is very likely to appear in the coil when the fan coil unit is adopted, which is not expected to occur. so in the current scheme, the coil is abandoned, which is replaced by the ordinary supplied air fan. the return air needs to pass through the outdoor air handling unit, which increases the burden of the outdoor air handling unit. the system is shown in fig. . . because there are - patients in the ward, the cooling and humidity loads are very small. if there is no need of cooling and humidity handling for the return air, return air will not pass through the outdoor air handling unit. the outdoor air handling unit is only responsible for the cooling and humidity loads from the outdoor air. in this case, there is no problem for formation of condensation water. liu hua proposed the specific scheme which is shown in fig. . . in this scheme, by reducing the dew point of the machine and increasing the outdoor air volume, the problem of the outdoor air handling unit to treat the entire humidity load is solved. when the outdoor air volume is increased, the air change rate of the outdoor air for the double-bed ward is only . h − , which only increases by h − . based on the meteorological condition in shanghai, the surface air cooler with six rows of coils in the outdoor air handling unit can meets the requirement of the design (t < °c and u < %). when other types of coils are used, eight rows of coils are enough. the system is shown in fig. . . . shows the schematic of the system which was designed by liu hua and liang lei. one example of the double-bed isolation ward for this scheme is shown in fig. . . the isolation ward is located on the th floor with area m . there are twelve negative pressure isolation wards and four ordinary wards. every two wards share the same anterior buffer room. each ward has its posterior buffer room. moreover, buffer room is placed at all the entrance and exit. this realizes the feature of "three-area-two-buffer". three-area means the clean, the potentially polluted and the polluted areas. two-buffer means the buffer room between the ward and the corridor, and the buffer room between the corridor and outdoors. the isolation capability is greatly increased. independent air conditioning system is used for each area. in the clean area, the scheme with the fan coil unit and the dedicated outdoor air handling unit is used. in the potentially polluted area, the dedicated all air system is used. in the polluted area, independent all air system is adopted for every isolation ward, which operates with two gears of velocity. in other regions, an independent all air system is adopted. the air change rates in the ward and the buffer room are and h − , respectively. the gradient of the pressure is also marked in fig. . . . simplified analysis . corridors are set in front and back of the ward, which realizes the separation of clean and dirty matter. . buffer rooms are set in front and back of the ward. buffer rooms are also set between the corridor and outdoors. these greatly increase the isolation fig. . plane layout of the isolation ward performance and safety. by adapted to local conditions, there is no obvious occupation of floor area. positive pressure should be kept in the buffer room . . the ward is set at one side, while the auxiliary rooms are set at the other side. the arrangement is uniform, which is good for usage and pollution control. . the opening direction for the door of the anterior should be opposite, since the pressure in the anterior is higher than that in the ward. "-" means there is no specific requirement, which needs to be determined by calculation or requirement and then tested; ( ) temperature in the buffer room should be the same as the entrance into the buffer room; ( ) when there is room for instrument and device, the temperature and air change rate should be determined by needs . air supply outlet should be placed on the ceiling above the middle of the two beds in the double-bed ward, which is beneficial to control the dispersion of pollutant. . since the leakage-free negative pressure high efficiency air exhaust device is installed at the return air grille, the return air can be switched on. because the bacterial removal efficiency of the hepa filter on the return air grille reaches more than . % and there is no leakage on the frame of air filter, one bacterium in the return air can penetrate through only when the indoor bacterial concentration reaches millions per cubic meter or even tens of millions per cubic meter. but the probability of this incidence is extremely small. . for the installation style of the fan coil unit on the ceiling, the problem for the accumulation and removal of condensation water once occurred should be solved. table . shows the design parameters of the negative pressure isolation ward for reference. aia, guidelines for design and construction of hospital and health care facilities isolation room and hvac design for sars rooms the safe distance of a biosafety lab considered from the angle of exhaust air diffusion introduction of cleanroom and design of its controlled environment key: cord- -oninjtsn authors: kowalski, wladyslaw title: commercial buildings date: - - journal: ultraviolet germicidal irradiation handbook doi: . / - - - - _ sha: doc_id: cord_uid: oninjtsn applications for uvgi systems in commercial buildings vary with the type of building, but virtually every type of building can benefit from the use of in-duct air disinfection and many buildings can benefit from the use of other types of uv systems. the health hazards and microbiological problems associated with various types of commercial buildings are often unique to the type of facility. the problem of air quality is paramount in commercial office buildings while the problem of biocontamination is of the highest concern in the food industry. other types of buildings have their own microbial concerns and even their own standards. the pharmaceutical industry has the highest aerobiological air quality standards (and lowest airborne microbial levels) while the other extreme, the agricultural industry, has the highest airborne microbial levels and unique aerobiological concerns. the individual problems of these facilities are addressed in the following sections, and industry experience relating to uv applications are discussed, along with recommendations for how uv systems can be applied. the specific types of uvgi systems are described in previous chapters and these should be referred to for detailed information on such applications. applications for uvgi systems in commercial buildings vary with the type of building, but virtually every type of building can benefit from the use of in-duct air disinfection and many buildings can benefit from the use of other types of uv systems. the health hazards and microbiological problems associated with various types of commercial buildings are often unique to the type of facility. the problem of air quality is paramount in commercial office buildings while the problem of biocontamination is of the highest concern in the food industry. other types of buildings have their own microbial concerns and even their own standards. the pharmaceutical industry has the highest aerobiological air quality standards (and lowest airborne microbial levels) while the other extreme, the agricultural industry, has the highest airborne microbial levels and unique aerobiological concerns. the individual problems of these facilities are addressed in the following sections, and industry experience relating to uv applications are discussed, along with recommendations for how uv systems can be applied. the specific types of uvgi systems are described in previous chapters and these should be referred to for detailed information on such applications. commercial buildings are the single largest and most common type of building in the united states today, in terms of total floor area. many common respiratory infections are regularly transmitted inside these structures due to daily occupancy and the extensive interaction of people within office buildings. proximity and duration of exposure are major factors in the transmission of respiratory infections between office workers (lidwell and williams ) . the risk of catching the common cold is increased by shared office space (jaakkola and heinonen ) . tuberculosis has also been show to transmit in office buildings between co-workers (kenyon et al. ). an association between respiratory tract symptoms in office workers and exposure to fungal and house dust mite aeroallergens was established by menzies et al. ( ) . the recent appearance of sars virus highlights the susceptibility of office workers to the spread of airborne viruses (yu et al. ) . sick building syndrome (sbs), often referred to as building related illness (bri) is a general category for a number of ailments, allergies, and complaints that are due to low levels of pollutants, synthetic irritants, fungi, bacteria or other factors that cause reactions in a certain fraction of building occupants (lundin ) . office buildings become contaminated with microbes brought in with the outside air as well as microbes that hail from indoor sources, including the occupants themselves. accumulation of microbes on the cooling coils and ductwork can contribute to indoor air quality problems (fink ) . the aerobiology of office buildings can depend on both indoor sources (i.e. occupancy and cleanliness) as well as the composition and concentration of microbes in the outdoor air. environmental microbes can enter via the ventilation system, via occupants (i.e. on clothes and shoes), and infiltration, especially from high-traffic lobbies that are under high negative pressure. office buildings provide an environment that sustains microorganisms long enough for them to transmit infections to new hosts, or sometimes allows them to persist indefinitely, as in the case of fungal spores (kowalski ) . the indoor airborne concentrations of bacteria and fungi increase with the presence of occupants, due to the fact that people release bacteria continuously and also because human activity stirs up dust that may contain fungi and bacteria. sessa et al. ( ) measured average office airborne concentrations of cfu/m for bacteria and cfu/m for fungi while levels were about four times lower when there were no occupants. most office buildings use dust filters in the merv - range to filter outdoor or recirculated air but these have a limited effect on reducing fungal spores, bacteria, and viruses. increasing filtration efficiency is one possible solution but retrofitting merv filters in the - range, which can be highly effective against most airborne pathogens and allergens, may be difficult in most buildings because of increased pressure losses and possible reduction in airflow (kowalski and bahnfleth ) . a suitable alternative to replacing filters is to add uv systems in the ductwork, which will not necessarily have any impact on airflow or pressure drop (see fig. . ). in-duct uvgi is the most economic approach to disinfecting the air of commercial office buildings provided there is space in the ventilation system. the economics of in-duct air disinfection can be greatly improved by locating the uv lamps at or around the cooling coils, thereby disinfecting the coils and improving their heat transfer capabilities. cooling coils can first be steam cleaned to remove biological contamination and then a uvgi system can be added to continuously irradiate the coils. this not only prevents existing microbial growth but will tend to restore cooling coils to their original design operating level of performance, thereby saving energy costs (kelly ) . another alternative for improving air quality in office buildings and reducing the incidence of disease transmission between office workers is to locate recirculating uv units or upper room systems around the building to deal with local problems. lower room systems may also be used to control microbial contamination at floor level, especially in hallways or lobbies that see heavy foot traffic. other applications of uvgi in office buildings may include overnight decontamination of kitchens, bathrooms, and storage areas with uv area disinfection units. uvgi may not be a complete solution to aerobiological problems if the cause is due to some other factor like moisture or water damage. for more detailed information on dealing with air quality problems in office buildings see kowalski ( ) . industrial facilities cannot be generalized in terms of the types of respiratory diseases to which workers may be subject because of their wide variety. industrial facilities that handle organic materials have greater microbiological hazards while those that process inorganic products usually have less microbial hazards and more pollution hazards. pollution, however, is a contributing factor in infectious diseases, including respiratory diseases. there are many types of occupational diseases, including asthma, and allergic reactions or hypersensitivity pneumonitis, which are not necessarily due to microbiological causes. air disinfection systems that use uv have little or no effect on non-microbiological contaminants but if pathogens or allergens are the cause of the problem then uv systems may be applied to reduce the hazard. airborne particulate dust in industrial environments may contain organic materials, chemicals, microbes, biological compounds, or inert materials, and form a substrate on which microbes can grow. allergen-bearing airborne particulates are causative agents of lung inflammation via their immunotoxic properties and can induce inflammatory alveolitis (salvaggio ) . occupational asthma occurs in - % of the asthmatic population and respiratory infection can be a predisposing factor for occupational asthma (bardana ) . workers who clean or enter rarely-used rodent infested structures may be at increased risk of exposure to rodentborne viruses such as hantavirus (armstrong et al. ) . industries that process wood or paper, or that make use of paper products, have airborne allergen hazards since cellulose provides a nutrient source for a variety of allergenic fungi. microbiological sampling in furniture factories found the most common airborne microorganisms included corynebacterium, arthrobacter, aspergillus, penicillium, and absidia (krysinska-traczyk et al. ) . microbiologial studies of the air in sawmills were conducted by dutkiewicz et al. ( ) , who found that the most common organisms were arthrobacter, corynebacterium, brevibacterium, microbacterium, bacillus spp., gram-negative bacteria (rahnella) and filamentous fungi (aspergillus, penicillium). inhalation anthrax and cutaneous anthrax still occur occasionally in the textile industry. in a mill in the usa where outbreaks had occurred, anthrax levels were measured at up to cfu/m (crook and swan ) . q fever, which can result from inhalation or exposure to coxiella burnetti, has been reported among workers in a wool and hair processing plant (sigel et al. ) . tuberculosis continues to be an occupational hazard in some parts of the world and is a growing problem elsewhere because of multi-drug resistance. in a study at russian plants by khudushina et al. ( ) the incidence of tuberculosis was highest at a foundry plant at . per , workers and in an automatic-assembly plant at . per , workers. health care workers, prison guards, and prison inmates may all be at higher risk for tuberculosis. a one-year prospective study of inmates in geneva showed that the prevalence of active and residual tuberculosis is - times higher among prisoners than in the general population (chevallay et al. ) . many prisons in the us incorporate filtration and uvgi systems to help control tuberculosis transmissions. occasional outbreaks of legionnaire's disease have continued to be sporadically reported in the work environment, including a large outbreak among exhibitors at a floral trade show where a whirlpool spa was on display (boshuizen et al. ) . water damage in any building increases the risk of workers to allergens if fungal mold growth has occurred. trout et al. ( ) documented extensive fungal contamination, including penicillium, aspergillus, and stachybotrys, in a water-damaged building. control measures for aerobiological contamination in the workplace are similar to those for any buildings in general, including improved air filtration, improved air distribution, and increased outside air combined with energy recovery systems. the use of uvgi for air disinfection can have positive benefits for almost any type of industrial building depending on the nature of the problem. in-duct uv air disinfection systems are likely to be the most economic recourse since they provide centralized control of the air quality, and can simultaneously be applied to the cooling coils (in most applications) to save energy while disinfecting the air. the use of local recirculation units can aid in resolving local microbial contamination problems, and both upper and lower room uvgi systems can be used to control biocontamination. the food industry comprises food and beverage processing facilities, food handling industries, food storage facilities other than agricultural, and kitchens in the restaurant and hospitality industry. there are at least four types of potential health hazards associated with food handling -foodborne human pathogens, spoilage microbes, microbial allergens, and food allergens. foodborne pathogens are generally transmitted by the oral route and almost exclusively cause stomach or intestinal diseases but some foodborne pathogens may be airborne at various stages of processing, storage, cooking, or consumption. the processing and handling of foods may also create opportunities for airborne mold spores to germinate and grow, resulting in secondary inhalation hazards. applications for uvgi in the food industry include both air and surface disinfection, including surface disinfection of packaging materials and food handling equipment. uv has been used for air and surface disinfection in cheese plants, bakeries, breweries, meat plants, for food preservation, and for the decontamination of conveyor surfaces, and packaging containers (koutchma ). one of the earliest applications of uv in the food industry involved the use of bare uv lamps to irradiate surfaces in the brewing and cheese making industries to control mold (philips ) . liquid food disinfection with uv has been approved by the fda but although uv has been highly effective for water disinfection, successful applications in disinfecting other liquids depends on the transmissivity of the liquid. the direct disinfection of food by uv is generally only effective in cases where only the surface of foodstuffs requires disinfection since uv has limited penetrating ability (fda , yaun and summer ) . some foods can be effectively disinfected of certain food spoilage microbes, and uv is most effective on food products that have smooth and clean surfaces (shama , seiler . uv irradiation can significantly reduce the mold population on shells of eggs in only min (kuo et al. ) . studies have demonstrated that uv can reduce levels of e. coli and salmonella on pork skin and muscle, listeria on chicken meat, and salmonella on poultry (wong et al. , kim et al. , wallner-pendleton et al. . begum et al. ( ) demonstrated that uv irradiation can inactivate food spoilage fungi like aspergillus, penicillium, and eurotium but that the type of surface impacted the degree of disinfection. marquenie et al. ( ) showed that botrytis cinerea and monilinia fructigena, two major post-harvest spoilage fungi of strawberries and cherries, could be reduced - logs by uv irradiation by doses of about j/m . stevens et al. ( ) reported that uv could effectively reduce the incidence of storage rot disease on peaches due to monilinia fructicola, reduce green mold (penicillium digitatum) on tangerines, and reduce soft rot due to rhizopus on tomatoes and sweet potatoes. liu et al. ( ) showed that tomato diseases caused by alternaria alternata, botrytis cinerea, and rhizopus stolonifer were effectively reduced by uv treatment. hidaka and kubota ( ) demonstrated a % reduction of aspergillus and penicillium species on the surfaces of wheat grain. seiler ( ) reported increases in mold-free shelf life of clear-wrapped bakery products after moderate levels of uv exposure. treatment of baked loaves in uv conveyor belt tunnels resulted in significantly increased shelf life (shama ) . valero et al. ( ) found that uv irradiation of harvested grapes could prevent germination of fungi during storage or the dehydration process for raisins, using exposure times of up to s. one specialized application of uv in the food industry involves overhead tank disinfection, in which the airspace at the top of a liquid storage tank is disinfected by uv to control bacteria, yeast, and mold spores. condensation of vapors in the head space of tanks, such as sugar syrup tanks, can produce dilute solutions on the liquid surface that provide ideal conditions for microbial growth. two types of tank top systems are in use -systems which draw the air through a filter and uv system and return sterilized air to the tank space, and systems in which uv lamps are located directly in the head space of the tank and irradiate the liquid surface and internal tank surfaces. see fig. . in chap. for an example of an overhead tank uv system. foodborne and waterborne pathogens represent the largest group of microorganisms that present health hazards in the food industry. in general, these do not present inhalation hazards, only ingestion hazards. however, some of these microbes can become airborne during processing and settle on foods, thereby becoming amenable to control by uv air and surface disinfection systems. modern foodborne pathogens are often uniquely virulent and hazardous, like salmonella and shigella, which are contagious and depend on either on excretion in feces or vomiting to facilitate epidemic spread. some agents of food poisoning, like staphylococcus and clostridium, are opportunistic or incidental contaminants of foods. many molds like aspergillus and penicillium are common contaminants of the outdoor and indoor air that can grow on food and although they are not food pathogens they are potential inhalation hazards for food industry workers. foodborne pathogens are predominantly bacteria but one virus has recently emerged and joined this class, norwalk virus. norwalk virus is a waterborne pathogen and has caused outbreaks on cruise ships (marks et al. ) . food spoilage microbes are less of a health hazard than they are a nuisance in the food industry because of the damage they can cause to processed food (samson et al. ) . a wide variety of yeasts may also be causes of spoilage. table . lists the most common foodborne and waterborne pathogens in the food industry along with the type of hazard they present -pathogenic, toxic, allergenic, or spoilage. many of the species listed in table . have uv rate constants as given in appendices a, b, and c. virtually all of the fungal spores listed in appendix c are potential contaminants in the food industry. toxins produced by microbes may be endotoxins, exotoxins, or mycotoxins, and these will grow only if the conditions (moisture, temperature, etc.) are right. the key to controlling these toxins is to control microbial growth and to control the concentration of microbes in the surrounding areas. ambient microbial levels can be controlled by food plant sanitation, adequate ventilation, and by various uv air disinfection technologies. most common food spoilage microbes have the capacity to transport in the air and therefore they are controllable to some degree by ventilation and by uv air disinfection systems. evidence exists to suggest listeria monocytogenes, a cause of many recent outbreaks, can settle on foodstuffs via the airborne route ( ) . studies indicate that salmonella can survive in air for hours (stersky et al. ). if air is recirculated through plant ventilation systems, organic material may accumulate inside ductwork and on air handling equipment, where fungi and bacteria may grow ( ). air filtration can go along way towards controlling the amount of organic debris that accumulates, but uv is an ideal technology for use in controlling microbial and fungal growth inside air handling units, ductwork, and on cooling coils. concerns about the breakage of bare uv lamps and mercury hazards has led to new lamps that are sealed in an unbreakable plastic coating, such as shown in fig. . . mold and biofilms can develop on surfaces and equipment in the food and beverage industry, including tanks and vats, cooking equipment, walls and floors, and cooling coils (carpentier and cerf ) . in general, standard cleaning and disinfection procedures are adequate to contain these problems but alternatives are available, including antimicrobial coatings like copper. uv irradiation of food processing equipment and surfaces, cooling coil disinfection systems, whole-area uv disinfection, and after-hours irradiation of rooms when personnel are not present are all viable options for maintaining high levels of disinfection in food industry facilities (philips , kowalski and dunn ) . uv air disinfection systems may also be useful in controlling airborne hazards that result from hazards are created by industrial food processes that forcibly aerosolize contaminants. pulsed uv light has seen increasing application in the food industry because of its rapid disinfection capabilities -see chap. for more information. educational facilities for children and students are focal points for disease transmission and as such they are ideally suited to uv applications that inhibit the transmission of contagious diseases. the concentration of young people in rooms causes cross-infections when even a single child comes to school with an infection such as a cold or a flu. inevitably children who attend school bring home contagious infections which are then transmitted to family members, thereby continuing the process of epidemic spread in the community. there are basically five types of educational facilities for children and students: day medical schools and colleges have also been subject to outbreaks of mumps and respiratory syncytial virus (rsv). table . summarizes many of the various common infections that have been associated with school facilities, with reference sources as indicated. many of the microbes in table . are susceptible to uv disinfection in air and on surfaces (see the uv rate constants for these species given in appendix a). fungal spores also accumulate in schools and are responsible for a variety of respiratory illnesses including allergies and asthma. the most frequently encountered fungal taxa identified in a study of dust samples from twelve schools in spain were alternaria, aspergillus, and penicillium (austin ) . guidelines for ventilation air in school buildings are provided in ashrae standard - (ashrae ) but many schools do not meet the minimum recommendations either because the buildings are older or because of attempts to save energy costs due to endless budget cutting. one way to make up for the lack of ventilation air is to provide uv air disinfection systems, including upper room systems and in-duct uv systems. a number of studies have been performed in schools to evaluate the effectiveness of uvgi systems on respiratory infections in schools. all of these studies involved upper room systems (see chap. for a summary of the results). most of the studies produced a reduction of disease transmission with a net average reduction in respiratory infections of approximately %, and were effective against measles, mumps, varicella, chickenpox, cold viruses and other respiratory infections. upper room systems can be especially effective in classrooms that have little of no ventilation air and that have high ceilings. there are no studies that have addressed in-duct uvgi systems, which would be likely to prove even more effective if they were adequately designed. materials and books that are kept in museums, libraries, and related archives may be both a source of allergens and a nutrient source for the growth of microorganisms, especially fungi. the growth of fungi and certain bacteria on stored materials contributes to biodeterioration, which is a major concern, and the aerobiology in bahlke ( ) museums and libraries may impact both the occupants as well as the stored materials. most books are made from cellulose and can be degraded by a variety of microbes and insects which may include allergens and a few potential pathogens. over microbial genera, representing species, have been isolated from library materials like books, paper, parchment, feather, textiles, animal and vegetable glues, inks, wax seals, films, magnetic tapes, microfilms, photographs, papyrus, wood, and synthetic materials in books (zyska ) . many of the fungi identified in library materials can produce mycotoxins and cause respiratory and other diseases. table . summarizes the variety of microbes that have been found in libraries and museums, and indicates the type of materials that they can grow on. the term 'deteriogen' in the table refers to microbes that can cause biodeterioration of materials. libraries often use carpeting to quiet the noise of foot traffic, but carpets tend to accumulate fungi and bacteria over time due to the fact that they settle in air or are brought in from the outdoors on shoes and clothes. in one study of carpeted buildings, carpet dust was found to contain , cfu/gm of fungi, , , cfu/gm of mesophilic bacteria, and , cfu/gm of thermophilic bacteria (cole et al. ) . foot traffic tends to aerosolize microbes and causes them to settle in other locations, including on books and materials. aerosolized microbes can also be inhaled, leading to allergies and asthma. carpets have a high equilibrium moisture content that favors microbial growth (iea ) . fabrics kept in museums, especially ancient cloth, are subject to biodeterioration from fungi and bacteria. fungi can grow extensively on cotton fibers at the right humidity and growth rates are highest on % cotton (goynes et al. ) . studies of biodeterioration caused by fungi that grow on paintings have isolated over one hundred species of fungi, with the most common species being alternaria, cladosporium, fusarium, aspergillus, trichoderma, and penicillium (inoue and koyano ) . ultraviolet light is an option for disinfecting surfaces and materials, but it can cause damage and discoloration to pigments and paint and therefore is not necessarily suitable for decontaminating books that are already damaged by microbial growth. uvgi is best used for disinfecting the air and especially for removing mold from air conditioning systems. in-duct uvgi can greatly aid in reducing airborne levels of bacteria and spores and in removing accumulated mold spores from air conditioning cooling coils, which are used extensively to control humidity in libraries and museums. keeping cooling coils disinfected will minimize the spread of spores through a building as well as reducing energy costs (see chap. ). uvgi systems can be used selectively in areas of museums and libraries that do not contain sensitive materials, such as cafeterias. lower room uv systems may also be ideal for hallways and entryways (where no materials are stored) where outdoor spores may be tracked into buildings. for more detailed information on technologies and techniques for dealing with biocontamination of sensitive materials in libraries and museums see kowalski ( ) . agricultural facilities pose a variety of occupational microbial hazards including infectious diseases from farm animals, allergies from animal dander and foodstuffs, and health threats from mold spores or actinomycetes. animal facilities like barns, poultry houses, swine houses, and kennels can have the highest levels of bioaerosols seen in any indoor environments. animal facilities may also include non-agricultural buildings used to house or service animals such as pet shelters and zoos. many animal pathogens can transmit to humans by direct contact or by the airborne route. the microorganisms of greatest concern are those that can become airborne in animal facilities and these are often respiratory pathogens and allergens. allergens can be produced as a byproduct of animal husbanding or from animal waste, animal feeds, or other farm produce. the actinomycetes are particularly common type of bacteria found in agriculture and can grow on moldy hay. farmers may be routinely exposed to very high concentrations of actinomycetes and may inhale as many as , spores per minute (lacey and crook ). farmer's lung represents a group of respiratory problems that often afflict farm workers who receive chronic exposure to high concentrations of actinomycetes (pepys et al. ) . table . lists some of the most common microorganisms that occur in animal and agricultural environments, and that can transmit to man by various routes. the diseases caused and natural source are identified. for information on the uv susceptibility of these microbes see appendices a, b, and c. most of these microbes can transmit by direct contact or by the airborne. table . provides a list of microbes found in sewage, many of which can become airborne. natural ventilation is common in agricultural facilities but mechanical ventilation will generally provide superior control of airborne microorganisms. however, filtration is often necessary to clean both outdoor air and indoor recirculated air. recirculated air in animal facilities can be cleaned more effectively through the use of uvgi combined with filtration, and this approach works well for viruses, which may not filter out easily. other applications for uvgi in animal facilities include upper room systems, and area disinfection systems. after-hours uv disinfection systems are also appropriate for animal facilities provide the animals can be periodically removed from bacteria pathogen the indoor areas in order to disinfect them. such an approach can be more economical than scrubbing with disinfectants, and can enhance the effectiveness of manual scrubbing procedures. for more detailed information on dealing with the complex bioaerosol and dust problems in agricultural and animal facilities see kowalski ( ) . facilities like malls and airports are characterized by large enclosed volumes where large crowds may be concentrated and where heavy cyclical occupancy may occur. places of assembly may include auditoriums, stadiums, theaters, gymnasiums, natatoriums, arenas, town halls, churches, cathedrals, temples, mosques, industrial halls, convention centers, atriums, shopping centers, and other places where large public gatherings may occur indoors. in such buildings infectious diseases may be exchanged by direct contact, indirect contact, or via inhalation, and large numbers of people may be exposed simultaneously. the large volumes of air enclosed in such facilities often ensure good mixing of air, even in naturally ventilated stadiums, and as a result the air quality is often acceptable. however, it is difficult to provide ventilation to all corners and therefore the actual airflow distribution is often uncertain. one of the most famous outbreaks of a respiratory disease in a heavily occupied building was the eponymous legionnaire's disease outbreak at a convention in philadelphia in that resulted in deaths (spengler et al. ) . it was traced to legionella contamination in a cooling tower that apparently wafted from outdoors into a crowded hallway through open doors. an outbreak of measles occurred inside a domed stadium in the minneapolis-st. paul metropolitan area during july that resulted in sixteen associated cases of measles in seven states (ehresmann et al. ) . several tuberculosis outbreaks have occurred in churches and mosques due to a single infectious person. dutt et al. ( ) reports one outbreak of tb in a church where one man exposed % of his congregation. a norovirus outbreak at a concert hall was reviewed by evans et al. ( ) in which a concert attendee who vomited in the auditorium and a toilet. gastrointestinal illness occurred among members of school children who attended the following day. transmission was most likely through direct contact with contaminated fomites that remained in the toilet area. large facilities that use % outside air provide little or no opportunity for the use of uv systems, since outside air is generally clean and free of airborne pathogens, but facilities that recirculate air may benefit from in-duct uv air disinfection systems. large facilities often have high ceilings and this provides an opportunity to use upper room systems for air disinfection, especially in cases where natural ventilation is employed and there is no other means for disinfecting the air. high power uv systems can be safely used in such applications since the uv lamps can be located far from the occupied floor areas. the use of uv area disinfection systems in public toilets is an appropriate means of dealing with potential fomites, or infectious particles left on surfaces. aircraft, trains, cars, and other compact enclosed environments can pose microbiological hazards from extended exposure due to the fact that risks due to proximity are increased regardless of whether the pathogen transmits through the air or by direct contact. large cruise ships may resemble hotels and apartment buildings in terms of their ventilation systems and health risks but smaller craft like cars and planes create extended opportunities for infectious exchanges due to the close quarters, shared breathing air, potentially extended periods of occupancy, and the limited amount of outside air that may be brought in, especially in cold climates. other microenvironments like elevators and city buses are unlikely to play a major role in the spread of contagious diseases due to their brief occupancy times. aircraft are one of the most crowded environments in which people remain for extended periods of time and the potential for airborne disease transmission is fairly obvious, except perhaps to airline owners who fly in private jets. airplanes are potential vectors for the transmission of airborne diseases between continents and play a role in the global dissemination of epidemic diseases (masterson and green ) . airline crews and passengers have a higher risk of contracting infections on long flights (nrc , ungs and sangal ) . respiratory pathogens that have been identified onboard airlines include adenovirus, chickenpox, coronavirus, influenza, measles, mumps, mycobacterium tuberculosis, neisseria meningitidis, and sars virus (kowalski ) . it has been reported that % of newer airplanes have hepa filters (gao ) . however, there is a common practice in the industry of referring to merv filters ( % dsp filters) as 'hepa-like' or 'hepa type' filters, which is misleading. merv filters, while being excellent filters for controlling spores and most bacteria, cannot guarantee protection against viruses and smaller bacteria. coupling a merv filter with a uvgi system can, however, can provide superior performance (kowalski and bahnfleth ) . furthermore, the energy costs associated with using hepa filters may not be justified when a simple combination of a merv - filter and an urv - uvgi system will provide comparable results at lower cost. uvgi systems can be installed in the recirculation ducts of airplanes as well as being located at individual seats (in the overhead 'gaspers'). the transmission of infectious disease aboard ships is a recurring phenomenon, with onboard transmission of some diseases such as norwalk virus and legionnaire's disease being favored. the incidence of respiratory disease aboard military ships increases as ship size decreases (blood and griffith ) . a study of a tuberculosis outbreak aboard a navy ship found that although proximity and direct contact played a role in transmission, airborne transmission of droplet nuclei, including via the ventilation system, was responsible for most of the secondary infections (kundsin ) . it is common for outbreaks aboard ships to consist of multiple viral and bacterial infections, including diarrheal illness and influenza (ruben and ehreth ) . noroviruses are responsible for million cases of illness each year and norwalk viruses have recently caused numerous outbreaks of gastroenteritis on cruise ships. they are largely attributed to fomites on ship surfaces. during , cruise ships with foreign itineraries sailing into us ports reported gastroenteritis outbreaks on cruise ships, of which most were identified as noroviruses (cramer et al. ) . in an influenza outbreak aboard a cruise ship from hong kong in , % of passengers came down with acute respiratory illnesses (berlingberg et al. ) . uv applications for ships include in-duct uv systems to interdict recirculated pathogens and allergens, and surface irradiation systems to control fomites. noroviruses may be particularly susceptible to after hours uv systems placed in hallways, bathrooms, and other locations where occupancy is intermittent. cruise ships can also be irradiated and decontaminated between voyages by portable uv systems. most of the microorganisms associated with waste are either water borne or food borne pathogens and allergens and workers in sewage, wastewater, and waste processing industries are subject to occupational hazards from these microbes. airborne hazards also exist since aerosolization of microbial pathogens, endotoxins, and allergens is an inevitable consequence of the generation and handling of waste material. table . lists the most common microorganisms that have been found to grow or to occur in sewage and waste (kowalski ) . many of these are human pathogens and they include bacteria, viruses, fungi, and protozoa. for information on the uv susceptibility of these pathogens refer to appendix a, which addresses most of these species. many of these species are potentially airborne and can cause respiratory infections, while most of the remainder are either waterborne or foodborne stomach pathogens. wastewater treatment workers are exposed to a variety of infectious agents and khuder et al. ( ) examined the prevalence of infectious diseases and associated symptoms in wastewater treatment workers over a -month period. the wastewater workers exhibited a significantly higher prevalence of gastroenteritis, gastrointestinal symptoms, and headaches over those in a control group but no significant differences were found with regard to respiratory and other symptoms. thorn et al. ( ) , however, found that sewage workers had significantly increased risks for respiratory symptoms, including chronic bronchitis, and toxic pneumonitis, as well as central nervous system problems, over workers in non-sewage industries. reduction of microbial hazards in the sewage and waste industries is probably best approached using source control methods, but there are potential applications for uvgi. in-duct air disinfection can promote healthier breathing air for workers inside plants and both upper room and lower room uvgi systems can provide disinfection of both air and surfaces where mold and bacteria may accumulate. area disinfection systems, like after-hours uv systems, may also provide a means of decontaminating areas during periods when they are not occupied (i.e. overnight). hantavirus pulmonary syndrome associated with entering or cleaning rarely used, rodentinfested structures standard : ventilation for acceptable indoor air quality pathogens in the environment effect of ultra-violet irradiation of classrooms on spread of mumps and chickenpox in large rural central schools occupational asthma and allergies rhinovirus infections in nursery school children inactivation of food spoilage fungi by ultraviolet (uvc) irradiation listeria: a practical approach to the organism and its control in foods acute respiratory illness among cruise ship passengers -asia epidemiology of adenovirus-associated virus infection in a nursery population ship size as a factor in illness incidence among u.s. navy vessels subclinical legionella infection in workers near the source of a large outbreak of legionnaires disease prevalence of mycoplasma pneumoniae in children in diyarbakir, the south-east of turkey biofilms and their consequences, with particular reference to hygiene in the food industry epidemiology of pulmonary tuberculosis in the prison environment biocontaminants in carpeted environments outbreaks of gastroenteritis associated with noroviruses on cruise ships -united states bacteria and other bioaerosols in industrial workplaces high pharyngeal carriage rates of streptococcus pyogenes in dunedin school children with a low incidence of rheumatic fever microflora of the air in sawmills as a potential occupational hazard: concentration and composition of microflora and immunologic reactivity of workers to microbial aeroallergens outbreak of tuberculosis in a church an outbreak of measles at an international sporting event with airborne transmission in a domed stadium an outbreak of viral gastroenteritis following environmental contamination at a concert hall ultraviolet radiation for the processing and treatment of food. food and drug administration mold in air conditioner causes pneumonitis in office workers more research needed on the effects of air quality on airliner cabin occupants seroepidemiological studies on the occurrence of common respiratory infections in paediatric student nurses and medical technology students a study of whooping cough epidemic outbreak in castellon biodeterioration of nonwoven fabrics prospective study of respiratory infections at the u.s. naval academy silent passage of echo virus type together with dyspepsia coli strains in a day nursery school study on the sterilization of grain surface using uv radiationdevelopment and evaluation of uv irradiation equipment an outbreak of scarlet fever, impetigo and pharyngitis caused by the same streptococcus pyogenes type t m in a primary school heat and moisture transfer: international energy agency pleurodynia among football players at a high school. an outbreak associated with coxsackievirus b fungal contamination of oil paintings in japan shared office space and the risk of the common cold frequency of serological evidence of bordetella infections and mixed infections with other respiratory pathogens in university students with cough illnesses shedding some light on iaq transmission of mycobacterium tuberculosis among employees in a us government office prevalence of infectious diseases and associated symptoms in wastewater treatment workers the optimal system of ambulatory examination of groups with high risk of tuberculosis at a large industrial plant transmission of mycobacterium tuberculosis among high school students in korea effects of uv irradiation on selected pathogens in peptone water and on stainless steel and chicken meat current trends in uvgi air and surface disinfection merv filter models for aerobiological applications aerobiological engineering handbook: a guide to airborne disease control technologies exposure to airborne microorganisms in furniture factories airborne contagion uv irradiation of shell eggs: effect on populations of aerobes, molds, and inoculated salmonella typhimurium fungal and actinomycete spores as pollutants of the workplace and occupational illness the epidemiology of the common cold application of ultraviolet-c light on storage rots and ripening of tomatoes on building-related causes of the sick building syndrome evidence for airborne transmission of norwalk-like virus (nlv) in a hotel restaurant inactivation of conidia of botrytis cinerea and monilinia fructigena using uv-c and heat treatment dissemination of human pathogens by airline travel pharyngitis associated with herpes simplex virus in college students aeroallergens and workrelated respiratory symptoms among office workers illness among schoolchildren during influenza season: effect on school absenteeism, parental absenteeism from work, and secondary illness in families the airliner cabin environment and the health of passengers and crew rheumatic fever-is it still a problem? farmer's lung: thermophilic actinomycetes as a source effect of ultra-violet irradiation of classrooms on the spread of measles in large rural central schools public health management of an outbreak of group c meningococcal disease in university campus residents maritime health: a case for preventing influenza on the high seas inhaled particles and respiratory disease introduction to food and airborne fungi prevalence, rate of persistence and respiratory tract symptoms of chlamydia pneumoniae infection in kindergarten and school age children preservation of bakery products microbiological indoor air quality in healthy buildings ultraviolet light q fever in a wool and hair processing plant indoor air quality handbook viability of airborne salmonella newbrunswick under various conditions integration of ultraviolet (uv-c) light with yeast treatment for control of post harvest storage rots of fruits and vegetables work related symptoms among sewage workers: a nationwide survey in sweden bioaerosol lung damage in a worker with repeated exposure to fungi in a water-damaged building flight crews with upper respiratory tract infections: epidemiology and failure to seek aeromedical attention effect of germicidal uvc light on fungi isolated from grapes and raisins foreign body prevention, detection and control the use of ultraviolet radiation to reduce salmonella and psychrotrophic bacterial contamination on poultry carcasses tb in leicester: out of control, or just one of those things reduction of escherichia coli and salmonella senftenberg on pork skin and pork muscle using ultraviolet light efficacy of ultraviolet treatments for the inhibition of pathogens on the surface of fresh fruits and vegetables evidence of airborne transmission of the severe acute respiratory syndrome virus strains of parainfluenza virus type , isolated in a day nursery fungi isolated from library materials: a review of the literature key: cord- - ag eskv authors: xu, zhonglin; zhou, bin title: three misunderstandings for design of negative pressure ward date: - - journal: dynamic isolation technologies in negative pressure isolation wards doi: . / - - - - _ sha: doc_id: cord_uid: ag eskv with the severe situation for the appearance of sars and the fear for the resultant consequence, at the early stage of the outbreak event wards were reconstructed with a simple way. newly constructed isolation wards were designed according to related literatures issued by cdc in , and the corresponding requirements were elevated blindly. in literatures, the technical measures related to negative pressure isolation ward was inclined to adopt high negative pressure, air-tight door and all fresh air, where it was considered safe only to increase the negative pressure as high as possible, to install air-tight door without infiltration air and to provide all fresh air. the so-called high negative pressure means that negative pressure should be kept between isolation ward and corridor or adjacent room. the negative pressure drop should be as high as dozens of pascal. it is meant to prevent the release of hazardous indoor air from flowing outwards. is it really effective to prevent the leakage of airflow outwards? is it better to adopt higher pressure drop? the positive pressure inside the ward could be utilized to prevent the invasion of infectious air through the gap into the ward, which is shown in fig. . . the negative pressure inside the ward could be applied to prevent the release of infectious air through the gap towards outside of the ward, which is shown in fig. . . the effect of pressure difference on the prevention of leakage though the gap appears only when all the openings between the isolation ward and the adjacent rooms are closed. therefore, the pressure difference is only the main measures to realize static isolation. this characteristic of the pressure difference is based on the time characteristic of the pressure difference. if the door is open, the pressure difference disappears. in total, the pressure of air at both sides reaches equilibrium. figure . illustrates the experimental result performed by a japanese scholar [ ] . results showed that for a room with the pressure difference of − pa from the outside, the pressure difference would decrease to within s when the inwardly opened door was open. for outwardly opening door and sliding door were open, the period for this decrease of pressure difference could be prolonged to s. all of them illustrate that there is no effect of pressure difference when door is open. it was also pointed out in the handbook of ashrae in that the original pressure difference between two regions would reduce to zero instantaneously when the door or the closed opening between two regions was open [ ] . therefore, it was confirmed in "guidelines for preventing the transmission of mycobacterium tuberculosis in healthcare facilities" issued by the centers for disease control and prevention (cdc) in u.s.a. in that "the crucial problem is to keep the door and the window between isolation ward and other region closed, except the case when people go inward or outward". it should be noted that here it only mention the state of close, not the sealing condition, which will be explained later. so the main purposed of the pressure drop is only limited to the static state of the closed openings. during the instantaneous moment for dynamic opening of door, the pressure drop is converted into the kinetic energy of airflow through the opening. the magnitude of airflow velocity reflects the ability to prevent the entrance of pollutant, which is not dependent on the magnitude of original pressure difference. for the given flow rate with compensation of pressure difference, the value of airflow velocity is fixed. in the past, there is an incomplete understanding that for isolation ward, isolation cleanroom and biosafety laboratory, the principle of isolation mainly depended on the effect of gradient of negative pressure (i.e., the negative pressure difference). the negative pressure was considered as the sole measures to prevent the release of pollutant outwards for isolation ward and biosafety laboratory. in the early study, we have investigated and found the instantaneous influence of opening and closing of doors and the entrance and exit of people on the counteracting effect by the pressure difference [ ] . further detailed investigation for the principle of isolation ward was carried out after the outbreak of sars [ ] . in the above-mentioned ashrae handbook, positive and negative pressure could also be considered as the measures to resist other factors. because of the opening of doors, movement of workers and patients, temperature difference, and the stack effect exaggerated by straight pipeline, elevator shaft and vertical ventilation shaft, it is difficult to control airflow reasonably between rooms. when some factor becomes larger than the actual controlled range, the influence of these factors could be minimized through the modification during the design of positive and negative pressure values in some rooms or regions. it has been pointed out by author that this incomplete understanding is caused because that they do not understand the invasion or release of pollution and they do not know that the pressure is not the sole factor [ ] . this can be analyzed from two aspects as follows. ( ) on the one hand, the air velocity through the door openings by the pressure difference is very small, which could not prevent the outward leakage or invasion of pollutant after the door is open. the flow rate of leakage through gap could be derived further by the air velocity through the gap, i.e., where l is the flow coefficient. it is usually between . and . , so we can use . . f is the area of the gap, m . dp is the pressure difference, pa. q is the air density, which can be assumed . kg/m . table . illustrates the flow rate of leakage for a room with area m under the condition of different pressure drops. in this room, the dimension of the gap on the air-tight door is m  . m, while that on the non air-tight door is m  . m. the dimension of the gap between the air-tight window and the delivery window is m  . m. the size of the gap on the wooden partition board is m  . m. it is shown in table . that when the non air-tight door is open, because of the high pressure difference (dp = − pa), the air flow rate of leakage in the whole room is converted into the flow rate of entrance air through the gap which is only . m /s. when air-tight door is open, it becomes . m /s, which corresponds to the average air velocity through door opening . m/s. it is larger than the convection velocity resulting from the temperature difference . °c by . m/s, which is very small and will be mentioned later. if the negative pressure difference is − pa, the resultant velocity will be much smaller than the convection velocity. therefore, it is essentially a subjective judgment to consider that "for a room with negative pressure when doors are closed, the flow rate during the opening of door mainly depends on the magnitude of negative pressure difference [ ] ". because of the small flow rate, the effect to prevent pollution dispersion by pressure difference is limited. therefore, it is also pointed in ref. [ ] by foreign researchers that negative pressure should be kept inside isolation room, but the table . shows the experimental data when atmospheric dust was applied to study the isolation room by chinese researchers [ ] . in the experiment, the following steps were adopted. at first, full fresh air without air filtration was ventilated through the ward, so that the stable high concentration of dust was reached. negative pressure difference was kept in ward related to buffer room. positive or zero pressure difference was maintained in buffer room related to outdoors, so that there was no disturbance of high concentration outdoors on buffer room. at first this value of negative pressure difference was ignored. although the negative pressure difference was only less than pa, the concentration inside buffer room was comparable to that of outdoors, which corresponds to condition in table . . table . shows the experimental data on the influence of the magnitude of the negative pressure difference on the outward leakage rate of pollution during the opening process of doors. this experiment was carried out in the same laboratory [ ] . enough time was provided for the self-purification of the buffer room, so that it reached the designed iso air cleanliness level. then the experiment for the opening and closing of doors within s was performed. in order to avoid the influence of supply air, indoor vortex and opening/closing of doors on the measurement of pressure difference, which should be paid attention to especially for small room, exterior hood should be placed at the original test hole and the vent hole should be set beneath the hood, which is shown in fig. . . the following conclusions can be obtained from table . : (a) as long as the relative pressure difference between the ward and the buffer room is not positive, there is no leakage of pollution outwards to the buffer room under the condition of door closing, even when the pressure difference is max. value appears at the st minute zero. the particle concentration inside the buffer room reached the level comparable with that after self-purification, which was about . % of the concentration in the ward. there was no trend of increase for the particle concentration in the buffer room when the pressure difference is zero. on the contrary, this appears the different trend which was related to the residual influence by door opening, entrance and exit of people. (b) under the condition of the same original particle concentration, when the negative pressure difference changed from to − pa, the maximum outward leakage of pollution was converted from pc/l at pa to pc/l at − pa, which was equivalent to the reduction rate of %. when the pressure difference changed from to − pa, the reduction rate was %. table . shows the dimensionless concentration ratio in outward leakage airflow, which was related to the subtraction of the background concentration from the stable concentration in outward leakage airflow. it is shown from , which did not match the variation of pressure difference. (c) when no people exits or enters with door opening and closing, the difference between the cases and pa is trivial. figure . vividly shows the relationship between the outward leakage concentration ratio and the pressure difference [ ] . if no people enters or exits, the relationship of variation is quite gentle. if people enters or exits, the variation becomes abrupt even when the pressure difference is only less than pa. this phenomenon is understandable. the same characteristic appears in the above experiment and the experiment performed by japanese scholar [ ] . in the latter experiment, the operation of addition of g additive was performed in a negative pressure room. after min, it was considered that released particles from operation had been dispersed evenly in the room. then the particle concentration at the return air opening was measured, until it recovered to the original concentration. based on the increased concentration value and the flow rate of return air, the released particle number could be obtained. in this experiment, the number of generated particles each time was .  pc. then the door was open and closed. once the door was closed, occupant walked towards the return air opening and measured the particle concentration near the return air opening in the corridor. the method was the same to the above-mentioned one. the relationship between the pressure difference and the dispersion of pollutant particles is shown in fig. it is shown in this figure that with the increase of the negative pressure difference value indoors, the number of particles dispersed outwards during opening and closing of doors reduces slightly. the sequence of the number of dispersed particles is that outwardly opening door > inwardly opened door > sliding door. according to the data provided directly from this literature, when the value of negative pressure difference between indoors and corridor increased from pa to − pa, the number of particles invading indoors each time during opening and closing of door varied from .  pc to .  pc for outwardly opening door, from .  pc to .  pc for inwardly opened door, from .  pc to .  pc for outwardly opening door, respectively. it could be estimated from fig. . that when the value of negative pressure difference varied from pa to − pa, the maximum reduction of dispersed particles was about %, which is comparable to % obtained by our experiment shown in table . . when the pressure difference changed from pa to − pa, the reduction of dispersed particles was about %, which is comparable to % obtained by our experiment shown in table . . therefore, it is obvious that no matter whether the pressure difference changes from to − pa, or even − pa, the phenomena of outward leakage of pollution cannot be prevented completely the test with experimental bacteria also proved this conclusion [ ] , which will be introduced later in the chapter about buffer room. colored b. subtilis spores were generated in the ward. the cfus in the ward were measured when the pressure difference between the ward and the exterior buffer room was − and pa, respectively. the cfu in the buffer room was then measured after people left the ward and entered into the buffer room by opening the door for once time. the temperature differences under two pressure difference values were almost the same. result showed that the cfu was not inversely proportional to the pressure difference. the influence of the pressure difference on cfu was little, which is shown in table . . in order to prevent the leakage of experimental bacteria outwards from the buffer room, negative pressure difference should be maintained between buffer room and outer room. there are no experimental bacteria in outer room. this is different from the before-mentioned test with atmospheric dust. ( ) on the other hand, the pressure difference is not the sole factor for the dispersion of pollutant. temperature difference also exists for such effect. with daily experience, air flows in and out with the effect of temperature difference, which cannot be weakened or offset by pressure difference. this will be explained later in detail. therefore the pressure difference is not the only measures to prevent the invasion or outward leakage of pollution. therefore, it is not only the pressure difference which plays a role in the isolation principle inside isolation ward, isolation cleanroom and bio-safety laboratory. as a result, it is indeed a misunderstanding that large negative pressure difference value must be maintained for negative pressure isolation purpose. it takes for guaranteed that door must be very air-tight in order to prevent the accidental outward leakage of pollutant airflow from indoors. here we do not assume that the pressure indoors is positive. even though the pressure difference indoors is positive and the door is air-tight, exchange of pollution airflow cannot be prevented during dynamic condition, such as opening and closing of doors. of course, in the static condition, i.e. when the door is closed, exchange of airflow can be guaranteed when sealing with good performance is provided on the gap. however, it should be noted that the door of the ward would be open frequently. the influence of door closing and opening on transmission of pollutant between indoors and outdoors is explained as follows. ( ) when the pressure indoors is negative and the outwardly opening door is open, air is pushed by the front face of the door, and the negative pressure formed temporarily in the movement region of door may be much lower than the negative pressure indoors. in this case, indoor air is likely to escape outwardly during the opening of doors. ( ) when the pressure indoors is positive and the inwardly opened door is open, air is also pushed by the front face of the door, and the pressure in the movement region of door becomes negative temporarily. in this case, outdoor air may also be sucked inwardly during the opening of doors. the above-mentioned phenomenon is termed as the entrainment effect by door. in , wolfe et al. also paid attention to it [ ] , which is shown in fig. . . it was pointed out that the quantity of the sucked air by opening of door for once time in room with positive pressure was about . m /s. because the negative pressure is formed by the external force from the movement of door opening, there is no air balance between entrance into and exit from the room. therefore it can be assumed that it does not necessarily sound good for the practice to open door outwardly for negative pressure room, or open door inwardly for positive pressure room. according to our measurement, the air velocity induced by opening of door without occupant passing through is between . and . m/s [ ] . suppose the area for door opening reaches . m , the quantity of entrained air is between . and . m /s, which is slightly larger than that estimated by wolfe. for the airflow with such large velocity, the generated airflow through the whole door opening cannot withstand it by the positive pressure from outdoor air or by the negative pressure from exhaust air. the air tightness of door belongs to the static performance of door, which the entrainment performance of door is mainly related to the dynamic characteristic of door. the dynamic characteristic of door means the feature of counter current, pressure difference, air velocity at the entrance of door, and the transmission of pollutant between indoors and outdoors during the instantaneous opening and closing of door. the counter current is the airflow from negative pressure room to positive pressure room, or the airflow from low pressure room to the high pressure room. based on the observatory laboratory with no temperature difference but with pressure difference shown in fig. . , japanese scholars performed investigation on the dynamic characteristic on three kinds of doors shown in fig. it is shown from the above figure that for the common side hung door, there must exit one phenomenon of strong visible counter current under four stages. this means people are able to see clearly the air flows in the way that it should be prevented. in this case, the isolation performance of air-tight door does not exist. the cost of air-tight door is very high. if interlock function is added, dangerous accident will occur once it is malfunctioned, which has already appeared in the past. the entrainment by occupant is inseparable from the entrainment by door. it is found from measurement that the air velocity reaches the maximum during the instantaneous period of door opening when occupant walks in or out. this instantaneous air velocity lasts for about s. experiment [ ] has shown that when occupant walks along the direction of door opening, the air velocity at the entrance is about . - . m/s; when occupant walks against the direction of door opening, the air velocity becomes . - . m/s. suppose the dimension of occupant is . m  . m, the maximum flow rate by occupant entrainment is . m /s. this phenomenon is termed as the effect of entrainment by occupant. wolfe has also discovered this, which is shown in fig. . [ ] . it has been introduced in previous chapter on pollution of negative pressure isolation ward that pollution cannot be dispersed outwardly when door is closed. however, door will be opened and closed frequently. during door opening and closing, pollution will be exchanged between indoors and outdoors under the influence of temperature difference. china academy of building research has performed the specific research on this aspect. based on the measurement results by different people, the phenomena by temperature difference are described under six conditions. there conditions are shown in figs the above-mentioned figures are summarized into table . . values of Δt and Δp at the right workshop are used as baselines [ ] . the following conclusions can be obtained from table . . ( ) when there is no temperature difference between indoors and outdoors, the direction of airflow complies with the direction of the pressure difference. when the pressure indoors is positive, the air flows outwardly, and vice versa. ( ) when there is temperature difference between indoors and outdoors, the direction of airflow mainly complies with the direction of the temperature difference. when the temperature indoors is larger than outdoors, or even the temperature difference is as small as . °c, the air flows outwardly at the upper region and inwardly at the lower region. for the case with small temperature difference, the region of convective airflow is small. when the temperature indoors is less than outdoors, or even the temperature difference is as small as − . °c, the air flows inwardly at the upper region and outwardly at the lower region. for the case with small temperature difference, the region of convective airflow is small. ( ) when the air supply outlet or return air opening is close to the door, or when the air velocity of supply is so large that it impacts the floor, their influence on convective flow by temperature difference is much larger than the influence by pressure difference. where q is the flow rate of the supply air; q is the flow rate of the leakage air sucked into or exhausted out of the room through the gap or hole of the gate; q is the flow rate of the return air or that of the exhaust air. after the door is open, convective flow occurs under the influence of temperature difference. indoor cold air flows outwardly through the upper region of the door opening, so there must be the same amount of cold air flowing inwardly through the lower region of the door opening. this can provide the balance between the air change rate and the pressure difference. in this case, we obtain: for pure convective flow by temperature difference, the principle of natural ventilation works. the area of intake flow is considered to be the same as that of the outtake flow. in the middle of the door opening, there is a interface where the interior and exterior pressures are the same, which is termed as the neutral plane. it is shown at the position labeled with in fig. . . on the intake and outtake flow planes, the pressure difference caused by the density difference can be expressed as: where g is the gravitational acceleration, m/s ; h is the height between centers of intake and outtake planes, m; h = h/ , and h is the height of door opening, m; q is the density for the intake flow or outtake flow, kg/m , which is shown in table . ; Δq is the density difference of air, kg/m . because the temperatures of intake and outtake flows are different, the density q of hot air is small, so v is large. while the density q of cold air is large, so v is small. since the thermal pressure is very small, illusion will be formed that the thermal prepared can be counteracted by the pressure difference easily. however, when door is closed, the intake flow rate by negative pressure difference is exerted on the small area such as door gap. when door is open, the convective flow rate by thermal pressure is exerted on a half of the door opening. when the value of pressure difference is equal to that of the thermal pressure, the former flow rate is much less than the latter. when the former flow rate was exerted on the door opening area, the air velocity formed cannot counteract the air velocity by the latter flow rate. the air velocity on door opening can be expressed as eq. ( . ) in chap. . because the area of the door opening is very large, which is different from the gap, the intake and outtake flow rates (q and q ) can be calculated with eq. ( . ). the maximum of the parameter u can be within . and . , which is different from sect. . . where f is the area of the outtake flow on the door opening; f is the area of the intake flow on the door opening. because the density difference Δq is very small, it can be simplified for calculation. it is supposed that q = q and f = f . equation ( . ) is different from eq. ( . ) which is used for calculation of the leakage flow rate through door gap. in eq. ( . ), l = eu, and e is the contraction coefficient of the flow. but for door opening, e % . according to eq. ( . ), when the height of the door is m, h = m. the average air velocity and flow rate under different temperature differences are shown in table . . during the calculation process, Δt = °c, Δq = . kg/m , the width of door is set . m, h = m and u = . . it is shown from table . that the flow rate of convective flow on door opening by . °c temperature difference reaches . m /s. it is equivalent to the table . . therefore, the influence of convective flow by temperature difference cannot be neglected. it is indeed difficult to counteract the influence of temperature difference only by pressure difference when door is open. this is consistent with the aforementioned measured flow direction on door opening. after door is open, the pollutant exchange rate induced by door opening, movement of occupant and temperature difference is proportional to the flow rate of intake and outtake flow. the exchange rate of flow by temperature difference is given by table . . from previous section, for the area of . m by door opening (usually the door will not be opened to the vertical position), the maximum flow rate induced by door opening within s is q = . m . the flow rate induced by movement of occupant within s is q = . m . therefore, the flow rate without temperature difference is: the exchange of flow rate within s when there is temperature difference is shown in table . . according to the flow rate in table . , the relationship between the pollutant exchange rates with/without temperature difference can be obtained, which is shown in fig. . . it is shown that when the temperature difference is larger than °c, the pollutant exchange rate will be greater by % from that without temperature difference. it is shown from fig. . that in theory the pollutant exchange rate for Δt = °c increases by % than that for Δt = . °c. the pollutant exchange rate for Δt = °c increases by % than that for Δt = . °c. but experiment shows that the maximum pollutant concentration (subtracted from the background concentration) for Δt = °c is . pc/l. the maximum pollutant concentration (subtracted from the background concentration) for Δt = °c is . pc/l. the maximum pollutant concentration (subtracted from the background concentration) for Δt = . °c is . pc/l. therefore in experiment the pollutant exchange rate for Δt = °c increases by % than that for Δt = . °c. the pollutant exchange rate for Δt = °c increases by % than that for Δt = . °c [ ] . based on the comparison between experimental data and theoretical data, the difference varies for different temperature differences. however, with the increase of temperature difference, the increasing trend of the pollutant leakage rate is consistent. for example, when the door of the ward opened firstly and then closed, the ratio of average concentration in the buffer room to that in the ward during the first min is shown in fig. . , which is about . - . %. the relationship between the concentration increase by temperature difference and the time is shown in fig. . . the phenomenon of aforementioned convective flow by temperature difference and its effect on pollutant exchange rate on door opening are rare in foreign standards and literatures. in "guidelines for preventing the transmission of mycobacterium tuberculosis in healthcare facilities" issued by the centers for disease control and prevention (cdc) in u.s.a. in , it was only mentioned that "indoor air distribution is affected by the temperature difference of air", but the influence of the temperature difference on the pollutant exchange was not noticed. in ashrae manual, this has been paid attention to. but it was only mentioned that when the door was open, "because convection occurs with temperature difference between two areas, air exchange by natural ventilation appears". there is no deep therefore it is m /h), pollutant will escape to the corridor. but this researcher did not pay attention to the impossibility for the formation of such a large exhaust flow in the ward. even in the normal condition, the pressure difference is unable to counteract the convection by temperature difference. this conclusion has not been proposed. on the contrary, until now it is believed that the pressure difference is able to counteract the convection by temperature difference (refer to the section about pressure difference). figure . shows the flow direction on the cross section of the door with width mm, when the temperature difference between two rooms reached . °c. it is shown that the air change rate at the height . m above the floor was almost , where can be considered to be the neutral plane. the air velocity in the lower region of the door opening from the corridor to the ward reached . m/s. the air velocity in the upper region of the door opening reached . m/s with the opposite direction. it was also pointed out that with the increase of exhaust air from the ward, the height of the neutral plane would move upwards. based on the above-mentioned description, experiment and calculation on several phenomena of door, no matter how airproof it is for the door of the isolation ward, the intake and outtake of air flow under dynamic condition cannot be prevented. therefore, the airproof door cannot play the role of effective isolation. therefore, it is again a misunderstanding that airproof door must be installed for negative pressure isolation ward (in extreme case, the door interlock is used, or even the airproof door used in submarine is applied). after sars epidemic, the design personnel are inclined to adopt the full fresh air scheme during the design of the negative pressure isolation ward. it is believed that the circulation air cannot prevent the air pollution. but when the related regulations abroad are referred, except the ashrae manual "health care facilities" issued in and the russian standard, full fresh air scheme is not necessary in other guidelines and the above-mentioned literatures revised after , which is shown in table . . in the ashrae manual, apparatus with circulation air is not allowed. in the russian standard, all the air should be exhausted outdoors. in the guidelines issued by cdc in u.s.a., there are two situations when full fresh air system is not necessary and circulation air is permitted: ( ) multi-room system. when air from these rooms should be recirculated to the hvac system, hepa filters should be installed at the individual exhaust (or return) air pipelines, instead of the total exhaust pipeline. ( ) single room. when three kinds of installation types for hepa filter are allowed: (a) hepa filter is installed at the return air pipeline of the room, so that return air is filtered and then delivered into the room; (b) when hepa filter is installed on wall or above the ceiling, indoor self-circulation air system is formed, so that the filtered air can be used again; (c) hepa filter is installed in the filtration unit, but it is not specified by cdc that this kind of the filtration unit should be installed above the ceiling or in the room. the main concern about the scheme to use full fresh air only and no circulation air in negative pressure isolation ward is that there may be pathogenic microbes with enough concentration in recirculation air. since the size of virus is very small, it is believed that they cannot be removed by hepa filter. it is also considered that there are basically no pathogenic bacteria in fresh air. the belief that virus cannot be removed by hepa filter means that the virus size is too small. indeed, the size of virus itself is too small, which is about . - . lm. but actually the virus is attached to its nutritious matters. they are released into the air by various forces such as coughing. this means that there are carriers for the existing virus (also including bacteria) in air. the diameter of these microbes with carriers was termed as the equivalent diameter [ ] . for example, the size of the bacteriophage in the processing of the monosodium glutamate factory is about - lm. selleris and herniman investigated the foot-and-mouth disease virus (fmdv) in the natural world. although the size itself is only - nm, after specified flow rate for dilution air and fresh air "guidelines for preventing the transmission of mycobacterium tuberculosis in healthcare facilities" issued by cdc in u.s.a., ashrae "ventilation of health care facilities" in new-built or renovated isolation ward for prevention of airborne transmission, the air change rate > h − and the fresh air volume > h − ashrae manual ( ) "health care facilities" [ ] in isolation ward, the flow rate of dilution air > h − (based on requirement for odor and thermal comfort) uk "guidance on the prevention and control of transmission of multiple drug-resistant tuberculosis" [ ] in new-built or renovated isolation ward for prevention of airborne transmission, the flow rate of dilution air ! h − and the fresh air volume ! h − cdc in u.s.a. "guidelines for environmental infection control in health care facilities" [ ] in newly-built ward, the air supply volume ! h − . in existing ward, the air supply volume ! h − aia in u.s.a. "guidelines for design and construction of hospital and health care facilities" [ ] in isolation ward for prevention of airborne transmission, consulting rooms for emergency or radiotherapy, the flow rate of dilution air ! h − and the fresh air volume ! h − dhhs in u.s.a. "guidelines for construction and equipment of hospital and medical facilities" [ ] in isolation ward for prevention of airborne transmission, the air supply volume ! h − and the fresh air volume ! h − . in the bathroom, laundry, waste disposal room, disinfection room, anteroom of isolation ward, the exhaust air volume ! h − australia "guidelines for the classification and design of isolation rooms in health care facilities" [ ] in negative pressure isolation ward, the flow rate of dilution air should be the larger value between h − and m /h usa "guidelines on the design and operation of hvac systems in disease isolation areas" [ ] in newly-built isolation ward, disposal room and mortuary, the flow rate of dilution air ! h − . in the bathroom, the exhaust air volume ! h − . in the consulting room for infectious patient, the flow rate of dilution air ! h − and the fresh air volume ! h − "guideline for design and operation of hospital hvac systems" (heas- - ) established by healthcare engineering association of japan in isolation ward, the total air supply volume should be h − , and the fresh air volume ! h − din - standard "ventilation and air conditioning -part : ventilation in buildings and rooms of health care" by deutsches institut fur normung e.v. in isolation ward, reception room and icu, the fresh air rate per person is m /h. in the ward containing isolated patients with infectious potential, the fresh air rate per person > m /h (it is known that it should be the circulation air) russian standard gost r - "air cleanliness in hospitals. general requirements" in infectious isolation ward (where local air cleaning equipment can be installed), the air change rate should be - h − , and total air is exhausted outdoors sampled with cascade liquid impactor, - % of the airborne particles containing virus have sizes larger than lm, and - % have sized between and lm, and only - % have sizes smaller than lm. therefore, is the number of particles containing virus with size . - . lm (or the virus particles with size . - . lm) too less [ ] ? experiment has shown that the efficiency of hepa filter for . lm particles is much larger than that for . lm, which is shown in table . [ ] . this also means that the equivalent diameter of virus is much larger than . lm. based on the above-mentioned introduction, it does not mean that the filtration efficiency for bacteria is large, while that for virus is small. figure . shows that the filtration efficiency for may virus is much larger than that for bacteria [ ] (fig. . ) . in total, the belief to use full fresh air only and no circulation air in negative pressure isolation ward is the third misunderstanding. dynamic characteristics of the door opening and closing operation and transfer of airborne particles in a cleanroom at solid tablet manufacturing factories fundamentals of air cleaning technology isolation principle of isolation wards air distribution design in a sars ward with multiple beds ultraviolet technology and intelligent pressure control solutions jointly provide true isolation rooms open operating room doors and staphylococcus aureus fundamentals of air cleaning technology and its application in cleanrooms air cleaning : the major measure for removing microbial aerosol particles methods for sampling of airborne viruses. microbiol multi-application isolation ward and its air conditioning technique without condensed water key: cord- -nyj o authors: xu, zhonglin title: movement of indoor fine particle date: - - journal: fundamentals of air cleaning technology and its application in cleanrooms doi: . / - - - - _ sha: doc_id: cord_uid: nyj o only when indoor airborne particles move towards the nearby of the precision product and then deposit onto the sensitive area, damage may be caused for the product. so it is important to understand the mechanism of particle movement and deposition for the control of environment. cleanroom comparatively. as for the movement of particles in the electric field, it has been introduced in the chapter about air filter, so both the electrostatic force and other kinds of forces with little significance are not discussed in this chapter. for the airborne particle shown in fig. . , it will be influenced by the gravity f , the buoyancy f , and the resistance f by the medium. for spherical particles, the gravity is: the buoyancy is equal to the weight of the medium with the same volume, i.e., ) the resistance equals to the multiplication of the relative velocity between the particle and the airflow, the projected area of particles, and the drag coefficient, i.e., where m p and m a are mass of particle and air, respectively (kg); ρ p and ρ a are density of particle and air, respectively (kg/m ); v is the relative velocity of particle (m/s); d p is the particle diameter (m); ψ is the drag coefficient. the unit of various kinds of force is n. when forces are acting on the particle, it deposits simultaneously. the settling velocity increases during the deposition process. when the resistance, the buoyancy, and the gravity are balanced, i.e., f À f ¼ f , it becomes the uniform settlement. then, the speed is v ¼ v s , which is called the settling velocity or stokes velocity. it can be calculated with the following expression: the drag coefficient ψ depends on the flow state where particle is suspended, i.e., the laminar flow or the turbulent flow. it is also dependent on the shape of particle. the flow state is decided by the reynolds number re of the particle with the relative movement. where μ is the gas viscous coefficient, pa · s. it is also called dynamic viscous coefficient, which is different from the kinematic viscous coefficient υ, υ ¼ μ ρ a . with the legal unit, for air with temperature c, μ ¼ .  À pa · s and ρ a ¼ . kg/m . for the movement of particle, re is usually less than . when re is smaller than especially smaller than . , the resistance for spherical particle can be calculated with the following formula: this is the famous stokes formula, where the resistance has the opposite direction to the movement. / of this resistance is the component of shape resistance for the particle, and / is the component of the frictional resistance for the particle. with eq. ( . ), the drag coefficient can be derived: therefore, the resistance is strictly related with the particle velocity. for the flow with larger re, the value of ψ is shown in table . [ , ] . for nonspherical particle, the drag coefficient should be multiplied by a correction coefficient β. this means the drag coefficient for nonspherical particle is ψ ¼ βψ . value of β is shown in table . . when eq. ( . ) is substituted into eq. ( . ), and let ρ p -ρ a % ρ p , then the settling velocity is: when square is performed on both sides, it becomes: two points should be paid attention to during the application of this equation: . in the field of aerosol technology, particle density is generally assumed ρ p ¼ , kg/m , while for atmospheric dust, particle density is generally assumed ρ p ¼ , kg/m . . the unit of μ is very confusing. in some literature, when the wrong unit is used, the calculated result can differ by ten times, where complete opposite conclusion can be obtained (for detailed information, please refer to the later chapter about isokinematic sampling). in this book, the legal system with international unit is adopted. the difference between this kind of unit and the engineering unit in the past is shown as follows: when the found value of μ is based on cgs unit, the corresponding value with legal unit is the found value divided by . when the found value is based on the engineering unit, the corresponding value with legal unit is the found value multiplied by . . when the found value of μ is based on kms unit, the corresponding value with legal unit is the found value divided by , . so, for atmospheric dust, the relationship between the settling velocity (m/s) and particle diameter with normal temperature can be obtained with eq. ( . ): v s % : ;  d p  À À Á :  À m s = ð Þ ¼  À  d p cm s = ð Þ or v s % :  À d p cm=s ð Þ ( . ) the calculation result is also shown in fig. . . it is shown that for particles with diameter μm, v s is only . cm/s. that means it only takes h for the deposition of particles from the working area ( . m above the floor) to the floor. but for particles with diameter less than . μm, the diffusional distance is even larger than the settling distance, and this is why it is not easily deposited. it should be noted that slip correction should be considered for particles with diameter less than μm. according to the aerosol mechanics, stokes formula is derived with the continuous flow condition, which assumes that there is no velocity jump on particle surface. that is to say, there is no relative velocity between the flow particles and the infinite thin medium layer attached to the surface, or there is a boundary layer on particle surface without relative velocity. for small particles, when the radius is close to the mean free path of gas molecule or the gas pressure is comparatively small, the movement of particle has the characteristic of molecular. particles will be so small that they will "slide" between gas molecules, namely, the relationship between the settling velocity and the particle diameter existence and movement of particle will neither influence the gas velocity distribution nor cause any airflow in gas medium. so the abovementioned boundary layer with zero velocity does not exist. conversely, there is a speed jump layer on the particle surface, namely, air slippage phenomena occur on the surface of the moving particle. obviously, the resistance caused by medium should be reduced, which is favorable for the stokes settling velocity. this is the reason to consider the slip correction for small particles. the decisive parameter for the flow in the slip flow range or others is called knudsen number: the specific division of flow range is shown in fig. . (table . ). let c the slip correction coefficient, which is also called cunningham correction coefficient, the settling velocity after correction becomes: table . shows the value of c with normal temperature and normal pressure by eq. ( . ). it is found that for particles with diameter μm, the corrected settling velocity will be faster by that without correction by %. the movement of particles under the action of inertia force means particle moves with inertia with initial velocity after the external force disappears. for example, particles on human body and equipment are affected by the mechanical force because of the activity of people and the movement of equipment. suppose initial horizontal velocity is obtained after particles leave the human body or equipment, the applied force disappear (now the airflow force and gravity are neglected), then particles decelerate with the inertia. according to the newton's law, the movement of particles with initial horizontal velocity v can be described with the following equation: where f is the external force. when only inertia force exists, here the slip correction should be considered. the expression of f with stokes equation becomes then, eq. ( . ) becomes: after integration, we get: ) the distance of movement in time t is: when t tends to infinity, the movement of particles becomes stable. the distance of inertia movement, expressed as s r , can be calculated with the following expression: inserting the expression of τ into eq. ( . ), the calculation results are listed in table . . it is shown that τ has the dimension of time, and it is called the "relaxation time" in aerosol dynamics. it is an important parameter to describe the movement of particles, and it is also termed as the characteristic time. it is the time needed for the transition from initial stable state to another stable state. for example, it is known from eq. ( . ) that after the force is removed, the velocity of particle with diameter μm will reach / of the initial velocity within the time t ¼ τ. so when t > τ, the movement status of particles will change a little. from table . , because of the rapid decline of velocity, the horizontal movement distance of a particle with initial velocity , cm/s is very short. it is impossible to be suspended with this mechanical force. due to the impact of air molecules with brownian motion, significant uneven displacement of airborne particles will occur, and the disorderly movement will be shown, which is shown in fig. . . after the collision, the movement direction and speed of molecules change suddenly. the trajectory is composed of many segments of straight lines. because the mass of particle is much larger than that of the air molecule, after the impact with air molecules, the velocity of particle can be reduced to be small enough to ignore. only after several times of impact, the direction and velocity of particle will change significantly. so the trajectory of particle is almost smooth curve. this kind of phenomena about disorderly movement for particle is called diffusional movement. although the displacement of particle in all direction with diffusional movement is random, pure linear displacement will occur when t >> τ and t ¼ s is enough. so the absolute value of average displacement during s in the given direction can be obtained with the following expression [ ] : where t is time (s); d is the diffusional coefficient of particle (cm /s). figure . gives the relations between d and particle size. table . gives the diffusional movement distance with different sizes. from the table, the movement distance of particle with diffusion is insignificant. usually it is thought that only diffusional deposition exists. this kind of diffusional deposition includes molecular diffusion and convection diffusion. for the room without air supply, indoor air will not keep stagnant because of the existence of convection. with the effect of convective diffusion, particles approach to the surface gradually at first and then deposit onto the surface with the molecular diffusion within a very thin layer near the surface, which is shown in fig. . . for the particle with a certain particle size, the molecular diffusion coefficient d is known, while the convective diffusion coefficient is unknown. fuchs solved this problem with a simplified method [ ] . in any deposition mechanism, the concentration variation of particles because of deposition is linearly proportional to the particle concentration n, i.e., the negative sign represents the decrease of concentration. after integration, the above expression becomes where n is the original concentration (pc/cm ); n is the concentration at the moment t after deposition (pc/cm ). then, the problem is attributed to find out the value of β related to the diffusional deposition mechanism. there is convection in the room without air supply. it means outside of the molecular diffusion layer, concentration becomes uniform with the effect of convection. and the concentration decreases continuously with time (with air supply, n is a constant). therefore, the particle number deposited onto the vertical surface with unit area within unit time is where v d is the velocity of diffusion deposition (m/s); n is the concentration which decreases continuously; i is the deposition rate [pc/(cm ·s)]; δ is the thickness of molecular diffusion layer. although it is difficult to specify the value, it is about μm on the order of magnitude according to the experimental results [ ] . so the variation of particle number in the space because of diffusion deposition within time dt is where v is the space volume (cm ); s is the area of vertical surface (cm ). inserting eq. ( . ) into eq. ( . ), we obtain: when it is inserted into eq. ( . ) and simplification is made, the number of particles deposited on vertical surface with unit area by diffusional deposition is: in order to have an idea about the value of n, an example is made as follows: assume s v ¼ ; cm À , t ¼ .  s, d ¼ .  À cm /s (for particle with diameter . μm), and the number of these particles is n ¼ pc/cm , so: n g ¼ ;  À e À : À Á  ¼ ;  :  ¼ : pc cm À Á deposition of particles on undersurface includes the settlement and the diffusion. and diffusion also includes the molecular diffusion and the convective diffusion. in fuchs' opinion, the convective diffusion coefficient is close to , because the convective velocity approaches zero when it is near the undersurface. it is only the molecular diffusion that plays a role in the very small distance from the undersurface, which will influence the particle concentration distribution near the bottom, but will not influence the total deposition rate. therefore, the number of particles settled down onto the bottom with area cm within time t is: as mentioned before, although concentration keeps uniform in the space of the room without air supply, it varies with time t. the reduction of particle number in the air column with height h is consistent with the number of deposited particles, which can be express as: when it is inserted into eq. ( . ), we know: with the same data of the example in previous section (for particles with diameter . μm, v s ¼ . cm/s, and assume h ¼ cm), fumiko and susumi proposed the expression for the deposition of particles on the interior surface in the room with air supply [ , ] : where f is the sedimentary area; t is the settling time; h s is the room height; h is the distance between the settling plane and the ceiling; n is the air change rate. since nh s v s is far greater than for . min À , the above expression can be simplified as it should be noted that eq. ( . ) is valid for the extreme case with room height h s ! for the room without air supply. only when the height is infinite ideally, the indoor particle concentration can be considered without variation because of deposition and considered as a constant. but there is no practical significance for the condition h s ! . in other words, this equation is not valid for the room without air supply. although eq. ( . ) is derived for the room with air supply, author thought it is not comprehensive to consider the particle deposition only, especially for the local plane. in the room with air supply, there are several ways for the deposition of particles onto plane, so the method to estimate the deposition efficiency for these ways is given. inertial deposition of particles on the plane is shown in fig. . . the inertial deposition efficiency is: figure . shows the relationship between η st and st [ ] . st is the inertial parameter, which has been introduced in chap. . table . presents the exact value of η st . in the table, u is the air velocity and d p is the particle diameter. interception deposition of particles on the plane is shown in fig. . . for the condition with large reynolds number (equivalent with the situation of cleanroom) with unknown re value, only the upper limit of interception deposition efficiency can be calculated, namely, table . gives the value of η r . r is the interception parameter, which has been introduced in chap. . sedimentation deposition of particles on the plane is shown in fig. . . the sedimentation deposition efficiency is where v s is the sedimentation speed; u is the air velocity. table . gives the value of η g for the general circumstance. for horizontal plane, there is a very thin layer close to it, where the height and the temperature gradient are extreme small. its vertical component of convective velocity is much less than the vertical component to the plane. it tends to zero, which means the convective flux is approaching zero. so the corresponding molecular diffusion flux towards the plane is greatly reduced. when the dispersity of particles is larger, the number of particles deposited on the vertical plane with fig. . inertial deposition of particles on the plane table . diffusion deposition is larger, while that on the horizontal plane is less. this means the diffusion deposition efficiency on horizontal plane is less than that on vertical plane, or the maximum number of deposited particles can be considered with vertical plane. when n ¼ pc/cm and the diffusional coefficient for particles with diameter μm is d ¼  À cm /s, we can obtain the value of i is . pc/cm within h according to eq. ( . ) . so the diffusion deposition efficiency for the velocity . m/s is [ ] for particles with diameter μm, of course, the value of η d for horizontal plane should be smaller than the above calculation result, or the maximum value can be determined with vertical plane. usually it could be ignored. when the circular monocrystalline silicon wafers with diameter and cm which is used for the production of integrated circuit are made as an example, the above deposition efficiency can be listed as follows: for particles with diameter μm on the plane with diameter cm on the plane with diameter cm on the plane with diameter cm on the plane with diameter cm from the above sequence, the probability of sedimentation deposition is the largest in the room with air supply. others should also be considered appropriately. but the larger the plane area is (such as the example with diameter cm), the lower the efficiency of both the interception deposition and the inertial deposition is (for the plane with diameter cm, η r % for particles with diameter μm, and η r <  À for particles with diameter μm). therefore, in order to make the estimation simple, the sedimentation deposition can only be considered with a deposition correction factor α. from the above sequence of efficiencies, it is known that for the circular silicon wafer with diameter cm, α can be . for particle with diameter μm, and it can be . for particle with diameter μm, while it can be about for particle with diameter . - μm. for the circular silicon wafer with diameter cm, α can be for particle with diameter larger than μm. with the above method, the value of α for particles with diameter μm when the plane diameter ! cm is shown in table . . for particles with the same diameter, values of α are different if the air velocity is different. the above data correspond to the air velocity . m/s. if the air velocity becomes . and . m/s, values of α are . and . , respectively, for particles with diameter μm on the plane with diameter cm. that means when the benchmark is based on the air velocity . m/s, the deposition rate will increase by . times in the room with the same particle concentration, if the air velocity increases to two times. when the air velocity decreases by half, the deposition rate can also be reduced to % of the original value. so we have the following correction formula: except for α, the influence factors of settlement amount include air velocity, particle settling resistance, particle density, and equivalent diameter. further correction can be made for the above express so that it can reflect the real situation well [ ] . the formula can be rewritten as: where α is the deposition correction coefficient; ω is the air velocity correction coefficient, which considers the correction of α by air velocity. (the previous calculation is based on the air velocity . m/s in cleanroom. when the air velocity differs, the value of α will change. so ω ¼ for the air velocity . m/s. when the air velocity increases to two times, the value of α will increase by . times, so ω ¼ . . in the room without air distribution, there is still flow movement, so the corresponding air velocity can be . m/s. meanwhile, the value of α will decrease to % of the original value, so Þ is the settlement resistance correction coefficient, which considers the influence of particle shape on the settling velocity during the natural sedimentation process. it is obtained by eq. . . (generally v s is calculated with spherical particle. but in reality dust particles are not completely spherical, and their surfaces are irregular. so the correction coefficient β considering the particle shape should be used. v s is linear proportional to the root of correction coefficient. for irregular particles, β is . - . , and generally it is . . correction is not needed for the unnatural sedimentation process.) ρ p =ρ ð Þ is the density correction coefficient. it can be obtained with eq. ( . ). (as mentioned before, the density for atmospheric dust is usually ρ p ¼ . but in the place where people density, activity, and dust are a lot, the particle density ρ p may be - . . in some experiment such as the liquid droplet, ρ p ¼ . so this kind of correction is not needed for the general situation.) it is easy to determine the value of v s in eq. ( . ) when particles are monodisperse. when airborne particles are polydisperse, it should be calculated with some kind of average diameter. the amount of deposited particles is dependent on the frontal resistance, which is related to the cross-sectional area. so the area weighted diameter should be adopted to describe the average diameter of whole particles, which is used to estimate the deposition amount. when the particle concentration of cleanroom is n ¼ , pc/l ¼ pc/cm , the area weighted diameter for airborne particles with diameter larger than . μm is d s ¼ . μm [ ] . that means the deposition amount for particles with diameter ! . μm can be considered as the deposition amount with particle diameter μm. so the total deposition amount of particles on the surface with area cm per hour can be obtained in the cleanroom, where the airborne particle concentration is , pc/l and the air velocity is . m/s. it is also called the unit deposition rate, which is the deposition concentration mentioned in chap. . as mentioned before, the calculated result only represents the possibility of the deposition amount of particles. it may be possible for the resuspension after deposition or no deposition because of the disturbance on the ground. the above data can only show the maximum probability of deposition, which is related to the surface exposure time and the actual dispersity of specific particles. table . shows the comparison of measured data and calculated data about the deposition amount of particles on the surface with unit area in the room with air supply. the experimental data are from the report of tan dade from institute of havc at chinese academy of building science. it was obtained with the microscope, when the total number of particle with diameter ! μm is counted on the steel disk. in the table, the calculated deposition rate was obtained with the standard particle size distribution for particle diameter - μm. the particle size distribution is as follows: other rooms are omitted. this result is much closer to reality compared with the calculation result with the average diameter as the equivalent diameter performed by author [ ] . with the calculation results in previous sections, the ratio of particle deposition amount on the vertical surface to that on the undersurface is very small. so it is unnecessary to use the material such as the advanced stainless steel for the wall in the cleanroom, and the requirement for the hygienic cleaning of the vertical wall is lower than that of the floor. from the discussions in previous sections, with the effect of gravity, inertia force (mechanical force), and diffusional force, the velocity and the distance are very small. for particles with diameter μm, the movement distances are . , . , and . cm, respectively. the indoor air velocity (including the air velocity with heat convection) is usually more than . m/s. in the flowing air, small particles will follow the movement of airflow with the same velocity [ ] . semiempirical equation can be used to calculate the flow in circular pipe, and the calculation result is well agreed with the experimental data. for the single spherical particle with diameter d p and density ρ p in the flowing air with density ρ p , when it follows the airflow completely, the force acting on the particle equals with that on the fluid whose volume is occupied by the particle, i.e., d dt where u a is the velocity of the fluid in the space which is occupied by the particle; t is the time. in fact, particles will not completely follow the airflow. the force exerted on the particle equals with the force component f r by the relative movement between particles and the fluid subtracted from the above force. so the governing equation for the movement of the particle is d dt where v p is the particle velocity; f r is equivalent to the resistance on the particle with velocity v pu a in the still viscous flow. the solution process of this equation is so complex that it will not be cited here. the study result is given: ω is the fluctuation frequency of turbulent flow (khz). except the semiempirical equation for the flow in circular pipe where both the calculation and the experimental results agree well with each other, so far there is no good result in this aspect for the cleanroom. but compared with the calculation result in circular pipe, the order of ω is only thousands hz in the cleanroom. so particles with diameter d p ¼ μm and this means the relative difference between the velocity of particle following the airflow when the diameter d p ¼ μm and the air velocity is less than À . this can be further verified by the research about the particle trajectory and the streamline trajectory at the control site (such as the bench) which was performed by shuji et al. [ ] . the obstacle at the control site will cause influence on the particle and generate the energy by the turbulent flow. this influence is larger than that at other places. these influences include the inertial force, the diffusional force, the buoyant force, and the electrostatic force. only when the gravity was considered, the x-and y-components of the velocity were calculated with the movement equation of the particle by fujii [ ] . the change rate was obtained with the integration in the small time Δt (  À s), and the movement coordinates of the particle is then calculated. figure . shows the calculation result about the particle trajectory. the initial condition of calculation is that the particle velocity is the same as the air velocity. the calculation terminates at the height with ordinate À . above the control site. the particle sizes used were . and . μm. it is shown from the figure that Δm x and Δm y are the difference between the particle trajectory and the streamline trajectory in x-and y-directions. the values are shown in table . . it is shown in the table that for particle with diameter . μm, when u a is less than . m/s, the relative deviation between the particle trajectory and the streamline trajectory is not possible to be larger than À , which agrees with the above velocity. so the conclusion of this research was that the particle trajectory at the control site is approximately the streamline trajectory. so in other places of the cleanroom, it is reasonable to consider that particle moves with the airflow together. from the above result, it can be thought that even for the case v p u a < : , the air velocity is much larger than that caused by settlement, diffusion, and inertia of particles. so the following velocity of particle is still the main factor that influences the distribution of particles, but there is a lag of time for the airflow. it will not cause any problem for the investigation, and it should be considered only for the study of laser doppler velocimetry. therefore, it is the air distribution that mainly influences the airborne particle distribution. indoor particles will be affected by the airflow from air supply (including the primary air and the secondary air), the flow caused by occupant's walk, and the flow by heat convection. except for the primary air from the supplied air, the influence of other kinds of flow will be introduced in this section. it is a concern for the people that under what kind of situation, resuspension of particles by the airflow will occur, after they deposit onto the surface. because resuspended particles may be taken away by vortex and then cause damage. this is the migration effect of airflow. when particles are assumed spherical, the force to suspend particles with the effect of horizontal airflow is a function of the weather area of the particle, i.e., where u c is the surface velocity, namely, the air velocity flowing along the surface of the particle (m/s); φ is the suspension coefficient. when the suspension force is larger than the particle weight, it can be expressed as: the suspension coefficient is an experimental value, which is difficult to determine. but for spherical particles, the suspension coefficient is approximately same as the resistance coefficient. so when re < , φ ¼ re can be inserted into eq. ( . ). when ρ a is ignored, we can obtain there is a boundary layer when air flows along the surface. the air velocity above the boundary layer is much larger than that within the boundary layer, and usually it reaches more than three times. so the air velocity to suspend particles should be when the air velocity reaches u, the migration of particles is formed in the following way. as shown in fig. . , with the effect of gravity, particles in the airflow will deposit on the bottom gradually and rotate forward and slide with the frontal airflow. when air passes through the rotating particles, vortex will be formed at the bottom and the side of the particle, which increases the pressure relatively. the pressure at the top of the particle reduces by the airflow. with the difference of the pressure between the top and the bottom, particles are suspended. when particles suspend to the height where the air velocity at the top is the same as that at the bottom, particles begin to deposit again with the gravity. particles near the surface undergone the migration process of deposition-rotationsuspension with the enough intensity of the horizontal airflow, and it repeats continuously. the migration velocity calculated with eq. ( . ) is very small. but experiment has shown that it is not easy for the very small particle on the plate to be blown away by the airflow, and the reason is that the molecular force of the interaction between the particle and the wall surface, as well as between particles, is not considered. it is shown in eq. ( . ) that the velocity u c needed for the suspension of the particle will be large when this kind of molecular force is added. but detailed experimental data in this aspect are very rare, and it is very difficult to determine the magnitude of this molecular force. however, the influence of the molecular force can be estimated from the experimental curve in fig. . [ ] . in the figure, the abscissa represents the particle radius. the curve shows that the air velocity needed to suspend particles with radius less than μm will increase. the solid line in the figure is the experimental data, and the dashed line for extrapolation is added by author. after suspended by the airflow, particles with diameter larger than μm will deposit soon. while for particles with diameter less than μm, the air velocity needed to suspend them is bigger, namely, these particles are difficult to be suspended. therefore, when air velocity should be controlled that particles will not be suspended, the control diameter can be μm. in the experiment, the grit was used. for the grit with diameter μm, u is about cm/s. if particles with the density which is / of the grit, u can be cm/s. this means the air velocity along the surface (mainly the floor) in the cleanroom should not be larger than cm/s (it is not limited for the horizontally unidirectional flow air cleanroom). for example, the backflow velocity for the side air supply mode should be determined with this consideration. from the analysis above about the particle deposition and suspension, for the deposited particles on the horizontal plane such as the floor in the cleanroom, big particles are more likely to suspend and migrate, which generate the secondary float. this is opposite with the common opinion that the smaller particles are likely to be blown away from the floor. for cleanroom, one large particle is more hazardous than one small particle. on the other hand, large particles are likely to deposit, and the number of deposited particles on the floor is large. so the cleaning work on the horizontal surface in the cleanroom cannot be neglected. surface cleaning treatment must be performed for the object entering the room, since the air velocity along the surface is much larger and particles on the surface are more likely to suspend than that on the floor. since particles follow the airflow almost with the same velocity of the air, except for the supply air, other local airflows will also have influence on the movement and distribution of particles. heat convection airflow is one kind of important factors. for example, the buoyant flow near the shadowless lamp can be . m/s [ ] , but its influence on the particle distribution in the cleanroom has not been noticed and investigated. there are three kinds of situations for the buoyant flow generated by heat convection airflow. the following part will introduce the method to determine the velocity for this kind of the airflow. the surface temperature of the heat wall is higher than that of the ambient air. convection will be generated near the wall surface because of the temperature difference. after the rise of the air, it will stretch out, which will promote the dispersion of particle pollution [ ] . author has ever observed the fluorescent lamp with w vertically installed on the wall (the bottom of the lamp was . m above the floor) as shown in fig. . [ ] ; the buoyant flow in a certain range of two ends was measured with thermometer velocimetry when no air supply was provided. at the top, the air velocity at the place cm from the lamp surface reached . m/s, and the thickness of the layer with obvious air velocity reached cm. when smoke was released to observe along the whole length of the lamp surface with cm away, the buoyant flow appeared. outside the layer of this buoyant flow and until about m away, backflow appeared with both the method of the silk thread and the smoke release. so it is advisable to consider the airflow within cm away from the surface turbulent, and that in the range between cm and m is eddy with uncertain direction. in ref. [ ] , it is also pointed out that there is usually three layers of airflow in the direction perpendicular to the vertical heat wall. except for the above two layers, the most inner layer is laminar flow with very thin thickness, which is difficult to distinguish. the combined thickness of laminar and turbulent flow is much thinner than the third layer. figure . shows the situation of parallel flow with air supply velocity . m/s. the two flow patterns observed in the above experiment near the fluorescent lamp the above observed phenomena show that: . the buoyant flow near the vertical heat wall such as vertically installed fluorescent lamp is very strong, and the influence range is very large. . under the situation of air supply with a certain velocity, the influence will be limited. when the particle source is . m outside of the lamp surface, the particle distribution will not be affected by this buoyant flow. experiment with the particle source located in the room center where is . m away from the lamp surface shows that even though the air supply velocity is as small as . m/s, particles released from the source will appear in the range m below the lamp. ref. [ ] also pointed out that if the pollution source is in the stagnant region of the lee side of the object, its influence is much larger than that in the backflow region. if there is also no pollution source in the backflow region, no influence will be generated. this is consistent with the above observed case when pollution source is far from the backflow region. since it is difficult to install the lamp at the ceiling of the unidirectional flow cleanroom and it also occupies the air supply area, someone has ever proposed to install the lamp on the vertical wall. from the above analysis, when there is air supply with a certain speed in the room where the indoor area is very small, the buoyant flow generated will cause very large influence, when the fluorescent lamp was installed at a relative high position of the vertical wall (such as above . m). fuchs gave the equation to calculate the buoyant flow velocity along the heat wall [ ] , (table . ): where l is the height from the bottom of the heat wall (m); t s and t a are the surface temperature of the wall and air temperature, respectively (k); β is the air expansion coefficient, which equals with /t a ; g is the gravitational acceleration (m/s ). but according to the experimental data provided by Батурин [ ] , eq. ( . ) should be modified to: in the environment with normal temperature c, the surface temperature of the fluorescent lamp with w was measured to be about c, namely, the temperature difference is c. table . shows the calculated velocity of the buoyant flow with eq. ( . ) and the measured velocity. they are close to each other. so it is appropriate to use eq. ( . ) to calculate the buoyant flow velocity near the heat wall. the velocity of the buoyant flow on the heat surface reaches the maximum at - cm above the surface [ ] . in author's opinion, human body can be treated as the vertical heat wall approximately [ ] . the relationship between surface temperature of the human body and the room temperature is shown in fig. . [ ] . when the temperature difference is and c, the calculated value of u with eq. ( . ) is . and . m/s, respectively. according to the measurement abroad [ ] , the velocity of the buoyant flow near the surface of human body reaches . m/s, which is consistent with the calculated result. it is clearly shown in fig. . that even with the down supply of table . velocity of the buoyant flow along the vertical heat wall (m/s) (wall height . m, human body located at two both sides with the white color. the white part in the middle represents the airflow. the white part below means the operating table parallel flow, backflow will appear near the surface of human body [ ] (of course the surface of human body is uneven). this explains the influence of the buoyant flow on the air distribution. as for the buoyant flow along the wall in the room with air-conditioning system in summer, the temperature difference between room and inner wall is about c, so the buoyant flow along the wall is weaker than that along the human body. Лыков gave the equation to calculate the velocity of the buoyant flow along the heat object with a certain volume [ ] : where l is the characteristic length, i.e., the length of the airflow around a body (m). for example, l ¼ l (l is the thickness of the plate) for the plate, l ¼ ðπd= Þ for sphere, and l ¼ h for the cube where its height is h. it is obvious that compared with the pure vertical heat wall, the velocity of the buoyant flow along the heat object with the same height is much larger, which can be explained by the fact that the coefficient in eq. ( . ) is much larger than that in eq. ( . ). figure . shows the electric furnace with two pipes. the velocities of the buoyant flow at the intervals of cm above the shell were measured, and the measuring positions are shown in the figure. the velocity of the buoyant flow increases and reaches the maximum ( . m/s) at about . m above the shell and then reduces gradually. it is not easy to choose the value of the parameter in eq. ( . ) when it is used for calculation. since the value of l is only several centimeters (when the porcelain tube is concerned) and the temperature difference is several hundreds, the order of magnitude for the calculated result is equivalent with that of measurement. it is obvious that eq. ( . ) is not suitable to describe this problem. Эльтерман has performed experimental study [ ] , and Куница derived the theoretical expression which agrees well with experiment [ ] : where z is the vertical height from the heat source surface (m); u z is the air velocity at z (m/s); Δt is the temperature difference between surface and ambient medium ( c); r y is the equivalent radius of planar heat source (m). for rectangular heat source where a is the length of long side on the rectangle (m); b is the length of short side on the rectangle (m). for circular heat source r y ¼ rðmÞ when z % . r y , the above equation can be simplified as the above equation shows that the velocity of the buoyant flow above the heat source increases from zero to the maximum which is at about z % . m and then reduces gradually when it is further above the heat source. figure . shows the curve by experiment abroad [ ] . it represents the boundary of the pollution (namely, the boundary of the particle distribution). the larger the air supply velocity is, the lower the height of the pollution boundary is. data on the right are the data added by author with the above equation. when the temperature of hot surface reaches c in the room without air supply, the maximum velocity of the buoyant flow is . m/s, which appears at z ¼ . m. at the height of . m, the measured velocity is . m/s, while the calculated value is . m/s. so the calculated result is close to the measure value. in the common references, people in cleanroom should not walk too fast. usually it is about . km/h ( m/s), because the secondary flow caused by people's walk will drive particles to move together. but there is no study about how much is the fig. . , and the following conclusions were obtained: . the maximum velocity of secondary flow. this value was not obtained with the velocity sampling at some place when people pass by (the intersection place "o" in the figure) but was the measured velocity at the place where people stop (a certain distance from the sampling place). meanwhile, the closer the distance from the human body is, the larger the velocity of secondary flow is. . the relationship between the maximum velocity of secondary flow and the speed of people's walk. figure . shows the measured velocities along x-and ydirections. although the relationship between the maximum velocity v max of secondary flow and the speed v of people's walk is not apparent, the boundary for the maximum value can be estimated with the following equation: the above measurement and analysis of the secondary flow caused by people's walk can be the basis to determine the lower limit of air velocity in horizontally unidirectional flow cleanroom. this will be discussed in chap. . airborne particles will become big particle because of the mutual collision and adhesion during the relative movement process (that caused by brownian motion, gravity, or aerodynamic force). this phenomenon is called coagulation of particles. with particle coagulation, particle size will become large, which is good for observation, measurement, and removal. the coagulation process can be classified as thermal coagulation and movement coagulation (the movement resulted from airflow movement and acoustic vibration). next the phenomenon of thermal coagulation will be briefly introduced. according to fuchs' derivation [ ] , the average time interval between two collisions is πdd p n . the relative dispersion coefficient of two contacting particles equals with the summation of dispersion coefficients of two particles. when two particles have the same size, it becomes d. so the number of particles which contact with one particle per unit volume in the time period t ¼ s is because there are n particles in total per unit volume, the time of collisions will be n πdd p n . the coefficient / was introduced because two particles will coagulate and become one particle when they collide with each other. the collision rate ðdn=dtÞ will be negative with the following expression: since d p d can be approximately constant, the change rate of particle concentration will become where k is called coagulation coefficient. it can be calculated with the following expression: when integration is performed on eq. ( . ), we obtain: so we get: where n is the initial concentration; n t is the concentration at the moment t, which can be obtained with the following expression: table . shows the value of k under standard condition. table . shows the variation of concentration during the thermal coagulation process for monodisperse particles when k ¼  À cm /s [ ] . from the above data, when initial concentration is less than pc/cm , the influence of coagulation can be neglected during measurement with time period min. if the measurement time is days, the concentration should be less than pc/cm so that the coagulation effect can be ignored. this aspect should be noticed during the experimental study, leakage detection of air filter, and selfpurification time with smoke release. the above sections have discussed various movement situations of single particle and the influence generated by local airflow. now the further study is presented about the particle distribution with particles released by the source in the flow field. the simplest case is the particle distribution with the point source in the parallel flow field. the specific aim is to determine the boundary of particle distribution, namely, the range of pollution. here it is called the enclosure line of pollution. in practice, there is the particle source which can be treated as point source, such as the spray of the leakage hole in one direction or several directions or the release of the leakage from the unsealed equipment. these particle sources exist in clean environment, and their size is very small; otherwise, they are not allowed to be inside the room. the meaning to study this problem is to find the basis for the air velocity which can be used to control pollution from various directions. this will also be discussed in chap. about the lower limit of air velocity in unidirectional flow cleanroom. figure . shows the case with point pollution source in parallel supply air. the flow field in the room is the combination of the parallel supply air and the flow field by point pollution source. now the spherical coordinate is adopted. r is the radial distance from point pollution source. θ is the intersection angle between r and z axis, and the anticlockwise direction is positive. the stream function of parallel flow field is: the stream function of point source flow field is: the stream function of the stack flow field is: where v is the air velocity of parallel supply air (m/s); q is the source strength, which is equal to the flow rate of polluted flow (m /h). when the air velocity equals with the velocity of polluted air, the polluted air along z axis direction is restrained at the position a (shown in fig. . ), which can be called the stagnation point. polluted air in other directions will be restrained at positions b and c. when the supplied air arrives at position a, it begins to turn round and moves forward when passing positions b and c (it is the same for other directions). this means when the polluted air flows through the lines a, b, and c, the component of velocity along z direction disappears. when the influence of molecular dispersion is not considered and that of flow fluctuation is very small, the polluted air cannot pass through this line and is strained under this line. therefore, this line can be called the enclosure line of pollution [ ] . so the enclosure line of pollution is the line passing through points a, b, and c. for position a, θ ¼ , so the stream function is: when the above two equations are combined, we obtain: cos θ ( . ) in fact, pollution source is not a geometrical point; instead, it should have a certain volume. suppose the radius is r and the velocity on the spherical surface with radius r is v (q ¼ πr v), the above expression can be simplified as this is the trajectory equation for the enclosure line of pollution which passes through points a, b, and c. now take the actual distribution of particles released by point pollution source simulated in parallel flow as an example, the test rig is shown in fig. . [ ] . the pollution source was the table tennis with radius r ¼ cm and many perforation on it. compressed air was used to spray the smoke from five cigarettes. the average pollution concentration supplied into the room is shown in table . . particle counter was used to measure the cross-sectional concentration in the center of the room at the working area height . m above the floor, when different conditions the data in the bracket is the flow rate (l/min) . enclosure line of point pollution in parallel flow with parallel air velocity and particle generation rate were provided. figures . , . , . , . , and . are several cases. in the figure, the abscissa represents the sampling position. the measured concentrations by particle counter were labeled. the sampling position without data means the measured value is zero. this means the average concentration in these positions is extremely low, so these places are not polluted. it is observed in the experiment that for pollution flow with velocity v ¼ . m/s from the pollution source, it disappears once leaving the hole. from the figure of concentration field, pollution can barely be measured at the same height of the pollution source. for pollution source with velocity . m/s, the elevated height of the polluted buoyant flow was observed only several centimeters. from the figure of concentration field, pollution can only be detected at the height of the pollution source. for pollution source with velocity . m/s, the increase of pollution concentration becomes larger. the elevated height of the buoyant flow was observed cm. it is shown from the figure of concentration field that pollution was detected at the height cm above the pollution source. in short, when the ratio of the polluted air velocity to the supply air velocity is less than , the elevated height of the polluted flow is within cm (in the figure of concentration field, there is not sampling point at cm below). experiment has also shown the situation of the buoyant thermal flow from the fluorescent lamp on the wall. the left of the concentration field is the situation when the lamp is turned on. since the downwards supply air velocity above the lamp is between . and . m/s and the dust source is . m away, polluted particles are not detected near the region above the lamp. the right of the figure shows that the downwards supply air velocity above the lamp is less than . m/s. three rows of measured data at . m away from the lamp show the obvious increase of pollution when the lamp is turned on. the pollution height reaches . m (shown in fig. . ). this is consistent with the previous case about the buoyant flow near the wall. difference is large between the calculated enclosure line with eq. ( . ) and the boundary of particle distribution by experiment. the range of the former case is relative narrow, while that of the latter case is much spacious. it can be found with the analysis of experimental concentration field that: . although the decrease rate of pollution flow is very fast, it is still slower than the calculated result with spherical coordinate. . the crosswise stretching range of polluted air is much larger than the range in the enclosure line. as for the first conclusion, the main reason is that the actual pollution source is not a uniform spherical dispersion source, and it has the characteristic of jet flow from small pore. the decline of velocity is very slow. after a certain distance, it declines like the spherical surface. as for this problem, there is no special investigation, and the data of perforated spherical air supplier performed by baturin can be referred [ ] , which is shown in fig. . and table . . as for the second conclusion, it has also been shown in the experiment performed by baturin, which was specially pointed out in fig. . . this kind of velocity field in different directions with θ is not uniform, and the crosswise stretch is much faster. the feature of the velocity field with the perforated spherical air supplier should be investigated further. a correction coefficient related to θ should be added for eq. ( . ). according to the in-site tested concentration field, the value of this correction coefficient can be ð À cos θÞ À : . so eq. ( . ) becomes the following semiempirical equation: r ¼ : À cos θ ð Þ À : r ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi ffi v v À cos θ ð Þ r ( . ) where r is called pollution radius. curves in figs. . , . , . , . , and . are the enclosure line calculated with this equation. as mentioned before, with the influence of thermal convection caused by the fluorescent lamp and the influence of the eddy caused by the frame between air filter and side wall (refer to chap. about the unidirectional flow cleanroom), the buoyant flow along the wall will drive the polluted flow towards two sides, so the two end of the pollution region from experiment is wider than the width of the calculated envelope line. it is also the case under the height of the return air grille. but compared with the calculated envelope line, it is still consistent for the pollution region above the return air grille. particles released from the pollution source are within the range of the envelope line. only when v v is larger than , some particles will go outside of the envelop line. it can be estimated that the theoretical result will match well with practice for the standard parallel line by full return air on the floor. the further discussion about eq. ( . ) will be performed in chap. about the lower limit of air velocity. the mechanics of aerosols (trans: gu zhenchao) dust removal in the crush and sieve workshop the mechanics of aerosols (trans: gu zhenchao) the mechanics of aerosols (trans: gu zhenchao) abstracts of the academic lectures by japan building institute (kanto) measurement of sterile environment relationship between the yield and the air cleanliness level of the environment impaction of dust and small particles on surface and body collectors exploration of the relationship between the deposition bacterial method and the airborne bacterial method following characteristic of discrete particles in turbulent flow investigation on the design of laminar flow cleanroom. abstracts of the academic lectures by the mechanics of aerosols (trans: gu zhenchao) influence of obstacle and thermal plume in laminar flow room theoretical basis of building thermal physics (trans: ren xingji, zhang zhiqing) lower limit of air velocity in parallel flow cleanroom indoor air dynamics (trans: zhou moren) the mechanics of aerosols (trans: gu zhenchao) industrial ventilation principle (trans: liu yongnian) Вопросы лучистого отопления fundamental and clinical study of vertical flow device in cleanroom Конвективные струи над нагретыми поверхностями environmental control in electronic manufacturing the mechanics of aerosols (trans: gu zhenchao) aerosol technology (trans: sun yufeng key: cord- -dvuwhpyq authors: garibaldi, brian t.; conger, nicholas g.; withers, mark r.; hatfill, steven j.; gutierrez-nunez, jose j.; christopher, george w. title: aeromedical evacuation of patients with contagious infections date: - - journal: aeromedical evacuation doi: . / - - - - _ sha: doc_id: cord_uid: dvuwhpyq most patients with infectious diseases, including biologic warfare casualties, can be safely transported by aeromedical evacuation (ae) using standard precautions. however, certain contagious diseases (e.g., tuberculosis, pneumonic plague, viral hemorrhagic fever) require transmission-based precautions to protect the other patients, medical personnel, and aircrew. ae planning for these patients must take into account international public health regulations. given adequate resources, foresight, and expertise, the ae of infected patients and biologic warfare casualties can be safely accomplished. this chapter provides a review of the aeromedical evacuation of patients with communicable diseases. topics include a review of the ecology of aircraft cabins and engineering features of aircraft ventilation systems that minimize the risk of disease transmission; examples of point source outbreaks related to air travel; in-flight preventive measures including the use of patient isolators; and us military and international policy and legal aspects of transporting patients with communicable diseases. examples include in-flight transmission of tuberculosis, severe acute respiratory syndrome (sars), smallpox, and measles.the chapter will also discuss experience in transporting patients with contagious diseases including viral hemorrhagic fevers and new patient isolation technologies that were used for the long-distance transport of patients with ebola virus disease during the – west african epidemic. the operational decision to evacuate patients with communicable diseases or those who are biologic warfare casualties is complicated by many factors, including the etiologic agent involved. unlike nuclear or chemical casualties, patients with contagious infections may transmit disease after external decontamination. further, theater medical facilities might be overwhelmed by a mass-casualty disaster after an epidemic or biologic warfare attack, necessitating rapid evacuation. a comprehensive review of the aeromedical evacuation (ae) of patients with contagious infections would have to contain elements from several diverse disciplines. these would include disaster medicine, air transport medicine, critical care medicine, the ergonomics and aerobiology of aircraft interiors, infection control, international aviation law and diplomacy, and the operational requirements and constraints of the us air force (usaf) and other military and civilian services. we have limited the discussion in this chapter to the ecology of aircraft interiors, disease transmis-sion onboard aircraft, and highlights of the elements of military and civilian ae capabilities for patients with contagious infections or biologic warfare exposures. unresolved issues will be identified with the goal of stimulating discussion and future research. the engineering parameters of aircraft ventilation and pressurization are well known and tested extensively by aircraft manufacturers. while most studies of aircraft cabin air quality have focused on tobacco by-products and other chemical contaminants, few have addressed the ecology of airborne microbes. the few available studies of the aerobiology of aircraft interiors suggest that the modern aircraft interior is a less likely venue for disease transmission than most public places [ ] . the risk of transmitting infections in modern aircraft under normal conditions is probably equal to, or lower than, the risks in other crowded enclosures. this is related to the excellent ventilation systems built into modem aircraft. however, when the ventilation system is not functioning (as is often the case prior to takeoff), the aircraft cabin environment increases the risk for transmission of airborne viruses such as measles and influenza. air vented into most aircraft cabins is sterilized during pressurization. to maintain an internal cabin atmosphere equivalent to less than ft. above mean sea level while at altitude, pressurized air is extracted from the main jet engine compressor, where it has been subjected to both high temperature (more than °c) and pressure ( psi). the air is then cooled by a series of heat exchangers and vented into the cabin [ ] . microbial survival times are also altered by variations in relative humidity [ ] . because air at altitude has low relative humidity ( - %), the resultant compressed cabin air does also. low humidity inhibits bacterial growth and stability but increases the survival and infectivity of cer-tain airborne viruses [ ] . the influenza virus was found to survive longer in dry air (relative humidity < %), while poliovirus survived longer in humid air (relative humidity > %) [ ] . the three most important factors that determine the incidence of infections spread by airborne particles in an enclosed space are the susceptibility of those exposed, the duration of exposure, and the concentration of infectious droplets or droplet nuclei. the concentrations of droplets and droplet nuclei increase when the generation rate is high, when the static volume of enclosed air is small, and when fresh air ventilation is low. ventilation of any enclosed space decreases the concentration of airborne organisms logarithmically, removing approximately two-thirds of the airborne droplets per air exchange [ ] . the mechanism by which air is circulated through most large aircraft cabins depends on several factors. when on the ground, fans recirculate cooled or conditioned air throughout the cabin. when the engines are off, ventilation is provided in one of two ways: either an auxiliary power unit runs the cabin ventilation system or preconditioned air is supplied by connecting a ground airconditioning unit to an air manifold. in some aircraft, no fresh air is taken in until pressurization is begun at altitude. however, older military transport aircraft (such as the c- hercules) use pressurized air from the engines for ventilation whether on the ground or aloft. at altitude, compressed air enters continually while air is vented overboard via an outflow valve. first-generation jet airliners (e.g., boeing s, boeing s, dc- s) and most military transports use % ambient (fresh) air for cabin supply [ ] . the airflow design for most large aircraft is either circumperipheral or longitudinal. for both designs, conditioned air typically enters the cabin at standing head level. with the circumperipheral design, air circulates from aircraft skin to midcabin and then down and back to the vents near the skin at floor level on the same side. with the longitudinal design, air circulates from the air-craft skin in the midsection to outflow valves either fore or aft. the outflow valves are sometimes along the hull (two on the boeing : one at the forward edge of the wings and the other near the tail) or elsewhere along the fuselage (below the right cockpit floor in the c- ). the type and direction of airflow during an ae flight have important implications for airborne spread of infection. in general, the circumperipheral mode is preferable to the longitudinal because it minimizes aircrew exposure to contaminated air. with the longitudinal design, the direction of airflow should be adjusted so that it is aftward by closing the forward outflow valves. in the c- a nightingale, cabin airflow is "top to bottom, front to back," and therefore, contagious patients are placed as far aft and as low as possible. the airflow for the c- takes on special importance because of its history as the main strategic ae airframe for the us military. this aircraft also had a longitudinal airflow design, where the air enters both on the flight deck and the aft cargo compartment. air then flows toward two outflow valves located above the aft pressure bulkhead [ ] . therefore, potentially infectious patients were placed as far aft and as high as possible. the ventilation patterns of the c- transport, which may assume some of the strategic ae missions in the future, remain to be characterized [ ] . the risk of airborne infection to the flight crew is related to the flight deck airflow design. in many commercial airliners, such as the b- , the flight crew is somewhat protected by the independent flight deck ventilation system. as noted previously, the c- flight crew is protected by the longitudinal system, where the air enters on the flight deck and flows aftward through the cabin. this is in contrast to the c- , where the flight deck personnel may be at increased risk because all cabin air is drawn to the cockpit, where it is vented out [ ] . commercial airline cabin airflow has two important design features that may reduce respiratory droplet or airborne transmission. first, most cabins feature a flow design that is both circumperipheral and laminar, with air entering overhead, flowing down the sides, and exiting through vents above the floor. second, they have relatively high air exchange rates, typically ranging from to exchanges per hour. this exceeds both the air exchanges per hour that maintain air quality in modern office buildings and the exchanges per hour recommended by the us centers for disease control and prevention (cdc) for the hospital isolation rooms of patients with active tuberculosis [ ] . unfortunately, the purging of air within the cabin may not always be uniform because of the laminar flow design. there may be decreased air circulation in fore and aft areas, resulting in stagnant zones; animal studies demonstrate that increased ventilation decreases airborne transmission in confined spaces [ , ] . it is important to remember that ventilation alone is not sufficient to prevent all transmission of airborne pathogens [ ] . jet engine efficiency is decreased by the extraction of compressor air for delivery to the cabin because this air is not available for additional thrust. to economize, commercial airliners use systems that partially recycle cabin air, rather than continuing to supply % fresh air from the engines. the fraction of recirculated air ranges from % to % [ ] . the use of recirculated air may reduce air quality due to the recirculation of aerosolized contaminants. to counter this, most airlines have installed highefficiency particulate air (hepa) filters in their recirculation systems. these are . % effective for removing particles of . μ(mu)m diameter or larger. although hepa filters were originally installed for passenger comfort (e.g., for removing tobacco smoke), they also appear to reduce the risk of transmission of airborne pathogens [ , ] . the droplet nuclei carrying measles, varicella, and tuberculosis are typically μ(mu)m or less in diameter. a study commissioned by the us department of transportation to evaluate the levels of bacteria, fungi, carbon dioxide, ozone, and tobacco products in recirculated airliner cabin air found that microorganism concentrations did not reach levels considered hazardous to health [ ] . in response to concerns generated by lethal viral hemorrhagic fevers, and a possible need to transport patients with these diseases by air, the ventilation and air-conditioning systems on pressurized, long-range transport aircraft were studied to evaluate the aerodynamics of aerosolized microorganisms [ ] . the two aircraft evaluated were the lockheed martin c- e hercules (the aircraft used for most tactical ae) and the boeing - c. at the time, the aviation engineering knowledge of ventilation and air pressure changes on these aircraft was extensive. the movement of smoke particles was observed, and the dispersion of aerosolized spores of a nonpathogenic organism (bacillus subtilis var. globigii) was assayed at multiple cabin sites under various pressure and ventilation conditions. results of both smoke and spore studies suggested that the optimal location for placing a highly infections patient in the would be the left rear of the cabin. when the aircraft was pressurized and the forward outflow valve was closed, contamination was largely restricted to the rear area, placing the flight crew at minimal risk if they stayed forward. in view of its airflow design, it was no surprise that there was substantial drift of smoke from the cargo hold of the c- into the flight deck [ ] . approximately % of the spores released in the aft cabin reached the flight deck, probably enough to transmit infection over a prolonged flight if the organism had been infectious. the relative locations of the bleed valves and outflow valve would make plastic diaphragms impractical. one conclusion of the study was that high-containment isolators would be required to evacuate patients with potentially lethal contagious diseases in a c- . these isolators would protect the flight crew and medical workers and allow refueling stops without alarming foreign governments, which might otherwise refuse international landing clearances (fig. . ). these types of isolators are still used by non-us military forces for ae transport [ ] . the us military and civilian transportation services have adopted a slightly different approach as will be discussed later. a second conclusion of the study was that such patients should only be transported in longrange jet aircraft with the air distribution characteristics similar to those of a boeing . however, significant air contamination occurs within the cabin while these aircraft taxi for takeoff with the recirculation fans functioning. to avoid this, the starboard engines should be operated with the forward outflow valve closed, thus ensuring rapid air exchanges within the cabin. potentially infectious patients should be boarded through the rear passenger hatch and then placed in the left rear of the cabin facing aft. to protect the flight crew, patients and medical workers should venture no further forward than mid-cabin and flight crew no further aft than that same point. these concepts were applied, without empiric validation, in , when the aft area in a was used to transport a patient with lassa fever [ ] . a was selected because it was capable of a nonstop flight to germany, obviating potential difficulties obtaining permission to refuel in a third country. this dedicated ae utilized extensive and unprecedented precautions to transport the patient (a german physician) from lagos, nigeria, to hamburg. the patient was isolated in the rear of the cabin, and a "neutral zone" was created using two polyvinyl chloride partitions. the outflow valves were configured to create a longitudinal pressure gradient in the cabin so that airflow was from the forward to the aft section. finally, to avoid microbial dissemination via recirculated air, the starboard engines were started to allow pressurization prior to boarding the patient through the aft door. after transporting the patient, the aircraft interior was fumigated with vaporized formalin for hours, and there were no secondary cases. between and , the air was sampled for microorganisms on domestic and international flights, including small and large jet airliners and turboprop commuter aircraft [ ] . it was assumed that all microbial contamination originated from passengers and crew because the air taken in from the engines was presumably sterile. it was also assumed that lower levels of microbial air contamination would correlate with a lower risk of disease transmission, although this has not been validated clinically. control samples were taken at urban locations such as buses, malls, streets, and airports. microorganisms were quantified by counting colony-forming units (cfus) after hours incubation, but no attempt was made to identify the organisms. this study found no significant differences between air at sea level and higher sites nor between coach, business, first-class, or galley sections [ ] . the highest counts came from samples taken near outflow vents, about foot above floor level. interestingly, the microbial air contamination found during flight was significantly lower than that found in cities, buses, and public buildings. decreased passenger movement (e.g., during sleep) correlated with lower numbers of cfu. the authors concluded that "the small number of microorganisms found in us airliner cabin environments does not contribute to the risk of disease transmission among passengers." [ ] disinfection of the aircraft is an important element to consider in the ae of infectious disease patients. the world health organization (who) specifies basic advice on hygiene and sanitation [ ] but does not provide details on standard operating procedures (sops) or disinfectants to use. in , the lufthansa group implemented and shared sops for the safe decontamination of commercial aircraft, taking into consideration passenger and crew safety, aircraft operability, aircraft instillations, and aircraft certifications. lufthansa technik central laboratories studied the effects of several alcohol-based, formaldehyde-based, and oxygen-releasing disinfectants on aircraft materials including glass, metal, electric conduits, synthetics, and seat covers to determine the safe application and techniques to be used on their airline fleet [ ] . the risk of transmitting infections in aircraft has probably been exaggerated [ ] . most reports of disease transmission onboard aircraft describe foodborne outbreaks on commercial airliners [ ] , a discrete area of relevance to ae. the following is a brief summary of the transmission of several common pathogens. tuberculosis is an obvious concern aboard ae aircraft because it is a common and serious disease usually spread via airborne transmission, especially in confined spaces [ ] . three conclusions about the risk of tuberculosis spread can be drawn from the limited number of published retrospective cohort studies of tuberculosis exposures aboard aircraft. first, the risk of tuberculosis transmission aboard an aircraft is apparently no greater than in other confined spaces, with reported conversion rates of - % [ , ] . second, the duration of exposure appears to be important, with several studies reporting no tuberculosis transmission after exposure to an infectious patient after flights less than hours in duration [ , ] . finally, the risk of conversion appears much greater for those seated within two rows of an infectious passenger on airlines with a laminar air flow system [ ] . based on this information, the cdc recommended that "those known to be infectious travel by private transportation rather than by commercial aircraft" [ ] . the cdc has also suggested three criteria to determine which passengers and flight crew members should be notified of the possibility of tuberculosis exposure [ ] . first, the person with tuberculosis was infectious at the time of the flight. infectiousness can be assumed if the person was symptomatic with acid-fast bacilli (afb) smear-positive, cavitary pulmonary, or laryngeal tuberculosis or has transmitted the disease to household or other close contacts. second, the exposure was prolonged (i.e., duration of flight exceeded hours). finally, passengers and flight crew who were at greatest risk for exposure based on proximity to the infectious passenger should be given priority for notification. routine tuberculosis screening for airline crew members has not been recommended as an occupational health measure. air travel has significantly altered the epidemiology of influenza. since the s, it has become clear that influenza pandemics have followed major air transportation routes. influenza has also been transmitted during flight. because of confinement in a closed space associated with flight, these cases most likely constitute common-source, single-exposure outbreaks rather than the usual linear "personto-person-to-person" epidemics. based on published reports, several conclusions can be drawn. first, prolonged ground delays may increase the risk, especially if the air ventilation system is not functioning. in one such report, % of the passengers became ill and there was a strong association of the rate of illness with the duration of exposure to the ill passenger [ ] . thus, a second conclusion is that the length of exposure is important. but, in contrast to tuberculosis, even patients exposed for less than hour appear to be at significant risk. third, the attack rate of influenza aboard a wellventilated airliner appears to be higher than the general community attack rate during epidemics ( - %) but less than the rate for boarding schools or nursing homes (> %) [ ] . a major problem with influenza is that individuals do not show signs of infection until several days after they have become infected. during this time, the influenza virus multiplies in the cells lining the upper respiratory tract and sheds into the environment around the infected individual. the infected person may feel slightly unwell but nowhere ill enough to miss work or travel, and they can transmit the virus to others around them. individuals infected with influenza a virus are usually infectious for at least - days before the onset of symptoms. after several days of infection, individuals develop fever and the other classical symptoms of influenza, and they remain infectious up to - days after becoming ill [ ] . infants and immunocompromised individuals can shed influenza virus particles for up to days. respiratory protection alone is not fully protective against influenza virus exposure, infection, and severe disease because the human eye is a target for entry of some influenza a virus strains into the human respiratory tract. both the cornea and the conjunctival epithelial cells contain the sialic acid molecules that serve as the receptors for the h protein of the influenza virus [ ] . when the human eye contacts a suspended small-particle influenza virus-laden aerosol from an infected patient's cough or sneeze, surface tension can draw the viral particles to the epithelial cells onto the ocular surface where they adhere. once adherent, the nasolacrimal drainage system can drain attached viruses from the eye surface through the tear ducts into the nasopharynx within minutes. measles is one of the most contagious infectious diseases, with an attack rate of about % among susceptible, casual contacts. spread by droplet nuclei, virions can survive in the air for several hours. during the early s, more than measles cases per year were either imported to the united states or acquired from imported cases. most of the imported cases were associated with air travel, and several secondary cases were acquired during flight [ ] . an important aspect of measles transmission is that it may occur before the patient becomes symptomatic, a day or two before the end of the incubation period. in one report, eight passengers became infected on a single flight even though no ill or coughing passengers were observed during the flight [ ] . during the intensified smallpox eradication program ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) , concern was extremely high that smallpox would be reintroduced to europe or the united states from endemic areas by air travel. consequently, smallpox vaccinations and boosters were recommended for national and international flying personnel [ ] . from to , of the known cases of smallpox imported to europe were associated with air travel. none were acquired during flight, as all case patients traveled during the incubation period [ ] . there is one case of potential infection during air travel, but it is unclear whether transmission occurred in the air or in a terminal [ ] . viral hemorrhagic fevers (vhfs) are caused by a taxonomically diverse group of rna viruses and feature a febrile syndrome with severe vascular abnormalities. in general, they are associated with high rates of morbidity and mortality. with the exception of lassa fever, little is known about their transmissibility during air transport. prior to the ebola outbreak of - , much of the attention paid to ae for viral hemorrhagic fevers focused on lassa fever. the mortality and communicability of lassa fever had engendered a cautious approach to these patients in the west from both the medical and aeromedical communities. as reported above, an infected patient transported from lagos to germany was the sole patient on a c- , and the patient together with the aeromedical crew were quarantined from the flight crew [ ] . perhaps the most unusual ae in history occurred when a cdc worker with lassa fever and his wife were transported from sierra leone to the united states on a c- [ ] . for lack of an isolation chamber, they were both sealed for the duration of the flight in an apollo space capsule that had been flown from a us military warehouse in germany. fortunately, the risk of transmission of lassa fever, both on the ground and during commercial flight, appears to be low. there have been two reports of inadvertent exposure of large numbers of susceptible individuals to patients with lassa fever in western hospitals without evidence of secondary transmission [ , ] . on at least four occasions, passengers with lassa fever have traveled on commercial overseas flights without a single secondary case occurring [ ] [ ] [ ] [ ] . this suggests that the apparently high transmission rate of lassa fever in west african hospitals may be due to local infection control practices [ , ] . based on these reassuring reports, it was suggested that lassa fever patients could be safely transported by ae using simple barrier infection control techniques [ , ] . however, the who strongly discourages the transport of lassa fever patients from endemic to non-endemic areas, stating that this should be undertaken only in exceptional circumstances and should be accomplished using special precautions including highcontainment isolators [ ] . the ebola outbreak of - provided the largest experience for the ae of patients with viral hemorrhagic fevers. a number of healthcare workers who acquired the infection while caring for patients in west africa were transported to healthcare facilities in developed countries for treatment. while several of these patients were transported by military services [ ] , the majority of patients were transported using civilian aircraft that were contracted to provide ae services by government agencies [ ] . phoenix air, a commercial transport service based in the united states, transported confirmed ebola patients and high-risk exposures [ ] . in all cases, ae providers used special precautions and some form of high-containment isolation system during transport. there were no reported cases of ebola transmission to the healthcare workers or personnel of these ae flights. the international spread of respiratory disease due to the severe acute respiratory syndrome (sars) coronavirus was accelerated by longdistance travel of symptomatic and incubating patients from hong kong to vietnam, canada, the united states, and europe [ ] . the risk of transmission during air travel was underscored by a cluster of cases acquired during a flight from hong kong to beijing, traced to a -year-old superspreader. however, another flight carrying four symptomatic patients led to only one secondary case, and a flight carrying a patient during incubation resulted in no additional cases [ ] . surveillance of passengers in seven flights carrying symptomatic sars patients to the united states identified no transmission events [ ] . an analysis of sars transmission during commercial flights carrying symptomatic sars patients to singapore disclosed transmission in only one of three flights, for an attack rate of less than %. the authors concluded that sars was less communicable than influenza during air travel [ ] . the most effective method to minimize disease transmission is to defer ae of infectious patients until after the period of communicability. unfortunately, there are many situations in which infectious patients must be evacuated, and ae planners must be ready to respond. early diagnosis of communicable diseases is the key to prevent transmission. only then can disease-specific, transmission-based precautions be promptly implemented. attempts are currently underway to develop portable, rapid diagnostic tests, such as enzyme-linked immunosorbent assays and genetic typing, which can be used in the field. in the presence of a biologic warfare threat, patients will be screened for incubating infections (e.g., smallpox) prior to being transported for other indications to minimize the risks of evacuation-related epidemics. when a casualty is determined to be infectious, the most obvious preventive measure would be to defer ae until after the communicable period. however, such casualties might need evacuation sooner for tactical or other reasons. the use of restricted flights for transportation of cohorts with specific communicable diseases would obviate the risk of patient-to-patient transmission but offer little protection to either the aeromedical or flight crews. when transporting any infectious patient, standard infection control practices are essential. additional transmission-based precautions are necessary for certain infections. cdc guidelines mandate the use of surgical masks for diseases transmitted by droplets (e.g., influenza) and fittested hepa-filtered masks for diseases transmitted by droplet nuclei (e.g., tuberculosis) in hospitals. these guidelines have been adapted for use in aircraft [ ] . the usaf is currently developing a comprehensive regulation on infection control on aircraft. judicious patient placement should be used to minimize the transmission of disease by respiratory droplet or droplet nuclei based on the ventilation characteristics of the specific aircraft. for example, infectious patients are placed as far aft and as low as possible in the c- a but as far aft and as high as possible in a c- [ ] . the ventilation pattern of the c- transport remains to be characterized [ ] . the c- is potentially the most problematic from an infectious disease perspective because cabin air is vented out through the cockpit [ ] . in high-risk situations, the flow of cabin air can be reversed aftward by opening the safety valve located in the cargo door [ ] . unfortunately, the aircraft cannot be pressurized in this configuration, necessitating an altitude restriction. as an additional protective measure, the recirculation fan in the cargo compartment can be turned off to prevent recirculation of droplet nuclei. in a commercial airliner, hepa filtration confers some level of protection. this may become an important factor in a large conflict, where boeing passenger aircraft might be used to transport a large number of potentially infectious ambulatory patients. however, this is unlikely to be a major benefit to ae, since the civil reserve air fleet (craf) program, wherein boeing s could be converted into air ambulances, no longer exists (see chap. ). another possible approach is airflow compartmentalization, where plastic partitions, neutral zones, contaminated zones, and pressure gradients are used in an attempt to minimize crosscontamination [ ] . although this approach might be considered in exceptional cases, no protocols for these measures currently exist for use in us ae aircraft, primarily because they have yet to be proven effective in practice. high-containment isolation systems can be used for transporting a limited number of patients with highly contagious, potentially lethal diseases. unfortunately, these isolators are limited in both number and capability and require specially trained teams of medical personnel. these isolators are necessary for the implementation of the extremely strict cdc infection control guidelines for the care and ae of patients with infections such as arenavirus, filovirus, and bunyavirus hemorrhagic fevers [ , [ ] [ ] [ ] [ ] . they have been deployed for evacuating patients with suspected or proven vhf and active pulmonary tuberculosis [ , , , ] . although valuable for evacuating limited numbers of patients, they would not be suitable for evacuating mass casualties. a number of isolators are currently available. the air transportable isolator (ati) is the oldest isolator that is currently in use (fig. . ) [ ] . phillip trexler developed the first model in to provide care for patients with severe immunodeficiency based on technology that was used for gnotobiotic animal research [ ] . two years later he developed a negative pressure version of the ati to isolate patients with high consequence pathogens [ ] . the ati is a transparent polyvinyl chloride envelope suspended on a portable frame ( cm × cm × cm; weight kg). the envelope incorporates gloved sleeves, "half-suits," and transfer and docking ports for patient ingress and egress and for introducing supplies. negative air pressure is maintained by an electrical air handling system powered by either the aircraft electrical system or rechargeable portable batteries. hepa filters are utilized on both the air intakes and exhaust. challenge studies demonstrated that the system contained aerosolized bacteriophage during isobaric and hypobaric conditions and could withstand rapid decompression. the isolator can be equipped with portable oxygen tanks, cardiac monitors, pulse oximeters, intravenous fluids and tubing, medications, sphygmomanometers, and defibrillators. to minimize the risk of puncturing the isolator, phlebotomy is minimized, and a needleless intravenous (iv) system can be used. sharp instruments are avoided. communication between patients and caregivers is limited by poor sound transmission through the envelope, noise generated by the air exchange ati air transportable isolator, abcs aeromedical biological containment system, cbcs containerized biocontainment system, tis transportation isolation system system, and background aircraft noise but can be improved with handheld two-way radios. physical examinations are difficult to conduct through the gloved sleeves. suction capabilities are limited, and mechanical ventilation is not feasible. contraindications to transport in the vickers ati included acute respiratory failure or the presence of gas trapped within closed body cavities that may pressurize at high altitudes (e.g., pneumothorax, ileus, or bowel obstruction) [ , ] . the us army medical research institute of infectious diseases (usamriid) used the ati as part of its aeromedical isolation team until [ ] . the ati was used in the ae of two ebola patients to the united kingdom by the royal air force (raf) during the - ebola outbreak. prior to the ebola outbreak, the raf had maintained three atis and had used them on only four occasions. during the outbreak, the raf increased their capacity to isolators. in , phoenix air was asked by the cdc to help develop a transport system for patients with sars. manufactured by production products in st. louis, the result was the aeromedical biological containment system (abcs) (fig. . ) . while the abcs was never used to transport sars patients, the us department of state enlisted phoenix air to use the abcs for ae of two us medical personnel who contracted ebola in west africa in . providers are required to wear personal protective equipment in order to enter the acbs containment area and provide care. this is in contrast to the ati, which contains the patient and allows providers external access. the abcs uses a metal exoskeleton to support an internal plastic liner that creates an airtight isolation chamber. the patient is placed in the chamber, and an anteroom allows healthcare personnel to don personal protective equipment (ppe) before entering. the chamber is maintained at negative pressure using an air pump, and both the air intake and exhaust are hepa filtered. exhaust air is pumped through a valve in the aircraft fuselage. the entire chamber is placed inside a modified gulfstream g-iii aircraft, in which the direction of cabin air has been reversed to flow fore to aft. the abcs was used for transports during the ebola outbreak of - [ , ] . recognizing that the abcs is only able to transport one patient at a time, phoenix air worked with the paul g. allen foundation, the us department of state, and mriglobal to create the containerized biocontainment system (cbcs) (fig. . ) . the cbcs is a -foot cargo container that can hold up to four patients who all have the same highly infectious disease. the container has a medical staff room, an anteroom, and a patient treatment area. the entire container is maintained under negative pressure, and air intake and exhaust are hepa filtered. two containers can fit in a modified boeing or a military cargo transport [ , ] . while the cbcs has not been used to transport a confirmed patient, it has been used in three large-scale drills, including the international transport of standardized patients from sierra leone to the united states as part of operation tranquil shift in [ ] . in response to the ebola outbreak, the usaf worked with production products to develop the transportation isolation system (tis). the tis is similar in design to the abcs in that it has an exoskeleton that is draped with plastic sheeting. the tis is modular and can combine two patient care pods, each with the capacity to hold four patients. the entire unit is under negative pressure and has an anteroom for providers to don ppe. all intake and exhaust air is hepa filtered. the tis can be loaded onto a c- or c- super hercules. in total, the air force commissioned tis units during the ebola outbreak [ ] . while it has never been used for confirmed case transport, the tis has been successfully deployed in several military exercises (fig. . ). the usaf has anticipated the possible future challenge of operating in a chemically contaminated environment by introducing the aircrew eye/respiratory protection (aerp) system, which is in essence a gasmask for aviators ( fig. . ) [ ] . transport aircraft have been equipped with the aerp system, and these could be used to protect aeromedical crew members from infection. the system consists of a mask- hood assembly, a blower, and an intercommunication unit. the c- a, which is no longer in service with the usaf, could be configured to carry eight aerp stations located throughout the aircraft. there are fewer such stations on the c- , c- , and c- aircraft. during flight, regulated aircraft oxygen is passed through the filter/manifold subassembly to the mask for breathing, while filtered ambient air is used to provide visor defogging. on the ground, filtered ambient air is used. the aerp blower is powered by the aircraft electrical system or by batteries. the aerp system is available in most aircraft used for military ae, and all aeromedical crew members routinely train for its use during emergencies [ ] . the newest usaf chemical biological protective system, the xm aircrew chemical, biological, radiological, and nuclear (cbrn) defense system, was developed in conjunction with the department of defense [ ] . this system is to be utilized by aviators from all four us military branches. the system is designed to be more comfortable and with decreased acquisition and sustainment costs. it is currently undergoing testing and evaluation to establish reliability and determine maintainability. the goal is to replace all aerps with the xm system for all aircrew members, regardless of the airframe they fly. aeromedical evacuation of us service members with contagious diseases has been routinely undertaken since the establishment of a military ae service in . during world war ii, c- commandos, c- skytrains, and c- skymasters were reconfigured to carry litters after unloading military cargo, becoming air ambulances on their return flights to the united states [ ] . air transportation was soon determined to be the most desirable method of evacuation for all but the sickest of active tuberculosis patients [ ] . those with large tension cavities or therapeutic pneumothoraces could not be moved by air because intrapleural gas volume would double as these unpressurized aircraft ascended from sea level to , ft. in most cases, patients were held at hospitals of embarkation until a sufficient number accumulated to fill a dedicated flight of tuberculosis patients. a trained nurse was usually present, and strict "sanitary precautions" and "proper isolation" were practiced. however, the aeromedical personnel were not screened with tuberculosis skin tests [ ] . consequently, the number of new tuberculosis infections occurring during these early air evacuations is unknown. in , the first aircraft specifically designed and dedicated to routine air medical transport, the c- a samaritan, entered service. it could carry specialized medical equipment and was capable of cabin pressurization. in , the boeing jet was modified by the military to become the c- stratolifter and soon became the mainstay of the first permanent intercontinental airlift system. meanwhile, the c- hercules began to see use for tactical ae. in , the c- starlifter began to replace the c- for strategic (i.e., overseas) ae. this jet aircraft represented a quantum increase in patient load, range, speed, and control of cabin environment. during the vietnam war, helicopters moved wounded from the battlefield to medical treatment facilities in rear areas. from there, c- hercules, c- providers, and c- caribous moved them to rear airfields, where c- starlifters embarked on intercontinental routes. ae became so efficient that evacuees were sometimes received in a continental us medical facility within hours of wounding. large-scale actions in vietnam in demonstrated the ability of the ae system to successfully respond to periodic surges of patients. in , the usaf received its first c- a nightingale, a military version of the mcdonnell douglas dc- specifically designed and dedicated for ae. new features included a special area for patient isolation and intensive care, a hydraulic ramp to facilitate enplaning of litter patients, integrated electrical and suction outlets, and medical supply and storage equipment cabinets. the c- a fleet was decommissioned in . the usaf currently conducts aeromedical evacuation by adapting a variety of aircraft including the c- and c- . the cornerstone of the current infection control program is adherence to the cdc guidelines for infection control. any infections thought to have been acquired during ae are to be reported to the air mobility command surgeon's office, scott air force base (afb), illinois. to date, no cases have been reported. military doctrine regarding all aspects of the medical management of biologic warfare casualties, including ae, is currently under development. much of the existing joint and usaf doctrine relevant for the ae of nuclear, biologic, and chemical casualties does not clearly differentiate between these three groups. clearly, there are significant differences among the diseases produced by these three weapons of mass destruction. the usaf surgeon general has developed interim guidelines for the ae of biologic warfare casualties. these guidelines are based on rational infection control procedures recommended for the infectious diseases caused by potential agents. before these interim guidelines can be implemented locally, they must be approved by the appropriate theater commander-in-chief (a nonmedical general officer) and theater surgeon. a key element of any successful approach to the treatment and transportation of biologic warfare casualties is early and rapid identification of exposure, clinical diagnosis, and laboratory confirmation using field diagnostic tests [ ] . to meet this need, the usaf is preparing to deploy multiple specialized teams and has developed a portable device that can quickly identify organisms by genetic typing. it is now projected that these teams will interface with the ae system as integral components of aeromedical staging facilities. in the s, widely publicized outbreaks of lassa and ebola fevers in africa spurred considerable interest among airline officials and public health authorities. in retrospect, inappropriate and unnecessary measures were instituted at airports in many countries to minimize the risk of disease importation. in commenting upon what he considered a deplorable state of affairs, michel perin of air france's central medical service wrote: most airline companies refuse to admit aboard passengers known, or believed, to have contagious diseases. such stringency can scarcely be justified by reference to laws or regulations, whether national or international. it introduces the risk of arbitrary, mistaken, or prejudiced conduct. it does not seem logical because airlines learn about only a small fraction of the contagious persons who travel, and public health is much more greatly endangered by unknown infectious persons. normal hygienic conditions aboard planes usually suppress the risk of contagion of most diseases. the possibility of refusing admission should be given to airlines in certain cases, according to their doctor's appreciation. [ ] perin suggested that exclusionary rules should be applied "only against someone who refuses to comply, or seems incapable of complying, with the conditions intended to make him harmless, or against someone who has such an infectious disease that it would be impossible to make him harmless to others" [ ] . insight into how the international community reacts to even rumors of highly contagious diseases among airline passengers can be gleaned from events of august and september . an epidemic of plague in the indian city of surat resulted in panic and chaos. many of the inhabitants, including most physicians, evacuated themselves from the city. panic spread rapidly to commercial air carriers, with all but two international airlines canceling flights to india. indians deplaning at airports around the world were evaluated for signs of plague, and, in canada, airport workers donned gloves and masks [ ] . eleven febrile indian passengers were promptly quarantined when they deplaned in new york city. none had plague, but four were found to have malaria, one had dengue fever, and one had typhoid fever [ ] . the most recent experience with ebola in - further highlighted the potential for panic in response to a highly infectious disease. after the start of the outbreak, several us lawmakers called for a complete travel ban on individuals from liberia, sierra leone, and guinea, despite the fact that such a ban would be extremely difficult to enforce and would have had a negative economic impact on those countries in the midst of a crisis [ ] . in a somewhat ironic display of paranoia, the louisiana department of health and hospitals, in conjunction with the governor's office for homeland security and emergency preparedness, banned individuals who had traveled to those west african countries from attending the american society of tropical medicine and hygiene conference in new orleans [ ] . ultimately, several countries, including the united states, implemented extensive travel screening protocols at airports to detect patients at risk for ebola and to monitor them for development of disease once they entered the country [ ] . the us restricted entry from ebola-affected countries to five designated airports [ ] . two individuals developed active ebola infection after arriving by international flight [ , ] . a third patient, a nurse who contracted the disease while caring for the first ebola patient in the united states, traveled by domestic airline before she became symptomatic [ ] . there were no reported cases of ebola transmission on any international or domestic flights. it has been postulated that enhanced travel and border health measures helped to curtail the spread of the outbreak [ ] . however, an extensive review by the department of homeland security inspector general found several serious deficiencies in the us ebola screening effort [ ] . the who international health regulations (ihr) ( ) [ ] stipulate that the pilot in command of an aircraft is required to inform authorities at destination airports of any health concerns stipulated by "article health part of the aircraft general declaration" (unless not required by the destination "state party") before or at the time of landing. the declaration requires reporting of passengers or crew who may have a communicable disease, described as a fever (temperature °c/ °f or greater) associated with one or more of the following signs or symptoms: appearing obviously unwell; persistent coughing; impaired breathing; persistent diarrhea; persistent vomiting; skin rash; bruising or bleeding without previous injury; or confusion of recent onset, as well as cases of illness disembarked during a previous stop, and information on treatments received during the flight. the ihr also stipulates that: the aircraft shall not be prevented for public health reasons from calling at any point of entry. however, if the point of entry is not equipped for applying health measures, the aircraft may be ordered to proceed at its own risk to the nearest suitable port of entry, unless the aircraft has an operational problem which would jeopardize safety. the aircraft may be restricted to a particular area of the airport with no embarking and disembarking. however, the aircraft shall be permitted to take on, under supervision of the competent authority, fuel, water, food and supplies. [ ] if disembarking is allowed, public health authorities may implement options that range from quarantine, isolation, and treatment, placing suspect persons under health surveillance, to no specific health measures. the us military services have regulations that govern the transport of infected passengers. one of the most relevant of these regulations for the ae of potentially contagious patients is usaf regulation - , which requires aircraft commanders to request an inspection by a quarantine official when an ill passenger has any of the following symptoms and signs: ( ) a temperature of °f ( °c) or greater accompanied by a rash, lymphadenopathy, or jaundice, or that has persisted for over hours; ( ) diarrhea defined as three or more loose stools or a greater than normal amount of loose stool for that person in a -hour period; and ( ) death due to illness other than physical injuries [ ] . the implications of this relatively imprecise and abstruse statement could be considerable. medical planners must be aware of these regulations because failure to implement their provisions may have international repercussions. certain aspects of our current understanding of the ae of contagious patients remain unresolved. we offer the following questions about issues that may warrant future research: . will additional smoke and simulant dispersal studies be done in various current ae aircraft to determine optimal aircraft type and patient configurations for ae of patients with contagious diseases? . would the use of hepa-filtered recirculated air reduce the risk of disease transmission in usaf aircraft that could potentially be used for tactical or strategic ae? . what is the utility of ultraviolet (uv) light in reducing transmission of airborne infections in aircraft? . what is the role of methods such as vaporized hydrogen peroxide in decontaminating aircraft after transport of patients with highly infectious diseases? . should the united states pursue international 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management of patients with suspected viral hemorrhagic fever an outbreak of measles associated with a new york/tel aviv flight air-transport, a main cause of smallpox epidemics today smallpox and its eradication. geneva: world health organization the coming plague: newly emerging diseases in a world out of balance safe intensivecare management of a severe case of lassa fever with simple barrier nursing techniques a case of lassa fever: experience at st thomas's hospital evidence against high contagiousness of lassa fever aeromedical evacuation of patients with lassa fever viral hemorrhagic fevers: report of the who expert committee the ebola business. business and commerical aviation special planes are lifeline for ebola patients sars and occupational health in the air transmission of the severe acute respiratory syndrome on aircraft risk of severe acute respiratory syndrome-associated coronavirus transmission aboard commercial aircraft short communication: low risk of transmission of severe acute respiratory syndrome on airplanes: the singapore experience preventing spread of disease on commercial aircraft: guidance for cabin crew flight manual, usaf series c- h aircraft (to c- h-l) update: management of patients with suspected viral hemorrhagic fever-united states isolation and biocontainment of patients with highly hazardous infectious diseases mobile high-containment isolation: a unique patient care modality air evacuation under high-level biosafety containment: the aeromedical isolation team isolation and handling of patients with dangerous infectious disease containment aircraft transit isolator plastic isolators for treatment of acute leukaemia patients under "germfree" conditions negative-pressure plastic isolator for patients with dangerous infections aeromedical evacuation of biological warfare casualties: a treatise on infectious diseases on aircraft the safety of the trexler isolator as judged by some physical and biological criteria: a report of experimental work at two centres containment care units for managing patients with highly hazardous infectious diseases: a concept whose time has come protection from contagion. business and commerical aviation the new weapon in the fight against ebola and other deadly pathogens unmc looks to expand cooperation with pentagon on highly infectious diseases mobile isolation unit for highly contagious fits air force cargo planes. stars and stripes human systems center (brooks afb, tex), products and progress flight manual, usaf series c- a aircraft (to c -a- ) new aircrew masks tested at dover air force patient airlift: from balloons to high-speed jets office of the surgeon general, department of the army draft of united states air force concept of operations (conops) for management of biological warfare casualties transportation in commercial aircraft of passengers having contagious diseases yellow fever, black goddess: the co-evolution of people and plagues. reading: helix books detection of notifiable diseases through surveillance for imported plague airlines point to additional problems of any ebola travel ban. reuters ebola policies that hinder epidemic response by limiting scientific discourse travel and border health measures to prevent the international spread of ebola enhanced ebola screening to start at five u.s. airports and new tracking program for all people entering u.s. from ebola-affected countries nurse who contracted ebola called cdc before flight, official says oig- - . ebola response needs better coordination, training and execution international health regulations quarantine regulations of the armed forces. departments of the navy, army, and the air force acknowledgments the opinions and assertions herein are those of the authors and do not purport to reflect official positions of the department of the army, department of the air force, or department of defense. the authors would like to thank michael flueckiger from phoenix air for providing information about biological containment systems. key: cord- - l d ew authors: lv, yang; hu, guangyao; wang, chunyang; yuan, wenjie; wei, shanshan; gao, jiaoqi; wang, boyuan; song, fangchao title: actual measurement, hygrothermal response experiment and growth prediction analysis of microbial contamination of central air conditioning system in dalian, china date: - - journal: sci rep doi: . /srep sha: doc_id: cord_uid: l d ew the microbial contamination of central air conditioning system is one of the important factors that affect the indoor air quality. actual measurement and analysis were carried out on microbial contamination in central air conditioning system at a venue in dalian, china. illumina miseq method was used and three fungal samples of two units were analysed by high throughput sequencing. results showed that the predominant fungus in air conditioning unit a and b were candida spp. and cladosporium spp., and two fungus were further used in the hygrothermal response experiment. based on the data of cladosporium in hygrothermal response experiment, this paper used the logistic equation and the gompertz equation to fit the growth predictive model of cladosporium genera in different temperature and relative humidity conditions, and the square root model was fitted based on the two environmental factors. in addition, the models were carried on the analysis to verify the accuracy and feasibility of the established model equation. with the large-scale use of central air conditioning system and the improvement of people's living standard, more and more attention has been paid to the increasingly serious problem of indoor air pollution. studies showed that air handing unit is an important source of microorganisms for indoor biological pollution, and some microorganisms tend to stay in the dust of air conditioning units with the appropriate temperature and humidity environment. the microorganisms grow and then enter the indoor space through the air, resulting in the destruction of indoor air quality [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . national institute for occupational safety and health (niosh) conducted a study of buildings, and the research results showed that among the sources of indoor air pollution, central air-conditioning system pollution accounted for % . summary of measurement by professor fanger showed that air-conditioning systems accounted for % in the indoor pollution sources . based on the supervision and inspection of air conditioning and ventilation system in the public places of china's provinces, municipalities and autonomous regions by china academy of building research and the chinese center for disease control and prevention, it was found that more than % of the central air conditioning systems could not meet china's national sanitary standard . thus, air conditioning system should eliminate negative impact caused by its own, on this basis, it may relate to positive effect of the ventilation. in recent years, h n , sars and other popular virus spread [ ] [ ] , and some researches showed that the hygienic, reasonable air conditioning systems were important to reduce damage [ ] [ ] . therefore, microbial pollution in central air conditioning system has become a critical topic in the field of indoor air pollution. studies showed that the filter, cooling coil, humidifier, and cooling tower in central air-conditioning system were easy to microbial breeding [ ] [ ] [ ] [ ] [ ] [ ] . in this study, a venue in dalian was selected as the research object. as the working condition of the air conditioning system was down, the environment parameters were measured, and microorganisms existing on the wind pipe, filtering net, surface cooler, and condensate water, on the floor and in the air were collected. besides, according to the tested microbial density and the identified genome sequence of collected microorganisms, the hygrothermal response experiment of dominant fungal was detected, and the fitting analysis was carried out based on the prediction model, followed by a series of statistical analysis. the aim of the present study was to clarify characteristics of the microorganisms in air conditioning systems, and the study would be helpful for policymakers and hvac engineers to develop the appropriate strategies and to conduct the bacteria and fungi characteristic assessments in hvac system. preliminary survey. the object of study is a venue in dalian, which covers a total area of m and building area is m . the aboveground part includes a swimming pool, ball training venues, gymnasium, the lounge room and the clinic. the underground part consists of a table tennis hall, air conditioning equipment rooms and reservoir area. the whole building is centralized-controlled by the central air conditioning room, which includes two air handling units. two measured units were all air system, which only had a coarse efficiency filter, and the unit is also provided with a heater, cooler and fan etc. both units are the primary return air system and the filters are removable types. the running time of the air conditioning system is from may to october, and the daily operation period is : - : . all components are cleaned every two years. when the measurement was carried on, the unit a and b were both cleaned a year ago. both units were closed during the sample collection. measurement method. the actual measurement is divided into two parts: the environment parameter measurement and air unit sampling. first, the temperature, humidity, and co concentration were automatically recorded by the temperature, humidity and co monitor (mch- sd, japan). second, the disinfected planktonic microorganism sampler (hkm series dw- , china) was installed where fresh air and return air mixed. once installing the sampler, we loaded medium in the sampler and set the parameter of air flow in sampler as l loaded medium. after the sample collection, the petri dishes must be sealed for preservation. finally, according to the hygienic specification of central air conditioning ventilation system in public buildings of china , we sampled the dust by using sterile non-woven ( mm* mm) on components of unit a and b, respectively, and each sampling point covered a cm* cm area at the sampling area. the non-woven fabrics were put into sterile water and stirred to make sure that organic substance on the non-woven was fully dissolved in sterile water. then, the samples of sterile water containing organic substances were prepared in times and times diluted concentration, respectively. there are sampling points in unit a and points in b, and two measuring point positions of the units are shown in fig. . the microorganisms collected in the air were directly cultured, and the samples in the dust were times and times diluted and μ l of the sample was inoculated into the two kinds of solid culture media. beef extract peptone medium was used for cultivating bacteria and potato dextrose agar was used for cultivating fungus , . each dilution was done in parallel samples to reduce the error, and final results showed the average value. the blank samples and test samples were set up for each of the cultures. if there is no colony detected on the blank sample, the test results are valid. both field test and laboratory measurements were performed in accordance with the hygienic specification of central air conditioning ventilation system in public buildings requirements . genome sequencing. only a small part of microorganisms are cultivable. therefore, the traditional cultivation method can not harvest all the species in ecological samples . fungal genome sequencing is an emerging method to identify the microbial genome, which could directly indicate related species information from environment samples . fungal amplicon sequencing analysis was used in this study, because the existing research showed that fungal spores have stronger vitality than other microorganisms in the air, and fungi dominated the microorganism in air conditioning systems. therefore, this method was mainly used to identify fungi in this study , - . environment parameters in air handling units. temperature, humidity and co concentration of unit a and b are shown in table . unit a is located in the ground floor (b ), and the unit b is located on the ground floor. compared to the unit b, the humidity of unit a is higher, and the temperature is lower. microbial colony analysis. the distribution density of bacteria and fungi in the unit a is obtained through statistics, as shown in fig. . the concentration of airborne fungus was cfu/m , and the concentration of airborne bacteria was cfu/m . the unit a showed the obvious microbial contamination status, though all components and airborne microorganism meet the hygienic specification of central air conditioning ventilation system in public buildings of china . the microbial distribution in filter net is central < edge < bottom and bacteria accounted for a larger proportion; the microbial distribution in surface cooler is center > against the wall > edge, and fungi accounted for a large. the fungal contamination in the air is more serious than the bacteria. the distribution density of bacteria and fungi in the unit b were obtained through statistics, as shown in fig. . the concentration of airborne fungus was cfu/m , and the concentration of airborne bacteria was cfu/m . parts of the measuring point in the unit b were polluted seriously. the bacterial colonies in the corner and the ground of the surface cooler were beyond the hygienic index (≤ cfu/cm ) in the hygienic specification of central air conditioning ventilation system in public buildings of china regulates . limited by unit placement, there were less measuring points in unit b, and we chose the same measuring points in both units for comparison (centre of surface cooler, surface cooler against wall, corner of surface, and ground of surface cooler). the comparison between unit a and b indicates that the bacterial density in unit a was less than that in the same sampling point in unit b, but the fungal density in unit a was more than that in the same sampling point in unit b. if the cleaning and disinfection is not enough before the air conditioning system running, it may make the fungus to enter the indoor environment, which results in make the pollution of indoor air. compared with cooling coil, the fungus contamination is worse in the floor dust and the air suspension. during the actual measurement, it is found that the unit internal is unprecedentedly narrow and low intensity of illumination in a closed state. according to the description by technicians, it is easy to trample damage to the underground pipes, which leads to the disinfection and cleaning work rarely in the unit. fungal genome sequencing analysis. in this study, we analysed the samples from the sampling points a , b , and b by amplicon sequencing information analysis, respectively named a a, b a, and b a. all collected samples in the air conditioner were transferred to the eppendorf tubes and processed with the extraction step. samples were resusponded in tens buffer with sds and proteinase k as described by vinod . after incubation at °c, phenol/chloroform/isoamyl alcohol was added to remove proteins, and the nucleic acid was precipitated with isopropanol and sodium acetate ( . m). total dna was dissolved in × te after washing with % ethanol. and then the quality and quantity tests were conducted by agarose gel electrophoresis, . for pcr product, the jagged ends of dna fragment would be converted into blunt ends by using t dna polymerase, klenow fragment and t polynucleotide kinase. then add an ' a' base to each ' end to make it easier to add adapters. after all that, fragments too short would be removed by ampure beads. for genomics dna, we use fusion primer with dual index and adapters for pcr, fragments too short would be removed by ampure beads too. in both cases, only the qualified library can be used for sequencing. the quality and quantity of libraries were assessed using the bioanaylzer (agilent technologies) and the steponeplus real-time pcr system (applied biosystems). the raw data generated by miseq and hiseq sequencers was processed to eliminate the adapter pollution and low quality to obtain clean reads. the qualified clean data was used for the further bioinformatics analysis. firstly, paired-end reads with overlap were merged to tags by software flash (v . . ) , and then tags were clustered to otu at % sequence similarity using usearch (v . . ) . secondly, taxonomic ranks were assigned to otu representative sequence using ribosomal database project (rdp) na, e bayesian classifier v. . . at last, alpha diversity, beta diversity and the different species screening were analyzed based on otu and taxonomic ranks by mothur (v . . ) . in order to fully understand the community structure of fungal sample and analyse fungus microbial diversity, while excluding errors that human operation brings, genome sequencing method in fields of molecular biology was employed in this study to obtain micro biological information. illumina company developed miseq method with higher flux and simple operation and lower cost for genome sequencing. besides, the synthesis of side edge sequencing method with higher reliability is more suitable for laboratory community structure. the high-throughput sequencing was found to be useful to characterize compositions and diversities of moulds. the gene sequence of the test samples from genome sequencing was dealed with, such as stitching and matching, and the sample had a total of high quality fungal sequences, with an average length of bp. the optimized sequence and the average length of the sample are shown in table . otu and abundance analysis. stitching and optimising the tags, in order to be the otu (operational taxonomic units) for species classification, gathering in the % similarity, and the statistics of each sample in the abundance of information in each otu were done , [ ] [ ] . rank otu curve is a form of species diversity in the sample, which can explain two aspects of sample diversity, that is, the richness and evenness of species in the sample. the richness of species in the samples represented by the horizontal length of the curve is wide, so that the sample species is more abundant. the uniformity of species in the samples from the curve reflects the longitudinal axis of the shape. that the curve is flat means that the sample has a higher composition of the species evenness. from fig. , the species composition of b a is the most abundant, and the uniformity is the highest. sample diversity analysis of observed species. alpha diversity is the analysis of species diversity in a single sample , including the species observed index, shannon index, etc. the greater the two indices are, the more abundant species is in the sample. the species observed index reflects the richness of the community in the sample, which also refers to the number of species in the community, without taking into account the abundance of each species in the community. shannon index reflects the diversity of the community, and the species richness and evenness of species in the sample community. in the case of the same species richness, the greater the evenness of the species is in the community, the greater the diversity of the community is. observed species exponential dilution curve. random sample in the processed sequence, draw the sequence number for the abscissa and the corresponding species number can be detected as the ordinate, so as to form a curve production dilution curve, shown in fig. (a) . with the increase of the sample quantity, the number of species increase and gradually become stabilized. when the curve reaches the plateau, it can be considered that the depth of the sequencing has been basically covered all the species in the sample. at the same time, the observed species index can reflect the richness of community in the sample, that is, the number of species in the community. it can be seen that the distribution of fungal species richness is b a > b a > a a. shannon exponential dilution curve. shannon index is affected not only by species richness in the sample community, but also by the evenness of species. in the case of the same species richness, the greater the evenness of the species is in the community, the more abundant diversity of the community is. it can be seen in the fig. (b) that the fungal species diversity of the unit b is significantly more complex than the unit a, and the similarity of species diversity in two sampling points of unit b was very high. composition of microbial samples. figure illustrates the species composition proportion of the three sampling points, and the proportion was redrew by removing the strains which were not detected in the sample. the results are shown in table . the species with the largest proportion is the dominant fungi. according to the fungal genome sequencing analysis results, fungal components in different units at the same sampling were different, and that in the same unit at different sampling points were roughly similar. they were caused by the different environmental conditions. on the center of air cooling coil in unit a, candida accounted for %; on the center and against the wall of the air cooling coil in unit b, cladosporium accounted for %, accompanied by alternaria, emericella and other fungus. cladosporium is usually rich in outdoor air, but they will also grow on the indoor surfaces when the humidity is high. existing research shows that the cladosporium spore is an extremely important allergen in the airborne transmission, which could cause asthma attacks or similar respiratory disease in patients with allergic reactions . some species of candida is a kind of conditional pathogenic fungi in the human body. growth prediction analysis of models. traditional microbial detection generally have the characteristics of hysteresis, which cannot play the role of prediction, but the use of mathematical models to predict the growth of microorganisms can timely and effectively predict the growth of microorganisms. therefore, it is very important to study the growth prediction model of the fungi in the air conditioning system. according to environmental conditions mentioned before, we established growth kinetics prediction model of cladosporium spp. to predict the rapid fungal growth in the experimental conditions, which can provide a theoretical basis for air microbial contamination prediction system and help evaluate the health risk inside buildings. the models were fitted by origin software (version ) and matlab r a, and the fitting conditions of logistic model and gompertz model were compared under different temperature and humidity conditions. the fitting effect between these two models and the fitting results of the two models were compared, and the corresponding model parameters were obtained. in addition, the square root model was fitted based on the two environmental factors. experimental study on the hygrothermal response of fungus. laboratory studies have revealed that fungal growth and reproduction are affected by water, temperature, nutrients, micro-elements, ph, light, carbon dioxide, and oxygen tension .the most relevant determinants of fungal proliferation in the building context are water/moisture and temperature, and to a certain extent those factors affect other environmental factors such as substrate ph, osmolarity, nutrient, material properties etc , .in order to lay the foundation for the fitting model, and to study the growth characteristics of fungi in different temperature and relative humidity, we set an experimental study on the hygrothermal response of fungus. from the results of fungal genome sequencing and literature research - , we selected cladosporium spp. and penicillium spp. as the research objects which are both common in air conditioning systems.this paper mainly studied the status of microbial contamination in air handling units so that the air temperature of each part of the air handling unit should be considered. the temperature gradient of °c − °c − °c and relative humidity gradient of %− %− %− % were selected as experimental hygrothermal conditions. the results of hygrothermal experiments are shown in figs , , . it can be known that growth rate of cladosporium spp. is faster than that of penicillium spp., in any experimental conditions, which is the essential characteristics of a strain, is hygrothermal response control method cannot change. these data indicated that low rh environments can reduce or even inhibit fungal growth. this observation agrees with findings by w. tang and pasanen , . growth prediction analysis based on logistic model. logistic model is a typical model of biological ecology, which has been widely used in the field of biological ecology . according to the actual research, the following formula equation ( ) was obtained after the appropriate change of the logistic equation. n was the colony growth diameter, cm; t was the microbial growth culture time, h; a , a , x , p as the model parameters. it can be seen from the table , the fitting curve of logistic model is similar to the experimental results. at °c and °c temperature conditions, the model's fitting effect is excellent, and r is greater than . ; at °c temperature conditions, the model fitting effect is not as good as other temperature conditions. predicting the growth of microorganisms. the pmp program developed by the ministry of agriculture to establish the model of pathogenic bacteria is the basic model for the study of gompertz equation. gompertz model has been widely used in the field of biology. gompertz model expression was as equation ( ): c n was the colony growth diameter, cm; t was the microbial growth culture time, h; a, a, k, x c as the model parameters. it can be seen from the table that the fitting curve of gompertz model is better fitted to the measured parameters. at the same temperature, with the increase of relative humidity, gompertz model fitting effect is better; the model is well fitted at the temperature of °c and the fitting effect is better than °c and °c temperature conditions. the fitting of logistic model to the growth of the fungus is better than that of the gompertz model. the two models are tested by the deviation factor b f and the accuracy factor a f in the mathematical model test. staphylococcus xylosus were studied by mcmeekin . they found that when t min is fixed, for each ϕ , the relationship between growth rate and temperature can be described by using the square root model. the combined effects of these two variables can be expressed by the modified equation ( ): in the formula, u is the growth rate of fungus, cm/h; b is the coefficient; t is the culture temperature, °c; t min is the most important parameter of square root equation, and it refers to the lowest temperature when the growth rate is zero, °c; ϕ is relative humidity of the cultivation, %. by using the logistic primary model, the predictive value of the growth rate of the cladosporium colony growth rate (instantaneous velocity) was obtained, as table shows. through the model fitting, the parameters of the square root model could be obtained, as table shows, and the model fitting of predicting growth of cladosporium was shown as fig. . the model equation of b f value was between . - . , indicating that the model used to predict the range of the experimental environment in cladosporium colony growth condition. at the same time, the a f value of the model was . that is closed to , which shows that the model has high accuracy. table . model fitting and model parameters of double factor square root. this study selected two central air conditioning systems at a venue in dalian as the objects. actual measurement and a series of studies were carried out on microbial pollution characteristic, and the results are shown as below: ( ) the bacterial colony forming units of the two measuring points in unit b were cfu/cm and cfu/cm , respectively, which exceeded the hygienic specification of central air conditioning ventilation system in public buildings of china (≤ cfu/cm ), and the rest of the test points met the relevant standards of china. the distribution of bacteria was more than fungi, and the concentration was higher. with the total characteristics of different distribution density, the area of dust associated microorganisms and the air pollution were more serious. ( ) alternaria spp., candida spp., cercospora spp. and cladosporium spp. existed in both units. the candida spp. accounted for % in unit a, and the cladosporium spp. occupied % in unit b. the composition of fungi in b was more complicated. two dominant fungi are both deleterious to health, so the timely maintenance and cleaning are required. it is suggested that the operating space should be reserved in the air conditioning room, so as to avoid incomplete cleaning and disinfection. ( ) within the experimental temperature and relative humidity, with the increase of relative humidity or temperature, the colony growth of the same strain showed an increasing trend. for the prediction model of the fungus growth, the study found that the overall fitting effect of logistic model is better, and r values were greater than . . logistic model for the cladosporium spp. growth was better than gompertz model. at the same time, considering the influence of temperature and relative humidity, the square root model can well predict the growth of cladosporium spp. it provides a theoretical basis for the growth of fungi in the air conditioning system under the hygrothermal environment conditions. why, when and how do hvac-systems pollute the indoor environment and what to do about it? the european airless project the control technology of microbial contamination in air conditioning system overview of biological pollution prevention methods in air conditioning system. heating ventilating and air conditioning relationships between air conditioning, airborne microorganisms and health. bulletin de l'academie nationale de medecine a review of the biological pollution characteristics, standards and prevention and control technologies of central air-conditioning system risks of unsatisfactory airborne bacteria level in air-conditioned offices of subtropical climates development of a method for bacteria and virus recovery from heating, ventilation, and air conditioning (hvac) filters microbial air quality at szczawnica sanatorium the national institute for occupational safety and health indoor environmental evaluation experience air pollution sources in offices and assembly halls quantified by the olf unit control and improvement of building indoor biological pollution a major outbreak of severe acute respiratory syndrome in hong kong epidemiological investigation of an outbreak of pandemic influenza a (h n ) in a boarding school: serological analysis of cases a study on the effective removal method of microbial contaminants in building according to bioviolence agents performance analysis of a direct expansion air dehumidification system combined with membrane-based total heat recovery hvac systems as emission sources affecting indoor air quality: a critical review testing and analysis for microbes and particles in central air conditioning systems of public buildings. heating ventilating and air conditioning endotoxins and bacteria in the humidifier water of air conditioning systems for office rooms investigation and review of microbial pollution in air conditioning systems of public buildings. heating ventilating and air conditioning study on the microbial secondary pollution and control in air conditioning system research on the dust deposition in ventilation and air conditioning pipe. heating ventilating and air conditioning hygienic specification of central air conditioning ventilation system in public buildings indoor air part : detection and enumeration of moulds-culture-based method macro genomics approach in environmental microbial ecology and genetic search application study of the microbiome in waiting rooms of a japanese hospital fungal colonization of automobile air conditioning systems changes in airborne fungi from the outdoors to indoor air; large hvac systems in nonproblem buildings in two different climates research on the microbial diversity analysis in the sediment and macro genomic library at the south pole, xiamen university isolation of vibrio harveyi bacteriophage with a potential for biocontrol of luminous vibriosis in hatchery environments fast length adjustment of short reads to improve genome assemblies highly accurate otu sequences from microbial amplicon reads ribosomal database project: data and tools for high throughput rrna analysis introducing mothur: open-source, platform-independent, community-supported software for describing and comparing microbial communities the silva ribosomal rna gene database project: improved data processing and web-based tools naive bayesian classifier for rapid assignment of rrna sequences into the new bacterial taxonomy study on the relationship between dominant fungi in the air and the allergic asthma in children field guide for the determination of biological contaminants in environmental samples separate effects of moisture content and water activity on the hyphal extension of penicillium rubens on porous media investigation and review of microbial pollution in air conditioning systems of public buildings. heating ventilating and air conditioning microorganisms and particles in ahu systems: measurement and analysis the indoor fungus cladosporium halotolerans survives humidity dynamics markedly better than aspergillus niger and penicillium rubens despite less growth at lowered steady-state water activity effects of temperature, humidity and air flow on fungal growth rate on loaded ventilation filters fungal growth and survival in building materials under fluctuating moisture and temperature conditions mathematical modeling of growth of salmonella in raw ground beef under isothermal conditions from to °c model for combined effect of temperature and salt concentration/water activity on the growth rate of staphylococcus xylosus the study is supported by the national nature science foundation of china ( ), beijing key lab of heating, gas supply, ventilating and air conditioning engineering (nr k ), the fundamental research funds for the central universities (dut qy ) and the urban and rural housing construction science and technology plan project ( -k - ). key: cord- -ttfmm authors: nenna, raffaella; evangelisti, melania; frassanito, antonella; scagnolari, carolina; pierangeli, alessandra; antonelli, guido; nicolai, ambra; arima, serena; moretti, corrado; papoff, paola; villa, maria pia; midulla, fabio title: respiratory syncytial virus bronchiolitis, weather conditions and air pollution in an italian urban area: an observational study date: - - journal: environ res doi: . /j.envres. . . sha: doc_id: cord_uid: ttfmm background: in this study we sought to evaluate the association between viral bronchiolitis, weather conditions, and air pollution in an urban area in italy. methods: we included infants hospitalized for acute bronchiolitis from to . all infants underwent a nasal washing for virus detection. a regional agency network collected meteorological data (mean temperature, relative humidity and wind velocity) and the following air pollutants: sulfur dioxide, nitrogen oxide, carbon monoxide, ozone, benzene and suspended particulate matter measuring less than µm (pm( )) and less than . µm (pm( . )) in aerodynamic diameter. we obtained mean weekly concentration data for the day of admission, from the urban background monitoring sites nearest to each child's home address. overdispersed poisson regression model was fitted and adjusted for seasonality of the respiratory syncytial virus (rsv) infection, to evaluate the impact of individual characteristics and environmental factors on the probability of a being positive rsv. results: of the nasal washings from the infants enrolled, ( %) contained rsv, ( . %) rhinovirus, ( . %) human bocavirus, ( . %) human metapneumovirus, and ( . %) other viruses. the number of rsv-positive infants correlated negatively with temperature (p < . ), and positively with relative humidity (p < . ). air pollutant concentrations differed significantly during the peak rsv months and the other months. benzene concentration was independently associated with rsv incidence (p = . ). conclusions: seasonal weather conditions and concentration of air pollutants seem to influence rsv-related bronchiolitis epidemics in an italian urban area. knowledge on lower respiratory-tract infections in infants, especially bronchiolitis, has changed over the years mainly owing to recent etiological, clinical and prognostic findings (turunen et al., ; midulla et al., ) . viral bronchiolitis is a common disease whose epidemiology is linked to seasonal changes in respiratory viruses. the possible link between climate factors, air pollution and increased childhood morbidity and mortality from respiratory diseases is therefore of interest (darrow et al., ) . previous studies have reported associations between air pollution and reduced lung function, increased hospital admissions, increased respiratory symptoms, and asthma medication use (simoni et al., ; jalaludin et al., ) . although many consider the first years of life an especially vulnerable period, few studies have focused on the effect of meteorology and air pollution on acute viral respiratory infections in this age group (ségala et al., ; vandini et al., ) . in this prospective study, we sought to assess the association between acute viral bronchiolitis, weather conditions and air pollution in infants hospitalized for bronchiolitis over years in rome, italy. to achieve this, we analyzed epidemiological data for respiratory viruses detected in nasal washing samples and mean weekly data for weather conditions (temperature, relative humidity and wind velocity) along with air pollutant concentrations from the regional agency for environmental protection (arpa) network (http://www.arpalazio.net/ main/aria/doc/pubblicazioni). we reviewed the clinical records of prospectively enrolled consecutive full-term young infants with a diagnosis of acute viral moderate-severe bronchiolitis, hospitalized in the pediatric emergency department, "sapienza" university, rome, italy during annual seasonal epidemics (october-may) from to (cangiano et al., ) . the university hospital of the "sapienza" university is a tertiary care and teaching center and is the second major pediatric hospital in rome, italy. it covers about / of roman children, in particular those who live in the center-and northern-east areas of the city. bronchiolitis was defined as the first acute lower-airway infection in children < year old, with a history of upper respiratory tract infection followed by acute onset respiratory distress with cough, tachypnea, chest retractions and diffuse crackles on auscultation (midulla et al., ) . exclusion criteria were underlying chronic diseases (including cystic fibrosis, chronic pulmonary diseases, congenital heart diseases and immunodeficiency) and prematurity. patients' demographic and clinical data were collected through the clinical records and from a structured questionnaire filled in by parents on enrollment. the research and ethics committee of the hospital policlinico "umberto i" approved the study protocol and the written informed consent that was acquired from parents of each child at admission in the study. as part of our routine, from to days after hospitalization, all infants underwent nasal washing obtained by injecting a -ml sterile saline solution into each nostril and collecting the respiratory specimen with a syringe. all samples were delivered on ice within - h to the virology laboratory and on arrival, if needed, were vortexed with beads to dissolve mucus. a µl aliquot for each respiratory specimen was subjected to nucleic acid extraction with the total nucleic acid isolation kit (roche diagnostics, mannheim, germany), and eluted with µl of the supplied elution buffer. a panel of either reverse transcriptase (rt)-pcr or nested pcr assays was developed for detecting respiratory viruses, including rsv, influenza virus (iv) a and b, human coronavirus (hcov) oc , e, nl- and huk , adenovirus, rhinovirus (rv), parainfluenza virus (piv) - , human bocavirus (hbov) and human metapneumovirus (hmpv), as previously described (pierangeli et al., ) . meteorological data for the geographic area of rome (temperature,°c ; relative humidity, % and wind velocity, km/h) were recorded from rome meteorological stations. data were analyzed by year of recruitment, based on the date of admission and on each patient's residential address; data were summarized as mean values for each week during the -year study. the air quality network, owned and operated by arpa lazio (http://www.arpalazio.net/main/aria/doc/pubblicazioni), currently has chemical measuring stations, some also equipped with meteorological sensors, distributed across five provinces with municipalities. the arpa network routinely measured air pollutants. we retained data from the urban background monitoring sites only. these sites are representative of ambient air pollution in the rome area. we obtained mean weekly concentration data for the day of admission, from the urban background monitoring sites nearest to each child's home address. we chose "a priori" to use mean exposure during the week before admission since the incubation period of bronchiolitis is very short (less than days). the following air pollution data were recorded: sulfur dioxide (so ) concentration (measured using ultraviolet fluorescence); nitrogen dioxide (no ) concentration (measured using chemiluminescence); carbon monoxide (co) concentrations (measured using a continuous analyzer based on the spectrophotometric technique of non-dispersive absorption of infrared radiation around nm according to the law of lambert-beer) levels of suspended particles with an aerodynamic diameter less than and . µm (pm , pm . , measured by absorption of beta radiation); ozone (o ) concentrations (measured using spectrophotometric technique of absorption, by ozone molecules, of ultraviolet radiation of nm wavelengths); benzene (bz) concentrations (measured using gas chromatography technique). continuous variables are expressed as arithmetic means ± sd or median (iqr) depending on their distribution and as the number and percentages for categorical variables. pearson's correlation was used to correlate the number of rsv-or rv-positive cases with meteorological variables and mean air pollutant concentrations. overdispersed poisson regression model was fitted to evaluate the impact of individual characteristics and environmental factors on the probability of a being positive rsv (fig. ). in this model the dependent variable was the monthly count of positive rsv and independent variables were the air pollutants no , pm , so , bz and o . in order to adjust for seasonality of the rsv infection, time trend was modelled by introducing the effect of month. as recommended by cameron and trivedi (cameron and trivedi, ) we used robust standard errors for the parameter estimates to control for mild violation of the distribution assumption that the variance equals the mean. robust standard errors and p-values were calculated accordingly. in order to evaluate if the proposed model captures the seasonality of the phenomenon we analyzed the residuals of the model according to the autocorrelation plot and the partial autocorrelation-the ljung-box test applied to the residuals of the model has been involved in order to reveal significant autocorrelations. we test the goodness of fit of the overall model using the residuals deviance. the residual deviance is the difference between the deviance of the current model and the maximum deviance of the ideal model where the predicted values are identical to the observed. therefore, if the residual difference is small enough, the goodness of fit test will not be significant, indicating that the model fits the data. all computations were done using r statistical software (http:// www.r-project.org/). the viral peak was determined as the months with the highest r. nenna et al. environmental research ( ) - number of virus detections. during the years of the study ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) , , children referred to the pediatric emergency department of policlinico umberto i of rome, with a mean of children/years and the mean of . % children/years were admitted to hospital for bronchiolitis. we enrolled consecutive infants hospitalized for bronchiolitis. their mean age was . ± . days (range - days), % of the infants were < month old, . % between and months, and . % between and months. fifty-five percent were male. the mean weight at hospital admission was . ± . kg. of the infants, % had siblings, . % of infants and . % of siblings were attending school. a total . % infants were breastfed and in % parents' questionnaire answers mentioned maternal smoke exposure. the nasal wash specimens tested positive for respiratory viruses in / infants enrolled. among the virus positive infants, pcr detected alone rsv in ( . %) infants, rv in ( . %), hbov in ( . %), and hmpv in ( . %). in . % of infants, pcr detected other viruses: piv- in children, piv- in children, hcov in children, and iva in children. specimens from recruited infants ( . %), contained more than one virus: rsv plus hbov in children, rsv plus rv in infants, rv and hmpv in infants, rsv and hmpv in infants, rsv and iva in infants, rsv and piv- in infant, hbov and hmpv in infant, hbov and piv- in infant and rv plus piv- in infant. specimens from only one infant contained viruses: rsv plus rv and hmpv. the most frequently detected pathogen was rsv. in all years studied, rsv-bronchiolitis epidemics had a winter trend and activity peaked from december to february. the second most frequently detected pathogen was rv, detected throughout from october to may with no peak activity (cangiano et al., ) . data comparing weather conditions in the annual epidemics showed that median (iqr) temperature and relative humidity differed during the months when rsv activity peaked (december-february) and during the other months (october-november and march-may) [tem-perature°c = . ( . - . )vs . ( . - . ), p < . ; relative humidity % = . ( . - . ) vs . ( . - . ); p < . ). wind velocity remained unchanged (km/h = . ( . - . ) vs . ( . - . ). the number of rsv-positive infants correlated negatively with temperature (r = − . , p < . ), and positively with relative humidity (r = . , p < . ). no correlation was found with wind velocity. of the infants enrolled, data for were included in the rome arpa network weekly pollution analysis and data for were excluded: children not included because they came from the rome province and children who lacked address data. thus for air pollution analysis we used data from infants. as expected, there was a high correction between temperature and most air pollutants. the trend of the pm remarkably resemble the trend of the temperature, with higher level of pm corresponding to the lower level of temperature. a similar behavior can be noticed for all the other air pollutants (see fig. ) with the exception of benzene (fig. ) whose level is not so clearly related with other factors. air pollutant concentrations differed significantly during the peak rsv months and the other months. except for o , many air pollutants increased more during the months when rsv activity peaked than during the other months (october-november and march-may, table ). the only significant predictors are the month, the total number of patients (considered as all the infants enrolled in the study) and benzene level (fig. ) . table shows the parameter estimates, the robust standard error, the corresponding % confidence intervals and the p values. the seasonality component, accounted by the effect of the month, was strongly significant: indeed, the model highlights that the number of rsv positive infants significantly increase in january, february, march, april and december. for example, the expected log count increases by approximately in january and in december and . in the other months. fig. shows the % confidence intervals of the month effect on the expected log count: as expected, a decreasing trend is evident with a significant decrease of the rsv positive patient in spring and in autumn. with respect to the pollutant, table shows a significant association between the number of rsv positive infants and benzene concentration: the expected log count of rsv positive patient for a one-unit increase in the benzene level is . , i.e. with a benzene level of . , the expected count of rsv positive patient would increase of about % ((exp( . * . ) − .) * ) = %. another important factor for the number of rsv positive patient is the total number of patient: for number of patient equal to , the expected number of rsv positive patient would increase of about % ((exp ( . * ) − ) * ) = %. in order to evaluate if the proposed model captures the seasonality of the phenomenon (the association between pollution and rsv), we analyzed the residuals of the model. the autocorrelation plot and the partial autocorrelation were not significant. the ljung-box test applied to the residuals of the model revealed that these autocorrelations were not significant (p value = . ) (see fig. ). insofar as, the goodness of fit test of the model has been evaluated according to the residual deviance criterion. therefore, if the residual difference is small enough, the goodness of fit test will not be significant, indicating that the model fits the data. when applied to the proposed model, the test leads to a pvalue = . allowing us to conclude that the model fits the data reasonably. in this prospective study enrolling infants hospitalized for acute viral bronchiolitis during seasonal epidemics in rome, italy we found a strong correlation between peak rsv activity (but not peak activity for the other viruses investigated) and cold temperatures, higher relative humidity and air pollutants, especially benzene. this new information clearly linking weather condition, various traffic-derived pollutants and the timing of epidemic, comes from a large series of infants, hospitalized over a long study duration. the most frequently detected respiratory virus in our hospitalized infants was rsv ( . % alone and . % in association with other viruses as others have reported (lanari et al., ) . in italy, as in other countries with temperate climates, rsv causes epidemics during the winter months (vandini et al., ; meerhoff et al., ) . the second most frequent virus we detected was rv (identified in . % alone and . % combined with other viruses), and the third was hbov ( . % alone and . % combined with other viruses). in our study neither rv nor hbov peaked during epidemics and were diagnosed with the same frequency throughout the epidemic seasons. during the -year study, as other studies in european countries confirm (forsberg et al., ; d'amato, ) , mean temperature and relative humidity in rome progressively increased, but these increase has not been reported in terms of regression. these climate changes could be influenced by numerous environmental factors, including air pollution. the meteorological data differed notably during peak rsv activity and during the other months, temperatures being lower and relative humidity higher. rsv transmission is inversely related to temperature (vandini et al., ; lanari et al., ) . climatic factors could promote viral infections in different ways: for example, by increasing virus survival, affecting their climate-dependent behavior (for example, greater persistence in closed and crowded ambient settings when temperatures remain low) and by acting on the pediatric population's immune response (cui et al., ; tang and loh, ; paynter, ; du prel et al., ; nelson and demas, ; haus and smolensky, ; vandini et al., ) . rsv is more active at cold temperatures because cold makes the virus' lipid envelope more resistant and therefore more stable in the secretions through which it is transmitted (vandini et al., (vandini et al., , cui et al., ; tang and loh, ) . equally important, cold temperatures might drive populations indoors where rsv spreads more readily (vandini et al., ; barnett et al., ) . crowding, along with a suitable susceptible population of newborns and infants, could trigger seasonal rsv epidemics. another major climatic factor that in our study correlates with rsv activity is relative humidity. many studies have underlined the association of increased humidity and rsv, hcov and piv detection rates (cui et al., ; vandini et al., ; welliver, ) . these observations support a previous finding that high average humidity ( %) favored virus survival (cui et al., ; tang and loh, ; vandini et al., ) . the other climatic factor we investigated, mean wind velocity, had no correlation with rsv-positive cases nor did it correlate with the peak rsv activity. previous studies disagreed on whether wind velocity influenced seasonal changes in rsv activity (cui et al., ; vandini et al., ) . in our infants hospitalized for bronchiolitis, neither temperature, relative humidity nor wind velocity affected rv detection. when we analyzed the association between the two major detected viruses (rsv and rv) and meteorological conditions and air pollutants pearson correlation showed that rsv-positive cases correlated positively with bz, no x , so and particulates (pm and pm . ) and negatively with o . the inverse correlation with rsv receives support from the finding that o values peaked in the summer whereas the other air pollutant concentrations we tested increased in the autumn-winter season (october-february). conversely, no correlation was found between air pollutants and the number of rv-positive cases. these new findings obtained by analyzing the correlation between bronchiolitis from viruses and environmental factors during seasonal epidemics corroborate and extend current knowledge on how environmental factors influence rsv seasonal bronchiolitis. moreover, we decided to correlate the week of admission because the incubation period of bronchiolitis is very short, less than days, and we thought that it was the week more closely correlated with times of virus acquisition, incubation, replication and clinical registration (ségala et al., ) . ample evidence has already shown a positive correlation between air pollutants and morbidity for viral respiratory infections and other respiratory conditions such as asthma and chronic obstructive pulmonary disease (lin et al., ; dong et al., ) . in another study conducted in italy, vandini et al. ( ) examined rsv bronchiolitis in bologna (italy) during three consecutive winter seasons and obtained a similar correlation between rsv peak and mean temperature but no correlation with relative humidity concentrations. unfortunately, they studied the correlation only between rsv and pm and pm . . as we did, they found a correlation between rsv and evaluated pollutants but in the regression model, neither were predictive factors for rsv bronchiolitis. conversely, ségala et al. ( ) showed a short-term relationship between air pollutants and daily numbers of emergency hospital consultation and hospitalization for bronchiolitis among children < years of age in paris. we found that the most predictive air pollutant for rsv peak activity, at constant temperature and relative humidity, was benzene. the main anthropogenic sources of air pollutants are mobile and stationary combustion sources, derived from traffic density, thermoelectric data are expressed as median and interquartile range (iqr). sulfur dioxide (so ), nitrogen oxide and dioxide (no x , no ); carbon monoxide (co); ozone (o ); benzene (bz); levels of suspended particles less than µm (pm ) and less than µm (pm . ) in aerodynamic diameter. a mann-whitney u test. nenna et al. environmental research ( ) - system, incinerators, industrial systems and domestic heating (kampa and castanas, ) . benzene is released to our environment from industry effluents, combustion of gasoline and other petrochemicals used in our cars and industries. evidence from experimental models has suggested the pathogenetic mechanisms underlying benzene-induced toxic damage to the respiratory airways causing apoptotic changes in the parenchymal components of the lungs (weaver et al., ; bahadar et al., ) . common cellular mechanism by which most air pollutants exert their adverse effects is their ability to act directly as lipid and protein pro-oxidants or as free radical generators, promoting oxidative stress and inducing inflammatory responses (menzel, ; rahman and macnee, ) . to bring air pollutants down we probably need to obtain more reliable information on the state of the air we breathe and to implement preventive maneuvers to minimize exposure to pollutants. although the possible pathogenetic mechanisms underlying the potentially clinical risk factors go beyond our objectives in this study enrolling infants hospitalized for acute viral bronchiolitis, our findings may indicate future research directions. infants and children differ strongly from adults in toxicokinetics. their peculiarity and vulnerability consist of lower body weight, higher relative liver weight, higher ratio between body surface and body weight, smaller lung caliber, higher particle deposition in the respiratory tract, and generally immature lungs (heinricha and slama, ; samuel, ) . our findings suggest that one way to reduce rsv bronchiolitis morbidity in infants may be to develop simple and inexpensive patient-centered measures that reduce infant exposure to indoor and outdoor pollution. for example, parents should avoid taking infants into polluted environments r. nenna et al. environmental research ( ) - in cool and humid weather conditions. a limitation in our study is that we were unable to obtain significant correlations for coinfections or for some viruses that we detected less often than rsv and rv. other limitations are that we had no information on travel history (outside of roma) of the children before their hospital admission and we could examined acute background air pollution exposure alone. moreover, we have no data on outpatients with mild bronchiolitis and on patients from other hospitals in rome. another important issue is that, insofar as infants spend the majority of their time inside the home, some variables such as ventilation, gas or oil heating or cooking, may be significant unmeasured confounders or causative agents. finally, this study was focused only on the meteorological and pollution exposure during the week before admission; it would be interesting in future studies to evaluate the maximum value for the meteorological and pollution data within the week before the admission. factors responsible for increasing the risk of virus-related bronchiolitis in italy probably include meteorological factors and chronic traffic-derived air pollution combined. current understandings and perspectives on non-cancer health effects of benzene: a global concern air pollution and child respiratory health: a case-crossover study in australia and new zealand microeconometrics using stata bronchiolitis: analysis of consecutive epidemic seasons viral aetiology of acute respiratory infections among children and associated meteorological factors in southern china effects of climatic changes and urban air pollution on the rising trends of respiratory allergy and asthma air pollution and acute respiratory infections among children - years of age: an -year time-series study gender differences and effect of air pollution on asthma in children with and without allergic predisposition: northeast chinese children health study an expert assessment on climate change and health -with a european focus on lungs and allergies biologic rhythms in the immune system fine particles, a major threat to children acute effects of urban ambient air pollution on respiratory symptoms, asthma medication use, and doctor visits for asthma in a cohort of australian children human health effects of air pollution prevalence of respiratory syncytial virus infection in italian infants hospitalized for acute lower respiratory tract infections, and association between respiratory syncytial virus infection risk factors and disease severity coarse particulate matter and hospitalization for respiratory infections in children younger than years in toronto: a case crossover analysis variation of respiratory syncytial virus and the relation with meteorological factors in different winter seasons the toxicity of air pollution in experimental animals and humans: the role of oxidative stress respiratory syncytial virus, human bocavirus and rhinovirus bronchiolitis in infants seasonal changes in immune function humidity and respiratory virus transmission in tropical and temperate settings human bocavirus infection in hospitalised children in italy are meteorological parameters associated with acute respiratory tract infections? oxidative stress and regulation of glutathione in lung inflammation williamson, fundamentals of air pollution, harlow. longman higher education winter air pollution and infant bronchiolitis in paris adverse effects of outdoor pollution in the elderly correlations between climate factors and incidence-a contributor to rsv seasonality the first wheezing episode: respiratory virus etiology, atopic characteristics, and illness severity respiratory syncytial virus infection in infants and correlation with meteorological factors and air pollutants immunological, viral, environmental, and individual factors modulating lung immune response to respiratory syncytial virus the effects of benzene exposure on apoptosis in epithelial lung cells: localization by terminal deoxynucleotidyl transferase-mediated dutp-biotin nick end labeling (tunel) and the immunocytochemical localization of apoptosis-related gene products the relationship of meteorological conditions to the epidemic activity of respiratory syncytial virus the authors thank jonathan grigg for the critical review of the paper and mrs. alice crossman for help with english style. key: cord- -q sbvjvx authors: xu, zhonglin title: calculation theory of nonuniform distribution in cleanroom date: - - journal: fundamentals of air cleaning technology and its application in cleanrooms doi: . / - - - - _ sha: doc_id: cord_uid: q sbvjvx due to the nonuniform distributions of airflow and dust particles, particles in cleanroom are actually not evenly distributed. this chapter will focus on the calculation theory of three-zone nonuniform distribution. because of the nonuniform distribution of particles in cleanroom, deviation is inevitable when results are based on the calculation theory of uniform distribution. in general, the larger the nonuniform distributions of indoor airflow and dust particles are, the larger the difference between the measured values and the calculated values according to the uniform distribution theory will be. for the nonuniform distribution discussed here, it is assumed that the generation of particles is uniform and stable, but the dust particle distribution is not uniform. even for this nonuniform distribution, it does not mean the nonuniform distribution at every place, but the regional nonuniform distribution. there is regional concentration difference. in the following sections, we will discuss the factors affecting the nonuniform distribution of indoor particle concentration separately. outlet and its position) according to the uniform distribution calculation method. the measured value will be higher than the calculated value only when the airflow distribution is not uniform, which weakens the dilution effect. both positive and negative deviations exist between the measured value and the calculated value for local perforated plate, top supply, and diffuser, which indicates that they are slightly better than the side supply mode in terms of uniformity. for the full perforated plate, all the measured values are almost lower than the calculated values, which mean the uniformity may be better. the effect of the position of air supply outlet is more obvious. for example, for the top air supply outlet with larger air supply velocity, if they are placed on the ceiling where is concentrated at one side of the room, the indoor airflow will become extremely uneven, where several vortex may appear. in this case, the measured particle concentration is much higher than the calculated value, which has been introduced in chap. . the air inlet quantity has significant effect on the uniformity of air distribution. table . is based on the experimental results of kayatawa [ ] . it can be seen from table . that with the same filters and air change rate, the lesser the number of air supply outlet is, the higher the average indoor particle concentration is, when it is compared with the calculated value by the uniform distribution method. because when the number of air supply outlets is small, the proportion of turbulent flow and the eddy area become large, and the uniformity becomes poor. when the number of air supply outlets is more, the average particle concentration is gradually lower than the calculated value. because when the eddy current area becomes small, the velocity field becomes more uniform, and the turbidity is reduced. moreover, with more air supply outlets, the extrusion effect of airflow increases. in addition, it has been mentioned in the chap. that with the same air change rate, when the number of air supply outlets increases, the air velocity reduces, which is helpful to reduce the deposition of particles on the surface of the workpiece. the air change rate has great impact on the uniform distribution of indoor airflow and particle concentration. in order to make the airflow and particle concentration fields uniform, there must be sufficient air flow rate to dilute, and the dilution area should be as large as possible, until the whole room. when the air change rate becomes less, the flow rate becomes insufficient, and the corresponding number of air supply outlets would become less, which is likely to cause more big vortex area. therefore the measured particle concentration is generally bigger than the calculated value, because in fact the effect of uniform dilution is not achieved at all. but when the air change rate is more than h À , the differences are generally not obvious. with the increase of the air change rate, more uniform field will be achieved in full chamber with dilution. the measured value will approach to the calculated value gradually. when the air change rate is about h À , both of them are roughly the same (this will be explained later). when the air change rate continues to increase, opposite situation will occur, where the measured value is generally lower than the calculated value. this is because not only the full uniform dilution has been reached, but also the extrusion effect of the airflow increases because of the increase of the flow rate and the number of air supply outlets (if the number of air supply outlets does not increase, the flow rate of one air supply outlet will be too large, which then causes the opposite result). in this case, the actual particle concentration is still lower than that calculated by uniform dilution method. in conclusion, there are two main aspects for the influence of the air change rate. for a small number of air change rate, the measured particle concentration is higher than the calculated value. for a large number of air change rate, the measured particle concentration is lower than calculated value. of course, this is only the general rule, which may not be absolutely true. different forms of air supply outlets have obvious effect in the turbulent flow cleanroom. several main types of air supply outlets are listed in fig. . . the following conclusions can be reached with the experiment [ ]: . self-purification times area different for various kinds of air supply outlets. type c with the extrusion airflow is the best, which is slightly better than the theoretical value with the uniform distribution method. type b with actively mixing flow is the next, which is close to theoretical value. type a with common airflow is the worst, which is worse than the theoretical value, which is shown in fig. . . . when there is indoor dust generation source, the indoor particle concentration with type c is very small. . for type b with actively mixing flow, due to the induction effect of suction, the dust generation near the head may have effect on the top of the table. . for the general type c, the diffusion performance near the head and foot is good. but since the current near the room end is weak and there is updraft, high concentration is prone to appear when particle is generated indoors. . when interferences occur when people are walking around, no matter what kind of air supply outlet is, the difference is not large. when the external disturbance is small, the advantage with type c appears. to sum up, in order to overcome the problem of deviation of calculated result with assumed uniform distribution method, and to deeply research the characteristic of cleanroom, it becomes an important topic to study the nonuniform distribution calculation method in cleanroom. in , dual zone model was proposed by kayatawa [ ] who tried to solve this problem, but the specific calculation method was not available. the three-zone nonuniform distribution model is shown in fig. . [ ] , which is divided into the mainstream area, the vortex area, and the return air area. the starting point is as follows: . in the mainstream area, because there is a certain air velocity above the working area, particles will not be dispersed into the whole mainstream area continuously and uniformly against the airflow by the dust source g a . as illustrated in front chapters, the probability of particle dispersion into the whole room with the effect of dispersion, deposition, and mechanical force is very small. they distributed mainly along the airflow. so it is more appropriate to term it as "distribution" instead of "diffusion." this is why all this book "uniform distribution" and "nonuniform distribution" are used, instead of "uniform diffusion" and "nonuniform diffusion." moreover, it is easy to wrongly consider the term "diffusion" as pure molecular dispersion diffusion movement. for particles generated from the dust source in the mainstream area, a part of them is uniformly driven into the boundary layer of the airflow along the eddy upwards and then downwards. according to the simple experiment, when there is a dust source in the air supply flow with enough width, it is unlikely to distribute crosswise to the whole cross section of the flow. when air velocity is . m/s, the expansion angle behind the dust source is only - [ ] . it has been clear when the lower limit of air velocity was introduced that it is enough to control the lateral spread of pollution with the release velocity of m/s, when the air supply velocity is . m/s. for pollution with smaller release velocity (such particle generation by occupant), it is less likely for particles to disperse against the airflow. according to the jet flow principle, the cross section of airflow expands, and the flow rate increases, which is mainly from the supplement of side eddy air. therefore, for particles generated in the mainstream area, they will move along the airstream direction with only slightly extension, and then enter the return air area, where a certain degree of mixture occurs. part of them is exhausted through the return air grille, and others return to the vortex area. in the vortex area, particles spread out and then go through the whole mainstream area uniformly with the airflow induced by the mainstream area. according to this mechanism, the unidirectional flow and the turbulent flow cleanrooms can be linked together. for the vertical unidirectional flow cleanroom, return outlets are placed on the floor, so the airflow in the entire cross section of the working area is the mainstream, and there is no eddy current area. so below the working area, there is no back vortex in the flow, where basically particle cannot be brought back upwards and then "disperse" again. if there is no eddy current in the upper part of the room, it is the ideal unidirectional flow. even if dust source exists in the upper part, dust particles will not spread into the entire mainstream area because no eddy current exists in this region. this situation is the basis for the analysis of particle concentration in unidirectional flow cleanroom which is discussed in the previous uniform distribution method. if eddy area exists in the upper part, such as the situation when filters are placed with intervals, the amount of particles entering into the eddy area then the mainstream area will be dependent on the ratio of blowing area, the eddy size, and the size of upper dust source. generally for the unidirectional flow cleanroom, the upper eddy area is very small, and dust source is also rare. so particles scattered in the mainstream area are few. therefore, in the unidirectional flow cleanroom, the influence of dust source on the particle concentration is very small. with the increase of eddy area, the particle concentration may be affected when the eddy area increases to a certain extent. in this case, it becomes the turbulent flow cleanroom. . there is a return air area where particle concentration is different from that in the mainstream and eddy areas. the actual test has showed [ ] that, for a unidirectional flow cleanroom with hundreds of air change rate and air return below both sides, the particle concentration of the working area in the mainstream area is equivalent to about % of the average concentration in the return air area (the height of return air outlet is about . m). the detailed data are shown in table . . according to the measurement by no. design institute of the former fourth ministry of machinery and industry, the air change rate in turbulent flow cleanroom reached h À . the particle concentration at the height between . and m is about % of the average concentration at the return air area. this is consistent with the results shown in the table above. the measured results also show that, for small value of air change rate, the average ratio is . . from the front analysis, particles generated in the mainstream area are concentrated in the return air area, and this is the important reason why the concentration at the return air area is higher than that in the mainstream area. but the concentrated area of particles should be very small. the above three points are the main content for three-zone nonuniform distribution model. according to the three-zone model, particle concentration n c at the return air area is composed of two parts: one is the concentration of the mainstream area, and the other is the concentration of the return air area where particles released from dust source g a are mixed with the total air volume (q + q ), that is, particle concentrations in other two areas should be calculated with the differential equations. let we know where n a is the concentration of the mainstream area (#/l); n s is the concentration at the air supply outlet (#/l); n b is the concentration of the eddy area (#/l); g a is the particle release rate in the mainstream area (#/min); g b is the particle release rate in the eddy area (#/min); q is the air supply flow rate (l/min); q is the induced flow rate by the mainstream area (l/min); v is the room volume (l); v a is the volume of the mainstream area (l); v b is the volume of the eddy area (l). for eq. ( . ), we know: after reorganization, we know: ( . ) so the differential equation can be rewritten as: we obtain: similarly we can get: the coefficients of k , k , k and k in above expressions are determined with the initial conditions. when t ! , we know: since the range of return air area is smaller, its volume can be ignored. the average concentration of the mainstream area and the eddy area is approximately the average room concentration, that is, when they are inserted into the expressions of g a and g b , and let g v : ¼ g [#/(m ·min)], eq. ( . ) can be rewritten as: equation ( . ) can be called the n-n general formula for cleanroom. . obviously, under the condition of uniform distribution: let the coefficient at the right of eq. ( . ): it can be used to express the difference of the particle concentration between uniform and nonuniform distribution conditions. for the conventional cleanroom with air cleanliness level below class for particles ! . μm, since the efficiency of hepa filter can reach above . (for ! . μm), n s is usually about . - . #/l when circulating air system is used. when full fresh air system is used and m is about #/l, n s is less than . #/l. for the cleanroom with air cleanliness level higher than class for particles ! . μm, since the efficiency of hepa filter can reach above . (for ! . μm) and the efficiency of prefilter is also required to be about . , n s is usually below . #/l when circulating air system is used. it is clear that n s in air cleaning system is very small, which can be approximated as: where n is the particle concentration with the uniform distribution calculation method; n v is the particle concentration with the nonuniform distribution calculation method; ψ is the uniformity coefficient. but for the cleanroom with air cleanliness level class for particles ! . μm when the full fresh air system is used, the maximum result of n v can be added with . so in eq. ( . ), we know: therefore, we obtain: this is like the situation in the test pipeline for air filter, where the downstream concentration of filter depends only on the inlet concentration. of course, this is only the ideal situation. (b) if filters are not fully placed on the ceiling, and there is a certain value of the ratio of blowing area, eddy area will exit. with the decrease of this ratio, both ψ and v b will increase, and β will reduce, so n v will also increase. this means the particle concentrations are different for the unidirectional flow cleanroom with different values of the ratio of blowing area. equation ( . ) can be used for calculation. similarly, the particle concentrations are different for the unidirectional flow cleanroom with different occupational densities. therefore, the number of occupants in the unidirectional flow cleanroom should be controlled appropriately. (c) for different turbulent flow cleanrooms, the size of the mainstream area, the size of the eddy area, and the volume of induced airflow are different. for example, the diffusion angle of diffuser is a little larger than hepa filter air supply outlet, so v b is smaller and ψ is larger. so the difference of particle concentrations in different turbulent flow cleanrooms is shown. in although the difference of the calculated results is not large in the final two cases between the uniform distribution calculation method and the nonuniform distribution method, the calculated results are only related to the air change rate, which has been illustrated in the uniform distribution calculation method for unidirectional flow in chap. . other factors are not reflected in these two cases. so the calculated results among the final three cases are basically the same. but it is obvious that in the th case, the calculated result is much different from the actual value. although in general the calculated results with the nonuniform distribution calculation method are more accurate than the uniform distribution calculation method, in some circumstances, opposite results may appear, which will be illustrated later. study of cleanroom ( ) application of air cleaning technology study of characteristics of air supply outlet in conventional cleanroom calculation method for the non-uniform distribution in cleanroom air conditioning and air cleaning translated by the th design research institute of the former fourth machinery industry department key: cord- - hiutrct authors: satheesan, manoj kumar; mui, kwok wai; wong, ling tim title: a numerical study of ventilation strategies for infection risk mitigation in general inpatient wards date: - - journal: build simul doi: . /s - - - sha: doc_id: cord_uid: hiutrct aerial dispersion of human exhaled microbial contaminants and subsequent contamination of surfaces is a potential route for infection transmission in hospitals. most general hospital wards have ventilation systems that drive air and thus contaminants from the patient areas towards the corridors. this study investigates the transport mechanism and deposition patterns of middle east respiratory syndrome coronavirus (mers-cov) within a typical six bedded general inpatient ward cubicle through numerical simulation. it demonstrates that both air change and exhaust airflow rates have significant effects on not only the airflow but also the particle distribution within a mechanically ventilated space. moreover, the location of an infected patient within the ward cubicle is crucial in determining the extent of infection risk to other ward occupants. hence, it is recommended to provide exhaust grilles in close proximity to a patient, preferably above each patient’s bed. to achieve infection prevention and control, high exhaust airflow rate is also suggested. regardless of the ventilation design, all patients and any surfaces within a ward cubicle should be regularly and thoroughly cleaned and disinfected to remove microbial contamination. the outcome of this study can serve as a source of reference for hospital management to better ventilation design strategies for mitigating the risk of infection. hospitals are designed to accommodate a large number of patients with varying degrees of disease severity. as inpatient care facilities such as general medical and surgical hospitals are used by patients, healthcare workers and visitors simultaneously, the susceptibility of these people to hospitalacquired infections (hais) or nosocomial infections is reasonably high (giannini et al. ). the largest nosocomial outbreak of severe acute respiratory syndrome (sars) in hong kong, china and the recent outbreak of middle east respiratory syndrome (mers) in south korean hospitals have had substantial morbidity and mortality (oh et al. ; tang et al. ) . the three widely known transmission routes of sars coronavirus (sars-cov) and influenza viruses are close contact, long-range airborne and fomite (xiao et al. ) . although close contact is generally regarded as the possible transmission route of mers coronavirus (mers-cov) (zumla et al. ) , studies have indicated that airborne and fomite are other possible modes of mers-cov transmission (kim et al. ; van doremalen et al. ) . there is also sufficient evidence to support that an association exists between ventilation strategies and dissemination of nosocomial pathogens in indoor environments . hence, it is essential to revise and update current ventilation design strategies to contain potential outbreaks caused by novel emerging viruses in the future. infections are explicitly considered in the ventilation requirements for healthcare facilities (li et al. ) . most general hospital wards have ventilation systems that drive air from the patient areas to the circulation areas. airborne pathogens can thus spread from a ward cubicle to the rest of the ward and lead to a potential for nosocomial outbreaks. although it is widely assumed that increasing the air change rate (ach) can reduce infection risks, it was shown that the risk of exposure to pathogens could increase with an increased ventilation rate under certain circumstances build simul https://doi.org/ . /s - - - satheesan et al. / building simulation (bolashikov et al. ; pantelic and tham ) . several studies have also emphasized that apart from ach, the design of a ventilation system is a determinant controlling contaminant flow paths (ghia et al. ; licina et al. ; memarzadeh and xu ; pantelic and tham ) . as there is a paucity of guidelines or strategies for general ward ventilation (beggs et al. ; chaudhury et al. ; roy and milton ) , a review of present nosocomial infection control practices for presumably low risk zones and unprotected areas such as a general ward is all-important (humphreys ; wan et al. ) . to get meaningful estimations of the transport and deposition of pathogens in a mechanically ventilated space, accurate prediction of airflow pattern is essential. with the advent of improved turbulence modelling and computing power, the application of computational fluid dynamics (cfd) to indoor environment simulation has been on an increasing trend (nielsen ) . under varied operating conditions in an indoor environment with high temporal and spatial resolution, cfd numerical simulation techniques provide insights into the overall airflow and bioaerosol distribution (chao et al. ; . in fact, cfd techniques have been used to estimate ventilation effectiveness for contaminant removal in healthcare facilities. as the number of research studies on ventilation systems for general inpatient wards with respect to air change rate and exhaust airflow rate is limited, this study evaluates the combined impacts of these two parameters on the airflow as well as infection risk distributions of droplet nuclei of size . μm (i.e. mers-cov) within an air-conditioned general inpatient ward cubicle. moreover, a simple yet cost-effective ventilation system design that can minimize the risk of infection in an existing hospital ward is proposed. the risk of infection increases with increasing pathogen exposure. even a single pathogen can initiate the onset of an infectious disease in a susceptible person (nicas et al. ; wells ) . based on the bioaerosol transport and deposition mechanism, this study classified the types of infection transmission in a general inpatient ward environment into two categories: ( ) cross infection within a ward cubicle; and ( ) infection from a ward cubicle to the corridor. the deposition of particles in patients due to the exhalation of pathogens by other patients accommodated in the same ward can lead to cross infection. the severity of cross infection among patients depends on the location of each patient and the overall airflow distribution pattern within the ward environment. exposure to infection due to the inhalation or deposition of particles expelled by other patients through sneezing (infectors) can be estimated for a patient i (receptor exposure): where e i is the fractional exposure count for patient i, e j is the fractional emission from patient j and n is the total number of patients. based on this expression, the locations with the maximum and minimum risks of cross infection can be determined for the patients within the same ward cubicle. general inpatient wards in hospitals are recommended to have a relative humidity between % and % (ashrae a). as mers-cov can survive for up to hours on plastic or steel surfaces at a room temperature of °c and a humidity of % (oh et al. ) and a portion of the exhaled particles will deposit to surfaces such as the ceiling, floor and walls in the ward, this study also took infection through surface contamination into account. based on the three deposition ratios expressed in eq. ( ), namely wall deposition ratio r w , ceiling deposition ratio r c and floor deposition ratio r f , the infection transmission through surface contamination under all ventilation scenarios considered in this study can be estimated. where n s is the number of particles expelled by an individual patient through sneezing, and n w , n c and n f are the numbers of particles from the sneezing deposited onto the walls, ceiling and floor respectively. the dispersion of particles that were expelled by sneezing from an infected patient in a ward cubicle to the corridor was taken as the infection from a ward cubicle to the corridor. it was noted that these particles could also spread to adjacent ward spaces connected to the corridor (chen et al. ). the number of particles being exhausted to the corridor n e can be estimated based on the exhalation rates of individual supine patients in their respective beds. using the exhausted ratio r e for individual patients as expressed in eq. ( ), locations of the patients who contribute the most and the least to the spread of infection to the corridor can be determined. e e s n r n = ( ) a typical semi enclosed six bedded general inpatient ward cubicle with dimensions . m (l) × m (w) × . m (h) and a between-bed spacing of m as illustrated in fig. was used in this study (li et al. ; yu et al. ). the cubicle was mechanically ventilated (with a positive pressure towards the corridor) and accommodated six supine patients. the supply air, i.e. mixed air estimated based on the room volume and air change rates ( h − - h − ), was delivered to the cubicle through four ceiling mounted diffusers. in the base case as shown in fig. (a) , the supply air and ward air exhausted to the corridor were set to be equal for all air change rates. for exhausting % and % of supply air (i.e. ea = % and ea = %), local exhaust grilles (grille size . m × . m) were installed as depicted in fig. after the extraction by exhaust grilles, the rest of the cubicle air was exhausted towards the corridor. the airflow distribution and the transport mechanisms of bioaerosols in the ward cubicle were investigated using a finite volume based cfd code (ansys fluent . ). the numerical simulation model consists of a continuum phase (air) and a discrete phase (droplet nuclei). in this study, the governing equations of continuity, momentum and energy for the continuum phase were based on an eulerian framework, and the discrete phase was modelled by a lagrangian framework (wong et al. ). the threedimensional airflow was modelled as a steady-state incompressible turbulent flow. cfd possess miscellaneous number of turbulence models, although it is very difficult to pinpoint one turbulence model that outperforms others for all class of problems. hence, the turbulence model selection is a compromise based on factors such as flow physics involved, established practice for predicting a particular set of problem, computational resources, accuracy level and simulation time (gao and niu ) . numerous studies on turbulent indoor airflow have been carried out through reynolds-averaged navier stokes (rans) simulations, whereas for some case studies large eddy scale simulations (les) have been preferred to provide accurate prediction of flow field variables. however, les demands much higher grid requirements as well as computational time compared to rans, which makes rans widely used (blocken ) . the reynolds-averaged navier stokes (rans) equation greatly reduces the complexity involved in the simulation of turbulent flows. the equations have time averaged flow field variables which would eliminate the turbulent fluctuations. although, this simplification leads to the creation of additional reynolds stress tensors which are unknowns within the equation and leads to closure issues. the eddy viscosity turbulence modelling provides closure to equations and the most preferred eddy viscosity turbulence model to simulate the indoor airflow distribution is the renormalization group (rng) k-ε. the rng k-ε model, was chosen to model the air turbulence in this study, as it offers better accuracy, stability and computing efficiency for low reynolds number as well as near wall flows (chen ; zhang and chen ; ). the diffuser inlets were defined as velocity-inlet, while corridor and exhaust grilles were treated as outflow boundary condition. ansys fluent treats outflow boundaries as having zero diffusion flux for all flow variables as well as it incorporates an overall mass balance correction. furthermore, outflow with flow rate weighting option enables the user to have multiple outflow boundaries with fractional flow rate through each boundary (ansys ). a second-order upwind scheme was applied to discretize the governing equations while the simple algorithm was used for the pressurevelocity coupling in the continuum phase. the metabolic rate of a reclining patient was assumed to be . met (ashrae b) and half of the heat ( . w·m − ) from each patient is assumed to be transferred through convection (qian and li ; hang et al. ) . a constant heat flux thermal boundary condition was uniformly imposed on the whole surfaces of the supine patients (shen et al. ) . apart from walls of heat sources (patients), all other walls were treated as adiabatic. smooth no-slip condition is applied at all walls. in order to reduce modelling complexity arising from density differences due to temperature gradients, the boussinesq approximation was employed (zeytounian ) . the computational domain of inpatient ward was split in to multiple fluid zones. icem-cfd . was utilized to generate hexahedral mesh for these individual computational cell zones. the individual mesh files are then merged together using the tmerge filter functionality. in tmerge, before the individual meshes are combined together to one mesh file, the required scaling factor, translation distance and rotation information of the meshes is specified. with the existence of non-identical mesh node locations as shown in fig. along the boundaries of the individual cell zones of the computational domain, non-conformal interfaces are established between individual cell zones. these interfaces connect each cell zones by transferring fluxes from one mesh to another (ansys ). the first cell height from wall is kept at a distance of . m and grid spacing of . is maintained throughout the domain. the near-wall mesh was made fine enough to resolve the viscous sublayer (y + < ) and the near-wall modelling was done through the enhanced wall treatment approach. the three grid systems, namely k (system ), k (system ) and k (system ), fig. non-identical mesh nodes along the boundary of two cell zones were created for the grid convergence study and airflow simulations were performed on each grid. to analyse the convergence of the three grid systems, the grid convergence index (gci) concept was applied (roache ; wong et al. ) . the root mean square of the relative error (e rms ) for the fluid flow mean velocities (u) detected at points along a vertical line in the centre of the ward cubicle was used to determine the gcis for the grid systems. the gci is calculated by: in the above equation, r is the grid refinement factor that is calculated as the ratio of the control volumes of fine and coarse grid systems, p is the order of the discretization method used, f s is the safety factor and e rms is determined by: using system as a reference, the gcis for systems and were . % and . % respectively. as system was adequate for studying the fluid flow characteristics, it was taken for further investigations by considering computational time as well as solution accuracy. the trajectories of individual particles were modelled using the lagrangian framework and the modelling assumptions made are listed below (tian et al. ; zhao et al. ):  the air-particle as well as particle-particle heat and mass transfers were neglected.  a particle would not rebound when hitting a surface such as wall, ceiling and floor.  particle coagulation was neglected in the deposition process.  all particles were modelled as spherical in shape. the droplets exhaled through exhalation activities such as sneezing will shrink in size due to evaporation within a short period of time (< . s) (xie et al. ). their dried out residuals, the droplet nuclei, may be carrying pathogens (wells ) . in this study, a small percentage (< %) of the total virus laden droplets from a vigorous sneeze was assumed. it was proved that with such a small percentage, virus particles will not form clusters (duguid ; gralton et al. ) . for simplicity's sake, droplet nuclei are referred to as particles in this article. the lagrangian particle tracking calculates the discrete trajectories of individual particles in the fluid flow separately by solving the following particle motion equation: where u a is the fluid velocity (m·s − ), u b is the particle velocity (m·s − ), μ is the molecular viscosity of air (kg·m − ·s − ), ρ a is the density of air (kg·m − ), ρ b is the particle density (kg·m − ), d b is the particle diameter (m), re is the particle reynolds number, c d is the drag coefficient, g a is the gravitational acceleration and f x is the auxiliary forces acting on the particles. the particle reynolds number is defined by, the drag coefficient c d for the bioaerosol particles is defined by, the drag constant k d for the bioaerosol particles as expressed in eq. ( ) is given by, the above equations were solved in cfd simulations to determine the transport mechanisms of bioaerosol particles in a lagrangian scheme. the validity of eqs. ( ) and ( ) was established for a range of particles with equivalent bioaerosol diameters (d b ) from . μm to . μm and further examined for particles with d b as low as . μm (wong et al. ) . apart from the drag force, forces that can influence particle motions include basset force, magnus force, virtual mass force, brownian force and saffman lift force. although the magnitudes of these forces are greatly influenced by the fluid flow conditions and particle properties, a few of these forces are small enough to be neglected in some analyses (zhao et al. ). due to the particle size and non-isothermal flow conditions in this study, brownian, thermophorectic and saffman lift forces were taken into consideration for predicting the particle motion trajectories. the dispersion of particles as a consequence of turbulence in the flow field can be tracked through stochastic tracking methods. the discrete random walk (drw) model, a popular approach that takes velocity fluctuations into account, was employed in this study (lai et al. ) . further details for the cfd simulations are summarized in table . the overall airflow distribution pattern based on ventilation strategies can have a great impact on the particle distribution within the space in a hospital ward. figure depicts the air velocity distribution and velocity vector plot across a horizontal plane located at y = . m for the base case, i.e. a typical ward cubicle without exhaust grilles. in fig. (a) , stagnant air with velocity less than . m·s − is observed near wall and fig. (b) depicts that the overall airflow pattern in the cubicle is directed towards the ward corridor. these results are consistent with those presented in our previous case study (yu et al. ). due to the existence of obstructions such as patients and beds, several eddies can be seen within the ward cubicle. figures and illustrate the temperature distribution as well as velocity vector plot across a vertical plane located at z = . m for an air change rate of h − and h − with ea = % respectively. as the thermal manikins cause thermal plumes, the effect of thermal plumes on the ward airflow pattern can be clearly seen from the vertical airflow distribution. there is an upward airflow (towards the ward ceiling) that returns to the floor level along the walls. recirculation zones, which may occur when the cold supply air from the diffusers interacts with the upward airflow caused by the thermal plumes, are observed. these zones can enhance the mixing of air within the ward space. moreover, the suction provided by the local exhaust grilles tends to alter the airflow pattern around a patient and thus can help to remove airborne contaminants in the immediate vicinity of the patient. in the base case, almost half of the virus particles exhaled from a patient's mouth deposited onto the patient's body and bed. according to fig. , there were considerable amounts of virus particles on different cubicle surfaces including walls, floor and ceiling. a maximum r c (≈ . ), resulted from the supine patients and their exhaled air velocities, can be seen at h − in fig. (a) . it can also be seen in the figure that r c decreases as the air change rate increases (e.g. r c ≈ . at h − (a % decrease) and r c ≈ . at h − (a % decrease)). in fact, the air supplied through the diffusers has a higher momentum with an increased air change rate and it moves the particles away from the ceiling to other spaces within the cubicle. as depicted in figs. (b) and (c), r w and r f were respectively greater than . and . in the base case for all air change rates. as shown in fig. (a) , patients in beds located at . m away from the corridor (i.e. patients and ) were most vulnerable to cross infection (with exposure risk (e) > . ) while those at . m away (i.e. patients and ) were least (with e < . ). with an increase in air change rate, a significant reduction in infection risk was observed for patients located farther away from the corridor. this can be explained by the general airflow patterns as illustrated in fig. . on average, the infection risk level of patients and was only half of that of patients and for all air change rates. figures and demonstrate that the local exhaust grilles not only facilitated the removal of a portion of exhaled virus particles but also tended to increase the particle deposition in the source patient's body and thereby reduced the residual viral load present in the air. as exhibited in fig. (a) , the recorded values of r c at h − were approximately . and . for ea = % and ea = % (i.e. decreases of % and %; comparing with the base case) respectively. for all other cases shown in the figure, similarly, r c decreased as the air change rate increased. according to figs. (b) and (c), wall and floor deposition ratios were also significantly reduced with ea = % and % (r w < . and r f < . ). however, deposition of particles was observed in all scenarios. as the deposition is random in nature and often happens irrespective of the ventilation system design, it highlights the importance of regular and proper ward housekeeping. furthermore, the randomness associated with particle deposition rates (r w , r c , and r f ) under different air change rate conditions can be attributed to the asymmetric airflow distribution patterns and locations of the infected patients. figures (b) and (c) indicate that the installation of exhaust grilles in close proximity to each patient can help prevent particle migration from an infected patient to different locations in the ward and significantly reduce individual patient exposures (e < . ). the results show that the location of an infected patient, exhaust airflow rates and air change rates within the cubicle work together influencing the mechanism of viral spread. the pathogen spatial distribution is dependent on the ward layout, ventilation strategy and location of the source patient. it can be observed in fig. (a) that exhausted ratio r e increases with air change rate in the base case. the maximum r e was recorded for patients and . from r e < . at h − to r e > . at h − , an abrupt increase in risk ( %) was noted for these patients. at higher air change rates, specifically at h − , the number of particles reaching the corridor due to the exhalation activities of patients and located at the rear end of the ward (i.e. . m away from corridor) was quite high ( . < r e < . ). this suggests that the use of a high air change rate such as h − can put the users of the corridor and its connected amenities at high risk of exposure to pathogens and facilitate infectious disease outbreaks in the whole healthcare facility. as shown in figs. (b) and (c), the installation of exhaust grilles considerably reduced the risk of infection transmission. the exhaust grilles lowered the r e values of patients and at h − to . with ea = % (i.e. a decrease of %; comparing with the base case) and < . with ea = % (i.e. a decrease of %; comparing with the base case). specifically, the supine patients at the rear end of the ward cubicle (i.e. patients and ) contributed the least to the spread of infection to the corridor (r e < . ). as the local exhaust airflow rate proved effective in reducing the risk of infection transmission, both the location and airflow rate of an exhaust grille are crucial factors for designing infection control strategies. this study investigated the transport mechanism and deposition patterns of mers-cov within an air-conditioned general inpatient ward cubicle. it demonstrated that both air change and exhaust airflow rates have significant effects on not only the airflow but also the particle distribution within a mechanically ventilated space. moreover, the location of an infected patient within the ward cubicle is crucial in determining the extent of infection risk to other ward occupants. hence, it is recommended to provide exhaust grilles in close proximity to a patient, preferably above each patient's bed. to achieve infection prevention and control, high exhaust airflow rate is also suggested. regardless of the ventilation design, all patients and any surfaces within a ward cubicle should be regularly and thoroughly cleaned and disinfected to remove microbial contamination. installation of uvgi lamps in the ward space is recommended to further enhance the risk mitigation strategies. the outcome of this study can serve as a source of reference for hospital management to better ventilation design strategies for mitigating the risk of infection. ansys fluent . documentation ashrae standard. ventilation for health care facilities ashrae fundamentals si handbook the ventilation of multiple-bed 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ventilated rooms comparison of the eulerian and lagrangian methods for predicting particle transport in enclosed spaces evaluation of various turbulence models in predicting airflow and turbulence in enclosed environments by cfd: part -comparison with experimental data from literature comparison of indoor aerosol particle concentration and deposition in different ventilated rooms by numerical method middle east respiratory syndrome this work was partially supported by the research grants council of hksar and the hong kong polytechnic university (project no. e). key: cord- -at nvda authors: de weerdt, annick; janssen, bram g.; cox, bianca; bijnens, esmée m.; vanpoucke, charlotte; lefebvre, wouter; el salawi, omar; jans, margot; verbrugghe, walter; nawrot, tim s.; jorens, philippe g. title: pre-admission air pollution exposure prolongs the duration of ventilation in intensive care patients date: - - journal: intensive care med doi: . /s - - - sha: doc_id: cord_uid: at nvda purpose: air pollutant exposure constitutes a serious risk factor for the emergence or aggravation of (existing) pulmonary disease. the impact of pre-intensive care ambient air pollutant exposure on the duration of artificial ventilation was, however, not yet established. methods: the medical records of patients, admitted to the intensive care unit (icu) of the antwerp university hospital (flanders, belgium), who were artificially ventilated on icu admission or within h after admission, for the duration of at least h, were analyzed. for each patient’s home address, daily air pollutant exposure [particulate matter with an aerodynamic diameter ≤ . µm (pm( . )) and ≤ µm (pm( )), nitrogen dioxide (no( )) and black carbon (bc)] up to days prior to hospital admission was modeled using a high-resolution spatial–temporal model. the association between duration of artificial ventilation and air pollution exposure during the last days before icu admission was assessed using distributed lag models with a negative binomial regression fit. results: controlling for pre-specified confounders, an iqr increment in bc ( . µg/m( )) up to days before admission was associated with an estimated cumulative increase of . % in ventilation duration ( % ci . – . ). significant associations were also observed for pm( . ), pm( ) and no( ), with cumulative estimates ranging from . to . %. conclusion: short-term ambient air pollution exposure prior to icu admission represents an unrecognized environmental risk factor for the duration of artificial ventilation in the icu. electronic supplementary material: the online version of this article ( . /s - - - ) contains supplementary material, which is available to authorized users. the usual outdoor traffic-related air polluting suspects comprise gaseous (e.g., nitrogen dioxide (no )) and particulate pollutants generated by combustion processes. particulate matter (pm) is a heterogenic mixture of solid and liquid particles of organic and inorganic substances, drifting in the air. mostly, sulfate, nitrates, ammonia, sodium chloride, black carbon, mineral dust and water are present, though heavy metals, polycyclic aromatic hydrocarbons, bacteria, viruses and even pollen can also be found [ ] . relevant to human health, inhalable particles are categorized by aerodynamic diameter: equal or less than (≤) µm (pm ), ≤ . µm (pm . ) or ≤ . µm (pm . ). black carbon (bc), a component of pm . formed through incomplete combustion processes, is often used-in addition to no -as a proxy of trafficrelated air pollution. the smaller the particle, the deeper the penetration in the respiratory system, leading to inflammatory reactions on the alveolar level, resulting in cytotoxicity and possible mutagenesis [ , ] . as such, ambient air pollution constitutes a serious risk factor not only for the emergence of respiratory infections, but also for the development of reduced pulmonary function and/or aggravation of existing pulmonary disease (e.g., asthma, cystic fibrosis, chronic obstructive pulmonary disease [copd]) [ ] [ ] [ ] [ ] . in analogy with the recent finding that patient preadmission medical and sociodemographic characteristics (e.g., medication use, immune status, frailty) can influence the course and outcome and even the degree of respiratory failure during intensive care unit (icu) admission [ ] [ ] [ ] , we investigated the association between short-term exposure to residential ambient air pollution and the duration of mechanical ventilation in icu patients. a detailed description of the methods is provided in an electronic supplement. we conducted a large-scale cohort study in the -bed tertiary icu of the antwerp university hospital (flanders, belgium). medical records of , patients, admitted from june , , up to and including april , , were analyzed for all modes of artificial (invasive and noninvasive) ventilation within h of admission. clinical data were primarily retrieved from the patient data management system (pdms) (metavision, imdsoft, düsseldorf, germany), while personal information (e.g., smoking status) was retrieved from other medical records. our study was approved by the ethical committee of the university of antwerp/antwerp university hospital (airpollutic trial, / / ). a total of patients were mechanically ventilated within the first h of admission for the duration of at least h. after exclusion of patients living outside of belgium (n = ), removal of patients with no data on smoking status (n = ) and elimination of children (< age years) (n = ), our final study population comprised patients (fig. ) . we obtained relevant demographic and clinical data in every patient and used the simplified acute physiology score (saps ) as a validated score for severity of illness [ ] . we also obtained information on apache iv [ ] . ventilation duration was calculated by summing the duration (in hours) of all consecutive (invasive and noninvasive) ventilation episodes during the same icu admission and was rounded to the nearest number of whole days. residential addresses were geocoded with arcgis software. residential pm . , pm , bc and no exposure levels (µg/m ) were modeled for each patient's address using a high-resolution spatiotemporal model [ ] . the model takes into account land cover data obtained from satellite images (corine land cover data set) and pollution data from fixed monitoring stations in combination with a dispersion model [ ] . we calculated the daily concentrations of air pollutants at the patient's residential address up to days before admission (lag to lag , with lag representing the day of admission). for a sensitivity analysis, we calculated the annual average air pollution levels (as a proxy for long-term exposure). short-term health effects of environmental stressors may become apparent only a few or more days after exposure, implying that exposures during several days (lags) before the effect on human health should be considered. instead of testing associations with lagged exposures in separate models, distributed lag (nonlinear) models [dl(n) ms] provide a flexible methodology to capture the temporal pattern of the association by entering different lags in one and the same model. the primary study outcome short-term ambient particulate and gaseous air pollution exposure prior to icu admission significantly prolongs the duration of mechanical ventilation irrespective of preexisting lung disease or icu admission diagnosis. this finding suggests that optimizing air quality could influence icu-related morbidity. was the duration of ventilation in days. the association between ventilation duration and air pollution exposure was investigated by negative binomial regression, using a separate model for each of the four pollutants. potential delayed effects of air pollution on ventilation duration up to days before icu admission (lag to lag ) were allowed by using dlnms [ ] , with lag representing the day of admission, lag the day before admission and so on. the exposure-response function was modeled using a natural cubic spline with df. seasonality and longterm trends were modeled using a natural cubic spline of time (day of the study period) with df per year. models were additionally adjusted for indicator variables for day of the week and for known determinants of duration of ventilation such as sex, age (modeled with a natural cubic spline with df ), bmi (kg/m ), disease severity (saps ), smoking status (non-smoker/active smoker), origin of the patient before icu admission (emergency department/ other) and admission diagnosis (non-respiratory/respiratory non-infectious respiratory infectious). in a secondary analysis, we adjusted our models for apache iv. in an effort to account for exposure misclassification in patients who were admitted to the hospital some days before icu admission (e.g., days at home, days in the hospital, then icu admission), we performed an analysis where we combined the daily exposure values derived at the home address with the daily exposure values derived at the hospital. alternatively, we excluded patients coming from another hospital icu to account for possible exposure misclassification (resulting in n = ). in another secondary analysis, we accounted for possible confounding due to respiratory comorbidities by excluding all patients with preexisting lung disease including copd and asthma (resulting in n = ) and by excluding all patients with preexisting respiratory and neuromuscular comorbidities (n = ). we then further restricted the study population to patients who left the icu alive (n = ) to account for early death. finally, to differentiate between short-and long-term effects, we added annual average air pollution levels (as a proxy for long-term exposure) to our main model. reported estimates represent the lag-specific and cumulative (lag - days) percentage change (with % confidence intervals [ci]) in ventilation duration for an interquartile range (iqr) increase in air pollution exposure. all analyses were performed with the statistical software r (r foundation for statistical computing, vienna, austria) using the "dlnm" package [ ] . demographic and clinical characteristics of the adult patients are summarized in table . . % of our study population were years or older. there were more men ( . %) than women ( . %), and nearly one-third ( . %) of our population were smokers. approximately % of our population was admitted with a non-respiratory diagnosis, only . % with a non-infectious respiratory disease and . % with a respiratory infection. the mean (± sd) ventilation duration was (± ) days with median ( th- th percentiles) daily air pollution exposures up to days before admission were . ( . - . ) μg/m for bc, . ( . - . ) μg/m for pm . , . ( . - . ) μg/m for pm and . ( . - . ) μg/m for no ( table ). the majority of participants lived in the province of antwerp, relatively close to the antwerp university hospital, where we observed the highest levels of pm . exposure in belgium (figure electronic supplement) the lag-specific dlm estimates of the association between ventilation duration and air pollutant exposures up to days before the icu admission are shown in fig. . the effect of all examined components of air pollution on ventilation duration was found to be acute, with significant effect estimates at lag (except for no ) and estimates close to zero after lag . an iqr ( . µg/ m ) increment in bc exposure up to days before icu admission was associated with a . % ( % ci . to . ) longer mechanical ventilation duration ( table ) . the corresponding estimates for pm . , pm and no were . % ( % ci . - . ), . % ( % ci . - . ), and . % ( % ci . - . ), respectively. correcting our models for apache iv or using data where we took into account possible exposure misclassification had a little effect on our estimates for all pollutants except that the estimates of pm . did not reach significance anymore (table ). excluding patients who had been hospitalized in another hospital icu, days prior to admission to our icu, also did not change our effect estimates substantially (table ). restricting our analysis to patients without preexisting copd and asthma resulted in stronger associations for all pollutants: . % ( % ci . - . ) for bc, . % ( % ci . - . ) for pm . , . % ( % ci . - . ) for pm , and . % ( % ci . - . ) for no even after excluding all patients with respiratory and neuromuscular comorbidities. further restricting the study population to patients without preexisting comorbidities, leaving the icu alive, resulted in a further increase in cumulative effect estimates for bc and no and similar (although no longer significant) estimates for pm . and pm . to differentiate between short-and long-term effects, we added annual average air pollution levels (as a proxy for long-term exposure) to our main model but found it not to be associated with the duration of ventilation. in our study of icu patients, requiring mechanical ventilatory support for a diversity of reasons, ventilation duration was significantly associated with pre-admission exposure to bc, pm . , pm and no . for an iqr higher air pollution exposure up to days before admission, the duration of ventilation was estimated to be . - . % longer. our data were obtained in a large and diverse icu population, and the relationship between air pollution exposure and duration of ventilation was shown irrespective of preexisting lung disease or icu admission diagnosis. it has been shown that medical and sociodemographic characteristics [ , , ] already present prior to icu admission contribute to the occurrence and severity of organ failure including respiratory failure as well as the outcome in the critically ill. however, pre-admission environmental factors have hardly been studied in this context, or studies have found no effect (i.e., sunlight exposure prior to icu admission has been found not to influence the incidence of icu-acquired delirium) [ ] . we are the first to report on the effect of pre-admission air pollution exposure on the duration of mechanical ventilation. the findings of this study are of critical public health importance because of the ubiquity of ambient air pollution. short-term ambient particulate air pollution is independently associated with daily all-cause, cardiovascular and respiratory mortality [ , ] . as such, air pollution has important molecular and physiological effects on the lung, an organ frequently failing in the critically ill. a few recent studies have demonstrated some effects of air pollution on the occurrence of (only) the acute respiratory distress syndrome (ards) and associated mortality. long-term ozone and pm . exposure are associated with an increased risk for ards among older adults in the usa [ ] and in patients at risk for ards (e.g., trauma patient, active smoker) [ ] . rush et al. [ ] described how chronic exposure to high levels of ozone and pm results in higher mortality rates in ards patients, and most recently, reilly et al. [ ] added long-term exposure to low to moderate levels of sulfur dioxide, no and carbon monoxide to the risk factors for ards in trauma patients. our results indicate the acute effects of air pollution on ventilation duration. significant associations were observed for lag , representing the day of icu admission, but positive estimates (close to significance for bc and pm . ) were also observed for lag . a similar lagged pattern (lag and lag ) has been shown in a recent study investigating the association between the short-term effect of ambient air pollution (pm and pm . ) and hospital admission for respiratory diseases [ ] . the mechanism of this lagged pattern is not completely understood, but (pulmonary and/or systemic) oxidative stress and inflammation might be plausible biological mechanisms. for example, in a prospective panel study, increased blood levels of c-reactive protein and icam- were observed for an increase in pm and ultrafine particles with a delay of - days [ ] . in individuals of the framingham heart study, elevated exposure to relatively low levels of ambient air pollution for a few days was associated with higher levels of biomarkers of systemic inflammation (including c-reactive protein, interleukin- and tumor necrosis factor receptor ) [ ] . therefore, it is reasonable to assume that acute air pollution-induced inflammation processes occur, at least in the lung, since this is the primary site of inflammation. the effects of air pollutants on the lung originate from extracellular activation of the inflammatory response and/or oxidative stress-mediated inflammation in airway epithelial cells [ ] . known detrimental effects of airway inflammation comprise a reduction in pulmonary function, increased airway reactivity with hypersecretion of mucus and alterations in mucociliary activity [ ] . the latter will of course contribute to a protracted exposure of the airway epithelium to toxic particles, thus generating a prolonged inflammatory response. we hypothesize that inflammatory reactions on the alveolar, airway and/or pulmonary capillary level result in gas exchange impairment, thus contributing to the lengthening of ventilation duration. the estimates represent the cumulative percentage change in ventilation duration for an iqr (μg/m ) increment in the air pollutant up to days before the icu admission all models were adjusted for long-term trends and seasonality, age, sex, bmi, smoking habit, saps , day of the week, icu origin and admission diagnosis a including preexisting copd, asthma and all other respiratory comorbidities modern critical care does not only focus on the prevention of primary ventilation-associated morbidities such as ventilator-associated pneumonia or barotrauma [ , ] but also tries to prevent long-term sequela related to prolonged mechanical ventilation by the use of short-acting sedatives and daily appraisal of the need for mechanical ventilation. indeed, duration of ventilation-related conditions such as cognitive impairment, depression, neuro-myopathy and pulmonary function alterations (e.g., reduced diffusion capacity) can persist in the icu survivor, resulting in a long-term need of medical, psychological and/or physiotherapeutic care, causing considerable economic burden [ , ] . our data thus represent a novel and potentially modifiable environmental risk factor, which, if improved, will not only ameliorate the post-icu quality of life but might also reduce health care costs. the incentive to "clear the air" will gain even more importance in the future, considering the projected increase in an aging [ ] population who are even more at risk for air pollution-related respiratory diseases due to an age-related defective mucociliary function in combination with decreased muscle strength, compromising the ability to clear inhaled particles [ , ] . our study was conducted in the northern part of flanders (belgium), where levels of air pollutants continued to decrease between and . in , the annual levels of air pollutants in our study population nearly reached the who standards for pm . ( . vs. µg/m ) and for pm ( . vs. µg/m ) and even dived under the limit for no ( . vs. µg/m ) (table electronic supplement) [ ] . the european union (eu) air quality directives are less stringent (annual limits μg/m for pm . , µg/m for pm and no ) than the who guidelines. in light of the fact that we found significant effects on duration of ventilation at air pollution levels well below the eu limits, our findings support a further down-revision of the current eu air pollution directives in the direction of the who guidelines. our findings need to be interpreted within the context of its strengths and limitations. although we used validated exposure models, there might be some exposure misclassification. for example, we interpolated daily exposure levels at the residence without taking the amount of exposure at the address of employment or the time spent indoors into account. however, considering the higher age and expected preexisting health problems in our study population, we may assume that a considerable portion of time before admission was spent at the home address. furthermore, a number of patients had been admitted to our hospital some days before icu admission, thus generating some exposure misclassification. however, it is reasonable to assume that the exposure misclassification is random, resulting in an underestimation of effect estimates [ , ] . moreover, our findings stayed robust after accounting for possible exposure misclassification and excluding patients coming from another hospital icu. in terms of validity of the exposure model, we showed that the estimated long-term residential exposure correlates with the internal nanosized carbon load in urine [ ] . secondly, we recognize the multifactorial character of ventilation duration, but we wish to emphasize that the use of short-acting sedatives, lung-protective ventilation and spontaneous breathing trials has been the mainstay of icu ventilation care in the antwerp university hospital before, during and after the study period. any differences in duration of ventilation are therefore not attributable to physician-specific particularities, but a priori to (preexistent) patient characteristics. additionally, our findings were robust after adjusting for apache iv, excluding all patients with preexisting lung disease (copd and asthma) or other comorbidities and even after excluding the patients that died in the icu to account for the competing risk of early mortality. thirdly, due to patient heterogeneity in the intensive care and random exposure misclassification-which cannot be ruled out in epidemiology-we observed relatively wide confidence intervals around our estimates. finally, we could not retrieve information on socioeconomic status (ses). although ses is important in long-term exposure outcomes, it is less likely to be an important confounder in acute exposure studies as no relation between shortterm temporal differences in air pollution exposure and ses is expected. 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effect of oxidative stress polymorphisms on the association between long-term black carbon exposure and lung function among elderly men epidemiology in medicine air pollution and risk of stroke: underestimation of effect due to misclassification of time of event onset children's urinary environmental carbon load. a novel marker reflecting residential ambient air pollution exposure? key: cord- -ca vhq authors: pařil, vilém; tóthová, dominika title: assessment of the burden on population due to transport-related air pollution: the czech core motorway network date: - - journal: nan doi: . /j.jclepro. . sha: doc_id: cord_uid: ca vhq abstract negative externalities of transport are a crucial issue in environmental discussion and policy. the mobility of our society is responsible for many negative environmental impacts, both on our planet and on human health. this paper aims to assess one aspect of a negative externality of transport related to air pollution from particulate matter up to micrometers in diameter (pm ) and its impact on human health, using the example of the key czech republic highway d . the assessment method precisely follows the geographical routing of this motorway through varying elevations in which different buffer zones are identified to assess pm concentration changes according to distance from the road in the – period. the resulting relation between pm and highway proximity is then discussed in an econometric analysis of the entire road transport network of the czech republic. in the final step, we assess the size and demographic structure of the population affected by the highway pm pollution problem, and we compare several methods to assess economically related morbidity. the results show falling levels of pm pollution, not only with increasing distance but also in intertemporal comparison, with concentrations lower by μg.m in the – period than in – despite increasing road traffic on the highway. this means a very significant reduction in the number of cases and economic value for all analysed endpoints between eur , and , . in response to global environmental threats, the european union (eu) has long endeavored to be a global environmental leader and to improve the environment through a range of instruments, such as environmental action programs and institutional and legislative frameworks. many environmental issues are related to human mobility and transport, which cause some of the most severe air pollution problems, especially in residential areas. the context of the assessment of external costs in cost-benefit analysis is primarily related to construction and maintenance. significant benefits concern the time saved and improvements in the overall level of accessibility (martens and di commo, ; forslund and johansson, ) . this approach is used for the analysis of specific problems linked to road transport, such as reducing air pollution (cavallaro et al., ; rotaris et al., ) . the research objective is to more accurately assess the impact of road transport on air pollution and consequently on population morbidity in monetized values. the research methodology is applied to the czech core highway d and its traffic-related air pollution, as represented by pm , over a -year period with an emphasis on long-term trends. cost-benefit analysis (cba) is considered to be one of best possible methods for transport project assessment, and it generally provides very important results for comparing different transport solutions. cba is used differently according to country and to policy-making decision processes (hansson and nerhagen, ) . recently, the emphasis on long-term strategic planning in the eu was enriched by territorial impact assessment (tia; ), which makes it possible to measure the regional impacts of strategic planning. however, this instrument has not yet been introduced in the czech republic as an integral part of the general planning process. it is instead used only for the purposes of separate assessments of regional development, regardless of whether it involves environmental or transport policy. the application of cba methodology in our study is a key factor that can provide better results in long-term transport project assessment in the czech republic and beyond, because it provides a way to integrate cba with a tia approach, with an emphasis on dynamic and long-term data (schade and rothengatter, ) . as shown in the research considering air pollution with regard to its geographical routing and demographical grouping, it is achievable and feasible, and there are already available data and methods to launch this important step, both in cba related to each transport project separately, as well as in the strategy and planning phases, when it is necessary to compare more variants of potential solutions. air pollution from transport is a growing problem, especially in developed countries, due mainly to the increasing demands for freight and passenger transport. the czech republic has a relatively dense network of expressways and motorways, often near residential areas. in addition, high volumes of traffic generate negative external costs in the form of noise (e.g. serrano-hernández et al., , hammer et al., and air pollution (e.g. watkiss et al., ; le boennec, ) . transport also has significant overall impacts on sustainability (de campos et al., ) . however, the highest risk to human health is air pollution from transport, which this article addresses. the research focus is usually on air transport emissions (monks et al., ) and road transportrelated air pollutants. in the czech republic, only . % ( out of ) of cba projects conducted from to included air pollution assessments (ministry of transport, ) . in all these cases, air pollution is automatically assessed in cba in calculations of passenger kilometers or ton-kilometers. this article aims to precisely identify the effect of road transport on health in the long term using the example of czech core highway d . the average daily intensity of vehicles on the d motorway is about , vehicles per day, and there are sections where the intensity reaches almost , vehicles per day (rsd, ) . according to the world health organization (who) ( ), common pollutants from transport include nitrogen dioxide, ozone, and other photochemical oxidants, particulate matter, and sulfur dioxide. in our paper, we focus on the assessment of air quality using pm (defined as particles below μm in aerodynamic diameter), which are considered one of the main pollutants (maibach et al., ) , usually bounding polycyclic aromatic hydrocarbons (pahs) (yin and xu, pollutants, pm is measured at all measuring stations in the czech republic. according to the who ( ) , pm is strongly correlated to other pollutants. thus it is an appropriate indicator with which to assess the impact of air pollution. the individual studies that we used to determine the exposure-response function (erf) often only follow the impact of pm concentration for this reason. based on the who ( ) recommendation, we did not set any lower limit for pm to indicate the level of pollution that is detrimental to health. adverse effects on health have been observed at levels not far from natural background concentration values of about μg/m (correia et al., ) . many epidemiological studies have demonstrated negative health consequences from excessive pm in the child and adult populations (kirshnan et al., ; sánchez et al., ; gouveia et al., ; künzli et al., ; abbey et al., ; englert, ) . the most frequent impacts of pm are related to cardiovascular, respiratory, cancer, and cerebrovascular effects, which are manifested in increased morbidity and mortality. a long-term concentration of particulate matter is associated with natural-cause mortality , especially for cardiovascular disease mortality or morbidity (kirrane et al., ; dabass, ; haikerwal et al., ; mills et al., ; metzger et al., ) . pm also has respiratory health effects that can lead to increased mortality and morbidity (kim et al., ; mathew et al., ; gehring, ; hoek et al., ; zanobetti et al., ; ostro et al., ) . a relationship has also been shown between exposure to pm and cancer, primarily lung cancer (dimitriou and kassomenos, ; raaschou-nielsen et al., ; pope et al., ; nyberg et al., ) and cerebrovascular disease (wettstein et al., ; staffogia et al., ; zhang et al., ; torén et al., ) . many authors have addressed the quantification of the health impacts of air pollution, but using different methods. a similar approach was used by seethaler et al. ( ) . they calculated air pollution-related health costs using a tri-national study of austria, france, and switzerland on health costs due to transport-related air pollution. meisner et al. ( ) assessed the magnitude of health impacts and economic costs of fine particulate matter pollution in the republic of macedonia. health impacts were converted to disability-adjusted life years (dalys) and then translated into economic terms. martinez et al. ( ) obtained particulate matter concentration data from air quality monitoring stations in the skopje metropolitan area, applied relevant concentration-response functions from the literature, and calculated the burden of disease and societal cost of mortality attributable to particulate matters. künzli et al. ( ) estimated the impact of outdoor traffic-related air pollution on public health in austria, france, and switzerland, using attributable cases of morbidity and mortality. health impact assessments in the area of traffic air pollution have been conducted, e.g. khreis et al. ( ) , tobollik et al. ( ), chart-asa and gibson ( ) , and boldo et al. ( ) . several studies have been conducted in the field of assessing damages from air pollution from transport, including the human health impacts on the population at the european level (eu projects and programs), such as escape, exiopol, heimtsa, need and other european studies (e.g. projects of the european environment agency or projects of the european topic centre on air and climate change) and at the national level. korzhenevych et al. ( ) consider these two studies on the assessment of the external costs of transport to be essential at the european level: heatco -developing harmonised european approaches for transport costing and project assessment (bickel et al., ) , and cafÉ cba -clean air for europe cost-benefit analysis (hurley et al., ) , which were evaluated in the heimtsa project -health and environment integrated methodology and toolbox for scenario assessment (friedrich et al., ) . both studies use the impact pathway approach, which was developed under the external cost of energy project (externe), with its own "externe methodology" calculating external environmental costs (for more on this methodology, see bickel and friedrich, ) . the impact pathway analysis identified the most significant impacts of emissions, their quantifiability and the monetary valuation of costs. other international organizations provide similar data. like the european studies mentioned above, the studies are based on epidemiological research. recommendations with relevant functions and economic values can be found, for example, in publications by the us epa ( ), and who ( ). this paper is structured as follows: the first chapter provides a concise description of the material and the scientific methods used in our research, focusing on data and sources. the second part of the paper contains the evaluation of economic consequences and achieved results. the last part contains a discussion, the limits of this study, and recommendations for practice. the method used in the research is based on the following data sources and methodological steps: -health impact assessment. these steps are described in detail in the following paragraphs. the first methodological point defines detailed geographical routing of the most important motorway in the czech republic, the d , which connects the three largest agglomerations in the country: prague, brno, and ostrava. we used this routing based on a publication on parts of the d motorway from the road and motorway directorate of the czech republic, from which we took detailed information on the route and type of motorway communication of all motorway sections (rsd, ) . the d motorway is an unfinished road project, and one section is still under construction from Říkovice near hulín to lipník nad bečvou; a distance of close to km is routed on first-class road number . we included this unfinished section in the analysis. the d motorway intersects with several regions: prague, central bohemia, vysočina, south moravia, olomouc, zlín, and the moravian-silesian region. we designated four distance zones in our research to compare changes in pm concentrations depending on proximity to the d motorway. this classification is based on the assumption that the closer an area is to motorway traffic, the higher the concentration of pm . we defined the first zone as the meter distance zone (intersected areas). it is based on the key decrease of pm exposure at a distance of m synthesized by karner et al. ( ) . we defined the second distance zone of m (neighboring areas) according to a more accurate study on distance from highway exposure depending on wind speed and rainy conditions, as reported by yazdi et al. ( ) . they showed that with high-speed wind (velocity > m/s), the pm concentration can increase to a distance of around m, after which it starts to decrease. the third distance zone of m (closer burdened areas) is used under the european commission approach in the development of a methodology to assess populations exposed to high levels of noise and air pollution close to major transport infrastructure (ritchie et al., ) ; this methodology defines high exposure zones for road infrastructure as those of less than m. the last category, with a , meter distance zone (broader areas), defines the average pollution level in the relevant geographical area (corresponding with the basic unit of settlement in the czech republic). the next methodological step is to identify the relevant affected population. we used this static approach in accordance with mommens et al. ( ) . we conducted this identification based on the population and housing census carried out by the czech statistical office (cso, ). we used the most detailed dataset based on population in basic units of settlement ( , units in the czech republic) according to its cadastral areas from the census registry (cso, ) . we used the czech national geoportal inspire (cng, ) to identify affected residential areas. then we combined residential areas with the esri arcgis program module, namely arcČr . (arcdata, ), through which we intersected the d motorway according to distance zones ( / / / , m) with the residential cadastral areas of individual basic units of settlement. with this approach, we identified an affected number of inhabitants in concerned basic units of settlement, and also identified the demographics and age structure of the relevant population. our research does not reflect the daytime variation of exposure because we can divide the population examined by the research into three basic categories: seniors, children, and the working-age population. we assume children pass half their daytime in the closest possible school and half at home; the census does not reflect children's daytime mobility (cso, ) . the second group, seniors, is expected to pass most of their time very close to their residence. the last population age category, working-age population, is the most time-space flexible class. the census (cso, ) provides data on the commuting of working people. the commuting datasets show that movements during the daytime vary but are largely directed towards larger cities in their vicinity. from this point of view, our final estimation of long-term exposure could be slightly underestimated. we can consider it as a lower limit of the burdened population. the key methodological step lies in the pollutant concentration analysis based on the statistics of the czech hydrometeorological institute, from which we took historical data on long-term kuenen et al. ( ) . these three dispersion models use czech national rezzo pollutant classification (including rezzo - categories for static emission sources and rezzo for mobile emission sources). the output results provide a nationwide grid network for pm , pm . , benzopyrene, nitrogen oxides, ground-level ozone, benzene, heavy metals, and sulfur dioxide. we separated pm concentrations and intersected the czech grid network with relevant distance zones. we analyzed three long-term periods in terms of pm concentration: - , - , and - . for distance zones, we achieved the following numbers of concerned basic units of settlement: the -meter zone included residential areas, the -meter zone included , areas, the -meter zone includes , areas, and the , -meter zone included , areas. this article discusses two interrelated issues that we address in the next two sub-chapters. first, an air pollution analysis in the czech republic was carried out near the motorway network, including a motorway network already in operation and a planned motorway network, as there are currently significantly higher traffic intensities on these routes than on surrounding routes. we based this section on data on long-term air quality monitoring (chmi, ) and the occurrence of harmful particles between and (last available dataset, with annual averages of concentrations). the traffic intensity was monitored by the transport censuses in the czech republic in republic in , republic in , republic in , republic in , and . we consider the change between and to be the most comparable and relevant period. in the next step we examined the impact of the motorways on the concentration of air pollution. we checked whether the existence of roads really has an effect on the pm air pollution concentration, primarily through the indicator of transport intensity. we included other variables such as population living in the vicinity of road infrastructure (as a high exposure zone) and population density. because air pollution is affected by changes in altitude (us epa, ; hoek et al., ) transport intensity of motor vehicles, population size in the area to m from the road, population density in the area to m from the road, and the average altitude in meters were selected as explanatory variables. the power of influence of the non-standardized regression coefficients is estimated by controlling the effect of other independent variables in the model. multiple regression through standardized regression coefficients also helps to determine the relative strength of the influence of independent variables on a dependent variable. here we find which variables have the most significant impact on the variance of a dependent variable and vice versa (mareš et al., ) . we can formally write the multiple regression model as (formula ): where is a dependent variable, is a constant, , , are regression coefficients, , , are independent variables, and is random error. parameters are estimated by the ordinary least squares method, formally written as (formula ): the aim of this method is to find those parameters (estimates for ) for which the error term is minimized (formula ): the last methodological step is to identify relevant pm health impacts according to the concerned population categories and distance zones ( / / / , m). we compared the results from several international studies on the long-term health impact of pm and defined the relevant impacts. in order to determine the health impacts on the population of the czech republic living near the d motorway with a focus on acute and chronic morbidity and the resulting monetary valuation, we selected three european studies to which we assigned the exposure-response function (erf cases / (year · person · μg / m )], and used their monetary valuation per case or per day based on individual health effects and risk groups (see table a -heatco -developing harmonized european approaches for transport costing and project assessment, (bickel et al., ) . all these studies calculate the economic valuation of health effects. an overview and description are given in table (korzhenevych et al., ) : bronchodilator use change in the probability of daily bronchodilator usage per μg/m pm the following formula (bickel and friedrich, , modified) is used to calculate the increase in the impact of air pollution from traffic on the population (formula ): i is case per year per average person. the c i is pm concentration, and s i is the slope of erf. we multiplied the calculated cases of individual health effects by the monetary values presented in the particular studies (eea, heimtsa, heatco). we converted this result into prices for the czech republic for expressed in euro (based on the externe methodology). we took inflation into account with the eu harmonized consumer price index (eurostat, ) and the exchange rate between countries based on the ppp-adjusted exchange rate (oecd, ) in the following sections, the results of two sub-studies are presented: the identification of the in table a . in the appendix, we identify municipalities with cadastral territory affected by the d motorway, and the affected residential zones with the basic settlement units affected at a distance of / / and , m. the affected resident population is included in the relevant age categories (which is important for assessing the health impacts caused by pm ; see below). entirely or partially affected in residential areas. in individual risk areas, there are residential zones of about , ( m zone), , ( m zone), and , ( m zone) residents affected by increased pollution of the air due to the motorway. figure the maps above show gradual, slight improvement in air quality on most of the d motorway route. the improvement is quantified in table , which shows the difference in the degree of pollution both between the individual distance zones ( / / / , m) and between the different periods of comparison. we cannot attribute this improvement only to lower pollutant concentration from transport. we ran a multivariate linear regression analysis to determine the impact of some explanatory variables on the level of pm air pollution. the initial model entered these variables: transport intensity (trans_int), population in the vicinity of road infrastructure (popul_num), population density in the area to m (popul_dens), and average altitude (alt_avg). to fulfil the assumption of normality, trans_int, popul_num, and popul_dens were logarithmized. the analysis finally includes four independent variables (see table ). all statistical analysis was conducted with the ibm spss software package. the multivariate regression analysis was carried out to find the best model for explaining the variability of the average concentration of pm in the vicinity of roads in the czech republic through the transport intensity, average altitude, and population. table clearly shows the main summary of the model. all of the entered variables were significant for the model. the results show that a set of estimated independent variables explains . % of the variance of the dependent variables. according to the adjusted r square that takes into account the number of regressors included in the model, the proportion of overall variability is . %. the analysis of variance in table indicates the results of the test if the explained variable is dependent on the explanatory variables. also, according to the f test in one-way analysis of variance, we can reject the null hypothesis about the insignificance of the model. in other words, the model including these variables is useful. coefficient b represents the influence of the independent variable on the dependent variable. we see that there is a positive relationship between the pm concentration and the variables transport intensity and population density, and a negative relationship between the pm concentration and the variables average altitude and population. thus, as transport intensity and population density increase, the pm concentration also increases, and as average altitude and population decrease, the pm concentration also decreases. according to the standardized beta coefficient, average altitude is the most important indicator influencing pm concentration. . % of the variance in the average pm concentration in the vicinity of road infrastructure in the czech republic data is explained by the variables transport intensity, population, population density, and average altitude. during our time periods ( - , - , - ) we see a moderate reduction in air pollution. when we try to evaluate the impact of the reduction of pollution on the health endpoints, we ask how health conditions improve and disease-related costs are reduced if the pm concentration improves by μg/m . we start with a comparison with the average concentration in - . as an example, we choose cases of chronic bronchitis, which represent the highest cost item (table a . in the appendix). from the results shown in figure , we can see that the decrease in concentration has a significant effect on the reduction of cases of chronic bronchitis. from the results, we can deduce that a reduction of pm in the air by μg/m will result in a reduction of cases or days of all health endpoints and monetary costs by %. even though we observed long-term improvements in air pollution, the resulting condition still carries high monetary values. this study has shown that high concentrations of pm in the vicinity of the d motorway in the czech republic have a significant impact on the morbidity of the affected population, which implies a considerable financial burden. some of our policy recommendations are aimed at long-term reduction of air pollution exposure through several tools, such as the integration of health information into the impact assessment of infrastructure projects as suggested by seethaler et al. ( ) , technical improvements in vehicles and fuels, a consistent application of the polluter-pays principle by internalizing the external costs of traffic-related air pollution into transport pricing and taxation schemes, and further travel demand management measures. similar studies have been conducted to assess the health impacts of air pollution. they are summarized in table . the research results cannot be compared because they employ different assumptions and approaches. however, all studies, including ours, have in common the fact that they show that air pollution (mostly from transport) affects a large part of the population with consequences for the total number of cases of mortality and morbidity, with a significant economic burden. a comparable approach was used by künzli et al. ( ) , who estimated the public-health impacts of current patterns of air pollution in three european countries. they also used an increase in pm to quantify the effects of air pollution using exposure-response functions. they modelled population exposure for each km with traffic-related fraction separation. they similarly concluded that the public-health consequences are considerable. our conclusion confirms the findings of ostro and chestnut ( ) there is a strong emphasis in the literature on greenhouse gas emissions with regard to climate change. according to the european commission handbook on external costs of transport ( ) air pollution burden achieves a very similar level with respect to all means of road transport (see figure ). studies usually show macroeconomic impacts as a total (e.g. , or focus on very local contexts, usually with regard to vegetation (bignal et al., (bignal et al., , . this study provides a comparison of health effects with monetary evaluation for more population risk groups in a long-term view. the commercial importance of technologies in road transport is usually looked at by comparing greenhouse gas emissions, but as is clear from the graph below, a similar emphasis should be placed on comparing pollutant emissions when generally formulating environmental regulatory requirements in road transport. this study, using the example of the key d motorway in the czech republic, where cargo linehauls account for more than % of traffic, outlines other options for assessing technologies in road transport. the emphasis lies not only on climate change, but also on differentiating the significance of other negative impacts in urbanized space and taking into account different risk groups in the population. this quantification also testifies to the potential effects of tightening environmental regulations in the automotive industry. this case demonstrates the long-run positive impact of coordinated eu policies on the environment and transport. for this reason, it is necessary to emphasize the coordination of sectoral policies. in transport policy, it is possible to propose suitable bypasses near urban areas. however, the territorial development policy, with other tools at the regional and municipal levels, should respect these findings and try to limit residential construction in the vicinity of express or heavy traffic roads, since long-term neglect of this process can have severe health and economic consequences. in addition to these generally accepted and targeted tools, it is necessary to monitor the concentrations of pollutants in the vicinity of motorways in the czech republic, in particular to obtain more accurate results that would enter into the environmental impact assessment, including the health impacts of each new transport project. regarding the planning of broader long-term emission reduction -not only in the vicinity of motorways -strategic planning of traffic infrastructure development should also be undertaken. tolmasquim et al. ( ) , for example, considered the strategic planning of sectoral development involving the quantification of health risks to be crucial, as the cost of environmental pollution may otherwise increase further. to discuss the limits of the research, it is necessary to consider the quality of secondary data used for both air pollution and traffic intensity. we used the most detailed territorial units statistically monitored in the czech republic (basic settlement units). population data are based on the census (cso, ) . a further limitation comes from the real daily mobility and temporality, because inhabitants may commute to work in another settlement unit and not be exposed to the highest emissions in their place of residence. however, such precise data are not available. a related limitation is the accuracy of the extrapolation model of air pollution, as the measuring station is not always located near the road. nevertheless, in its model, the czech hydrometeorological institute provides raster data with accuracy much higher than that of population records. a related limitation of our study concerns the dataset provided by the czech hydrometeorological institute, which covers long-term average concentrations and not detailed daily concentrations in the relevant units. the availability and compatibility of corresponding data from different original sources are important in this research. this is because a different authority is responsible for every agenda used, e.g. the transport census is provided only once a year and population information is also provided annually but demographic structure is collected only once every decade, in the population census. these regulatory related data limitations are very relevant for further research where smart monitoring systems will hopefully provide better conditions in the future. as far as air pollution assessment regarding human health is concerned, the results of our study are limited by several factors. we took into account the linear exposure-response function in all studies, resulting in equally significant gains in the number of cases of health endpoints, even though a non-linear relationship is observed in reality (e.g., liu et al., ) , which may also vary due to air pollution mix, climate, and the health of the population (samoli et al., ) . exposureresponse functions were then taken from particular epidemiological studies (recommended projects heatco, eea, and heimtsa), which do not reflect the detailed specific socio-demographic characteristics of the population in the area, but only relevant target age groups. the same studies also included estimates of the monetary values of the health endpoints, which were transferred to czech republic prices on the eu hicp and the ppp exchange rate. unfortunately, this may be a very inaccurate estimate that would be more appropriately replaced by results from a survey in the czech republic. the disadvantage of this environmental impact assessment is that it is impossible to add the outcomes to health endpoints due to different types of outcomes (cases, days). furthermore, these were selected, classically monitored endpoints that do not cover all health effects, so it is not possible to quantify the overall health effects of pm pollution around the d motorway. our results can be a starting point for further research. we see an opportunity especially in the comparison of more relevant similar motorway examples with completely different geographical conditions across more countries. another point of further research would be to compare air pollution caused by motorways with lower hierarchical road networks; in the case of municipal roads located in sparsely populated areas, it is possible that traffic does not play a key role in air pollution. this paper estimates the health cost of morbidity-related health endpoints from the concentration of pm in the surroundings of the d motorway in the czech republic. we succeeded in identifying the areas where it is possible to closely monitor the impact of traffic and the transport infrastructure on the population or to monitor their health impacts. the article uses a precise methodological framework of assessing and analyzing the long-term impacts of road transport on the population with the application example of the d motorway in the czech republic and increased air pollution with pm . from the first part of the analysis, the importance of the route of high-speed roads in the proximity of towns or urban agglomerations can be seen. these sections can have a very significant impact on the population, which is subsequently exposed to an increased environmental burden and may experience negative health consequences with corresponding economic impacts. moreover, these urban areas are usually located at lower altitudes, which means worse conditions to handle the pollutant concentration naturally through meteorological circumstances, as we show in a regression analysis. the existence of highways with traffic intensity from , to almost , cars a day near residential areas decreases air quality with regard to pm in the range of . to . μg/m compared with the outer zone of , m (see table ). the impact mentioned above is relevant for at least , inhabitants living less than m from the d highway. this population represents an average czech district town. a long-term comparison of the air pollution burden in the vicinity of the highway in the - and - periods shows a decrease between . % and . % (see table ). as no safe concentration of pm that would not adversely affect human health has been established, any reduction in concentration may also reduce the number of individual health endpoints and the total costs per year. at the same time, it is clear from the results of the analysis that during the ten years under review, an average reduction in pm pollution of μg/m (see figure ) source: andersen, ; friedrich, ; bickel et al., czech statistical office register of 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biodiversity and marked degradation in air and water quality due to atmospheric pollution, thereby causing upsurge in infectious and non-infectious diseases. environmental health has emerged as an important part of medicine. the world health organization (who) estimates that % of global disease burden and % of all deaths can be attributed to environmental factors. deaths from heart disease, cancer, respiratory disorders and many vector-borne diseases such as malaria, dengue, chikungunya and cholera have increased due to changes in climate, especially in developing countries. besides limited attention to sanitation, hygiene, as well as quality of food and drinking water, factors such as deforestation, increasing vehicular traffic, migration from rural to urban areas, decreasing water resources and inadequate drainage systems contribute to increase incidence of diseases. the need of the hour is to sensitize ourselves about the way our ecology is being degraded and the health effects it is causing. a holistic view is needed to address the problem of environmental health where agriculture, animal husbandry, public health, water safety and air pollution need to be looked at in a combined manner for education, planning and resource allocation. therefore, a close association between scientists, public health professionals and administrators is needed for integrated design and development of framework to attain harmony between man and nature. an ecosystem is defined as a community of living beings surviving and interacting in mutual and interdependent relationship with their physical environment. for thousands of years, man has lived in harmony with their natural surroundings. environment has played a crucial role in his economic, social and cultural behaviour as well as on his health. the role of environment in various diseases has been well documented, both in communicable and non-communicable diseases. since the dawn of industrialization era in europe years ago and its subsequent spread to the rest of world, economic development and physical comfort for mankind have increased at a tremendous pace. this increase is perhaps the most rapid over the last three decades. often this has been done, knowingly or unknowingly, at the cost of our environment. the last years have witnessed a sharp increase in the global temperature from its levels around years ago, owing to industrialization (mann et al. ; marcott et al. ) . moreover, other concerns such as depletion of carbon fuels at alarming rates, damage to the ozone layer and rise in seawater levels, combined with global warming, have damaged our environment extensively, leading to changes in the aquatic biodiversity and to the extinction of many species of plants and animals (thomas et al. ) . increase in urbanization has led to loss of dense forests. air pollution has risen to the extent that many big cities in the world have a highly toxic air quality. however, very little has been done by various governmental and non-governmental agencies with almost no visible results. the need of the hour is to sensitize the scientific community, as well as the common man, about the way our ecology is being degraded and the health effects it is causing and to suggest ways to get remedies for this situation. environmental health has emerged as an important part of medicine, due to the rapid environmental changes linked to industrialization and urbanization. it is being increasingly recognized that environmental factors play a key role in human health and are linked to many chronic and infectious diseases. deaths from heart disease and respiratory illness are increasing, and many diseases such as malaria, dengue, chikungunya and cholera are sensitive to changes in the climate (mcmichael et al. ; patz et al. ) . according to the world health organization (who), 'in its broadest sense, environmental health comprises those aspects of human health, disease and injuries that are determined or influenced by factors in the environment. this includes the study of both direct pathological effects of various chemical, physical and biological agents, as well as effects on health of the broad physical and social environment, which include housing, urban development, land use and transportation, industry and agriculture'. the who estimates that % of the global disease burden and % of all deaths can be attributed to environmental factors. moreover, environmental factors have a much bigger impact in developing countries than developed ones, and this effect is seen much more in the vulnerable population such as children and elderly. in a developing country like india, the burden of various diseases is increasing due to environmental factors and the changes in our environment. it is estimated that % diarrhoeal disease burden may be attributed to environmental factors such as unsafe food and drinking water, as well as poor sanitation and hygiene. similarly, in india there is strong evidence linking lower respiratory tract infection to indoor air pollution caused by the use of solid fuels in household. almost % of acute lower respiratory tract infections in developing countries are attributable to environmental factors. besides this, a close association of vector-borne diseases and environmental conditions has been established. furthermore, factors such as deforestation, increasing vehicular traffic, migration from rural to urban areas, decreasing water resources and inadequate drainage system are important environmental and ecological factors that contribute to infectious diseases. the temperature of the earth has increased by about . °c over the past years (griggs and noguer ; mccarthy ) . winters are shortening and average temperature is rising. intergovernmental panel on climate change (ipcc) of united nations predicts that the global temperature will rise by . - . °c by the turn of this century, if no remediable actions are taken (houghton et al. ). this will lead to rise in sea level by - cm and drowning of coastal cities, which comprise % of world's major cities (crutzen ; fitzgerald et al. ; nicholls and cazenave ) . higher temperatures will lead to melting of polar ice, melting of glaciers, floods and droughts (patz et al. ) . average temperature shall rise during both summers and winters. heat waves will increase, and average annual precipitation will also increase correspondingly. heat waves, floods and droughts lead to natural calamities, shortage of food supplies, increased risk of infectious diseases and increased human mortality (haines et al. ). clean water is essential for the survival of humans. water pollution due to environmental changes therefore constitutes another serious risk to the health of our planet. water pollution occurs when energy and substances are released and degrades the quality of water for other users. anything that is added to water, which is more than its capacity to break it down, constitutes water pollution. anthropogenic activities such as industrial waste effluents, sewage disposal and agricultural activities are some of the major causes of water pollution (manivasakam ; tilman et al. ) . chemical pollution of surface water causes major health problems as it can be used directly for drinking or it may contaminate shallow wells, used for drinking. ground water, which is much deeper, has very few pathogens as it gets filtered when it passes through many underground layers. it can be polluted by toxic chemicals such as fluoride and arsenic which may be present in the soil or the rock layers. similarly, pollution of coastal water can cause contamination of sea food (guleria ) . changing environment has a serious effect on safe water, affecting not only human health but also changing the ecology of plants. the global effect of water pollution has not been studied in detail and is limited to mainly outbreaks of waterborne infections or certain chemical toxins in limited areas, such as arsenic in drinking water in bangladesh, 'minamata' disease in japan, etc. (argos et al. ; harada ) . the burden of waterborne diseases is grossly underreported in india due to lack of data, poor surveillance and reporting. according to a report from the ministry of health and family welfare, nearly million people are affected by waterborne diseases such as diarrhoea, enteric fever, amoebiasis and helminthic infestations, every year. who estimates > , deaths annually, in india alone, due to contaminated water consumption. moreover, floods and droughts also affect human health. floods lead to physical injury as well as spread of waterborne diseases such as diarrhoea, enteric fever and viral hepatitis. overcrowding occurs and sanitation is affected, leading to respiratory infections. diseases such as malaria and dengue may turn into epidemics. on the other hand, drought leads to lack of sanitation, decreased food production and ultimately malnutrition. another aspect of waterborne diseases is chemical contamination leading to diseases such as fluorosis and methemoglobinemia, due to contamination of soil water owing to fluoride and fertilizers. chronic exposure to contaminated water can cause significant health effects and can lead to liver and kidney damages. this occurs due to chronic exposure to copper, cadmium, arsenic, mercury, chromium and chlorobenzene. endocrine effects have been reported, and problems relating to reproduction, development and behaviour have also been observed. enso is a cycle of seawater temperature and pressure changes occurring over the southern pacific ocean at an interval of - years and lasting for - months. this leads to episodes of floods in the southwest united states, mexico and western coast of latin america and droughts in southeast asia and the pacific islands (kovats et al. ). this may be followed by cold waves called la niña. higher global temperatures are predicted to lead to more frequent and severe ensos, and this will lead to significant effects on human health, in the coming years (bouma et al. ). change in the global climate has led to higher temperatures, humidity and floods, which has made the environment more conducive for parasites such as mosquitoes and fleas (patz et al. ) . malaria, dengue and other vector-borne diseases are expected to increase both in magnitude and their geographical reach (haines et al. ) . people living at higher altitudes may also likely experience resurgence in vector-borne diseases, due to a rise of average temperatures in these regions. moreover, these diseases can spread to any part of the world in a very short time (at times during the incubation period) and cause an outbreak in a community where these diseases do not usually occur, resulting in diagnostic difficulties. this has recently been seen during the ebola and the mers coronavirus outbreaks. other factors such as breakdown of public health infrastructure, shortage of medical supplies and changes in land use also contribute to adversities in health, due to water pollution. air pollutants affect the human body through the inhalational route. environmental changes due to industrialization have drastically altered the quality of the air we breathe. there are hundred substances that pollute the air and may harm human health. pollutants are generally classified as primary or secondary pollutants. chemicals that are directly emitted from a source are known as primary pollutants. these include sulphur dioxide, nitrogen oxides, carbon monoxide, volatile organic compounds, etc. moreover, particulate matter emitted due to combustion from automobile exhaust, heating, cooking and industrial sources are also primary pollutants. secondary pollutants, such as formaldehyde, nitric acid and different aldehydes, on the other hand, are formed from chemical or photochemical reaction in the atmosphere. on exposure to sunlight, volatile organic compounds and nitrogen oxides react photochemically, producing pollutants such as ozone. air pollution and occupational exposure may cause a variety of negative health outcomes, including reduced lung function in children as well as increased susceptibility to infections, airway inflammation and cardiovascular diseases. respiratory disorders due to air pollution are emerging to be a major contributor to mortality, according to recent epidemiologic studies. moreover, low-level air pollution is recently being recognized as a risk factor for lung diseases and death from copd (bosson and blomberg ) . with newer insights into the immunopathogenesis of asthma, the contribution of air pollution to allergen sensitization and airway hyperresponsiveness are being established. for example, increased exposure to nitrogen dioxide during infancy correlates with increased risk for asthma in later childhood. ozone can produce significant adverse effects on human health (gryparis et al. ; teague and bayer ; uysal and schapira ) . moreover, recent research is now linking air pollution to increased risk of respiratory symptoms and duration of respiratory tract symptoms. international agency for research on cancer recently designated diesel exhaust as a human carcinogen. sulphur oxides are produced mainly from industrial activities processing materials that contain sulphur, such as generation of electricity from coal, oil or gas, as well as by combustion of fossil fuels. sulphur dioxide is also present in motor vehicle emission. together with ozone, it is known to cause foliar injury and reduction in plant growth (smith ; tingey and reinert ) . it is mainly absorbed in the upper airways as it is water soluble. its exposure is known to cause symptoms such as nose and throat irritation. it may travel to the lower airways and cause bronchoconstriction and dyspnoea, especially in asthmatic individuals, thus worsening their condition (balmes et al. ; ierodiakonou et al. ) . nitrogen oxides are emitted primarily from motor vehicle exhausts, as well as from stationary sources such as electric utilities and industrial boilers. compounds such as sulphur and nitrogen oxides cause chemical reactions in air and acid rains. although acid rains do not affect humans radically, they may indirectly cause health problems, particularly difficulty in breathing and, in extreme cases, lung problems such as asthma or chronic bronchitis. moreover, nitrogen oxides are the main precursors in the formation of tropospheric ozone. they also form nitrate particles and acid aerosols. exposure to nitrogen dioxide for a short term leads to changes in airway responsiveness and deterioration in pulmonary function in individuals with underlying lung disease. long-term exposure may lead to increased chances of recurrent respiratory tract infections and alter lung mechanics (berglund et al. ) . carbon monoxide is produced mainly due to motor vehicle emission. in urban areas more than % of the carbon monoxide emission may be due to motor vehicles. besides this, the combustion of coal, oil and gas also leads to carbon monoxide production. moreover, tobacco smoke is one of the main sources of indoor pollution of carbon monoxide. high levels of carbon monoxide are extremely dangerous to humans, more so because it is colourless, tasteless and odourless and therefore cannot be detected by humans. early symptoms of carbon monoxide include weakness, headache, nausea, dizziness, confusion, disorientation and visual instability. carbon monoxide quickly enters the blood stream and forms carboxyhaemoglobin which causes more systemic effects. it reduces oxygen delivery to the tissues and may have a serious health threat to those with underlying heart disease (badman and jaffé ) . prolonged or severe exposure may result in lethal arrhythmias, electrocardiographic changes, pulmonary oedema, various neurological symptoms as well as death, most likely due to cardiac failure. carbon monoxide is known to cause foetal development disorders, brain lesions and, in extreme cases, even mortality (raub et al. ) . the atmospheric levels of lead have decreased due to the use of unleaded fuel. however, lead toxicity continues to be a problem, due to the exposure occurring in drinking water. lead exposure leads to adverse effects on the central nervous system, causing neurological symptoms such as sleep disorders, fatigue, trembles in limbs, blurred vision and slurred speech, as well as kidney and liver disorders (kampa and castanas ) . lead toxicity can lead to lower intelligence, learning deficits and behavioural disturbances. ozone is an important secondary pollutant and is a component of photochemical smog. it is a pulmonary irritant and an oxidant. it may produce significant adverse effects on human health. exposure to ozone causes airway inflammation, airway hyperreactivity and a decline in lung functions. ozone exposure causes cough, chest tightness and wheezing. the increase in the levels of tropospheric ozone is associated with reduced baseline lung functional as well as structural abnormalities, exacerbation of asthma and premature mortality. recent studies have shown increased admissions for chest complaints and worsening of asthma on exposure to even low levels of ozone. studies looking at long-term exposure to ozone suggest that a cumulative long-term exposure in childhood may affect lung function, especially that of the small airways of the lung, in adult life (künzli et al. ) . ozone also affects mucous membrane and causes pulmonary inflammation and has both a local and systemic effect on the immune system. patients with underlying respiratory illness such as asthma and chronic obstructive airway disease are more prone to the harmful effect of ozone. high ozone concentrations have been linked with increased hospital admissions for pneumonia, copd and asthma (gryparis et al. ; teague and bayer ; uysal and schapira ) . particulate matter consists of liquid or solid mass contained in an aerosol. it is a mixture of numerous different chemicals, with varying properties. major sources of particulate matter are factories, power plants, incinerators, motor vehicles, construction activities, fire and dust. broadly particulate matters from . to μm in diameter are coarse particulate matter. coarse particulate matter consists mainly of airborne soil dust and elements such as silicon and aluminium. fine particles of less than . μm are composed mainly of sulphate and organic material. particulate matter in air is associated with allergic rhinitis, lung inflammation, pulmonary disorders, cardiac arrhythmia, ischemic cardiovascular events, higher incidences of cancer and shortening of life (carlsten and georas ; dockery et al. ; kampa and castanas ; pope iii et al. ; raaschou-nielsen et al. ) . only recently we began to understand the cardiovascular effects of air pollution. high levels of air pollution worsen underlying heart disease. but now it is becoming clear that persistent exposure to high levels of air pollution may also lead to heart disease. this is especially true for particulate matter. inflammation in lungs also causes inflammation in the blood, leading to atherosclerosis and an increase incidence of coronary artery disease that may be fatal (fig. . ). many well-conducted studies have demonstrated a - % higher risk of coronary artery disease in individuals exposed to high levels of air pollution, for many years (cesaroni et al. ; miller et al. ). this increased risk has been linked to higher levels of pm . in the ambient air. studies have also looked at subclinical atherosclerosis, which is the pathological process associated with coronary artery disease. a positive association between subclinical atherosclerosis in the carotid and the coronary arteries has been observed with long-term exposure to high levels of air pollution (künzli et al. ; künzli et al. ) . there is therefore now a significant body of evidence linking air pollution to cardiovascular diseases and increased mortality. many investigators argue that air pollution should now be considered as a preventable risk factor like smoking and dyslipidemia for the development of coronary artery disease, and steps should be taken to bring down the exposure to air pollution. indoor air pollution and its effect on human health are important as individuals spend more than % of their time indoors. cooking is an integral part of indoor human activity. the who has estimated that about % of the world's population, or about billion people, still uses solid fuel for their household energy needs. of these, about . billion people use biological material (wood, charcoal, crop waste and dung), and the remaining use coal. in india, about % of the population has been estimated to depend upon wood, and about % depend upon dung for energy. although this number is slowly decreasing and moving towards the use of other fuels such as liquefied petroleum gas (lpg) and kerosene, it is still very significant. in india in , of the . billion people, about million still used solid fuel for cooking or heating. many studies over the last three decades have documented the link between solid fuel exposure and different respiratory diseases. lim et al. ( ) estimated more than million premature deaths per year due to indoor air pollution, because of solid fuel used for cooking purposes. exposure to high concentrations of harmful substances in smoke during use of biomass fuel causes significant illness amongst homemakers and young children. it has been shown that biomass fuel is a less efficient means of energy production and a number of carcinogenic constituents are released during biomass combustion (chafe et al. ; smith and sagar ) . inhalation of these particles in high concentration leads to 'lung overloading' and sustained inflammation. this results in the release of reactive oxygen that causes deoxyribonucleic acid (dna) damage. indoor smoke produced due to burning of solid fuel contains many pollutants. particulate matter, nitrogen oxides, carbon monoxide, benzene, . butadiene, polycyclic aromatic hydrocarbons, free radicals and volatile organic compounds are many of the toxic substances that have been found in smoke produced by burning solid fuels. chronic exposure to these harmful substances leads to lung fibrosis and subsequently the development of lung cancer. the evidence for the development of lung cancer due to biomass exposure has been shown in experimental animals, but the evidence in humans is not that strong. indoor air pollution thus accounts for a significant proportion of the global burden of disease in developing countries. the link between solid fuel exposure and chronic obstructive lung disease in women and acute respiratory tract infection in children is strong. the commendable initiative by the government of india called 'give it up' is a step in trying to decrease the effects of indoor air pollution on human health. also steps to improve ventilation in kitchens or use smokeless stoves chulla may also help in reducing the exposure to indoor air pollution (reddy et al. ). waste generated from used electronic devices and household appliances constitutes e-waste. it comprises of a wide range of equipments and devices falling under 'hazardous' and 'non-hazardous' categories such as computers, mobile phones, refrigerators, washing machines, air conditioners, personal stereos, consumer electronics, etc., that are discarded by users (puckett et al. ) . pollution due to electronic and electrical waste has rapidly grown over the last decade due to progressive increase in production of electronics, lack of proper disposal facilities in india and dumping of e-waste from developed countries. in alone, india generated about . million tons of e-waste (double the amount as compared to ), which is progressing rapidly. e-waste may contain many toxic substances which may be harmful to the environment and human health. this can have a significant economic and social impact on society. iron and steel constitute about % of the e-waste followed by plastics ( %), nonferrous metals ( %) and other constituents ( %). others include nonferrous metals like copper, aluminium, silver, gold, platinum, palladium, etc. the presence of elements such as lead, mercury, arsenic, cadmium, selenium and hexavalent chromium, with flame retardants beyond threshold quantities of e-waste, classifies them as hazardous waste. manual recycling of e-waste is done predominantly via the unorganized sector, and the work force involved consists predominantly of individuals with low literacy and hardly any training to protect themselves from ill effects and to identify warning signals of toxicity. accordingly, a significant percentage of health problems due to e-waste results from direct contact with harmful materials and inhalation of toxic fumes. moreover, these materials may get accumulated in the food and water and are consumed. heavy metals such as lead can cause kidney failure, neurologic manifestations and hypertension. mercury toxicity can lead to central and peripheral nervous system damage and hepatic and renal toxicity (guleria ) . furthermore, uncontrolled burning, disposal and dismantling of e-waste can cause a number of problems including air pollution and water pollution. there is a lack of an environmentally effective recycling infrastructure for e-waste, and this leads to pollution of the environment. this is gradually changing our ecology. there is, therefore, a need to increase public awareness about the harmful effects of e-waste and develop an effective recycling and disposal plan, to prevent or minimize air and water pollution. there should be general awareness of how changes in climate and environment lead to significant acute and chronic effects on human health. these effects can be both for infectious and non-infectious illnesses. a holistic view is needed to address the problem of environmental health where agriculture, animal husbandry, public health, water safety and air pollution need to be looked at in a combined manner for education, planning and resource allocation. general population should also be made aware about the ways to reduce harm to our environment. intergovernmental efforts should be made to check climate change, avoid deforestation and use alternative sources of energy like solar energy instead of petroleum products. ultimately, as embedded in its definition, ecosystem is a community, and unless all people in community put efforts to conserve it, no amount of individual effort can suffice. therefore, a close teamwork between scientists, public health professionals and administrators is needed for integrated vertical and horizontal planning. arsenic exposure from drinking water, and all-cause and chronic-disease mortalities in bangladesh (heals): a prospective cohort study blood and air pollution; state of knowledge and research needs symptomatic bronchoconstriction after shortterm inhalation of sulfur dioxide health risk evaluation of nitrogen oxides update in environmental and occupational medicine global assessment of el niño's disaster burden update in environmental and occupational lung diseases long term 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long-term exposure to air pollution and incidence of cardiovascular events in women sea-level rise and its impact on coastal zones effects of environmental change on emerging parasitic diseases the potential health impacts of climate variability and change for the united states: executive summary of the report of the health sector of the us national assessment impact of regional climate change on human health particulate air pollution as a predictor of mortality in a prospective study of us adults exporting harm: the high-tech trashing of asia. basel action network. e-waste/technotrashfinalcom air pollution and lung cancer incidence in european cohorts: prospective analyses from the european study of cohorts for air pollution effects (escape) carbon monoxide poisoning-a public health perspective domestic cooking fuel and lung functions in healthy non-smoking women air pollution and forests: interactions between air contaminants and forest ecosystems making the clean available: escaping india's chulha trap outdoor air pollution: asthma and other concerns extinction risk from climate change forecasting agriculturally driven global environmental change the effect of ozone and sulphur dioxide singly and in combination on plant growth effects of ozone on lung function and lung diseases key: cord- - ighp gx authors: bhagat, rajesh k.; davies wykes, m. s.; dalziel, stuart b.; linden, p. f. title: effects of ventilation on the indoor spread of covid- date: - - journal: nan doi: . /jfm. . sha: doc_id: cord_uid: ighp gx [figure: see text] florence nightingale, born years ago this year, remarked that 'the very first requirement in a hospital is that it should do the sick no harm' (nightingale ) . she recommended that wards should have high ceilings, natural light and be well ventilated, principles that guided the design of 'nightingale wards' in uk hospitals for the best part of a century. and, while it is still remains controversial that sars-cov- , the virus causing covid- , can be spread by airborne transmission (fennelly ; lewis ; morawska & milton ; zhang et al. ) , poorly ventilated places are considered to be high risk and, on a precautionary principle, current advice is for buildings to be as well ventilated as possible (who ) . with the approach of winter and cooler weather in the northern hemisphere, where approximately % of the world population reside, there is a clear tension between this requirement and the ability to maintain thermal comfort in buildings without excessive energy consumption. since the oil crisis in , and with increasing concerns over the emission of greenhouse gases and climate change, the focus of studies of building ventilation has been on energy efficiency and occupant comfort. this, and generally improved construction standards, has led to tighter buildings and specific ventilation strategies such as mixed-mode ventilation (part natural ventilation, part mechanical ventilation) to reduce the environmental costs of air conditioning in summer. over the past few years there has been a rising concern about the health impacts of air pollution and, as a consequence, there has been a shift towards considerations of the pollution levels indoors, which taken with temperature and relative humidity constitute indoor air quality (known as iaq). this shift in emphasis has come to the fore during the present covid- pandemic, driven by the possibility of infectious aerosols being carried around a building by the ventilation system lu et al. ; morawska & milton ; stadnytskyi et al. ; zhang et al. ) . a number of outbreaks in confined indoor crowded spaces such as offices, churches, restaurants, ski resorts, shopping centres, worker dormitories, cruise ships and vehicles indicate that virus transmission is particularly efficient in these types of indoor environments (leclerc et al. ) . qian et al. ( ) studied covid- outbreaks with three or more cases of transmission, and in all except one, the virus transmission occurred in indoor spaces. park et al. ( ) reported an incidence of covid- outbreak in an eleventh-floor office of a call centre in south korea where . % of the occupants ( out of people) were found to be infected; however, the rate of secondary infections to the household members of the symptomatic patients was only . %. increased rates of transmission occur not only for buildings, but also on public transportation where people are likely to be in the presence of an infected person in a crowded indoor space for relatively long periods of time and, therefore, exposed to airborne particles (e.g. hu et al. ) . there is also clear evidence that poor ventilation contributes to the spread of other airborne diseases, such as tuberculosis and sars . in this article, we examine the role of ventilation on the distribution of airborne contaminants in a space. the primary aim of building ventilation is to provide fresh air for breathing and to remove unwanted heat and contaminants from a space. in winter, there is little unwanted heat and the main requirement is to provide fresh air -the industry recommended rate is litres per second per person (l.s.p.). in summer, this flow is generally not sufficient to remove heat generated within a space by the occupants, equipment and solar gains, and higher ventilation rates or mechanical cooling are often employed, particularly in modern buildings. the importance of ventilation is expressed in the wells-riley equation, which states that the probability p of airborne transmission of an infectious agent indoors is where n i is the expected number of people who become infected by being in the room, n s is the number of susceptible people present in the room for a period t s , n e is the number of people emitting infectious 'quanta' (describing the mean viral load required for infection) at a rate γ i (giving the total emission rate Γ = n e i= γ i ), q is the time-average volume flux of exhaled air per person and q is the volume flux of fresh (uncontaminated) air entering the room (riley, murphy & riley ) . this assumes that ventilation is uniform across a space. however, as we shall see, local flows can be significant. ventilation, whether natural ventilation or mechanical ventilation, has two main modes. the most common, certainly in air conditioned buildings, is mixing ventilation where inlets and outlets are designed to generate flow that keep a space well mixed so that the temperature and any contaminants are uniform throughout the space. the other extreme is displacement ventilation, in which the vents are arranged so that an interior stratification is established with a cool lower zone beneath a warm upper zone. in displacement ventilation, the system is designed to keep occupants in the cool lower zone and so extractors are located in the upper part of the space. a schematic showing these modes is given in figure . we discuss the implications for airborne transmission in these ventilation modes and the impacts of other factors important to air movement in buildings. in particular, we show that a significant amount of bio-aerosol expelled during exhalation can remain airborne and be carried around the building by the ventilation flow. since carbon dioxide is also exhaled and carried by the ventilation flow we propose that concentration levels of co can be used to indicate the potential presence of sars-cov- in the air, and that high levels should trigger remedial action to reduce the risk of infection. transmission of respiratory diseases occurs via expiratory droplets produced by coughing, sneezing, speaking, singing and laughing (stelzer-braid et al. ; yan et al. ) . human exhalation contains droplets in the range . - μm (bake et al. ) . the medical infectious disease community divides droplets into two classes: droplets larger than - μm in diameter are classified as respiratory droplets, whereas droplets smaller than μm are referred to as aerosols (who ; milton ) . droplets are considered to fall quickly to the floor close to the source, whereas aerosols are expected to remain airborne for long times. the cutoff between respiratory droplets and aerosols is somewhat arbitrary: in practice, droplets larger than μm can remain in suspension for long times allowing them to be recirculated within or removed from the room. airborne transmission occurs when a person is exposed to an infectious load of pathogen-laden aerosols. droplets and bio-aerosol produced due to intermittent violent expiratory events such as coughing and sneezing have attracted much attention (bourouiba, dehandschoewercker & bush ; bourouiba ) , and this subject has recently been reviewed by mittal, ni & seo ( ) . however, under normal circumstances, the cumulative amount of bio-aerosol produced by low frequency violent intermittent events of coughing and sneezing is much less than that of breathing and talking. compared with a person intermittently coughing every minute, in the same period the simple act of breathing or talking produces times the amount of exhaled air (gupta, lin & chen ) . furthermore, recent evidence suggests that asymptomatic/presymptomatic airborne transmission, particularly in crowded indoor environments, cannot be ruled out (he et al. ; leclerc et al. ; park et al. ; qian et al. ) . the infectivity of covid- patients peaks before the onset of symptoms, and preventing presymptomatic and asymptomatic transmission is the key to contain the spread of the virus (matheson & lehner ) . at the early stage of the disease, upper respiratory tract symptoms and the presence of high concentrations of sars-cov- virus in oral fluids are common (wölfel et al. ) , supporting recent findings identifying speech droplets to be a potential cause of transmission (stelzer-braid et al. ; anfinrud et al. ; stadnytskyi et al. ) . conversational speech produces a wide range (submicron up to o( μm) of droplets) while the majority of aerosol particles in exhaled breath are < μm (fennelly ) . however, the viral load associated with different aerosol sizes is unknown, making estimates of infectivity, required as input to ( . ), very difficult. when droplets are exhaled they evaporate at a rate that depends on droplet size and composition, and the relative humidity and temperature of the air. redrow et al. ( ) compared the evaporation time and resulting nuclei sizes of model sputum, saline solution and water droplets. they showed that sputum droplets containing protein, lipid, carbohydrate, salt and water leave larger nuclei than salt solution. they also calculated the time scales of evaporation of water droplets at room temperature, for relative humidities between % to %, to be . - s for droplets less than μm and - s for μm droplets. therefore, it is expected that droplets larger than μm settle on the floor or other nearby surfaces (liu et al. ) , while droplets smaller than approximately μm tend to form nuclei and are transported as passive scalars (xie et al. ) . the final size of exhalation droplets depends upon many factors including the initial size, non-volatile content, relative humidity, temperature, ventilation flow and the residence time of the droplet. marr et al. ( ) gave the equilibrium size for μm sized model respiratory droplets containing mg ml − nacl, mg ml − protein and . mg ml − surfactant to be . and . μm at relative humidities of % and < %, respectively. we begin the discussion of ventilation by considering some typical flows in a space. consider a (generous) one-person office of floor area × m with a floor to ceiling height of h = m. a person gives off approximately w of heat in the form of a convective plume that rises towards the ceiling. the person breathes at a rate of - l min − (gupta et al. ) and this exhaled breath carries . %- % of the body heat. the recommended ventilation rate is l.s.p., which is equivalent to one air change per hour (ach) for this room and is much greater than the volume of air breathed, but is needed because the concentration of co in exhaled breath is around - parts per million (p.p.m.). note for comparison that background external co concentrations are currently approximately p.p.m. in practice, ventilation rates are set between - ach, although higher values are used in specialised facilities such as operating theatres. the speed v of volume-average flow in the room is v = nh = mm s − for n = ach (v = mm s − for n = ach) and this average flow is hardly perceptible to an occupant. to put this in perspective, the stokes settling velocity of a d = μm droplet is . mm s − , while the asymptotic fall speed of a d = μm droplet is mm s − . droplets with d μm have a settling velocity greater than the volume-average ventilation velocity, even at ach and, ignoring any evaporation or air movement, the fall time for a μm droplet from the release height of . m is s reducing to s for droplets d = μm. evaporation, however, means that the μm droplet will take longer than this to reach the floor, and indeed may not do so as its settling velocity decreases rapidly as it loses mass. however, this is by no means the whole (or even the main) story. in practice, air is introduced through a vent or a window that is usually quite small compared with the floor area. for example, the average speed of flow through a vent measuring . × . m is mm s − for ach, much greater than the volume-average velocity. if this is a ceiling vent, the resulting jet (ignoring buoyancy) will still have a velocity of ∼ mm s − when it reaches the floor. similarly, the plume above a person giving off w is also approximately mm s − , again much greater than the volume-average flow. consequently, the air flow patterns within a space are crucial for determining the distribution, transport and fate of any airborne contaminants. predicting these flow patterns is extremely challenging since they depend critically on both the boundary conditions (e.g. the location of inlet and outlet vents) and on the internal dynamics of the fluid, particularly buoyancy forces associated with temperature differences. this should be contrasted to, say, aerospace where flow round an aerofoil does not depend on the dynamics of the air, and geophysical fluid dynamics where boundary conditions are often unimportant. further, flows in buildings and other enclosed or semi-enclosed spaces often take place in very complex geometries, making computation of these turbulent flows particularly challenging. we will now summarise various typical forms of ventilation: mixing ventilation, natural and mechanical dispacement ventilation, and wind-driven ventilation. in mixing ventilation, the concentration c of aerosol suspended in the air is, by design, uniform, and in the absence of any continued input of aerosol satisfies where v r is the room volume and, as in § , q is the volume flux of fresh (uncontaminated) air. in a mechanical system, q can be assumed constant and the concentration decays exponentially with a time scale v r /q. a reduction of the initial concentration by a factor of e n then takes time (in hours) τ n = n/n, where n is the number of air changes per hour. for example, a decrease by a factor of e ∼ . takes τ = min (e ∼ would take τ = min) for n = ach. if there is a source of infection in the room, we can extend this and relate it back to the wells-riley equation ( . ) by adding the total emission rate Γ as a source term to the right-hand side of ( . ), giving and requiring a time of o(v r /q) to attain the equilibrium concentration Γ /q from an initial concentration c at t = . for a known emission rate Γ , ( . ) gives the concentration of aerosols in a mixing ventilation scenario, which can subsequently be used to calculate occupant exposure. however, knowing the source strength, Γ = n e i= γ i , is challenging due to the inherent variability associated with the source physiology, pathogen concentration at the source, physical properties of the exhaled aerosol, and the relative humidity and the temperature of the indoor space. nevertheless, in practice, co concentration calculated from ( . ) can be a good indicator of the presence of bio-aerosols produced by the occupants (rudnick & milton ) . in displacement ventilation, on the other hand, the goal is to minimise mixing within the lower occupied zone, allowing the heat and contaminants to rise to the top of the space where they are extracted through upper-level vents. the lower occupied zone is supplied with fresh, uncontaminated air through vents located near the bottom of the space, as illustrated schematically in figure . in practice, these 'low-level' inlets can be windows or doorways, provided there are high-level outlets available. in stack-driven natural ventilation, warm buoyant air (due to body heat and the heat generated by solar gains, equipment and appliances) rises towards the ceiling and exits through an upper-level opening. this, in turn, draws in cooler (higher density) outdoor air that flows across the floor of the room. the stratification produced by the indoor temperature gradient drives the flow inside the building (figure a). the average flow is upwards, removing airborne contagion away from the occupants towards the ceiling, where it gets flushed out of the building. the stratification resulting from a single constant heat source consists of two layers, each of uniform temperature, with an interface at a height h separating the cool unpolluted region below from the warm polluted region above (linden, lane-serff & smeed ) . in practice, heat sources (such as a person or a piece of equipment) produce plumes released from various heights in the space, and the volume of the room below the lowest heat source plays no role as it contains air at the ambient outdoor temperature. thus the effective height of the room is h − h v , where h is the floor to ceiling height and h v is the 'virtual origin' of the lowest plume (i.e. the height at which the plume would start if it was a pure plume of buoyancy from a point source). in practice, it is quite difficult to determine h v and we return to this issue in § . in the case of n occupants (n ≥ n s + n e ), represented by equal strength plumes with the same virtual origin heights, the interface height is independent of the strength of the heat sources and is determined solely by the amount of open area according to with the empirical constant c ≈ . (morton, taylor & turner ; linden ) . this effective openable area a * depends on a combination of the total areas a t and a b of the top and bottom openings, respectively, given by the relation where c ≈ . is a discharge coefficient that accounts for flow contraction and the pressure losses at the openings. note that when the top opening is small (a t a b ), a * ∼ √ ca t , implying that the flow is controlled by the smaller opening. in practice, this allows the interface height to be controlled by a centrally operated upper opening. from ( . ), it is clear that, as noted by florence nightingale, buildings with high ceilings and with large openings are optimal for natural displacement ventilation. buildings usually have lower-level openings such as windows and doors, but often lack large upper-level openings. in situations where the required opening area is not available or the space is not tall enough, natural ventilation can be supplemented or replaced by mechanical extraction from the upper part of the space. in this case the height h of the lower clean zone is determined by matching the total extraction rate q with the flow of warm air from the occupants, etc., into the upper warm zone. for n occupants, this is given by the formula where b = n i= (w i g/ρc p t) is the buoyancy flux produced by n sources with heat fluxes w i , g is the acceleration due to gravity and c p is the specific heat of air. in air a heat flux of kw corresponds to b = . m s − . note that now the height of the space is no longer important, but the depth h of the clean zone depends on the heat input and is set by the extraction rate. in principle, h − h v can be set to any height using a suitable mechanical ventilation rate. in displacement ventilation, the equivalent room volume for removal of a contaminant is simply the volume near the top of the room containing the contaminant. consequently, the removal time scales are shortened by a factor − h/h compared with those obtained in mixing ventilation. it is, therefore, advantageous for the interface of the contaminated upper zone to be as close to the ceiling as possible. wind can also drive natural ventilation in a space, with different models applying for single sided (opening on one side of a space) and cross-ventilation (openings on two sides of a space). existing models for single-sided ventilation rates driven by wind and buoyancy are based on empirical fits to data from field studies and wind tunnel experiments (degids & phaff ; warren & parkins ; larsen & heiselberg ) . these models generally underestimate ventilation rates in full-scale tests (larsen et al. ; gough et al. ) . this is likely to be useful in the context of calculating the time to ventilate a room as this will provide estimates with a safety margin. the combined effect of wind and buoyancy for cross-ventilation can be modelled using a function of the densimetric froude number fr = u/ g h, where u is the wind speed, h is the opening height, g = g × Δt/t, Δt is the indoor-outdoor temperature difference and t is the room temperature in kelvin (davies wykes, chahour & linden ). if the incoming flow is sufficiently energetic to mix the space, the concentration of any contaminants will decay exponentially, as in the well mixed case. however, if there is a significant indoor-outdoor temperature difference, the room can stratify, trapping contaminants in the region of the room above the top of the downwind opening, which then remain for long times. a similar trapping effect can occur for buoyancy-driven single-sided exchange ventilation through a window or door (phillips & woods ) . it is a truism that 'hot air rises'. in a room, air that is heated by internal heat sources (occupants, equipment, solar radiation, heaters) will rise and tend to accumulate near the ceiling. the well mixed assumption which is implicit for mixing ventilation is only valid if the ventilation is able to mix this warm air throughout the space. since this process involves moving warm, buoyant air downwards, it requires a source of energy for mixing. consider the energy required to mix down a layer of air near the ceiling that is . m deep and k warmer than the air lower in the room. an energy balance (details not given here) assuming a mixing efficiency of . implies that volume-average velocities of approximately mm s − are required. this average flow in the space we are considering requires over ach! consequently, for a more reasonable ach, we expect the space to be stratified even when a mechanical system is introducing cool air at high level. typically, heat sources within a space are neither equal nor located at the same height, and the resulting stratification for displacement ventilation is more complicated than the simple two-layer form discussed above. one example is the stratification known as the 'lock-up effect', which refers to the possible trapping of exhaled breath below the warm ceiling layer. since exhaled breath is warm, it rises as a secondary plume and, if it is not immediately entrained into the main body plume, it first settles at an intermediate height and then ultimately is entrained and carried into the upper layer (figure b). the additional ventilation rate needed to ensure a lower layer of the same height can be calculated by considering the combined effect of two unequal plumes (cooper & linden ) and is a factor of approximately + (w ex /w) / ((h − h m )/(h − h v )) / , where w ex is the heat flux in the exhaled breath, h m the height of the mouth. typically, w ex ∼ %w and, for a typical case of h m ∼ . m, h v ∼ m and an upper layer height of h = . m, this requires an approximately % increase in the ventilation rate. the size of this increase emphasises that the wearing of face coverings, which block the forward momentum of the exhaled breath and trap it in the body plume, is particularly beneficial as discussed in more detail in § . thermal stratification will not only result in a higher temperature near the ceiling than near the floor, but will also tend to result in a stratification of any contaminants produced by people. figure shows that co accumulates at the ceiling in a naturally ventilated office even though the density of co is approximately . times that of fresh air. the office also has a stable temperature stratification with the ceiling temperature approximately k higher than the floor (equivalent in density terms to approximately p.p.m. co ), which is more than sufficient to counteract the density of co at the measured concentration. other examples of co stratification have been reported in mixing-ventilated spaces (mahyuddin & awbi ; pei et al. ) . stratification can be reduced by the use of ceiling or personal fans, or by the stirring induced by the motion of occupants, which can supply additional kinetic energy to the space. whether or not stratification is beneficial in a space will depend on the type of ventilation method employed. if the contaminants of concern are carried passively by the flow, then displacement ventilation provides the least contaminated breathing region (bolster & linden ). however, one concern related to stratification is the possibility that particles originally transported towards the ceiling may settle out of the warm, contaminated air to land on or be inhaled by someone else (bolster & linden ) . mingotti & woods ( ) showed there were several regimes for transport of heavy particles when they were introduced into a plume in a displacement-ventilated space. in steady-state, particles with a settling speed smaller than the volume-averaged velocity, v s < q/a, are well mixed throughout the upper layer and any particles settling into the lower layer are re-entrained by the plume. however, for particles with larger settling velocities, a fraction ( − q/av s ) of the particles added to the space will not be transported out of the space, but will instead settle to the floor. this process will be additionally complicated by the evolution of a droplet distribution by evaporation. upwards transport of aerosols in the body (and other) plumes in the space is a critical and generally unaccounted for feature when modelling the likely exposures of occupants of a space. this topic will be discussed in the next section. building occupants are often a source of trouble for designers and building managers. one room temperature does not suit all and, consequently, occupants often complain that it is too hot or too cold, and mess with thermostats and windows in ways that designers had not intended. from the fluid mechanical viewpoint, they can also be a source of considerable complication. as mentioned above, body heat causes a plume to rise above a person and its form and strength depend on body weight and metabolism, posture, the amount and type of clothing, activity level and even hair style. weak turbulence and other airflow within the room will buffet the plume, causing it to meander as it rises, increasing the entrainment into the plume (hübner ). as mentioned above, displacement-ventilation models are based on the height of the 'virtual origin' of the plume -the height at which the actual plume would have started if it were heated by a point source, and this is often difficult to estimate. the body plume and the interaction with exhaled breath can be visualised by observing the temperature-induced refractive index variations in the air using differential synthetic schlieren (dalziel, hughes & sutherland , dalziel et al. ) . figure shows the qualitative version of this technique with images capturing d/dt|∇ xzρ |, whereρ is the line-of-sight mean density and ∇ xz represents the gradient normal to the line of sight. the choice of this diagnostic emphasises the breath of the subject relative to the plume from the body. here, the test subject is dressed in jeans and a long-sleeved jumper. in figure (a-c) no face covering is worn and the subject is breathing out through their nose (figure a), speaking at a conversational level (figure b) and laughing (figure c). in figure (d-f ) the test subject exhibits the same breathing patterns wearing a mass-produced three-ply disposable non-surgical mask (complying with en : ). in all images the thermal plume driven by the heat flux from the surface of the body is visible, gently wafting upwards. as the test subject is seated, part of this heat flux drives convection from the subject's legs, positioned out of view beneath the image, although here the clothing makes this signal weak. the plume from the body surface is relatively gentle but turbulent and entrains the quiescent ambient air as it rises. although representing only . %- % of the total heat flux, the thermal signal from the various breathing patterns is clear and, in the absence of a mask, the resulting flow, which will carry the majority of the infectious . differential synthetic schlieren images of the thermal plumes produced by a person in a quiescent environment. in panels (a-c) no mask is worn, while in panels (d-f ) a non-surgical three-ply disposable mask is worn. the subject is (a,d) sitting quietly breathing through their nose, (b,e) saying 'also' when speaking at a conversational volume and (c,f ) laughing. video sequences of each of these can be found in the supplementary material. droplets, follows a different evolution to that of the thermal plume from the body. video sequences of each of these scenarios may be found online in the supplementary material available at https://doi.org/ . /jfm. . . in the absence of a face covering, an exhaled breath takes the form of a buoyant starting jet. exhalation from the nose (figure a) is typically inclined downwards and the air is around o( ) k above room temperature. mean exhalation velocities are around m s − over a period of around s, giving a specific momentum flux m = × − m s − and a buoyancy flux b = . × − m s − . the length before the buoyancy dominates the initial momentum, known as the jet length, is given by l j = m / b − / ∼ m. so even though the breath is directed downwards, we expect its momentum is sufficient for it not to be entrained directly into the body plume. (here, as the subject is sitting, the nasal breath interacts with air rising from the legs, allowing more of it to be entrained into the body plume than would be the case if the subject was standing.) on the other hand, as shown in figure (d) , a face covering significantly reduces the momentum and most of the exhaled breath is then entrained into the body plume and carried upwards. when speaking, the shape of the oral cavity, air flow and aperture of the lips all change rapidly, leading to source conditions that change for each syllable in a word or sentence. a mouth opened widely imparts little momentum on the (turbulent) air that is emitted, leading to a thermal signal that rises nearly vertically from the point of exit. some consonants such as 'b' or 'p' can lead to sudden ejections of air that roll up to form turbulent puffs or vortex rings with significant horizontal momentum, while others such as 'f' or 'v' direct the flux downwards as a strong jet in an orientation similar to that of the nasal emissions. figure (b) illustrates part of a spoken phrase. here the phrase 'there were also. . . ' has just been spoken, with the two distinct structures visible, propagating at different angles, come from the word 'also'. specifically, the 'al' sound produced a buoyant starting jet directed horizontally that was then reoriented to a more downward trajectory as 'so' was sounded. we may reasonably expect the droplet content of the air emitted to also depend on the phrase that is spoken, leading to complex patterns of droplet emission and distribution from normal speech, with some utterances being incorporated into the body plume while others undergo significant dilution before merging with the lock-up layer. of the utterances shown here, laughing produces the greatest air and heat fluxes, although without direct measurements we are unable to compare the droplet fluxes with those of speaking. what is clear, however, is that the jet produced from a laugh (figure c) has significant momentum that carries it down and away from the test subject, diluting it and preventing it from being entrained directly into the body plume. the degree of entrainment in this jet is such that it will be less buoyant than the air exhaled from speaking or normal breathing by the time it reaches its equilibrium height, and so will reside at the bottom of the lock-up layer. whereas nasal breathing and speaking produced quite distinct patterns of transport for exhaled breath when the test subject was not wearing a facial covering, there is relatively little to distinguish the distribution of exhaled air in the two cases when a non-surgical three-ply disposable mask is worn (figure d,e), although the duration of the airflow pulses differ. in both cases, the dominant flow of exhaled air is through the gap between the nose and mask, an issue common with many mask designs, with a low-momentum plume forming that hugs the forehead before merging with the body plume. there is little if any leakage evident from other edges of the mask, and any transport of warm, moist air through the mask itself is minimal. in these cases, it is reasonable to expect that the exhaled air will end up in the same layer as the majority of the heat from the surface of the body to form the main ventilated layer at the top of the room. the case of a laugh, however, is a little different from normal breathing or speaking. the higher volume flux still primarily exits the mask through the gap at the top (this gap is likely to be slightly larger due to the increased pressure associated with the airflow), although some of the flux can also be seen leaking from the bottom of the mask. the leakage from the top now has a more jet-like character to form an upward-directed buoyant jet that separates from the forehead. this separation prevents it from being entrained directly into the body plume. the leakage from the bottom of the mask, however, hugs the body and ends up being incorporated into the body plume. additionally, some flux through the mask itself is visible in front of the mask, although this is much smaller than the flux at the top of the mask and will have a lower proportion of larger droplets due to the filtering of the mask. a person walking through a building has a significant wake. for example, walking at a moderate pace of m s − = . km h − implies reynolds numbers based on the girth of (c) air exhaled by nasal breathing is swept around the head by the motion and entrained into the wake. (d) although laughing still produces a jet that reaches in front of the subject, it is soon overtaken and the associated breath is incorporated into the wake. an average person are ∼ at full scale, implying the wake is turbulent. the wake velocity is approximately % of the person speed, implying flows behind a person of the order of . m s − are possibly the largest in a space, capable of resuspending material deposited on surfaces and transporting airborne particles. experiments on a cylinder passing through an air curtain in a doorway, show that the air curtain is strongly disrupted by the passage and a large volume is transported through the doorway (jha, frank & linden a; jha et al. b) . enhanced longitudinal dispersion by the repeated movement along a corridor has also recently been reported (mingotti et al. ) . the motion of the person also has a profound effect on the structure of the thermal plume generated by the body. rather than natural convection leading to a coherent thermal plume rising from a localised source, the forced convection imposed by the motion sheds much of the heat flux from the body into the inertially dominated wake. figure (a) , generated using synthetic schlieren to visualise |∇ xzρ |, shows clearly this asymmetry with no temperature fluctuations in front of the person, the thermal boundary layer separating at the top of the head (there is a similar separation from the side of the head, but that is not directly visible in the visualisation), and a complex thermal structure in the wake behind them. the mixing that occurs in this wake distributes the (slightly increased) heat flux over a significantly larger volume of fluid, which is less strongly affected by buoyancy and so remains lower in the space for longer periods (figure b shows the thermal signature one second after the passage of the person remains confined at a level below the top of the head). although the person in figure (a) is not exhaling, the motion of the person through the air also has a noticeable effect on how their exhaled air is incorporated into the overall thermal structure of the room. figure (c) shows that the jet from nasal breathing is quickly swept back around the person to be incorporated into the wake, whereas figure (d) demonstrates that while a laugh has the momentum to extend some distance in front of the person, it may still end up being entrained into the wake if the person does not change direction. in addition to the flow induced by the wake of a person, transient effects occur when a person enters or leaves a space. how long does it take after a person enters an initially unoccupied space for a steady state to be established? the relevant time scales are set by the ventilation time scale v r /q, and the 'filling-box' time v r /cb / h / (baines & turner ) , which is the volume of the space divided by the volume flux in the body plume at the top of the space. the ratio of these time scales τ = cb / h / /q determines whether the steady state is determined by the ventilation rate (τ < ) or by the buoyancy-driven flow (τ > ). for a single person b ≈ × − m s − and in a m high room, the transition τ = corresponds to q ≈ . m s − (or n ≈ ach in our office) so in practice the time scale is usually set by the convective heat flow from the occupant. in a lecture theatre holding people the transition ventilation rate is n ≈ ach, so again the relevant time scale is the 'filling box' time. for a lecture theatre measuring m × m × m, this time is approximately s. we have shown room flows are 'turbulent' in the sense that spatiotemporal variations of the flow are larger than the mean flow. they take place in complex geometries where the placement and sizes of inlets and outlets determine overall flow patterns, superimposed on which are significant perturbations associated with often transient events such as the movement of occupants, the opening and closing of doors, and (for naturally ventilated buildings) variations in the external conditions. the dispersal of a second phase in such an environment is complicated, as droplets are released over a continuum of sizes and they evaporate and reduce in size with time. however, our analysis suggests that airborne transmission of the virus can occur in particles with fall speeds that are lower than typical velocities found in the room and so are advected through the space effectively like a passive tracer. in that case it seems reasonable to consider co as a marker for air that has been exhaled. indeed, it has been shown that co concentration can be linked to the probability of infection predicted by the wells-riley equation ( . ) (rudnick & milton ) . even though co is denser than air, our observations show that it is carried with the flow as would virus particles. a simple balance of a person breathing out at a concentration of p.p.m. at a rate of l min − and supplied with the recommended l.s.p., implies that a steady concentration above the background would be p.p.m. carbon dioxide concentrations above this value, especially at the breathing level, may indicate that the ventilation is inadequate and that remedial action should be taken. the risk of infection is thought to increase with exposure time. it is also the case that co levels increase over time once people begin to occupy a space. consequently, it may be appropriate to add some exposure time as well as simply the co concentration level to a warning system. despite the various mechanisms generating disturbances indoors, it is clear that in many cases stratification 'wins'. a small temperature difference across a doorway or window will organise the flow so that the cool air flows through the lower part and warm air through the upper part of the opening (linden & simpson ) . it is notoriously difficult to mix a stratified space with mixing efficiencies (the ratio of the kinetic energy needed to change the potential energy required) typically well below % (linden ) . the presence of stratification emphasises the need to measure co at a height where individuals are breathing, and away from sources of fresh air such as an open window, where concentrations are typically much lower than the room average, if one is to obtain an estimate for the load of potentially infectious particles. consequently, if designed properly, displacement ventilation, which encourages vertical stratification and is designed to remove the polluted warm air near the ceiling, seems to be the most effective at reducing the exposure risk. mixing ventilation distributes the air throughout the space and does not provide any potentially clean zones. it also has to work against the tendency of the room to stratify, while displacement ventilation takes advantage of it, and can simply and cheaply be implemented by installing extraction vents or fans at the top of the space. however, there remain some interesting questions on the behaviour of lock-up layers, particularly regarding the behaviour of particulates in the flow that need to be understood to optimally configure the system. our observations show that face coverings are effective at reducing the direct ejection of breath and bio-aerosols away from the person and, when wearing a mask, the majority of the breath is entrained into the body plume. however, many questions remain about aspects of this and other issues discussed in this paper. for example, when a person is moving their wake also entrains part of the breath and the body plume, but how this partition depends on walking speed is unknown, as is the stirring effect of a walking person on the stratification in a room or corridor. the interaction of wakes and body plumes of people passing each other is unexplored: is it different in a narrow corridor compared with an open plan office? the role of other buoyancy-driven flows such as circulations set up by open refrigerator shelves in a supermarket on aerosol dispersion is unknown. further, the conditions 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control of epidemic-and pandemic-prone acute respiratory infections in health care. world health organization. who q&a: ventilation and air conditioning in public spaces and buildings and covid- virological assessment of hospitalized patients with covid- how far droplets can move in indoor environments -revisiting the wells evaporation-falling curve infectious virus in exhaled breath of symptomatic seasonal influenza cases from a college community identifying airborne transmission as the dominant route for the spread of covid- this work was undertaken as a contribution to the rapid assistance in modelling the pandemic (ramp) initiative, coordinated by the royal society, and was supported by the uk engineering and physical sciences research council (epsrc) grand challenge grant 'managing air for green inner cities' (magic) grant number ep/n / . we thank dr m. dadonau for assisting with the body plume and breathing visualisations. we thank dr s. fang for the co measurements. the authors report no conflict of interest. supplementary movies are available at https://doi.org/ . /jfm. . . key: cord- -kbv kh z authors: singer, gregor; graff zivin, joshua; neidell, matthew; sanders, nicholas title: air pollution increases influenza hospitalizations date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: kbv kh z seasonal influenza is a recurring health burden shared widely across the globe. we study whether air quality affects the occurrence of severe influenza cases that require inpatient hospitalization. using longitudinal information on local air quality and hospital admissions across the united states, we find that poor air quality increases the incidence of significant influenza hospital admissions. effects diminish in years with greater influenza vaccine effectiveness. apart from increasing vaccination rates, improving air quality may help reduce the spread and severity of influenza. seasonal influenza is a global health threat, with an average of - million severe cases per year and , to , respiratory deaths ( , ) . the disease exhibits variability in spread and severity across individuals, regions, and over time. prior research has produced two broad sets of findings to explain this variation: a) meteorological factors that affect the spread of the virus, such as temperature, sunlight and humidity ( , , , , , ) ; and b) individual level host factors, such as age, sex, underlying health and smoking that affect the intensity of symptoms ( , ). we know considerably less, however, about how air pollution affects influenza spread and severity, a surprising gap given the pervasiveness of air pollution around the world and the well-established policy tools available to control it. air pollution could affect influenza hospitalizations via both susceptibility and exposure ( ). like smoking ( ), air pollution can impair the respiratory functioning of patients, e.g., by damaging the respiratory epithelium, thereby facilitating the progression of influenza virus beyond the epithelial barrier into the lungs ( , , , ) . existing medical research finds exposing in vitro respiratory epithelial cells to air pollution increases susceptibility and penetration of influenza ( ), and experimental exposure of mice to air pollution before influenza infections increased morbid-ity and mortality ( , ) . like humidity and temperature ( , , , , ) , air pollution particles could also impact the airborne survival of viruses outside the body ( , , , , , ) and thus increase the probability of disease transmission. we build on the existing evidence that links ambient air pollution with influenza spread and severity ( , , , , , , , , , , , , , , ) with two significant advancements toward improving causal inference ( ). first, we exploit a long panel of influenza-specific hospital admissions from numerous states across the united states (u.s.) to estimate statistical models that exploit both spatial and temporal variation within counties over time, limiting threats from confounding factors. second, to better understand the causal link, we explore the role of the influenza vaccine in moderating this relationship. if the vaccine reduces infections and the probability of influenza spread, seasons in which the vaccine is more effective should weaken the link between air pollution and influenza ( ). our analysis utilizes patient level data on inpatient hospitalization ( ), which allows us to focus on severe cases specifically limited to influenza (for details on data, descriptives, and empirical methods see supplementary appendix s. , s. and s. ). our principal outcome of interest is the number of inpatient ad-missions per county-month where the primary diagnosis is influenza according to the international classification of diseases (icd) ( ). we combine this with high frequency air pollution readings of local ground monitors across the u.s., as well as data on local temperature, specific humidity, precipitation and wind speed ( ). the richness of our data allows us to control for a wide variety of both regional and temporal controls. our preferred specification includes county-by-year and month-byyear fixed effects. county-by-year effects control for differences in unobserved characteristics such as demographics, socio-economic factors, and health care access and protocols that influence pollution exposure and health outcomes across counties separately for each year. the month-by-year fixed effects control for general monthly and seasonal trends within each year in both influenza and pollution ( ). as our measure of pollution, we use the u.s. environmental protection agency's air quality index (aqi), which we aggregate to county-bymonth-by-year to match outcomes. the aqi is a measure of overall air quality based on the primary criteria pollutants specified in the clean air act. aggregation of pollutants means there are no real "units" for the measure. it is designed such that higher aqi values indicate worse air quality. to ensure we capture exposure to air pollution before diagnosis, we lag the aqi by one month. in all of our analyses, we focus on the influenza season (october to march). figure shows the seasonality of inpatient hospitalizations in our data (figure a) , which matches closely with general influenza-like illnesses reported by the centers for disease control and prevention (cdc) (figure b ). figure c shows the age distribution of hospital admissions, which has important implications for vaccine effectiveness, described in more detail below. figure a shows a clear positive correlation between air quality and count of influenza admissions in the raw data; higher aqi correlates with more influenza admissions ( ). figure b shows the correlation after adjusting both variables for fixed effects and weather controls. after this adjustment, a strong, positive correlation remains. table shows estimates from poisson pseudo-maximum likelihood regressions given the count nature of the dependent variable. the coefficients represent the change in the expected log of inpatient admission counts, which approximates a percentage change in number of county-year-month admissions within our data ( ). column ( ) implies a -unit increase in the lagged monthly aqi results in a . % increase in inpatient influenza admissions. to put this estimate in national context, a one standard deviation increase in aqi ( . -unit increase in our data) amounts to approximately , additional inpatient hospitalizations for the -month influenza season in the u.s. ( ). column ( ) replaces our continuous measure of air quality with the count of days in a month with air quality the epa classifies as "unhealthy for sensitive groups" (aqi ≥ ). these days are rare: in our data, the average county has around . such days per month. an additional unhealthy air quality day raises admission counts by approximately %. continuing with our u.s.-wide calculation, an additional unhealthy air quality day in each county generates , additional inpatient hospitalizations per influenza season. we next interact our air quality measure with a measure of influenza vaccine effectiveness. every year, the cdc reports results from small-scale studies of that season's influenza vaccine effectiveness rate by age group (see details in supplementary appendix s. ). based on the histogram in figure c , we use the vaccine effectiveness for the two age groups traditionally susceptible to health complications from influenza: children up to and adults and older. this group comprises % of inpatient hospitalization in our data. figure shows the regression-adjusted relationship between aqi and influenza admissions separately in seasons of low vaccine effectiveness and high vaccine effectiveness for the up to -year-old group and -year-and-older group, as determined by a median sample split ( ). for both age groups, the relationship between air quality and admissions rates flattens and effectively disappears in years of high vaccine effectiveness. columns ( ) and ( ) of table show a similar story using a more continuous measure of vaccine effectiveness. a vaccine effectiveness of % for the up to year-old group or % for the -yearand-older group nullifies the link between air pollution and influenza hospitalizations ( ). while our fixed effects can address many unobservable factors, there remain possible confounders in establishing a causal link between pollution exposure and influenza hospitalizations. air quality could trigger health problems in sensitive populations (e.g. asthmatics) who would then go to the hospital, where they might be observed to have influenza. for this reason, our analysis focused on patients whose primary diagnosis is influenza and ignore occurrences of influenza in secondary diagnoses. we also repeat our analysis using two alternative measures: patients where influenza is the only diagnosis and patients where any diagnosis is influenza. supplementary appendix s. shows that our results are robust to either of these alternatives. we perform various falsification tests by repeating our analysis using health outcomes that should not correlate with air quality and health: diabetes mellitus with complications; urinary tract infections; skull and face fractures; and osteoarthritis ( ). the result of a falsification test in column ( ), using the combined number of the above health outcomes, indicates a precise zero to the thousandth decimal place. we present estimates on each of these four falsification outcomes individually in supplementary appendix s. with similar results. supplementary appendix s. ex-plores heterogeneity and conducts further sensitivity analysis and robustness checks. our estimates are stable across gender and age groups. we find suggestively larger effects for blacks and hispanics, but the estimates are not statistically different from those for whites. we show robustness to (i) different weather controls, (ii) additional fixed effects, (iii) multilevel clustering of standard errors, (iv) different winsorization and interpolation of the raw aqi data, (v) including out-state patients at hospitals, (vi) focusing on states with a long time series only, (vii) using missing values instead of zeros for county-months with no hospital admissions, and (viii) using a linear ordinary least squares instead of a poisson pseudo-maximum likelihood estimator. we also show the effect of air pollution on outpatient hospitalization is larger than for inpatient hospitalizations, consistent with the notion that emergency department encounters are more frequent (but also less severe) than those requiring admission to the hospital. as a final consideration, we shift from additional influenza cases to an economic endpoint. column ( ) of table shows ordinary least squares estimate of the effect of aqi on hospitaliza- tion charges for influenza admissions. this suggests a one-unit increase in aqi increases hospital billing by approximately $ , per month in the average county during influenza season. across the u.s., a one standard deviation increase in aqi ( . -unit increase) generates an additional $ . billion inpatient hospital charges per influenza season. using a rich longitudinal dataset, we provide causal evidence that air pollution increases hospitalization rates for seasonal influenza. our findings offer novel evidence important for policy making, highlighting the heightened importance of increasing vaccination rates in polluted urban centers ( ). this is especially important in developing countries, which house the most polluted cities in the world and have very low baseline vaccination rates ( ). they also imply pollution controls can provide an important hedge against antigenic drift or shift in the influenza virus that renders the vaccine significantly less effective in some years, helping reduce global medical spending, avoid lost productivity, and reduce loss of human life. if our results generalize to other respiratory viral infections, they will significantly understate the infectiousdisease related benefits from environmental protection ( ). they may also provide important insights for the ongoing fight against the covid- pandemic ( ). social distancing and large scale reductions in economic activity aimed at reducing viral spread have also reduced air pollution ( ), which may be helping reduce the impacts of the disease. as countries relax restrictions and economic activity resumes, they may choose to reduce environmental regulations in exchange for a more rapid return to economic growth: the u.s. epa recently announced plans to suspend enforcement of environmental laws during the pandemic ( ). our results suggest there could be additional disease-related social costs to consider when worsening air quality during the economic recovery. [ ] a. i. barreca, j. p. shimshack, absolute humidity, temperature, and influenza mortality: years of county-level evidence from the united states. american journal of epidemiology , s ( ). [ ] a separate literature shows air pollution has mortality effects through and on top of concurrent influenza episodes ( , , ). [ ] g. diamond, d. legarda, l. k. ryan, the innate immune response of the respiratory epithelium. immunological reviews , ( ). [ [ ] for our baseline results we count patients whose primary disease icd code is influenza, but show robustness to alternative definitions. that is we exclude, for example, patients with bacteria related pneumonia or other respiratory diseases as their primary diagnosis. [ ] we include weather controls to address the link between both influenza and weather (temperature and humidity can both influence influenza transmission rates) and weather and pollution (different climatic conditions can lead to different levels of air quality, all else held constant). [ ] in models where we interact vaccine effectiveness, we control for county-by-influenza season effects since vaccine effectiveness varies by season. the baseline model is robust to controlling for countyby-influenza season fixed effects (see supplementary appendix s. ). [ ] this relationship can be spuriously driven by external factors that affect both pollution levels and admission rates. for example, more populated counties typically have higher pollution levels and (mechanically) higher hospital admissions. seasonality can also be a factor, as particulate matter and carbon monoxide, two common lung irritants included in the aqi, peak in winter months just as influenza admissions. our set of fixed effects can address both of these issues. [ ] we cluster all standard errors at the county level and provide further robustness checks in supplementary appendix s. . [ ] we multiply the . -unit increase by . , by the average inpatient admissions per countymonth ( . ), the total number of us county equivalents according to the us census bureau ( ) ( ) and by the months within a influenza season. since reporting is voluntary, our hospital data are not exhaustive. if reporting behavior does not correlate with the likelihood of influenza infections, the . % relative increase in admissions should not be affected. however, the translation into absolute admissions is likely underestimated. [ ] for the up to -year-olds median vaccine effectiveness is % and for the over -year-olds the median is %. [ ] vaccine effectiveness during our study period ranges from - % for those up to and - % for those and older. [ ] these four diseases are a random selection of disease groups we think are unlikely to be correlated with air pollution, and also occur a sufficient number of times in the hospitalization data. see the supplementary appendix s. and s. for details on icd codes, estimation and results. [ ] in a study of the spanish flu in , ( ) show cities with higher coal-fired power generating capacity saw higher mortality rates, potentially through exposure to higher air pollution aggravating either of these vectors. our data allows us to more narrowly investigate this link by directly assessing the impact of air pollution readings on influenza diagnosed hospitalizations across the u.s. during the modern pollution control era. [ ] c. tables s. to s. all rights reserved. no reuse allowed without permission. author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/ . / . . . doi: medrxiv preprint hospitalization data: we use hospital admission data from the healthcare cost and utilization project (hcup) and focus on the inpatient data from hospital stays ( ). we exploit patient level information on diagnosed diseases per international classification of diseases (icd) codes, patient zip codes, admission months, age, gender, race as well as hospital charges. the data are available for a subset of u.s. states and years from (see table s . ). we convert monetary hospital charges to common us$ using a gdp deflator from the world bank ( ) . to identify influenza hospitalizations, we count patients whose primary diagnosis is a strain of influenza. we use the clinical classifications software (ccs) from the agency for healthcare research and quality (ahrq) to classify relevant influenza icd codes. these are the following icd- -cm codes: , , , , , , , , , , , , , , ; and, for the period from october when the system was changed to icd- -cm, the following icd- -cm codes: j x , j x , j x , j x , j , j , j , j , j , j , j , j , j , j , j , j , j , j , j , j , j . we exclude patients whose primary diagnosis is not influenza, even if influenza is included among secondary diagnoses. counting primary influenza diagnoses reflects a middle ground between two extreme alternatives for which we perform robustness checks. in one robustness check, we count patients who have any (primary or secondary) influenza diagnosis. in another robustness check we only count patients for whom influenza is their only diagnosis. we exclude patients whose zip code is from a different state than the hospital in which they are treated. hospitalization data are available at the patient zip code-by-month level, which we aggregate to the county-by-month level. we assign a zero value for admissions to counties in the months with no reported influenza admission. we only do this for counties and months in states that report data in the given year. during the influenza season from october to march, % of county-months have no influenza related hospital admissions in the hcup data. our results are robust with and without using the zero valued county-months in our estimations. in four falsification tests, we use outcomes less likely to be affected by air quality: primary icd codes associated with (i) diabetes mellitus with complications, (ii) urinary tract infections, (iii) skull and face fractures, and (iv) osteoarthritis. we use the categories and icd codes from the clinical classifications software (ccs) from the agency for healthcare research and quality (ahrq). see section s. . for details. for a further robustness check, we use outpatient data from emergency departments ( ) instead of the inpatient data, with the same strategy of counting influenza patients as above. to measure air quality, we use the epa air quality index (aqi), which measures air quality derived from ground monitors ( ) . the aqi captures pollution from particulate matter (pm . ), sulfur dioxide (so ), carbon monoxide (co), nitrogen dioxide (no ) and ozone (o ). further details on aqi calculation are provided by the epa ( ). we use the daily, county level, pre-aggregated data and further aggregate up to the county-by-month level. for missing county-months, we take the average value of the adjacent counties in the same month. we use the average value of the aqi within a month as well as the number of days with air at least "unhealthy for sensitive groups" according to the epa (aqi≥ ). we winsorize the aqi at the top and bottom % for the main analysis and show robust results without winsorization. for our analysis, we take the one month lagged aqi to identify exposure to air pollution before influenza diagnosis and not afterwards. we use pre-aggregated monthly weather averages from ( , ) , including temper- all rights reserved. no reuse allowed without permission. author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/ . / . . . doi: medrxiv preprint ature, specific humidity, wind speed, and precipitation, and aggregate grid points up to the county-bymonth level. we use data on the timing of national influenza-like illnesses from the cdc ( ) to identify the main influenza months: october through march (see figure b ). this coincides with the reported influenza season in various cdc publications. we restrict our main analysis to this influenza season. vaccine effectiveness: we use the estimated vaccine effectiveness, for different age groups, by influenza season, from the cdc ( ) . underlying cited studies are available from / . since vaccine effectiveness can vary across age groups during the same influenza season, we use the reported effectiveness of the two age groups most relevant for our study: children up to years old and for people years and older. figure c shows these are the main age groups observed in the hcup inpatient data with primary influenza diagnoses. we use the categories from the clinical classifications software (ccs) from the agency for healthcare research and quality (ahrq) to identify the relevant icd codes. e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e x , e x , e x , e x , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e x , e x , e x , e x , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e x , e x , e x , e x , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e x , e x , e x , e x , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e , e . , , , , , , , , , , , , , , , , , , , , , , , , , ; all rights reserved. no reuse allowed without permission. author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/ . / . . . doi: medrxiv preprint table s . contains states and years with available admission months and patient zip codes in the inpatient hospitalization data we use. table s. contains summary statistics for inpatient hospital admissions with a primary influenza diagnosis, average monthly aqi per county-month, and the number of days with aqi ≥ . we use the standard deviation of the aqi during the influenza season ( . ) as well as the average inpatient hospitalization numbers ( . ) for the calculation of absolute effects based on our poisson pseudo-maximum likelihood estimation. arizona arizona , arizona , arizona , arizona , arizona , arizona , arizona , arizona , arizona , arizona , arizona , arizona , arizona , arizona , arizona , arizona , arizona , arizona , arizona , arizona , arizona , arizona , arizona , arizona , , , , , , , , , , , , , , , , , , , , , , , , new york , , , , , , , , , , , , , , , , , , , , , oregon , , south dakota utah vermont washington , , , , , , , , , , , , , , , , , , , wisconsin , notes: the table shows the states and years used in the main analysis. we estimate the relationship between influenza-related inpatient hospitalizations h cym and the lagged air quality index aqi cym− at the county c by calendar month m by year y level using a poisson model: h cym = exp(βaqi cym− + x cym δ + γ cy + µ ym + cym ). we include county-by-year fixed effects γ cy to control for changing factors such as population size, income, demography and influenza testing procedures across counties and time. this also captures all rights reserved. no reuse allowed without permission. author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint (which was not peer-reviewed) is the . unobserved annual shocks at the county level that affect both air pollution and hospitalizations. calendar month-by-year fixed effects µ ym control for a flexible overall time trend. results are robust to including additional fixed effects such as state-by-calendar month or county-by-influenza season fixed effects. while county-by-year fixed effects capture the bulk of climatic differences across counties, we also control for within-year differences with a vector of weather control variables x cym . this includes temperature, specific humidity, precipitation, and wind speed in various combinations. temperature and humidity has been shown to affect both virus survival (see ( , , , , ) and air pollution ( , , ) . in our baseline we include three temperature (c) bins (< , ≥ & < and > ), five bins based on the quintiles of specific humidity, and linear terms for precipitation and wind speed. we lag the aqi by one month to account for hospital admissions data at the monthly level. the goal is to capture pollution exposure prior to the influenza diagnosis, not after. in principle, air pollution could also affect patient progression after diagnosis, but we focus on the effect of pollution leading up to the diagnosis. we estimate the model with a pseudo-maximum likelihood estimator ( , ) , which performs well with a large number of zeros and is consistent with over-or under-dispersion in the data ( ) . we cluster standard errors at the county level to allow for arbitrary heteroskedasticity and serial correlation in the errors, and show robustness to two-way clustering at the added state-year level. table s . provides falsification tests with outcomes unlikely to be correlated with air pollution. column repeats our baseline results for influenza patients. the next four columns use inpatient hospitalizations with a primary diagnosis of diabetes mellitus with complications, urinary tract infections, skull and face fractures, and osteoarthritis. coefficients and standard errors indicate a precise zero effect for these outcomes. table s . explores heterogeneous effects by age, gender and race. estimates across different groups are statistically indistinguishable from one another, however, the point estimates for blacks and especially hispanics are larger than for whites. table s . explores robustness of our main results to different controls, fixed effects, and standard error calculations. column ( ) replicates the baseline results, and reports the estimates for our weather controls (reporting was suppressed in the manuscript for simplicity). temperature and humidity controls are included as dummies for separate bins. while the coefficients on temperature are not statistically significant (county-year fixed effects absorb much of the large-scale variation), the sign is as expected. temperatures below zero c as well as above c lead to fewer observed hospitalizations (see also ( , ) ). humidity decreases hospitalizations consistent with ( , , , ) , while precipitation and wind speed have no statistically or economically significant effects. in column ( ) of table s . , we drop weather controls, and in column ( ) we include alternative functional forms of the weather controls using second order polynomials in temperature and humidity with a full set of interactions. in columns ( ) and ( ) we include county-by-influenza season (oct -mar) fixed effects and state-by-month of the year fixed effects. columns ( ) and ( ) replicate ( ) and ( ), but cluster standard errors on the county level as well as on the state-by-year level to allow additional arbitrary spatial correlation of errors across counties within a state-year. table s. reports from further robustness checks. column ( ) replicates the baseline results. column ( ) does not winsorize the aqi data. column ( ) drops county-month cells with missing aqi all rights reserved. no reuse allowed without permission. author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint (which was not peer-reviewed) is the . measures (rather than interpolating them based on the average value of the adjacent counties). column ( ) includes patients whose zip code is from a different state than the hospital in which they are treated. column ( ) restricts to states with at least seven years of reported data: arizona, colorado, kentucky, massachusetts, new jersey, new york, and washington. column ( ) drops county-months with no reported influenza admissions (rather than assigning a zero value for admissions). column ( ) contains results from an ordinarily least square (ols) regression instead of a poisson pseudo-maximum likelihood regression. columns ( ) and ( ) use alternative assumptions on who to count as an influenza patient. our baseline only counts patients whose primary diagnosis is influenza. column ( ) counts patients where all diagnoses are influenza, i.e., there are no other diagnosed conditions. column ( ) counts all patients with any influenza diagnosis, primary or non-primary. columns ( ) and ( ) use the data on outpatient (instead of inpatient) hospitalizations as the outcome variable. the effect of aqi is slightly larger on outpatient hospitalizations, consistent with the notion that these are less severe but more frequent than inpatient hospitalizations. all rights reserved. no reuse allowed without permission. author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/ . / . . . doi: medrxiv preprint the dependent variable is the count of hospital admissions with diagnosed influenza within a county and month. we include only the influenza intensive months of october through march. the results are from a poisson pseudo-maximum likelihood regression with specified fixed effects and control variables, except the last column ( ), which is an ols regression. the number of included observations can vary across different outcomes due to fixed effects and varied counts in each county-month cell. temperature controls consist of three separate bins, specific humidity controls consist of five separate bins, precipitation and wind speed are linear terms. all weather variables are based on the monthly county averages. a higher aqi means worse air quality. standard errors in parentheses are clustered at the county level. all rights reserved. no reuse allowed without permission. author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/ . / . . . doi: medrxiv preprint influenza vaccines for the future estimates of global seasonal influenza-associated respiratory mortality: a modelling study epidemic influenza and vitamin d on the epidemiology of influenza influenza virus transmission is dependent on relative humidity and temperature absolute humidity modulates influenza survival, transmission, and seasonality absolute humidity and the seasonal onset of influenza in the continental united states air pollution and case fatality of sars in the people's republic of china: an ecologic study world bank emergency department databases (sedd) (healthcare cost and utilization project, agency for healthcare research and quality air quality system data mart (us environmental protection agency technical assistance document for the reporting of daily air quality (united states environmental protection agency continental-scale water and energy flux analysis and validation for the north american land data assimilation system project phase (nldas- ): . intercomparison and application of model products nldas primary forcing data l monthly . x . degree v (goddard earth sciences data and information services center (ges disc) cdc, seasonal flu vaccine effectiveness studies (centers for disease control and prevention, national center for immunization and respiratory diseases (ncird) airborne micro-organisms: survival tests with four viruses pseudo maximum likelihood methods: applications to poisson models ppmlhdfe: fast poisson estimation with high-dimensional fixed effects the log of gravity skull and face fractures icd- -cm codes: skull and face fractures icd- -cm codes: s xxa osteoarthritis icd- -cm codes we thank luisa osang and jeffrey shaman for helpful discussions. all errors are our own. the irb for access to the hcup data through the national bureau of economic research (nber) was approved by the nber. funding: no specific grants were connected to this project. author contributions: gs, jgz, mn and ns conceptualized the study, gs analyzed the data, and gs, jgz, mn and ns wrote the manuscript. competing interests: the authors declare no competing interests. data and materials availability: the replication code and materials for both the manuscript and the supplementary materials will be made publicly available at harvard dataverse. the restricted access data can be accessed at ( ). notes: the dependent variable is the count of hospital admissions with diagnosed influenza within a county-month. we include only the influenza intensive months of october through march. results are from a poisson pseudo-maximum likelihood regression with specified fixed effects and control variables. the number of included observations can vary across different outcomes due to fixed effects and varied counts in each countymonth cell. a higher aqi means worse air quality. standard errors in parentheses are one-way or two-way clustered as indicated. key: cord- -ra njvcz authors: kumar, sanjay; lee, heow pueh title: the perspective of fluid flow behavior of respiratory droplets and aerosols through the facemasks in context of sars-cov- date: - - journal: nan doi: nan sha: doc_id: cord_uid: ra njvcz in the unfortunate event of current ongoing pandemic covid- , where vaccination development is still at the initial stage, several preventive control measures such as social distancing, hand-hygiene, and personal protective equipment have been recommended by health professionals and organizations. among them, the safe wearing of facemasks has played a vital role in reducing the likelihood and severity of infectious respiratory disease transmission. the reported research in facemasks has covered many of their material types, fabrication techniques, mechanism characterization, and application aspects. however, in more recent times, the focus has shifted towards the theoretical investigations of fluid flow mechanisms involved in the virus-laden particles prevention by facemasks. this exciting research domain aims to address the complex fluid transport that led to designing a facemask with a better performance. this review paper discusses the recent updates on fluid flow dynamics through the facemasks. key design aspects such as thermal comfort and flow resistance are discussed. furthermore, the recent progress in the investigations on the efficacy of facemasks for prevention of covid spread and the impact of wearing facemasks are presented. finally, the potential research directions for analyzing the fluid flow behavior are highlighted. the person-to-person transmission of infectious respiratory diseases occurs primarily due to the transportation of virus-laden fluid particles from the infected person. the contagious fluid particles originate from the respiratory tract of the person and are expelled from the nose and the mouth during breathing, talking, singing, sneezing, and coughing. [ ] [ ] [ ] these particles have been broadly classified into two types: aerosols (aerodynamic particle size < µm) and droplets (aerodynamic particle size ≥ µm- µm). [ ] [ ] [ ] the finding indicated that the transmission phenomena of these expelled virus particles by patients would be dependent on droplet sizes. larger respiratory droplets, once expelled from the mouth or nose, undergo gravitational settling before evaporation; in contrast, the smaller droplets particles evaporate faster than they settle, subsequently forming of the aerosolized droplet nuclei that can be suspended in the air for prolonged periods and travel in air over long distances. the research studies have revealed that the severe acute respiratory syndrome (sars) epidemic in and the current global pandemic of coronavirus disease (covid- ) predominantly transmitted by contact or through the airborne route. [ ] [ ] [ ] [ ] several preventive strategies such as safe distancing, contact tracing, isolation of the infected person, hand hygiene, and facemasks have been widely employed against the rapid spread of these diseases. [ ] [ ] [ ] [ ] among them, the use of the facemasks have proven to be one of the most effective protective measures against the airborne virus transmission. [ ] [ ] [ ] [ ] [ ] [ ] the research suggested that face coverings could essentially reduce the forward distance traveled by a virus-laden droplet, and thus has a great potential to provide personal protection against airborne infection. , recently, the world health organization who has recommended using facemasks for initial control of covid- spread. in general, facemasks fall in the category of respiratory protection equipment (rpe) whose primary function is to protect the wearer from airborne viruses and contaminated fluids. there are various rpe types, ranging from simple homemade reusable cloth-based masks to surgical facemasks and n respirators to self-contained breathing apparatus. , [ ] [ ] [ ] [ ] different types of masks provide different levels of protection to the wearer. surgical facemasks are loose-fitting, fluid-resistant, single-time use, and disposable, designed to cover the mouth and nose. these masks are fluid resistant and intended for reducing the emission of large respiratory droplets released during coughing and sneezing. , however, there is a possibility of leakage around these facemask's edge during the inhaling and exhaling process. such a dynamic leakage allows the direct contact of fluid droplets from the outside air to the wearer and vice-versa. such respiratory masks may also not provide adequate protection against extremely fine aerosolized particles, droplets, and nuclei. for efficient trapping of droplets, the facemask filters should contain microscopic pores; however, the minute-sized pores prevent air ventilation, which creates an uncomfortable situation for the wearer. hence, a better tradeoff between the pore sizes and the breathability is desirable for the suitable facemasks. some mask types come with inbuilt respirators such as filtering facepiece respirator, p respirator/gas mask, self-contained breathing apparatus, full face respirator, and kn respirators provide better breathability of the users. the name designation 'n ' in the n respirators refers to the filtration of . μm sized particles with % efficiency. the filtration mechanism of n facemasks operates on three possible principles: diffusion, inertial impaction, and electrostatic attraction. the smaller particles (< micron) usually get diffused and stuck on the filter's fibrous layers. whereas particles of typically micron or larger realize the inertia effect, preventing them from flowing across the fibers in the filtration layers slam into the mask layers and filtered. n masks are designed for single-use because of potential contamination of filter layers, resulting in rapid degradation of their filtration efficiency. however, several innovative techniques have been demonstrated for decontaminating and reusing n masks. , some recent n respirator masks are fabricated using the electrocharged polymers or electrospun nanofibers. , these materials have intrinsic electrostatic properties to attract the small-tolarge oppositely charged particles, which help in better filtration of small-size particle transmission. , because of the ongoing covid- pandemic, a significant demand for facemasks has been reported worldwide, while stimulating research about their efficacy for filtering expelled droplets from the mouth and nose of the infected person. in this regard, considerable efforts have been made in the past for the evaluation of facemasks performance. the quantitative performance of the facemasks has been typically characterized by evaluating the filtration efficiency (fe) and the total inward leakage (til). [ ] [ ] [ ] [ ] the filtration efficiency refers to the percentage of blocked particles by the tightly-fitted facemasks. the filtration efficiency can be calculated as = ( − ( ⁄ )) × %, where , are the particle count in the upstream feed prior to filtration and in the downstream filtrate, respectively. til is defined as the percentage of particles entering the mask through both the filter and the leakage between mask and face. the total inward leakage is calculated by dividing the particle concentrations on the outside and inside the facemasks. the protection factor of the facemasks can be determined from the expression; pf = /til. higher pf value of the masks perform better in virus transmission control. furthermore, the fluid penetration resistance performance of the facemasks have been evaluated as per the astm f /f m - standards. , however, this test method does not evaluate facemasks' performance for airborne exposure pathways or in the prevention of the penetration of aerosolized fluids deposited on the facemask. in recent times, some qualitative analysis has been demonstrated for the rapid design characterization of facemasks. while these experimental studies are essential for the broad characterization and design evaluation of respiratory facemasks, further theoretical and numerical methods and algorithm-based investigations provide a better insight into the facemask's fluid flow dynamics and the droplet leakage through the facemask openings. if the facemask is donned for a prolonged period, the captured fluid vapor on the filter surface may reduce the filtration efficiency. this saturation effect of the facemasks has been usually neglected in the experimental studies. to involve these factors, an alternative approach, the computational fluid dynamics (cfd) method, can be invaluable for understanding the fluid-particle flow behavior through the facemasks. the fluid dynamics based numerical techniques have gained momentum in the field of the facemask research domain. the computational fluid flow models have shown their potentials in an improved prediction of the spreading of respiratory virus-laden droplets and aerosols, sensitive to the ambient environment, and crucial to the public health responses. this review paper focuses on the fluid flow aspects of the facemasks and their efficacy in virus transmission control. following a brief introduction to the respiratory infectious diseases and their control strategies (section i), the respiratory droplet transportation mechanisms in conjunction with the possible governing equations required for estimating the transport phenomena have been presented in section ii. then, the droplet transport behavior through the facemasks has been described in section iii. key design aspects for the facemasks have been explained in section iv. section v covered the recent progress in investigating the efficacy of facemasks for preventing virus spread. the impact of using the facemasks have been discussed in section vi. the concluding remarks and a brief outlook for future research directions are summarized in section vii. during the sneezing or coughing process, the dispersion of saliva droplets or aerosols from the mouth to the ambient, and eventually on the floor accomplish in several stages. the complete transmission cycle involves complex flow phenomena, ranging from air-mucous interaction, breaking of droplets, turbulent conical jets, droplet evaporation and deposition, flow-induced particle dispersion, and sedimentation. after exhalation from the mouth or nose, the saliva droplet movement is initially led by the inertia force, followed by the formation of a conical jet (vortical flow) near the mouth. once the droplets are expelled from the mouth, the inertia force gradually decreases, and other forces like gravity control the dispersion of larger size droplets, while drag and brownian forces control the smaller size droplets. after traveling up to a particular distance, these virus-laden droplets settle down on the floor. thus, there are two major possible pathways for the respiratory virus transmission: airborne inhalation of smaller droplets, which are suspended in ambient air for a more extended period and carrying to the longer distance, and contact (direct or indirect between people and with contaminated surfaces) of large size droplets. the fluid flow behavior of these droplets has been modeled using two different phases: continuous phase for the small size droplet nuclei and discrete phase for large size droplets. the fluid flow is governed by the navier-stokes and mass transfer equations which are as follows. continuity: momentum: where , , ⃗ , , , denotes the density ( − ), time ( ), flow velocity ( − ), pressure ( ), diffusion coefficient and kinetic viscosity, respectively. the conservation laws can be written in tensor form as: here, ⃗ represents the flow velocity (m/s) and is the source term that represents other forces such as gravity, lorentz force, etc. which also leads to momentum accumulation. for the newtonian fluids, there is a linear relationship between shear stress and velocity gradient. so, the viscous stress tensor can be defined by: in the overall vector form of the constitutive equation, where t denotes the transpose of the second velocity gradient outer product. for a newtonian fluid with constant µ and ρ, the momentum equation can be rewritten as: also, the fluctuation velocity component for the laminar-to-turbulent airflow field can be predicted by the reynolds-averaged navier-stokes equations (rans) model. where are the damping factors to reflect the anisotropic magnitude of the fluctuation velocity in the near-wall region. these are the random numbers from the standard normal distribution. the cough spreading phenomena can be predicted by solving the diffusion equation ( ) in conjunction with some source and sink terms. vuorinen et al. developed diffusion-based monte-carlo models to realize a transmission phenomenon via inhalation of aerosols in the ambient flow field. the source and sink terms have been included in conjunction with eqn. ( ) . the source term represented the transient location of the infected persons while the sink term has been used for the ventilation surface. the developed models were capable of predicting the aerosol dispersions at more realistic locations like generic public place and supermarkets where cough may release from the walking person. for the droplets with the high droplet-to-air density ratio, the droplet trajectories have been predicted by solving a series of translation equations (lagrangian approach) of the discrete phase with the assumptions of stationary droplets and limited thermophoresis. continuous dispersion of saliva droplets throughout the computational domain has been considered in the computations. also, some basic parameters like velocity, mass, and position of each droplet have been computed at every time step. the translational equation for the saliva micro-droplet trajectory is given by, where , , , are the stokes drag force, gravity, lift or buoyancy force, and brownian motioninduced force, respectively. also, , , , , ⃗ are the mass, radius, volume, density, and velocity vector of the saliva droplets, respectively. , ⃗ are the fluid density and the fluid velocity vector, respectively. the drag coefficient values depend on the droplet's reynolds number and can be calculated from, here, = |⃗ ⃗ −⃗ ⃗ | . in above expressions, the droplet distribution is an important factor as their size decides the travel path distance, and eventually the infection risk. so, for coughing simulation the droplet breakup approach is used. pendar and páscoa used rosin-rammler breakup approach in their coughing simulation work which is expressed as: where and are the exponential factors and average radius of the droplet, respectively. these parameters are based on the saliva flow rate. recently, several studies have attempted to understand the dynamics of droplet formation and transport. cummins et al. investigated the dispersion of spherical droplets in the presence of a sourcesink pair flow field. the maxey-riley equation was used to describe the finite-sized spherical particle motion in an ambient fluid flow. the presented non-dimensional mathematical models were based on the newton's second law of motion in which the forces acting on the particle involved the gravity force, the drag force, an added mass force, the force due to the undisturbed flow, and a basset-boussinesq history term. the analytical results suggested that droplets with a smaller size (< μm) moved a greater distance because of gravity's smaller impact. in comparison, the larger size droplets (> μm) traveled a relatively long distance before getting pulled into the sink by their more considerable inertia. however, the dispersion of intermediate size droplets ( μm - μm) was found to be complicated under the influence of both drag and gravity forces. busco et al. used the computational fluid dynamics approach to predict droplets and aerosols spread. the biomechanics of a human sneeze, including complex muscle contractions and relaxations, were included in the simulation by imposing a momentum source term to the coupled eulerian-lagrangian momentum equations ( ) . the instantaneous magnitude of the sneezing momentum source term has been defined as | ( )| = ( )⁄ , where p(t) is the experimental pressure signal, and l is the characteristic equivalent length of the human upper-respiratory system ducts. the experimental results validated the developed model for the estimation of droplets and aerosols spreads. das et al. investigated the airborne virus transmission through sneezed and coughed droplets and aerosols. the ejected droplet motions were estimated both for still and flowing air conditions by solving the langevin differential equation using monte-carlo numerical method. the langevin equations for the transport of the droplets of mass (m) in the still air is given as, and are the coordinate and velocity shift in each discrete time step , respectively, and stands for the cartesian components of the position and velocity vectors. the first term in the righthand side of eq.( ) represents the dissipative force. the second term stands for the diffusive (stochastic) force where ξ(t) that is regulated by the diffusion coefficient d. is the gravitation force term acting on a droplet of mass m. in the expression, the value of the drag coefficients is obtained using the stokes formula, = , here is the droplet radius and is viscosity. the diffusion coefficient d is obtained from the einstein relation, = , where = . × − ⁄ is the boltzmann constant and t is the temperature in kelvin. as shown, the langevin differential equations contain a stochastic source term (diffusive force), which is usually ignored in the eulerian-lagrangian approach. also, environmental factors such as temperature, humidity, and airflow rate, which could influence the air droplet dynamics, were included. the results revealed that the small droplets travel a larger distance and remain suspended in the air for a longer time under the influence of airflow, supporting the mandatory use of facemasks to prevent the virus. vadivukkarasan et al. experimentally investigated the breakup morphology of expelled respiratory liquid. it was revealed that the droplet formation from the ejected fluid during coughing or sneezing occurred due to three possible mechanisms: kelvin-helmholtz (k-h) instability, rayleigh-taylor (r-t) instability, and plateau-rayleigh (p-r) instability in sequence. the flapping of the expelled liquid sheet was the result of the k-h mechanism, and the ligaments formed on the edge of the rim appeared due to the r-t mechanism, and finally, the hanging droplet fragmentation was the result of the p-r instability. droplet evaporation is one of the crucial factors that affect transmission phenomena. the evaporation rate of the droplets depends on the difference between the saturated vapor pressure of the fluid droplet surface and the vapor pressure of the surrounding air (ambient temperature and humidity). the other factors, such as the mass-diffusion coefficient and the relative velocity between the droplet and surrounding gas, influence the evaporation rate. the non-dimensional parameters such as reynolds, nusselt, and sherwood numbers govern the droplet evaporation phenomena. moreover, the condensation and evaporation effects between the ambient water vapors and the water liquid in cough droplets can be considered by solving the mass and energy balance for each droplet. mass balance: energy balance: where is the average mass flux of evaporable component on the surface that can be expressed as: where is the density of the ambient air, , and ,∞ are the mass fractions of evaporable component on the droplet surface and in the gas phase far from the droplets, respectively. ℎ is the sherwood number. several other researchers have studied the flow behavior of evaporating droplets. recently, weiss et al. investigated the clustering and evaporation of droplets using the gas phase and droplet coupling equations. the evaporation of droplets and spreading of vapors into the ambient condition were mostly governed by few parameters: the reynolds number, which is related to the shear rate, the stokes number, and the mass loading, which is the ratio between the mass of the liquid to the gas phase. the results suggested that the clustering and evaporation of droplets are primarily affected by the mass loading and stokes number while the taylor-scale reynolds number was small. when the mass loadings decreased, and the stokes number increased, the droplets dispersed more evenly with a faster evaporation rate. chaudhuri et al. presented a chemical reaction mechanism based collision rate model for prediction of the growth rate of the infected population for the early phases of a covid- like pandemic. besides, they developed a theoretical model for the aerodynamics of respiratory droplets by considering the evaporation characteristics of levitated droplets. the evolution of the droplets was characterized by a complex interaction of aerodynamics, evaporation thermodynamics, and crystallization kinetics. the fidelity of proposed model was further confirmed by the experimentation. respiratory droplet transmission is considered critical for the rapid spread and continued circulation of viruses in humans. in recent years, the respiratory droplets flow behavior through the facemasks has typically well-predicted using the computational fluid dynamics (cfd) techniques. the navier-stokes equations have been used as basic governing equations to solve the velocity field in a multi-dimensional computational domain. these equations have been used for the analytical assessment of the respiratory performance of the facemasks and other respirators. dbouk and drikakis performed the fluid dynamics analysis of the respiratory droplets transmission through and around a facemask filter. the compressible reynolds-averaged navier-stokes equations and the k-ω turbulence model were employed. zhang etl. analytically investigated the carbon dioxide co transportation performance inside the ventilator mask. the d model of the ventilator mask is shown in fig. a. classical navier-stokes theorem and masstransport equations were used to estimate the co residual concentrations below the nostrils. the governing equations were solved using the finite element solver ansys fluent . software. the following governing equations were used in the simulation; (i) at the entrance of the ventilator mask, the inlet pressure = . × , the average concentration of co = . %. (ii) at the exhaust holes: outlet pressure = , (iii) inlet boundary condition at the nostrils: the averaged velocity = × sin ( ), expiratory phase time t = ~ . s, inspiratory phase time t = . ~ . s, and the averaged concentration of co excreted from the nostrils was set as %. the airflow inside the ventilator mask was considered to be turbulent flow. fig. b shows the distribution of the average residual co concentration inside the ventilator mask varying with time during a complete respiratory cycle. as shown from the curve, initially, the co concentration increased with the increasing exhaled air and reaches the peak value of . %, and then it declined gradually with the decrease of the exhaled air and reaches down to the value of . % at the end time of expiratory cycle. based on these results, the ventilator mask was redesigned by changing the exhaust hole to the bottom side and the local residual co concentration was decrease to . %. bates et al. performed computational fluid dynamics simulations to access the respiratory airflow in the human upper oral airway with airway wall movement. the breathing flow rate data was acquired by imaging the breathing cycle of the participant while wearing of a size- anesthesia facemask (fig. c) . the air pressure drop and flow velocity were estimated by solving the navier-stokes equations for the moving mesh vertices in the finite volume domain. the governing equations for moving mesh of the finite volume form is given by: momentum equation: where is time, is the volume of each cell in the mesh, is the air density, ⃗ is the air flow rate, ⃗⃗⃗⃗ is the mesh velocity as calculated from the mesh displacement for each control points, is a vector representing the surface of each mesh cell, is the identity matrix, and is the viscous stress tensor. these equations were solved using the large eddy simulation (les) techniques. the instantaneous air flow resistance was calculated as the pressure loss between two locations divided by the air flow rate through them. fig. d shows the estimated airflow resistance through several different regions of the extra thoracic airway during the complete breathing cycle. the aerosol droplets transmission phenomena through the facemasks have also been investigated analytically. the facemask leakage factor has been considered in the analytical models. lei et al. predicted the fluid leakage between an n filtering facepiece respirator (ffr) and a headform using the computational fluid dynamics (cfd) simulation approach. the mass flow rate at the faceseal and through the filter medium was calculated under three different boundary conditions: varying breathing velocity, varying viscous resistance coefficients of the filter, and the freestream air flows. the filter-to-faceseal leakage (ftfl) ratio for the respirator was obtained by dividing the mass flow rate through the filter medium and the faceseal leakage. a higher ftfl ratio refers to the higher percentage of airflow passing through the filter medium than the faceseal leakage. the results revealed the nonlinear increase in the ftfl ratio with increasing breathing velocity values and decreasing the filter viscous resistance coefficient values. furthermore, the freestream flow had limited influence on the airflow inside the respirator resulting in nonsignificant variations on the ftfl ratio. perić et al. thermal comfort is an essential aspect of a facemask as it may affect the compliance of the use of facemask during summer or in tropical countries. there were reported incidence of skin rashes, increased heat stress, sweating, and discomfort due to prolonged wearing of a facemask in hot and humid conditions. to improve the thermal comfort level of facemasks, researchers have developed some unique facemasks by using the nanocomposites. polymer-based nanofibers with large surface area-to volume ratio have shown great potential for use in facemasks to achieve both high filtration efficiency and sufficient air permeability. . (a-c) show the schematic, photographs, and scanning electron micrographs of the proposed hybrid nanofiber-based facemask. the comparative pm capture efficiency and air permeability results have demonstrated the superiority of presented facemask over the commercial masks (fig. d, e) . moreover, the thermal image revealed that the fiber/nanope facemasks had high transparency to the human body radiation (cooling effect). in contrast, the commercial facemasks blocked a large portion of it. they further modified the nanope substrate with ag coating and demonstrated that fiber/ag/nanope had a warming effect. zhang et al. reported the use of an active ventilation fan to reduce the dead space temperature and co level. an infrared camera (irc) method was used to elucidate the temperature distribution on the prototype ffr's outside surface and the wearer's face, surface temperature was found to be lowered notably. both inside and outside temperature resulted from the simulation were found to be in good agreement with experimental results. however, the inward blowing fans may compromise the filtering effectiveness of the facemask. there are commercially available facemasks fitted with one-way valve for facilitating the removal of humidity and expired air within the space between the facemask and the face. however, during the covid- pandemic, one of the main reasons for wearing the mask is not only to protect the inhalation of virus, but also to prevent the spread of virus into the air if the wearer happens to be a carrier of the virus. if the wearer is a healthy subject, the use of a one-way valve and ventilation fan would indeed mitigate the buildup of humidity and carbon dioxide within the dead space. zhu et al. reported a three-dimensional model of normal human nasal cavity to simulate the volume of fraction of both fresh air and respired air within the nasal cavity. the model consisted of large rectangular domain outside the nasal cavity representing ambient air, human nasal cavity and partial of the pharynx. this was the first reported piece of work that modelled the details of nasal cavity instead of just the nostrils as openings for the flow simulations. the advantage for this simulation was that the flow field within the space between the nostrils and facemask could be more accurately simulated as the boundary condition could be specified away from the nostril at the pharyngeal area. two cases were simulated. case i refers to a human face with a n respirator onto human face, and case ii refers to a human face without a respirator. the results showed that above % of inspired air was respired air in case i compared to less than . % in case ii. during expiration, the volume of fraction (vof) of respired air in both cases was above %. the streamlines at peak inspiration were relatively smooth while entering the cavity in both cases; while at peak expiration large vortex was observed within the air space between human face and respirator in case i. for future studies, one could explore the in vivo experimental studies with the use of miniaturized and wireless sensors for monitoring not just the temperature, but also the humidity and carbon dioxide content within the space between the nostrils and the facemask. the sensors need to be small so as not to disrupt the flow fields. if a single sensor cannot be small enough for the measurement of all the three parameters, one may need to have separate sensors and repeat the experiment for the same human subject. another important parameter affecting the comfort of the wears is the flow resistance of the facemask. in principle, if the flow resistance is lower while maintaining the same filtering efficiency, the comfort level will be enhanced. however, the facemask's flow resistance is just an indicator and does not specify the wearer's breathing resistance. while the flow resistance could be measured using a typical setup for correlating the fluid flow rate to the pressure drop across the facemasks, the breathing resistance could only be measured using a human subject or a replica of the nasal pharyngeal system. lee and wang presented the pioneering work of measuring the nasal airflow resistance during inspiration and expiration using a standard rhinomanometry and nasal spirometry. a modified full-facemask was produced in-house to measure nasal resistance using n ( m ) respirators. the results showed a mean increment of % and % in inspiratory and expiratory flow resistances, respectively, with n respirators. there was also an average reduction of % in air exchange volume with the use of n respirators. the same group did a follow-up study investigating the change of human nasal functions after wearing an n respirator and surgical facemask. the human subject study involved healthy healthcare workers. each of the volunteers attended two sessions and wore an n respirator in session (s ) and surgical facemask in session (s ) for hours. the mean minimum cross-sectional area (mmca) of the two nasal airways via acoustic rhinometry and nasal resistance via rhinomanometry was measured before and immediately after the mask. the equipment could not perform in vivo measurement with the facemask on. rhinomanometry was repeated every minutes for . hours after the removal of masks. a questionnaire was distributed to each of the volunteers during the hours mask-wearing period to report subjective feelings on the discomfort level of breathing activity. among volunteers who completed both the two sessions, the mean nasal resistance immediately increased upon removing the surgical facemask and n respirator. the mean nasal resistance was significantly higher in s than s at . hours and . hours after removing the masks (p< . ). there was an increase of nasal resistance upon removal of the n respirator and surgical facemask, potentially due to nasal physiological changes. n respirator caused higher post-wearing nasal resistance than surgical facemask with different recovering routines. this was the first time that the effect of long duration wearing a facemask was objectively monitored. however, the during of three hours for the wearing of a facemask was deemed to be too short under the current covid- simulations, and human subject study for a longer duration of wearing facemask should be attempted. the research could also be enhanced using miniaturized pressure, temperature, humidity, and gas sensors for in vivo monitoring of the air condition within the space between the nostrils and the facemask. such experimental data would be useful for validating numerical models for assessing the comfort level for wearing different types of facemask. another potential approach is to develop a replica for replacing human subject for such long duration study, similar to the use of an acoustic head for replacing human subjects in the more extended duration noise exposure study. zhu et al. reported another investigations on effect of long duration wearing of n and surgical facemasks on upper airway functions. a total of volunteers of national university hospital singapore were participated for the study. each of the volunteers wore both n respirator and surgical facemask for hours on two different days. during the period of mask wearing, relative airflow rates were recorded. the study revealed that the increased level of discomfort to the user with time while wearing the masks. moreover, n respirator caused higher post-wearing nasal resistance than the surgical facemask with different recovering routines. the current studies recognized that the airborne transmission of aerosols produced by asymptomatic individuals during speaking and breathing as a key factor leading to the spread of infectious respiratory diseases such as covid . , [ ] [ ] [ ] however, the spread of these airborne diseases has been successfully controlled up to a certain extent by using the facemasks. , , , [ ] [ ] [ ] in the ongoing global pandemic of the covid , where vaccine developments still at a phase trial stage, the respiratory protective equipment such as facemasks has proven to be a complementary countermeasure against the spread of the novel coronavirus. in this regard, several researchers have performed theoretical and experimental investigations of virus transmissibility through the facemasks and alternatives. stutt et al. developed the holistic mathematical frameworks for assessing the potential impact of facemasks in covid pandemic management. the results revealed that professional and home-made facemasks were highly efficacious to reduce exposure to respiratory infections among the public. also, when people wear the facemasks alltime at the public places, the certain epidemiological threshold, known as the effective reproduction number, could be decreased below , leading to the prevention of epidemic spread. ngonghala et al. developed a parametric model for providing deeper insights into the transmission dynamics and control of covid- in a community. they used the covid data from new york state and the entire us to assess the population-level impact of the various intervention strategies. the results suggested that the consistent use of facemasks could significantly reduce the effective reproduction number. the highly efficacious facemask, like surgical masks with estimated efficacy of around %, could lead to the eradication of the pandemic if at least % of the residents use such masks in public consistently. the use of low efficacy masks, such as cloth masks with an estimated efficacy of %, could also lead to a significant reduction of covid- burden. yan et al. evaluated the effectiveness of different respiratory protective equipment in controlling infection rates in an influenza outbreak. they used a previously developed risk assessment model to show n respirators' efficacy, low-filtration surgical mask (adult), high-filtration surgical mask (adult), high filtration pediatric mask, and low filtration pediatric mask. the study revealed that donning these masks with a % compliance rate resulted in a significant reduction in transmission risk, and with % compliance rate nearly eradicated the influenza outbreak. prasanna simha and rao quantitatively investigated the distance of travel of typical human coughs with and without different masks: disposable three-ply surgical masks and n masks. in their study, the schlieren method, a highly sensitive, non-intrusive flow imagining technique, was used to visualize the human cough flow features. the experimental statistics showed that the propagation of a viscous vortex ring mainly governed cough flow behavior. while wearing regular face masks, the cough droplets traveled approximately half the distance traveled by expelled droplets without a mask. however, n was found to be most effective in limiting the spread of cough droplets. leung et al. performed experimental studies to investigate the efficacy of surgical facemasks to prevent respiratory virus shedding. the surgical facemasks' efficiency was measured against the coronavirus, influenza virus and rhinovirus of two broad particle sizes, respiratory droplets (≥ µm) and aerosols (droplet nuclei with aerodynamic diameter ≤ µm). the results indicated that surgical facemasks could efficaciously prevent transmission of human coronaviruses and influenza viruses into the environment in respiratory droplets, but no significant reduction in aerosols. moreover, the steep rise in demand for medical facemasks during the current pandemic covid has resulted in a subsequent breakdown of the global supply chain that led to an acute shortage in the market. to mitigate this discontinuous supply chain system, scientists have put much effort into exploring alternative fabrics with sufficient filtering capacity that are readily available and affordable. kähler and hain performed a detailed analysis of the efficacy of facemasks to prevent virus spread. in the first step, the transmission of droplets released by the mouth when breathing, speaking, and coughing was characterized. then, the filtering capacity of the various facemasks was analyzed. the experimental results have shown that most household materials tested do not provide much protection against the virus transmission via droplets and, therefore, unsuitable as materials for protective masks. however, filtering facepiece respirators (ffr) performance-based masks such as ffp (europe en - ), n (united states niosh- cfr ), ds (japan jmhlw-notification , ), and kn (china gb - ) offer adequate protection, as they are only permeable to a tiny fraction of few micron-sized droplets. konda et al. evaluated the filtration efficiency of various commonly available fabrics, including cotton, silk, chiffon, flannel, various synthetics, and their combinations, which were used in the fabrication of cloth masks. the filtration performance of these fabrics was conducted by generating the aerosol particles at the cloth sample's upstream side. the aerosol particulates ranging from ~ nm to ~ ten μm scale sizes, particularly relevant for respiratory virus transmission, were produced by commercial sodium chloride (nacl) aerosol generator. also, the air with a controlled airflow rate was drawn through the sample using a blower fan. the filtration efficiency of each sample was computed by measuring the particles' concentration upstream and downstream as = − × , where and are the mean particle concentrations per bin upstream and downstream, respectively. moreover, the pressure drop across the facemasks and the air velocities were measured using a digital manometer and a hot wire anemometer. the experimental investigations revealed that the materials such as natural silk, a chiffon weave ( % polyester− % spandex fabric), and flannel ( % cotton− % polyester blend) provided good electrostatic filtering of particles. also, fabric with tighter weaves and low porosity, such as cotton sheets with high thread count, have resulted in better filtration efficiencies. for instance, a tpi (thread per inch) cotton sheet can provide average filtration efficiencies of ± % (in the nm to nm range) and . ± . % (in the nm to μm range). a cotton quilt with batting provides ± % ( nm to nm) and . ± . % ( nm to μm). surprisingly, four-layer silk (e.g., scarf) was found to be effective with an average filtration efficiency of > % across the ten nm− μm particle size range. moreover, the hybrid masks made by combinations of two or more fabric types, leveraging mechanical and electrostatic filtering, could be an effective approach for better filtration (fig. a) . verma et al. performed the qualitative investigations for assessing the effectiveness of easily available facemasks such as bandana (elastic t-shirt material, threads/inch), folded handkerchief (cotton, threads/inch ), stitched mask (quilting cotton, threads/inch) and other commercial masks. they observed that a stitched mask made of quilting cotton was most effective, followed by the commercial mask, the folded handkerchief, and, finally, the bandana. their observations also suggested that a higher thread count by itself is not sufficient to provide a better droplet filtration capability. the material types and fabrication techniques have a significant impact on the performance of facemasks. davies et al. examined the efficacy of homemade masks as an alternative to commercial surgical masks. various household materials such as % cotton t-shirt, scarf, tea towel, pillowcase, antimicrobial pillowcase, vacuum cleaner bag, cotton mix, linen and silk were evaluated for the capacity to prevent bacterial and viral aerosols transmission. the performance of these household facemasks was compared with the standard surgical mask. the experimental outcomes showed that these homemade masks could reduce the likelihood of infection, but not efficient for the complete elimination of risks. a similar conclusion has been made in a previously published review article by rossettie et al. and loupa et al. recently, ho et al. investigated the droplet filtration efficiency of the self-designed triple-layer cotton masks, their performance was compared with the standard medical mask. all tests were performed in two different locations; in a regular bedroom and a car with air conditioning. the particles with a size range of - nm were taken into consideration, and the filtration efficiency was measured. other factors like environmental conditions (temperature and relative humidity) and cough/sneeze counts per hour were measured for each measurement. the results revealed that cotton and surgical masks could significantly reduce the number of microorganisms expelled by participants with the filtration efficiency of . % and . %, respectively (fig. b) . however, the surgical mask was three times more effective in blocking transmission than the cotton mask. in a recent study, fischer et al. performed testing of different facemasks or mask alternatives ranging from the kind worn by healthcare professionals to neck fleeces and knitted masks. fig. c shows the photographs of the facemasks and alternatives considered in the investigation. a comparison was made on the dispersal of droplets from a mask wearer's breath while wearing one of the face coverings to the results of a controlled trial where their mouth was fully exposed. the study revealed that some mask types matched standard surgical masks' performance, while some mask alternatives, such as neck fleece or bandanas, offered little protection against infection. the neck fleece was found to increase the risk of disease by having a "droplet transmission fraction" of % (fig. d) . besides, they demonstrated a simple optical measurement method to evaluate the efficacy of facemasks to reduce respiratory droplets transmission during regular speech. fig. e shows the schematic of developed setup. the proposed optical system is inexpensive and easy-to-operate, even by non-experts. furthermore, the use of face shields has widely been used along with standard face masks. face shields are generally made of transparent plastic sheets. they offer several advantages: comfortable to wear, easy-to-clean, clear conversations between the speakers with visible facial expressions, and reduce autoinoculation by preventing the wearer from touching their face. also, face shields prevent the user's face from the direct contact of liquid droplets. more recently, verma et al. investigated the effectiveness of the face shields and exhalation valves in the respiratory droplets transport context. they performed experimentation in an emulated coughing and sneezing environment for qualitative visualizations analysis. the results indicated that although face shields block the initial forward motion of the fluid jet, the expelled droplets can move around the visor with relative ease and spread out over a large area depending on environmental conditions. also, for the facemasks equipped with an exhalation port, the droplets pass through the exhalation valves. based on the observations, they opined that high-quality cloth or surgical masks perform better than the face shields and exhalation valves. in the past few decades, especially post-outbreak of the severe acute respiratory syndrome (sars) in , wearing the facemasks has grown extensively. the people from asian countries like china, singapore, thailand, japan, etc. can be easily seen donning facemasks in public places. there are well proven-studies about the prevention of airborne pathogens transmission by covering the mouth and nose using the facemasks. the recently published article by gandhi and rutherford, claimed that the universal facial masking might help reduce the severity of disease and enhance the wearer's immunity. however, prolonged use of facemasks has some side effects on human respiratory health, such as carbon dioxide builds up, drowsiness, and breathing problems because of restricted fresh airflow, and unusual heart rate. , if a facemask is donned for a longer period, the filter gets wet because of facial sweat, and vapor is formed inside the facemasks due to the breathing, resulting in clogging of particulates. also, wearers get a false sense of security, encouraging them to spend more time in public places. other potential side-effects of facemasks wearing include skin irritation, uncomfortable feeling due to the arrival of exhaled air into the eye, comprised quality and the volume of the speech during the conversations. , , moreover, there are some environmental concerns associated with the use of single-use facemasks. some of these facemasks are made from layers of plastics, which may not bio-degrade easily, thus creating a massive burden on the environment. a recent analysis has reported that if every person in the uk used one single-use facemask each day for a year, it would create , tonnes of contaminated plastic waste, roughly ten times higher than that of using reusable masks. the new coronavirus is continuously evolving and spread all over the world. researchers from all disciplines, especially the medical professionals and engineers, are continuously working on the facemasks design improvement for a better performance against the virus transmission. zhou et. al. presented an electrospun polyetherimide (pei) electret nonwoven material based bi-functional smart facemask to remove the sub-micron particulate matter and generate electricity. the facemask could harvest sufficient energy from the airflow to supply power to the inbuilt lcd panel. the lcd screen was used to display the measured breathing rate. hossain et al. developed a rechargeable n facemask that composed of a charged polypropylene electret fiber made an intermediate layer for capturing the foreign particles. these particles are trapped through the electrostatic or electrophoretic effects of the polypropylene terephthalate (pet) layer. the mask has a provision for the in-situ recharging of the polypropylene electret for maintaining its filtration performance. williams et al. proposed a facemask used for the sample collection of respiratory sars-cov- virus. they have successfully presented a facemask prototype the detects exhaled mycobacterium tuberculosis, a deadly lung infection, and now working for sampling for the sars-cov- virus. the facemask consisted of four d printed polyvinyl alcohol (pva) sampling strips attached inside it. the sampling matrices trapped the particulates during exhalation and was further post-processed for the virus diagnosis. face-mask sampling offered a highly efficient and non-invasive method for respiratory disease diagnosis. the presented approach showed great potential for diagnosis and screening, particularly in resource-limited settings. moreover, several innovative facemask prototypes with better filtration performance are available in the market. recently, korean electronics and appliance company lg® ltd. has developed an air purifier wearable mask (puricare™) equipped with battery-operated miniature fans that draw in the fresh air and help reduce stuffiness. the massachusetts institute of technology and brigham and women hospital, boston's researchers have developed the, a silicone-based transparent reusable facemask with a comparable performance level with n respirators. the facemasks have shown their potentials for preventing the spread of respiratory disease. a variety of facemasks ranging from a simple homemade cloth mask to the ventilated respirators, have played their role in the current covid- pandemic. in general, the facemasks have been experimentally characterized by determining the filtration efficiency and total inward leakage ratio. also, the fluid flow dynamics-based numerical methods have gained much attention to investigating the facemask performances. the present article has also highlighted the insufficiencies of assessing the breathing resistance of the wearers with the facemask by just examining the flow resistance of the facemask. in the longer term, there may be a need for a more elaborate system approach including the study and modeling of how the human lung would respond to the increase in breathing resistance due to the use of facemask, drawing the analogy of modeling the behavior of the heart for the blood circulation system. this article summarizes the perspective of the fluid dynamics of the facemask filtration performance, including droplet and aerosol transports, droplet evaporation, and facemask aerodynamics. furthermore, recent investigations for the efficacy of the facemasks in the context of respiratory virus transmission have been discussed. proc. natl. acad. sci infection prevention and control of epidemic-and pandemic-prone acute respiratory infections in health care national center for immunization and respiratory diseases (ncird), division of viral diseases face masks and coverings for the general public: behavioural knowledge, effectiveness of cloth coverings and public messaging advice on the use of masks in the context of covid- : interim guidance standard test method for evaluating the bacterial filtration efficiency (bfe) of medical face mask materials using a biological aerosol of staphylococcus aureus, astm f /f m - , standard test method for resistance of medical face masks to penetration by synthetic blood (horizontal projection of fixed flow analyses to validate sars-cov- protective masks the southwest respiratory and critical care chronicles lg revolutionizes personal clean air with puricare™ wearable air purifier engineers design a reusable, silicone rubber face mask the first author would like to acknowledge the financial support from the ministry of education rsb research fellowship singapore. the data that support the findings of this study are available from the corresponding author upon reasonable request. key: cord- - eslhs authors: chandrappa, ramesha; chandra kulshrestha, umesh title: air pollution and disasters date: - - journal: sustainable air pollution management doi: . / - - - - _ sha: doc_id: cord_uid: eslhs many disasters lead to air pollution and vice versa. this chapter elaborates major air pollution issues due to earthquake, tsunami, volcanic eruption, epidemics, extreme temperature, insect infestation, mass movement, wars, and fire accidents. where, q i release rate of pollutants into atmosphere m i measured air concentration of pollutants c i dilution factor (calculated under assumption of unit release rate) total release of pollutant is calculated using following equation most of the natural disasters in urban area trigger technological accidents. such incidents/accidents that lead to technological accidents due to natural disasters are called "natech" (campedel ) or natural-technologic or na-tech events (young et al. ) . several effects could take place in industries and in the storage sites, resulting in damage of pipelines, storage tanks, and process equipment resulting in the release of hazardous materials. examples of natech include flood in at the samir refinery in mohammedia, morocco; kocaeli earthquake that occurred in in turkey; nuclear disaster in the year at the fukushima nuclear power plant in japan. natural disasters are prominent mechanisms of hazardous material (hazmat) releases. na-tech releases may be small (e.g.: paints, solvents, and other chemicals stored in household) or large (e.g.: explosion of fuel storage tank). disaster-related hazardous material releases may affect large areas and people. smoke from indonesian wildfires spread to kuala lumpur and singapore (swinbanks ) , where outpatient attendance for haze-related conditions increased by % (emmanuel ) . figure . air pollutants released from disaster. table . shows scale of disaster due to air pollution. disaster-related hazardous substance releases can have an effect on large geographic areas and people (young et al. ). many na-tech releases from inadequate building structure, poor storage well (whitman ) . pollutants released to the environment cycles between air, land, as well as water until it is finally removed from the system through burial in lake sediments or deep ocean sediments and through entrapment in secure mineral compounds. disasters can increase the release of the pollutants accumulated in living/non-living things. while the wild fires release the chemicals entrapped in biomass, volcano/tsunami/earthquake can release the elements/compounds present in earth/seabed. methylmercury, the most toxic substance is mainly formed in aquatic environments by natural microbial processes. subsequently mercury escape to air and washed into water bodies. a geothermal activity emits mercury to the atmosphere as well as releases it to the deep oceans (unep ). figure . shows biogeocycle of pollutants that are disturbed during disasters there by releasing air pollutants. air pollution during disasters are not researched and documented because monitoring of air pollution is not a priority activity during disaster and lack of funds towards research with respect to air pollution during disasters. further even if the monitoring devices exist in disaster prone area, the devices will get affected and stop functioning due to damage or power cut. land use planning should evade hazard zones such as -year flood plains and fault lines for locating landfills, waste lagoons, chemical storage facility as well as industrial facilities. using special designs for pipeline supports and tanks can improve structures' capacity to withstand the disaster (selvaduray ) . release of petroleum during the northridge earthquake as well as ammonia releases during flooding in brazil might have been prevented by proper engineering design and location of facilities. nuclear power stations and industrial facilities that have been particularly designed to withstand natural catastroph. floods usually occur due to rain, destruction of dams, overflow of water bodies, and cloud burst. it is usually assumed the flood will not lead to air pollution. but the pollutants like methane and hydrogen sulphide may be released during flood due to purification of organic matter. presence of pyrite in flooded area may undergo a water-reactive substance like alkali metals, iron sulfide, uranium, lithium, sodium, potassium, rubidium, calcium, phosphorous, caesium, sulphuric trioxide and oleum release air pollutants due to reaction. some chemicals are also pyrophoric and will ignite releasing air pollutant. standing water due to flood will become breeding ground for microbes and can become airborne and be inhaled resulting in lung disease. the contaminants and microorganisms left behind after flood pose health risk. due to the time spent in emergency camps may increase the risk of infectious diseases. damp buildings as well as furniture promote the growth of dust mites, microorganisms, mold and cockroaches that can aggravate asthma, allergies, wheeze, cough and hypersensitivity pneumonitis. leakage of variety of gas both in residences and industry can lead to health as well environmental hazard. the geothermal water from underneath the glacier may lead to release of hydrogen sulphide when exposed to air during flood which may include glacial outburst flood. a flood can expose people to lead from contaminated soil, deteriorating paint, and dust from chipping or peeling paint. further asbestos in flood debris can also contribute to air pollution. drought is affecting millions of people, especially poor as well as underprivileged. their vulnerability is increased by ongoing environmental degradation as well as inefficiency of governance. drought are classified into three types: meteorological, agricultural, and hydrological. meteorological drought is shortage of precipitation from "normal rainfall". agricultural drought is shortage in water to crop. hydrological drought is shortage in surface/subsurface water supplies, resulting in shortage of water to meet normal water requirements. s witnessed drought followed by infamous dust storms (schubert et al. ) . the drought and dust storms created major environmental catastrophes in usa and led to the popular description of most of the southern great plains as the dust bowl (worser ) . the dust bowl, during the s is also popularly phrased as dirty thirties. severe drought and unanchored soil lead to formation of dust clouds that sometimes blackened the sky. these billows of dust often referred as "black blizzards" or "black rollers" reached washington, d.c. as well as new york city and reduced visibility to a meter or less. extended drought in resulted in exposure of ploughed field to wind erosion. emissions of isoprene as well as terpenes from vegetation which has a significant impact on ozone as well as fine particle formation will be reduced due to drought. the overall pollution will increase as gross leaf areas in the vicinity of drought prone area will decrease and so as scrubbing effect due to absence of precipitation. dry, clear skies influence light available for enhancing photochemical reactions. changes in soil moisture will change height to which pollutants in the air can mix in the atmosphere. climate change brings numerous economic activities with it. increase in heat enhances demand for cool drinks, ice cream, sunburn creams, and electricity demand towards air-conditioning/refrigeration which may increase electricity demand and associated emissions. several years of drought resulted in desiccation of old wives lake, in southern saskatchewan. the wind generated airborne silt, sodium sulfate, and clay due to which residents reported nasal, respiratory and eye irritation (gomez et al. ). wild fire is fire in an area of combustible vegetation in the wilderness area that include forest and grass land. wildfire occur due to lightning, spontaneous combustion, sparks from rock falls, volcanic eruption, coal seam fires, cooking in forests, sparks from equipment discarded cigarettes, intentional fire by terrorist, shooting by poachers, preparation of forest land for agriculture by firing, and power line arcs. during wild fire, burning logs can roll downhill igniting dried vegetation in lower elevation. dry climbers become fire ladders and burns trees. methane formed due to litter decomposition catches fire easily thereby spreading fire. lower precipitation, higher temperature, drop in humidity increases spread of fire. millions of hectares of the forests are destroyed by wild fires every year resulting in air pollution. annually fires burn about million hectares of open forests, woodland, tropical as well as sub-tropical savannahs; - million hectares of tropical forests; and - million hectares of boreal as well as temperate forest (goldammer ) . air quality of thousands of km is affected by wildfires (sapkota et al. ) . apart from smoke comprising of unburnt carbon particle, the emission from wild fire comprises carbon monoxide, ash participles, methyl chloride, methyl bromide, polynuclear aromatic hydrocarbons, aldehydes, vocs. due to intervention of anthropogenic activity, forests have become dump yards for waste that include hazardous waste. fires in such area contribute to toxic air pollutants. the pollutant concentration and type depends on the nature of substance burnt and hence it is highly difficult to characterise emissions. the notable massive forest fires often occur at southeast asia. the southeast asian haze caused mainly due to slash and burn agricultural practice was worsened by quasi-periodic el nino drought. large area of southeast asia were affected by emissions of , km of vegetation burnt on indonesian islands of kaliman and sumatra resulting in concentration of total suspended solids of more than µg/m in locations close to extensive fire activity. the resulting haze covered more than million km affecting indonesia, singapore, thailand wild fires can significantly contribute to illnesses of the respiratory system (who ; bowman and johnston ; moore et al. ) . indonesia fires increased cardiovascular and respiratory diseases, and affected living in south-east asia (sastry ; frankenberg et al. ; mott et al. ) . smoke containing ozone, sulfur dioxide, nitrogen dioxide, carbon dioxide as well as particulate matter resulted in hospital admissions of at least in malaysia during the indonesian forest fires in (swinbanks ) . fatalities due to too much carbon monoxide concentrations only or along with other pollutants were reported during wild fires in côte d'ivoire ( ) ( ) , china ( ) and australia ( ) (schwela et al. ). wild fire not only destroys wild life habitats that include nests and burrows, it affects healthy wild life as well in. the young and weak animals/birds are easily get killed due to wildfire. wildfire suppression can be as simple as beating the fire with sticks or throwing sand. advanced suppression methods include use of silver iodide to encourage snow fall, dropping fire retardants and water by unmanned aerial vehicles. fire retardant may also be applied prior to wildfires as a precautionary measure. the secondary impact of the application of aerial fire retardants includes impact on land, water and vegetation. spreading of smoke in hilly terrain depends on the narrowness of valleys and may get stagnated for many days thereby forcing displacement of large animal and birds. small animals may die to exposure due to small lung size and large quantity of polluted air. earthquake is shaking of land due to seismic waves. the majority earthquakes occur along the boundaries of the tectonic plates. nations around the pacific ocean frequently experience earthquakes as they are situated in boundary of the pacific plate. about % of the world's major earthquakes are felt along a belt around the pacific ocean. hence this belt often refered as 'ring of fire'. earthquake, in taiwan on september , and march , was preceded by abrupt increase in so concentrations several hours prior to the earthquake possibly due to seismic triggered degassing (hsu et al. ) . air pollution in the affected areas due to the great hanshin earthquake in hyogo, japan on th january resulted in maximum tsp concentration of µg/m at five locations (gotoh et al. ) . after earthquake in kobe city, japan in , dust and irritants generated during demolition work were considered as a factor in the worsening condition of asthma patients (nukushina ) . hazardous substance (like asbestos; fiberglass; mercury; chemicals from leaking transformers and broken chemical containers etc.,) exposures accounted for % of after-earthquake work-related injuries after loma prieta earthquake in the year near santa cruz, california (durkin et al. ; nathan et al. ) . impact on air quality of earthquake prone area depends on activities and infrastructure in the area. an area with atomic power plant or nuclear research centre will result in emission of radioactive material during earthquake. damage to petroleum storage area and subsequent smoke during earthquake will result in emission of pollutants due to combustion of petroleum product. the damage to industry may result in emission of stored chemicals. on th march , earthquake in the northeastern coast of japan and tsunamis occurred over the east coast of the tohoku region (nagamatsu et al. ) that resulted emissions from failure at the fukushima nuclear power plant. the whittier narrows quake in october resulted in at least two hazardous material incidents: ( ) the release of / of a -ton chlorine container at a facility in santa fe springs; and ( ) chemical spills, a major fire and asbestos contamination in california state university, los angeles (tierney ) . tipping of -gallon container storing sodium metal during the quake resulted in fire. water leaking from ruptured safety shower reacted with the sodium generating hydrogen gas that ignited and spread, vaporizing mercury as well as exposing asbestos (lindell and perry ) . earthquake in northridge, california in usa resulted in nine petroleum pipeline ruptures, natural gas line breaks, emergency hazmat incidents that included release of sulphuric acid during train derailment perry , ) . hazardous releases were reported from about laboratories, industrial facilities and commercial activities (like drug stores, hair salons as well as restaurants) and residences after the loma prieta quake at california. three of the largest releases associated this quake were between and , pounds of ammonia from a food processing plant, , gallons of aqueous solution from a semiconductor facility, and , yard of fuel from underground storage containers (young et al. ). tsunami is series of water waves due to displacement of a large quantity of water in water body. air contaminants released during tsunami depends on the development and activities of the tsunami affected area. the flooding of sea/lake water over land is likely to emit pollutants associated with flood already discussed in sect. . . the nuclear disaster at the fukushima nuclear power plant in japan on march , lead to meltdown of three of the plant's nuclear reactors when the plant was hit by the tsunami activated by the tōhoku earthquake. the disaster resulted in release of substantial quantities of radioactive materials becoming the largest nuclear after chernobyl. the disaster caused the month-long emission of radioactive substance into the atmosphere (chino et al. ). severe pneumonia known as 'tsunami lung', was reported in region affected by the indian ocean tsunami (chierakul et al. ; allworth ; athan et al. ) a disease that occur due to inhalation of salt-water contaminated with bacteria and mud. a volcano is a hole on the crust of a planetary mass such as the earth, which allows volcanic ash, gases and hot lava to escape from below the surface. earth's volcanoes occur as the planet's crust is made up of major, rigid tectonic plates that float on magma. erupting volcanoes can pose threat to aircraft, as ash particles can be melted in engine and then adhere to the turbine blades disrupting the functioning of the turbine. large eruptions can obscure entry of solar rays and cool the troposphere; but they also absorb heat released from the earth, resulting in warming of stratosphere. historically, volcanic winters have resulted in catastrophic famines (texsor et al. ) . volcanic activity is linked to the active zones of plate tectonics. the emission from volcano depends on the pressure, temperature and chemical composition of magma type. most of the magma erupted is of basaltic composition and erupt commonly along mid-oceanic ridges in deep sea water. in some locations, such as in iceland and the azores these volcanoes erupt into the atmosphere. such eruptions into atmosphere are called subaerial eruptions. the composition of volcanic gases is generally controlled by the equilibrium among exsolved gas at the top as well as the silicate melt in the magma (symonds et al. ). the composition varies widely between volcanoes and depends on volcano's state of activity. there are three common types of magma: andesitic, basaltic and rhyolitic. andesitic magma erupts explosively since it tends to have high gas content. it is viscous and hence traps gas, and explosively erupts due to pressure built by gases. high viscosity in andesitic magmais related to high silica content. basaltic lava flows easily due to low viscosity (due to low silica content) and low gas content. rhyolitic magma erupts catastrophically since it has high gas content. it is viscous (due to presence of high silica content) and traps gas, builds pressure resulting in explosive eruption. as per baxter et al. ( ) and bernstein et al. ( ) co , co, h s, radon, hydrogen fluoride, silica as well as halogenated hydrocarbons are released during volcanic events. and % of volcanic emission comprises water vapor and - % comprises of carbon dioxide by volume. sulfur gases in volcanic emission vary typically from to % by volume. hydrogen chloride forms with - % of emissions from volcano. hydrogen bromide will be in the range of − parts per volume and hydrogen fluoride forms less than ppm of volcanic emission (texsor et al. ) . stratospheric aerosols generated by short lived volcanic eruption will have small to moderate volume impact compared to moderate ( - km ) volume basaltic flood lava eruption. iceland is the only place on the earth where eruption of this scale is occurring releasing - megatons of so per km of magma erupted (thordarson and self ) . lakiflood lava eruption in the year - at iceland emitted megatons of so and maintained a sulfuric aerosol mask over the northern hemisphere for more than five months. the volcano resulted in release of megatons of so into the lower stratosphere/upper troposphere with eruption columns extending - km (thondarson and self ). quiet escape of hot sulphur-rich gases from new volcanic bodies known as solfataric activity have been studied by isidorov et al. ( isidorov et al. ( , isidorov ) at kamchatka volcanoes located in the siberian peninsula, identified several organofluorines in the volcanic solfataric gases. volcanoes also emit mercury when they erupt. geothermal activities also emit mercury present in the underground to the atmosphere as well as discharge it to the deep oceans. as per unep ( ) some recent studies suggest that natural sources account for around % of the about - tonnes of mercury presently being emitted/re-emitted from all sources to the atmosphere. not all epidemics pose same importance with respect to air pollution. the transportation of pollutants that is biologically active like microbes are responsible for swine flue, avian flue and severe acute respiratory syndrome (sars) may not change the air quality beyond the legal ambient air quality limits but harm human and animal life to great extent. sars caused by the sars coronavirus caused an eventual cases and deaths between november and july . within weeks, sars spread to in countries in early . influenza a (h n ) a human-to-human transmission disease is transmitted by direct body contact or respiratory droplets. heat and cold waves (also referred extreme heat and cold temperature) cause human discomfort and ailments. a heat wave is a prolonged time of excessively hot weather. a heat wave is measured comparative to the normal weather in the area. old wave or cold snap or deep freeze is weather phenomena distinguished by cooling of air over al large area. rising temperatures can result in smog pollution and increase rate of formation of secondary pollutants like ozone. higher temperature can increase pollen production plants and enhance wildfire risks. on the other hand cold wave reduces dispersion of pollutants and traps pollutants. as per airparif ( ), an intense cold wave in february and an average high temperature in march are favorable to pollution of particulate matter. but people with asthma, allergies, and other respiratory diseases face the most serious threats, since exposure to increased pollution heightens sensitivity to allergens. insect infestation is pervasive influx as well as development of insects affecting humans/animals/crops/material. locusts and grasshoppers are main economic pests of crops as well as grasslands all over the world's dry zones. chemical pesticides have been used for controlling locusts and grasshoppers for decades. the main classes of chemical pesticides used to control desert locust are organochlorines, organophosphates, carbamates, synthetic pyrethroids, phenyl pyrazoles, and biological pesticides (wiktelius et al. ) . biological pesticides which comprises of spore of microorganism capable of killing target insects are used to avoid impact of chemical insecticide on environment. aerial spraying with aircraft is widely used to control insect infestation. the pesticide is usually applied as an ultra low volume (ulv) formulation, with drop size ranging between and µm. desert locust control is emergency operations and hence it is difficult to get trained personnel and pesticides with least environmental impact. aerial spraying often cover large surfaces of unpolluted areas and often take place over different ecosystems and landscapes affecting flora and fauna. birds feeding on locusts may be enormously vulnerable to aerial spraying of pesticide (mineau ) . the birds will get affected due to shortage of food due to death of insects and toxic food due to chemicals that may present on food the birds ultimately feed on. these compounds are harmful for humans (reichhardt ) , aquatic organisms, honeybees as well as other insects (mullié and keith ; krall ) . a reduction in insect availability may lead to shortage of food to resident predatory species that consume locusts during the outbreaks (culmsee ). mass movement disasters include dry land movement and wet land movement. mass movement include landslide and avalanches. a landslide or landslip is the outward and downward movement of soil/rock material on slopes. mass movement depends on slope angle, slope orientation, weather, snowfall, terrain, snow pack conditions and vegetation. mass movement can be triggered by both natural as well as anthropogenic causes. mass movement is triggered due to ground movement like deep failure of slopes, rock falls, and flow of shallow debris in sloppy terrain. landslides may occur due to natural or artificial causes. one or more of following condition can lead to land slide: ( ) jointed rocks, ( ) steep slope, ( ) fine-grained permeable rock or sediment, ( ) large quantity of water, ( ) clay or shale layers subject to lubrication and ( ) volcanic activity. even though landslides usually occur in mountainous areas, they can also occur in roadway and building excavations, lateral spreading landslides, river buff failures, collapse of mine-waste piles, collapse in open-pit mines and quarries. airborne arthrospores dislodged from soil during landslides at northridge, usa, in the year (schneider et al. ). anthropogenic disasters are hazards caused due to human intent; error; negligence; or involving a failure of anthropogenic system. this includes social hazards (such as wars and conflicts) and technological hazards (like fire accidents, structural collapse). the notable industrial disaster at bhopal in occurred in at the union carbide india limited, india exposed more than , people to methyl isocyanate (mic). the major wars in the history of mankind have severely caused air pollution and so as act of terrorism and mutiny. the terror attack on twin towers in usa on september , resulted in thousands of tons of toxic debris comprising more than contaminants spread across lower manhattan (anita ) . about , people developed illnesses due to toxic dust (shukman ). wars and conflicts are part of civilisation since beginning of the civilisation. invention of fire and weapons are used for self protection followed by defence and attack. the wars and conflict occur for innumerable reasons but end up with loss of lives and property. war and conflict restricted to land in old days was extended to water and air. people built forts to protect themselves. this was followed by naval and air force. it is essential to know the ongoing conflicts and possible air pollution as the pollutants gradually move to neighbouring countries and beyond. the failure of nuclear plants or testing of nuclear weapons are usually kept secret. but the ill effect will spread beyond boundaries and affect own cities as well as that of neighbouring countries. emission from war and conflicts include emission from use/manufacture of ammunition, fuel use in transportation, manufacturing of ammunition, destruction of infrastructure. urban settlements, fuel storage, power station, military camps, roads, bridges, airports, ports are main targets of wars to weaken the opponents. mutiny and terrorism will aim haphazard use of explosives due to absence of planning, training and information. the use of chemical, biological and nuclear weapons will have different impacts on environment. the emissions from these weapons vary depending on constituents of the weapon. biological warfare also known as germ warfare use of biological toxins or agents like microbes to kill or incapacitate people, animals or plants as an act of war. a chemical weapon uses chemicals formulated to impose death or injure human beings. a nuclear weapon is made up of radioactive material used for mass destruction. conflict in kuwait in january ended up in the discharge of about - million barrels of oil, followed by the fire of more than oil wells and destruction of sewage treatment plants. the total estimated crude oil burned during gulf war was . million metric tons generating smoke of . t/d/well resulting in . million metric tons of so and . million metric tons of no x (khordagui and al-ajmi ) . oiling and petroleum hydrocarbon pollution was restricted largely to the northwestern region of the gulf, while air pollution from the burning oil wells were more widespread (price et al. ). fire accident can occur at homes, commercial establishments, industries or forests. it can occur due to many reasons. the accidents can occur due to natural disasters or due to negligence of people. the accident can be associated with explosion. the duration of fuel and pollutants released depends on the availability of fuel and substance present at the place of accident. the chernobyl disaster that occurred on th april at the chernobyl nuclear power plant, ukraine due to fire and explosion, resulted in release of radioactive material into the atmosphere that spread over western ussr and europe. the quantity of radioactive material released was times more than the quantity of radioactive material released during the atomic bombing of hiroshima. chernobyl nuclear accident led to contamination higher than in the previous two decades in the human environment of republic of croatia (lokobauer et al. ). releases and succeeding transfers of radionuclides through foods, air, and water exposed people to radiation who continued to live in the regions and those evacuated from nearby settlement (bennett et al. ) . even though in the cs levels in the environment were higher than those of sr, sr transfer to the food chain from soil is considerably more than for cs, in the following years (lokobauer et al. ) . fire accident at indian oil corporation limited (iocl) located at sitapur, india on th october resulted in a very high fire flames resulting in emission of black plumes resulting in death and injury of people. air quality in jaipur as well as nearby area of sitapur increased values of spm, rspm no x and so (sharma and mishra ) . coal fires associated with inactive/abandoned mines are reported from mining areas across the world (glenn et al. ; prakash and gupta ; stracher and taylor ) and surface expressions of underground coal fires include areas of dead vegetation, baked rocks, land subsidence, gas vents and fissures (glenn et al. ; stracher ) . coal fires in abandoned mines, unmined outcrops as well as waste banks, constitute safety and environmental hazards. such fires cause subsidence and air pollution. coal fire started in , was active until at least in the pittsburgh seam in pennsylvania (eavenson (eavenson , . lewis and clark, in their exploration in , reported that burning coal ridges were visible in the bluffs along the missouri river (lavender ). outcrop fire that was burning since around - years in southeastern montana, has affected a acres (shellenberger and donner ) . hundreds of coal-bed fires are on fire in the powder river basin (prb) in the usa and studies have shown that such fires have been occurring since thousands of years in the area (heffren et al. ) . coal fires can be extinguished by ( ) physically separating coal from the burning mass; or ( ) oxygen removal by introduction of an inert gas; or ( ) isolation of the fire zone from fresh air; or ( ) heat removal by moving a heat-absorbing agent such as inert gas or h o. usually the chance of reignition is small if temperature is below °c (kim and chaiken ) . fuel-removal by excavation is the most successful fire-control techniques (chaiken ) wherein burning is removed and cooled to extinguish the fire by spraying with water or by spreading it out on the ground to cool in air. the reappearance of excavated fires is normally due the failure to completely excavate or lower the temperature past the reignition point (kim and chaiken ) . inundation methods for extinguishing coal fires involve the use of water to reduce the temperature of the burning matter. to increase the water level, dams are constructed. the water level must cover burning coal and overlying heated rock. this method is used for small fires that are fairly accessible and near the water table. another method provides use of water by continuous pumping or by gravity flow. apart from water, underground fire zone is extinguished by fine, noncombustible solids like sand, red dog, crushed limestone, silt, and fly ash. air or water is normally used to carry the material through a borehole. grout slurries can also be pumped underground burning area to form fire control barriers. cement slurry solidifies to form a seal. grout slurries can be added with foaming agents as well as incombustible materials, such as sand/soil. surface sealing is a comparatively cheaper method of controlling fires in abandoned mine. it is planned to slow down ventilation of the fire zone. if the seal is maintained while all the heat in mine dissipates, the fire may ultimately be extinguished. normally most surface seals fail within one to three years after construction due to settling, drying, shrinkage, or increased fire activity. in western usa % of fire abatement projects were surface seals due to the topography of the area, the relatively low cost, and the lack of water needed to employ other methods (shellenberger and donner ) . if the seals are maintained for about - years, the fire may be put off. surface seals sufficiently inhibit unsightly venting, control subsidence, and limit the emission of harmful fumes. surface seals with regular as well as periodic maintenance provide a sufficient control method (kim and chaiken ) . air quality in paris region summary tsunami lung: a necrotising pneumonia in survivors of the asian tsunami buildings rise from rubble while health crumbles. the new york times melioidosis in tsunami survivors health hazards of volcanic gases health effects of the chernobyl accidents and special health care programmes introduction to the epidemiological aspects of explosive volcanism wildfire smoke, fire management, and human health analysis of major industrial accidents triggered by natural events reported in the principal available chemical accident databases extinguishment of wasted coal fires: a critical review-new directions melioidosis in six tsunami 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tight deadlines and data gaps fan the fight on pesticide safety impact of the canadian forest fires on particulate matter air quality in baltimore city forest fires, air pollution and mortality in southeast asia a coccidioidomycosis outbreak following the northridge, calif, earthquake on the cause of the s dust bowl who health guidelines for vegetation fire events earthquake hazard reduction at japanese petroleum production facilities emission of atmospheric pollutants during iocl-sitapur, jaipur fire controlling fires in unmined coal deposits and abandoned coal mines in the western united states and alaska toxic dust legacy of / plagues thousands of people geology of coal fires: case studies from around the world coal fires burning out of control around the world: thermodynamic recipe for environmental catastrophe forest fires cause pollution crisis in asia emissions from volcanoes atmospheric and environmental effects of the laki eruption: a review and reassessment secondary hazards resulting from earthquakes hazardous materials emergencies and high-rise fires sources, emissions, releases and environmental transport the prognosis for earthquake hazard mitigation injury chart book: graphical overview of the burden of injuries ( pp). geneva: world health organization desert locust dust bowl: the southern great plains in the s natural and technologic hazardous material releases during and after natural disasters: a review key: cord- -pv q authors: kuo, nae-wen; chiang, hsin-chen; chiang, che-ming title: development and application of an integrated indoor air quality audit to an international hotel building in taiwan date: - - journal: environ monit assess doi: . /s - - - sha: doc_id: cord_uid: pv q indoor air quality (iaq) has begun to surface as an important issue that affects the comfort and health of people; however, there is little research concerned about the iaq monitoring of hotels up to now. hotels are designed to provide comfortable spaces for guests. however, most complaints related to uncomfortable thermal environment and inadequate indoor air quality appear. in addition, microbial pollution can affect the health of tourists such as the legionnaire’s disease and sars problems. this study is aimed to establish the comprehensive iaq audit approach for hotel buildings with portable equipments, and one five-star international hotel in taiwan was selected to exam this integrated approach. finally, four major problems are identified after the comprehensive iaq audit. they are: ( ) low room temperature ( . °c), ( ) insufficient air exchange rate (< . h(− )), ( ) formaldehyde contamination (> . ppm), and ( ) the microbial pollution (total bacteria: , – , cfu/m( )). the high level of formaldehyde may be due to the emission from the detergent and cleaning agents used for housekeeping. there have been an increasing number of instances where occupants of a building have complained of a general feeling of being uncomfortable (zweers et al. ; mendell ) . these symptoms often appear to be flu like, however the symptoms usually disappear when people are away from the building. this phenomenon is appearing in the medical literature as a concept called "sick building syndrome" (mendell and smith ) . sick building syndrome (sbs) is a term used to describe a collection of symptoms that have been associated with the indoor air quality of buildings. in taiwan, there has been growing concern in the past decade over health complaints attributed to the so-called "sick building." the reasons could be related to an increase in public awareness of health implications, and people spending more time in air-conditioned environments. indoor air quality (iaq) has begun to surface as an important issue that affects the comfort and health of people and even the productivity of office workers (singh ) . hotels, one type commercial buildings, are designed to provide high levels of comfort for guests; however, the thermal comfort and inadequate indoor air quality are often complaints (bohdanowicz and martinac ) . in addition, the severe acute respiratory syndrome (sars) broke out in a four-star hotel in hong kong has increased the public awareness to indoor air quality of hotels (radun et al. ) . iaq may become one of the important issues for hotel management, and audit methods and technologies should be established first in order to identify the indoor air problems. some iaq monitoring methods have been developed in taiwan and most of them are applied to the office buildings and the hospital buildings. however, the iaq monitoring approach that is suitable for the hotel buildings has not been developed. hence, the purpose of this study is to develop the iaq audit approach with portable equipments in order to establish a comprehensive iaq profile of the hotel buildings. the data collected from this approach can be used to assess the air quality in the hotel buildings and to identify the indoor air problems. consequently, the iaq audit approach proposed here may be helpful for the hotel managers to reduce the health risk from hotel buildings and increase the comfort for guests. an arab oil embargo in triggered off an energy crisis worldwide, with the building industry implementing various measures to conserve energy. in the effort to minimize heat loss and maximize the efficiency of air-conditioning, the building's interior is closed off the outside as much as possible. however, the indoor air becomes stale as a result of the accumulation of pollutants such as excess dust, bacteria, and chemicals. the poor iaq will make occupants uncomfortable and increase the risk of health. during the past few decades, various symptoms and illnesses have increasingly been attributed to non-industrial indoor environments. in general, unlike industrial or accidental exposures (high level), such exposures are very common and usually sustained. problems associated with the indoor environment are a common environmental health issue that is faced by doctors and health practitioners. this sick building syndrome (sbs) has received much attention over the years, and as originally defined by the world health organization (who ) , refers to nonspecific symptoms including eye, nose, and throat irritation, mental fatigue, headaches, nausea, dizziness and skin irritation, which seemed to be linked to the indoor climate (bholah et al. ) . although not life threatening nor disabling, the incidence of sbs among working people does have an economic repercussion (singh ) . sbs might affect the productivity of working people, the sleep quality of people at home, and even affect the recreation experience when tourists are on vacation. sbs has over the years been identified as a significant problem in taiwan as well as in singapore, canada, australia, japan, and america (wargocki et al. ; wu et al. ) . jantunen ( ) also concluded that an average man spends up to % of his time indoors including time spent at workplace, leisure places, and home. therefore, the indoor air in public amusement places, entertainments facilities, offices, schools and other enclosed premises are of decisive importance for human health. factors contributing to indoor air pollution include building location and air intake; building design, building materials and furnishings; and indoor activities (who ; olesen ) . some of the common causes of indoor air problems giving rise to poor air quality are the presence of indoor sources of pollution; poorly designed, maintained or operated air-conditioning and mechanical ventilation (acmv) systems; and uses of the building that were unplanned for what the building was designed or renovated. a ventilation system performs a vital role in the removal of pollutants originating in the air space. in addition, the performance of the mechanical ventilation system influences thermal comfort; for example, cold draughts can produce an unpleasant environment for the guests and the staff. some studies have shown that ventilation systems in buildings are largely responsible for sbs such as morey and shattuck ( ) . these ventilation systems are either designed incorrectly or they are poorly maintained. hotels are designed to provide multi-facetted comfort and services to guests frequently accustomed to, and willing to pay for exclusive amenities, treatment, and entertainment. comfortable indoor environments, safety, and reliability are some of the amenities valued by guests. however, little research is concerned about the indoor air quality of hotel buildings up to now and most hotel managers often ignore these important issues. state-of-the-art technical infrastructure is typically utilized in hotels to provide high levels of comfort, especially thermal comfort (bohdanowicz and martinac ) . however, using energy-intensive space-conditioning systems does not mean warrant absolute guests satisfaction. guests frequently complain about thermal discomfort, even where expensive and sophisticated systems are operated. complaints most commonly in hotels are related to uncomfortable air temperatures (too high or too low), and the difficulty or impossibility of individual adjustment (bohdanowicz and martinac ) . moreover, space conditioning (heating, cooling, and ventilation for the purpose of maintaining high standards of air quality and thermal comfort) typically accounts for about half the total energy consumed in hotels (rada ) . hence, most hotels designers and managers always pay attention only to the energy consumption of hotels operation. however, inadequate air quality as well as the lack of air circulation is another frequent complaints (teeters et al. ) . in addition, the indoor air quality of hotel buildings affects the health of guests especially in bacteria sector. for example, legionnaire's disease broke out in one usa hotel ( people illness and deaths in ) and more than outbreaks worldwide in hotels, hospitals and offices were reported (lane et al. ). in addition, the severe acute respiratory syndrome (sars) broke out in "m" hotel in hong kong has increased the public awareness to indoor air quality of hotels (radun et al. ) . in , sars was carried out of guangdong province by an infected medical doctor who had treated patients. he brought the virus to the ninth floor of a four-star hotel in hong kong. days later, guests and visitors to the hotel's ninth floor had seeded outbreaks of cases in the hospital systems of hong kong, viet nam, and singapore. simultaneously, the disease began spreading around the world along international air travel routes as guests at the hotel flew home to toronto and elsewhere. since sars is primarily transmitted bioaerosol droplets or direct personal contacts and li et al. ( ) have concluded the need for the development of improved ventilation and air-conditioning systems. people pay much attention to the indoor air quality and related health issues of hotel rooms as well as that in the closed airplane are after sars (chien and law ) . the major problem that most hotels fact is the challenge to improve the indoor air quality without increasing energy consumption and other related costs (stipanuk ) . since the hotel industry is one of the most energy-intensive sub-sectors of the tourism industry, with about % of the overall energy consumption due to space conditioning (rada ) . the thermal comfortable standards applied in defining the required levels of thermal comfort in hotels have a substantial effect on the overall energy use in this sector. the iaq audit follows a systematic approach with portable equipments and is carried out in a five-star hotel building in kaoshoung, taiwan. the systematic approach involves the measurement of physical parameters, the monitoring of the concentrations of selected indoor air pollutants, and the measurements of microbial. the international hotel selected is built in and its interior space has been decorated in . it is a twenty-story building and its airconditioning system is a centralized chilled water system with the fan coil unit (fcu) ventilation system. the main area of interest for this iaq audit is the guest room; hence, two guest rooms (double room type) are chosen by random as the sample sites. the thermal comfort level of the indoor environment is measured using an indoor climate analyzer, shibata ies- . the measurements taken through this equipment include room ambient temperature (dry bulb), relative humidity, and air velocity. in addition, the concentrations of carbon dioxide (co ), carbon monoxide (co), and the suspended particulate (pm : for particulate≦ μm) are also can be collected from the shibata ies- at the same time. the air exchange rate in the room was measured using the tracer-gas decay technique. this technique involved an initial injection of sulphur hexafluoride (sf ) tracer gas into the air space through the fan section to provide a better tracer and air mixing in the room. the tracer gas was allowed to mix for min to establish a uniform concentration in the air space. the bruel & kjaer (b&k) multi-gas sampler and analyzer are used to collect and analyze the concentration of tracer gas over time. the concentration-decay of the tracer-gas profile was analyzed to determine the air-exchange rate for the guest room. evaluation of the air change effectiveness in a building is crucial as it provides information about the ability of the air distribution system to deliver ventilation air to a building, zone or space. chemical indicators (co , co, hcho and tvocs) continuous real-time chemical monitoring of carbon dioxide (co ), carbon monoxide (co), formaldehyde (hcho), and total volatile organic compounds (tvocs) were carried out at three indoor sampling points and one ambient point in each room. these points are coupled to the b&k multi-point sampler and analyzer. this monitoring system comprises a photo-acoustic based gas analyzer connected to a multi-point sampler and controlled via proprietary software from a laptop computer. since two equipments (the shibata ies- and the b&k multipoint analyzer) used here can monitor the real-time concentrations of co and co at the same time, the monitoring data can be compared each other. portable air sampler for agar plates (burkard) was used to carry out the biological sampling. the medium that is used for the collection of bacteria is tryptic soy agar (tsa), while the collection of fungi is potato dextrose agar (pda). each of these measurements was taken over a period of min. after incubation is completed, they will be counted and the unit of measurement is in colony-forming units per cubic meter (cfu/m ). the thermal comfort parameters measured are listed in table . the air temperature recorded in the guest rooms is ranged between . and . °c. this is slightly below the recommended range for acceptable indoor air ( - °c) from the local indoor air quality guideline (su and chiang ) . although the individual adjustment is designed in each room, it fails to change indoor temperature in both two-guest rooms sampled. too cold temperature will not only make tourists uncomfortable, it will also result in more energy consumption in air-conditioning. the relative humidity of each room is well within the recommended range ( - %). in addition, although the mean air velocity is quiet different in the two guest rooms sampled, the results are all below the recommended threshold. the air exchange rate in the guest rooms is determined by using the concentration-decay method of the tracer-gas. the air exchange rate and fresh air quantities are computed and shown in table . the air change per hour (ach) is different when the airconditioning is adjusted; for example, the ach is . when the air-conditioning is low, while the ach is . when the air-conditioning is high in room . according to the findings of this study, the air exchange rate is below the acceptable value ( . h − ) in both guest rooms sampled even when the air-conditioning is high. in addition, the amount of su and chiang ( ) fresh air is also inadequate (< m /h) and this indicates that the provision of outside air for ventilation is insufficient. when the air change effectiveness is insufficient, the indoor air of guest room will become stale and may result in the accumulation of pollutants. hence, the american society of heating and air conditioning engineers (ashrae) ( ) suggests that the amount of fresh air must exceed . m /h in the bedrooms in the hotel buildings further. the recommended threshold level for suspended particulate matter (pm : for particulate≦ μm) is μg/ m in taiwan (su and chiang ) and hong kong (iaq management group ) . table shows the average concentration of particulate indoor ranged between . and . μg/m . there is no cause for concern in terms of indoor particulate pollution. the average concentration value for outdoor environment is . μg/m and this is also below the recommended outdoor air quality standards of μg/m (epa ). the concentration of carbon dioxide in the guest rooms varied between locations. measurements were taken over a period of days. the measured concentration of carbon dioxide ranged between and , ppm. the average concentrations of room , and room are about , and , ppm. during night hours, the concentration level of co increases and this may be attributed to the guests in the rooms and the ventilation rate is insufficient. for example, the average concentration of co in room during night hours is , ppm. these monitoring values are higher than the recommended value ( , ppm) in taiwan (su and chiang ; epa ) and hong kong (indoor air quality management group ). the recommended values of exposure for carbon monoxide should not exceed . ppm in taiwan chiang ) and hong kong (indoor air quality management group ) . the concentration of carbon monoxide measured in this study (no smoking activity) ranged from . to . ppm, and the results are well within the recommended thresholds. in general, smoking is the major sources to contribute the carbon monoxide in indoor space. if the tourists smoke in the hotel room, the concentration of carbon monoxide may increase and it may become another problem when the ventilation system is not sufficient. the concentration of formaldehyde measured in this study ranged between . and . ppm, and the average concentrations of room , and room are . , and . ppm. these values exceed the recommended threshold level ( . ppm) in taiwan (su and chiang ) . many building materials and consumer products contain formaldehyde such as insulating materials, medium-density fiberboard, plywood, particleboard, textiles, adhesive, and cleaning products. these relatively high concentrations may be regarded to be attributed to the materials used for interior decoration (jowaheer and subratty ) . in addition, the concentration of formaldehyde in the guest rooms varied with monitoring time. it is very surprise that the concentration of formaldehyde increases rapidly during eight to eleven clock in the morning, and this results are repeated everyday during our monitoring work ( days). the average concentrations of formaldehyde during eight to eleven clock in the morning are extremely high ( . ppm in room , and . ppm in room ). this high level of formaldehyde may be due to the emission from the detergents and cleaning agents because the housekeepers always use such chemicals (containing formaldehyde) during eight to eleven clock in the morning. epidemiological and clinical studies have shown that exposure to formaldehyde could induce sensitization of skin, irritation of eye, some allergic asthmatic syndromes and a variety of low-level symptoms (sardinas et al. ; dally et al. ; garrett et al. ) . moreover, formaldehyde is a probable human carcinogen (group a) (iarc ) that may cause carcinogenic effects by reacting with amino groups of proteins and nucleic acids of nasal mucous membranes (swenberg et al. ). hence, the hotel managers must pay more attention to the problem of formaldehyde and try to reduce the emission of formaldehyde in the hotel buildings. there is no general agreement on the threshold values for total volatile organic compounds in the indoor environment, but a recommended standard for acceptable indoor air quality is ppm in taiwan (su and chiang ; epa ) . it is observed that the average concentrations of tvoc of room , and room are . , and . ppm, and these are below the threshold value. the continuous monitoring of tvoc also shows that the monitoring curve is very similar to the results of formaldehyde; in particular, the concentration of tvoc also increases during eight to eleven clock in the morning. hence, cleaning agents that housekeepers use may also emit volatile organic chemicals. the recommended threshold value for total bacteria and fungi is cfu/m in taiwan (su and chiang ) and hong kong (indoor air quality management group ). the measured data are shown in table and these results indicate that the microbial pollution in guest rooms is serious. in terms of bacteria, the concentrations in both room and exceed the recommended value, in particular in the bathroom. in addition, the value of i/o ratio (indoor/ outdoor) exceeds means that the bacteria pollution is more serious in the indoor environment. it also indicates that this bacteria pollution may be born indoor and not transferred from the outdoor environment. with regard to the total fungi, the concentrations in both room and are all below the cfu/m threshold. the values of i/o ratio for total fungi count are all below , and these results may indicate that the fungi pollution is more serious in the outdoor environment than that in the indoor space. according to the findings of this study, the results of iaq audit are agreement with the complaints from guests about hotel building. the indoor air quality seems to have some problems and the major problems may include the following: ( ) the air temperature is too low, ( ) the air exchange rate is not sufficient, ( ) the concentration of formaldehyde exceeds the recommended value, and ( ) the microbial pollution is also serious. however, the iaq issues are often ignored among the complex affairs in the hotel management. in general, no hotels report their iaq annually and little staff really recognizes the iaq issues; for example, what activities they make will affect the iaq. in addition, the hotel rating system is just a little related to the levels of thermal comfort (table ) , and no comprehensive iaq issues are taken into account. since the iaq problems really exist in the hotel industry, and these problems will affect the comfortable and health of tourists, the hotel managers need pay more attention to the iaq issues. one pilot project was implemented in the hilton o'hare building to monitor the air quality of hotel rooms to address air quality for guests afflicted with sensitivities and reactions to dusts, molds and chemicals. three components that result in poor indoor air quality are identified in this project. these components are bio-aerosols, which are made up of spores; particulates, which are largely dust particles, and volatile organic compounds (vocs) that are emitted from almost everything in a room, especially furniture, carpet and cleaning supplies. the "environmental award" established by international hotel & restaurant association (ih&ra ) pays much attention to the issues about energy and indoor air quality in hotels and restaurants. their assessment criteria including: evidence of long-term commitment to sustainable hotel and restaurant management; use and description of technologies and approaches to energy and air quality management and monitoring; results of energy savings and improvements in indoor air quality over time; quality of environment and energy management training provided to employees and chief engineers; the means by which employee and guest complaints on energy and indoor environment are handled and resolved. consequently, the iaq issues will become more and more important in the hospitality management. guests want a comfortable environment in order to be productive at meetings and enjoy their leisure time, be it in their rooms, in restaurants or around establishment premises. at the same time, employees also need good air quality to concentrate to work efficiently and creatively. the european union 'eurobarometer' survey has showed that good air quality was a key criterion for selecting holiday destinations (european commission ) . air quality will not only affect the choices of tourists but also have great influence on the tourists' recreation experiences. poor indoor air as well as contaminated outdoor air is related to the comfortable and health of tourists, especially when they stay in the accommodation or enjoy in the indoor entertainment facilities. in addition, the sars and other air-bone diseases have increased the awareness of tourists to choose hotels or other indoor facilities with good iaq. hence, iaq has become one of the important issues that hotels managers need to care to meet the demand of tourists. however, the hotel managers are used to care about the energy consumption of air-conditioning to reduce the operation cost and always pay little attention to the indoor air problems in the past. in addition, managers do not know how to implement iaq audit. hence, one feasible approach to indoor air quality audit for hotel management was proposed here to identify the problems associated with the indoor environment of the hotel buildings. this approach can also help hotels managers to find the optimal operation procedures, which can improve the indoor air quality without increasing energy consumption and other related costs. for example, the air temperature measured in this case study is too cold. when this problem has identified, managers can adjust the air temperature set to make tourists feel comfortable and also reduce the energy consumption in air-conditioning. moreover, the indoor air quality criteria of hotels should be investigated and established in the future since the standard of accommodation is one of the key factors in determining the risks which travelers may central heating and comfort cooling available in entire premise. individual heat and air conditioning control in all rooms. high quality equipment with very low noise emission level. be exposed (who ) . for example, the hotel rating system in taiwan and other countries should not only concern about the luxury facilities and services, the indoor air quality should be taken into account in order to provide health and comfortable spaces both for the guests and the staff. sick building syndrome in 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workers: a review and summary of the epidemiologic literature consistent pattern of elevated symptoms in air-conditioned office buildings: a reanalysis of epidemiologic studies role of ventilation in the causation of building-associated illnesses international standards for the indoor environment designing and building eco-efficient hotels. green hotelier: magazine of the international hotels environmental initiative sars: retrospective cohort study among german guests of the hotel 'm health effects associated with urea-formaldehyde foam insulation in connecticut health, comfort and productivity in the indoor environment hotels' energy management in and beyond: operational options that reduce use and cost guidelines for good indoor air quality in office building in taiwan formaldehyde toxicity the future of indoor air quality: legal and economic implications ventilation for acceptable indoor air quality ashrae standard - perceived air quality, sick building syndrome symptoms and productivity in an office with two different pollution loads indoor air pollutants: exposure and health effects world health organization (who) ( ) international travel and health risk assessment of formaldehyde in typical office buildings in taiwan health and indoor climate complaints of office workers in buildings in the netherlands key: cord- -iizj l authors: cumbo, enzo; gallina, giuseppe; messina, pietro; scardina, giuseppe alessandro title: alternative methods of sterilization in dental practices against covid- date: - - journal: int j environ res public health doi: . /ijerph sha: doc_id: cord_uid: iizj l sars-cov- , and several other microorganisms, may be present in nasopharyngeal and salivary secretions in patients treated in dental practices, so an appropriate clinical behavior is required in order to avoid the dangerous spread of infections. covid- could also be spread when patients touches a contaminated surface with infected droplets and then touch their nose, mouth, or eyes. it is time to consider a dental practice quite similar to a hospital surgery room, where particular attention should be addressed to problems related to the spreading of infections due to air and surface contamination. the effectiveness of conventional cleaning and disinfection procedures may be limited by several factors; first of all, human operator dependence seems to be the weak aspect of all procedures. the improvement of these conventional methods requires the modification of human behavior, which is difficult to achieve and sustain. as alternative sterilization methods, there are some that do not depend on the operator, because they are based on devices that perform the entire procedure on their own, with minimal human intervention. in conclusion, continued efforts to improve the traditional manual disinfection of surfaces are needed, so dentists should consider combining the use of proper disinfectants and no-touch decontamination technologies to improve sterilization procedures. a dental office is an environment in which bioaerosols are regularly present, which are generated especially during the use of ultrasound or other hand pieces that produce sprays. the production of these microparticles, created mostly inside the patient's mouth, are therefore microbially contaminated and seem an inevitable phenomenon, because they are closely linked to the activity of the dentist. it is known that if patients carry microbes in the mouth and respiratory tract, they can spread them into the air by aerosolization [ , ] . as a result, dentists can easily be exposed to infections due to the short distance between them and their patients, who could also transmit microbes by sneezing, coughing, or simply speaking. paradoxically, if a patient tries to reduce the spread of his disease by coughing on the hand, as a consequence, he produces more aerosols of small particles that are potentially more suitable for diffusion in the air. there are also other conditions to consider, such as the reduced spaces of dental operating rooms and, consequently, the sharing of a small space and the breathed air that could easily lead to the transmission of biological agents. an adult man breathes about l of air per hour, and, in the event of hyperventilation (which can occur if the patient is anxious or frightened due to dental treatment), the total amount of air breathed per hour can significantly increase; the more air you breathe, the greater the risk of a microbiological transmission. life-threatening viruses, such as sars-cov- , responsible for a severe acute respiratory syndrome that, according to who, has a mortality rate of . %, could be present in the respiratory tract [ , ] . in dental offices, any surface can be contaminated with viruses through contact with infectious body fluids or through the sedimentation of airborne viral particles [ ] . on those infected surfaces, in order to represent a source of infectious risk, the virus involved must be able to survive until it encounters a new sensitive host; in fact, viruses, in general, are the so-called "obligate parasites", because they cannot multiply or propagate outside specific host cells. in order to effectively fight viral infections, it is essential to know the behavior of viruses in different environmental conditions in order to improve countermeasures, making them effective especially when the infection in question assumes particular importance because it is able to put patients' lives at risk. although, in the field of medicine, doctors are well-prepared on how to fight virus-based diseases, a new enemy like sars-cov- , also known as covid- , can test the entire healthcare system. this microbe belongs to a family of single-stranded rna viruses (well known as coronaviridae) that are said to be zoonotic or transmitted from animals to humans. at present, there is no effective medicine for sars-cov- , so the only drugs used are those targeted for side effects in infected patients. in this case, the best defense weapon against the spread of the virus seems to be the attempt to limit the passage from an infected patient to a new host in order to minimize the exponential spread. cov- . to transmit the infection to a sensitive host, it must be able to survive the aerosol process and persist in the air for a long enough time to allow transfer from one person to another. numerous factors influence the survival of viruses in the air: ( ) particle size, ( ) atmospheric temperature and relative humidity (rh), ( ) nature and composition of the aerosol, ( ) atmospheric gases, and ( ) irradiation [ ] . all the factors mentioned are involved differently in promoting or delaying the survival of pathogenic viruses in aerosols, which are substantially airborne particles of various sizes. particles behave differently depending on their size: the larger ones settle quickly, but smaller-sized particles can remain suspended in the air for a long period of time. in a room with calm air, particles with a diameter of only nm that fall through a height of m take about min to stabilize; under the same conditions, particles with a diameter of nm would only take s. furthermore, in the presence of turbulence or a simple flow of air, particles can move very far from the point of their generation, or they can remain suspended for several minutes. the smaller particles of an aerosol have a greater transmission potential for infections, because they can better penetrate and settle in the smaller passages of human lungs. the biggest threat of airborne infection in dentistry is known to be from particles smaller than µm due to their ability to stay airborne and the potential to enter the respiratory tract [ ] . the largest particles, greater than microns in diameter, are called "splatters" and behave in a ballistic way; in fact, these droplets are expelled like bullets in a trajectory initially quite straight that, secondly, becomes curved. finally, they contact a surface or fall to the floor. these particles are too large and heavy to remain suspended in the air and are suspended in the air only for a short time. however, if the droplet starts to evaporate, its size becomes smaller and smaller and acquires the potential to remain in flight for a longer period of time. therefore, splatter droplets can be considered a potential source of infection in a dental environment; in fact, they have been implicated in the transmission of various diseases, such as sars and herpes. several studies show that the evaporation of water from small aerosol particles depends on the atmospheric temperature and the relative humidity level (rh). the evaporation of water leaves behind a residual particle that can contain organic and inorganic materials, as well as biological agents that, if not damaged by the drying process, are potentially infectious for sensitive guests [ ] . therefore, the problem related to the resuspension in the air of previously dried infectious materials that could remain on work surfaces is of fundamental importance; in fact, if the infectious agents manage to survive, the direct or indirect contact of sensitive hosts with these surfaces could lead to the spread of infections. aerosol humidification studies have shown an increase in the recovery of infectious particles from certain types of viruses, such as the flu virus, indicating that the simple rehydration of virus particles in the air leads to their reactivation [ ] . in contrast, other studies have shown that humidification can reduce the recovery efficiency of some types of viruses [ ] . in any case, temperature and rh are the two most important factors, which often act in combination, in determining how long viruses survive in the air state. in general, the ability of viruses to survive in the air state is inversely proportional to air temperature, but there are exceptions. numerous studies on the infectivity of viral aerosols provide clues to understand how different climates influence the onset of many viral diseases. meteorological parameters are in fact important factors influencing infectious diseases, such as severe acute respiratory syndrome (sars) and influenza. yueling et al. showed a significant negative association between covid- mortality and room temperature, as well as absolute humidity. indeed, the daily mortality of covid- appears to be positively associated with the daytime temperature range (dtr) but negatively with the absolute humidity. hence, temperature and humidity are factors influencing covid- mortality [ ] . it is generally believed that lipid-containing viruses survive better at low rh levels, and high rh levels are more conducive to aerial survival than lipid-free viruses [ , ] . under certain experimental conditions, some types of viruses were found capable of surviving well at high and low rh levels but were sensitive to inactivation in the medium rh range; an example of such viruses is the flu virus [ ] . contrary to this, other studies of the human coronavirus have shown that they survive the air state better at • c when the relative humidity is maintained at %. other studies conducted on the human coronavirus have shown that, when the aerosols were kept at • c/ % relative humidity, its half-life was only h. reducing the air temperature to • c/ % relative humidity can cause an increase in the half-life of the coronavirus to almost h [ ] . the ability of low temperatures to overcome the effect of rh on a wrapped virus such as coronavirus suggests that a reduced fluidity of the lipid bilayer may be involved in limiting the access of inactivating factors to the virus' nucleic acid or protein components. it is known that the stability of an aerosol in the air is influenced by the composition of the fluid from which the virus is aerosolized [ ] . some studies on viral aerosols have been conducted using artificial spray fluids, and other studies have used natural substances such as saliva. consequently, the decay rates of artificially generated viral aerosols, under laboratory conditions, can be different from the natural aerosols of the same virus derived from body secretions, and in general, a protective effect of the natural spray is recognized. in dentistry, bioaerosols can be considered a mix of natural secretions, such as saliva mixed with blood, microorganisms, mucous membrane cells, restoration materials, dental particles, and water from handpieces normally used in dental practices. such aerosols are very common during different treatments, such as scaling and root planning using ultrasonic scalers or air polishing procedures; washing or drying with air-water syringes; and preparing the teeth with rotating instruments such as high-speed dental turbines, handpiece micromotors, or air abrasion [ , ] . all experimental studies in this area have attempted to discover and develop chemicals in order to prevent the transmission of viruses by air. the viruses present in aerosols can be inactivated by the action of chemical gases such as propylene glycol vapors, which, for example, are effective against flu virus aerosols [ ] . other studies have been conducted on hydrogen peroxide, chloramine, and hexylresorcinol tested on various viruses present in the air. the minimum concentrations of these compounds, necessary to determine a . % reduction in min, varied from to mg/m ; however, much higher concentrations of the same disinfectants were needed to bring about a . % reduction in the virus titer on a contaminated surface. in order to improve the effectiveness of these chemical gases, their use has been proposed in combination with controlled rh levels; this combination could offer prospects for the effective disinfection of recycled air. both ionizing and nonionizing electromagnetic radiation affect the biological activities of microorganisms such as viruses depending on the wavelength, and their effects on biological materials differ significantly. radiation energy is also absorbed by materials around the microorganism, and these phenomena can indirectly influence the virus; in fact, radiation could alter, first of all, this material that becomes harmful to the virus due to the absorption of radiated energy that can be secondarily transferred to the virus, damaging it. uv radiation can introduce changes in bioaerosols, but its composition can influence what happens to the virus. although various changes in proteins and nucleic acids are known to be caused by radiation, it is important to evaluate whether they are relevant to the loss of the biological activity of viruses. among the ionizing radiations, we must also mention gamma rays, widely used in the field of sterilization, which are electromagnetic radiation derived from the radioactive decay of atomic nuclei. gamma rays have electromagnetic waves of shorter wavelengths and, consequently, transmit the maximum energy of the photon, with an enormous ability to penetrate and kill living organisms; in fact, among their applications, there is the sterilization of medical equipment [ ] . dentists could treat, during daily practice, asymptomatic patients unaware of having been infected with sars-cov- , which, in these cases, could be dangerously present in their nasopharyngeal and salivary secretions; therefore, an appropriate clinical behavior is needed in order to avoid the uncontrolled spread of the infection [ , ] . covid- could also spread when dental patients touch a surface contaminated with infected droplets and then touch their nose, mouth, or eyes [ ] ; if proper precautions are not taken, the dental office can expose patients to cross-infections. there are two different ways to deal with the problem: the first is to identify infected patients and postpone treatments (if possible) or refer them to the appropriate hospitals; the second is to consider all patients highly dangerous because they are potentially infected. it is time to consider a dental practice quite similar to a hospital surgery room, where particular attention should be paid to problems related to the spread of infections caused by air and surface contaminations, especially a time when viruses such as sars-cov- have emerged as an important public health problem due to their ability to spread through close person-to-person contact. there are so many aspects to focus on in order to reduce the spread of this dangerous viral infection and include environmental treatments, air ventilation, the use of personal protection, etc. in dentistry, conventional cleaning and disinfection have been used for several years, but their effectiveness can be limited by several factors-first and foremost, the right choice of products and the procedure adopted [ ] [ ] [ ] [ ] . serious errors such as the use of incorrect chemicals, inadequate dilutions, inadequate contact times, inadequate or numerically inadequate microfiber cloths or paper towels, and incorrect application methods that can spread pathogens from one surface to another can also occur. therefore, the dependence of the human operator appears to be the weak aspect of all procedures. the improvement of these conventional methods requires the modification of human behavior, which is difficult to achieve and sustain [ ] [ ] [ ] . as alternative sterilization methods, there are some that do not depend on the operator, because they rely on devices that perform the whole procedure on their own, with minimal human intervention. these methods, which are often called noncontact disinfection systems (ntd), can be applied in the field of dentistry, especially now that important sterilization problems have arisen due to covid- . ozone (o ), also known as trioxygen, is an inorganic gaseous molecule; under standard conditions, its color is pale blue, and its presence is characterized by a pungent odor reminiscent of chlorine; most people hear it at concentrations of just . ppm in the air. o as an oxygen allotrope that is much less stable than the diatomic allotrope o ; in fact, it breaks down into oxygen, with a half-life of about min. ozone is produced from o through ultraviolet light or atmospheric electrical discharges and is present in very low concentrations, with its maximum concentration in the so-called "ozone layer" of the stratosphere, which absorbs most of the sun's ultraviolet radiation. ozone is used commercially only at low concentrations, so any concern about its instability and the risk that both concentrated gas and liquid ozone may explosively decompose at high temperatures appears insignificant [ ] . the antiviral and antimicrobial properties of o have been well-documented, and several macromolecular targets may be involved; this gas has been shown to kill the sars virus, which structure is quite similar to the new sars-cov- . more precisely, ozone destroys viruses by spreading through the protein coating in the nucleic acid nucleus, causing damage to viral rna. at higher concentrations, ozone destroys the capsid or the outer protein shell by oxidation. most research efforts on the viricidal effects of ozone have focused on the propensity of ozone to break down lipid molecules in multiple-bond configuration sites. in fact, once the lipid envelope of the virus is fragmented, its dna or rna nucleus cannot survive. wrapped viruses, such as sars-cov- , are generally more sensitive to physicochemical challenges than naked virions. although the effects of ozone on unsaturated lipids are one of its best documented biochemical actions, ozone is known to interact with proteins and carbohydrates. unlike liquid sprays and aerosols, gaseous ozone can easily penetrate all areas within a room, including cracks, fixtures, fabrics, under furniture surfaces, and on the floor [ ] . ozone, with its great oxidizing power, therefore has many applications in the field of medical sterilization, especially when it is necessary to sterilize different types of surfaces (smooth or porous) containing dry or wet films of different viruses in the presence and absence of cellular debris and biological fluids [ ] . such conditions are substantially present in any dental practice; therefore, its use could be widely adopted in these environments, especially in the case of the pandemic spread of dangerous viruses such as covid- . in this regard, some studies have shown that ozone gas is able to effectively kill the viruses transmitted by aerosols, with a reduction in the presence of viruses up to % [ , ] . certainly, its use requires some precautions, because its high oxidizing potential makes ozone a powerful respiratory and polluting hazard; its presence, above concentrations of about . ppm, can cause damage to mucous and respiratory tissues in humans and, also, to plant tissues [ ] . if the dental office has more than one operating room, this toxicity problem can be easily solved by using these rooms alternately; when a room is without people inside, the ozonator can be switched on without any risk. furthermore, to speed up the disinfection procedure, ozone can be converted into oxygen fairly quickly by means of a catalyst, and, in the absence of the latter, as an alternative method, strong ventilation is suggested. it is also important to emphasize that, when an ozone generator is used, some other precautions should be taken, such as the use of the remote control on the device or a timer, in order to always remain outside the room during the sterilization process; the procedure must also be performed with closed windows. other significant disadvantages are its ability to corrode and ruin certain materials, such as natural rubber, especially in the event of prolonged exposure; therefore, these materials can be temporarily removed if necessary [ ] . during environmental sterilization by ozone, there is a correlation between the rh and efficiency of this procedure; in fact, it is assumed that the maximum enhancement effect is obtained by first increasing the ozone to the maximum level, followed by a burst of water vapor for increased rh greater than %-preferably, > %. otherwise, at ambient rh, the degree of inactivation is lower and more variable; therefore, the concentration of ozone, rh, and the exposure time seem to be fundamental. there are other important considerations that have emerged from studies in the literature-for example, both dry and wet virus films were found to be equally sensitive to ozone treatment and, at the same time, the nature of the surface on which the viruses are located, not that it makes any difference. the latter aspect can be considered positively, because the surfaces of fabric, plastic, metal, and glass are equally sterilizable, even when cellular debris, including blood, is present [ ] . comparative studies have shown results on different sterilization procedures for operating theaters, and, in conclusion, the effectiveness of ozone seems to be comparable to the use of uv radiation or % glutaraldehyde, but without wasting products, ozone is also easy to insulate and does not require washing [ ] . an air ionizer is a device which, through high voltage, can generate negative ions, which are particles with extra electrons, which give a net negative charge to the particle; conversely, the positive ions lack the electrons for which they have a positive net charge. ionizers use metal surfaces charged with electricity to create ions from air or electrically charged gases that attach to airborne particles that are then electrostatically attracted to a charged collector plate [ ] . the simpler ionizer scheme contains a row of wires and a stack of large flat metal plates; between those wires and plates, a negative voltage of several thousand volts is applied. for safety reasons, the collector plates have a very low current (< µa); however, a high voltage ionizer can produce several billion electrons per second. the air flow first flows through the spaces between the wires and, then, passes through the stack of plates. thanks to the high voltage, an electric corona discharge ionizes the air near the electrodes, which ionizes the particles in the air flow, which are diverted to the grounded plates due to the electrostatic force; finally, the air flow removes the particles accumulated on the plates [ ] . ionizers, which have been used to eliminate or reduce both bacterial and viral infectious agents suspended in the air [ , ] , can be divided into fanless ionizers and fan ionizers. fanless ionizers are generally smaller and quieter devices that are less efficient in air purification; fan ionizers clean and distribute air much faster. some of these devices are called generations of wind electrons (ewg), which are filtration systems capable of purifying the ambient air from bioaerosols whose presence can be dangerous, for example, in operating rooms. usually, they are small devices capable of generating continuous air circulation through a network of electrodes; then, the air flow, which is drawn into the device, is sterilized by the electric field. numerous studies have been conducted over the years to develop different air purification procedures. among the various air sterilization technologies, filtration methods have become very popular [ ] . the ewg air treatment significantly changes the characteristics of the microbes present in the air and shifts the main peak of the dimensional distribution of the microorganisms present in the air in the coarser bioparticles. the use of ewg sterilization seems to considerably reduce the concentration of live microbes present in rooms; in fact, several studies have shown that sterilization using the ewg system seems to be very promising, because the microbial load inside the chamber is greatly reduced thanks to the high voltage field (from kvolt to kvolt), which causes irreversible damage to the cellular film and disturbances in the replication of microbes following breakages of double-stranded dna [ ] . however, the effectiveness of the sterilization process depends on several factors-for example, the size of the room and the number of people inside it, the working time of the device, and, consequently, the volume of air treated per hour. the best results are reported in confined spaces (e.g., m ) with no more than three people. due to the high voltage, significant ozone emissions have been demonstrated during ewg air filtration; it is known that the ozone emission can further reduce the number of live microorganisms in the air; however, the increase in the concentration of ozone in the rooms adversely affects the health of people. fortunately, studies have shown that applying a carbon filter to the ewg device results in a massive reduction in ozone emissions; of course, the addition of these special carbon filters also helps to collect biological and nonbiological aerosol particles [ ] . numerous studies have shown a significant reduction in the spread of viral infections also among animals, and these results represent the hope of further applications in the human medical field [ , ] . the electronic wind generator system allows people to stay in the operating room while it is turned on, with the advantage of not interrupting the workflow. all these devices are portable, so that they can be moved from one operating room to another to optimize time; obviously, this system does not work on contaminated surfaces but only against air contamination; therefore, it must be integrated with other methods, such as those based on chemical products. photocatalytic oxidation (pco) is a technology in the heating, ventilation, and air conditioning (hvac) sector. the main function of typical hvac systems is to control the temperature and relative humidity of the ambient air; moreover, thanks to the presence of mechanical or electrostatic filters, it is also possible to remove polluting air particles. if a carbon filter is present in the system, the gaseous contaminants or vapors emitted are eliminated. however, it is well-proven that filters, used to remove particles from the air, can pollute the air instead of cleaning it, especially if the humidity is high. in the case of absorbent filters, if the temperature or humidity increases, the volatile organic compounds (vocs) can be desorbed instead of being absorbed by contaminating the air [ , ] . instead of adsorbing vocs on the absorbent filter, the photocatalytic process is able to oxidize them in co and h o and control biological contaminations. it is important to specify that pco, which can use uv radiation to energize the catalyst (usually tio ) and oxidize bacteria and viruses, is not a filtering technology, as it does not trap or remove particles but is sometimes simply coupled with technologies filtering for air purification; in fact, it can be mounted on an existing forced air hvac system. the effectiveness of the photocatalytic filter depends on several parameters, such as the total air change speed, the type of filter, and the relative humidity; in any case, further research is necessary to establish whether this system is valid as a control of biological contamination in the field of dentistry [ , ] . the decontamination system based on hydrogen peroxide in aerosols is a "no-touch" method that uses hydrogen peroxide ( % to %), which can be combined with the addition of silver ions (< ppm). this method, also called "hydrogen peroxide in dry mist", is based on the injection of an aerosol with particles ranging from to µ in size; this first phase is followed by passive aeration. the results obtained from these procedures are controversial; some studies have shown a significant reduction in microbes, including spores, but other researchers have shown incomplete eradication. like many other infection control strategies, there are currently no randomized controlled trials on the effectiveness of these systems in preventing healthcare-associated infections [ ] [ ] [ ] . in this system, a heat generator is involved to create, from h o , a high-speed air/steam flow ( - %). these generators are remotely controlled and may be able to measure the concentration of hydrogen peroxide vapor; some systems also have an integrated ventilation unit and dehumidifier designed to reach a humidity level set before the cycle starts [ , ] . studies of these procedures have shown some efficacy against a variety of pathogens, including viruses and prions [ , ] . ultraviolet (uv) light is an electromagnetic radiation invisible to the human eye, since its wavelength is shorter than the visible one and is between nm and nm, although, in some conditions, young people may be able to see ultraviolet light up to wavelengths of approximately nm [ ] . the uv spectrum, as a function of frequency, is divided into five segments: uv under vacuum ( - nm) , uv far ( - nm), uvc ( - nm), uvb ( - nm), and uva ( - nm) [ ] . although uv rays are present in nature because the sun is a primary natural source, there are also artificial sources such as curing lamps, tanning booths, germicidal lamps, black lights, halogen lamps, mercury vapor lamps, discharge lamps high intensity, fluorescent and incandescent sources, and some types of lasers. due to its ability to provoke chemical reactions and to excite fluorescence in materials, uv light has a large number of applications in various fields, including medicine. in dental diagnostics, uv lights are used for the fluorescence of teeth with radiation exposure in small areas and doses not exceeding j/cm [ ] . uv rays are also one of the oldest known methods for decontamination from viruses, bacteria, and fungi; uvc germicidal lamps ( - nm) are mainly used in sterilization procedures, but the optimal wavelength for the best results is about . nm, since the maximum absorption wavelength of a molecule of dna is nm. after uv irradiation, the dna sequence of microorganisms can form pyrimidine dimers, which can interfere with dna duplication, as well as lead to the destruction of nucleic acids and make viruses noninfectious [ ] . in addition, the viral nucleic acid type, the host cell repair mechanisms, and the capsid structure of the virus play an important role in virus inactivation. uv radiation restructures the nucleic acid of the germs and destroys its replication ability; this is the reason why the viral nucleic acid type can play a critical role in the inactivation of the virus by uv rays. more precisely, viruses with rna or dna may be less sensitive to uv rays; important seems to be the presence or absence of the cell wall and its thickness. these are the reasons why ultraviolet radiation can be used in the field of sterilization-in particular, in environmental control against air and surface contaminations. uv irradiation seems to be effective even on surgical instruments, but if they have overlapping parts that remain in the shade, these procedures are not recommended; as a result, uv-c rays are mainly used in air and water purifications with good results; therefore, research on uv disinfection continues today [ ] . ultraviolet light has proven effective against corona viruses and, therefore, could be used against covid- both in the case of bioaerosols and in the sterilization of contaminated environmental surfaces in which this microorganism is present-in particular, on products of unstable composition that cannot be treated by conventional means [ , ] . contrary to most chemical disinfectants, uv rays have been well-recognized as an effective method for inactivating microorganisms, but their effectiveness for inactivating germs has been related to several parameters, such as the level of irradiation, the duration of irradiation (in general, the uv dose for a % viral reduction is two times higher than for a % viral reduction), and rh; at a high rh, a higher uv dose is required to inactivate viruses on contaminated surfaces [ ] . the intensity of the uv light is dissipated with the square of the distance from the source, and this unfortunately limits the ability of the individual uv-c devices to disinfect large areas. a uv lamp intensity of µw/cm in the center of the work area is recommended to ensure surface decontamination; however, there are several sources that provide a list of uv dosages needed to kill a wide range of microorganisms [ ] . the doses of lethal uv radiation necessary for viruses in the air are lower than those of viruses on surfaces; this can be explained by the fact that viruses can form aggregations on surfaces and that viruses can be less sensitive to uv rays if associated with water [ , ] . it is known that all pathogens are sensitive to uv radiation, but this susceptibility between them is different. to classify this vulnerability to uv light, there is an index called z; the higher the index, the more vulnerable the microorganism to uv exposure [ ] . in dentistry, there are two different methods of achieving a significant reduction of microorganisms by uv; the first method is based on devices capable of being effective only on microbes present in the air. in order to improve the quality of the ambient air, the air is forced into the device where the uv source is present, and, after adequate sterilization, it is released into the environment. this procedure allows people to stay in the room when the device is turned on, because there is no exposure to dangerous radiation, so air sterilization can be done for several hours without any risk. on the other hand, these devices are not effective on surfaces, including the floor, where microbes can be widely present. the second method is completely different, because it is based on the exposure to uv rays of the entire environment through the use of fixed uv-c sources strategically positioned to expose the largest possible area. alternatively, mobile supports can be used for a better and more flexible orientation of uv light towards contaminated surfaces. when considering uv-c irradiation to inactivate viruses on surfaces, special attention must be paid; in fact, the growth of microorganisms may occur in shaded areas, such as cracks or crevices where uv radiation may not arrive. the use of a mobile uv sterilization system could be the way to overcome this problem, even if the procedure becomes operator-dependent. this method, which exposes the entire room to uv rays, has the advantage of being effective simultaneously on surfaces and in the ambient air but cannot be performed if people are in the area due to negative health effects, such as the risk of skin erythema and photokeratitis. fortunately, most dental offices have two operating rooms; while one is in use, the other can be treated with uv radiation. all uv systems have numerous advantages; first of all, they are easy to use, and, unlike chemical gases such as ozone, they do not require the sealing of doors or air intakes; another advantage is that the whole procedure is relatively short. indeed, depending on the reflective surfaces in the room, an effective cycle can last differently, becoming shorter and more efficient if reflective objects and surfaces are widely present in the irradiated area. another side effect with the use of uv rays is the damage or discoloration of surfaces, especially if they are made of plastic [ ] . among the different types of active and passive air purification technologies, the latter is based on units with special air filters capable of permanently removing any pollutants. these filters allow to obtain the right degree of purification based on the sizes of the particles; in fact, the air is forced through a filter, and the impurities are physically captured inside it. among the different types of filters, the high efficiency particulate stop filters (hepa) remove a very high percentage of particles and, especially, the highest classes remove at least . % of . -µm particles (defined by the united states department of energy) and are usually more effective at removing larger particles. following the specifications of the european union, the filtration capacity of hepa filters is divided into several classes ranging from > % to > . %. hepa was marketed in the s, and today, this term is used to indicate a highly efficient generic filter [ ] . hepa filters are used in various fields when contamination control is required, such as pharmaceutical production, as well as in hospitals [ ] . the composition of the hepa filters is quite particular, because it is basically a randomly arranged fiber mat made of glass fiber with diameters between . and . µm. although the air space between the fibers is generally much greater than . microns, these filtration systems are designed to trap much smaller particles and pollutants, because they remain staked thanks to different mechanisms such as diffusion, interception, inertial impaction, and electrostatic attraction. in order to improve the level of filtration, hepa systems are also equipped with prefilters (activated carbon) that remove the coarser impurities (pm and pollen particles/ µm) so that the final hepa fine filter remains more efficient for several hours, reducing the need to replace or clean it frequently. in any case, to ensure that a hepa filter works efficiently, it must be checked and replaced periodically. not changing a hepa filter when necessary is a risk, because it could cause, first of all, stress on the device itself and, secondly, an insufficient removal of harmful polluting particles from the air; in addition, attention must be paid to the amount of air passing through the filter, avoiding it bypassing the hepa filter. unlike other air purification systems, hepa filters do not generate harmful products such as ozone. some studies have revealed that it is possible to highlight the growth of microorganisms in bioaerosols in operating rooms even after sterilization, disinfection, and washing due to high humidity, poor ventilation, insufficient disinfection, and floor sweeping. hence, a hepa filtration system could help reduce the bioaerosol levels in these environments, including dental environments [ ] . the dental literature shows that different dental procedures produce both bioaerosols and droplets that are contaminated with microorganisms mixed with blood, saliva, dental debris, restoration materials, etc. these aerosols represent a real potential pathway for the transmission of diseases between patients and dentists, but there is also the possibility of cross-transmissions between the patients themselves if the decontamination procedures are not ideal. in particular, if we focus our attention on bioaerosols, it seems clear enough that, even if the dental instruments and all surfaces are well-sterilized, an operating room with contaminated air could spread diseases among patients, considering that they spend most of their minutes with their oral cavities open. probably the easiest way to eliminate a contaminated bioaerosol is to ventilate the room for several minutes to allow a complete exchange of air, but there is no rapid clinical verification method that certifies that the air present in the operating room is free of contaminants; it is necessary to ensure that all contaminated air has been replaced with fresh and pure air. furthermore, simply opening the window may not be sufficient to guarantee the necessary exchange of air; in this case, you should rely on a forced ventilation system. this method could also be in contrast with maintaining the room temperature at constant and predetermined values, especially in very hot or very cold seasons. at this point, given the uncertainties of the results and the technical complications that could arise in the implementation of this exchange of air, it would be more appropriate to rely on more scientifically validated systems capable of treating the contaminated air and reducing, if not even zeroing with percentages close to %, microbial contaminations. now that the risk of spreading covid- is very high, it is necessary to pay particular attention to all the sterilization procedures that should be reviewed, improved, and perhaps used in combinations to obtain a final result that aims to complete the sterilization of all structures present in the operating room, including air, which for some dangerous diseases, such as sars-cov- , is the transmission route. the latest "no-touch" decontamination technologies could help dentists achieve this important goal. in conclusion, continuous efforts are needed to improve traditional manual surface disinfections. in addition, dentists should consider combining the use of appropriate disinfectants and noncontact decontamination technologies to improve the sterilization of dental operating rooms, especially since the latter methods are independent of the operator. aerosol transmission of experimental rotavirus infection the scope of aerobiology. in airborne transmission and airborne infection; hers available online an 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decontamination of rooms after patients are discharged cycle times for hydrogen peroxide vapour decontamination a call for clarity when discussing hydrogen peroxide vapour and aerosol systems prion inactivation using a new gaseous hydrogen peroxide sterilisation process evaluation of hydrogen peroxide gaseous disinfection systems to decontaminate viruses intraocular lenses should block uv radiation and violet but not blue light status of iso draft international standard for determining solar irradiances (dis ) ultraviolet illumination as an adjunctive aid in dental inspection* the application of ultraviolet germicidal irradiation to control transmission of airborne disease: bioterrorism countermeasure far-uvc light: a new tool to control the spread of airborne-mediated microbial diseases uv air cleaners and upper-room air ultraviolet germicidal irradiation for controlling airborne bacteria and fungal spores the history of ultraviolet germicidal irradiation for air disinfection monitoring ultraviolet lamps in biological safety cabinets with cultures of standard bacterial strains on tsa blood agar comparative inactivation of enteric adenoviruses, poliovirus and coliphages by ultraviolet irradiation inactivation of virus-containing aerosols by ultraviolet germicidal irradiation the importance of bioaerosols in hospital infections and the potential for control using germicidal ultraviolet irradiation an investigation of the changes in poly(methyl methacrylate) specimens after exposure to ultra-violet light, heat, and humidity the vacuum cleaner: a history protective effect of hepa-filtered operating room air ventilation with or without laminar airflow on surgical site infections concentration and type of bioaerosols before and after conventional disinfection and sterilization procedures inside hospital operating rooms key: cord- -sh julcb authors: dutheil, frédéric; navel, valentin; clinchamps, maëlys title: the indirect benefit on respiratory health from the world’s effort to reduce transmission of sars – cov- date: - - journal: chest doi: . /j.chest. . . sha: doc_id: cord_uid: sh julcb nan pollution is recognized as a global public health issue. exposure to environmental air pollutants amplifies respiratory illness. [ ] [ ] [ ] [ ] the world health organization estimates that ambient air pollution causes % of copd cases (ie, million cases) and % of respiratory infection deaths (ie, , preventable deaths per year). air pollution, particularly fine particulate matter and nitrogen dioxide, is also associated with asthma and pneumonia prevalence among children. in december , pneumonia cases of unknown origin appeared in wuhan, hubei province, china. analysis showed that symptoms were caused by a novel coronavirus labeled coronavirus disease (covid- ). the movement of people, through worldwide tourism and business travel, led to rapid increases in the numbers of cases and countries affected. on to fight the increase in cases, local authorities of affected areas established quarantine periods that resulted in a decrease in industry activities, mass transit, and individual car circulation. all of these elements contribute to air pollution. , pollution-monitoring satellites of nasa and the european space agency have detected significant decreases in nitrogen dioxide across china from january to , (before the quarantine), to february to , (during the quarantine). nitrogen dioxide pollution was drastically reduced first near wuhan, and eventually reduced across china and around the world (fig ) . a decrease of % in global pollution was measured following the decrease of global activities due to the coronavirus pandemic. the public health benefit of the world's efforts to reduce transmission of covid- may have indirect health benefits by lowering the impact of air pollution. association of particulate matter air pollution and hospital visits for respiratory diseases: a time-series study from air pollution exposures from multiple point sources and risk of incident chronic obstructive pulmonary disease (copd) and asthma air pollution and noncommunicable diseases: a review by the forum of international respiratory societies' environmental committee, part : air pollution and organ systems air pollution and noncommunicable diseases: a review by the forum of international respiratory societies' environmental committee, part : the damaging effects of air pollution world health organization. ambient air pollution what is the impact of outdoor pollution on children's asthma? arch pediatr short-term association between ambient air pollution and pneumonia in children: a systematic review and meta-analysis of time-series and casecrossover studies key: cord- -uifevl o authors: ye, jin; qian, hua; ma, jianchao; zhou, rong; zheng, xiaohong title: using air curtains to reduce short-range infection risk in consulting ward: a numerical investigation date: - - journal: build simul doi: . /s - - - sha: doc_id: cord_uid: uifevl o air curtains is promising in reducing the short-range infection risk in hospitals. to quantitatively evaluate its performance, this paper explores air curtains equipped on normal consulting desk to avoid doctor’s direct exposure to the patient exhaled pollutants. a numerical investigation is conducted to evaluate the effects of supply air velocity and angle on cutting off performance. simulation results show that the average mass fraction of exhaled pollutants decreases significantly ( %– %) in the consulting ward, indicating satisfying performance of air curtains. increasing supply air velocity is demonstrated to be conducive in forming full air curtains, whereas an excessively high supply air velocity may be of adverse effects by entraining exhaled flow. besides, the supply air angle is also critical due to its coupling with supply air velocity. it is found that larger angle ( °– °) is better where velocity is less than m/s, otherwise a small angle ( °) is preferable where velocity is larger than m/s. exhaled flow could be well suppressed at the supply air angle ° but moves over air curtains at °. this study can provide effective and intuitive guidance in applying air curtains in consulting wards. electronic supplementary material (esm): supplementary material is available in the online version of this article at . /s - - - . the esm files include the animation of patient exhaled droplets from the droplet birth at s to s under the supply air angle °, °, °, at supply air velocity m/s. hundreds of millions of people suffer and four million people die prematurely from respiratory diseases each year (ferkol and schoraufnagel ) . the emerging outbreak of novel coronavirus diseases has caused globally , infection cases in countries, , of which occurred in china by feb , (who . pointing to the risk to medical staff, the chinese center for disease control and prevention (ccdc) suggested that a total of health workers have been infected ( , confirmed cases) and five deaths of health workers have been reported (novel coronavirus pneumonia emergency response epidemiology team ). this ongoing respiratory infectious disease covid- again alarmed and focused on precaution and protection of health staff in hospital environments. respiratory infectious diseases can be transmitted by direct/indirect contact, fomite (such as droplets from respiratory tract) and airborne over large distance (eames et al. ). liu et al. ( b) proposed the short-range transmission mode, which includes both the conventional large droplet route and the newly-defined short-range airborne transmission with a threshold distance of . m. much higher infection risk is observed within the short-range distance (lidwell and williams ; xie et al. ; liu et al. b) . further studies showed that the threshold range of short-range airborne may be related to relative humidity and temperature gradient in the room (lidwell and williams ; nielsen et al. ; gil-lopez et al. ) . face to face between an infector and a doctor in short range distance is very common in hospital consulting wards. in these wards, there is generally a consulting desk located，by which a doctor and a patient sit oppositely. the distance between the doctor and the patient is normally . m- . m, resulting in the doctor being directly exposed to the exhaled flow of the patient. build simul https://doi.org/ . /s - - - ye et al. / building simulation abundant studies have explored airborne transmission of respiratory infections in hospitals and its prevention since the sars outbreak in (li et al. ; zhou et al. ; saarinen et al. ; liu et al. ) . increasing the distance from the infection source is a practically easy way to avoid high infection risk within the short-range distance (xie et al. ; nielsen et al. ; liu et al. b) . but it may not be feasible in consulting wards because the doctor need to communicate in close proximity with the patient to collect medical information. medical (or surgical) masks and respirators are widely used for protection of the patient as well as the health care workers (maclntyre et al. (maclntyre et al. , (maclntyre et al. , . previous studies suggest that masks worn by the infection source works more efficiently than worn by susceptible person (inouye et al. ; tang et al. ). tang et al. revealed that both surgical and n masks thwart human coughing from projecting a rapid turbulent jet into the surrounding air ). but in many cases, patients are not aware of the significance of wearing masks, resulting in seeing doctor without wearing a mask. the facts encourage us to consider an engineering method to reduce short-range airborne infections. the air curtains, generated from certain equipment, are widely used for pollutant control, thermal and moisture control, such as thermal and moisture control to save energy (goubran et al. ) , the sealing entrance of cold storage rooms (gil-lopez et al. ) , the openings of refrigerated food display cabinets (cao et al. ; laguerre et al. ) , smoke confinement (shih et al. ) . the protected occupied zone ventilation (pov) and protected zone ventilation (pzv) technique apply air curtains and display good performance in cutting off the airborne transmission route (cao et al. ) . the protection efficiency is found to vary from % to % depending on the supply air velocity, exhaust location and the usage of partitions (cao et al. ) . cao et al. ( ) found that the dimensionless concentration with the supply air velocity increased to m/s in the downward plane jet is % lower than for fully mixed ventilation. these studies also found that the cutting off performance of air curtains in controlling pollutants is determined by multiple variables, including supply velocity, ejection angle, and room geometries (amin et al. ; shih et al. ). shih et al. ( presented an application of using an air curtain to resolve the personnel safety concern for emergency management in a contaminated cleanroom and found an optimal sealing outcome of air curtains realized at ejection velocity m/s (varying m/s, m/s, m/s) and ejection angle ° (varying °, °, °). zhao et al. ( ) numerically investigated the airborne pollutant separation by the air curtain installed on the ceiling level and revealed that the sealing efficiency increases positively with ejection velocity. however, the performance of air curtains in mitigating the short-range transmission in hospital consulting wards has not been studied yet. in respect to the specialty in consulting wards, this paper proposed the new application of air curtains equipped on consulting desk to reduce the doctor's direct exposure to the patients' exhaled pollutants. a numerical investigation was carried out to explore the cutting off performance of air curtains. different key supply air parameters, i.e. supply air velocity and supply air angle were studied. the airflow pattern and the dispersion characteristics of patient's exhaled droplets were discussed. the dimension of consulting ward is m (l) × m (w) × m (h), which is common in most hospitals. the consulting desk is placed in the central of the ward with the doctor and patient models respectively sitting at each long side, shown in figure . to study the exposure of the susceptible doctor, thermal breathing manikins (topp et al. ) are employed to simulate the infectious patient. the air curtains are installed on the consulting desk with the dimension of . m (l) × . m (w) × . m (h). the return air is discharged from two return air vents with the size of . m (l) × . m (w) located at both sides of the consulting desk. hepa (high efficiency particulate air) is installed inside the consulting desk to ensure clean supply air. the air curtains contribute as inlets, providing supply air after being purified by hepa. the two outlets were located on both sides of the consulting desk to collect return air and then purify it with hepa. to provide stable and moderate airflow, slots with size of . m (l) × . m (w) were employed in air curtains. as shown in figure , the slots were double distributed along with air curtains, which were . m away from the edge of the desk. totally slots were fig. the layout of consulting ward with a consulting desk between the doctor (d) and the patient (p) located, i.e. , , on length (l), width (w), and height (h) directions, respectively. ( ) only exhalation from the patient' mouth and inhalation of doctor's mouth is considered to explore the exposure of the doctor to the patient exhaled pollutants. ( ) liquid droplets begin to evaporate until the inner nuclei are left as soon as they leave the patient's mouth. during the evaporation process, droplets remain spherical hypothetically (ji et al. ). ( ) only gravity, buoyancy and drag force are considered, while other forces are able to be neglected according to literature (xie et al. ; ji et al. ) . the droplet density is set to be . kg/m and its specific heat capacity is kj/(kg k). the realizable k-ε model (zhai et al. ) and the simple algorithm (versteeg and malalasekera ) are employed in this study. heat and mass transfer between indoor air and liquid droplets are considered. species transport model and discrete phase model are applied to calculate the evaporation and dispersion process of patient's exhaled flow (ji et al. ) . co was selected as tracer gas to simulate the patient exhaled pollutants with the background concentration of co in the simulation model was . the initial mole mass fraction of co is set to be %, which is close to the natural fraction of co in exhaled flow (wei and li ) . there are no other heat sources in the ward with adiabatic walls, except for the doctor and patient model. the patient's mouth has a hydraulic diameter of . m, a stable exhalation temperature of k, an initial breathing velocity of m/s and a heat source intensity of w/m , without considering the radiation or latent heat (liu et al. a ). the temperature of supply air is k with different supply air velocity ( , , , m/s) and supply air angle ( °, °, °). detailed boundary conditions of the cases are listed in table . in order to compare the cut-off performance of air curtain, we set case without air curtain as reference case. in terms of the dilution effects of airflow generated by air curtains, two air outlets on the left bottom side of the consulting desk are transferred into one air inlet and one air outlet to make exhaled velocity is m/s and the mole fraction of tracer gas is . sure the same airflow volume in the consulting ward. the equivalent ventilation rate was set to . ach, which equals to case . taking case as an example, three different meshes were generated to identify the least required amount of meshes. mesh details were shown in figure , where grids around the human body were particularly refined with size varied from . m to . m to fit dramatic gradients of velocity field and temperature field surrounding human body. figure displayed that the velocity in z-coordinate under mesh ( , , cells), mesh ( , , cells) and mesh ( , , cells) almost overlap with each other. some small differences were probably accounted for the occasionality of cfd calculation (liu et al. b ). thus, the grid independence of meshes has been verified and the smallest required grids in mesh is used for the following simulations. the cutting-off performance of air curtains can be evaluated by the airflow patterns, the dispersion of exhaled pollutants, the horizontal variation of exhaled pollutants, the concentrations on average and at the doctor's mouth, the dynamic process of exhaled droplets. . airflow patterns in the consulting ward figure showed velocity vectors under various supply air parameters. when the supply air velocity is m/s, the velocity of airflow around the doctor's area was smaller with the increasing supply air angle from ° to ° shown in figures (b) , (e) and (h). thus, less patient exhaled flow moved into the doctor's breathing zone. for the supply air velocity m/s, strong turbulence was observed behind the patient at supply air angle ° shown in figure (f), which enhanced mixing airflow in the consulting ward and increases the doctor's exposure to the patient exhaled pollutants. the air curtains formed by the supply air angle ° was close to the patient's mouth and the airflow around the patient came into a vortex-like flow shown in figure (i). thus, most of the patient exhaled pollutants were controlled in a circular range and the mass fraction of tracer gas near the doctor's mouth was lower than that at supply air angle °. then as the supply air velocity increased to m/s，turbulence was much stronger along with air curtains upward the ceilings and then backward the patient at supply air angle ° shown in figure (g). the entrainment of air curtains also got stronger, which helped strengthen the isolation performance of air curtains and protect the doctor's area. to maintain stable airflow pattern in the consulting ward, the two supply air inlets on the table were removed and the two outlets on both sides are changed into one inlet and one outlet respectively on each side of the normal consulting desk. the exhaled pollutants flowed upside due to buoyance of hot exhaled air and plume generated by thermal manikin. then the patient exhaled pollutants dispersed towards the doctor at lower height compared height compared to that with air curtains. compared with the consulting desk with supply air velocity m/s and supply air angle °, stable air curtain was observed in front of the doctor shown in figure (b), preventing the patient exhaled flow from directly flowing to the doctor breath zone. though the patient exhaled flow first moved vertically towards the ceiling but then moved horizontally towards the doctor's area in a certain height, the pollutant concentration in the head and breath zone of the doctor were kept at a lower level compared to the consulting desk without air curtain in figure (a) . to explore the effect of supply air velocity on the dispersion of patient exhaled flow, figure displayed the species distribution of tracer gas in the ward under different supply air velocity varying from m/s, m/s, m/s with different supply air angle, i.e. °, °, °. nine cases were divided into three scenarios, i.e. case to case (shown as figures (b) to (d)) at supply air angle °, case to case (shown as figures (e) to (g)) at supply air angle °, case to case (shown as figures (h) to (j)) at supply air angle °. compared to figures (c) and (d), the height of air curtains was limited and lower in figure (b). the patient exhaled pollutants flowed upward the patient's head and began to flow horizontally from a lower height that was only a little higher than the doctor's head. figure (c) showed the supply air forms relatively complete air curtains at the supply air velocity m/s and the patient exhaled flow was blocked on the left zone of air curtain. figure (d) showed that the supply air with m/s also forms strong air curtains to isolate figures (e) to (g) presented the patient exhaled flow at supply air angle °. due to the tilted angle of supply air, the patient exhaled pollutants was suppressed by air curtains and moves upwards and rearwards the patient. the air curtains were partly formed and the exhaled pollutants were still able to move over the air curtains under supply air velocity m/s and m/s, shown in figures (e) and (f). with supply air velocity increased to m/s, complete air curtains were formed, enabling the patient exhaled flow mainly concentrated on the patient zone, shown in figure (g). it was found that the patient exhaled flow moved much higher along with the stronger air curtains, which could be accounted by the supply air entrainment. figure (h), indicating that patient exhaled flow was not suppressed by air curtains but easy to penetrate to the breathing zone of the doctor. it may be attributed to the jet (air curtains) that was attached to the surface of the consulting desk, failing to separate the patient and the doctor. with the supply air velocity increased, the jet flowing to the patient became stronger, pushing the patient exhaled flow and plume backward, making the tracer gas concentration around the doctor's zone lower. however, it would cause a sensation of draught to the patient, clearly shown in figures (h)-(j). to explore the effect of supply air angle on dispersion of patient exhaled flow, nine cases were divided into three scenarios, i.e. cases , , (shown as figures (b) , (e), (h)) with supply air velocity m/s, cases , , (shown as figures (c) , (f), (i)) with supply air velocity m/s and cases , , (shown as figures (d) , (g), (j)) with supply air velocity m/s. figures (b) , (e) and (h) displayed the patient exhaled flow under different supply air angle with supply air velocity m/s. compared to figure (a) at supply air angle °, the air curtain generated by supply air angle ° can effectively control the exhaled flow of the patient blocked in a small zone behind the patient shown in figure (e). as the supply air angle increased to ° shown in figure (h), the patient exhaled pollutants flowed towards the doctor over air curtains and the doctor was directly exposed to the pollutants, increasing the infection risk in real consulting ward. figures (c), (f) and (i) presented the patient's exhaled flow under different supply air angle with supply air velocity m/s. the patient exhaled pollutants flowed forward to the doctor's area at supply air angle ° shown in figure (c), but it flowed backward the patient at supply air angle ° shown in figure (f). similarly, the patient exhaled pollutants was partly suppressed at the supply air angle °. figure (i) showed that the patient exhaled pollutants flowed around the patient and some moves towards the doctor area while others move backward the patient at supply air angle °. figures (d) , (g) and (j) showed the patient exhaled flow under different supply air angles with supply air velocity m/s. obvious concentration boundary of tracer gas was observed at supply air angle ° shown in figure (d) and the patient exhaled pollutants flowed a little forward the doctor's area. when the supply air angle increased to ° shown in figure (g), the patient exhaled pollutants moved straight to the ceiling wall and then down to the back area of the patient. when the supply air angle increased to °, the specific area of tracer gas concentration around the patient showed that the patient exhaled flow distributes in a small area around the patient's head. species profiles of tracer gas co suggested that both supply air velocity and supply air angle played an important role in the dispersion of patient exhaled pollutant. air curtains were observed significantly at the supply air angle °. when the supply air velocity was low, i.e. m/s and m/s, air curtains were partly formed and patient exhaled flow can move towards the doctor. for larger supply air velocity, i.e. m/s, air curtains were completely formed from the supply air outlets on the consulting desk until the ceiling wall. what's more, the simulation results about cut-off performance of air curtains in this present study conformed to previous results in literature. yang-cheng et al. found that the air curtain device realized the optimal sealing performance at the moderate ejection velocity of m/s with the variation from m/s to m/s (shih et al. ) . besides, the larger ejection angle of ° (ranging from ° to °) didn't showed maximum sealing efficiency, which is consistent with results in this study that small angle ( °) is preferable where velocity is larger than m/s. the variation of mass fraction of tracer gas co with the initial mass fraction . indicated the dispersion of patient exhaled pollutants. figure shows the concentration of tracer gas varies along with the horizontal distance from the patient mouth. the mass fraction of tracer gas declined rapidly in the first . m from the patient's mouth and then varies at a lower concentration, except case (supply air angle °, supply air velocity m/s). the mass fraction of tracer gas in case decreased similarly with other cases for the first . m but then begins to decrease slowly, and it comes the lower concentration until . m from the patient's mouth. for case without air curtains, the lowest mass fraction of tracer gas, i.e. . appeared at . m from the patient, followed by a slight increase between . m and . m. then it remained approximately . between . m and . m, but decreased near the doctor's mouth between . m and . m. on the contrary, the stable mass fraction for consulting desk with air curtains ranged from . to . at different horizontal distance between . m and . m, which was much lower than that without air curtains. the lowest mass fraction of tracer gas depended on different supply air angle and supply air velocity. figure displayed the detailed variation of the mass fraction of tracer gas and the minimum value, shown in red circle. it was found that the mass fraction of tracer gas at supply air velocity m/s and m/s varied similarly. a significant decrease of the mass fraction of tracer gas appears at . m at supply air angle °, which forms vertical air curtains more easily. however, at supply air angle °, the mass fraction of tracer gas fell greatly at . m, which was closer to the patient due to the inclination towards the patient. compared to supply air angle ° and °, the mass fraction of tracer gas under supply air angle ° increased at about . m and then decreased at about . m. then the lowest concentration appeared around at . m. this indicates that the air curtains made a difference on the dispersion distance and the lowest concentration of patient exhaled pollutants appeared within air curtains flow, which was linked to the supply air angle. to assess overall performance of air curtains, the mean concentrations of the consulting ward were analyzed based on the simulation results. figure showed the mean concentrations of patient exhaled pollutants in the consulting ward and the reduced percentage to normal consulting desk without air curtains. significant decrease ( %- %) of the mean concentration of exhaled pollutants was observed in the consulting ward with air curtains compared to the normal consulting desk without air curtains. in the consulting ward of normal consulting desk without air curtains, the mean concentration is . at the stable condition. notably, the mean mass fraction of co decreased to . - . varying from different supply air velocity and angle. the lowest average mass fraction of co occurred at supply air angle ° and supply air velocity m/s. greater supply air velocity showed better performance in terms of average mass fraction of co . with supply air velocity increasing from m/s to m/s, the average mass fraction of co fell down for supply air angle ° (from . to . ), ° (from . to . ), ° (from . to . ). on the contrary, the optimal supply air angle is linked to supply air velocity. for the supply air velocity at m/s, increasing supply air angle reduced the average mass fraction of co . for the higher supply air velocity, i.e. m/s and m/s, the average mass fraction of co first went up and then dropped down. to evaluate the doctor's direct exposure to the patient exhaled pollutants, the mass fraction of co at the doctor's mouth were investigated under various supply air parameters, shown in figure . the mass fraction of co at the doctor's mouth of consulting desk with air curtains were significantly lower than that without air curtains, suggesting the great importance of employing air curtains on the consulting desk. it was found that increasing supply air angle was beneficial to reduce the mass fraction of co at the doctor's mouth at lower supply air velocity. the mass fraction of tracer gas decreased . %, i.e. from . to . , for supply air velocity m/s shown in red dots in figure . however, increasing supply air angle was not always good for controlling the patient exhaled pollutants near the doctor's mouth for larger supply air velocity. the mass fraction of tracer gas first increased and then decreased with the increasing supply air angle for supply air velocity m/s and m/s respectively shown in blue dots and green dots in figure . in collaborate to the steady distribution of patient exhaled pollutants, the dynamic dispersion characteristics of patient exhaled droplet were investigated under different supply air angle. the dpm model (discrete phase model) was employed to calculate the two-phase flow, i.e. droplets and air. in this study, scenario (cases , , ) with supply air velocity m/s was selected as an illustration and the dispersion of patient exhaled droplets at s was displayed below in figure . both of evaporation process and dispersion process were considered in this simulation. detailed animation of droplet trajectories can be found in the electronic supplementary material (esm) in the online version of this paper. figure (a) presented the droplet trajectory from the droplet birth at s to s under the supply air angle °. air curtains were formed vertically from the supply air outlets and mix with ambient air in the ward. the droplets were exhaled from the patient and then evaporated into dry droplet nuclei. most of the droplets concentrated on the left of the air curtains, i.e. the patient's side. some droplets moved upwards to the ceiling wall once being exhaled from the patient and a small amount of droplets fell downwards to the ground. the initial droplets have almost arrived near the ceiling at time s. figure (b) demonstrated the droplet trajectory from the droplet birth at s to s under the supply air angle °. similar with figure (f), most droplets focused on the left of the air curtains. the droplets were effectively suppressed by the air curtains and moved backward of the patient. at s, the initial droplets appeared at the medium height of the ward, with was a little higher over the patient's head and then tend to drop down to the ground. figure (c) displayed the droplet trajectory from the droplet birth at s to s under the supply air angle °. unlike the supply air angle at ° and °, the droplets dispersed completely different at supply air angle °. most droplets appeared on the right of the air curtains and moved upwards and forward to the doctor's area. this could be accounted for the lower position of air curtains caused by the greater supply air angle. the droplets moved more uniformly at different time step and the initial droplets appeared at close height as they appear at supply air angle ° but in different direction. the new application of air curtains on the consulting desk is of great potential in reducing the short-range infection risk in consulting wards. the numerical simulation in this paper revealed that the average mass fraction of exhaled pollutants decreases significantly ( %- %) in the consulting ward with air curtains. both supply air velocity and supply air angle have great effects in its cutting-off performance. besides, the patient exhaled flow can be suppressed by air curtains under suitable air angle, which is coupled with the supply air velocity. it is found that larger angle ( °- °) is better where velocity is less than m/s, otherwise a small angle ( °) is preferable where velocity is larger than m/s. for air curtains with supply air velocity larger than m/s, exhaled flow could be well suppressed at the supply air angle ° but moves over air curtains at °. moreover, higher supply air velocity is better for reducing the patient exhaled pollutants around the doctor's area. however, air curtains with high supply air velocity would easily entrain patient exhaled flow 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the large building enclosure: infiltration efficiency and partial enclosure ventilation rate the lock-up phenomenon of exhaled flow in a stable thermally-stratified indoor environment this work is jointed supported by the national natural supplementary material is available in the online version of this article at https://doi.org/ . /s - - - . the esm files include the animation of patient exhaled droplets from the droplet birth at s to s under the supply air angle °, °, °, at supply air velocity m/s. key: cord- -y zm z y authors: ma, qingxin; qi, yu; shan, qiuli; liu, sijin; he, hong title: understanding the knowledge gaps between air pollution controls and health impacts including pathogen epidemic date: - - journal: environ res doi: . /j.envres. . sha: doc_id: cord_uid: y zm z y sustainable development calls for a blue sky with quality air. encouragingly, the current mass reduction-oriented pollution control is making substantial achievements, as the data from chinese environmental monitoring stations show a significant drop in the annual average concentrations of particulate matters (i.e., pm( ) and pm( . )) and so( ). but many challenges and knowledge gaps are still confronted nowadays. on one hand, long-term health impacts of fine air particles have to be closely probed through both epidemiological and laboratory studies, and the toxic effects owing to the interactions between particles and associated chemical pollutants should be differentially teased out. on the other hand, due to sole mass control, there are significant changes of overall pollutant fingerprint, such as the increase of ground-level ozone concentration, which should be taken into account for altered health effects relative to the past. moreover, the interplays with air pollutants and air-borne pathogens should be scrutinized in more details. in other words, it is worth investigating likely spread of pathogens (even for sars-cov- ) with aid of aerosols. here, we recapitulate the current knowledge gaps between air pollution controls and health impacts including pathogen epidemic, and we also propose future research directions to support policy making in balance mass control and health impacts. air pollution poses an outstanding challenge to sustainable development, human health and even pathogen epidemics. according to the report of world health organization (who) in , air pollution ranked in the first place of top threats to human health. under this setting, air pollution control and according health risks have popularly emerged in both academic research and strategic agendas worldwide. although significant achievements have been reached due to the efforts in improving air quality in recent decades, there still exist many hurdles with respect to health issues to be addressed, e.g., geographical differences in pathophysiological responses to air pollution, insufficient long-term epidemiological data, uncertainty on the divergent toxicities due to the complicated interactions among versatile environmental factors from different sources, and previously neglected or underestimated adverse effects. moreover, as the mass of particulate particles (such as fine particulate matter, pm . ) falls, the ground-level o concentration arises (figure ), which may cause unknown threats to humans. importantly, mounting data evidence the implications of air pollution in pathogen spread and epidemics. air pollution has been recently found to correlate to increased risk of active tuberculosis and influenza . strikingly, the current outbreak of novel coronavirus pneumonia (covid- ) caused by the novel coronavirus (sars-cov- ) is attracting global attention. however, there is still no insight into the reasons for its outbreak from the eco-environmental and climate aspects. it would be great interest to embark on the role of aerosols, especially in indoor circumstance and airtight space, in enhancing the transport, viability and infection of the sars-cov- virus. [ ] [ ] thus, the sole mass decline of total air pollutants may not be able to reflect the full profiles of health impacts (figure ). to this end, here we summarize the current knowledge gaps page of between air pollution controls and health impacts, and discuss the future development in health impact assessment upon air pollution. in recent decades, china has been suffering serious air pollution, especially the high loading pm . . challenged by diverse serious problems caused by air pollution, the chinese government has largely increased investment in basic research on air pollution formation and control. these studies greatly expand the understanding of the formation mechanism and fundamental principles of air pollution. it is now recognized that air pollution in china is a new type of haze chemical smog, different from london smog and los angeles photochemical smog. the complexity of air pollution resides in its versatile sources, including coal combustion emissions, vehicle emissions, agricultural emissions, industrial emissions and high concentration of natural dust aerosol. in the meanwhile, the numerical model for early warning and forecast of air pollution has been greatly upgraded, and the prediction accuracy has also been significantly improved, providing an important scientific support for taking effective pollution control measures and the health assessment of air pollution. on the basis of these scientific understandings, chinese government has strengthened the furious regulations on the control of these critical source emission in recent decades. in fact, over a long-term timescale, the reduction of frankly speaking, the situation of pm pollution varies from place to place and from time to time in china, in that numerous industrialized cities undergo heavier pollution than western countries, giving rise to greater challenges in pollution control and health impact evaluation. nonetheless, recent epidemiological studies indicate that pm pollution would increase the occurrence of incident stroke, ischemic heart diseases and even impaired fetal growth. [ ] [ ] moreover, many in vitro models have been developed for the regarding toxic effects of pollutants that are adhered on pms has also been a highly active topic. the high-risk components in pms exhibit significant temporal-spatial variation. [ ] [ ] therefore, it has been argued that the infrastructure of pms and laden pollutants (e.g., polycyclic aromatic hydrocarbons (pahs) and heavy metals) on pms together account for the overall net toxicity (figure ). pahs and toxic heavy metals are often integrated into pms through anthropogenic atmospheric emissions. studies actually suggest that pahs and heavy metals on pms are deemed to be the determining causes of a range of diseases, ranging from asthma, emphysema to lung cancers. [ ] [ ] however, the bio-availability of such pollutants once integrated on pms, namely their release from particles in biological page of system, as well as their individual toxic effects, still remain elusive (figure ). in addition, due to complex interplay of chemicals and unknown surface properties on pms, the desorption mechanism of chemicals from pms in biological settings and likely "trojan horse" (i.e. vehicle-conduced delivery) effects are intertwined and could not be readily differentiated. third, little is known about the potential bio-transformation of pms in biological systems. due to the large surface area and ample active functional groups, pms would react with bio-molecules (e.g., surfactants, enzymes and lipids), [ ] [ ] and pms may catalyze the formation of reactive oxygen species (ros) undermined cellular oxidative potential, leading to oxidative stress and even cell death. [ ] [ ] this process might also induce bio-transformation of pms, which may alter their physicochemical properties, such as aggregation state, enzyme-mediated changes of functional groups and even degradation by biomolecules ( figure ) . , [ ] [ ] the bio-transformation would consequently alter the bio-reactivity and bio-safety profiles of particles. thus far, future work should aim to interrogate the toxicity mechanisms underlying pms per se and their transformation under biological conditions. importantly, another previously underestimated issue is the transmission of pathogens through pms and aerosols in the atmosphere as well as the indoor environments ( figure ). so far, only a few studies have looked into the interplay between pathogens (i.e., viruses and bacteria) and air pollution. , [ ] [ ] although most reports documented that influenza virus dissemination relies on short-distance dispersion of droplets from cough or sneeze, mainly through indoor aerosols, a crucial role of pms in facilitating virus transport in longer distance has been also proposed. [ ] [ ] moreover, mounting evidence suggests that air pollutants, e.g., so and pms, positively correlated together, the mass reduction oriented-control policy is desirable when the air pollution was serious in the past years. with the great decline in the total mass of air pollutants, more efforts should be devoted to accurate prediction of air pollution, precision control of specific components, and adequate insights into health effects under chronic exposure and upon altered pollutant profiles. under this setting, many obstacles should be addressed in the future, such as the health risks of pms and adherent pollutants, the interplays between the spread of air-borne pathogens and air pollution, and the synergistic health effects of o and other air pollutants. hence, the focuses on health risks of air pollution should involve diverse fields, such as molecular biology, toxicology and environmental chemistry, epidemiology and even clinical medicine. the laboratory experimental systems also need to be improved to reach realistic atmosphere standards. moreover, a more openly shared database for air conditions, toxicological results and epidemic data could be commonly shared and integrated worldwide. thereby, filling in these fundamental knowledges would be surely beneficial in gaining new insights into health risks, a prerequisite of for policy-making of precision control of air pollution. anthropogenic drivers of - trends in summer surface ozone in china effects of air pollutants on the transmission and severity of respiratory viral infections ambient air pollution and risk of tuberculosis: a cohort study temporal and spatial associations between influenza and asthma hospitalisations in new york city from to : a longitudinal ecological study aerosol and surface stability of hcov- (sars-cov- ) compared to sars-cov- correlation between environmental pollution indicators and covid- pandemic: a brief study in californian context atmospheric "haze chemistry": concept and research prospects mineral dust and no x promote the conversion of so to sulfate in heavy pollution days drivers of improved pm . air quality in china from long term exposure to ambient fine particulate matter and incidence of stroke: prospective cohort study from the china-par project ambient air pollution and markers of fetal growth: a retrospective population-based cohort study of . million term singleton births in china pulmonary oxidative stress, inflammation and cancer: respirable particulate matter, fibrous dusts and ozone as major causes of lung carcinogenesis through reactive oxygen species mechanisms pulmonary diseases induced by ambient ultrafine and engineered nanoparticles in twenty-first century the role of oxidative stress in ambient particulate matter-induced lung diseases and its implications in the toxicity of engineered nanoparticles. free radic quantitative assessment of atmospheric emissions of toxic heavy metals from anthropogenic sources in china: historical trend, spatial distribution, uncertainties, and control policies polycyclic aromatic hydrocarbon (pahs) geographical distribution in china and their source, risk assessment analysis southeast asian smoke haze: fractionation of particulate bound elements and associated health risk the role of particle composition on the association between pm . and mortality release of polycyclic aromatic hydrocarbons from biochar fine particles in simulated lung fluids: implications for bioavailability and risks of airborne aromatics unveiling the molecular structure of pulmonary surfactant corona on nanoparticles the biotransformation of graphene oxide in lung fluids significantly alters its inherent properties and bioactivities toward immune cells oxidation potential reduction of carbon nanomaterials during atmospheric-relevant aging: role of surface coating influence of functional groups on toxicity of carbon nanomaterials the enzymatic oxidation of graphene oxide biotransformation of graphene oxide nanosheets in blood plasma affects their interactions with cells effect of air pollution on the total bacteria and pathogenic bacteria in different sizes of particulate matter season and size of urban particulate matter differentially affect cytotoxicity and human immune responses to mycobacterium tuberculosis impact of atmospheric dispersion page and transport of viral aerosols on the epidemiology of influenza aerodynamic analysis of sars-cov- in two wuhan hospitals effects of air pollutants on occurrences of influenza-like illness and laboratory-confirmed influenza in hefei the short-term effects of air pollutants on influenza-like illness in jinan impact of ambient fine particulate matter (pm . ) exposure on the risk of influenza-like-illness: a time-series analysis in beijing pm . in beijing-temporal pattern and its association with influenza modification by influenza on health effects of air pollution in hong kong respiratory syncytial virus bronchiolitis, weather conditions and air pollution in an italian urban area an observational study airborne transmission may have played a role in the spread of highly pathogenic avian influenza outbreaks in the united states factors associated with chronic obstructive pulmonary disease exacerbation, based on big data analysis the association between respiratory infection and air pollution in the setting of air quality policy and economic change ambient ozone exposure and mental health: a systematic review of epidemiological studies the effects of ozone on human health longitudinal distribution of o absorption in the lung: gender differences and intersubject variability acute associations between pm . and ozone concentrations and asthma exacerbations among patients with and without allergic comorbidities the insert shows the ratios of annual average concentrations of o to those of pm . . (data collected from chinese bulletin on environmental conditions page of the authors declare no competing financial interest.page of the authors declare no competing financial interest. key: cord- -jnic o j authors: ravazi, maryam; butt, zahid; lin, mark h.e.; chen, helen; tan, zhongchao title: in situ measurement of airborne particle concentration in a real dental office: implications for disease transmission date: - - journal: nan doi: nan sha: doc_id: cord_uid: jnic o j recent guidelines by who recommend delaying non-essential oral health care amid covid- pandemic and call for research on aerosol generated during dental procedures. thus, this study aims to assess the mechanisms of dental aerosol dispersion in dental offices and to provide recommendations based on a quantitative study to minimize infection transmission in dental offices. the spread and removal of aerosol particles generated from dental procedures in a dental office are measured near the source and at the corner of the office. we studied the effects of air purification (on/off), door condition (open/close), and particle sizes on the temporal concentration distribution of particles. the results show that in the worst-scenario scenario it takes min for . um particles to settle, and that it takes a shorter time for the larger particles. the indoor air purifier tested expedited the removal time at least . times faster than the scenario air purifier off. airborne particles may be transported from the source to the rest of the room, even when the particle concentrations in the generation zone return to the background level. these results are expected to be valuable to related policy making and technology development for infection disease control in dental offices and similar built environments. in august , the world health organization (who) guidelines recommend delaying routine nonessential oral health care amid covid- pandemic and call for more research on indoor aerosol generated by dental procedures. the reason is that dental professionals, staff, and patients in dental offices are exposed to aerosol droplets, particles, and pathogenic microorganisms in the saliva and blood of the infected patients. the infectious microorganisms transmitted from saliva and nasopharyngeal secretions include pneumonic plague, legionella pneumophila, tuberculosis, influenza viruses, herpes viruses, sars virus (a form of coronavirus), pathogenic streptococci and staphylococci, hiv, and hepatitis viruses [ , ] . airborne and spread to the room. extraoral high volume evacuators (ehve) can also be used to remove the aerosol particles near to the area of particle generation [ ] ; however, its performance depends on the volumetric rate of evacuation and particle generation rate. in addition, using extra devices around the dental unit causes a restricted environment and inconvenience to the dentists. recent covid- outbreak has resulted in increased use of portable air purifiers in dental offices, despite the scarcity of published research on their performances in dental offices [ , ] . further research on the protective effectiveness of air purifiers in dental clinics was recommended [ ] . the portable air purifiers can be located at the corners in the dental offices, and they cause much less inconvenience during dental operations than extra-oral high evacuators do. in addition, these portable air purifiers do not require modification to existing ventilation systems. despite earlier research on number concentrations for micron [ , ] and nano-size particles [ ] [ ] [ ] related to the dental processes, to the best of our knowledge, no research has been done on the dispersion or transport of airborne particles lingering in different parts of the office. the nature of the extensive surface area in dental offices may enhance the losses of particles onto various surfaces. furthermore, research on the effects of air purifiers is needed to develop guidelines and protocols to reduce waiting time between patients and ensure the safe operation of dental offices. the objective of this study is to understand the spatial and temporal concentration-distribution of airborne particles generated from dental procedures in dental offices. the remainder of this paper is presented as follows. section presents the experimental design of concentration measurements in the dental office. section . reports the number concentration distribution of particle under the effects of operating conditions during the generation; section . , the spatial and temporal change of particle concentrations distribution under the effects of operating conditions at the generation zone; section . , at the corner of the office. the results reveal the effective removal mechanisms that depend on particle size. finally, section summarizes the entire work. results in this paper are deemed valuable to the best practices for particle removal from dental offices. the concentrations of micron and submicron particles were measured on may , in a dental operation room on the second floor of the dental clinic in toronto, ontario, canada. figure shows the schematic of the operatory and layout of the instruments. this typical dental operatory room is m wide, m long, and m high; it has one central dental unit. the mechanical ventilation system was turned off and the window was closed throughout the test. the temperature and relative humidity of the room air were . c and %, respectively. range of . - µm in diameter and those smaller than . µm. the aps was located on the left-hand side of the doctor, to prevent any inconvenience for the doctor during dental operations. a stainless-steel sampling tube, which is / -inch of inner diameter and . m long, was connected to the inlet of the aps for sampling air cm away from the operation area (i.e., the patient's mouth). both opcs were running continuously. one opc was located beside the aps, and another opc was . m away from the source. both opcs report particles with diameters of . , . , , , , µm. the first opc is calibrated against the aps. before the operation, the room was unoccupied for hours before the background concentrations were measured at the source without air purification. as seen in figure , all particles in the background air were less than #/cm and those larger than m in diameter were less than #/cm . airborne particles were generated over min of continuous drilling operation (high-speed handpiece) using a pig jaw. pig teeth are commonly used for dental studies because of similarities between the structure of human and pig enamel and dentin [ , ] . the particle number concentrations were measured during min of continuous dental operation and afterward until the number concentrations reached the background. then we measured the airborne particle concentrations under six scenarios. conditions. for all scenarios, the smaller the particle size, the higher concentration is. in closed-door scenarios, by comparing the scenario that no air purifier is running (figure .a) with the scenario that the air purifier is running at the beginning of operation (figure .b), it can be observed that particles have a wider distribution in figure .b, which means particles are growing to the larger sizes. for instance, the concentration of higher than #/cm is observed for . - . m particles in figure .a, while, this range of concentration is observed for . - . m particles in figure from this observation, it can be inferred that running the air purifier from the beginning causes air circulation in the room. the air circulation can enhance the interaction between airborne particles leading to agglomeration in the area that particles are generated [ ] . thus, the particles may grow to the larger ones when the air purifier was on at the beginning of the operation. growing to larger sizes is preferable in terms of particle removal. removal by hepa filter is size dependant; the larger sizes, the more probable filtration is. the filtration of micron particles is due to interception and impaction [ ]. growing particles to larger sizes during the first min while the air purifier was running from the beginning of the operation. the concentration of higher than #/cm is observed for . - m particles in figure .a (air purifier off), while, this range of concentration is observed for . - . m particles in figure .d. moreover, the concentration of - #/cm is detected for - . m particles in figure .c, however . - . m particles have this concentration range in figure .d. the particles generated in the -min long operation gradually spread in the room, and their concentrations were decreased by different mechanisms. they are introduced in the next sections. table summarizes the times it takes for the number concentrations to reach their background levels (removal times) for all six scenarios. in the worst-scenario scenario, when the door is closed and no air purifier is running in the room, it takes min for . m particles to return to the background level. air purifier. figure a shows the lowest particle concentrations in the room when the high-speed air purifier is running from the beginning of the operation. however, the removal time is almost the same for all these scenarios: low-speed air purification after the dental operation, high-speed air purification after the dental operation, and high-speed air purification from the beginning of the operation. it can be inferred that particles were captured with the hepa filter and activated carbon filter installed in the air purifier. in addition to filtration, enhancing air circulation in the room by the air purifier leads to faster particle settlement on the surface areas. these results suggest that air purifier has a crucial role in removing airborne contamination of dental offices in the generation zone. is recommended as a short term solution for the dental offices without air filtration systems. the particle removal time varies with particle size although the air purifier and open door help reduce the concentration of all-size particles in the generation zone. the next section elaborates on the size dependency of particle spread and removal because smaller particles probably carry more infectious microorganisms because the concentration of smaller particles is higher than the larger ones. table . at the beginning of the dental operation there are several mechanisms of particle removal from the air including settling, air circulation, and air filtration. first, all particles in a closed-door room without air circulation or filtration settle down because of gravity. it is well-known that the larger particles have higher gravitational settling velocity and that their removal times are shorter than the smaller particles. figure a further confirms this mechanism. for example, . -m particles disappeared faster than those that were smaller. second, air circulation leads to the dispersion of particles and their subsequent removal by settling on the surface areas or exiting the room or both. the drag force on a particle is also size-dependent. it usually takes a longer time for a larger particle to disperse than the smaller ones do. figure e indicates that air circulation through the open door expedited the particle removal, although the air purifier was off. in addition, figure e shows expedited removal of smaller particles and confirms that air circulation is the dominant mechanism in this scenario. third, the filtration efficiency is also size dependant and it increased with the particle size for micron particles [ ] . moreover, figure .b, .c, and .d show that the removal times do not vary with particle size. therefore, a combination of settling, air circulation, and air filtration all play roles in particle removal for these scenarios. comparing these scenarios with that in figure f demonstrates the strong effects of air circulation due to the open door. in summary, an air purifier running at high fan speed may ensure the removal of . to m particles, while air circulation is more effective for smaller particles. since the door of dental offices might be open frequently, an air purifier with a strong fan may help prevent cross-contamination from one room to the other through the door. nonetheless, our study herein does not undermine the effectiveness of external highvolume evacuation (ehve) and suction, which are often used near to the generation zone. however, it does not mean that the room is completely cleaned even when the particle concentrations in the generation zone dropped back to the background. the particles may be transported from the source to the rest of the room. dental staff walks around in the same room, and they often remove their masks for a short break at the corner, where there is little air circulation. it is necessary to investigate the spread of particles by analyzing the concentration at the corner of the room, and the results are presented in the next section. these results indicate the effectiveness of high-speed high-efficiency air purification. generally, it can be inferred that the peak is observed in the corner when the rate of particle settlement and removal from the air is lower than particle transport to the corner. table indicates that it took min for the concentration peak to reach the corner when the travel time of the concentration peak and peak concentration ratios are close to each other for the three closed-door scenarios including air purifier off (figure a ), low-speed air purifier running after the operation (figure b) , and high-speed air purifier running after the operation (figure c) . thus, the same fraction of particles reaches the corner at the same time for these scenarios. this is surprising because these results imply that the air circulation result from the air purifier has little impact on the air movement to the corner of the room (see figure ). removal mechanisms. second, the peak is observed in the corner when the rate of particle settlement and removal from the air is lower than particle transport to the corner. thus, a fraction of , . m particles, which is not removed from the air, traveled to the corner. the following conclusions can be drawn from the results of this study: • in the worst-scenario scenario with no protection system in the closed-door office and continuous high-speed drilling, it takes min for . m particles to return to background level and that it takes a shorter time for particles larger than . m to be removed from the air. in the real operations with the patient, which usually is less than five minutes, air may be cleaner because of other measures like suction from the source (i.e., the mouth). • there are three size-dependent mechanisms for particle removal: gravity settling, air circulation, and air filtration. technologies that combine all of them are the most effective in air cleaning. the air purifier expedited the removal time at least . times faster than the scenario with no air purifier in the generation zone. running high-speed air purifier at the beginning of the operation is the most effective scenario in reducing airborne particle concentrations. the air purifier at one corner could not eliminate the concentration peak in the other corner of the room except for the scenario when the door was closed and the air purifier was running at the highest speed from the beginning of the operation. • in the second part of this study, the number concentrations were measured for three dental operations with real patients. the air ventilation system was blocked, and the door was closed, however, it was opened several times during the operations. the first operation was conducted in parts, shown in by patterned area. the higher concentrations entered the room from outside. after closing the door, the number concentration was reduced by the air purifier. moreover, the concentration peaks were observed, in the moments that the door was open. the major fraction of particles was generated in the second part of the operation. during this time, the air purifier was running at low speed in min and turbo speed in min. in the first min, the removal rate was . (#/cm min) and the second min was . (#/cm min), times faster than the time with low speed. the second operation was conducted in a single part, and no considerable particles were measured. similar to the fist operation, the number concentration of outside was higher than inside. the number concentration in the third operation was higher than the first two operations. the third operation was conducted in parts. higher values of concentration coming from outside are observed in this operation comparing to the first two because aps was closer to the door in rd operation. characterization of aerosols and fine particles produced in dentistry and their health risk assessments aerosols and splatter in dentistry: a brief review of the literature and recognition of aerosol transmission of infectious agents: a commentary it is time to address airborne transmission of covid- modes of transmission of virus causing covid- : implications for ipc precaution recommendations: scientific brief lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution safe handling of nanotechnology global air quality and climate high secondary aerosol contribution to particulate pollution during haze events in china the contribution of outdoor air aerosol and bioaerosol particles in a dental office measurement of particle concentrations in a dental office. environmental monitoring and assessment d'arcy, assessing potential nanoparticle release during nanocomposite shredding using direct-reading instruments nanoparticle release from dental composites nanoparticle concentrations and composition in a dental office and dental laboratory: a pilot study on the influence of working procedures enamel microstructure and microstrain in the fracture the authors would like to acknowledge the financial and technical support from the natural sciences and engineering research council of canada (rgpin- - ), the gci ventures capital, surgically clean air, and waterloo filtration institute. key: cord- -fue ri h authors: schafer, benjamin; verma, rulan; giri, aswin; he, hankun; nagendra, s. m. shiva; khare, mukesh; beck, christian title: covid- impact on air quality in megacities date: - - journal: nan doi: nan sha: doc_id: cord_uid: fue ri h air pollution is among the highest contributors to mortality worldwide, especially in urban areas. during spring , many countries enacted social distancing measures in order to slow down the ongoing covid- pandemic. a particularly drastic measure, the"lockdown", urged people to stay at home and thereby prevent new covid- infections. in turn, it also reduced traffic and industrial activities. but how much did these lockdown measures improve air quality in large cities, and are there differences in how air quality was affected? here, we analyse data from two megacities: london as an example for europe and delhi as an example for asia. we consider data during and before the lockdown and compare these to a similar time period from . overall, we find a reduction in almost all air pollutants with intriguing differences between the two cities. in london, despite smaller average concentrations, we still observe high-pollutant states and an increased tendency towards extreme events (a higher kurtosis during lockdown). for delhi, we observe a much stronger decrease of pollution concentrations, including high pollution states. these results could help to design rules to improve long-term air quality in megacities. cities around the world are facing numerous environmental challenges. air pollution in cities is among the most pressing topics. air of persistently low quality that citizens are forced to breathe has a detrimental impact on their health and wellbeing. one third of deaths from stroke, lung cancer and heart disease are due to air pollution [ ] . overall, air pollution is linked to various diseases, like lower respiratory infections, strokes, cancers, asthma attacks, coughs, and chronic obstructive pulmonary diseases [ ] [ ] [ ] . as per the state of global air [ ] , long-term exposure to outdoor and indoor air pollution contributed to nearly million deaths in . out of these, million deaths are directly attributed to particulate matter of . microns or smaller (p m . ). furthermore, high pollutant concentrations also damage the environment [ ] [ ] [ ] . there are many sources contributing to air pollution, including emissions from vehicles, industrial emissions, combustion of biomass, solid waste, and fossil fuels (coal, diesel, and gasoline), construction activities, resuspension of road dust, domestic sectors and small manufacturing industriesall contribute towards the deteriorating air quality in cities [ , ] . the covid- pandemic has lead to increased social distancing and more working hours spent at home. many countries have initiated a "lockdown", asking or forcing citizens to stay at home, some factories have stopped production as their workers could not keep proper distancing. for example in the uk, on march , the government imposed a lockdown banning all "non-essential" travel and contact with people outside one's home (including family and partners), and shutting down almost all schools, businesses, venues, facilities, amenities and places of worship. those with symptoms, and their households, were told to self-isolate, while the most vulnerable (the over s and those with certain illnesses) were told to shield themselves. road traffic was significantly reduced, plummeting by % to levels not seen since [ ] . some lockdown restrictions in the uk were gradually eased in may and june. in india, the strongest lockdown measures were imposed from march to april . these were then gradually eased afterwards in various stages. the reduced load of commuters and thereby overall reduction in traffic flow, as well as the reduction of industrial activity during lockdown is expected to improve the air quality, especially in cities. but how much, and in which specific ways, did the lockdown improve air quality and how were different cities affected? continued urbanisation leads to an increasing population in cities and the formation and growth of new megacities. due to their high population density, these centers face particular challenges when it comes to air pollution [ , ] . here, we focus on an analysis of air quality in two megacities, namely london and delhi, and use them as representatives for two major classes of megacities. london as an example of an established western megacity and delhi as an asian megacity in an emerging region. the comparison between the two cities will yield important insight on how air quality differs in general between the two locations but also how it can be improved by regulatory means. within this paper, we first give an overview of the air quality in both london and delhi. next, we compare measurements from the lockdown period in march to april with measurements from march to april of the previous year . in particular, we analyse individual trajectories, probability distributions but also higher statistical moments. then, we continue with a discussion of which sources cause which type of air pollution and how adequate guidelines could improve air quality in cities, especially after the current pandemic stops. we conclude that air quality is much easier improved in emerging regions by taking regulatory actions, while western cities can still profit from reduced traffic and should also investigate residential and background pollution. air pollution is having adverse effects on everyone who lives and works in megacities, such as london or delhi. particularly affected are vulnerable groups, like children, elderly people and those with heart and respiratory conditions. people living in deprived areas are also more affected by poor air quality, because often these areas are near busy roads or near industrial areas. many different pollutants contribute to low air quality, including sulphur dioxide (so ), nitrogen dioxide (no ), nitrogen oxides (nox), particulate matter (pm and pm . ), lead, benzene, carbon monoxide (co), benzo(a)pyrene, ozone (o ). most megacities developed regulations to define thresholds and improve air quality. for example, the uk air quality standards regulations sets standards for major pollutants. similar classifications were developed by the central pollution control board (cpcb) in india. the two megacities we study here in detail have very different properties when it comes to climate and pollution. in terms of climate, london has a temperate oceanic climate, whereas delhi features a dry-winter humid subtropical climate. like in other megacities, pollution levels in delhi city are very high and it is identified as being among the world's most polluted regions [ ] . during the winter months, pm concentrations were observed times higher than the annual averages, due to stable meteorological conditions [ ] . high pm pollution levels in the city cause six million asthma cases and , - , premature deaths annually [ ] . in contrast, air quality in london has improved in recent years as a result of policies to reduce emissions, primarily from road transport, such as low and ultra low emission zones. further information on air quality in delhi and london is provided in supplementary note . the covid- lockdown has shown a significant reduction in air pollution levels across many countries. for example, air quality in delhi-ncr and the indo-gangetic plain have been reported to be significantly better than before. the current situation is a unique opportunity to understand the baseline emissions both in delhi and london environment under lockdown conditions in contrasting areas of the cities (suburban, traffic, and urban). in contrast to previous studies on air pollution during covid- lockdown, such as [ ] [ ] [ ] , we investigate the detailed probability distributions of different pollutants, analysing various locations within the cities. also, we analyse higher statistical moments and compare two very different megacities in detail. to quantify the impact of the lockdown, we compare the "covid- -lockdown" in with the "business-as-usual" scenario from . hence, we select dates from mid march to april that will cover the strictest lockdown states in each city. furthermore, we utilize data from as a reference. this allows us to better quantify how much pollutant concentrations have changed during the lockdown. the reason to compare the march-april values with the same period in , instead of january to february is that there is a clear seasonal dependence in air quality, e.g due to the efficiency of catalysts depending on ambient temperature [ ] . in both megacities, we use ten randomly chosen locations to reduce bias in sampling site selection for assessing the air pollutants data. for london, we utilize open data available from the london air quality network [ ] . from the available data, we select a total of ten locations for our analysis: three urban, suburban and road locations each and one industrial location (in the london data set very few industrial locations are available). the approximate locations are marked in fig. . as lockdown period, we chose the dates from march at : up to may at : . the uk closed off schools [ ] on march and went into a wider lockdown on march. we also monitor a moving average of key quantities over the full period march to may . we note that all measurements are marked as "provisional" by londonair and still need ratification. to quantify the air quality, we monitor certain pollutant concentrations in both cities. in particular, we monitor nitrogen oxides (n o and n o denoted as n o x , where no distinction is made during the recording) as well as small particles, i.e. particulate matter of size less than . and micrometers (p m . and p m ). throughout this article, we will focus on p m concentrations as well as n o x concentrations. not only do n o x themselves have harmful impact on health but they are also commonly used to indicate the presence of other pollutants [ ] . in supplementary notes and , we also present plots for p m . and further analysis in which n o and n o are analysed individually for the london data set, instead of being aggregated into n o x . to obtain an initial impression of the data, we plot the temporal evolution of the pollution time series for individual locations and pollutants. the pollutant concentrations display very large fluctuations but with a considerable drop in overall pollutant concentration after the lockdown was initiated around march , see fig. . the trend of decreasing pollutants is also observable for other pollutants (see supplementary notes and ). from the time series plots, we can see that had similar trends and sometimes even higher pollutant concentrations than before the lockdown. specifically, for delhi, we observe a reduction in all pollutant levels after th march . during the lockdown, we can see some instances of an increase in pollutant concentrations in early to mid april. these may be due to the dust storms that occurred in delhi during those days. this effect can be clearly seen on the p m trajectory. for london, we notice a reduction of pollutants for the baseline n o x concentration (fig. a) . furthermore, pronounced peaks are visible in concentrations, both for n o x and for p m . these peaks persist after the lockdown is enacted and we will return to their systematic analysis via kurtosis values later. before moving on to probability distributions and moments,we have to point out that delhi has a much higher concentration of p m due to its sub-tropical climate and the high frequency of dust storms [ , , ] but also the decrease due to the lockdown is much more impressive than in the overall less-polluted london. next, we analyse how much the pollutant concentrations vary over the full lockdown period from mid march until end of april in , compared to the reference year of . to visualize how likely certain pollution concentrations are reached, we visualize the empirical probability density functions (pdf) for n o x (fig. ) and pm ( fig. ) at an urban, a suburban and a road location. overall, the lockdown in led to lower pollutant concentrations. the pdfs in tend to be broader than in , i.e. reaching higher pollution states more frequently. consistently, the distributions have a much more pronounced peak at low concentration levels. as expected, the pollution levels at the suburban location are generally lower than at the two other sites. we note that the london distributions are all very similar in their peak near concentration with a following decay. in contrast, the delhi data displays a maximum probability density at non-zero values, see e.g. the suburban measurement site. this might be explained by the different distributions observed when comparing n o and n o [ ] . in supplementary note , we further disentangle the impact of n o and n o for london. we continue to analyse the data more systematically, using the first and (normalized) forth moments of the empirical distributions. in particular, we compute the mean concentration µ = where u i is the pollutant concentration at step i, σ is the standard deviation and n is the number of measurements available. the mean µ reports the average pollution concentration and thereby provides a quantitative measure of whether pollutant concentrations did indeed drop systematically and by how much. the kurtosis on the other hand quantifies how many extreme events occur in the pollution concentration time series, i.e. how often highpollution states are assumed. as a reference consider the following: a gaussian distribution has a kurtosis of , while an exponential distribution has a kurtosis of . such exponential distributions were shown to approximate n o concentrations within short time windows [ ] . to exclude singular effects specific to one measurement site, we compute the moments for all ten measurement sites in both delhi and london. with the mean analysis, we quantify a clear trend: the mean of both n o x and pm concentrations for all locations is lower in than it was in . the observed drop in n o concentrations is quite substantial within some locations, such as r in london, recording a decrease from more than µgm − down to merely µgm − . the relative changes in other measurement sites are also impressive: at the u site, the mean dropped from approximately µgm − very close to . the same trend of decreasing mean values is also observed for particulate matter (p m in this case). however, the observed concentrations did not drop as much as the n o x did. this is likely linked to background sources and non-human factors such as pollen or dust contributing substantially to p m concentrations, see also section on attributing pollutants to sources. in contrast to the mean, the kurtosis in often exceeds the values recorded in substantially. this observation is valid for both n o x and p m and might be explained as follows: while on average the pollution levels were reduced, we still observe the similar maximum pollution states. these extreme pollution states contribute to a much higher kurtosis in than in , where large pollution concentrations were more likely. hence the probability density as such has changed during the lockdown. interestingly, the kurtosis and hence the tendency to observe (local) extreme we have seen decreasing pollution concentrations in during the lockdown period but still very high kurtosis values, in particular for london. here, we are answering two important questions: how much of the improved air quality could be attributed to weather effects, such as increased ventilation? secondly, do high-pollution snapshots differ between and ? the ventilation coefficient (vc) indicates the dispersive ability of the atmosphere. it is directly proportional to the assimilative potential or carrying capacity of the atmosphere [ ] . high ventilation carries more pollutants away from the region and typically reduces overall pollutant concentrations in megacities. details of how to compute the vc as a function of the planetary boundary layer (pbl) are explained in the methods. we determine the average ventilation coefficient for delhi during and as v c delhi, = m /s and v c delhi, = m /s, respectively. whereas for london it is determined as v c london, = m /s and v c london, = m /s, see fig. for detailed trajectories. even though delhi lies in a sub-tropical region and has a higher pbl height, its vc is lower than that for london due to relatively lower wind speeds [ ] . the national meteorological centre, usa and atmospheric environment services, canada, defined criteria for ventilation coefficients [ , ] . the criteria for high pollution potential are v c < m /s and mean wind speed < m/s. the dispersion potential is classified as low [ ] for v c < m /s, medium for m /s < v c < m /s and high for v c > m /s. thus, both the cities show a low dispersion and hence high potential for pollution. furthermore, the increased ventilation in london during has to be considered as small and cannot account for drastic changes in pollution levels. further analysis of wind statistics is given in supplementary note . in the previous subsection, we used the ventilation coefficient analysis to show that both london and delhi have the potential to display high-pollution states. here, we compare typical high-pollution states in and to better understand the effect of the lockdown. we select data with a typical time window of length t = days. details of how such windows are selected based on superstatistical approaches [ , ] can be found in [ ] . we select a snapshot within the data so that the variance of this snapshot is maximal, i.e. we select a local high-pollution state and then repeat this selection for . analysing these two high-pollution snapshots in fig. , we note that the data in can also reach high-pollution levels, almost as high as in (for london). however, these high pollution levels are less likely in then they were in . pm . high-pollution snapshots between and are almost identical, see supplementary notes and . let us discuss how the observed pollutant concentrations can be attributed to individual emitters, and how they changed during the lockdown. air pollution in london is a mixture of emissions created locally and those that come from outside the city. in the city, emissions are contributed from the activities of the . million population (population density of per sq.km). past studies estimated that about per cent of pm pollution and % of n o in the city originated from outside the city itself, while road transport is considered one of the main contributors of nox ( %) and pm ( %) pollution within the city. contributing to road transport are the . million licensed motorized vehicles, which are mainly cars ( . million) [ ] . therefore, to achieve clean air in london both local and national policies are required [ ] to reduce emission from within and from outside the city. in delhi, air pollution arises from a variety of local and regional emission sources. the city has a total population of . million with a population density of per sq.km, much higher than for london. the number of licensed vehicles in the city is . million, this time with a dominant share of two wheelers ( . million) [ ] . past studies estimated that about % of the pm pollution and % of the n o x emission in the city are contributed from the road transport sector. about % of n o x emissions is attributed to industrial sources [ ] . the transport sector is one of the most relevant anthropogenic sources which cause air pollution in delhi city. the continuous growing fleet of heterogeneous traffic in the city has resulted in heavy traffic congestion as well as decrease in vehicle speed on roads, leading to an increase in emission from vehicles. while in delhi the air quality situation has become worse over recent years, in london it has become better. a low emission zone was introduced for london in , and restrictions on polluting traffic have become more stringent since then, with hefty fees discouraging the use of cars in the inner city, in particular old diesel cars. the impact of the ultra low emission zone, which was introduced in april , is expected to be significant [ ] . it should lead to significant reduction in the number of people living in areas of poor air quality (where levels of no may exceed legal limits) -by per cent in central london and per cent london wide. there have also been average reductions in no levels at roadside sites of more than per cent (with weather effects removed) [ , ] . let us interpret these observations and sketch guidelines how air quality could be improved both in western and eastern cities alike. for delhi, the drastic reduction in pollutant concentrations is easily attributed to a substantial reduction in vehicular and industrial activities. not only did cars and industry emit fewer pollutants but also less dust was raised [ ] . hence, for the future, road traffic regulations and dust distribution should be monitored. for london, traffic and industrial activities in london and its surrounding decreased during the lockdown. hence, also pollutant concentrations dropped but the new mean distributions in n o x for example were higher than the lockdown n o x concentrations observed in delhi. with road and industrial activities contributing less, it leaves the residential areas, the geographical surroundings and background sources [ ] . all of these should be monitored more thoroughly and regulations should be considered to improve air quality in the long term. summarizing, we have compared the impact of covid- induced lockdown measures on the air quality in two major cities: delhi as an example for an asian city in an emerging country and london as an example of a western city, well developed but with a complicated brexit-induced future. mean pollution values tend to drop due to lockdown across all pollutants and for almost all investigated measurement sites. this holds for both london and delhi. however, we also noted certain significant differences: while pollutant concentrations dropped both in london and delhi, the reduction of nox and pm was much stronger in delhi than in london. a specific observation for london is the change of the probability distributions, manifesting itself as an increase of kurtosis during lockdown. this is explained by the fact that temporary high-pollution states during and before the lockdown are not qualitatively different in london, but persist. contrary, not only did the mean drop but also the extremely polluted states are much rarer in delhi during lockdown than before. contrary to an earlier analysis for the london data [ ] , we did not observe a statistically significant increase in particulate matter (pm) concentrations during lockdown. in delhi, there was a very substantial drop in pm concentrations. note that we compared the spring season with the spring season, while [ ] compared it to the winter . hence, the increase in pm concentrations reported in [ ] might be a seasonal effect. another study comparing the effect of the lockdown on different cities uses data based on daily air quality indices [ ] . this is different from our study, where we make use of higher-resolved time series and also study higher moments systematically, such as the kurtosis. the comparison between delhi and london during the lockdown provides insightful lessons on air quality control: a very strict lockdown in london did improve the air quality significantly, in particularly in terms of nox, highlighting the effectiveness of e.g. decreasing the traffic of vehicles with combustion engines. simultaneously, it also shows that a very drastic improvement by regulating traffic or industry alone will not suffice but pollution caused by other causes, such as residential or background, has to be taken into account as well. the picture for delhi is quite different: without a lockdown, the pollutant concentrations are regularly to times as high as in london, indicating a much worse air quality in general. the lockdown in delhi improved air quality very drastically. this points to the great potential of clean air in delhi if traffic and industrial emissions were reduced in the future by suitable control or regulation mechanisms. there still remain many open questions, such as: how did a lockdown affect other cities, e.g. on the american continent or in africa? which residential effects in western cities and which traffic effects in eastern cities can further be reduced to guarentee a long-term improvement in air quality? the lockdown was at an enormous economic cost, but can a small change in behaviour or a well-designed and balanced control mechanism lead to a sustainable and significant improvement in air quality in the future? in the aggregated moments, we introduced several road (r), urban (u) and suburban (su) locations, here we give the key to these abbreviations: for when plotting individual locations, we use the " " index, i.e. r , u and su if not specified differently. technically, the vc is given as a function of the height of planetary boundary layer (pbl) and wind speed, namely where we typically measure height in meters, wind speed in meters per second and hence the vc in m /s. to compare delhi and london and with , we obtained the approximate pbl height by using radiosonde data from the university of wyoming [ ] as follows. the pbl is the layer above the ground surface in which the pollutants are mixed and dispersed effectively. right above the pbl is an inversion layer, which prevents the vertical movement of each air parcel. here, we identify the pbl height as the lower boundary of this inversion layer, utilizing changes in potential temperature, relative humidity, moisture level, etc. the altitude corresponding to the maximum gradient of the potential temperature, mixing ratio and relative humidity profiles is taken as the pbl height similar to [ ] . all data that support the results presented in the figures of this study are available from the authors upon reasonable request. furthermore, the london air pollution concentrations are available on the londonair webpage [ ] . the delhi air pollution concentrations were provided by the delhi pollution control committee (dpcc), new delhi, but are unfortunately not publicly available. the code to reproduce figures, along with the publicly available londonair data is also uploaded here: https: //osf.io/jfw n/?view_only= b d cf c a ad dff a f b how air pollution is destroying our health contribution of nitrogen oxide and sulfur dioxide exposure from power plant emissions on respiratory symptom and disease prevalence short term exposure to air pollution and stroke: systematic review and meta-analysis state of global air nitric oxide: a multitasked signaling gas in plants nitric oxide production in plants: an update silk provides a new avenue for third generation biosensors: sensitive, selective and stable electrochemical detection of nitric oxide lung cancer and exposure to nitrogen dioxide and traffic: a systematic review and meta-analysis uk road travel falls to levels as covid- lockdown takes hold megacities and atmospheric pollution new directions: air pollution challenges for developing megacities like delhi pollution concentrations in delhi india during winter - : a case study of an odd-even vehicle strategy health impacts of particulate pollution in a megacity-delhi, india the effect of covid- lockdown measures on air quality in london in effect of restricted emissions during covid- on air quality in india effect of lockdown amid covid- pandemic on air quality of the megacity delhi, india superstatistical approach to air pollution statistics environmental research group (erg) at king's college london. london air coronavirus: strict new curbs on life in uk announced by pm suspended particulate matter distribution in rural-industrial satna and in urban-industrial south delhi variations in mass of the pm , pm . and pm during the monsoon and the winter at new delhi assimilative capacity and air quality index studies of the atmosphere in hebbal industrial area, mysuru ventilation coefficient trends in the recent decades over four major indian metropolitan cities the air pollution potential forecast program (us department of commerce, environmental science services administration the national air pollution potential forecast program air quality index, ventilation coefficient and pollution potential studies over bareilly city, uttar pradesh physica a: statistical mechanics and its applications from time series to superstatistics department for transport and driver and vehicle licensing agency . licensed vehicles by body type (quarterly): great britain and united kingdom up in the air: how to solve london's air quality crisis information on registered vehicles air pollution in delhi: an analysis low emission zones health and exposure to pollution high resolution vehicular pm emissions over megacity delhi: relative contributions of exhaust and non-exhaust sources lockdown caused by covid- pandemic reduces air pollution in cities worldwide atmospheric soundings an automated monitoring of atmospheric mixing height from routine radiosonde profiles over south korea using a web-based data transfer method the authors would like to thank the delhi pollution control committee (dpcc) new delhi for their support and cooperation to this study. this project has received funding from the european union's horizon research and innovation programme under the marie sklodowska-curie grant agreement no . the authors would also like to thank the delhi pollution control committee (dpcc) new delhi for their support and cooperation to this study. b.s., s.n., m.k. and c.b. conceived and designed the research. b.s., r.v., a.g. and h.h performed the data analysis and generated the figures. all authors contributed to discussing and interpreting the results and writing the manuscript. the authors declare no competing interests. key: cord- -c wkmt authors: moelling, karin; broecker, felix title: air microbiome and pollution: composition and potential effects on human health, including sars coronavirus infection date: - - journal: j environ public health doi: . / / sha: doc_id: cord_uid: c wkmt polluted air poses a significant threat to human health. exposure to particulate matter (pm) and harmful gases contributes to cardiovascular and respiratory diseases, including allergies and obstructive lung disease. air pollution may also be linked to cancer and reduced life expectancy. uptake of pm has been shown to cause pathological changes in the intestinal microbiota in mice and humans. less is known about the effects of pollution-associated microbiota on human health. several recent studies described the microbiomes of urban and rural air samples, of the stratosphere and sand particles, which can be transported over long distances, as well as the air of indoor environments. here, we summarize the current knowledge on airborne bacterial, viral, and fungal communities and discuss their potential consequences on human health. the current data suggest that bacterial pathogens are typically too sparse and short-lived in air to pose a significant risk for infecting healthy people. however, airborne fungal spores may exacerbate allergies and asthma. little information is available on viruses including phages, and future studies are likely to detect known and novel viruses with a yet unknown impact on human health. furthermore, varying experimental protocols have been employed in the recent microbiome and virome studies. therefore, standardized methodologies will be required to allow for better comparisons between studies. air pollution has been linked to more severe outcomes of sars (severe acute respiratory syndrome) coronavirus (sars-cov) infections. this may have contributed to severe sars-cov- outbreaks, especially those in china, northern italy, iran, and new york city. air quality is commonly described by the concentrations of pm (ranging in diameter from μm or smaller (pm ) to below . μm (pm . )) and of the gaseous pollutants, ozone (o ), nitrogen dioxide (no ), and sulfur dioxide (so ) [ - ] . current recommendations for pm . and pm by the world health organization (who) are and μg/m on average per year, respectively, while upper limits for no , o , and so are , (at ground levels), and μg/m , respectively (table ) . other agencies including the european union (eu), the chinese ministry of environmental protection, and the united states environmental protection ammonia (nh ) can form pm . , termed secondary fine dust, in a gas-to-particle conversion process [ ] . agriculture is the leading source of pm . secondary fine dust in many parts of the world including europe, which partially originates from nh of fertilizers (figure (b) ) [ ] . e major health problems described for exposure to air pollution are likely caused by pm and mainly affect the airways and the cardiovascular system [ ] [ ] [ ] [ ] [ ] [ ] [ ] . both pm and pm . can cause eye irritations, allergies, and rhinitis [ ] [ ] [ ] . globally, air pollution contributes to most deaths by chronic obstructive pulmonary disease (copd) and to large proportions of fatalities caused by lung cancer, ischaemic heart disease, stroke, and cardiovascular diseases (figure (c) ). pm can also carry heavy metals that are associated with cancer and other diseases [ , ] . e "beijing cough" is caused by polluting particles from inhaled smog [ ] . a recent study described a correlation between pm and hospital admissions for respiratory diseases [ ] . pm . can reach deeper into the lung tissue than larger particles [ ] . long-time exposure has been correlated with increased risks of chronic diseases, including copd that can develop into lung cancer (table ) [ ] [ ] [ ] ] . cardiovascular diseases linked to pm . include ischaemic heart disease and stroke [ ] . emerging evidence suggests causal associations between pm . and type diabetes, decreased cognitive functions, attention-deficit/hyperactivity disorder, autism, and neurodegenerative diseases [ ] . pm . may also be linked to premature birth, low birth weight, and sudden infant death syndrome [ ] . however, these potential effects of air pollution remain to be better established and quantified. ultrafine nanoparticles (pm and pm . ) can penetrate the skin, blood vessels, and the lymphatic system and are thereby distributed throughout the body; they can also act intracellularly [ ] . short-term exposure has been implicated in exacerbation of the abovementioned diseases, but long-term consequences are largely unknown [ ] . however, nanoparticles have been found to induce oxidative stress, which is associated with neurodegenerative disorders, cancer, chronic fatigue syndrome, and cardiovascular and gastrointestinal diseases [ , ] . moreover, exposure to ultrafine nanoparticles has been linked to cardiovascular diseases in a recent cohort study [ ] . worldwide, about . million people die prematurely from outdoor air pollution each year [ ] , and additional about . million due to household pollution, mostly in developing countries where cooking with open fires is common practice [ ] . of these people, % die from pneumonia, % from copd, % from lung cancer, and % due to cardiovascular diseases [ ] . in western countries, life expectancy is estimated to be reduced by an average of . months due to exposure to pm . [ ] . globally, the effect of air pollution on life expectancy is estimated to be more than twice as strong as the effects of water, soil, and occupational pollution combined [ ] . e estimated million premature deaths annually due to indoor and outdoor air pollution exceed those estimated for smoking (about million) and major infectious diseases (aids, tuberculosis, and malaria combined account for about million premature deaths) [ ] . recently, the journal bmc infectious diseases published a special issue on the airborne microbiome, emphasizing on the spread of pathogens via human breath [ ] . here, we focus on pathogens [ ] and urumqi [ ] in china, seoul in south korea [ ] , and milan in italy [ ] . additional studies investigated the subway systems of new york city, usa [ ] , oslo, norway [ ] , and hong kong [ ] . in these studies, air filters were used to collect pm; microbial nucleic acids were isolated, processed, and sequenced. however, experimental conditions varied which limits direct comparison of the results. in beijing, pm . and pm levels of a severe smog event were analyzed over seven days and the extracted dna was sequenced on an illumina hiseq sequencing system to determine microbial compositions [ ] . sequencing library preparation included a pcr step since amounts of dna extracted from the air samples were too small for direct sequencing, and generated reads were aligned to nonredundant ncbi complete genomes for taxonomic assignment [ ] . e detected microbes included bacteria ( . % and . % of reads in pm . and pm , respectively), eukaryotes ( % and . %), . % archaea, and . % viruses in both samples (figure (a) ). e most abundant bacteria belonged to the proteobacteria phylum, followed by actinobacteria, firmicutes, bacteroidetes, and cyanobacteria. most inhalable microorganisms were soilassociated and nonpathogenic. however, microbes known to cause allergies and respiratory diseases were detected, including the bacterium streptococcus pneumoniae, the fungus aspergillus fumigatus that can cause asthma and respiratory aspergillosis [ ] , and human adenovirus c that causes respiratory, gastrointestinal, and urinary tract infections [ ] . rna viruses such as influenza, coronaviruses, or rhinoviruses were undetectable by the employed method. e authors concluded that there was likely no risk for contracting infectious diseases from pollutant-associated microbes, but they recommended fixing soil by vegetation to reduce the amount of airborne microbes originating from fecal and terrestrial sources, including potential allergens [ ] . in this context, it is noteworthy that in , china announced to promote revegetation and to increase forestation levels from about % in to % by to tackle air pollution [ ] . like in the air of beijing, proteobacteria and actinobacteria were abundantly detected in the air of the city of urumqi in northwest china (figure (b)) [ ] . is study also used dna from filtered pm as the starting material, but taxonomic assignment was based on pcr-amplified s rrna genes (prokaryotes) and s rrna genes (eukaryotes) [ ] . several bacteria that may cause diseases in immunocompromised individuals but are typically harmless to the healthy population, such as acinetobacter, delftia, serratia, and chryseobacterium were detected. some of the detected fungal spores are associated with allergies [ ] , such as ascomycota, basidiomycota, and zygomycosis. beijing is known for the "beijing" cough, which affects many inhabitants independent of their age [ ] . is condition may pose an increased risk for other lung diseases such as infection by sars-cov- . indeed, exposure to smog has been linked to an increased incidence of respiratory infections [ ] and air pollution (such as pm and no ) correlates with increased severity of diseases caused by infections with coronaviruses such as sars-cov- and sars-cov- [ ] [ ] [ ] [ ] [ ] . sars-cov- may also be spread more efficiently in polluted air by attaching to pm [ ] . a virome study from seoul identified dna viruses at different locations, industrial, residential, and a forest (figure (c)) [ ] . after removal of particles larger than . μm by filtration, samples were concentrated by tangential flow filtration and virus particles were purified by cscl density centrifugation. dna was extracted and, without pcr amplification, subjected to pyrosequencing. reads were assigned to viral sequences using the camera databases and were taxonomically assigned with megan [ ] . e study was not designed to detect any rna viruses. e authors identified predominantly plant-infecting singlestranded dna (ssdna) viruses of the gemini-, nano-and circoviridae families. nanoviridae are aphid-transmitted plant viruses with circular ssdna segments [ ] . circoviridae also have circular genomes and infect plants, birds, pigs, fish, and insects [ ] . geminiviridae consist of two capsids, each containing a circular ssdna of opposite polarities [ ] ; some members can significantly damage crops [ ] . in addition, microviridae, ssdna phages infecting enterobacteria, were identified. e authors also detected caudovirales, tailed phages with double-stranded dna genomes. microviridae and caudovirales comprise the most abundant phage populations in the human intestinal tract [ ] and have also been identified in marine environments [ , ] . no human pathogenic viruses were detected. however, previously unknown ssdna viruses were identified. further studies will be necessary to address potential risks of the airborne virome on human health and on crop productivity. a study in milan, northern italy, evaluated forty air samples from ten days of sample collection during different seasons for bacterial and fungal communities ( figure (d)) [ ] . e study relied on extracted bacterial dna and pcramplified s rrna genes that were sequenced on an illumina genome analyzer iix; taxonomic assignment was carried out with the rdp bayesian classifier [ ] . around , mainly soil and plant-associated, bacteria per cubic meter of air were detected, with actinobacteria and proteobacteria dominating [ ] . significant seasonal and temperature-dependent variations were observed, for instance, with more actinobacteria on colder days. e authors did not address whether potentially pathogenic or allergy-inducing species were detected. e air of the new york city subway system was found to contain microorganisms mainly originating from outdoor air with a minor proportion from human skin [ ] . here, dna extracted from filtered air samples was subjected to pcr to amplify s and s rrna genes, the amplicons were subsequently sequenced by pyrosequencing, and taxonomic assignment was achieved using the silva database [ ] . on average, samples contained . % proteobacteria, . % actinobacteria, % firmicutes, . % bacteroidetes, . % cyanobacteria, and a complex mixture . surprisingly, no known human pathogens were detected, but some of the detected fungi may cause allergies. e severity of the outbreak of sars-cov- in new york city may have been partly due to the high population density, high mobility, pollution, and also preexisting conditions such as obesity, which affects about % of the us population and may be a factor contributing to more severe outcomes of covid- [ , ] . in oslo, aerosols were found to contain bacterial populations comparable to those of new york, with different genera in total, some of them of skin origin [ ] . concentrations were about -fold lower at night [ ] . similarly, the air of the hong kong subway system predominantly contained proteobacteria and actinobacteria (figure (f )) [ ] . is study relied on extracted dna subjected to pcr amplification of s rrna genes and illumina miseq [ ] . bacterial communities of air samples obtained in the subway systems of new york city [ ] (e) and hong kong [ ] (f ). bacterial communities observed for the troposphere [ ] (g) and on sand grains [ ] (h). sequencing. taxonomic assignment was achieved by aligning reads against the greengenes rrna gene sequence database using the uclust program [ ] . as observed in the new york city subway, bacterial communities showed significant similarities with those of outdoor air samples, with some human skin-associated bacteria also being present. again, known pathogenic bacteria were not detected in this study. besides soil bacteria, the beijing study identified fecal bacteria as a prominent component of air pollution, possibly originating from rural animal farms. in addition, human fecal bacteria from sewage are a possible origin [ ] . a study of the air microbiome of the graingrowing region vaud, switzerland, found a strong correlation between aerosolized and grain dust-associated fungal communities [ ] . e presence of allergenic and mycotoxigenic species in most samples suggests that these fungal species may contribute to work-related respiratory symptoms of grain workers who, however, are exposed to much higher concentrations than the general population [ ] . a study comparing rural and urban areas of the us found that urbanization leads to homogenization of the airborne microbiota, with urban communities exhibiting less geographic variability than rural areas [ ] . e rural air microbiome was found to contain large numbers of fungi that are known triggers of allergies, including alternaria and cladosporium [ ] . further studies are needed to assess to what extent diseases may result from exposure to the rural air microbiome and how they correlate with concentrations and exposure times. ere is evidence that microbes can be transported across very long distances and to high altitudes [ ] . bacteria represented on average % of particles between . and μm in diameter in either cloud-free or cloudy air obtained during the hurricanes earl and karl at - km altitude in the troposphere [ ] . numerous bacterial taxa were identified, including acetobacteraceae, burkholderiaceae, streptomyces, and pseudomonadaceae. proteobacteria was the dominant phylum ( figure (g) ). ere were significant differences in microbial communities between samples from the two hurricanes. however, bacterial and fungal species were common across all samples and may represent core members of the stratospheric microbiota [ ] . due to the poor resolution of the sequencing approach, the authors were unable to determine if any human pathogenic bacteria were present [ ] . e vertical distribution of bacterial communities in the atmosphere above the noto peninsula, japan, between -and , -meter altitudes, has also been shown to vary substantially and mainly contained soil and marine bacteria [ ] . e authors detected bacilli and proteobacteria, taxa that include known plant, animal, and human pathogens, which they speculated may be dispersed over large distances through high altitudes [ ] . whether these airborne pathogens can cause an infection after exposure to high altitude remains to be shown. sand grains can be transported over thousands of kilometers and transport bacteria, such that their populations may even be globally connected [ ] . sand grains of - μm in diameter from a german shore were shown to bind to bacteria composed of , to , different species, mostly of soil and marine origin [ ] . a core bacterial community was determined, with % of the bacteria present on all sand grains, and the other half varied. proteobacteria was the dominant phylum, followed by bacteroidetes and actinobacteria (figure (h) ). e identified bacteria were not discussed as potentially harmful for people. dust from desert soil was shown to transport diverse assemblages of bacteria to the mediterranean [ ] . e dust microbiome of the gobi desert was found to contain large amounts of alphaproteobacteria [ ] . soil bacteria were more abundant during dust storm events, while the relative abundance of bacteria of anthropogenic origin decreased [ ] . anthropogenic bacteria included those carrying antibiotic resistance genes, suggesting that the air microbiome may contribute to the spread of antibiotic resistance over long distances, whereby these genes may get diluted. no human health risks have been described [ ] . a concern, however, is the presence of antibiotic resistance genes in the sewage of livestock production that can be transported by water or through air [ ] . indoor pollution has been analyzed systematically using household air [ ] [ ] [ ] . here, western households must be distinguished from those in developing countries where open fires used for cooking contribute to pollution, a major health concern and cause of premature mortality [ ] . in western households, major sources of microorganisms are humans, pets, plants, plumbing, heating, ventilation/air conditioning, mold, and dust from outdoors [ ] . people typically stay most of the day indoors, and the air microbiomes differ significantly between environments such as schools, offices, households, and transportation and even between different rooms of the same household [ ] [ ] [ ] . one cubic meter of indoor air typically contains of both virus-like and bacteria-like particles, about a tenth of the concentrations found in outdoor air [ ] . fungal spores are less abundant and vary in numbers from around up to colony-forming units. humans emit around copies of bacterial and fungal genomes per hour [ ] . human stool can contain up to particles per gram of fecal-transmitted pathogens such as norovirus, shigella, or salmonella [ ] . it should be noted that humans carry microorganisms on their skin and × in their digestive tract [ ] and are the dominant sources of bioaerosols in indoor environments [ ] [ ] [ ] . key factors that determine the composition of the indoor fungal and bacterial microbiome appear to be moisture, age of the home, and dog ownership [ ] . potential effects on health may come from fungi as a significant source of allergens and mycotoxins [ ] , whereby indoor fungal communities are dominated by species originating from outdoors [ ] . fungal and bacterial spores can infect animals, plants, and humans [ ] , are highly stable, and can survive dormant for years. fungi such as cryptococcus spp. can cause fatal disease in immunocompromised populations, such as aids patients and transplant recipients [ ] . however, most microorganisms are benign and protect against harmful microbes, assist in the digestion, train the immune system, and lower the risk of autoimmune diseases [ ] . high doses of pathogens are, however, a risk under poor sanitary conditions and exposure to droplets and aerosols from infected people with high titers of pathogens. not surprisingly, the indoor air microbiota of hospitals contain a larger percentage of potential bacterial pathogens than do outdoor samples [ ] . indeed, many healthcare facilities are affected by the spread of sars-cov- and the resulting infection of healthcare workers and other patients. microbiome studies of hospitals may help to reduce exposure to pathogens; for example, rooms with higher airflow and humidity were associated with fewer airborne human pathogens [ ] . us, architectural design may help to reduce transmission of pathogens in healthcare facilities. ventilation systems of trains and airplanes typically recycle cabin air which is passed through filters that do not efficiently remove viruses. during the sars-cov- pandemic, this has resulted in almost complete shutdown of long-distance traffic and public transport in many countries. spread of the virus may only be prevented if all passengers are confirmed negative for sars-cov- infections via antibody testing or real-time viral tests indicating a virus-free status. such tests are available for influenza virus; they provide rapid results but are often less reliable than laboratory tests. yet, that may be the only fast solution for long-distance travel in trains or airplanes. keeping a safety distance and masks can only help to contain the spread of sars-cov- to a certain extent. much less is known about airborne viruses than about bacterial and fungal communities. e international committee on taxonomy of viruses (ictv) lists approximately , known viruses, of which about , can cause diseases [ ] . patients acutely infected with influenza virus can harbor up to virus particles per cubic centimeter in the blood stream and release approximately , aerosolized viruses by coughing or sneezing [ ] . indoors, influenza virus can reach concentrations of up to . × particles per cubic meter [ ] . even more infectious by airborne transmission is measles virus, which leads to almost % infections upon contact with an infected person [ ] . measles virus causes severe disease during childhood and can also be dangerous for adults, especially for pregnant women [ ] . noroviruses are relatively stable and can persist in the environment for several weeks [ ] . as few as to , norovirus particles can cause an infection [ ] . noroviruses account for about % of infectious diarrhea in humans. ere are at least genotypes and acquired immunity is short-lived and not cross-protective, so that a person may encounter several norovirus infections per year. norovirus is usually not seriously harmful to healthy adults, but to young children and the elderly [ ] . closed environments such as cruise ships are commonly affected by norovirus outbreaks. coronaviruses are single-stranded positive-sense rna viruses, with seven known to infect humans, including sars-cov- , mers-cov, and sars-cov- [ ] . e four others contribute to about - % of the seasonal acute respiratory infections [ ] . other seasonal viral infections are caused by influenza a and b viruses, respiratory syncytial virus, and rhinoviruses. respiratory viruses such as influenza or coronaviruses, including sars-cov- , are transmitted by respiratory droplets (larger drops emitted by coughing, sneezing, or talking) and aerosols (particles smaller than micron in diameter) when they reach susceptible mucosal surfaces of the eyes, nose, or mouth. indirect contact through smear infections from contaminated surfaces may occur but the amount of viable viruses may be small. e transmission of respiratory viruses can be limited by wearing face masks, which reduce the spread of droplets and aerosols between people. outdoors, the viruses are normally too sparse to pose a significant risk for infecting healthy people if a safety distance from other people is maintained. even though droplets may travel a distance of about cm before they sink, a safety distance for up to meters has been proposed to contain the spread of sars-cov- . face masks covering the nose and mouth can reduce droplet-based viral infections, while only surgical masks may protect against viral aerosols. air pollution as reviewed here can cause lung damage. is is a prominent problem mainly in large cities and manifests itself as "beijing cough," a dry cough highly prevalent in large and polluted cities [ ] . ere is evidence that people exposed to severe air pollution are more susceptible to infection with the present sars-cov- pandemic virus and experience stronger symptoms, not only in large cities of china but also in other parts of the world [ ] [ ] [ ] [ ] [ ] [ ] . pollution, including pm and no , likely contributed to the spread of sars-cov- and severity of disease in northern italy where pollution is severe [ , , , ] . in addition to air pollution, preexisting conditions such as overweight may contribute to disease severity, which may especially be relevant for the us, where close to % are clinically obese [ ] . sars coronaviruses have a history as pollutant through plumbing [ ] . for example, sars-cov- spread through the plumbing of the amoy gardens building in hong kong, which was not aerosol-tight and thereby allowed the virus to spread from the th floor of the -story building with contaminated sewage [ ] . also, in the hotel metropole in hong kong, twelve people were infected within hours, causing a chain of infection of up to , people [ ] . sars coronaviruses are extremely contagious [ ] . strict regimens for infected people in singapore successfully contained the sars-cov- outbreak. however, the virus even escaped twice from researchers working under high safety laboratory conditions [ ] . journal of environmental and public health phages, the viruses of bacteria, are abundant on our planet, in the oceans, air, soil, and other environments [ ] . ey can integrate into bacterial genomes but can also replicate by lysing the bacteria. about - % of bacteria in the oceans are lysed daily by phages [ ] . it is not trivial to characterize phages in an environmental sample; they typically require purification, concentration, and pcr amplification steps prior to sequencing and taxonomic assignment [ , ] . e identification of phages in human samples has recently been discussed in detail [ ] . phages were identified in the air of seoul and may therefore spread through the air [ ] . yet, they are not known to pose a risk for human health. pollution. an important question is whether air pollution influences the composition of the host microbiota. e gastrointestinal tract harbors the highest number of microbes and may be indirectly affected by high concentrations of pollutant pm [ ] . in humans, inhaled pm is rapidly cleared from the lungs and transported into the intestine where it may cause alterations in bacterial community compositions [ ] . in a mouse model of inflammatory bowel disease (ibd), orally administered environmental pm at a concentration representing a dose that could occur during periods of high levels of air pollution has been shown to significantly affect the gut microbiota [ ] . e proportion of firmicutes was increased, while bacteroidetes decreased and inflammatory responses and gut permeability were promoted (figure ) [ ] . epidemiological evidence suggests that air pollutants are also linked to an increased risk for ibd in humans [ ] . it has been suggested that air pollution, in general, and pm, specifically, may promote gastrointestinal diseases in humans [ ] . recently, it has been shown that pm inhalation may alter the intestinal microbiota in humans [ ] . as observed experimentally in mice, an increase in bacteroidetes and a decrease in firmicutes were observed, with health consequences yet to be determined. in addition to ibd, exposure to air pollution has been linked to type diabetes and obesity, possibly due to effects on the intestinal microbiota [ , ] . specific families of gut bacteria correlated with no x exposure; bacteroidaceae (phylum bacteroidetes) increased, while coriobacteriaceae (phylum actinobacteria) decreased [ ] . ese changes were associated with increased fasting glucose levels characteristic of developing type diabetes. in addition, polycyclic aromatic hydrocarbons and other organic pollutants present in pm can be metabolized by gastrointestinal bacteria and thereby alter the composition of the microbiota [ ] . alterations in the lung microbiome have been linked to various diseases such as cystic fibrosis, copd, and asthma [ ] . for example, patients with asthma and copd have increased relative abundances of proteobacteria compared to healthy individuals. interestingly, it has been shown that individuals exposed to higher levels of pm from household air pollution in malawi showed alterations of their lung microbiome, including higher relative abundances of potentially pathogenic bacteria of the genera streptococcus and neisseria [ ] . moreover, domestic biomass fuel use was associated with the presence of an environmental bacterium, petrobacter, which is normally not present in the lung [ ] . in summary, there is evidence that environmental pollution can affect the composition of both the gastrointestinal and the lung microbiota, with potential negative effects on human health. us, air pollutants, without directly transporting microbes, can indirectly affect the body's inherent microbiota. we are only beginning to understand the composition of aerial microbiomes and their potential impact on human health. however, from the current data, the following trends emerge for bacterial, viral, and fungal communities, despite the varying methodologies employed by the different studies. e bacterial communities of urban air microbiomes appear to be mainly composed of the phyla proteobacteria, actinobacteria, and firmicutes (figure ) , while less abundant populations such as bacteroidetes and cyanobacteria are more variable among samples [ , , [ ] [ ] [ ] [ ] . is is reminiscent of bacterial and viral microbiota of the oceans and the human intestinal tract that are composed of abundant core members and less-abundant variable populations [ , ] . potential human pathogens are typically below the detection limit in air samples even from closed environments such as subway systems, which means that there is not likely a significant risk for infection [ , , [ ] [ ] [ ] [ ] . likewise, ambient air appears to not contain significant amounts of known viral pathogens [ ] . however, only a small fraction of all viruses found in the environment are known, which makes it difficult to estimate potential effects of the air virome on human health [ ] . a major constituent of the airborne virome is bacteriophages that are not known to pose a risk for humans but may affect bacterial populations contributing to the spread virulence and antibiotic resistance genes [ ] . coronaviruses. sars-cov- is the cause of the current covid- pandemic of / , which has led to outbreaks of varying severities. high infection and death rates were observed, for example, in wuhan city and other parts of china, lombardy in northern italy, northern iran, new york city, usa, manaus, brazil, and johannesburg, south africa. in some cases, the severity of the outbreaks may have been linked to air pollution in conjunction with a high population density. other risk factors may comprise overweight/obesity, chronic cough, lung diseases such as copd, and infectious diseases such as tuberculosis and hiv/aids [ - , , , ] . sars-cov- most efficiently spreads through contact with infected people in indoor environments [ ] . is has prompted restrictions of public transport and long-distance travel in many countries worldwide. outdoors, virus-containing droplets or aerosols typically do not travel through air beyond the proposed safety distance of one to two meters in amounts sufficient to cause an infection. a major risk for human health is airborne fungi that can exacerbate diseases including allergies and asthma [ , , ] . studies on fungal air microbiomes may help to identify measures to reduce the abundance of fungal species linked to allergies, asthma, and other diseases in outdoor and indoor ambient air. for indoor environments, it has been shown that the abundance of specific components of the airborne microbiota can be altered by architectural design, humidity, and the degree of air flow [ ] . us, hypoallergenic architectural design can be envisioned. ere is evidence that fungal spores are particularly abundant in rural air [ ] . interestingly, exposure to indoor dust-borne alternaria spp. was found to be linked to a reduced occurrence of asthma, whereas indoor airborne aspergillus fumigatus and alternaria spp. were positively correlated with asthma [ ] . us, exposure to fungi may have both positive and negative consequences for human health, depending on the species and the type of exposure (e.g., dust-borne vs. air-borne). in general, however, it is difficult to compare current studies, as they relied on varying protocols. in the future, standardized methodologies will be helpful to allow for better comparisons between studies. on a larger scale, there is evidence that the microbiome is globally connected [ ] and that microbes may be transported over thousands of kilometers by dust and fine sand [ , ] and through high altitudes up to the troposphere [ , ] . whether potential pathogens can cause an infection after exposure to high altitude and the associated radiation, however, remains to be shown. while a direct effect of microbes transported over long distances on human health, such as infections, is unlikely, a potential concern is the dissemination of virulence factors and antibiotic resistance genes [ ] . exposure to pm, even without attached microorganisms, has been shown to alter the intestinal microbiota and may be linked to diseases such as ibd [ ] [ ] [ ] and type diabetes [ , ] . whether exposure to specific airborne microbes also influences these diseases remains to be determined. e authors declare that they have no conflicts of interest. karin moelling and felix broecker contributed equally to this work. figure : changes in intestinal microbiota due to pm in a mouse model. il- knockout mice, a model for inflammatory bowel disease, were fed with either standard mouse chow (left) or standard mouse chow 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global demand for ventilators. this demand has led to the development of numerous low-cost ventilation devices, but there has been less emphasis on training health professionals to use these new devices safely. the aim of this technical report is twofold: first, to describe the design and manufacturing process of the automated inflating resuscitator (air), a d-printed ventilator training device which operates on the principle of pushing a bag valve mask; second, to present a simulation scenario that can be used for training health professionals how to use this and similar, low-cost, d-printed ventilators in the context of ventilator shortages caused by covid- . to this end, the air was designed in an expedient manner in accordance with basic functionality established by the medicines and healthcare products regulatory agency (united kingdom) for provisional clinical use in light of covid- . in late , a cluster of pneumonia cases with unknown etiology were identified in wuhan, china. despite significant containment efforts, covid- has since spread widely. as of june , , there have been , global mortalities, with , of those coming from canada [ ] . critical covid- cases are characterized by respiratory failure requiring mechanical ventilation. in some countries, the demand for ventilators has far exceeded existing supplies. in italy, for instance, physicians have been forced to allocate ventilator access on the basis of triage criteria such as age and likelihood of survival [ ] . there is therefore an urgent need for alternative ventilators, which has led to the development of numerous devices. however, there has been less emphasis on how to train health professionals to use these new devices safely. consequently, in this report we describe the design and development of the automated inflating resuscitator (air), a d-printed ventilator training device. this technical report begins by considering the design elements that went into the air prototype, with reference to guidelines recently established by the medicines and healthcare products regulatory agency (mhra, united kingdom) [ ] . air contains the core components of a functional ventilator, with the possibility of further modular augmentation. in addition to the description of the ventilator, we also present a simulation case using air to train safety, operational ability, crisis resource management, and communication skills. the development of the air prototype followed mhra guidelines of the minimally acceptable ventilator to be used in hospitals during the current covid- pandemic [ ] . these guidelines influenced the choice of materials, design, and operative functions. this section discusses these considerations by focusing on four areas: . bag valve mask . oxygen flow . pressure valve . infection control the bag valve mask (bvm) was chosen for the construction of the air as it is inexpensive, easy to use, widely available, and already has its own safety features. bvms were created to temporarily replace mechanical ventilators during situations where mechanical ventilators are not available, and they function by manually providing positive pressure ventilation for patients who no longer have the ability to breathe [ ] . by incorporating the bvm, the air is intended to keep patients who need mechanical ventilation on ventilatory support, temporarily stabilizing their condition until a traditional mechanical ventilator becomes available. there are two main types of bvm: flow-inflated and self-inflated. flow-inflated bvms require a continuous gas flow or must be connected to an electrical source. self-inflated bvms expand after the bag is uncompressed. therefore, a self-inflated bvm, known also under the proprietary name ambu® (ambu a/s, copenhagen, denmark), was chosen for the air because it has this characteristic and because it is portable and easy to use [ ] . a bvm has four parts: exhalation port, patient valve, self-inflated bag, and an oxygen inlet. optional components include a positive end-expiratory pressure (peep) valve, an oxygen reservoir, and a pressure gauge [ ] . figure a presents a mechanical diagram of bvm components and is intended for engineering purposes. figure b illustrates how these components are assembled on an actual device. each air component was purchased, fabricated from commonly available commercial material, or printed using a d printer (see appendix ) . the self-inflated bag is placed separately from electrical components for safety purposes, which also allows it to be easily removed or replaced. the speed of the motor and the position of the bag can be adjusted to control the breath rate and tidal volume (tv) respectively. solidworks design model and stereolithography (stl) files can be downloaded from github here. figure provides a design overview of the air model. table . the operator can select their own motor system if the following requirements are met: the rated rotation speed falls in the range of - rotations per minute (rpm); rated torque is at least newton centimetres (n⋅cm). ventilation mode vcv influence the positive expiratory pressure (pep) and tv generated regardless of the bvm brand [ ] . in adults, resuscitators must be able to function properly with high oxygen flows, as during an emergency the flow meter can be changed and the resuscitator must remain in optimal condition. this consideration must be reviewed by all professionals who will eventually use the air. a malfunctioning manual or automatic resuscitator can put the patient at risk by providing an inadequate amount of oxygen [ ] . there are clinical situations in which professionals must personalize the amount of oxygen and, consequently, the percentage of oxygen mixed with atmospheric air offered to each patient. some bvms have been tested using oxygen flows of , , and litres per minute (l/min) with and without an oxygen reservoir, and this oxygen flow influences the fraction of inspired oxygen (fio ) offered to the patient [ ] . it is therefore important to know how an oxygen reservoir can influence the fio offered by the bvm device. evidence suggests that a bvm that allows the oxygen reservoir to be coupled, when tested without this accessory, reaches % fio when patients receive an oxygen flow greater than or equal to l/min [ ] . therefore, due to the possibility of variation in the performance of the bvm as a function of the oxygen flow used, healthcare professionals must adjust the flow so that the device provides the adequate amount of oxygen for each specific situation. in this case the healthcare professional must choose the specific venturi valve printed on a d printer and connect it to air so that fio best adapts to the patient's condition [ ] . the principles that govern bvm function also apply to the air; therefore, since the former can supply ambient air when no gas source is connected, the latter can be used in situations requiring limited fio , such as fio at % of the ambient air [ ] . when connected to the source of % oxygen, it is recommended to use a flow of to l/min at the entrance of the bag. the professional handling the air or bvm must also be aware that the position of the oxygen inlet, differences in oxygen flow supplied to the bvm, use of the oxygen reservoir, and the type of oxygen inlet valve can each contribute to fio variability for different resuscitator brands [ ] . the professional handling the air or bvm should keep in mind that the position of the air inlet, differences in oxygen flow supplied to the bvm, use of the oxygen reservoir, and type of air inlet valve can each contribute to fio variability for different resuscitator brands [ ] . there are two valves in the reservoir. a safety outlet valve relieves pressure inside the reservoir if excessive airflow is provided or if there is no manipulation of the bag. if the volume of gas in the reservoir is insufficient to fill the bag, another safety inlet valve allows the entry of ambient air. the peep valve can be attached to the expiratory port of the air. it prevents alveolar derecruitment during manual or automatic ventilation [ ] . another important consideration is the addition of the pressure relief valve to the bvm. in clinical practice health professionals do not usually monitor pressures while using a bvm. instead they use experiential knowledge based on direct patient observation. these professionals usually adjust the pressure by evaluating the expansion of the rib cage and resistance to ventilation, perceived subjectively by the operator's hands. however, in an emergency situation, one may not be able to view chest expansion continuously, or adequately perceive resistance to insufflation. for this reason, a pressure relief valve must be added to the bvm to ensure performance and safety of the device based on the needs of each patient. the pressure relief valve is not found on all brands of bvm. one must be added if there is none. when connecting the bvm to the device, it must be used with the pressure regulating valve unlocked and the pressure should be monitored with a manometer if one is available [ ] . mhra protocol guided the addition of the following features [ ]: . all parts coming into contact with the patient's breath are disposable or designed to be reusable. . all working components are contained within an impermeable casing. healthcare workers are able to manually wipe clean all external surfaces. . the air can connect to a viral hygroscopic filter. the air must be used by a professional who is familiar with the characteristics of bvms and the factors that impact ventilatory outcomes with these devices. in the event of power failure or component breakdown, the self-inflated bag can be easily removed from the air so that ventilation can continue manually. in this case, air will function similar to an unmodified bvm, although we have added safety mechanisms to air following protocols established by the mhra [ ] . the successful operation of air, therefore, incorporates two sets of skills: handling the bvm air's self-inflated bag, or bvm, can be used automatically or manually. this bag is made of a malleable material and must expand after each compression. the frequency of re-inflation determines the maximum minute volume, which in turn impacts the expiratory flow rate and thus the inspiratory:expiratory (i:e) ratio [ ] . as mentioned, the use of the oxygen reservoir will impact the fio offered [ ] . in addition, fio can be modified with venturi valves, which can be printed on d printers [ ] . operators should be able to manipulate fio using both of these components. air should be used only by qualified and trained professionals. for optimal use, training scenarios should prioritize both technical skill related to the device itself, and nontechnical skill related to the environment in which the device will be used. these skills can be organized into four categories: safety, operation, crisis resource management, and communication. . safety: proper knowledge and use of personal protective equipment (ppe) must be demonstrated at all times. also, the air non-rebreathing valve can become contaminated with patient fluids during ventilation. for this reason, it is necessary to frequently check the equipment throughout ventilation. other infection and contamination protocols must be adequately and regularly observed, and the participant should demonstrate sufficient functional knowledge to use air safely in each of its operative settings. the participant should gain a thorough understanding of the air's operative range and capacity. this understanding should be accompanied by technical skill, exhibited by the ability to quickly choose, interconvert, and modify operating modes in response to changing patient conditions. this operative competence is essential for patient safety. inaccurate compressions of the bvm bag can cause hypoventilation, hyperventilation, barotrauma, and reduced cardiac output. therefore, the same logic must be followed for air and similar devices. . crisis resource management: since the air is intended for limited-resource, high-acuity environments, participants should engage in scenarios that simulate these conditions. participants should be able to assess environmental cues, identify possible constraints, and prioritize action accordingly. successful assessment of this measure will require that participants demonstrate situational awareness, which can be divided into three stages: perception (recognizing basic features and dynamics of scenario); comprehension (integrating perceptions into holistic image and understanding relationship to goals); and projection (extrapolating information from first two stages to determine future status of situation) [ ] . communication is an important component in patient outcomes, and high-fidelity simulations have been identified as a method of promoting communication skills relevant to emergency procedures [ , ] . training scenarios should therefore emphasize communication between and within healthcare teams. successful assessment of this measure will require that participants demonstrate effective communication in the following three stages: information (accurately exchanging information using a technique such as 'read back, answer back'); understanding (constructing an acceptable, shared picture of the situation based on information); and coordination (working with others in synchronous, collaborative manner based on understanding) [ ] . communication with the patient and their family is also essential, particularly (in the context of covid- ) as a method of contact tracing. the following is presented to the participants as a stem of the simulation case: bvm, but the risk of the viral propagation remains great. there is only one traditional mechanical ventilator in the hospital and it is already being used by a -year-old female patient with severe respiratory failure but not covid- . referral hospitals are not receiving transfers due to the high influx of covid- patients." the patient's history is reported by his -year old son, who is waiting in hospital reception with his fiveyear-old daughter (the patient's granddaughter). seven days ago the patient started a dry cough with a fever. the dry cough worsened in the last two days, becoming productive and associated with severe shortness of breath. earlier this morning he was found in his bed, unconscious and breathing heavily. ten days ago, the patient's son and granddaughter returned from italy. on the evening of their return they visited the patient for dinner. today the child has a mild runny nose. the patient's son had a mild cold three days ago and is feeling well today. in this scenario, three individuals are infected by sars-cov- (the virus that causes covid- ) and the entire simulation will be based on the necessary care relevant to this information. the main areas of focus are safety, including the proper use of ppe; operating air when there is no mechanical ventilator available; crisis resource management; and effective communication during a high-acuity clinical event. these learning objectives are displayed in table . . safety: participants should be able to properly select and use, or describe the selection and use of all relevant ppe prior to interaction with the patient and air. this simulation can be performed in a controlled environment using a manikin with realistic lungs or an actor. respiratory parameters should be adjusted to simulate a critical covid- patient. these parameters must be measurable from the point of view of being stabilized by our air for a period of time determined by the facilitators. benchtop simulators can be used for the development of relevant psychomotor/technical clinical skills, such as airway management with the insertion of oropharyngeal airways (opa), endotracheal intubation, insertion of the chest tube, and other procedures. this simulation is intended for healthcare professionals operating in a ventilation shortage, who will have to use air or similar devices. therefore, other devices can be used if their basic operative function is sufficiently similar to air. facilitators should make this determination ahead of time in order to modify relevant portions of the scenario and also the assessment of operative skill ( table : learning objective ) as required. this simulation will be performed in a rural or remote hospital environment with few resources. the recommended materials, drugs, and equipment are listed in appendix . upon request, participants receive a list of patient data, including allergies, medications, and medical history (see appendices and ). the facilitators will be also given a list of the sequence to be followed in the patient's intubation procedure (figure ) . the facilitators choose the best path to be taken by the participants. ideally, the simulation is intended for healthcare professionals working in emergency care in rural areas or seeking additional training in the treatment of patients with severe respiratory failure. as the simulation takes place in a hospital environment, there is access to images and laboratory investigations. however, these resources may be limited or not. this will be at the facilitators' discretion and in accordance with local capacity. further, the facilitators should decide which regional, national, or international protocols will be observed. since these guidelines are currently being developed, we will not adopt any in particular. two healthcare professionals, both of whom are comfortable caring for patients with severe respiratory failure, should act as facilitators. these professionals should have experience with the use of traditional ventilators and manual resuscitators. one should be designated as the primary facilitator, providing guidance to the participants and helping with the general organization and execution of the case, while the second facilitator will be present to assess individual performance. facilitators are responsible for providing participants with the appropriate information as requested, including vital signs and other relevant physical examination results (see appendices and ). facilitators should examine the scenario in advance to identify possible limitations or technical problems, and they should also take time to fully familiarize themselves with air's functionality. the participants start the case in an emergency room (er), which contains a doctor and a nurse (the number of professionals can be changed). the only traditional mechanical ventilator is already in use by a non-covid- patient, who has required ventilatory support since last night. this small hospital is km from toronto where, despite a far greater number of intensive care unit (icu) beds with ventilators, there is a long list of patients who also need this equipment. the toronto hospital informs your staff that it is unable to receive new critically ill patients. however, the local team has access to a mechanical ventilator that was developed from a bvm. this is the only available device capable of keeping a patient with severe respiratory distress alive for a prolonged period of time. in this simulation case, we presented three people that are infected by sars-cov- . a -year-old elderly man with severe respiratory failure, an asymptomatic year-old adult man, and a -year-old child with only a mild runny nose (these last two are in the waiting room). before starting the simulation, participants must be submitted to the fictional contract, which recognizes that all processes occurring during the simulation should be treated as if they were "real", so that the objectives of the simulation can be achieved. during this period, facilitators present the simulation scenario and all necessary precautions, before introducing the air and describing its function. finally, participants are encouraged to assign roles in preparation to receive the patient. if there is a limited supply of participants, the paramedics team can only be reported by the facilitators, as the main objective of this simulation is training with the use of air and care involving a patient with covid- . figure displays the sequence to be followed in the patient's intubation procedure. justification: they can be contaminated and contaminate people nearby. guide the correct use of the surgical mask for those with respiratory symptoms (cover mouth and nose). findings: the patient's son and granddaughter are having trouble using the mask correctly. justification: misuse of the mask can contaminate people nearby. determine the availability of room used for infection control (e.g., negative pressure room). if none is available, adjust airflow through receiving room to minimize risk of airborne transmission. make seasonal modifications as necessary. findings: in the summer: the window is closed, the fan is on and the door is open. in winter: the draft heater is on. justification: the air stream can carry aerosols to other rooms and contaminate nearby environments. confirm that the team has properly disinfected the room and instruments used (including air) before and after patient visits with % alcohol or % sodium hypochlorite. findings: participants did not ensure the room, instruments, and air were adequately cleaned before receiving the patient. justification: failure to adequately and regularly clean surfaces before and after patient visits increases infection risk. wash hands with water and liquid soap or use % alcohol before using ppe. justification: lesions of the mucosa of the uvula and posterior wall of the hypopharynx, compressions of vessels, evolving with cyanosis of the tongue and macroglossia for a few hours, compression of the lingual nerve, with anesthesia in endotracheal tube or cricothyroidotomy ( figure ) . topography of the path of this nerve, compression of the recurrent laryngeal nerve and, consequently, uni or bilateral vocal fold paralysis, leading to dysphonia and compression of the hypoglossal nerve, with transient paralysis of tongue movements. verbalize intention to exchange the laryngeal mask for a definitive airway (endotracheal tube or cricothyroidotomy) (figure ). findings: participants do not verbalize their intention to change the non-definitive airway to a definitive one. justification: lack of coordination among team members can lead to loss of time in requesting the necessary equipment for this procedure. pre-oxygenate the patient using the bvm with sufficient flow to guarantee o to % (minimum l/min) (figure ). adjust air parameters prior to patient connection (table ) . findings: participants do not adjust air parameters before connecting patient. justification: time is wasted adjusting air parameters after patient is connected. transfer patient from bvm to air using a kelly clamp (figure ). findings: participants do not clamp the tube before switching from bvm to air. justification: a kelly clamp is important for clamping the tube when there is a need to change circuits/ventilators, in order to minimize aerosol production ( figure ). initiate continuous sedation. target rass: - ( figure ) . ration equipment and medications appropriately. findings: participants waste tubes, drugs, etc. justification: resources are already limited and wasting equipment and medications can lead to huge losses. request laboratory/imaging tests only when required (see appendix ) . findings: participants order laboratory or imaging tests when they are not necessary. justification: wasting laboratory/imaging tests will prevent these resources from helping patients who need them. collect information about medical care limitations from the referral hospital before patient arrival obtain all relevant patient information from paramedics and/or prehospital team. findings: participants do not collect patient information from paramedics, such as why they were called, how they found the patient, vital signs, who their companions are, where they are and how many there are. justification: not collecting information from the prehospital team can lead to poor patient care and a high risk of contamination by the team because they are not prepared to receive a suspect from covid- . share patient information with the rest of their team. findings: participants who collected complete patient information do not share it with the rest of the team. justification: failure to share information with the rest of the team can put patient care at risk and also a high risk of contamination by the team. clearly and confidently communicate a plan based on patient information. findings: participants neglect the importance of the correct use of ppe, the importance of exchanging a non-definitive airway for a definitive one, the importance of requesting a mechanical ventilator for long-term use and / or transfer to an icu and the importance of an effective communication to gather all information about the lack of available resources. back' to maintain a shared understanding of the situation, allowing them to develop collaborative action accordingly. obtain patient's medical history. findings: participants do not collect the patient's complete medical history. justification: failure to collect a complete patient history can lead to diagnostic errors, ineffective treatment, risk of contamination by the medical team and ineffective isolation conduct with family members suspected of being infected with covid- , causing them to contaminate close people. make an effort to establish trust and rapport with the patient's family. during this session, the "debriefing with good judgement" model can be used [ ] . this model uses an advocacy-inquiry approach to initiate a process of self-reflection, frame analysis, and behavioural change. in this method, facilitators address unexpected actions by first indicating their own expectation regarding correct action (advocacy), and then testing that expectation by investigating the cognitive frame that led to participant action (inquiry). the rationale behind this strategy is to clearly identify discrepancies between expected and performed actions without eliciting a defensive or otherwise counterproductive response on the part of the learner [ ] . in this way, the facilitator attempts to cultivate favourable conditions for selfreflection. participants should have the opportunity to share their positive and negative experiences, and facilitators should invite suggestions on how the simulation can be improved. this can be followed by a didactic session in which facilitators demonstrate appropriate use of ppe, as well as operative functions of the air and bvm. facilitators can also take this time to share and discuss strategies for nontechnical skills relevant to crisis resource management and team communication. lastly, facilitators may provide details relevant to the medical regulation of communication between institutions and local ambulance teams. the aim of this technical report was twofold: first, to describe the design and manufacturing process of the air, a d-printed ventilator training device which operates on the principle of pushing a bvm; second, to describe a simulation scenario that can be used for training health professionals how to effectively and safely use this and similar, low-cost, d-printed ventilators in the context of ventilator shortages caused by covid- . the development and manufacturing of the ventilator followed an iterative design cycle between clinical experts (er doctors), mechanical engineers, and education researchers. the team used mhra guidelines to develop the initial ventilator. the development and manufacturing took four weeks, with equipment costs of $ cad, and human resource commitments: doctors - hours, engineers - hours, researchers - hours. proper assessment of the clinical functioning of this prototype is outside of the scope of this technical report, and will be presented in a follow-up case study. based on the recommendation of scalese et al. describing the effectiveness of simulation training for highacuity clinical environments, we have also developed a simulation scenario [ ] . our scenario helps front line health professionals become familiar with the use of air in terms of safety and operations. further, the scenario was aimed to train crisis resource management and communication skills when operating air in the context of a ventilation shortage. while the scenario is based on covid- , it can be adapted to various settings where access to care and resources may be limited. our scenario also emphasizes the care of every patient who needs ventilatory support, not only those caused by covid- , as the deficiencies here can significantly impact care for all types of critically-ill patients. the air prototype exhibits most of the minimum mhra specifications, but additional components should be added prior to clinical use [ ] . to this end, the most urgent areas of future research are described below: gas or electricity supply failure; inspiratory airway pressure exceeded; inspiratory and peep pressure not achieved (equivalent to disconnection alarm); tv not achieved or exceeded. tv; frequency; peep; fio ; ventilation mode; actual current airway pressure. monitors should display continuously so the user can verify settings and modify as needed. if pressure support mode is provided there must be real time confirmation of each patient's breath and an alarm if below acceptable range. the first aim of this report was to describe the design and manufacturing process of a d-printed ventilator training device, the automated inflating resuscitator (air), which operates on the principle of pushing a bag valve mask (bvm). the current air prototype exhibits many of the mhra safety requirements, but an assessment of clinical viability falls outside the scope of this report. the modular design does however provide a template upon which further functions can be added. the second aim of this report was to describe a simulation scenario that can be used for training frontline workers in how to use air and similar ventilators. the scenario was designed to train safety, operative ability, crisis resource management, and communication skills. the context focused on ventilation shortages caused by covid- , but it may be adapted to simulate other conditions where similar ventilation devices are used. videolaryngoscope (disposable blades number and ) (if available); . conventional laryngoscope (curved blades numbers and , straight blade number ); . orotracheal tube epinephrine: mg/ml; . . % nacl solution or ringer lactate ml; . norepinephrine: mg/ml. equipment . mechanical ventilation circuits (bvm and air); . monitor & capnograph (if available); . infusion pump with channels or infusion pumps; . for peripheral access: pair of procedure gloves, alcohol swab, micropore cm, scissors, tourniquet, peripheral venous catheter, two-way connection, tray; . for central access: single, double or triple lumen catheter, central access puncture tray, chlorhexidine degermante, alcoholic chlorhexidine, sterile apron, gloves, mask, cap, glasses, micropore tape; ml and ml syringes world health organization: coronavirus disease (covid- ) situation report - resuscitation and intensive care: clinical ethics recommendations for the allocation of intensive care treatments in exceptional, resource-limited circumstances medicines and healthcare products regulatory agency: rapidly manufactured ventilator system manual resuscitators and spontaneous ventilation-an evaluation self-contained resuscitation equipment alterations in peak inspiratory pressure and tidal volume delivered by bras pneumol comparison of the fio delivered by seven models of the self-inflating bag-mask system evaluation of adult disposable manual resuscitators . respir care textbook of neonatal resuscitation covid- and the role of d printing in medicine to bag or not to bag? manual hyperinflation in intensive care the use of a pressure manometer enhances student physiotherapists' performance during manual hyperinflation the effect on expiratory flow rate of maintaining bag compression during manual hyperinflation design and evaluation for situation awareness enhancement city mouse, country mouse: a mixed-methods evaluation of perceived communication barriers between rural family physicians and urban consultants in newfoundland and labrador emergency management of anaphylaxis: a high fidelity interprofessional simulation scenario to foster teamwork among senior nursing, medicine, and pharmacy undergraduate students non-technical skills for surgeons system handbook v debriefing with good judgment: combining rigorous feedback with genuine inquiry simulation technology for skills training and competency assessment in medical education animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. this can be constructed out of a trash bag; . shoes: shoes that are easily cleaned and don't need to be touched are preferred. shoe covers aren't recommended as removing them may increase exposure. seven days ago the patient started with a dry cough associated with headache and fever of . °c. he used paracetamol, which improved headache and lowered fever to . °c for one day and returning to - °c the next day. the dry cough became productive days ago associated with severe dyspnea and a fever that did not go down with the medication. this morning his son tried to call him but unsuccessfully. going to his house he found him unconscious and breathing hard in his bed. the patient was admitted by paramedics, under positive pressure ventilation, using a laryngeal mask and using a bvm with filters to contain virus. medications nonemedical history appendectomy at age . bacterial pneumonia at age , treated with azithromycin and recovered fully. has never smoked or drank alcohol. swims every day and has eaten well for years. father died in a car accident years ago and his mother died years ago of natural causes. no history of diseases. no siblings. human subjects: all authors have confirmed that this study did not involve human participants or tissue. key: cord- -for qa s authors: chandrappa, ramesha; chandra kulshrestha, umesh title: major issues of air pollution date: - - journal: sustainable air pollution management doi: . / - - - - _ sha: doc_id: cord_uid: for qa s environmental issues change from place to place and time to time. the issues include local as well as global issues. the understanding of issues is necessary to find solution. air pollution issues have changed over a period of time. issues like atmospheric brown cloud, climate change, hazardous air pollutants, black/muddy snow which are hardly discussed few decades back have now gaining importance. this chapter elaborates major issues due to air pollution. atmosphere and its layers when the solar system condensed out of "primordial solar nebula" which is nothing but interstellar cloud of gas and dust, the situation was not as complex as today and air pollution was not an issue. the early atmosphere of this planet was believed to be blend of carbon dioxide, nitrogen, water vapour and hydrogen. the early atmosphere of this planet was slightly reducing chemical mixture as compared to present atmosphere which is strongly oxidizing. with lapse of time, distinct layers of the atmosphere were formed with distinct characteristics. these are described below. troposphere: it is the lower most layer of atmosphere extending from the earth's surface to - km altitude depending on time and latitude ( fig. . ). this layer is characterised by declining temperature with height and rapid vertical mixing. temperature at the ground is about °c and it decreases gradually till the tropopause is reached. the tropopause is the boundary having constant temperature which separates the troposphere and stratosphere. the decrease of atmospheric temperature (t) with height (z) is called as lapse rate (α) which is expressed as follows the change in temperature of a mass of air as it moves upwards is called as adiabatic lapse rate. the dry adiabatic lapse rate (dalr) and the moist adiabatic lapse rate (malr) are . and . °c/km respectively. actual change of temperature with altitude for the stationary atmosphere or temperature gradient is known as environmental lapse rate (elr). generally, decrease of . °c/km is considered as environmental lapse rate. in the troposphere, atmospheric pressure also decreases rapidly with the altitude. one can understand that climbing to an altitude of . km, would put you above % of the atmosphere's molecules where atmospheric pressure is mb only. actually, the heating of the surface creates warm air at surface. the warm air rises, but air expands as it rises and cools as it expands (adiabatic cooling). typically, the troposphere is characterized by warm air at surface and cooler air above. if the cooler air exists at surface and the warmer air above, this is called as buoyancy. if a rising air parcel becomes saturated condensation occurs. the condensation warms the air parcel due to the release of latent heat. so, a rising parcel cools less if it is saturated the atmosphere near earth's surface is divided into different layers based on wind behaviour: the laminar sublayer also called the viscous sublayer, is the region in which the flow is laminar. with respect atmosphere it is usually less a centimetre. the surface layer extends from ≤ - m. the heat and vertical turbulent fluxes in this layer are constant. the ekman layer is the layer in a fluid where force balance between pressure gradient force, turbulent drag and coriolis force are balanced. it was named after scientist vagn walfrid ekman who explained the phenomena for the first time. ekman layer extends to height of - m. in this layer wind direction is affected by earth's rotation. wind speed his layer generally increases with height. free atmosphere is the layer above ekman layer in which the effect of the surface friction on the air motion is negligible. stratosphere: it is positioned just above the troposphere extending from - km. in the stratosphere, temperature increases with altitude, from − °c at base to °c at the top of the stratosphere. the increase in temperature is basically due to the absorption of solar energy by the ozone layer. ozone (o ) is effective absorbing species for solar uv radiation ( - nm with a maximal absorption at about nm) in the stratosphere. generally, uv-c ( - nm) which is highly harmful is entirely screened out by dioxygen (< nm) and ozone (>about nm) before km height. uv-b ( - nm) radiation is mostly screened by ozone layer. uv-a ( - nm) reaches earth surface having small damage e.g. premature ageing of skin etc. mesosphere: just above the stratosphere, the mesosphere exists extending from - km altitude, the space shuttles orbit in this layer of the atmosphere. due to decrease in solar heating, temperature decreases with altitude in the mesosphere, °c at base, − °c at the top of the mesosphere. the top of the mesosphere is the coldest region of atmosphere. polar mesospheric clouds of water ice are seen in this layer which are known as noctilucent clouds. these are highest clouds in earth atmosphere and are seen mostly during summer months between and degree n and s. the d layer of ionosphere also exists in mesosphere which is seen during the day time. meteors burn up in the mesosphere while entering the earth atmosphere. thermosphere: thermosphere is the last layer of the atmosphere which exists at km and above up to exosphere. in the thermosphere, the temperature increases with altitude as atoms of this layer are accelerated by solar radiation. temperature at the base of the thermosphere is − °c but it is °c at km and °c at upper part. though the temperature of this layer is very high but the heat content negligible. auroras exist in thermosphere. the auroras are seen due to the effect of energetic particles (electrons and photons) coming in the solar wind. charged particle entering the atmosphere ionize atmospheric constituents. the aurora can be seen best in the dark sky or 'magnetic midnight' time. in northern latitudes, the effect is known as the aurora borealis (or the northern lights), named after the roman goddess of dawn, aurora, and the greek name for the north wind, boreas, by galileo in . international space station orbits in upper part of thermosphere ( - km). in the thermosphere, ionization occurs due to uv rays. e and f regions of ionosphere exist in this layer. at the exosphere (beginning - km), the atmosphere turns into space. ionosphere: in fact, the ionosphere extends from - km covering partly mesosphere and thermosphere. it has diurnal and seasonal variation as the ionization depends upon sun and its activity. as mentioned earlier, the d region of the ionosphere exists in the mesosphere while e and f regions of the ionosphere exist in the thermosphere. ionosphere is a shell of electrons and electrically charged atoms and molecules. e and f regions are present at nights. d region is formed during day time when the e and f regions become much stronger. often during the day, the f region is further differentiated into f and f regions. in the d region, uv rays ionize no and x-rays ionize o and n . in the e region, x-rays and far uv ionize o À . e region can reflect radio waves lower than mhz. extreme uv rays ionize o in the f-region during nights. f layer is responsible for short wave (hf) radio communication for long distances. ever since the discovery of fire, air pollution has been a problem. "heavy air of rome" in a.d., has been recorded by roman philosopher seneca. in , king edward i prohibited burning of coal in london (william and lou ) . by the s, people were using coal as fuel in processes like limekilns and metalworking leading to air pollution which had black smoke as well as oxides of sulphur. late th and early th centuries saw dramatic changes in manufacturing, agriculture, mining, production as well as transportation. invention of electric power in the nineteenth century resulted in coal fired electric generation in s. very famous example of air pollution is the smog formation around los angeles during the s which led to the passing of first state environmental legislation in usa. in , the air pollution control act was enacted in usa which was the first federal environmental legislation in the country. later on in s, oil overtook coal as the source of primary energy. extensive use of oil led to the emissions wherever vehicles moved. with the industrial revolution in the post eighteenth century economy changed to machine-based manufacturing in many of the present developed countries. mechanization of the textile industries and iron-making techniques increased demand for fuel and their by air pollution in those areas of such activities. the developments in th century led to second industrial revolution. the construction activity also saw shift in construction material as well as technology. the invention of cement replaced mud walls ( fig. . ) and increase in cement demand lead to emissions from this sector. as the european and american markets were saturated, asian markets opened up for vehicles which are currently unbalanced where in poor people ride on bus top or trucks while rich people ride in individual cars ( fig. . ) . while the economic crisis in greece resulted in reduction of air pollution (vrekoussis et al. ) china witnessed dramatic air quality detonation last decade. analysis of data from monitoring network created by who and unep in cities in developed as well as developing countries shows that over the past - year indicate that the lessons of earlier experiences in the now developed countries have yet to be learned. air pollution in of the megacities shows that ambient air pollution at levels where serious health effects (david et al. ) . the rise of population in the developing countries in future with a lack for air pollution control will worsen in many more cities. in the beginning of s when the rapid growth in europe lead to environmental pollution and air pollution of london which resulted in death of more than people was fresh in memory the united national conference of the human environment in stockholm in lead to foundation of international cooperation in this regard. this is followed by series of development that aimed to bring down air pollution. convention on long-range transboundary air pollution in was signed unece countries. governments of unece member states signed the convention on long-range transboundary air pollution on november . the lphur protocol or % protocol aimed to bring down % so at national level by countries of unece region. all business decisions affect the air and atmosphere. hence, like water which is purified, packaged and priced, soon pure air will also be priced. there are oxygen bars opened up in many parts of the world to supply oxygen to customers. however, inspite of urgent need of stringent air pollution policies and regulations in several parts of the world, air pollution control is still not a political priority as compared to the business and economy in many parts of the world. as a result the pollution is continued in one form of other, many forms are not even monitored and controlled. over the years only few conventional air pollutants such so , no , fig. . traffic from a developing asian country particulate matter, o etc. are monitored by the researchers and the pollution control authorities. pollutants such as persistent organic pollutants (pops) were neglected in the past but have been considered recently for continuous monitoring due to their severe health effects. both organic as well as inorganic air pollutants cause deadly deceases and hence, their monitoring is very important for humans and environment. while many developing countries took the matter seriously others were only keen to satisfy international community. even though environmental legislations were enacted all over the world, the capacity of enforcing agencies was limited mainly due to insufficient knowledge and research capacity with enforcing agency. many organisations had very few staff to start with limited budget to monitor and travel. the absence of expertise had either lead to improper monitoring by selecting improper sampling site/methodology and poor analysis. many organisations till date are dogged with insufficient manpower to the extent of one to ten technical/scientific staff for a million of citizens. what makes air pollution most challenging compared to other pollution is its complexity. as mentioned above, unlike water which can be contained in a container for easy study it is difficult to simulate the atmospheric setup in a laboratory. further, aerodynamics at earth's surface cannot be easily explained by mathematics as it occurs in nature. a variety of factors like radiation, friction, flow pattern, chemical reaction, influence by biological setup, changing climate, changing weather, changing living style, new inventions, social changes, law of the land, attitude of the people, physiology of people, economic changes of the region together is responsible for the scenario at a given time at a given reason. due to complexity of problem, air pollution has not been thoroughly understood by many developing countries and is not a priority. issues like the poor governance, low research capability, illiteracy, corruption, national/international conflicts and political instability has often cause of low attention to air pollution in spite that millions die due to air pollution all over the world. in spite of magnitude of the problem, the loss of life and wealth due to air pollution is invisible to many government servants. this could be attributed to low emotional intelligence of people responsible to serve the people who act as trustees of the country to protect interest of people and property of the country. illiteracy among the citizens was also cause for not complaining about the pollution. the use of staff for other duties like election/census/sports has also one of the many reason for poor implementation of environmental laws. many of the enforcing agency are worried about financial expenditure rather pollution control as misappropriation of financial resource could end up officer responsible for appreciation in jail. on the other hand, the unaccounted pollution is not at all fault as serious as financial misappropriation. the environmental laws can also be misused to raise funds or cause inconvenience to rivals by people in power. as shown in fig. . , issues, causes, influencing factors and impacts of air pollution can be attributed to many aspects which are not quantifiable. the corruption among governance, low ethics among industries, non availability of technology, incapability to adopt new technology and low research capability plague many countries. in spite of enthusiasm shown by many international agencies to support the cause it is often denied or poorly adopted by beneficiary countries. the major sources of pollution are combustion process, industry, transportation, waste disposal, use of agro chemicals, and respiration of living organisms (famhy et al. ). none of these sources can be avoided as they are meant for survival of the humans. apart from these sources other sources like accidental fire; wind storms; natural disasters; education/research; decomposition of dead and decaying matter; wars; bursting of crackers; use of explosives; sports/events; testing/practicing of use of war weapons; launching satellites; volcanic eruption; construction; methane generation in rice fields due to biodegradation; demolition of buildings; methane generated by ruminant animals during digestion of food; painting; processing of grains; soil erosion and weathering of rock/minerals add to pollution. service sectors like healthcare, software, business process out sourcing (bpo) also contribute air pollutants while using equipments/air conditioners/ transportation. release of pathogens from health care establishment, animal rearing, slaughtering, and research can be far more detrimental compared to conventional pollutants. unlike war and crime effect of air pollution usually happen in slow manner taking years before actual impact is visible. some of the acute impact in recent past like episode in chernobyl and bhopal has been faded away from memory of people due to other burning issues at individual regions. common air pollution issues are discussed below. the term "acid rain" is commonly used to refer the wet (fog, rain, cloud water, snow, sleet, and dew) and dry (acidifying gases and particles) deposition of acidic components. in this regard, it is important to know that "clean" or natural rain is also slightly acidic (but usually will not be lower than . ) due to carbonic acid carbonic acid formation in atmosphere according to the following reaction (charlson and rodhe ) : due to this fact, ph value of . is considered as the ph of natural precipitation, below this value, the precipitation is called as acid rain. sometimes, natural rain can also contain nitric acid formed due to electric discharge such as lightning. it can also have acidity due to organic acids contributed by vegetation (galloway et al.) . basically, acid-base reactions in the atmosphere determine the ph of precipitation. as we know that the atmosphere is highly oxidizing medium, gases such as so and no x are oxidised to sulphuric and nitric acids respectively. such oxidation occur through homogeneous or heterogeneous pathways as described below oxidation of so gas phase homogeneous oxidation reaction so þ oh ! hso ð : Þ aqueous phase oxidation reaction homogeneous aqueous-phase oxidation of so takes place by its dissolution and dissociation in water heterogeneous oxidation however, so is also oxidized through heterogeneous reactions involving calcareous soil dust and carbon soot infact, pathway of the reaction ( . ) is the major route of so oxidation which controls occurrence of acid rain in dusty regions. the soil-dust which is generally dominated by caco effectively scavenge atmospheric so forming calcium sulphate in the atmosphere (kulshrestha et al. ) . due to this reason, in the regions where ambient levels of suspended particulate matter are very high violating the limits of national ambient air quality standards (naaqs), the ph of rain water has also been reported very high (kulshrestha ) . in these regions, the levels of ambient so are recorded very low due to same reason. figure . a shows that even at higher sulphate levels, the ph of rain water is higher in indian region but in the acidified regions such as united states, the ph of rain water is highly acidic decreasing with the increase in sulphate concentrations ( fig. . b ). this suggests that in the acidified regions, sulphate is present as sulphuric acid whereas in dusty regions, sulphate is present as calcium sulphate in rain water. rain water dominated by crustal components or mineral dust such as calcite or dolomite or dolomite has lower acidity. most of indian soils have very high ph. the ph of rain water in india (table . ) has been termed as the mirror image of the ph of soil of that area (kulshrestha ) . long-term measurement in lhasa, of tibetan revealed that ph values, such as . were observed during - period due to alkaline as well as soil-borne continental dusts (zhang et al. ) . the ph of precipitation during - , in israel is mostly alkaline with ph . ± . (mamane et al. ). oxidation of no no is oxidized by oh no þ oh ! hno ð : Þ such no oxidation process is faster than so oxidation by oh. further, through ozone and no radical reactions, nitric acid is formed. during daytime, no radical is formed during nighttime, no radical so formed reacts with no resulting in the formation of hno hno further reacts with dust and sea salt particles acid rain can damage monuments and buildings. figure . shows the corrosion impact of acid rain on a statue and the roofing of a building. the damaged walls of the buildings and monuments leave a rough surface along with the moisture, which is a favorable place for the growth of microorganisms. acid rain can corrode sculpture and architecture, railway tracks, paints of cars, and joints of bridges and flyovers. over the past few decades, huge amount of coal and petroleum are consumed for meeting energy demand of mankind. burning of such fuels has ended with the accumulation of excess concentrations of gaseous and particulate pollutants in the atmosphere disproportionately. as seen in figs. . and . , the sulphur and (berresheim et al. berresheim et al. ) . around tg of no x are emitted by the lightening, stratosphere and the soils representing the natural input of no x . fossil fule and biomass burning are the major sources of no x which contribute around tg no x per year (ipcc ). in addition, anthropogenic activities such as industries and automobiles also inject an array of metals and other chemicals in the atmosphere which ultimately have adverse effects on human health and the environment. since industrial emissions have contributed gigatonnes of green hosue gases (ghgs). according to latest report published in climate change journal, / of these emissions ( gigatonnes) are contributed by companies across the globe (ref) out which belong to oil and natural gas sector, coal producers and cement producers. former ussr entities, chinese government run the change in land use has also changed the generation and migration of natural air pollutants like volcanic ash, dust, pollen grains, spores, virus and bacteria. the changing climate has changed wind patterns leading to migration of pollutants in a pattern which was totally different as compared to past. global competition for creation of wealth and infrastructure has engulfed hills, river sand, minerals and rocks beneath the earth. the waste this activity created has contributed to methane, chemical pollutants yet to be identified and named. the new multistoried building has changed path air traversed before it was setup. the population explosion followed by urban migration has left agricultural fields barren and increased urban foot print within a span of few decades. the "greenhouse effect" is the rise in temperature of the earth's atmosphere due to the existence of greenhouse gases (ghgs) in atmosphere. generally, the solar radiation received by earth drives the climate system. about % of the incoming 'short wave' solar radiation is absorbed by the earth while around % of it is reflected back to the space. when earth cools down, it releases the heat as long wave radiation. ghgs present in the atmosphere absorb this outgoing 'long wave radiation' from earth which enhances atmospheric temperature. greenhouse is a phenomenon used in greenhouses to increase temperature capturing long wave radiation to facilitate optimum growth condition for plants. the term "greenhouse" is borrowed to explain increase in temperature due to trapping of long wave radiation in the atmosphere. swedish scientist svante arrhenius first time demonstrated global warming. arrhenius ( ) who was awarded nobel prize in chemistry in showed that a doubling of the atmospheric co concentration would lead to - k warming of the earth surface due to greenhouse effect. ghg increase has resulted in an increase of . °c in global mean surface temperature since the th century. it is expected that this will further increase up to . - . °c by . according to ipcc, ghgs have altered the climate in past few decades resulting in impact on food, water, economy, raw materials, plant/animal health, energy, and biodiversity. it is worth mentioning that the existence of most of biosphere is due to greenhouse effect. fig. shows that without greenhouse effect earth's temperature would have been − °c (fig. . ) . a rise of > °c in the atmospheric temperature made human life possible on the earth. what worries is the sharp rise as seen during past few decades which has adverse direct and indirect effects such as global warming, sea level rise, monsoon disturbance, floods, cyclones etc. net radiative forcing is affected by the presence of aerosols in the atmosphere. aerosols can absorb or reflect radiation depending on the properties of aerosols. dark aerosols such as soot absorb radiation and light colored aerosols such as showing its importance for sustainable temperature for biosphere sulphate reflect radiation. it is to be noted that the combined effect of present increase in co , n o and ch would lead to an increase of atmospheric heating by . w m- which is % lesser that of expected from observed increase in concentrations of major ghgs due to aerosol effect. however, aerosol radiative forcing calculations have huge uncertainties which need to be corrected. the higher uncertainties are primarily due to lack of measurements from the sites of different characteristics such as rural, background, urban, desert, forest, high altitude especially from tropical regions. considerable uncertainties also exist in quantifying the role of dust aerosols in climate variability due to the difficulty in assessing direct and indirect effects of aerosols on clouds. aerosols alter radiative balance as well as the cloud density of the atmosphere resulting in changes in atmospheric stability and cloud microphysics, which can either foster or suppress the development of clouds and precipitation (li et al. ) . increase in particulate matter in the atmosphere can affect cloud development resulting in reduce precipitation in dry regions/seasons and increasing precipitation in wet regions/seasons. figure . shows impact of climate change. global warming is expected bring changes in weather patterns which may lead to disasters like storms, flood and droughts. ghg sources can be tracked to-energy generation, industry, transport, residential and commercial building, land use change, agriculture, waste disposal. these activities have resulted in rise in ghgs over past decade. combustion of fuel, degradation of organic matter in rice cultivation and waste disposal has contributed to ghg in addition to escape of ghgs manufacture in industries. the naturally occurring ghgs are water vapor, carbon dioxide, methane, nitrous oxide and ozone. table . gives major ghgs and their abundance and characteristics. anthropogenic activity has increased the concentration of these ghgs and contributed gases like perfluorocarbons and hydroflurocabons (hcfs) (ramesha et al. ) . some selected ghgs were phased out during execution of montreal protocol. per capita co emissions of different countries are shown in fig. . . australia, usa canada are the three top nations which have highest ghg emissions while china, egypt and india contribute the least ghgs. overall, the consequences of global warming (especially indirect) would be region specific and can not be generalized. this will mainly depend upon overall tolerance of that geographical area against the change in atmospheric composition and circulations due to increase of ghgs and other pollutants. the increase in atmospheric temperature due to presence of ghgs in higher concentrations will not be uniform throughout the earth. the uneven temperature which is also cause for wind patterns across the globe will change both in direction and speed bringing shift in normal pattern of rain which means rains could come during harvest time and destroy crop and rain may not come at sowing season. further the shortage of rain could cause drought in one region while excess rain could cause flood in other reason. the excess temperature could favor reproduction of pests where as it could alter reproduction patter in plants and animals. flowering date can be shifted and so as rise in sea level due to excess water inflow due to melting ice caps in mountains as well as polar ice can submerge coastal area and bring in loss of economy. due to climate change global land precipitation has increased by nearly % since the beginning of the twentieth century (jones and hulme ; hulme et al. ) and change is not uniform neither spatially nor temporally (karl and knight ; doherty et al. ) . as a result of climate change annual snow-cover extent (sce) has decreased by nearly % in northern hemisphere since mainly due to decline in spring and summer from the mid- s over eurasian as well as american continents (robinson ) . the flood, storm, tornadoes, extreme temperate, cyclone formed due to climate change can trigger mass movement (land slide and avalanche) in hills and mountains leading to further disaster. the climate change has resulted in drought in north china and summer floods in south china. change in precipitation pattern since a.d. is mainly due to human-made absorbing aerosols. long range transport (lrt) and trans-boundary driven air pollution long range transport (lrt) and trans-boundary air pollution affect distance sites. convention on long-range transboundary air pollution signed on is considered as pioneering international instrument which has paved the way for fruitful cooperation among parties in europe (harald et al. ). since, air has no boundaries, pollutants are transported globally from one geographic area. several times remote and background sites are affected by lrt. there are examples where states having no air pollution sources are affected by lrt of pollution from distance or nearby countries or states. rodhe ( ) demonstrated air pollution transport through air mass trajectory calculations and established that acid rain occurrence in northern europe was mainly due to industrial sources located in the south and west. dust from the thar desert has been the primary potential source of particulate pollution in the indian subcontinent. also, the suspended particulate matter from the dust storms originated in oman and other middle eastern regions has been reported to have influence on air quality in south asia (begum et al. ). long-range transport of dust aerosols over the arabian sea and indian region has been reported by badarinath et al. ( ) . kulshrestha and kumar ( ) have reported lrt of pollution and its influence on rain water chemistry at himalayan sites. according to the study, most of the acidic components such as sulphate and nitrate are transported from western airmasses and are deposited through precipitation having long term adverse impact on himalayan ecosystem. similarly, air pollution is the issue of transboundary transport of air pollution is an important issue between and within the countries. for example recent air pollution problem in new delhi can be termed as transboundary pollution problem (kulshrestha ) . in s, exhaust of diesel driven buses was mainly responsible for air pollution in delhi city but after the supreme court decision, all the busses were replaced by cng driven buses. this gave a big relief to the citizens of delhi. but surprisingly, so and no levels were recorded extremely high during winter season of crossing micrograms per cubic meter violating the naaqs limit of micrograms per cubic meter. such observations were never reported in recent past winters. such sudden increase can be explained on the basis of transboundary air pollution contributed by a number of new established brick kilns being operated in nearby states such as uttar pradesh, haryana and punjab (kulshrestha ) . in addition, diesel driven heavy duty trucks entering from outside of delhi also contribute significant amount of carbon and sulphur oxides making delhi air polluted (gupta et al. ) . global competition for creation of wealth and infrastructure has engulfed hills, river sand, minerals and rocks beneath the earth. the waste this activity created has contributed to methane, chemical pollutants yet to be identified and named. the new multistoried building has changed path air traversed before it was setup. the population explosion followed by urban migration has left agricultural fields barren and increased urban foot print within a span of few decades. the abundance of ozone at a point in the stratosphere is controlled by production, destruction, and transport of ozone as well as other substance. the key mechanism for the generation of stratosphere ozone is the breaking of molecular oxygen by solar uv with wavelengths of less than nm by photolysis to make nascent oxygen atoms which in turn combines with molecular oxygen to make ozone. ozone destruction occurs by reactions of oxygen atoms with ozone and reactions involving certain naturally occurring species like nitrogen oxide radicals (no x : mostly no and no ), odd-hydrogen radicals (ho x : oh and ho ), and/or halogen radicals. the natural ozone concentration vary daily (due to changing weather); seasonally; and multiannually and interannually. the concentration of stratospheric ozone can be changed by anthropogenic activity. chemicals in emissions from anthropogenic activities responsible for deletion of stratospheric ozone are called the ozone-depleting substances (odss). since the s it has been recognized that a numerous chemicals emitted by anthropogenic activities deplete stratospheric ozone. in order to understand the impact on layer ozone, national oceanic and atmospheric administration (noaa) has developed the ozone depleting gas index (odgi) derived from noaa's measurements of chemicals containing chlorine and bromine at various remote surface sites around earth's surface. index is defined as at the crest in ozone depleting halogen profusion and zero for the level. two different indices are derived one relevant for the ozone hole over antarctica (the odgi-a), and other relevant to ozone layer at mid-latitudes (the odgi-ml). odgi-a in was . and odgi-ml in the beginning of was . . benchmark halogen level over antarctica will be reached sometime around considering and that over mid latitude will be reached sometime in (daniel et al. ) . ods restricted by the montreal protocol, were declining in the atmosphere by with notable exceptions being halon- (a bromine-containing chemical used mostly in fire extinguishers) and hcfcs, that are used as substitution for cfcs in various applications. decline in reactive halogen concentrations are mainly due to the rapid phase-out as well as atmospheric decline of short-lived odgs such as methyl bromide and methyl chloroform (montzka et al. (montzka et al. , . the reduction related to cfc- as well as cfc- , has been less because of continuing emissions as well as their lifetimes are long ( - years). though concentrations of hcfc's continue to rise in the background atmosphere production is not scheduled for a total phase-out until . main pathways of ozone destruction are hydroxy radical (oh) chlorine and bromine radical (cl and br) the montreal protocol adopted in montreal in , [and subsequently amended in london ( ), copenhagen ( , vienna ( ) , montreal ( ) and beijing ( ) ] control of production and consumption of ods. nitrogen oxides from natural and anthropogenic activity catalytically destroy ozone through following reaction (crutzen ; jonston ) . the relative contributions of odss to depletion of ozone layer are quantified by ozone depletion potential (odp). in spite of many similarities between n o and odss it is not considered to be an ods in montreal protocol (ravishankara et al. ). air pollution transported across the continents as well as ocean basins has resulted in trans-continental and trans-oceanic plumes of atmospheric brown clouds (abcs) made up of sub micron size aerosols. abcs interrupt sunlight by reflecting and absorbing reflecting resulting in large surface dimming. on the other hand, black carbon as well as some organics augments atmospheric heating increasing global warming. black carbon is mainly emitted due to wildfires; and combustion of biofuel, coal, diesel and gasoline. as per ramanathan and feng ( ) abc warms atmosphere at elevated levels from to km, resulting in retreating of glaciers as well as snow packs in the hindu kush-himalaya-tibetan glaciers. aerosols may nucleate additional cloud droplets enhancing dimming effect ( fig. . ) . the dimming decreases evaporation of water from the earth's surface, slowing down the hydrological cycle. according to some studies, in south asia due to abc dimming north-south gradients in sea surface temperatures as well as landocean difference in surface temperatures, have slowed down the monsoon circulation and reduced rainfall over the continents. the following figure shows global estimates of dimming. impact of air pollution on flora can be observed in the form of discolourations of the leaf due to internal cellular damage thereby reducing the market value of agricultural crops such as tobacco and spinach where visibility is important. the air pollution can also result in reduction of the leaf surface and can provide points of entry for pathogens. air pollutant can affect plant physiological or biochemical processes resulting in significant loss of growth/yield as well as changes in nutritional quality (ashmore and marshall ) . so entering leaves through stomata are absorbed by mesophyll (cells between the lower and upper epidermis layers of a leaf) of leaves causing toxicity due to reducing property of gas. when the limiting concentration exceeds the cells are inactivated by plasmolysis and then killed. many industries that emit fluorides like aluminium reduction; smelting of iron and non-ferrous ores; ceramics and phosphate reduction as well as phosphate fertilizers. the fluorides are emitted due to volatilization of molten cryolite in aluminium industry and volatilization fluoride which may present as impurity in raw material in other industry. fluorides are of great concerns with respect to air pollution as all fluorides tend to accumulare in forage and build up concentration which causes fluorosis when consumed by cattle or sheep. further hydrogen fluoride and silicon tetrafluoride are toxic to some plants even at the concentration as low as . ppb (thomas ) . air pollution has been recognized as reason for injury to vegetation in europe and north america in the past few centuries. entire forest communities were lost up to km downwind of the smelter complex located at sudbury, canada in s due to so and metal emissions with other ecological effects observed at a greater distance (winterhalder ) . the areas where cells are killed collapse and dry up. if only few cells in an area are injured the area will become chlorotic (yellowing c) dimming due to abcs (w/m ) fig. . global dimming estimates (ramanathan and carmichael ) or whitening of usually green plant tissue due to decreased amount of chlorophyll) or brownish red in color. the lesions (abnormality in the tissue) due to ozone are usually confined to upper surface and are uniformly distributed as brown or white flecks or stipples or blotches. ozone flecking was observed on grape, avocado, citrus, and other broad leaf plants in outlying regions of los angels valley as well as surrounding hills (thomas ) . among the many mechanisms by which foot and mouth disease can be spread by transport of virus through the wind. even though this is uncommon infection can be carried across borders and seaways (donaldson and alexandersen ) . air pollutants affect photosynthesis and respiration of plants. the effect differs from species to species and each species will have threshold limits after which it is vulnerable for adverse effect. the pock mark type injury on the upper side of leaf has been attributed to acid aerosols associated with fog as it contains acid and other toxicants. the no x concentration in atmosphere is too low to cause plant damage. chlorine is around three times phytotoxic as so . hydrogen chloride at a concentration of ppm for few hours can cause pant damage. ammonia has around same phytotoxicity as hcl. h s is slightly phytotoxic (thomas ) . the change in land use has also affected the production and transport of natural air pollutants like dust, pollen grains, spores, virus and bacteria. vegetation cover is drastically reduced in the urban areas due to sudden increase in built area. developing countries are facing significant air pollution impact of land use change due to rapid urbanization. more significant effect is seen due to expansion of the cities for housing purpose which emits a huge amount of dust during the construction of buildings. the emissions of air pollutants from these residential colonies become a continuous source of polluted air. according to the data, about % of agricultural land in delhi has been transformed into nonagricultural area resulting in decrease in net sown area from , to , ha (mohan et al. ) . same is the case for most of the cities. the urban dust has been reported highly rich in carbon and sulphate (kulshrestha et al. ; kumar et al. ; gupta ) . dust sulphate significantly affect various biochemical constituents and the morphology of the plants (gupta ) . figure . shows an increase in ascorbic acid and proline content of foliar with the increase in sulphate levels correlating with the increase in stress level. more severe effect is reported for the industrial area as compared to the residential areas due to more stress of pollutants at industrial site which affects plant physiology and morphology. soil dust coming out from the digging of land and the construction activities could be the sources of microbes. the relationship between different types of house dust and the concentration of fungi has reported by kaarakainen et al. ( ) . investigation of animals following the air pollution at donora, pennsylvania in disclosed that many animals were ill and died during the week of smog. dogs were most susceptible species during the episode with . % reported to be sick and canine deaths. investigators attributed canine sickness to three syndromes-signs of respiratory syndrome, digestive syndrome, and anorexia (poor apatite). % of the birds affected by episode died. during the london fog in a number of prise cattle were severely affected. five of the cattle died where as were subjected to emergency slaughter. post mortem examination revealed emphysema, bronchiolitis and right heart failure. hydrogen sulphide released during pollution disaster in at poza rica, mexico was responsible for death of % canneries and about % of the other exposed animals in the area. the important long-term effect due to air pollution of radioactive substance are cancer; shortening of life span, and genetic or mutation effect (catcott ) . health forests across the world is being affected by air pollutants due to increasing tropospheric ozone concentrations, raise atmospheric carbon dioxide concentrations, as well as acidic precipitation. emissions of sulphur dioxide, oxides of nitrogen, and other pollutants like ammonia affect forests in rapidly industrializing areas. increasing levels of uv-b radiation from stratospheric ozone depletion are possibly a threat to health of forest (percy and ferretti ) . bioaccumulation and biomagnification of chemicals in food web would further worsen the ecological balance. bioaccumulation is an increase in the pollutants concentration over time in a biological organism. compounds accumulate in living organisms as they are stored faster than they are disintegration or excretion. biomagnification is raising accumulation of a pollutant in living beings as it moves from one level to other in a food chain. lead which is now drastically reduced in ambient air in many parts of the world is toxic to flora, fauna and micro-organisms and bioaccumulates in most organisms. generally, . ppm of lead in the blood of water birds is considered toxic although toxic symptoms may appear at . ppm lead. lead in at . ppm or more in liver of water birds is considered to be lethal. reduced survival has been reported for some sensitive species of birds, at of - ppm body weight. further, dietary levels of ppm affect reproduction. mortality during experimental studies in water birds normally occurs at dose concentrations of - ppm lead in with lethal levels varying from doses of - ppm (unep ) . lead concentrations of - mg/kg soil cause visible effects on, growth, photosynthesis or other parameters (ipcs ) . crop failure can occur due to-(a) impact of air pollutants on crop's health, ( ) climate change, ( ) uv ray penetration due to damage to ozone layer. figure . shows dust deposition on the three. such deposition is likely to cause impact on health of tree depending on the constituents of dust. ozone is the most destructive air pollutant to crops as well as ecosystems (heagle ) as it is a strong oxidant. surface level ozone is a secondary air pollutant created in the atmosphere from the oxidation of no x under bright sunlight as well as volatile organic. ozone as well as its secondary byproducts damage plants by reducing photosynthesis as well as other physiological functions, resulting in weaker, undersized plants with inferior crop quality and decreased yields (fiscus et al. ; booker et al. ; avnery et al. ) . crops next to thermal power plants in india suffered most in past decades due to inefficient air pollution control equipments which emitted fly ash that deposited on the crop. the pollution during mining, construction roads and operation of hot mixing plats in developing countries have resulted damage to crop to great extent. air pollution damages materials and involved three components-expenditures to repair, preventive measures, and loss of amenity. impact of materials fall into four categories: soiling, material loss, discoloration, and structural failure. the atmospheric corrosion of materials depends on acidification of the air, due to gases such as so and hno . as per the reviews damage to siliceous stones is not significant, and therefore attention is restricted to calcareous stones (harter ; lipfert ; lipfert ; napap ; ) . impact on material sulphuric acid aerosols attack building material mainly those containing carbonates like marble ( fig. . , . and . ) , limestone, slate and mortar which can be explained by following equation. the calcium sulphate formed is washed away. the deterioration of calcareous stone can be explained in three stages: simple dissolution of calcium carbonate; dissolution of calcium carbonate followed by the fall-out of less soluble particles; and steady build-up of salts if the calcium carbonate is not washed away. statues and other ornamental material may get discolored due to deposition of air pollutants. figure . shows statues covered with plastic covers in bangalore, india to avoid dust deposition and soiling of statues. mortar contains sand, calcium hydroxide as well as other carbonate phases. cement in concrete is susceptible to acid attack leading to discoloration/soiling (fig. . ) , surface erosion, spalling and corrosion of embedded steel. damage to reinforced cement concrete structure will be insignificant if the steel is provided with sufficient cover of good quality concrete. paint and polymeric materials can be affected due to acidic deposition as well as photochemical oxidants, particularly ozone. impacts on this material include fig. . marble within siliceous stones damaged due to air pollutants erosion of polymer surfaces, loss of gloss and soiling, interaction with sensitive pigments and fillers loss of paint adhesion from and substrates. contamination of substrate before to painting can lead to premature failure due to embrittlement and cracking. atmospheric corrosion of metals ( fig. . ) is an electrochemical process occurring when the surface is wet. corrosion rate mainly depends on humidity, precipitation, temperature as well as levels of atmospheric pollutants. so causes most damage, on metals even though chloride plays play a significant role in coastal area. as per the studies conducted by tzanis et al. ( ) in athens, greece metal and alloy specimens exposed the highest weight change is observed for unalloyed carbon steel at the level of m, and lowest weight change was observed at m. values of weight change for zinc and copper specimens were about four times lower than steel and almost constant with the height. the weight loss of unalloyed carbon steel was found to be more than times higher than other materials. copper and bronze suffered less by atmospheric corrosion with almost equal mass loss. zinc mass loss was nearly % greater than that of copper and bronze. sulfuric acid mist can damage, nylon, cotton, linen and rayon. excess exposure to so accelerates corrosion of metals. hydrogen fluoride will corrode many substances except polyethylene, lead, wax, and platinum. human health can be adversely affected by air pollution depending on the pollutant, quantity of pollutant and path of entry into body. human receptors include the eyes, nose, skin, or respiratory system. eye is more susceptible to damage as well as irritation compared to the skin. figure . shows common forms of exposure response relationship. relationship between the level of exposure (or dose) as well as the degree of effect (or response) usually occur in four ways: ( ) effect/response increases with exposure without threshold, ( ) effect/response increases with exposure with threshold, ( ) effect/ response versus exposure takes curvilinear shape, or ( ) effect/response versus exposure takes s-shape (david ) the clinical course of a disease is shown in fig. . . the living organism after exposing to disease casing factor like air pollutant can either recover or recover with disability or die. before end results human beings usually starts therapy as soon as symptoms of disease appear. the disease need not have to occur only to organs exposed to air pollutants. the toxins easily get absorbed by blood and varied to all parts of the body. for example chronic inhalation of cyanide compounds affects central nervous system, cardiovascular system, thyroid gland, respiratory system, eyes as well as skin. some gases like so cause irritation and some gases like acetylene and carbon monoxide cause asphyxiation (cause death without significant physiological effect). carbon monoxide causes a chemical asphyxiation since it impairs the oxygen transport in blood vessels as affinity of co for haemoglobin is three hundred-fold more than oxygen. lead in air can cause severe health damage as it is toxic at very low exposure levels. organo-lead compounds, like tetra-alkyl-lead and tri-alkyl-lead compounds, are more toxic compared to inorganic forms of lead. lead has acute as well as chronic effects on health of humans as it is a multi-organ system toxicant. it can the evidence indicates humans who are responsible for air pollution are adversely affected. children's health is adversely affected due to air pollution due to incomplete metabolic systems, ongoing process of lung development and growth, high rates of infection by pathogens immature host defenses, and activity specific to children can result in higher exposure to air pollution (who ) . figure . shows impact of air pollution on human health. figures . , . , . , . and . shows lungs affected by air pollution. figure . shows food items exposed to atmosphere are often contaminated with air pollutants leading to food spoiling. the lung of developing fetal and the infant is more vulnerable to injury by lung toxicants. air pollutants interact with environmental exposures, like four million deaths between and all over world were due to respiratory infections (who ) . particulate and gaseous pollutants can act on upper and lower airways to initiate as well aggravate cellular inflammation. nasal allergy to pollen is termed as pollinosis, and allergy particularly to grass pollen is termed hay fever. plants whose pollens are dispersed by air currents are air pollutants can get into the body through food contamination through food or water exposed to polluted air. pollutant entering into body can remain on skin or in the respiratory/digestive system or move into the blood. pollutants entering the bloodstream can be transported to all body parts. as pollutants moves through the body it can undergo many chemical changes, becoming more or less toxic (figs. . and . ) . the contamination of meuse river valley of belgium resulted in death of people in the first week of december . the findings of investigation revealed that weather patterns had a major impact on sulfur dioxide concentrations, especially during temperature inversion (shy ) . air pollution along the monongahela river near pittsburgh, usa in october , , resulted in death of people due to cardiac as well as respiratory diseases (goldsmith and friberg ) . as per ostro ( ) outdoor air pollution was accounted for approximately . % of total mortality and it is the cause for . % of all disability-adjusted life years (dalys) as well as % of all cardiopulmonary disease. in estimates released by who ( a), around million people died in as a result of air pollution exposure. this confirms that air pollution is now the world's largest single environmental health risk. as per the who ( b), . million deaths related to household air pollution in . . million deaths occurred in the south east asia and . million deaths occurred in western pacific regions. about , deaths occurred in africa, , in europe, , in the eastern mediterranean region, , in the americas and , deaths occurred in high income countries. in a total . million deaths linked to ambient air pollution (who c). . million death occurred in western pacific region and , deaths occurred in south east asian. about , deaths occured in the eastern mediterranean region, , in europe, , in the americas, , in africa, , in high-income countries of europe , in americas, , in western pacific, , in eastern mediterranean ( , ) . breakdown by disease due to ambient air pollution are: ( ) %-ischaemic heart disease; ( ) %-stroke; ( ) %-chronic obstructive pulmonary disease (copd); ( ) %-lung cancer; and ( ) %-acute lower respiratory infections in children (who a, c) . breakdown by disease due to household air pollution are: ( ) %-stroke; ( ) %-ischaemic heart disease; ( ) %-copd; ( ) %-acute lower respiratory infections in children; and ( ) %-lung cancer (who a, b) ( fig. . ) . lung cancer is one the leading reason of cancer death in both men as well as women. apart from smoking air pollution is one of the main reason. cancer can originate from lung or other parts of the body. cancer originating from lung cells is known as primary lung cancer. it can start in the bronchi) or in the alveoli. as per studies by siegel et al. ( ) lung and bronchus cancer would cause death of % of male cancer patients and % of female cancer patients in usa. smoking key reason of lung cancer (u.s. department of health and human services ), other causes include radon (national academy of sciences ) secondhand smoke (u.s. department of health and human services ) and air pollutants like benzene, formaldehyde, as well as asbestos. the size of lung may increase (due to increase in mucus) or collapse partially/wholly due to lung cancer. many people affected due to sars (severe acute respiratory syndrome), avian flu and swine flu due to transmission of virus through air in last decade. diesel and gasoline exhaust are probably and possibly carcinogenic to humans (iarc ) and children living near places with high traffic density have more risk of cancer (savitz and feingold ) . more than , people lost their lives in the year due to deadly acute air pollution that occurred due to temperature inversion over london. more than people lost their lives instantly due to methyl isocyanate poisoning in and hundreds of thousands were disabled permanently. dioxins and furans created during manufacture of certain chemicals like herbicides; pulp and paper industry during bleaching the wood pulp; burning waste (like municipal solid waste and medical waste) or substance which has chlorine; secondary copper smelting; forest fires; cement kilns; coal fired power plants; residential wood burning; burring bodies in crematorium or open fire. dioxins and furans are known carcinogens and can change hormone levels. high doses of dioxin can lead to skin disease called chloracne. dioxins and furans can bring changes in development of the fetus, decrease ability to reproduce and suppress immune system. mercury which is emitted from combustion of coal and waste/substance with mercury can lead to neurological and behavioral disorders, kidney disorder ranging from augmented protein in the urine as well as kidney failure. aerobiology plays an important role in the spreading of infectious diseases. aerobiology is the study of the course of action involved in the microorganisms' movement in the atmosphere from one location to another. airborne particles can remain in air for many days (wells ; wells and stones ; duguid ) . large quantities of infectious pathogens expelled in hospitals can spread via airborne. blockage of sunlight due to air pollution can promote spread of harmful microbe in atmosphere resulting in spread of infection. epidemiological studies have revealed that exposure to air pollutants during fetal development as well as early postnatal life is connected with numerous health problems including very low birth weight (vlbw); low birth weight (lbw); congenital defects; intrauterine growth restriction (iugr); preterm birth (ptb); behavioural problems, intrauterine and infant mortality; decreased lung growth, childhood asthma, increase in rates of respiratory tract infections, and neurocognitive decrements (wang and pinkerton ) . silicosis due to inhaling silica particles and asbestosis due to inhaling asbestoses is long known to scientific community. studies by kathleen and boguang ( ) revealed that occurrence rates of silicosis increased by years of dust exposure. pm air pollution increases risk for cardiovascular diseases (miller et al. ; pope et al. ) and people with diabetes are more susceptible to cardiovascular health effects connected with pm air pollution (o'neill et al. ; whitsel et al. ; ursula et al. ) . certain microorganisms, transforming a less toxic species into toxic derivative like produce methyl iodide, which reacts with substance like mercury, arsenic, selenium, and tellurium to form their methyl derivatives by process is known as methylation. black snow and outbreak of red-tide in lacustrine systems was observed during early in the kashmir himalayan valley, india. the occurrence of muddy snowfall in may at more than m above sea level in afarwat glaciers of kashmir, india has been attributed to changing environmental scenario of the region (lone et al. ) . the occurrence of "black snow" on the mountain peaks of gund, sonamarg in kashmir, india observed in march, was due to the burning of oil-fields for the period of gulf war (kawosa ) . occasional muddy rains were also observed in some regions of the kashmir valley in april (lone ) . the occurrence of muddy snowfall in the alpine zone of kashmir himalaya evoked environmental concern as it has bearing on drinking water supplies as well as ecology of many natural snow-fed streams. the chemical composition shows that the particulate deposition approximately comprises % of lime stone, . % of clay, % of gypsum and . % of iron ore. such a chemical composition suggests that these particulates might have origin from stone quarrying activities or cement manufacturing units. air pollution contributes substantial quantities of contaminants to snow. the asian part of the russian federation as well as europe contributes all but a minute percentage of the lead reaching the arctic through air out of which - % is anthropogenic (unep ). most of the air pollutants in atmosphere either settles down itself or get scrubbed by rain/snow/hail/dew unless otherwise it reacts with other pollutants to from secondary pollutants or absorbed/adsorbed by other living/nonliving things. the pollutants entrapped in precipitation would either stay in snow for year to come or reach surface/ground water bodies over the course of time. the material settled on the surface of solid bodies also gets washed over course of time. the acids/alkali formed in the atmosphere can dissolve chemical on the surface of the earth before reaching the water bodies. the water not only gets contaminated due to conventional pollutants, it also scrubs radioactive material released into atmosphere. rainwater was collected in the nijmegen area of netherlands after chernobyl accident, in first three weeks of may revealed presence of radioactive material (dennis ) . summarises the findings of studies of rainwater from scandinavia and great britain after chernobyl accident shows that the issue is far from easily understood (lucas and john ) . the organic compounds with diverse chemical structures, sources, as well as uses such as industrial compounds, pesticides, persistent degradation products, byproducts of fossil fuel combustion, and impurities during manufacture of chemicals are transported atmospherically and deposited into remote environments. such deposition can affect plants and animals including human health. nitrogen controls productivity and eutrophication of estuaries. elevated nitrogen inputs to water bodies leads to harmful algal blooms; loss of sea grasses; hypoxic and anoxic bottom waters; and reduced fish stocks (valiela and costa ; hallengraeff ) . these eutrophication problems are consequence of increased population growth and air pollution (lee and olsen ; nixon ; vitousek et al. ) . a significant nitrogen inputs to estuaries in new york may be due to atmospheric deposition (jaworski et al. ) . lead is important for scientific community in environmental science as may enter surface waters due to erosion of lead-containing soil though lead is not very mobile in soil (unep ) . estimated residence times of biological particles with lead in surface waters, up to two years(unep ). many of the air pollutants do not remain in atmosphere for ever. most of the air pollutants will settle on soil or water causing soil and water pollution. airborne pollutants from anthropogenic as well as natural sources deposit on land and water bodies. air pollutants can travel to great distances from the source. pollutants in soil and water bodies include nitrogen compounds, heavy metal, sulfur compounds, pesticides, and other toxics. airborne pollutants can fall to the ground simply due to gravity. such deposition is termed as "air deposition" or "atmospheric deposition". mercury extracted for centuries from sulfide ore or cinnabar has become a global pollutant. mercury can be released into the atmosphere from many anthropogenic activities, such as municipal trash incineration, combustion of high sulfur coal which contains cinnabar, use of mercury based fungicides. mercury has low reactivity in its elemental state and has long atmospheric residence time while the oxidized forms are removed by wet/dry deposition (fogg and fizgerald ) . oxidized reactive gaseous mercury is very soluble in water and hence is effectively deposited on water and land by rain/snow/hail/due. particulate forms of mercury settle as dry deposition (keeler et al. ) . the total quantity of mercury in the atmosphere is around - metric tons, and nearly % of that was produced by human activities (fitzgerals and watras ) . concentrations mercury in atmosphere peaked between s and s (engstrom and swain ) . anthropogenic activities contribute - % of the gross annual mercury emissions and % of mercury vapor exists as elemental mercury (fitzgerald ) . rest of the mercury exists as reactive gaseous mercury as complexes of divalent mercury, and/or in the organic form (stratton and lindberg ) . while deposition of h þ , so À and ca þ in numerous central european forests has declined in the last decade, deposition of no À and nh þ remained high or increased resulting in depletion of soil al-pools, release of so À formerly stored soil, accumulation of nitrogen in soil increasing nitrogen availability to trees and reducing ca þ concentration in the soil. soil acidification as well as increased nitrogen availability will decrease the fine root and change the rooting zone to upper layers of soil. such shift in rooting zone will decrease the root/shoot ratio causing increased drought susceptibility of trees (matzner and murach ) . thirty-three years study of atmospheric heavy metal deposition in denmark along with european emission inventories revealed concentrations of lead, cadmium, copper, zinc, vanadium, nickel and arsenic in soil at remote forest plantation on the island of laesoe, denmark. the accumulation of heavy metals was more in the top soil (hovmand et al. ) . deposition of particles from mineral processing and stone crushing can settle on soil leading to change in quality of top soil. the escape of materials which include by-product and products from chemical industry can contaminate soil to great extend. as per data published by unep ( ) concentration in soil next to roadways and in towns was up to several thousand mg pb/kg, and soils adjacent to smelters as well as battery factories were up to , mg pb/kg. study of production, distribution as well as consumption of goods and services is called economics. an economic system of a region or nation is referred as economy. the economy differs widely between, and within, countries due to differing environments, cultures, and government systems. the direct consequences of air pollution can cause millions of dollars if measured in terms of cost of treatment to heal sickness, lost productivity, missed educational/development opportunities. the economic loss due to climate change and disasters triggered by air pollution can take away good share of gross domestic product (gdp) of any country. even though air pollution is spread across the world, it is most severe in cities of developing countries (david et al. ) . but considering the spatial distribution, it is difficult to generalize the issue. every country will have pockets of polluted areas as well as clean area. but developing world has disadvantage of high population growth rate in cities and poor infrastructure. it means poorly paved roads which rises dust increasing suspended particulate matter. the adulteration of fuel and old vehicles would add smoke to atmosphere. air pollution in cities of developing countries can cost the nation after a decade due to unhealthy senior citizens. the immediate air pollution threat can come due to loss of tourism and crop. the soiled buildings, corroded structures and degraded construction material due to increase in acidic air pollutants can cost the owners a hefty amount even though it contributes to gdp of a country. fires to clear forest to accommodate large scale rubber and oil palm plantations in indonesia resulted in major air pollution in asia during april to november of due to wide spread of forest fires. the disaster was cause of thick smoky haze which covered indonesia, malaysia, singapore, brunei, southern thailand and philippines. the fires destroyed a large area of rainforest that included endangered species. while the fire destroyed commercial timber, plantations and farmland, air pollution resulted in tourism. the smoke was also cause of temporary shutdown of industry and commerce as well as increase in health care costs. much mortality occurred malaysia in the period due to air pollution from indonesia. as per, teresa and leonardo ( ) reduced cognitive potentials due to preventable childhood lead exposure translate into economic losses of $ . , $ . , and $ . billion international dollars at africa, asia, and latin america/caribbean, respectively amounting to . % of the global gdp. lifetime economic productivity (lep) associated due to childhood lead exposure in low and middle income countries (lmic) currently amounts to $ billion annually (teresa and leonardo ) . visibility is the maximum distance in a given direction at which an object can be visually recognized with unaided eyesight (wark et al. ). the destruction of visibility is mainly due to the absorption and scattering of visible light by suspended particles (chan et al. ) . pm . , are believed to be mainly responsible for the scattering of visible light (sloane et al. ) . fine particulate matter is the main pollutant in the majority fig. . reduced visibility with time . am, . am and . am on clear day in another location in bangalore urban areas in china (zhang et al. (zhang et al. , and other countries. hence it has acquired worldwide attention for its bad impacts on visibility (ghim et al. ) as well as public health (hong et al. ) . the visibility is affected by meteorology and concentration of pollutants. as could be seen from figs. . and . the visibility is not affected much at . am clock due to less traffic and low concentration of pollution. at . am as the number of vehicles on road increased visibility decreased as concretion of suspended particles in atmosphere increased and low temperature hindered dispersion of pollutants. at . am the pollutants dispersed mainly due to increase in temperature and therefore dispersion of pollutants. on the inûuence of carbonic acid in the air upon the temperature of the ground. the london, edinburgh and dublin philosophical magazine ozone impacts on agriculture: an issue of global concern global crop yield reductions due to surface ozone exposure: . year potential crop production losses and economic damage under two scenarios of o pollution long-range transport of dust aerosols over the arabian sea and indian region-a case study using satellite data and ground-based measurements long range transport of soil dust and smoke pollution in the south asian region chemical composition and climate of the atmosphere the ozone component of global change: potential effects on agricultural and horticultural plant yield, product quality and interactions with invasive species effect of air pollution on animals source apportionment of visibility degradation problems in brisbane (australia) using the multiple linear regression techniques factors controlling the acidity of natural rainwater the influence of nitrogen oxides on the atmospheric ozone content a focus on information and options for policymakers environmental pollution and the global burden of disease urban air pollution in megacities of the world radioactivity in rainwater following the chernobyl accident a gridded reconstruction of land and ocean precipitation for the extended tropics from - predicting the spread of foot and mouth disease by airborne virus the size and the duration of air carriage of respiratory droplets and droplet nuclei recent declines in atmospheric mercury deposition in the upper midwest air pollution control technologies compendium. international centre for sceince and high technology and united nations industrial development organization crop responses to ozone: uptake, modes of action, carbon assimilation and partitioning is mercury increasing in the atmosphere? the need for an atmospheric mercury network (amnet). water, air, and soil pollution mercury in surficial waters of rural wisconsin lakes mercury in southern new england rains visibility trends in korea during the past two decades effects of air pollution on human health industrial dust sulphate and its effects on biochemical and morphological characteristics of morus (morus alba) plant in ncr delhi a review of harmful algal blooms and their apparent global increase clearing the air - years of the convention on long-range transboundary air pollution acidic deposition-materials and health effects ozone and crop yield effects of air pollutants on acute stroke mortality atmospheric heavy metal deposition accumulated in rural forest soils of southern scandinavia precipitation sensitivity to global warming: comparison of observations with hadcm simulations diesel and gasoline engine exhausts and some nitroarenes. lyon: international agency for research on cancer lead-environmental aspects. environmental health criteria atmospheric deposition of nitrogen oxides onto the landscape contributes to coastal eutrophication in the northeast united states reduction of stratospheric ozone by nitrogen oxide catalysts from supersonic transport exhaust calculating regional climatic time series for temperature and precipitation: methods and illustrations microbial content of house dust samples determined with qpcr secular trends of precipitation amount, frequency, and intensity in the usa risk of silicosis in a colorado mining community environmental chemistry of a rare muddy snowfall occurrence on alpine zone glaciers of gulmarg particulate mercury in the atmosphere: its significance, transport, transformation and sources proceedings of first composition of atmospheric deposition (cad) workshop held at tsukuba. japan acid rain some facts about recent air pollution problem in delhi estimation of so contribution by dry deposition of so onto the dust particles in india airmass trajectories and long range transport of pollutants: review of wet deposition scenario in south asia carbon as major constituent of atmospheric aerosols at urban sites in india eutrophication and management initiatives for the control of nutrient inputs to rhode island coastal lagoons long-term impacts of aerosols on the vertical development of clouds and precipitation effects of acidic deposition on the atmospheric deterioration of materials atmospheric damage to calcareous stones: comparison and reconciliation of recent findings environmental chemistry of a rare muddy snowfall occurrence on alpine zone glaciers of gulmarg radioactive contamination in nijmegen rainwater after the chernobyl accident contribution of alkaline and acidic sources to precipitation in israel. the science of the total environment soil changes induced by air pollutant deposition and their implication for forests in central long-term exposure to air pollution and incidence of cardiovascular events in women dynamics of urbanization and its impact on land-use/land-cover: a case study of megacity delhi present and future trends in the atmospheric burden of ozone biological effects of ionizing radiation (beir) vi report: the health effects of exposure to indoor radon coastal marine eutrophication: a definition, social causes and future concerns quantitative assessment of worldwide contamination of air, water and soils by trace metals diabetes enhances vulnerability to particulate air pollution-associated impairment in vascular reactivity and endothelial function outdoor air pollution: assessing the environmental burden of disease at national abd local levels. geneva: world health organisation an assessment of global and regional emissions of trace metals to the atmosphere from anthropogenic sources worldwide air pollution and forest health: toward new monitoring concepts cardiovascular mortality and long-term exposure to particulate air pollution: epidemiological evidence of general pathophysiological pathways of disease global and regional climate changes due to black carbon air pollution, greenhouse gases and climate change: global and regional perspectives coping with climate change: principles and asian context nitrous oxide (n o): the dominant ozone-depleting substance emitted in the st century critical review on natural global and regional emissions of six trace metals to the atmosphere. (prepared for the international lead zinc research organisation, the international copper association hemispheric snow cover and surface albedo for model validation a study of the sulfur budget for the atmosphere over northern europe association of childhood cancer with residential traffic density atmospheric chemistry and physics of air pollution health effects of air pollution cancer statistics size-segregated fine particle measurements by chemical species and their impact on visibility impairment in denver measurement of gas phase ionic mercury (ii) species in ambient air. abstracts of papers of the economic costs of childhood lead exposure in low-and middle-income countries effects of air pollution on plants on the corrosion and soiling effects on materials by air pollution in athens final review of scientific information on lead-version of traffic-related air pollution and incident type diabetes: results from the salia cohort study the health consequences of smoking. a report of the u.s. surgeon general the health consequences of involuntary exposure to tobacco smoke: a report of the surgeon general-executive summary eutrophication of buttermilk bay, a cape cod coastal embayrnent: concentrations of nutrients and watershed nutrient budgets human alterations of the global nitrogen cycle: causes and consequence economic crisis detected from space: air quality observations over athens/greece air pollutant effects on fetal and early postnatal development air pollution-its origin and control on air-borne infection: study ii. droplets and droplet nuclei on air-borne infection heart rate variability, ambient particulate matter air pollution, and glucose homeostasis: the environmental epidemiology of arrhythmogenesis in the women's health initiative the world health report -health systems: improving performance. geneva: world health organization effects of air pollution on children's health and development a review of the evidence million premature deaths annually linked to air pollution burden of disease from household air pollution for burden of disease from ambient air pollution for principles and practices of air pollution control student manual environmental degradation and rehabilitation of the landscape around sudbury, a major mining and smelting area chemical characterization and source apportionment of pm . in beijing: seasonal perspective alkaline rains on the tibetan plateau and their implication for the original ph of natural rainfall asian emissions in for the nasa intex-b mission key: cord- -ubw chrf authors: newbold, stephen c.; finnoff, david; thunström, linda; ashworth, madison; shogren, jason f. title: effects of physical distancing to control covid- on public health, the economy, and the environment date: - - journal: environ resour econ (dordr) doi: . /s - - - sha: doc_id: cord_uid: ubw chrf physical distancing measures are important tools to control disease spread, especially in the absence of treatments and vaccines. while distancing measures can safeguard public health, they also can profoundly impact the economy and may have important indirect effects on the environment. the extent to which physical distancing measures should be applied therefore depends on the trade-offs between their health benefits and their economic costs. we develop an epidemiological-economic model to examine the optimal duration and intensity of physical distancing measures aimed to control the spread of covid- . in an application to the united states, our model considers the trade-off between the lives saved by physical distancing—both directly from stemming the spread of the virus and indirectly from reductions in air pollution during the period of physical distancing—and the short- and long-run economic costs that ensue from such measures. we examine the effect of air pollution co-benefits on the optimal physical distancing policy and conduct sensitivity analyses to gauge the influence of several key parameters and uncertain model assumptions. using recent estimates of the association between airborne particulate matter and the virulence of covid- , we find that accounting for air pollution co-benefits can significantly increase the intensity and duration of the optimal physical distancing policy. to conclude, we broaden our discussion to consider the possibility of durable changes in peoples’ behavior that could alter local markets, the global economy, and our relationship to nature for years to come. in the initial months of the covid- pandemic, most nations have attempted to control the spread of infections by reducing the rate of contacts between people who carry the virus and those who have not yet been exposed. the various methods to achieve such reductions in contacts are referred to generically as "physical distancing" measures-also known as "social distancing" or "spatial distancing" (abel and mcqueen ) . while physical distancing can reduce the death toll of the pandemic, it also can impose large costs on society as exemplified by the sharp declines in gdp and employment in the months following the initiation of physical distancing measures in the united states (sachs ; u.s. department of labor ) . this suggests there could be substantial gains from properly calibrating the intensity and the timing of physical distancing restrictions. in this study, we characterize the time path of physical distancing that minimizes total economic damages from controlling the covid- epidemic in the united states, accounting for a potentially important category of environmental co-benefits. we develop an integrated epidemiological-economic model that includes a standard model of disease transmission, the monetized value of covid- deaths averted and lives saved from exposure to air pollution, and the short-and long-run costs of physical distancing. the model includes the main features of the disease spread process and the economic trade-offs associated with broad-based physical distancing measures that represent the main approach to controlling the spread before a vaccine or effective treatments are available. we expand the model used in on our earlier benefit-cost analysis of physical distancing in several ways (thunström et al. ) . first, we explicitly connect the intensity and timing of physical distancing to both lives saved from the infection and the income lost from reduced work hours and lowered productivity. second, we incorporate the co-benefits of reduced mortality risks from declines in air pollution during the period of physical distancing. this extension is motivated by a striking side-effect of physical distancing, as indicated by visibly reduced levels of ambient air pollution in many areas around the world (iea ; venter et al. ) . globally, outdoor air pollution is responsible for around . million premature deaths per year (world health organization a), and recent estimates for the u.s. range from around , to , premature deaths per year attributable mainly to pm . (burnett et al. ; bowe et al. ; goodkind et al. ) . adding an air pollution component to our model allows us to account for the lives saved from reductions in pollution emissions as a co-benefit from physical distancing measures whose primary purpose is to control the spread of infections. third, we include a putative link between air pollution and the virulence of covid- . several recent studies have attempted to identify an interaction effect between air pollution and covid- transmissibility or case fatality ratios ogen ; persico and johnson ) . initial results of these studies suggest that airborne particulate matter could have a significant positive mediating influence on covid- fatalities, so we use our model to explore the potential effect of this link on the optimal physical distancing policy. our study draws on a mature literature that integrates economics and epidemiology to examine a wide variety of infectious diseases in humans (e.g. gersovitz and hammer ; rowthorn et al. ; perrings et al. ; fenichel et al. ; gersovitz ; fenichel ; philipson ) . we also add to a growing collection of recent studies that apply optimal control theory or computational dynamic optimization techniques to the covid- outbreak in particular (e.g. acemoglu et al. ; alvarez et al. ; eichenbaum et al. ; farboodi et al. ; gonzalez-eiras and niepelt ; kruse and strack ; piguillem and shi ; toxvaerd ) . a comprehensive review of these studies would take us too far afield, so here we briefly describe several closely related studies to highlight points of comparison between our work and that of others in the literature. farboodi et al. ( ) develop a continuous-time optimal control model with a vaccine backstop and endogenous physical distancing by optimizing individuals. they show that without regulation, individuals choose a sub-optimal level of physical distancing, reducing economic activity too late to achieve the socially optimal level of disease suppression. the optimal policy is characterized by an initial rapid ramp-up and a long duration of an intermediate level of physical distancing until a vaccine is developed. the authors apply a calibrated version of the model to the covid- epidemic in the united states, which shows that the optimal policy delays the peak of infections to buy time for a vaccine. eichenbaum et al. ( ) examine macroeconomic impacts of pandemics by modeling the behavioral responses of individuals to the evolving tradeoff between consumption and health risks during an infectious disease outbreak. they assume that the risk of infection increases with consumption, which leads to a decline in both market demand and supply during a pandemic, resulting in an economic recession. alvarez et al. ( ) and kruse and strack ( ) also study the optimal timing of physical distancing, accounting for both deaths due to infection and the economic costs of physical distancing, assuming that a vaccine or fully effective treatment will be developed within one year. in both cases, the optimal policy response allows infections to rise until they are close to the medical system capacity, and then physical distancing measures are rapidly implemented to keep the number of infections below the medical system's capacity constraint for a period of time that dampens or eliminates a second wave of infections. acemoglu et al. ( ) include multiple risk groups in a pandemic control model, where the groups are characterized by differing interaction behaviors and by age, which affects their fatality risk if infected. the authors use the model to examine the effects of targeted lockdowns, and find that differentiated lockdown policies will outperform those that are uniformly applied to the whole population. gonzalez-eiras and niepelt ( ) consider the implications of non-optimally timed physical distancing programs, and find that the net benefits of the policy can be drastially reduced if controls are initiated too early or kept in place too long. toxvaerd ( ) characterizes the equilibrium (unregulated) behavior of individuals in a model of infectious disease spread with no risk of death but with reduced flow utility in the infected state and with a linear cost of physical distancing. the equilibrium path of physical distancing has the effect of flattening the curve of infections at a characteristic level of infections determined by a combination of epidemiological and economic parameters. our model differs in the details but shares many of the same basic features as those reviewed above, including a traditional epidemiological model of disease spread and a representation of the influence of physical distancing on deaths from the infection and economic output or income. our main modeling innovation is to incorporate a link between physical distancing and air pollution, as well as the interaction between pollution and the covid- fatality rate. to our knowledge, our study is the first to examine this link in an optimal control framework, which allows us to assess a potentially important category of co-benefits from physical distancing. a final note before proceeding to the details of the model. we view our approach, like the studies described above, as closer to the "streamlined" than the "elaborated" end of the spectrum of possible models. we include the main features of the system relevant to our primary research questions, but otherwise we intentionally simplify as much as possible. we agree with pindyck ( ) that calibrated sir models applied to the covid- outbreak should be viewed as only rough approximations to reality and taken with a grain of salt. at the same time, even if they cannot provide precise forecasts and definitive policy prescription, we believe that strategically simplified models roughly calibrated to the stylized facts can be useful for developing qualitative insights and for generating preliminary comparisons of alternative control scenarios. to project the number of infections and deaths under various physical distancing policies, we use a discrete-time sir compartment model (kermack and mckendrick ; hethcote ) . we modify the standard model to represent the influence of physical distancing on the contact rate and the endogeneity of the case fatality ratio as the health care system becomes overwhelmed by a surge of infected individuals seeking medical care. we include a link between physical distancing and mortality from air pollution, as well as an interaction between air pollution concentrations and the covid- case fatality ratio. the shortand long-run economic costs of physical distancing depend on the average distancing fraction prior to the arrival of a vaccine and the assumed speed of economic recovery. the equations of motion for susceptible, infected, and recovered individuals are and in eq. ( ), is the contact rate without physical distancing, and x t is the fractional reduction in the number of potential transmission encounters that all individuals-both susceptible and infected-have in period t (alvarez et al. ) . we refer to x t as the "distancing fraction," which will serve as the control variable in the regulator's optimal control problem. in eq. ( ), is the rate of recovery from infection (the reciprocal of the average duration that individuals remain infected and able to spread the virus), and d t is the number of deaths due to infection in period t. denoting the case fatality ratio by t , the number of infected individuals who die in period t is note that t is the probability of dying from the infection before recovering, not the per period probability of death for infected individuals (keeling and rohani , p ) . we model the case fatality ratio as endogenous to the system, and indirectly responsive to the physical distancing policy through its influence on the evolution of infections. as the number of infected individuals requiring medical care increases, the health care system becomes stressed. this leads to infected individuals receiving a lower standard of care as scarce medical resources are spread ever more thinly. we represent this feedback by a logistic function of infections, ( ) where lo is the lower-bound case fatality ratio, which will obtain when i t is much lower than a critical value of infections, Ĩ (corresponding to the inflection point of the logistic function), and hi is the upper-bound case fatality ratio, which will obtain when i t is much higher than Ĩ . the parameter k controls the steepness of the logistic function, so for high k the relationship approaches a step function with lo for all i t <Ĩ and hi for all i t >Ĩ , as assumed in thunström et al. ( ) . we assume that recovery from infection yields immunity to the virus, although this has not been firmly established for covid- . while a number of studies find that people develop antibodies from the infection, the extent of protection from subsequent infections is still uncertain (world health organization b). equations ( )-( ) comprise the modified sir model with physical distancing and endogenous case fatality ratio. we use this model to project the number of infections and deaths under various physical distancing policies represented by the time path of the distancing fractions, x t . the regulator's task is to find and enforce the sequence of x t 's that minimizes the total damage from the outbreak, which includes the value of lives lost due to infection, minus the value of lives saved due to reduced pollution, plus the value of current and future income lost due to the reduced economic activity associated with physical distancing. we account for the value of lives saved from air pollution in the period of physical distancing due to lower emissions from reduced economic activity. to do so, we use a proportional hazard model (cox ; harrell ) , which implies that the number of deaths averted in a time period due to a reduction in pollution concentration from z to z is where m is the initial deaths from all causes in the time period, z is the initial level of air pollution, z is a lower level of pollution due to reduced economic activity caused by physical distancing, and is the air pollution hazard coefficient. to compress notation in what follows, we define the fractional reduction in the average pollution concentration during the period of physical distancing as z x , so z − z = z x z . air pollution emissions increase with overall economic activity, with an especially strong link to activity in the transportation sector. to represent this linkage, we assume that air pollution emissions on day t are a possibly non-linear function of the physical distancing fraction, x t . specifically, the fractional reduction in the average pollution concentration during the period of physical distancing is where days are indexed by t, and t is the duration of the physical distancing policy in days. the exponent controls the shape of the response of pollution to physical distancing. = is the linear case, for which z x = t ∑ t t= x t , while < ( > ) implies a sub-linear (supra-linear) response of emissions to distancing, in which case the fractional reduction in pollution with physical distancing would be less than (greater than) the distancing fraction. to understand how a non-linear response could arise, suppose that the average individual's inter-personal contacts are evenly split between contacts with co-workers at the workplace and contacts with friends and neighbors close to home. also suppose that commuting to and from work accounts for more (less) than half of the average individual's vehicle miles travelled and associated pollution emissions. if early increments of physical distancing mainly involve work-from-home policies, then, under the prior suppositions, the average person's inter-personal contacts would be reduced by half while her pollution emissions would be reduced by more (less) than half, which implies > (<) . here we use = , which we view as natural default assumption. several recent studies have examined possible links between air pollution and covid- related deaths. long-term exposure to air pollution contributes to many of the underlying health conditions that put people at higher risk for severe consequences from covid- , particularly respiratory diseases. such respiratory conditions also might be exacerbated by contemporaneous air pollution concentrations, which could compromise the body's ability to mount an effetive immune response to covid- . focusing on the u.s., find that a g ⋅ m − higher long-term average concentration of pm . (between the years - ) is associated with an % increase in the covid- fatality risk. other researchers have examined the possibility that airborne particulate matter (pm) facilitates the transmission of sars-cov- through the air (martelletti and martelletti ; di toppi et al. ; setti et al. ) , which could increase force-of-infection for repiratory disease transmission (tang et al. ). persico and johnson ( ) used the suspension of u.s. environmental protection agency enforcement activities as a natural experiment to estimate the impact of short-run decreases in pollution on covid- fatalities at the county level, and find large effects. to examine the potential importance of such a link for the optimal physical distancing policy, we include an interaction between air pollution and the covid- case fatality ratio, which appears in eq. ( ) above. this allows us to compare the overall deaths from infection and lives saved from air pollution between otherwise equivalent model runs with and without the interaction included. when the interaction is included, the case fatality ratio in each period is adjusted by a factor that depends on the overall reduction in air pollution due to physical distancing, i.e., where is the air pollution-infection interaction coefficient. to value lives saved from infection or air pollution, we use a central estimate of the "value per statistical life" (vsl). this quantity represents the average marginal willingness to pay for reducing the probability of death in a time period, i.e., the marginal rate of substitution between money and mortality risk (viscusi ). here we use a constant vsl, though some authors use age-adjusted vsl values, typically declining for older individuals (e.g. greenstone and nigam ) , and others value the expected loss of life-years rather than expected deaths (e.g. hall et al. ). pindyck ( ) also suggests that a lower average vsl value should be used when the number of deaths averted is large, due to diminishing marginal willingness to pay for risk reductions. the influence of age on the vsl has been examined in a number of previous studies (e.g. shepard and zeckhauser ; kniesner and viscusi ; evans and smith ; hammitt ) , but no clear consensus on a ( ) � t = t e − z x z , singular strategy to adjust for age has yet emerged in the literature. in the meantime, we follow u.s. federal agency recommendations and use a fixed central value of the vsl for all ages in our benchmark runs ( the relationship between the extent of physical distancing and lost income in society is typically taken to be linear (e.g. alvarez et al. ; toxvaerd ; kruse and strack ; piguillem and shi ; bolzoni et al. ; hansen and day ; lee et al. ). yet the possibility exists that the amount of income lost may be lower or higher than the physical distancing fraction. we introduce flexibility into the physical distancing cost function by allowing for non-constant returns to the rate of interpersonal contacts; specifically, we assume that per capita income on day t is a possibly nonlinear function of contacts, i.e., y t ∝ ( − x t ) , where = is the linear case and < ( > ) implies decreasing (increasing) returns, in which case the fraction of income lost with physical distancing would be less than (greater than) the distancing fraction. if mixing can be reduced initially by some people working remotely, traveling less, minimizing face-to-face meetings, etc., without being furloughed or losing their jobs, then would be less than . considering that some fraction of the workforce can reduce mixing with relatively little loss of productivity, we view = as a conservative benchmark assumption. we account for both the short-run and long-run cost of physical distancing. the shortrun cost is the present value of lost income during the period of physical distancing, where y is aggregate income per day with no physical distancing, and r ′ is the daily discount rate. the long-run cost of physical distancing is the present value of lost income after the period of physical distancing, which will depend on the speed of economic recovery after the initial decline in aggregate income. to represent the long-run cost, we assume that income growth will be temporarily elevated as the economy recovers from the shock, and the post-outbreak growth path will asymptotically approach the counterfactual no-outbreak growth path at a constant rate . based on these assumptions, and discounting future income at a constant rate r, the present value of lost income after the period of physical distancing is is the fractional loss of aggregate income during the period of physical distancing, y is aggregate annual income before the outbreak, and r is the annual discount rate. combining the relevant elements specified above, the total damage function is equation ( ) combines the value of covid- deaths, the value of averted air pollution deaths, and the value of lost income in the short-run and the long-run. note that the control variables, x t , are implicit in eq. ( ), through the definitions of z x , y x , v, and v, and through the dependence of the d t 's on the x t 's as determined by eqs. ( )-( ). following thunström et al. ( ) , we use r = . (liu et al. ; ferguson et al. ; aronson et al. ), = / . (liu et al. ; lauer et al. ) , lo = . , and hi = . (riou et al. ; wilson ; yang et al. ; dorigatti et al. ; unwin et al. ). in a sensitivity analysis, we use r = . , which is closer to the more recent estimate reported by sanche et al. ( ) . to specify the inflection point of the case fatality ratio function, Ĩ , we assume that if × hospital beds are occupied by covid- patients-roughly half of the . × staffed beds in u.s. hospitals (american hospital association )-then the case fatality rate would be at the mid-point of its possible range between lo and hi . wu and mcgoogan ( ) reported that % of covid- cases in china were "critical," so we assume that % of covid- infections will require the use of a hospital bed. this gives Ĩ = × . ÷ . = infected individuals. that is, if on any given day million people are infected by the virus, then a fraction ( lo + hi )∕ would not be expected to survive. we set the steepness parameter, k, to give a pronounced s-shape but not a severe step function. to calibrate the air pollution hazard coefficient, , we rearrange the proportional hazard function in eq. ( ) in our benchmark model we do not include an interaction between air pollution and the covid- case fatality ratio, so we set = . a causal link between these variables could have a profound impact on the optimal physical distancing policy, so we examine the implications of such a link in model variations using two preliminary estimates of this association. first, persico and johnson ( ) find that a short-run increase in pm . of g ⋅ m − is associated with a doubling of the covid- case fatality ratio, so in a "strong link" model variation we set = ln ( ) . second, find that differences in long-run average pm . concentrations among u.s. counties of g ⋅ m − is associated with an percent increase in the covid- case fatality ratio, so in a "weak link" model variation we set = ln ( . ). to quantify the benefits of lives saved, we use a benchmark vsl value of $ million. this is a central estimate from hedonic wage studies of the value per statistical life (viscusi ; kniesner and viscusi ) , and is consistent with u.s. federal agency benefit-cost guidelines (u.s. environmental protection agency ; u.s. department of transportation ). in a sensitivity analysis we use a lower value of $ . million, which is consistent with the average age-varying vsl used by greenstone and nigam ( ) to monetize the impact of physical distancing in the u.s. to specify , which controls the long-run costs of physical distancing, we make an assumption about the time required for aggregate income to recover to its counterfactual no-outbreak path. specifically, we define the recovery time, t r , as the time required for the gap between the actual gdp path and the no-outbreak path to shrink by %, i.e., e − t r = . , so = −t − r ln ( . ) . we assume t r = years, double the average recovery time among all bear markets since (sachs ), which gives = . yr − . finally, to compute the present value of future income losses, we use a u.s. federal agency recommended discount rate of r = . to solve the model, we use a numerical policy iteration approach (bertsekas ) . first, we initialize the distancing fraction to zero for the entire time horizon, x t = ∀t . then we compute the gradient of the objective function ( where Δ is a suitably small step size), and repeat for i = , , , ..., i max iterations. for consistency and reproducibility we use i max = , which appears to be sufficient to achieve convergence for all cases examined in this paper. we use the model to characterize the optimal timing and intensity of physical distancing to control the covid- outbreak in the u.s., and to examine the influence of air pollution co-benefits on the optimal physical distancing policy. considering the uncertainty surrounding many aspects of the system, our benchmark parameters described above and shown in table are meant to serve mainly as a point of comparison for alternative cases. to maintain continuity with previous work, our benchmark parameters are largely consistent with thunström et al. ( ) , aside from the new model features. three key parameters that drive the model results are the basic reproduction number, r , the value per statistical life, vsl, and the curvature of the physical distancing cost function, . results for our benchmark case and two additional cases involving variations in one or two of these key parameters are presented in figs. , , and table . the graphs in fig. show results for our benchmark case, which uses our preferred central parameter values and most closely resembles our prior analysis (thunström et al. in all four air pollution variations, the optimal policies shown in panel (a) are initiated with an abrupt increase in the distancing fraction just in time to arrest the early rapid spread of the pathogen and prevent the number of infections from exceeding the critical threshold of the health care system. as i t approaches the threshold, it is optimal to nearly instantaneously increase the physical distancing fraction from to around . , which in our benchmark case is initiated on day . ignoring air pollution altogether (solid line), after the immediate rapid increase the physical distancing fraction is then reduced nearly linearly until around day . the policy then increases again, modestly and temporarily, before finally decreasing to zero by day . at the other extreme, when air pollution co-benefits and a strong link between pollution and covid- deaths are included (dotdashed line), the policy begins with nearly identical timing and intensity but is maintained at a higher intensity for a longer duration, decreasing to zero by day . qualitatively, the optimal policies in all four air pollution co-benefit variations involve an early rapid increase in the distancing fraction, then a gradual decline over the course of nearly a full year. the influence of air pollution co-benefits on the shape of the optimal policy is negligible if no link between pollution and covid- is included, but is prominent if the link is strong. the horizontal line in panel (b) corresponds to Ĩ , the inflection point of the case fatality ratio function, and the vertical line corresponds to n( − ∕r ) , the herd immunity threshold for susceptible individuals. the phase diagram in fig. shows that all four controls lead to similar s−i curves, each turning down shortly before the critical threshold is reached and extending to just beyond the herd immunity level, which serves to prevent a second wave of infections after physical distancing restrictions are lifted. the rapid increase in the distancing fraction for all variations shown in panel (a) flattens the curve of infections, as shown in panel (b). the general pattern is similar to those found in other optimal control studies, including alvarez et al. ( ) and kruse and strack ( ) . key outcomes for the benchmark case are provided in the first column of table . using our benchmark parameters, the uncontrolled outbreak results in just over million covid- deaths. this is a result of nearly million cases of infection and the elevated case fatality ratio due to the critical threshold of the health care system being exceeded for a large portion of the duration of the uncontrolled outbreak. the controlled scenarios all save nearly . million lives or more relative to a no-distancing scenario, depending on the influence of air pollution in each variation. when air pollution co-benefits are excluded altogether, . million covid- deaths are averted by physical distancing, which also leads to an initial decline in gdp of nearly . percent. when air pollution co-benefits are included but with no link between air pollution and covid- deaths, the control policy becomes slightly more stringent, as indicated by the slightly larger immediate decline in gdp of . percent. in addition to the . million covid- deaths averted, , air pollution deaths due are averted due to the temporarily reduced levels of pm . during the period of physical distancing. this is roughly percent of the baseline air pollution deaths ( , ), so the lives saved from air pollution are roughly proportional to the immediate decline in gdp. in the third variation, which includes a weak link between air pollution and covid- deaths ( = . , based on , the control policy is now discernably altered from the "no air pollution" variation. with a weak link, . million covid- deaths are averted, which includes an additional , averted deaths due to the interaction between air pollution and the covid- fatality risk. this is nearly ten times larger than the , deaths averted due to the direct effects of air pollution on mortality. the final variation includes a strong link between air pollution and covid- deaths ( = . , based on persico and johnson ). in this case more than million covid- deaths are averted, including more than . million due to the interaction with air pollution, and , deaths are averted due to the direct effects of air pollution. the stronger interaction between air pollution and covid- deaths in this variation leads to a control policy that is sustained at a higher stringency and for a longer duration, which in turn leads to a larger immediate decline in gdp of . percent. in all four air pollution variations the optimal control policy concludes well before the time horizon of the model, which is years ( days). this suggests that if a vaccine will not be available before that time, then the vaccine would not affect the optimal physical distancing policy. the vaccine still would be useful in reducing the risk of future infections from imported cases, but it would not be necessary to eliminate the risk of a future outbreak due to community spread because the number of susceptible individuals would have already been decreased below the herd immunity threshold. childhood vaccinations also might be warranted after this time to prevent the number of susceptible individuals from climbing back above the herd immunity threshold over time as immune individuals die and new cohorts enter the population without immunity. and if infection does not confer lifelong immunity, then the role of a vaccine increases further still. results for the second case are shown in fig. and the second column of table . in this case, all parameters are held at their benchmark values except the curvature of the physical distancing cost function, which is here set to = . . this implies a concave relationship between interpersonal contacts and income, which means that the first increments of physical distancing, which involves a reduction in the rate of interpersonal contacts, are less costly than later increments. in this case the proportional decline in income is less than the physical distancing fraction. the effect of this assumption is to make physical distancing less costly overall, which leads to an optimal policy that is more stringent and of longer duration than our benchmark case, as shown in panel (a) of fig. . here the control policies start around day and conclude between days and . with a less costly physical distancing technology, the influence of including air pollution co-benefits is more pronounced. even the variation with no interaction between pollution and covid- fatalities is discernible in panel (a), and the variations with a weak and strong link extend the duration of the policy roughly months and months, respectively. the quantitative differences in outcomes can be seen in table . when air pollution co-benefits are excluded entirely, more covid- deaths are averted ( . million) at a lower immediate decline in gdp ( . percent) relative to our benchmark case in column . accounting for air pollution co-benefits reveals that an additional , deaths are averted due to reduced air pollution exposure, but otherwise the outcomes are nearly identical to the no air pollution variation. assuming a weak link between air pollution and covid- deaths, the policy adjusts to avert . million covid- deaths, which includes , deaths averted due to the interaction with air pollution. assuming a strong link with air pollution leads to a dramatic increase in the duration of the policy and the number of deaths averted for about the same cost as in the benchmark case, as reflected in the nearly equivalent immediate gdp decline of . percent. in addition, given the increased stringency and duration of the program, the relative influence of air pollution co-benefits is magnified. panel (a) in fig. demonstrates the significant difference in optimal physical distancing with and without air pollution cobenefits, and the cumulative numbers of pollution deaths averted increases significantly. while total costs in this case increase, the increased numbers of deaths avoided more than compensates and therefore extends the duration of physical distancing measures. by comparison to our benchmark case, these results suggest that large gains in efficiency could be achieved if the cost heterogeneity of component physical distancing measures is high, and if we are able to deploy the component measures in decreasing order of their cost-effectiveness (newell and stavins ) . results for the third and final case we examine in this paper are shown in fig. and the third column of table . in this case we vary two parameters: r is increased to . [closer to the estimate reported by sanche et al. ( ) ], and vsl is decreased to $ . million [to match the average value used by greenstone and nigam ( ) ]. the optimal control policies and associated outcomes are qualitatively different in this case. relative to our first two cases, here the optimal policy rapidly increases to a much higher level of stringencybetween . and . -but is sustained for a much shorter duration-between about and days. as a result, the curve of infections is not immediately flattened as in cases and . in this case, it is optimal to let infections exceed the medical system threshold before initiating physical distancing. infections are allowed to grow past million in the variation with no air pollution co-benefits, and past million in the variation with a strong link between infection fatality risk and air pollution. when physical distancing restrictions are initiated, the high stringency of the measures quickly reduces the number of infections back below the medical system threshold. thereafter, physical distancing measures are gradually released until herd immunity is achieved. when air pollution co-benefits are included and a strong link between pollution and covid- deaths is assumed, the peak of infections under the optimal control policy is just over one third of the uncontrolled peak. here again we see that a strong link between pollution and covid- deaths has a large influence on the shape of the optimal control policy, but even in this variation the curve of infections is not completely flattened below the critical threshold of the health care system. the optimal policy fails to flatten the curve in this case for two reasons. the obvious reason is that with a lower vsl the demand for saving lives is lowered. assigning a lower value to mortality risks reduces the implied damage to society from the outbreak and results in reduced net benefits of the control policy. the less obvious reason is that with a higher r , physical distancing is less effective at stemming the spread of the virus: reducing r from a very high level to a high level prevents fewer infections than reducing r from a high level to a medium level (thunström et al. ). these two effects combine to yield an optimal policy that allows a much larger number of deaths than cases and . (in other cases not reported here, we found that the infection curve is flattened with r = . and vsl = $ million, and is nearly flattened with vsl = $ . million and r = . .) physical distancing has so far been the most widely used policy to control the spread of sars-cov- . while the benefits to physical distancing are large, given the substantial number of lives saved, such measures also impose significant private and social costs. in this study we characterized the intensity and timing of physical distancing that minimizes total economic damages from controlling covid- , and we examined the co-benefits of lives saved from air pollution and a potential link between air pollution and covid- fatalities. our model jointly considers physical distancing that results from policies (mandates or recommendations) and individual decisions to self-protect, independent of policies. benefits from physical distancing are recorded as lives saved, while costs are measured as the loss of income in both the short run (during the period of physical distancing) and the long run (as the economy recovers from the initial shock). on the benefit side, lives saved result both from averted covid- deaths and averted air pollution deaths. in our integrated epidemiological-economic model of covid- in the u.s., deploying a physical distancing policy with optimal timing and intensity saves millions of lives and generates significant net benefits in comparison to an uncontrolled scenario with no physical distancing. we also find that thousands more deaths are averted due to the reduction of air pollution emissions from physical distancing, and hundreds of thousands more covid- deaths are averted if we assume a strong causal link between air pollution concentrations and the covid- fatality risk, which is suggested by some preliminary evidence of this association. more than million deaths from infection are predicted in the uncontrolled scenarios, and even in the optimally controlled scenarios more than million deaths are predicted. to provide some context for these results, fig. shows the imputed time path of the effective reproduction number, r e , which is proportional to the contact rate as it changes over the course of the outbreak (aronson et al. ) , and the physical distancing fraction, x t , from march through june , in the united states. the graphs are based on u.s. centers for disease control and prevention (cdc) reports of the cumulative number of infections (cdc ), assuming that the spread of the virus evolves according to an sir model similar to the one used in our optimal control scenarios (see the "appendix" for details). the the number of infections and deaths relative to a counter-factual scenario with no physical distancing. compared to the number of cases so far reported in the u.s., which provide the basis of the graphs shown in fig. , the optimal control paths shown in figures , , and allow a much larger number of infections to accumulate early in the outbreak before the rapid escalation of physical distancing [consistent with other recent studies, e.g. alvarez et al. ( ) and kruse and strack ( ) ]. this strategy provides a head start on achieving herd immunity while still preventing the number of people who are infected at any one time to exceed the critical threshold of the health care system. if aggressive physical distancing measures are implemented before many infections have occurred and are maintained at a sufficiently high intensity to keep the number of infections very low over time, then when physical distancing measures are relaxed a second wave of infections will occur because the number of susceptible individuals would still be very high. at least two categories of control options not considered here could change the character of this result. either the widespread use of cloth masks (eikenberry et al. ; howard et al. ) , or a program of diagnostic testing and self-quarantine (piguillem and shi ; taipale et al. ; allen et al. ) , or a combination of these, might allow the relaxation of physical distancing and avoid a second wave of infections while awaiting the development of a vaccine or effective treatment. if a vaccine or treatment were to become available before the optimal distancing policies in figs. , , and are concluded, then a higher intensity and shorter duration physical distancing policy may be optimal. cloth masks and testing and self-isolation measures might also serve as effective substitutes for physical distancing restrictions at all stages of an outbreak, so incorporating these additional control measures into our model would be a useful extension in follow-up work. several other limitations of our model also should be highlighted. first, we value only the reduction in the fatality risks from infection to the exclusion of all other adverse health outcomes short of death. in benefit-cost studies of environmental regulations, fatality risk reductions typically comprise percent or more of the monetized health benefits (e.g. cropper et al. ), but it is not clear whether this will apply to covid- cases. second, the narrow peaks of the infection curves in figs. , , and are characteristic of a single well mixed population. in reality, the u.s. may be better represented as many connected population centers in a spatially explicit model of disease spread, which could produce a series of overlapping and interacting infection curves more closely matching the observed patterns of cases (unwin et al. ) . we also do not distinguish between individuals of different ages or pre-existing health conditions that may make them more vulnerable to covid- (acemoglu et al. ) , nor do we distinguish between symptomatic and asymptomatic cases (stock ) . we also do not model the un-coordinated physical distancing responses of individuals in an unregulated scenario. rather, we compare the optimal physical distancing policy to a completely uncontrolled epidemic, in which individuals engage in no self-protective behaviors. (as might occur if covid- were widely but erroneously viewed as no more dangerous than the seasonal flu.) standard economic theory predicts that if the true risks are known then people would choose to distance themselves to a degree that their individual net benefits are maximized (toxvaerd ). with high enough infection and fatality risks, we would expect some voluntary physical distancing, but generally less than the economically efficient level. because our net benefit estimates presented in table are calculated with respect to a no-physical distancing counterfactual scenario, they provide an upper bound on the net benefits of externally imposed physical distancing restrictions. we also ignore a number of other potentially important side-effects of physical distancing, which may include increased incidence of domestic abuse as families spend more time at home (van gelder et al. ), increased fatality rates from other adverse health conditions as people delay treatment to avoid infection in hospitals (lazzerini et al. ) , reductions in crime rates (mohler et al. ) , adverse mental health effects of school closures (lee ) , and increased rates of suicide due to social isolation (gunnell et al. ) . finally, we focus on economic efficiency and do not address the equity implications of the disease risks or the economic effects of physical distancing. like for covid- related deaths, the adverse health effects of air pollution are asymmetrical across race and income (e.g. bowe et al. ) , and we would expect the economic costs of physical distancing also to be borne disproportionately by marginalized groups and low income households. to conclude, we discuss some potential environmental implications of the pandemic beyond the links between covid- , physical distancing, and air pollution examined in our optimal control model. our aim in this closing section is two-fold: to acknowledge the narrow focus of our control model, and to highlight opportunities for further research by environmental economists going forward. our brief discussion here is complementary to helm ( ) , iges ( ), and barbier ( ) , who provide broader discussions of the potential long-run environmental impacts from covid- . a key question highlighted by these articles is whether the necessary fiscal stimulus implemented to accelerate the economic recovery will have the effect of re-entrenching the status quo or helping societies "build back better" by improving economic resilience and environmental quality in tandem. we organize our closing discussion by considering possible long-run changes in how people will work, rest, eat, and play after covid- . first, among the most important components of physical distancing measures widely adopted during the early months of the pandemic are work-from-home policies, reduced international and domestic travel for in-person meetings, and distance education. to the extent that technical change involves learning by doing, this could lower the cost and thereby increase the long-run prevalence of remote work and online learning. this could in turn reduce polluting emissions from ground and air traffic and make durable a portion of the short-run decline in emissions observed in the early days of the pandemic, thereby slowing the rate of climate change and reducing the incidence of adverse health effects due to pollution. covid- also could accelerate the contraction of globalization, reducing the trade of goods and services and the movement of people among nations. this re-animates a large literature on the impacts of globalization on the environment (boyce ; gallagher ). another possibility, likely to vary considerably among nations, is that the cost of economic recovery could crowd-out existing environmental regulations. if there is a de facto constraint on the overall size and scope of government regulations in a country, then an expanded role for government in the provision of public health may lead to a diminished role in the provision of environmental protection. closer to home for readers of scholarly journals like this one, we wonder about the implications of this episode for the conduct of economic research and science communication, including the publication and promotion through popular media of rapid results prior to formal peer review. we see pros and cons of the current emergency response by academics to the pandemic. rapid dissemination of pre-prints may allow for more timely and actionable science to reach the decision-makers who need it, but also might lead to a higher rate of false results (e.g. freedman ; joseph ; majumder and mandl ). striking the right balance between false positives and false negatives in published results during normal times is a complicated (and we think understudied) problem, and it is not clear whether and how the balance should change in times of a public health crisis like covid- . second, will covid- have a lasting influence on where people choose to rest-that is, where they choose to live? if large cities are engines of economic growth-a conventional but not a consensus view (e.g. annez and buckley ; parkinson et al. ; frick and rodríguez-pose )-but also come be known as engines of infectious disease outbreaks (stier et al. ) , what are the implications for the optimal spatial patterns of human settlements? any such influence would have important long-run implications for the environment (newman ) . for example, if the covid- pandemic helps to slow or reverse the trend of migration from rural areas to urban centers in the u.s. (harris poll ), this would in turn change the overall amount and the spatial pattern of pollution and habitat loss. if compact human settlements are better for biodiversity, then a reversal of the trend toward agglomeration in urban centers could have adverse effects on nature and the provision of valuable ecosystem services. this would increase the importance of learning how to design dispersed human settlements that are closely connected to nature with minimal environmental impact, rather than reducing impact by concentrating human settlements into smaller areas. third, will covid- have long-run implications for food production and consumption? the pandemic could reduce both the demand and the supply of meat products due to increased concerns about safety on the part of consumers and increased costs of production if stricter safety regulations are imposed on producers. shifting away from animal to plant based proteins has the potential to significantly reduce impacts on the environment, including carbon dioxide emissions (tukker et al. ) . preferences for domestically produced food also might increase, as the covid- crisis highlights the urgency for securing a sufficient domestic food supply as a means of enhancing the resilience of local economies in the face of heightened risks of pandemics or other large scale disruptions in the future. whether this will positively or negatively affect land conservation or the climate depends on the policy choices made about the changes to food supply. finally, will the pandemic have a lasting influence on how people spend their leisure time? if people become motivated to shift a portion of their time use to outdoor recreation activities-which might pose lower risks of infection than leisure activities indoors or outdoors in large crowds (rice et al. ; venter et al. ; samuelsson et al. )-this could increase the instrumental value of a clean environment and untrammeled wilderness areas. it also could expand the health benefits from exercise outdoors (lippi et al. ; mattioli and ballerini puviani ; gössling et al. ) and the more general well-being benefits from spending time in nature (bratman et al. ; white et al. ). on the other hand, if people withdraw from travel both abroad and at home and spend more time indoors watching screens, or if yet another case of a pathogen jumping from an animal species to humans (zoonosis) (andersen et al. ; berry et al. ) makes some people more fearful of close contact with nature, the health benefits of outdoor recreation might contract rather than expand. the results from our control model presented in this paper suggest that there may be important environmental side-effects that could alter the optimal intensity and duration of physical distancing policies used to manage the covid- epidemic. many interventions designed to affect consumer behaviors have been shown to work in the short run, but people typically revert back to their prior behaviors after the intervention is removed (e.g. nisa et al. ) . so the safe bet may be that the salutary environmental side-effects of physical distancing will dissipate as fast as economic activity resumes after the outbreak. on the other hand, some past public health crises have led to lasting and high-impact changes in behaviors. these include long distance migrations in the united states during the th century to escape unhealthy living conditions in eastern cities (baur ; abrams ) , and improved personal and public hygiene practices that today we take for granted such as regular health care visits and hand washing habits (agüero and beleche ; foss ) . if covid- leads to behavioral changes as durable as those spurred by past epidemics, the environmental implications of the outbreak may extend far beyond the short-term air pollution impacts examined here. the covid- pandemic calls for spatial distancing and social closeness: not for social distancing! on the road again: consumptives traveling for 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regulatory analysis covid- : reducing the risk of infection might increase the risk of intimate partner violence urban nature in a time of crisis: recreational use of green space increases during the covid- outbreak in oslo spending at least minutes a week in nature is associated with good health and wellbeing case-fatality risk estimates for covid- calculated by using a lag time for fatality world health organization ( a) air pollution immunity passports" in the context of covid- . scientific brief exposure to air pollution and covid- mortality in the united states: a nationwide cross-sectional study characteristics of and important lessons from the coronavirus disease (covid- ) outbreak in china: summary of a report of , cases from the chinese center for disease control and prevention mortality in the united states early estimation of the case fatality rate of covid- in mainland china: a data-driven analysis to produce the graphs in fig. of the main text, we assumed that the spread of the virus evolved according to an sir model with an effective contact rate that varies over time with changes in physical distancing . referring back to equations ( )-( ), the effective contact rate on day t is t = ( − x t ) , and the number of new infections on day t is t s t i t , where is the contact rate with no physical distancing, and x t is the distancing fraction on day t. the u.s. centers for disease control and prevention (cdc) reports the cumulative number of infections since january , (cdc ). denoting the cumulative number of infections reported prior to day t as c t , we can write c t+ − c t = t s t i t . ignoring deaths for simplicity, this leads to the following sequential procedure for imputing t , r e,t , and x t based on the reported values for c t and an assumed value of : key: cord- -vpw g authors: zhang, l.z.; zhu, d.s.; deng, x.h.; hua, b. title: thermodynamic modeling of a novel air dehumidification system date: - - journal: energy build doi: . /j.enbuild. . . sha: doc_id: cord_uid: vpw g a novel air dehumidification system is proposed. the proposed system incorporates a membrane-based total heat exchanger into a mechanical air dehumidification system, where the fresh air flows through the enthalpy exchanger, the evaporator and the condenser subsequently. thermodynamic model for the performance estimation of the combined system is investigated. processes of the fresh air and the refrigerant are studied. two additional specific programs are devised to calculate the psychrometrics and the thermodynamic properties of the refrigerant r a. annual energy requirement is . × ( ) kj per person, or % saving from a system without energy saving measures. it is often necessary to control and modify the water vapor content in the air: the operation is quite usual in air conditioning. normally the water vapor content of atmospheric air is small, some tens of grams per kilo of air; nonetheless, due to the very high heat of vaporization, the latent heat content in air conditioning is of the same order of the sensible one. the relative importance of latent load increases with the ventilation rates to buildings. higher ventilation rates are dictated both by better comfort requirements and by the most recent standards such as the ashrae / [ ] . more recently, people's concern on indoor air quality has been greatly deepened since the outbreak of the severe acute respiratory syndrome (sars) epidemic that molested south china and some other parts of the world in this spring and caused a loss of . billion us$ (or . % gdp) in china alone and billion us$ globally [ ] . the mechanisms of sars virus spreading is complex and remains a mystery till now. however, it is believed that enough fresh air ventilation is helpful in decreasing the possibility of being infected by the disease. ventilation air is the major source of moisture load in air conditioning. as shown in fig. for a moisture load estimation of a medium size retail store [ ] , ventilation air constitutes about % of the total moisture load in most commercial buildings. as a consequence, treatment of the latent load from the ventilation air is a difficult and imminent task for hvac engineers, especially in hot and humid climates like south china. traditionally, latent load and sensible load are treated in a coupled way. because air is not only for ventilation, but also a heat transfer medium, and large quantities of air is needed to extract the sensible load, energy requirements are very high. another problem with this technique is that in transit seasons, humidity will lose control [ ] . there is an increasing trend to separate the treatment of sensible and latent load by using an independent humidity control system. according to this concept, the latent load of a room is treated by an independent humidity control system, while the sensible load is treated with some other alternative cooling techniques such as chilled-ceiling panels. since the circulating air is dramatically reduced, energy consumption can be reduced substantially. another benefit is that chilled water or suction temperatures can be raised, resulting in increased equipment efficiency and decreased operating costs. it is estimated that % of the energy used www.elsevier.com/locate/enbuild energy and buildings ( ) - could be saved with chilled-ceiling panels combined with independent humidity control system, in comparison to a traditional coupled system [ , ] . nevertheless, due to the hot and humid climates in south china, energy for moisture control with an independent humidity control system still accounts for % of the total energy for air conditioning. thus, energy recovery measures must be combined to an independent humidity control system. in this study, a novel air dehumidification system, namely, mechanical dehumidification with membrane-based total heat exchanger, is proposed. the thermodynamic modeling of the system is performed. through hour-by-hour analysis, the annual primary energy consumptions for the systems proposed are discussed. a schematic of the new air dehumidification system modeled in this work is shown in fig. (a) and its psychrometrics are shown in fig. (b). in this system, a membrane based total heat exchanger is used to pre-cool the fresh air before it is pumped to a refrigeration system for air dehumidification. the total heat exchanger has a membrane core where the incoming fresh air exchanges moisture and temperature simultaneously with the exhaust air. in this manner, the total heat or enthalpy from the exhaust is recovered, and both the temperature and the humidity of the fresh air are decreased, which results in energy saving. then the cooled and dehumidified fresh air is flowed through the condenser of the refrigeration system, to satisfy the requirements of supply air: g/kg humidity and c in temperature. this system is relatively simple, since the membrane system has no moving parts, and is compact. desiccant wheels may be another choice, however, in some circumstances, gas or other thermal heat may be difficult to find. the control of the new system is easier than a conventional compression dehumidification system, because no other components except a membrane system is added to the system. the differences are the operating parameters are changed, and much fan power is needed. the membrane system operated in near atmospheric pressure condition, the maintenance is easy. this study is to estimate the energy performance of a novel air dehumidification system by thermodynamic analysis. the modeling methodology of the refrigeration cycle is a steady-state one. they are sufficient to reflect the coefficient of performance or the energy performance of the refrigeration cycle. even though more detailed models are proposed by some authors, see [ , ] , they are compli-list of symbols a tot total exchange area (m ) c constants in sorption curves cop coefficient of performance c p specific heat (kj kg À k À ) d wm water diffusivity in membrane (kg m À s À ) h specific enthalpy (kj/kg) k s convective mass transfer coefficient in supply side (kg m À s À ) m_ mass flow rate (kg/s) dp total pressure rise (pa) q heat (kw) cated and case-sensitive. in other words, the distributed parameter models in such studies are strongly based on design parameters of a specific refrigeration system. those detailed models just gave very generalized equations for the calculation of heat and mass transport in each component and rely heavily on manufacturers' product empirical data. further, this study gives a general view of energy savings in sub-tropical regions, which do not rely on a specific system. furthermoreover, the more detailed partial difference models in other studies are difficult and slow in finding a solution. it is difficult to use such models in a wholeyear-hour-by-hour simulation. those more complicated models are usually necessary to study transient responses and start-up characters of a refrigeration cycle, which is beyond the scope of this study. the effects of the refrigeration cycle on the whole system are demonstrable. a thermodynamic model of the refrigeration system is formulated based on the processes of refrigerant r a shown in fig. . saturated r a liquid at point flows through an expansion valve and becomes wet vapor at point . refrigerant at this state flows to the evaporator (also the dehumidifier) where it chills and dehumidifies the fresh air and evaporates to point and further superheats to point . then the refrigerant vapor is pumped by a compressor to point where the vapor is displaced to the condenser and condensates from state to through . the superheat is set to c. it should be noted that the exact degree of superheating may be affected by many factors, such as evaporator, expansion valve, and compressor, and are strongly related to operating conditions, control strategies. experiments found superheating are in the range of - c; and the superheating increases with air tempera- ture in the evaporator, from to c when the expansion valve is fully open. from viewpoint of energy use, too large superheating is not good. generally, - c superheating are possible. refrigerant superheating refers to the superheating in the evaporator. superheating from tubes can be neglected with well tube-insulating, since superheating from such sources is harmful to energy performance and should be prevented. the effects of heating in the compressor are included in the compressor's isentropic efficiency. the specific enthalpy of the refrigerant at the compressor exit is calculated by where h s is the isentropic efficiency; h , is the specific enthalpy at the condensing pressure by isentropic compression from the evaporating pressure. experimental results have shown that the isentropic efficiency is a weak function of the displacement volume, and varies linearly with the compressor speed. in this analysis, a constant isentropic efficiency of . is assumed, neglecting the rotational speed of the compressor. the specific enthalpy after the expansion valve is calculated by the degree of dryness at the inlet of the evaporator where h , is the specific enthalpy of the saturated liquid refrigerant at the evaporating pressure. the electricity consumed by the compressor where m_ f is the mass flow rate of refrigerant (kg/s); h motor is the motor efficiency, which is considered as . . the energy load of the evaporator heat rejected in the condenser refrigeration efficiency cooling and dehumidification of the incoming fresh air are performed in the evaporator. a detailed modeling of the evaporator and the condenser are rather complicated [ , ] . usually, they are divided into regions associated to the phase of the refrigerant. each region constitutes a separate heat exchanger. in the case of the condenser, the superheated vapor, the condensation and subcooled liquid regions are considered, whereas for the evaporator it is divided into the evaporating and superheated vapor regions. for each region, the refrigerant side and air side convective heat transfer coefficients need be calculated from the established correlations for single-phase and two-phase flow. for the evaporator, when the average fin surface temperature is calculated to be less than the local water dew point of the air stream, moisture condensation will occur. under these conditions, the air heat transfer coefficients can no longer be calculated as in dry conditions, and a water mass balance must be carried out. in this case, the enthalpic method, proposed by threlkeld [ ] and introduced in ashrae handbook [ ] was most adequate for use. according to this procedure, the driving force for heat transfer is assumed to be the difference between the saturated enthalpy of the air flowing over the fins and a fictitious saturated air enthalpy evaluated at the refrigerant temperature. the analysis of air cooling and dehumidifying coils requires coupled, non-linear heat mass transfer relationships. while the complex heat mass transfer theory that is presented in many textbooks is often required for cooling coil design, simpler models based on effectiveness concepts are usually more appropriate for energy estimation. these techniques are resulted from basic heat and moisture transfer equations for simultaneous heat and moisture transport. therefore, in this study, to ease the analysis, thermal performance of the heat exchangers regions is evaluated by the (e, ntu) method. according to this procedure, the heat exchanger effectiveness is defined as where t hi and t ci are the inlet temperatures of the hot and cold fluids, respectively (k). because the operations are set to fluctuate around the design points, constant evaporator and condenser effectiveness are assumed in the simulations. then the air states at the outlets of evaporator and condenser could be obtained. the heat extracted in the evaporator is calculated by where m_ a is the mass flow rate of fresh air stream (kg/s); h ab and h ac are the specific enthalpies of air at point b and c, respectively. similarly, heat rejected at this portion of the condenser is governed by it should be noted that an energy balance requires that eq. ( ) equals to eq. ( ); while q c calculated from eq. ( ) is only a portion of that calculated by eq. ( ). in the study, the evaporating temperature is fixed to c, while the refrigerant flow rate and the condensing temperature varies according to the cooling load of the evaporator and the outside weather conditions. usually, a c log mean temperature difference between the condensing refrigerant and the air flowing through it is required. energy saving for conditioning fresh air can be achieved by the application of heat recovery ventilators, in which a fraction of energy is recovered from the exhaust air to the supply air. there are presently two kinds of techniques available for heat recovery ventilators: sensible heat exchangers and energy wheels. the sensible heat exchangers are simple and reliable, but they cannot recover latent energy. energy wheels, which could save latent energy, are problematic due to rotating moving parts. hydrophilic polymer membranes provide a new alternative. some membranes such as polyethersulphone, cellulose triacetate, and polyvinylchloride, are useful in separating moisture from the vapor/air mixture, due to their strong affinity to the water molecule. the strong affinity also leads to the high permeation difference between water and air. the permeability ratio of water to air ranges from to , . in other words, gases other than vapor can hardly permeate through the membrane. these features have led to the development of a novel ventilator, the so-called membrane based enthalpy exchanger in which both the sensible heat and the moisture are transferred simultaneously through the membrane. since the membranes are very thin, both the heat and the moisture transfer rates can be very high. furthermore, no water condensation happens in the membrane system, which prevents hygienic problems of microorganism growth that is common for cooling coils. in this study, a membrane-based enthalpy recovery ventilator developed in the laboratory is used [ ] . two effectiveness: sensible effectiveness (e s ) and latent effectiveness (e l ) are defined. air state at point b in fig. is calculated by: the membrane-based energy recovery ventilator is just like a traditional plate-type heat recuperator. the only difference is that hydrophilic membranes are used in place of metal plates. a total number of transfer units is used to reflect the sensible heat transfer in an exchanger. for the membrane exchanger that has equal area on both sides of the air streams, the total number of transfer units for sensible heat is [ ] : where u is the total heat transfer coefficient (kw m À k À ), a tot is the total exchange area (m ), m_ a is the mass flow rate (kg/s), and c pa is the specific heat of air (kj kg À k À ). the sensible effectiveness is a function of two dimensionless parameters, ntu and c min =c max , the ratio of minimum to maximum heat capacity rate of the two air streams. for un-mixed cross flows, it can be expressed as [ ] [ ] moisture transfer is more complicated due to the couplings between moisture transfer and operating conditions, as well as membrane materials. by clarification of moisture resistance in membrane, a form similar to eq. ( ) for latent effectiveness has been proposed and validated by the authors as e l ¼ À exp expðÀntu : l m_ min =m_ max Þ À ntu À : and and where k s is convective mass transfer coefficient in supply side (kg m À s À ); d the membrane thickness, and d wm is the water diffusivity in membrane (kg m À s À ); c and w max are constants in sorption curves, which determine the equilibrium between the membrane and moisture at its surface by where u is the moisture uptake in membrane at two surfaces (kg kg À ). the convective mass transfer coefficient k can be estimated from convective heat transfer coefficient by a sensible effectiveness of . is easily obtained with a membrane system, and the latent effectiveness is about . of the sensible effectiveness according to a case study in [ ] [ ] . fan energy is an important factor in the annual energy consumption of an hvac system. fan (pump) performance can be characterized by its efficiency, which itself is dependent on operational air flow rate. mostly, rated volumetric flow rate, pressure rise and efficiency are available from the manufacturer. then rated power can be calculated as where v a is air (water) volumetric flow rate (m /h), dp is total pressure rise (pa), h fan is fan (pump) efficiency. the simulations are conducted on an hour-by-hour basis. the air flow rates are dictated as kg/h per person. the operating hours are from : to : . fan efficiency is selected as . . for the convenience of comparison, energy consumed in the form of electricity is converted to primary energy by a factor of . . in addition, two specific programs was written to calculate the psychrometrics and the thermodynamic properties of r a. it is based on a cubic equation of state [ ] . the calculations are on a per person basis. it is recommended that each person has kg/h of fresh air. the cop varies with both the evaporating temperature and the condensing temperature. the influence of the condensing temperatures on the cop is shown in fig. . as can be seen, the cop decreases with increasing condensing temperatures. when the condensing temperature increases from to c, the system cop decreases from around . - . . following correlation could be formulated for the relation for the refrigeration evaporating at c: the effects of the evaporating temperature on the cop are shown in fig. . the system cop rises with increasing evaporating temperatures. in fact, when the evaporating temperature increases from À to c, cop is improved from . to . . a correlation has been formulated for the analysis of the system performance: cop ¼ : t e þ : t e þ : t e þ : ( ) where the condensing temperature is fixed as c. fig. shows the distribution of the cop of the refrigeration system during a year. as indicated, in winter, the system has higher performance, in contrast, when it's hot in summer, the system cop decreases, which will in return deteriorate the energy requirements. in the analysis, the system is used to treat the latent load solely, and the sensible load of the room is around w/m , which will be extracted by chilled-ceiling panels. results indicate that the annual total energy requirement is .  kj per person. in comparison, an air dehumidification with no energy recovery measures would consume more than .  kj per person of primary energy. in other words, energy saving is %. considering local primary energy price of . usd/mj, the annual economic return for each person would be usd, which is not a small amount, considering china is still a developing country and the energy price is low. with oil prices growing very fast now, we believe the savings potential could be higher in future. fig. plots the primary energy requirements by the dehumidification system for each person in each month in a year. in hot and humid regions like guangzhou, air dehumidification is required most of the year. the energy values vary from .  to .  kj per month per person. in january and february, when it is the dry season, energy requirements are the least. in august, it is the most humid season, required energy is the largest. in office buildings, the moisture load from ventilation air comprises almost all the moisture load. the percentages of the energy required in each month to the annual total energy are shown in fig. . five months from may to september account for . % of the yearly energy load. other months account for the rest . %. south china has a long hot and humid summer. the energy for air dehumidification is substantially large. to save energy while ensuring a healthy built environment with enough fresh air ventilation, an independent air dehumidification system with energy recovery is necessary. concerns on indoor air quality have prompted the researches of novel air dehumidification techniques. this study proposed a new air dehumidification system in which a mechanical dehumidification is combined with a membranebased enthalpy exchanger. an hour-by-hour simulation reveals that the novel independent air dehumidification system could save % of primary energy. with this system, the annual total primary energy used for independent air dehumidification is around .  kj per person. standard - , ventilation for acceptable indoor air quality economic toll of sars, china youth daily dehumidification equipment advances energy savings potential of chilledceiling combined with desiccant cooling in hot and humid climates indoor humidity behaviors associated with decoupled cooling in hot and humid climates thermal comfort and energy consumption of the radiant ceiling panel system, comparison with the conventional all-air system cyrano: a computational model for the detailed design of plate-fin-and-tube heat exchangers using pure and mixed refrigerants numerical simulation of a variable speed refrigeration system thermal environmental engineering energy estimating and modeling methods membrane-based enthalpy exchanger: material considerations and clarification of moisture resistance effectiveness correlations for heat and moisture transfer processes in an enthalpy exchanger with membrane cores thermophysical properties of , , , -tetrafluoroethane (r a) this project is supported by national natural science foundation of china. this project is also supported by the natural science foundation of south china university of technology. key: cord- -xsh wkqy authors: bandaly, victor; joubert, aurélie; le cann, pierre; andres, yves title: the fate of mengovirus on fiberglass filter of air handling units date: - - journal: food environ virol doi: . /s - - - sha: doc_id: cord_uid: xsh wkqy one of the most important topics that occupy public health problems is the air quality. that is the reason why mechanical ventilation and air handling units (ahu) were imposed by the different governments in the collective or individual buildings. many buildings create an artificial climate using heating, ventilation, and air-conditioning systems. among the existing aerosols in the indoor air, we can distinguish the bioaerosol with biological nature such as bacteria, viruses, and fungi. respiratory viral infections are a major public health issue because they are usually highly infective. we spend about % of our time in closed environments such as homes, workplaces, or transport. some studies have shown that ahu contribute to the spread and transport of viral particles within buildings. the aim of this work is to study the characterization of viral bioaerosols in indoor environments and to understand the fate of mengovirus eukaryote rna virus on glass fiber filter f used in ahu. in this study, a set-up close to reality of ahu system was used. the mengovirus aerosolized was characterized and measured with the electrical low pressure impact and the scanner mobility particle size and detected with rt-qpcr. the results about quantification and the level of infectivity of mengovirus on the filter and in the biosampler showed that mengovirus can pass through the filter and remain infectious upstream and downstream the system. regarding the virus infectivity on the filter under a constant air flow, mengovirus was remained infectious during h after aerosolization. many buildings, especially office buildings, create an artificial climate by using heating, ventilation, and airconditioning (hvac) systems. these systems manage and deliver fresh air with a well-controlled temperature (t) and relative humidity (rh) and a reduction in the concentration of particles from the outside air (seppänen and fisk ) . good maintenance of air handling units (ahus) leads to health benefits and better productivity. some individualized biological elements like spores, bacterial cells, and viruses are present in the indoor air and included in the term ''bioaerosol'' (douwes et al. ) . particles can be classified on a scale of . - lm. closed environments are - times more polluted than outside (jones ) . a few studies have provided the number of hours that people spend in closed environments like offices, homes, shops, and gyms. in , export enterprises sa published the number of hours spent indoors per day in different countries in the world. they estimated an average of . h per day, equivalent to % of the day (export enterprises sa ). according to neuroscience research, people sleep for - % of their day (aritake et al. ; siegel ) while another sociological study revealed that people spend % of their day at home (turcotte ) . respiratory viral infections are one of today's most important public health topics due to their high contagiousness. most of them are easily transmitted by direct contact, droplets, or aerosolization. these infections can evolve from an ordinary viral infection to an outbreak (tellier ) . all particles smaller than lm in size can invade a room very rapidly (morawska ) . it is estimated that mg of particles less than lm in size can be emitted by coughing (zhu et al. ) . the study of fabian et al. ( ) demonstrated that a person infected with influenza can exhale - influenza viruses per min with just normal breathing. another study of coxsackie virus explained that viral particles are emitted during sneezing and coughing (couch et al. ; downie et al. ). on average, l of air are breathed by an adult in h (hermann and cier ) . the studies of couch et al. ( ) and downie et al. ( ) observed that infected people can generate . - viruses l - h - and proved that two infected people simply breathing (without coughing or sneezing) and occupying an office of m for h can contaminate indoor air with . virus l - m - (with no renewal of air). an air handling unit is composed of several sections of mixing, heating, cooling, humidification, and filtration. three main filter types are distinguished according to the efficiency of filtration: g -g (low efficiency), m -m ( baverage efficiency \ ), f -f ( baverage efficiency \ ), and e -e /h to h /u -u (very high efficiency [ ) (en : , en : ). air filters consist of clusters of fibers (mats, felts, papers, glass). the efficiency of the air filter is based on four mechanisms (sieving, inertia, interception, and diffusion) (bailly ) . filters in ventilation systems could be a source of microbial air pollution in the closed environment (bluyssen et al. ) . some studies have shown that ventilation systems and ahus spread and transport viral particles inside buildings (ezratty and squinazi ; fabian et al. ; tang et al. ) . in a meta-analysis, studies out of proved the direct contribution of ventilation and airflow to spreading indoor infectious airborne viruses in office buildings during the sars outbreak and other viral outbreaks (li et al. ) . some recent studies have detected airborne bacteria and some specific viruses on hvac filters in a daycare center (prussin et al. ) and large public buildings (goyal et al. ) . myatt et al. ( ) analyzed filters of ahus used for h and showed that filters were contaminated with % picornavirus, % corona virus, and % parainfluenza virus. the temperature and the relative humidity (% rh) in the ahu can have an effect on the persistence of viral particles; as temperature and humidity decreases, the persistence of influenza viruses increases. for example, with a temperature of - °c and % rh, the persistence of the influenza virus is higher than at % rh. the persistence decreases when humidity increases to % (harper ; lowen et al. ; schaffer et al. ). the mengovirus exhibits rapid inactivation at rh between and % (songer ) . there are few studies concerning the behavior of viral aerosols in ahus. this study aimed to develop and standardize an experimental set-up closer to reality to study the spread of viruses in indoor air. it investigates what happens to mengovirus after aerosolization and its fate downstream of the fiberglass filter in closed environments used in air handling units. the performance of the filter in the ahu is assessed in order to reduce the risk of viral transmission in closed environments and have a good indoor air quality and a good life quality. the infectious mengovirus strain mc (atcc vr- ) was used throughout this study. mengovirus is an rna animal virus of the picornaviridae family. this respiratory virus presents a similar structure to the rhinovirus responsible for the common cold with a size of nm. renal epithelial cells, type bgm (buffalo green monkey kidney), enabled the replication of mengovirus. bgm cells were grown in minimum essential medium eagle (meme) (sigma, m , missouri, united states) supplemented with % fetal calf serum (sigma f ), % non-essential amino acid ( ) (sigma, m missouri, united states), and % antibiotic-antimycotic ( ) (sigma, a , missouri, united states) at °c under an atmosphere enriched with % co . a high-efficiency filter classified f according to the standard en ( ) was chosen for this study (camfil farr, stockholm, sweden) because it is commonly used in ahu systems in commercial buildings. this filter is made of fiberglass felt with a developed surface area of ± cm . the f is a highly ventilated multi-layered medium. the filtration velocity is . m s - and the median fiber diameter is ± . lm. in this study, a circular filter of . cm was used in each output (gonzález et al. ) . the experimental design consists of a vertical column made of polymethyl methacrylate where the viruses will be generated and homogenized in the upward air flow. this generation is carried out by the medical nebulizer (omron c -compair pro, hoofddorp, the netherlands) which ensures an air flow of . l min - supplied by compressed air. at the end of the cylinder, four circular outputs of food environ virol ( ) : - diameter cm, which accommodate the filters, are arranged perpendicular to the flow. three of the four outputs are equipped with the filter to be studied. downstream of the filters, the biosampler (skc inc., pennsylvania, usa) samples the particles passing through the filters. the sampling rate is l min - at the entry of each biosampler (skc inc., pennsylvania, usa). two volumetric pumps are set downstream of the device to ensure the flow of air treated through the filters. the frontal filtration velocity at each filter is . m s - and is representative of the velocity observable in the ahus on a pleated f filter. the device is positioned under a laminar flow hood with clean and sterile air. the biosampler (skc inc., pennsylvania, usa) is based on the principle of particle sampling. with a curved inlet tube, it simulates the entry of air through the nasal passage by separating the respirable particles from the non-respirable particles. air samples are collected on ml of meme medium at l min - for or min because the liquids are evaporable (faure ) . the biosampler shows an efficiency greater than % for particles larger than . lm, more than % for particles with a size between . and lm and more than % for particles larger than lm. in this study with a virus size of nm, the efficiency of the biosampler is up to %. the collecting liquid can be analyzed. in order to monitor the amount of particles generated at each of the four filter gates, a fluorescein (cas number: - - , merck kgaa, darmstadt, germany) solution was generated by the medical nebulizer through the filter device, with or without a filter, at a rate of . l min - . after min of aerosolization, the absorbance of the collection liquids contained in the biosamplers and the liquid extracted from the filters was measured at the wavelength k = nm corresponding to fluorescein. it was thus possible to deduce the fluorescein mass retained in the system from a calibration curve (absorbance of fluorescein as a function of the fluorescein concentration in deionized water). this validation was carried out in triplicate. on average, up to . mg of the total fluorescein recovered in the system was collected (biosampler, filter and tube) from an initial fluorescein mass of . mg leading to a set-up efficiency of . %. table shows an example of the system validation by the mass balance of fluorescein. after multiplication of the mengovirus in the bgm cells and taking into account the fragility of the virus, the virus suspension to be aerosolized was obtained directly from the cell culture medium. the culture was centrifuged for min at g to remove cell debris and the supernatant containing the virus was recovered. the aerosol size was analyzed by the electrical low pressure impactor (elpi tm , dekati, kangasala, finland) and the scanning mobility particle sizer (smps tm , tsi, marseille, france). the elpi tm can characterize the aerodynamic size of particles from nm to lm and consists of several removable trays to extract the deposit. the smps tm can characterize the electrical mobility size of particles from nm to lm. mengovirus rna was extracted using a nuclisens Ò easy-mag tm platform (biomérieux, marcy l'etoile, france). the reverse transcription was done on the mengovirus arn and then was quantified using a standardized real-time taqman pcr carried out by the brilliant ii qrt-pcr master mix kit (agilent technologies, california, usa) with the reverse primer mengo ( -gaagtaacatatagacagacgc acac- ), the forward primer mengo ( -gcgggt cctgccgaaagt- ), and the fam-mgb probe men-go ( -atcacattactggccgaagc- ) (pintó, costafreda, and bosch ) . the qrt-pcr program was as follows: min at °c for rt activation, min at °c for enzyme activation, cycles of s at °c for denaturation, and min at °c for annealing-extension. it was carried out on a pcr platform agilent mxpro p (agilent technologies, california, usa). the rna extract of mengovirus was used as pcr positive control. two pcr negative controls were adopted for this study: the extraction of the medium (meme) without virus and the water used in the qrt-pcr mix. the virus was quantified by the standard curve, based on the calibration of mengovirus initial solution. the tcid test was used to determine the infectivity of mengovirus upstream or downstream of the system. this test was carried out on the bgm cells seeded in -well plates, infected with serial dilutions of the sample and then incubated for h at °c with % co . the plates were examined under a microscope to count the positive wells (with a cytopathic effect). infectious titers were then calculated using the spearman-karber method (ramakrishnan ) . the filters were rinsed in ml of the preheated culture medium (meme) with stirring for min at rpm in two stages. the medium was recovered and treated with chloroform to remove any other microorganisms that may be parasitic. an extraction of the virgin filter showed no filter effect on bgm cells when using the tcid test. mengovirus was quantified per genomic unit (gu) on a filter to test the loss of quantity by using this extraction method. from . gu cm - of mengovirus theoretically deposited on the filter, . gu cm - was detected by rt-qpcr. thus, a loss of . log of virus was calculated for this extraction method, giving a yield of %. the medium without virus was aerosolized for min in the experimental set-up. the temperature and relative humidity were measured at the level of the filters. the temperature remained constant at °c ± °c. after min of aerosolization, the rh% increased from to % and reached a max of % in min. then, the rh decreased to % in min and to % after min of aerosolization (fig. ) . particle size distributions of the mengovirus suspension generated by the medical nebulizer were measured with the elpi tm and the smps tm and are presented in figs. and . the polydisperse particle size distribution measured by the elpi tm presents a median aerodynamic diameter (d ae. ) of nm (fig. ) . the particle distribution measured by the smps tm presents a median electric mobility size (d el. ) of nm (fig. ) . the particles collected on the different stages of the elpi tm were extracted in the meme. a rt-qpcr was carried out on each extract to detect and quantify the virus. mengovirus was detected on all the collected fractions above . nm except for the fraction at nm. the virus was quantified based on the concentration of nebulized virus in the initial solution (fig. ) . following the calibration of mengovirus detection by rt-qpcr, the limit detection of this virus was defined to be less than viral particles per liter of air. in the based on the rt-qpcr measurement, the total initial output of mengovirus aerosolized and the viruses recovered in the system (filters and biosampler) were measured. comparing the quantity of mengovirus downstream in the absence of a filter and viruses recovered on the filter, the filter f shows an efficiency between . and . %. with reference to the efficiency curves of the four filtration phenomena (bailly ) and the size of the particles, the experimental set-up used with the virus presents results coherent with filtration performance. the average quantification of experiments showed that from . gu l - air of mengovirus aerosolized for min, . gu cm - was collected on three filters and . gu of mengovirus per liter of air passed through the filters. the output without a filter (biosampler ) was . gu l - air (table ) . comparing the initial concentration aerosolized and the concentration of virus collected downstream of the system without a filter, there was a loss of one log of virus in the system. referring to the fluorescein validation, this loss is attributed to the presence of viruses on the column and pipes, which are difficult to recover. a few microliters of the viral suspension remained in the omron containing . gu of mengovirus. comparing the concentration of the virus in the rest of the omron to the initial solution, no concentration effect was observed during aerosolization (data not shown). according to the infectivity levels of tcid l - air aerosolized upstream of the system and . tcid l - air downstream of the system in the absence of a filter, a loss of . log of infectivity of mengovirus could be estimated (table ) . this result demonstrates an aerosolization effect on the infectivity of the virus. the tcid test showed that mengovirus remained infectious in the air passed through filters (downstream of the system) with . tcid l - air ,whereas . tcid cm - was recovered on the three filters. the infectivity of the mengovirus remaining in the omron was tested. comparing the infectivity of the virus in the rest of the suspension of the omron and the initial one, the virus did not lose infectivity during aerosolization (data not shown). quantification versus infectivity of mengovirus (fig. ) quantification and infectivity were compared on filters and in biosamplers using the plaque forming unit (pfu) ( tcid is equal to . pfu). the results measured from the output without filter (biosampler ) showed . gu l - air of which . pfu l - was infectious. thus, logs of virus lost infectivity during the min of aerosolization. concerning the comparison between the infectivity and quantification of mengovirus on the filters, . gu cm - was detected of which . pfu cm - remained infectious, whereas logs of virus lost infectivity. in the biosamplers, . pfu l - of . gu l - air remained infectious, whereas logs of virus lost infectivity. in the figure, the highest and the lower values of three different essays were shown. electrical mobility diameter (nm) fig. particle size distribution of the mengovirus suspension generated by the medical nebulizer measured with the smps tm (d(n) = number of particles; dp = particle diameter) in this part of the study, the effect of time on the infectivity of mengovirus on the filters was tested. the air flow in the system remained continuous during , , , , and min with min of aerosolization of mengovirus. from an average of . pfu l - of initial solution of virus aerosolized, . pfu cm - of infectious mengovirus was detected after min of air flow. the infectivity increased to . pfu cm - after min, then remained constant until min ( h), and then decreased to . pfu cm - for min ( h) of continuous air flow. the detection of infectivity at min corresponded to the detection limit of the virus with the tcid test. after infectivity ( min ( h), no virus infectivity was detected. with a continuous air flow in the system, the persistence of mengovirus was assessed at different times and showed infectivity on the filter up to h after aerosolization (fig. ) . in the figure, the highest and the lower values of three different essays were shown. in recent years, we have seen the benefits of efforts in the development of indoor air treatment techniques and evolving knowledge of the microbial ecology of bioaerosols, which may play an important role in human health. the experimental set-up used in this study represents a model of the real-life functioning of an air handling unit. the pilot was validated using fluorescein and then confirmed with mengovirus showing an efficiency between . and %. the loss observed in the pilot validation is due to viruses that are retained on the walls of the pipes and the column (difficult to extract), the efficiency of the biosampler collector ( %) and of the filter extraction ( %). the filter used in this study (f -compair) is commonly used in ahus and shows the same filtration speeds ( . m s - ) and an effectiveness of between . and . %. this calculated effectiveness was confirmed in the study of bailly ( ) on the efficiency of the air filter resulting from curves of the four filtration phenomena. the dynamics and characteristics of bioaerosols are an important topic. the size of mengovirus was determined by the study of faulkner et al. ( ) as nm. in this study, some hypotheses can be made: the nebulized mengovirus cannot be aerosolized as a single virus as no virus was detected on the elpi tm stage with the specific size of the virus. the aerosol could be constituted of groups of viruses (more than viruses). the virus could be associated with proteins or debris cells present in the centrifuged medium. this can be confirmed in real life as infectious respiratory viruses are expelled with cell debris and mucus. based on the quantification and detection of infectivity in the system by rt-qpcr and tcid measurement, the study shows that viruses stopped by the filter and those that passed through the filters remained infectious. this loss of infectivity confirms the study of songer ( ) who showed the rapid inactivation of the mengovirus due to the rh% between and % measured in this study during the min of aerosolization. goyal et al. ( ) did not detect any infectious virus in used ventilation filters from two large public buildings but they were able to detect viruses by pcr. farnsworth et al. ( ) showed the difficulty of detecting the persistence of viruses in ahus since most viruses present on ahu filters are deactivated within a day. the study of vasickova et al. ( ) focused on the inactivation rate of viruses on different supports. the review of gerba ( ) revealed different inactivations between viruses. they pointed out differences in inactivation between enveloped and nonenveloped respiratory viruses. for example, they found that the inactivation rate was . log . h - for rhinovirus and . log h - for the respiratory syncytial virus (rsv). they concluded that non-enveloped respiratory viruses can survive longer than enveloped viruses. this shows the importance of using mengovirus in this study, which is a model of non-enveloped rhinoviruses. the who review about the potential transmission of avian influenza (h n ) through water and sewage ( b) reports that, in general, virus half-lives are of the order of hours. the literature states that the virus support, for example, here the filter samples, can play a role in reducing infectivity. the who report on the stability and resistance of the sars coronavirus ( a) indicates that the persistence of this virus on wood and cotton cloth is only h. other studies like sizun et al. ( ) have proved that human coronavirus can persist for only - h on sterile sponges while the study of hall et al. ( ) pointed out that rsv can persist for . h on cloth gowns and h on paper towels. thus, time has an effect on the infectivity of the virus; this study showed that, with a continuous air flow in the the gap between what we know and what we would like to know in this research field remains quite large as recent studies have focused on bioaerosols like bacteria and fungi. this study thus presents new information about the survival of viruses in indoor environments and their fate in air handling units. in further studies, we need to investigate how to reduce the risk of viral transmission in closed spaces using different parameters to improve ahus. time estimation during nocturnal sleep in human subjects traitement de l'air et climatisation-généralités why, when and how do hvac-systems pollute the indoor environment and what to do about it? the european airless project effect of route of inoculation on experimental respiratory viral disease in volunteers and evidence for airborne transmission bioaerosol health effects and exposure assessment: progress and prospects the recovery of smallpox virus from patients and their environment in a smallpox hospital pandemic influenza virus inside buildings: is there a risk of transmission by ventilation or air conditioning systems? influenza virus in human exhaled breath: an observational study influenza virus aerosols in human exhaled breath: particle size, culturability, and effect of surgical masks development of a method for bacteria and virus recovery from heating, ventilation, and air conditioning (hvac) filters studies on protein and nucleic acid metabolism in virusinfected mammalian cells. . the isolation, crystallization and chemical characterization of mouse encephalomyocarditis virus purification de l'air ambiant par l'action bactericide de la photocatalyse evolution of microbial aerosol behaviour in heating, ventilating and air-conditioning systemsquantification of staphylococcus epidermidis and penicillium oxalicum viability occurrence and transmission of food-and waterborne viruses by fomites. virus in food and water filtration performances of hvac filters for pm and microbial aerosols-influence of management in a lab-scale air handling unit detection of viruses in used ventilation filters from two large public buildings possible transmission by fomites of respiratory syncytial virus airborne micro-organisms: survival tests with four viruses précis de physiologie, : bioénergétique et rations alimentaires, sang, lymphe, compartiments liquidiens de l'organisme, circulation du sang, respiration. éd. révisée. vols. précis de physiologie indoor air quality and health role of ventilation in airborne transmission of infectious agents in the built environment-a multidisciplinary systematic review influenza virus transmission is dependent on relative humidity and temperature droplet fate in indoor environments, or can we prevent the spread of infection? indoor air detection of airborne rhinovirus and its relation to outdoor air supply in office environments norme de filtration en par camfil risk assessment in shellfish-borne outbreaks of hepatitis a seasonal dynamics of the airborne bacterial community and selected viruses in a children's daycare center determination of % endpoint titer using a simple formula survival of airborne influenza-virus-effects of propagating host, relative humidity, and composition of spray fluids summary of human responses to ventilation why we sleep survival of human coronaviruses e and oc in suspension and after drying onsurfaces: a possible source ofhospital-acquired infections influence of relative humidity on the survival of some airborne viruses factors involved in the aerosol transmission of infection and control of ventilation in healthcare premises review of aerosol transmission of influenza a virus time spent with family during a typical workday who first data on stability and resistance of sars coronavirus compiled by members of who laboratory network who review of latest available evidence on potential transmission of avian influenza (h n ) through water and sewage and ways to reduce the risks to human health study on transport characteristics of saliva droplets produced by coughing in a calm indoor environment acknowledgements this study was supported by the imt-atlantique bretagne-pays de loire and the ecole des hautes etudes de santé publique (ehesp). the authors are thankful for the mengovirus eukaryote rna virus provided by the prof. albert bosch from the enteric virus laboratory, universitat de barcelona, spain and grateful for the buffalo monkey african green kidney cell (bgm) provided by the inovalys laboratory, nantes, france. key: cord- - agf j authors: ciofi-silva, caroline lopes; hansen, lisbeth lima; almeida, alda graciele claudio dos santos; kawagoe, julia yaeko; padoveze, maria clara; graziano, kazuko uchikawa title: negative pressure of the environmental air in the cleaning area of the materials and sterilization center: a systematic review date: - - journal: rev lat am enfermagem doi: . / - . . sha: doc_id: cord_uid: agf j objective: to analyze the scientific evidence on aerosols generated during cleaning activities of health products in the central service department (csd) and the impact of the negative pressure of the ambient air in the cleaning area to control the dispersion of aerosols to adjacent areas. method: for this literature systematic review the following searches were done: search guidelines, manuals or national and international technical standards given by experts; search in the portal and databases pubmed, scopus, cinahl and web of science; and a manual search of scientific articles. results: the five technical documents reviewed recommend that the csd cleaning area should have a negative differential ambient air pressure, but scientific articles on the impact of this intervention were not found. the four articles included talked about aerosols formed after the use of a ultrasonic cleaner (an increased in the contamination especially during use) and pressurized water jet (formation of smaller aerosols μm). in a study, the aerosols formed from contaminated the hot tap water with legionella pneumophila were evaluated. conclusions: there is evidence of aerosol formation during cleanup activities in csd. studies on occupational diseases of respiratory origin of workers who work in csd should be performed. aerosols are generated and released by humans in various activities, such as breathing, talking, coughing and sneezing; bathing with contaminated water; aerosolization of sewage waste in toilets or drainage system for outdoor environments; cleaning and rinsing surfaces indoors; spraying in agriculture ( ) . aerosols are defined as smaller particles or equal to μm, that may or may not contain an infectious agent and, due to their size, can remain suspended in the atmosphere for hours, slowly being transported over long distances and achieve adjacent areas ( ) . aerosols containing an infectious agent that remain in the environment can be inhaled by susceptible individuals, even if there is no close contact with the disposing source, or contaminated surfaces ( ) . the main diseases transmitted by aerosols are tuberculosis, measles and chicken pox. however, there are reports of aerosolization of other microorganisms such as fungi, clostridium difficile and staphilococcus aureus ( ) ( ) . the droplets that are larger than μm, remain suspended for a few seconds and quickly lay on the floor or other surfaces due to gravity. its liquid portion can evaporate, depending on the environmental conditions, resulting in aerosols. there are slight variations of the nomenclature and definition of sizes, however the brazilian national health surveillance agency (anvisa) uses the definition that aerosols are smaller than μm, which was adopted for this study ( ) ( ) . ventilation systems and air conditioning in various establishments promote comfort, and are useful in the prevention and treatment of diseases transmitted via aerosols. the use of these systems in health services (hs) requires special attention. the basic differences stem from the need to restrict the dispersion of air within an environment to adjacent areas; the specific requirements for ventilation and filtration aiming to dilute and eliminate contamination; the different requirements of temperature and humidity for each area; and sophistication that is demanded for the project ( ) . among hospital sectors that require air pressure control, temperature and humidity we highlight the central service department (csd). the csd is responsible for medical device (md) from one use to another, it must contain a reception and cleaning room; a preparation and sterilization room; a chemical disinfection room (where applicable); a monitoring area of the sterilization process and a storage and distribution of sterile materials room ( ) . the rdc resolution , of march , from anvisa, disposes on the good practice requirements for the processing of md and other measures. according to this resolution, the csd class ii (which processes complex materials) and processing companies must maintain a negative differential air pressure between the cleaning area and adjacent areas ( ) . the areas adjacent to the reception and cleaning room consist mainly of the preparation and sterilization room of md and circulation areas of other professionals. differential ambient air pressure means that there is a difference in measuring the relative air pressure between two areas. this parameter works to provide a positive or negative pressure within a particular area in order to prevent air from migrating from one to the other. if a room has a negative air pressure it means that the air supply is less than the exhaustion ( ) . with the growing concern for the safety of patients and health professionals, there is a need for implementation of best practices that should be based on proven scientific evidence. thus, the objective of this systematic literature review was to analyze the scientific evidence for the formation of aerosols during the md cleaning activities in csd and the impact of negative air pressure, or to the safety of the material to be sterilized, and for health professionals in the adjacent areas too. the steps of this systematic review followed the guidelines published in the preferred reporting items for systematic reviews and meta-analysis (prisma) statement, which aims to help the authors to carry out complete and clear records of a systematic review and meta-analysis ( ) . numerical assignments, level zero being considered low risk and level three the ambient with high-risk health problems related to air quality. the csd was classified as level one "an area where it was not found the risk of health problems related to air quality, but some authorities, organizations and researchers suggest that the risk should be considered." all the technical documents analyzed ( , ( ) ( ) ( ) ( ) in brazil, the nbr / ( ) is followed, referring to csd in the cleaning area, which resembles the international recommendations, as shown in figure . documents ashrae* ( ) ( the four scientific articles included ( ) ( ) ( ) ( ) are studies in english: three ( ) ( ) ( ) published between the decades of - and only one in the s ( ) ; three ( ) ( ) ) are laboratory experimental studies and one is transversal ( ) (held in hospital bathrooms); three ( - ) studies conducted in the united states and one in australia ( ) . no studies that evaluated the negative air pressure in md cleaning areas were found on the searches. therefore, studies that evaluated the formation of aerosols during cleaning products or surfaces were included, even if not specifically made in a csd environment. in three studies ( ) ( ) ) , experiments were performed to analyze the aerosol recovery generated from equipment commonly used in the csd: ultrasonic cleaner and scrubbers with pressurized water. in the study conducted with the ultrasonic cleaner ( ) , air samples above the water surface in the washer tank were collected (the air gatherer had a flexible termination that was placed inside the washing machine), aiming to recover aerosols with pseudomonas aeruginosa. air specimens were obtained in four moments: before the washer was turned on (during comparative analyzes using statistical tests were not performed. in another study ( ) , in order to evaluate the formation of aerosols during household activities, a car cleaning experiment was conducted in a controlled environment, sealed with plastic. two ways of using the hose with pressurized water were tested: spraying (used for rinsing) and a water jet with controlled flow (used to remove dirt), conventional (low pressurization -manual trigger) and efficient (high pressurization). the authors used three gauges of particle sizes not aiming to identify microorganisms in aerosols. it was observed that when used in higher pressurization (efficient method), more and smaller particles were identified (up to μm). however, there were no statistically significant differences between the methods: efficient and conventional or between the spray modes and jet. the authors reported that they observed the formation of visible fog in the tent where the experiments were carried out, especially after the high pressurization method, and cogitated they were hydrated aerosols, possibly lower than ηm. a study ( ) was included considering the possibility that the csd could be equipped with hot tap water. in the summary of the results is shown in figure . high-pressure hose with manual trigger device (conventional method) and high pressurization (efficient method); two types of water flows (spray and jet). three particle gauges ( ηm to μm). the average of aerosols produced by the high pressurization device were higher in all experiments (high standard deviations) when compared to the conventional, and a greater number of particles smaller than μm (more than % went until μm). high-pressure devices: greater concern with air transmission of microorganisms. partially air samples were positive for legionella pneumophila in six of the areas. there was variation in the water samples ( -> cfu) and air ( , - , ufc / ft ). there was correspondence between subtypes of water and air strains. shower heads and taps may produce aerosols with a reduced number of l. pneumophila during routine use, that may penetrate the lower respiratory system. inconclusive. increase of times of aerosols compared to the initial contamination, with the lid of the washer on, and times without the lid (respectively, p = . and p = . ). higher contamination during operation. air contamination from the washer may be minimized by daily cleaning of the cleaning solution storage using germicide in it. use lid washer. partially conclusive. braymen, ( ) / experimental laboratorial intentional contamination of the wall; automatic washer with pressurized jet, with water and disinfectant solutions. air samples to determine the particle size (during and after the procedure). after spraying, about % of the particles were up to μm (aerosols). after brushing, approximately . % were greater than μm (droplets). all disinfecting solutions reduced the number of viable microorganisms in aerosols. microorganisms are aerosolized in a number enough to contaminate susceptible individuals or products. healthcare professionals that clean must use respiratory personal protection equipment. partially conclusive. cleaning area, the construction of an anteroom should be considered ( , ) . the influence of the movement of doors and people traffic in the negative pressure air efficiency in isolation rooms was demonstrated in the study by adams, johnson and lynch ( ) . the air pressure differentials were measured between the room and the anteroom and between the room and the hallway. the average in the aerosol count per m where larger when there were greater movement of people and doors, however the aerosol score decreased as the air pressure differential increased. the authors indicate a negative air pressure differential of pa when there is heavy traffic between areas. in this context, there is a need for routine monitoring of the pressure differential between the areas, for example, by testing with the observation of the direction of smoke flow or specific gauges ( ) . other parameters shown in figure and creating air flow patterns ( ) . the need for negative air pressure in isolation rooms is strongly evidenced in the literature, aiming to reduce the risk of exposure microorganisms transmitted by aerosol infected people to uninfected people (especially other patients or professionals). the advent of diseases such as severe acute respiratory syndrome, avian flu and drug resistant tuberculosis raises concern for health authorities in relation to the isolation of patients ( , ) . in the selected technical papers for this review, there is a consensus of the need for negative pressure air in cleaning and decontamination areas of the md in csd. this directive corresponds to the norms of the rdc anvisa / ( ) , where it is stated that in class ii csd a negative differential ambient air pressure (minimum , pa) should be kept between adjacent areas. however, it was found that both the national and international technical documents do not cite scientific references that prove, with conclusive evidence, the risk of environmental exposure to aerosols for both the md and for professionals. the classification of csd as level one, related to the risk of adverse health events by exposure to ambient air ( ) , states that this risk is not scientifically proven, but based on expert opinions, which reinforces the need for research to generate data for the support of laws, rules and recommendations. as mentioned in the introduction of this study, microorganisms in the air of the csd environment can be related to two issues: inhalation by professionals and depositing of them on the clean material in the preparation area. regarding the last issue, considering that the md will be sterilized before use and that this also there is no consensus on the number of air changes per hour in isolation rooms ( ) . the release of aerosols also occurs in other sectors of the health system. in the study of verde and collaborators ( ) , the goal was to characterize the air pollution levels in different areas of the hospital (emergency room, surgical ward and operating room). after finishing the procedure, it was detected an increase in the concentration of bacteria in the air. however, the contamination level returned to baseline values (collected in the empty operating room) after cleaning procedures. bronchoscopy is a procedure recognized for its potential to generate aerosols, by stimulating coughing patient leading to the contamination of the environment and professionals. in the study by lavoie and collaborators ( ) , although it is not the main goal of the authors, sizes and aerosol concentrations were compared in two bronchoscopy rooms, (one with negative differential air pressure and one without). after statistical analysis, it was shown statistically significant increase in the average concentration of aerosols per m in a non-negative differential room during the performance of bronchoscopy, and there was no significant increase in the room with differential. these or dirt adhered to products) ( ) . despite using the same principle, the equipment currently available are modern, of different dimensions and efficiency when compared to the washer used in the study included in this review ( ) , and the fact that they are usually operated capped. a limitation of this study was the definition for the recovery of only one microorganism (pseudomonas aeruginosa) and it was rated as partially conclusive. in the studies included in this review ( , ) , it was shown that using pressurized water cleaning devices generate more aerosol when compared to conventional methods (brushing and low pressurization of water). considering the guiding question of this review and the fact that these experiments were not performed in a csd environment they were classified as partially conclusive. on csd, the pressurized water guns are used for crude dirt cleaning. compressed air guns are used for drying products with lumen and complex conformation ( ) . about the size of the particles, it was evidenced in this review that the aerosol generated after the use of pressurized water surface cleaning devices were smaller than μm ( , ) . in the study of bollin and collaborators ( ) , there are reports that legionella pneumophila aerosols generated by the tap were larger than the ones in the shower, however, there is no detailed description of the sizes. particles larger than μm are more likely to remain on the surface of the upper airways and not penetrate into the lower lung regions. however, the smaller the particle size, the easier it is its moving until the alveoli ( ) . researchers say less than μm aerosols can be easily inhaled and it moves slowly with speed lower than m / h ( ) . the size of the aerosol is the factor that most influences in its biological properties and displacement. the permanence of aerosols in ambient air undergoes action of physicochemical processes such as evaporation, interaction with other particles, transportation, gravity, temperature, relative humidity and air currents, among others. there are reports that aerosols remain suspended in the same environment for years ( ) . therefore, there is evidence of air pollution in the csd cleaning area; however, data on the permanence in the air and displacement of aerosols to adjacent areas is lacking. a limitation of the studies included in this review was the lack of control of environmental factors where the experiments were carried out, which may have underestimated or overestimated the recovery of aerosols. in a study of this review the contamination of water and air by legionella pneumophila was evaluated and it was identified that the strains detected in aerosols were of the same subtype of the samples of shower water and hot tap water ( ) . this study has limitations regarding the collection of data because there has been no standardization of the number of samples, time and air collection instrument, furthermore, the authors collected water samples a week before the air samples, which resulted in its classification as an inconclusive study. water ( ) . infection by these bacteria generates concern especially for immunosuppressed people. in a retrospective study in elderly care institutions ( ) , ( ) . there were no scientific evidence on occupational diseases related to the cleaning activity in csd. greater emphasis is given to accidents with sharp objects, chemical or ergonomic exposure. the use of ppe in csd is problematic due to the compliance to the use and discomfort reported by the professionals working in this sector ( ) . nurses should the responsibility to raise awareness and motivate the csd team of the obligation and benefits of using ppe. considering the occupational health of the csd workers, the environment temperature control contributes to the comfort of the professional ( ) . the control of this parameter, and the relative humidity is possible through thermo hygrometer installation. however, maintenance of air quality with microbiological approach, based on the values recommended by ashrae ( ) , it is impractical in the reality of the csd. in this sector there is no full control of conditions of environmental contamination, as carried out in a controlled production structure, found in the pharmaceutical industry, considering that microorganisms can be released both by professionals (eg, movement of people, sneezing, coughing, expiration, speech) and by the activities carried out there. droplet fate in indoor environments, or can we prevent the spread of infection? indoor air curso básico de controle de infecção hospitalar -caderno c métodos de proteção anti-infecciosa guideline for isolation precautions: preventing transmission of infectious agents in healthcare settings roles of sunlight and natural ventilation for controlling infection: historical and current perspectives aerial dispersal of meticillin-resistant staphylococcus aureus in hospital rooms by infected or colonised patients american society of heating, refrigerating, and air-conditioning engineers (ashrae). health-care facilities ventilating and air conditioning application. si edition the prisma extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations associação brasileira de normas técnicas healthcare infection control practices advisory committee. guidelines for environmental infection control in health-care facilities. recommendations of cdc and the healthcare infection control practices advisory committee (hicpac) disponível em: www.cdc.gov braymen dt. survival of micro-organisms in aerosols produced in cleaning and disinfecting bacterial aerosolization from an ultrasonic cleaner aerosols containing legionella pneumophila generated by shower heads and hot-water faucets risk in the mist? deriving data to quantify microbial health risks associated with aerosol generation by water-efficient devices during typical domestic water-using activities the effect of pressure differential and care provider movement on airborne infectious isolation room containment effectiveness hospital and community acquired infection and the built environment -design and testing of infection control rooms american society of heating, refrigerating, and air-conditioning engineers (ashrae). hvac design manual for hospital and clinics microbiological assessment of indoor air quality at different hospital sites evaluation of bioaerosol exposures during hospital bronchoscopy examinations indicadores de avaliação do processamento de artigos odonto-médico-hospitalares: elaboração e validação the role of particle size in aerosolised pathogen transmission: a review dispersion of exhaled droplet nuclei in a two-bed hospital ward with three different ventilation systems characterization of infectious aerosols in health care facilities: an aid to effective www potential in-hospital modes of transmission of legionella pneumophila: demonstration experiments for dissemination by showers, humidifiers, and rinsing of ventilation bag apparatus legionella bacteria in shower aerosols increase the risk of pontiac fever among older people in retirement homes uso dos equipamentos de proteção individual entre trabalhadores das centrais de material e esterilização key: cord- -ct xyntw authors: lemey, philippe; rambaut, andrew; bedford, trevor; faria, nuno r.; bielejec, filip; baele, guy; russell, colin a.; smith, derek j.; pybus, oliver g.; brockmann, dirk; suchard, marc a. title: the seasonal flight of influenza: a unified framework for spatiotemporal hypothesis testing date: - - journal: nan doi: nan sha: doc_id: cord_uid: ct xyntw global mobility flow data are at the heart of spatial epidemiological models used to predict infectious disease behavior but this wealth of data on human mobility has been largely neglected by reconstructions of pathogen evolutionary dynamics using viral genetic data. although stochastic models of viral evolution may potentially be informed by such data, a major challenge lies in deciding which mobility processes are critical and to what extent they contribute to shaping contemporaneous distributions of pathogen diversity. here, we develop a framework to integrate predictors of viral diffusion with phylogeographic inference and estimate human influenza h n migration history while simultaneously testing and quantifying the factors that underly it. we provide evidence for air travel governing the global dynamics of human influenza whereas other processes act at a more local scale. global mobility flow data are at the heart of spatial epidemiological models used to predict infectious disease behavior but this wealth of data on human mobility has been largely neglected by reconstructions of pathogen evolutionary dynamics using viral genetic data. although stochastic models of viral evolution may potentially be informed by such data, a major challenge lies in deciding which mobility processes are critical and to what extent they contribute to shaping contemporaneous distributions of pathogen diversity. here, we develop a framework to integrate predictors of viral diffusion with phylogeographic inference and estimate human influenza h n migration history while simultaneously testing and quantifying the factors that underly it. we provide evidence for air travel governing the global dynamics of human influenza whereas other processes act at a more local scale. global public health is repeatedly and increasingly challenged by the emergence of highimpact pathogens [ ] . novel influenza strains, severe acute respiratory syndrome (sars) virus and methicillin-resistant staphylococcus aureus represent only a few examples of pathogens that exploited today's complex and voluminous human traffic and mobility to rapidly disseminate in our globalized world. the worldwide air transportation network is by far the most extensively studied mobility system in the context of human infectious disease dynamics [ ] . indeed, air travel represents an obvious driving force for the global circulation of seasonal influenza a (h n ) viruses, and may explain the absence of locally persistent strains in between epidemic seasons [ ] . retrospective modeling of the 'hong kong flu' pandemic spread demonstrated that the h n virus diffused through a network of global cities interconnected by air travel [ ] . numerous modeling studies have subsequently examined the influence of air travel on influenza spread (e.g. [ , , , ] ), but far less work has attempted to verify such models against underlying patterns of host movement [ ] . two studies on the timing and rate of seasonal influenza spread across the united states have highlighted the difficulty of resorting to standard epidemiological data to disentangle the contributions of different human transportation systems to influenza spread. using weekly time series of excess mortalities between and , [ ] demonstrated that the patterns of timing and incidence across the continental united states are significantly associated with euclidean distance and various measures of domestic transportation (including airline travel), but most strongly with rates of movement of people to and from their workplaces. in the same year, brownstein et al. ( ) [ ] demonstrated that the rate of inter-regional spread and timing of influenza in the united states, as measured using weekly influenza and pneumonia mortality statistics from to , is predicted by domestic airline travel volume in november. because both studies implicated a different key driver of seasonal influenza spread across the united states, the findings were subject of debate [ ] , in particular in the light of a mounting threat of an influenza pandemic [ , ] and the need for decisions on implementing travel restrictions. insights at the global scale are also revealed by simulation studies (e.g, [ ] ), and empirical analysis using global mortality data may prove even more challenging. as a historical record of epidemic spread, viral genetic data may offer a valuable alternative for empirical verification of epidemic models. the power of fitting statistical models of evolution to observed sequence data has clearly been demonstrated by a number of seminal studies, e.g. by revealing the genetic dynamics of influenza a h n seasonality [ ] and spatial patterns of global h n circulation [ , ] . more generally, viral phylogenetic and epidemiological insights have culminated into a phylodynamic framework that unifies evolutionary and ecological dynamics to explain patterns of viral diversity [ ] . although model-based inference is increasingly used to reconstruct viral diffusion through time and space, these attempts typically fit parameter-rich models to sparse spatial data, and post-hoc interpretation of phylogeographic patterns are then difficult to relate directly to underlying ecological and evolutionary processes [ ] . here, we present a novel model-based approach to simultaneously reconstruct spatiotemporal history and test the contribution of potential diffusion predictors. our phylogeographic reconstruction considers discrete sampling locations defined by geographical and administrative boundaries as well as air communities identified through direct analysis of the global air transportation network. by parameterizing the discrete diffusion process in terms of the inclusion and contribution of predictors, our approach generally requires considerably fewer parameters compared to standard phylogeographic inference. we demonstrate how this model allows for the integration of viral genetic data and human mobility measures to draw inference about key drivers of global influenza dynamics. we compiled hemagglutinin sequences with known date and location of sampling previously obtained by [ ] . these sequences were sampled globally from to and are representative of a larger sampling ( , isolates) used for antigenic analysis [ ] . we explored different spatial and air travel-assisted subdivisions with subsampling to examine the impact of discrete sampling allocation and sample numbers per locations on our phylogeographic estimates. in an attempt to include all sequence data while keeping the number of samples per location as balanced as possible, we first divided all the sequences into geographic regions (table ). since these spatial partitions sometimes required arbitrary subdivisions (e.g. breaking up usa, china, japan and australia), we also applied a discrete location scheme that accommodated a single location for these spatially and administratively coherent regions, arriving at geographic regions ( table ). within each sampling year, we randomly down-sampled the five locations with the highest number of samples relative to their population size (usa: from to ; australia: from to ; new zealand: from to ; japan: from to ; south korea: from to ) and analyzed three different subsampled data sets. because passenger flux emerged as the main predictor in our phylogeographic model (see . . ), we also identified discrete air communities in the worldwide air transportation network (see . . ) and applied these as location states to our sequence sample. to increase sequence numbers for under-sampled air communities, we also complemented the hemagglutinin gene sequences with publicly available sequences from africa (n = ), usa (hawaii, n = ), central america (n = ), south america (n = ) and canada (n = ). from this data set, we removed six sequences that appeared to be outliers in a root-to-tip divergence versus sampling time regression analysis, resulting in a total of sequences. within each sampling year, we randomly down-sampled the four locations with the highest number of samples relative to their population size (usa: from to ; oceania: from to ; japan: from to ; southeast asia: from to ) and analyzed three different subsampled data sets discretized according to the air communities. the worldwide air transportation network is defined by a passenger flux matrix that quantifies the number of passengers traveling between each pair of airports. we use a dataset provided by oag (official airline guide) ltd. (http://www.oag.com), containing , airports and the number of seats on scheduled commercial flights between pairs of airports during the years - . the number of seats on scheduled commercial flights from airport i to j is given by Ψ ij , which we take to be proportional to the number of passengers traveling. for the location scheme, we summarized the number of passengers from the full aviation network for each pair of locations based on all the airports in the respective regions. to facilitate the identification of air communities, we focused on a -largest-airport network that represented % of the passenger flux of the full aviation network by excluding the lowest contributing airports. by focusing on this subset of largest airports, we exclude a large number of very small community airports; details and plausibility of this reduction are discussed in [ ] . to identify air transportation communities, we approximate a maximal-modularity subdivision of the -largest-airport network by employing a recently described stochastic monte-carlo approach [ ] , a generalization of the method introduced in [ ] . modularity provides a measure of how well the connectivity of a network is described by partitioning its nodes into non-overlapping groups. for any given partition, modularity will be high if connectivity within groups is high and connectivity among groups is low. in large networks, it is generally computationally impossible to find the optimal subdivision. to approximate the optimum a variety of approximative methods have been introduced. the method we employ here generates an ensemble of high modularity subdivisions and computes the consensus in this ensemble by superposition, for details see [ , ] . for an ensemble of modularity subdivisions we quantify the uncertainty by an affinity matrix that, for each pair of locations, summarizes the fraction of partitions in which these locations are in the same community. based on a partition encompassing a reasonably large number of air communities (n = ), we subsequently obtain the average affinity for each airport to the communities in this partition. we assign each airport to the community for which it shows the highest average affinity, but we take into account its uncertainty by also considering assignments that yield affinities that are > / of the highest affinity score. this cut-off resulted in ambiguous airport assignments. finally, we partitioned the sequence data according to the air community assignment and accommodate ( %) ambiguous sequence locations, i.e. those sequences related to airports with ambiguous community assignments, using ambiguity coding in our phylogeographic approach. we integrate genetic, spatial and air transportation data within a single full probabilistic evolutionary model and simultaneously estimate the parameters of phylogeographic diffusion using markov chain monte carlo (mcmc) analysis implemented in beast [ ] . we introduce novel models and inference procedures in the section below. to model sequence evolution, we partition the hemagglutinin codon positions into first+second and third positions [ ] and apply a separate hky [ ] ctmc model of nucleotide substitution with discrete gamma-distributed rate variation [ ] to both. we assume a flexible bayesian skyride prior over the unknown phylogeny [ ] . exploratory runs using the data for the locations indicated that a relaxed molecular clock represented an over-parametrization [ ] . a strict clock was therefore used in subsequent analyses. because the exact date of sampling was not known for some additional publicly available sequences, we integrated out their dates over the known sampling time interval [ ] . we capitalize on beagle [ ] in conjunction with beast to improve computational performance on our large data sets. mcmc analyses were run sufficiently long to ensure stationarity as diagnosed using tracer. we used the treeannotator tool in beast to summarize trees in the form of maximum clade credibility (mcc) trees. we develop a novel model-based approach to simultaneously reconstruct spatiotemporal history and test the contribution of potential predictors of spatial diffusion. this approach builds on recently developed bayesian phylogeographic inference methods to simultaneously reconstruct phylogenetic history and discretized diffusion processes [ ] . these processes are modeled as continuous-time markov chain processes parameterized in terms of a k x k infinitesimal rate matrix of discrete location change ( Λ). here, we extend this model by adopting a generalized linear model (glm) approach that considers every rate of movement (Λ ij ) in Λ as a log linear function of an arbitrary number of predictors x, such that: for n predictors, where β represents the effective size for the predictor log p, quantifying its contribution to Λ ij , and δ is an ( , )-indicator variable that governs the inclusion or exclusion of the predictor in the model. the incorporation of indicator variables allows bayesian stochastic search variable selection (bssvs) [ , ] , which estimates the posterior probabilities of all possible linear models that may or may not include the predictors. when an indicator equals , this predictor is included in the model, demonstrating that it helps to explain the diffusion process in the phylogenetic history with high probability. we complete this glm specification with variable selection by assigning independent bernoulli prior probability distributions on δ, effectively placing equal probability on each predictors inclusion and exclusion. lemey [ , ] to express how much the data change our prior opinion about the inclusion of each predictor. these bfs are calculated by dividing the posterior odds for the inclusion of a predictor with the corresponding prior odds (here, : odds). where p i is the posterior probability that the predictor is included, in this case the posterior expectation of indicator δ i , and q i is the prior probability that δ i = . we specify that a priori the β's are normally distributed with mean and a variance of . we implement the glm-diffusion parametrization in the software package beast [ ] and approximate the joint posterior and its marginalizations using standard markov chain monte carlo (mcmc) transition kernels. an important, novel extension to the standard mcmc machinery in beast lies in generating an efficient metropolis-hastings proposal distribution for the glm coefficients β. given the potential for high correlation between predictors x, attempting to update one coefficient β j at a time while holding the remaining constant returns high autocorrelations times. instead, we exploit the fixed correlation structure x x between predictors to generate a multivariate proposal β . in particular, if we assume β are the current realized values, then we draw where α is an auto-tunable variance scalar. motivation for this proposal stems from imagining that the marginal posterior distribution of β under our phylogenetic glm should partially approximate a simple linear regression model involving β, whose posterior variance is proportional to x x. we consider a 'bit-flip' operator on the bernoulli rate indicators; this transition kernel is further discussed in [ ] . we extended the phylogeographic inference techniques to take into account ambiguous location states in order to accommodate the uncertainty of the modularity maximization procedure in assigning airports to distinct discrete air communities (see . . ). depending on the location state partitioning scheme, we considered several potential predictors of global influenza diffusion: • average and minimum distance. to test whether geographical proximity predicts influenza diffusion we considered two different great-circle distance measures: (i) the average distance between two locations based on the pairwise distances between all pairs of airports from the two locations and (ii) the minimum distance amongst those pairwise distances. • absolute latitude. absolute latitudes for each region/community were calculated as the absolute values of the average latitudes of the sequence sampling locations (sequences from unknown locations within specific countries were assigned to the capital of that country) and are listed in tables , and . • passenger flux. the total number of passengers traveling between each pair of locations per day (see . . ). • population size and density. demographic estimates obtained from www.citypopulation. de or geographica [ ] are listed in tables , and . origin and destination population sizes/densities were included as separate predictors. • viral surveillance data. to test the predictive power of viral surveillance data, we essentially aimed at capturing the nature and degree of synchronicity of yearly incidence profiles in each region. to this purpose, we extracted the number of influenza viruses a(h ) detected per country from week in to week in from flunet/who (www.who.int/flunet) for relevant countries in the discrete partition schemes. taiwanese surveillance data was obtained from [ ] . we focused on the influenza a(h ) incidence counts between - or as close as possible to this time period when insufficient data was available. average incidence counts were used when data from multiple countries per region/community was available. we subsequently calculated average incidences per week across multiple years for each region/community, normalized these weekly averages and smoothed them with a gaussian standard deviation of weeks. figure depicts the resulting incidence profiles for the air communities. we derived several potential predictors from these incidence profiles, including incidence overlap, origin incidence versus destination growth rate, peak time difference, and incidence in the origin location at fixed times prior to peak incidence in the destination location. the incidence overlap summarizes the overlapping area under the origin-destination incidence curves for each pair of locations. the origin incidence versus destination growth rate sums the product of origin incidence and destination growth rate for each week of the year. peak time difference quantifies the difference in peak incidence for each origin-destination pair. for the latter, we summarized the donor incidences at , , , , and weeks prior to peak incidence in the destination location as potential predictors. • antigenic evolution. because antigenic evolution can provide insights into the seeding dynamics of seasonal h n [ ] , we sought to include the average antigenic divergence for each region as phylogeographic diffusion predictors. based on the available antigenic cartography data for the strains in our phylogeographic analyses, we performed a local regression (loess) of the principle antigenic component, obtained from a multidimensional scaling analysis of hemagglutination inhibition assay measurements [ ] , against time. the resulting scatter plot with strains colored according to air community is presented in figure . distances from the spline (residuals) were calculated for each antigenic measurement and average residuals were obtained for each region/community, which reflects whether a location is on average antigenically leading or trailing [ ] . these average residuals are listed in tables , and . we considered the exponentiated residual and exponentiated negative residual as a measure of efflux and influx respectively for each location and included these as separate origin and destination predictors. • sample sizes. to test the impact of sampling effects, we considered origin and destination sample sizes (number of h n sequences included per discrete location state in the phylogeographic analysis) as separate predictors. although sampling sizes are expected to have an impact on the number of location transitions, support for other factors in addition to sampling size predictors may suggest that they are robust to potential sampling biases. all predictors were transformed to log space and standardized prior to their incorporation in the glm approach. although we generally desire to simultaneously reconstruct sequence and discrete/continuous trait evolution using our bayesian statistical framework, integrating over tree-space becomes a computationally daunting task for a large number of taxa. the main limiting factor in bayesian mcmc analysis of evolutionary history is typically the efficiency with which topology proposals sample phylogenetic tree space [ ] . to side-step these limitations and reduce time to convergence, we seek to approximate phylogenetic uncertainty in our phylogeographic estimates in cases where sampling tree space needs to be performed repeatedly (e.g. when comparing different diffusion models). to this purpose, we follow [ ] and implement proposal mechanisms to randomly draw from an empirical posterior distribution of trees, which, in our case, were solely inferred from sequence data. because the likelihood of a tree topology will largely be dominated by an informative sequence alignment compared to a single discrete (location) site, we expect such an empirical distribution to closely approximate the phylogenetic uncertainty in the joint inference approach. to identify key factors in seasonal influenza dispersal, we inferred the phylogeographic history of globally sampled a/h n viruses between and , while simultaneously evaluating the contribution of several potential diffusion predictors using a novel bayesian model selection procedure. our approach draws from recent developments in stochastic phylogenetic diffusion models [ ] , and extends these by parameterizing pairwise diffusion rates as a function of a number of potential predictors, distinguishing between the statistical support for a predictor and the magnitude of its effect (see methods). we discretized the global sampling locations into and geographically defined regions (table and respectively) as well as into distinct air travel communities (table ) . to identify this community structure in global air travel, we determined partitions with high intra-module connectivity and low inter-module connectivity in a passenger flux network of airports. although this approach is blind to the geographic locations of the airports, the global air communities are spatially compact with few exceptions (figure ) . we compared a panel of possible predictors of phylogeographic diffusion using a generalized linear model (glm) approach (see methods). here, we considered geography, air travel (in the form of the number of passengers traveling between each pair of locations), demography, viral surveillance data, viral phenotypic evolution and sampling sizes as possible explanatory variables (figure ). our phylogeographic test does not attribute any importance to geographical proximity, absolute latitude (to model source-sink behavior between the tropics and northern/southern hemisphere, [ ] ), population size and density, antigenic divergence or h incidence for the air communities and the geographic regions. instead, we provide consistent and overwhelming evidence for passenger flow driving the global h n diffusion dynamics, as reflected table . in the posterior support and a conditional effect size close to unity on a log scale for both the air community and geographic partitions. despite efforts to down-sample presumably oversampled regions or communities (see methods), there is still a role for sample size in both the air community and geographic partitions. explicitly including sample sizes as diffusion predictors allows us to absorb potential effects of sampling bias, offering more credibility for other predictors that are included in the model. when applied to geographic regions, which further partitions geographically and administratively coherent regions like us, china, japan and australia (table ) , our model also takes an important negative contribution from geographic distance and, correlated with this but with lower coefficients, population densities. here, distance most likely represents the role of other human mobility processes such as commuting, which has been shown to play a key role in the spread of influenza in the us [ ] . the negative population density effect may suggest that commuting is to some extent less likely to occur out of or into dense subpopulations. influenza prevention and control critically relies on our understanding of its geographical transmission patterns. here, we demonstrate the ability to jointly reconstruct phylogeographic history while identifying the factors that contribute epidemic spread from viral genetic data. our analysis of global influenza transmission provides evidence for the key role of air travel, which is highly intuitive and has long been predicted by modeling studies (e.g. [ ] ), but remained difficult to ascertain from empirical data. the predictors of influenza diffusion will undoubtedly be scale-dependent as indicated by the role of geographic distance within more confined geographic areas (figure ) , and this may represent other forms of human mobility such as commuting [ ] , which can be tested in future applications. more generally, our novel phylogenetic diffusion approach may be applied to different infectious diseases problems and provide entirely new opportunities for testing how host ecology shapes the distribution of pathogen genetic data. diffusion fundamentals iii (leipziger universitätsverlag handbook of optimization in complex networks theory of probability. oxford classic texts in the physical sciences geographica: the complete illustrated atlas of the world we thank guandi li for matlab assistance, hsin-fu for providing the taiwanese h incidence data and jessica hedge for collecting the coordinates for the h n sequences. key: cord- - an u authors: ijaz, m. khalid; zargar, bahram; wright, kathryn e.; rubino, joseph r.; sattar, syed a. title: generic aspects of the airborne spread of human pathogens indoors and emerging air decontamination technologies date: - - journal: am j infect control doi: . /j.ajic. . . sha: doc_id: cord_uid: an u indoor air can be an important vehicle for a variety of human pathogens. this review provides examples of airborne transmission of infectious agents from experimental and field studies and discusses how airborne pathogens can contaminate other parts of the environment to give rise to secondary vehicles leading air-surface-air nexus with possible transmission to susceptible hosts. the following groups of human pathogens are covered because of their known or potential airborne spread: vegetative bacteria (staphylococci and legionellae), fungi (aspergillus, penicillium, and cladosporium spp and stachybotrys chartarum), enteric viruses (noro- and rotaviruses), respiratory viruses (influenza and coronaviruses), mycobacteria (tuberculous and nontuberculous), and bacterial spore formers (clostridium difficile and bacillus anthracis). an overview of methods for experimentally generating and recovering airborne human pathogens is included, along with a discussion of factors that influence microbial survival in indoor air. available guidelines from the u.s. environmental protection agency and other global regulatory bodies for the study of airborne pathogens are critically reviewed with particular reference to microbial surrogates that are recommended. recent developments in experimental facilities to contaminate indoor air with microbial aerosols are presented, along with emerging technologies to decontaminate indoor air under field-relevant conditions. furthermore, the role that air decontamination may play in reducing the contamination of environmental surfaces and its combined impact on interrupting the risk of pathogen spread in both domestic and institutional settings is discussed. indoor air can be an important vehicle for a variety of human pathogens. this review provides examples of airborne transmission of infectious agents from experimental and field studies and discusses how airborne pathogens can contaminate other parts of the environment to give rise to secondary vehicles leading air-surface-air nexus with possible transmission to susceptible hosts. the following groups of human pathogens are covered because of their known or potential airborne spread: vegetative bacteria (staphylococci and legionellae), fungi (aspergillus, penicillium, and cladosporium spp and stachybotrys chartarum), enteric viruses (noro-and rotaviruses), respiratory viruses (influenza and coronaviruses), mycobacteria (tuberculous and nontuberculous), and bacterial spore formers (clostridium difficile and bacillus anthracis). an overview of methods for experimentally generating and recovering airborne human pathogens is included, along with a discussion of factors that influence microbial survival in indoor air. available guidelines from the u.s. environmental protection agency and other global regulatory bodies for the study of airborne pathogens are critically reviewed with particular reference to microbial surrogates that are recommended. recent developments in experimental facilities to contaminate indoor air with microbial aerosols are presented, along with emerging technologies to decontaminate indoor air under fieldrelevant conditions. furthermore, the role that air decontamination may play in reducing the contamination of environmental surfaces and its combined impact on interrupting the risk of pathogen spread in both domestic and institutional settings is discussed. © published by elsevier inc. on behalf of association for professionals in infection control and epidemiology, inc. air, a universal environmental equalizer, affects all living and nonliving forms on planet earth. for humans, it has profound health implications in all indoor environments where we normally spend most of our time. [ ] [ ] [ ] air quality is also forever changing because of the influence of many controllable and uncontrollable factors that are virtually everywhere. indoor air, in particular, can expose us to noxious chemicals, particulates, and a variety of infectious agents, as well as pollen and other allergens. , emerging pathogens, such as noroviruses and clostridium difficile, have also been detected in indoor air, with a strong potential for airborne dissemination. pathogens discharged into the air may settle on environmental surfaces, which could then become secondary vehicles for the spread of infectious agents indoors. the possible transmission of drug-resistant bacteria by indoor air adds another cause for concern. a combination of on-going societal changes is adding further to the potential of air as a vehicle for infectious agents. [ ] [ ] [ ] the quality of indoor air is therefore a prominent public health concern , that requires a clear understanding of the transmission processes for the development and implementation of targeted infection prevention and control measures. although direct and indirect exposure to pathogens in the air can occur by other means, infections from the inhalation and retention, including translocation and ingestion after inhalation of droplet nuclei, are generally regarded as true airborne spread. aerosols of various sizes that contain infectious agents can be emitted from a variety of sources, such as infected or colonized individuals or flushing toilets, and may expose susceptible persons either directly (droplet transmission) or by remaining suspended in the air for inhalation (airborne transmission). , contrary to the conventionally held belief, modeling work has redefined the wells evaporation-falling curve, , revealing that expelled large droplets could be carried > m away by exhaled air at a velocity of m/s (sneezing), > m away at a velocity of m/s (coughing), and < m away at a velocity of m/s (breathing), leading to potential transmission of short-range infectious agents that contain aerosols. airborne transmission requires that pathogens survive the process of aerosolization and persist in the air long enough to be transmitted to a susceptible host. aerosolized pathogens may settle onto environmental surfaces in the immediate vicinity, leading to genesis of secondary vehicles (fig ) . this review provides current information on the spread of human pathogens by indoor air, with a focus on the major classes of human pathogens from experimental and field studies, and on emerging air decontamination technologies, including test protocols developed to assess their performance under field-relevant conditions. the study of aerosolized human pathogens requires the ability to produce them experimentally at the appropriate size, store them, and sample them for residual infectious content over a predetermined time period. the equipment must also simulate naturally occurring environmental conditions and the duration of exposure to accurately assess aerosol survivability. various analytical methods and air samplers have been used to characterize airborne pathogens and overcome the challenges of collecting and analyzing them. relevant studies have been reviewed in detail elsewhere. , , aerosolized microbes must survive the prevailing environmental conditions to potentially infect a susceptible host. multiple factors affect airborne survival of microbes indoors (table ) . , the effect of these factors on different types of microbes varies, and generalizations can be difficult because of differences in the experimental methodologies used. air temperature, relative humidity (rh), and turbulence are among the more important factors affecting the fate and spread of infectious agents indoors. the analysis of air samples for microbes now includes methods that are based on the polymerase chain reaction (pcr). however, pcr-based methods typically cannot differentiate between viable and nonviable microbes. a recent study found that pcr substantially overestimated the quantity of infectious airborne influenza virus, but the differences in infectious versus noninfectious virus over time were similar to data from quantification by plaqueforming units, which determined that virus losses were evident within - minutes postaerosolization. generally, enveloped viruses survive better at lower rh, but there are many exceptions. other factors that affect aerosol activation in relation to rh include evaporative activity (ie, dehydration, rehydration), surface areas of particles, and ph. although studies with experimental animals have determined the susceptibility to airborne pathogens and the minimal infective inhalation dose of a given pathogen, there are wide variations sources of airborne pathogens indoors and potential for environmental surface contamination. these sources may include humans; pets; plants; plumbing systems, such as operational toilets and shower heads; heating, ventilation, vacuuming, mopping, and air-conditioning systems; resuspension of settled dust; and outdoor air. the yellow and red dots represent human pathogens or harmless microorganisms. adapted with permission from biomed central. in their test design. first, the number of inhaled microbes may not be known or it may be unrealistically high. second, the test protocol may not have fully excluded microbial exposure by means other than inhalation. third, there may be incomplete recording of the environmental conditions (eg, rh, air temperature) to assess their impact on microbial viability. fourth, pertinent differences may exist between laboratory-adapted strains of the tested microbe compared with strains in the field. studies using the actual pathogen aerosolized in body fluids provide the strongest evidence of pathogen survivability. in contrast, field studies face their own set of challenges, which include the noise, bulk, and expense of inefficient air collection devices. moreover, passive impingers may not adequately collect low concentrations of pathogens found in the clinical environment. slit sampling does not impose size exclusion and may be more effective at recovering viable pathogens of any size. from a methodologic perspective, field studies also must control for potential variables, such as air turbulence or human activity in areas proximate to sampling, such that sampling occurs before, during, and after an area is occupied and should include functioning ventilation systems. we have previously reviewed published studies on the airborne spread of viruses of animals and humans. , table summarizes key human pathogens with evidence of aerosol transmission. a number of these pathogens causes severe disease, and their classification as high risk by the u.s. centers for disease control and prevention and the world health organization emphasizes the need for appropriate control measures. experimental studies have used surrogates for human pathogenic enveloped and nonenveloped viruses, such as cystovirus (ϕ ) and bacteriophage ms- , respectively. enteric viruses are transmitted primarily by the fecal-oral route, but airborne transmission has been reported. airborne transmission of norovirus may be possible via aerosolization of vomitus and toilet flushing, which are regarded as potential sources of both indoor air and environmental surface contamination. enteric bacteria and viruses have been recovered from indoor air and environmental surfaces in areas sur-rounding toilets. , , we reported that aerosolized simian rotavirus sa- survived best at midrange rh. , these results contradicted a prior study by moe and harper, in which the uk strain of calf rotavirus was reported to survive best at low and high rh, but not at high temperature. subsequent studies on human rotavirus, murine rotavirus, and a uk strain of calf rotavirus, aerosolized under the same experimental setup, confirmed the behavior of all strains of rotaviruses are similar in airborne state. , furthermore, studies of different picornaviruses (poliovirus type [sabin] and human rhinovirus) and a human coronavirus (an enveloped virus) that used the same experimental conditions produced results that were consistent with the published literature, suggesting that the experimental design did not introduce bias toward the behavior of aerosolized rotaviruses. , , among the respiratory viruses, influenza virus is present in the air around infected individuals, and airborne transmission via droplet nuclei has been demonstrated in experimental models and in reports of influenza spread on-board aircrafts. low rh favors airborne survival and transmission; however, high air exchange rates facilitate dilution of virus-containing aerosols, regardless of their size. a recent study confirmed recovery of influenza virus from the air emitted by infected persons at distances of . - . m, which could reach the breathing zone of susceptible individuals, including health care workers. surprisingly, and in spite of much study, the exact mode of and the relative importance of various types of vehicles for transmission of rhinoviruses, which are the most frequent cause of the common cold, remain shrouded in mystery. , the behavior of experimentally aerosolized rhinovirus type , which represents typical picornaviruses (as previously mentioned), coupled with rhinovirus recovery from both indoor air and outdoor air, substantiate the role of air as a vehicle in spread of some of these picornaviruses. taken together, an overall assessment of the available evidence suggests a role for airborne spread and for the role of contaminated hands and environmental surfaces in rhinovirus dissemination. coronaviruses are the second leading cause of the common cold and are also responsible for the severe acute respiratory syndrome (sars) and the middle east respiratory syndrome. sars is thought to be transmitted via direct contact, but airborne transmission is also suspected because the virus has been detected in air samples that were collected from rooms where a patient was recovering from sars. , the virus is spread through droplets and can remain viable on surfaces for several days at room temperature. the use of aerosol-generating procedures, such as intubation, bronchoscopy, and oxygen delivery vents, may promote dispersal of sars via enhanced release in mists of exhaled pulmonary gases. , our earlier work on the behavior of aerosolized human coronaviruses e further substantiates the potential role of air in their aerial spread. aerosol transmission of the ebola virus is biologically plausible. the virus is present in saliva, stool, blood, and other body fluids; therefore, it could be aerosolized through symptoms associated with infection or via health care procedures. the ebola virus has been shown to survive in the air when the half-life of the virus ranged from (zaire ebola virus) to minutes (reston ebola virus), and the time for % biologic decay of the aerosolized virus held in rotating drum (at %- % rh and °c ± °c) was estimated to be between and minutes. additionally, infection of rhesus monkeys via experimentally aerosolized ebola virus has also been reported. these findings raise concerns for aerosol transmission and control of this serious pathogen; however, thus far, there is no clear evidence for the airborne spread of this virus in humans. epidemiologic evidence indicates transmission is associated with direct physical contact or contact with body fluids; however, the possibility of aerosolized spread has been postulated by ebola virologists. , bacteria approximately one-third of humans carry staphylococcus aureus, with the anterior nares as a common site of colonization, and environmental contamination plays an important role in the transmission of methicillin-resistant s aureus. shedding of the bacteria is highly variable, but transmission likely occurs via skin squames that settle out on environmental surfaces in the vicinity. smaller particles may remain airborne, particularly if there is air turbulence. , an important characteristic of the staphylococci is their ability to survive over a wide range of temperatures, rh, and exposure to sunlight. mycobacterium tuberculosis is transmitted via droplet nuclei expectorated from infected persons during coughing, sneezing, and talking. , control measures include expensive negative-pressure ventilation and less expensive, but climate-dependent, natural ventilation. upper-room ultraviolet (uv) light or negative air ionization may help reduce the airborne spread of m tuberculosis. nontuberculous mycobacteria are found in soil and water sources and can form biofilms under domestic environments, such as shower heads. transmission to humans is uncertain, but droplet aerosolization is a suspected route of pulmonary disease, with shower heads considered a common source. , contamination of hospital water supplies and medical equipment are suspected in nosocomial outbreaks of disease. similarly, legionella spp become airborne by active aerosolization of contaminated water and form biofilms in air conditioning systems. legionella-like amoebal pathogens are a subset of bacteria that grow within amoebae and often are coinfectious agents with other bacteria and fungi. clostridium difficile spores have been recovered from the air near symptomatic patients, especially those with recent-onset diarrhea. air samples were positive for c difficile in % of patients, and the highest levels of surface recovery were in areas closest to the patient. the isolates recovered from the air were indistinguishable from those recovered from fecal samples and from the environment in the same settings. additionally, c difficile has been recovered after toilet flushing, and leaving the lid open when flushing increases contamination of surrounding environmental surfaces. airborne infection of bacillus anthracis is affected by environmental factors that include room size, ventilation rate, and host factors, such as pulmonary ventilation rate. secondary aerosolization of viable b anthracis spores was reported after contamination of a u.s. senate office, with > % of particles being in the respirable size range of . - . μm. as ubiquitous microorganisms, fungi pose a health threat in indoor environments. fungal infections can be particularly serious in immunocompromised patients, especially airborne spores of aspergillus spp that are blown in from natural ventilation sources. fungal spores are aerosolized from municipal water supplies and dust and can be effectively transported over long distances by wind and air currents. , the evolution of the fungal spore has enabled them to travel long distances and be more capable of withstanding environmental insults. the most important factor of fungal growth in indoor environments is humidity ; therefore, control measures include dehumidification of the air and high-efficiency particulate arrestor filtration. recent research suggests that airborne fungal particles are heterogeneous and comprise spores and submicrometer fragments. , these fragments are of significant interest with regard to health because they remain in the air longer and are easily inhaled. there are also a variety of fungal components that have been identified in air, including mycotoxins, ergosterols, glucans, and microbial volatile organic compounds, and these require unique analysis methods. taken together, these findings provide a foundation for the definition of sick building syndrome. high humidity within sick houses and buildings allows for growth of fungi indoors, particularly species of aspergillus, penicillium, and cladosporium and stachybotrys chartarum, an indoor mold that was associated with sick building syndrome several decades ago. , , these fungi can be found in dust, furniture, carpets, and ventilation systems at concentrations ranging from - , colony-forming unit (cfu)/m . in fact, carpet has been described as a sink for fungi, but it is also a source for resuspension of fungal particles into the air. various respiratory conditions (eg, wheeze, cough, asthma) have been linked to fungi and their biologic components in the indoor environment. fungal species found outdoors include cladosporium and alternaria spp, which are responsible for triggering hypersensitivity reactions, including rhinitis, sinusitis, and asthma. , the clear recognition of indoor air as a vehicle for pathogens has incurred a corresponding upsurge in the marketing of products and technologies with claims for safe and effective decontamination of air. although many technologies are available for environmental surface decontamination, the number and variety of those for decontamination of indoor air remain limited and of questionable veracity ( table ). the air-decontaminating claims of many such technologies are not based on testing under field-relevant conditions with pathogens relevant to human health, and scientifically valid and standardized protocols to generate field-relevant data for label claims for review by regulatory and public health agencies and the public at large remain unavailable. here, we address this gap in the development of a test platform for standardized testing of commercially available devices for decontaminating indoor air of vegetative bacteria that represent airborne human pathogens. we know of only one guideline that directly relates to this topic. it specifies the size of a sealed enclosure for experimental contamination of the air with aerosols of vegetative bacteria to assess technologies for their temporary reduction. therefore, the text that follows relates directly to that guideline. the studies of microbial survival in indoor air, as well as proper assessment of methods for its decontamination, emphasize numerous challenges and highlight the need for specialized equipment and protocols. proper expertise and suitable experimental facilities for such investigations remain uncommon. several of the available sites with testing claims are neither experienced in, nor equipped to conforming with, the u.s. environmental protection agency's (epa) guidelines on testing the sanitization of indoor air. based on our considerable experience in the study of airborne human pathogens, , , , , we have built an aerobiology chamber (fig ) designed to meet the requirements of the epa guidelines and have used this to study the effects that a variety of air decontamination technologies have on the airborne survival and inactivation of vegetative bacteria, viruses (bacteriophage), and bacterial spore-formers (sattar et al, unpublished data) . additional details about the operational aspects of the aerobiology chamber, described elsewhere, are discussed briefly. any meaningful assessment of air decontamination requires that the aerosolized challenge microbe remain viable in the experimentally contaminated air long enough to allow for proper differentiation between its biologic decay or physical fallout and inactivation or removal by the technology being assessed. there- fore, initial testing is required to determine the rate of biologic decay of the test microorganism(s) under the experimental conditions to be used for testing potential air decontamination technologies. for this, the test microorganism(s) was aerosolized into the chamber, and -minute air samples were collected at different intervals using a slit-to-agar (sta) sampler over an -hour period. the culture plates were incubated at °c ± °c, the cfu on them was recorded, and the data were analyzed to determine the rate of biologic decay. the results of the tests on the airborne survival of types of vegetative bacteria are shown in figure . acinetobacter baumannii (atcc ; atcc, manassas, va) proved to be the most stable in air, followed by s aureus (atcc ; atcc) and klebsiella pneumoniae (atcc ; atcc). three types of commercially available indoor air decontamination devices that were based on uv light and high-efficiency particulate arrestor filtration were tested for their ability to reduce the levels of viable bacteria in the air of the chamber ( table ). the air within the chamber was first experimentally contaminated with aerosolized test bacterium suspended in a soil load. the test device, placed inside the chamber, was remotely operated, and samples of the chamber air were collected directly onto petri plates using sta and were incubated for cfu determinations. as shown in figures a and b , the air decontamination devices that were tested could achieve a -log reduction in viability of s aureus and k pneumoniae in - minutes (table ). so far, such testing has been conducted only once with a baumannii using device , and as the data presented in figure show, it reduced the viability of a baumannii by log in minutes (table ) . in this experiment, device was tested for its ability to manage ongoing fluctuations in the microbiologic quality of indoor air. a suspension of s aureus was nebulized into the chamber at separate time points, while the device operated continuously. as shown in figure , the device's efficacy after the challenges with aerosolized bacteria was almost the same. the times at which the device demonstrated -log reductions after each nebulization were found to be , . , and . minutes. the mean of the -log reduction times was . ± . minutes, giving an average biologic decay rate of aerosolized bacteria of . ± . cfu/m /min after the nebulizations. as previously mentioned, larger particles of aerosolized pathogens often settle onto environmental surfaces in the immediate vicinity, leading to contamination as a secondary vehicle of trans- fifteen sterile plastic plates were placed in groups of on the floor of the aerobiology chamber, with one set in each of the corners and one in the center. the lids of the plates were removed. a suspension of s aureus in a soil load was nebulized into the chamber with the muffin fan operating for minutes to evenly distribute the airborne bacterial particles. a -minute air sample was then collected from the chamber using an sta sampler to determine the initial level of airborne contamination. ten minutes were allowed to elapse for circulation of the airborne bacteria in the chamber. the muffin fan was then turned off and the airborne bacteria were allowed to settle for minutes. at the end of this period, the petri plates were retrieved and eluted for cfu to determine the titer of microbial contamination deposited on each one. such testing allowed us to determine the levels of airborne bacteria that could settle on the plates without air decontamination procedures. the experiment was repeated in exactly the same manner, but with the test device in the chamber activated and allowed to work for minutes. at the end of this period, the petri plates were retrieved and eluted for cfu to determine the titer of microbial contamination deposited on each plate. the results indicated that the nebulization of the microbial suspension for minutes produced . log cfu/m of air in the chamber. the average level of cfu on the control and test petri plates held in the chamber was ± and . ± . , respectively. the device could reduce the contamination of the plates from airborne bacteria by % as compared with the controls. recognition that human pathogens can be transmitted via indoor air emphasizes the need for the development of control procedures that limit exposure and reduce the risk of infection in susceptible individuals. this need is heightened by an increase in the aging population and numbers of the immunosuppressed. we must also be prepared for an intentional or accidental release of infectious aerosols. standardization of sampling and analytical methods is crucial to developing an understanding of airborne pathogens and technologies for their effective control. we have described the creation and application of an aerobiology test chamber that complies with the relevant guideline of the epa. the chamber was successfully used ( ) to study the airborne survival of types of vegetative bacteria under ambient conditions; ( ) to test the ability of commercial indoor air decontamination devices to abate experimentally generated aerosols of types of vegetative bacteria; ( ) to test one of the devices for its ability to deal with repeated microbial challenge with vegetative bacteria in simulation of situations in which indoor air is contaminated on an on-going basis; and ( ) to test one of the air decontamination devices for its effectiveness in reducing the level of microbial contamination of environmental surfaces as a function of reducing airborne bacteria. each of these experiments was completed successfully, thereby demonstrating the suitability of the aerobiology chamber and the protocols for aerosol generation and sampling. the use of the sta sampler proved particularly effective for providing event-related information on the levels of viable bacteria in the air of the chamber. the testing with a baumannii clearly demonstrated that it is more suitable than k pneumoniae as a surrogate for gram-negative bacteria. a baumannii is not only a relevant airborne pathogen that is more resistant to aerosolization, but it also is more stable in the airborne state. therefore, it is recommended that it be considered as an alternative for k pneumoniae by regulatory agencies, such as the epa, for testing and registration of air decontamination technologies. table regression coefficients, p values comparing decay rates of efficacy tests with stability in air, and times required to achieve log reductions device the experimental facility and test protocols described here are suitable for work with other types of airborne human pathogens, such as viruses, fungi, and bacterial spore formers. the aerobiology chamber also could be readily adapted to assess emerging technologies of indoor air decontamination. although the work reported here was performed in a sealed and empty chamber, as specified in the epa guidelines, the aerobiology chamber can be modified to represent air exchanges, and furniture can be introduced to simulate a typical room under both domestic and institutional settings. air, in general, is crucial to the establishment and maintenance of the indoor microbiome, and the continual redistribution of microbes indoors occurs at the air-surface-air nexus. although classic airborne spread of pathogens occurs via droplet nuclei, droplets can potentially contaminate environmental surfaces, depending on their size and prevailing environmental conditions, thereby creating secondary vehicles for pathogens. therefore, targeting airborne pathogens could potentially provide an additional advantage by reducing environmental surface contamination. our preliminary findings indicate that a reduction in the level of viable airborne bacteria using active air decontamination can also reduce bacterial contamination on environmental surfaces in the same setting. therefore, targeting airborne pathogens could entail additional benefits, such as preventing or reducing the deposition of harmful microbes on secondary vehicles that include frequently touched environmental surfaces and also preventing or reducing their resuspension from these surfaces back into the air via a variety of indoor activities (fig ) . , , , , further studies should investigate the role air decontamination may play in reducing the contamination of environmental surfaces and its combined impact on interrupting the risk of pathogen spread in both domestic and institutional settings. aerobiology and its role in the transmission of infectious diseases hospital airborne infection control a comparative study on the quality of air in offices and homes bioaerosols in indoor 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characterizing airborne fungal and bacterial concentrations and emission rates in six occupied children's classrooms evaporation and dispersion of respiratory droplets from coughing we thank dr john a. mitchell (wordsmith scientific and regulatory, llc, bozeman, mt) and elizabeth bruning (rb, montvale, nj) for their critical review and feedback. key: cord- -scwhwurr authors: zhu, shengwei; demokritou, philip; spengler, john title: experimental and numerical investigation of micro-environmental conditions in public transportation buses date: - - journal: build environ doi: . /j.buildenv. . . sha: doc_id: cord_uid: scwhwurr this study examines both numerically and experimentally the micro-environmental conditions in public transportation buses. a computational fluid dynamics (cfd) model was developed and experimentally validated. the developed cfd model was used to calculate the spatial distributions of the mean age and mean residual lifetime of air in the bus environment and evaluate the efficiency of the bus ventilation system. additionally, the passengers’ exposures to a variety of environmental conditions were experimentally monitored in “real world” field campaigns using the harvard university shuttle bus system. real time continuous monitoring systems were used to assess indoor environmental quality in the buses. it was found that co levels were very low, while the levels of particulate matter varied and were influenced by the ambient air penetrated into the bus through the operation of the doors and the ventilation system. the co( ) level was found elevated and greatly affected by occupancy conditions. the elevated co( ) level indicates that the current bus ventilation is insufficient to dilute air pollutants in the bus especially under heavy occupancy conditions. this lack of sufficient ventilation indicates an elevated risk for airborne transmitted diseases in such a popular public transportation system. commuting occupies around % of the daily time of people who live in urban areas [ ] with the americans spending approximately . % of their typical day inside a vehicle [ ] . and the bus transportation system is considered to be one of the most available and popular transportation modes around the world [ ] . there are a number of published field studies focusing on air quality and thermal comfort in the bus microenvironment. in a study performed in munich, germany showed that the concentrations of pm in buses and trams depended on the ambient sources and the road traffic conditions [ ] . in a similar study performed in another urban setting, guangzhou, china, the parameters such as poor vehicle emission controls, poor vehicle maintenance and high-density traffic conditions were linked to poor indoor air quality in buses. furthermore, it was found that the concentration levels of carbon monoxide (co) and pm in buses could be lowered substantially by using a hvac system [ ] . this is due to the "protective" effect of mechanically ventilated and air-conditioned buses which results to a lower indoor penetration factor for a variety of air pollutants (co, pm . , pm , etc) [ ] . chan [ ] also reported that co concentration could be up to times higher than outdoor concentrations under overcrowded conditions, which is usually the case during rush hours. however, there are a limited number of studies focusing on the effect of ventilation strategies on diluting or removing air pollutants generated inside the buses. in addition, in terms of health effects linked with the unique microenvironment in the buses, nausea, dizziness and respiratory allergies have been identified in previous studies [ , ] . it also became apparent in recent years, that airborne transmitted diseases, such as tb, severe acute respiratory syndrome (sars), avian influenza and swine influenza (h n ), may impose a serious global health and economic burden. therefore, there is a need to further study and understand the transmission of airborne infectious diseases in the indoor environment, and the bus environment might be one of the most challenging ones because of the very close proximity of the people. in recent years, with the rapid development of computer technology and advanced numerical methods, investigators were also able to successfully use computational fluid dynamics (cfd) models to study the microenvironments in a various of public transportation systems, including aircraft [ e ], trucks [ ] and cars [ , ] . those advanced numerical methods have been proved an effective tool to obtain the detailed spatial and temporal distributions of temperature, velocity and contaminants in microenvironmental settings, which are usually very difficult and expensive to be obtained in experimental measurements. the thrust of this investigation is two-fold: (a) develop and use a cfd model to understand the bus micro-environmental conditions, especially the ventilation effectiveness and air distribution system, and how they may affect the dilution and removal of any internally generated air pollutant; (b) perform an extensive field campaign using the harvard university shuttle bus system and monitor continuously the indoor environmental quality as well as the personal exposure levels of passengers for a variety of air pollutants including co, co , and particulate matter in its various respirable size fractions such as pm . , pm and ultrafine particles (ufps). this bus uses the widely used mixing ventilation method. six linear air supply diffusers are located near the ceiling. on each side of the bus, there is a two-slot diffuser supplying air downwards and a one-slot diffuser supplying air horizontally (fig. ) . the total area of the air supply openings is . m . the exhaust opening with an area of . m ( . m  . m) is placed in the ceiling close to the rear door. in the cfd simulation, the bus was modeled with all of the doors and windows assumed to be closed. the air infiltration through leakage pathways was also omitted. fig. shows the geometry of the air diffusers. the total air supply rate was . m /s, which accounts for an air exchange rate of . ach assuming no air recirculation in the bus. in addition, solar and long wave radiation as well as occupancy was not considered in the developed model. a d cfd model based on the reynolds-averaged navierestokes (rans) equations [ ] was used to simulate the bus airflow, temperature and scalar contaminant fields. the cfd model is based on the conservation equations of mass, momentum, energy, scalar concentration, turbulent kinetic energy, and dissipation rate of turbulent kinetic energy, that govern the transport phenomena in the bus. the aforementioned governing equations can be closed with appropriate boundary conditions at all of the boundaries such as air supply openings, air exhaust opening, and wall surfaces. the detailed boundary conditions are summarized in table . for air supply openings, the actual values of air temperature, velocity and turbulence intensity were measured in the field experiments, and used as boundary conditions (see following sections). the turbulence scale was calculated as one-half of the width of the linear opening. fig. (c) shows the location and direction of the supplied airflows in cross section beb . at the surfaces of floor, windows and lights, the temperatures were fixed based on the data obtained in the field experiment. the rest of wall surfaces were assumed adiabatic. moreover, the standard wall function [ ] was used for the near wall boundary layer. in this study, the spatial distributions of the mean age and mean residual lifetime of air [ ] were used as the indices to estimate the ventilation efficiency in the bus. the mean age of air is defined as the mean time that it takes for the air from the supply openings to be transported at a specified location; the mean residual lifetime of air is defined as the mean time that it takes for the air at certain location to be exhausted. numerically, these distributions can be obtained using the mathematical methods of sve and sve (scale for ventilation efficiency and , see table ) [ e ], under the assumption that the air pollutant ("tracer gas") is generated uniformly and continuously in the bus. based on the so-called sve method, the mean age of air can be calculated by solving the following transport equation [ ] . if q is assumed to be generated uniformly and continuously throughout the bus, the air mass from a supply opening is gradually contaminated as it is regarded proportional to the time elapsed from the time the air mass leaves the supply opening until it reaches the point. the total amount of tracer gas generated in the room divided by the airflow rate of ventilation is termed a "perfectly mixed concentration c (kg/kg)". under a steady state condition, this is equivalent to the concentration averaged over the exhaust opening. because the age of air averaged over the exhaust opening is equivalent to the inverse of the air exchange rate, the distribution of trace gas c in the room can be converted to the distribution of the mean age of air. similarly based on the so-called sve method, the mean residual lifetime of air is computed by applying the same computational procedure as sve , except that the time sequence of the flow field is reversed. the cfd numerical grid system used in the model consists of , triangular surface meshes and , , tetrahedral fluid cells, which were created using gridgen v . at a growth rate of . . a good grid was ensured with over . % of the meshes of less than . in equiangle skewness, which represented the maximum ratio of the cell's inner angle to the angle of an equilateral element. note: the total air supply rate of . m /s was calculated by mutiplying the velocity of the supply airflow by the total area of the air supply openings. it resulted in an air exchange rate of . ach based on the assumption that there was % outside air supplied in the bus and no air recirculation which may not be the case in real world operations. in addition, the previous studies reported high ach in automobiles. for example, the air exchange rate was measured between . and . ach in an automobile with windows and doors closed and ventilated on % fresh air under stationary conditions [ ] , and averagely ach at a speed of km/h [ ] . therefore, the air exchange rate of . ach agrees with the published studies. the commercial cfd software, star-cd v . , was used to solve the governing equations together with the standard ke model and implicit simple algorithm [ ] . the finite volume method with the first-order upwind scheme (ud) was adopted for discretizing the governing equations [ ] . in order to validate the developed cfd method, a field experiment was also conducted under stationary conditions using a bus table ). the averages of the total data points (for min) were recorded. the velocities and temperatures of the supply airflow at the linear diffusers were also measured using a hot-wire anemometer (tsi , see table ) at an interval of s for the duration of min in order to obtain the boundary conditions for the air supply openings. the measurements were performed at four bus locations (in the front and rear compartment at each side of the bus). the average of the data points was used as the value for that location. in addition, turbulence intensity was calculated automatically as the percent of the standard deviation of the turbulent velocity fluctuations to the mean velocity over the measuring period at each location [ ] . the averages of those results were also used as the boundary conditions for air supply opening. it should be addressed that while the average values for temperature and velocity were used at the walls and supply inlets, in real life these parameters vary as a function of time based on weather and other operating conditions. the harvard university shuttle bus system was used for our field investigation study. the harvard university shuttle service is the main transport mode for the students, staff and faculty commuting throughout the cambridge and allston campuses of harvard university. it is estimated that over , passengers per week use the harvard university shuttle service. two different routes were selected. both routes have similar traffic conditions of primary and secondary streets. a typical route consists of four stops and takes approximately min. at each stop, it usually takes approximately s for boarding/unboarding passengers. the age profile of passengers is also unique since % of the passengers are under years old on our survey investigation. four full day field campaigns were performed in the fall of (november th, th, th and th). all buses were daimler slf , same as that used in the field experiments for cfd model validation. the buses were air-conditioned, and all of their windows were fully closed when in operation. outdoor air infiltrated through the doors and the ventilation system. the field campaigns started early in the morning before : am, with a lunch break around noon and continued until : pm in the afternoon. it is worth pointing out that typical traffic patterns in the cambridge campus area were reflected in our field campaigns. the drivers were also asked to operate as usual without intervening in the temperature setup and the ventilation settings in the bus. continuous instruments were used to monitor indoor environmental conditions in the bus. air temperature, relative humidity and the concentration levels of co , co and particulate matters in three size fractions, pm and pm . , and ultrafine particles (ufps) were continuously measured in the bus. real time measurements for the above ieq parameters were recorded at an interval of s. the instruments were placed in two mesh boxes made by coarse wire, which were hanged at the shoulders of two of our field personnel at a height between . and . m from the floor. the field personnel remained standing in the middle of the front compartment for the whole trip as shown in fig. (a) . moreover, since there was only one particle counter used in the table scales for ventilation efficiency and . age of air at position x sve (x) residual lifetime at position x c x (x) concentration at position x where contaminant is uniformly generated throughout a room in total generation rate q table summarizes the instruments used in the continuous measurements of the aforementioned ieq parameters. fig. shows the spatial distribution of air velocity in the bus. as shown in cross section aea , the air close to the front windshield was heated and moved upward, an indication of a "drafty" condition in the proximity of the driver. moreover, an eddy was generated in the mid upper region as shown in cross section beb . in cross section ded , a large eddy was shown at each side of the bus. these eddies are indicative of the highly turbulent nature of the flow in the bus environment. however, overall, the air velocities were mostly distributed under . m/s in the bus. this is almost satisfactory based on the ashrae standard - [ ] , which has a limit of . m/s for air velocity. fig. shows the spatial distribution of air temperature in the bus environment. air temperatures were within ae c of the set point ( . c) in the passenger compartment with the exception of the area close to the windows and floor. as shown in cross sections beb and cec , large air temperature gradients were present close to the floor, primarily because of the high thermal losses and the very poor air circulation under the seats. the same large temperature gradients were also shown close to the front windshield and the floor in the driver's space. there was not a great agreement between measured and simulated results. this is expected since it is a known limitation of the standard wall function used in the model for the wall surfaces covered by a low reynolds number turbulent flow. this might be also attributed to a cold air infiltration close to the floor, which was not considered in the cfd model. fig. shows the spatial distribution of the mean age of air in the bus. for the driver's breathing zone, the mean age of air was calculated to be generally in e . s. in the front compartment, it was mainly in the range of . e s. in the rear compartment, it was mostly less than s (with the exception of the area involved in the developed eddy as shown in fig. (d) ). it is worth to point out that in general, fresh air can reach most of the area covering passengers' breathing zone within . s. similarly, fig. shows the spatial distributions of the mean residual lifetime of air. it was found that the mean residual lifetime of air varied significantly from to over . s in the bus. as expected, it was minimum in the area directly under the exhaust opening (less than . s), and increased very quickly with the distance from the air exhaust opening. in conclusion, the polluted air in passengers' breathing zone will be exhausted within min. table shows the weather conditions occurred during the experimental campaigns. table summarizes the measured air temperature and relative humidity in the buses for each day of the field campaign. figs. and show the bus air temperature and relative humidity respectively, as a function of time. here, only the data for a representative campaign day (nov. th) were plotted in the figures since the results were similar on other days. moreover, please also note that the number of passengers as a function of time was also presented in the figures. as shown in tables and , the air temperature in the bus was independent of outdoor weather conditions and the passenger occupancy. additionally, the door operation showed little influence on the air temperature in the bus as shown in fig. . this is an indication that the bus hvac system can maintain really well the temperature set point. on the contrary, as shown in tables and , relative humidity in the bus was affected greatly by the weather conditions with its daily mean value ranged from . % when it was raining to . % when it was sunny. the high relative humidity on the rainy day was caused by the water drops taken into the bus by the passengers or entering the bus when the doors were opened to load/unload the passengers. in addition, as indicated in fig. , relative humidity was greatly affected by the opening of bus doors during loading/unloading of the passengers. also, it was as expected that relative humidity depended on the occupancy load, primary because of the latent heat generation from the human occupancy. the thermal comfort range for winter as it is recommended by ashrae standard - [ ] was presented in fig. . this was made possible by plotting the experimental data points of the hourly mean air temperature and relative humidity measured in the bus throughout the field campaigns. it is necessary to point out that this is under the assumption that the measured air temperature in the bus is equal to the operative temperature and the clothing conditions of the passengers and drivers is clo as stated in the ashrae standard. operative temperature was not measured in the field experiments and it can be higher than the air temperature if thermal radiation is considered. therefore, fig. is considered just an approximation of the thermal comfort conditions in the bus. as shown in fig. , most of the results were distributed at the "warmer side" of the thermal comfort zone but still in the comfort zone based on the ashrae standard - . table summarizes the measured concentration levels of all the air pollutants monitored continuously in the bus (co, co , pm . , pm and ufps). similarly, fig. also illustrates the co concentration levels and the occupancy load as a function of time. additionally, figs. ande show the concentration levels of co, pm . , pm and ufps as a function of time, respectively. the door open/ close status was also indicated on those figures. in addition, also only the data for a representative campaign day were plotted in the figures since the results were similar on other days. as it was shown in the aforementioned figures, the co concentration level in the bus varied widely during the field campaigns. it usually varied from around ppm, and sometimes reached the levels of over ppm. it is worth to point out that based on the guidelines of the national institute for occupational safety and health (niosh) for indoor environments, co concentration levels higher than ppm is an indication of inadequate ventilation [ ] . furthermore, fig. reveals that co concentration levels in the bus were linked with the passenger occupancy. as it was expected, the co concentration level increased with higher occupancy load. moreover, the co concentration level decreased sharply when the doors were open and increased soon after doors were closed in most cases due to the dilution effect from infiltrating air. the co concentration levels were below . ppm, much lower than the -hour average limit of ppm, which was recommended by the us national ambient air quality standards (naaqs). additionally, as it is shown in fig. , the co concentration level generally reached its peak values when the doors were open to load and unload passengers. this is a clear indication of the influence of the traffic conditions in the street on the co concentration level. the mass concentrations of pm . and pm were always below mg/m , with the daily mean values to be much lower than the recommendation by the naaqs ( mg/m for pm . and mg/m for pm ). as it is shown in fig. , pm . concentration generally did not exceed mg/m except for the "heavy traffic hours" in the morning and afternoon (before : am and after : pm). it is worth pointing out that pm . concentrations during peak hours were found to be an order of magnitude higher. this is due to the high traffic conditions during peak hours and pm . particles are well correlated with mobile sources (traffic conditions). similar to the co concentration level, the pm . concentration level reached its highest values when the doors were open to load and unload passengers, a clear indication of particle penetration from outdoors. similar trend for the pm concentration level is shown in fig. . ufps concentration level also varied widely over time, and reached its peak values when the doors were open, a clear indication of the influence of the traffic conditions. this is expected since ufps are primarily emitted from combustion engines related to mobile sources such as cars, buses, etc. the daily mean ufps concentration levels were found to be in the range of .  e .  pt/cm . this is in line with the findings from the similar studies in other cities in the us ( .  e .  pt/ cm in ann arbor, mi, .  e .  pt/cm in chicago, and .  e .  pt/cm in atlanta [ ] ). as it was shown in both the simulation results and the experimental results previously presented, there was overall thermal satisfaction based on the ashrae - . however, the low relative humidity levels below % on sunny days documented in the field campaigns raise a health concern in terms of the airborne transmission of certain viruses. for example, according to the previous animals studies [ , ] , the most favorable relative humidity levels for the airborne transmission of influenza virus was in the range of e %. our field campaign results imply that the low relative humidity found in this microenvironment may elevate the risk for influenza transmission. as outlined in the previous result section, the concentration levels of co, pm . and pm were found in compliance with the existing standards for indoor air quality. their concentration levels were always very small when the doors were closed and generally reached their peak values when the doors were open. since there are no indoor sources of co, the only reasonably explanation for this change is that the use of mechanical ventilation in the bus provided a "shielding effect" in terms of particulate matter and co. this agrees with the results from the previous studies on air-conditioned buses [ ] . however, the co concentration levels were found to be usually high and not in compliance with indoor environmental guidelines and standards. this is an indication of inadequate ventilation that is linked to an increased risk for airborne transmitted diseases. the simulation results also confirmed the lack of ventilation efficiency and found the mean residual lifetime of air in the bus for the breathing zone of passengers to exceed s in some areas of the bus. the developed cfd model can be used to predict the ventilation efficiency in the passenger's breathing zone and evaluate alternate operational scenarios related to the ventilation system. the simulation results of mean age and mean residual lifetime of air indicate very good ventilation efficiency in an empty bus with % fresh air supply (no air recirculation), under the conditions different from those in the "real world" field campaigns on ieq in the buses. based on both our numerical and field investigation on the bus environment, there is a need to further study and identify ventilation strategies and alternate air distribution methods in order to improve the ventilation efficiency in this important microenvironment. additionally, due to the very close proximity of people in the bus environment, supplementary air filtration and air disinfection methods such as upper room uv irradiation might be necessary to be explored as a mean to minimize the risk of airborne infectious diseases. we plan to use the developed cfd model to parametrically analyze the impact of the operational conditions of ventilation system, such as air recirculation, air distribution method, etc. the field experiments indicated that the thermal comfort conditions were found on the warmer side of the ashrae recommended comfort zone for winter conditions. it was also found that the ventilation system provided a "shielding effect" and protected the passengers from the harmful exposures to ambient air pollutants infiltrating indoors, such as co and particulate matter. the high co concentration levels found in the field campaigns is a good indicator of insufficient venitlation in the buses. these results reveal an increased risk for the airborne transmitted diseases. therefore, alternate ventilation strategies and possible air filtration/purification systems may be needed in order to safeguard the health of people using this public transportation system. activity patterns of californians: use of and proximity to indoor pollutant sources the national human activity pattern survey (nhaps): a resource for assessing exposure to environmental pollutants commuter exposure and indooreoutdoor relationships of carbon oxides in buses in hong kong dust exposure in munich public transportation: a comprehensive -year survey in buses and trams exposure level of carbon monoxide and respirable suspended particulate in public transportation modes while pm mass concentration level and door operation condition in the bus as a function of time ufps particle concentration level and door operation condition in the bus as a function of time (nov. th). commuting in urban area of guangzhou influence of in-tunnel environment to in-bus air quality and thermal condition in hong kong combined comfort model of thermal comfort and air quality on buses in hong kong numerical simulation of airflow and airborne pathogen transport in aircraft cabins e part i: numerical simulation of the flow field numerical simulation of airflow and airborne pathogen transport in aircraft cabins e part ii: numerical simulation of airborne pathogen transport novel air distribution systems for commercial aircraft cabins prediction of indoor thermal comfort in vehicle by a numerical thermoregulation model and cfd analysis of flow patterns and heat transfer in generic passenger car mini-environment ventilation characteristics of modeled compact car (part ) estimation of local ventilation efficiency and inhaled air quality progress in the development of reynolds stress turbulence closure the numerical computation of turbulent flows the use of moments for ventilation assessing air quality in ventilated room new ventilation efficiency scales based on spatial distribution of contaminant concentration aided by numerical simulation new scales for ventilation efficiency and their application based on numerical simulation of room airflow new scales for evaluating ventilation efficiency as affected by supply and exhaust openings based on spatial distribution of contaminant study on inhaled air quality in a personal air-conditioning environment using new scales of ventilation efficiency numerical heat transfer and fluid flow star-cd version . -methodology turbulence intensity measurements. application note af- of tsi instruments ltd standard - : thermal environment conditions for human occupancy. atlanta: american society of heating, refrigerating and air conditioning engineers indoor environmental quality: building ventilation. national institute for occupational safety and health a multi-city investigation of the effectiveness of retrofit emissions controls in reducing exposutres to particulate matter in school buses. clean air task force experimental airborne influenza infection. i. influence of humidity on survival of virus in air influenza virus transmission is dependent on relative humidity and temperature measurement of air exchange rate of stationary vehicles and estimation of in-vehicle exposure simultaneous measurement of ventilation using tracer gas techniques and voc concentrations in homes, garages and vehicles we express our deepest gratitude to harvard university transport service for accommodating and assisting during the field campaigns. we would like to acknowledge the contribution of xuan du and anna algevik, the students of harvard extension school, who participated and helped in the study. and we are very grateful for dr. kato shinsuke, from the institute of industrial science, at the univeristy of tokyo, who shared his cfd resources with us. key: cord- -de o q authors: bagshaw, michael; nicolls, deborah j. title: aircraft cabin environment date: - - journal: travel medicine doi: . /b - - - - . -x sha: doc_id: cord_uid: de o q nan the physiology of the human being is optimized for existence at sea level. most individuals, however, can ascend to around - ft ( - m) above sea level before hypoxia begins to have ill effects and reduces performance. with increasing altitude, there is a fall in the atmospheric pressure, together with a decrease in density and temperature. the pressure at sea level in the standard atmosphere is mmhg and this falls to half at ft ( m), where the ambient temperature is about − °c. the composition of the atmosphere remains constant up to the tropopause ( ft or m), the most abundant gases being nitrogen ( %) and oxygen ( %), with the remaining % being argon, carbon dioxide, neon, hydrogen and ozone. the relationship between the oxygen saturation of hemoglobin and oxygen tension minimizes the effect on the human of the reduction in partial pressure of oxygen. ascent to an altitude of ft ( m) produces a fall in the partial pressure of oxygen in the alveoli, but only a slight fall in the percentage saturation of hemoglobin with oxygen. once altitude exceeds ft ( m), however, the percentage saturation of hemoglobin falls quickly, resulting in hypoxia. indeed, above ft ( m), the effects of lack of oxygen will begin to appear and a decrease in an individual's ability to perform complex tasks and a reduction in night vision can be measured. figure . shows the oxygen dissociation curve of blood. the concentrations of physically dissolved and chemically combined oxygen are shown separately and the curve illustrated is the average for a fit young adult. the actual shape of the curve will be influenced by factors such as age, state of health, tobacco use and ambient temperature. healthy individuals can tolerate altitudes of up to - ft ( - m) with no harmful effects. however, in the case of the elderly or of individuals suffering from some diseases of the respiratory or circulatory system, there is less tolerance of the mild hypoxia at even this altitude. in an ideal world, the cabin would be pressurized to maintain sea level conditions. to achieve this would require an extremely strong and heavy aircraft structure with severe implications on load carrying capacity, fuel consumption and resulting effects on the external environment. as a result, a compromise has to be struck, and airworthiness regulations (us federal aviation regulations and european joint aviation requirements) state that 'pressurized cabins and compartments to be occupied must be equipped to provide a cabin pressure altitude of not more than ft ( m) at the maximum operating altitude of the aeroplane under normal operating conditions.' pressurization is achieved by tapping bleed air from the engine compressors and passing this flow of air through the air-conditioning packs into the cabin. the outside air is very dry and cold, and the temperature is controlled via the air-conditioning packs. the cabin pressure is maintained at the desired level by regulating the flow of air overboard. figure . illustrates ambient and cabin altitudes for a typical flight. section as a result of the required cabin pressure change during climb and descent, it is possible for individuals to suffer discomfort as a result of expansion of gas trapped within the body. in particular, gas can be trapped within the gut and within the middle ear and sinuses. normally, this trapped gas is able to escape without any problem, but there may be occasions when this is not so, such as when the individual is suffering from upper respiratory tract congestion due to infection or allergy. in particular, the human ear is very sensitive to rates of pressure change, the threshold for detection being . psi ( . kpa). this is equivalent to a change in cabin altitude of ft ( m) at sea level. in the human ear, the cavity of the middle ear is separated from the outer ear by the tympanic membrane. it communicates with the nasopharynx and, in turn, the atmosphere by way of the eustachian tube, the proximal two-thirds of which has soft walls that are normally collapsed. during ascent to altitude, the gas in the middle ear cavity expands and escapes along the eustachian tube into the nasopharynx, equalizing the pressure across the tympanic membrane. the pharyngeal portion of the eustachian tube acts as a one-way valve, thus allowing expanding air to escape easily to the atmosphere. this can be sometimes felt as a 'popping' sensation as air escapes from the tube during ascent. during descent, air from the nasopharynx must enter the middle ear to maintain equilibrium. in some individuals, the one-way valve mechanism of the eustachian tube can prevent passive flow of air back into the middle ear cavity. this causes a relative increase of pressure on the outside of the tympanic membrane, pushing it into the middle ear cavity and causing a sensation of fullness, a decrease in hearing acuity and eventually pain. it is possible to perform active maneuvers to open the eustachian tube, such as swallowing, yawning, and jaw movements. in some people, these simple maneuvers are not effective and it may be necessary to occlude the nostrils and raise the pressure in the mouth and nose to force air into the middle ear cavities. this increase in pressure can usually simply be achieved by raising the floor of the mouth with the glottis shut, while other individuals raise the pressure in the lungs and the respiratory tract by contracting the expiratory muscles while forcibly exhaling (valsalva's maneuver). in addition to regulating the airflow rate required to pressurize the aircraft, the environmental control system controls the flow rate of outside air required to remove contaminants and controls the temperature in the cabin. this requirement is facilitated by the practice of recirculation of approximately % of the cabin air. this is achieved by extracting air from the cabin and mixing it with conditioned outside air. recirculation provides two benefits: one, it allows the total airflow rate to be higher than the flow rate of the outside air, so good circulation in the cabin can be maintained independently of the outside airflow; and two, the conditioned air is mixed with comparatively warm recirculated air before being introduced into the cabin. as a result, the conditioned air is supplied at a much lower temperature without causing discomfort from cold drafts. the recirculated air will also have picked up moisture from the cabin occupants and the cabin activities, improving the humidity level. in older generation jet aircraft, all the air supplied to the cabin came from outside air, without the benefits of recirculation (improved humidity, reduction in perceived drafts). this practice was inefficient with a substantial energy, and hence environmental, cost. in pressurized jet aircraft manufactured since the beginning of the s, the recirculated air is passed through filters. these are high efficiency particulate (hepa) filters, which have an efficiency of . % for . μm particles. they are effective in removing bacteria and viruses from the recirculated air, so preventing their spread through the cabin by this route. air filters are changed during routine aircraft maintenance, as specified by the manufacturer in the servicing schedule. recirculated air is obtained from the area above the cabin or under the floor; air from the cargo bay, lavatories and galleys is not recirculated. the flow rate of outside air per seat ranges from . to . l/s ( . - . cubic ft/min) with the percentage of recirculated air distributed to the passenger cabin being of the order - % of the total air supply. the result of filtering the recirculated air is a significant improvement in cabin air quality by the removal of particles and biological microorganisms. it is not necessary to pass the compressed air from outside through hepa filters, because the ambient air at high altitude is free of microorganisms and particulates. the use of recirculation has been common in the design of building environmental control systems for many years. building environmental systems are commonly designed and operated with up to % of recirculated air, which compares with the maximum recirculated air flow in aircraft of %. the air supply to the flight deck (or cockpit) is derived from the same source, but is delivered at a slightly higher pressure than the air supplied to the cabin. this ensures a positive pressure differential to prevent the ingress of smoke or fumes to the flight deck in the event of a fire or similar in-flight emergency. the flow rate of the flight deck air supply is also slightly higher than that to the cabin because this supply is used for cooling the avionics and other electronic equipment. humidity is the concentration of water vapor in the air. relative humidity is the ratio of the actual amount of vapor in the air to the amount that would be present if the air was saturated at the same temperature, expressed as a percentage. saturated air at high temperatures holds more water vapor than at low temperatures, and if unsaturated air is cooled, it becomes saturated. high humidity can lead to passenger and crew discomfort when it is accompanied by high temperature. high humidity can cause condensation, dripping and freezing of moisture on the inside of the aircraft shell, which may lead to safety problems such as corrosion. condensation can also give rise to biological growth thus causing adverse effects on cabin air quality. at a typical aircraft cruising altitude of ft ( m), the outside air temperature is in the region of − °c and is extremely dry, typically containing about . g/kg of moisture. for pressurized aircraft flying at these levels, the conditioned air entering the cabin has a relative humidity of < %. exhaled moisture from passengers and crew, together with moisture from galleys and toilet areas, increases the humidity to an average level of - %, which is below the % normally accepted as comfort level. research has shown that the maximum additional water lost from an individual during an -h period in % humidity, compared with normal day-to-day loss, is around ml. the sensation of thirst experienced by healthy individuals in the low humidity environment is due to local drying of the pharyngeal membranes, and this itself may lead to the spurious sensation of thirst. there is no evidence that exposure to a low-humidity environment itself leads to dehydration, although local humidity can cause mild subjective symptoms, such as dryness of the eyes and mucous membranes. , no significant effect has been shown on reaction time or other measures of psychomotor performance, although there can be some changes in the fluid regulatory hormones. , it is unlikely that low humidity has any long-or short-term ill-effects, provided overall hydration is maintained by drinking adequate amounts of fluid. the body's homeostatic mechanisms ensure that central hydration is maintained, although the peripheral physical effects can lead to discomfort. dry skin can be alleviated by using moisturizing aqueous creams, particularly just before flight, and dry eye irritation can be alleviated by the use of moisturizing eye drops. individuals prone to develop dry eyes are advised not to wear contact lenses during long flights in pressurized aircraft. a national academy of sciences report identified humidity as one of the areas deserving more attention in future research concerning aircraft cabin environment. the aircraft cabin is similar to many other indoor environments, such as homes and offices, in that people are exposed to a mixture of external and recirculated air. the cabin environment is different in many respects (e.g. the high occupant density, the inability of the occupants to leave at will and the need for pressurization). in flight, there is a combination of environmental factors including low air pressure and low humidity, as well as low frequency vibration and constant background noise. although the noise and vibration can contribute to fatigue, the levels are all below those which are accepted as potentially harmful to hearing. , ozone ozone is a highly reactive form of oxygen found naturally in the upper atmosphere. it is formed primarily above the tropopause as a result of the action of uv light on oxygen molecules. the amount and distribution of natural ozone in the atmosphere varies with latitude, altitude, season and weather conditions. the highest concentrations in the northern hemisphere are generally found at high altitude over high latitude locations during the winter and spring. the effects of high ozone concentration on human beings can include eye irritation, coughing due to irritation of the upper respiratory system, nose irritation and chest pains. as a result of this, the airworthiness regulatory authorities (e.g. us federal aviation authority, european joint aviation authorities) require that transport category aircraft operating above ft ( m) must show that the concentration of ozone inside the cabin will not exceed . parts/million by volume (sea level equivalent) at any time, and a time weighted value of . parts/million by volume (sea level) for scheduled segments of > h. for this reason, long haul transport jet aircraft are now equipped with ozone catalytic converters that break down or 'crack' the ozone before it enters the cabin air circulation. natural radiation consists of cosmic rays from outer space (galactic radiation) and the gamma rays from rocks, earth, and building materials. cosmic radiation is produced when primary photons and alpha particles from outside the solar system (galactic cosmic radiation) interact with components of the earth's atmosphere. a second source of cosmic radiation is the release of charged particles from the sun, which becomes significant during periods of solar flare ('sun storm'). cosmic radiation is an ionizing radiation; ionizing radiation also includes x-rays and that from radioactive materials. ionizing radiation is a natural part of the environment in which we live and is present in the earth, buildings, food we eat, and even in the bones of our bodies. the other type of radiation is known as non-ionizing radiation and this includes uv light, radio waves and microwaves. humans, animals and plants have all evolved in an environment with a background of natural radiation and, with few exceptions, it is not a significant risk to health. the amount of cosmic radiation that reaches the earth from the sun and outer space varies and depends on the latitude and height above sea level. the amount of cosmic radiation entering the atmosphere follows an -year cycle, with the intensity of galactic radiation being lowest when solar activity is at its highest. this is because during high levels of solar activity, the resulting magnetic flux between the sun and the earth deflects much of the galactic cosmic radiation. cosmic radiation is effectively absorbed by the atmosphere and is also affected by the earth's magnetic field. the effect on the body will depend on the latitude and altitude at which the individual is flying and also on the length of time in the air. cosmic radiation may be measured directly using sophisticated instruments, as was done in the concorde supersonic transport and subsonic long range aircraft, or can be estimated using a computer software program. these programs look at the route, time at each altitude and the phase of the solar cycle, and calculate the radiation dose received by the aircraft occupant for a particular flight. a number of airlines and research organizations have compared actual measurements taken on board an aircraft with the computer estimations, and the two are very similar. the effect of ionizing radiation depends not only on the dose absorbed, but also on the type and energy of the radiation and the tissues involved. these factors are taken into account in arriving at the dose equivalent measured in sieverts (sv). however, doses of cosmic radiation are so low that figures are usually quoted in microsieverts (μsv, millionths of a sievert) or millisieverts (msv, thousandths of a sievert). when ionizing radiation passes through the body, energy is transmitted to the tissues, which affects the atoms within the individual cells. very high levels of radiation, such as that from a nuclear explosion, will cause severe cell damage in a human being, particularly to the bone marrow cells and the reproductive cells, which cannot be repaired by the body. low-level doses of radiation, such as cosmic radiation or medical x-rays, do not cause such severe damage to the cells and in most cases, any such damage is repaired satisfactorily by the body's own mechanism. it is not possible to predict a maximum safe threshold of exposure to low levels of radiation, because individuals vary in their biological response. , the international commission for radiological protection (icrp) recommends maximum mean body effective dose limits of msv/ year (averaged over years) for workers exposed to radiation as part of their occupation (including flight crew), and msv/year for the general population, with an additional recommendation that the equivalent dose to the fetus should not exceed msv during the declared term of pregnancy. when the concorde supersonic transport aircraft was flying, the effective dose rate for the occupants at cruising altitude was measured to be in the range of - μsv/h. on ultra long-haul flights at high latitudes, such as a boeing - flying between london and tokyo, the effective dose rate at cruising altitude is around μsv/h. on short-haul commercial operations, the effective dose rate in europe is in the region of - μsv/h. for typical annual flight schedules, crew members accumulate around or msv/year operations, and between and msv/year on european short-haul operations from cosmic radiation. for airline passengers, the icrp recommended limit for the general public of msv/year equates to about flying hours/year on the trans-equatorial routes. there are essentially two types of airline passenger: the occasional social traveler and the frequent business traveler. the public limit ( msv/year) will be of no consequence to the social traveler but could be of significance to the frequent business traveler. the msv annual limit would be exceeded if the business traveler were flying more than eight transatlantic or five antipodean return journeys per year. business travelers are exposed as an essential part of the occupation, and it is entirely logical to apply the occupational limit of msv/year to this group. cosmic radiation is of no significance at altitudes below about ft ( m) because of the attenuating properties of the earth's atmosphere. there is no evidence from epidemiological studies of flight crew of any increase in incidence of cancers linked to ionizing radiation exposure, such as leukemia. in general terms, as far as the risk of developing cancer induced by radiation exposure is concerned, it has been calculated that an accumulated dose of msv/year for years increases the risk of developing cancer (in the general population) from - . %, i.e. an increase of risk of . % over years. compared with all the other risks encountered during a working life, this is very low. cosmic radiation is both a complex and emotive subject. it cannot be seen, touched, smelled or tasted and yet it is present all around us. while it is known that there is no level of radiation exposure below which effects do not occur, all the evidence indicates that there is an extremely low probability of airline passengers or crew suffering any abnormality or disease as a result of exposure to cosmic radiation. the world health organization and the international civil aviation organization recommend that aircraft arriving through countries reporting certain indigenous infectious diseases, be treated with pesticides. this remains a controversial issue. while it is understandable that countries such as new zealand would not want to risk the entry of certain vector-borne diseases transmitted by mosquitoes, there remains concern about the safety and efficacy of various pesticides used, particularly while passengers are in the cabin (top of descent spraying). there appears to be less concern about using residual pesticides during routine aircraft maintenance. at this time, however, the us environmental protection agency has not promoted the registry of any pesticides in the usa for use in aircraft disinsection on american carriers. as vector-borne diseases re-emerge, however, these policies may need re-evaluation in order to prevent the transmission of disease. further education of air crew and passengers will be needed, and these issues are being reviewed. there are five main routes by which microorganisms may be transmitted to humans: contact (direct and indirect), droplet, air-borne, common-vehicle, and vector-borne. all of these modes have been implicated, at least anecdotally, in the transmission of disease aboard an aircraft; [ ] [ ] [ ] [ ] however, there has been increasing concern over the respiratory spread of infections during air travel, via droplet and air-borne transmission. droplet transmission may occur whenever a person coughs, sneezes, or talks. droplets are relatively large particles (> μm) that can travel only a short distance through the air; they do not remain suspended. infection occurs when microorganisms within the droplets come into contact with the conjunctivae, nasal mucosa, or mouth of a susceptible person. in air-borne transmission, smaller respiratory particles (≤ μm), called droplet nuclei, are inhaled by a susceptible host. these particles remain suspended in air indefinitely and may spread over long distances, depending on environmental factors. humans are the most important reservoirs of infectious agents on aircraft. most microorganisms that have been isolated from occupied spaces, including aircraft cabins, are human in source, including bacteria that have been shed from exposed skin and scalp, as well as from the nose and mouth. these microorganisms are typically part of the normal human flora and very rarely cause infections. studies have shown no statistically significant differences in the concentrations of bacteria and fungi sampled from the aircraft cabin: ▪ among different aircraft, airlines or flight durations ▪ between aircraft cabins and other types of public transport vehicles ▪ between aircraft cabins and typical indoor and outdoor urban environments. when microorganisms are spread by droplet transmission, the risk of acquiring infection is highest for the passengers seated closest to a source person, typically within feet. in contrast, microorganisms that are spread by air-borne transmission potentially could distribute throughout the entire aircraft cabin. in reality, however, this does not occur. microorganisms suspended in cabin air are removed by the high efficiency particulate (hepa) filters during the air recirculation process; unfortunately, these filters provide no protection from the cough or sneeze emitted by an infected neighbor. the natural or acquired immunity of most individuals prevents the development of infectious disease. limited data are available on the true risk of disease transmission during air travel. studies of potential infectious disease transmission on aircraft have considered tuberculosis, influenza, measles, meningococcal disease, sars, and acute respiratory infections, such as the common cold. , tuberculosis the transmission of mycobacterium tuberculosis (tb) during air travel has been most extensively studied. tb is transmitted by the inhalation of droplet nuclei (air-borne transmission). two of six investigations conducted by the centers for disease control and prevention (cdc) between and have indicated that the transmission of tb from a symptomatic person to other passengers or crew members does occur during air travel. , in one investigation, a flight attendant was diagnosed with cavitary pulmonary tuberculosis in november, . of the flight crew who worked with this flight attendant between august and october, , . % had a positive tuberculin skin test (tst) result. two of these contacts had documented conversion of tst status. tst positivity and conversion was associated with a cumulative flight-time exposure of h or more. in the second investigation, a foreign-born passenger developed symptomatic pulmonary tuberculosis while visiting friends in the usa. she traveled from baltimore, maryland to chicago, illinois ( h flight) and then from chicago to honolulu, hawaii ( h and min flight). three of the passengers on the baltimore to chicago flight had a positive tst, two were foreign-born. fifteen of the passengers on the flight from chicago to honolulu had a positive tst. four of these passengers converted their tst. in both investigations, all of the new infections were latent tb infection; none developed active tuberculosis. the hepa filters used in newer commercial aircraft are able to filter out tb bacteria from the recycled air and are also used in hospital respiratory isolation rooms to prevent the spread of tb within the hospital setting. the number of air exchanges per hour in aircraft exceeds the number recommended for hospital isolation rooms. furthermore, the prevalence of transmissible tuberculosis among air travelers is estimated to be - / passengers, depending on the route of the plane. the risk of tb transmission on a commercial aircraft, therefore, remains low. mathematical models estimate that the chance of acquiring tb during air travel while sitting near a highly infectious source is approximately in . human influenza virus is spread by droplet and air-borne transmission. one of the first well-documented outbreaks of influenza on a commercial airline was published by moser and colleagues in . thirty-eight of passengers and crew members became ill after exposure to a passenger with symptomatic influenza infection. another two passengers showed serological evidence of infection without becoming ill. the outbreak was attributed to an engine malfunction, which required the aircraft to remain on the runway for approximately . h without adequate ventilation. most of the passengers remained on the plane during the delay, and the clinical attack rate varied with the amount of time spent aboard the aircraft. another outbreak of presumed influenza that was associated with air travel occurred among workers traveling from a remote mine in northwestern australia. one worker became symptomatic with an influenza-like illness prior to the flight, which lasted h and min. over the - days that followed the flight, workers presented with similar complaints and were unable to work. an additional five workers reported upper respiratory tract symptoms when questioned but were able to continue working. there was no ventilation system malfunction reported for the aircraft associated with this outbreak. a significant limitation of this report is the lack of etiologic confirmation. since , a new strain of avian influenza virus (h n ) has been responsible for a number of outbreaks involving a large number of birds, and rarely, humans. from december -february , laboratory-confirmed human infections were identified in asia and se asia, and have primarily been due to direct contact with poultry. , limited, non-sustained person-to-person spread has also been described in a few cases. as with sars, the airline industry will look to public health authorities for guidance in the event that an (avian) influenza pandemic should occur. the severe acute respiratory syndrome (sars) was first identified in southern china in november, , and recognized as a global threat by march, . it was caused by a novel coronavirus, the sars-associated coronavirus, and was spread primarily via droplet transmission, although spread by air-borne and contact transmission could not be ruled out. despite the clear role of international travel in the spread of sars during the outbreak, , there had been only one case of likely in-flight transmission. limited transmission probably occurred aboard aircraft, but the risk was felt to be low. fortunately, no suspected cases of sars have been reported since may, . neisseria meningitidis is a leading cause of meningitis and sepsis in children and young adults and is spread by droplet transmission. meningococcal disease has been documented in travelers, particularly those traveling for the hajj; however, transmission due to exposure while aboard an aircraft has not been definitively documented. guidelines for the management of airline passengers who have been exposed to meningococcal disease are based on information available from investigations of tb transmission aboard aircraft. us guidelines are online and available at: http://www.cdc.gov/travel/menin-guidelines.htm measles is a highly contagious viral disease that is spread by air-borne transmission. a person infected with measles is contagious from the first onset of vague symptoms (up to days before rash appears) to approximately days after the development of rash; therefore the potential for disease transmission during air travel exists. from to , of the cases of imported measles into the usa developed a rash directly before or on the day of air travel. from these imported cases, only one documented case of in-flight transmission was reported. despite the risk, few cases of measles occur as a direct result of inflight exposure. , amornkul and colleagues investigated the extent of measles transmission aboard an international commercial flight after exposure to an infected passenger. of the potentially exposed passengers, % completed a follow-up questionnaire, including passengers who reported close contact with the ill passenger before, during, or after the flight. none of the contacted passengers reported symptoms consistent with measles. available data indicate that infectious agents can be transmitted from person-to-person aboard an aircraft on the ground and during flight, just as they can in any other situation where people find themselves in close proximity. from investigations of disease outbreaks associated with air travel, two main risk factors for the spread of communicable diseases have been identified: flight duration (> h, including ground time) and seating proximity to the source. there is no evidence that the pressurized cabin itself makes transmission of disease any more likely. once the aircraft doors are closed, airconditioning is provided from the auxiliary power unit until it can be supplied from the aircraft engines, thus ensuring the filtration benefits of air recirculation. there does appear to be increased risk of disease spread when the aircraft ventilation system is inoperable. guidelines are in place to assist flight crew in the management of ill passengers and can be accessed from www.who.org, www.cdc.gov, or www.iata.org. in general, good respiratory and hand hygiene practices should always be encouraged, and people with febrile illnesses should postpone air travel whenever possible. aircrews, particularly of international fights, are at risk for the same illnesses to which other travelers are exposed. because of their very short-term stays, and stays that are generally in major cities, they may not be as intensely exposed to some illnesses as others. however, their lifestyle may predispose them to other risks. because of their frequent international travel, flight crews should receive health recommendations that are specifically geared to their travel patterns, itineraries, and lifestyles. for example, an international pilot flying frequently to sub-saharan africa would do well not to take routine anti-malarial medication, but should take precautions to avoid insect bites, may carry a self-treatment regimen if desired and if the layovers are extended, and should be instructed to seek medical attention immediately if a fever occurs. the medical department of international carriers should either be able to provide good information and appropriate immunizations to aircrew, or should have an arrangement with a travel clinic for appropriate education of flight crews. other than transmission of infectious agents, flight crews have other health concerns that though briefly mentioned here, are best reviewed in an occupational health setting. issues that have surfaced with regard to pilot health have included the safety of refractive surgery, the use of serotonin re-uptake inhibitors, safety of pilots to fly with insulin-dependent diabetes mellitus or even with the human immunodeficiency virus, as well as issues related to pilot fatigue. flight attendants' concerns have ranged from reproductive health problems, menstrual disorders, chronic back pain, to fears of an increased risk of breast cancer. epidemiological studies have shown an increased prevalence of malignant melanoma among flight crew members. this is thought to be a result of a lifestyle, allowing exposure to sunlight that is perhaps increased during layover periods. flying as a passenger should be no problem for the fit, healthy, and mobile individual. but for the passenger with certain pre-existing conditions, the cabin environment may exacerbate their underlying problems. although many problems relate to the physiological effects of hypoxia and expansion of trapped gases, it should be remembered that the complex airport environment can be stressful and challenging to the passenger, leading to problems before even becoming air-borne. although passengers with medical needs require medical clearance from the airline, passengers with disabilities do not. disabled passengers do need to notify the requirement for special needs, such as wheelchair assistance or assignment of seats with lifting armrests, and this should be done at the time of booking. an area of little exploration has been air travel stress and anxiety. whereas typical issues such as fear of flying have been addressed by the airlines in the past, problems that have surfaced related to terrorism and airline security have increased. passenger lines, terminal crowding, lesser personal services due to cost-cutting, etc. have taken a toll on the ease in which air travel is currently perceived. addressing these potential problems with the air traveler, particularly with those who have any underlying illness or general anxiety, is helpful. the objectives of medical clearance are to provide advice to passengers and their medical attendants on fitness to fly, and to prevent delays and diversions of the flight as a result of deterioration in the passenger's well-being. it depends upon self-declaration by the passenger, and upon the attending physician having an awareness of the flight environment and how this may affect the patient's condition. most major airlines provide services for those passengers who require extra help, and most have a medical advisor to assess the fitness for travel of those with medical needs. individual airlines work with their own guidelines, but these are generally based on those published by the aerospace medical association on fitness for travel. (copies of the asma guidelines may be obtained from the association online at: www.asma.org or tel: .) the international air transport association (iata) publishes a recommended medical information form (medif) for use by member airlines (fig. . ) . the medif should be completed by the passenger's medical attendant and passed to the airline, or travel agent, at the time of booking to ensure timely medical clearance. medical clearance is required when: ▪ fitness to travel is in doubt as a result of recent illness, hospitalization, injury, surgery or instability of an acute or chronic medical condition ▪ special services are required (e.g. oxygen, stretcher or authority to carry or use accompanying medical equipment such as a ventilator or a nebulizer). medical clearance is not required for carriage of an invalid passenger outside these categories, although special needs (such as a wheelchair) must be reported to the airline at the time of booking. cabin crew members are unable to provide individual special assistance to invalid passengers beyond the provision of normal in-flight service. passengers who are unable to look after their own personal needs during flight (such as toileting or feeding) will be asked to travel with an accompanying adult who can assist with these needs. it is vital that passengers remember to carry with them any essential medication, and not pack it in their checked baggage. deterioration on holiday or on a business trip of a previously stable condition -such as asthma, diabetes, or seizure disorder -can often give rise to the need for medical clearance for the return journey. a stretcher may be required, together with medical support, and this can incur considerable cost. it is important for all travelers to consider supplemental travel insurance, which includes provision for the use of a specialist repatriation company to provide the necessary medical support. if yes, describe and indicate for each item, (a) segment(s) on which required (b) airline arranged or arranging third party, and (c) at whose expense. provision of special equipment such as oxygen etc. always requires completion of part overleaf. if yes, add below fremec data to your reservation requests. if no, (or additional data needed by carrying airline(s)), have physician in attendance complete part overleaf. if yes, specify below and indicate for each item, (a) the arranging airline or other organisation, (b) at whose expense, and (c) contact addresses/phones where appropriate, or whenever specific persons are designated to meet/assist the passenger this form is intended to provide confidential information to enable the airlines' medical departments to provide for the passenger's special needs. to be completed by attending physician • when fitness to travel is in doubt as evidenced by recent illness, hospitalisation, injury, surgery or instability. • where special services are required, i.e. oxygen, stretcher, authority to carry accompanying medical equipment. completion of the form in block letters or by typewriter will be appreciated. specify if any** in determining the passenger's fitness to fly, a basic knowledge of aviation physiology and physics can be applied. any trapped gas will expand in volume by up to % during flight, and consideration must be given to the effects of the relative hypoxia encountered at a cabin altitude of up to ft above mean sea level. the altitude of the destination airport may also need to be taken into account in deciding the fitness of an individual to undertake a particular journey. the passenger's exercise tolerance can provide a useful guide on fitness to fly; if unable to walk a distance > m without developing dyspnea, there is a risk that the passenger will be unable to tolerate the relative hypoxia of the pressurized cabin. more specific guidance can be gained from knowledge of the passenger's baseline sea level blood gas levels and hemoglobin value. a good source of guidance is provided by the british thoracic society website. table . shows the guidelines recommended by one international carrier. this list is not exhaustive, and it should be remembered that individual cases might require individual assessment by the attending physician. the prolonged period of immobility associated with long-haul flying can be a risk for those individuals predisposed to develop deep venous thrombosis (dvt). pre-existing risk factors include: ▪ blood disorders and clotting factor abnormalities ▪ cardiovascular disease ▪ malignancy ▪ major surgery ▪ lower limb/abdominal trauma ▪ dvt history ▪ pregnancy ▪ estrogen therapy (including oral contraception and hormone replacement therapy) ▪ > years of age ▪ immobilization ▪ pathological body fluid depletion ▪ smoking ▪ obesity ▪ varicose veins. although many airlines promote lower limb exercise via the in-flight magazine or videos, and encourage mobility within the cabin, those passengers known to be vulnerable to dvt should seek guidance from their attending physician on the use of compression stockings and/or anti-coagulants. there is currently no evidence that flying, per se, is a risk factor for the development of dvt, but those at high risk should avoid any form of prolonged immobilization such as is associated with travel. in addition to the reduction in ambient pressure and the relative hypoxia, it is important to consider the physical constraints of the passenger cabin. a passenger with a disability must not impede the free egress of the cabin occupants in case of emergency evacuation. there is limited leg space in an economy class seat and a passenger with an above-knee leg plaster or an ankylosed knee or hip may simply not fit in the available space. the long period of immobility in an uncomfortable position must be taken into account, and it is imperative to ensure adequate pain control for the duration of the journey, particularly following surgery or trauma. even in the premier class cabins with more available legroom, there are limits to space. to avoid impeding emergency egress, immobilized or disabled passengers cannot be seated adjacent to emergency exits, despite the availability of increased leg room at many of these positions. similarly, a plastered leg cannot be stretched into the aisle because of the conflict with safety regulations. there is limited space in aircraft toilet compartments and if assistance is necessary, a traveling companion is required. the complexities of the airport environment should not be underestimated, and must be considered during the assessment of fitness to fly. the formalities of check-in and departure procedures are demanding and can be stressful, and this can be compounded by illness and disability, as well as by language difficulties or jet lag. the operational effect of the use of equipment such as wheelchairs, ambulances, and stretchers must be taken into account, and the possibility of aircraft delays or diversion to another airport must be considered. it may be necessary to change aircraft and transit between terminals during the course of a long journey, and landside medical facilities will not be available to a transiting passenger. there is often a long distance between the check-in desk and the boarding gate. not all flights depart from or arrive to jetties, and it may be necessary to climb up or down stairs and board transfer coaches. passengers should specify the level of assistance required when booking facilities such as wheelchairs. in addition to the main gaseous system, all commercial aircraft carry an emergency oxygen supply for use in the event of failure of the pressurization system or during emergencies such as fire or smoke in the cabin. the passenger supply is delivered through drop-down masks from chemical generators or an emergency reservoir, and the crew supply is from oxygen bottles strategically located within the cabin. the drop-down masks are automatically released en masse (the socalled 'rubber jungle') in the event of the cabin altitude exceeding a pre-determined level of between and ft. this passenger emergency supply has a limited duration if provided by chemical generators, usually in the region of min. the flow rate is between and l (ntp)/min, and is continuous once the supply is triggered by the passenger pulling on the connecting tube. oxygen supplied from an emergency reservoir is delivered to the cabin via a 'ring main', and in some aircraft it is possible to plug a mask into this ring main to provide supplementary oxygen for a passenger. sufficient first-aid oxygen bottles are carried to allow the delivery of oxygen to a passenger in case of a medical emergency in-flight, at a rate of or l (ntp)/min. this cannot be used to provide a pre-meditated supply for a passenger requiring it continuously throughout a journey, however, since it would then not be available for emergency use. if a passenger has a condition requiring continuous ('scheduled') oxygen for a journey, this needs pre-notification to the airline at the time of booking the ticket. most airlines charge a fee: one major british international airline charges gb£ (us$ , euro€ ) per sector, whether the supply is derived from gaseous bottles or via a mask plugged into the ring main. for us carriers, a fee of approximately us$ (€ ) is charged for providing oxygen during flight. some airlines also allow passengers to use their own portable oxygen concentrators, provided the unit meets certain specifications. an additional fee may be charged for medical clearance by an airline representative. passengers who require continuous oxygen during travel should be made aware that airlines provide oxygen service only during the flight, and not during the time spent in the airport terminal. passengers need to make arrangements for oxygen to be supplied at their destination upon arrival. oxygen bottles, regulators and masks must meet minimum safety standards set by the regulatory authorities, and the oxygen must be of 'aviation' quality, which is a higher specification than 'medical' quality. an in-flight medical emergency is defined as a medical occurrence requiring the assistance of the cabin crew. it may or may not involve the use of medical equipment or drugs, and may or may not involve a request for assistance from a medical professional traveling as a passenger on the flight. it can be something as simple as a headache, or a vaso-vagal episode, or something major, such as a myocardial infarction or impending childbirth. the incidence is comparatively low, although the media impact of an event can be significant. one major international airline recently reported incidents occurring in something over million passengers carried in year. the breakdown of these incidents into generalized causes is shown in table . . , the top six in-flight emergency medical conditions reported by the same airline are shown in table . . , any acute medical condition occurring during the course of a flight can be alarming for the passenger and crew because of the remoteness of the environment. cabin crew members receive training in advanced first aid and basic life support and the use of the emergency medical equipment carried on board the aircraft. many airlines give training in excess of the regulatory requirement, particularly when an extended range of medical equipment is carried. although the crew are trained to handle common medical emergencies, in serious cases they may request assistance from a medical professional traveling as a passenger. such assisting professionals are referred to as 'good samaritans'. cabin crew members attempt to establish the bona fide of medical professionals offering to assist, but much has to be taken on trust. the international nature of air travel can lead to complications in terms of professional qualification and certification, specialist knowledge, and professional liability. an aircraft in flight is subject to the laws of the state in which it is registered, although when not moving under its own power (i.e. stationary at the airport) it is subject to the local law. in some countries, it is a statutory requirement for a medical professional to offer assistance to a sick or injured person (e.g. france), whereas in other states no such law exists (e.g. uk or usa). some countries (e.g. usa) have enacted a good samaritan law, whereby an assisting professional delivering emergency medical care within the bounds of his or her competence, is not liable for prosecution for negligence. in the uk, the major medical defense insurance companies provide indemnity for their members acting as good samaritans. some airlines provide full indemnity for medical professionals assisting in response to a request from the crew, whereas other airlines take the view that a professional relationship is established between the sick passenger and the good samaritan and any liability lies within that relationship. at the time of writing, there has been no case of successful action against a good samaritan providing assistance on board an aircraft. recognition by the airline of the assistance given by the good samaritan is complicated by the special nature of the relationship between the professional, the patient, and the airline. indemnity, whether provided by the airline or the professional's defense organization, depends upon the fact that a good samaritan act is performed. if a professional fee is claimed or offered, the relationship moves away from being that of a good samaritan act to one of a professional interaction with an acceptance of clinical responsibility. this implies that the professional is suitably trained, qualified, and experienced to diagnose, treat and follow-up the particular case, and the good samaritan indemnity provision no longer applies. follow-up of the outcome for the passenger after disembarkation is frequently difficult, because the sick passenger is no longer in the care of the airline and becomes the responsibility of the receiving hospital or medical practitioner. responsibility for the conduct of the flight rests with the aircraft captain who makes the final decision as to whether or not an immediate unscheduled landing or diversion is required for the well-being of a sick passenger. the captain has to take into account operational factors as well as the medical condition of the sick passenger. in practice, it is rarely possible to land immediately, even if a suitable airport is in the immediate vicinity. the aircraft has to descend from cruising altitude, possibly jettison fuel to reduce to landing weight, and then fly the approach procedure to land. consideration has to be given to the availability of appropriate medical facilities, and in many cases, it is of greater benefit for the sick passenger to continue to the scheduled destination where the advantage of appropriate facilities will outweigh the risks of continuing the flight. operational factors to be considered include the suitability of an airport to receive the particular aircraft type. the runway must be of sufficient length and load-bearing capacity, the terminal must be able to accommodate the number of passengers on the flight, and if the crew go out of duty time, there must be sufficient hotel accommodation to allow an overnight stay of crew and passengers. the cost to the airline may be substantial, including the effects of aircraft and crew unavailability for the next scheduled sector, as well as the direct airport and fuel costs of the diversion. in making the decision whether or not to divert, the captain will take advice from all sources. if a good samaritan is assisting, he or she has an important role to play, perhaps in radio consultation with the airline medical advisor. many airlines use an air-to-ground link, which allows the captain and/or the good samaritan to confer with the airline medical adviser regarding the diagnosis, treatment, and prognosis of the sick passenger. the airline operations department is also involved in the decision-making process. some airlines maintain a worldwide database of medical facilities available at or near the major airports; others subscribe to a third party provider giving access to immediate medical advice and assistance with arranging emergency medical care for the sick passenger at the diversion airport. the link from the aircraft is made using either radio-telephone voice or datalink (vhf or acars), high-frequency radio communication (hf) or a satellite communication system (satcom). satcom is installed in newer, long-range aircraft, and is gradually replacing hf as the industry norm for long-range communication. the advantage is that satcom is unaffected by terrain, topography or atmospheric conditions, and allows good transmission of voice and data from over any point on the globe. digitization and telephone transmission of physiological parameters is a well established practice, particularly in remote areas of the world. an aircraft cabin at ft ( m) can be considered a remote location in terms of availability of medical support, and the digital technology used in satcom is similar to that used in modern ground-to-ground communication. the advent of satcom has enabled the development of air-to-ground transmission to assist in diagnosis. pulse oximetry and ecg are examples of data that can assist the medical advisor to give appropriate advice to the aircraft captain, although the cost/benefit analysis has to be weighed very carefully. national regulatory authorities stipulate the minimum scale and standard of all equipment to be carried on aircraft operating under their jurisdiction, which includes emergency medical equipment. these standards stipulate the minimum requirement, although in practice many airlines carry considerably more equipment. tables . and . give the minimum standard of equipment mandated by the federal aviation administration (faa) to be carried by aircraft registered in the usa, while table . gives the standard determined by the joint aviation authorities (jaa) for aircraft registered in european states. in determining the type and quantity of equipment and drugs to include in the medical kits, the airline must fulfill the statutory requirements laid down by the regulatory authority. other factors to be considered are: ▪ the route structure and stage lengths flown. different countries of the world vary in their regulations on what might be imported and exported, particularly in terms of drugs. for example, it is illegal to import morphine derivatives into the usa, even if securely locked in a medical kit approved first aid kits required by β . must meet the following specifications and requirements: the approved emergency medical kit required by β . for passenger flights must meet the following specifications and requirements: . each first aid kit must be dust and moisture proof, and contain only materials that either meet federal specification gg-k- a, as revised, or are approved. . approved emergency medical equipment shall be stored securely so as to keep it free from dust, moisture, and damaging temperatures. . required first aid kits must be distributed as evenly as practicable throughout the aircraft and be readily accessible to the cabin flight attendants. . one approved emergency medical kit shall be provided for each aircraft during each passenger flight and shall be located so as to be readily accessible to crew members. . the minimum number of first aid kits required is set forth in the following table: . the approved emergency medical kit must contain, as a minimum, the following appropriately maintained contents in the specified quantities. it is important to audit the incidence and outcome of in-flight medical emergencies and maintain a review of the kit content. this review should also take into account changes in medical practice ▪ space and weight. the medical equipment must be accessible, but securely stowed. some airlines divide the equipment and drugs between basic first-aid kits, which are readily accessible on the catering trolleys, and a more comprehensive emergency medical kit that is sealed and stowed with other emergency equipment. space and weight are always at a premium within the cabin, and the medical kits must be as light and compact as possible ▪ shelf life and replenishment. a tracking system for each kit must be in place to ensure that contents have not exceeded their designated shelf life. similarly, after use of a kit, there has to be a procedure for replenishment. in practice, the aircraft can depart if the kit contents meet the statutory minimum, even though drugs or equipment have been used from the non-statutory part of the kit. many airlines subcontract the tracking and replenishment to a specialist medical supply company. although basic cardiopulmonary resuscitation (cpr) techniques are an essential part of cabin crew training, the outcome of an in-flight cardiac event may be improved if appropriate resuscitation equipment is available. this can range from a simple mouth-to-mouth faceguard, to a resuscitation bag and mask and airway, to an all crew members will receive initial training on the emk and on the location, function, and intended operation of an aed. flight attendants will receive initial and recurrent training in cpr and on the use of aeds. medical personnel are frequently onboard and can assist fellow passengers during an in-flight medical event. in addition, a 'good samaritan' provision in the aviation medical assistance act of limits the liability of air carriers and non-employee passengers unless the assistance is grossly negligent or willful misconduct is evident. the following should be included in the first aid kits: note: an eye irrigator, while not required to be carried in the first aid kit should, where possible, be available for use on the ground. in addition, for aeroplanes with more than nine passenger seats installed, an emergency medical kit must be carried. the following should be included in the emergency medical kit: sphygmomanometer -non-mercury stethoscope syringes and needles oropharyngeal airways (two sizes) tourniquet coronary vasodilator (e.g. nitro-glycerine) anti-spasmodic (e.g. hyoscine) epinephrine : adrenocortical steroid (e.g. hydrocortisone) major analgesic (e.g. nalbuphine) diuretic (e.g. furosemide) antihistamine (e.g. diphenhydramine hydrochloride) sedative/anticonvulsant (e.g. diazepam) medication for hypoglycemia (e.g. hypertonic glucose) antiemetic (e.g. metoclopramide) atropine digoxin uterine contractant (e.g. ergometrine/oxytocin) disposable gloves bronchial dilator, including an injectable form needle disposal box anti-spasmodic drug catheter a list of contents in at least two languages (english and one other). this should include information on the effects and side-effects of drugs carried. endotracheal tube and laryngoscope, to an automatic external defibrillator (aed). the decision on the scale of equipment to be carried has to take account of the same parameters used in determining the content of the emergency medical kits (table . ). in addition, a cost/benefit analysis has to balance the cost of acquisition, maintenance and training against the probability of need and the expectation of the traveling public. the european resuscitation committee and the american heart association endorse the concept of early defibrillation as the standard of care for a cardiac event both in and out of the hospital setting. however, the protocol includes early transfer to an intensive care facility for continuing monitoring and treatment, which is not always possible in the flight environment. despite this inability to complete the resuscitation chain, it is becoming increasingly common for commercial aircraft to be equipped with aeds and for the cabin crew to be trained in their use. this has been mandated in the usa by the faa (table . ). experience of those airlines which carry aeds indicates that there may be benefits to the airline operation as well as to the passenger. some types of aed have a cardiac monitoring facility, and this can be of benefit in reaching the decision on whether or not to divert. for example, there is no point in initiating a diversion if the monitor shows asystole, or if it suggests that the chest pain is unlikely to be cardiac in origin. lives have been saved by the use of aeds on aircraft and diversions have been avoided, so it could be argued that the cost/benefit analysis is weighted in favor of carrying aeds as part of the aircraft medical equipment. nonetheless, it is important that unrealistic expectations are not raised. an aircraft cabin is not an intensive care unit and the aed forms only a part of the first aid and resuscitation equipment. many airlines have in place a procedure for the follow-up of crew members involved in a distressing event, such as a serious medical emergency. this can be valuable in avoiding long-term posttraumatic stress disorder, and also in reinforcing the training that the crew member has already undergone. the pressurized aircraft cabin provides protection against the hostile environment encountered at cruising altitudes. ▪ although the partial pressure of oxygen is less than at sea level, it is more than adequate in a pressurized aircraft cabin for normal healthy individuals ▪ the cabin air, although dry, does not cause systemic dehydration and harm to health. dry skin and eyes can lead to discomfort, which can be alleviated by the use of moisturizing creams and eye drops ▪ although up to half of the air in modern pressurized aircraft is recirculated, the amount of fresh air available to each occupant exceeds that available in air-conditioned buildings. recirculating the air has the advantage of reducing cold draughts and increasing the humidity ▪ in modern aircraft, all the recirculated air is passed through high-efficiency particulate filters which remove > % of particles, including bacteria and viruses ▪ there is an extremely low probability of airline passengers or crew suffering any abnormality or disease as a result of exposure to cosmic radiation. the passenger cabin of a commercial airliner is designed to carry the maximum number of passengers in safety and comfort, within the constraints of cost-effectiveness. it is incompatible with providing the facilities of an ambulance, an emergency room, an intensive care unit, a delivery suite, or a mortuary. the ease and accessibility of air travel to a population of changing demographics inevitably means that there are those who wish to fly, who may not cope with the hostile physical environment of the airport, or the hostile physiological environment of the pressurized passenger cabin. it is important for medical professionals to be aware of the relevant factors, and for unrealistic public expectations to be avoided. transmission aboard aircraft of illnesses, such as tuberculosis, sars and other respiratory diseases, has been reported, but is infrequently documented and probably rare. there is no evidence that a properly functioning environmental control system contributes to increased disease transmission aboard an aircraft. most airlines have a medical advisor who may be consulted before flight to discuss the implications for a particular passenger. such pre-flight notification can prevent the development of an in-flight medical emergency that is hazardous to the passenger concerned, inconvenient to fellow passengers, and expensive for the airline. for those with disability, but not an acute medical problem, preflight notification of special needs and assistance will reduce the stress of the journey and enhance the standard of service delivered by the airline. the importance of adequate medical insurance coverage for all travelers cannot be over-emphasized. finally, as is the case in commercial aviation, there is a continuing audit of activity and an ongoing risk/benefit analysis. the industry is under constant evolution, and is now truly global in its activity. application of basic physics and physiology, and an understanding of how this may affect underlying pathology, will minimize the medical risks to the traveling public. ernsting's aviation medicine airworthiness standards, transport category airplanes aircraft ventilation systems study. final report. dtfa- - -c- . dot/faa/ct-tn / -i ozone and relative humidity in airliner cabins on polar routes: measurements and physical symptoms dehydration and long haul flights study of the effect of cabin environment on insensible water loss low relative humidity and aircraft cabin air quality human performance and limitations in aviation the airliner cabin environment and the health of passengers and crew. report of the national research council hearing loss on the flight deck -origin and remedy us federal aviation regulations far . and far cosmic radiation measurements in airline service who. recommendations on the disinsecting of aircraft guidelines for environmental infection control in health-care facilities staphylococcal food poisoning aboard a commercial aircraft an outbreak of influenza aboard a commercial airliner why aircraft disinsection? impact of travel-related health impairments exposure to patients with meningococcal disease on aircrafts -united states exposure to passengers and flight crew to mycobacterium tuberculosis on commercial aircraft, - transmission of mycobacterium tuberculosis associated with air travel risk of travel-associated tuberculosis estimation of tuberculosis risk on a commercial airliner the writing committee of the world health organization (who) consultation on human influenza a/h . avian influenza a (h n ) infections in humans influenza outbreak related to air travel cumulative number of confirmed human cases of avian influenza a/(h n ) reported of who update: outbreak of severe acute respiratory syndrome -worldwide transmission of severe acute respiratory syndrome on aircraft in-flight transmission of severe acute respiratory syndrome (sars): a case report china's latest sars outbreak has been contained, but biosafety concerns remain -update low risk of measles transmission after exposure on an international airline flight imported measles in the united states mortality from cancer and other causes among male cockpit crew in europe anxiety and health problems related to air travel air transport medicine committee, aerospace medical association. medical guidelines for air travel traveller's thrombosis: a review of deep vein thrombosis associated with travel la santé des passagers telemedicine in british airways key: cord- -xs lot s authors: culmer, p.; ashton, s.; latham, m.; murdoch, s.; brettle, d.; kapur, n. title: delivering oxygen-enriched cpap respiratory support using a non-invasive ventilation device date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: xs lot s here we report an investigation to adapt existing non-invasive ventilators (niv) capable of delivering cpap for use with oxygen to deliver enriched ventilation of %+ fio . our intention is to maximise use of existing resources available to hcps, as niv and sleep apnoea (cpap) machines are widely available, to deliver therapeutic benefit and potentially avoid the need for positive pressure ventilation during the covid- pandemic. the nippy + (breas medical) was selected due to its robustness and widespread availability in the locality. in cpap mode, the system generates - cmh ( . - . kpa) using an internal centrifugal fan to pressurise atmospheric air. this offers the possibility to entrain o either at the system's low pressure air inlet, or in the pressurised air-stream near the ventilation mask as shown in figure . we modified a standard nippy + system to allow entrainment of oxygen at the intake port and evaluated the efficacy of these two approaches. the system was configured to operate at a pressure of cm h o with l/min oxygen flow, combined with a model lung operating at bpm with tidal volume of . l. an oxygen meter was used to measure the effective fio inhaled by the patient. our results showed that entrainment of oxygen at the low pressure intake brought only modest increases in fio (ca. %) in comparison to entrainment near the mask which achieved significantly higher fio (ca. %). the difference in performance can be attributed to the single-arm breathing circuit in which air-flow is reversed during the expiration phase and part of the air column is vented to atmosphere. this results in losses of oxygen when entraining at the air intake, but entrainment near the patient benefits from the pressurised air-column created between the patient and hepa filter, which acts as a 'buffer' to preserve oxygen and avoid losses. although this testing model precludes gas exchange, it all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . is representative of the relative performance of these two configurations and suggests that relatively low flow-rates of oxygen can be used to obtain therapeutic fio levels. the fio can be readily altered by altering the oxygen flow-rate with reference to idealised dilution levels (e.g. % fio for air:o at : l/min, or % fio for air:o at : l/min). however, the ultimate fio delivered by this system varies with respiratory function and is not explicitly controlled by the system. rather it requires external monitoring by a suitably qualified healthcare professional based upon the patient's spo level and vital signs. in conclusion, positive pressure ventilators can provide an effective means to deliver cpap with oxygen-enriched air for therapeutic intervention using standard equipment and fittings, whilst minimising the oxygen demands on hospital infrastructure when treating large numbers of patients. this enables rapid deployment to provide flexible treatment pathways which reduce the burden on icu for hcps that are facing surges in demand on ventilation during the covid- pandemic. critical care crisis and some recommendations during the covid- epidemic in china, xie et al guidance for the role and use of non-invasive respiratory support in adult patients with coronavirus (confirmed or suspected) managing the respiratory care of patients with covid- life saving breathing aid developed to keep covid- patients out of intensive care we would like to thank our multidisciplinary team; graham brown, sam flint, kevin meloy, mick china, james naylor, hardy boocock and the numerous healthcare professionals at leeds teaching hospitals (uk) who have helped make this research possible. key: cord- -jlwctmxw authors: marchand, geneviève; duchaine, caroline; lavoie, jacques; veillette, marc; cloutier, yves title: bacteria emitted in ambient air during bronchoscopy—a risk to health care workers? date: - - journal: am j infect control doi: . /j.ajic. . . sha: doc_id: cord_uid: jlwctmxw background: health care workers are at risk of occupational infections, and some procedures are known to increase this risk. the aim of this study was to qualify and quantify bioaerosol concentrations during bronchoscopy to estimate the occupational risk. methods: full-day sampling was conducted in rooms while bronchoscopies were performed on patients. two microbial air samplers were used, a wet wall cyclonic sampler and an impactor, on culture media. identification of the culturable bacterial flora was performed with chromatographic analysis of cellular fatty acid of the isolated strain and additional biochemical tests if needed. specific polymerase chain reaction analysis was completed on wet wall cyclonic samples for the detection of influenza a and b and mycobacterium spp. results: a wide variety of bacteria were collected from the ambient air. all samples yielded at least staphylococcus species. although most of the culturable bacteria identified were normal nonpathogenic flora, such as streptococcus spp, neisseria spp, and corynebacterium spp, some opportunistic pathogens, such as streptococcus pneumoniae, were found. neither mycobacterium spp nor influenza virus was detected with the polymerase chain reaction method during this study. conclusions: culturable bacteria from oral, nasal, and pulmonary flora are aerosolized during bronchoscopy and could be inhaled by medical staff. the potential presence of pathogens in those aerosols could represent an occupational infection risk. health care workers (hcws) are at risk of occupational infections due to the nature of their work. even when safety protocols are implemented, hcws are still considered to be at continued occupational risk of many infectious diseases transmitted from ill patients. although transmission of highly infectious diseases from patients to hcws is uncommon, a number of cases have been reported. several cases of transmission of streptococcus pyogenes to hcws have been described. [ ] [ ] [ ] [ ] neisseria meningitis, haemophilus influenza, and acinetobacter baumanii are other well-documented occupational pathogen infections acquired by hospital personnel. , [ ] [ ] [ ] the risk of influenza pandemics, emerging infections, and antimicrobial resistance of bacteria has raised concerns about the health of hcws and therefore about prevention practices that should be followed during particular procedures. worldwide, hcws are reported to account for % of all cases of acquired severe acute respiratory syndrome. some medical procedures increase the risk of occupational infections because of exposure to airborne pathogenic microorganisms. staff can be infected during routine endoscopy procedures. accordingly, endoscopists show a higher seropositivity to helicobacter pylori. , transmission of tuberculosis from infected patients undergoing bronchoscopy is another recognized occupational risk. , catanzaro calculated that during intubation and bronchoscopy, more than units per hour of infectious mycobacteria are aerosolized from a patient. intubation with a bronchoscope stimulates a patient's coughing reflex. , coughing produces droplets of various sizes, many of which are inhalable and can be drawn deep down into the lungs. [ ] [ ] [ ] particles of saliva, mucus, and pathogenic microbes can be emitted when a patient coughs. because particles of this kind originate from a deeper area of the respiratory system, the droplets released by coughing may be more infectious than those from sneezing. [ ] [ ] [ ] [ ] many of these particles are small enough to remain suspended in the air for a long time, and through evaporation, larger particles can become small enough to remain suspended in the air for an extended period also. from the perspective of infectious disease spread by the airborne route, inhalable particles include particles in the size range from . - μm in diameter. if particles carrying pathogens are inhaled, they may be deposited in parts of the respiratory tract where they are likely to cause infection and disease. , although some researchers have reported on the infectious risk to hcws performing high-risk procedures, to our knowledge, no study has ever documented, during bronchoscopy procedure, the real bioaerosol exposure of hcws. davies et al reported in their review that "no quantitative study has yet been carried out on aerosol generating procedures," and that "uncertainty surrounding aerosol generating procedures make it difficult to construct effective infection control policy." the aim of this study was to qualify and quantify bioaerosol concentrations during bronchoscopy to evaluate the occupational risk to hcws. knowing the real exposure is essential to encouraging hcws to implement better prevention protocols and wear personal protective equipment if needed. this study has been approved by the ethics boards of the involved hospitals and by the university of quebec in montreal ethics board. two bronchoscopy rooms in different hospitals were investigated. the first room had a volume of m and was located in a recently constructed building. it had negative pressure in relation to its anteroom, with air changes per hour. room b was smaller, with a volume of . m . three air outlets equipped with highefficiency particulate air filters expelled the air directly outdoors. the room is located in an older hospital built in the s. extensive renovations have been done over the years, and the current configuration dates from . bacteria collected were analyzed by culture, whereas mycobacterium spp and influenza a and b viruses were analyzed by molecular biology methods. one full day of sampling was carried out in each bronchoscopy room. depending on the bronchoscopy procedure time, up to samples were collected per patient. in room a, bronchoscopies were performed during the sampling day, for a total of culturable samples. in room b, bronchoscopies were performed, for a total of culturable samples. the measurements were taken consecutively for all steps in the bronchoscopy procedure, from the arrival of the patient through his or her departure. at the beginning of the day, before the first bronchoscopy, samples were taken to establish the background concentrations in the room. at both hospitals, member of the research team was permitted by the medical staff to remain in the bronchoscopy room. all samples were collected at a fixed station located within a radius of . m from the patient's mouth and the workers' breathing zone. sampling continued for minutes at the end of the day to determine whether bioaerosol concentrations would return to their morning background levels during this time. twenty minutes was chosen because that is the recommended waiting time before re-entering a room after a procedure has been performed on a patient with tuberculosis. on average, people (research team member, doctor, nurse, and patient) were present in the room. the sampling devices used to assess the bioaerosols were the andersen n impactor (andersen instruments, atlanta, ga) for the culturable bacteria and the coriolis μ biological air sampler (bertin technologies, montigny-le-bretonneux, france) for the molecular biology analysis. the andersen impactor is known as a standard for culturable bioaerosol analysis. five-minute sampling periods were used. the pump flow rate was adjusted in the bronchoscopy room to . lpm using a tsi mass flowmeter (tsi inc, shoreview, mn) and checked between patients. the total volume of air sampled was used to calculate the culturable bacterial concentrations. the andersen samplers were loaded with -mm petri dishes containing trypticase soy agar media to which % defibrinated sheep blood was added (oxoid, ontario, canada). all dishes were incubated at °c for hours. all colonies were enumerated according to the total count method. the limit of detection was cfu/m air for the andersen impactor. the cyclonic coriolis μ sampler was used at a flow rate of lpm. fifteen milliliters of sterile × phosphatebuffered saline solution, ph . (life technology, ontario, canada), were placed in the conical vials. a sampling time of minutes was used to obtain an adequate detection limit of , genomes. as with the andersen impactor, > sample was taken for some patients. identification was performed with the sherlock microbial identification system (midi, newark, de) using fatty acid extraction analysis by instant fame (fatty acid methyl ester) on pure culture of each isolated strain. the clinical aerobes (iba) method following the manufacturer's protocol was used. each strain was grown on trypticase soy agar blood and incubated at °c for ± hours. some slow grower strains needed an extra hours. two to mg bacteria cells were harvested for the fatty acid extraction. identification to the species level was completed if the similarity index was > . ; the gram stain and the phenotypic characteristics needed to match. when identification was not possible with the sherlock microbial identification system, the gen-iii microplate (biolog, hayward, ca) or the microscan neg id type panel or pos id type panel (beckman coulter, mississauga, ontario, canada) was used to complete the identification. even with the systems, some strains could not be identified to the species level. aliquots of coriolis μ air samples ( . ml) were centrifuged ( minutes at , × g) and the pellets were stored at - °c until extraction. total genomic dna was extracted using the powerlyzer ultraclean microbial dna isolation kit (mo bio laboratories, carlsbad, ca) according to the manufacturer's instructions. the dna extraction homogenization was performed with a mixer mill mm (retsch, düsseldorf, germany) at movements per minute for minutes. total dna was eluted in μl elution buffer. the rna was extracted with the magmax viral rna isolation kit (thermo fisher scientific, waltham, ma). amplifications were performed using the bio-rad cfx thermocycler (bio-rad laboratories, mississauga, ontario, canada). previously published primers and probes were purchased from integrated dna technologies (coralville, ia). the detection systems used were specific for influenza a and b viruses and for bacteria of the genus mycobacterium. [ ] [ ] [ ] the polymerase chain reaction mixture contained μl dna/rna template, . μmol/l (each) primer, . μmol/l probe, and μl × quantitect probe pcr master mix (qiagen, mississauga, ontario, canada) in a -μl reaction mixture. the results were analyzed using bio-rad cfx manager software, release . . . (bio-rad laboratories). an analysis of variance statistical test followed by a tukey-kramer multiple-comparison test was performed on log-transformed concentrations measured in the rooms to determine whether a difference could be observed between the periods. four periods were compared: the background measured in the morning, the waiting and preparation of the patient, the bronchoscopy procedure, and the return to background at the end of the day. the average concentrations (colony forming units/meters of air) and the standard deviations of the culturable bacteria measured in the bronchoscopy rooms are presented in table . the bacterial identifications obtained are shown in table . because of the high bacterial diversity found, pure culture isolation was done on the most frequently observed colony phenotypes to perform the strain identifications. all the staphylococcus spp strains were confirmed not to be staphylococcus aureus. the average concentrations measured in room a varied from - cfu/m air. in room b, the average concentrations were higher, ranging from - cfu/m . the highest concentration ( cfu/m air) was measured during the second bronchoscopy procedure of the day in room b. neither mycobacterium spp nor influenza a and b viruses were detected in our investigations. the results of the tukey-kramer test done on the logtransformed concentrations are presented in figure . the test confirmed that the concentrations, measured during the bronchoscopies and the preparation of the patient, were significantly higher than the ones measured during the return to background at the end of the day. the morning background concentrations, on the other hand, were not significantly different, although they appeared to be lower than those found during the medical procedures. to our knowledge, this is the first study to measure and identify the actual bacterial flora present in the ambient air of a room while bronchoscopies are being performed on patients. although bronchoscopy has been identified as a high-risk procedure for hcws, , , , this recognition had until now been based on risk guesstimate and epidemiologic studies, but actual exposure had never been documented as it is here. sampling of the ambient air of the bronchoscopy rooms yielded a wide diversity of bacteria. many sources of bioaerosols were identified, including outdoor air, medical staff, patients, and resuspension from surfaces. during the background and medical procedure periods, the concentrations and diversity of bacteria in the rooms were noticeably different. according to brandl and mandal, the main factors affecting the levels and diversity of airborne microorganisms in the indoor air of hospitals are the lack of cleanliness of the hospital, human activities, organic materials brought in from outdoors, and the efficiency of the hospital ventilation system. in general, the predominant genera of airborne bacteria reported in hospitals by other researchers are staphylococcus, bacillus, micrococcus, and corynebacterium. [ ] [ ] [ ] this was confirmed by our study, because at least species of staphylococcus spp was identified in every sample. microorganisms from environmental and human sources were anticipated, and their presence was confirmed by our investigations. some of the bacteria identified are known to originate from the human buccal cavity and respiratory tract. patients undergoing bronchoscopy cough numerous times, especially when the bronchoscope is being inserted. because it is well known that coughing produces a high number of aerosol particles, , [ ] [ ] [ ] it would seem logical to attribute a proportion of the microorganisms found in the ambient air to the patient's respiratory system. short-term variation in, or sporadic appearance of, specific bacteria cannot be attributed to the background hcws because they are present during all bronchoscopies. certain bacteria most definitely originate from the patients, such as the streptococcus pneumoniae found in room b during the second bronchoscopy. the fact that culturable bacteria from patients were found in the air . m from their mouths indicates that hcws in closer proximity can be exposed to some pathogenic microorganisms. the survival capacity of microorganisms is often overlooked, but it can greatly affect the bioaerosol content of the air in a room. nosocomial pathogens can persist on inanimate surfaces. like dust, microorganisms deposited on the floor or other surfaces can be resuspended in the air as a result of people moving around, rolling stretchers in and out of the room, or any other air disturbance that might occur. , pathogens present in the air can therefore originate from previous patients, which underscores the importance of thorough room cleaning. the higher concentrations measured during the waiting/preparation period may well be explained by bacteria from the floor being resuspended in the air by the rolling of stretchers and by nurses walking around the room during that period. in this study, whereas most of the culturable bacteria identified (brevundimonas diminuta, corynebacterium pseudodiphthericum, gordonia terrae, moraxella sp, psychrobacter phenylpyruviens, and actinomycetes) are nonpathogenic to humans in good health, some opportunistic pathogens (streptococcus pneumoniae, acinetobacter radioresistens, acinetobacter lwoffi, and escherichia sp) were found. mycobacterium spp and influenza a and b viruses were not detected. pathogens present in the air are undoubtedly dependent on patient pathology, and the absence of any specific pathogens from the samples collected in this study does not mean they will always be absent. the identification of streptococcus pneumoniae, neisseria sp, and corynebacterium sp shows that culturable bacteria from oral, nasal, and pulmonary flora were present in the air of the rooms during bronchoscopy procedures. hcw exposure to bioaerosols needs to be managed by implementation of prevention protocols and by providing them with appropriate personal respiratory protection if necessary. as previously pointed out, the main problem is not the treatment of known tuberculosis patients, but that of patients admitted for other problems with unsuspected or undiagnosed tuberculosis. , because hcws never know what is hiding in the lungs of their patients, emphasis must be placed on prevention and protection. bioaerosol concentrations in the working zone of hcws are certainly higher than those reported here. in fact, given the distance between the sampling zone and the hcws, the concentrations measured may well have been reduced as a result of dilution or sedimentation of the particles. the implication is that a sampling zone located closer to a patient's mouth would have revealed higher concentrations and perhaps the presence of other strains of microorganisms. sample size was also a limitation of the study. our presence in the room needed to be accepted by the medical staff. only sampling day was allowed in each hospital, and the number of bronchoscopy procedures was limited on those days. still, in this study, the number of bronchoscopies necessary to be statistically representative (p ≤ . ) with an acceptable error of % was calculated to be . nevertheless, this study still raises concerns about the occupational hazards to which hcws are exposed. it provides clear evidence of the presence of culturable opportunistic bacteria originating from the respiratory tract of patients in the air of bronchoscopy rooms. the presence of pathogenic microorganisms in the air of these rooms is to be expected from time to time, depending on patient pathology. quantifying the risk of respiratory infection in healthcare workers performing high-risk procedures lessons learned: protection of healthcare workers from infectious disease risks transmission of bacterial infections to healthcare workers during intubation and respiratory care of patients with severe pneumonia surveillance for hospital outbreaks of invasive group a streptococcal infections in ontario an outbreak of group a streptococcal infection among health care workers an outbreak of fatal nosocomial infections due to group a streptococcus on a medical ward nosocomial bacteraemia in hospital staff caused by haemophilus influenzae type b nosocomial outbreak of group c meningococcal disease occupational transmission of acinetobacter baumannii from a united states serviceman wounded in iraq to a health care worker a randomized clinical trial of the immunogenicity of -valent pneumococcal conjugate vaccine compared to -valent polysaccharide vaccine in frail, hospitalized elderly sars plague: duty of care or medical heroism? public health agency of canada. infection prevention and control guideline for flexible gastrointestinal endoscopy and flexible bronchoscopy. ottawa (on): public health agency of canada helicobacter pylori prevalence in endoscopy and medical staff occupationally acquired infections in health care workers: part ii nosocomial tuberculosis , occupationally acquired infections in health care workers: part i cough frequency and infectivity in patients with pulmonary tuberculosis occupational tuberculous infections among pulmonary physicians in training coughgenerated aerosols of mycobacterium tuberculosis: a new method to study infectiousness quantity and size distribution of cough-generated aerosol particles produced by influenza patients during and after illness cough-generated aerosols of pseudomonas aeruginosa and other gram-negative bacteria from patients with cystic fibrosis airborne transmission of disease in hospitals understanding the symptoms of the common cold and influenza global physiology and pathophysiology of cough: accp evidencebased clinical practice guidelines protecting the faces of health care workers: knowledge gaps and research priorities for effective protection against occupationally-acquired respiratory infectious diseases toward understanding the risk of secondary airborne infection: emission of respirable pathogens a review of the risks and disease transmission associated with aerosol generating medical procedures evaluation of eight bioaerosol samplers challenged with aerosolof free bacteria new sampler for the collection, sizing, and enumeration of viable airborne particles identification of bacteria by gas chromatography of cellular fatty acids preliminary evaluation of biolog, a carbon source utilization method for bacterial identification multiplex pcr assay for immediate identification of the infecting species in patients with mycobacterial disease evaluation of three influenza a and b real-time reverse transcription-pcr assays and a new h n assay for detection of influenza viruses world health organization. cdc protocol of real-time rtpcr for swine influenza a (h n ) aerosol generating procedures and risk of transmission of acute respiratory infections to healthcare workers: a systematic review environmental and occupational medicine bioaerosols in indoor environment-a review with special reference to residential and occupational locations distribution characteristics of airborne bacteria and fungi in the general hospitals of korea airborne bacteria and antibiotic resistance genes in hospital rooms dispersion and exposure to a cough-generated aerosol in a simulated medical examination room how long do nosocomial pathogens persist on inanimate surfaces? a systematic review elevated personal exposure to particulate matter from human activities in a residence human occupancy as a source of indoor airborne bacteria the hazard is relative sampling strategies for airborne contaminants in the workplace. leeds: h and h scientific consultants the authors thank yves beaudet, carole pépin, and nancy lacombe for their technical assistance. key: cord- -y lewk t authors: zhang, li-zhi title: fabrication of a lithium chloride solution based composite supported liquid membrane and its moisture permeation analysis date: - - journal: j memb sci doi: . /j.memsci. . . sha: doc_id: cord_uid: y lewk t a novel composite supported liquid membrane has been prepared for ventilation air moisture recovery. the membrane is composed of three layers: two hydrophobic protective layers and a sandwiched hydrophilic support layer in which licl solution is immobilized to facilitate water vapor transfer. a test is conducted to measure the moisture permeation rate through the composite membrane. various resistances in the cell and in the composite membrane are clarified. linear equilibrium relations between humidity, temperature, and licl concentration in the liquid solution layer are obtained to aid in the model set-up. it has been found that the mean moisture permeation rate through the composite membrane is around . × (− ) kg m(− ) s(− ), almost two times higher than that through a solid hydrophilic cellulose acetate membrane with comparative thickness. further, the supported liquid layer only accounts for % of the total moisture transfer resistance in the cell, indicating that there is much potential for further performance improvement. people's concern on indoor air quality has greatly deepened since the outbreak of the severe acute respiratory syndrome epidemic (sars) that devastated south china and some other parts of the world in the spring of . increased fresh air ventilation is the most efficient and necessary way to have a better indoor air quality, either in eliminating disgusting odors, diluting vocs, or decreasing the possibility of being infected by viruses. increased ventilation rates usually lead to high-energy consumption in air-conditioning. this is because the relative humidity in an occupied building must be controlled to within - % for health and comfort reasons. it has been proved that ventilation air constitutes about % of the total moisture load in most commercial buildings [ ] . as a consequence, treatment of the latent load from the ventilation air is a difficult and imminent task for hvac engineers, especially in hot and humid climates. * tel.: + ; fax: + . e-mail address: lzzhang@scut.edu.cn. to save energy in treating fresh air, various techniques for independent air dehumidification have been proposed [ , ] . among those drawn much attention is one that involves membrane technology-the so called membrane based total heat recovery (mthr) [ ] [ ] [ ] [ ] . mthr is an air-to-air heat exchanger where the two incoming streams (fresh air and exhaust air) exchanges heat and moisture simultaneously through membranes. the fresh air represents outdoor air (fresh air intake for a hvac system). the exhaust air represents stale room air that would normally be exhausted to the outside. the core material of an mthr ventilator are vapor-permeable membranes, therefore both heat and moisture are transferred between these two air streams when they flow through the unit. thus, heat and humidity would be recovered from the exhaust stream in winter and excess heat and moisture would be transferred to the exhaust in order to cool and dehumidify the incoming air in summer. in this way, large quantities of energy in hvac could be saved. hydrophilic polymer membranes that are permeable to vapor, but impermeable to air, have been considered for mthr ventilators. nafion [ , ] , regenerated cellulose [ ] , cellulose triacetate [ ] , sulfonated poly(phenylene oxide) [ ] , polyether-polyurethane [ ] , siloxane-amido copolymer [ ] , polystyrene-sulfonate [ ] , polyvinylidene fluoride and polyethersulfone [ ] , and cellophane [ ] are good choices since they have already been used in air dehumidification applications which have similar moisture transfer mechanisms to moisture recovery. however, moisture diffusion coefficients in such polymer membranes are usually very low, in the order of − to − m s − [ , ] , while mthr ventilators only have limited transmembrane vapor partial pressure difference, consequently performances are quite limited currently. in contrast to solid membranes, moisture diffusion in liquid membranes (∼ − m s − [ , ] , diffusion coefficients) is several orders higher than that in solid membranes. due to this reason and the inherent high selectivity, in recent years, there has been much effort in progressing the researches of supported liquid membranes (slm) in various fields: air dehumidification [ ] , so /co separation [ ] , h s/ch separation [ ] , wastewater treatment [ ] , metal ions concentration (uphill transport) [ ] , separation of isomeric amines between two organic phases [ ] , to name but a few. to improve the performances of mthr ventilators, in this study, a novel membrane, a composite slm, which employs licl liquid solution immobilized in a porous support membrane to facilitate the transport of moisture, is prepared. to protect the slm, two hydrophobic polyvinylidene fluoride (pvdf) layers are formed on both surfaces of the slm. the concept is shown in fig. . the sweep represents exhaust air. moisture permeation through this membrane is of great interest. moisture transfer characteristics will be the focus of this study. three types of commercial membrane were obtained from a supplier. very hydrophilic cellulose acetate (ca) membranes with nominal pore diameter . m a thickness - m are used as the support media to immobilize licl solution. two hydrophobic pvdf membranes (equal nominal pore diameter . m, thickness m) are used as the protective layer. crystals of licl·h o with laboratory class purity is used as the solute. before the preparation of composite membrane, each membrane is experimented and observed for their basic microstructures. figs. and show the scanning electron photomicrograph (sem) graphs of the ca membrane and pvdf membrane, respectively. under room temperature, well-stirred licl solution with % mass fraction is first prepared in a closed glass container. vacuum degassing is applied for h for the three membranes, after which, the ca membrane is dipped into the licl solution. after h, the ca membrane is moved from the solution and placed onto a clean glass plate which is cleaned by alcohol. surplus licl solution on surfaces of ca membrane is blotted off with paper tissue. to be sure that no ionic liquid is removed from the membrane pores, the cleaning procedure is very gentle. at this stage, pvc glue is brushed on one surface of the two pvdf membranes, and at the same time on both surfaces of the ca membrane. after a few seconds, the two pvdf membranes are glued to the ca membrane and are pressed together gently for a few seconds. the prepared composite membrane is placed in a constant-temperature-constant-humidity chamber for another h, before experiment is performed. for comparison, a composite membrane with no licl solution immobilized in the ca membrane is also made with the same procedure. the cross-section sem views of the two composite membranes are shown in figs. and , respectively. to prevent the microstructure being destroyed by knife crushing when preparing cross-section samples, the membranes are first frozen in liquid nitrogen before they are broken off to see the cross-sections. as seen from fig. , there are some gaps between different layers. some big cavities in the support layers are also observed, which are presumed to be imperfections in membrane fabrications. however, they have no adverse effects for this study because during operation, they will be filled with liquid solution. in the preparation process, some thickness of the ca membrane is dissolved by the glue, resulting in a lesser support layer thickness than raw material. fig. with licl solution shows that the ca layer and pvdf layer connect to each other very closely and have a dense and continuum interface. there are more big cavities in the support layer. the reason behind this may be that with licl solution soaked, the wetted molecular chains in ca membrane structure become more flexible and they will swell and expand to two sides. the boundaries between different layers are pressed together and linked to each other closely. the final ca layer thickness is m. the membrane module is a circular cell having an exchange area of . cm . it is composed of two parts: the lower chamber and the cap, as shown in fig. . when testing, the flat sheet membrane is placed on the lower chamber inside which saturated salt solution is contained. the cap is then covered on the membrane surface and forms a sandwiched structure. the membrane and the inner surface of the cap form a cone-shaped cavity. the air is supplied through the air slits in the cap. it is introduced through two diametrically positioned inlets (symmetrically placed) into a circular-shaped channel at the perimeter, from where the air is distributed over the membrane surface through the circular air slit. the air flows inward radially, until it exits the cap outlet in the center. the cap is designed that a constant axial air velocity is realized. when flowing across the membrane, the air stream exchanges moisture with the salt solution through the composite slm, and is humidified. this test uses nacl solution since it can ensure outlet humidity not saturated, for the protection of rh sensors. the whole experimental set-up is shown in fig. . the cell is supplied with clean and humidified air from an air supply unit. the supply air flows from a compressed air bottle and is divided into two streams. one of them is humidified through a bubbler immersed in a bottle of distilled water, and then re-mixed with the other dry air stream. the humidity of the mixed air stream is controlled by adjusting the proportions of air mixing. the air flow rates are controlled by two air pumps/controllers at the inlet and outlet of the cell. the humidities and temperatures to and from the cell are measured by the built-in rh and temperature sensors, which are installed in the pumps/controllers. a detailed description of the test procedure is given in [ ] . in the test, the vapor evaporation is slow, and the cell is well conductive. therefore, only moisture transfer is considered, by neglecting thermal influences. moisture transfer from the saturated nacl solution to air stream above membrane, is depicted in fig. . variations of air humidity along the transfer path are shown in fig. to simplify the mass transfer model. there are totally five resis- tances that can be clarified: resistance in the lower chamber air gap ( - ); resistance in the first protective layer l ( - ); resistance in the supported liquid membrane l ( ) ( ) ; resistance in the other protective hydrophobic layer l ( ) ( ) ; and resistance in the air stream h d ( ) ( ) , as demonstrated in fig. . the moisture permeation rate from the solution surface to the air stream can be summarized by where r tot is the total resistance from the solution surface to air stream and ω is the humidity difference between the solution in lower chamber and air stream above membrane. where subscripts l and d represent solution in lower chamber and air in air duct, respectively. the mean moisture permeation rate across the whole membrane surface in the cell is calculated by where ω lm is the logarithmic mean humidity difference between the solution surface and air stream, and it is calculated by where subscripts o and i represent outlet and inlet of air stream, respectively. the total resistance is comprised of five parts as where r l , r , r , r , r d are resistances in air gap, in the first protective layer, in the liquid membrane layer, in the second protective layer, and in air stream, respectively. moisture resistance below the membrane can be represented by the vapor diffusion distance from solution surface to the membrane lower surface. where l is the height of air gap (m), ρ a the dry air density (kg m − ), and d va is the vapor diffusivity in dry air (m s − ). moisture transfer resistance (m s kg − ) in the composite membrane comprises three layers: where where δ i is membrane thickness in ith layer (m) and d ei is the equivalent diffusivity of moisture in ith membrane, i = - . the two protective layers on both sides of the liquid membrane are highly hydrophobic. the established theory of gas diffusion in such membranes considers three mechanisms: poisseuille flow, ordinary molecular diffusion, and knudsen diffusion, or a combination of them. the governing quantity that provides a guideline in determining which mechanism is operative in a given pore under given operating conditions is the ratio of the pore size to the mean free path λ, which is calculated for a species i using the following expression [ ] : where σ i is the molecular collision diameter (m), . and . Å for water vapor and air, respectively [ ] , k b the boltzmann constant, . × − j k − , p m the mean total pressure within the membrane pores (pa), and t is the absolute temperature (k). for gaseous mixtures of two components, the mean free path and the collision diameters are different from the corresponding quantities for the pure component. the following relationship can be applied for vapor-air mixtures [ ] : under room temperature and atmospheric pressure, calculated λ for air is . m; while under vacuum conditions, mean free path for air may be several microns to several meters. knudsen number, where d p is mean pore diameter (m). when kn ≥ , the knudsen flow is dominant, the poisseuille mechanism may be neglected [ ] . actually, in most cases for hvac industry with microporous membranes, knudsen number is larger than , and poisseuille flow can be neglected, then the flow is considered to be combined knudsen and ordinary diffusion. ordinary diffusion coefficient of water vapor molecule in air is expressed by ref. [ ] d = c a t . where c a = . × − . the terms v v and v a are molecular diffusion volumes and are calculated by summing the atomic contributions: v a = . , and v v = . [ ] . m v and m a are molecular weights of vapor and air in kg mol − . m is . kg mol − for water vapor and . kg mol − for air, respectively. knudsen diffusion coefficient [ ] where r is gas constant, . j mol − k − . the effective diffusivity of combined knudsen and ordinary flow is [ ] moisture flux (kg m − s − ) is expressed by where ω is humidity difference between the two sides of l or l . consequently, water transfer in liquid membrane [ ] : where d wl is water diffusivity in liquid membrane (m s − ) and c w is the difference of water concentration in liquid membrane solution (kg m − ) between the two sides of liquid membrane. water vapor partial pressure, temperature, and licl solution concentration are governed by a thermodynamic equation [ ] log where in this equation p v , is in kpa, t in k, and m is molality of the electrolyte (mol licl/kg water). water concentration in solution is where ρ sol is solution density (kg m − ), and it is calculated by the following equation [ ] : where ρ w is pure water density at temperature t, and ρ i are given below [ ] : in moist air, water vapor partial pressure is calculated by ref. [ ] p v = ωp ω + . ( ) humidity ratio in ambient air is in the range of . - . kg/kg, therefore the above equation can be simplified to p v = . ωp ( ) as can be seen, the relations between the air humidity and water concentration in solution are rather complicated and need iterations to find solution. calculations of thermodynamic equilibrium chart of licl solution with eqs. ( )- ( ) found that under isothermal conditions, a linear equation similar to henry's sorption law can be used to express the water concentration in the solution as where k p is called the henry coefficient (kg m − pa − ) and c w is a constant (kg m − ). table lists the curve regressed values of k p and c w under different temperatures. this table gives the following correlations to estimate k v and c w from temperature: table values of k p and c w for licl solution the moisture diffusion resistance in the liquid membrane layer can be expressed by where the equivalent diffusion coefficient of vapor in liquid membrane is convective moisture resistance on air stream side is where k is convective mass transfer coefficient (m s − ). convective mass transport in the cell has been investigated by the author and co-workers previously [ ] and is expressed in terms of a correlation by where sh, re, and sc are sherwood number, reynolds number, and schmidt number, respectively. they are defined as where v is the kinematic viscosity of air (m s − ), r the radial coordinate (m), r the radius of the cell (m), and u a is the air velocity (m s − ) in radial direction. moisture conservation in air stream is represented by a onedimensional steady-state equation: boundary conditions: ref. [ ] . others are from manufacturer's specifications. mean moisture permeability across the whole membrane surface (kg m − s − )/(kg/kg), is calculated by where a c is the cross-section area of air duct (m ) and a t is the transfer area of membrane in the cell (m ). the permeability pe here represents moisture transfer rate (kg s − ) for unit area of membrane under unit transmembrane humidity difference (kg vapor/kg dry air). it reflects the performance of membrane. dimensionless radius table lists the values of operating conditions and system configurations. for each test, several minutes are needed for the system to become steady state. after outlet rh reaches steady state, water vapor permeability can be calculated with eq. ( ). this is the experimental data. the outlet rh can also be predicted with eq. ( ) . this is the model prediction. in calculations, the cell radius is divided into grids. fig. plots the relative humidity of outlet air under different air flow rates. the model predictions are also plotted in the figure. they are in agreement. maximum difference is %. fig. shows the distributions of equivalent air relative humidity on both surfaces of liquid membrane and in air stream, along cell radius. they have lower values at inlet and higher values at outlet, indicating moisture emits continuously from salt solution in lower chamber to air stream. fig. plots the distributions of equilibrium mass fraction of licl in liquid on both surfaces of liquid membrane, along cell radius. before the test, liquid membrane has a uniform mass fraction of %. during the operation, new equilibrium between liquid membrane and surrounding air relative humidity has been set-up. as a result, licl concentration in the liquid membrane re-distributed and forms a non-uniform mass fraction field. under the gradients of licl (or water) concentrations, moisture is transferred from the lower gap to the air stream. the liquid solution layer also acts as a barrier to air transfer since little air is dissolved in licl solution. fig. shows the local vapor emission rate along cell radius. as seen, the emission rate exhibits a non-uniform distribution on membrane surface. it decreases from × kg m − s − at air inlet to . × − kg m − s − at air outlet. the mean moisture emission rate is . × − kg m − s − , which is two times higher than the performance of ca membranes in our previous study with the same system ( . × − kg m − s − ) [ ] . the resulted mean permeability is . (kg m − s − )/(kg/kg). with models just proposed, various resistances in moisture transfer can be estimated. fig. shows the percentages of various resistances to total resistance, . m s kg − . as seen, the fig. . percentages of various resistances to total moisture transfer resistance, v = l min − . current cell fluid dynamics has a relatively larger convective moisture transfer resistance, accounting for % of the total resistance. the two protective layers account for % of the total resistance each. the air gap diffusion resistance amounts to less than % of the total resistance. the supported liquid layer, licl solution layer, only accounts for % of the total resistance. in real applications in mthr ventilators, only membrane resistance and convective resistance are considered. as a result, to further improve performances in future, the resistances in protective layers and flow channels should be lowered as a priority. one efficient measure may be to lower the thickness of protective layers-to a dozen micrometers, for instance. using turbulent flow arrangement such as cross-corrugated parallel plates may be the good way to lower resistance in flow channels. a composite supported liquid membrane for moisture recovery has been developed. the supported liquid layer and the two protective layers are in good contact, from sem observations. the microstructure and the performances are good, though there are some undesired cavities formed in the support layer. the measured water vapor permeation rates are two times higher than a hydrophilic solid membrane with comparative thickness. various resistances in the composite membrane and in the test cell have been clarified. it is found that the liquid layer only accounts for % of the total resistance, therefore there should be much potential for further performance improvement in future, by decreasing other resistances. that is the direction currently being pursued. dehumidification equipment advances energy wheel effectiveness. part i. development of dimensionless groups performance comparisons of desiccant wheels for air dehumidification and enthalpy recovery membrane modules for building ventilation heat and mass transfer in a membrane-based energy recovery ventilator effectiveness correlations for heat and moisture transfer processes in an enthalpy exchanger with membrane cores membrane-based enthalpy exchanger: material considerations and clarification of moisture resistance water transport in ionic polymers water transport properties of nafion membranes. part i. single-tube membrane module for air drying removal of water vapor and vocs from nitrogen in a hydrophilic hollow fiber gel membrane permeator permeation of water vapor through cellulose triacetate membranes in hollow fiber form studies on the sulfonation of poly(phenylene oxide) (ppo) and permeation behavior of gases and water vapor through sulfonated ppo membranes. ii. permeation behavior of gases and water vapor through sulfonated ppo membranes interaction of polyetherpolyurethane with water vapor and water-methane separation selectivity hollow fiber air drying water transport across polystyrenesulfonate/alumina composite membranes membrane porosity and hydrophilic membrane based dehumidification performance temperature influence on moisture transfer through synthetic films water vapor permeability and diffusivity through methylcellulose edible films diffusion-mass transfer in fluid systems on the application of a membrane air-liquid contactor for air dehumidification dehumidification of air by a hygroscopic liquid membrane supported on surface of a hydrophobic microporous membrane liquid membranes for flue gas desulfurization hydrogen sulfide separation from gas streams using salt hydrate chemical absorbents and immobilized liquid membranes equilibrium and mass transfer characteristics of -chlorophenol removal from aqueous solution by liquid membrane instability mechanisms of supported liquid membranes supported liquid membranes using ionic liquids: study of stability and transport mechanisms evaluation of moisture diffusivity in hydrophilic polymer membranes: a new approach pervaporation and vacuum membrane distillation processes: modelling and experiments mass transfer of hcl and h o across hydrophobic membrane during membrane distillation thermodynamic properties of aqueous electrolyte solutions. . vapor pressure of aqueous solutions of licl, libr, and lii properties of aqueous solutions of lithium and calcium chlorides: formulations for use in air conditioning equipment design laminar fluid flow and mass transfer in a standard field and laboratory emission cell (flec) this project is supported by national natural science foundation of china. the author also acknowledges help from graduate students-miss zhang mingrui and mr. xu xueli in doing experiments. knudsen number l height of air gap (m) m molality of electrolyte (mol licl/kg water) m molecule weight (kg mol − ) p partial pressure (pa) key: cord- -a bn ul authors: ghosh, bipasha; lal, himanshu; srivastava, arun title: review of bioaerosols in indoor environment with special reference to sampling, analysis and control mechanisms date: - - journal: environ int doi: . /j.envint. . . sha: doc_id: cord_uid: a bn ul several tiny organisms of various size ranges present in air are called airborne particles or bioaerosol which mainly includes live or dead fungi and bacteria, their secondary metabolites, viruses, pollens, etc. which have been related to health issues of human beings and other life stocks. bio-terror attacks in as well as pandemic outbreak of flue due to influenza a h n virus in have alarmed us about the importance of bioaerosol research. hence characterization i.e. identification and quantification of different airborne microorganisms in various indoor environments is necessary to identify the associated risks and to establish exposure threshold. along with the bioaerosol sampling and their analytical techniques, various literatures revealing the concentration levels of bioaerosol have been mentioned in this review thereby contributing to the knowledge of identification and quantification of bioaerosols and their different constituents in various indoor environments (both occupational and non-occupational sections). apart from recognition of bioaerosol, developments of their control mechanisms also play an important role. hence several control methods have also been briefly reviewed. however, several individual levels of efforts such as periodic cleaning operations, maintenance activities and proper ventilation system also serve in their best way to improve indoor air quality. as a class of airborne pollutants "bioaerosols" are particulate matter usually associated with compounds of biological origin. this definition includes all pathogenic or non-pathogenic, live or dead fungi and bacteria, bacterial endotoxins, mycotoxins, peptidoglycans, β ( , )-glucans, viruses, high molecular weight allergens, pollens, etc. (douwes et al., ) . they are ubiquities, highly variable and complex and are natural or manmade in origin. air contains a significant number of bioaerosol particles which vary in size and composition. the majority of bioaerosols are of respirable size, namely of the order of . μm for viruses (taylor, ) , from . to μm for bacteria (thompson, ) , from to μm for plant pollens (stanley and linskins, ) , and from to μm for fungi (gregory, ) . the inhalable fractions are of primary concern as major portions of bioaerosol are susceptible to reach the deeper parts of the respiratory system. composition mainly depends on the source, aerosolization mechanisms and environmental conditions prevailing at the site (pillai and ricke, ) . two types of factors that influence the bioaerosols according to several studies are physical characteristics and environmental factors. physical characteristics includes size, density, and shape of droplets or particles while environmental factors include the moisture content of building material, density of the air, relative humidity and temperature (droffner et al., ; foarde et al., ; pasanen et al., ) , air exchange rates (kulmala et al., ) , and human activities (buttner and stetzenbach, ) . high average temperature and higher relative humidity favor microbiological growth on proper substratum thereby acting as a proper source of bioaerosol (jones and harrison, ) . light intensity, magnitude of air currents, wind direction and wind speed also play major roles in bioaerosol concentration and their transportation and displacement from one environment to another . bioaerosols ranging in size between . and . μm generally remain in the air, whereas larger particles are shortly deposited on surfaces (mohr, ) . as environmental factors play a major role in bioaerosol distribution, several studies related to spatial and temporal distribution of bioaerosol have also been conducted in different parts of the world. in beijing, china the highest airborne bacterial concentration was observed in summer and fall (fang et al., ) . almost similar results were observed in washington d.c., montreal of canada and moscow, wherein bacterial concentrations were at their peak in the summer and lowest in the winter season due to regional climatic conditions (jones and cookson, ; kelly and pady, ; vlodavets and mats, ) . in case of fungal bioaerosol, their distribution nature had also been studied wherein in suburban areas of washington airborne fungal concentration was similar to bacterial concentration, i.e., the lowest in winter and the highest in summer and fall (jones and cookson, ) . similar pattern of fungal distribution was also observed in beijing with the highest in summer and autumn and the lowest in spring and winter (fang et al., ) . seasonal variability of airborne mold was conducted in single-family residence in ny with no visible water damage or leaks and wherein - % rh and - °c temperature was maintained in winter while - % rh and - °c temperature in summer. the study revealed that fungal levels in summer were times higher in comparison to winter (lebouf et al., ) . similar to the above studies, seasonal variability of airborne bacteria were conducted in the restrooms different indoor environments such as a shopping centre, hospital, subway system, public library and old and new university lecture building in republic of korea. among the six locations, all five sites revealed significantly smaller bioaerosol concentration in winter than in summer except the restroom in hospital lobby which may be due to the maintenance of almost similar indoor air conditions by air conditioning system artificially in both summer and winter (lee et al., ) . several studies have revealed various sources for bioaerosol in different indoor environments. indoor upon outdoor (i/o) ratio in several studies has shown that outdoor concentration had always acted as one of the sources of bioaerosol in different indoor environments . apart from outdoor concentration building condition, occupancy level and human activities also determine the varying concentrations of bioaerosols (nasir and colbeck, ) . in fact human beings have been attributed to be one of the most important sources of airborne bacteria (stetzenbach, ) . increased human shedding of skin cells and activities such as talking, coughing and sneezing force air under pressure through nose. this process ejects microbes from upper respiratory tract into the air (terkonda, ) . sneezing is the most vigorous of these mechanisms, by generating as many as one million droplets lass than . μm in diameter (campbell et al., ) , and presence of such organic particulates in air gives added protection to bacterial cells and result in enhanced survival of the air borne microbes. sweeping of floors and dusting of objects, movement of people and air currents also have been found leading to the suspension of dust particulates and generation of airborne microorganisms (kallioski et al., ) . food stuffs, house plants, flower pots, pets and their beddings, furniture stuffing also release various fungal spores into the air (cox and wathes, ; kalogerakis et al., ) . according to certain studies higher level of dust and macromolecular organic components (proteins) were found in carpet dust than floor dust, hence it can be said that human movement across such a carpeted floor covering ejects trapped debris and dust into the air (gravensen, ) . as indoor air is highly dynamic so several studies have been carried out to keep a check on the indoor air quality (iaq) especially for occupational and public health (bonetta et al., ) . during different iaq studies it has been found that bioaerosols contribute to about to % of indoor air pollution (wanner et al., ; srikanth et al., ) . hence it is an important criterion to take into account the microbiological air quality so as to provide a safe environment while designing indoor workplaces. this review provides a brief description of various sampling and analytical techniques that are generally used to characterize bioaerosols. this review also provides the information on the concentration levels of various airborne microorganisms in different indoor environments, their associated health effects as well as various bioaerosol control mechanisms worked upon till now. the objective of this review is not only to acquire knowledge about bioaerosol and their associated health effect in order to apply measures to reduce them by various controlling mechanisms, but also to find out the advantages and limitations of each sampling and enumeration technique from all the previously assembled works so as to facilitate future researchers in deciding upon the correct bioaerosol assessment protocol accordingly. at present a wide variety of bioaerosol sampling methods are in use and numerous other methods are in the developmental stage (grinshpun and clark, ; muilenberg, ; reponen et al., ) . till now there is neither a single sampling method suitable for the collection of different types of airborne microorganisms nor a standard protocol available (grishpun et al., ) . in any bioaerosol monitoring design depending upon the objective of sampling the method used and incorporated are often aimed at documenting the specific sources of the bioaerosols collected. active sampling method is usually used for collecting bioaerosol from air. in general the sampling efficiency of any sampling devise is the product of the aspiration, transmission and collection efficiency; each of which depends upon particle aerodynamic diameter, wind velocity, direction as well as inlet characteristic, which itself is dependent upon bioaerosol particles sampled under various conditions (grishpun et al., ) . the three major collection methods used for the sampling of bioaerosols are impaction, impingement and filtration (grishpun et al., ) . apart from the principle techniques alternative methods such as gravity sampling, electrostatic precipitation and cyclone have also been employed in many cases with respective advantages and disadvantages as shown in table . impactors are economically feasible samplers due to their low costs and easiness of handling (zollinger et al., ) . the basic principle behind impactors is impaction that collects microorganism and particles in the air. the impaction sampler draws in air and forces to change its direction which causes particles with high inertia to get impacted over collecting surfaces (henningson and ahlberg, ) . generally particles which are larger than a particular aerodynamic size get impacted onto a collection surface forcing the smaller particles to proceed through the sampler (hinds, ) . a number of samplers available commercially using impaction based methods are one of the common approaches to collect bioaerosols (gangneux, ; pillai and ricke, ) . impactors differ in the characteristics of inlet size and shape, number of collection 'chambers' within the sampler and whether the microorganisms are impacted onto a solid (glass slide) or semi-solid (agar plate) surface, or, a filter or gelatin (macher and hansson, ) . collection and recovery efficiencies of the samples are strongly influenced by the inlet characteristics of the samplers where inlet (and collection) efficiency highly depend on wind velocity at the time of sampling, and the orientation of sampler during sampling. with wind velocity above ms - and the inlet aperture facing the wind almost % of overestimation of μm sized particles are done while when the sampler is in an upright position (with wind blowing across the inlet aperture), less than % of μm particles were collected (willeke et al., ) . it has been seen that the mass of particles smaller than cut-diameter (d ) that are generally collected are equal to the mass of particles larger than the d that pass through the impactor. in fact it has been found that the collection efficiency of the impaction samplers is % when the aerodynamic diameter is greater than d (hinds, ) . it has been seen that for the same aerosol sample which shares the same geometric standard deviation, the mass and count particle distributions will show distinctive good collection efficiency because of reduced particle bounce and loss through re-entrainment sterilization process easy due to evaporation of liquid medium problem of loss may be encountered thermal precipitator good collection efficiency for smaller sized particles and helps in determining size distribution of the particles. air flows freely through the sampler, thereby pressure drop is small and vacuum source is not needed. collection rate very low. collection area small. high temperature affects the viability of the microorganisms collected. major processing time period is very less ultrafine bioaerosol particles can also be sampled and detected easily. viability of the microorganisms maintained throughout. complex system requiring expertise to handle. means and medians. the mass median aerodynamic diameter (mmad) describes the mass distribution which equals the diameter where particles larger than mmad contribute half the collected mass while those particles smaller than mmad contribute the other half. the median of the number of particles in the particle distribution is named as count median aerodynamic diameter (cmad). sampling time and impaction velocity also plays a very important role in the collection and viability of the airborne collected microorganisms. at a constant time if impact velocity is increased it may cause particle bounce, decreasing the actual collection efficiency (especially for spores) and also affects the viability of stress sensitive microorganisms (juozaitis et al., ) . although aerosolized fungal spores are often collected over glass slide and semi-solid agar surface is used to collect bacteria (hinds, ) however, generally agar plates are mostly used for the collection of both fungi and bacteria predicala et al., ; sanchez-monedero and stentiford, ) and are called culture based impactors. as seen the collection medium is that the collected microorganisms are cultured and then counted on the plates requiring no post-sampling processing to determine the numbers of microorganisms present (except for incubation at the required temperature) nesa et al., ) . disadvantage of using agar plates is of becoming over loaded by microorganisms making enumeration of the colonies difficult as they overlap and become indistinguishable from one another. a statistical "positive hole correction" is thus needed to evaluate highly loaded plates (feller, ; andersen, ) . desiccation related problems are also associated with impaction sampling as surface moisture is removed by air stream passing over the agar plate limiting the ability to impact more particles due to reduced surface stickiness (cox and wathes, ) . a number of impactor samplers are commercially available each of which show differences in number of nozzles, nozzle dimension and shape, jet-to-plate distance and number of stages. when a single nozzle is used to suck in air the shape is usually rectangular as in slit sampler (e.g., burkard manufacturing co. ltd., hertfordshire, united kingdom; new brunswick scientific co., edison, n.j.; casella london ltd). in this sampler for proper spreading out of the collected bioaerosol particles the collection surface may be moved under the slit. such sampler has been used for both indoor and outdoor sampling of airborne microorganisms . cascade impacter such as anderson sampler (graseby andersen, smyrna, ga, usa) have several stages with successively smaller nozzles such as the six stage anderson sampler used to quantify both fungal and bacterial bioaerosol in different indoor environments such as hospital, student dorm, laboratory, hotel room etc., in beijing (xu and yao, ) . this allows separation of bioaerosols according to their aerodynamic diameter. mas (merck, germany) is one of the single stage impactors which consists of a perforated plate with holes each of . mm diameter through which the collected air is aspirated either vertically or horizontally and with the speed of . ms - is propelled onto a solid agar plate. the sampling volume is adjusted to l/m after passing through an airflow meter (meir and zingre, ) . consistent performance was found when mas was used for sampling aspergillus fumigatus and other thermotolerant fungal bioaerosol (engelhart et al., ) .when the number of nozzles increases usually circular in shape it takes the appearance of a sieve thus forming another sampler named sievetype sampler (spiral system instruments, bethesda, md.). rotorod sampler (ted brown associates, los altos hills, ca) and rotoslide sampler (oak ridge reproduction service, oak ridge, tn) are rotating impactors generally used for outdoor sampling collects particles larger than μm (mandal and brandl, ) . sampling by such samplers are done by sweeping the collecting surface which may be a rod or a slide through the air. fraction of particles impacted on the collecting surface from the volume of air swept by the rotating surface defines the collection efficiency of the samplers (juozaitis et al., ) . among all the above-mentioned impactor samplers slit sampler was specifically described for collecting airborne microorganisms long back (bourdillon et al., ) . this type of sampler is best applicable to monitor the effect of "people activity" as well as operational variation and material movements over the production and distribution of bioaerosol and hence have been widely used in settings such as agricultural environments that are highly contaminated (blomquist et al., ) as well as in domestic environments (verhoeff et al., ) . for collecting large airborne particles (such as large fungal spores, clumped spores and pollen grain) slit sampler is very useful and hence had been mostly employed to determine the fungal bioaerosol in domestic settings (kozak et al., ) instead of bacterial cells and small spores. as slit sampler provides information about bioburden in respect to time and activity without regarding particle size, both cascade impactor and sieve type sampler determine the particle size distribution of the bioaerosols. cascade impactor and stacked sieve six stage anderson viable impactor can be used to collect both bacterial and fungal spores and fragments unlike slit sampler. in case of six stage anderson viable impactor, sampling of airborne bacterial and fungal with mass median aerodynamic diameter (mmad) less than may result in an overloaded sample if the concentration is greater than - cfu/m while for the same diameter range sieve personal sampler can be used satisfactorily for sampling (jensen and schafer, ) . hence sieve sampler seems to best fit for sampling in highly contaminated environments while anderson sampler can be used when positive hole correction factors are used for proper calculation of the number of particles collected when overloaded (blomquist et al., ; macher, ) . in comparison to the above-mentioned rotorod sampler mainly helps in qualitative assessment of bioaerosols rather than quantitative (cox and wathes, ) . rotorod has been found to collect greater number of large sized airborne particles such as pollen grains instead of bioaerosol spores per unit of air (cage et al., ) . impingement-based methods operate almost similar to impactionbased approaches, except that the micro-organisms are collected into a liquid medium (mandal and brandl, ) . generally air is sucked in through a narrow inlet tube onto the collecting medium where the flow rate of the sampled air depends on the diameter of the inlet nozzle. suspended particles get impinged on the collecting liquid as soon as the air strikes the liquid. on completion of sampling the aliquots are cultivated on proper growth media to enumerate viable microorganisms. impingers are generally needed to be sterilized before re-use. in fact replicate samples require a 'fresh' impinger, which increases costs of impingement based sampling than impaction-based sampling (cartwright et al., ) . collection and recovery efficiencies of impingers are found to be influenced by the inlet characteristics of the sampler. reduced recovery efficiency has been found to be correlated with increased flow rate (ogden and raynor, ) . similar to impaction-based samplers, the collection and recovery efficiency of impingers are highly affected by wind speed at the inlet. studies carried out by scientist in may ( ) revealed that at . m s − wind speed across the inlet, the collection efficiency turned out to be . %, whereas after creating a still air condition by using a baffle, the collection efficiency jumped upto % (sanchez-monedero and stentiford, ) . although impingement-based samplers generally use a liquid collection medium, the type of liquid used sometimes vary with only one common element i.e., the liquids should be an isotonic or buffered solution so as to avoid osmotic stresses being imposed on micro-organisms following their collection. as for example betaine or peptone solutions are recommended so as to protect bacterial cells from osmotic shock (eduard and heederik, ) . use of an improper buffered water medium such as ringers solution affects the collection efficiency of the device as buffer gets lost from the sampler through evaporation when the sampler is used for long periods of time (willeke et al., ) . a number of commercial impinger samplers are currently available which include the all glass impinger (agi- ), the skc biosampler, the burkard multistage sampler, the modified personal impinger (mpi), the multi-orifice impinger (moi), and the multi-stage liquid impinger (mli). as most of the impinger samplers are made up of glass they are cheaper than metal samplers such as the andersen sampler, but affecting their robustness in the field. agi- is a single stage impinger with a cylindrical reservoir under vacuum that contains a suitable collection liquid for concentrating bioaerosol from the air through a central jet raised mm from the base of the cylinder. agi- consists of an electrical powered pump capable of drawing . l/min at a pressure drop across the impinge jet of kpa with a typical sampling time of - min. the agi- sampler (ace glass inc., n.j., usa) is a cheap but less efficient sampler (ding and wang, ) . agi- comes with a disadvantage of foaming that can be induced in several collection solutions through the impingement process (dillon et al., ) . the most popularly used sampler is "biosampler" liquid impinger (skc, eight four, pa, usa). this sampler is a good example of an all-glass, swirling aerosol collector. it mainly consists of an air inlet, three tangentially arranged nozzles and a collection vessel . the biosampler also consists of a pump capable of drawing in air at the same rate as that of agi- but the sampling duration is very high . to h. the greatest advantage of the sampler is its ability to be used in highly contaminated environment with sampling duration up to min with aqueous based sampling media and up to several hours by using a viscous sampling medium (dillon et al., ) . filtration based samplers are relatively simple and less expensive. they are highly effective means of collecting bioaerosols. in filtration method airborne microorganisms are collected by passing air through porous membrane filters made of glass fiber, polyvinylchloride (pvc), polycarbonate or cellulose acetate (incubated by transferring onto the surfaces of growth agar media) or gelatin. out of these gelatin filters offers a much better environment (mandal and brandl, ) . the forces that are responsible for collection of particles are inertial forces, diffusion and electrostatic attraction (gilbert and duchaine, ). the filter method is generally used in personal samplers (such as worn by workers at relevant facilities) rather than in general sampling due to their small size. in fact filter-based samplers when used as nonpersonal samplers were more suitable for qualitative assessments of airborne micro-organisms only (predicala et al., ) . according to size fraction bioaerosol collection can be done by using polyurethane foam inserts (kenny et al., ) . when filtration based samplers are used in highly contaminated environment enumeration of bioaerosol becomes impossible just similar to impaction samplers due to overloading of filters with microorganisms (eduard and heederik, ) . desiccation/drying off of microorganisms on the filters post collection is another problem related to filtration based samplers (hinds, ) . though some microorganisms such as fungi and spore forming bacteria are sometimes found alive on the filters, vegetative bacterial cells such as gram negative bacteria cannot tolerate the desiccation stress at all . in fact sampling time and relative humidity plays a major role in determining the loss incurred due to desiccation. it has been reported that when temperature exceeds °celsius and relative humidity increases from to % fungal propagules are still viable while many vegetative bacterial cells become nonviable . the filters when vortexed help in the recovery of bacterial cells (douglas, ) . gravity sampling which is a non qualitative method is done by exposing an agar medium to the environment over which airborne microorganisms are collected by gravity (grishpun et al., ) . due to this large particles mostly settle down on the collection surface rather than smaller particles resulting in the misrepresentation of the airborne microorganisms due to exclusion of smaller particles (burge and solomon, ; solomon, ) . gravitational settling method gives information about the total number (or mass) of the collected bioaerosol only and does not quantify their concentration as the volume of air from which the bioaerosols originated is unknown. however some scientists also believe that this method is reproducible and reliable along with the fact that many places in an environment can be checked at the same time helping the operators to compare and understand without disturbing the air (pasquarella et al., ) . electrostatic precipitation sampler follows the basic principle of particle precipitation in which airborne particles are precipitated from an airstream by the application of an external force such as electrical force on charged particle (knutson and whitby, ) . in an electrostatic precipitation sampler the biological particles are charged at the inlet. the charged airborne biological particles are then exposed to an electrical field inside the sampler resulting in their cross sectional migration eventually depositing over charged plates. finally from the charged plates the microorganisms are extracted and analyzed. this technique provides a much better means of collection especially for stresssensitive microorganisms as the particle velocity component perpendicular to the collection medium is almost two to four order lower than those found in bioaerosol impactors and impingers at comparable sampling flow rate (mainelis et al., ) . the collection efficiency is found to be dependent on applied voltage, flow rate, dimension of the precipitators and initial particle charging level (mainelis et al., ; mainelis et al., a mainelis et al., , b . by limiting the initial charge on airborne microorganism at the inlet the loss due to viability can be controlled (mainelis et al., c) . generally low power is required for maintaining the sampling flow through an electrostatic precipitator as it is an open channel. moreover since very little power is also needed to create precipitation voltage, this method turns out to be highly feasible for low power monitoring of bioaerosol in a counter bioterrorism network. several studies have shown that electrostatic precipitation can also be implemented without the use of additional charging at the inlet of the sampler (mainelis et al., d) . a recently developed electrostatic precipitator had no charging unit in the inlet while the physical collection efficiency strongly depended on the precipitation voltage which eventually depended on the charge present on the airborne microbes naturally due to aerosolization (kunkel, ; flagan, ) thereby making collection possible by differentiating between the positively and negatively charged microorganisms by adding a signature to the bioaerosol particle sampled (lee et al., a; ; lee et al., b) . during the effort made for electrostatic sampler's development and evaluation, important information was found regarding the electro biological properties of microorganisms that is related to electric potential of their membrane which is further determined by the transmembrane potential between the extracellular fluid and cytoplasm, and surface potentials at the external and internal interfaces of the membrane. according to the information gained bacteria that are dispersed from a liquid through pneumatic nebulization generally possess a wide and bipolar electric charge distribution. the viability of the bacteria was also found to be affected by the electric charge imposed on it during aerosolization due to removal of some fragments of bacterial surface and counter ions (mainelis et al., ) . since the basic metabolic activity of the bacterial cells depend on the membrane potential (cevc, ) , ion transporters/channels and metabolically essential proteins, atpase are significantly affected by this change in membrane potential (bond and russel, ) eventually making the microbes nonviable. due to the limitations related to the viability of the collected bioaerosol through impactors and impingers new bioaerosol samplers such as niosh one-stage bioaerosol cyclone, cip -m, niosh twostage cyclone, coriolis®, wwc, and pas- by rct & hrb were developed. in cyclone samplers microorganisms are captured into a liquid (aerosol to hydrosol) using swirling air and centrifugal force. such samplers are advantageous as they are less susceptible to particle 'bounce' and re-entrainment (willeke et al., ) . these samplers are relatively easy to sterilize and play an important role when multiple samples are needed to be taken (cartwright et al., ) . since water is used as the sampling medium in both the samplers cyclones and impingers, studies related to their efficiency was done revealing the recovery efficiency of cyclone samplers to be ± % relative to agi- impinger for gram negative bacteria (henningson et al., ) . guidelines that are generally looked upon for matching the appropriate technique (depending upon their advantages and disadvantages) with the bioaerosol of interest are given in table . the bioaerosol of interest is mostly categorized as culturable bioaerosol sampling and non viable bioaerosol sampling with subcategories of free bacteria and fungi. free bacteria (i.e., mostly single cells), free fungi (i.e., mostly single spores) as well as clumped bacteria and fungi with mmad μm are in general bioaerosols of interest in environmental investigations hence it is noted that the samplers must collect these aerosol (wright et al., ; lee et al., ) . this is one of the oldest sampling techniques based on thermophoresis principle in which air laden with aerosol and bioaerosol is passed through a narrow channel containing a temperature gradient perpendicular to the air flow. on entering the temperature gradient the airborne particles tend to move away from the hot surface towards the cooler surface and depositing over it, a phenomenon known as thermophoretic motion (waldmann and schmitt, ) .the hot surface is generally heated up to °c while the other collecting surface is cooled by a circulating water heat exchanger. immediate microscopic examination can be done is glass microscopic cover slips that are used as the cooler collection surface or if collected over filter paper from which the deposits could be transferred to agar plates to allow colonies to grow and examined thereafter (kethley et al., and orr et al., ) . the collection efficiency of such sampling technique is very high for small particles ranging from b . μm to μm, when the temperature gradient is sufficiently maintained all throughout the sampling time, and thus this method is used to determine the particle size distribution (watson, ) . although its collection efficiency for smaller particles is high yet its collection rate is very low in comparison to other samplers ranging from cm min − to l min − (cox and wathes, ) . thus because of such low rate sampling and requirements of very precise adjustments, such samples are not commonly used in industries (kang and frank, ). bioaerosol sampler using condensation technique consists of a number of parts attached together such as vacuum pump, humidifier, a heating source, a liquid source, amplifier, a cooling source and a biomass spectroscopy system for proper sampling and analysis of bioaerosol collected. in such sampler, air is drawn in through a vacuum pump into humidifier first. the humidifier consists of a heating source that evaporates liquid source such as water (usually a biocompatible source) to create a humid environment (with relative humidity % or higher) to temperature higher than the room temperature i.e., °c but lower than °c so as to prevent the deactivation of microbes collected. the air sample is then drawn into the amplifier via vacuum action. the amplifier consists of a cooling source that eventually reduces the temperature to as low as °c. due to this low temperature the air volume in the amplifier is subjected to condensation with supersaturated vapors. here the sampled bioaerosol acts as the condensation nuclei from which the particle grows or amplifies, however maintaining the viability of the microorganism. particle size amplification of bioaerosols due to condensation of super saturated vapors can occur at the order of nanometer and/or submicron to a greater size such as μm and above. the time period required for condensation amplification is as less as s or even lesser. thus amplification increases the bioaerosols dimensions indirectly increasing the detection efficiency. the amplified bioaerosol then can directly sent into a biomass spectroscopy system (such as maldi-tof) for in-line and continuous identification. due to such technique very small bio-species/ bioaerosols such virus that cannot be sampled or detected by conventional systems can be amplified and studied upon (wu et al., ) . enumeration of microorganisms forms the second major step in the monitoring strategy. the technique is divided into two broad groups namely culturable and non culturable approaches. culture based approach is a simple and low cost method that involves collection of airborne microorganisms and culturing of the sampled microorganisms on some semisolid growth medium with results expressed as colony forming units after a proper incubation (conditions including time, temperature and available oxygen). as it is assumed that single colony is formed from a single microorganism so the cfus give the information of the number of microorganisms present in the sample. the major limitation of this approach is that a very small proportion (almost %) of the microorganisms present in the environment can be cultured and identified (heidelberg et al., ; torsvik et al., ) . several studies have shown that culture conditions also limit the growth of the viable and culturable microorganisms with examples such as mesophilic bacteria namely escherichia coli and bacillus subtilis exhibit proper colony formation at temperatures between to °c (droffner et al., ; pillai and ricke, ) while thermophilic microorganisms namely thermoactinomyces sp. prefer culture temperature above °c (neidhart et al., ) . several studies have been conducted across the world till date in order to evaluate microbial load (isolating, quantifying and identifying) in various indoor environments such as occupational, residential and educational using culture based techniques and their important findings have been shown in table . airborne biological particles sampled from air onto glass slides, semisolid media and filters fitted to samplers can be enumerated and identified using microscopic examination. after processing the sample through a proper technique designed identification of taxa or species can be done. identification is mainly based on the morphological characteristic of the microorganisms and their spores (especially for fungi). in classical microscopy various types of stains available are used for identifying and describing fungal spores so as to differentiate between different fungal spores and organic debris (burge, ) . as shown in table although classical microscopy id one of the easy performing technique that has the advantage of identifying specific taxa of both fungi and bacteria, however does not act as a representative of all the microbes in bioaerosol. such methods are mostly used only for quantification of microorganisms present in liquid samples where actual counting is not done and mostly depends on statistical calculations (makkar and casida, relatively swift and easy to perform being a statistical test it does not measure actual numbers of micro-organisms. as the micro-organisms are grown in liquid media such technique is less susceptible to the culturability issues that affect selective isolation plate methods . aggregates of cells may affect the result, thereby limiting the suitability of this method to analysis of bioaerosols. sometimes difficult to quantify due to collisional quenching of the excited state and potential photochemical effects. measurements are spatially resolved and can be further extended to laser imaging. not all excited species fluoresces causing improper measurements. cheap technique and easy to operate the compound (such as proteins) to be analyzed should be in the databases. highly sensitive this technique is generally not suitable for compounds less than da in size due to intense matrix signal. very mild ionization technique used, thereby making analysis of mixture possible there is limitation in the resolution of this technique which can only be increased significantly by a reflector and or a delayed extraction. very little or no sample preparation is required that results in increased throughput, greater convenience and fewer opportunities for contamination to occur. limited usage due to increased cost and system complexity very sensitive and requires very small amount of sample (thus sometimes referred to as "nondestructive" method) sometimes regarded as semi quantitative technique as obtaining suitable standards is difficult. possibility of multi-elemental analysis simultaneously there are possibilities of large interference effects that include matrix interference as well as potential interference of particle size in case of aerosol. has the potential for direct detection in aerosols less precision ranging from to % depending upon excitation properties of laser, sample homogeneity and sample matrix simple process with rapid analytical capability as in a single step ablation and excitation process is carried out. both culturable and nonculturable cells can be counted making the results more representative of total numbers of micro-organisms in the bioaerosol. restricted ability to identify specific taxa of micro-organisms relatively cheap operating costs fluorochromes if binds to abiotic particles may result into false positive results. high throughput of samples possible if image analysis system used image analysis system may count abiotic particles within the same size parameters as microbial cells. not suitable for counting aggregates of cells overestimation due to binding to abiotic material may take place pcr technique remarkably sensitive technique the efficiency and size ranges of bioaerosol high volume samplers should be completely characterized which can otherwise affect the quantification by quantitative pcr. applicable to any biological matter containing nucleic acid possibility of inaccurate bioaerosol quantification due to improper sample preparation steps like filter elution/concentration and nucleic acid extraction detection and identification can be made independent of culturing thereby removing the need of specialized labs to perform cell cultures which require extensive biosafety infrastructure. results may get affected by the presence of inhibitory pcr compounds in the samples. results are provided rapidly on the order of hours as compared to days or weeks. certain taxa of micro-organisms can be identified. no standard approach available for monitoring of biomarkers so as to provide certain information. as whole cells are not measured, this technique is not prone to many of the limitations of culturable or nonculturable methods lal assay types biomarker tests which are significantly used in bacterial bioaerosol analysis are affected by dust or other microbial cell components. this is likely to be a significant problem. ). in this method serial dilution of the sample is done in order to quantify the density of microorganisms present on the probability the basis of the probability that positive results will emerge after incubation from each microorganisms. possibility of detection of microorganisms by this method is more as the liquid medium used for growth imposes much less stress over the microbes rather than the semisolid medium. as mostly there is good probability that aggregates of cells will be found in the inoculation medium, this applicability of this method for enumeration ends as it is only used when single cells are found. laser induced fluorescence (lif) is a spectroscopic method mostly used for studying the structure of molecules and detection of selective species (especially bacteria). after the air samples are collected through impaction, the cultivated bacterial species is excited by a laser light whose wavelength that is selected is often the one at which the species has its largest cross section. within a few nanoseconds or microseconds the species de-excite and emit light (with wavelength longer than the excitation wavelength) (zare, ) . this emitted fluorescent light is then recorded by a photomultiplier tube (pmt) or filtered photo diode. lif is highly advantageous over absorption spectroscopy because the detection sensitivity is very high as the signals are observed against dark background and two to three-dimensional images can be obtained as emitted fluorescent radiation can be obtained in all possible angle (zare, ) . the classified fluorescent signals can be confirmed by correlating with morphology, gram staining or family (rösch et al., ) . as seen in table in lif as analysis and detection is done on the basis of emitted fluorescence light from the species, probability of improper measurement exists as all the species do not fluoresce. moreover lif technique is mostly used for bacterial identification. matrix-assisted laser desorption/ionization (maldi) is a soft ionization technique that is mostly used in mass spectrometry for analyzing biomolecules (microorganism and biopolymers such as dna, proteins, peptides etc.) as well as large organic molecules which generally becomes fragile and fragment when conventional ionization methods are applied. maldi is a two step process where uv laser beams are used to trigger desorption first. the uv laser light is absorbed by the matrix material leading to ablation of the upper layer (~ μm) of the material. during ablation the hot plume that is produced contains several species such as neutral and ionized matrix molecules, protonated and deprotonated matrix molecules, nanodroplets and matrix clusters. in the second step the matrix molecules get ionized in the hot plume. the matrix mainly consists of crystallized molecules with , -dimethoxy- -hydroxycinnamic acid (sinapinic acid), , dihydroxybenzoic acid (dhb) and α-cyano- -hydroxycinnamic acid (alpha matrix) most commonly used (strupat et al., ; beavis et al., ) . with the use of highly purified water and an organic solvent which is usually acetonitrile or ethanol a solution of any of these molecules are made and used as a matrix. tof (time of flight mass spectrometer) has large mass range, it is mostly used with maldi. in the maldi-tof instrument an 'ion mirror' is present that reflects ions using an electric field, thereby doubling the ion path and increasing the resolution. for the identification of bacteria and fungi maldi-tof spectra can be used. after having been collected of airborne microorganisms on growth media via impaction and after their proper growth, a colony in question is smeared on the sample target directly. it is then overlaid by the matrix and mass spectra generated. the spectra are then analyzed with software present with the instrument. for proper identification comparison with the stored profiles are done. however even in the absence of prior cultivation it is possible to obtain a mass spectrum of a single airborne particle by on-line measurements using instrumental improvements (kleefsman et al., ) . in comparison to other immunological and biochemical tests identification of species by this process is highly economical and accurate (seng et al., ) however as shown in table it can only analyze compounds greater than da in size such as proteins, and peptides, available in database forms due to intense matrix signal thereby restricting its identification range. recently libs is being considered as a process for rapid real time detection of microbes responsible for biological warfare attacks and illness both in the fields and in laboratory settings. it is a time resolved atomic emission spectroscopic analytical technique based on optical emission following pulsed laser ablation of a sample (radziemski and cremers, ; schechter et al., ) . in this process when the laser is focused onto a small area at the surface of the specimen, it ablates a very small amount of material (in nanograms to picograms) which generates a plasma plume with temperature in excess of , k. at such high temperature the ablated materials breakdown into excited ionic and atomic species. during this time, the plasma emits a continuum of radiation which does not contain much information about the species present which is useful. during this emission of radiation within a very small time frame the plasma expands at supersonic velocities and cools. at this point the characteristic atomic emission lines of the elements can be observed which gives the information about the specimen. libs is mostly used for bacterial detection. it is important to note that libs analysis does not depend upon identifying the genetic differences between the species (the libs analysis does not rely on the elements that comprise dna or proteins such as carbon, nitrogen, hydrogen and oxygen), it is rather the difference in the inorganic chemical composition of the outer membrane that is detected. in fact the chemical composition varies between bacterial species as a function of the genetic variation between those species. in recent studies by using libs with both nanosecond and femtosecond laser pulses bacterium e. coli was identified (baudelet et al., ; diedrich et al., ) . e. coli a nonsporulating gram negative bacterium has specific outer membrane that contains mg + and ca + (singleton, ) . the ionized and neutral mg and ca emission lines act as the dominant spectral features in the libs spectrum of e. coli. thus for a particular bacterium for creating a "spectral fingerprint", measurement of emission lines from these and other trace inorganic elements such as iron, potassium, sodium, phosphorus and manganese are done. however, there are chances of less precision of result obtained ranging from to % depending upon excitation properties of laser, sample homogeneity and sample matrix as mentioned in table . as already mentioned above all of the culturable techniques can analyze microbes by isolating and characterizing them over commercially available growth media such as nutrient agar, and luri-bertani agar (kirk et al., ) . less than % of total microbial species in any environmental sample can be analyzed by this technique (hugenholtz, ) while the rest though viable in nature are nonculturable in laboratory conditions remaining in the "viable but nonculturable" stage (oliver, ) . with the evolution of fluorochromes staining the microorganisms collected in liquid medium quantification of all viable microbes (both culturable and nonculturable) were possible. a major shift in the paradigm of microbial analysis was seen with the advancement in the fields of genomics and sequencing technologies as well as analysis of microbial community using nonculturable molecular techniques such as genetic fingerprintings, metagenomics and next generation sequencing helping in not only identifying and quantifying the microbial load but also helps in understanding the probable changes taking place in the community as well. a wide array of scope of microbial identification also evolved with the analyses of metabolites and constituents of microorganisms without directly counting them (such as mycotoxins, and endotoxins) by advanced techniques like chromatographic, immunoassay and pcr based methods. the following are the few nonculturable techniques applied. by using fluorescent stain (a fluorochrome), microorganisms collected in liquid buffer solution or filters are stained and counted by epifluorescent microscopy (eduard and heederik, ) . different types of fluorochromes are available that indicate cell viability by showing differences in electron transport chain activity, cytoplasmic redox potential, enzymatic activity, cell membrane potential and membrane integrity (kepner and pratt, ) . dapi ( , -diamidino- -phenylindole) and acridine orange ( , bis[dimethylamino]acridinium chloride) two fluorochromes that are applied for bioaerosol monitoring are nucleic acid stains and allow microorganisms to be distinguished on the basis of color. in general acridine orange binds to dna and rna and depending upon single stranded and double stranded nucleic acid different colors fluoresces such as orange and green respectively. in case of dapi when it binds to dna it fluoresces blue or bluish-white and yellow when bound to non dna material (kepner and pratt, ) . the basic advantage of this technique is that it facilitates all viable cells of both bacterial and fungal bioaerosol (culturable and nonculturable cells) to be counted as it is a nonculturable approach as mentioned in table . moreover if it is attached with a computer based image analysis system, the counting gets automated and a high throughput of samples are achieved (kildeso and nielsen, ) . however the disadvantage of this technique (as shown in table ) is binding of the fluorochrome to abiotic material, error in counting the microorganisms by human as well as differentiating between microbial cells and abiotic material such as dust (pillai and ricke, ) . although as mentioned before by using an image analysis automated system one can improve enumeration yet limitation still persists as it will only count particles which will fall within the size parameters of the programmer (crook and sherwood-higham, ). thus the overlapped cells are most likely not to be counted. in order to minimize the "false positive" results generated from binding of fluorochromes to abiotic particles baclight fluorescent stain can be used as this stain is less susceptible to binding to such materials in respect to acridine orange that is found to bind with humic material (kildeso and nielsen, ) . thus for enumeration of airborne microorganisms both baclight and acridine orange are used maximally (terzieva et al., ) . in the pcr technique a specific region of a genome is copied and amplified to a millionfold making them available for further analysis (georgakopoulos et al., ) . conventional polymerase chain reaction (pcr) assay has been used as an alternative method for analyzing total bacterial load in bioaerosol samples which also provide qualitative assessment when gel electrophoresis is used to visualize the resulting pcr amplicon (saiki et al., ) . in order to analyze air samples for the presence of endemic microorganisms (alvarez et al., ) , biowarfare agents (higgins et al., ) , airborne mycobacteria (schafer et al., ) and fungi generally associated with health effects (cruz-perez et al., ; williams et al., ) conventional pcr assay has been applied. identification of a particular microbe can also be done by using specific primer set and rapidly produce results on the order of hours in comparison to days and weeks. however as mentioned in table possibility of inaccurate bioaerosol quantification is one of the major disadvantages of pcr technique mainly due to improper sample preparation such as filter elution and nucleic acid extraction. in recent phase real-time pcr (rt-pcr) is evolving as a technique capable of giving accurate measurements of total microorganism concentrations in environmental samples. unlike the conventional pcr, rt-pcr analysis is not done via gel electrophoresis. it is in fact attached to a thermal cycler coupled to an optical module which measures the fluorescence intensity of reactions generated by hybridization probes (such as taqman, melocular beacon, fluorescence resonance energy transfer) as well as by double stranded dna dyes such as sybrgreen green (sybr) (stetzenbach et al., ) . depending upon the background fluorescence the data analysis software provided then calculates the cycle number ct (at which the fluorescence in the sample crosses the threshold) which is inversely correlated with the microorganisms concentration in the sample. studies have proven that standard curves can be produced by using known microorganism concentration as templates. these standard curves can then help to quantify the total microorganism concentration in the unknown sample (ana et al., ) . in recent past two real time pcr systems were developed in order to quantify levels of cladosporium, one of the most common molds found both in indoors and outdoors environments (zeng et al., ) . flow cytometry is a technique in which both fungi and bacteria can be quantified on the basis of component or structural features of cells via optical means (muirhead et al., ; porter et al., ) . in flow cytometry the cells are required to be in aqueous solution, hence the types of sampling technique used to collect the bioaeorosols are impingement, filtration or cyclone. once the cells are in suspension, a continuous flow of a fine stream of the suspension in the form of a single file moves through a laser beam. as the stream passes through the laser beam the amount of light scattered by each cell is measured which is dependent on the size of the particles and the presence or absence of specific cell surface features. in different environmental samples such as bioaerosols light scatter characteristics are not sufficient to differentiate cells so different types of fluorochromes are required. hence combination of flow cytometry with fluorescent in situ hybridization (fish), where fish labels specific nucleic acid sequences inside intact cells using so-called phylogenetic stains for quantifying and differentiating cells ( porter et al., ) . according to certain studies the major advantage of flow cytometry is that it can count thousands of cells within seconds (davey and kell, ) similar to epifluorescence microscopy (table ) . again just like epifluorescence microscopy, along with the microbial cells, counting of abiotic particles having the same size as of cells is one of the limitations of this technique. the other disadvantage is that it can only count microorganisms that are found as single cells. in case of bioaerosols along with single cells aggregates of cells can also be sampled, which will then be required to be vortexed or agitated in order to break the cell clusters before analyzing using flow cytometer. this process may again lead to some other disadvantages such as affecting the viability of some of the cells present as well as increasing the cell numbers (terzieva et al., ; jensen et al., ) . although flow cytometry has been used for quantification as well as identification of airborne bacteria (day et al., ) , when applied along with different dye stains it actually provided more rapid and accurate viability assessment (chen and li, ) . quantitative analytical comparison was carried out between flow cytometry (fcm) and culture method by analyzing bacterial bioaerosols (especially pseudomonas aeruginosa) collected from swine barn wherein it was found that in comparison to fcm, microorganism concentration was underestimated by orders of magnitude by the culture method (lange et al., ) . metagenomics also known as community genomics or environmental genomics is a powerful centerpiece that helps ion genomic analysis of a population of uncultured microorganisms directly from environmental samples. metagenomic analysis involves various steps such as isolation of dna from the required environmental sample followed by cloning of the extracted dna into a suitable vector. soon after that the clones are transformed into a host bacterium. the transformants are then screened such as s rrna and rec a for phylogenetic markers, or for multiplex pcr (stein et al., ) , or for specific trait expression as for example enzyme activity (lorenze et al., ) , or can be randomly sequenced (tyson et al., ) . in recent studies "shotgun" is being largely used to get unbiased samples of genes from the sample community members (eisen, ) . advancement in the refinement of dna amplification as well as proliferation of computational power have helped the analysis of dna sequences extracted from environmental samples thereby allowing the adaptation of shotgun sequencing to metagenomic samples. although previously clone libraries were used yet at present cloning step is omitted due to the advancement of next generation sequencing techniques that yields greater sequencing data without labor intensive step. thus with the help of high throughput sequencing technologies shotgun metagenomics not only provide information about the type organisms present in the environmental sample but also informs about the possible metabolic processes in the community (segata et al., ) . whole genome sequencing has also been applied to study the airborne microbial community in various indoor and outdoor environments of nyc after collecting air samples using a wet cyclone portable air sampler at the flow rate of l/min (yooseph et al., ) . next generation sequencing (ngs), a catch-all term describing all the modern sequencing technologies that help in quicker and cheaper sequencing of dna and rna in comparison to traditional sanger sequencing (table ) is also known as high-throughput sequencing and is applicable for both bacteria and fungi. the throughput requirement also seems to be quite less, only one or two instruments for the completion of the experiment. the work process of next generation sequencing-ready libraries consists of a few steps. firstly, ligation of specific adaptor oligos at both ends of the dna fragment and hence prepared for sequencing. in ngs it is important to note that relatively very little dna input (only a few grams at the most) is required and by using slightly modified library processes the platforms can also sequence the paired ends of the of a given fragment. moreover in comparison to the capillary sequencers (where long read lengths of - bp are produced), depending upon the platforms shorter read lengths ( - bp) are produced by the next generation sequencers. apart from theses generally shared features, the commercially available sequencers significantly differ from each other such as illumina sequencing is based on "sequencing by synthesis" i.e., sbs (ansorge, ) , rocha ( ) sequencing operates on the principle of "pyrosequencing" (margulies et al., ) , solid sequencing (mardis, ) , etc. thus as seen in table the obvious disadvantage of ngs apart from high startup cost and requirement of multiple days of run the major disadvantage is limited phylogenetic characterization capability as it works on only short read lengths (b bp). the comparative metrics and performance of the above-mentioned next generation sequencers are given in table . in the past few years ngs has been used to characterize microbial community in various environmental samples by using illumina sequencing (bartram et al., ) and pyrosequencing (monard et al., ) . illumina sequencing has also been used in studying the microbial diversity in airborne microbiological samples causing organic dust toxic syndrome (odts), where sequencing data revealed the presence of more than bacterial and fungal genera in the air sample (madsen et al., ) . the understanding of the pattern of genetic diversity in a microbial community has been provided by genetic fingerprinting techniques such electrophoretic separation of low molecular weight rrna molecules such as s rrna and trna that were extracted from natural samples in high resolution polyacrylamide gels for more than a decade (hofle, ) . recently, dgge of ribosomal dna fragment amplified by pcr has been introduced as another genetic fingerprinting technique in microbial ecology (muyzer et al., ) . once the dna fragments of multiple organisms are extracted and amplified using pcr, they are subjected to dgge where dna fragments of different sequences but same length are separated. in dgge a constant heat of °c and an increasing concentration of dna denaturants i.e., mixture of urea and formamide are used to unwind the dna molecules. since in electrophoresis molecular weight, shape and electrical charge of dna, rna and proteins play the major role in the separation process (creighton, ) , similarly in dgge, positive electrodes attract the negatively charged dna fragments and are forced to migrate through the polyacrylamide gel. while moving through the gel they encounter the denaturing reagent mixture which in the presence of constant temperature breaks the hydrogen bonds between the base pairs unwining them or as termed partially melting them (muyzer et al., ) . the melting domains are thus determined which are eventually defined as stretch of base pairs having specific identical melting temperatures (muyzer et al., ; muyzer and kornelia, ) . difference in melting temperatures due to variation of sequences within theses melting domains causes the differential migration of the sequences to different positions in the gel (muyzer et al., ) . almost % of sequence variant up to bp can be detected in dna fragments using dgge (myers et al., ) , which can be increased to almost % by attaching on one side of fragment a gc clamp i.e., a gc rich sequence which prevents the complete dissociation of the double stranded dna into single stands due to high melting domain (sheffield et al., ) . pcr dgge as a culture independent approach was used in assessing the seasonal effect of winter and summer on bacterial bioaerosol community in few swine confinement buildings (scb) in canada, wherein the dgge profile showed similar patterned dna bands for each scb even though the indoor temperature and ventilation rate differed from each other in both the seasons suggesting that the major microbial community such as lactobacillales and clostrida did not change with season as their origin remains the same (nehme et al., ) . in another study carried out in a dairy barn in eastern quebec, dna from the airborne dust was extracted using a qiagen qiaamp dna extraction kit and was analyzed using pcr dgge along with gc clamps to reveal several archeal (such as - % representation of methanobacteriaceae group while % representation of methanobrevibacter of all the dgge bands sequenced) and bacterial (such as - % homology with staphylococcus gallinarum, agrobacterium tumefaciens, crocebacterium ilecola, oxalobacter sp., cornynebacterium variabile, agrobacterium sp., clostridium quinii, staphylococcus sp. and cornynebacterium xerosis) species from both the domains (lecour et al., ) . as one of the alternatives to direct counting or culture-based techniques, constituents or metabolites of the microorganism can be measured as an estimate to microbial exposure (pillai and ricke, ; crook and sherwood-higham, ) . biomarkers generally measured include fatty acids, ergosterol, muramic acid (marker of peptidoglycan, therefore bacterial biomass) (pillai and ricke, ) and microbial volatile compounds (dillon et al., ) . other agents that are also measured due to their toxic potency are β ( ➙ ) glucans and bacterial endotoxin (aketagawa et al., ; douwes et al., ) . thus not only toxic (such as mycotoxins) or pro-inflammatory (such as endotoxins) components are measured as biomarkers but nontoxic components also serve as markers of either large groups of microorganisms or specific microbial genera or species. the use of various advanced methods such as polymerase chain reaction (pcr) based reaction, immunoassays, chromatographic techniques etc. for measuring biomarkers, thereby helping in detection and speciation regardless of whether the organisms are culturable or not. table gives an overview of different assessment methods for microbial constituents and markers. limitations of the 'whole cell' techniques such as culturability and non specific binding of fluorochromes can be easily avoided my measuring biomarkers and other microbial constituents. moreover as most of the health effects are caused due to exposure to the microbial products such as endotoxins, mycotoxins, etc. instead of the viable microorganism themselves, so in order to assess the exposure monitoring the levels of such compounds are more relevant than measuring the microorganisms themselves. bioaerosol poses serious health hazards for people and animals living in their vicinity. microbiological pollution is spread in the form of bioaerosol containing viruses, bacteria, actinomycetes and fungi (fernando and fedorak, ) . it is important to note that, the small size of these particles means that they can enter the lungs easily if inhaled. hence, it may become a potential cause of respiratory and various other infections in people. in addition, these small particles can be very easily carried away by the wind to long distances ranging from a few hundred meters to several kilometers (recer et al., ) , again posing a potential biological hazard not only to the nearby areas but also to residents of distant areas. bioaerosols, especially with pathogenic or allergic micro-organisms, may cause respiratory and other health disorders. the potential health hazard caused by bioaerosols depends on the pathogenicity of specific micro-organisms as well as other factors such as the environmental conditions which determine the survival of the microorganisms in the air (mohr, ) , the meteorological conditions (especially wind speed and wind direction) which controls the airborne dispersion from the emissions points (katzenelson et al., ) , provides the pathway to bioaerosol to enter the body and also the immunologic response of the body. the main pathways for transmission of micro-organism to humans are: by direct contact with contaminated sources such as through mucous membranes or skin, by ingestion through hands or accidentally and by inhalation process. and, there are evidences which indicate that enteric diseases prevailed in communities that may be associated with aerosols generated from waste water containing enteric pathogens (katzenelson et al., ) . as it is known that, enteric bacteria are the good indicator of water pollution. bioaerosol transmission is a key mode of transport for some of the world's most contagious, lethal and infectious diseases, such as tuberculosis (al-jahdali et al., ) , severe acute respiratory syndrome and influenza (klontz et al., ) . the major groups of diseases associated with bioaerosol exposure are infectious diseases, respiratory diseases and cancer (moreno-lopez, ; . bioaerosols are also associated with non-infectious diseases such as hypersensitivity, allergies, and asthma (olenchock, ) . a number of studies have already indicated the important role of bacterial and fungal airborne micro-organisms as potential opportunistic human pathogens. for instance, continued exposure to large concentrations may lead to a sensitization and to the development of occupational diseases, such as allergical veolitis, asthma and organic dust toxic syndrome in humans (lacey, ; lacey and dutkiewicz, ) . infectious diseases may be categorized into bacterial, fungal and viral diseases. such infectious diseases arise from viruses, bacteria, fungi, protozoa and helminthes and involve the transmission of an infectious agent from a reservoir to a susceptible host through airborne transmission. legionellosis, tuberculosis and anthrax are bacterial diseases that cause significant public health concern even due to bacterial bioaerosol low infectious dose (hussong et al., ) . legionella pneumophila causes human legionellosis, an airborne disease often caused as a result of active aerosolizing processes such as aeration of contaminated water. the transmission of tubercle bacilli occurs through the inhalation of aerosolized bacilli in droplet nuclei of expectorated sputum-positive tuberculosis patients during coughing, sneezing and talking. the transmission of anthrax occurs due to inhalation of the spores of bacillus anthracis and its outbreaks are often linked to bioterrorism. viruses readily transmitted by airborne route include, severe acute respiratory syndrome (sars) virus , enteric viruses of intestinal origin produced at sewage treatment facilities, respiratory syncytial virus source: mardis ( ) . (rsv), hantavirus from rodent feces (mojica, ) , varicella -zoster virus, measles, mumps and rubella viruses. sars, caused by novel corona virus, is a highly contagious and responsible for respiratory infection of significant morbidity and mortality, and may also cause very severe atypical pneumonia. besides the above-mentioned diseases, airborne fungi are also often reported to be an important cause of respiratory complaints in atopic individuals (howard, ) . atopy is the genetic predisposition of an individual to produce high quantities of ige in response to allergens in the environment (pollens, house dust mites, molds, cat dander, foods, etc). a great threat is also connected to the presence of microbial allergens and endotoxins, lipopolysaccharide which are produced by gramnegative bacteria that is considered as the most important health hazard. studies have demonstrated that endotoxins could be the cause of airway and intestinal inflammation and work-related symptoms (for example: diarrhea, fatigue and nose irritation) in various occupational sectors. in fact non-allergic work related asthma symptoms known as "irritant induced asthma" (bernstein et al., ) was found in farmrelated occupations and were assumed to be caused by bioaerosol exposure (anonymous, ) . airborne fungi causing respiratory infections and allergic reactions include penicillium, aspergillus, acremonium, paecilomyces, mucor and cladosporium (kanaani et al., ) . most infections, specifically aspergillosis can occur in immune compromised hosts or as a secondary infection, which is caused due to inhalation of fungal spores or the toxins produced by aspergillus fungus (swan et al., ) . fungal metabolism produces many volatile compounds that are capable of inducing sensory irritation to eyes and upper respiratory tract. aspergillus species that can grow indoors include aspergillus fumigatus and aspergillus flavus and can cause nosocomial infections, allergic broncho-pulmonary aspergillosis (abpa) and sinusitis. cladosporium, alternaria, penicillium, and aspergillus are the genera of fungi which cause many diseases in human beings and are mostly found in various environments as shown in table . alternaria sp., cladosporium sp., and penicillium sp., are three fungi which have been associated with causing asthma and rhinitis. penicillium species with spores of to μm (mm) have apparently been responsible for several hypersensitivity pneumonitis epidemics (kreiss and hodgson, ) . the "moldy" or "mildew" odors in some indoor environments are associated with low levels of volatile organic compounds (vocs) in the air produced by fungi (kaminske et al., ) . health effects have not been directly attributable to these vocs to date, but the vocs and/or the organisms which produce them may be contributory factors to complaints of headache, eye and throat irritation, nausea, dizziness, and fatigue in subjects occupying contaminated interiors (burge, a) . bacterial bioaerosols are responsible for diseases such as tuberculosis (mycobacterium), legionnaires' disease (legionella pneumophila), and hypersensitivity pneumonitis (thermoactinomyces). airborne transmission occurs when an infected person is coughing, sneezing, actively shedding fresh organisms into air close to susceptible individuals, or even talking or singing (burge, b) . thermophilic bacteria such as saccharopolyspora rectivirgula or thermoactinomycetes vulgaris have been found to contaminate hay and act as a source of allergen to farmer's lungs (reboux et al., ) as well as to mushroom growers (van den bogart et al., ) . some examples of viral bioaerosols which infect humans and are spread by aerosols, rather than by direct contact only, are influenza (influenza a and b), measles (rubella), mumps, and chicken pox (kundsin, ) . till date although no uniform international standard have been established in relation to levels and acceptable limits of bioaerosol loads (wong et al., ) yet certain terminologies are used that are different in different countries such as "maximum acceptable values" (de aquino neto and de góes siqueira, ) , "orientation values" (suva, ) , "acceptable maximum value, amv" (becher et al., ; jo and seo, ) , "threshold limit value, tlv" (american conference of governmental industrial hygienists (acgih), ). in fact due to lack of data in accordance to exposure-response relationships acgih has totally nullified the general tlv for culturable bioaerosol concentration (american conference of governmental industrial hygienists (acgih), ). since no-observed-adverse-effect-level (noael) or lowest-observed-adverse-effect level (loael) depending upon dose-response approach has not been established for bioaerocol concentration, health effects in relation to exposure limits on the basis of data from epidemiological and toxicological studies could not be developed till date (swan et al., ) . however, several published values in relation to acceptable concentrations of fungal and bacterial bioaerosol have been found that differ from country to country such as for total bioaerosol concentration in korea and netherlands are cfu/m and , cfu/m respectively (jo and seo, ; eduard, ) ; fungal concentration in brazil, germany, portugal and switzerland are cfu/m , , cfu/m , cfu/m and cfu/m respectively (de aquino neto and de góes siqueira, ; institut für arbeitsschutz der deutschen gesetzlichen unfallversicherung (ifa), ; pegas et al., ; suva, ) and bacterial concentration in finland, germany and netherlands are cfu/m , , cfu/m and , cfu/m respectively (nevälainen, ; institut für arbeitsschutz der deutschen gesetzlichen unfallversicherung (ifa), ; eduard, ). most of the guidelines are found to be in relation to specific microorganism such as penicillium (eduard, ) or specific group microorganism such as gram negative bacteria (suva, ) . thus it is very evitable that till date no work has been done that can describe health effects solely on the basis of overall fungal or bacterial concentration present, rather many research have worked in the direction revealing that health effects are dependent on the combination of three factors namely, the genera of the airborne microbe, their size range (depicting till what level they may penetrate in the respiratory system) and their concentration in the concerned environment. this statement can be supported by the study done on sawmill workers exposed to . - . × fungal spores/m mainly of rhizopus and penicillium by roponen et al., wherein a noaec in relation to nasal inflammation was suggested i.e., mere exposure to high microbial concentration does not evoke inflammation, rather the type of microbe or microbial product in the environment determines the potential of proinflammation of microbial exposure (roponen et al., ) . although all the three factors work in a combined way, yet most of the studies have been carried out emphasizing a single effect or combination of two. certain health effect studies in relation to concentration reveal that threshold concentration spore/m of alternaria were found to evoke allergic symptoms (gravensen et al., ) while in some other sick building syndrome were found to be potentially associated more spores/m of aspergillus sp. (holmberg, ) . in case off size dependent and genera specific health effects bacterial bioaerosol such a. lwoffi and a. johnsonii mostly found in . - μm size range have been associated with bacteremia and meningitis (ku et al., ) while streptococcus mitis and streptococcus pneumoniae generally found in the particle size ranging from . to . μm, apart from meningitis have been found to cause acute otitis, pneumonia as well as bacterial sinusitis (balsalobre et al., ) . among other airborne bacteria haemophilus parainfluenzae of particle size range of - . μm have been linked to acute bacterial meningitis to young children and infants as well as effects adults by causing chronic pulmonary disease (foweraker et al., ) . sphingomonas species falls in higher size range of n . μm which is an opportunistic human and plant pathogens and induces various nosocomial infections (ammendolia et al., ) . various microbial compounds such as endotoxins, mycotoxins, microbial volatile compounds (mvcos), have also been found to induce several diseases as well. among all the three, standard for the exposure concentration of eu/m for endotoxin was published by dutch expert committee on occupational standards (decos) in (decos, ) which was re-evaluated to eu/m in on the basis of respiratory effects such as inflammation of airway (samadi et al., ) . apart from decos, in netherlands for general population an exposure limit of eu/m was also suggested by health council of the netherlands (health-council-of-the-netherlands, ). study carried out in several buildings of mid-western usa correlated pulmonary and respiratory problems with endotoxin levels in the indoor, some reports being as low as eu/m (reynolds et al., ) . mycotoxins, as the name suggests are secondary metabolites of fungi (fungal specific) that are highly toxic to both animal and human health. among different mycotoxins aflatoxin b released from aspergillus sp., (bennet and klich, ) have been found to cause liver cancer, hepatitis (ross et al., ) ; deoxynivalenol released from fusarium graminearum (bennet and klich, ) have been found to cause vomiting and nausea (rotter et al., ) while fumonisin b released from fusarium nygamai (bennet and klich, ) has the ability of probable esophageal cancer in humans (bucci et al., ) . in comparison to mycotoxins, mvocs have always received less attention although some studies revealed mvocs associated with "sick building syndrome" (molhave, ) as well as headache, lethargy, sore throat, nasal congestion, cough and wheezing (araki et al., ) . among different mvocs, cytotoxicity study of -octen- -ol when exposed to human volunteers for h have reported minor irritation of nose, eye and throat (walinder et al., ) . interestingly, bioaerosols is also used as biological weapons. the deliberate release of pathogenic bioaerosols has become an act of terrorism or warfare that has become a troubling possibility and a frightening reality. in , bacillus anthracis spores were mailed in envelopes in u.s. around the country and its outbreak resulted in killing people, sickening others, and contaminating several senates, post, and media offices (klietmann and ruoff, ) . smallpox (variola virus) is considered to have the greatest bioweapon potential (henderson, ) . other potential bioweapons capable of getting released into the air include francisella tularensis, yersinia pestis, brucella spp., variola virus, and coxiella burnetii (atlas, ) . bioweapons are predicted to be the weapons of mass destruction (wmd) of the future due to many reasons for example: they are inexpensive to use, provide high probability of delivering considerable devastation and large scale panic (henderson, ) . in order to prevent or reduce adverse health effects of bioaerosols along with detection immediate controlling mechanism is also essential which includes inactivation, removal or collection at specific locations. in recent past many methods have been developed in order to control bioaerosol each of which has advantages as well as weakness regarding their economic requirements and environmental impacts. thermal energy has been used to control bioaerosol for a larger period of time in two forms such as moist heat (using steam under pressure) and dry heat (high temperature without moisture). the potential applicability of thermal energy has been studied by several researchers (jung et al., ; grinshpun et al., ) . bioaerosol treatment by thermal energy released from electrical heating coils is highly advantageous due to easy installation in buildings as well as low production of byproducts. research has shown that exposure to temperature of - °c for sub seconds can inactivate airborne bacteria (lee and lee, ) decrease the size of fungal bioaerosol their concentration as well as reduce the amount of ( → )-β-d-glucan (a key agent in bioaerosol-induced inflammatory responses) (jung et al., ) . denaturation of proteins followed by damage of microorganism is also seen when exposed to very high temperature (madigan and martinko, ) . although thermal energy was used to control bioaerosol by louis pasteur around years ago and its use continued thereafter for a longer period of time yet currently due to the need of energy conservation its use has been restricted (lee, ) . as bioaerosols exhibit similar physical behavior as that of nonbiological aerosols, air ion emission technique can be definitely used to transfer bioaerosols from air to walls, ceiling and floor as proven by research revealing that when air ions of density - e ± cm - are emitted for min removes % and % of . μm and μm particles respectively in indoor air along with the natural effect of decreasing aerosol concentration due to gravity and diffusion (lee et al., a; lee et al., b) . the biocidal effect of air ions on bacterial and fungal species has been proved by several scientists kerr et al., ) with few suggesting that in addition to ozone exposure electro poration mechanism played a primary role (fletcher et al., ; kim et al., ) . however most the studies revealed effect of air ions on static microorganisms rather than airborne microorganisms. hence more experimental work is needed to find out the effect of air ions on bioaerosol as well as to treat the side effect of bioaerosols being deposited on ceiling and walls where they grow and re-emit additional bioaerosols in the air. apart from thermal energy the other most commonly used method for controlling bioaerosols in indoor environment is ultraviolet (uv) irradiation. the germicidal effect of uv was found to be dependent on irradiation dosage, moisture content of the air and the movement pattern of the air along with the size of the room (kujundzic et al., ; beggs et al., ) . ultraviolet germicidal irradiation (uvgi) disinfects air by using ultraviolet light at sufficiently short wavelength between and nm destroying the nucleic acid of the organism leaving them unable to perform any vital cellular functions, eventually killing the microorganism (madigan and martinko, ) . several studies related to the dosage response of uvgi have been done revealing that high doses are required to inactivate fungal bioaerosol than vegetative bacterial bioaerosols (lee, ) . as for instance uvgi dosage of . × μw s/cm was found to be required for log decrease in the concentration of fungal bioaerosol (kujundzic et al., ) while fold reduction in bacterial bioaerosol were seen at μw sec/cm uvgi exposure (lidwell, ) . in comparison to thermal treatment uv irradiation technique utilizes very less energy along with simplified installation technique of uv lamps. hence due its user friendliness uv lamps are usually installed and used to inactivate bioaerosols in indoor environments. generally though common filters are useful in removing aerosols from indoor environments yet in case of bioaerosols they act as breeding ground where once trapped they grow by absorbing air moisture and nutrients in the dust and on instances of reverse airflow they get introduced back into the air. hence several researchers have developed filters with anti-microbial components such as iodine and other membrane breaking enzymes (lee et al., a; eninger et al., ) . such anti-microbial filters are however useful for only short period of time because of its ineffectiveness caused by the accumulated dust particles over them. hence by combining different bioaerosol control methods, hybrid methods are developed by scientists, as for example deposition of silver nanoparticles over filters rendered % inactivation of bacterial bioaerosol (lee et al., b) while under low relative humidity condition the death rate tolled up when exposed to high number of silver nanoparticles . apart from use of silver nanoparticles over filters, integration of thermal energy and uv irradiation in a single method had also proven to enhance the inactivation and control of bioaerosols compensating the respective weakness of the constituting methods (hwang et al., ) . apart from the already mentioned controlling mechanisms renovation and periodic mechanical cleaning operations have also shown to reduce both bacterial and fungal aerosols by approximately % and % respectively (berent et al., ) . along with these maintenance activities increasing the ventilation rate (dilution ventilation) by various mechanical or natural systems are few individual levels of efforts that can play an important role in improving the indoor air quality (cox and wathes, ) . bioaerososl is present in most of the enclosed environments due to its ubiquitous nature (jones and harrison, ) . in general when we breathe we inhale . l of air, thereby taking in almost microbial cells per day (mandal and brandl, ) . moreover as potential health effects of bioaerosol are highly diverse including acute toxic effects, allergies, infections and cancer, assessment of bioaerosol is highly essential. without detailed information about sampling and enumeration technique interpretation of exposure level is very difficult. hence both advantages and disadvantages of all the methods should be known before deciding upon the suitable one for use. high bacterial count as well as presence of several allergenic fungal genuses in indoor environment represents a highly allergic environment. hence apart from assessment, suitable steps are also necessary for controlling the airborne microbes. although several control techniques have evolved as has been already mentioned controlling mechanisms such as periodic cleaning operations, maintenance activities as well as increasing the ventilation rate by various mechanical or natural systems are few individual efforts that can eventually improve the indoor air quality. although several studies in relation to health effects of bioaerosol have been conducted and have also been reported in this review yet none of the studies have been found providing suitable dose-response relationship that could eventually 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stemming and crushing key: cord- -nzigx k authors: lipinski, tom; ahmad, darem; serey, nicolas; jouhara, hussam title: review of ventilation strategies to reduce the risk of disease transmission in high occupancy buildings date: - - journal: nan doi: . /j.ijft. . sha: doc_id: cord_uid: nzigx k an unforeseen pandemic is facing the world caused by a corona virus known as sars-cov- . numerous measures are being put in place to try and reduce the spread of this deadly disease, with the most effective response to the outbreak being mass quarantines, a public health technique borrowed from the middle ages. the widely accepted main transmission mechanism is through droplet borne pathways. however, many researchers and studies are considering that this virus can also spread via the airborne route and remain for up to three hours in the air. this is leading to questions as to whether enough is being done regarding ventilation to reduce the risk of the spread of this or other diseases that may be air borne. ventilation and air conditioning systems are the main focus when it comes to the transmission of such deadly pathogens and should be appropriately designed and operated. this paper reviews and critically evaluates the current ventilation strategies used in buildings to assess the state of the art and elaborates if there is room for further development, especially for high occupancy buildings, to reduce or eradicate the risk of pathogen transmission and adapt ventilation measures to new threats posed by pandemics. an unprecedented viral disease has brought our globe to a halt, impacting most of mankind's activities. at the time of writing, more than , people are dead worldwide, the global economy is on the verge of an unprecedented depression, with the covid- pandemic still raging and a second wave predicted as inevitable. covid- belongs to the group of coronavirus, also known as severe acute respiratory syndrome corona virus (sars-cov- ) [ ] . this virus has already surpassed the number of infections of two other epidemics in this century [ ] . current measures introduced worldwide, and designed to control the spread of the virus include lockdowns, selfisolation, social distancing, use of face masks and the recommendation to wash hands as frequently as possible, [ ] . n masks have been recommended by who and have been known to help prevent infected individuals from spreading the virus if not necessarily preventing healthy individuals from contracting it from others [ ] , [ ] . covid- is one of the most contagious viruses that mankind has experienced, spreading across most of china in only days [ ] , then worldwide within a couple of months. the widely accepted mechanism of covid- transmission is by droplet and contact methods as backed-up by the who, but the possible air transmission route has been broadly documented by new scientific research [ ] and the who is not ruling out this possibility. as individuals are infected with the respiratory disease, the rate of expiratory events increases which in turn increases the generation and dispersion of droplets containing the virus. such expiratory events include not only coughing and sneezing but also talking [ ] . considering how fast this disease has spread across the world, many researchers [ ] state that an additional mode of transmission, nuclei borne by air droplets, plays an important role in the spread of this virus. flow dynamics of air particles can be complex and include turbulent jets, droplet evaporation, airmucous interaction and particle sedimentation amongst others [ ] . these flow dynamics and particle interaction with air is at the core of transmission of the covid- virus. as mentioned previously, a variety of physical containment methods have been introduced, such as wearing the recommended personal protective equipment (ppe) and improving personal hygiene. however, since the vast majority of infections occur indoors [ ] , it has been noted that ventilation strategies can play a vital role in controlling or at least reducing the risk of respiratory infections [ ] . droplet nuclei are fine air particles that remain airborne for a considerable length of time. any air particles below micrometres are classified as being able to be airborne. sars-cov- is yet to be officially classified as an airborne disease by the who, however, a weight of emerging evidence is being established for aerosol driven infections [ ] [ ] [ ] [ ] . the chartered institution of building services engineers, cibse, recently provided guidance on using ventilation as a way of diluting airborne pathogens. it is stated that: "there is good evidence that demonstrates room occupants are more at risk of catching an illness in a poorly ventilated room than in a well-ventilated room." besides this, new evidence that has been found shows high rates of infection in poorly ventilated spaces [ ] . since sars-cov- has spread around the world at an unprecedented pace, infecting millions of people, and further aerosol driven infections are highly likely to emerge, ventilation plays a key role in efforts to limit the transmission rate of this and other diseases. this paper will discuss the factors affecting air particle properties in-terms of flow dynamics and critically analyse current ventilation strategies and mechanisms and identify areas for improvement in the search for the reduction of indoor infections. thoughtful modifications to the built environment -to how schools, offices or health-care facilities are designed, operated and maintained -could help curb the spread of infectious disease, reducing the toll of future outbreaks as well as the current covid- pandemic. this section will review the current state-of-the-art covering characteristics of respiratory particles, the ability of viruses to spread as well as the mechanisms for airborne transmission and how current ventilation strategies can affect the risk of transmission. respiratory particles are formed during any respiratory activity such as coughing, sneezing, talking and breathing. once the particles are released into the surroundings, the mechanisms in-which they flow and settle depend on the fluid dynamics of the particles and the conditions in the vicinity. fluid dynamics can characterise the evaporation rate of the particles which allows the determination of the prevalence of small droplets and nuclei droplet transport [ ] . covid- belongs to the betacovs pathogen group and has an approximate diameter of - nm. the shape of the virus can be spherical or ellipsoidal [ ] . particle trajectories depend primarily on their size and the balance of various forces acting on the particle in the air. gravitational and aerodynamic forces are the two primary forces acting on such particles, where the latter force dictates the flow behaviour of the particle. figure shows the trajectories for particles of various sizes ranging from . µm to µm [ ] . figure : trajectories of particles with various sizes [ ] . stokes law explains the frictional force relation exerted on spherical objects with very small reynolds numbers in viscous fluid. to help explain the trajectories of air particles, the aerodynamic drag coefficient (cd), shown in equation of a spherical particle relative to reynolds number, shown in equation , is not constant. reynolds number is a ratio between inertial and viscous forces that originate from interactions between a body and a fluid. the equation for reynolds number is shown below. where fd is the aerodynamic drag force, and a is the frontal area. using reynolds equation, for natural ventilation systems with air velocity of . m/s and a particle size of nm, the reynolds number is calculated at . . this shows that for such air flow environment, the flow is laminar whereby the viscous forces prevail. therefore, drag coefficient for viscous non-separated flow around a sphere can be defined by equation . however, this equation implies that drag force is proportional to the diameter which is not entirely accurate. the resistance coefficient may decrease with increasing diameter, but the drag force increases linearly with the diameter. however, since the gravitational force increases with the mass, it increases with diameter cubed, thus, more rapidly than the drag force as the diameter increases. therefore, larger particles have the tendency to settle [ ] . this phenomenon helps to explain why smaller particles are more likely to be airborne. the drag coefficient for a sphere as a function of reynolds number can be plotted to show the influence of changing flow regime on the drag coefficient. this is shown in figure , whereby a sphere exhibits a reduction in drag coefficient until the flow regime becomes turbulent causing a sudden dip. furthermore, when the boundary layer on the leading surface becomes turbulent, the separation occurs farther round the sphere and the drag coefficient decreases. a rough surface, such as on a golf ball, promotes an earlier transition to turbulence. the numbers on figure refer to various flow regimes and their corresponding changes in the drag coefficient. flow regime on the figure refers to stokes flow and steady separated flow, whereby the reynolds number is less than which is typical for fluid velocities are very slow and the viscosities are very high. flow regime on the figure refers to separated, unsteady flow, whereby a laminar flow boundary is formed upstream of the separation and producing vortex street. flow regime refers to separated unsteady flow with a laminar boundary layer at the upstream side and chaotic turbulent wake downstream of the sphere. regime refers to a turbulent boundary layer [ ] . a graph of aerodynamic drag coefficient against reynolds number [ ] . various parameters affect the transmission of droplet borne infections, including density, initial velocity and the size distribution of the droplets that are released during respiratory activities, as well as indoor air velocity and direction. many research studies have been carried out to measure these characteristics [ ] . sneezing is the respiratory activity that ejects the most droplets, in the range of or more. the droplets from sneezing have initial velocities in the range of m/s. other respiratory activities release droplets at a significantly lower density and lower initial velocities. table shows the droplet densities and velocities for the common respiratory activities. the terminal velocity at which any spherical particle settles due to gravity in a fluid can be explained by stokes' law for fine particle size and newton's law for coarse particles. both equations have been shown below. where = gravitational acceleration = density of solid and fluid respectively d = particle diameter = drag coefficient μ = fluid viscosity the terminal velocity equations shown above have been used to generate graphical representations of the expected particle speeds at various conditions as shown below in figure . since covid- has an approximate diameter of - nm [ ] , stokes' law applies for ventilation in buildings whereby the air flow exhibits a laminar behaviour. figure shows that at very small diameter particles of less than . µm, the terminal velocity is almost negligible which further amplifies the fact that if covid- was proven to be airborne then the virus and its potent materials could be airborne for long durations especially if enclosed environments are not ventilated adequately. a mathematical model by c.p cummins et al. shows that particles with a diameter smaller than µm (stoke's number ≤ . × − ) are almost unaffected by the gravity and air extraction is very efficient at removing these fine particles [ ] . this is explained by the major impact of the drag forces on the particle's movement for this diameter. the settling velocity calculated by stokes' law (equation ) is proportional with the diameter squared. particle terminal velocities remain elusive due to a vast number of factors, such as droplet diameter, droplet density, contributing to this phenomenon and primarily due to the difficulty in making measurements of such parameters [ , , ]. pathogen transmission can occur through different routes: direct contact, indirect contact, droplet borne or airborne such as shown in figure [ ] [ ] [ ] . the direct contact route covers any contact between a contagious person and a susceptible person: touching, kissing, sexual contact, contact with skin lesions or oral secretion. this route is well documented and outside the scope for this paper. in the indirect contact transmission mode, the contagious person touches or expels contaminated droplets containing infectious organisms which settle on an inanimate object, such as a doorknob or an elevator button, called "fomite". the person being infected touches this fomite and then an area where the pathogen can enter the body such as the eyes, nose, or mouth [ ] . droplet transmission can occur when infective large droplets expelled from a contagious person reach an uninfected person. airborne transmission occurs when very small particles ( - µm in diameter) or small droplets evaporating to a small enough size [ ] , are expelled by coughing, sneezing, speaking, or breathing. these droplets are small enough to remain airborne for long periods of time (up to several hours), until they are inhaled by or land on the uninfected person. airborne transmission is not yet widely accepted for various transmissible respiratory diseases. in the case of sars-cov- , the world health organisation only recognizes the risk for airborne transmission under certain medical procedures producing large amounts of infective respiratory particles [ , , [ ] [ ] [ ] . there is now growing pressure on the who from the scientific community to relax the dogmatic and outdated division between aerosols and small droplets and acknowledge the mounting evidence for the indoor spreading of the covid- infection through the air [ ] . in the case of sars-cov- and mers-cov, retrospection on the different outbreaks and multiple studies make a strong case for the route as an opportunistic transmission, meaning that the virus will transmit preferably through other routes but can potentially infect by means of respiratory particles when conditions are met. another factor explaining the elusive validation of airborne transmission is the dilution of small particles after they are emitted. indeed, people standing farther away from a contagious emitter see an exponentially decreasing concentration of droplet nuclei. the potential transmission over larger distances are by nature more difficult to identify especially in the context of an outbreak or a pandemic when the sources are multiple. furthermore, when the transmission happens close to an identified source, the transmission is indiscernible from that due to droplets or indirect transmission [ , ] . in order for viruses to be transmitted through the airborne route, some conditions must be satisfied: the virus must be able to remain viable outside of the host, withstand the external conditions and be transported to a susceptible area of a new host. the effect of evaporation, light, humidity and temperature on the concentration and virality (capacity to infect and reproduce) of the pathogen need to be further researched to make conclusions on the threat level of the airborne route [ ] . there are already multiple pathogens for which the airborne route is acknowledged. such viruses including adenovirus, influenza, measles, meningococcal disease, mumps, pertussis, parvovirus b , respiratory syncitial virus, rubella, tuberculosis and varicella, can spread by droplet nuclei [ ] . measles and tuberculosis for example are proven to be preferentially airborne transmitted diseases [ ] . but the fact that these diseases have been controlled with widely available drugs and vaccines resulted in a decrease in research effort into airborne transmission mechanisms. recent sars-cov- and mers-cov outbreak have given a new impetus to research on this subject. indeed, sars-cov- is thought to be transmissible by direct, indirect, and droplet contact, the amoy garden case identifies a strong possibility of airborne transmission. during the outbreak, the virus spread from a faulty dried-out bathroom drainage system and rose to a extraction fan, then was carried by the wind into the adjacent building infecting several occupants [ , , , , , ] . ribonucleic acid, rna, and even viable viruses have been detected in aerosols in healthcare facilities for some respiratory viruses such as seasonal and avian influenzas virus, mers-cov and respiratory syncytial virus [ ] . in the case of mers-cov, samples taken in hospitals and isolation wards in south korea confirmed the airborne transmission. some patients of the same ward were infected, even though they were standing more than two meters away from the source. air samples and surrounding areas, including regularly disinfected accessible and inaccessible surfaces, were all contaminated by mers-cov [ ] . this experimental data challenges the previously recognized transmission routes, acknowledging the high possibility of airborne transmission as an opportunistic route at close range and even long range when the conditions were favourable and concentrations at the source were high. sars-cov- shares the same modes of transmission as the sars cov- and, although the viability and virality of an air sample has not been proven at the time of writing, it cannot be ruled out. the airborne route, being opportunistic [ ] , is by its nature difficult to interpret. air samples take time before being tested after which the concentration might be too low, through dilution, to establish with confidence the presence of viable virus on droplet nuclei. rna detection is also not usually enough to interpret the risk of airborne transmission [ ] . a number of studies indicate airborne or droplet borne transmission [ ] , and to the authors' knowledge, there is no study yet demonstrating the lack of infection in a situation where only airborne transmission is permitted (and with particles in high concentration). this would be the only definitive way to disprove the mode of transmission [ ] . recent superspreading events also support the argument for airborne transmission. during a choir rehearsal in mount vernon (washington), although precautionary care was taken to suppress direct contacts and keep distance between the singers, out of the participants caught the disease [ ] and at least two people were reported to have died [ ] . the aerosol stability of sars-cov- was recently tested in laboratory conditions. a three-jet collison nebulizer created contaminated aerosols (< µm) fed into a goldberg drum. in this environment, the sars-cov- remained viable with a half-life between . and . hours ( % credible interval . to . h) as shown in figure . the researchers compared the results with sars-cov- and found similar half-life results ( % credible interval . to . h). the reduction in infectious concentration (titer) during the -hour long tests was from . to . tcid (fifty-percent tissue culture infective dose) per litre of air for sars-cov- . this reduction was similar to that observed with sars-cov- , from . to . tcid per litre of air [ ] . in order to better understand how to combat airborne transmission, one must understand the relation between the particle emission and deposition mechanisms. droplets can be generated from different places in the respiratory tract of the infected person with various resulting diameters. once deposited on the uninfected individual they then infect the conjunctiva or mucous membranes in the upper respiratory tract of the new host [ , , ] . small particles can be generated during speech in the alveoli of the lungs and vocal cord vibration by a fluid film burst mechanism [ , ] . it was reported that vocalization emits times more particles than breathing, and some speech super-emitters can (for reasons unclear yet) expel times more particles than average [ ] . this could be an explanation to the mount vernon choir outbreak: the higher concentration of infected particles added to the need for extra deep breathing required for singing facilitates airborne transmission. coughing and sneezing also generate large numbers of particles, the majority of which are inhalable (< μm in size): . - . % for coughing and . % for sneezing. furthermore, between . - . % of cough expelled particles and . % of particles produced by sneezing were under μm in diameter [ ] . these smaller particles penetrate deeper and can deposit further in the respiratory tract. generally, particles above µm do not reach the alveoli whereas particles above µm deposit in the upper respiratory tract as shown in figure [ , , , , , ] . [ ] . transmission that occurs in the lower respiratory tract, shown in figure due to smaller particles potentially leads to aggravated symptoms and a higher mortality rate, whereas deposition in the upper respiratory track by larger aerosols necessitates a larger number of viruses for the host to develop symptoms [ ] . this is due to the fact that the nasal and tracheobronchial regions have an additional defence system. the nasal tracts are covered by a mucus layer that entraps deposited particulates. the continuous movement of cilia pushes the captive infected particles up to the gastrointestinal track where they cannot infect the host [ , ] . research studies have shown that small particles still present a substantial risk of infection [ ] , and it was reported that for some respiratory diseases, a single virus can cause illness. in the case of sars-cov- , a minimum required viral load has not yet been confirmed [ , , ] . once the virus finds a susceptible cell, it can infect individuals through binding its pike proteins to the cell wall then uses the cell to replicate before bursting it. thereafter, it releases more viruses that can either contaminate other cells, be destroyed by the immune system or be expelled from the body and potentially transmit to a new host [ ] . studies have shown that that the ensuing incubation period is on average . days, but can range from to days [ ] . the virus remains detectable for a median of days [ , ] . a critical specificity of sars-cov- is the serial interval (or the time lapse) between an infection of a host and the transmission to a susceptible uninfected person. an average of . days, with a % credible interval between . and . days, and median of . days, with credible interval between . and . days, were reported [ ] . the small-time delay and possible overlap between the end of the incubation period and the secondary infection shows that pre-symptomatic transmission is very likely. it is believed that the infectiousness starts . days before the first symptoms of the disease and peaks when the symptoms are starting [ , ] . this would be the major cause of the rapid spread of the pandemic. the speed of the spread is represented by the basic reproduction, ro, number which is the average number of susceptible persons infected by a single host [ ] . for sars-cov- ro is estimated to range between . to . (mean, . ; median, . ) [ ] . furthermore, the ro is rapidly evolving and other studies have found values of ro between and before intervention to limit the spread [ ] . the basic reproduction number corresponding to pre-symptomatic transmissions alone is estimated to be . , with % credible interval between . and . . a ro value superior to means the virus will spread exponentially, indicating these transmissions are almost sufficient to sustain the pandemic [ ] . at the beginning of the wuhan outbreak, the contribution of pre-symptomatic cases accounted for % of all infections, with % for asymptomatic cases, and it is now widely accepted that seemingly healthy people can spread the virus, though uncertainty remains over how much they have contributed to the pandemic. though estimates vary, models using data from hong kong, singapore and china suggest that to percent of spreading occurs when people have no symptoms [ , , ] . as the body starts to build antibodies against the virus, the concentration begins to decrease, and the infectiousness of the disease declines significantly after days [ ] . when a significant portion of the population stops being susceptible to the virus, the ro falls below and the number of new infections drops below the sustaining rate. this can be achieved through vaccination or by building immunity after recovering from the disease -thus the state of herd immunity may be achieved [ ] . although mutation from the virus and decay of the immune system memory could still pose a challenge to achieving this goal. in order to supress or slow the progression of the pandemic, efforts must be made to reduce ro. precautionary measures must consider the entire population since pre-symptomatic and asymptomatic transmissions are a critical factor in the spread of sars-cov- . if the virus can spread from seemingly healthy carriers or people who had not yet developed symptoms, the publicawareness campaigns, airport screening and 'stay-home-if-you're sick' policies might not stop it. more targeted measures are required including a considered re-design of indoor environments, especially aspects handling the air buildings' ventilation systems [ ] . both the airborne and or droplet borne routes cannot be ignored. pre-symptomatic and asymptomatic hosts do not cough or sneeze extensively [ , , ] . when doctors in wuhan, china, where the new virus first emerged, studied early cases, they concluded that percent of patients had most likely contracted the disease in the hospital [ ] . therefore, the hypothesis stating that infection through small particles plays a more important role in the transmission along with the direct and indirect (fomites) routes can be used. thus, ventilation plays an important role in reducing the risk of transmission through dilution and removal of the infected particles within the indoor environment [ ] . preparedness to fight airborne disease is essential and sars-cov- offers the chance to research and apply mitigating ventilation solutions which could prove life-saving now and in the future when another virulent and deadly pandemic arises [ ] . ashrae standard . : defines acceptable indoor air quality as "air in which there are no known contaminants at harmful concentrations, as determined by cognizant authorities, and with which a substantial majority ( % or more) of the people exposed do not express dissatisfaction". [ ] if airborne infectious particles are to be counted as harmful even in small concentrations, as explained in the previous section, either the amount of fresh air supplied to a room needs to be dramatically increased or the ventilation strategy needs to be reconsidered to protect the occupants. this paper focuses on high occupancy buildings such as schools or office spaces where the occupants are static most of the time. current standards already have predetermined values to meet the acceptable indoor air quality. for example, the ashrae standards dictate a minimum ventilation rate of l/s per person or . l/s.m in educational facilities. for office buildings, the minimum values are . l/s per person or . l/s.m [ ] . having said that, due to variability in ventilation methodologies, similar ventilation rates may translate to significantly different indoor transmission outcomes. fresh air can be provided in a number of ways, relying on many different technologies and having different extraction, dilution and air distribution effectiveness. the british standards bs en - : defines basic types of ventilation systems: [ ] . system type fan assisted air volume flow in only one direction. this system is balanced by air transfer devices within the building envelope. fan assisted system operates in supply and exhaust directions. bidirectional ventilation system natural ventilation relies on natural driving forces. natural ventilation system hybrid systems rely on natural and mechanical mechanisms. any combination of the ventilation mechanisms can be used depending on the situation. several factors play a role after a ventilation solution is selected that affect the final system performance and indoor air quality. the poor initial design of a selected ventilation solution could be due to various reasons such as error in sizing, reduced performance due to lack of maintenance, lack of operator knowledge or the intentional reduced use in order to save energy or reduce noise and all can be detrimental to the occupants' health. several studies have demonstrated that in classrooms, the ventilation rates have often failed to reach the minimum standard required. the peak co concentration, which can be used as an indicator of the ventilation rate in occupied spaces, often exceeded the recommended levels. in a study, the reported co measurements in several thousand classrooms has shown that all classroom averages exceeded ppm ( . %) which is an indicator of a ventilation rate lower than l/s/person at default occupancy. in many instances, the average co levels were above ppm with peak concentrations between and ppm [ ] . this discrepancy between the building standards and reality demonstrated the need for a thorough reconsideration of ventilation design and ventilation systems specified in high occupancy buildings well before the impact of coronavirus. in the light of sars-cov- pandemic there is an even more desperate need to address the ventilation design and effectiveness. improved ventilation has been noted to deliver a positive health impact with a noticeable reduction in illnesses and absences. in particular, reduced respiratory health effects, such as mucosal and allergy symptoms are significantly reduced with increased ventilation rates [ ] . a study based on californian schools demonstrated that an increase in the ventilation rate by l/s/person resulted in a . % reduction in illness related absences [ ] . poor ventilation has also been linked to many adverse health effects: transmission of infectious diseases, acute respiratory symptoms and impaired cognition performance [ ] [ ] [ ] . it expresses the dilution of the said pollutant as a function of the ventilation rate effectiveness which can be engineered to suit the room, occupant type, and the risk at hand. in the case of infected particles, the recommendations from rehva, the federation of european heating, ventilation and air conditioning associations, are to supply as much outside air as possible. according to rehva, mechanical ventilation should be activated more often ( / when possible with lower rates during quiet times) and at least to start ventilating before and after busy hours while the density of occupancy needs to be decreased when possible this will increase the distance between people and lower the pollutant emission rate. with or without mechanical ventilation, window airing should be used to boost the air exchange rate. toilet windows on the other hand need to remain closed and mechanical extraction activated at all times to create negative pressure and prevent contaminated particles from entering other parts of the building though doors or by an unforeseen route through nearby open windows [ ] . prior to covid- , densely packed open-plan offices were already suspected of making employees sick [ ] . viruses and other pathogens are not the typical pollutants and even small and temporary exposure has been proven to lead to infections. studies of viral infections spread through indoor spaces document clearly that mechanically induced, mixing airflow can pose a greater risk of infection spread as it pushes turbulent air deep into rooms, possibly picking up infected droplets along the way [ ] . further research by the university of oregon demonstrated how air conditioning or hybrid ventilation can spread the pathogens much farther than feet, even when the host is positioned a long distance from the fan driven system [ , ] . it appears that it is not just the rate of supply of fresh air that needs to be considered but also the air flow dynamics and air distribution pathways through occupied spaces that urgently need review, which include the type of airflow, velocity, its turbulence and its direction. keeping indoor environments virus-free plays a key part in reducing or slowing the transmission of various airborne infections. since viruses have an approximate diameter of nm, they can be easily carried by aerosol droplets in the air and linger afloat for many minutes and sometimes hours. an inappropriate or inadequate ventilation strategy can dramatically increase the risk of disease transmission. a research study conducted by a team of scientists at the defence science and technology laboratory on the aerosol survival of sars-cov- in artificial saliva and tissue culture media and high humidity found that covid- could be transmitted via airborne droplets in addition to physical contact with droplets deposited onto surfaces [ ] . the study used the sars-cov- england variant which was suspended in the air using tissue culture media at medium and high relative humidity, - % and - %. the outcome of the study has shown that the virus was still detectable after minutes. taking the above-mentioned publications into account, ventilation and comfort strategies have been categorised by airflow characteristics and their potential impact on pathogen spread through occupied spaces in the next section. considering the dynamics of droplet and aerosol spread indoors, various ventilation and air conditioning strategies can be grouped into three main categories:  recirculating ventilation (frequently called mixing or hybrid ventilation) and conditioning systems that either move the indoor air around (typical split ac or vrf system or even a ceiling fan) or mix indoor air with outdoor air before pumping it into the room (such as hybrid or 'heat recycling' ventilation systems that have been lately installed in many schools). this ventilation method generally produces turbulent air flows with stale air either partly or fully recirculated back into the affected rooms.  mixing ventilation systems that are designed to distribute fresh air throughout the occupied space ensuring all occupants experience similar air quality, with air supplied through specific ventilation outlets or diffusers. they are predominantly mechanical systems such as large, centralised air handling units (ahu) or smaller, localised mechanical ventilation systems with heat recovery (mvhr). this ventilation method generally produces turbulent, mixing air flows within rooms.  displacement ventilation systems that remove contaminated indoor air and supply fresh outside air in a predominantly even, buoyancy assisted fashion, effectively displacing it with no or little disruption. they are primarily passive systems such as natural ventilation cowls, façade louvres or automatically opening windows. this ventilation method generally produces a laminar airflow within rooms (outside of very windy conditions). typical ventilation measures are listed and grouped in the table below, complete with a brief description: building integrated measures designed to displace stale air and supply fresh air using buoyancy including elements such as windows, passive stacks or solar chimneys. natural ventilation systems natural ventilation products or systems utilising buoyancy in their operation including roof cowls, wall mounted iaq responsive louvres or iaq controlled window openers. the recirculating approach has been popular choice for new schools in recent years for both ventilation and comfort provision, mainly due to its low capital cost and simplicity. some recirculating systems are used for ventilation with the recirculated stale air mixed with fresh, outside air, in order to increase the temperature of the air supplied to the classroom, necessary to reduce discomfort in absence of a heat exchanger. the diagram, shown in figure , illustrates the concept of hybrid ventilation: the mixed, partly recirculated, air is fan driven in such a way as to reach far into the classroom up to m from the system and to supply enough fresh air, mixed with stale air for comfort, to maintain co levels below an average of ppm. as this requires fresh air flows rate in a range of l/s, when combined with stale air it may reach a volume flow rate of l/s or higher which, considering the small size of the air diffusers, can generate substantial air velocities in occupied spaces -leading to high air turbulence. according to a recent study and modelling conducted by the university of oregon, this type of airflow has the potential for high spread of coronavirus infected droplets within densely occupied spaces, even with just one person exhaling the virus droplets [ , ] . apart from the recirculation itself, the transmission appears to be facilitated by the type and velocity of turbulent airflow designed to reach deep into the occupied space as shown in figure . this covers most of the air conditioning systems used commercially with the mode of operation similar to the hybrid ventilation systems mentioned above with the exception of containing no fresh air in its supply path -all is constantly recirculated. air is pulled into the system from the room, conditioned, either cooled or heated, and then supplied back into the room at high enough velocity to reach to the end of the occupied space. since the systems are designed to ensure that conditioned air gets to every area of the room, providing comfort, the pathogens picked up by the circulating air can travel much further than m [ , , ] . a typical ac airflow can be illustrated by the computational fluid dynamics picture in figure : ceiling fan is another recirculating comfort system and is designed to either reduce air stratification in the room, bringing the warm air down from the ceiling, or to introduce enough air movement to cool the occupants through wind chill effect. both actions are designed to improve comfort while displacing the need for more power-hungry ac or excess space heating. as it can be seen in the cfd snapshot in figure , ceiling fans also ensure that air within the room is fully mixed. as much as there can be various iterations of the above approach, the unifying factor is that ceiling fans continuously mix air within spaces where they serve, such as classrooms, lecture theatres or offices. consequently, any contaminated droplets and aerosols sneezed, coughed or exhaled can travel significant distances within the rooms and reach occupants who are much farther away from the infected host than metres [ ] . the research carried out by jaakkola et al. [ ] shows the importance of the introduction of fresh air into any occupied room, with recirculation of the air posing a significant risk with many of the air borne diseases not just being carried from person to person by the airflow but also entering the ventilation system itself, possibly being trapped in the air filter. however, many of the pathogens may escape filters causing further infections and droplets can be carried for long distances across spaces by fan induced turbulent airflow without having to enter the recirculating system. since the vast majority of air conditioners in high occupancy buildings utilise air recirculation, it raises the question over their safety and indicates the need for further research into such comfort, ventilation and indoor air quality provision so that the occupant safety can be improved, especially in the light of the covid- pandemic [ ] . air handling units are generally located in the basement or lower floors of a building such as office blocks (us) or on top of the building (uk). ahus are tasked to supply hundreds of m of air per second across the whole building and generally dehumidify, heat and cool the incoming fresh air as required. the air is supplied through floor or ceiling grills generating positive pressure within the building, it then moves across the ventilated space mixing with existing, stale air along the way and is exhausted through various building fabric openings, exhaust ducts or atria created for that purpose as shown in figure . in some cases, buildings can utilise a hybrid solution combining both natural ventilation principles (even natural free cooling) and mechanical assistance. figure : typical ahu ventilation arrangement with supply ducts located in ceiling voids [ ] . a cfd study of a simplified room, with one simulated occupant, using a positive pressure mixing ventilation system can be seen in figure . however, as the fresh air is supplied, a significant degree of mixing will occur within the occupied space. the general design of ahu ductwork, as well as deep floor plan offices exacerbate the fan induced mixing throughout occupied spaces leading to increased risk of long-distance droplet movement. these balanced ventilation systems are generally localised and mounted within the ceiling void of the room or classroom they serve, extracting air from the occupied space, passing it through the air to air heat exchanger to recover the heat and warm up the incoming fresh air, as shown in figure . as much as both air flows are channelled through the same box, there is generally no mixing between the two paths. these systems allow for higher thermal efficiencies due to heat recovery but with an electrical penalty of two fans running constantly. a typical classroom mvhr ventilation arrangement can be seen in figure constructed through simulation software, whereby an air plume generated by supply airflow in façade mounted mvhr system. mvhr systems have been documented to deliver adequate indoor air quality as well as expected comfort levels. their design is to deliver fresh, tempered air to every area of the ventilated space, as it can be seen on a cfd of the façade mounded mvhr below, which, in case of the risk of infection, appears to have similar airflow flow characteristics as recirculating ventilation modelled by the university of oregon. more turbulent air flow at higher velocity is much more likely to mix with existing air and carry larger droplets further into the room, possibly spreading virus contaminated droplets around the room and leading to a higher risk of infection spread. as this is specific to air delivery design rather than the system characteristics, it may be possible to reduce the risk of infection by a careful redesign of the ductwork, its size as well as inlet and outlet location and sizing. it may also be theoretically possible to use mvhr as displacement ventilation in some cases if a complete change of installation design is possible. as much as this is an important area for further research, specific ventilation ductwork design or ventilation design guidance are outside the scope of this paper. piv is very similar in its airflow characteristics to positive pressure air handling units described beforehand with the main difference being the local placement of the fan powered unit or system. the unit supplies the air into an occupied area with enough velocity to evenly distribute it throughout the space. due to its design, it has similar air mixing characteristics as ahus. although mechanical ventilation usually comes with better controllability, it can increase both capital and operating costs which are some of the drawbacks. the need for higher maintenance and the loss of performance when not effectively managed also need to be factored in. it was demonstrated that the severity of symptoms associated with sick building syndromes can be linked with the cleanness of the air filters and hvac system. the occupants' symptoms were recorded by questionnaire before and after cleaning a part of the hvac system and changing the filters. in the renovated section, the severity of the symptoms decreased while they remained identical in the untouched section. when using dirty filters, which is often the case in many high occupancy buildings equipped with such mechanical ventilation, the emissions from the used filters were found to increase with the outdoor airflow rate. increasing the ventilation did not improved the air quality, while raising the operation costs [ ] . the main difference between mixing and displacement ventilation can be seen in figure . as much as the risk of recirculation is significantly lower or negligible within the ductwork, virus contaminated droplets can still be carried for long distances across occupied spaces by fan induced turbulent airflow. it may be theoretically possible, however, to design the air distribution ductwork and room diffusers in such a way as to reduce in-room mixing and thus the risk of airflow induced infection spread. furthermore, there is even a possibility of adapting existing building services with covid- specific office floor alterations. further research into the possible development of such comfort, ventilation and indoor air quality provision is urgently needed so that designers, engineers and facilities managers can ensure occupant safety, especially in the light of the covid- pandemic. displacement ventilation systems can be broadly divided into mechanical and natural. mechanical displacement systems can service the entire building, often using a simplified version of air handling units with centralised extract systems or with specific rooms, office floors or classrooms using localised extract systems. continuous extract ventilation is more frequently used in domestic buildings and is currently used predominantly in bathroom areas in high occupancy buildings. natural displacement ventilation approaches can include whole building integrated systems, room specific systems, ventilation products, such as passive ventilation cowls or specific wall integrated louvres. they can also rely on windows, either automated or manually operated, in which case they may be placed at the opposing ends of the room and at different heights with the exhaust located at a high level close to the ceiling, providing maximum displacement ventilation benefit. brief examples of each approach are listed below: conventionally, the most economical way to provide ventilation was to rely on natural forces acting on air, taking advantage of atmospheric pressure differentials such as wind pressure moving air sideways or making use of the buoyancy of warmer air moving upwards. figure the warmed stale air floats to the exhaust opening faster while drawing air from all connected floors, increasing the ventilation rate [ ] . even though natural ventilation methods, including operable windows that are either manual or automatic, are one of the simplest methods of providing ventilation they frequently suffered the most from drawbacks such as bad design and implementation. main design issues included calculating full window area as an opening, which in reality is often less than / th of the window, locating windows in the wrong area or at the wrong height. as much as varied height cross ventilation can be effective, a row of short windows at mid height will generate almost no air movement, no solar shading and window related overheating, cold draughts, noise, incompatibility with interiors such as blinds or with the user behaviour. the study by the university of oregon [ , ] observed that natural ventilation with a plentiful supply of fresh air dilutes and removes contaminated air much more effectively than fan driven, recirculated air movement, significantly reducing the risk of infection, as shown in figure . however, ventilation design that requires the stale air to move across the entire floor plan, or through common areas such as hallways and staircases before being exhausted from the building, is understandably more likely to spread infection than when the stale air is exhausted at the source, directly to the outside. considering the research conducted so far, if designed and implemented appropriately, natural ventilation measures, or a combination of localised mechanical exhaust and large cross section natural inlets, can provide an adequate displacement ventilation solution, significantly reducing the risk of infection. [ ] . a frequently quoted drawback of natural ventilation measures is the perceived lack of control and dependence on external factors such as wind speed and air temperature to provide fresh air. moreover, the need to reduce the internal airflow resistance and maintain large openings and air pathways in large, building-integrated natural solutions reduces the possibilities for noise dampening or provision of adequate temperature management. in noisy, hot or cold environments, this ventilation strategy is often rejected in favour of mechanical ventilation solutions which are simpler to design and do not require familiarity with building physics. as opposed to building integrated ventilation methods or measures such as opening windows, the natural ventilation systems are products that can include roof mounted cowls and/or façade integrated elements. they can be designed or sized specifically for the application, be it a classroom or a sports hall. the systems rely on either the roof cowls to both supply fresh and extract stale air or on façade elements entirely, in which case, they would be placed at the top and bottom of each space to maximise the stack effect. some natural ventilation products can include heat recovery or comfort cooling. most of these systems can ensure displacement ventilation with little contaminated air mixing, as long as used with appropriate internal air dividers, as illustrated in figure . various examples are listed below: roof mounted natural ventilation systems: these have been available for many decades and successfully used in schools and other low-rise high occupancy buildings. their use has declined in recent years due to comparatively higher capital costs than simple mixing systems and the lack of a heat recovery function, although overall energy consumption is reduced due to the lack of fans and the associated electricity use and heat recovery systems have recently become available. these systems are available from several uk manufacturers. roof mounted natural ventilation systems with heat recovery: these are relatively new additions to the natural ventilation product range, even though the addition of heat recovery to natural ventilation has been researched considerably with several academic publications considering heat transfer with heat pipes or thermal wheels in order to improve natural ventilation whilst saving energy. their operation is broadly similar to the standard roof cowl systems in terms of air movement, and can also include façade integrated ventilation for boost, with the addition of heat recovery capability which reduces ventilation related heat loss, further increasing energy efficiency. an example of this mechanism is shown in figure : ventive windhive (natural ventilation with heat recovery) systems. figure . numerous academic papers covered the use of natural ventilation systems, both with and without heat recovery, and demonstrated that, when appropriately sized and designed, they work very effectively [ ] [ ] [ ] . façade mounted natural ventilation systems, these could be stand alone or have additional heating: these are generally automatically actuated façade openings with a room matching grille on the inside and a weather louvre on the outside, located at both high and low level in the room. depending on co concentrations, one or both dampers would open automatically to provide the required, buoyancy driven airflow. in some cases, these systems may include a heating coil, to reduce the cold drafts that could be generated during winter in the absence of a heat recovery function. if required, they can also include a bank of acoustic attenuators to reduce external noise transfer to the indoors as shown in figure . intelligent façade mounted systems with heat pump: latest technology developments include the addition of a heat pump to façade mounted natural ventilation systems to provide both the heat recovery feature. this feature is implemented by transferring heat from the exhaust vent to the supply vent with the help from a low power compressor as well as heat pump driven summer cooling as shown in figure . the general operation is the same as for the twin façade system noted above -fresh air is supplied at low level with the exhaust mounted at high level. however, unlike the above, the incoming air is tempered to improve occupant comfort using the exhausted air energyeither warmed in winter or cooled in the summer. the usual electrical consumption of the compressor is, in part, offset by the reduced electrical consumption due to the absence of fans. the other potential benefit of the system is that the summer cooling tends to boost natural ventilation by heating the exhaust air above the ambient temperature enabling the natural ventilation equipment to maintain adequate air flows all year round. a school in grong in norway implemented hybrid bidirectional ventilation, shown in figure , for the provision of the required indoor air quality based on a balance between supply and exhaust air. underground ducts connect the basement of the building to the wind tower. the mechanism in which this ventilation strategy works relies on air entering the tower further down the school field either naturally or using a fan, depending on the available buoyancy. the air is then driven under the school through a duct entering the rooms through the lower level then rising due to buoyancy, leaving the building through the chimney-like stack. the ventilation rate for each room is controlled by the degree of opening of the exhaust damper and the optional extraction fan. this type of system is simple mechanically, and offers fresh air either naturally, during winter, or using fans when buoyancy is too weak to drive the airflow, with compressor driven heat recovery that utilises a centralised concept for ventilation [ ] . [ ] . a study in a school in new-zealand highlights the positive effects of a better ventilation strategy on airborne particles. two adjacent classrooms were monitored and compared, one with continuous mechanical extraction ventilation solutions and the other where the occupants were relied on to open windows. the levels of inorganic airborne particles were monitored to show how they were removed from the breathing space. the first room was equipped with a unidirectional ventilation system consisting of a fan assisted solar roof prototype with a double-layer roof made of a polycarbonate layer over a steel corrugated north-facing roof, where outdoor air was passed between the two layers, while the other classroom had no specific ventilation system with manually operable windows as the only means of ventilation. the goal of the study was to assess the air quality and the effect of ventilation on reducing respiratory and cardiovascular diseases associated with poor air quality. air samples were measured to identify the number of inorganic particles sizing under μm. the exhaled airborne particle concentration and dilution provided by the ventilation system follow the same trend, since, at this size, aerodynamic forces prevail over gravitational forces as explained in section . . the ventilated system provided . l/s of tempered outside air, or approximately . air change per hour, for a classroom volume of m . the unidirectional ventilation system reduced the average co concentrations by %, from ppm to ppm, and average moisture content by %, from . g of water per kg of dry air to . g of water per kg of dry air. the actively ventilated classroom had on average a % lower concentration of airborne particles sizing under μm than the unventilated classroom as shown in figure [ ] . [ ] . displacement ventilation systems, such as natural ventilation, naturally assisted extraction ventilation and continuous mechanical extraction ventilation, appear to be the most promising ventilation solution in terms of reducing the spread of viruses and other pathogens indoors this is mainly due to the lower air flow velocity, non-turbulent air flow characteristics and a much lower likelihood of air mixing occurring within the ventilated spaces. this observation is investigated further using computational fluid dynamics in the next section. two of the above listed displacement ventilation systems have been selected for further analysis of room specific airflow dynamics and its potential impact on exhaled droplet and pathogen distribution through occupied spaces to assess their impact on the potential spread of infection: ) roof mounted natural ventilation with heat recovery and ) the façade mounted naturally intelligent ventilation system with heat pump. due to their similarity to each group of the natural ventilation systems mentioned above, we consider the results of the cfd modelling to be representative across the roof mounted and façade natural ventilation range. both of the selected systems appear thermally and physically well designed to be able to passively ventilate occupied spaces whilst recovering heat through either passive or active methods, using wind speed, wind pressure and air buoyancy to drive the air flow. under normal circumstances, a natural ventilation strategy has many benefits over mechanical or fan-powered systems, including lower carbon emissions, reduced operating costs, and ease of installation. according to the research mentioned above, it also appears to have measurable advantages when it comes to reducing the risk of infection spread indoors -this is further investigated below. to aid in the assessment of expected airflow and classroom comfort levels achieved in-situ for two displacement systems, a computational fluid dynamics study has been carried out. the cfd study aims to quantify the steady state performance within a school classroom for the following two natural ventilation systems with heat recovery: ventive windhive and ventive active. the overall ventilation performance will be quantified in terms of the simulated co concentration levels within the classroom alongside more specific modelling results of the temperature and, most importantly, air velocity and airflow characteristics. the global setting for the analysis of the two ventilation systems is that of a fully enclosed classroom, with dimensions h x d x w (mm), where: h is height, d is depth and w is width. the classroom is occupied by seated students with corresponding chairs and tables as shown in figure for the ventive windhive system. to enable a true representation of the natural ventilation system's working environment an additional region is included to represent the outside ambient with dimensions , h x , d x , w (mm). although the two ventilation systems will be modelled in the same working environment, the configuration and set-up of each unit is different, and therefore each will be presented separately for clarity. the windhive system, shown in figure , is a roof-mounted unit, with the indoor diffuser located at an arbitrary central location such that it is not positioned directly above any person. the ventive active system, shown in figure , has a different buoyancy driving set-up utilising the external wall of the classroom with the supply unit located no more than mm from the floor level and the extract unit located at the top of the room (preferably . m from the finished floor level or higher). following the finalisation of the geometry an idealised room specific d model of each set-up was created using cad software before being imported into star-ccm+ v . . to help reduce the computational expense of the simulations in terms of mesh and physics several modelling assumptions were made, these are listed below:  simplified geometry for the children and desks to act as the sole obstacles in the classroom  u value of . w/m /k applied to the walls to account for an average heat flux  each child assumed to act as a heat source producing w (equating to a total heat source of w)  wind, solar gain and equipment loads including lighting and airtightness are ignored  grill losses located on the invent active and passive are accounted for through specification of a porous medium with an effective opening of % and a porous inertial (α) and viscous (β) resistance of . and . m/s, respectively  to achieve a realistic outside ambient a small constant velocity field ([ . ] m/s) is active across the length of the domain, in order to account for natural wind and to help initiate a flow solution. this is adopted also for the additional ambient region within the invent passive simulation to account for the open window.  ambient and initial temperature field is equal to °c  initial classroom co level is set at ppm whilst the ambient/environment is equal to ppm  each child is presumed to provide a co release rate of . m /h equating to a bulk class co supply of . m /h the aim is to complete two independent cfd simulations, one for each of the natural ventilation systems. each simulation will operate with a multi-component gas as the working fluid, separated such that the co and other components of air are modelled independently. the chosen software package for all simulations is that of the commercial cfd package, starccm+ v . , supplied by siemens. this is a well validated cfd code that is widely used throughout both industry and academia. to provide a solution domain suitable for the cfd solver the d model must be discretised into a series of smaller fluid volumes by successively splitting nominally hexahedral cells until a desired cell size is achieved. the accuracy of a given simulation is largely controlled by the size and quality of the cells and therefore a number of refinement regions in areas of interest were created. it should also be noted that a grid independent solution is achievable, at this point further reduction of the cells will only account for a higher computational cost instead of improved accuracy. all meshes presented here have been generated using a trimmed cell mesh with local refinement regions and prism layers to account for the near wall effects. each mesh is illustrated below with the total number of cells for each specified. the total number of cells used for the windhive model is . million. an image of the mesh for windhive is shown in figure . the total number of cells used for the invent active model is . million. an image of the mesh for windhive is shown in figure . figure shows the velocity scenes for the two cases for vertical and horizontal cross-sections. for both systems it can be seen that the greatest flow speeds are experienced at the inlet and outlet locations, with both the ventive windhive and ventive active showing the greatest velocities regarding the inlet stream. it also provides a top down projection of a m velocity slice, directly inline with the heads of the seated students. this image shows more clearly the locations and magnitude of the incoming air stream of the windhive. it must be noted that the ventive active's inlet is below this point. table indicates the mass and volume flow rates calculated at the inlets and outlets of the two respective systems. the greatest flow rate is provided by the windhive ( l/s) even without the wall purge opening whilst the active is somewhat lower in the fully passive operation mode ( l/s). the stated flow rates relate to values of . l/s (ventive windhive), and . l/s (ventive active) per person with reference to children and teacher. an important factor aiding in achieving a desired level of co within a room is the total rate of air change in one hour. based on a classroom area of m the estimated number of air changes per hour for the two configurations (based on the inlet flow rates provided in table ) are calculated as: • windhive = . air changes per hour • ventive active = . air changes per hour stagnation regions are possible for such systems according to the model whereby figure shows the velocity profiles. however, people within such environment tend to stand up and move around slightly which will induce further air movement within the stagnated air regions. the cen report cr ventilation for buildings states that if seated occupants are the only source of pollution then the co concertation should be below ppm for category a, ppm for category b and for category c, where the outdoor ambient level is quoted as ppm. category a represents a high level of expectation, recommended for fragile and sensitive persons like young children, elderly, sick or handicapped persons. category b is the normal level of expectation that should be considered for new buildings or renovations. category c represents moderate level of expectation that may be used for existing buildings [ ] . expectedly the windhive configuration provides the most air changes over a given period due to its higher flow rates, and this correlates to a more favourable mass fraction of co , as shown in figure figure . although it should be noted that despite having a lower rate of air change, the ventive active reduces the levels of co comparably to the windhive. both these systems appear to be able to maintain the initial co conditions through the regular exchange and circulation of air throughout the room. the distinct airflow profiles of both natural ventilation systems shown above are of great interest in relation to spread of coronavirus and other pathogens indoors. the supplied fresh air is observed to distribute evenly at low level (well below the breathing, and especially exhaling, area) at a higher volume but lower velocity than fan induced ventilation (thus is much less likely to pick up heavier droplets already dropping to the floor) while the stale air appears to move steadily upwards before being exhausted out of the building, with no observed mixing indoors. this, in combination with the low observed co levels (which are a good proxy for contaminated, exhaled air) as well as the prior research listed above (where, unlike mechanical and recirculating ventilation, the cloud of droplets and particles is not pushed around the room but instead travels in a fairly direct line from window to the exhaust vent, resulting in fewer people being exposed to it), indicates that natural ventilation has a much lower risk of spreading the droplet and aerosol borne infection indoors than other ventilation methods. this displacement and stacking effect in interesting also since it protects the occupant regardless of the configuration off the room: for example, younger children often sit around large table instead of rows. by moving the stale air upward the concentration at the breathing level is reduced as well as the infection risk. airborne disease transmission is highly contagious in enclosed environments and especially in buildings with inadequate or inappropriate ventilation systems. the theory shows that small droplets of less than µm in diameter have the potential to remain in the air for hours since their terminal velocities would be at mm/s, depending on various characteristics and conditions at the time. with the unprecedented pandemic of the covid- spreading through the society at an extremely fast pace, many academics and industry professionals are raising the question of whether the current ventilation strategies are outdated and inadequate for such contagious diseases. even though the widely accepted mechanism of sars-cov- transmission to the date of writing this article has been through droplet borne pathways, the who is accepting the possibility that the deadly virus could be transmitted through the air. many research studies have shown that with appropriate ventilation, the risk of transmission is greatly reduced, further emphasizing the need for research into and adaptation of current ventilation methodologies. furthermore, an insufficient ventilation rate and inappropriate ventilation strategy (mixing of in-room or recycled air, poor mechanical ventilation maintenance) have been linked to degraded health outcomes for the users of high occupancy buildings. this includes facilitated airborne transmission of diseases, sick building syndrome, increased sickness absence and reduced cognition. this paper has reviewed widely used ventilation strategies adopted in high occupancy buildings such as schools and offices. the currently accepted approach to reducing airborne disease transmission recommended by various industry associations (ashrae, cibse) as well as the world health organisation is to increase the ventilation rate using plentiful fresh air to dilute the contaminant to a safe level. in many schools and other high occupancy buildings, the target ventilation rates are rarely met. the benefits of better health and attendance and resultant economic outcomes largely outweighed the capital investment of installing, renovating, or retrofitting appropriate ventilation solutions, even before the covid- pandemic. as can be seen above, the most commonly used ventilation approaches are inadequate when it comes to lowering airborne transmission risks. different strategies were reviewed with cfd examples to consider their impact on the pathogen propagation indoors. it seems beyond doubt that recirculating ventilation strategies should be avoided as they limit and prevent the dilution of harmful particles while also facilitating the distribution of stale, possibly contaminated air throughout occupied spaces. as the occupancy of the room increases (expressed in time and number of people), so does the exposure. mixing ventilation approaches are also disadvantageous as they may increase the range of infectious particles within the room and the range of sizes of particle that can sustainably remain airborne. displacement ventilation with a generously sized natural inlet is preferred as it can move stale, contaminated air directly to the exhaust of the room in a laminar fashion whilst the concentration of small droplets and airborne particles in the indoor air is significantly reduced. the mode of ventilation can be achieved by either fully natural ventilation or natural supply with a mechanical extraction strategy. natural displacement ventilation offers many other advantages such as reduced power consumption and low maintenance costs. on the other hand, some natural ventilation systems may lack controllability or a heat recovery, both of which can be addressed through careful system selection (ensuring sensor-based responses as well as automatic actuators for the supply and exhaust openings) and good design practice. mechanical solutions have an energy consumption penalty due to the use of fans and may require larger capital investment and maintenance costs. if balanced mechanical systems are to be considered, a significant, research based, re-design effort is required with larger ductwork and openings to avoid high air velocity and in-room mixing ventilation dynamics which currently can defeat the purpose of ventilation by increasing the concentrations and the range of the infectious particles. it has also been demonstrated that the use of filters can prove detrimental when not properly maintained and regularly cleaned or changed. on the other hand, the use of mouth and nose covering, such as ply masks for example, directly impact the quantity of droplets and particles emitted by the occupants in the indoor volume. in practice, the constant use of these masks can reduce the comfort level of the occupants and may be difficult to enforce in high occupancy buildings since it relies on the cooperation of each individual and following procedures. whereas, the implementation of a natural displacement ventilation systems passively offers an additional form of transmission risk reduction. two ventive natural displacement ventilation systems were chosen for study using cfd simulations. the large air volume combined with low airflow speed allow sufficient quantities of fresh air to be supplied into the space, distributing evenly through the bottom of the room and gradually displacing the stale air to the top of the space thanks to the buoyancy-driven stack effect. the advantages of this type of ventilation strategy is that it can significantly reduce the risk of airborne disease transmission. it provides large volume ventilation at low air speed, which facilitates a stratification effect. this stratification effect along with the appropriate placement of air inlets and outlets allow a natural and almost universal upward flow of air to the top of the room and out through the appropriate exhaust vents. this restricts the horizontal movement of airborne particles which contain pathogens that are produced when infected individuals breath, speak or cough, capturing the smaller droplets to migrate almost upwards, while allowing larger droplets to fall out of breathable level air, vastly reducing the risk of disease transmission via indoor air. the large volume of fresh air supplied into rooms lowers the concentration of other contaminants in the room and increases the iaq to desired levels. as an added benefit, in both closely studied systems, the heat recovery capability and dynamic, connected controls both increase comfort levels, making the high air refresh rate more bearable for occupants, and enable remote adaptation of ventilation provision, which improves the response of facilities managers to risk levels. building services of high occupancy buildings must be better adapted as a matter of urgency to facilitate the reduction of disease transmission resulting from inappropriate or inadequate ventilation. the covid- pandemic has exposed areas requiring urgent development to protect both our health, wellbeing and the economy by providing safe indoor environments for employees or students. this paper has demonstrated possible routes for indoor disease transmission, the mechanisms in which diseases can spread, facilitated by conventional ventilation systems, the gaps in current knowledge and technologies and areas of interest for future research and development. although many cases of disease transmission can be reduced by social distancing or wearing the recommended ppe, the air surrounding us indoors requires much better management to safely remove air borne pathogens. many of the current ventilation strategies that rely on centralised air distribution and ceiling level supply or recirculation can provide the optimum conditions for rapid disease spread in high occupancy buildings. on the other hand, displacement ventilation strategies, such as the natural ventilation or naturally assisted ventilation explored above, can provide an effective starting point for reclaiming our buildings for safe use. however, significant gaps remain in the knowledge needed for the development of more personalised ventilation mechanisms at an economic level to allow for adaptation of already installed ventilation systems to help mitigate the risk of infections in existing buildings. none world health organization, coronavirus disease (covid- ) situation reports epidemiological characteristics and transmission model of corona virus disease in china mass masking in the covid- epidemic: people need guidance advice-on-the-use-of-masks the flow physics of covid- size distribution and sites of origin of droplets expelled from the human respiratory tract during expiratory activities the coronavirus pandemic and aerosols: does covid- transmit via expiratory particles? an analysis of the transmission modes of covid- in light of the concepts of indoor air quality factors involved in the aerosol transmission of infection and control of ventilation in healthcare premises role of 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transmission indoor airflow simulation inside lecture room: a cfd approach cfd modeling approach for turbomachinery using mrf model | learncax air recirculation and sick building syndrome: a blinded crossover trial grounding hvac motor shafts: protecting bearings and lowering repair costs -construction canada mixing ventilation i simscale mechanical ventilation simulation and optimization with sav systems ventilation filters and indoor air quality: a review of research from the international centre for indoor environment and energy, indoor air sustainable ventilation strategies in buildings: cfd research performance of a natural ventilation system with heat recovery in uk classrooms: an experimental study makris-makridis, s. consultant, passive ventilation with heat recovery in an urban school: performance in use performance of a natural ventilation system with heat recovery in uk classrooms: an experimental study towards sustainable, energyefficient and healthy ventilation strategies in buildings: a review the effect of ventilation on air particulate matter in school classrooms on the definition of ventilation requirements in iaq standards -a method based on emission rates of pollutants on the definition of ventilation requirements in iaq standards -a method based on emission rates of pollutants rua luis reis santos key: cord- -rsifxvtj authors: lim, meng-kin title: global response to pandemic flu: more research needed on a critical front date: - - journal: health res policy syst doi: . / - - - sha: doc_id: cord_uid: rsifxvtj if and when sustained human-to-human transmission of h n becomes a reality, the world will no longer be dealing with sporadic avian flu borne along migratory flight paths of birds, but aviation flu – winged at subsonic speed along commercial air conduits to every corner of planet earth. given that air transportation is the one feature that most differentiates present day transmission scenarios from those in , our present inability to prevent spread of influenza by international air travel, as reckoned by the world health organization, constitutes a major weakness in the current global preparedness plan against pandemic flu. despite the lessons of sars, it is surprising that aviation-related health policy options have not been more rigorously evaluated, or scientific research aimed at strengthening public health measures on the air transportation front, more energetically pursued. air transportation has undoubtedly been a boon to humankind -bringing together peoples, cultures and values, and profoundly changing the way we live. but it has also greatly aided the global transmission of infectious disease. in the old days, geographical distance provided a measure of protection as signs and symptoms had time to develop and those afflicted could be screened at border entry points. today, with hardly an airport unreachable within hours from any point on our planet, the speed -and pattern -of microbial movements has altered dramatically. in , the institute of medicine report emerging infections: microbial threats to health in the united states correctly identified "microbial adaptation and change" and "expanding international travel and commerce" as two of the major factors contributing to disease emergence and re-emergence [ ] . severe acute respiratory syndrome (sars), in retrospect, epitomized this new model of disease outbreak. the previously unrecognized sars-cov coronavirus mysteriously surfaced in guangdong province, china, in november , simmered there for three months, and arrived in hong kong on a jet plane. from that busy aviation hub, it quickly spread to vietnam, singapore, and canada, eventually afflicting countries and taking lives [ ]. thankfully, sars did not progress to a full-blown pandemic as was widely feared. for reasons that are still unclear, the disease fizzled out, leaving us unsure as to whether we licked it or were just plain lucky. with avian flu now on everybody's mind, it is worth recalling the grim images of those dark days not so long ago -when some of the busiest airports in the world lay deserted as panic-stricken, would-be travelers stayed home. anxious aircrew clamored for adequate protection at work [ ] while medical and airline industry officials rejected the notion that the virus could be transmitted on airplanesuntil the world health organization (who) weighed in to say that travelers seated within two rows of an infected person could be in danger. we now know that passengers sitting eight rows away are not any safer, and that out of a total of commercial air flights investigated for carrying sars infected passengers, five have been found to be associated with probable onboard transmission of sars, involving passengers in all [ ] . the first in-flight transmission of sars occurred in a female flight attendant who caught it from a family of three singaporeans incubating the virus on a singapore airlines flight between new york and frankfurt on march [ ] . soon after, more cases were reported, such as when a cluster of thirteen passengers from hong kong was infected during an air china flight to beijing on march , with a year fellow passenger believed to be the source [ ] . then there was the pandemonium which broke when a certain -year-old man with symptoms of sars was discovered to have flown on lufthansa from hong kong to munich, barcelona, frankfurt, london, munich again, frankfurt again, and back to hong kong before entering a hospital on his own accord. on april , the hong kong department of health had to desperately appeal for passengers and aircrew from all seven flights to consult their doctors [ ] . as the fear of sars became more contagious than the contagion itself, stock markets tumbled and billions of dollars were lost. coming close at the heels of / and the iraq war, sars dashed hopes of recovery for the ailing airline industry. the latter is understandably not saying very much these days about any avian flu contingency plans they might have; one certainly hopes that appropriate preventive measures are being put into place. but that may be just the problem: what is the evidential base for effective public health interventions in the aviation industry, and how rigorously have the relevant aviation policy options been evaluated in the intervening years since the sars episode [ ] ? take thermal scanners for instance -first deployed in singapore's changi airport and enthusiastically adopted by other "high-risk" airports around the world, in answer to the international civil aviation organization's (icao) call for mass-screening of arriving and departing passengers and crews for raised temperature [ ] . it was an innovative application of military technology to address an urgent need. to date, however, we are none the wiser regarding the sensitivity, specificity, or cost effectiveness of this screening tool for sars, much less its usefulness for influenza. about all we know is that canadian officials reportedly screened million passengers with thermal scanners at an estimated cost of can$ . million, without detecting a single case of sars [ , ] . no one knows for sure what preventive measures all airlines and airports of the world should uniformly adopt in order to mitigate the spread of infectious diseases by air. the who's global influenza preparedness plan merely acknowledges, without elaboration, that "air travel might hasten the spread of a new virus, and decrease the time available for preparing interventions" [ ] while icao's current website repeats the same general measures that it had posted for sars [ ] . with the threat of an influenza pandemic looming, which by all accounts will make sars pale in comparison, all we have to go by today is the same generic advice on hand washing and personal hygiene for airline workers, and a negative assurance of sorts from the us centers for disease control and prevention (cdc) that "there is no evidence that avian influenza is spread through contact with baggage, packages, or other objects..." [ ] . apart from the desperate culling of affected poultry, much of the current global preparatory activities against avian flu pandemic revolve around surveillance, diagnostics, hospital infection control, vaccines production, and stockpile of antiviral agents. these efforts are necessary and laudable, but might they not also reflect the "medical" bias of existing paradigms? the sars episode had highlighted the importance of enlisting travel industry workers and travelers as frontline fighters in the global response. if and when sustained human-to-human transmission of h n becomes a reality, the world will no longer be dealing with sporadic avian flu borne along migratory flight paths of birds [ , ] but aviation fluwinged at subsonic speed along commercial air conduits to every corner of planet earth. surely any global battle plan against pandemic flu should entertain the notion of stopping the enemy at the gates, or along the corridors of its advance, before it reaches our homes, hospitals and clinics? alas, the who report avian influenza: assessing the pandemic has dismally concluded that "if only a few countries are affected, travel-related measures, such as exit screening for persons departing from affected areas, might delay international spread somewhat, but cannot stop it. when large numbers of cases occur ... entry screening at airports and borders will have no impact" [ ] . granted, if a substantial portion of transmission occurs during the incubation or asymptomatic phase of disease, entry screening is unlikely to be effective in preventing or delay-ing an epidemic resulting from the importation of influenza [ ] ; and granted, the short time lag for scrambling upon discovery of a sentinel case will pose serious challenges to effective quarantine and contact tracing measures; but are we acquiescing on this critical front too readily? sensible actions depend on knowing precisely what is going on, which in turn depends on good quality data. the fact of the matter is, we have simply not invested enough in the kind of multidisciplinary research needed, involving epidemiology [ ] , mathematical modeling [ ] , computational simulation [ ] , electronic tracking [ ] , and biological detection technology [ ] , to name a few, to elucidate the dynamics of microbial transmission associated with air travel, be it in aircraft cabins, toilets, or transit lounges. four years after sars, and we are no clearer regarding the complex spatial interactions of travelers converging on busy air terminals; or how best such human traffic may be channeled to minimize the risk of viral transmission; or what impact stringent screening impositions would have on passenger reaction and behavior. if the economic and wider arguments for maintaining continuity of air traffic flow (without which many nations could find their ability to keep going during a pandemic severely impaired) are not well researched and understood beforehand, arbitrary and capricious actions such as panic closure of borders, possibly leading to an abrupt global shut-down, could well result. the current view is that under most scenarios, restrictions on air travel are likely to be of little value in delaying the proliferation of epidemics, unless almost all travel ceases very soon after epidemics are detected [ ] . but if the technology for picking out passengers capable of transmitting deadly pathogens and setting off killer epidemics does not exist today, should we not be pursuing it as energetically as we do, the technology for stopping terrorists from boarding a plane? against a conservatively estimated us$ billion a year that a human pandemic of avian influenza could cost the global economy [ ] , not to mention the incalculable cost in terms of human lives [ ] , it seems incredible that the aviation lessons of sars have not led to an acceleration of scientific research and health policy evaluation aimed at strengthening public health defenses on the air transportation front. to put things in perspective, we are engaged in a millennia-old, interspecies struggle between man and microbes. while the unseen enemy thrives because of its capacity for relentless adaptation and opportunistic spread, our own record of survival and progress owes much to the fact that at every critical turn, we have somehow managed to ask the right questions and looked hard enough at the right places for the right answers -be it in quarantine and vaccination strategies or an armamentarium of antibiotics and antiviral agents. in the coming epic battle against pandemic flu, the stakes have never been higher. if our strategies (read: health policies) are to work, they must be reliably informed by accurate intelligence (read: health research) which must cover all bases. given that international air travel is the one feature that most differentiates present day transmission scenarios from those in , it is surely relevant to ask, just how flu-ready are the airlines and airports of the world? the call is for more scientific research devoted to this critical front. two aspects deserve particular attention: (a) the science of transmission of infection between individuals and nations via air transportation and (b) the rigorous examination of policy options, based on the evidence and taking into consideration the economic trade-offs required. resolving the tension between these aspects (and between the concerns of doomsday modelers and real-world policy makers in government, world health and air transport organizations) will improve the confusing impasse we seem to be in at present. emerging infections: microbial threats to health in the united states. committee on emerging microbial threats to health. institute of medicine the association of flight attendants: flight attendants demand protection from sars. afl-cio press release transmission of infectious diseases during commercial air travel sars and occupational health in the air. occupational and environmental medicine transmission of the severe acute respiratory syndrome on aircraft using lessons from the past to plan for pandemic flu icao takes action on sars. aviation international news border screening for sars. emerg infect dis quarantine and isolation: lessons learned from sars. a report to the centers for disease control and prevention institute for bioethics world health organization department of communicable disease surveillance and response global influenza programme: who global influenza preparedness plan-the role of who and recommendations for national measures before and during pandemics airport readiness for possible pandemic benefits from experience with sars guidance for airline cleaning crew, maintenance crew, and baggage/ package and cargo handlers for airlines returning from areas affected by avian influenza a (h n ) highly pathogenic h n influenza virus infection in migratory birds avian flu: h n virus outbreak in migratory waterfowl world health organization: avian influenza: assessing the pandemic threat entry screening for severe acute respiratory syndrome (sars) or influenza: policy evaluation global epidemiology of influenza: past and present a mathematical model for the global spread of influenza assessing the impact of airline travel on the geographic spread of pandemic influenza uk home office publictechnology.net. e-borders will fence uk & use it to track and identify passengers research and development in biosensors delaying the international spread of pandemic influenza avian and human pandemic influenza-economic and social impacts bird flu may kill m, warns un the author(s) declare that they have no competing interests. key: cord- -wk cf b authors: corpus-mendoza, asiel n.; ruiz-segoviano, hector s.; rodríguez-contreras, sergio f.; yañez-dávila, david; hernández-granados, araceli title: decrease of mobility, electricity demand, and no emissions on covid- times and their feedback on prevention measures date: - - journal: sci total environ doi: . /j.scitotenv. . sha: doc_id: cord_uid: wk cf b the spread of coronavirus disease (covid- ) on has affected human activities in a way never documented in modern history. as a consequence of the prevention measures implemented to contain the virus, cities around the world are experiencing a decrease in urban mobility and electricity demand that have positively affected the air quality. the most extreme cases for cities around the world show a decrease of , , and % in mobility, electricity demand, and no emissions respectively. at the same time, the inspection of these changes along the evaluation of covid- incidence curves allow to obtain feedback about the timely execution of prevention measures for this and future global events. in this case, we identify and discuss the early effort of latin-american countries to successfully delay the spread of the virus by implementing prevention measures before the fast growth of covid- cases in comparison to european countries. as hypertension (shin et al., ) , cardiovascular disease (mann et al., ) , chronic pulmonary disease (euler et al., ) , and a diminished response to viral and bacterial infections (ciencewicki and jaspers, ) . moreover, it is also proposed that the same pollutants can participate directly in the transmission of covid- as a coronavirus carrier (bontempi, ; sasidharan, et al., wu et al., ; zoran et al., ) . however, this last observation is not yet demonstrated, since high levels of air pollutants are usually evident in cities with high human population and hence, high human interaction (pisoni and van dingenen, ) . therefore, in this article, we conduct a broad evaluation of the impact of the covid- pandemic on the urban mobility, electricity consumption, and no emissions as a whole for several countries around the world rather than for a single region or sector affected as in previous literature. at the same time, we analyse the evolution of confirmed covid- cases and compare them with the start of prevention measures and changes in sectors affected in different countries to discuss the effectiveness in time in which they are applied. we think that the combination of these two approaches can not only explain how the pandemic affects human activities and the environment, but also how these changes allow us to obtain feedback of the prevention measures applied for this and future events. are obtained from the global health expenditure database (who ghed, ) . these datasets are used to find the date of the th covid- case (d ) for each country in order to evaluate their daily incidence (i c ) and death incidence (i d ), which show the quantity of confirmed cases and deaths per habitants respectively. then, it is possible to obtain the incidence rate (i cr ) from the slope of i c versus time curve during the fastest infection period, as well as the threshold day (t d ) from the x-axis intercept of the slope, which estimates the quantity of days after d in which the infection grows the fastest, as shown in fig. for italy. this analysis of the i c curve is inspired by the evaluation of the turn-on voltage and series resistanc of electronic devices such as diodes, and it is a simple approach to assess and compare the evolution of i c between countries. here, i cr is useful to evaluate the spread speed of the virus, whereas t d identifies the moment in time in which fast growth starts. the combination of these parameters allow to estimate and discuss the effectiveness of the actions implemented to stop the spread of the virus, and to plan for future and similar events. however, the disadvantage of this method is its lagging nature, since the fast growth region of the i c curve is often confirmed at late stages of the pandemic. another dataset used is the #covid government measures dataset (acaps, ), which collects daily country-level data from news, social media, and articles about the prevention measures implemented around the world to fight the pandemic. these measures are classified in categories in the original dataset, however, we reclassify them and discuss them in terms of their effects on health, and economy, but mainly on the environment by analysing changes in mobility, electricity generation, and air quality index (aqi) before and after the pandemic. here, the mobility around transit stations such as subway, bus, and train stations is selected as the parameter to study rather than mobility around residential areas, grocery shops and pharmacies, or retail and recreation areas since transit stations usually involve a high concentration of people. this information is obtained from the covid- community mobility reports by google (google, ) and presents the percentage change in the number of people visiting transit stations compared to a baseline level, which is the median value for each day of the week during january rd and february th, . also, hourly and daily electrical power consumption is obtained for countries from their respective transmission system operator (tso) in order to evaluate their daily percentage change in electrical energy consumption between march st and june th for and . here, the daily data is adjusted to compare days of the week rather than dates. this adjustment is applied because power consumption during the weekends is usually different than during the weekdays. data for most european countries are available at the european network of transmission system operators for electricity (entsoe, ) , whereas other sources are j o u r n a l p r e -p r o o f journal pre-proof used for italy (terna, ) , spain (red eléctrica de españa, ), russia (soues, ), uk (elexon, ), india (andrew, and posoco, ) , japan (tepco, ), singapore (ema, ), turkey (exist, ), bolivia (cndc, ), brazil (ons, ), chile (cen, ), colombia (xm, ), mexico (cenace, ), peru (coes, ), uruguay (adme, ), and usa (eia, ). finally, daily aqi index for no measured by monitoring stations is analysed for capital cities around the world to compare the percentage change between the first half of and . here, we select capital cities assuming that they represent a significant amount of population and human activities affected by the pandemic. also, no is chosen as the air pollutant to study instead of other pollutants such as co, co , so , pm . , or pm , since most of the no in cities is produced by combustion vehicles while driving, a common activity worldwide. these and other environmental data are available at the world air quality index project (waqip, ). j o u r n a l p r e -p r o o f another point to consider besides the development of the pandemic around the world is the impact that it has in modern life, since the execution of prevention measures implies an adjustment on the usual human activities, and therefore, the environment. some of the measures applied until now are classified as shown in fig. , with many of them affecting more than one category. particularly, the mobility of people around transit stations is clearly lower in terms of percentage for all countries compared to their baseline levels at the beginning of the year, as shown in fig. . also, the average mobility curves by continent reveal that the drop in mobility starts in the middle of march for europe, asia, and the americas, reaching levels of approximately - % compared to the baseline, whereas the change in africa is lesser and later. however, there is a significant difference in the average d by continents, since the average mobility curve in europe is still close to the baseline before its average d . this means that the pandemic in that region had already started by the time mobility measures were applied, whereas some asian countries and most of the americas and africa had already restricted their mobility similarly to mobility, the electrical energy consumption around the world is also affected by the pandemic, as shown in fig. , which reveals a decrease of the average electricity consumption curve by continents since the middle of march, compared to the values of despite people spending more time at their homes. therefore, we attribute this change to a decrease of industrial activity, closure or partial operation of transit stations and retail sector, as well as flexible times to work from home. fig. also shows the dates in which some countries recommended or enforced their citizens to stay at home. these dates do not differ significantly between the nations analysed, which once again demonstrates an early action by most of latin-america. finally, the percentage change and absolute change in terms of gwh is shown in fig. d ), where it is observed that electricity consumption decreased in most countries analysed j o u r n a l p r e -p r o o f activities which are probably not heavily affected by the pandemic, which could explain the difference in electrical consumption compared to the other countries. supplementary material (fig. s ). finally, fig. shows the percentage decrease in the aqi for no , which is a measure of the air pollution by no , where higher values represent a higher risk to health. particularly, the aqi for no in cities depend mainly on the combustion of fossil fuels and therefore, driving. also, the aqi for this and other air pollutants is affected by the weather seasons, with winter slowing the dilution and dispersion of pollutants . this explains the decrease in the it is now observed that the prevention measures applied limited human activities and caused the decrease of urban mobility as well as electricity consumption, which led to a decrease of no emissions. therefore, the appearance of the virus paradoxically had a positive effect on the air quality to the point that many authors consider the decrease of no has saved more human lives than covid- has claimed (dutheil, ) . some studies now indicate that to premature deaths per month have been avoided in china due to an improved air quality , whereas the total covid- deaths in the same country are less than . however, the reopening of human activities after the lockdown demonstrate that the improvement in air j o u r n a l p r e -p r o o f quality is unsustainable (zambrano-monserrate), since pollution levels are back to the normal trend compared to previous years (liu et al., ) . these observations should serve as the basis to design and implement actions oriented towards the improvement of human health and air quality, for example, traffic control, investment in public transportation, replacement of face-toface work with online work, renewable energy projects, electric vehicles infrastructure, and more. detailed data for rome, italy in the inset. philippines had an approximate % decrease of mean no quality index for the period evaluated. details by country in supplementary material (fig. s a and fig. s b ). in summary, the adoption of prevention measures to mitigate the impact of covid- on human health has caused a decrease of mobility in transit stations as well as a decline in electricity demand around the world. as a consequence, the air quality has been positively j o u r n a l p r e -p r o o f affected as observed by the decrease of no in multiple capital cities. therefore, these observations can be used to implement traffic control programs, investment in public transportation, replacement of face-to-face work with online work, electric vehicles infrastructure, and other green energy projects oriented towards the improvement of air quality and, therefore, human health. at the same time, the analysis of changes in mobility and electricity demand along the evaluation of t d and i cr from the i c curves allow to discuss the timely execution of the prevention measures, which works as a feedback to consider and plan actions for the current pandemic or future global events. here, it is observed that european the assessment capacities prpject. #covid government measures dataset administración del mercado eléctrico first confirmed detection of sars-cov- in untreated wastewater in australia: a proof of concept for the wastewater surveillance of covid- in the community india's daily electricity generation covid- lockdown effects on air quality by no in the cities of barcelona and madrid (spain) changes in u.s. air pollution during the covid- pandemic understanding european network of transmission system operators for electricity energy exchange istambul. transparency platform covid- : air pollution remains low as people stay at home. air qual the influence of covid- on air quality in india: a boon or inutile the short-run and long-run effects of covid- on energy and the environment covid- community mobility reports modified from original picture on freepik covid- , city lockdowns, and air pollution: evidence from china. the hong kong university of science and technology temporary reduction in daily global co emissions during the covid- forced confinement spatiotemporal impacts of covid- on air pollution in california effects of temperature variation and humidity on the death of covid- in wuhan air pollution and hospital admissions for ischemic heart disease in persons with congestive heart failure or arrhythmia covid- pandemic and environmental pollution: a blessing in disguise? assessing nitrogen dioxide (no ) levels as a contributing factor to coronavirus (covid- ) fatality operador nacional do sistema elétrico assessing nitrogen dioxide (no ) levels as a contributing factor to coronavirus (covid- ) fatality", by ogen power system operation corporation limited a vulnerability-based approach to human-mobility reduction for countering covid- transmission in london while considering local air quality effect of restricted emissions during covid- on air quality in india association between road traffic noise and incidence of diabetes mellitus and hypertension in toronto, canada: a population-based cohort study amplified ozone pollution in cities during the covid- lockdown system operator of the unified energy system (Системный оператор Единой энергетической системы) last time accessed on jult th severe air pollution events not avoided by reduced anthropogenic activities during covid- outbreak world air quality index project emergency committee regarding the outbreak of novel coronavirus ( -ncov) who coronavirus disease (covid- ) dashboard world health organization. global health expenditure database last time accessed on spatiotemporal variations of air pollutants in western china and their relationship to meteorological factors and emission sources indirect effects of covid- on the environment assessing the relationship between ground levels of ozone (o ) and nitrogen dioxide (no ) with coronavirus (covid- writing -original draft, writing -review & editing. hector s. ruiz-segoviano: data curation, formal analysis, investigation, visualization, writing -review & editing. sergio f. rodríguez-contreras: data curation, formal analysis, investigation, visualization, writing -review & editing. david yañez-dávila: data curation, formal analysis, investigation, writing -review & editing. araceli hernández-granados: data curation, formal analysis, investigation, writing -review & editing ancm thanks the support of cátedras by consejo nacional de ciencia y tecnología key: cord- -y b pe authors: xu, zhonglin title: characteristics of air filters date: - - journal: fundamentals of air cleaning technology and its application in cleanrooms doi: . / - - - - _ sha: doc_id: cord_uid: y b pe air filter is the main equipment in the field of air cleaning technology, and it is an indispensible equipment to create the clean air environment. so it is necessary to know the characteristic of air filters and its design principle so as to use it correctly and effectively. note: when the measured efficiency value meets the requirement for two types at the same time, the higher type is used for assessment sub-high-efficiency particulate air filter. it is used as final filter in the cleanroom to obtain a certain class of air cleanness (please refer to chap. ), prefilter for hepa filter to further improve the cleanness of supply air, and final filter of fresh air system to improve the fresh air quality. it is mainly used to capture submicron particles with diameter less than μm, which is similar as that of high-efficiency filter. hepa filter. it is mainly used as final filter in cleanroom. the purpose is to provide various cleanness classes corresponding to . μm, while its efficiency is usually tested with particle diameter . μm. if cleanness class corresponding to . μm is needed, its efficiency should be tested with particle diameter . μm and it is called ulpa filter. it is usually used as the final filter. there are several types of roughing air filters and medium-efficiency air filters, such as panel-type air filter, bag air filter, and folded media-type filter. it's better to choose air filters with larger filtration area. there are several types of high-efficiency filters, such as bag filter, cartridge air filter, and folded media-type filter. there are several types of sub-high-efficiency particulate air filters, such as cartridge air filter and folded media-type filter. the former is a type of low-pressure drop, which is a patent product of institute of hvac of china academy of building research. there are several types of hepa filters, such as folded media-type filter which could be classified as separator hepa filter and no-separator hepa filter. table . presents the comparison between air filter standards home and abroad. this kind of comparison is only for information and may not match well, so care should be taken before selection of air filters. the foreign classification methods for general ventilation air filters are quite confusing, which will not be introduced here [ ] . since , iest classified hepa filters into two categories. one is hepa filter, and the other is ulpa filter. afterwards these terms are used frequently. the most important four indexes to evaluate the performance are face velocity (or filtration velocity), efficiency, pressure drop, and dust holding capacity. there are also other indexes, such as weight, energy consumption, and regeneration feature, which are mainly related to filter media. it is important to choose which kind of filter media is used to make air filters. except for the impacting factor of filter media, filter structure is also one of the important impacting determinants for the performance of air filters. for example, both the pressure drop and dust holding capacity are different, when the same filter media is used to make panel filter, bag filter, or wedge filter. so it is another important link to find reasonable optimal structure for air filter. these four performance indexes are introduced in the following section. both face velocity and filtration velocity can be used to describe the ability of airflow through the air filter. face velocity is defined as the airflow velocity passing the cross section of air filter (m/s), i.e., where q is the flow rate, m /h; f is the cross-sectional area of air filter or frontal area, m . so face velocity represents the passing capacity and installed area of air filter. the larger the face velocity is, the less the occupied area is. therefore, face velocity is an important parameter to reflect the structural characteristic of air filter. filtration velocity is defined as the airflow velocity passing the area of filter media, and it is expressed with the unit l/(cm · min) or cm/s, i.e., v ¼ q  f   where f is the net area of filter media, i.e., the subtraction of binder area from the total area, m . during the sample test on filter media, the unit of v is l/(cm · min), while it is cm/s for the sample test on air filter. the multiplication of the former value with . equals with the latter value. filtration velocity represents the ability of passing airflow of filter media, especially the filtration performance of filter media. generally speaking, the smaller the filtration velocity is, the higher the efficiency is. when the allowed filtration velocity of filter is smaller, the pressure drop of filter media is larger. for given structure of filter, the nominal flow rate can be used to reflect both face velocity and filtration velocity. with the same area of cross section, the larger allowed nominal flow rate is preferred. when the air filter is operated under lower flow rate, the efficiency increases and the pressure drop decreases. filtration performance of air filters can be described with efficiency, penetration, and decontamination factor. when weight concentration is used to describe the particle concentration in the airflow, performance is evaluated with arrestance. when particle counting concentration is used, performance is evaluated with particle counting efficiency. when other physical parameter is used, performance is evaluated with dust spot efficiency or turbidity efficiency. . to describe the efficiency with particle concentrations at both the inlet and outlet airflow, i.e., where g , g refer to particle mass or counting number at inlet and outlet airflow (mg/h or pc/h), respectively; n , n refer to particle concentration at inlet and outlet airflow (mg/m or pc/l), respectively; q is the airflow rate passing through air filter (m /h or l/h). this expression is valid for both arrestance and particle counting efficiency. . to describe the efficiency with particle concentrations upstream of air filter and particle mass captured on air filter, i.e., where g is the particle mass captured on air filter, mg/h. this expression is only used for arrestance. the value of η calculated by this method is termed as dust removal efficiency in some countries. . to describe the efficiency with particle concentrations downstream of air filter and particle mass captured on air filter, i.e., this expression is also used to describe the arrestance. . to describe the efficiency with fractional efficiency corresponding to various particle size channels, i.e., where η À η n is the fractional efficiency for various particle size, which is expressed in decimal; n À n n is the percentage of particles for various particle size in the total particle group, which is expressed in decimal. it should be emphasized that which kind of method is used to obtain the efficiency when the efficiency value is mentioned. for example, when the arrestance with atmospheric dust is %, it will bring misunderstanding or error when the efficiency is only said to be % or the arrestance is %. this will be explained in detail in chap. . in most cases, people care not only how many particles are captured on air filters but also how many have penetrated through air filters. the concept of penetration (or penetrating coefficient) can be used to represent the extent of the result, although the basic meanings are the same. in the exhaust cleaning system, penetration is used to replace filtration efficiency. it is customary to label penetration with k, i.e., for cases of η ¼ . and η ¼ . , the difference between them is not substantial. when penetration is used, we get k ¼ . % and k ¼ . %, which means k is two times of k . when a filter with penetration k is used, the number of particles penetrating through the filter is two times of the filter with penetration k . this will attract people's attention. decontamination factor k c is defined as the reciprocal of penetration, i.e., it means the extent of the decrease of particle concentration when air passes through filters. when k ¼ . %, this means the difference between upstream and downstream of air filter is ten thousands. pressure drop of air filter is composed of two components: filter media and structure of air filter. pressure drop of airflow entering and exiting air filters is usually constant, which is about pa and could be added as a fixed value. the following part will emphasize on the aforementioned two parts of pressure drop. in some literature and monograph, actually only the pressure drop of filter media layer is mentioned during the introduction of pressure drop of air filter, which will cause misconception to readers. for fibrous filter, pressure drop of filter media is caused by the frontal resistance during the airflows through fibrous layer. pressure drop depends on whether the airflow through fibrous layer is laminar or turbulent. generally speaking, extreme small fiber and low filtration velocity will result in extreme small re number, so airflow is laminar. for the isolated cylinder with unit length, when its long axis is perpendicular to the airflow, the force acting on its surface is a function of the cross section and dynamic pressure, i.e., where f is the drag force, n/m; c is the drag coefficient; ρ a is the gas density, kg/m ; v is the filtration velocity, m/s; d f is the fiber diameter, m. the drag force acting on all fibers inside filter media is fl where l is the total length of fibers. the drag force acting on all fibers inside filter media equals with the force that the filter media bears. when it is equally shared to the surface area, the pressure drop is obtained, which is expressed as Δp and shown in eq. ( . ) . is the fiber length per unit volume; h is the thickness of filter layer; s is the area of filter media, i.e., filtration area. inserting eq. ( . ) into eq. ( . ), we could get this is the theoretical expression of pressure drop. the problem is how to determine the drag coefficient c . because the value of c is related to the arrangement of fibers, solid fraction and re number, it is impossible to obtain the relationship between Δp and every parameter directly. therefore, experiment needs to be carried on. results from experiment on the five obvious factors show that [ it is known that Δp / α m , so replace α in the above equation with α m and c becomes c m , i.e., with the experiment on fibers with different cross section and different re number, the relationship shown as the straight line in fig. . could be obtained, i.e., where c m is the correction factor of pressure drop when influencing factors such as cross-sectional shape are considered while the influence of α is ignored; k ¼ ; inserting eq. ( . ) into eq. ( . ), we could get: in this equation, the relationship between Δp and every parameter is consistent with the experimental results. for example, Δp of filter media is linearly proportional to filtration velocity v, filter layer thickness h, and α m , while it is inversely proportional to d f . this means the equation is valid. according to eq. ( . ) which is the method of susumu and other equations by related literatures, pressure drops of three kinds of fibrous layer can be obtained, which is presented in table . . substantial difference exists between calculated results by various methods and actual experimental data. result given by norio method has the largest difference. there are many aspects for the difference, of which the accurate determination of every parameter is also important. it is comparatively easy to calculate by eq. ( . ), while it is complex to use other two methods which will not be introduced in detail here. for given air filter, the filter media is chosen, so h, α, d f, and φ are fixed. equation ( . ) can be simplified as this means for given particles, pressure drop is linearly proportional to filtration velocity in quite large range of filtration velocity, where a is a structural coefficient to reflect the structural characteristic of fibrous layer. give experimental results for nonwoven coarse filter media, medium-efficiency air filter media, and sub-high-efficiency particulate air filter media [ ] . in these figures there are "front and rear." fibers near the front side are relatively large. inside the coarse filter media, fibers are inherently large and spaces between fibers are loose, so difference is small between front and rear. inside medium-efficiency air filter media, fibers near the rear are relatively dense and they will interference with the airflow. sub-high-efficiency particulate air filter media used here is not only polypropylene fiber filter paper, but it is composed of prefilter layer, main filter layer, and enhanced gauze. when the enhanced gauze is placed windward and leeward, the function of preventing filter media from stretching and deformation is different, so the resultant pressure drops are different. for common polypropylene fiber filter paper without enhanced gauze, the difference is not obvious. from above figures, we could see that for high-efficiency filter media, v is below . m/s; for sub-high-efficiency particulate air filter media, v is below . m/s; for medium-efficiency air filter media, v is below . m/s; and for coarse filter media, v is below . m/s. pressure drops of various filter media: foreign aec filter medium, wire glass fibrous filter paper, synthetic fibrous filter paper, wire glass fiber filter paper, Φiiii- cloth, synthetic fiber no. iv filter paper, eight wire glass fibrous filter paper, synthetic fiber no. filter paper; synthetic fiber no. ii filter paper; five wire glass fibrous filter paper, chemical microporous membrane for these four situations, the following approximated relationship is valid, even the filtration velocity is larger than the limit: except for the pressure drop of filter medium, structural pressure drop of air filter must be added to form the total pressure drop of air filter, where pressure drop of inlet and outlet of airflow occupies very small proportion. there is one view that except for the inherent structure of air filter, pressure drop of structure is also affected by filter media performance. the penetrating performance of filter media may influence the flow state passing through air filter; thus, the pressure drop of structure is affected. this view needs further experimental validation. experiments show that pressure drop of structure is no longer linearly proportional to the airflow velocity. the main reason to nonlinear relationship is that face velocity u is used to describe the airflows through filter frame, which has the magnitude of m/s and is much larger than the filtration velocity passing through filter media layer. the structural size of filter frame is much larger than that of fiber, so inertial force cannot be ignored at large re number flow (usually re > ), and the flow is not laminar. in this situation, pressure drop is not linearly proportional to the velocity but is proportional to u n . therefore, pressure drop of air filter structure can be expressed as where b is the drag coefficient of air filter structure. the total pressure drop of air filter is: it is obvious that values of a and b are different for different air filters. taking a domestic-made gb- hepa filter for an example, experiment shows that n ¼ . . when expressed with unified filtration velocity v, the total pressure drop can be written as: [ ] , from which we can see that for hepa filter, the value of m is slightly larger than when v ≯ m/s, i.e., the flow rate is slightly larger than nominal flow rate. so the resultant error will not be big when the relationship between pressure drop and flow rate is considered to be linear. sub-high-efficiency particulate air filter has similar feature, which will be illustrated in fig. . . however, as for coarse filter and medium-efficiency air filter, since their structures differ a lot, the above characteristic is no longer common. dust holding capacity is an index directly related to the lifetime of air filter. when the final pressure drop of air filter at operation is about two times of the initial pressure drop (if two times is too low, other ratio can be set), or when the efficiency becomes less than % of the initial efficiency, the dust weight deposited on air filter is called the standard dust holding capacity of this air filter, which is called dust holding capacity for short. when the flow rate is , m /h, the dust holding capacity of common folded nonwoven air filter is about g and that of glass fibrous air filter and hepa filter are - g and - g, respectively. even for the same kind of air filter, dust holding capacities are different for different size. it is shown that if the relationship is approximated with straight line, error is not large when it is below the standard dust holding capacity or the pressure drop increase is smaller than two times of initial pressure drop. the maximum difference of pressure drop for these three filters is within pa. the less the upstream concentration is, the stronger the linear relationship is. so when prefilter especially one with high efficiency is usually placed before hepa filter, this characteristic appears. if the filtration velocity is larger than ordinary value or dust deposited weighs more than standard dust holding capacity, the pressure drop will increase sharply with the increase of the deposited dust. the increase of pressure drop is usually linearly proportional to the increase of deposited dust for medium-efficiency air filter. during the deposition of dust, the efficiency of filters with low efficiency will increase at first and then decrease. this is because the dust deposited is comparatively large for air filters with low efficiency and the filter medium is sparse, which will cause particles to penetrate when pressure drop increases and cause deposited particles to rebound and resuspend. during the operation of hepa filters, efficiency usually increases with the increase of deposited dust. classification of air cleanness at home and abroad is mainly evaluated with particle number of those with diameter ! . μm per unit volume air, while various kinds of air filters are evaluated with the fractional efficiency corresponding to certain particle size. therefore, during the design process in air cleaning technology field, efficiency of these certain particle size needs to be converted into these particles with diameter ! . μm. before delivery or during characterization, hepa filter is evaluated with monodisperse particles with diameter . μm, which has been introduced in the former chapter. in order to convert into efficiency with particle diameter ! . μm, the efficiency corresponding to . μm needs to be known. according to foreign experimental data, an empirical expression has been derived for the relationship between penetration of hepa filter and particle size [ ] , i.e., where k , k refer to penetration of particles with diameter . μm and certain diameter which is larger than . μm, respectively; d . , d are the particle diameter . μm and certain diameter which is larger than . μm, respectively. the above equation was used to perform calculation on measurement data published abroad [ ] , which is shown in table . . in the table, k and k are measurement data and k is the calculated data with eq. ( . ) . from the comparison between the last two columns, we can see that except for the comparatively large difference for the data on the first row, differences of other data are extreme small. this empirical equation is only valid for hepa filter with . μm, while it is not useful for hepa filter with . μm. although the test methods for the efficiency of hepa filter are different at home and abroad, the results are almost consistent with that of particle counting efficiency with particle diameter . μm, which is shown in chap. . efficiency for hepa filter with particle diameter . μm is usually considered as the reference baseline, so eq. ( . ) is used to obtain the relationship of hepa filter between . μm and . μm, which is shown in fig. . for reference. meanwhile, fig. . shows the curve in ref. [ ] , from which we can see that these results match well with each other. efficiency η in the figure is represented with decimal. according to the above curve and the particle diameter distribution of atmospheric dust introduced in chap. , the efficiency with particle diameter ! . μm can be derived, which is shown in table . . according to national standard "high-efficiency particulate air filter," filter with efficiency larger than . % is called hepa filter. for filter with efficiency equals with . %, efficiency with particle diameter larger than . μm becomes . %, which is shown in table . . since efficiency of common hepa filter is actually larger than this limit value, it is reasonable to consider efficiency of particle diameter ! . μm to be . %. with the above conversion method, we compare the experimental data performed on hepa filter in the cleaning equipment with calculated data and find they are consistent. there is no literature abroad specially dealing with this problem. in ref. [ ] , it is said that "for obtaining class clean environment with all the fresh air when the particle concentration of outdoor air is about  relationship between efficiency of hepa filter and particle size pc/l (! . μm), it's necessary to set filters with minimum efficiency . %. so hepa filter with efficiency larger than . % is recommended to use as the main filter." here hepa filter with efficiency . % (for . μm) is thought to have efficiency . % with particle diameter ! . μm. for comparison, according to the above conversion method, when particle efficiency is . % for particle diameter . μm, its corresponding efficiency for particle diameter . μm becomes . %. domestic-made medium-efficiency air filters include glass fibrous mediumefficiency air filter and foam medium-efficiency air filter. at present the most commonly used is nonwoven medium-efficiency air filter, which is actually a kind of fiber felt air filter. particle counting efficiency of glass fibrous medium-efficiency air filter (d f ¼ μm, h ¼ mm, α ¼ . , v ¼ . m/s) with atmospheric dust was performed at institute of hvac of china academy of building research, which is shown in table . . in the table, average efficiency corresponds with the arithmetic average diameter of atmospheric dust, and efficiency is obtained with the theoretical curve of fig. . with this average diameter. this theoretical curve is obtained by the method of structural nonuniform coefficient. since the grouping range of particle diameter is comparatively large, difference between average particle diameter and actual value is large. but it is shown from the table that the efficiency calculated with average particle diameter is close to the actual measured data, fig. . relationship between efficiency of hepa filter and particle size [ ] which is satisfactory. the calculation method has certain reference value. it is also shown from the figure that difference between calculated efficiency and experimental one is comparatively large when experimental coefficient method and the value of η Σ with eq. ( . ) are used. figure . shows the experimental data of glass fibrous air filter and foam air filter at home and abroad. it is shown that the difference of efficiency between . and . μm is quite small, as well as the difference of efficiency between ! . and ! . μm. this is because filtration mechanism for medium-efficiency air filter for small particles has little difference. from fig. . , the following approximated relationship exists when η < . : in actual air cleaning system, filters are usually placed in series. here the efficiency of air filters in series is emphasized. in filtration theory, for filtering polydisperse aerosol with the same kind of air filter (e.g., they are all fibrous medium-efficiency air filter or hepa paper filter), the penetration of second air filter should be larger than that of the first one, i.e., the efficiency of second air filter decreases. this is resulted from the selectivity of particles by filter medium, which has been introduced before. in short, mainly because the filtration mechanism for different particles is different, the dispersity of particles after the first air filter varies, which results in the change of total efficiency for the second air filter. from eq. ( . ) to derive the efficiency corresponding to various particle diameters, we can see that in order to calculate the efficiency of second air filter, the particle size distribution after the first filter and efficiency of various filers for different particle size must be known. these two problems have been solved, so detailed calculation can be made. table . presents the calculation results for two hepa filters in series (when the atmospheric dust concentration m ¼ pc/l) [ ] . under normal conditions, atmospheric dust concentration is m < pc/l. with the decrease of m, the absolute quantity of large particles decreases. so the number of large particles passing through the first air filter is close to zero, which makes the proportion of large particles upstream of the second filter smaller. efficiency of the second filter for particle diameter !d is approaching to that for particle diameter equals with d. this means the penetration of the second air filter is close to be two times of the first filter. therefore, when the third hepa filter is placed, its efficiency for particle diameter !d is much closer to that for particle diameter equals with d of the first filter. when d is . μm, efficiency decreases from . to . , or the penetration increases two times from . to . % and then reaches stable. if monodisperse aerosol is filtered, the change of efficiency for various stages of air filter is small. reports on the problem of efficiency for air filters in series are rare [ ] . both theoretical calculation and experimental data in field have proved that the efficiency of the second filter decreases a lot. there are two reasons: one is that particle concentration becomes extremely small after passing through the second air filter and so on, so data is not accurately measured because of the limit of measurement techniques, and even reverse conclusions are obtained, which has been clearly mentioned in the "nuclear air cleaning handbook" [ ] ; the other is that during the field test, particle concentration will increase downstream of air filter in case of sealing problem during installation or even the trivial leakage. field test data from japan are listed below [ ] : the increase of penetration between the third hepa filter and the second one is larger than the calculation result. tester have pointed out that this is caused by leakage. if there were no leakage made by improper installation, there would be no much difference of efficiency between the third and the second filter. for this aspect, the strict experimental data cited by "nuclear air cleaning handbook" denied the opinion that the efficiency of air filter in series will decrease. according to the data from "nuclear air cleaning handbook," the decontamination factor of the first hepa filter is , and that of the second hepa filter remains the same, while that of the third hepa filter is  . it is known that so k is two times of k , which is consistent with the calculated result which increases from . to . %. therefore, it is suitable to choose hepa filters with these recommended penetrations for exhaust cleaning system: the first hepa filter k ð!dÞ the second hepa filter k ¼ k ð!dÞ the third and later hepa filters k ðdÞ . efficiency of air filters in series k (d ) means the penetration of the third and the following hepa filters for particle diameter !d equals with that for particle diameter d. in the inlet air cleaning project, efficiency for two hepa filters in series is quite large, so the influence of the decrease of the efficiency of the second air filter is too small to be neglected. the total efficiency can still be written as: there are two aspects of meaning to prove the small decrease of efficiency for hepa filters in series: . in the application field of exhaust cleaning system. as pointed out in nuclear air cleaning handbook, the emission permission for radioactive elements concentration (such as plutonium or other super uranium substance) is extreme low, so it is not enough to only install one hepa filter in the exhaust system. since the efficiency of air filter in series does not decrease, it is preferred to install two or more filters in series, which is easy to increase the efficiency of the first filter. . in the application field of cleanroom for cleanness higher than class . when a hepa filter is installed in series in the fresh air system, the influence of leakage is smaller. some cleanroom projects in china have adopted this method and the effect is satisfactory. for two medium-efficiency air filters in series, the efficiency of the second filter almost remains the same. if both filters are glass fibrous filters, in theory η ! . ¼ . and η ! . ¼ . . we can obtain that the percentage of particles with diameter ! . μm decreases from to %. the efficiency for particle diameter ! . μm is . and that of particle diameter ! . μm is . which remains the same. so the total efficiency of coarse and medium-efficiency air filters in series can be written as: the weight of dust deposited on air filter can be expressed with the following equation: where p is the weight of deposited particles on air filter, g; t is the lifetime of air filter, d; n is the particle concentration upstream of air filter, mg/m ; q is the flow rate, m /h; t is the operational time per day of air filter, h; η is the arrestance of air filter. when air filter is operated under the rated flow q and the pressure drop increases to several times of initial pressure drop (usually it is two times), the air filter can no longer be used, and the weight of deposited particles is called standard dust holding capacity p . the used time of air filter is called lifetime t , i.e., where n can be calculated with the method in chap. , i.e., where m is the atmospheric particle concentration, mg/m ; s is the recirculation air ratio; n r is the return air concentration. for cleanroom with class , the concentration is between . and . mg/m ; η n is the arrestance of air filter in the fresh air ventilation system; η r is the arrestance of air filter in the return air ventilation system. for different systems with different η n and η r , the detailed calculation method will be introduced in chap. . for example, p ¼ g for flow rate , m /h, filter), q ¼ , m /h, the service life of hepa filter can be calculated to be day. if the operational time per day is h, t can be prolonged to be , day, which is . years. since particles will also be deposited onto other surfaces, the lifetime of hepa filters is longer than that of calculation. figure . shows the relationship between operational time and the increase of pressure drop of hepa filter [ ] . in the figure, the dust spot efficiency of prefilter in curve b is - %, which is equivalent with the arrestance with atmospheric dust shown in chap. . the service time of air filter is close to the data in the above example. it should be mentioned that there is one opinion that the increase of pressure drop of hepa filter is faster than that of dust holding capacity, so it is unsafe to calculate the service time with dust holding capacity [ ] . actually it is not clearly pointed out here. since the concept of dust holding capacity has included the increase of pressure drop, the service time or lifetime calculated with dust holding capacity equals with the operational time needed when the pressure drop becomes two times of the initial pressure drop (or other certain times). the following relationship is obtained from eq. ( . ): it should be noted that t is not the lifetime of air filter under that flow rate q but is the time needed for the weight of deposited particles on air filter to be p under the flow rate q . for example, if and vice versa. here t , is the lifetime under the flow rate q . operational pressure drops are different when q ¼ q . experimental data were given which is given in fig. . [ ] . it is shown that when q ¼ q , the lifetime is larger than t . when we denote q q ¼ k and the pressure drop h, tu guangbei obtained the following equations based on these curves [ ] : the following comprehensive equation was obtained when log-log plot paper was used with k as the abscissa (fig. when h ¼ h , t becomes the lifetime t . the value of t is only positive. however, the above expression was obtained from one test case, and it is inconvenient to use it for calculation, which is not obvious to obtain the characteristic at a glance. so it is still unsure whether the relationship between t and k is also universally valid. from another point of view, author proposed an approximation method for the theoretical analysis of relationship between t and k [ ] . when both the operational and rated flow rates are known, the change trend of the lifetime can be calculated. for example, the increase of pressure drop is Δh under the rated flow q when the initial pressure drop is h and standard dust holding capacity is p , so the final when the flow rate becomes , what is the time t , when the pressure drop reaches h + Δh? simplification was made with the assumed condition Δh % h . from the aforementioned introduction, we know the increase of pressure drops of hepa filter and sub-hepa filter are linearly proportional to the weight of dust deposited under this condition. . from eq. ( . ), it is known that the operational time is reversely proportional to the flow rate, i.e., . after operation time t k under flow rate q , the weight of deposited particles becomes the standard dust holding capacity p , but the finial pressure drop at this time is still far from h + Δh. from figs. . , . , . , and . , it is shown that h is approximately linearly proportional to q (when q is less than q or slightly larger than q ). since the final pressure drop is ( À k ) times less, continuous dust loading process is needed to increase the pressure drop. it is known the pressure drop increase is approximately linearly proportional to the weight of deposited particles, and the weight of deposited particles is also linearly proportional to the time, so the time needed for continuous particle loading process or the increased time is: . according to the relationship between h and q, the initial pressure drop decreases to kh under the flow rate q , this is ( À k) times less. if the operational flow rate is q and ( À k ) times of original pressure drop is added, the prolonged time needed is ( À k )t . now the operational flow rate is q , so the time should be reversely proportional to q , i.e., the actual prolonged time is . therefore, for the case k < , the time needed for the pressure drop to become the final pressure drop with k ¼ should be . so the reciprocal of prolonged time q /q is obtained, which is the shortened time. with the above equations and principles, the relationship between k and t , for reaching the final pressure drop with rated airflow, which is shown in table . . in the table, k ¼ . , which is equivalent with k ¼ it is equivalent to the reciprocal of its multiple of t , which is obtained with the value . . taking fig. . as an example, the lifetime t of air filters for different k is calculated with the above analysis method, which is illustrated in table . , together with the measurement value and the calculated result with eq. ( . ). from the above comparison, results from three methods are almost consistent. so it is feasible to adopt the analysis estimate method which reflects the general laws. equation ( . ) is also thought to reflect the general relationship, although it was derived from single case. one important conclusion from the above analysis is obtained. the operational flow rate of air filter is suggested to be about % of the rated flow, and the lifetime of air filter will be doubled, which is beneficial for both economic operation and energy saving. in practice, it is impossible to directly estimate how much particles have been deposited onto filters. it is usually to determine whether to change air filters according to the measured pressure drop or the outlet velocity of air filter. for air filters used in the radioactive exhaust system, except for the index of dust holding capacity or pressure drop, the index of surface contamination is also used to determine the service time. air filters must be replaced when each index reaches the specified value. the extent of surface contamination of air filter is determined according to the specific situation of usage. eq arrestance of air filter is used to calculate the service time of air filter in previous section. experimental data of arrestance can be used if it is available. but in the current national standard the fractional efficiency with atmospheric dust is used to assess the efficiency of air filters in general ventilation. therefore, the particle counting efficiency should be converted into arrestance. here an estimation method is introduced [ ] . taking the data in table . as an example, particle size distribution between . and μm can be divided into the following parts according to the relationship shown in table table . , when the particle counting efficiency for particles with diameter ! . μm is %, at least % of particles by weight are filtered. weight of particles with diameter less than . μm occupies % of the total weight. since part of particles with diameter less than . μm will be captured, the penetration will be less than %. this can be omitted since it is a small value. that is to say, when the particle counting efficiency for particles with diameter ! . μm is %, the arrestance cannot reach % in theory, but it can be still considered as % because the error is less than %. from the above analysis, we know when the particle counting efficiency for particles with diameter ! μm is %, at least % of particles by weight and . % of particles with diameter larger than . μm will be captured. since part of particles with diameter between . and μm will also be captured, the total arrestance will be slightly larger than %. for the convenience of estimation, this excess value can be omitted. therefore, when the particle counting efficiency for particles with diameter ! μm is %, the corresponding arrestance can be estimated as % or %. when the particle counting efficiency for particles with diameter ! μm is %, . %  . ¼ . % of the total number with particle diameter ! . μm will be captured, so less particles with diameter between . μm and μm will be filtered (because efficiency for particles with diameter ! μm is less, the corresponding efficiency for smaller particles is much less, which can be omitted). therefore, the arrestance corresponding with the particle counting efficiency . % with particle diameter ! . μm can be used to express the particle counting efficiency %, i.e., . %. but when only the particle counting efficiency with particle diameter ! μm is known without any information about the efficiency with particles diameter between and μm, the above method to estimate the arrestance is not valid since the weight percentage of these particles cannot be omitted. according to the above analysis, the data in table . are used to plot fig. . . the arrestance found in the figure is an estimation value or the minimum limit value. fig. . conversion from particle counting efficiency to arrestance: % efficiency curve for with particle diameter ! . μm, % efficiency curve for with particle diameter ! μm, % efficiency curve for with particle diameter ! μm, % efficiency curve for with particle diameter ! μm characteristics of air filters now the filter-paper hepa filter is one typical example of folded filter-paper filter, which was developed in the nuclear industry in the second world war to remove radioactive particles. the main characteristic is its extreme low resistance because the filter paper is thin and filtration area is dozen times of frontal area by the folded structure, which makes the practical use of filter-paper filter possible. in the folded filter-paper hepa filter was first manufactured in the usa and put into the market for sale in . in hepa filter was imported into japan from the usa. later in japanese began to develop their own product, which appeared in the market in [ ] . in s, chinese began to develop hepa filter, which passed the identification and began the mass production. the first filter-paper material used in the air filter of nuclear industry was plant fiber together with blue asbestos fiber. blue asbestos fiber is very fine with diameter between . and μm. the yield is very low. it is thought that asbestos fiber will cause cancer, so it is gradually replaced by popular ultrafine glass fiber and glass fiber filter paper, which promotes the application of high-efficiency filter-paper filter and the development of air cleaning technology. filter-paper hepa filters can be classified according to the type of filter media material, and they can also be divided based on whether separator is used; whether the diameter of filtered particle is . μm (it is called common hepa filter or . μm filter) or . μm (it is called ultrafine air filter or . μm filter); whether the frame material is board, laminate, plastic plate, aluminum alloy plate, steel plate, or stainless steel plate; whether the structural shape is flat or v type; and whether it is able to endure high pressure, endure high humidity, and endure acid and alkali, high resistance, low resistance, or sterilization. at present there are three types of structure in filter-paper filter, i.e., with separator, with inclined separator, and without separator. the product of air filters with inclined separator is rare, while the other two types are popular. structures of these three types are shown in figs. . , . , and . . inside hepa filters, separator is placed between two sides of folded filter paper to provide the airflow channel, which is the standard practice. so it is called as separator hepa filter. separator is also called as corrugated separator. after hot rolling stamp, high-quality kraft paper can be used to make the separator with different crests and pitches. in order to prevent the particle emission from the stretch of separator caused by the cold, hot, dry, or wet conditions, as well as to fix the separator shape, both sides of separator should be immersed into some kind of coating material, which has the disadvantage of abnormal odor. now chrome papers gluing at two sides are used to make separator. but some practical experience has shown that there is some hidden danger: particles will be released as the pollution source because of its stretch deformation with the variation of temperature and humidity. so aluminum and plastic can also be used to make separator. for the separator air filters, corrugation angle is one important parameter, which has great influence on the pressure drop. practice has shown that º corrugation angle is suitable. the influence of cross-sectional area on the pressure drop is not large. with the large cross section and same filtration velocity and thickness along the flow direction, the corrugation height has comparatively large influence on the pressure drop, which will be analyzed in detail later. the traditional practice to make the separator air filter is to glue at both edges of the corrugation at first, then the endsealing glue is added to the inner side at both two edges of wooden frame painting so as to make the glue sides in order and to prevent leakage. but practice has shown that the endsealing glue has little effect on the leakage prevention, and once there is leakage, it is more difficult to detect the leakage and make repair. taking the current gb- type air filter as an example, the cross-sectional area of filter cartridge is about . m  . m ¼ . m and the width of endsealing glue is . cm. when it was considered as cm, the corresponding cross-sectional area of filter cartridge is about . m  . m ¼ . m , which means the cross-sectional area without endsealing glue is % larger than that of with endsealing glue. when the net area of filter paper increases, the pressure drop will decrease to some extent. therefore, the practice to use the endsealing glue on air filter is canceled, which is replaced with potting glue method or inserting glue method. for traditional separator air filter, the cross-sectional areas of air channel formed by the corrugations on the separator are the same. when the concept of area variable cross sections is applied on air filter, inclined air filter is created, whose projection shape is a right-angled trapezoid when the separator is erected. the cross-sectional area is large when air enters into the channel. as air goes through the filter paper, the air volume near the channel terminal is the minimum, so is the cross-sectional area. in this way, both the length of filter paper around each separator and the number of corrugations increase. according to the product specification abroad, the filtration area will increase by % for inclined separator air filter compared with vertical separator air filter, so the pressure drop under the same flow rate will be much less. another method of improvement on traditional hepa filter is to cancel the separator. it is beneficial for the mechanized production of mini-pleat filter. one case is to cancel the separator, and the filter paper is folded with corrugation matching corrugation and point matching point after corrugation and salient point are pressed on filter paper. the other case is to replace the separator plate with other separator, such as the streak formed by thermosol on filter paper, the dipping flame retardant silk thread, glass fiber thread, or filter strip pasted on filter paper. during the process of folding filter paper, filter strips are inserted from the two sides of corrugation and they are held with the friction force. it should also be mentioned that the cross-sectional size of domestic-made hepa filter includes mm  mm, mm  mm, etc., which are quite irregular. national standard issued in canceled the specification of maximum overall dimension. it also requires that ( ), ( ) separator plate is - mm lower than the frame edge, and ( ) the filter element is - mm lower than the separator edge. the national standard also provides the following specification: ( ) the frame width is mm (when the side length is less than or equal to mm) or mm (when the side length is equal to or larger than mm). this is a way to guarantee the quality of air filter, but some manufacturer does not pay attention to it. during the calculation related to air filter, these data should also be considered. in order to enlarge the filtration area, double folding structure is also adopted. the first folding structure is for filter paper itself, which means a piece of folded filter material is used. the second folding structure is the w type structure inside the frame. the structure is shown in fig. . . in early times, the former ussr made transversely placed large cylindrical filter with ϕii- - . filter fabric which is hard to be folded but can be pasted, which is shown in fig. . . strictly speaking, that is a kind of equipment, not a single air filter. ycg-type low-resistance sub-hepa filter is one typical example of filter-paper filter, which was one type of air filters with lower structural resistance innovated firstly in china [ ] . hundreds of filter cylinders are hot welded with polypropylene fiber filter paper. filter cylinders are plugged onto the panel with the plastic cap stopper with wings. wings are meant to support the filter cylinders and separator the air channel into two parts. adhesive-free product, so secondary pollution caused by peculiar smell does not exist, which is suitable for the application with stringent environmental requirement. . light. the weight is only half of the hepa filter with the same size. structural calculation of this kind of air filter will be introduced in chap. . it usually means the filter paper made by plant cellulose. several domestic-made air filters with performance similar as sub-hepa filter are made of short cotton lint filter paper. the characteristic of this kind of filter paper is that its efficiency is between medium efficiency and sub-high efficiency. the efficiency is small for low filtration velocity. efficiency increases with the increase of filtration velocity. the performance differs for different kinds of particles. table . shows the filtration efficiency of one cellulose fiber filter paper with psl [ ] . it is shown that for particles with diameter smaller than . μm, the efficiency is the minimum for filtration velocity . - cm/s. moreover, the minimum efficiency corresponds with smaller particle size with the increase of filtration velocity. the surface dust holding capacity of this kind of filter paper is slightly larger than that of glass fiber filter paper by - %, but it is smaller than that of membrane filter. this kind of filter paper has high efficiency and high resistance. since the surface dust holding capacity is also very high, even higher than that of glass fiber filter paper, it is usually applied in the exhaust treatment system for nuclear facility. this kind of filter paper also has high efficiency. efficiency changes little with the change of particle type and filtration velocity. the relationship between efficiency and composite proportion of glass fiber inside the filter paper is shown in table . [ ] . the pressure drop is smaller than that of cellulose-asbestos fiber filter paper. fiber diameters inside glass fibrous filter paper become smaller. in s diameter of foreign made filter paper reduces to . μm, and the value of domestic made reduces to . μm. figure . presents statistical analysis of the fiber diameter distribution inside domestic-made filter paper using sem graph, where all the average diameters are slightly smaller than . μm. in s the diameter of domestic-made glass fiber was smaller than that of foreign made, which reduced to . μm. efficiency increases apparently and that of some filter paper was higher than that made in the usa. however, the most obvious shortcomings of domesticmade filter paper are fiber shedding and the amount of particles deposited by filter media itself is great, which is related to the inaccurate control of manufactory environment and production process. furthermore, pressure drop of common hepa filter paper is very high under the usual filtration velocity, and that of most ulpa filters is even much higher [ ] . since the synthetic fiber has high resistivity and can bring large amount of electrostatic charge, it is an ideal material for making electrostatic material. perchloroethylene ϕii filter fabric produced in the former ussr in s is one of the kinds of fibrous filter paper. penetration is % when filtration velocity is . m/s, while it is . % when filtration velocity decreases to . m/s and the corresponding d max is . μm [ ] . polypropylene fibrous filter paper developed in the late s is another example. its performance is much better than ϕii filter fabric. polypropylene slice is used to make ultrafine fiber through the meltblown process. further filtration material is manufactured, which is a soft nonwoven felt. diameter of single fiber is - μm (usually it is μm). the sodium flame efficiency with standard specific velocity is - . %. it is quite difficult to make the fiber diameter smaller. fibers are not uniformly distributed inside the filter media. electrostatic charge on the filter media fades away gradually, so at present it cannot be used to replace glass fibrous hepa filter. but it is indeed a promising filter media. except for the features mentioned in the above chapter and sections in this chapter, polypropylene fibrous filter media has the following characteristics: . pressure drop. under the same efficiency range, the pressure drop is only / that of glass fiber. table . presents the pressure drop of several domesticmade polypropylene filter paper when the filtration velocity is cm/s. the reason for small pressure drop is that the fiber diameter is comparatively large and particles can penetrate deeper (several hundred micrometer). but particles can only penetrate tens of micrometers from the surface of glass fibrous filter paper. . stability of electrostatic charge. after passing through the corona discharge, filter media become the electrets which carry large amount of electrostatic charge, and the surface electrostatic potential can reach , v. with the electrostatic effect, the penetration decreases by - order of magnitude. after the filter media is immersed into the alcohol and then dried in the vacuum, the electrostatic charge is neutralized and the efficiency decreases a lot, which is shown in figs. . [ ] and . [ ] . at the same time, it is also found that the electrostatic potential increases by the friction effect when air flows through the filter media, which is shown in table . . the potential at smooth side is high, so the efficiency using this side as the frontal face is high, while the pressure drops using both sides facing upstream is almost the same ( but experiment was performed on the electrets air filters with polyolefin fiber which concluded that efficiency decreased from . to . % after years' operation without any prefilters. the reason is that the electrostatic effect is shielded by the deposited particles [ ] . when it is placed in the environment with relative humidity %, no obvious influence is made on both the efficiency and pressure drop [ ] . . temperature characteristic. the operating temperature is À to + c. when it is baked under the temperature c for h, no obvious change appears in both efficiency and pressure drop [ ] . but efficiency decreases when the operating temperature is above c. the melting point is - c. . density. it is . g/cm . the solid fraction is . with measurement [ ] . . characteristic of acid and alkaline resistance. except chlorosulfuric acid, concentrated nitric acid, and some oxidants, it has good performance of resisting acid, alkaline, and organic solvent. strength. the transverse tensile strength is larger than g/  cm, and the longitudinal tensile strength is larger than , g/  cm. the strength is more than two times of glass fibrous filter paper. it is fold resistant. . environmental property. nontoxic, odorless, no borer, and it can be disposed by combustion. . ability to absorb oil. it can absorb oil with weight equals with - times of self weight. . bonding characteristic. it is difficult to bond with the glue, but it's easy to bond with iron. the gel type microporous filter membrane is the main form, which is made of the nitrocellulose. the gel is the mixture of the ether alcohol with the fibers of nitrate ester, and it is also called celloidin. when the celloidin is diluted with the acetone and the pentanol, the gel used for make the membrane is formed. this kind of filtration membrane has very high efficiency and surface particle deposition rate, so it is usually used to act as a standard filter paper to measure the efficiency of other filter papers. it is also used to capture radioactive particles, but it is not convenient to use since the pressure drop is high and the tensile strength is low. pores on the surface of microporous membrane are irregular, which is similar as that of foam. their sem figures are shown in figs. . and . [ ] , where the spheres are methylene blue particles. nuclear microporous membrane is also one kind of membrane filter paper. it is called nuclear track microporous membrane, which is developed in the late s. thermal neutron during the nuclear reaction is used to bombard the heavy element such as u. then the fission fragment from u is used to bombard the plastic film such as polycarbonate film or polyester film, or the heavy element such as k r and x e accelerated by the accelerator is used to bombard these films, so track injury is left. afterwards, they are etched with chemical reagent, and pores appear on the surface. its strength is good. it is fold resistant and can bear high temperature - c. pore density can be controlled when both the bombardment intensity and time are monitored. pore size can be controlled when the reagent concentration, temperature, and etching time are controlled. the thickness of nuclear microporous membrane is usually between several micrometer and dozens of micrometer. the thickness of domestic-made nuclear microporous membrane is μm. diameter of pore size is between Å and tens of micrometer, and it is usually about μm. the porosity is about %. the monodisperse of pore size is better than chemical microporous membrane. since the surface is quite smooth, it is suitable for qualitative analysis of aerosol sampling and study of bacteria filtration. the pressure drop of nuclear microporous membrane is large, so it is not suitable for common air filter, but it is very useful for special filtration (for the application field where particles with diameter larger than certain value are not allowed to penetrate). it is shown from fig. . that almost no particles appear on the rear face when the frontal surface is already clogged. it is widely used in the medical applications. as for the filtration mechanisms of nuclear microporous membrane, domestic scholars have already made detailed investigation [ ] , which will not be introduced here. except for the above five kinds of filter paper, there is also plastic fibrous filter paper, which is not illustrated here. special attention should be paid on the representative features during the selection of filter paper, which is presented in table . . it is hoped that the larger tensile strength and smaller fiber are preferred. while larger thickness and larger solid fraction will result in high efficiency, but the pressure drop will increase dramatically at the same time. the content of metal component is one important feature for filter paper. when the content of metal component in the captured particles is investigated, the background value in the filter paper itself is needed. there is little study in this aspect home and abroad. for reference purpose, table . presents the contents of several metal components inside the common glass fibrous filter paper according to the literatures home and abroad. it is shown in table . that the largest shortcoming of this kind of glass fibrous filter paper is the weak tensile strength. the ability to bear the shock press is extreme low. during the manufacturing process, it is too fragile to be damaged if it is not careful enough. experiment of the compressive strength of hepa filter was performed using the shock tube. protection device was developed to increase the ability to bear high shock force. common hepa filter with tensile strength of filter paper no less than g and other air filters were used in the test. different conditions were compared when no baffle was placed and different baffles were set cm upstream of the air filter. the test results for common hepa filters are shown in table where the white part means the damaged part of filter paper which turned outwards [ ] . moreover, the stiffness and rigidity of filter paper have decisive influence on the height of corrugation and pressure drop. from the test results shown above, the pressure for damaging domestic-made glass fibrous filter paper (or filter paper) used in common hepa filters is less than . kg/cm . according to american air force design manual (ad , tdr- - report), the pressure to cause damage on aec filter from us atomic energy commission is only . kg/cm . therefore, when glass fibrous filter is installed on the pipeline with shock press, the protection device must be installed, and the most common measurement is to place the baffle plate. the tensile strength of glass fibrous filter paper is very small, and it decreases a lot under the high wet environment, so it is easy to be blown through. if special treatment is made on filter paper, its tensile strength can be improved. domestic researchers have proved that when the filter paper is treated by spraying with "soft no. " leather treatment agent, the tensile strength can be increased by ten times, while the pressure drop does not increase too much and the efficiency remains the same [ ] . experimental results are summarized in table . . table . is the experimental result of pressure drop with high filtration velocity . m/s. pressure drop data for low filtration velocity are not available. with low filtration velocity, the rise velocity of pressure drop is slower than that of high filtration velocity. the filter paper is still undamaged when it is treated with "soft no. " leather treatment agent and then with steam. this means it can bear high temperature environment of steam for sterilization, so it is useful for pharmaceutical and biological clean rooms. it is dependent on the application and performance to choose what kind of components including filter paper, frame, and separator (corrugation) for making air filter, especially hepa filters. for information, table . shows the general performance of air filter made by components with different materials. because the filter paper is too fragile to be damaged during the manufacturing process, the efficiency of filter-paper air filter is usually smaller than that of small filter-paper sample by "half ," and the poorest performance difference could be less than "one ." therefore, for making hepa filter with efficiency for particle diameter . μm to be above "three " (i.e., . %), filter paper with efficiency "four " must be used. with the development of science, technology and manufacturing process, both the standard and test methods for hepa filters in many countries are developing, which will not be introduced here [ ] . more stringent requirement for filter-paper air filter will be put forward. there are following requirements [ ] : . efficiency for particle diameter . μm should get close to . %, or for particle diameter . μm should get close to "eight ," which is called ulpa filter and shown in fig. . . . it is more stringent to make requirement on the chemical pollution of filter paper. at present, most of hepa filter is composed of filter media with ultrafine glass fiber which is made from silicon boric acid. % of its component is sio . in s the requirement of silicon pollution was proposed. silicon particles volatilize and emit from the hydrophobia material, which cause harmful effect on the production of hard disk drive. in s the problem of phosphorus pollution was put forward. phosphorus pollution comes from the seal glue of air filter, which may cause pollution to the wafer. in the late twentieth century, the problem of boron pollution was put forward, since about % of the component in the filter media is b o . except for the boron pollution of atmospheric air as the main source, air filter is also one important source. under high-humid environment, hydrofluoric acid will make corrosion on glass fiber and produce gaseous boric acid if hydrofluoric acid exits, which will pollute the wafer. . the pressure drop with rated flow is smaller than pa. . the deposited particles are unlikely to reenter into the flow. . no crack exits inside the structure of air filter, so no seal material is needed and no leakage appears on it. leakage test before delivery is not needed. . the lifetime is more than years. . it is easy to handle after usage. in the late of twentieth century, ptfe filter with filter media made by microporous ptfe membrane appeared in the market. the average diameter of the pores the time of filter paper with width . mm and length mm having fractures during the repeated process of stretching and folding, when its one side is fixed and the other side is connected with an eccentric wheel which has an eccentricity mm and speed , r/min the main characteristics of ptfe filter is: it has strong ability to anticorrosion including acid and alkali. the volatile amount of chemical substance is extremely low. for example, the volatile amount of boron and sodium is only / to / of that from glass fiber filter. the pressure drop is very small, which is less than common hepa filter by %. at present the price of ptfe filter is comparatively high and the dust holding capacity is a little small. as for the structure of nonleakage air filter with the requirement as item ( ) mentioned above, it has been replaced by author's invention patent of zero leakage air supply outlet. when common air filter is installed in this air outlet, no leakage into the room can be realized. fibrous layer filter is mainly composed of a fibrous filling layer. the fiber used can be divided into three categories: one is natural fiber such as wool and cotton fiber, another is chemical fiber which is made with chemical method to modify the characteristic of raw material, and the third is artificial fiber which is separated from the raw material with fibrous shape by physical method or formed to be fibers from raw material. for the second type, the chemical feature of fiber is totally different from that of raw material. for the third type, the chemical feature before and after fiber formation remains the same, such as spinning after the melt of glass. the surface feature of fiber has great influence on the filtration effect. taking natural fiber including wool and cotton as an example, the particle capture efficiency is higher than that of smooth plastic fiber because of the scale shape and fibrous shape. the efficiency of glass fiber improves after treatment with hydrofluoric acid [ ] . in order to prevent the fiber abscission during operation, binder is sprayed onto fibers. fibers with different diameter can be chosen to make packed bed with different solid fraction. particles with large diameter are captured by crude fiber layer. posterior fine fiber layer is used to filter small particles. in this way, the needed filtration efficiency and dust holding capacity are guaranteed, and the resultant pressure drop is not too high. fibrous layer made by nonwoven manufacturing process can also be used to make air filter. figure . shows the nonwoven bag filter. the common techniques include needle injection sticking method and hot melt method. fibers with different diameters are used as raw material. it forms the web shape after loose carding and folding. movement of thousands of needles on the needle board of the needle machine makes fibers move along the perpendicular direction. after going forward and backwards, certain numbers of fibers entangle together on the fiber web because of this movement. the glue is sprayed on the surface and then dried. this is called the needle injection sticking method. if fibers with low melting point such as polypropylene are added into fibers such as polyester, the fiber web formed by folding is placed into the hot melt equipment and heated to certain temperature, then fibers with low melting point are melted and binding other fibers to form the filter media. this is called the hot melt method. nonwoven fabric made by this kind of method is in the range of coarse efficiency, which is suitable for making rolling filter material. in terms of nonwoven fabric shape, it is one kind of felt fibrous layer. the thickness of this fibrous layer is between less than mm and dozens of micrometer. the efficiency range is so large to cover the coarse efficiency and sub-high-efficiency ranges. taking one kind of domestic-made polypropylene nonwoven fabric pp-k for an example, its thickness is mm and the pressure drop is about pa with the filtration velocity . l/ (cm · min). the particle counting efficiency with atmospheric dust is % when particle counter is used. it is comparatively cheap and is only several yuan for each meter squared. table . presents the characteristic of several fibers, which could be used for reference during selection of filter material [ ] . fibrous layer air filter has small solid fraction, so its pressure drop is very low. it is especially suitable for the application of hvac air cleaning system as medium-efficiency air filter. there are two principles during the design and selection of fibrous layer air filter. one is based on a single index. it is the priority to consider the requirement of efficiency during the design of air filter. so with the same filtration efficiency, the optimum of certain index is expected. for example, the minimum pressure drop is expected, when requirements of other indexes should follow this requirement of pressure drop. this is a simple case. the other is based on the comprehensive index. with the same filtration velocity, the optimum comprehensive index is expected. when this comprehensive index is labeled with e, chen proposed to use the ratio of efficiency and pressure drop [ ] , i.e., it is obvious that this index is only related to the technical performance of air filter, while its economic performance is not included. if the cost of filter material was considered, the comprehensive index reflecting the usage of filter material should be used [ ] . when this index is denoted with j, we get, where w f is the usage amount of filter in the filter layer per each meter squared. it is shown from the above two expressions that e is larger when the efficiency is larger or the pressure drop is smaller. j is smaller when e is larger or the usage amount of filter material w f is more. therefore, the smaller value of j is preferred when the efficiency of air filter is given. moreover, comprehensive analysis with the fuzzy method was performed [ ] . it is comprehensive, but it is not easy for visual understanding because of so many influencing factors. the weight of each factor is determined subjectively by the interest of referee. the comparability of this index is weakened. whatever evaluation method is adopted, the filtration efficiency requirement is of the priority, and then other comprehensive indexes are considered. the following items should be noted during the design of air filter: first of all, filter material with suitable fiber diameter should be selected. it is known from filtration theory that efficiency decreases with the increase of fiber diameter, but the decrease velocity is slower than the decrease velocity of pressure drop caused by the increase of fiber diameter. meanwhile, for the given filtration velocity and solid fraction of fibrous layer, thicker fibrous layer is needed for large fiber diameter in order to obtain the same efficiency. although the usage amount of filter material is obviously much for thicker fibrous layer, the pressure drop still decreases compared with that of small fiber diameter. therefore, suitable fiber diameter should be determined according to the design requirement. secondly, the fibrous layer thickness should be determined. this index depends on the structure and operation condition of air filter. thirdly, it should be remembered to keep the structure from being too close or too loose. it seems that the corrugation number could be increased, but this will cause two unreasonable consequences. one is that air does not flow thoroughly near the corrugation edge and stagnant airflow space is formed, so the effective filtration area reduces. at the same time, the corresponding support for filter material increases, so part of filtration area reduces by - % since the filter material is sheltered by the support. the other is that distance of filter material in each corrugation is very close when the corrugation number increases. under the airflow pressure, the soft filter material between two corrugations squeezed together, which increases the pressure drop. in order to obtain the maximum effective filtration area, comprehensive consideration of various factors including filter thickness, ridge distance, ridge angle, and filter material thickness. take bag-type air filter with frame of fixed volume, for example. when bag number increases from two to four, the filter material area increases and the pressure drop of filter material decreases. but the pressure drop of structure will increase because the flow channel is narrowed to increase the pressure drop of structure. when the number of bags is not large, the pressure drop decreases with the increase of the number of bags. on the contrary, when the number of bags is comparatively large, the pressure drop increases. the decrease of pressure drop of filter material cannot offset the increase of pressure drop of structure. meanwhile, when the number of bags is large or they are too long, the two walls of neighboring bags almost contact each other under the effect of airflow. so it is meant to increase the filtration area by increasing the bag number, but the result is different. it can be improved by setting formed line inside the bag or setting frame outside the bag. with the formed line, walls of bags will be tightened and bags will not be stretched outside. with the frame, walls are kept from stretching outside. for the filtration velocity between . and . m/s, the pressure drop can decrease by - %. there are similarities between folded air filters and the bag filter. if no frame is placed, with the same total filtration area, the more the number of bag is (or the smaller the bag is), the narrower the airflow channel is, and the larger the structural pressure drop is. since the pressure drop of filter material is the same, the total pressure drop increases. this is consistent between experiment and theoretical analysis [ ] . foam air filter is a combination of individual pin hole. membrane between pin holes is melted with the chemical treatment, so that air can flow through it. it is then used as filter material. foam plastic filter is one example. it is composed of three dimensional net skeletal frames, whose cross section is not circular. the size of this skeletal frame differs a lot. when the skeletal frame is considered to be fibers inside the filling layer, the filtration efficiency can be derived with the application of fibrous filtration mechanism [ ] . figure . is the calculation plot for efficiency. in the figure, the number of pores is counted with microscopic after the surface of foam plastic is dyed. the usage of foam plastic filter is rare. in this section, the mechanism and device of electrostatic precipitation will not be introduced comprehensively. only one kind of popular electrostatic precipitation equipments -electrostatic cleaner is presented. in the turbulent cleanroom, eddy current forms near the four corners of rooms because of the limit of air supply mode, where the cleanness cannot be improved by air distribution. because of the eddy current and the dust source, the cleanness of the room will be greatly influenced. in order to reduce the particle concentration in these regions, local cleaning equipment can be used. air is cleaned when the local air goes through the air cleaner repeatedly. the pressure drop of electrostatic cleaner is very small, and it is usually only - pa. the axial fan can be used and the noise level is low. besides it has the advantage of flexibility and convenience to use. so it is especially suitable for self-purification of indoor air. in the past, the electrostatic cleaner was called electrostatic self-purifiers in china. if a layer of activated carbon filter is added into the electrostatic cleaner, it also has the effect of gas and carbon dioxide adsorption. now this kind of electrostatic cleaner can be used as self-purification in rooms where the air cleanness is required. for example, it can be applied in meeting room, guest room, and living room. test has shown that when an electrostatic cleaner with two-stage ionization and efficiency of % operates in room with area m for . h, the dust concentration reduces to / of the original value, and the colony count becomes / of the original value. in cleanrooms, electrostatic cleaner should not be used as final filter, which has already specified in related standards. this is because the air delivery rate is very small. moreover, particle resuspension caused by power failure, shutdown of the device, and discharge will cause unexpected result. it efficiency is less than that of sub-hepa filter and hepa filter. it is mainly used in the air handling system of fresh air. it is shown in the expression that for given particle group, u e is proportional to n d p when other conditions remain the same. however, as mentioned before, for particles with diameter less than μm, n d p is stable. so u e will approach stable and do not decrease. when it is noticed that the slip correction coefficient c will increase with the decrease of particle size (introduced in chap. ), the separation velocity will be a little larger. that means the decrease of u e becomes stable. therefore, compared with other kinds of air filters, electrostatic cleaner is more suitable for capture of fine particles. when particle diameter is larger than μm, u e is proportional to d p because n d p is proportional to d p (because n is proportional to d p ). inside the electrostatic cleaner, the electric field usually has two forms: single zone and double zones, which are shown in fig. . . for the case of electric field with double zones, ionization electrode and dust collecting electrode are separate. in this way, the voltage of ionization electrode can be reduced from tens of thousands of voltage, which is used in single zone, to ten thousands voltage. several dust collectors can be used to increase the collecting area. the distance between collecting plates reduces so that the voltage can be as low as several thousands, which is much safer. therefore, the electrostatic cleaner with double zones is applied in the field of air-conditioning and cleaning system. the main difference between electrostatic cleaner used in air-conditioning and cleaning system and electrostatic precipitator used in industrial application is the discharge by positive corona instead of negative corona. for positive corona, it is easy to convert from corona discharge into spark discharge. so only lower charge voltage can be exerted, which reduces the generated ozone. for the occupied space, the concentration of ozone generated is limited. when positive corona is used, high enough dc positive voltage is exerted on the metal wire of ionization electrode, and two sides of polar plates are grounded. in this way, nonuniform electric field is formed near the ionization electrode. a few free electrons in the air obtain energy from the electric field. they collide with air molecules fiercely, which generates collision ionization, and incomplete discharge appears, which is called corona discharge. around the ionization electrode, a ring of light blue halo could be seen, which is termed as corona. so ionization electrode abounds with positive ions and electrons. electrons move towards metal wire and neutralize on it, while positive ions move regularly under the effect of electric field, and they attached onto neutral particles when they encounter each other. in this way, particles become positive, which is the first kind of charge mechanism, i.e., electric field charge. secondly, except for the movement under the effect of electric field, ions have thermal motion. ions attach onto particles during the process of thermal movement, which makes particles positive. this is called the second kind of charge mechanism, i.e., diffusion charge. according to the electrostatic theory, electric field charge mainly has influence on the particles with diameter larger than μm. the maximum charge particles can obtain is where e is the electric field intensity in the space of ionization electrode, e.s.u. ( v/cm ¼ e.s.u.); n is the number of charge; e is the unit charge, .  À e.s.u.; d p is the particle diameter, cm; k is the coefficient, k ¼ ε εþ ; the average is between . and . ; ε is the dielectric constant; the average value is - . diffusion charge has the main influence for particles with diameter less than μm, especially less than . μm. however, no simplified expression has been obtained for the maximum diffusion charge so far. it is known from eq. ( . ) that the charge on particles with diameter larger than μm is proportional to the square of particle diameter. but with the effect of diffusion charge, the charge on particles with diameter equal to or less than μm is larger than that obtained by eq. ( . ) . so the ratio of charge and its particle size n d p keeps stable. it will not decrease inversely proportional to the square of particle size. charged particles enter into the space composed of parallel thin aluminum plates. since aluminum plates are placed by staggered rivets with one aluminum plate positive and the other grounded, an uniform electric field is formed in the space. with the coulomb force in the electric field, charged particles obtain repellent force from the positive plate, and they settle down onto the grounded plate. the repellent force can be expressed as where f e is the coulomb force; q is the charge on particle (e.s.u.). for the flow with small re (usually less than ), the pressure drop of spherical particles is obtained by eq. ( . ). when the pressure drop is balanced with the coulomb force, i.e., πμd p v ¼ nee , the motion velocity u e of particles in the electric field is obtained when the slip correction is considered, which is also called separation velocity or migration velocity. it can be expressed as where μ has the cgs unit (shown in chap. ), and other symbols have already been explained. it is shown in the expression that for a given particle group, u e is proportional to n d p when other conditions remain the same. however, as mentioned before, for particles with diameter less than μm, n d p is stable. so u e will approach stable and does not decrease. when it is noticed that the slip correction coefficient c will increase with the decrease of particle size (introduced in chap. ), the separation velocity will be a little larger. that means the decrease of u e becomes stable. therefore, compared with other kinds of air filters, electrostatic cleaner is more suitable for capture of fine particles. when particle diameter is larger than μm, u e is proportional to d p because n d p is proportional to d p (because n is proportional to d p ). electrostatic cleaner is composed of box, power supply, fan, dust collecting electrode, ionization electrode, activated carbon filter, and prefilter. figure . shows the structure of domestic jzq-ii electrostatic self-purifier [ ] . the box is made by single layer of thin steel plate. with the requirement of air tightness, the box gates are connected with circlip, which is used for the convenience of maintenance. the ionization electrode is a nickel chrome silk with diameter . mm. dust collecting electrode is composed of rigid aluminum alloy plates with thickness mm and inter-plate spacing mm (between opposite plates). each polar is made of pieces of plates with area of each plate . m  . m. the surface of these plates has been electropolished to get rid of the burr and sharp corner, so the phenomena of spark discharge will not occur and the voltage between plates will be decreased. figure . presents the structure of jzq- electrostatic self-purifier with one time ionization method. the height of jzq electrostatic self-purifier is . m and the net cross-sectional area is . m  . m. during the design of structure, the leakage inside the structure is usually neglected, which will greatly reduce the dust capture efficiency. there are mainly two reasons: one is caused by the electric wire when it goes through holes (such as the separator between layers); the other is the leakage between frame of each layer and box. it should be noted during the design of structure that two grounded plates must be added at both sides of ionization electrode (metal wire) and dust collecting electrode (metal plate). if both the ionization wire and the electrode plate near the edge are only connected with the power and without being grounded, both the airflow and particles will not be easily ionized and particles will not deposit readily, which will lower the total efficiency. since the volume of electrostatic cleaner is small, silicon rectified circuit is used for the power supply. in order to reduce the output voltage of transmitter so as to insulate, four times voltage circuit is usually adopted. figure . shows the circuit of jzq-ii electrostatic cleaner. when too much dust has been deposited on the dust collecting plate, the indicator light will turn dark. the plate should be taken out for clean in time so that the dust collecting efficiency will not be affected. the following steps can be used to derive the dust collecting efficiency of electrostatic cleaner when the dust collecting electrode is plate. suppose the concentration at x distance from the inlet of dust collecting plate is n x , the airflow velocity between plates is v, the total flow rate through the dust collecting plate is q, the total effective area of dust collecting plate is f, and the length of plate is l. during the time dt, the decrease of dust along the dust collecting plate (perpendicular to the flow) equals with the number of deposited particles at this section of dust collecting plate, i.e., when the concentration at x ¼ l , i.e., the outlet concentration, is n l , and the concentration at x ¼ , i.e., the inlet concentration, is n , integration is performed on the above equation and the following expression is obtained: then the dust collecting efficiency is it is obvious that η increases with the increase of the separation velocity u e . for given particles, u e mainly depends on the voltage between the ionization electrode and the dust collecting plate. when the voltage of the dust collecting plate increases, the electric strength in the space between dust collecting plates also increases, which will increase the separation velocity. however, when the electric strength between dust collecting plates is too high, the phenomena of electrode discharge are likely to appear. even through the electropolishing, the surface of plates will inevitably unsmooth, especially burr exists near the edge. even through the surface is very smooth, discharge will occur when a large dust especially fiber deposits on the surface, which will decrease the electric strength rapidly. during the process of discharging, sounds with cracking will be heard. for common manufacturing level, the electric voltage of the dust collecting plate can be increased to , - , v, which is equivalent to the electric strength about kv/mm. when the voltage of the ionization plate is elevated, particles will be charged more, which increases the separation velocity u e . but the extent of voltage increase is limited by the manufacturing precise. too much voltage will cause electric discharge. so the voltage is usually less than , v. the separation velocity u e calculated from eq. ( . ) is only a theoretic value. in practice there are many influencing factors which are not included in this equation. these influences include: distribution of air and airborne particles at the cross section between plates, movement characteristic of air in the channel, coagulation of particles, and re-entrainment of particles deposited on plates. therefore, the actual separation velocity is much less than theoretical value. research performed on industrial electrostatic cleaner shows that the actual velocity is half of the theoretical value. but the situation is better for electrostatic cleaner used in air cleaning system, because the distance between dust collector plates is small, and velocity is small so that the flow is laminar. the particle size distribution at inlet is comparatively uniform. so the disturbance extent on u e is small. therefore, the actual separation velocity of electrostatic cleaner is a little higher than that of industrial electrostatic cleaner. for the given height (width), the larger the effective area is, which corresponds to the larger length, the higher the efficiency derived by eq. ( . ) is. the effective area of plate mentioned in literature means the area which is effectively used in structure. according to the expression of efficiency, efficiency will reach % when the area is large and the plate is lengthy. but in reality not all the area of the plate along its length can collect dust efficiently. test on jzq-i electrostatic cleaner with length cm shows that only / of the area along the length collect dust. if all the particles are deposited on the plate along this / length, the efficiency of this electrostatic cleaner approaches %, while in fact it is only - % which can been seen from the comparison table about efficiencies. this is not caused by the length of plate which is not long enough so that particles do not have time to deposit but by part of particles which is not charged or whose electric charge is not enough. for particles whose charge is not enough and u e is small, it is effective to prolong the length of dust collector plate. however, for particles which are not charged at all, they will not be deposited on plate even when its length is prolonged. since particles without charge do exist, a concept "effective length of dust collector plate" is proposed. it means that under certain electric field, only certain part of the plate has effect on dust collecting. when it is longer than this length, the efficiency of the left part of the plate cannot be described by eq. ( . ), which implies that no more particles can be captured or not all the particles can be collected. why do some particles carry very few charges or no charges? according to the theory of electric corona discharge, there are mainly two reasons: . since the electric ionization polar is a metal wire, the electric field with high electric strength only appears near the small distance around it, while the electric strength far from it is very weak. for the latter situation, the movement velocity of ions is very slow and the air in that region is not ionized (if all the air between plates is ionized, the electric field will be penetrated when spark discharge appears and short electric circuit is formed, thus the electrostatic cleaner stops). . as mentioned before, with certain voltage of electric ionization polar, the ionization strength for air is fixed and the charge amount is determined. if the dust concentration of air entering electrostatic cleaner is high, charge on every particle is not enough or some particle cannot be charged at all. it is obvious that the former reason is mainly for electrostatic cleaner. from the above analysis, if the effective length of dust collector is measured, the actual separation velocity can be derived from the dust collector efficiency. it is obvious that the less the flow rate of electrostatic cleaner, the higher the efficiency is. but for particles without charge, efficiency will become stable when the flow rate is less than a certain value. according to the above analysis, in order to increase the efficiency of electrostatic cleaner with one-stage ionization, the extent of particle charge must be increased. so author proposed a scheme "two-stage ionization" which put two electric fields in series. with this method, air molecules not ionized in the first electric field will be likely to be ionized in the second electric field. in the late of s, institute of hvac at china academy of building science and the former tianjin medical equipment factory invented and manufactured jzq-ii electrostatic cleaner together, which adopted this method. it is meaningless if the height of the equipment with two-stage ionization is two times that of the original equipment. according to the above analysis, the effective dust collector length under the given conditions is about . m. so the length of dust collector of jzq-ii electrostatic cleaner is . m under the condition of compact structure, which is the same as that of the one-stage ionization. with the scheme of two-stage ionization, the predicted effect of electrostatic cleaner is realized. related experimental data are presented in the following tables. table . is the experimental data about the relationship between efficiency and voltage of dust collector. table . is the experimental data about the relationship between efficiency and velocity between plates of dust collector. table . is the experimental data about the relationship between efficiency and capacity of capacitor in the rectifying circuit. the influence of capacity of capacitor in the rectifying circuit on efficiency is large. when the capacity is small, the decrease of voltage on each octave band pressure level will be large, which reduces the particle capture efficiency, while increasing the capacity will smooth the wave profile after rectifying and the effective voltage approaches the summit value. but it is not safe if the capacity of capacitor was too big. for jzq-ii electrostatic cleaner, it is feasible to choose , μμf as the capacity of capacitor. according to eqs. ( . ) and ( . ) with the cgs unit and e.s.u. of e and e , the separation velocity for the condition with c ¼ , k ¼ (for oil mist from the transformer, k ¼ . ; for marble particles, k ¼ . ), and both e and e are e.s.u. becomes u e ¼ d e e π  :  À d % : e e d  cm=s when d ¼ .  À cm, c ¼ . , e ¼ , v % . e.s.u., and e ¼ , v % . e.s.u., the derived separation velocity is u c ¼ cm/s (which is equivalent with the calculation result based on average particle size of atmospheric dust). according to eq. ( . ), the relationship between fu e q and η is where is the number of dust collecting surfaces. each dust collecting plate has two surfaces. since the most outer two sides do not play a role, they are not included and the total number of dust collecting surfaces is . so the actual separation velocity of each section for given efficiency can be calculated, which is shown in table . . from table . , the average of actual separation velocity is . m/s, which is slightly higher than half of theoretical separation velocity. it is consistent with the aforementioned analysis. for jzq-ii electrostatic cleaner with two-stage ionization method, the comparison of its turbidity efficiency measured by photoelectric turbidimeter with the foreign similar products is shown in table . . in terms of efficiency, results obtained by the turbidimetry method are usually smaller than that of dust spot method and weighing method. so the performance of jzq-ii electrostatic cleaner is better than that presented in table . . for simplifying the structure, cylindrical electrostatic cleaner appears in the market. thin metal plate is used to make the cylinder with circular or hexagonal cross section. it acts as the grounding plate. circular electrode with cusp is placed in the center of cylinder, where high-voltage electrostatic is applied. it becomes the high-voltage discharging electrode in the electrostatic field, which is shown in fig. . . but the efficiency of this kind of cylindrical electrostatic cleaner is very low. table . shows the test data from mao huaxiong [ ] . more attention has been paid on the influence of chemical pollution inside cleanrooms (please refer to chap. ), so people starts to care about activated carbon filter. activated carbon filter has functions of both physical adsorption and chemical adsorption, so in fact it is an adsorber. the adsorption ability of activated carbon has selectivity. for these chemical substances which cannot be removed by physical adsorption mechanism, different chemical agents must be used as adsorbent during the process of impregnation. with the chemical reaction between adsorbent and adsorbate, the property of adsorbate is modified and it becomes nontoxic and harmless. many monographs and literatures have introduced the general application of activated carbon filters, which will not be mentioned in this section. only several aspects are emphasized here: . at present there are three kinds of activated air filters. one is the activated carbon particulate filter where the size of particle varies from small to large. the second is activated carbon particles with diameter . mm pasted on multiply layers of porous polyurethane foam material. since the air permeability of foam material is good, its pressure drop is smaller than that of the former kind and the corresponding adsorption efficiency reduces. the third is activated carbon fibrous filter by carbonization of fibrous media. it is thin, and both the pressure drop and adsorption efficiency are comparatively small. . the problem of invalid layer exists in the activated carbon filters. invalid layer is meant to adsorb a certain amount of chemical pollutants. the larger the activated carbon particle is, the thicker this layer is. this problem is usually ignored. figure . shows the theoretical relationship between the invalid layer thickness and the amount of pollutant adsorbed. when the amount does not reach a certain value, it is called the non-protective time. figure . is the result performed with cyan chloride [ ] . the existing of this invalid layer is related to the adsorption mechanism of chemical pollutant by activated carbon. when polluted airflows through activated carbon, the pollutant diffuses towards the whole surface of activated carbon particles. then it goes towards to the pore interior surface of the particles and the surface of pores. so chemical reactions occur inside the particle interior surface to decompose the pollutant by adsorption of pollutant molecules and between adsorbed chemical pollutant and chemical agent (catalyst) dipped with activated carbon or between adsorbed oxygen and water. if several adsorption mechanisms inside a layer with certain thickness do not have enough time to play a role, for example, pollutant only diffuses onto the particle surface while they do not have time to diffuse towards the interior surface of pores and then adsorbed and decomposed, but it has already penetrated this layer, the pollutant concentration cannot be reduced to allowable value or has no time to be reduced at all, this layer is called invalid layer. if the activated carbon is within the invalid layer, there is no effect of adsorption. with certain physical and chemical property of activated carbon and temperature/humidity conditions, the thickness of invalid layer is only related to the specific velocity and pollutant concentration. when both the specific velocity and concentration are fixed, the thickness is constant, which is not related to the thickness of whole activated carbon layer. . since the pressure drop of activated carbon filter filled with particulate activate carbon is very large, the allowable specific velocity cannot be very large. therefore, it is necessary to understand the specific velocity-pressure drop characteristic of this kind of activated carbon filter. . when the activated carbon filter is designed to be circular cylinder, it has been proved by the author that the performance is better when the polluted air flows from outer towards inside, which improves the amount of adsorption [ ] . since the risk of microorganism becomes higher, antibacterial filters develop in the usa and japan. this kind of filter is made by adding bactericidal substance in the filter media. however, doubt about its effectiveness exists. one kind is only to spray the additive onto the surface of filter media, so not all the filter layer have the ability to kill bacteria. the second kind is only to add bacteriostatic agent, which cannot kill the bacteria and instead may cultivate the ability of drug resistance of the bacteria. the third kind may generate some gaseous substance or odor which is harmful for people. it should be emphasized, which will also be introduced in chap. , that it is difficult for the bacteria captured on the windward side of the hepa filter made by inorganic material to reproduce and even penetrate. only with the suitable conditions of temperature and humidity, they are likely to survive. so the final conclusion of the necessity to use the antibacterial filter has not been reached. ashrae has warned as for this issue and suggests using antibacterial product in hvac system cautiously, so as not to produce any chemical pollution and new harm to the indoor environment and people. application of air cleaning technology air filtration ( ) filtration of aerosols by fibrous media particle capture performance of fibrous filling layer filter and influence of fiber cross sectional shape tu guangbei) ( ) fibrous filter media and air filter, science and technology information reference room at tianjin university study of influencing factors for the performance of air filters institute of hvac of china academy of building research ( ) assembly cleanroom calculation of cleanroom performance test of domestic air sampler and high efficiency filter media status of industrial cleanroom planning and design of cleanroom calculation and verification of in-series efficiency of hepa filters experimental study of the safety of hepa filter used in nuclear fuel facilities air cleaning handbook (trans: shi youren et al) japan refrigeration and air conditioning industry association ( ) handbook of refrigeration and air conditioning (application) air conditioning and air cleaning absolute filter of cambridge filter corporation discussion of standard flow rate for hepa filter influence of non rated flow volume on the life time of hepa filter conversion method between the particle counting efficiency and the arrestance with atmospheric dust the latest filter cleanroom technology (trans: yu zhaoji) tgg and ygf low resistance and sub-high efficiency air filter characteristic of filter paper used for collection of radioactive particles recent development of particulate capture system evaluation and performance study of air cleaner optimization design of corrugated sub-high efficiency air filter without separator performance of polypropylene fibrous media performance evaluation of electret hepa filter monodisperse aerosol generator, institute of hvac at china academy of building research study of nuclepore membrane filter structure and its filtration performance institute of hvac at china academy of building research ( ) two kinds of type protective air filter soft leather treatment agent for treating with ultra-fine glass fibrous paper for air filtration introduction to chinese current standardization system on high efficiency particulate air filter performance and prospect of hepa filter used in cleanroom the mechanics of aerosols (trans: gu zhenchao) development status and trends in the filtration dust study on the filtration of ultrafine particles study of the application of electrostatic air cleaner for improving institute of hvac at china academy of building research ( ) two kinds of type protective air filter key: cord- -qvub v e authors: chen, chun; zhao, bin; lai, dayi; liu, wei title: a simple method for differentiating direct and indirect exposure to exhaled contaminants in mechanically ventilated rooms date: - - journal: build simul doi: . /s - - - sha: doc_id: cord_uid: qvub v e many airborne infectious diseases can be transmitted via exhaled contaminants transported in the air. direct exposure occurs when the exhaled jet from the infected person directly enters the breathing zone of the target person. indirect exposure occurs when the contaminants disperse in the room and are inhaled by the target person. this paper presents a simple method for differentiating the direct and indirect exposure to exhaled contaminants in mechanically ventilated rooms. experimental data for cases were collected from the literature. after analyzing the data, a simple method was developed to differentiate direct and indirect exposure in mixing and displacement ventilated rooms. the proposed method correctly differentiated direct and indirect exposure for out of the mixing ventilation cases and out of the displacement ventilation cases. therefore, the proposed method is suitable for use at the early design stage to quickly assess whether there will be direct exposure to exhaled contaminants in a mechanically ventilated room. the airborne transmission of infectious diseases in indoor environments has been become a major public health concern worldwide (wei and li ). an infected person can exhale particles carrying infectious viruses when breathing, coughing, or sneezing (nicas et al. ) . these airborne contaminants can be transported to the breathing zone of other persons via the air in a room. if the infectious contaminants are inhaled by susceptible individuals, cross infection of the disease may occur (morawska ) . many outbreaks of airborne infectious diseases have occurred indoors through this transmission route, including influenza (moser et al. ) , measles (bloch et al. ) , tuberculosis (menzies et al. ) , and severe acute respiratory syndrome (sars) (olsen et al. ) . furthermore, a strong association has been found between the indoor airflow pattern and transmission of airborne infectious diseases . therefore, it is crucial to investigate the indoor exposure to exhaled contaminants in mechanically ventilated rooms to improve air distribution design and reduce the risk of infection. numerous experimental studies have been carried out to measure person-to-person contaminant transport in mechanically ventilated rooms. bjørn and nielsen ( ) , olmedo et al. ( olmedo et al. ( , , nielsen et al. ( ) , and liu et al. ( ) studied the impact of inter-person distance on personal exposure to exhaled contaminants in displacement, mixing, and downward ventilated rooms. qian et al. ( qian et al. ( , , and yin et al. ( ) investigated the effectiveness of build simul ( ) : - https://doi.org/ . /s - - - mixing, downward, and displacement ventilation in removing exhaled contaminants in simulated hospital wards. nielsen et al. ( ) investigated the impact of personalized ventilation on personal exposure in a room ventilated by textile terminals. wong ( , ) measured transient exposure to exhaled particles in small-scale laboratory chambers with different ventilation modes. nielsen et al. ( ) investigated the influence of ventilation rates on person-to-person contaminant exposure in a hospital ward. cao et al. ( ) proposed protected zone ventilation for reducing personal exposure to exhaled contaminants indoors. these studies have provided great insights and rich experimental data on personal exposure to exhaled contaminants in mechanically ventilated rooms. in general, there are two modes of personal exposure to exhaled contaminants: direct exposure and indirect exposure olmedo et al. ; chen et al. a) . direct exposure occurs when the exhaled jet carrying contaminants from the source person directly enters the breathing zone of the target person. thus, direct exposure is determined primarily by the impact scope of the exhaled air . in contrast, indirect exposure occurs when contaminants disperse in the room and are inhaled by the target person. therefore, indirect exposure is determined primarily by the ventilation in the room. at the early stage of ventilation design, it may be desirable to have a simple method to quickly assess personal exposure to exhaled contaminants. if the assessment shows that direct exposure may occur, we should consider separating individuals by altering the design for the interior layout, for example by increasing the distance between seats. if the assessment shows that only indirect exposure will occur, we should focus on how to achieve a healthier indoor environment by improving the design of the air distribution system. therefore, to better support decision making at an early design stage, it is worthwhile to develop a method for differentiating direct and indirect exposure to exhaled contaminants. direct and indirect exposure can be differentiated by either experimental measurements (e.g., olmedo et al. ; liu et al. ) or numerical simulations (e.g., li et al. ; chen et al. a,b) . however, these methods are time consuming and therefore may not be appropriate for the early stage of design. therefore, this study aimed to develop a simple method for differentiating direct and indirect exposure to exhaled contaminants in mechanically ventilated rooms. we first collected experimental data of normalized personal exposure to exhaled contaminants from the literature to form a database. the data were then analyzed to capture the major influencing factors. based on this analysis, a simple method consisting of the calculation of the impact scope of exhaled air and a simple decision-tree model was developed to differentiate direct and indirect exposure. finally, the accuracy of the proposed method was assessed by comparing the results with the collected experimental data. review of experimental data from the literature we first collected the experimental data of personal exposure to exhaled contaminants from scientific papers (bjørn and nielsen ; qian et al. qian et al. , nielsen et al. nielsen et al. , nielsen et al. , olmedo et al. olmedo et al. , cao et al. ; liu et al. ) to create a database. data for cases of personal exposure to exhaled contaminants were extracted from the figures or tables in the literature. table summarizes the ventilation mode, ventilation rate, inter-person distance, and normalized exposure to exhaled contaminants reported in these studies. when collecting the data, we focused on two major types of ventilation mode: mixing ventilation and displacement ventilation. downward ventilation was categorized as mixing ventilation based on the findings of qian et al. ( ) . other ventilation modes, such as protective ventilation and personalized ventilation were not included. there were mixing ventilation cases and displacement ventilation cases. the tested ventilation rate ranged from . to ach (air change per hour). the studied person-to-person distance ranged from . to . m. personal exposure to exhaled contaminants was normalized by the concentration at the exhaust of the room as follows: where c exp (#/m ) is the exhaled contaminant concentration measured in the breathing zone of the target person, and c r (#/m ) is the exhaled contaminant concentration measured at the exhaust. in a well-mixed condition, the normalized exposure is equal to . . among the cases, the normalized exposure varied significantly from . to . , deviations from the well-mixed condition of more than one order of magnitude. figure shows the distribution of normalized personal exposures for the mixing ventilation cases and displacement ventilation cases. the vertical axis is the fraction of cases falling within the range of normalized exposures. for example, out of ( %) mixing ventilation cases had a normalized exposure to exhaled contaminants of between . and . . for mixing ventilation, the majority of cases occurred around the well-mixed condition with a normalized exposure of . . that means a considerable proportion of the cases could be regarded as well-mixed cases. however, there are also many cases with a normalized exposure significantly larger than . , which indicates unacceptably high exposure to exhaled contaminants. it is suspected that direct penetration of the exhaled air jet into the breathing zone of the target person was the main reason for the high exposures. for displacement ventilation, the peak fraction of cases did not occur around the wellmixed condition. there were many cases with a normalized exposure significantly lower than . . to differentiate the direct-exposure cases and indirectexposure-only cases, a cutoff value of normalized exposure should be defined. if the room air is well-mixed in all of the cases, the cutoff value of normalized exposure can be set at . . however, it is difficult to achieve the well-mixed condition in actual engineering applications. there must be a certain degree of non-uniform distribution in the room. therefore, this study set the cutoff normalized exposure at . for mixing ventilation, i.e. % higher than the theoretical value. that is to say, if the normalized exposure is lower than or equal to . , this indicates no direct exposure, only indirect exposure to the background concentration in the room. a number of indirect-exposure-only cases with a normalized exposure ranging from . to . were found in nielsen et al. ( ) , olmedo et al. ( ) , and nielsen et al. ( ) . in contrast, a normalized exposure value higher than . thus indicates serious direct exposure. using this definition, there were direct-exposure cases and indirect-exposure-only cases for mixing ventilation in the database. using the same definition, there were directexposure cases and indirect-exposure-only cases for displacement ventilation in the database. to develop an effective method, we first analyzed the factors influencing person-to-person contaminant transport in mechanically ventilated rooms. person-to-person distance, ventilation mode, and ventilation rate are among the most important influencing factors (chen et al. b) . figure plots the normalized exposures to exhaled contaminants relationship between normalized exposure to exhaled contaminants and person-to-person distance for cases extracted from the literature against the person-to-person distance for the cases. it can be seen that when the inter-person distance was greater than or equal to . m, the normalized exposure for most of the cases was lower than . . note that these cases included both mixing ventilation and displacement ventilation. in theory, the normalized exposure for mixing ventilation is . . assuming a certain degree of non-uniformly distributed airflow, some cases might have a normalized exposure slightly higher than . , e.g. % higher or . . when displacement ventilation is designed appropriately, the normalized exposure can be considerably lower than . . clearly, the collected data included such desirable scenarios. in general, when the inter-person distance was greater than . m, direct exposure was avoided. however, when the inter-person distance was less than . m, there were many cases with a normalized exposure significantly larger than . (as high as . ). in these cases, direct exposure significantly increased the risk of cross infection. even so, it was also observed that a considerable number of cases had a normalized exposure of around . or lower when the distance was less than . m. thus, the inter-person distance may not be an appropriate indicator by which to differentiate the direct and indirect exposures to exhaled contaminants. in addition to inter-person distance, ventilation rate is an important factor influencing personal exposure to exhaled contaminants. in general, a higher ventilation rate results in lower exposure because of the principle of dilution. the normalized exposure takes into account the influence of ventilation rate. the contaminant concentration at the exhaust can be determined by where s  (#/s) is the generation rate of exhaled contaminants, q  (m /s) is the airflow rate of the ventilation, α (h − or ach) is the ventilation rate, and v (m ) is the volume of the room. therefore, in theory, the ventilation rate should have almost no influence on the normalized exposure to exhaled contaminants. figure plots the normalized exposures to exhaled contaminants against the ventilation rate for the cases collected from the literature. note that the data from nielsen et al. ( ) are not included in this figure because information about ventilation rates was not provided in that paper. the plotted data indicate that low ventilation rates occurred mainly in displacement ventilation cases, while high ventilation rates occurred mainly in mixing ventilation cases. in general, the data do not show any correlation between normalized exposure and ventilation rate, which is consistent with the theory. therefore, as long as normalized exposure is used as the index, there is no need to include the ventilation rate when developing a method for differentiating direct and indirect exposure to exhaled contaminants. another important influencing factor is the ventilation mode. figure compares normalized exposures to exhaled contaminants under mixing ventilation and displacement ventilation and shows the minimum, th percentile, median, th percentile, and maximum values. the median value for mixing ventilation was . , which is very close to . , i.e. the well-mixed condition. however, the median value for displacement ventilation was . , % higher than that of a well-mixed condition. this contrasts with the classical theory that displacement ventilation exhibits a higher ventilation efficiency or contaminant removal efficiency than mixing ventilation. this is because the data included many cases with a short inter-person distance. when the influence of inter-person distance overwhelms that of ventilation mode, the advantage of displacement ventilation in removing contaminants may not be observed. furthermore, exhaled air can be locked in a thermally stratified layer at the height of the breathing zone created by displacement ventilation (bjørn and nielsen ; qian et al. ; olmedo et al. ). in such cases, the target person, especially if close to the source person, may be exposed to a very high level of exhaled contaminants in the stratified layer. when the breathing zone of the target person is below the stratified layer, exposure can be very low because the air in the lower zone of the room is much clearer. such additional influencing factors increase the uncertainties of the normalized exposure under displacement ventilation, as shown in fig. . therefore, it is necessary to develop separate models for differentiating direct and indirect exposure in mixing ventilation and displacement ventilation scenarios. based on the analysis above on the experimental data collected from the literature, we developed separate models for differentiating direct and indirect exposures in mixing ventilation and displacement ventilation conditions. figure shows the typical scenarios of person-to-person contaminant transport in a mixing ventilated room. the source person exhales air with contaminants through breathing, coughing, or sneezing. the breathing zone of the target person is defined as a cube with a volume of . m in front of his/her mouth (osha ; chen et al. a). as illustrated in fig. (a) , when the breathing zone of the target person is within the impact scope of the exhaled air, serious direct exposure to the exhaled contaminants may occur. in contrast, when the breathing zone of the target person is far away from the impact scope of the exhaled air, only indirect exposure will occur, as shown in fig. (b) . another common scenario, as shown in fig. (c) , is the source and target facing in the same direction, such as people in a concert audience or students seated in a classroom. in such cases, even though the target person is close to the exhaled air, direct exposure may be avoided because the pathway to the breathing zone is blocked by the head. fig. (d) shows another scenario related to the thermal plume generated by the target person, which has been proven to be important in the near-body airflow field and contaminant transport (liu et al. ; yan et al. ) . when the exhaled air penetrates the lower zone of the thermal plume boundary layer, the contaminants may move upward with the vertical airflow driven by the thermal plume and enter the breathing zone. in this case, direct exposure may occur. we included these four scenarios in the developed method for differentiating direct and indirect exposure to exhaled contaminants. to determine the impact scope, it is crucial to understand the nature of the exhaled air. exhaled air is usually at a relatively high temperature, approximately °c, compared with the room air temperature. therefore, the exhaled jet is non-isothermal with a curved trajectory as shown in fig. . after leaving the mouth or nose, the exhaled jet mixes with the room air and grows thicker. a free round jet consists of an initial section and a main section. in the potential core of the initial section, the centerline velocity of the jet is equal to the initial velocity at the mouth/nose and the radial velocity component is zero. the air velocity distribution in the mixing layer of the initial region is similar to that in the main section, but the maximum velocity is from the centerline to the edge of the potential core. in the main section, the centerline velocity decreases with the increase in the distance from the mouth/nose. for a non-isothermal round jet, the trajectory equation of the curved centerline can be determined by the following equation (baturin ): where a (m ) is the area of the mouth/nose opening, t (k) is the temperature of the exhaled air, t r (k) is the room air temperature, and ar is the archimedes number, which can be calculated by where g (m/s ) is the gravitational acceleration, α (k − ) is the thermal expansion coefficient of air, and u (m/s) is the initial velocity at the mouth/nose. note that, when the exhaled air direction is not horizontal, the coordinate system shown in fig. should be altered accordingly. with the curved centerline trajectory of the exhaled air, the relative coordinates of the breathing zone center point, s and r, can be determined as illustrated in fig. . line_ is a tangent line to the curved trajectory of exhaled air centerline at the cross point (x c , y c ). line_ is perpendicular to line_ and passes through both the cross point (x c , y c ) and the breathing zone center point (x b , y b ). therefore, the relationship between the slopes of the two lines, β and β , is where the slope of line_ can be determined by the derivative the cross point coordinates (x c , y c ) can then be calculated by solving eqs. ( ) to ( ) together. therefore, the relative coordinates of the breathing zone center point to the exhaled jet centerline, s and r, can be calculated by with the relative coordinates of the breathing zone center point, s and r, the local air velocity at this point can be calculated using jet theory. in this case, we used the jet expressions from bocksell ( ) , which were also used by xie et al. ( ) . the centerline velocity can be calculated by m . u u s = where u m (m/s) is the centerline velocity, and u (m/s) is the initial velocity at the mouth/nose, and s (unitless) is the dimensionless centerline distance, which is defined as ( ( ) ) ( )( ( ) ) where σ is equal to . , a is equal to . , b is equal to . , and η is defined as where r (m) is the distance from the target location to the centerline. therefore, the velocity magnitude at a location in the jet with the coordinates of s and r, u (m/s), is equal to based on similarity theory, the contaminant concentration at a given location in the jet is correlated to the local air velocity (berlanga et al. ) . therefore, we used the local air velocity (u) at the center of the target person's breathing zone calculated by the model above as an indicator to differentiate the direct and indirect exposure to exhaled contaminants. when the local air velocity is significantly higher than a certain threshold, u * , (to be determined later), the local contaminant concentration in the breathing zone also tends to be significantly higher than the background concentration in the room. in such cases, the breathing zone of the target person is within the impact scope of the exhaled air, so that direct exposure may occur (scenario ). in contrast, if the local air velocity is lower than the threshold, the local contaminant concentration in the breathing zone should be similar to the background concentration in the room. in such cases, it is considered that there is no direct exposure but only indirect exposure to the background concentration in the room (scenario ). two special scenarios, scenarios and (shown in fig. ) should be further considered. when the pathway from the exhaled air to the breathing zone is blocked by the head of the target person, (e.g. two persons facing in the same direction, one behind the other), the exposure is considered to be indirect only (scenario ). to determine whether the thermal plume generated by the target person will result in direct exposure, more calculations are needed, as illustrated in fig. . in the coordinate system shown in fig. , the function of the exhaled air centerline trajectory can still be described by eq. ( ). line_ is a line along the body of the target person across the breathing zone center point. this line can be roughly regarded as the pathway of the upward thermal plume. line_ is perpendicular to line_ ; thus, the slop of line_ can be calculated by where θ is the angle between the x-axis and line_ shown in fig. . therefore, the function of line_ is where c is a constant which can be determined by because the breathing zone center point (x b , y b ) is also on line_ . by solving eqs. ( ) and ( ) together, the coordinates of the cross point (x t , y t ) can be obtained. if the cross point is below the breathing zone center point (i.e., y t ≤ y b ), the cross point is considered to be within the boundary layer of the thermal plume generated by the target person. the next step is to calculate the local air velocity at the cross point, u t , by eq. ( ). if this local air velocity is greater than the threshold local air velocity, the exhaled contaminant concentration at the cross point is significantly higher than the background concentration. that means a considerable amount of exhaled contaminants enter the boundary layer of the thermal plume. here, we assume that these contaminants will move upward with the thermal plume to the breathing zone of the target person (scenario ). figure shows a simple decision tree model used in the proposed differentiation method. first, eqs. ( ) to ( ) are used to determine whether the breathing zone of the target person is within the impact scope of the exhaled air. if yes, the face-to-face orientation is examined to see if the pathway of exhaled air to the breathing zone is blocked by the head of target person. if it is not blocked, direct exposure will occur; if it is blocked, only indirect exposure will occur. if the breathing zone is not within the impact scope of exhaled air, eqs. ( ) to ( ) will be used to examine if the exhaled air can enter the lower zone of the thermal plume boundary layer of the target person. if yes, it is considered that the contaminants will move upward with the thermal plume and cause direct exposure. otherwise, only indirect exposure will occur. with this differentiation strategy, the remaining problem is how to define the threshold local air velocity, u * , to determine the impact scope of the exhaled air. the next step is to determine the threshold of the local air velocity, u * , to differentiate the direct and indirect exposures. we used the experimental data from the literature to determine the threshold local air velocity. note that this study set the cutoff normalized exposure at . to differentiate the direct-exposure cases and indirect-exposure-only cases for mixing ventilation as defined in the last paragraph of section . . figure shows the error of the proposed method under different threshold local air velocities. when the threshold local air velocity was . m/s, the error of the proposed method was the lowest, at . %. thus, the proposed method could correctly differentiate the direct (c exp /c r > . ) and indirect (c exp /c r ≤ . ) exposure for out of the mixing ventilation cases. therefore, the threshold local air velocity was set at . m/s in the method for differentiating the direct and indirect exposure to exhaled contaminants in mixing ventilated rooms. the proposed method was used to differentiate the direct and indirect exposure to exhaled contaminants for the mixing ventilation cases. figure shows the distribution of the measured normalized exposure for the predicted direct-exposure cases and indirect-exposure-only cases. from the experimental data, there were direct-exposure cases and indirect-exposure-only cases for mixing ventilation. the proposed method correctly identified direct-exposure cases and indirect-exposure-only cases. fig. measured normalized exposure for the predicted indirectexposure-only and direct-exposure cases in mixing ventilation (the th , th , median, mean, th , and th percentile values are shown) fig. the simple decision tree model used in the method for differentiating direct and indirect exposure to exhaled contaminants in general, with a threshold local air velocity of . m/s the proposed method can reasonably differentiate direct and indirect exposure to exhaled air in mixing ventilation conditions. the median value for the predicted indirectexposure-only cases was . , which is close to the theoretical value of . . in contrast, the median value for the predicted direct-exposure cases was . , which is significantly higher than . , owing to the direct exposure to exhaled contaminants. figure shows the typical scenarios of person-to-person contaminant transport in a displacement ventilated room. the four scenarios are similar to that shown in fig. , but there are two major differences. first, if the target person is far away from the impact scope of exhaled air, the clean air supplied from the displacement ventilation diffuser may directly enter the breathing zone so that exposure can be reduced. therefore, in general, the indirect exposure under displacement ventilation is lower than that under mixing ventilation (chen et al. b) . second, the exhaled air may be locked in the thermal stratification layer created by the displacement ventilation (bjørn and nielsen ; qian et al. ; olmedo et al. ). in such cases, the exhaled air tends to move more horizontally and have an impact over a greater distance. zhou et al. ( ) developed a very decent model to predict the exhaled jet centerline trajectory in thermally stratified environments. they found that the lock-up height was lower with a smaller archimedes number fig. schematic of person-to-person contaminant transport in a displacement ventilated room: (a) direct exposure: the breathing zone of the target person is within the impact scope of exhaled air; (b) indirect exposure: the target person is far away from the impact scope of exhaled air; (c) indirect exposure: the pathway of exhaled air to the breathing zone is blocked by the head of the target person; and (d) direct exposure: exhaled air penetrates the thermal plume boundary layer generated by the target person and a greater temperature gradient. to consider the lock-up phenomenon in the thermal stratification layer but still keep the method as simple as possible, we assumed that the exhaled air moves horizontally even though the archimedes number is not zero. note that this assumption tends to result in an over-estimation of direct exposure, because the actual trajectory of the exhaled air is still curved to some extent at the beginning and the lock-up height can be higher than the starting point of the exhaled air (zhou et al. ) . therefore, to compensate for this effect, the threshold local air velocity was determined separately for displacement ventilation. in theory, the threshold local air velocity for displacement ventilation should be greater than that for mixing ventilation. we used the collected experimental data from the literature to determine the threshold local air velocity for displacement ventilation. note that this study set the cutoff normalized exposure at . to differentiate the direct-exposure cases and indirect-exposure-only cases for displacement ventilation as defined in the last paragraph of section . . figure shows the error of the proposed method for different threshold local air velocities for displacement ventilation. when the threshold local air velocity was . m/s, the error of the proposed method was . %, the lowest among all of the tested local air velocities. this means that the proposed method could correctly differentiate direct (c exp /c r > . ) and indirect (c exp /c r ≤ . ) exposure for out of the displacement ventilation cases. therefore, the threshold local air velocity was set at . m/s in the method for differentiating the direct and indirect exposure to exhaled contaminants in displacement ventilated rooms. as predicted, the threshold local air velocity for displacement ventilation is lower than that for mixing ventilation, so that the overestimation of direct exposure due to the assumption of non-curved exhaled air trajectory can be compensated. the proposed method was applied to differentiate direct and indirect exposure to exhaled contaminants for the displacement ventilation cases. figure shows the fig. the error of the proposed method with different threshold local air velocities for displacement ventilation fig. the distribution of measured normalized exposure for the predicted indirect-exposure-only cases and direct-exposure cases for displacement ventilation (the th , th , median, mean, th , and th percentile values are shown) distribution of the measured normalized exposure for the predicted direct-exposure cases and indirect-exposure-only cases. the experimental database contained direct-exposure cases and indirect-exposure-only cases for displacement ventilation. the proposed method correctly identified direct-exposure cases and indirect-exposure-only cases. in general, with a threshold local air velocity of . m/s the proposed method can reasonably differentiate direct and indirect exposure to exhaled air for displacement ventilation. the median value for the predicted direct-exposure cases was . , which is significantly higher than . , owing to the direct exposure to exhaled contaminants. in contrast, the median value for the predicted indirect-exposure-only cases was . , which is lower than that for mixing ventilation. that is because when the target person is not impacted directly by the exhaled air, the exposure is reduced by the clean air supplied from the lower zone of the room directly entering the breathing zone. furthermore, the variation of the normalized exposure for displacement ventilation was greater than that for mixing ventilation. for example, the range between the th and th percentile values for displacement ventilation was from . to . . this indicates that, with an appropriate design, displacement ventilation has a better chance of achieving excellent performance in reducing indirect exposure to exhaled contaminants. a simple method for differentiating direct and indirect exposure to exhaled contaminants was developed based on experimental data collected from the literature. to keep the proposed method as simple as possible for the early stage of design, the lock-up phenomenon in the displacement ventilation cases was largely simplified in this study. the exhaled air was assumed to move horizontally even though the jet might be locked up at a greater height in reality. to compensate the potential over-estimation of direct exposure due to this assumption, the threshold local air velocity was set greater than that for mixing ventilation based on the experimental database. however, when detailed design is required, the proposed method may not be sufficiently accurate. in that case, computational fluid dynamics (cfd) simulation can be used, although the computing cost is much higher. recently, zhou et al. ( ) developed a numerical model to accurately predict the exhaled airflow trajectory in thermally stratified environments by solving six ordinary equations of the exhaled jet. these equations include the continuity, momentum, density difference flux, and centerline trajectory equations. importantly, this model takes both the archimedes number of the exhaled jet and the vertical temperature gradient in the room into account. a smaller archimedes number and a greater temperature gradient can lead to a lower lock-up height (zhou et al. ) . therefore, this model is very suitable to adopt when detailed design is required, because it is more accurate than the proposed method but less computationally costly than cfd. furthermore, the proposed method is for quickly differentiating the direct and indirect exposure to exhaled contaminants in mechanically ventilated spaces. however, it is not for predicting the exposure levels. in general, it is difficult to accurately predict the direct exposures at the stage of design, because the information of many individual parameters is unavailable. these individual influencing factors include the exhaled air velocity and direction as well as the height and metabolic rate of the persons. in principle, direct exposures should be avoided through separating individuals by altering the design for the interior layout, if possible. therefore, from the perspective of design, identifying the possible existence of direct exposure may be more practical than accurately predicting the exposure level. on the other hand, the indirect exposure can be predicted more accurately because it is mainly determined by the ventilation system. at the early stage of design, empirical models can be used to estimate the indirect exposures. for mixing ventilation, the indirect exposure may be roughly estimated by assuming the normalized exposure equal to . as demonstrated in fig. . for displacement ventilation, the prediction is more challenging because the uncertainty is greater as shown in fig. . if the breathing zone of the target person is in the lower zone of the room, the normalized indirect exposure can be significantly lower than . , because the exhaled contaminants move upward and are directly removed from the exhaust at the ceiling level. however, if the exposure height is above the stratification height, the indirect exposure would occur in the upper mixing layer with a normalized exposure at around . . several empirical models for estimating indirect exposure under displacement ventilation can be used for quick estimation (e.g. habchi et al. ) . at the stage of detailed design, cfd simulation again can be utilized. the study has some other limitations such as the universality of the method. as the proposed method is very simple, it may not be sufficiently accurate when applied to certain complex air distribution systems, such as personalized ventilation (nielsen et al. ; zhao and guan ) , protected zone ventilation (cao et al. ) , or a space with air cleaners or ultraviolet germicidal irradiation devices (kanaan et al. ) . the localized air distribution may significantly influence the trajectory of exhaled air, which cannot be predicted by the simple jet equations used in this study. furthermore, the collected data focused on normal rooms or hospital wards. therefore, the proposed method may not be applicable to other enclosed environments, such as aircraft cabins (you et al. ) and high-speed trains (zhang and li ) . note that the size of exhaled droplets ranges from the sub-micrometer to super-micrometer scale chao et al. ), and the trajectory of exhaled droplets greatly depends on the particle size (xie et al. ; yang et al. ). however, this study did not consider the influence of the size of exhaled droplets because most of the studies in the literature used a tracer gas to represent the exhaled contaminants. therefore, the proposed method is only applicable to fine particles which behave similarly to gaseous contaminants. large droplets whose trajectories do not follow the exhaled air tend to deposit onto the floor by gravitational settling instead of being inhaled by the target person (xie et al. ; . in addition, this study did not consider the transient features of person-to-person contaminant transport because the method was developed for quick differentiation of direct and indirect exposure at the early stage of design. it should be acceptable to start from the steady-state analysis at the early stage of design, especially given that the proposed method is simple with low computing cost. in the stage of detailed design, both experimental measurements (e.g., chen et al. ; liu and novoselac ) and numerical simulations (e.g., hang et al. ; chen et al. b,c; yan et al. ) can be used to consider in detail the transient features of personal exposure to exhaled contaminants. in addition, the thermal plume generated by the infected person with relatively large metabolic rate may significantly affect the weak exhaled jet (rim and novoselac ; ge et al. ) . however, at the stage of design, it is difficult to have the information of the metabolic rate and exhaled air velocity. therefore, it would be safer to assume that the exhaled jet could penetrate the thermal plume in order to avoid any under-estimation of the risks. when more information is available at the stage of detailed design, cfd simulation (rim and novoselac ; ge et al. ) can be used to further consider this influencing factor. this investigation developed a simple method for differentiating direct and indirect exposure to exhaled contaminants in mechanically ventilated rooms. first, a database was formed by collecting experimental data from the literature. then, the data were analyzed to capture the main influencing factors. finally, a method for differentiating direct and indirect exposure was developed for both mixing and displacement ventilation. within the scope of this research, the following conclusions can be drawn: ( ) direct exposure to exhaled contaminants is determined primarily by the impact scope of the exhaled air. ( ) indirect exposure to exhaled contaminants is determined primarily by the ventilation mode and ventilation rate. 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pollutants in a two-bed hospital ward with a downward ventilation system transport of particulate and gaseous pollutants in the vicinity of a human body airborne spread of infectious agents in the indoor environment how far droplets can move in indoor environments-revisiting the wells evaporationfalling curve numerical investigations of the effects of manikin simplifications on the thermal flow field in indoor spaces person to person droplets transmission characteristics in unidirectional ventilated protective isolation room: the impact of initial droplet size distributions of respiratory contaminants from a patient with different postures and exhaling modes in a single-bed inpatient room investigating the impact of gaspers on cabin air quality in commercial airliners with a hybrid turbulence model dispersion of coughed droplets in a fully-occupied high-speed rail cabin quantify impacted scope of human expired air under different head postures and varying exhalation rates modeling particle dispersion in personalized ventilated room the lock-up phenomenon of exhaled flow in a stable thermally-stratified indoor environment this work was supported by the national natural science foundation of china (no. ). key: cord- -bbjxd y authors: xia, tian; zhu, yifang; mu, lina; zhang, zuo-feng; liu, sijin title: pulmonary diseases induced by ambient ultrafine and engineered nanoparticles in twenty-first century date: - - journal: natl sci rev doi: . /nsr/nww sha: doc_id: cord_uid: bbjxd y air pollution is a severe threat to public health globally, affecting everyone in developed and developing countries alike. among different air pollutants, particulate matter (pm), particularly combustion-produced fine pm (pm( . )) has been shown to play a major role in inducing various adverse health effects. strong associations have been demonstrated by epidemiological and toxicological studies between increases in pm( . ) concentrations and premature mortality, cardiopulmonary diseases, asthma and allergic sensitization, and lung cancer. the mechanisms of pm-induced toxicological effects are related to their size, chemical composition, lung clearance and retention, cellular oxidative stress responses and pro-inflammatory effects locally and systemically. particles in the ultrafine range (< nm), although they have the highest number counts, surface area and organic chemical content, are often overlooked due to insufficient monitoring and risk assessment. yet, ample studies have demonstrated that ambient ultrafine particles have higher toxic potential compared with pm( . ). in addition, the rapid development of nanotechnology, bringing ever-increasing production of nanomaterials, has raised concerns about the potential human exposure and health impacts. all these add to the complexity of pm-induced health effects that largely remains to be determined, and mechanistic understanding on the toxicological effects of ambient ultrafine particles and nanomaterials will be the focus of studies in the near future. air pollution is a major global problem associated with human health in both developing and developed countries [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . the most common sources of air pollution include particulate matter (pm), ozone, nitrogen dioxide and sulfur dioxide [ , , , ] . pm can be defined by their different size ranges, including coarse (< μm), fine (< . μm) and ultrafine particles (ufps, < nm) [ ] [ ] [ ] ] . because numerous studies have shown that fine pm . particle levels can be linked to premature mortality and adverse health effects, pm . levels are often used as a major surrogate for air pollution [ , [ ] [ ] [ ] [ ] , ] . according to the world health organization (who) ambient air pollution database that comprises urban air-quality data for about cities from countries for the years - , almost % of the urban population endured a pm . concentration exceeding the annual mean values of μg/m in the who air-quality guidelines [ ] . in addition, who reported that, in , around million people died-one in eight of the total global deaths-as a result of air pollution exposure [ ] . the new data revealed a stronger link between both indoor and outdoor air pollution exposure and the development of respiratory diseases, including acute respiratory infections, chronic obstructive pulmonary disease (copd) and lung cancer, as well as cardiovascular diseases such as strokes and ischemic heart disease [ , , ] . this finding further confirmed that air pollution is now the world's largest single environmental health risk factor and reducing air pollution could save millions of lives. globally, we are witnessing two opposing trends in terms of changes in the air pollution levels in different countries. using new high-resolution global review xia et al. satellite maps of air quality indicators, nasa scientists tracked air pollution trends from to in various regions and cities globally [ ] . according to the research findings, the usa, europe and japan have improved air quality owing to strict emission-control regulations. as a result, in the usa, reductions in pm . were associated with lower premature mortality and improvement in life expectancy. long-term improvements in air quality were associated with statistically and clinically significant positive effects on lung-function growth in children [ ] . on the contrary, china, india and the middle east countries, with their rapid population growth, fast-growing economies and vastly expanding industrialization, have shown alarming increases in air pollution, along with increased mortality and disease burden in those countries [ ] . on a positive note, in recent years, china's overall air quality has seen early signs of improvement due to a decrease in coal consumption, increase in renewable energy sources and stricter emission control. it is worth noting that, although air pollution mostly is considered a local or regional problem, studies have shown that air pollution could be transported over long distances, even across continents, in the troposphere [ ] . thus, mitigation of local air pollution could have far-reaching health benefits and a collective effort between every country involved would be important. despite the progress in our understanding of air pollution-induced diseases, much research remains to be done [ , , , , ] . for instance, among the pm fractions, ufps possess the highest particle number and surface area, carrying higher chemical contents than pm . [ , [ ] [ ] [ ] [ ] . studies have shown that ufps have detrimental effects on both the respiratory and cardiovascular systems, and exacerbation of asthma [ ] [ ] [ ] , , ] . however, our understanding of ufps is still incomplete because of a deficiency in extensive ufp-monitoring networks, rapid physicochemical characterization techniques, and limited epidemiological and toxicological studies. in addition, the rapid advances in nanotechnology lead to production of high volumes of nanomaterials and increasing use in commercial products [ , , ] . the use of nanomaterials increases the potential for human exposure to nanomaterials that could generate adverse health effects. for instance, ceria (cerium dioxide) are used in diesel as a catalyst to promote the combustion process, which are released in the diesel exhaust, potentially leading to lung exposure. the addition of ceria to diesel fuel resulted in ceria-concentration-dependent emission reductions of co , co, total particulate mass, formaldehyde, acetaldehyde, acrolein and several polycyclic aromatic hydrocarbons; however, it also led to decreases in the size of emitted particles and a substantial increase in the number of ufps (+ %), together with increases in certain other air pollutants, specifically nox (+ . %) and the particle-phase benzo[a]pyrene toxic equivalence quotient (+ %) [ ] . this shows the complexity of the potential impacts introduced by nanomaterials. given the health concerns related to ufps and increasingly produced and used nanoparticles, further research is needed to evaluate the health risks associated with these tiny particles. evidence that links ambient pm to a decrease in life expectancy and increase in premature mortality came from epidemiological studies that have been extensively reviewed before [ , , , , [ ] [ ] [ ] . in a recent study, chen et al. presented findings that implicated long-term exposure to air pollution particles contributed to enormous loss of life expectancy in china [ ] . these results were based on an experimental design making use of a chinese policy that provided free coal for heating in cities located north of huai river, but not in the south, which produced an arbitrary discontinuity for pm air pollution, where the major difference was coal combustion. as a result, mean life expectancy is about . years ( % conficence interval (ci): . , . ) lower in northern compared with southern china due to an increased incidence of cardiorespiratory mortality [ ] . this finding correlated well with a study by pope et al. that used a temporal difference in pm levels observed since the s, when air quality across cities in the usa improved substantially. they found that there was an association between reductions in pm . and an increase in life expectancy; a reduction of μg/m was associated with an increase of . years in life expectancy [ ] . there was also a strong evidence base for morbidity and mortality associated with both short-term (days to weeks) and long-term (years to decades) pm exposures. early evidence linking ambient pm to mortality came from welldocumented short-term extreme air pollution episodes (that lasted for days) in the s to s [ ] . more recently, numerous daily time-series and case-crossover studies have observed a small but statistically robust relationship between daily mortality and short-term (days to weeks) elevation in pm [ ] . in addition, short-term air pollution exposure could also increase the mortality rate of patients with respiratory diseases. for example, cui et al. evaluated air pollution using the air pollution review figure . the contribution of outdoor air pollution sources to premature mortality on a global scale. the data were derived from a global atmospheric chemistry model that links premature mortality to outdoor air pollution, mostly by pm . . study found that, in , outdoor air pollution, mostly by pm . , leads to . million premature deaths per year worldwide, predominantly in asia. unit of mortality was expressed as deaths per area of km × km (color-coded). in the white areas, annual mean pm . and o are below the concentration-response thresholds where no excess mortality is expected. the figure was originally published by [ ] and has been approved for reuse by nature publishing group. index (api) derived from the concentrations of particulate matter, sulfur dioxide, nitrogen dioxide, carbon monoxide and ground-level ozone and their relationship with the case fatality of severe acute respiratory syndrome (sars) in china [ ] . case fatalities of patients from regions with high apis (api > ) and moderate apis ( - ) were compared with that of patients from regions with low apis (api < ). the study showed that the case-fatality rate increased with the increment of api (case fatality = - . + . × api). the correlation coefficient between api and sars fatality was . (p = . ) [ ] . short-term exposure demonstrated that sars patients from regions with moderate apis had an % increased risk of dying from sars compared with those from regions with low apis (relative risk (rr) = . , % ci: . - . ). similarly, sars patients from regions with high apis were twice as likely to die from sars compared with those from regions with low apis (rr = . , % ci: . - . ). for long-term studies, two large-scale prospective cohort studies in the usa showed that there were statistically robust associations between mortality risk and pm . exposure even after smoking and other risk factors were controlled for [ , ] . long-term air pollution exposure could also increase the mortality rate of patients with respiratory diseases such as sars [ ] . although ecologic fallacy and uncontrolled confounding effects might have biased the results, the possibility of an effect of air pollution on the prognosis of sars patients was indicated [ ] . in a recent study, lelieveld et al. used a global atmospheric chemistry model to investigate the link between premature mortality and ambient pm . concentrations [ ] . the authors found that more than . million deaths per year could be attributed to outdoor pm . exposure. the majority of the mortality happened in asia, which strongly influenced the global mortality rate. the highest number of deaths was in the western pacific, where china was the main contributor ( . million per year). southeast asia had the second highest premature mortality, where india was the main contributor ( . million per year) ( fig. ) [ ] . this was in addition to the estimated . million deaths per year caused by indoor air pollution resulting from biomass or coal combustion for cooking and heating [ ] . the cause of premature mortality includes lung diseases, such as chronic obstructive pulmonary disease (copd), lung infection and cancer (described in detail below), as well as cardiovascular diseases and cerebrovascular diseases, etc. [ ] . in addition, many birth cohort studies have linked pm . exposure to asthma and allergic diseases [ , ] . altogether, a large amount figure . general toxicological pathways linking pm lung exposure to cardiovascular and cerebrovascular diseases that cause morbidity and mortality. the first line of defense against pm is the lung, where pm can induce or exacerbate lung diseases including copd, asthma, lung infection disease and lung cancer. furthermore, ufps could translocate out of the lung into the blood stream and can cause systemic inflammation and oxidative stress that negatively impact blood and blood vessel, heart function and brain. of literature provided evidence that breathing combustion-related pm . , even at exposure levels common to urban populations worldwide, contributed to cardiorespiratory disease mortality and diminished the lifespan [ , , , , ] . there was also encouraging evidence showing that improvement in air quality benefited human health and increased the lifespan [ , ] . for example, long-term improvements in air quality were associated with a significant improvement in lung function in children [ ] . however, there are no conclusive data yet available for the human health impacts of ambient ultrafine particles and engineered nanoparticles, which warrant further studies. the lung is the first target organ for air pollution and pm exposure is associated with reduced lung function, increased lung inflammation, asthma, respiratory infections, lung cancer and exacerbation of copd, which lead to systemic inflammation and oxidative stress affecting blood, vasculature, heart and brain, ultimately contribute to the premature mortality ( fig. ) [ , , , ] . it is notable that the acute adverse health effects of pm are most often found in susceptible populations, including children, elderly people and those with chronic diseases [ , ] , while not obvious for short-term exposure in normal healthy people except at very high concentrations [ ] . however, air pollution exposure could induce adverse health effects to normal healthy people [ ] . a panel study conducted among chinese healthy adults during the beijing olympics found that peak expiratory flow levels increased in % of the participants when compared with the during-and pre-olympics time points, while peak expiratory flow levels decreased in % of participants for the post-and during-olympic periods comparison [ ] . children are more susceptible to air pollution because they have smaller airways, higher breathing rates per body mass, immature detoxification and metabolic systems, and they are more frequently exposed to outdoor air [ , ] . the elderly population and people with chronic diseases are susceptible likely because of less efficient particle clearance in the lung or impairment of immune functions. the adverse effects induced by air pollution are not limited to review the lung, pm could induce systemic inflammation and oxidative stress, and nano-sized particles could even translocate out of the lung to other tissues and organs, which induces pathological changes in blood, vasculature, heart and brain ( fig. ) [ , ] . the main pulmonary diseases that are associated with pms are the following. copd is not only associated with smoking, but also has high incidence among non-smokers [ , , ] . the risk factors for copd among non-smokers include indoor air pollution from biomass combustion and second-hand tobacco smoke, as well as occupational exposures and outdoor air pollution [ ] [ ] [ ] . epidemiological studies from both developing and developed countries have shown the association between outdoor pm exposure and copd. in addition to pm, ozone and no could also exacerbate copd. an increase in ambient pm . could induce acute exacerbations and mortality from copd, while improvement in air quality decreases the incidence of copd [ ] [ ] [ ] . abundant evidence has shown that air pollution could induce and exacerbate asthma [ ] . in a recent meta-analysis of several birth cohort studies, the authors suggested that early childhood exposure ( - years old) to traffic-related air pollution (trap) containing ufps and pm . were associated with increased incidence of asthma and risk of sensitization to common allergens [ ] . furthermore, a -year longitudinal study of , adults from eight european countries showed an association between trap exposure and increased incidence of asthma [ ] . the authors found that adult asthma incidence was positively associated with exposure metrics, including pm , pm . , nitrogen oxides, traffic load and intensity. further research with improved personal-level exposure assessment (vs. residential exposure assessment only) and phenotypic characterization was recommended by the authors [ ] . in october , the international agency for research on cancer (iarc) of who announced that outdoor air pollution and pm were classified as a group i carcinogen, which was determined based on the most recent data from human, animal and mechanistic studies [ ] . in one of the first studies of lung cancer among female non-smokers in china with measured indoor exposure to pm , pm . , pm , pm and total suspended particulate (tsp), mu et al. reported that the pm levels in cases were more than three times higher than those in the controls. every μg/m increase in pm is associated with a % increased risk of lung cancer [ ] . multiple studies in recent years have shown a correlation between air pollutants including pm . and no and lung cancer risk [ , [ ] [ ] [ ] . in alone, , deaths from lung cancer worldwide were associated with air pollution [ ] . recent data showed that air pollution was associated with respiratory infections, due to the impaired immune functions of the lung and the susceptible population including children, elderly people and those with chronic diseases [ , ] . two recent epidemiological studies demonstrated associations between air pollution (trap and ozone) and acute respiratory infections as well as increased emergency department visits in young children [ , ] . the most common sources of air pollution include pm, ozone, nitrogen dioxide and sulfur dioxide [ , , ] . among these components, pm has been shown to play a major role in human morbidity and mortality [ , , ] ; thus, we will focus our discussion on pm. pm comes from natural and anthropogenic activities and processes [ , , , , ] . anthropogenic sources of outdoor pm are hightemperature processes (e.g., welding, smelting), combustion (e.g., power generation, land traffic, residential and commercial heating and cooking), industrial and other processes, including agriculture, dust and biomass burning. indoor pm sources are mostly biomass and coal combustion for cooking and heating purposes [ , , , , ] . although the physiochemical properties (chemical composition, metal content, etc.) of pm are different worldwide, they are all associated with adverse human health effects although at different potency levels [ ] . pm is referred to the mass of particles collected with % efficiency for particles with an aerodynamic diameter equal to or less than μm; it should be noted that all particles down to the ultrafine size range were collected [ ] . at this size range, according to the international standards organization thoracic convention, the mass fraction of inhaled particles could penetrate beyond the larynx to the airways [ ] . pm . refers to the respirable fraction . tem images of ambient ultrafine particles and engineered nanoparticle as well as particle characteristics that promote or contribute to ros generation. (a) photoactivation effects of nps, such as the formation of electron-hole pairs during ultraviolet exposure of tio ; this effect has been associated with the generation of oxidative stress and inflammation by tio ; (b) discontinuous crystal planes and material defects of nps that lead to oxygen radical generation due to the active electronic state of the material surface; (c) redox cycling contributes to ros production. this can occur due to the presence of transition metals or redox-cycling organic chemicals on the pm, ufp and np surfaces. pms and ufps, for example, contain organic compounds such as quinones, which can generate ros through redox cycling. moreover, transition metals can generate hydroxyl radicals through the fenton reaction. the fenton reaction is one of the mechanisms by which metal impurities on the cnt surface can induce ros production. finally, (d) particle dissolution (e.g. zno, cdse, cu) can produce free ions that are capable of inducing ros generation and oxidative stress in cells. metal fume fever is a real-world example of this toxicity, commonly for welders. that also contains the ultrafine component, which penetrates to the unciliated regions of the lung and is now being considered worldwide as the standard [ ] . ultrafine particles are found to a large extent in urban air as both singlet and aggregated particles (fig. ) , and indeed are the predominant particle type by number in urban pm and pm . , although they contribute insignificantly to mass [ , , , ] . pm from combustion processes characteristically has an elemental or organic carbon core carrying trace metals, sulfate, ammonium, and volatile and semi-volatile components [ , ] . the composition of combustion-generated pm usually depends on fuel type, burn conditions and atmospheric conditions. compared with pm and pm . , traffic-derived ufps are challenging to characterize geographically or spatiotemporally, as their concentrations decrease sharply downwind from sources, and ufps shift in size from nucleation mode to accumulation mode with time and distance from their emission point due to agglomeration and condensation [ ] [ ] [ ] . for combustion sources, the fuel, combustion conditions and pollution controls will alter the particle numbers and size distribution of the pm emitted [ , ] . however, studies have shown that ufps carried more organic chemicals due to their significantly larger surface area; many of these compounds were redox-active and had the ability to generate reactive oxygen species (ros) [ , ] . studies have shown that ufps were more toxic than their larger counterparts; however, more research is needed to clarify the role of ufps [ , , ] . nanoparticles (nps) are intentionally created with specific size, shape, surface characteristics and functionality that are required for their applications [ , ] . there are similarities between nps and ufps; however, there are also major differences (table ) . nps and pm including ufps could both generate ros or release toxic ions through dissolution, through similar or different mechanisms (fig. ) [ , , ] . although currently there is no definitive evidence to link np exposure to any human disease, much experimental data indicate that some nps with certain physicochemical properties may be potentially hazardous [ , [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . obviously, more research is needed on this front. the potency of pm in causing an adverse health impact is dependent, in part, on its deposition in the airways and chemical composition [ , ] . the main deposition mechanisms in the respiratory tract for inhaled pm include impaction, sedimentation, interception and diffusion [ ] . pm in different size ranges has drastic differences in distribution and deposition in the lung [ ] . this is clearly demonstrated in fig. , which shows the differential deposition of inhaled particles with different sizes in the nasopharyngeal, tracheobronchial and alveolar regions of the human respiratory tract [ ] . for ufps and nps that are in the size range of - nm, the particles could penetrate deeper into the alveolar region and deposit there at high percentages. for larger particles including pm and pm . , they generally deposit in the nasopharyngeal and laryngeal region and poorly deposit in the alveolar region (fig. ) [ ]. the different deposition profiles among particles with diverse sizes could at least partially explain their different health effects [ , ] . for example, the deposition site determines the clearance rate of particles [ , ] . for large particles including pm and pm . , the majority deposited in the upper airways could be removed with the mucus via the mucociliary escalator (fig. ) . the small frac-tion of particles that could pass through upper airways into the alveolar region (fig. ) , such as pm . fine particles, could be easily endocytosed and removed by alveolar macrophages (fig. ) . however, for ufps and nps, the majority of these particles could pass through the airways into the alveolar region. although they also deposit in the larger airways, this only accounts for a small percentage of review xia et al. figure . scheme for physicological and toxicological events occurring after pm . and ufp/np exposure. pm . mostly sticks to the airway, where they are cleared by mucociliary escalator. the remaining pm . particles that get inside the alveoli will be phagocytosed by resident macrophages. however, for ufps and nps, the majority of the particles will get inside the alveoli, where the cellular uptake of nano-sized particles by macrophages is impaired, leading to delayed clearance of particles and generating oxidative stress and pro-inflammatory effects by macrophages and epithelial cells because of prolonged exposure to particles. the prolonged interaction between particles and the epithelium also lead to extrapulmonary translocation to the lung interstitium and even into the circulation. adapted from [ ] . the total number of particles in the lung. furthermore, the particles are so tiny and in such vast numbers that macrophages could not take them up effectively (fig. ) [ , ] . the interactions among particles, epithelial cells and macrophages could generate oxidative stress and pro-inflammatory effects in the lung, and there are reports showing that nano-sized ufps could be more toxic than their larger counterparts (which will be discussed in later sections) [ , , , ] . in addition, extrapulmonary translocation across the epithelium could occur because of the reduced removal rate and longer retention of ufps and nps that allows transcytosis of these nano-sized particles [ , ] . this could lead to secondary deposition of these particles in other tissues and organs, which may contribute to further adverse health effects (fig. ) [ , ] . emerging evidence has shown that, among different particles, ufps are potentially the most dangerous owing to their small size, deep penetration, large surface area/volume ratio, high content of redox-cycling organic chemicals, alveolar deposition and high rates of retention in the lung [ , , ] . compared with pm and pm . , traffic-derived ufps are capable of carrying more organic chem-icals on their significantly larger surface; many compounds (polycyclic aromatic hydrocarbons (pahs) and quinones) are redox-active and have the ability to generate ros [ , [ ] [ ] [ ] , , ] . while pm and pm . can be easily removed by phagocytosis, the extremely small size of ufps enables them to evade such a process and ufps could have more interactions with other cell types in the lung (fig. ) [ , ] . these specific features of ufps can significantly contribute to the adverse effects through ros over-production by the redox-active organic chemicals and metals on particle surface, resulting in cellular oxidative stress [ , , , , ] . oxidative stress has been identified as a major mechanism for pm -, pm . and ufp-associated health effects, including exacerbation of asthma and copd, and promotion of atherosclerosis [ , , , , , ] . some nps, including carbon nanotubes, silver nanoparticles, zno, cuo, etc., have also been shown to be able to generate ros and oxidative stress [ , , , , , ] . at the cellular level, particleinduced oxidative stress can activate a cascade of signaling pathways that mediate the production of pro-inflammatory cytokines/chemokines and induce apoptosis (figs and ) [ , , ] , resulting in inflammation and tissue injury in the respiratory and cardiovascular systems [ , , ] . pm-induced ros production in biological systems and targeted cells originates from a variety of sources ( fig. ) [ ] [ ] [ ] [ ] , , ] . these include: (i) carbon core of pm and ufps could induce ros generation and oxidative stress; (ii) catalytic conversion of pahs to quinones by cytochrome p in the endoplasmic reticulum; (iii) quinone redox cycling by nadph-dependent p reductase in microsomes; (iv) mitochondrial perturbation leading to electron leakage in the inner membrane; and (v) nadph oxidase activity in the macrophage surface membrane and associated phagosomes. both the carbon cores as well the chemicals coated on their surface play a role in these biological events [ , , ] . this also includes the involvement of transition metals in generating ros by a fenton reaction [ , , ] . the pm backbone is formed by chain-like carbon-based nanoparticles. to see whether the particles themselves could induce ros and adverse effects, ultrafine carbon black was selected as the model particle. studies found that ultrafine review figure . sources of pm-and ufp-induced ros production and their cellular effects. quinones, under the catalytic influence of nadph-cytochrome p reductase, can redox cycle to produce ros in the endoplasmic reticulum. phagocytosis can induce the assembly and activation of nadph oxidase to produce superoxide. ufps can interfere in electron transduction in the mitochondrial inner membrane as well as perturb the pt pore to generate ros. ros induce lipid peroxidation in the cell membrane, cross-linking of protein thiol (sh) groups and dna damage. ros can also deplete glutathione (gsh), resulting in oxidative stress in the cell. depending on the levels of oxidative stress, the response could range from induction of nrf release to the nucleus, activation of mapk and nf-kb signaling cascades, or cytotoxicity. according to the hierarchical oxidative stress hypothesis, nrf interaction with the antioxidant response element (are) leads to heme oxygenase and other phase ii enzyme expression at lower levels of oxidative stress (tier ), while, at a intermediary level of oxidative stress, activation of the mapk and nf-kb signaling cascades can induce pro-inflammatory responses (e.g. cytokine and chemokine production) (tier ). at the highest oxidative stress level (tier ), ros can induce the opening of the mitochondrial pt pore, followed by cytochrome c release, caspase- activation and induction of programmed cell death. carbon black could generate ros in cell-free systems and cause oxidative stress to cultured cells [ , , ] . in addition, ultrafine carbon black caused systemic pro-inflammatory responses in the lung including modest neutrophil influx and protein leak [ , ] . there was evidence of systemic oxidative stress in the plasma and increased production of plasma factor vii, which is an independent risk factor for cardiovascular disease [ , ] . redox-cycling organic chemicals on pm surfaces, such as quinones, are capable of generating ros in cellular targets such as bronchial epithelial cells, macrophages and endothelial cells [ , , ] . quinones are byproducts of fossil fuel combustion, as well as the enzymatic conversion of pah in the lung. redox-cycling quinones undergo one-electron reductions mediated by nadph-cytochrome p reductase to form semiquinones. these semiquinones are metastable and donate electrons to o , leading to the formation of o •− . due to their high content of organic chemicals, ambient ufps contribute proportionally more redox-cycling chemicals than larger particles [ , , , ] . catalytically active metals adsorbed on the pm surface have been shown to contribute to oxidative stress in vitro and in vivo [ , , ] . pm contains a number of transition metals (coarse > fine > ufp) that contribute to ros production. among the transition metals, fe, al, cu, ni, mn, zn, cr, ba and sr are the most abundant [ ] . in the presence of hydrogen peroxide, some of these metals, including fe + , have the ability to generate the hydroxyl radical ( • oh) through catalysis of a fenton reaction: the • oh radical is more reactive than o •− and hydrogen peroxide by several orders of magnitude. besides ros generation, transition metals also have the ability to directly perturb the function of the mitochondrial permeability transition (pt) pore [ , , ] . transition metals may also act synergistically with other pm components in impacting mitochondrial function, ros generation, atp production and cell viability [ , , ] . pm components could perturb mitochondrial function, leading to generation of ros and cell death [ , ] . mitochondria have been shown to be a direct subcellular target for ambient ufps. for example, ambient ufps have been found to lodge in the mitochondria of target cells and cause mitochondrial damage [ ] . although the mechanism of mitochondrial localization is still elusive, we hypothesize that particle size, hydrophobicity and presence of organic chemicals may play a role in the process. in addition to direct effects, studies have found that organic pm chemicals are capable of generating ros by their ability to interfere in these electron transfer events. this includes the effect of polar chemicals such as redox-cycling quinones to disrupt electron transfer in the inner membrane [ ] . this disruption in electron flow could favor the formation of ubisemiquinones, thereby contributing to mitochondrial o •− production. in addition, organic chemicals such as quinones and pahs also have the capability to perturb the mitochondrial pt pore (fig. ) [ , ] . the pt pore is a redox-, ph-, calcium-and m -dependent protein complex, which plays a pivotal role in regulating mitochondrial function and controlling cellular apoptosis. opening of the pt pore could lead to mitochondrial swelling and rupture of the mitochondrial outer membrane, by which various proapoptotic proteins such as cytochrome c, smac, apoptosis-inducing factor (aif), etc., are released . potential mechanisms of pm-, ufp-and np-induced nlrp inflammasome activation and il- β production. activation of nlrp inflammasome complex can be induced by various stimuli including pm and np particles, and the pro-il- β is processed by the inflammasomes to produce mature il- β, while il- β plays a major role in inducing the pro-inflammatory and pro-fibrogenic effects in the lung. nlrp inflammasome activation requires two signals in vitro. for signal , pathogen-associated molecular patterns (pamps) such as lps is recognized by toll-like receptor (tlr ) residing on the cell membrane, which further leads to nf-κb activation and the production of pro-il- β and nlrp proteins. nlrp inflammasome activation mechanisms include ros generation, potassium efflux, lysosomal damage and cathepsin b release. after phagocytosis of pm, ufps and nps, nadph oxidase is activated to generate ros. the over-production of ros may cause the destabilization and permeabilization of lysosomes and cathepsin b release, which will initiate the inflammasome activation cascade. mitochondrion is another important source of ros in cells. over-production of mitochondrial ros could lead to release of mtdna and cardiolipin that could induce nlrp inflammasome activation. in addition, potassium efflux induced by particles could also induce mitochondrial and cellular ros production leading to nlrp inflammasome activation. levels of activated nlrp inflammasomes are tightly regulated by autophagy. into the cytosol where they activate a number of apoptotic pathways, ultimately leading to programmed cell death [ , , , , , ] . pm-, ufp-and np-induced oxygen radical generation can result in cellular and tissue injury responses such as inflammation, apoptosis, necrosis, fibrosis and carcinogenesis [ , , , ] . cellular oxidative stress can generate a wide range of responses that can be experimentally detected, including damaged dna-mainly dna single-strand breaks or generating -oxo- -deoxyguanosine ( oxo-dg) that promote cell turnover and proliferation [ ] . at the lowest level of oxidative stress (tier ), the induction of antioxidant and protective responses is mediated by the transcription factor nrf , which regulates the activation of the antioxidant response element in the promoters of phase ii genes [ , ] . as the levels of oxidative stress increases (tier ), this protective re-sponse may yield to pro-inflammatory responses because ros induces redox-sensitive signaling pathways such as the mitogen-activated protein kinase (mapk) and nuclear factor-kappa b (nf-κb) cascades [ , , , , ] . at the highest level of oxidative stress (tier ), a perturbation of mitochondrial inner membrane electron transfer and the open/close status of the pt pore can trigger cellular apoptosis and cytotoxicity. this outcome is also known as toxic oxidative stress (fig. ) [ , , , , ] . using this three-tier screening platform, we have also shown for ambient airpollution particles that one can link the hierarchical oxidative stress paradigm to the in vivo outcomes in animal disease models [ , , , , ] . oxidative stress is also involved in mutagenesis [ ] . future screening could also include dna damage and mutagenesis tests to assess their carcinogenic potential. nps are intentionally created with specific size, shape, surface characteristics and functionality that are required for their applications [ , , , , , ] . although currently there is no definitive evidence to link np exposure to any human disease, experimental data indicate that many nps may be potentially hazardous [ , [ ] [ ] [ ] [ ] [ ] [ ] [ ] , , , , ] . the physicochemical characteristics of nps that may have health implications include particle size, shape, aspect ratio, composition, surface reactivity, solubility and ability to generate ros [ , , ] . similar to ufps, the nano-scale size can enhance np translocation and deposition by interfering with their clearance [ , ] . np composition or modification may affect particle surface reactivity such as the ability to generate ros, which is an important mediator involved in various human diseases. however, ufps and nps are inherently different in many aspects, such as source, morphology, organic chemical content, homogeneity, ros production, possible exposure route and the potential adverse health effects (table ) . extensive in vitro and in vivo studies have been performed to elucidate the toxic effect of engineered nanomaterials (enms) and physicochemical properties of enms, including morphology, size, dissolution, aspect ratio, surface coating, surface reactivity, bandgap and aggregation, have been suggested to determine their toxicity potentials [ , , , , ] . for example, ceo has excellent antioxidant properties that are enabled by the duality of the cerium ion to easily cycle review between ce + and ce + ; it is widely used as a catalyst or fuel additive in diesel to facilitate the combustion process and is released into the air as exhaust. there are reports over the past few years that utilize the antioxidant property of ceo in treating diseases such as cancer, alzheimer's, cardiac arrest, radiation-induced cell death and aging [ ] . however, a recent study found that ceo nps could lead to a decrease in cell viability and the treated cells exhibited characteristic hallmarks of apoptosis [ ] . in this case, ceo np toxicity is caused by mitochondrial damage leading to aif release, but not caspase activation or ros production. moreover, ceo np exposure leads to autophagy and inhibition of autophagy partially reverses cell death by ceo nps [ ] . obviously, more research should be done to clarify the effects of ceo under in vitro and in vivo conditions. tio is the most widely produced nanomaterial and is found in cosmetics, sunscreen, paint, vitamins, toothpaste, food colorants, nutritional supplements, etc. however, study has shown that tio nanoparticles could cause oxidative stress-mediated acute lung inflammation. oberdorster et al. have shown that, on a mass-dose basis, ultrafine tio is more toxic than fine tio [ ] . however, when the doses of particles were expressed in forms of particle surface area, the responses of ultrafine and fine tio particles fell on the same dose-response curve. this suggests that surface area is an important property for nps when considering their toxic potential. also, there is a study showing that tio in anatase form was more potent in ros generation than in rutile form, revealing the important role of crystal structure [ ] . under low levels of ultraviolet light, tio nanoparticles could generate ros and induce cytotoxicity because of their photoactivation property [ ] . another example is zno nanoparticles, which have received significant attention due to their wide use in sunscreens, electronics, optics and photonics. however, pulmonary exposure of zno nanoparticles could lead to transient increases in acute lung inflammation, similarly to a disease called metal fume fever. it has been shown that the toxicity of zno is dependent on the particle dissolution property and shedding of toxic zn ions, which induce oxidative stress and pro-inflammatory effects in vitro and in vivo [ , , ] . in addition to oxidative stress paradigm, recently studies have found nod-like receptor protein (nlrp ) inflammasome activation plays a major role in pm-and np-induced chronic effects such as lung fibrosis [ ] [ ] [ ] , , , [ ] [ ] [ ] [ ] . nanomaterials including rare earth oxides (reos), high-aspectratio materials including carbon nanotube (singlewalled and multi-walled), tio nanobelts and ceo nanorods, d materials including graphene and graphene oxide could induce nlrp inflammasome activation and a series of events leading to epithelial mesenchymal transition and lung fibrosis. carbon nanotubes (cnts) are a type of long-aspectratio nanomaterial which is drawing wide interest because of their potential applications in electronics, optics, drug delivery and cancer therapy. however, animal studies have shown that they could promote the production of pro-fibrogenic cytokines and growth factors (il- β, tgf-β and pdgf-aa, etc.) that may lead to lung fibrosis [ ] [ ] [ ] [ ] . the mechanism involves cellular uptake of cnts, overproduced ros by nadph oxidase activation, lysosomal damage induced by the surface reactivity of cnts and the release of lysosomal protein, cathepsin b, which activates nlrp inflammasome and produces il- β. il- β plays a major role in inflammation and fibrosis by activating epithelial mesenchymal transition in the lung (fig. ) [ , [ ] [ ] [ ] [ ] . wang et al. showed that the dispersal state, hydrophobicity and purity of multi-walled carbon nanotubes (mwcnts) could affect the pro-fibrogenic cellular responses that also correlate with the extent of pulmonary fibrosis [ ] [ ] [ ] [ ] . furthermore, other long-aspect-ratio enms also showed similar effects. ji et al. demonstrated the toxicological effects of long-aspect-ratio nanomaterials using a library of inhouse-made ceo nanoparticles [ ] . in vitro toxicity study demonstrated that, at lengths ≥ nm and aspect ratios ≥ , ceo nanorods induced progressive pro-inflammatory effects and cytotoxicity [ ] . the relatively low 'critical' length and aspect ratio were associated with small nanorod/nanowire diameters ( - nm), which facilitates the formation of stacking bundles that could pierce through cell membrane, causing the release of cathepsin b and further the activation of nlrp inflammasome. the same ceo nanorods could also induce significantly higher lung fibrosis than spherical particles in vivo [ ] . our recent studies show that rare earth oxide nanoparticles (reos), which are widely used in electronics and upconversion nanoparticles for bioimaging, are unstable in the acidic physiological environment, including the lysosomal compartment of the cells [ ] [ ] [ ] . these reos can dissolve and the dissolved ions could bind to phosphates strongly; as a result, the particles transform from spheres to 'sea-urchin'-shaped or mesh-like structures with composition changes to the repo . the sources of phosphates are not limited to free phosphate ions in the lysosomal compartment; they also include phosphate groups on intracellular proteins and membranes. on the one hand, biotransformation of reos could lead to dephosphorylation of phospholipids on the lysosomal membrane, which destabilizes the membrane, leading to lysosomal damage. released cathepsin b from lysosomes to the cytosol review xia et al. will activate nlrp inflammasomes to produce il- β, which initiate a cascade of events that culminate in pulmonary fibrosis [ , , ] . on the other hand, stripping of phosphate groups from lysosomal proteins will lead to loss of enzymatic activities of the proteins, resulting in lysosome dysfunction, which leads to lysosome and autophagosome fusion inhibition and compromised autophagosome degradation in the autophagy flux. this leads to accumulation of activated nlrp inflammasomes because autophagy is the major homeostatic mechanism to remove activated inflammasomes [ ] . the above examples show that the physicochemical properties of nps determine their toxic potential to human health, and more research is needed to understand these interactions between numerous other types of nps and biological systems occurring at the nanobio interface [ , , , , ] . studies have shown that exposure to ufps and nps has the potential to cause adverse health effects in humans [ , , , , , ] . in order to assess the toxic effects of these nano-sized particles, we advocate a predictive toxicological approach with the goal of linking particle physicochemical properties to their toxic effects [ , , ] . to establish this predictive toxicological paradigm, there are five major requirements. the first is to comprehensively characterize their physicochemical properties that may lead to biological injury. it also requires the establishment of nanomaterial libraries with property variations, which allows building the link between material property and the biological/toxicological activities. the second requirement is to develop in vitro cellular screening assays that reveal particleinduced injury mechanisms and pathways such as oxidative stress and nlrp inflammasome activation. third, where possible, it is important to develop high-throughput screening platforms to assess the large number of material physicochemical properties, dosage and time points that are likely to lead to biological injury. fourth, the in vitro data could be used for in silico modeling to establish hazard ranking and structural-activity relationships that can be used to predict enm toxicity. finally, the in vitro hazard ranking and structural-activity relationships will then need to be validated by limited in vivo animal experiments to establish the 'predictiveness' of this approach. we have successfully demonstrated the usefulness of the predictive toxicological approach for the hazard assessment of over different nano-materials and development of major structure activity relationships for groups of nanomaterials. we are confident that this approach would facilitate research on the toxicological effects induced by pms, ufps and nps [ ] . convincing evidence has established the association between pm and many pulmonary diseases that contribute to early mortality and reduced life expectancy. however, for 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sublethal effects key: cord- -k rl f authors: detrick, barbara; gangaputra, sapna; palsgrove, doreen n.; heaney, christopher d.; hooks, john j.; nida sen, h. title: elevated serum levels of il- and cxcl in autoimmune retinopathy (air) patients date: - - journal: journal of neuroimmunology doi: . /j.jneuroim. . . sha: doc_id: cord_uid: k rl f abstract autoimmune retinopathy (air) is a rare immune-mediated retinopathy associated with circulating antiretinal antibodies (aras). other prominent features of air include visual field deficits and photoreceptor dysfunction in the setting of progressive unexplained vision loss. the role of inflammation is poorly understood in air. since cytokines play a central role in the initiation and development of inflammation, we evaluated the presence of proinflammatory cytokines and chemokines in air patient sera. we demonstrate that il- and cxcl are both elevated in air patient sera. moreover, the presence and concentration of these molecules appear to correlate with air patient disease severity. this cytokine profile, il- and cxcl , has been described to participate in a variety of autoimmune and inflammatory diseases. our study provides support for an activated inflammatory process in air and identifies possible mechanisms that can drive autoimmunity in this disease. autoimmune retinopathy (air) is an inflammatory-mediated retinopathy characterized by otherwise unexplained progressive vision loss, abnormal photoreceptor function and presence of serum antiretinal antibodies. in most cases, the ophthalmic exam, including retinal exam is unremarkable making the diagnosis difficult (comlekoglu et al., ) . autoimmune retinopathies can be classified into paraneoplastic (pair; cancer associated retinopathy and melanoma associated retinopathy) and non-paraneoplastic air (npair) (grange et al., ) . for the purposes of this study we will focus on the latter. since the first reports more than two decades ago, npair remains an ill-defined disorder. despite an unremarkable exam early in the disease course, patients have abnormal electroretinography and visual fields (fox et al., ) . typically, patients have no chorioretinal lesions; some may have low-grade intraocular inflammation. as the disease progresses retinal atrophy, retinal vascular attenuation and optic disc pallor may ensue along with further vision loss. interestingly, antiretinal antibodies can also be found in healthy controls, patients with degenerative retinal disorders and patients with systemic autoimmune diseases with no ocular disease (heckenlively et al., ; shimazaki et al., ) . thus, unlike paraneoplastic air, the specificity and the role of antiretinal antibodies in npair are poorly understood. clinical response to immunomodulatory agents has also been variable, casting doubt on the inflammatory nature of this disease. nevertheless, antiretinal antibodies and visual dysfunction are the hallmarks of npair and most patients are typically treated with immunomodulatory agents with the hope of slowing down the progression of disease (forooghian et al., ; davoudi et al., ; adamus, ) . in general, a critical component of autoimmune diseases and inflammatory disorders is a dysregulation of the immune response leading to inflammation. over the years, several key cytokines have been increasingly identified as mediators of inflammation (hunter and jones, ) . newer technologies, including multiplex cytokine platforms, have made cytokine testing more accessible for clinical samples. il- is a multifunctional cytokine that displays a broad and diverse range of biologic activities including control of cell growth and cell survival (hunter and jones, ) . in addition, il- has been shown to mediate and regulate the immune system most notably through proliferation and activation of cytotoxic t cells, and growth and differentiation of memory b cells and plasma cells. furthermore, il- is especially well-known for its ability to trigger inflammation by inducung the acute phase response and in this way il- impacts acute and perhaps chronic inflammation. although il- is most often considered to be a potent inflammatory cytokine, it has also been demonstrated to have anti-inflammatory properties. il- has a complex signaling system consisting of two distinct signaling pathways and depending on the cell type, a different pathway is initiated. recently, il- antagonists (anti-il- r antibody) have been developed to block il- from binding to its receptor, il- r, and ameliorate inflammation. a variety of cells produce il- and several stimuli trigger il- production, such as, other cytokines, (i.e. tnf-α or il- β) and tlr ligation (hunter and jones, ) . over the years data have been generated that support the association of il- in autoimmune diseases (hirano, ) . for example, the il- pathway has been implicated in the pathogenesis of rheumatoid arthritis (ra), psoriasis, autoimmune liver disease and crohn's disease (tanaka and kishimoto, ) . studies have revealed that a number of serum (and intraocular) cytokines and chemokines, such as il- , il- , il- , tnf-α and vegf have been reported as elevated in ocular inflammatory diseases (jawad et al., ) . more recently, cxcl has been identified as a contributor to the inflammatory process. cxcl , an ifn-triggered chemokine, is a member of the chemokine superfamily of small proteins that participate in immune and inflammatory reactions, specifically, in the induction of t cell and nk cell migration. the ifn molecules and the upregulation of the ifn signature genes are frequently seen as a major factor in autoimmune diseases, such as systemic lupus erythematous (sle) (hooks et al., ; niewold, ) . in addition, cxcl has been described to play a role in the pathogenesis of certain autoimmune diseases, including ra, giant cell arteritis and sle (simpson et al., ; loos et al., ) . in order to evaluate possible inflammatory components in air, we screened for the presence of il- β, il- , il- , gm-csf, ifn-γ and cxcl with a multiplex immunoassay. in this report we demonstrate by eia that il- is upregulated in air patient sera. moreover, we show that cxcl , which attracts t cells to specific target organs, is also elevated in this disease. the presence and concentration of this cytokine signature appear to correlate with air patient disease severity. this data supports the concept that these two bio-regulatory molecules may contribute to the pathologic processes observed in air patients. air patients who were seen at the uveitis clinic at the national eye institute were included and all patients provided written informed consent to participate in research studies. patients were seen under clinical research protocols, that were approved by the institutional review board at the national institutes of health (nih), adhered to the tenets of the declaration of helsinki, and complied with the health insurance portability and accountability act (hipaa) and ex nt. all patients met the criteria for air as determined by the consensus of several uveitis experts, including a negative malignancy workup and confirmed positive antiretinal antibodies. air was defined as the absence of fundus abnormalities with abnormal electroretinogram (erg) and goldman peripheral visual fields (gvf) in the presence of circulating antiretinal antibodies (fox et al., ) . our cohort included patients at different clinical stages of disease (early and late stage) and severity. all patients had at least one antiretinal antibody detected on western blot or had positive immunohistochemical staining with patients testing positive for multiple antibodies on western blot. antiretinal antibody tests were done in different laboratories though the majority of the patients had their testing in one commercial laboratory in the usa (supplemental table) . seven patients were not on treatment at the time of first sample collection, whereas patients were on systemic immunosuppressive treatment or corticosteroids. five of the "currently untreated" patients were treatment naïve, meaning they never received any systemic treatment. four of the currently treated patients were receiving rituximab infusions during the study period (supplemental table) . there is currently no evidence-based scale to assess for disease severity in air. measurable outcomes of the severity of disease involve gradual changes in erg and gvf, which could be used as surrogates for disease progression and, hence, markers of disease severity. erg can vary considerably between visits (intersession variability) for the same subject and have been reported to be up to - % even among normal eyes, with possibly more intersession variability in eyes with advanced retinal disease (fishman et al., ; bach et al., ) . taking into account the intersession variability, for the purposes of this study, we defined air disease severity as mild if there were - % loss of function and moderate/ severe if there were > % loss of photoreceptor function on erg below the defined lower limits of normalcy (iscev). the supplemental table shows the raw erg data for each eye of the enrolled participants at their first visit. this table also shows changes in erg for the patients that had more than one sample. four of the participants had stable poor erg and showed modest decline despite addition of another immunomodulatory agent. a total of frozen serum samples from air patients were received at the johns hopkins hospital from the nei, nih. the air patients had an age range of - years with a gender distribution of females and males. in addition, blood was obtained from normal individuals at the johns hopkins hospital and these serum samples served as controls in this study. eighteen normal individuals in an age range of - years and a gender distribution of females and males were used in the il- assay. similarly, eighteen normal individuals in an age range of - years with a gender distribution of females and males were used for the cxcl assay. serum was collected after centrifugation at g for min at °c. all samples were then stored in a − °c freezer until analyzed. cytokines were evaluated using two technologies: multiplex immunoassay and enzyme-linked immunosorbent assay (eia). all air samples were analyzed on the multiplex system in a masked fashion. after analysis it was determined that patients had more than one serum sample. therefore, the serum sample obtained on the first clinic visit was used for further data analysis. using a -plex, bio-plex® immunoassay (bio-rad laboratories, hercules, ca), samples were analyzed for il- β, il- , gm-csf, ifn-γ, cxcl and il- . this assay uses a bead-based flow cytometric platform designed as a capture sandwich immunoassay format, similar to eia. custom kits with labeled beads were purchased from bio-rad laboratories. these antibodycoated magnetic beads were specific for il- β, il- , gm-csf, ifn-γ, cxcl and il- . the median fluorescent intensity (mfi) was determined on a luminex® ™ instrument (luminex corporation, austin, tx) using the bio-plex manager™ software version . (biorad laboratories, hercules, ca). standard curves were established for the individual cytokine analyzed and the corresponding concentration value (pg/ml) was determined according to manufacturer's instructions. all samples were run in duplicate and in a masked fashion. the mean value was used as the final concentration for that cytokine. it should be noted that the lowest concentration detected in ifn-γ system was pg/ml. multiplex analysis revealed that the mean concentration of cxcl in normal individuals was . pg/ml with a range of . to . pg/ml. in order to examine the predictive value of cxcl as a marker for air case status, we examined samples above versus below the th percentile ( pg/ml) of the cxcl distribution among normal individuals. a positive value of cxcl was identified as the concentration greater than the th percentile (> pg/ml). serum il- levels were confirmed using eia (quantikine il- , r&d systems, inc. minneapolis, mn), which is a very sensitivity assay to quantitate low levels of serum il- . all serum samples were tested in duplicate and in a masked fashion, according to the manufacturer's instructions. the plates were read immediately after application of the stop solution. the optical density of each sample was determined using versamax™ tunable microplate reader (molecular devices, sunnyvale, ca). results were calculated from a standard curve and reported accordingly in picograms per milliliter (pg/ml). the mean minimum detectable dose (mmd) for il- was < . pg/ml and the standard curve range is . pg/ml to pg/ml. the reference range for serum il- was established in the cytokine laboratory at the johns hopkins university using serum samples from normal individuals analyzed by the eia r&d systems, inc. il- assay. the mean serum value for il- was . pg/ml with a range of . to . pg/ml. in order to examine the predictive value of il- as a marker for air case status, we examined samples above versus below the th percentile ( . pg/ml) of the il- distribution among normal individuals. a positive value of il- was identified as the concentration greater than the th percentile (> . pg/ml). the data was analyzed using the wilcoxon rank sum test (mann-whitney u test). we compared the mean concentrations of cxcl and il- , respectively, among the following: ) untreated air cases and normal individuals, ) treated air cases and normal individuals, and ) all air cases (treated and untreated) and normal individuals. all statistical analyses were completed using stata version (statacorp, llc, college station, tx). a p value < . was considered significant. twenty-four serum samples from air patients were initially analyzed by a multiplex immunoassay system for the presence of cytokines and chemokine. as is seen in table , all samples tested for il- β were below the lower limit of quantitation (lloq). gm-csf and il- were detected in only of samples and ifn-γ was detected in of samples. in contrast, il- was positive in of samples ( %) of patient sera and cxcl was positive in of samples ( . %) of the patient sera tested. sera from individual air patients were further evaluated for possible correlations of treatment versus no treatment and disease severity. a comparison of cxcl levels detected in the sera from air patients and normal individuals is shown in table . the mean concentration of cxcl in normal individuals was . pg/ml with a range of . to . pg/ml. all of the samples from the normal individuals had cxcl levels below the th percentile and were considered negative. sixty one percent ( / ) of the air patient sera were positive for cxcl with a mean concentration of . pg/ml (table ) . of note, seven of the air patients in this study were not on treatment at the time the sera were collected. as seen in fig. a , out of these patients had elevated levels of cxcl (mean of pg/ml). a statistically significant difference was observed when all air patient sera were compared to normal individual sera (p < . ). moreover, a significant difference was observed when normal individual sera were compared to untreated air patient sera (p < . ) or compared to treated air patient sera (p < . ). there is also a clear distinction when cxcl levels are compared in the sera from untreated patients (n = ) and treated patients (n = ). the mean concentration of cxcl was pg/ml in untreated patient sera and pg/ml in treated patient sera (fig. a) . using il- eia, additional testing of air patient sera was performed. as is seen in table , il- was detected in the sera from normal individuals at levels below the th percentile, and therefore, considered negative. however, il- was detected at positive levels in sera from individuals with air. thus, il- was identified in % of air patient samples (mean value of . pg/ml) compared to normal individuals (mean value of . pg/ml). a comparison of il- levels in treated and untreated patients is seen in fig. b . four out of untreated patients had elevated levels of il- (mean of . pg/ml). a significant difference for il- was observed when untreated patient sera were compared to sera from normal individuals (p < . ). there is also a clear distinction when il- levels are compared in the sera from untreated patients (mean of . pg/ml) and treated patients (mean of . pg/ml). it is of interest to note that out of these untreated patients ( %) had elevated levels of either il- or cxcl . the air patients were stratified into two levels of disease severity, mild ( of ) disease and moderate/severe ( of ). of the four patients with mild disease, one had elevated levels of il- and cxcl and another patient had elevated levels of cxcl . the last two patients with mild disease did not have elevated levels of either cytokine. the one patient with elevated il- and cxcl was seen at a very early time point in the disease course and was not on treatment. in the remaining patients'sera with mild disease, the mean level of il- was . pg/ml, while the mean level of cxcl was pg/ml. of the fourteen patients, with severe disease, % ( of ) had elevated levels of il- and % ( of ) had elevated levels of cxcl . in total, out of the patients with severe disease had elevated levels of either il- or cxcl . in these patients' sera, the mean level of il- was . pg/ml while the mean level of cxcl was pg/ml. these data indicate that when there is an increase in disease severity there is a trend toward elevated il- or cxcl . five patients had multiple serially collected serum samples tested. a comparison of il- and cxcl in serially collected samples is shown in table . the first two patients had severe disease with high levels of both il- and cxcl . the third patient also had severe disease that was associated with a high level of il- ( out of samples) but normal levels of cxcl . in contrast, the last patients who had mild disease showed normal levels of il- ( out of samples) and normal levels of cxcl ( of samples). the data presented in this study demonstrate increased inflammatory molecules, il- and cxcl , in the sera of air patients. moreover, an increase in air disease severity was found to be associated with an increase in the proportion and concentration of positive samples for both cytokines. in contrast, none of the other cytokines analyzed, il- β, gm-csf, ifn-γ or il- was significantly increased in the air patient cohort. although the presence of cxcl and il- was not always detected in the same serum sample, patients with severe disease more frequently had elevated cxcl , il- or both cytokines in their sera. furthermore, il- and cxcl levels were higher when only patients that were not on any systemic immunomodulatory treatment were considered, strengthening the possibility that inflammation may play a role in the pathogenesis of air. however, whether a lower cytokine concentration among treated patients corresponds to clinical improvement has yet to be determined. our findings of elevated il- and cxcl underscore the prominent role of these cytokines in inflammatory and autoimmune processes. however, our selection of cytokines herein was small and it is very possible that numerous other cytokines may be elevated or depressed and this cytokine milieu may contribute to the elevation of cxcl and il- . additional research is needed and may reveal other cytokines that participate in this degenerative process. il- stimulates the inflammatory process while chemokines, such as cxcl , orchestrate immune cell migration into specific tissues (islam et al., ) . increasing evidence for il- and cxcl has clearly implicated the involvement of these mediators in the development of autoimmune diseases. for example, the persistent production of il- has been associated with causing the onset and development of autoimmunity (hirano, ; hunter and jones, ) . in these disorders il- acts as a b cell stimulatory factor and activates b cells into antibody producing plasma cells. il- can also mediate t cell development in autoimmunity. in combination with tgf-β, il- induces the differentiation of cd t cells into th cells, thereby, making il- available within the autoimmune environment. alternatively, il- has been reported to inhibit the ability of tgf-β to induce regulatory t cells. it is this th /t-regulatory imbalance that is implicated in the onset and progression of autoimmune diseases (tanaka and kishimoto, ) the presence of ifn in human autoimmune diseases was first described in sle patients in , where its detection correlated with disease activity (hooks et al., ) . the presence of ifns in many of these autoimmune diseases is now recognized as an integral component of their pathologic process (niewold, ) . ifn-α and ifn-γ are the cytokines that trigger the expression of cxcl , cxcl and cxcl . a major function of cxcl is to attract t cells that contain cxcr on their surface to the site of inflammation (islam et al., ) . this chemokine plays a critical role in the migration of t cells from the blood vessel into the brain or retina (lee et al., ; morrell et al., ) . recently, cxcl has been identified in patients with autoimmune diseases and in animal models of autoimmunity. in humans cxcl has been implicated in the pathogenesis of ra and multiple sclerosis (loos et al., ; simpson et al., ) . furthermore, the cxcl signature was enhanced in a murine model of a retinal degenerative disease, experimental coronavirus retinopathy (ecor). ecor is a disease triggered by a coronavirus in genetically susceptible animals (balb/c mice) and is associated with antiretinal autoimmune reactivity (detrick and hooks, ) . the virus also replicates in the retina of genetically resistant mice (cd- ) but these animals do not develop a retinal degeneration nor do the mice develop antiretinal antibodies (hooks et al., ; detrick and hooks, ) . in addition, elevated levels of ifn-γ, cxcl and cxcl were detected in the sera and enhanced gene expression for cxcl and cxcl was noted in the retina early in this disease . notably, this cytokine profile was observed one day prior to infiltration of cells into the retina. these studies implicate cxcl expression in the development of retinal autoimmunity. another example of cxcl involvement in autoimmunity was demonstrated by lang and associates in which they show that cxcl production in the liver was required for the development of murine autoimmune liver disease (lang et al., ) . in this system liver-specific cytotoxic cd t cells were able to migrate, infiltrate and destroy liver cells that expressed cxcl . together, these data underscore the important role of cxcl in the development of autoimmune pathology. since air is characterized by retinal pathology a potential source of il- and cxcl may be within the retina . the retinal pigment epithelial (rpe) cell and the retinal vascular endothelial cell are rich sources of il- and cxcl (lee et al., ; nagineni et al., ) . the rpe cell possesses tlrs with a high concentration of tlr which can drive cytokine production (kumar et al., ) . in humans, elevated cxcl in serum of patients with ocular inflammatory diseases associated with sarcoidosis has also been shown to correlate with disease activity (takeuchi et al., ) . interestingly, elevated serum cxcl along with il- and other proinflammatory cytokines have also been reported in a patient with crb -associated retinal dystrophy. in this patient cytokine levels were decreased in response to immunomodulatory treatment. these findings suggest that there may be a significant contribution by inflammation in known genetic retinal dystrophies where activated resident retinal cells may be responsible for proinflammatory cytokine production (verhagen et al., ) . clearly, the presence of il- and cxcl in air patients is not specific to this disease since these molecules can be identified in systemic inflammatory and autoimmune processes. moreover, il- and a cxcl related chemokine, cxcl , have been identified in other retinal disorders (ambati et al., ) . a notable example is seen in age related macular degeneration (amd), in which il- is an independent prognostic marker associated with the disease progression (seddon et al., ) . additional studies identified that cxcl is highly expressed in the retina of amd patients (mo et al., ) . whether or not these cytokines contribute to retinal pathology is still unknown. nevertheless, the data presented here provides support to the hypothesis that air pathogenesis may be associated with an inflammatory processes. cytokine-mediated pathways are pivotal to the development of autoimmune diseases. while elevated il- and cxcl are not unique to air, the data presented here indicate that the inflammatory cytokine signature of elevated il- and cxcl may contribute to the retinal pathology observed in air patients. continued studies on these pathways will be useful in the discovery of future strategies for air diagnosis and management. impact of autoantibodies against glycolytic enzymes on pathogenicity of autoimmune retinopathy and 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experimental cerebral malaria regulation of vegf expression in human retinal cells by cytokines: implications for the role of inflammation in age-related macular degeneration connective tissue diseases: targeting type interferon in systemic lupus erythematosus progression of age-related macular degeneration: prospective assessment of c-reactive protein, interleukin and other cardiovascular biomarkers frequency of anti-retinal antibodies in normal human serum expression of interferon -gamma inducible chemokine, ip- and mig and their receptor, cxcr elevated serum levels of cxcl /monokine induced by interferon-gamma and cxcl /interferon-gamma-inducible protein- in ocular sarcoidosis targeting interleukin- : all the way to treat autoimmunity and inflammatory diseases systemic inflammatory immune signatures in a patient with crb linked retinal dystrophy supplementary data to this article can be found online at https:// doi.org/ . /j.jneuroim. . . . key: cord- - i wr authors: nag, pranab kumar title: sick building syndrome and other building-related illnesses date: - - journal: office buildings doi: . / - - - - _ sha: doc_id: cord_uid: i wr sick building syndrome (sbs) and building-related illnesses are omnipresent in modern high-rise buildings. the sbs is a complex spectrum of ill health symptoms, such as mucous membrane irritation, asthma, neurotoxic effects, gastrointestinal disturbance, skin dryness, sensitivity to odours that may appear among occupants in office and public buildings, schools and hospitals. studies on large office buildings from usa, uk, sweden, finland, japan, germany, canada, china, india, netherlands, malaysia, taiwan, and thailand, substantiate the occurrence of sbs phenomena. the accumulated effects of a multitude of factors, such as the indoor environmental quality, building characteristics, building dampness, and activities of occupants attribute to sbs. a building occupant manifests at least one symptom of sbs, the onset of two or more symptoms at least twice, and rapid resolution of symptoms following moving away from the workstation or building may be defined as having sbs. based on the peer-reviewed documentation, this chapter elaborates the magnitude of building-related health consequences due to measurable environmental causations, and the size of the population affected. the mechanisms and causative factors of sbs and illnesses include, for example, the oxidative stress resulting from indoor pollutants, vocs, office work-related stressors, humidification, odours associated with moisture and bioaerosol exposure. related regulatory standards and strategies for management of sbs and other illnesses are elaborated. challenging lawsuits to redress grievances. the term sbs has been in use for some time now and widely recognized, in spite of suggestions for alternative names, such as problem buildings, building-related occupant complaint syndrome, abused building syndrome. acknowledging that the incidences of sbs symptoms are straightforward, its characterization and linkages to an indoor exposure require more in-depth analysis. an impediment towards this effort is to make the primary distinction as to whether the problem is chemical, biological, physical, or psychogenic. the questions to examine are the mechanism how workplace or environmental processes trigger physical health symptoms, and whether some individuals are more prone to illnesses. further, it calls for a review on the kind of critical work settings that precipitate illness conditions, and how the work or environmental aspects influence building occupant's psychophysiological threshold, making oneself hypersensitive even to mild irritants. priority is placed on exploring organizational interventions to restrict the spread of the syndrome and efficiently manage causes of building-related illnesses. several researchers indicate the sbs as a phenomenon that occurs among building occupants, perhaps one out of five building occupants reports symptoms associated with their respective place of work and attributed to the iaq. the interactions of a multitude of factors, such as the site, climate, building system, construction materials, building dampness, contaminant sources, activities of occupants, affect the quality of indoor air. typically, maintaining allowable iaq in office buildings depends on effective ventilation systems in operation. ineffective or inadequate ventilation systems result in inefficient removal of pollutants from indoor air and display signs of sbs among the occupants. health impact assessment addresses qualitative or quantitative evaluation of the magnitude of health consequences due to measurable environmental causation or metric, and the size of the population affected (fehr et al. ; mesa-frias et al. ) . apparent relationships exist between the external stimuli, kinds of human responses and about the type of building environment. therefore, the discomfort and symptoms of occupants in the building require acknowledging that an exposure scenario exists, and the discomfort and disease have a strong association with psychologic or physiological components. a structured questionnaire (table . ) may be used to ascertain the sbs of the respondents in an office building. the office workers who had at least one symptom of sbs and onset of two or more symptoms at least twice weekly, overnight resolution of symptoms after leaving the workstation or building, and the absence of known medical causes, may be defined as having sbs (ooi et al. ). the prevalence of symptoms among building occupants is linked to personal exposure to the indoor environment. the symptoms may vary during the day, in the course of changes in the concentrations of indoor pollutants. further, the prevalence of syndrome might differ with the specificity of criteria for the definitive diagnosis of a case. accordingly, there may be a shift in the frequency distribution of affected workers when the requirements were changed to one symptom, instead of two or more symptoms (ooi et al. ) . for measuring the concentration of indoor air pollutants, one may adopt area sampling by placing an environmental monitoring device in general building locations and placing a personal sampling device close to the nose of the person that better represents the inhaled dose of individuals. chapter is dedicated to indoor environmental quality (ieq) assessment, concerning primary exposures. the exposure assessment based on area sampling and recording of symptoms of occupants from the vicinity of the samplers may indicate some dose-response relationships between exposures and symptoms. however, there are limitations to extrapolate the relation to other buildings, since the problem situations in buildings are unlikely to be similar. epidemiological evidence is abundant of the occurrence of sbs in real-world settings all over the world. within the limited scope, and the author's comprehension on the subject, only a selected number of cross-sectional studies that have been reported in the recent years are briefly summarized in table . . different research groups emphasized on the association of prevalence of sbs symptoms among the office workers with the organic floor dust concentration, the floor covering of the workplaces, the age of the building, and the kind of ventilation system in operation. the size of the office and the number of occupants in the office were critical, presumably because of likely rise of pollutants during the day. the shelf factor was identified as a risk factor for mucosal irritation, and the fleece factor, such as fleecy surfaces, paper, and cardboard was recognized for general symptoms in the office buildings (skov et al. ; mølhave ) . despite that carpets give a cozy atmosphere and an aesthetic acoustic environment in a building, carpet fibres and accumulated dust, especially the organic part of the dust, have been found to be associated with sbs, namely mucosal irritation. further details of work and building-related respiratory illnesses are elaborated elsewhere in the chapter. the us epa building assessment survey and evaluation (base) study (apte and erdmann ) is a landmark study covering large office buildings and extensive measurements of both sbs symptoms and environmental monitoring. the occupant must have reported an occurrence of one sbs symptom, at least - days per week during the month, and resolution of the symptoms when the occupant moves away from work. analysis indicated dose-dependent associations in many of sbs symptoms with the delta change in indoor and outdoor co concentrations. voc sources had a direct association with mucous membrane and lower respiratory irritation. the whitehall ii sbs study is a longitudinal health survey of uk office-based civil servants, commenced with males and females, exploring the significance of the physical and psychosocial work environment to the occurrence of sbs. analysing ten sbs symptoms among participants from buildings, marmot et al. ( ) did not observe the significant relation between most aspects of the physical work environment and sbs symptom prevalence. the features of the psychosocial work environment, such as high job demands and low support, appear to be more determining in explaining differences in the prevalence of sbs symptoms, than those attributed to local aspects of the physical environment of office buildings. examined the occurrence of sbs related symptoms, chronic respiratory symptoms, and respiratory infections, using a questionnaire survey of office workers in finland. a case definition of sbs was taken as symptoms of nasal (dryness or itching of nose, blocked or a runny nose, or sneezing), eye (dryness and irritation, watering, or redness), throat (dry irritative cough, sore throat, or hoarseness), skin (dryness, irritation, redness patches, itching, sore skin, or urticaria), and non-specific symptoms (headache and fatigue), which workers had more sbs symptoms in buildings that were humidified or air-conditioned. complaint: lethargy ( %), nasal congestion ( %), dry throat ( %), headache ( %). symptoms (mean building sickness index) were more in women than in men and were independently more frequent in clerical workers, secretaries than in technical and professional employees and managers skov et al. ( ) were more among females than males might have occurred during the past year, at least - days per week and mainly during workdays or work shifts. there were significant health effects due to office work exposures, adjusting confounders such as psychosocial factors at work. exposures to paper dust and carbonless paper that contains solvents and colour-forming chemicals increase the risk of a headache and fatigue, chronic breathlessness, and chronic bronchitis (a chronic cough and phlegm production). exposure to carbonless paper through its touching can cause sinus infections, middle ear infections, and increased risk of eye symptoms and diarrhoea. gupta et al. ( ) undertook a questionnaire-based investigation on the prevalence of the sbs at a multi-story centrally air-conditioned airport authority of india building in new delhi. qualitative analysis included the relationships between sbs score, co and other parameters related to building and work environment. quantitative analysis included monitoring of pollutants, namely no x , so , co, and suspended particulate matter. despite that the concentrations of pollutants complied with iaq standards were generally within limits, the prevalence of sbs (a headache- %, lethargy- %, and dryness in body mucous- %) was higher in the third floor as compared to other floors and the control tower. the third floor and the control tower of the airport were affected by infiltration, mainly from entrance doors. hengpraprom et al. ( ) showed the influence of airborne fungi on allergic rhinitis among office occupants ( %) of a high-rise building in bangkok. allergic rhinitis was defined as having the symptoms of nasal congestion, an itchy nose, sneezing, and running nose without a cold in the past months (teeratakulpisarn et al. ) . work-related allergic rhinitis was defined as (a) having the above symptoms with a cold at least twice in the past month; (b) expressing the manifestation at work or seeing it worsen at work; and (c) the frequency of manifestation occurred at least - days per week. indoor humidity was strongly correlated with airborne fungi concentrations. however, the fungal concentration was not associated with work-related allergic rhinitis. asthma and asthma-like symptoms among office workers, respiratory sensitization with exposure to hot or cold weather, the presence of visible mould, and carpeting resulted in a positive association with allergic rhinitis. syazwan et al. ( ) compared the data of sbs and iaq of office workers in old and new buildings in kuala lumpur city. the investigators suggested that improvement in ventilation effectiveness and increase in ventilation rates per person may reflect on the reduction of indoor pollutants and also reduction in the prevalence of sbs in buildings. norhidayah et al. ( ) investigated associations between iaq parameters and sbs in three buildings in malaysia. the prevalence of sbs symptoms, having to symptoms per week, was similar in the buildings. the co concentration and fungal counts were not significantly different between the buildings. however, the observed co concentration and climatic factors suggest that the predictors of sbs might be ventilation and accumulation of contaminants within the indoor environment. many abiotic agents from building materials and interiors like wall coverings, synthetic paints (a&b-pinene), thinners, glue, floor coatings of linoleum and pvc, solvents, such as formaldehyde, hairspray, perfume, photocopiers and printers, disinfectants and detergents (members of linear alkylbenzene sulphonates), and soap as cleaning agent (sodium or potassium salts mixed with fatty acids) add to air pollution to cause sbs symptoms (guo ; mcdonnell and burke ) . therefore, it may be reiterated from reviewing voluminous literature that no one single cause explains most sbs complaints, but instead assumes that multiple factors interact to manifest occupant complaints. the symptoms typically grow worse during the workday and disappear or diminish after the person leaves the building. women appeared to show a higher prevalence of sbs symptoms as compared to men in the same buildings. individual characteristics, such as education level, working conditions, job characteristics, and other psychosocial factors, can also influence sbs prevalence positively or negatively in men and women. the technical factors associated with the increased prevalence of sbs are the building factors, such as the age of the building, indoor dampness, presence of some photocopiers and humidifiers in the building (sundell ) . zweers et al. ( ) examined occupants ( % female) in office buildings in the netherlands and noted that occurrence of sbs symptoms was related to air conditioning and humidification in buildings. females had more prevalence of sbs (e.g., skin/eye/ nasal symptoms) and complaints of indoor climate, such as temperature, air quality, lighting, and noise. carrying out of study on office workers ( % female) in sweden, stenberg and wall ( ) observed a higher prevalence of sbs among females (or = . ) than males. questionnaire survey and ergonomic data from the german proklima-project (brasche et al. ) also substantiated a significantly higher prevalence of sbs symptoms among women, as compared to men folks, both under the most favourable and most unfavourable job characteristics. undoubtedly, the physical and psychological disposition, on the one hand, and work-and job-related factors, on the other hand, are risk factors on the perception of the indoor environment and the pathogenesis of complaints. with a sample size of office workers (* % females) from office buildings in the usa, reynolds et al. ( ) observed that the psychosocial factors were positively correlated with the incidences of sbs in females. however, the environmental factors were correlated with symptoms in males. by examining occupants ( % female) in office buildings in quebec, canada, donnini et al. ( ) observed no significant differences in thermal neutrality between males ( . °c) and females ( . °c). females expressed significantly higher thermal dissatisfaction ( % female vs. % male). nakano et al. ( ) examined japanese office workers ( % females) and noted a significant difference in thermal neutrality, i.e., females ( . °c) and males ( . °c), while females reported a higher frequency of sbs symptoms, as compared to the male group. in a study on office occupants ( % female), in office buildings in australia, cena and de dear ( ) noted the votes of thermal unacceptability, and females complained of significantly higher thermal dissatisfaction than those of males. choi et al. ( ) had a similar observation by studying office workers (* % females) from office buildings in the usa. runeson et al. ( ) investigated the prevalence and change of sbs symptoms in buildings with suspected indoor air problems about antonovsky's sense of coherence (soc), a psychological measure of life attitude. the study was conducted on a cohort of workers from swedish buildings with indoor environmental problems between and . information on sbs symptoms was gathered, as well as the soc measure was administered in a postal follow-up. after adjusting for age, gender, history of atopy, and ets, runeson et al. ( ) noted that sbs was more common in women, younger ones, and those with a history of atopy. a low soc was related to a higher prevalence of ocular, nasal, and throat symptoms, tiredness, and headache. also, subjects with a low soc developed more symptoms during the follow-up period. saijo et al. ( ) undertook postal self-administered questionnaire survey to , dwellings from municipal, and prefectural apartment buildings in the city of asahikawa, japan, and questionnaires were finally analysed. from the questionnaire about moisture condensation and visible mould on window panes, walls, closets, bathrooms, the perception of mouldy odour, and water leakages, a building dampness index was defined as the sum of positive dampness indicators. sbs symptoms recorded for the preceding -month period were-fatigue, feeling heavy-headed, headache, nausea/dizziness, difficulty in concentrating, irritation of the eyes, running nose, dry throat, cough, dry or flushed facial skin, itching of the scalp, ears, and hands. the symptoms were significantly higher among females than males. the building dampness index was also significantly related to all sbs symptoms, as also noted by engvall et al. ( ) in the study covering multi-family buildings ( , dwellings) in stockholm. saijo et al. ( ) noted allergic diseases as risk factors for sbs development, and therefore, the history of allergic diseases was taken as a confounder for sbs symptom analysis. the us niosh study in office buildings also found a positive association between moisture and debris in the ventilation systems and lower respiratory tract symptoms (mendell et al. ) . kim et al. ( ) undertook a comprehensive literature survey, based on north american post-occupancy evaluation (poe) database (n = , ). the survey indicated that the satisfaction levels of female occupants were significantly lower than males on all fifteen ieq factors (such as thermal comfort, air quality, lighting, acoustics, office layout, furnishings, cleanliness, and maintenance). the results were consistent, even after controlling the potential confounders, such as age and work characteristics. chronic fatigue syndrome (cfs) manifests as a clinical entity characterized by prolonged severe and disabling fatigue (fukuda et al. ) . the syndrome usually occurs sporadically, but occasionally may appear as epidemics. typically, the syndrome follows a cyclical course, alternating between periods of illness and relatively good health. the onset of cfs has been related to a variety of psychological, environmental, and behavioral factors (pizzigallo et al. ) , and exposure to pesticides, organophosphates, solvents, and other chemicals (bell et al. ) . in tropical areas, many cfs-like cases follow an episode of gastroenteritis due to food toxins from ciguatoxic fish (pearn ) . ciguatera consists of a food-chain disease that starts with a reef-dwelling dinoflagellate, gambierdiscus toxicus (gillespie et al. ), which is heat-stable. individuals can be poisoned from eating fresh or frozen fish, or fish products. symptomatology of some outbreaks of sbs resembles cfs, associating with building characteristics, such as old buildings, inadequate ventilation, non-functioning windows, and inefficient hvac system (chester and levine ) . thousands of gulf war veterans, even years after the operation desert storm in , remained ill with vague symptoms that resemble cfs. these veterans were exposed to an array of hazards, such as extremes of climate, dust, and smoke from oil well fires, petroleum fuels and products, depleted uranium (used in artillery shells), chemical warfare agents, pesticides, infectious diseases, and pervasive psychological and physical stress. the veterans were administered with pyridostigmine bromide (as pre-treatment for potential poison gas exposure), anthrax and botulinum toxoid vaccines (landrigan ) . haley et al. ( ) identified six different syndromes among the war veterans, namely: syndrome (impaired cognition)-reported by veterans wearing flea collars during the war than those who never wore them; syndrome (confusion-ataxia)-reported by veterans involved in chemical exposure (e.g., pyridostigmine bromide); syndrome (arthro-myo-neuropathy)-exposure to insecticides containing % deet (n,n-diethyl-m-toluamide); syndrome (phobia-apraxia); syndrome (fever-adenopathy); and syndrome (weakness-incontinence). the case definition of cfs (fukuda et al. ) a. persistent or recurrent fatigue (lasting > months) . recent and or well-defined onset; . not secondary to excessive physical activity; . not resolved by rest; and . inducing reduction of previous levels of physical and mental activities. b. presence of more than four symptoms (for > months), not previous to fatigue onset: . impaired memory or concentration; . a sore throat; . tender cervical or axillary lymph nodes; . muscle pain; . multi-joint pain; . new headaches; . unrefreshing sleep; and . post-exertion malaise. if the combined number of elements of a and b present exceeds , a case of cfs would be considered. the multifactorial aetiology of sbs in office buildings is yet to understand clearly. evidence favours that the accumulated effects of building characteristics and ieq manifest in health outcomes, including sbs symptoms, allergy, asthma, and other respiratory illnesses. the health effects, in turn, cause adverse impacts on job satisfaction, work performance, productivity, and healthcare costs (fisk ) . the potential environmental stressors that might be responsible for causing sbs symptoms are briefly mentioned herewith. further details of iaq associated with different pollutants in the indoor environment are described in chap. . indoor air pollutants include oxides of nitrogen (no x ), co, co , vocs, and particulates, which are emitted from building materials, office equipment, and as combustion by-products. the intrusion of pollutants from the outdoor air through leakages and ventilation systems is a critical component. the build-up of co may be considered as a surrogate for many occupant-generated pollutants in the indoor built environment. review of studies of sbs symptoms in office buildings indicated increased indoor co levels were associated with an increase in the prevalence of one or more sbs symptoms (seppänen et al. ) . findings from more mechanically ventilated and air-conditioned buildings indicated a significant association between an increase in co and sbs symptoms, and total symptom scores. as mentioned earlier, the base dataset ( - ) yielded significant dose-response relationships between the delta change in indoor and outdoor co concentrations, and the sbs symptoms, such as a sore throat, nose/sinus irritation, mucous membrane symptoms, and tight chest (apte et al. ) . headaches represent the single most common symptom in almost all indoor environmental studies ). the current knowledge highlights different forms and mechanisms of a headache, such as a migraine, or a tension-type headache, or any plausible exposure to chemical toxicants, e.g., co or pesticide poisoning. whereas, many of the events do not provide a precise characterization of the office environment (schneider et al. ) , such headaches are no less significant given the productivity implications, and the potential for active intervention in the office environment. volatile organic compounds (vocs)-vocs are ubiquitous indoors, due to human activities, building product emissions, including floorings, linoleum, carpets, paints, surface coatings and furniture, and infiltration of the outdoor air. for new or renovated buildings, vocs are primarily emitted from building products. secondary emissions of vocs result from ageing of building products, by chemical decomposition (e.g., moisture build-up or inadequate maintenance) or physical damage due to heat and uv light (wolkoff ) . furniture coatings release nearly vocs (aliphatic and aromatic aldehydes, aromatic hydrocarbons, ketones, esters, and glycols) (salthammer ) . office equipment and supplies, such as laser printing toners, emit vocs, ozone, formaldehyde, resin, and other particles. use of perfumes indoors may release vocs. indoor fungi are also a source for the production of vocs. many vocs are known toxic compound, with potential for carcinogenicity, mutagenicity, or teratogenicity. documented evidence strongly affirms that occurrence of sbs follows predictable dose-response relationships with increasing concentrations of mixtures of vocs. the vocs, such as o-xylene, styrene, d-limonene and other terpene compounds may readily react with ozone and no x entrained from outdoors and produce highly reactive compounds, including aldehydes and ultrafine particles, leading to sensory irritant symptoms (sarwar et al. ; sundell ). these effects have been observed in case of carpet emissions, latex paint off-gassing, and other office pollutants. it has been viewed that sbs may be related to the lost vocs, i.e., the difference in the concentration of vocs entering the room to that leaving the room. in california healthy buildings study, brinke et al. ( ) adopted an approach in developing voc metrics and identified relationships between sbs symptoms and clusters of vocs by its possible emission sources. the principal component analysis (pca) allowed to cluster vocs into a reduced set of principal component (pc) vectors and further estimated the association between sbs symptoms and the voc exposure metrics, using logistic regression analysis. a similar approach was taken by apte and daisey ( ) in exploring the causal associations between sbs and environmental stressors, using a subset of data from office buildings of the us epa base study. four source-based pc vectors were derived that identify sources as photocopiers, automotive emissions, ets, and latex paints. regression analyses indicated significant associations between mucous membrane-related symptoms and the photocopier vector, after adjustment for age, gender, smoking status, the presence of carpeting, and thermal exposure. sore throat symptoms were associated with the paint vector. analysis of dataset of all base buildings revealed vocs, formaldehyde and acetaldehyde corresponded to buildings, whereas vocs were available in all buildings. the pca yielded ten pcs identified as the voc sources (apte and erdmann ) . seven components referred to as furniture coatings (pc ), paint (pc ), construction materials (pc ), printing materials and processes (pc ), carpet and undercarpet (pc ), parking garage (pc ), and cleaning products (pc ) met the criterion of having eigenvectors . . oxidative stress and sbs-several studies suggest that a shallow concentration of vocs in indoor environment may cause sbs symptoms, but how such symptoms generate disability at such low levels remains unexplained. little is known about the likely oxidative stress that can attribute to the occurrence of sbs due to exposure risks of air pollutants or other factors of the environment. reactive oxygen species (ros) are components found in many of the air pollutants and can cause oxidative damage to lipids, proteins, and nucleic acids. urinary -hydroxydeoxyguanosine ( -ohdg) is a known biological marker of oxidative stress on dna. accumulation of ets, vocs, formaldehyde in the building due to insufficient ventilation can result in the rise of urinary -ohdg levels among occupants (calderon-garciduenas et al. ) . lu et al. ( ) gathered data from self-reported questionnaires and analysis of on-site air pollutants and urinary -ohdg of employees in government offices of eight high-rise buildings in taipei city. the urinary -ohdg was significantly associated with vocs and co levels in offices, and the -ohdg level were significantly higher among the employees with sbs symptoms than in those without such complaints. a positive dose-response effect between -ohdg levels and the number of symptoms was suggestive that the urinary -ohdg as a viable non-invasive marker can be taken as a predictor for sbs. office exposures and work stress-office work-related exposure to paper dust emanated from carbonless copy paper and fumes from photocopiers and printers are health concerns, including respiratory illness among office occupants. observations of substantiated that the exposure to paper dust and carbonless papers carries potential risks of chronic respiratory symptoms, respiratory infections, and other health concerns in an office environment. the stress of work, including extended hours of work, reflects as different work stressors and consequent health impacts among occupants in modern office buildings. there are multiple aspects of work, including physiological, motivation, technical, psychosocial, environmental, perceptual as well as organizational that attribute to work stress. as mentioned earlier, outbreaks of psychogenic illness (sbs) are perhaps a symptom of underlying stress at work and workplace (selvamurthy and ray ) . mizoue et al. ( ) carried out a cross-sectional survey of municipal employees from different buildings in a japanese city. findings indicated that both ets exposure and overtime work contributed to the development of sbs. working overtime for or more hours per month was also associated with sbs symptoms, but the occurrence of sbs reduced by / th after adjustment for variables associated with overtime work and about an-half after further adjustment for perceived work overload. runeson et al. ( ) undertook a postal questionnaire survey as regard to sbs on a sample of subjects ( - years of age), including the three-dimensional model of demand-control-support, regarding social support in actual work situations. results indicated that males and females perceived psychosocial work conditions differently and reacted differently to job stressors. that is, the psychosocial work environment was as important as gender and atopy as a predictor of sbs symptoms. nag and nag ( ) examined the work stresses of women vdt-cum-telephone operators in selected office buildings (telephone exchanges) and observed that the behavioural response to the work stressors, and health and well-being dimensions did vary with the work schedules. the pca analysis of the ergonomics checkpoints yielded five aspects of work, as organizational (pc -describing job design needs, workplace interventions, and constraints of vdt workstations), environmental (pc -covering illumination-, climate-, and noise-related hazards), mechanistic (pc -referring to job specialization, pace of work, information handling), perceptual and motor (pc -describing visual and auditory displays and controls), and motivational (pc -referring to personal job characteristics and core dimensions). the loading of the work stressors explained in pc to pc appeared autonomous, irrespective of the shift schedules at which the women were engaged. the operators in the rotating shift had higher sensitivity to the stressors related to pc . the day workers responded greater to the stressors related to the core job dimensions that reflect growth needs (pc ). the sleep disturbance, flexibility to sleeping habits, and personality dimension (neuroticism) were negatively correlated with pc . the digestive problems, social and domestic disruption, and languidity dimensions were positively correlated to pc and pc . the operators in rotating shift had increased demand in the perceptual and motor, and the motivational aspects of work, and thus causing greater negative influence on physical health symptoms, and social and domestic disruption. the job design interventions tailoring to delay the morning shift and adjust the shift length based on the work and climatic load (that is, reduce work hours in the evening shift to avoid peak workload, and extend hours of day work during the hot summer months) might alleviate work stress and enhance health and well-being. manifestations of work-related stress call for organizational analysis and job design interventions in structuring the workplace. thermal discomfort-exceedance beyond the thermal comfort range is associated with increased symptoms, such as a headache, fatigue, and mucosal irritation. besides the relative effectiveness of ventilation systems, uses of increasing numbers of electronic devices in the offices add to the heat loads in buildings. in real-life work environment, a significant proportion of the population remains in uncomfortable situations and shows thermal discomfort. clothing habits in different seasons may also contribute to the causes of thermal discomfort in a hotter environment. humidification-a sensation of air dryness and irritative symptoms from eyes, skin, and upper airways are common factors in the sbs (stenberg et al. ) . by examining employees from four geriatric hospital units in southern sweden, nordstrom et al. ( ) evaluated the effect of steam air humidification on sbs and perceived air quality during the heating season. air humidification was raised to - % rh in two units during a four-month period, whereas the other two units were maintained at - % rh. after four months of air humidification during the heating season, % of the employees reported a weekly sensation of dryness in humidified units, compared with % in controls, indicating that air humidification during the heating season in colder climates can decrease symptoms of sbs and perception of dry air. in a tropical environment, rh remains at a much higher level even in an indoor office environment; therefore, incidences of sbs in such situations may be attributed to factors other than air dryness or humidification. odours-odours associated with moisture and bioaerosol exposure are familiar in buildings and best considered in the context of disease with physiological indicators. the odour characteristics are the basis to investigate the possible adverse effects of moulds on human health, in what is often referred to as sbs. from mouldy buildings, the fungal vocs (such as -octen- -ol and -octanone) can produce a range of musty odour (morey et al. ) , as listed (table . ). odour recognition thresholds are usually several orders of magnitude below the irritant thresholds (cometto-muniz and cain ) . fanger ( ) proposed an unit of pollution, olf (for olfactory) for arbitrarily defining the emission rate of air pollutants from a standard person (white male, - years of age, showering . time/day, wear no perfumes, and energy expenditure equivalent of one met for person sitting at rest). the number of olfs is indicated on the initial perception of the odour, referring to discomfort from irritation and annoyance from odour, and overall acceptability. this method was deployed in a project assessing air quality in offices/assembly halls in copenhagen, and external judges adjudged the air quality in unoccupied and occupied, and with or without ventilating systems in buildings. about % of the perceived defects in air quality was due to ventilation systems, % was due to combined occupant activities and occupants themselves, and % due to building materials. the stated method has limitations of efficacy since the raters assess the pollution level in a site within minutes of entering the site. the majority of the occupants may not be able to rate odours consistently, and also the odour annoyance is generally perceived most severe early on first exposure and recedes over time. the building professionals may be amazed at recognizing how the proliferation of fungi in buildings damages the building materials and affects the health of occupants, and more importantly to the causation of sbs and building-associated illness. inadequacy in the ventilation system, moisture controls, and dirt management thrive microbial proliferation in the hvac systems and office carpeting. water incursion into the building envelope is a common cause of moisture build-up and fungal growth. there could be visible mould growth on surfaces, the wall behind wallpaper or under the floor covering, suspended ceiling panels, localized damp areas between a wall and a large item of furniture, and in cavity wall spaces (lugauskas and krikstaponis ) . through the routes of inhalation or ingestion, propagules of fungi and bacteria may elicit symptoms of illness, like bronchial irritation and allergy (britton ; beezhold et al. ). broadly, bioaerosol contains fungal and bacterial cells and cellular fragments, and by-products of microbial metabolism build-up in the buildings. particles that range in size from to µm remain suspended in the air, whereas larger particles are deposited on the surfaces (martinez et al. ; horner et al. ). it is not within the present scope to elaborate on the classification of fungi, which are grouped by phylum (division), class, order, family, genus, and species, in the order. khan and karuppayil ( ) indicated that * species of fungi are in contact with humans and * of them are frequently described in epidemiologic studies on indoor environments. in the present context, several fungal species have been referred to by the researchers about an infestation in building materials and contamination of the indoor environment. some of the species are listed in table . . wood, wooden building materials, and kiln dried wood surfaces are vulnerable to fungal attack, with infestation by cladosporium and penicillium (penicillium brevicompactum and penicillium expansum) (sailer et al. ) . acylated wooden furniture, plywood, and polyurethanes used in wood composites for insulation are found to be susceptible to infestation by aspergillus, trichoderma harzianum, paecilomyces variotii, and penicillium species (yazicioglu et al. ; doherty et al. ) . prefabricated gypsum board that is used as inner wall materials in buildings favours the growth of stachybotrys chartarum. sterflinger et al. ( ) examined five different indoor insulation materials, i.e., bloated perlite plaster, bloated perlite board, loam and reed, soft wooden board, and sprayed cellulose, for their biosusceptibility. a. versicolor, alternaria, cladosporium, and penicillium species grow in fibreglass insulation and ceiling tiles (erkara et al. ) . galvanized steel accumulated with dust or lubricant oil residues allows the growth of fungi (rene et al. ; yau and ng ) . dampness can cause chemical degradation of polyvinyl chloride (pvc) floor coverings, including formation and emission of -ethyl- -hexanol, -butanol (tuomainen et al. ) . acrylic painted surfaces are attacked by alternaria, cladosporium, and aspergillus (shirakawa et al. ) , and also aureobasidium pullulans can deteriorate the paints (lugauskas et al. ) . moisture damage of building frames was characterized by meklin et al. ( ) , studying wooden and concrete or brick school buildings. aspergillus versicolor, stachybotrys, and acremonium were detected in samples from moisture-damaged buildings. observations indicate that moisture damage of the building did not alter the fungal concentrations in wooden school buildings, whereas, in concrete schools, the effect of moisture damage was seen with higher fungal concentrations. the presence of oidiodendron and elevated concentrations of cladosporium and actinobacteria were associated with moisture damage in concrete schools. most fungi are mesophilic, and the optimum temperature for fungal sporulation (number of conidiophores and conidia formed in each conidiophore) is within the range of - °c (burge ) . incidently this temperature range corresponds to the human comfort indoors, at which fungi flourish in working environments (burge ) . the relative humidity and air currents influence the release of conidia. fungal growth is favoured at a water activity (a w ) of . - . , which is a ratio of the partial vapour pressure of water in a substance to the standard state partial vapour pressure of water. ph range of - . in building materials allows better growth of most of the fungi (vacher et al. ; hoang et al. ) . the thermophilic and xerophilic (dry tolerant) fungi are found more in hot-dry climates, than in cooler wetter environments. in tropical and subtropical places, thermophilic and xerophilic fungi tend to be abundant in outdoors with optimal heat and moisture. however, an array of factors are necessary for optimal growth of different kinds of fungi. cladosporium, penicillium, and aspergillus produce high numbers of small and light spores (< µm in size). penicillium and aspergillus can grow in substrates with water activity lower than . . the smaller particles can penetrate into the alveolar region when inhaled, evade phagocytosis by macrophages, and transport through systemic circulation (reponen et al. ; seo et al. ), whereas the larger spores and other fragments get deposited in the nasopharynx. kildeso et al. ( ) studied the release of particles from indoor fungi growing in wetted wallpapered gypsum boards, for weeks. when penicillium chrysogenum were subjected to air currents, only spores were released from the colonies, but with aspergillus versicolor, both spores, and fragments were released. with trichoderma harzianum, particles released are-groups of spores ( - µm), individual spores ( - µm) and fragments ( . - µm). seo et al. ( ) reported the release of fragments and spores from aspergillus versicolor and stachybotrys chartarum growing on the surface of ceiling tiles, wallpapered gypsum board, and culture medium. the studies are suggestive that long-term mould damage in buildings may increase the contribution of fungal fragments to the overall mould exposure. in non-culture-based methods, fungal spores in samples and its morphological identification are determined by light microscopy. components or metabolites of fungi can also be used to quantitate fungi population. specific assays can detect extracellular polysaccharides for partial identification of fungal genera in indoor environments (jovanovic et al. ) . polyclonal antibody-based assays detect a broad range of fungal antigens but cannot detect the spores (mitchell et al. ). molecular methods for quantitation of fungi include the use of genus-/ species-specific probes, polymerase chain reaction (pcr)-based methods, restriction endonuclease analysis, and karyotyping. mitochondrial dna can be used for restriction enzyme analysis and dna fingerprinting for fungal identification. the typical approach for fungal detection in a building utilizes culture and microscopy. different surface and air sampling methods are used for detection and counting of fungi, fungal spores and fragments in ambient air and settled dust, pieces of wallboard, duct linings, carpets (asadi et al. ; reponen ) . surface sampling allows determining the degree and the types of microbial growth on environmental surfaces (cabral ) . adhesive tape sampling method examines the fungi and the hyphal fragments in the specimens using a compound microscope (aydogdu et al. ) . in air sampling of fungi, the principles of impaction, impingement, and air filtration have been used. in the impactor method, the airstream is passed through progressively narrower slits into a culture medium and microscopic glass slides covered with an adhesive substance or tape strip is used to collect the sample, and counted by optical microscopy (zhen et al. ). andersen six-stage impactor is used for collection of particles on culture medium. in andersen sampler, in a petri dish could grow colonies. fast-growing colonies may grow above the slow growing and hinder in counting colonies (stetzenbach et al. ). the dichloran-glycerol- agar (dg- ) culture medium with fungistatic properties prevents the growth of the fast-growing fungi (horner et al. ) . liquid impingers collect the samples into the fluid, and the micro-organisms are retained in the liquid until they are cultivated, or evaluated by techniques like biochemical or immunoassays (jo ) . shipe sampler, agt- glass impinger, midget, multi-stage, and micro impingers are common impinger devices (gralton et al. ) . air filtration is used to collect the samples of indoor air in volume. in this method after sampling, the filters are agitated or sonicated in a solution (bazaka et al. ) . readers may refer to standard manuals for analytical details. however, the choice of air or surface sampling techniques depends on the purpose of measurement (jung et al. ) . air sampling by impingement has some advantages over impaction on solid surfaces; for example, if the concentration of microbes in the atmosphere is too high, the liquid could be diluted before adding to the culture medium. collection of the cells in a liquid avoids desiccation resulting from impaction on solid surfaces (stetzenbach et al. ). impaction directly onto agar plates may maximize survival of culturable organisms. in addition to impaction and impingement, other methods like filtration by aspiration and sedimentation sampling have been used. in filtration, three types of filter media are used, such as porous fibrous filters with overlapping fibres, porous gel membrane filters, and capillary pore filters. filter materials include glass fibre, mixed cellulose esters, polytetrafluoroethylene, polyvinyl chloride, gelatin, and polycarbonate (martinez et al. ) . membrane filters can be placed directly on the surface of culture medium or washed with a liquid, and this added to culture medium. specific filters (namely gelatin) are dissolvable in warm liquids, and the resulting suspension can be plated on agarized medium. that is, filtration devices are adaptable for air sampling of wall cavities or roof spaces to pinpoint foci of contamination. sedimentary sampling (e.g., the gravity slide and the settle plate techniques) is the simplest of all methods. in the gravity slide method, microscopic glass slides, smeared with an adhesive substance, are exposed during a specified period. in the settle plate method, open petri dishes with appropriate culture medium are left open for a given time, depending on the air contamination load. after a certain period of incubation, colonies are counted. an index of microbial air (ima) contamination was proposed; that is, a standard petri dish (dia: cm) containing plate count medium is left open to the air, for h, m from the floor and at least m away from walls. after h incubation at °c, the colonies are counted, and the number of colonies is the ima. five ima classes were defined, as - very good; - good; - fair; - poor; and > very poor. the conventional sampling apparatus gives values for fungal particles present in the atmosphere, at the time of sampling; however, other spores and fragments can be attached to the colonies and be released later. the fungal spore source strength determines the maximum amount of fungal particles that can be released from contaminated materials by the action of air currents. from the counting of released particles, the maximum fungal load for a given indoor environment can be calculated (gorny ; sivasubramani et al. a, b) . damp concrete floor and visible mould in buildings are constant sources of risk of respiratory tract symptoms, infections, and exacerbation of asthma (lanier et al. ; araki et al. ) . mucociliary clearance represents the first strategy for removal of fungi/mould from the human respiratory tract. hypersensitivity syndromes, such as hypersensitivity pneumonitis (both acute and chronic) or extrinsic allergic alveolitis, can occur in individuals exposed to conidia, hyphae, or fungal fragments, mycotoxin (trichothecene) (eduard ; franks and galvin ) . hypersensitivity pneumonitis is generally associated with high igg antibodies concentrations in response to alveolar or bronchiolar inflammation caused by fungi or other allergens. the patients may present neutrophilic inflammation with increased production of tnfa and il- , and symptoms such as fever, chilliness, dry cough, dyspnoea, changes in nodular bilateral x-ray, fatigue, and headache (eduard ). aspergillus spp. develops allergic bronchopulmonary aspergillosis and pulmonary aspergilloma (kawel et al. ) . undoubtedly, exposure to fungi in indoor environments elicits an ige-mediated hypersensitivity response that precipitates into rhinitis and other forms of the allergic syndromes, such as upper airway irritation, eye irritation, and sinusitis (yike ) . during this process, antigen-specific ige is produced that attaches to receptors on mast cells which are concentrated on the gastric and respiratory mucosa. the principal fungal allergens, such as ( - )-b-d glucan or water-soluble glycoproteins, may become airborne and when its concentration exceeds ng/m , susceptible individuals may show non-specific inflammatory airway reactions and that affect the immune system (kalyoncu ; tercelj et al. ) . ( - )-b-d glucan, a cell wall component of filamentous fungi, is readily detected in moisturedamaged building materials, dust samples, and textile floor coverings (reponen et al. ; rylander ) . ergosterol is found in the cell membranes of fungi, but its content varies with the fungal species (heinrich ) . besides, people who inhabit mouldy buildings (presence of s. chartarum and aspergillus spp. in air samples) were reported with cognitive defects and difficulties in concentration (drappatz et al. ). in mouldy buildings, occupants complain of dermatological symptoms, gastrointestinal problems, reproductive effects, rheumatologic, and other immune diseases. breda et al. ( ) recorded that the rheumatic diseases (inflammation and stiffness in muscles, joints, or fibrous tissues) are exacerbated by indoor environmental conditions, including dampness and fungi infestation. rheumatoid arthritis, ankylosing spondylitis, sjogren's syndrome, and psoriatic arthritis have been observed among occupants in water-damaged buildings with mould growth (muise et al. ). various fungi produce mycotoxins that are low molecular weight and non-volatile compounds, and potentially carcinogenic, teratogenic, and mutagenic. mycotoxins can also be isolated from fungi-contaminated building materials and house dust (engelhart et al. ) . the production of mycotoxins by indoor fungi growing in building materials is usually lower than that cultivated in vitro in building materials (e.g., gypsum board, chipboard) (nielsen ; nieminen et al. ) . aflatoxins, trichothecenes, and ochratoxins are common mycotoxins in indoor environments (zain ; halios and helmis ) . other toxins (e.g., t- , ht- , deoxynivalenol (don), nivalenol, diacetoxyscirpenol, satratoxins, trichoverrols, verrucarol, verrucarins, trichoverrins) have been described in this group. trichothecenes are a family of mycotoxins produced by species such as cladosporium, aspergillus, penicillium, fusarium, trichoderma, myrothecium, trichothecium, stachybotrys, cephalosporium, giberella, memnoniella (tuomi et al. ) . a possible causal relationship exists between mycotoxin exposure and building related illnesses (sen and asan ; di giulio et al. ) . the effects of trichothecenes exposure in humans include internal burning, vomiting, and diarrhoea with blood, cutaneous necrosis, and internal haemorrhages. evidence gathered that exposure to higher concentrations of penicillium and aspergillus in the indoor environment could induce health problems and sbs symptoms. severe asthma and acute exacerbations of asthma have been associated with alternaria sensitivity and increased airborne concentrations of alternaria spores (salo et al. ) . vance and weissfeld ( ) warned that the presence of s. chartarum indoors is a concern since its growth requires water saturation of cellulose-based materials such as paper, cardboard, wood, and gypsum board (menetrez and foarde ; gottschalk et al. ) . it is likely that plumbing and roof leaks provide the needed moisture for the fungus to grow. the small size, ellipsoid shape stachybotrys spores can reach the lower respiratory tract (murtoniemi et al. ) . the causal relationship between s. chartarum and sbs has been debated, with the view that health effects may be due to the presence of other pollutants, like vocs (mvocs), endotoxins, respirable dust, and other compounds in the indoor environment (bloom et al. ). don, a trichothecene mycotoxin mainly produced by fusarium molds, like other mycotoxins, is an immunomodulator that can enhance or suppress the immune system depending upon the dose and duration of exposure (lee et al. ; zhou et al. ). the t -toxin, which is produced by species of fusarium and diacetoxyscirpenol, has been shown to modulate apoptosis in human promyelocytic leukaemia cells (yoshino et al. ; yang et al. ) . several types of research explore the potential association of sbs with particular microbes, biotoxins, or other complex exposure mixture components observed in the water-damaged buildings . trichothecene mycotoxins produced by stachybotrys, satratoxin, and roridin have been identified in serum using an elisa assay. generally viewed that the mixture components, including fungi, bacteria, mycotoxins, endotoxins, and lipopolysaccharides, interact synergistically, through the feedback control of pro-inflammatory cytokine production and induce sbs (huttunen et al. ). the onset of sbs is typically observed following chronic exposure in water-damaged buildings, extending for many months. needless to mention that health risk assessment for sbs has many uncertainties, such as the extent of toxin accumulation in tissues, interspecies differences in susceptibility, and threshold shifts of the repair mechanisms during chronic exposure (shoemaker and house ; . there is an evident need to make the focus on innovative and effective therapeutic interventions (e.g., cholestyramine (csm) therapy) to remove biotoxins from the body, caused by toxic mould exposure. there are nearly vocs of fungal origin that often referred to as microbial vocs (mvocs). these mvocs produce mixtures of simple hydrocarbons, heterocycles, aldehydes, ketones, alcohols, phenols, thioalcohols, thioesters, and their derivatives, including benzene derivatives, and cyclohexanes (korpi et al. ; ortiz-castro et al. ). currently, gas chromatography-mass spectrometry (gc-ms) is the primary method for the detection of mvocs (matysik et al. ). the electronic nose (e-nose) is an alternative non-invasive technique to detect essential fungi and mvocs. the instrument combines an array of electronic chemical sensors, a pattern recognition processing unit, and a reference library for recognizing odours baietto , ) . molhave ( ) emphasized the exposure to mvocs as the aetiological agents associated with sbs, including lethargy, headache, as well as irritation of the mucous membranes. however, the types and concentrations of mvocs in mould-infested buildings vary with the ventilation rate indoors, moisture level, the composition of mould population, and other parameters (schleibinger et al. ) . for example, penicillium, aspergillus, and stachybotrys are vocs as well as mycotoxin producers (matysik et al. ) . mvocs are produced by the cells and released to the indoor environment, whereas mycotoxins are present inside the cells and fragments (reponen et al. ). in healthy individuals, the fungal spores and fragments are destroyed by cells of the immune system, but a small number of mycotoxins can still enter in the systemic circulation with possible chronic or sub-chronic toxic effects (straus ). the fungal release of vocs is sometimes referred to like products of secondary metabolism, and these compounds remain reasonably stable in a range of growth media and conditions (moularat et al. ) . moularat et al. ( a, b) described the assay of vocs produced by aspergillus niger, a. versicolor, and penicillium brevicompactum and identified nineteen compounds resulting from fungal metabolism. mvocs also cause indirect metabolic effects. fungal colonization in urea formaldehyde insulation materials results in the cleavage of urea from the polymer releasing formaldehyde (shinoj et al. ; asan et al. ) . like other sources of vocs, the exposure of mvocs even at deficient concentrations has been linked to symptoms such as a headache, nasal irritation, dizziness, fatigue, and nausea, independent of exposure to other allergenic fragments and toxins (weinhold ; burton et al. ). researchers have attempted to distinguish between the sbs and building-associated illness tsai et al. ) . as discussed, the sbs represents multiple non-specific symptoms among the building occupants, but its occurrence is correlated with some factors, such as the type of ventilation and the condensation or the leakage of water in building indoors. on the other hand, building-associated illness consists of different diseases with known aetiologies (craig and mindell ) ; for example, allergic alveolitis, with specific aetiologies, is usually linked to ventilation-based, wet microbial breeding places, such as humidifiers, air washers, heater/cooler units. in multifactorial causal situations, however, several components attribute to creating complex environmental conditions. ventilation inadequacy in indoor spaces may aggravate ieq, resulting in health symptoms, sbs or br and other communicable respiratory illnesses, such as allergy and asthma symptoms, respiratory infections and cardiovascular diseases. the literature emphasizes association of building characteristics, iaq, and inhaling of bioaerosol with the prevalence of respiratory illnesses among building occupants. for easy understanding by the professionals from other building sciences, some common forms of respiratory illnesses are briefly described herewith. details of the respiratory illnesses are found in several online sources, e.g., http://www.mayoclinic.org/ diseases-conditions/copd/symptoms-causes/dxc- . increased prevalence of asthma has long been known as the impacts of outdoor and indoor exposures to air pollutants, and lifestyle habits, as well (eder et al. ). asthma can be adult onset or occupational in origin. from a clinical point of view, bronchial asthma is a well-known lung condition, defined as a chronic inflammatory disease, due to the contraction of the bronchial muscles, increased mucous production or decreased clearance, and muscle tightening, causing variable airflow obstruction (fig. . ) . coughing, wheezing, chest tightness, shortness and shallow breathing, anxiety, and tachycardia are the common signs and symptoms of asthma. the inflammation causes airway hyper-responsiveness and is the reason for the appearance of variable and reversible airflow obstruction. occupational asthma is caused by breathing substances present at workplaces, such as chemical fumes, gases or dust which are irritating or sensitizing. exposure to these substances develops an immune response either to respiratory irritants (gas, fume, or vapour), usually of low molecular mass at high concentration, referred to as irritant-induced occupational asthma, or to sensitizing agents (e.g., high molecular mass-glycoproteins of biological origin), referred to as sensitizer-induced occupational asthma. these exposures are characteristically associated with symptoms at work with relief on weekends and holidays. with early diagnosis and treatment, occupational asthma may be reversible. table . includes the most common asthmagen agents. irritant-induced acute occupational asthma (also termed as reactive airway dysfunction syndrome-rads) may occur following a short-duration single high-level irritant exposure to substances, such as chlorine or oxides of nitrogen, or multiple exposures to gas, smoke, fume, or vapour characterized by irritant capacity. respiratory symptoms (a cough, wheezing, chest tightness, and dyspnea) may persist for months. low-molecular mass agents probably become antigenic after conjugation with a body protein (e.g., serum albumin), and its response clinically manifest as direct epithelial cell injury. the procedure to diagnose rads includes analysis of occupational history, inventory of exposures in the workplace, pulmonary function tests (pft), serial peak expiratory flow measurement on work days and days off, histamine or methacholine challenge, and immunological tests, such as specific ige and skin prick, epicutaneous tests (fishwick et al. ; tarlo et al. ). the pft may show evidence of airway obstruction (fev /fvc ratio less than . ), although the absence of airway obstruction does not exclude a diagnosis of the disease. for irritant-induced asthma due to indoor environmental exposures, specific bronchial challenges may not diagnose; also the peak expiratory flow (pef) is not diagnostically specific. however, conventional approach of observing an elevated diurnal variation in pef might suggest the presence of asthma. bronchodilator response may be seen in individuals with acute irritant-induced asthma. a chest radiograph is usually normal, although it may show no specific signs associated with coexisting respiratory infection. a bronchial biopsy may indicate possible inflammation with lymphocytes and plasma cells, as a manifestation of epithelial cell injury. sensitizer-induced occupational asthma is characterized by a latency period, which may last from several weeks to months or years, between first occupational exposure to a respiratory sensitizer and the development of immunologically isocyanates (e.g., toluene diisocyanate), acid anhydrides (e.g., phthalic anhydride), amines (e.g., ethylenediamine), fluxes (e.g., colophony), metals (e.g., platinum salts), drugs (e.g., penicillin), plastics (e.g., acrylates), wood dust (e.g., western red cedar) auto-spray painting, varnishing, metal grinding, platinum refineries, pharmaceutical manufacturing, sawmill work, woodworking, other chemicals biocides (e.g., glutaraldehyde), polyvinyl chloride fumes, organophosphate insecticides janitorial work, meat packaging mediated symptoms. once the subject is sensitized, asthma attacks are provoked even with exposure to a shallow concentration of the sensitizing agent. diagnosis is typically achieved from the evidence of reversible variable airway limitations, along with asthmatic trends between periods of work and rest. pft may become normal rapidly after the cessation of the exposure. a serial pef (about four recordings a day) over three weeks has high specificity and sensitivity in making the diagnosis of occupational asthma. serum-specific ige may assist in making a diagnosis, due to its likely presence in persons exposed to allergens with high molecular weight and some chemical agents. skin prick tests may also be positive for the workplace allergen. increased bronchial reactivity to challenge with the agents, such as histamine, methacholine, is evidence of sensitizer-induced occupational asthma, and this may be carried out sequentially over time. allergens that cause occupational asthma can also cause allergic rhinitis (nasal symptoms) that may precede the onset of occupational asthma symptoms or may commence at the same time as asthma symptoms. simoni et al. ( ) showed that upper respiratory tract symptoms were more prevalent in poorly ventilated classrooms. that is, with co levels exceeding ppm had a higher risk of a dry cough and rhinitis. increased ventilation rate (> . l h − ) was associated with a decreased prevalence of allergic symptoms among college students living in dorms in china (sun et al. a ). the occurrence of wheeze decreased with the increase in ventilation rates when co concentration reduced from to ppm. the prevention of occupational asthma requires environmental intervention and medical management. the primary prevention of exposure, such as improved ventilation and dust control for elimination of the formation of dust, and localized aspiration, is the direct approach towards reducing the incidences of the disease. avoiding cold temperature and air dryness, wearing ppe, and in some cases, adopting prophylactic pharmacological treatments can mitigate asthma symptoms. population screening for early detection is the secondary prevention. the term asthma-like (suspected asthma) is indicative that all asthma-like symptoms are not associated with asthma. these include chronic obstructive pulmonary disease, chronic bronchitis, chronic cough, hyperventilation, mechanical obstruction of the airways, congestive heart failure, pulmonary embolism, gastro-oesophageal reflux, multiple chemical sensitivity/idiopathic environmental illness, sbs, sjogren's syndrome, vocal cord dysfunction. the chronic obstructive pulmonary disease is characterized by a slowly progressive reduction of pulmonary ventilation due to a combination of emphysema and bronchiolitis with obstruction of the small airways. ets is a critical aetiological factor. chronic cough has different aetiologies-a cough at night or associated with physical exercise may be indications of asthma. the asthma tests such as reversibility to a bronchodilator and increased levels of exhaled nitric oxide should be positive (chatkin et al. ) . hyperventilation syndrome is indicated by symptoms induced by physiologically inappropriate hyperventilation or voluntary hyperventilation. shortness of breath, accelerated/deepened breathing, and feeling of inability to breathe deeply are asthma-like. symptoms reproduced by a hyperventilation test and a slow recovery of co in blood or expired air are the two criteria for establishing the diagnosis (ringsberg and akerlind ) . rads is an illness with asthma-like symptoms that may occur as the direct consequence of excessive toxic inhalation exposure. the bronchial histological changes show an increase in inflammatory cells. however, eosinophils and mast cells do not dominate. multiple chemical sensitivity (also named as idiopathic environmental intolerance) is a disease caused due to some low dose of exposure to chemical toxicants, manifesting diverse symptoms (e.g., headache, weakness, memory problems, inability to concentrate, throat soreness, abdominal pain, and discomfort). one may suffer from nasal congestion and asthma-like symptoms such as cough and chest tightness. as elaborated earlier, sbs is a complex disease caused primarily due to building characteristics of the indoor environment, including inadequacies in air-handling systems. sjogren's syndrome is a systemic rheumatic disease. vocal cord dysfunction is characterized by episodic or acute attacks of breathing troubles similar to attacks of asthma. in asthma-like disorder, treatment compliance with conventional therapy is low (schmier and leidy ; chan et al. ) . medication with steroids are the most potent drugs in the treatment of asthma. sensory hyper-reactivity (earlier referred to as functional breathing disorder) manifests common symptoms, such as heavy breathing, cough, and increased secretion, difficulty in getting air, and chest pressure (lowhagen et al. ) . the symptoms are often induced by trigger factors, such as allergens, chemical irritants, ets and strong scents, cold air, viral infections, physical exercise (millqvist and lowhagen ) . symptoms, such as difficulty in breathing and breathlessness, which indicate asthma, may also be indicators of sensory hyper-reactivity. the diagnosis of sensory hyper-reactivity is a clinical challenge; pft is sometimes difficult to obtain due to inability to perform an adequate forced expiration, giving a false indication of bronchoconstriction (ringsberg et al. ) . asthma-like symptoms can be provoked by a sensory nerve-mediated disturbance of the respiratory pattern; for example, a capsaicin inhalation test provokes these kinds of symptoms . extrinsic allergic alveolitis (eaa, also termed as hypersensitivity pneumonitis) is type iii and iv hypersensitivity reaction of the alveolar and bronchiolar tissue and interstitium of the lungs, in response to inhaled antigens. a range of environmental allergens, including fungi, bacteria, plant proteins, and other reactive chemicals, may be related to the occurrence of eaa (simon-nobbe et al. ; robertson et al. ). farmer's lung caused by mouldy forage is a well-studied form of eaa. microbiological contamination of air conditioners or humidifiers has been reported to cause of eaa in an office environment. the eaa may manifest as an acute, sub-acute, and chronic form. the former form is more natural to recognize, with symptoms, like a cough, chest tightness, febrile chills, and flu-like illness appear - h after exposure, fades away gradually over a few hours, and may reappear on subsequent exposure. the sub-acute form presents as progressive shortness of breath, dry cough, and weight loss. the chronic form may show the slow development of interstitial fibrosis. diagnosing eaa requires identifying the source of exposure to contaminants, recording exposure history, including worksite visit and environmental measurements. in physical examination, crackles in the lower fields of the lungs may be noticed. a chest x-ray may show fine interstitial infiltrates in acute and sub-acute forms of the disease, whereas in the chronic form, irregular scarring may indicate diffuse pulmonary fibrosis. in pft, typically patients may show restrictive impairment, i.e., the fev /fvc ratio reduced in comparison with its normal range. the eaa is a diffuse parenchymal disease, and thus, the diffusion capacity of the lungs is affected (both dl co and k co ). bronchoscopy with bronchoalveolar lavage (bal) and transbronchial biopsy may be carried out when investigating a patient with suspected eaa. bal typically shows increased total cell count, with an increased proportion of lymphocytes (> %). t-helper to t-suppressor ratio is usually reduced to less than . after acute exposure, neutrophils are transiently increased. the histopathologic findings include diffuse interstitial infiltrate, scattered non-caseating granulomas, and cellular inflammation of the bronchioles. an inhalation provocation test with the specific antigen can be performed to confirm the diagnosis; a worksite challenge test is a conventional approach, with pft before and after workplace exposure. management of eaa primarily demands to remove the affected persons from the source of exposure. drug intervention with corticosteroids is given at the acute episodes. any dampness or mould problems in buildings should be repaired promptly. humidifier fever, like in eaa, is also termed as a disease related to bioaerosol exposure from contaminated humidifier water, often referred to as monday morning fever. the affected person experiences fever, nausea, sweating, and myalgia, sometimes with breathlessness, about - h after exposure, which is very similar to those described in outbreaks of eaa. the symptoms diminish towards the end of the working week, and over the weekend, for example, the episode may be worse again. humidifier fever differs from eaa in that the affected person may have specific igg antibodies to the micro-organisms growing in water reservoirs as a sign of exposure. regular maintenance of humidifiers and air conditioners is the best approach to prevent humidifier fever (pal et al. ) . legionnaires' disease presents as pneumonia, due to infection with legionella pneumophila, a bacterial micro-organism that may be found in wet surroundings and capable of forming colonies in cooling towers and hot water systems in hospitals and office buildings. an outbreak of legionella pneumophila in philadelphia in (fraser et al. ) with the source identified at the ventilation and humidification system of a hotel, affected persons, with about % mortality. the incubation period of the disease is about a week. the early symptoms include illness, headache, myalgia, fever and mild cough, blood in the sputum, and watery diarrhoea (cunha ) . there may be a neurological symptom of severe encephalopathy. a chest x-ray may show unilateral lobe infiltrate, with rapidly progressive infiltrations of legionella. complete recovery of the infiltrates may take several weeks to months. urinary antigen detection is a rapid test. however, it is less sensitive than culturing respiratory secretion. superheating of hot water to > °c and flushing the water distribution systems are crucial to prevent legionella infections. office environment exposures through handling of self-copying paper that contains ink, solvent and dust, acrylate glues used in flooring, pvc, phthalate compounds, and wall-to-wall carpet might induce airway inflammation in humans jaakkola and knight ) . professional cleaners in buildings are regularly exposed to cleaning chemicals containing ammonium, bleach, chlorine, and some disinfecting substances, and these people may develop irritant-induced asthma (zock ) . table . includes different environmental, physical, and social factors, which may cause one or more signs and symptoms related to sbs. second-hand tobacco smoke exposure (shs), containing irritant substances, can potentially induce mucus hypersecretion and inflammation in the airways (jaakkola et al. ; gilmour et al. ) . in adults with asthma, shs exposure is related to increased occurrence of respiratory symptoms, reduced lung functions, increased use of bronchodilator and steroid medications, and increased bronchial hyper-responsiveness (jaakkola and jaakkola ) . fisk et al. ( ) from a meta-analysis of epidemiological studies on dampness and mould problems revealed - % increased risk of asthma about indoor dampness and mould problems in buildings. the ige-mediated hypersensitivity reactions to fungal allergens and mycotoxins produced by fungi and inflammatory reactions caused by fungal cell wall components ( , -b-d-glucan, ergosterol) are the suggested mechanisms that could lead to asthma. there is a whole range of airborne pathogens, such as aspergillus and bacillus spp., that may be found in the built environment and also during construction or renovation activities (balm et al. ; fournel et al. ) . particular focus is on hospitals and healthcare buildings, to create healthy conditions. natural ventilation and availability of sunlight in buildings serve as effective strategies in infection control of diseases, such as measles, tuberculosis, smallpox, chickenpox, influenza, sars and h n . the transmission of pathogen takes place through contact, dust, respiratory droplets, and droplet nuclei, e.g., inhalation of large droplets from contagious individuals or contaminated surfaces. the transmission depends upon the number and size of particles produced, the velocity at which they are produced, micro-organisms contained within the droplets, and proximity of a susceptible target (gralton et al. ) . the longevity of the pathogens depends on temperature and humidity, ultraviolet (uv) radiation, and atmospheric pollutants (tang ). depending on the size and density, residues of suspended droplet nuclei can remain suspended and penetrate deep into the lung tissues. droplet nuclei that are exhaled during normal breathing are only a small fraction than those aerosols produced when coughing or sneezing (gralton et al. ) . factors, such as local ventilation, the activity of occupants indoors, and thermal gradients produced due to office equipment influence the movement of the suspended droplets (nielsen ; eames et al. ; clark and de calcina-goff ) . towards controlling infection in healthcare and other building facilities through sunlight and natural ventilation, transmission and control of some pathogens are briefly described herewith. influenza is assumed to be transmitted by large droplets. however, the aerosol transmission, such as h n avian influenza that demonstrates high virulence and lethality involves the lower respiratory tract (tellier ; tang and li ) . direct contact with diseased poultry and other birds may cause h n transmission through the air, without recombination in an intermediate host (herfst et al. ) . severe acute respiratory syndrome (sars) epidemic in was assumed direct contact as the primary transmission route. the hong kong, amoy gardens outbreak, is an affirmative indication of the airborne transmission of the sars virus (mckinney et al. ) , such as transmission of virus-laden aerosol through inadequate ventilation, the ventilating shaft of adjacent buildings, floor drainage. before the sars epidemic, hantavirus transmission causing the pulmonary syndrome in humans has been demonstrated, due to the inhalation of aerosolized excreta and saliva from wild rodents (kimmel et al. ; clement et al. ) . the primary prevention is to clean the ventilation system of buildings that show signs of rodent infestation. norovirus that causes gastrointestinal illness is transmitted via contact with food materials, contaminated surfaces, and the spread of aerosolized particles from vomiting or liquid diarrhoea (marshall and bruggink ; greig and lee ) . tuberculosis is mainly contracted through airborne droplets; that is, transmission of m. tuberculosis to a non-infected person is possible if there are overcrowding and confined environment, and poor indoor ventilation (beggs et al. ) . earlier it was presumed that smallpox virus spreads by face-to-face contact. however, airborne transmission of the virus is evident now. occupants in hospital, health care, and allied facilities are at potential risk from staphylococcus aureus (kerr ) that get deposited throughout a room. nasal cavities of susceptible adults become colonized with s. aureus by inhaling particles from the air. there are many other pathogens found in an aerial spread in building facilities, such as escherichia coli, klebsiella, acinetobacter, pseudomonas, clostridium difficile (wu et al. ) . persons infected with c. difficile may shed spores in faeces, and therefore, when a toilet is flushed without a closed lid, aerosol production may contaminate the surrounding environment (best et al. ). office goers and building occupants are usually not exposed to high levels of physical, chemical, or biological compounds potentially hazardous to health. office environments have traditionally been considered as safe. however, an ample body of the literature is available on sbs and building-associated illnesses (bri) from different kinds of studies, including epidemiological cohort and cross-sectional studies, population questionnaire surveys, and experimental studies. the risk of sbs may occur at different levels, for example, (a) building level-indoor environmental quality, different sources pollutants, and exposure to bioaerosols, (b) personal level -interpersonal differences (women, younger and the elderly people, persons predisposed with chronic disease show more sbs related complaints), and (c) workplace stressors-aspects of work and psychosocial environment of the building occupants, and ones' ability to cope with the conditions of workplace and workspace. since all these levels are simultaneously present, one major problem emerges in sbs and bri is its lack of generalizability. on a simplistic way, the overall impression of the building environment may be rated by the occupants on an ordinal point scale, against the stated levels of ieq, personal characteristics, aspects of work and the psychosocial environment. the summated scores are scaled into an overall dissatisfaction score for the building occupants. mitigation of iaq problems may require the involvement of building management and related people of responsibility in facility operation and maintenance, housekeeping, policy-making, and staff training. three methods have been suggested to improve the iaq, namely source control, increase ventilation, and air cleaning. the source control is the most cost-effective approach to mitigating iaq problems in which point sources of contaminants can be identified. conventional pollution source control method, such as adsorption by microporous activated carbon and chemical scrubbers, has reasonable efficacy to mitigate pollutants. thermal catalytic oxidation (everaert and baeyens ; roark et al. ) and photocatalytic oxidation (carp et al. ) are promising technologies for air purification. however, the former is not economically feasible at low pollutant concentrations. photodegradation may be more cost-effective for air purification since the process takes place at room temperature and pressure. tio , a popular photocatalyst, is employed for removal of vocs from indoor air (wang et al. (wang et al. , . by incorporating tio catalyst with adsorbent may yield better results for adsorption of pollutants and oxidation efficiency. this type of catalyst, however, exhibits high catalytic activity at uv light. the literature suggests a robust affirmative link between ventilation and the respiratory health of building occupants (seppänen and fisk ) . due to the random character of natural ventilation during different seasons of the year, emphasis among the building designers goes in installing mechanical ventilation and hvac systems. the natural ventilation no longer provides optimal distribution of fresh air in the buildings. however, several views have been put forward with regard to mechanical ventilation systems and acute health symptoms (sbs/br), asthma and allergy symptoms among occupants in buildings. mendel et al. ( mendel et al. ( , , examining us niosh data of office building, emphasized that improperly maintained ventilation systems increase the adverse health effects among the occupants, particularly the asthmatics, due to exposure to accumulated pollutants and microbiological growth. comparing with naturally ventilated systems, the presence of air-conditioning increased respiratory symptoms in office buildings located in a hot and humid climate (graudenz et al. ) . takahashi et al. ( ) reported that the presence of a ventilation system was associated with increased allergic symptoms, probably due to the entry of large quantities of pollen into the dwellings through the air ducts and other factors, not directly related to the ventilation system. dwellings installed with air conditioners, and those had poor maintenance of ventilation systems, resulted in increased prevalence of sbs (wong et al. ; coelho et al. ) , as compared to those in naturally ventilated dwellings. some multidisciplinary reviews on relationships between ventilation rate and health outcomes are summarized in table . . table . case studies on the influence of indoor ventilation rate on health outcomes godish and spengler ( ) increasing the ventilation rate up to l/s per person may be useful in reducing the prevalence of sbs symptoms and occupant dissatisfaction with air quality. the use of ventilation as a mitigation measure for iaq problems should be dealt with factors that may limit its effectiveness seppanen et al. ( ) ventilation rates below l/s per person in different building types were associated with significant worsening in one or more health or perceived air quality outcomes. some studies determined that increasing ventilation rates above l/s to * l/s per person significantly decreases the prevalence of acute health symptoms or improvement in the perceived air quality. the sbs symptoms continued to decrease significantly with decreasing co concentrations below ppm wargocki et al. ( wargocki et al. ( , ventilation rates below l/s per person increase the risk of acute health (sbs) symptoms, increase short-term sick leave, and decrease productivity mendell and heath ( ) no substantial evidence on the causal relationships between indoor pollutants or thermal conditions in schools and the performance of students. suggestive evidence links low ventilation rates in buildings to decreased performance in children and adults seppanen et al. a - % improvement in average performance was associated with an increase in ventilation rate by l/s per person. the performance increase per unit increase in ventilation was more substantial with ventilation rates in the range - l/s per person, and almost negligible with ventilation rates over l/s per person li et al. ( ) strong evidence of the association between ventilation, air movements in buildings, and the transmission/spread of infectious diseases. data insufficiency to define the ventilation rates that can reduce the spread of infectious diseases via the airborne route in hospitals, schools, offices, homes, and isolation rooms. overcrowding is a risk factor related to the ventilation of buildings and also infection transmission via direct contact fisk et al. ( ) reduction in ventilation rate from to l/s per person led to increased prevalence of sbs symptoms by * % ( - %). increase in ventilation rate from to l/s per person led to the decreased prevalence of acute symptoms by % ( - %) sundell et al. ( ) ventilation rates, up toper person, were associated with reduced prevalence of sbs symptoms in offices. ventilation rates in homes above . ach are associated with a reduced risk of allergic manifestations among children in a nordic climate the above stated studies provide a fair understanding that ventilation (air change in a built environment) plays a central role to exhaust pollutants of both non-biological and biological agents of the occupied space or generate pollutants within systems. chapter elucidates the design, installation, operation, and maintenance of ventilation systems in buildings. ventilation inadequacy may be due to poor building design, inadequate ventilation system, and its improper maintenance and operational strategies. lack of control of hvac systems aggravates the growth of microorganisms. besides, the quality of outdoor air, building materials, and accumulated dust are also sources of microbial contaminants in indoor environments. the presence of mould, spores, musty smell, and water intrusion are warning signs, reflecting the inefficiency of a building's ventilation system (radon et al. ) . it is emphasized that the strength of elimination of pollutants from building space is the determinant of exposure-associated adverse health effects of occupants. in spite of differing views, ventilation rates below l/s per person would increase the risk of symptoms of sbs (jaakkola and miettinen ) . the assertion from the base study of the association of sbs with the increasing difference in concentration of co between indoor and outdoor brings forward the suggestion that a relative increase in the ventilation rates per person in an office building may reduce the prevalence of sbs symptoms. a concentration of co ( ppm) has been suggested as a control limit value. erdmann and apte ( ) observed a remarkable reduction in mucosal symptoms ranging from to % when co levels in offices dropped in the range from to ppm above outdoor levels. frequent contributors to biological pollutants are water damage in buildings, leaks in plumbing, roofs or air conditioners, and humidifiers (mckernan et al. ; li et al. ) . given that some airborne moulds may always be present in the indoor environment, various guidance limits and remediation measures have been proposed (baubiologie maes ) . ec guidelines state that mould count greater than cfu/m may be considered an intermediate level of exposure for a building occupant, whereas > cfu/m is a high level of exposure in indoor non-industrial workplaces. levels more than these guidelines do not necessarily imply unsafe or hazardous conditions. in the usa, there are no exposure levels for airborne concentrations of mould (us osha ) . every country must establish the requisite legislation and environmental standards and guidance concerning building maintenance specifications. also, building-associated illnesses manifest in multiple forms of symptoms, and often in combinations of asthma, hypersensitivity pneumonitis, and interstitial pneumonitis (bornehag et al. ) . evidence of markers for individual susceptibility might separate normal from more sensitive groups. symptoms of allergy and asthma may be triggered by allergens in the indoor air including those from house dust mites, pets, fungi, insects, and pollens. as elaborated earlier, asthma symptoms can be evoked by irritating chemicals or sensitizing agents. there are approaches to reducing allergy and asthma symptoms via changes in buildings and indoor environments. reductions in allergy and asthma symptoms would be expected by a substantial reduction in the associated allergens and irritants, from indoors. overall, intervention and management of sbs and bri may encompass measures, as described herewith. for new buildings, the prevention measures in reducing mould contamination include, for example, (a) minimizing moisture accumulation in construction materials, (b) maintaining the integrity of building impermeable envelope, and (c) ensuring the effectiveness of hvac system to control thermal comfort and relative humidity. in the existing buildings, corrective measures include (a) repair and maintenance of water leakage in ceilings, walls, and draining systems, (b) deep cleaning of building interiors and hvac systems, (c) control of the reservoirs of visible mould in ceiling and carpets, and (d) periodic assessment of iaq. once a mould problem is established, a well-documented action plan may be followed to notify people for (a) rectifying the underlying moisture problem, (b) minimizing spread of contamination, by cleaning of ventilation pathways and enhancing ventilation to exhaust the relevant pollutants from indoors, and (c) removing mouldy materials. it is important to consider that fungal spores are continually entering into the indoor environment and a remedial measure to fungal contamination is the maintenance of dry conditions in a building. as part of remediation, an entire or part of a building may be heated to a temperature that should kill most of the fungal spores. caution is needed that heat may not damage specific equipment and plastic materials. apart from dilution of airborne pathogens, high ventilation of outdoor air results in an adverse effect on viability and virulence of micro-organisms, including influenza and the category iv pathogen, francisella tularensis (hood ). infection of rhinoviruses causes adults to suffer the frequent common cold. myatt et al. ( ) provided evidence of aerosol transmission of rhinovirus in mechanically ventilated office buildings that resulted in an increased risk of inhaling infectious droplets. in student rooms having a ventilation rate of about l/s per person, the frequency of common colds was six times more among % of the students. the number of common colds was higher in winter. reported common colds were higher when some students shared a room. by increasing the ventilation rate to l/s per person, the self-reported common colds dropped to a mere % (sun et al. b ), suggesting that ventilation from outdoor-to-indoor bears greater significance in diluting and dispersing virus-laden droplets (mendell et al. ) . milton et al. ( ) observed a reduction in short-term sick leave among office workers when the outdoor air supply rates increased from to l/s per person in an office building. mendell et al. ( ) reported the relative decrease of illness absence of about . % for each additional ventilation rate of l/s per person. natural ventilation brings many advantages, whereas entry of unfiltered air containing free contaminants such as fungal spores (bartley et al. ; phares et al. ) is a possible disadvantage of natural ventilation. natural ventilation can be more effective than mechanical systems for preventing transmission (kembel et al. ) . despite that an outbreak of infectious disease is an outcome of several factors, as stated above, the evidence is supportive that ventilation is a modifying factor in the transmission of infection. following the incidents of anthrax attacks, preventive intervention is to relocate air intakes to publicly inaccessible locations, e.g., secure roofs. coughing and sneezing activities can carry infectious aerosols a long distance within a built environment (zhu et al. ) . intervention in building ventilation airflow patterns (chen and zhao ) can thwart particle transport from a source to a receiver. the exposed concentration of aerosol from sneezing, at the breathing zone of a receiver occupant is slightly higher under displacement ventilation, dv than mixing ventilation, mv system (seepana and lai ) , due to its low local air velocities. high discharge velocity air curtains provide a strong momentum to redirect coughing and sneezing jets and minimize cross infection (aubert and solliec ; nino et al. ) , and also influence heat gain/loss in a facility (foster et al. ) . with a protected occupied zone ventilation, pov system, the intake fraction of coughed particles in the breathing zone of the receiver occupant decreased to a significant extent, as compared to an mv system (liu et al. ) . a narrowly concentrated plane jet was more effective at reducing the direct exposure to expiratory particles than with multiple low-velocity jets. the majority of micro-organisms that cause airborne infections cannot tolerate sunlight. direct sunlight passing through an ordinary window can kill m. tuberculosis and meningococci within a few hours. streptococcus pyogenes cannot survive more than min under sunlight, compared with more than an hour in diffuse daylight. lethality of sunlight against staphylococci is due to radiation at - nm; in addition to bactericidal effect, solar radiation is mutagenic. ordinary window glass absorbs solar radiation at < nm, which permits entry of solar uv-a and small amounts of uv-b. research indicates that uv wavelengths inactivate microbes by causing cross-links between constituent nucleic acids; the formation of intra-strand cyclobutyl-pyrimidine dimers within dna leads to mutations and cell death (maclean et al. ). exposure to high-intensity visible violet light at nm is likely to be associated with photoexcitation of porphyrin molecules, resulting in the production of reactive oxidative species that are strongly bactericidal (hamblin et al. ) . the contemporary modern building envelopes 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trichothecene vomitoxin (deoxynivalenol) study on transport characteristics of saliva droplets produced by coughing in a calm indoor environment world at work: cleaners health and indoor climate complaints of office workers in buildings in the netherlands key: cord- -ei faruy authors: zheng, xiaohong; li, kejun; wang, ruzhu; zhao, liping; xu, lisa x.; chen, yazhu; jin, xinqiao; gu, bo; bai, jingfeng; liu, hongmin; ye, xiaojiang title: experimental investigation of integrated air purifying technology for bioaerosol removal and inactivation in central air-conditioning system date: journal: chin sci bull doi: . /bf sha: doc_id: cord_uid: ei faruy in this research, high voltage static electricity and ultraviolet technologies were integrated to an air purifying device which can be used to trap and kill airborne bacteria and viruses in central air-conditioning systems. an experimental platform was built to mimic the central air system, in which the efficacy of the newly built device was examined. in addition to the standard physical and chemical tests, bacteriophages were used to simulate airborne viruses in the experimental system. the bacteriophage suspension was aerosolized into the air with ultrasonic wave atomization. the result showed that more than % removal efficiency of micro-particles (< micron in diameter) were removed after the device was in operation in a building and more than % of bacteriophages in the experimental system. it is concluded that the integrated air purifier is suitable for controlling air quality and preventing virus transmission through the central air system. since the winter of , severe acute respiratory syndrome (sars) affected nearly countries in all the continents, resulting in deaths by july , as reported by world health organization (who) [ ] , , ) . some research indicated that the sars virus was predominantlyspread by liquid droplets, and/or by direct and indirect close contact [ ] . the central air-conditioning system has been considered as a probable means of sars transmission in hospitals or office buildings. international scientific community has been in the forefront of fighting against sars in discovering the means of sars transmission and searching for effective ways of prevention [ ] . fresh air circulation can dilute the virus concentration inside a room and was found effective in preventing virus spread. but it cannot completely eliminate the sars virus from an air conditioned environment. thus, it is necessary to trap and kill bacteria and viruses in the central air conditioning system. in this work, a central air purifying device was developed by integrating high voltage static electric field and ultraviolet irradiation technologies. an experimental platform simulating central air-conditioning system was built to perform some physical and chemical tests of the device. further, one bacteriophage strain jd-ii- isolated from the environment was used as a viral simulant to examine the efficiency of the device for bioaerosol removal and inactivation. experimental studies ( ) test system. this test system consists of an experimental chamber of m , a test section and an airconditioning section including an ultrasonic humidifier, a finned tube heater, a finned tube heat exchanger and a fan. fig. shows the schematic of the whole system which is completely sealed. air flow is uniform and re-circulated from the chamber to the test section, and then the air-conditioning section. air change per hour (ach) can be adjusted with the speed of the fan. the rest section could be easily replaced by any kind of air purifying device and used to examine the dust-cleaning and bacteria-killing efficiency of the device by circulating micro-particles and bacteriophages in the system. furthermore, the micro-environment (i.e. temperature, relative humidity, etc.) can be adjusted in the system to investigate the climate effect on the virus sensitivity, infectivity, and transmissivity. ( ) integrated air purifier. fig. shows the integrated air purifier installed in the test section. it was built by integrating high voltage static electric field, ultraviolet ray, composite silver electrodes, and an active carbon fiber filter. large particles can be first filtrated by active carbon fibers. small particles and virus aerosols are mainly polarized and trapped by high voltage static electrical field. the silver electric plates of v high voltage together with ultraviolet ray completely kill the trapped bacteria and viruses within minutes. upon binding onto the bacteria cell membrane, silver ion can penetrate and react with sulfhydryl (-sh) to damage the cell synzyme activity, leading to cell death [ , ] . but the silver ion does not react on mammal cells because of the totally different cell membrane structure. the major emission band of the c waveband ultraviolet light is around nm wavelength which is mainly adsorbed by nucleoprotein (> %). when the nucleic acid absorbs high-frequency ultraviolet waves, the chemical bond of the nucleic acid molecule would be damaged, resulting in abnormal decompose or denaturalization to cause death of bacteria and viruses. ( ) bacterophage as a viral simulant for sars and other airborne viruses. bacteriophages are the viruses of bacteria and they have specific host range, one phage strain only infects a limited number of strains in one bacterial species. they do not infect animals or human beings. it is thus safe to use bacteriophage as viral simulant in the place of sars or other severe animal or human viruses [ ] . the amount of the viral simulant particles in the air can be collected and measured for plaque formation units per sample by using a double layer plating technique. four phage strains named jd-ii- , jd-ii- , jd-ii- and jd-ii- were isolated from an aquatic sample by using e. coli mg as the host strain. resistance to environmental extremes including temperature and dryness was tested for all the four phage strains. table shows that the resistance of jd-ii- to both temperature and dryness was superior to sars cov virus. this provides a basis for using this particular phage strain as a viral simulant in place of sars cov and other airborne viruses in the tests for evaluation of bioaerosol removal and inactivation by different types of air purifiers. disinfectant a) the initial bacteriophage titer was pfu/ml. the data were expressed as the percentage of phage particles survived from the treatments. ( ) bioaerosol generating and sampling technique for the viral simulant. it is a key technology in this research to disseminate the bacteriophage stock culture in the air to simulate the virus aerosol caused by actions such as sneezing. ultrasonic humidifier was used to evaporate the phage suspension to create the bioaerosol of the viral simulant. the bacteriophage suspension was aerosolized into the air with ultrasonic wave atomization. aerosolization velocity was measured by quantifying the mass difference of the suspension before and after atomization per unit time. the effects of viral concentration, ion strength and viscosity of the viral suspension on aerosolization speed were also measured in this work. no significant differences were found between the aerosolization speed of pure water and viral suspension containing different ratios of culture medium (between . % %). the aerosolization speed remained constant at . ± . ml/min with all the tested variables. no significant impact on viability of the phage particles was observed with repeated and lengthened treatment under ultrasonic wave in the humidifier. the bacteriophage particles were collected by using a semisolid plate via the impaction of the airflow at m/s in the test tube. gelatin is viscous and becomes liquid after incubation at for min. three kinds of gelatin plates were prepared for testing their sampling efficiency of airborne phage particles. the mp plate contained % of gelatin. ten milliliter % gelatin was added on lb plate to compose glb double layer plate. the gsm double layer plate was constituted with . % agar as bottom layer and % gelatin in sm buffer solution as top. the centimeter diameter plates were arranged at different sites horizontally or tilted toward the incoming airflow to collect phage aerosol. ( ) testing the dust-cleaning efficiency of the integrated air purifier. the particle generation source, such as mosquito-repellent incense, was ignited in the experimental chamber at the beginning of the experiment and closed until the pm concentration measured by the tsi dusttrak monitor reached a preset value. the humidity was controlled around %. the air was circulated through the system and the chamber temperature was controlled by the air-conditioning section. all experiments were performed at a constant air velocity of m/s, a constant temperature of . the deposition of particles onto the inner surfaces of the system were researched by measuring the pm concentration in the center of the experimental test chamber with respect to time, to establish the baseline measurement. then, the pm concentration was measured with the air purifier at v voltage in operation under the same condition. ( ) testing the sterilizing efficiency of the integrated air purifier. the ultrasonic humidifier containing bacteriophage suspension generated homogeneous bacteriophage droplets into recycling airflow. the gsm plates were used to collect bacteriophage particles in the airflow at the beginning and end site in the test tube with airflow at m/s for min. each test repeated times. the plates containing bacteriophage were incubated at for h to melt the gelatin. all the liquid was transferred to a centrifuge tube. ml of the phage liquid was mixed well with . ml of the host bacterial suspension (at od nm = . ). after standing still for min at room temperature, the suspension was mixed with ml melted soft agar and poured quickly onto lb plate. the solidified plates were incubated at overnight. the number of plaques per plate was recorded to calculate phage particles collected. fig. shows that the pm concentration decreases with time or without the air purifier in the experimental chamber. with the air purifier, the pm concentration decreased from . to . mg/m following an exponential decay over one-hour period while it took more than h to reach the same level via natural deposition. to simplify the analysis, it is reasonable to assume that the air is fully mixed and the particulate concentration is uniform inside the test chamber. the air purifier has a filter system capable of trapping and retaining . % to . % of all mono-dispersed particles of micrometers or less in diameter ) when the effect of deposition, resuspension and adsorption with chamber inner surface are considered. the high concentration smoke particle was extraordinary irritant to eyes and nose of tester. the device helped eliminate the irritating smoke and odor in one hour. the pressure drop of the device meets the standard of a high efficiency filter which is around pa at m/s wind velocity measured by an inclined tube micronanometer [ , ] . according to the indoor air quality standard in china gb/t - ) , the ozone in indoor air should be less . mg/m . it is possible that the hydroxyl and negative oxygen ion might be ionized from water vapor in air with the high voltage and ultraviolet ray. the ozone density can be tested with eco ozone monitor. under the situation of using high voltage static electric field and ultraviolet ray, the ozone density fluctuated from . to . mg/m , while the average ozone density is . mg/m using high voltage static field only and . mg/m using ultraviolet ray only. therefore, the air purifier does not introduce the secondary ozone pollution. fig. (a) shows that the plaques formed on a gsm plate were used to sample the airflow containing phage aerosol generated with a source suspension with pfu/ml when the integrated air purifier was turned off. more than plaques were formed in one such plate. shown in fig. (b) , less than plaques were found in one plate when the integrated air purifier was turned on. a % bioaerosol removal efficiency was thus achieved with the integrated air purifier in action. after the treatment of the integrated air purifier, phage concentration in the airflow was reduced to a minimum. it is very important to assure enough accuracy for phage measurement at such a low concentration. in this experiment, removal rate of bacteriophage solely depended on the high voltage static equipment without active carbon fiber film, and no plaque was detectable when the system coupled with the active carbon fiber film. thus, we need to increase the phage titer at the source suspension to ensure accurate detection of airborne phages. fig. shows the phage particles collected from the test tube with the air purifier on or off when the concenrifier was installed in place and turned on. the integrated air purifier reduced airborne viral particles by orders of magnitude. it was demonstrated that the aerosol generation and sampling technology used in this work was able to evaluate the performance of the integrated air purifier effectively in a biologically and statistically sound way. tration of bacteriophage stock culture in the humidifier was at a titer of pfu/ml with one minute sampling time. through the statistic test, the difference of removal efficiency was significant under . % degree of confidence with or without turning the air purifier on. the aerosolization and collection of phage particles were thus reproducible. when the test tube was void of any purifying measures, phage particles collected at the end of the test tube was ( . . ) pfu/plate, the number dropped to ( . . ) pfu/plate if the integrated air pu- the air purifier was also used in the central air-conditioning system of an office building at shanghai jiao tong university and the sixth people's hospital of shanghai. two supply diffusers were disposed on the right side wall and two exhaust grilles were laid on the upper side wall in the test room of the building. the particle removal efficiency was tested in a low initial concentration with one or two air purifiers installed in the exhaust or without fresh air to avoid the environmental effect. fig. shows the total average removal efficiency of . % and thus the bacteria removal efficiency is estimated to be more than % according to the ashrae applications handbook [ ] . fig. . removal rate of particles by the air purifier in the central air-conditioning system in an office building. , natural deposition; , using one hybrid purifier in one supply diffuse; , using two hybrid purifier in two supply diffuse. in addition to particle removal test, airborne bacteria were also sampled in the experimental room with the integrated air purifier. two sampling methods were used to collect the airborne bacteria. depositional sampling was used to sample airborne bacteria by placing culture plates at sites in the room. impaction sampler was used at . l/min speed to measure bacteria in per unit volume of the air. the result showed that the bacteria decreased from . to . cfu/plate, falling by . % after the integrated air purifier was in action for min. the bacteria collected with the impaction sampler showed a decrease by one to two order of magnitude. this demonstrated a significant effect of the integrated air purifier for cleaning the indoor air in a real world building. based upon the integrated technology of high voltage electric field, ultraviolet ray, composite silver material, and activated carbon fibers, an air purifying device has been developed to prevent airborne bacteria and virus spread through central air-conditioning system. an experimental platform mimicking the central air-conditioning system was built to examine the efficacy of the device. in addition to the physical and chemical tests, bacteriophage was successfully used as a viral simulant in the place of sars cov virus to evaluate the viral removal efficiency of the air purifier. it has been demonstrated that the test methods are feasible and that the integrated air purifier has significant removal and inactivation effects both in the laboratory and in real world building. the integrated air purifier holds great promise in prevention of airborne viral transmission and improvement of indoor air quality in the future. emergency measures in hvac systems against sars, heating ventilation & air conditioning & sars overview of disinfection methods of biologic pollution in hvac systems stochastic dynamic model of sars spreading catalytic materials evaluated by adsorption and inactivation of parainfluenza virus cytotoxicity of mammalian cells destruction of living cells by pulsed highvoltage application a continuous treatment system for inactivating microorganisms with pulsed electric fields standard test method for resistance of materials used in protective clothing to penetration by blood-borne pathogens using phi-x bacteriophage penetration as a test system an experiment study of cylinder-shaped hepa filter the theory of air-cleaning technology chapter : health care facilities key: cord- -ngez hwb authors: d'agostino, d.; greco, a.; masselli, c.; minichiello, f. title: the employment of an earth-to-air heat exchanger as pre-treating unit of an air conditioning system for energy saving: a comparison among different worldwide climatic zones date: - - journal: energy build doi: . /j.enbuild. . sha: doc_id: cord_uid: ngez hwb a great fraction ( - %) of primary energy is required for building air conditioning, so the use of renewable energy sources is increasing. the geothermal energy for heating, ventilating and air conditioning (hvac) systems can be used considering an earth-to-air heat exchanger (eahx). this work analyses the performance of an eahx through a mathematical model ( d), as a function of diameter and length of the air ducts. the problem is solved with finite element method. a case study office building is analyzed. the air conditioning plant is characterized by fan-coil units and primary air; the eahx is positioned upstream the air handling unit (ahu) to pre-cool/pre-heat the air. the building is virtually placed initially in six italian cities (different climatic zones according to italian regulation dpr / ) and subsequently in eight worldwide cities according to köppen climate classification. the following parameters are calculated: air temperature variation and thermal efficiency of the eahx; the decreasing of cooling and heating capacity of the coils into the ahu. the best results refer to a duct length of m for ottawa (warm-summer humid continental climate, % capacity reduction), the worst ones for rio de janeiro (tropical wet and dry climate, maximum % reduction). buildings are attributed the responsibility of accounting for % - % in the global energy consumption of developed countries, often overcoming the industry and transport fields. within the building sector, heating ventilation & air conditioning (hvac) systems represent the greatest source of energy demand ( % of the total energy consumption of the sector) that represents - % of global energy consumption [ ] . indeed, the energy policies prescribe as primary goal to adopt energetically optimized solutions, also with reference to ventilating and air conditioning systems. thus, restrictive standards are fixed to keep these prescriptions such providing energy certificates for buildings that incorporate all the aspects concerning with them (materials, the standardization of the checks for the regular maintenance, etc...). in most of the cases, the vapor compression systems could not overcome certain energy limits; consequently, the adoption of hvac systems exclusively based on vapor compression would not satisfy the energy efficiency guidelines prescribed by these policies. therefore, many worldwide directives push towards a spread utilization of energy from renewable sources to satisfy the energy constraints, and this also applies to buildings. as a matter of fact, to encourage these aspects, the european directives on renewable sources issued the "green-building" standards. nowadays % of the worldwide energy demand is addressed by means of renewable energy sources [ , ] and the global goal is to bring this figure to grow significantly in the next decade. the research for solutions that could supply or integrate vapor compression systems for refrigeration and hvac, constitutes a spur in the development of renewable energy-based systems for exploiting green energy and, thus, for counteracting the enormous energy demand connected to these fields. among the most used renewable energy sources (wind, solar, biomass, waves, tides, …), geothermal energy is very useful for air conditioning systems of buildings. in fact, beginning from certain depths, the soil temperature is almost constant during all the year; moreover, it is frequently higher than the temperature of the outside air in winter, lower in summer. clearly, the specific value of the temperature is a dependent variable of the geographic location, but the common denominator is the possibility of taking advantage from this property for projecting geothermal systems with the capability of air cooling during the summer and air heating during the winter [ ] . consequently, the ground assumes a double role: a sink when the system operates in cooling mode; a source when it works in heating mode. the results are that a part of the primary energy could be preserved and the environmental impact [ ] [ ] [ ] of the systems could be mitigated [ , ] . specifically, the use of geothermal energy for improving the thermal indoor environment is typically addressed by means of the following three solutions [ ] :  earth homes;  ground-source heat pumps (gshps);  earth-to-air heat exchangers (eahxs). the first solution refers to buried buildings, so the contact with the soil reduces their heating and cooling loads. ground source heat pumps are systems where the secondary fluid (typically water or antifreeze glycolwater mixtures) circulates throughout banks of underground ducts, in closed loop circuits, to exchange heat with the soil. earth-to-air heat exchangers are systems formed by a number of ducts, horizontally or vertically placed and buried in the ground at a depth useful to exploit the ground property of exhibiting, under undisturbed conditions, constant temperature during the whole year. the heat transfer fluid to be used in eahxs is typically air: in the most common configurations the eahx is inserted in a mechanical ventilation system, more rarely in a primary air circuit. as the ground temperature, below about m depth, is often higher in winter and lower in summer than air temperature [ ] , the eahx gives rise to a pre-heating of the external ventilation air in winter and pre-cooling in summer. the eahxs should be adequately projected to let the air, during the ducts blowing, brings its temperature (heated or cooled). subsequently the air is either sent directly to the building that has to be ventilated/airconditioned or carried in a conventional air handling unit (inside a hvac system) to be further heated or cooled and then sent to the building. the open loop system provides that the air, after has completed its "conditioning" task, would be expelled directly from the building into the atmosphere. in the closed loop systems, at the end of the air conditioning process (heat exchange with the ground through flowing in the ducts and heat transfer with the building to be conditioned) the air is fed back at inlet of the eahx ducts to be recirculated. therefore, in a closed loop eahx system, after several circulations, the air needs to exchange a relatively lower amount of heat with the ground compared to an open loop system. in general, the closed loop configuration is energetically more efficient than the open loop one, also allowing to reduce the problem of undesired water condensation in the ducts due to the humidity rate of the external air introduced in the eahx (a typically summer problem). however, the open loop system is often preferable because it also allows the air exchange in the building, which is not possible for the full air recirculation systems; moreover, the air recirculation can carry to the contamination of the hvac systems by coronavirus or other viruses. eahx systems can be characterized by vertical or horizontal air ducts. the arrangement of the pipes plays a fundamental role since the portion of the ground required for the installation of the eahx systems in order to satisfy the heating/cooling demand depends on the design and layout of the pipes; indeed the air conditioning potential of an eahx system is strongly linked to its geometric configuration. horizontally oriented pipes are generally used in eahx systems, mainly because they present a simpler and cheaper type of installation than the vertical ducts, since the former requires a shallower excavation. a further classification in the eahx system with horizontal ducts can be made between single-layer configuration, with all the ducts buried at a single depth level, and multi-layer configuration where the ducts, horizontally oriented, are buried one on the other at various depths in the ground and separated by vertical drops. single layer configurations are by far the most used among the solutions proposed in literature [ , ] . at the best of our knowledge, very few are the investigations performed on multilayer eahx systems but worthy of attention is the work proposed by de jesus freire et al. [ ] . they made a comparison in an eahx between multilayer pipes and single layer configurations, on equal number of tubes and distance between one each other, as well as the same were the duct design parameters (diameter, length, air velocity) [ ] . on equal amount of heat transfer surface, number of tubes and air velocity, they detected % and % decreasing in temperature span, respectively considering the two-and three-layer configurations with respect to the single layer one. on the other side, the two-and three-layer configurations analyzed required a reduction of the available flat surface for installation estimated, respectively, on % and %, if compared to the single-layer one. indeed, despite of slight energy performances decreasing, the multi-layer configuration could prove very promising in urban contexts with limited installation surfaces. earth-to-air heat exchanger is a very promising technology but mandatory is the optimization of the system to the purpose of appropriately setting the design parameters (such as diameter, length and number of tubes, displacements of the tubes, air velocity), according to the installations specifics and limits as well as to the geographical zone, in order to let the eahx system showing the highest energy performances [ ] . to pursuit this goal, before the installation of the system, it is important to widely test the projected eahx system. this crucial point could be addressed by means of the development of an accurate numerical model able to predict the energy performances under a wide number of working conditions. a lot of mathematical models are present in the scientific literature: many models are commented in the next paragraph (state-of-the art). based on the literature analyses, it is therefore possible to briefly summarize the main advantages in using and investigating eahx systems: i) the working fluid is air (unlimited and free available); ii) the energy consumptions of stand-alone eahx or eahx/hvac-coupled systems are lower than the traditional hvac systems, as well as higher are the coefficients of performances too; iii) the eahx system is simple, therefore it requires few maintenance and operating costs; iv) the environmental impact deriving from the operation of the eahx systems is reduced with respect to the traditional ones, since the former is supplied by a renewable energy source and, furthermore, it requires less use of compressors and high-gwp (global warming potential) refrigerants. however, it must be pointed out that the use of the eahx is not yet widespread. this is due to both the space problems related to the installation of buried pipes, which can be problematic in widely urbanized contexts, and the excavation costs necessary for burying the pipes. in this section many of the numerical models or computational methods reported in the scientific literature for the analysis of the eahx are reviewed and summarized. bordoloi et al. [ ] in their review paper classified and compared the energy performances of the main eahx systems describing the most relevant analytical and experimental studies on the different combinations of eahxs, up to the year . another very appropriate classification was proposed by bisoniya et al. [ ] in their review where, specifically, the numerical models of eahx were categorized based on the method they are solved through and the dimensions of the geometry investigated. anyhow, the common denominator of both the reviews is to propose an overview of the worldwide research scenario on this type of geothermal system; the emerging data is the really huge number of eahx systems and models proposed. an accurate numerical model should be able of evaluating punctually both the conductive (from/to duct/ground) and the convective (related to the air flowing in the duct) heat transfer mechanisms acting in the eahxs. even if a number of commercial software like trnsys or energy plus allows to easily model geothermal systems, providing qualitative data on their performances ("black-box approach"), they are not able to provide punctual (in space and time) indications on the heat transfer and temperature fields in the whole systems. indeed, to perform accurate heat transfer investigations on the operation of earth-to-air heat exchangers, the most appropriate solution is represented by computational fluid dynamics (cfd)-based models, founded on the discretization of the domain in finite differences/volume/elements despite of the method adopted for solving the differential equations that govern the heat transfer problem. in open literature, various -d, -d, and -d models of earth-to-air heat exchangers were presented and described. over the years, the beginning investigations on eahxs founded on the development of one-dimensional models with simple balances made to derive the inlet-outlet relations for the air parameters. in kabashnikov et al. [ ] introduced one of the first one-dimensional models of an earth-to-air heat exchanger; the mathematical model was very simple as well as few were the results collected: based on fourier integral for evaluating the temperature in the system, a mathematical investigation was carried out, by varying length, diameter and depth of the ducts. as main result the model can provide an analytical expression giving the mathematical value of the length and the diameter that optimizes the heat exchange between the air and the ground. subsequently, in kumar et al. [ ] presented a parametric analysis carried out through a -d finite differences numerical model of an earth-to-air heat exchanger that couples simultaneously the heat and mass transfer equations. the tool was developed through a matlab code and validated with experimental data, coming from a system placed in india, and a good agreement (± . % relative error) was found. the peculiarity is that the model of kumar et al. has been one of the first to investigate the transient behaviour of the eahx for a whole day in summer and in winter, as well as the humidity of the air flowing was considered. in the same year, de paepe and janssens [ ] shared with the scientific community their one-dimensional analytical model where the convective heat exchange is accounted through the calculation of the convective coefficients by means of dimensionless numbers approach. they evaluated the influence of pressure drop as function of volumetric flow rate, of diameter and length of the duct. they noticed that smaller diameters provide higher thermal performance, but greater pressure drops. the solutions they suggested is to project eahx with more ducts placed in parallel to counteract these contrasting trends. through the one-dimensional mathematical model proposed in by cucumo et al. [ ] the effect of burial depth of the tubes on the energy performances of earth-to-air heat exchanger systems was evaluated. the model is able to provide the results following two methods: superposition principle, green functions. they performed the investigation in a sandy soil, and they asserted that optimal deepness belongs to the range - m. the effect of burial depth was also investigated by sehli et al. [ ] by means of a finite volume cfd model. the convective heat exchange of the fluid flowing under turbulent motions was evaluated through the k-ε method. they identified m as optimal depth and they noticed that, as soon as reynolds number increases, the inlet-outlet temperature span decreases due to the less time spent by the air in tube and, consequently, for the heat exchange with the ground. among the -d models that are worthy of mention, there is the one developed by su et al. [ ] since the approach is very unconventional: the eahx was modelled through a sequential computing algorithm an intense study is the one of serageldin et al. [ ] that, with their one dimensional cfd transient model of eahx experimentally validated, asserted that with reference to egyptian weather: i) the larger are duct diameter, length and distance, the higher is the inlet-outlet temperature span; ii) greater air flow velocities reduce the inlet-outlet temperature span; iii) the duct material does not affect significantly the heat exchange between the air and the ground. another interesting contribution was given in by niu et al. [ ] where, through a regression algorithm applied to a -d steady state model, the cooling capacity of an earth-to-air heat exchanger was predicted with extreme accuracy. the polynomial regression model bases on six calibration parameters: temperature, relative humidity and inlet velocity of the air, surface temperature, length, and diameter of the tube. the obtained formula could be of wide usage in designing the eahx systems. among the latest -d models proposed, worthy of note is the one of cuny et al. [ ] published in , where, following the multi-criteria optimization based on genetic algorithms, the pareto front for an eahx systems was determined. three were the criteria selected, two energy and one economic, and they were applied to the operation of an eahx with reference to french climates. the optimum combination suggests large duct length ( m), whereas small should be duct diameter ( . m) and air flow velocity ( . m s - ). a good compromise between performances and cost for burial depth could be . m. furthermore, in , a one-dimensional model was used by lin et al. [ ] to quantify the correlation between the moisture of the ground and the logterm energy performances of an earth-to-air heat exchanger. three different cases were considered: partially and fully saturated, fully dry. the results show that the eahx energy performance is not affected by the soil moisture when the air velocity is low (up to m s - ) but for higher velocity the effect of the moisture in the soil affects significantly the energy performances, since also basing on their operative condition the flow evolves in turbulent. the performances are higher the more is the soil saturation and a % difference in energy performances between the fully dry and fully saturated grounds was appreciated. moreover, they asserted that the maximum air flow velocity in the tube should not overcome . m s − . one-dimensional models show some limits: they cannot calculate the field of speed and temperature of the air into a transversal section of the duct, neither the temperature field of the soil when the depth varies. the keller shooting method was employed for solving the model. it was detected that the saturation of the ground is mostly sensitive to its initial temperature, the air inlet temperature and flow rate. a two-dimensional model of an earth-to-air heat exchanger was also approached through the concept of artificial neural network by kumar et al. [ ] in . they developed two models, a deterministic and an intelligent one: the former was needed to concurrently study the heat and mass transfer of the eahx; the latter is the employment of data driven model founded on artificial neural network. the most salient parameters of the ground to air heat exchanger were considered as influencing meters of the energy performances and the investigation revealed that the intelligent model predicted the outlet temperature of the air from the duct with a ± . % error with respect to the ± . % proper of the deterministic one. in , bisoniya et al. [ ] , through the development of a quasi-steady state cfd -d model, focused on the energy payback period, the annual thermal performances and the seasonal efficiency ratio of an experimental eahx system installed in bhopal (central india). they asserted that considering years as lifetime, the eahx system allows the reduction of . tons of co whereas the total carbon credit has estimated being around $ . always about considering the operation of the eahx for many years of system life, interesting is the concept of "derating factor" introduced by bansal et al. [ ] , that accounts the degradation of the thermal performances over the time. it is defined as instantaneous inlet-outlet temperature span detected on the corresponding steady state one. indeed, due to the saturation of the soil, the smaller is the ratio, the greater is the degradation of the thermal performances. the study on the effect of different displacements of the ducts in an earth-to-air heat exchanger is a crucial concept that has been deepened through -d models in various works. in , congedo et al. [ ] performed a comparative investigation for evaluating the thermal and energy performances of three different duct configurations: linear, helical and slinky and the effect of the variation of geometrical and functional parameters were studied for each one. the investigation was made by means of a -d cfd tool developed in fluent ambient and the eahx was supposed to be placed in south italy. for all the geometrical configuration, the optimal buried depth in terms of costs and performance is . m. in terms of energy performance, the better design resulted to be the helical one but, on the contrary, the installation costs are higher that the linear one. in mathur et al. [ ] investigated about the straight and spiral configurations for a ground to air heat exchanger. the performances of the system were analysed over a year while it operates in cooling and heating modes. the comparison was made also in terms of cop and, on equal design and operative parameters, they observed that the cooling/heating mode cop are . as for -d and -d, the artificial neural network approach was applied also to a -d model, through a deterministic model developed by mihalakakou [ ] where the author found that this approach could accurately estimate the outlet temperature of the tubes. a well-designed eahx system can be used independently but it can also be coupled to a traditional hvac system to meet the heating/cooling requirements of the buildings. in the inherent scientific literature, a number of interesting works investigated the energy performances of hvac plants coupled to/integrated with earth-to-air heat exchangers systems. in , bansal et al. [ ] analysed the energy saving and economic impact deriving from integrating the earth-to-air heat exchanger technology into an evaporative cooling system. specifically, by means of a cfd tool, they considered four base cases of air-conditioning and electric heater systems characterized by three diverse blowers: energy efficient blower, standard blower, and inefficient blower. with reference to these cases, the energy saving and the payback period related to the use of the eahx were evaluated. they found that a years payback period for integrating eahx with an efficient blower evaporative system is very convenient. on the other side, for inefficient blowers the integration of an earth-to-air heat exchanger would result in a financially unviable choice. the authors showed that the energy saving was hardly affected by the electricity tariff and the blower efficiency. in ascione et al. [ ] analysed the effects on energy efficiency and environmental impact of employing an earth-to-air heat exchanger in the air conditioning system enslaving a nearly zero energy building (nzeb) through the software energy plus. the hvac plant based on an air-to-water heat pump supplying fan-coil units plus mechanical ventilation: the eahx was employed as pre-treating unit (pre-heating in winter and pre-cooling in summer). they observed that the eahx integration carried up to a % energy saving in winter and - % in summer, for a global yearly saving rate of - %. in , li et al. [ ] analysed, from energy, environmental and economic point of view the integration of eahx in an air-to-air heat recovery unit based on mechanical ventilation with respect to the case of coupling a heat pump to a primary air handling unit. the eahx was tested in a parametric analysis with two parallel horizontal ducts buried at . m and m with m and m as space between the tubes. the results showed that for severe cold climates, the eahx-based solution carries to remarkable benefits with respect to all the three above aspects. the static and dynamic payback periods for the eahx-based system were about . and . years (with return rate of %); a reduction of % in equivalent emissions of co was also calculated. the most promising results were obtained with m distance between the two ducts. d'agostino et al. [ , ] evaluated the thermal performances of eahx compared to air-to-air heat exchangers providing promising energy savings also for this configuration but with higher economic costs. indeed, the above state-of-the art on numerical models of earth-to-air heat exchanger systems revealed the limits shown by one-dimensional models, especially in the impossibility of drawing the temperature and velocity profiles of the air flowing in the pipes, as well as the temperature range established around the pipes. as a matter of fact, even if these limits could be overcome through the development of both two-or threedimensional models, currently, the vast majority of the numerical eahx tools is d because the latter represents a good compromise in accuracy and computational costs. anyhow, for complex geometries or particular placements of the pipes, where is needed, the d model is used. at the best of our knowledge, the state-of-the-art lacks a worldwide comparison on the performances of a hybrid hvac system where an eahx is installed upstream the air handling unit (ahu). specifically, the present paper aims to fill this gap. at this aim, a case study office building is analyzed and virtually collocated in various climatic zones around the world. -the eahx has been commonly investigated as a component added to a usual mechanical ventilation system, while this paper analyses a hybrid air conditioning system in which the eahx is inserted upstream the air handling unit to minimize the energy requirements; -for various climatic zones around the world, the thermal efficiency of the eahx is evaluated, and also the decreasing of cooling and heating capacity of the coils into the ahu. the methodology of this paper is based on a d mathematical model of an eahx to obtain the system performances under different outdoor air temperatures. the eahx is considered not only as an air pretreatment device placed inside a mechanical ventilation system, but as a component to pre-treat the air to be conditioned into an air handling unit inside a hvac system. in this way it can ensure a relevant energy saving. the investigation is conducted on a hvac system for an office building. the building is spread over two floors for a total area equal to m and a volume equal to m . in figure a and the climatic conditions of the localities where the system is installed, affect the eahx thermal performance. therefore, to make a comparison, the office building is virtually placed in six different cities of italy, chosen to belong to six different climatic zones identified by d.p.r. / [ ] . for a further comparison, the building is subsequently placed in eight cities of the world following the köppen climate classification [ ] (the italian cities are also included). during the analysis on the eahx, the diameter of the air ducts is varied to optimize the system, but the airflow rate necessary for the building must remain constant, so the speed of the air varies consequently. the temperature of the air at the exit of the eahx is evaluated; this air is then sent to the air handling unit before it is supplied to the building. the following parameters are evaluated: the variation of air temperature in the eahx; its thermal efficiency; the decreasing of cooling and heating capacity of the coils into the ahu when comparing with the solution without eahx. the analysis on the coils of the ahu is performed for winter, summer and for the whole year. according to d.p.r n. of [ ] , as shown in figure , the italian territory is divided into six to make a comparison, six italian localities have been considered in this analysis (lampedusa, catania, naples, rome, milan, pian rosa) belonging to the different six climatic zones. the weather data considered were identified through ashrae climatic data [ ] . table shows, for each of the six localities, the design values of the outside air temperature, the relative humidity and the solar incident radiation in winter and summer. the köppen climate classification [ ] is based on the evaluation of the local vegetation in each zone, since it was known, from the first publication in th century, that in a certain region the concentration of the vegetation depends on both the temperature and precipitation. the köppen classification subdivides the earth area into five main climatic zones based on temperature criteria, apart from the second zone (b) in which it is assumed that the dryness of the zone is the main key factor for vegetation's concentration. the principal zones are identified with a capital letter as follows [ ] : zone a: equatorial or tropical climates (the minimum monthly temperature value during the year is equal to or greater than °c). this zone includes the warmest climates. zone b: dry climates (annual mean value of precipitation is less than a specific limit). this zone includes deserts and steppes. zone c: mild temperate climates (monthly average temperature of the warmest month is equal or greater than °c, monthly average temperature of the coldest month ranging from - °c to °c). zone d: continental climates (monthly average temperature of the warmest month is equal or greater than °c, monthly average temperature of the coldest month is equal or lower than - °c). zone e: polar climates (monthly average temperature of the warmest month is less than °c). each climatic area can be also divided in subareas by means of a second letter to take into account precipitations; in some cases, also another sub-criterion (based on temperature) is considered, by adding a third letter. table . pian rosa was omitted since it is characterized by extreme and not very generalizable climatic conditions. furthermore, in the summer season it does not require a cooling system. and d zones, respectively, based on the classification proposed by köppen, whereas zone e (polar area) is not considered. table shows, for these three towns, the design values of outside air temperature, relative humidity and solar incident radiation in winter and summer. according to this classification, rio de janeiro belongs to aw (tropical wet and dry climate) climate zone; dubai to bwh (hot desert climate) and ottawa to dfb (warm-summer humid continental climate). the air conditioning system is characterized by fan coils and primary air. a reversible (invertible) heat pump provides hot and cold water for both the coils of an air handling unit, in order to treat the primary air, and the fan-coil units located in each room of the building. the design external (or outdoor) air flow has been set at - m s - per person, for a total of m h - . the design thermo-hygrometric conditions to be • guaranteed inside each room are: -indoor air: temperature of °c for winter and °c for summer, relative humidity (ϕ) of % for both winter and summer; -supply primary air: temperature of °c and ϕ of % for winter, °c and ϕ of . % for summer (this value of ϕ is calculated after evaluating the specific humidity ω by means of a mass balance for each room, referred to water). two air conditioning systems are analyzed: figure shows the traditional one characterized by only the ahu for primary air (without eahx), whereas figure shows the system where the eahx is placed upstream the ahu. the first one is a usual hvac system with only the ahu (without eahx) and fan-coil units: the air treated in the ahu is outdoor air. the second air conditioning system is instead characterized by the eahx which pre-heats or pre-cools the outside air before being handled into the ahu. the ahu is composed of the following main components:  filters;  pre-heating water coil;  cooling and dehumidifying water coil;  humidifying section;  re-heating coil;  supply fan. (a) (b) in the figures (a) for summer and (b) for winter the transformation in the ahu on the psychometric chart are reported. during the summer (fig. (a) ) the processes that the humid air undergoes are: cooling and dehumidification from point "o" (outdoor air conditions) to point "a" and subsequent re-heating from point "a" to point "s" (supply air conditions). the cooling coil is supposed to be ideal with a by-pass factor equal to % (i.e., ϕ a = %). during the winter (fig. (b) ) the processes are: pre-heating from point "o" to point "a", humidification with liquid water from point "a" to point "b" and re-heating from point "b" to point "s" which coincides with the thermohygrometric conditions to be maintained in the room (point "r"). the humidifier is supposed to be ideal (with saturation efficiency of %). when the eahx is used for pre-cooling/pre-heating the air flow, the point "o" (outside air) is substituted with the point eahx (air conditions at the exit of the eahx, individuated through the d model below described). to evaluate the coils capacity, the mass and energy balances are carried out on the control volumes shown in figure (a) and figure (b). during the summer (fig. (a) ) the running components of the ahu are: the cooling coil and the re-heating coil. the energy balance equation for calculating the cooling capacity (with reference to control volume of fig. (a)) is: the re-heating coil power (control volume of figure a) can be evaluated as: during the winter, as shown in figure (b), the active components are: the pre-heating coil, the humidifier with liquid water and the re-heating coil. the pre-heating coil capacity (control volume of figure (b)) can be evaluated as: the mass flowrate of humidification water (control volume of figure (b)) can be evaluated as: the re-heating coil capacity (control volume of figure (b)) is obtained from the equation: when the eahx is in use, the reduced capacity of the ahu coils both for summer and winter has been evaluated. consequently, the reduction of the coils' capacity obtained by the introduction of the eahx technology compared to the ahu without this heat exchanger is calculated, considering the coils operating in winter season, summer season and all over the year. in this research, the open-loop earth-to-air heat exchanger was d modeled through a finite element method software. the eahx was made of five horizontal ducts. the horizontal disposition was chosen since vertical one usually involves with higher installation and maintenance costs. the number of tubes has been chosen to obtain, at fixed air volumetric flowrate, a range of air velocity between . and . m s - that is a good compromise between effectiveness of heat transfer and pressure drops. . m is the distance d stemming between two adjacent ducts: this value is chosen to avoid thermal interaction between the two air ducts. the computational domain of the model consists of one circular buried duct (for air flowing) surrounded by a ground volume of m deep. this value of deepness was chosen to consider the ground as undisturbed [ , ] . the buried duct is installed at . m deep from the soil surface because, in agreement with other studies [ ] , for deepness more than m, the soil temperature is about undisturbed and close to the annual mean values of the outdoor air. burying the pipe between m and m is a good compromise [ , ] between yearly temperature excursion and excavation costs. the mass flowrate of the air entering each pipe is evaluated as: , the outside airflow of m h - must be provided to the building, so the modification of the duct diameter leads to a modification in the air speed. in table for each diameter the air velocity and the reynolds number are reported. the table clearly shows that the airflow rate can be always considered in fully turbulent developed regime.  the soil considered as an isotropic medium. the air entering the ducts is humid air. the thermodynamic properties of humid air (dry bulb temperature; relative and specific humidity) can be punctually evaluated, in time and space, through the model. therefore, the condensed water flow rate can be also evaluated. for the fluid domain the following differential equations can be numerically solved:  the mass conservation of the humid air: where is a negative term that represents the mass of water vapor condensed;  the conservation momentum of the air flow is guaranteed by the navier-stokes equations for turbulent flow: ( ) where is the turbulent viscosity defined as: with , that is one of the constants of the k-model for turbulent flow [ ] ;  the energy equation for the air flow: where is the effective conductivity defined as the sum of the conventional thermal conductivity of the fluid ( ) and the thermal conductivity of the turbulent flow ( ) and thus modeled as: , ( ) = +  using the k-model for turbulent flow, the turbulence kinetic energy equation is: can be evaluated as: the specific dissipation rate equation is: the experimental constants of the k-model are reported in table . the differential equation of conduction in solid domain numerically solved is: the soil humidity is considered balancing water and solid properties throughout the porosity ( with the following equation: for each locality of the analysis the thermal properties of the soil are evaluated and reported in table . table reports the weather data used in equation ( ) and the resulting undisturbed ground temperature for each locality of the present analysis: a time dependent solver is used to solve the mathematical model, while the implicit bdf (backward differentiation formula) is used as time step procedure. the implicit bdf procedure utilizes backward differentiation equations that present accuracy from one (named as the backward euler method, too) to five. bdf procedures were often utilized due to their stability characteristics. on the other hand, they could show some damping effects, mainly when considering the lowest order methods (some high frequencies are often damped). although one could expect a solution with sharp gradient, a frequently smooth solution is obtained due to the above-mentioned damping effects. the use of bdf could be characterized by high order if possible, and lower order when it is indispensable to reach stability. the strategy of the solver selected for the model used in this work is bdf with "free time stepping": in this way, the solver can set greater or smaller time steps to satisfy the required tolerances. in fact, the solver tries to calculate with the largest possible time step, but, when the solution starts to rapidly vary and therefore the (relative and absolute) tolerances are not verified, it as clearly visible from the figure we found a substantial overlapping between the temperature profiles with and elements and a good agreement between the solution with elements (maximum difference lower than . k). since the computational time for elaborating the solution does not differ appreciably if we simulate with and elements, we opted for the finer meshing ( elements). to ensure the reliability of the results obtained with the numerical code, the model is validated by in table is reported the absolute and relative error on the outlet air temperature: the maximum relative deviation between the experimental and the numerical data is . % (at m of tube length). that is, the maximum difference between the predicted and the experimental air temperature at the outlet of the eahx is °c. in addition, the eahx model has also been validated by means of some of the experimental results provided by khabbaz et al. [ ] , related to an earth-to-air heat exchanger system located in marrakech table is reported the absolute and relative error on the outlet air temperature. it can be noted that the maximum relative deviation between the experimental and the numerical data is . % (at m of tube length). the maximum difference between the predicted and the experimental air temperature at the outlet of the eahx is . °c (lower than the experimental uncertainty on the measured temperature). reynolds number follows in the transition between laminar and turbulent flow. in this range the numerical model uses the laminar solution. the experimental temperature was detected with t-type calibrated thermocouples, with an error following in the normal range with deviations between the thermocouples reading and that of a standard one (beta calibrator tc- ) of + . - . °c. in figure is reported a comparison between experimental and numerical air temperature as a function of the tube length: the figure clearly shows that the numerical model always overpredicts the experimental data. figure .experimental and numerical air temperature alongside the pipe of the earth-to-air heat exchanger. in table the absolute and relative error on the outlet air temperature is reported. it can be noted that the maximum relative deviation between the experimental and the numerical data is . % (at . m of tube length). the maximum difference between the predicted and the experimental air temperature at the outlet of the eahx is . °c. from all these analyses we can conclude that the presented model is able to predict the thermal performance on a horizontal eahx not only in fully developed turbulent flow but also in laminar or transition regime. in this paper the thermal and energy performances of an eahx pre-treating unit coupled to an ahu are evaluated. the thermal behaviour of an eahx is not the same on the globe but depends on the climatic context, the soil temperature, and the configuration of the eahx. the soil temperature is very similar to the annual mean temperature of the place in which eahx is installed; therefore, it is often higher than air temperature in winter and lower in summer. the aim of this paper is to compare the performances of an eahx in: i) six localities of italy belonging to different climatic zones according to the italian d.p.r. / classification; ii) nine cities with different climatic conditions based on the classification proposed by köppen. the described eahx is tested by means of a mathematical model; each simulation is carried out until the steady state regime is obtained. at this point, all the parameters are calculated. in figure the temperature variation along the tube length in winter and in summer varying the inner tube diameter for the six localities is reported. figure the figure clearly shows that temperature variation is more marked for milan, a city characterized by cold winter and hot summer (with a maximum value greater than k). the lowest values are those pertaining to lampedusa, a locality characterized by very mild climate (maximum value lower than k). in figure is reported the variation between the outlet and the inlet temperature of the eahx for the six localities in winter season. it could be noted that the greatest temperature variation can be obtained for pian rosa, a locality characterized by very cold winters (maximum value of . k), whereas the lowest is for lampedusa (maximum value of . k). from the data plotted in figures and the following considerations can be drawn:  the temperature variation that can be obtained with an eahx at fixed tube length is always greater in the summer than in the winter season. this is due to the greater temperature difference between the external air and the soil during the summer for each of the tested localities;  the temperature of the undisturbed ground is almost constant and very similar to the yearly average value for the outside air. so, the lowest temperature of the ground is for zone f, while the highest occurs for the zone a. the temperature difference between the ground and the outside air represents the principal driving force in the heat exchange process. where the difference between the air temperature at the inlet of the heat exchanger (corresponding at l= in figures ) and the undisturbed soil is more marked, the more efficient is the heat transfer process. the greatest values of driving force can be obtained in the localities with greater temperature excursions between summer and winter (pian rosa, milan).  lampedusa shows the lowest temperature span because it has very mild winters with moderate rainfall and hot, dry summers. so, the temperature span along the eahx is minor than °c, although a relevant length of m is considered for the air duct (Δt belongs to . ÷ . k in summer and to . ÷ . k in winter). figure is reported the efficiency of the eahx as a function of the tube length for the six localities for an inner tube diameter of . m. from the results obtained, the efficiency in winter and summer is almost the same, this is the reason why there is only one graph that can be used for both seasons. the graph also shows that at fixed tube length the efficiency is independent on the climatic zone where the eahx is installed. indeed, the effectiveness of the heat exchange mainly depends on the convective heat transfer coefficient that at fixed inner tube diameter is almost constant for the different localities (because constant is the air flow velocity too). furthermore, the figure clearly shows that the increase of the efficiency is very pronounced up to about m: for longer lengths, the increase becomes moderate. an optimal efficiency value of about % is ensured with a length duct of m. this result is also relevant in the possible comparison between the analyzed eahx and an air-to-air heat recovery unit. in fact, the latter is characterized by a mean efficiency of about %- % [ ] [ ] [ ] . moreover, air-to-air heat exchangers are usually more dangerous due to the risk of spreading sars-cov- or other viruses. the efficiency is a strong function of the inner tube diameter (and of the consequent fluid velocity). as an example, in fig. is reported the efficiency for the different tube diameter for the city of milan during summer. similar results can be obtained in winter and for the other examined italian localities. the eahx also implies a relevant decreasing of the heating and cooling capacity of the coils inside the air handling unit. figure reports the heating and cooling capacity of the operating coils during winter (i.e. preheating coil and reheating coil) (a), during summer (i.e. cooling coil and reheating coil) (b), all over the year (c), as a function of the tube length for an inner tube diameter of . m for the different localities. figure also shows the heating and cooling capacity values for the system without the eahx. finally, the figure also reports the decreasing (in percentage) of these capacity values when the eahx is considered, for various lengths of the air ducts. from the figure the following considerations can be drawn:  increasing the tube length carries to an augmentation of the capacity reduction, too. therefore, the best results can be obtained with the duct m long;  during the winter (fig. (a) ) the capacity reduction using the eahx to pre-heat the air flow is more marked in zone a (maximum value of %) than in zone f (maximum value of %). indeed, in lampedusa, the southernmost point of italy with a very mild winter and hot, dry summer, the capacity reduction is greater than in pian rosa (with a short and cool summer and a long, freezing, and snowy winter);  an opposite trend is observed during the summer (fig. (b) ): the capacity reduction using the eahx to pre-cool air flow is more marked in zone e (maximum value of %) than in zone a (maximum value of %);  with reference to winter and summer (fig. (c) ), the highest total decrease in capacity of the coils occurs for zone e (milan -decrease of % for a duct length of m), while the lowest value occurs for zone a (lampedusa -maximum decrease of capacity equal to %). so, in italy the annual utilization of the eahx linked to an air handling unit is useful in all the national territory, even if preferable in zone e (i.e. in the climatic areas showing a high temperature excursion between winter and summer) compared to zone a. from a comparison among figures , and , the emerging data is the greatest coils capacity reduction that can be achieved considering the smallest diameter of . m (maximum global power reduction of % in milano). the previous analysis has shown that the best results can be obtained with the smaller inner tube diameter considered ( . m). therefore, in this analysis the tube diameter is fixed at . m. in figures is reported the temperature variation in eahx as a function of the tube length in summer (a) and in winter (b) season. according to the köppen classification, the analyzed italian localities belong to the zone c (mild temperature climates) except lampedusa that belongs to the zone b (dry climates).  the temperature span between the inlet and the exit of the eahx, in the italian localities, is lower in winter than in summer, while an opposite result is obtained for ottawa, dubai and rio de janeiro. this depends on the temperature span between the soil and the outside air. this difference in italy is not so dissimilar between summer and winter and slightly greater in summer. instead, the contrary is found for dubai, rio de janeiro and ottawa (in this last case there is a strong variation between summer ( . k) and winter ( . k);  in summer conditions, the maximum eahx temperature difference between the inlet and the exit is obtained for milan (higher than °c), while the minimum temperature difference is obtained for rio de janeiro (maximum value lower than °c);  during summer, the best results can be obtained in milan (maximum value greater than k), whereas the worst results are registered in rio de janeiro (maximum value lower than k);  during winter ottawa shows the greatest temperature variation in the eahx (maximum value of . k), on the contrary rio shows the lowest (maximum value . k);  the temperature of the undisturbed ground is almost constant and very similar to the yearly average temperature of the outside air, in all the considered climatic areas. the temperature difference between ground and outside air is the principal driving force in the heat transfer process related to the eahx: its highest values occur in the climatic areas with higher temperature excursion between winter and summer. so, the most relevant results occur for zones c and d (mild temperate climatic areas and continental climatic areas, respectively), while the less relevant results occur for equatorial or tropical climatic areas (zone a). figure shows the eahx efficiency in summer, when varying the air duct length, for the eight analyzed towns. indeed, in winter the results are almost the same. it can be shown that the efficiency depends slightly on the climatic and soil characteristics of the area in which the exchanger is installed. for all the climatic areas the efficiency exceeds % at m tube length.  in dubai and rio de janeiro, the temperature of the air at the exit of the air duct is higher than °c, even when the duct length is only m. moreover, the couple dry bulb temperature -specific humidity of the air at the exit of the air duct is very similar to those required for comfort conditions in winter. so, the air exiting the eahx can be supplied to the building without any hvac system (only a suitable filtration of the air is obviously required). therefore, in these cases the decreasing of the heating capacity of the coils rises % for the air handling unit working in heating operating conditions;  the heating capacity reduction using the eahx to pre-heat the air flow is more marked in a and b zones (maximum value of %) than in c or d zones (maximum value of %). from figure (b), referred to summer, one can notice that:  the air temperature in the duct decreases below the dew point temperature ( . °c) in ottawa, for duct lengths higher than m; it means that the air has been dehumidified. length;  in ottawa, with a tube length of m the air flow reaches temperature and relative humidity values such that the air can be directly conveyed in the building without using the air conditioning plant. therefore, the percentage cooling capacity reduction in cooling mode is %;  the capacity reduction using the eahx to pre-cooling the air is more marked in d and c zones (maximum value % for ottawa) than for a and b zones (maximum value of % for rio de janeiro). from figure (c) it can be seen that the highest decreasing of cooling plus heating capacity for the coils occurs for dubai while low values of the length of the air duct are considered (up to m), whereas for higher lengths of the air ducts the best results occur for ottawa. therefore, one can conclude that the best results can be obtained for tube length of m in the city of ottawa (reduction of % of heating + cooling capacity using the eahx) that belongs to the dfb zone according to the köppen classification. this city is characterized by the greatest temperature span between winter and summer season, with a very cold winter (with frequent snowfalls) and a hot-humid summer. in this paper the thermal and energy performance of an earth-to-air heat exchanger are investigated. a two-dimensional unsteady numerical model of a horizontal eahx has been developed. the eahx is formed by horizontal circular ducts, displaced in parallel at . m depth. two adjacent ducts are . m spaced apart. the d model represents one of the five circular horizontal buried ducts of the eahx surrounded by a ground volume m deep; the problem is solved through finite element method. the model has been validated with experimental results found in literature: the maximum relative deviation between the experimental and the numerical data is . %, the absolute deviation is always lower than °c. the eahx is considered as a component of an air conditioning system for an office building. the air preheated or pre-cooled in the eahx is not directly supplied to the building, but it is successively treated into the air handling unit. since the thermal performance of the eahx depends on the climatic conditions of the place where it is installed, the office building was firstly virtually placed in six different localities of italy (lampedusa, catania, naples, rome, milan, pian rosa), which belong to different climatic zones according to the italian law d.p.r. / , based on heating degree-days. for a further comparison, the building was subsequently placed in eight cities of the world according to köppen climate classification (dubai, rio de janeiro, ottawa, plus five of the abovementioned italian localities). the eahx is simulated and optimized as a function of the diameter and length of the air ducts. the following parameters are calculated: the variation of air temperature in the eahx; its thermal efficiency; the decreasing of cooling and heating capacity of the coils into the ahu when comparing with the solution without eahx. the analysis on the coils of the ahu is performed for winter, summer and for all the year. the following main conclusions are obtained.  at the eahx outlet, a temperature of the air close to the undisturbed ground temperature (knee point) is obtained for tube length of about m for all the localities. therefore, a duct length of m represents an acceptable compromise considering thermal performances, pressure drops and eahx costs.  decreasing the tube diameter, the air velocity increases enhancing the convection heat transfer coefficient and, as a result, the heat exchange becomes more efficient. therefore, with the lowest value of the inner tube diameter ( . m) a greater air temperature variation can be obtained in the eahx.  for all the analyzed climatic zones the undisturbed soil temperature is about constant and close to the annual mean values of the external air. temperature gradient between ambient air and soil is the main driving force for the heat transfer in the eahx. the greatest values of driving force can be obtained in the locality with the greatest temperature excursions between summer and winter. therefore, the worst results in terms of temperature variation in the eahx can be obtained in the zone a (according to köppen climate classification, it refers to tropical or equatorial climates) and the best in zones d (continental climates) and c (mild temperate climates).  among the italian localities, lampedusa shows the lowest temperature span between the inlet and outlet of the eahx, always smaller than k even with a tube length of m (Δt belongs to . ÷ . k in summer and to . ÷ . k in winter). milan (with a maximum value greater than k) and pian rosa in winter (whose maximum temperature span is . k) show the highest temperature spans.  according to the climate classification of köppen, during summer the best results can be obtained in milan (maximum value greater than k), whereas the worst results are registered in rio de janeiro (maximum value lower than k). during winter ottawa shows the greatest temperature variation in the eahx (maximum value of . k), on the contrary rio de janeiro shows the lowest (maximum value of . k).  the efficiency of the eahx is almost independent on the climatic zone where the eahx is installed and its increase is very pronounced up to about m: for longer lengths, the increase becomes moderate. indeed, m as length of each duct ensures the achievement of an optimal efficiency value, around %.  considering the reduction of heating and cooling capacity of the coils inside the ahu (deriving from the placement of eahx upstream the ahu) for the whole year, the best case is milan (zone e) with a heating + cooling capacity reduction of % for a tube length of m, whereas the worst case is lampedusa (zone a) with a maximum value of reduction equal to %. therefore, when the yearly operation period of the ahu coupled to an eahx is considered, in italy the use of an eahx is recommended in all the climatic zones, but more in e than in a zone. the best results can be obtained in the localities with a great temperature excursion between summer and winter.  considering the reduction of heating and cooling capacity of the coils inside the ahu based on köppen climatic zones, one can conclude that the best results can be obtained for tube length of m in the city of ottawa (reduction of % when using the eahx) that belongs to the dfb zone. this city is characterized by the greatest temperature excursion between winter and summer season, with a very cold winter (with frequent snowfalls) and a hot-humid summer. on the contrary, the worst results can be 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dynamics simulation. energy conversion and management eahx -earth-to-air heat exchanger: simplified method and kpi for early building design phases an energy exchange efficiency prediction approach based on multivariate polynomial regression for membrane-based air-to-air energy recovery ventilator core cascade ventilation-air exchange efficiency in living rooms without separate supply air author contributions: all the authors have contributed in the same manner to the various aspects of the research activity described in the paper all authors have read and agreed to the published version of the manuscript [ ] ☒ the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.☐the authors declare the following financial interests/personal relationships which may be considered as potential competing interests:[ ]  earth-to-air heat exchanger uses geothermal energy for air conditioning systems  a d mathematical model of the eahx is developed to obtain the system performance  a case study office building is analysed for eight worldwide localities  air temperature variation along the eahx and eahx efficiency are calculated  reduction of thermal capacity of the coils inside air handling unit is evaluated [ ] key: cord- -uo h ku authors: button, kenneth title: the economics of africa's floriculture air-cargo supply chain date: - - journal: j transp geogr doi: . /j.jtrangeo. . sha: doc_id: cord_uid: uo h ku this article examines the economics of africa's emerging air cargo supply chains, taking floriculture as a case study. floriculture is an important employer, and earner of foreign exchange for several regions of central/southern and eastern africa including more recently ethiopia. air transportation often plays a critical role when the supply-chain involves high-value, non-durable, relatively light-weight, and compact consignments such as flowers, and geographically when regions are difficult to access by other trunk modes. the success of air cargo chains, however, depend as much on the quality of surface modes serving various “last mile” access and egress functions, as well as efficient nodal interchange points and the availability of suitable airport and airline capacity. the last, because of the important role of belly-hold space, includes consideration of passenger as well as cargo specific services. to meet the needs of africa's floriculture sector, a variety of supply-chain models have emerged that embrace air and surface links, as well as storage at various points in the chain. the paper considers the nature of these chains, the reason d'être for their structures, and their limitations. the most dynamic trading regions are now those that have become linked into the network of global value chains. unfortunately, africa is not a significant player in these networks. drivers for the development of global value chains are considered to be low transportation costs; information and communication technologies; high quality telecommunication infrastructure; technological innovations; education and skills of the workforce; competitive labor costs; political, social, and cultural environments; stable legislation and ability to enforce contracts; proximity to supply sources; and proximity to market. in general, africa falls short in most of these. the focus of this paper is on the peculiar economic challenges associated with africa's floriculture aviation supply chains. the requirements of this industry differ considerably from the traditional view of supply chains in africa with their focus of bulk raw materials and cheap consumer goods. the modes used differ, the organization of the various links in the supply chain differ, the perishability of the products differ, the informational needs differ, the linking of the long and the short hauls differ, and so on. and, importantly, the aviation supplychain dominates the delivery of transportation to the floriculture industry. africa has the world's worst road, railroad, and airport infrastructures in terms of both quantity and quality (gwilliam, ; buys et al., ) . it also has the least number of commercial aircraft per capita. having said this, the forecasts for aviation activities are relatively optimistic. boeing commercial airplane ( ) predicts that intra-africa revenue passenger kilometers flown will grow an average annually by . % between and , and those between africa and the middle east and europe by . % and . % respectively. physically, air cargo is projected to grow between africa and europe by . % per year, between africa and east asia by . %, and between africa and north america by . % per year. but this is from a small base. this paper looks at the economic challenges that still confront aviation-based floricultural supply chains in africa, and how they are being confronted. this is done largely within a managerial-economics framework. i am much less concerned with the other significant challenges these supply chains encounter, such as culture and ethics issues (hughes, (hughes, , , although there is some discussion of the various forms of governance and government set within williamson's ( ) new institutional economics. methodologically, the article is an exercise in what used to be called "descriptive economics"; and which should not be taken as a pejorative term. it involves gathering and compiling data about the economy and entails economists making observations, noticing patterns and recording facts. descriptive economics is mainly qualitative and inductive in its nature. initially, the general characteristics africa's floriculture sector are outlined, and the aviation services available are described. i then move to the specific challenges of the floriculture supply chain. finally, attention is paid to the main african chains, with a focus on the alternative structural models in place. these chains involve the linking of short-haul domestic african routes and their interface with intercontinental, trunk-haul airline services as well as the air transportation itself. africa's modern commercial flower production began in the s. it has always been largely an export orientated industry. flowers are neither a major part of most african cultures nor used much in decoration. outside of africa, prior to the s demands for cut flowers in europe and north america were met by local production. in europe, which still has the largest per capita consumption of stems in the world, and about eight times that of the us, production was concentrated in the netherlands. with the coming of expedited movements within the eu, it also became possible to economically produce cut flowers in southern europe. the energy crisis in put producers in northern europe under further pressure because of the higher costs of greenhousing. subsequently, the supplying of cut flowers to european markets began to shift to lower cost producing regions with climates that allow continuous production without high-energy consumption. growing exportable floriculture products in africa then became concentrated in kenya and south africa, with uganda, tanzania, and especially ethiopia rising in importance over recent years. zimbabwe's output declined dramatically from the early s with the country's land reforms but there has been some recent recovery (english et al., ) . at the same time, new markets are being developed for floriculture products in east asia, the middle east, and the us. kenya's current t of daily exports of flowers, for example, end up in national markets. ethiopia's growers, and exporters, while continuing to encourage trade with traditional european partners, have also begun exporting to saudi arabia, qatar, and bahrain. accompanying this have been tighter controls imposed by importing markets and, in particular, on the quality of products and on the environmental implications of their cultivation (kuiper and gemählich, ) . this has increased costs of production, and particularly so for some of the newer regions. the traditional distribution channels, notably the flower auctions in amsterdam, are responding to this. the auction systems have been computerized and the auction houses have taken on new roles including acting as intermediaries between growers and buyers when flowers go directly to final consumers (mwangi, ) . competing auctions have also emerged, most notably in dubai (babalola et al., ) . despite these developments, africa's floriculture industry is at the micro-level, geographically specific. there are variations in the needs of the varieties of plant grown, with each depending on appropriate amounts of sunlight, a narrow temperature range, and water supply, as well as specific soil compositions. altitude can be important in some cases. there are also differences in the ideal agroecological conditions for cultivating plants and cuttings for export as opposed to stems. the regions around lake victoria are, for example, ideal for long-stemmed cut roses as are ha on lake tana in ethiopia, the source of the blue nile, and another ha on the blue nile itself. the majority of floriculture in africa is located within relatively short distances of international airports. most of ethiopia's floriculture is, for example, within a kms radius of addis ababa airport. similarly, kenya's flower farms are mainly situated around lake naivasha, about kms northwest of nairobi airport. from an employment perspective, however, they do not bring more farm jobs to rural areas, but rather work is focused close to major cities, reinforcing urbanization trends. one reason for this is the cost structure of the industry. although this can vary a lot according to location, climate, and product type and quality, for an -ha farm near lake naivasha the cost per stem was estimated in at $ . to $ . for growth and $ . to $ . for transportation. a stem would sell wholesale for $ . to $ . . given that production costs are largely fixed -wages are often already low and most operating capital is tied up in such as irrigation systems, cold storage, and ventilating systems -transportation is major variable element in the cost function. linked to this, another key factor influencing location is the lack of durability of stems. this means production has to be close to the trunk mode and there must be appropriate intermodal transfer facilities. flowers and cuttings, for example, need be at the retail market within days of cutting; e.g. roses last for three to five days, carnations seven to ten days, standard chrysanthemums seven to days, and pompon chrysanthemums ten to days. on average, for every extra day spent travelling flowers lose around % of their vase lives. africa's surface transportation infrastructure, despite considerable investment over the past decade, is seriously deficient in both quantity and quality. physical proximity to a major airport is, therefore, important to the floriculture industry. regarding regional economic effects, floriculture's impacts are highly geographically specific. unlike many other agricultural products, floriculture workers migrated to and live in areas that have become urbanized as the flower business has developed around them. as noted earlier, this has contributed to urbanization rather than slowed it as intended with agricultural retention programs (hall et al., ) . the industry is important because it creates employment and development possibilities, and especially because it provides relatively steady work throughout the year unlike other agricultural activities (mitullah et al., ; kabiru et al., ) . it is also a major employer of female labor, which constitutes about % of workers in kenya's flower production (kuiper, ) . although increasing over time, along with improved working conditions, farm workers' wages are in general still low. while the majority of those employed in floriculture in kenya earn wages above the agricultural legislated monthly minimum (dettmer et al., ) they still often fall below local poverty lines (kazimierczuk et al., ) . there are also often problems of displacement. in the lake victoria the approach has an established pedigree and is, for example, referred as one of several branches of economics by jevons ( ) , generally seen as the father of mathematical economics, in his seminal work on the theory of political economy. in doing this there are inevitable caveats regarding the quantity and quality of data. while global bodies, such as the world bank and the african development bank, and national governments, collect some aggregate statistics, much of the information regarding specific african supply chains is piece meal, often gained from case studies or profession bodies in individual countries, and sometimes from the grey literature. additionally, up-to-dated information can be found at the website of organizations cited in the text. individual cut flowers are "stems". https://www.floraldaily.com/article/ /zimbabwe-making-flowerexports-blossom-again/ https://gro-intelligence.com/insights/articles/east-african-floricultureblossoming taking kenyan shillings are about $ . region, for example, workers migrating to the area have led to tension with local society which has traditionally been supported by grazing. floriculture's dependence on lake waters and the need for farmland not only raises concerns over ecosystem preservation but results in competition for water access and for land with local masai herders. cultural, conflicts also exist between the herders and kikuyu flower growers (kuiper, ) . economic theory highlights the key market characteristics required for viable aviation networks, but africa is an awkward "shape" for any of these (scotti et al., ) . the us is good for hub-and-spoke systems with its contiguous states forming a virtual square embracing large populations at each corner that act as gateways for international traffic as well as large markets for domestic fights. major cities in the center act as domestic hubs. europe is ideal for discrete, short-haul, nonconnecting services emanating from bases, such as in ryanair's business model. the bulk of its population and economic activity is located a dense economic corridor stretching from north wales to northern italy; the "blue banana". china, with its concentration of economic activity in the south and west, in many ways, parallels that of europe. the linear networks found in such as norway facilitate "bus-stop routes", with planes maintaining their load factors by picking-up and dropping passengers as they move along routes. most of africa's human geography does not conform to any of these patterns. institutional structures have not helped the situation. until the s, intra-africa air services were regulated on a piece-meal basis by restrictive, bilateral national agreements with nearly all carriers stateowned and lacking a commercial focus. airlines were characterized by mismanagement, political interference, high operating costs, and outdated equipment. their focus was on inter-continental traffic, with the intra-africa network taking a secondary role. the yamoussoukro decision sought to readdress this. it was a commitment to deregulate air services and to open regional air markets to transnational competition. the expected gains have yet, however, to materialize on any scale, although in those regions where yamoussoukro has been implemented, frequencies have often increased and privately funded airlines have emerged (njoya, ) . but the impact is patchy. the creation of a single african air transport market (saatm), which has been planned since , may offer another opportunity for enlargement of air services. most analyses of africa's aviation supply chains have focused on tourism (e.g. sifolo, ; steyn and mhlanga, ) . this is not surprising given the overall economic contribution of the sector to africa's economy. the world travel and tourism council ( ) estimated that in tourism accounted for . % of the continent's gdp. but, as we have also seen a number of africa's regions have the geography to grow quality flowers in volume. like tourism, floriculture has a high labor content and its localized economic impacts are often where unemployment is high and labor productivity has been rather low. further, because africa's floriculture is almost exclusively an export industry, it is a major source of foreign exchange. fig. stylizes the stages in air cargo supply chains. it is conceptually identical for passengers with some differences in terminology; e.g. warehousing would be hotels and integrators would be inclusive package tour operators. basically, shippers can make all or some the decisions concerning modes of movement, routing, warehousing, distribution etc., or can engage integrators or forwarders to act as agents and carry out all or some of the stages. some of these decisions are of a purely technical nature (yang et al., ) , but other, partly due to market uncertainties, are more subjective. the generic pattern of air cargo logistics and the branches in the decision tree are similar irrespective of whether the logistics involves developed or developing countries. the range of options, however, tends to be smaller when developing countries are involved, and some of the options may be of lower quality. this is particularly so with cold chains that require actions and equipment designed to maintain a product within a specified low temperature range from harvest to consumption. an increase in temperature beyond four degrees at any point in the cold chain, for example, compromises the quality of cut flowers. at a more macro level, there are two broad frameworks typifying aviation supply chains, or at least to significant elements of then. one consists of a series of interacting free markets involving suppliers of various services and shippers -a set of standard neoclassical economic models. looking again at fig. , this does not mean that at each stage there is competition in selling services. in some cases, to minimize coasian transactions costs, or to reap various forms of economies of scale, there may be vertical integration of suppliers of logistics services. thus, as seen later, while kenya has a largely competitive chain, it falls short of the neoclassical ideal. the alternative is a more command-andcontrol approach with the government, or a quasi-state corporation, controlling the supply chain, or key links in it. this, although not completely, is the model ethiopia has adopted in its relatively recent move into floriculture. the authorities provide a considerable degree of "direction' in the chain. a challenge in developing efficient aviation-supply chains lies in the size of the market. economies of scale can be particularly pronounced, at least up to a point, in the provision of airport logistics centers (martín and voltes-dorta, ) and forwarder/integration services. economies of density, scope and other network features are relevant when providing airline services and regional distribution. in the african context, barros and wanke ( ) , for example, find economies of scope are the most important variables for explaining levels of airline efficiency, although the impact of fleet mix and public ownership are also important. this generally means that passengers fares (important when cargo is carried as a complementary revenue source in a plane's hold) and freight rates are higher for leaner markets combined with more spartan schedules. it also means that many air cargo services are indirect, collecting traffic along "bus-stop routes" rather than being direct between the flower growing regions and destinations. thinner markets also tend to be associated with less competitive airline conditions, affording users less opportunity to exercise any monopsony power they may have over fares and freight rates. there is something of a paradox here. while concentration of business in the hands of a few airlines and other actors along the aviation-supply chain can help reap the gains of various scale effects, lack of competition can lead to both allocative and x-inefficiencies, with suppliers having no incentive to minimize their rates. in this sense, the thin aviation markets found in much of africa are below the threshold required to bring about a reasonable level of competition between airlines. a recent change in africa has been the emergence of gulf and turkish carriers (pirie, ) . not only have these expanded dedicated freight services, but their extensive use of wide-bodied long-haul passenger jets has added belly-hold freight capacity on many corridors (heinz and o'connell, ) . inbound into africa, the gulf carriers have diverted traffic away from africa's airlines. this includes flying out of major european cities such as london and amsterdam, as well as their own hubs (pirie, ) . for example, emirates' cargo-only service flew to five african cities in . in the same year qatar airways launched a specialized freighter service into djibouti when already operating freighters to accra, entebbe, johannesburg, khartoum, lagos, nairobi, and etihad increased its freighter links to africa with the launch of a twice-weekly service between abu dhabi and brazzaville, via lagos. airports council international reports that africa had none of the world's top cargo airports in . the main african hubs are at johannesburg, addis ababa, cairo, and nairobi, with lagos and khartoum being somewhat smaller, and with much of their activity involving aid imports. other countries, such as uganda and ghana, have sought to increase their presence in the cargo market but suffer from inadequate landside facilities and poor access. most international air cargo operations confront challenges associated with asymmetric patterns of trade caused by natural market imbalances and institutional factors. these pose backhaul problems restricting maximum utilization of aircraft capacity and, given limited fifth-freedom rights, add to the risk of service withdrawal (behrensa and picard, ) . emirates' weekly inbound service to lilongwe transporting mainly merchandise and pharmaceuticals was, for example, near capacity in the mid- s, but very lightly loaded outbound, calling at nairobi to load additional cargo for europe. electronic items, often for onward regional distribution, dominate emirates' cargo into kenya while outbound traffic comprises mainly flowers and fish. the airline has also long flown pharmaceuticals from india, automotive parts from germany and general cargo from china into johannesburg, taking outbound loads of manufactured goods and fresh produce (campbell, ) . africa's air passenger capacity, jointly supplied with belly-hold capacity, has grown. the centre for aviation (capa) estimates intra-africa business grew from about million return seats in , to million in , to million in . added to this has been the growth in activities of foreign carriers. much of the expansion in intercontinental capacity between and was associated with middle east airlines that roughly doubling their share to about % with european carriers maintaining about a third. (pirie, (pirie, , . in particular, there was growth in inter-continental connections, much of which involved traditional hubs in europe. but the middle east also enjoyed increased connectivity. this has led to africa's airports becoming more dependent on a limited number of airlines which enjoy quasi-monopoly power (scotti et al., ) . the floriculture industry is highly sensitive to geography, and in particular to climate, water supply and altitude. unlike some more footloose industries, where transportation can have significant effects on their locations, transportation is largely a facilitator that releases the natural flower-growing potential of an area. but having an airport nearby is not sufficient, it has to be accessible and offer appropriate transit facilities. surface access to africa's airports, however, varies considerably. unlike seaports that require heavily engineered access routes, those serving flower farmers, both because of relatively infrequent truck movements and light loads, can be less-substantial and are generally built to a lower design standard. congestion and poorly maintained roads can, however, reduce the reliability of the local justin-time supply chain that floriculture relies on to connect to relatively infrequent flights. the temporal and temperature fragility of perishables normally means that a cold-supply chain is adopted. this involves rapid harvesting of the product when at the ideal stage in its life cycle, the movement of relatively small units, often in chilled containers, and storage at suitable consolidation facilities prior to long-distant movements to final customers. the perishable supply-chain, excepting capital outlays on the storage facilities, almost exclusively involves forward integration. from the perspective of economic development, this has major advantages in conservation of foreign exchange and in generating domestic jobs. the quality of the supply chain, and its associated labor, has also evolved as the floriculture sector has moved to higher value-added products. kenya, for example, has shifted away from exporting lower value to higher-value stems and onto bouquets (kuiper and gemählich, ) . the quality of any supply chain is dependent on its weakest link, and thus while aviation may be an important element in chains involving flowers, even good aviation infrastructure and services may not lead to successful flower production. in the case of the cold chains, the roles of large forwarders and agents are important (babalola et al., ) . delays often mean the loss of produce, and excessive storage time is costly in terms of ultimate shelf lives. in many cases, the trunkhaul aviation link is tied directly to local forwarders that own reefer trucks and warehouses. such forwarders are often, in turn, tied to larger, international companies active in the global supply chain that generate cost economies of scope and density, as well as ensuring quality control. dettmer et al. ( ) , using south africa's international trade data, shows air transportation generally has a comparative advantage when the trunk-haul movement is over relatively long distances, the perishables involved are light weight, low volume and high value items, and especially if the shelf-life of the product is short. in many cases, the aviation supply chains can be combined with those of other goods, or passenger supply chains. in the case of landlocked countries, or those with no easy access to major markets, the air transportation supply chain has considerable advantages for the export of perishables (world bank, a , b . the chain is, however, expensive, with estimates by africa's flower exporters, and particularly those in kenya, that logistics represent % to % of the cost of production of stems. the development of wide-bodied aircraft has produced significant economies of scope as larger planes can combine passengers and bellyhold cargo. this offers an alternative aviation product to specialized air freighters. the movement, albeit slow and incomplete towards more liberal markets, both within africa and inter-continentally, has led to passenger flights being more frequent, less expensive, and more widely available. but in the adherence to tight timetables, belly-hold cargo may get bumped at the pilot's discretion if it misses its loading time. freighters usually offer better temperature control, fewer inspections, and additional capacity, which is particularly valuable for large quantities of short-season goods. but dedicated freighters can be costlier, may fly less often and to fewer locations, and may sit until they reach capacity, endangering perishables. services with several stops are also common to increase the load factor. the aviation infrastructure in africa also often limits when and where large planes, both passenger and cargo, can operate, restricting the hubs and routes that may be served (world bank, a , b . being a network industry, cost minimization in cargo aviation involves consideration of economies of density as well as those of scope. this raises challenges of balancing two-way traffic flows. the majority of passengers make return journeys, whereas freight consignments are usually unidirectional. in the case of africa's trade, much of the cargo suitable for air transportation involves imports of such things as components and spare parts. these are generally higher value commodities than perishables such as flowers, less dependent on just-in-time services, and are more easily handled. in many cases, therefore, inbound freight is treated as the primary cargo, and capacity decisions based upon it, with exports of flowers seen as the marginal cargo -the return load. the development of hub-and-spoke networks has allowed consignments from diverse origins and destinations to be consolidated and transshipped to a wide range of destinations. again, however, there are trade-offs (chung and han, ) . trans-shipping consignments through hubs can, through help in traffic consolidation thus increasing load factors on planes and as a result, reduce costs. but consolidation and transshipment add to the time costs of a movement, increase the possibility of a consignment being damaged or mis-routed, as well as adding direct handling costs of transference. finally, there are technical reasons for having both light and heavy products on a plane to ensure balance. thus, there appears to be a strong incentive for the flower and vegetable industries of a country to collaborate in developing air cargo routes and negotiate prices with the airlines. producers of floriculture products sell their stems in two main ways. many still go through a competitive, spot-auction markets and especially the amsterdam flower market (the bloemenmarkt located in aalsmeer). there are, for example, floral cargo flights from kenya to amsterdam in a regular week. the alternative is to sell directly to retailers and wholesalers where the price is known in advance (hughes, ) . the latter has the advantage of facilitating a more certain supply chain for growers, with buyers largely taking the market risk, and offers opportunities for providing value-added services, such as labelling. it also avoids the costs of middlemen and usually gets the stems to the retailers more rapidly than through an auction, thus maintaining the quality of the product. in addition, if the business is regular, forwarders can arrange block space agreements with airlines that reserves capacity for the producer; this can reduce air cargo rates and guarantee capacity will be available, as well as ensuring revenue for the carriers. but direct selling may not realize the highest current price. prices are agreed before cutting. direct selling can have important cascade effects on floriculture supply chains (nolan et al., ; kuiper and gemählich, ) . in the flower industry, inter-firm coordination occurs when a supermarket chain acts as lead firm in partnering with a brand-name global consolidator-exporter. the aim is to ensure a consistent, high volume supply of quality, certified flowers by simplifying the supply chain seen in fig. by taking produce directly from farmers to supermarkets (riisgaard and gibbon, ) . more direct selling has, though, led to a wave of consolidation among farmers to counter the power of supermarkets. for the consolidator, as the main point of contact for the large supermarkets, consignment size matters. the large consolidators have developed deeply integrated, networks of growers to source from, and invested in innovative technical and logistical capabilities enabling them to meet demands consistently and on time. smaller consolidators are better suited to non-traditional markets which demand smaller quantities of niche varieties and can provide the types of relationships often desired by smaller producers and buyers. since the s, the traditional african floriculture producing areas have encountered challengers from new supplying areas. some of these, however, have been handicapped by major transportation problems. rwanda, for example, has been trying to develop its flower exporting industry, but it remains small (chantal et al., ) . it has the natural advantage of high altitude, ranging from to over m, fertile soils, plenty of rainfall throughout the year, cheap labor, and a relatively good road network. it has seen a joint venture between the rwandan government and kenya's shalimar flowers to bring kenyan expertise to rwandan undeveloped flower sector. but, along with lack of adequate quality controls and suitable labor, long-haul transportation remains a serious impediment to development. belly-hold capacity to amsterdam, brussels and dubai is available, but involves connecting flights, while the dedicated cargo capacity to amsterdam provided by martin air is via nairobi. some of the smaller suppliers are seeking to circumvent air transportation limitations by increasing the self-life of their products and reducing the associated high costs of transportation. they have begun growing variatals of flowers and plant materials suitable for drying. south africa has an established record in this market, and rwanda has recently been developing such products. durability means they can be exported using standard road and air services to a global market without the need for a cold chain. in summary, the floriculture supply chains in africa are technically challenging and, in many instances, lack adequate investment in hard, soft, and orgware. there is evidence that floriculture supply chains can be inflexible and susceptible to disruption because of difficulties in adapting to emerging international protocols, certification requirements, and to regulations (mckinnon et al., ) . the result has been, even for the more well-established growing regions, periodic squeezes on profits. the euro crises from was an example of the problem. more recently, the hoped-for pick-up in demand after the great recession did not materialized to the extent many had hoped, and the onset of covid- has resulted in collapses of many markets. https://www.flowerweb.com/, transportation damages attract "quality remarks" presented to bidders at dutch auctions that adversely affect sale prices by up to %. https://lot.dhl.com/kenyan-flower-exports-in-full-bloom/ steen and gjolberg ( ) while there are standard requirements to sustain a successful floriculture supply chain, there are several ways these requirements can be met. the role of government has been important in the choices that have been made. in particular in the role of the authorities in controlling elements of the chain and in providing public finance has proved significant. the two main growing areas have developed under somewhat different economic structures and with differing degrees and forms of government intervention in their supply chains. flower production in kenya goes back to british colonial times, and with this the application of the anglo-saxon approach to government intervention. the country's floricultural industry is largely market driven with state involvement only when this is seen to enhance outcomes. the support of the kenyan government in promoting the floriculture industry has been mixed and has not been the decisive factor in its development (kazimierczuk et al., ) . kenya's main comparative advantage derives from its climate and low labor costs, but it has benefitted from less stringent environmental regulation, government controls over land rights, and lower trade barriers (jaffee, ; rikken, ) . in addition, farmers utilize modern technologies including drip irrigation, fertigation systems, net shading, pre-cooling, cold storage facilities, bouqueting, recycling systems to prevent wastage, wetlands for waste-water treatment, artificial lighting, grading/ packaging sheds, and reefer trucks. the use of hydroponics reduces the water used in production and makes it independent of the soil quality (bolo, ) . as early as , kenya's industry exported , tons of floricultural produce, climbing to , tons in , , in , , in , but falling slightly to , in . it then rose to , tons in (mwangi, ) . the country's flower industry employs about , people directly and up to two million indirectly, mostly women. physical quantities are not, however, the whole story. the export-oriented nature of kenya's industry makes it is vulnerable to global macroeconomic cycles and shocks. the global economic crisis of , for example, led to significantly lower flower prices, and even when exports in / grew by %, the value of stems dropped by %. slow economic growth caused foreign consumers, and by extension their grocery stores, to encourage price wars between suppliers that depressedthe prices obtained by farmers. the problem was made worse in the short term by the higher air freight rates associated with the "icelandic ash cloud" (kazimierczuk et al., ) . subsequently, with eventual economic recovery, the kenya flower council estimated the country's flowers exports in contributed $ . billion in exports, compared with $ . billion in . although there are some commercial flower growers of all sizes, about % of such exports are produced by a few dozen large and medium producers. these larger farms are better equipped than rivals in other african countries to control their entire production process, allowing integration into complex, expansive product chains. as with many sectors of africa's trade, there has been a widespread adoption of thirdparty logistics service providers as part of the chains (sohail et al., ) . kenya is the largest external supplier to the european flower market with a % market share. its major competitors, colombia, ecuador, and israel each have only half this. about % of the exports by weight are shipped to the wholesale markets in the netherlands to be sold retail in other eu countries and the uk. as noted earlier, while the dutch auctions have historically been the most important channel, changes in consumption patterns and supermarket supply chain rationalizations have led to more direct contracts. currently, about % of the exports to europe are sold directly to uk and germany providing an opportunity for value added at source through sleeving, labelling, and bouquet production. table provides an indication of the geographical spread of sales by value. lake naivashasa's location permits year-round production and facilitates the growth of the medium-sized roses that are often found in the floral sections of eu supermarkets, as well as of larger blooms favored in russia. these natural advantages have been supplemented by governmental support for the sector through reduced duties and taxes on crucial imported inputs and facilitating cooperation with the industry. the availability of air freight, with nairobi airport being a regional cargo hub, and good surface transportation provides high levels of accessibility to markets. this is combined with a ready supply of workers; kenya had an unemployment rate in of about . % according to the international labor organization. cut flower exports began in the late s when wide-bodied jets were introduced and offered additional cargo capacity to the fresh produce industry. foreign investors and partners played a critical role in launching and expanding the floriculture industry in kenya. dutch and israeli advisors, for example, were important sources of technical support. although kenyans of foreign descent or members of the kenyan elite, were initially involved in developing the industry, smallholders were also present and remain so. in , approximately large flower farms and numerous smallholder farmers were involved in the flower production, although the former dominated output (zylberberg, ; kazimierczuk et al., ) . the latter generally cooperate with the larger producers who in turn coordinate the logistics of getting flower to market. the success of the industry is, to an extent, the result of the capacity of the private sector to develop independently from the state and its capacity to quickly adapt to changing circumstances (jaffee, ; tyce, ) . while the initial shipments were exclusively carried as belly-hold cargo, as demand grew, economies of scale made dedicated freighter services viable. the industry is well organized. in , the kenya flower council was established to coordinate the efforts of independent growers and exporters and ensure implementation of acceptable international standards. its members produce over % of the country's flower exports. about % of these are rose stems which make a fast supply chain particularly important. the larger forwarders block space on flights from kenyatta airport both on passenger airlines and freighters that offer day services to europe and the middle east. a range of aviation services are available at nairobi airport, provided both by domestic and foreign airlines. as much as % of the shipments to the uk are carried as belly cargo on kenyan airways with lufthansa cargo and cargolux, providing dedicated cargo space to frankfurt and maastricht. about % of the flowers are grown around lake naivasha, some to km northwest of nairobi. good road links allow, for example, flowers picked in the morning to reach amsterdam by evening. the airport handles the vast majority the there are few detailed comparative studies of south american floricultural supply chains. vega ( ) is an exception but it is dated. https://www.voanews.com/africa/kenyas-flower-producers-eye-us-market kenya grows a number of flower types. roses have the advantage of taking only weeks between flower to bloom whereas, carnations take , alstroemeria, , and lilies, . dansk chrysanthemum kultur (dck) drove kenya's flower exports during this period (english et al., ) . established in , dck's owner reputedly gave shares in its east african subsidiary to the agriculture minister and attorney general, which helped to secure a comprehensive support package that included a low-cost long-term lease on ha of land, unlimited expatriate work permits and a -year guarantee against changes to taxation and profit repatriation laws. for example, amiran brought consultants from israel to advise the future flower growers of kenya on the adoption of large-scale greenhouses. flowers exported. nairobi enjoys significant advantages over entebbe in terms of the scale and scope of the air services offered, its terminal facilities, and its land access. in the latter context, the main growing areas are served by the major road networks in kenya. the lake naivasha region is served by nairobi -nakuru highway, the thika region by the thika road while the athi river and kitengela areas are served by mombasa road (ong'uti, ) . these major routes, although not always well maintained, provide easy access into the city center and into the airport. the feeder roads into the interiors of growing regions that move the flowers to the integrators and forwarders as seen in fig. , are of lesser quality but went through some upgrading and improved maintenance in the s. there are both charter and scheduled carriers based at the airport. as an example of global access, kenya airways' passenger services directly link nairobi with african and intercontinental destinations including london and amsterdam, and together with its strategic partners provides a cargo network involving over destinations (amankwah-amoah and debrah, ) . the airport also has significant cold-chain capacity both within its perimeter and immediately outside, although rapid transfers from road to aircraft keeps down its use. where there have been issues these have been in cold-chain warehousing prior to movements to the airports. a report by tilisi developments ltd. based on warehouse owners and tenants questioned in found that almost two-thirds were facing capacity shortages. there were also issues of poorly ventilated spaces, leakages, power shortages, and poor structural planning. in addition, there was increased stock contamination, causing flower product deterioration during storage. added to this, a case study of equator flowers located in eldoret ( km from nairobi) found the most significant causes of disruptions to the supply chain were natural disasters, logistics process design, labor union actions such as slow-downs and strikes, and production function mechanics (kangogo et al., ) . in terms of the transportation supply chain, road movements seem to pose the biggest problems, with breakdowns and congestion leading to reductions in the vase life of flowers. there can also be periodic shortages of capacity, but to facilitate market access and minimize post-harvest losses, the horticultural crops directorate has provided stand-by capacity with reefer trucks for hire by farmers, built marketing centers, and collection depots this is coupled with damage done at the packaging stage of the chain, and when there is inadequate cold-storage capacity at times of peak demand. turning to uganda, like kenya and tanzania, it has perfect conditions for commercially growing flowers. the country's cut flower business dates to , with the cut rose business beginning in and shooting chrysanthemum production in . it steadily built up a floricultural industry during the s to become africa's fourth largest producer. various forms of assistance were given to the industry including a withholding tax exemption on interest, tax exemptions on raw material, plant and machinery and on time tax refunds. in , it exported nearly $ million of cut flowers and over $ million of live plants. despite early setbacks, including growing flowers that were not suited for the climate and not meeting the quality standards of recipient countries in the eu, the industry has become a significant contributor to the national economy. in the uganda flower exporters association recognized firms as involved in the flower industry. the majority of these are in the growing and exporting stages of the value chain, with two also being transporters with the rest outsourcing their transportation. one company is a broker and wholesaler while another is a grower and broker. there are no local breeders and only one freight forwarder that provide cold chain logistics forthe industry. while uganda's ten largest flower farms export about % of their production, worth $ million annually as well as directly employing some workers with another , indirectly dependent through industries like transportation and storage, they are small compared to kenya. the flower-growing area is about ha, compared to in kenya, and there are many fewer producers. this limits the economies of scale that can be reaped in the supply chain. given the small overall size of the industry, even using forwarders to get economies from consolidation still makes it difficult to negotiate block-spaced agreements with the airlines, and there are additional risks of suitable capacity not being available when needed. the largest market for uganda's chrysanthemum shoot cuttings is the netherlands, about % of roses are handled by european middlemen (msogoya and maerere, ) , witrhretailers in norway, the uk, sweden and germany taking most of the remainder. most flower farms are located near entebbe international airport. but landing taxes and the lack of dedicated air freight for flowers mean that flying costs are around $ per kilo of flowers higher than in neighboring kenya and tanzania where dedicated air cargo is available, as well as space on passenger airlines. as a consequence, about % of the flowers are moved through kilimanjaro international airport which can only offer belly-hold space, with the remainder being exported through nairobi which also has easier, if longer, surface transportation access as well as significantly more air cargo capacity, south africa is the most mature producer of floriculture products in africa, with an industry dating back to the s and s. partly because of its historic links with the netherlands, the country has a well-established bulb exporting industry that is not reliant on a coldsupply chain and can be shipped as general cargo. the cut flower industry has just under large and medium producers of roses, chrysanthemum cuttings, carnations, gypsophila, asiatics, and irises that are mostly located within km of o.r. tambo johannesburg international airport (reinten et al., ) . the airport is easily accessed using a high-quality road network and offers a global span of passenger and cargo airline options as well as cold storage and handling facilities. the flower export industry, however, has been in something of a plateau since , at about $ million per annum, after rapid growth following the demise of apartheid. in part this is because, despite a very good aviation-supply chain, with large capacity, good surface access, and a well-developed forwarder system, it is further from some of its markets than other producers, but mainly it is because of higher labor costs. there are also imports into south africa by both road and air from zimbabwe, kenya, and zambia of cut flowers varietals that cannot be produced locally. these amounted to about $ million in . the south african industry, besides its up-to-date logistics that enables produce to arrive in good condition, maintains itself largely through the sale of its indigenous flowers. to some extent counteracting the stagnation in the cut flower business, which by value is now about % of floriculture exports, there has been growth in the export of higher value seedling, foliage and decorative plants. these are, however, particularly sensitive to local conditions necessitating care in the transportation supply chain. ethiopia is a relatively newcomer to the floriculture industry and, as such, has benefitted from not being a first mover. it has profited from being able to learn from the experiences of established growing regions, and in particular recognizing the importance of meeting international standards (gebreeyesus, ) . the development of the necessary infrastructure for a successful export industry should also be set within the broader context of national priorities to improve the country's domestic logistic systems more generally (tefera et al., ) . ethiopian floriculture involves more state participation and direction than similar industries of the former british colonies. the economy is not as strictly controlled as it was under the former derg regime, but there is still a very large public sector, most notably involving banking, telecommunications, and land and air transportation. floriculture was begun by the derg in with the growth of hypercium, erigrinium, gypsophilia, and carnation on state farms for export. growth accompanied assistance from the world bank and from the dutch in the case of several local flower growing companies, but wilted towards the end of the s seemingly due to a lack of government interest (melese and helmsing, ) . the dutch program for emerging markets (psom) not only promoted the expansion of production through joint ventures but facilitated the establishment of supporting logistics; e.g. by financing the ethiopian perishables logistics company. both local and international transportation in particular has been coordinated with the development of floriculture as part of national economic planning -the state-owned national airline, for example, provides discounts to horticultural exporters -and there have been major investments in perishable handling facilities at addis ababa's international airport. the latter have been specifically designed for flower handling and largely funded by direct foreign investment. ethiopia is the second-largest flower exporter in africa, with about flower growers on the ha of land in production. the industry earned $ million from floriculture export in , some % it's foreign trade earnings. the region's climate is ideal for several forms of floriculture, with land south of addis ababa at m above sea level providing near perfect environment for growers. the country also has the advantage of a fairly flexible labor market (mano et al., ) . the relatively large size of the producers, partly due to the difficulties smaller producers have in raising finance, facilitates economies of scale throughout much of their supply-chains. this has also led to consolidation with significant numbers of take-overs (mano and suzuki, ) . most of the growers are large enough to have their own cooled processing and packing warehouses and reefer trucks (melese and helmsing, ) . problems have arisen in recent years, however, with attacks on producing units and the burning of crops by groups opposed to the government. unfavorable movements in currency exchange rates have also had adverse impacts (belwal and chala, ) . with few exceptions, first movers and early imitators were supported by the national government and foreign aid, and involved domestically owned firms. foreign growers, either by engaging in joint ventures or through full ownership, started to enter after . a significant number of the these came from other african countries, including kenya, uganda and zimbabwe, although more recently investment has come from a wider range of countries including the netherlands, the uk and india, and regional states such as nigeria, sudan and oman. to attract foreign direct investment, the government gave implicit guarantees of stability through its control of ethiopian airlines and bole airport, and initiated financial incentives including a five-year tax holiday, duty free imports, access to bank loans and farmlands, as well as a % exemption from payment of export customs duties (mushir and hailemariam, ; bekele, ) . the biggest market for ethiopian roses is the netherlands which takes about % of the country's exports, with state-owned ethiopian airlines offering in two cargo flights of flowers a day each carrying tons. the airline also moves horticultural products to other destinations in europe, the middle east and other areas on more than flights a week. addis's state-owned bole international airport has been through major enlargement and modernization, partly funded by chinese finance. it now has africa's largest perishable produce terminal including a , square meters cold storage unit complex that was completed in . the new airfreight facility can process about , tons of cargo a year mainly for transportation to europe. given the synergies in storage, the combination of floriculture and horticulture products, reduces the unit cost of pre-flight cold storage. the effects on the blue nile region's economy and population has been somewhat mixed. this was already an area with small scale farms. the arrival of the floriculture has involved taking land from established smallholders and putting it in the hands of large, often foreign owned producers. set against a typical smallholding of one hectare supporting a household consisting of five members, a hectare production of flowers can employ as many as fifty people. there are clear macro-economic benefits from the conversion, but it has the tendency to cause enclave formation and moves away from the country's objective of food selfsufficiency, or "endogenization". added to this, those displaced in recent years are among those engaged in civil unrest. one consequence of these actions has been burnings of rose crops. this paper has considered the important role that air transportation plays in africa's floriculture supply chains, and the technical, geographical, institutional, but primarily, economic complexities confronting those engaged in it. there is a particular focus on the important interface between short-distance, surface transportation at africa's end of the chain and the intercontinental air-transportation haul to markets in europe and, increasingly, asia. much of the account in qualitative. not only is there a dearth of data for conducting any comprehensive econometric analysis, but in practice qualitative factors tend to dominate many decisions along the supply chain. africa's nations are among the poorest on the planet. there are signs, however, that some of their economies are growing more robustly in recent years. much of this growth is through international trade, and the gradual evolution of aviation supply chains has played a part in this. https://www.cargoforwarder.eu/ / / /addis-ababa-airport-onway-to-challenge-dubai/ https://globalriskinsights.com/ / /radar-foreign-investors-attackethiopia/ the latter has been important in the growth of high export earning sectors such as tourism and "exotics", as well, as other industries that can make use of africa's abundant labor supply. the emerging problem is that other regions of the globe are also rapidly developing their tourism and flower production capacities; tourism often being a compliment to floriculture because of the belly-hold air cargo capacity it provides. generally, africa lacks competitive advantage in high export earning industries because its air transportation logistics are thin, fragile, and incomplete even for the sectors in which it has a comparative advantage in production. these weaknesses extend across hardware, software and orgware. changes are coming as foreign investment takes place, deregulation of the african aviation industries are occurring, and as the presence of non-african airlines is increasing. the emerging longterm challenge is to get sufficient investment, including human capital, into the air cargo supply chain; and to do this when unified-mega economies such as china and india, as well as some south america countries, are enjoying greater access to pertinent funding. it is also unclear at this point whether the longer-standing, free market approach to air transportation logistics pursued by traditional african supplying regions can compete with the more planned approach of emergent floriculture suppliers, notably ethiopia. while the former offers more flexibility, as well as incentives for innovation, the discrete nature of many elements in the floriculture aviation supply chain requires "chunky investments" that, even according to adam smith, are sometimes best provided with state financing. the developments around lake victoria and in ethiopia highlight some of the differences in development paths to date, but it is premature to offer conclusions as to eventual outcomes. what is also important, and still under researched, is the more general question of whether floriculture is an efficient way to expend scarce resources even if a nation has a comparative over other african countries. the market for flower production is becoming increasingly global, and perhaps africa as region has limited comparative advantages. looking forward, while the free market in african air services hoped for in has not materialized and air transportation across the continent is still far from seamless, some new impetus is promised. this comes from the signing in january of an agreement between state to cooperate in a saatm and in march by members of the africa union of a provisional agreement establishing the african continental free trade area. ratification, and subsequent operationalization of the agreements, would significantly improve the continents' aviation supply chains. this is a personal research paper. credits to referees etc. are contained in the paper. logistics and global value chains in africa. the impact on trade and development the evolution of alliances in the global airline industry: a review of the africa experience. thunderbird int cold chain logistics in the floral industry an analysis of african airlines efficiency with two-stage topsis and neural networks transportation, freight rates, and economic geography road and development in ethiopia catalysts and barriers to cut flower export: a case study of ethiopian floriculture 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from ethiopia a 'private-sector success story'? uncovering the role of politics and the state in kenya's horticultural export sector the transportation costs of fresh flowers: a comparison between ecuador and major exporting countries. inter-american development bank the new institutional economics: taking stock, looking ahead africa infrastructure country diagnostic: air transportation challenges to growth air freight: a market study with implications for landlocked countries an analytic network process approach to the selection of logistics service providers for air cargo bloom or bust? a global value chain approach to smallholder flower production in kenya an earlier version of this paper was presented as the keynote lecture to the german aviation research society's workshop on aviation in africa, held at the university of applied science, bremen in june . numerous useful comments for improving the paper were gratefully received. i would also like to thank both the editor of the journal and two reviewers of the paper for their views. the final product remains my responsibility. key: cord- - sfv p authors: azuma, kenichi; yanagi, u; kagi, naoki; kim, hoon; ogata, masayuki; hayashi, motoya title: environmental factors involved in sars-cov- transmission: effect and role of indoor environmental quality in the strategy for covid- infection control date: - - journal: environ health prev med doi: . /s - - - sha: doc_id: cord_uid: sfv p the severe acute respiratory syndrome coronavirus (sars-cov- ), a new zoonotic agent that emerged in december , causes coronavirus disease (covid- ). this infection can be spread by asymptomatic, presymptomatic, and symptomatic carriers. sars-cov- spreads primarily via respiratory droplets during close person-to-person contact in a closed space, especially a building. this article summarizes the environmental factors involved in sars-cov- transmission, including a strategy to prevent sars-cov- transmission in a building environment. sars-cov- can persist on surfaces of fomites for at least days depending on the conditions. if sars-cov- is aerosolized intentionally, it is stable for at least several hours. sars-cov- is inactivated rapidly on surfaces with sunlight. close-contact aerosol transmission through smaller aerosolized particles is likely to be combined with respiratory droplets and contact transmission in a confined, crowded, and poorly ventilated indoor environment, as suggested by some cluster cases. although evidence of the effect of aerosol transmission is limited and uncertainty remains, adequate preventive measures to control indoor environmental quality are required, based on a precautionary approach, because covid- has caused serious global damages to public health, community, and the social economy. the expert panel for covid- in japan has focused on the “ cs,” namely, “closed spaces with poor ventilation,” “crowded spaces with many people,” and “close contact.” in addition, the ministry of health, labour and welfare of japan has been recommending adequate ventilation in all closed spaces in accordance with the existing standards of the law for maintenance of sanitation in buildings as one of the initial political actions to prevent the spread of covid- . however, specific standards for indoor environmental quality control have not been recommended and many scientific uncertainties remain regarding the infection dynamics and mode of sars-cov- transmission in closed indoor spaces. further research and evaluation are required regarding the effect and role of indoor environmental quality control, especially ventilation. in late december , a cluster of severe pneumonia cases emerged in humans in wuhan, hubei province, china [ , ] . the causative pathogen was identified as a novel coronavirus that was named the severe acute respiratory syndrome coronavirus (sars-cov- ) [ , ] . the disease rapidly spread internationally, raising global public health concerns, and was subsequently termed coronavirus disease [ , ] . the most common clinical manifestations of patients with covid- are fever, cough, shortness of breath, and fatigue. some patients have also shown radiographic ground-glass lung changes and eventually died of acute respiratory distress syndrome (ards) [ , ] . the world health organization (who) declared covid- as a global pandemic on march , [ ] . sars-cov- is mainly transmitted human-to-human through close contact, respiratory droplets, fomites, and contaminated surfaces [ ] [ ] [ ] [ ] . the who adapted a m social distancing policy, based primarily on the assumption that the virus is transmitted through largely isolated droplets within this range [ ] . however, the possibility of airborne transmission through airborne particles with diameters smaller than μm has been suggested [ ] . several factors are involved in the transmission of sars-cov- between individuals, including the environment in buildings and human behavior [ ] [ ] [ ] [ ] [ ] [ ] . similar to the transmission routes of other respiratory viruses, such as influenza or human coronavirus [ ] [ ] [ ] , possible exposure pathways for covid- infection by the sars-cov- are finger contact with virus-contaminated surfaces (fomites) and subsequent finger contact with the facial membranes; inhalation of the virus carried in airborne particles (inhalable or respirable particles) exhaled from cough or vocalization; and droplet spray, the direct projection of the virus carried in particles exhaled from cough or vocalization onto the facial membranes. therefore, environmental factors in buildings, including temperature, humidity, stability on fomites, and ventilation and filtering systems, such as in public places, healthcare settings, restaurants, hotels, recreation facilities, or residential houses where people are close together, could have a significant influence on the infection. adequate control of these environmental factors and proper human behavior in accordance with these environmental conditions play a significant role in preventing the spread of covid- [ ] . as most people spend more than % of their daily lives inside buildings, it is essential to understand the potential transmission dynamics of sars-cov- inside a building, the spatial dynamics, and the building operational factors that potentially promote and mitigate the transmission of sars-cov- and the spread of covid- . this article aimed to review the effect of environmental factors in buildings, spatial dynamics, and building operational factors. in addition, a strategy to prevent sars-cov- transmission in building environments based on indoor environmental quality control recommended by the japanese ministries is also summarized. the characteristics of environmental air quality and environmental surfaces contaminated by the virus are important factors that determine the infectivity retention and extent and speed of the spread of the virus. the long-time persistence of these environmental factors influences the spread of covid- [ ] . the sars-cov- genetic material, ribonucleic acid (rna), was detected in the rooms of both symptomatic and asymptomatic cruise ship passengers up to days after the cabins were vacated [ ] . the sars-cov- rna was detected on the surfaces of the floor around the toilet, in the bedroom, bed pillow, phone, table, television remote control, chair arm, toilet flush button, toilet seat, and other items in the cruise ship [ ] . although the infectiousness of those materials is not known, the environment around the covid- cases was contaminated extensively with sars-cov- during the covid- outbreak on the cruise ship. the persistence of sars-cov- in aerosols in different environmental conditions has been reported. the results are summarized in table . van doremalen et al. compared the survival rate and half-life of sars-cov- and sars-cov- within h of aerosolization at a temperature of °c- °c and a relative humidity (rh) of %. both viruses were detectable after h of aerosolization and the median half-lives were . and . h for sars-cov- and sars-cov- , respectively [ ] . these results showed that the stability of sars-cov- was similar to that of sars-cov- . smither et al. reported that sars-cov- is more stable at a medium rh of - % (decay rate, . %/min) compared with a higher rh of - % (decay rate, . %/min) in tissue culture media (tcm), whereas the converse was observed in artificial saliva, with a decay rate of . % per minute at a medium rh and . % per minute at a higher rh [ ] . the results of the half-life obtained with tcm at a medium rh were similar to those described above [ ] . although the infectious dose in humans is not known, sars-cov- may be able to remain viable and infectious in aerosols for hours (depending on the inoculum shed), if the virus is produced within smallparticle aerosols. sars-cov- is susceptible to heat treatment but can persist for at least days at refrigerated temperatures of °c. with an increase in the incubation temperature, the time for virus inactivation was reduced dramatically to days at °c and to min at °c [ ] . sars-cov- demonstrates tendencies similar to those of sars-cov- [ ] . in simulated saliva on a stainless steel surface, sars-cov- exhibits negligible decay over min in darkness but loses % of its infectivity every . - . min, depending on the intensity of simulated ultraviolet (uv) b radiation levels, when exposed to simulated sunlight representative of the summer solstice at °n latitude at sea level on a clear day [ ] . these data indicate that sunlight may inactivate sars-cov- rapidly on surfaces, suggesting that persistence and subsequently exposure risk may vary significantly between indoor and outdoor environments. experimental studies using sars-cov- aerosols produced from artificial saliva found that simulated sunlight inactivates the virus rapidly [ ] . in dark conditions, the half-life of aerosolized sars-cov- is approximately min in simulated saliva. the high-intensity sunlightsimulated summer was found to show a % reduction in infectious concentration after min. even with the low-intensity sunlight-simulated late winter or early fall, a % reduction was observed at min. however, relative humidity ( , , , and %) had no significant effect on the survival of the aerosolized virus. these data indicate that sunlight is useful in mitigation strategies to minimize the potential for aerosol transmission. stability on surfaces of fomites sars-cov- can persist on plastic, stainless steel, and glass surfaces between and days at room temperature (table ) [ , ] . the persistence of sars-cov- on those surfaces was similar to that of sars-cov- [ , , ] . the survivability of these viruses on metal surfaces differed according to the type of metal. both sars-cov- and sars-cov- survived for shorter periods on copper ( and h, respectively) than on stainless steel surfaces [ ] . the antimicrobial properties of copper and copper alloy have been reported against various viruses [ , ] . several mechanisms have been proposed regarding copper-induced cellular toxicity to the virus. reactive oxygen species generated by free copper ions cause the cells to commit metabolic suicide. copper ions can induce protein destabilization on the virus. copper ions have a direct effect on virus inactivation by causing aggregation of virus particles [ ] . this might explain the short survival of sars-cov- and sars-cov- on copper surfaces compared with other metal surfaces. studies have reported that copper alloys (≥ % copper) reduced the surface microorganisms when incorporated into various hospital furnishings and fittings [ , ] . the use of copper in combination with optimal infection-prevention strategies may further reduce the risk of patients and healthcare workers acquiring covid- infection in healthcare environments. sars-cov- showed variable persistence on different porous surfaces, such as paper, cardboard, wood, cloth, and mask. sars-cov- survived on the inner and outer layers of surgical facemasks for and days, respectively [ ] . in other words, the infectious virus can be recovered from a surgical mask after days ( °c, % rh). sars-cov- survived for day on cardboard, wood, and cloth [ , ] . it survived for days on banknote paper [ ] . however, the virus survived for only min on paper and tissue paper, with complete decay after h [ ] . under the same conditions, sars-cov- survived for a longer time ( day) than sars-cov- , which survived for only h [ ] . interestingly, the stability of sars-cov- was enhanced when present with bovine serum albumin, which [ ] is used commonly to represent sources of protein found in human sputum [ ] . conversely, sars-cov- decayed more rapidly when either the humidity or the temperature was increased, but the droplet volume and surface type (stainless steel, plastic, or nitrile glove) did not impact the decay rate significantly. at room temperature ( °c), the virus half-life ranged from . to . h depending on the relative humidity but was reduced to . - . h when the temperature was increased to °c [ ] . these findings suggest that a potential for fomite transmission may persist for hours to days in indoor environments and that the survivability of fomites is affected by temperature and relative humidity, as well as by the presence of protein found in human sputum. in summary, virus survival decreases with an increase in temperature. maintaining temperatures above °c for more than min usually inactivate most viruses [ ] . sars-cov- is also susceptible to heat treatment. persistence of sars-cov- on dry inanimate surfaces was range for - days. the persistence of influenza virus, rhinovirus, and norovirus was reported at - days, h − days, and h − days, respectively [ ] . thus, sars-cov- can remain infectious on the surfaces compared with the influenza virus. however, the persistence of sars-cov- was significantly low on copper as compared with other surfaces such as plastics, stainless steel, glass, and fabrics. in addition, sunlight can rapidly inactivate sars-cov- . these findings droplet and contact transmission have accounted for the main routes of infection related to covid- . in addition, the who announced the possibility of aerosol infection in specific circumstances, such as endotracheal intubation, bronchoscopy, etc. [ ] . on the other hand, some researchers have claimed a risk of short-and medium-range person-to-person distance in aerosol transmission, but evidently, airborne transmission (longrange distance) has not been acknowledged [ ] . nicas et al. estimated that the relative contributions of four influenza virus exposure pathways, namely ( ) virus-contaminated hand contact with facial mucous membranes, ( ) inhalation of respirable cough particles, ( ) inhalation of inspirable cough particles, and ( ) the spray of cough droplets onto facial mucosa, account for , , . , and % risk of influenza infection, respectively [ ] . the transmission routes for these cough particles can be categorized as "droplet transmission," where droplets (> μm diameter, traveling < m) containing viable viruses make contact with the nose, mouth, eyes, or upper respiratory tract; and "airborne transmission" where droplet nuclei (< μm diameter, which can travel > m) are inhaled by susceptible individuals [ ] . the who has stated that airborne transmission is different from droplet transmission as it refers to the presence of microbes within droplet nuclei, which are generally considered to be particles smaller than μm in diameter, can remain in the air for long periods of time and can be transmitted to others over distances greater than m [ ] . from the view of this statement, the covid- virus can be transmitted by direct contact via infected people and indirect contact via surfaces in the immediate environment or with objects used by the infected person, not by airborne transmission through small airborne particles. recently, researchers insisted on the potential risk of indoor airborne transmission of sars-cov- and the importance of sufficient and effective ventilation, particle filtration, and air sterilization as infection control measures inside buildings [ ] . the who recognized the potential risks of the airborne spread of covid- [ ] . however, a recent experimental study using transgenic mice indicated that sars-cov- could be experimentally transmitted among mice by close contact, through respiratory droplets, but is hardly transmitted through exposure to airborne particles [ ] . a recent study also indicated that the role of airborne particles as carriers of the virus diffusion is not evident [ ] . in discussing the airborne transmission of sars-cov- , it is important to understand the characteristics of aerosol particles emitted by cough and speech in indoor environments. this section describes briefly the size distribution of droplets, the emission rate of droplets by cough and speech, and the resuspension of particles deposited on floor surfaces. sars-cov- has a diameter of - nm, with characteristic spikes ranging from to nm [ ] . johnson et al. determined an aerosol droplet size distribution ranging from nm to mm, generated by breathing, speech, and voluntary coughing by using the expired droplet investigation system with an aerodynamic particle sizer (aps) and a droplet deposition analysis (dda) [ ] . in the case of speech, three different droplet size distribution modes were identified, with median diameters at . , . , and μm. in the case of voluntary coughing, the modes were located at . , . , and μm. therefore, a wide range of droplet sizes is emitted by speaking and coughing. the key point in this study was that small droplets can be emitted not only by speaking and coughing but also through breathing. individuals infected by sars-cov- without symptoms can also transmit the infection to others. the emission by natural breathing without coughing or sneezing is also important to understand the transmission from infected individuals without symptoms. asadi et al. placed aps in a laminar flow hood to characterize the number and size distribution of particles emitted by individual human volunteers while performing various vocalizations and breathing activities [ ] . the results showed that the rate of particle emission during normal human speech is correlated positively with the loudness (amplitude) of vocalization, ranging from approximately to particles per second ( . to particles/cm ) for low to high wavelengths, regardless of the language spoken (english, spanish, mandarin, or arabic). the results also indicated that the droplets could be emitted not only by speech but also by singing a song, cheering loudly for sports games, and so on. rahmani et al. reviewed the methods for the sampling and detection of coronaviruses, especially sars-cov- . most of the samplers used, such as polytetrafluoroethylene filters, gelatin filters, and cyclones, showed a suitable performance to trap sars-cov and middle east respiratory syndrome (mers)-cov, followed by polymerase chain reaction (pcr) analysis [ ] . some studies reported detecting sars-cov- from patients' rooms in hospitals, although it seems difficult to discriminate whether these were airborne or transmitted through respiratory droplets because sampling conditions (i.e., the patient's distance from the sampler, patient's activities, coughing and sneezing during sampling time, etc.) can affect the results. liu et al. investigated airborne sars-cov- by measuring viral rna in aerosols in two different hospitals in wuhan during the covid- outbreak in february and march [ ] . the unique point in this study was to investigate the size distributions of airborne sars-cov- droplets. aerosol samples were collected using a miniature cascade impactor (sioutas impactor, skc) that could separate aerosols into five ranges (> . , . - . , . - . , and . - . μm on -mm filter substrates and - . μm on -mm filters) and determined through the quantification of their genetic material (rna). sars-cov- aerosols were found to include mainly two size ranges, one in the submicrometer region (d p . - . μm) and the other in the supermicrometer region (d p > . μm), in isolation wards of ventilated patient rooms and medical staff areas. the authors hypothesized that the source of the submicrometer virus-laden aerosols may be resuspension from the surface of the protective apparel worn by medical staff while they are removing the equipment. the resuspension occurs largely because of the particle surface properties, human activities, environmental conditions, and so on. resuspension occurs mainly as a result of human activities, especially walking in indoor spaces. qian et al. reviewed particle resuspension owing to human walking in indoor environments [ ] . from the results presented, resuspension is an important source compared with other indoor sources, such as cooking and stoves, and resuspension increases with particle size in the range of . - μm. many researchers proposed resuspension terms, such as a resuspension rate coefficient (h − ), a resuspension fraction (-), an emission rate (mg/h), a resuspension factor (m − ), and a resuspension emission factor (mg/mg). rosati et al. experimentally investigated the characterization of the size distribution of resuspended particle matter from the carpet during walking events [ ] . the resuspension emission factor by particle size was defined as the resuspension emission rate by particle load on the carpet by particle size. the emission factors were approximately − to − of particle diameter to μm. therefore, a small portion of particles deposited on the floor can be resuspended in indoor air. the resuspension is progressively more likely to occur by larger particles than by smaller ones. although there are a few studies on bioaerosols, and especially virus particles, bioaerosol resuspension is clearly not the same as infectious virus resuspension. it is important for airborne transmission to understand the droplet diameter emitted from patients. previous studies indicated that an aerosol droplet size distribution was ranged from nm to mm, generated not only by speaking and coughing but also through breathing. from the field measurements in the hospital, sars-cov- aerosols could be detected to include mainly two size ranges, . - . μm and larger than . μm, in isolation wards of ventilated patient rooms and medical staff areas. moreover, the resuspension is progressively more likely to occur by larger particles than by smaller ones, but bioaerosol resuspension cannot be clearly the same as infectious virus resuspension. the number of secondary infections of covid- varies widely, and most outbreaks of many secondary infections occur under common indoor environmental factors [ , ] . given the lack of data to define environmental control measures against covid- based on quantitative analysis, it is important to understand the conditions common to outbreak cases and to take measures to minimize the indoor environmental factors that promote infection. in this section, we summarize the cases of outbreaks in which indoor environmental factors, including human behavior, are believed to have facilitated infection, as well as the environmental survey of sars-cov- . on january , , a covid- outbreak occurred in a restaurant in guangzhou, china, infecting ten people in three families. the minimum length of time during which the index-infected person was present with the secondary infected person was min, and the possibility of contact infection was considered to be low based on in-store camera recordings. fifty percent (five of ten) of those at the same table as the infected person were found to be infected within the next days. at the adjacent leeward table, % (three of four) were infected. two of the seven people at the windward table were infected. other diners who were located away from the airflow around the infected tables, as well as the staff, were not infected. lu et al. concluded that the airflow from the air-conditioners promoted droplet infection and recommended that distances between people are maintained and ventilation improved [ ] . in this case, li et al. conducted a detailed investigation of the indoor environment by measuring the ventilation rate and conducting a numerical thermo-fluid analysis. as a result, they found that only the ventilation fan in the restroom was in operation. the ventilation fan on the wall of the restaurant was sealed and not in operation, and the ventilation rate ranged from . to . air changes per hour (ach) and . to . l/s per person. they suggested that poor ventilation may have been the primary cause of the spread of the infection by aerosol transmission [ ] . ninety-four people tested positive for the virus on one floor of the call center, where employees worked. [ , ] . meat-processing plants have emerged as hotspots for sars-cov- around the world. an outbreak of sars-cov- at germany's largest meat-processing facility resulted in more than confirmed infections during tests conducted a month after the initial outbreak. guenther et al. conducted a causal investigation into the may outbreak. it was suggested that the infected person, who was the first example of a supplemental case, transmitted the virus to a colleague more than m away over consecutive working days. the low temperature in an environment with the low intake of outside air and air circulation through the airconditioning system in the hall, combined with the high physical workload of workers with heavy breathing, have been suggested as factors that enabled transmission over distances greater than m by virus-containing aerosol particles. they stated that under these circumstances, distances of . - m are not sufficient to prevent infection and that the wearing of masks, improved ventilation and airflow, and the installation of filtering devices are necessary to reduce the risk of infection [ ] . these outbreaks strongly suggest that in a confined, crowded, and poorly ventilated environment where conversations, loud vocalizations, and heavy breathing take place, sars-cov- can spread through the air at a distance of m or more and may result in a large number of secondary infections. the who defines droplets and droplet nuclei as respiratory aerosols more than μm in diameter and the residue of dried respiratory aerosols up to μm in diameter, produced by the evaporation of droplets coughed or sneezed into the atmosphere or aerosolized infective material, respectively [ ] . based on field measurement results at wuhan hospitals during the covid- outbreak, liu et al. reported that the peak concentration of sars-cov- aerosols appears in two distinct size ranges: at the submicron scale with dominant aerodynamic diameters between . and . μm; and at the supermicron scale with diameters greater than . μm [ ] . the main sources of sars-cov- aerosols are coughs and sneezes by infected persons. the capacity for droplets to travel long distances in airflow is determined largely by their size. most communicable respiratory infections are transmitted via large droplets over short distances or contact with contaminated surfaces. large droplets (diameter, > μm) tend to settle quickly from the air, and thus the risk of pathogen transmission is limited to individuals in close proximity to the saliva droplet source. small droplets (diameter, ≤ μm) may be involved in short-range transmission (i.e., when the distance between individuals is less than m) and are likely to evaporate into droplet nuclei (diameter, < μm) in favorable environments, making them candidates for long-distance aerosol transmission [ ] . the terminal settling velocity of a particle increases rapidly with its size, as it is proportional to the square of particle diameter. the terminal settling velocity of a particle up to μm in size is less than . cm/s ( . m/s) [ ] , and because the particle diameter decreases as a result of the evaporation of the droplets during settling, droplets will remain suspended for a longer time indoors based on the relative indoor humidity [ ] . therefore, aerosols up to μm in diameter are carried easily over long distances (final inlet air) by the indoor airflow generated by air conditioning or ventilation equipment. field measurements show that the largest and average velocities in occupant space are . and . m/s, respectively [ , ] . it is possible to control aerosols containing a virus with a proper indoor airflow plan. regarding the indoor airflow plan, there are different types of ventilation systems such as piston flow ventilation and mixing-type ventilation. when the infected individual's position can be fixed, piston flow ventilation or push-pull ventilation is applicable. however, as the positions of infected people cannot be pinpointed in general environments, mixing-type ventilation is more effective because it dilutes the infectious aerosols to decrease their concentration in the air. to describe the relationship between the air exchange rate and the probability of infection, the wells-riley model was used: this model is based on the assumption that the air in the room is well mixed, leading to a uniform concentration of bioaerosols throughout the space. to estimate the probability of infection in a room, the quantum generation rate must be determined. a quantum represents the minimum dose that can cause infection in the host [ ] , and the quantum generation rate is the number of quanta produced per hour per infectious individual. table provides the values of quantum generation rates reported for different infectious aerosols [ ] . dai and zhao estimated the quantum generation rate of covid- by fitting the relationships between known rates and r (the basic reproduction number) of the infectious agents listed in table [ ] . the results indicate that the quantum generation rate for covid- ranges from to h − . figure shows the schematics of the two typical heating, ventilation, and air-conditioning (hvac) systems used in japanese office buildings. system a is the centralized hvac system (cs) and system b is the individual hvac system (is). the ventilation rates of the cs are generally approximately ach for outdoor air and ach for return air. moreover, the cs normally uses an air filter with a collection efficiency approximately equivalent to a minimum efficiency reporting value (merv) of , indicating a removal efficiency of % of droplets from human respiration activities, most of which are less than - μm in diameter [ ] [ ] [ ] . in this case, the equivalent change rate is approximately . ach (= ach + ach × %). figure shows the probability of infection plotted against the equivalent air change rate (hourly rate of room ventilation with clean air) based on eq. ( ). the prediction conditions are shown as i = person, p = . m /(hour⋅person), t = h, room floor area = m , ceiling height = . m. the higher the equivalent air change rate (the room ventilation rate with clean air/ room volume), the lower the probability of infection. furthermore, the cs shows a lower probability of infections than the is because of the larger amount of clean air. the use of highly efficient particle filtration in centralized hvac systems reduces the airborne load of infectious particles [ , ] . the collection efficiency of air filters for suspended particles by particle size is given in table . in japanese office buildings, medium-efficiency air filters (merv - in table ) are typically used, whereas high-efficiency particulate air filters (hepa: . % or higher particle collection efficiency for particles sized . μm at the rated airflow volume) are used for rooms such as hospital operating rooms that demand high air cleanliness. it is known that ultraviolet germicidal irradiation (uvgi) systems are used for air and surface disinfection. investigations of the bactericidal effect of sunlight in the late th century planted the seed of air disinfection by uv radiation. the first to nurture this seed was wells, who both discovered the spread of airborne infection by droplet nuclei and demonstrated the ability of uvgi to prevent such a spread. with modern concerns regarding multi-and extensive drug-resistant tuberculosis, bioterrorism, influenza pandemics, and severe acute respiratory syndrome, interest in uvgi continues to grow [ ] . the centers for disease control and prevention (cdc) [ ] and the american society of heating, refrigerating and air-conditioning engineers (ashrae) [ ] recommend the application of uvgi to fight airborne diseases. microbes are uniquely vulnerable to light of wavelengths at or near . nm because the maximum absorption wavelength of a deoxyribonucleic acid (dna) molecule is nm. the chemical compound pyrimidine in a dna base strongly absorbs uv light. after irradiation, the dna sequence where two pyrimidines link can form pyrimidine dimers. these dimers can change the dna double-helix structure and interfere with dna duplication, as well as lead to the destruction of the replication ability of cells and thus render the cells noninfectious [ , ] . regarding the sterilization or inactive performance of uvc, the population st of microbes exposed to any biocidal factor is described by the characteristic logarithmic decay equation: where k = the standard decay-rate constant (cm /mw⋅s), i = the intensity of uvgi (mw/cm ), and t = the exposure time (s). the standard decay-rate constant of the influenza a virus has been reported as . cm /μw⋅s [ ] [ ] [ ] . recently, upper-room uvgi and in-duct uvgi have been the two primary applications of uvgi air disinfection. in-duct uvgi is designed to disinfect air as it passes through the hvac system before it is recirculated or exhausted, and it has been also suggested to reduce nonspecific building-related illnesses [ , ] . in summary, since small droplets (diameter, ≤ μm) are likely to evaporate into droplet nuclei (diameter, < μm) in favorable environments, and the terminal settling velocity of a particle up to μm in size is lower than . cm/s ( . m/s), it is possible to control aerosols containing a virus with a proper indoor airflow plan and sufficient ventilation rates. moreover, filtration is effective in the reduction of aerosol concentration. ventilation and filtration can contribute to the reduction of indoor infection probability. on the other hand, it is well-known that uvgi is an effective measure against microbes. the who, the cdc, and the ashrae recommend the application of uvgi to fight airborne diseases. the application in japan will be expected. it is important to decide the adequate measures against a new infectious agent by analyzing actual infection cases and to execute them as soon as possible. as of february , , the ministry of health, labour and welfare (mhlw) covid- response team examined a total of cases among clusters and investigated who acquired infection from whom. all clusters were associated with close contact in indoor environments, including fitness gyms, a restaurant boat on a river, a club with live music, healthcare facilities, and a snow festival where there were eating spaces in tents with minimal ventilation rate [ ] . therefore, the mhlw published a document titled "prevention of the covid- clusters" abbreviation: sars-cov severe acute respiratory syndrome coronavirus fig. traditional japanese office building hvac systems: a a centralized hvac system; and b a centralized ventilation system with an individual air-conditioning system on march , [ ] , showing the need for adequate ventilation in buildings because a ventilation standard for infection control has not been established in general buildings in japan and the characteristics of indoor spaces where the clusters occurred might include poor ventilation and crowding. therefore, the " cs," namely, "closed spaces with poor ventilation," "crowded spaces with many people," and "close contact," such as from intimate conversations, loud cheering, singing, or exercise within a short distance from other individuals, were proposed as important factors that result in a covid- cluster [ , ] . the mhlw published "ventilation to improve "closed spaces with poor ventilation" in commercial facilities" on march , , based on the analysis by the mhlw covid- response team concerning the actual ventilation state against the standards in the law for maintenance of sanitation in buildings, and recommended adequate ventilation rates in accordance with the standards of the law and the increase in the ventilation rates by adjusting the ventilation systems and opening the windows [ ] . furthermore, this recommendation was added in the "measures to prevent the large-scale spread of covid- in workplaces" on march , [ ] . on april , , a document titled "maintenance of air-conditioning and ventilation systems in specific buildings" was published and adequate ventilation was requested again [ ] . moreover, on april , , the managers of commercial facilities were informed of the "methods of ventilation for improving "closed spaces with poor ventilation," and the guidelines of ventilation measures in both specific buildings and other buildings were provided [ ] . in these documents, the required ventilation rate of approximately m /h per person was recommended [ ] . when this ventilation rate was determined, the results of studies on tuberculosis [ ] [ ] [ ] and measles [ ] , which are infectious diseases known to be spread by airborne transmission, were considered [ ] . the ventilation rates needed are indicated not per room but per person and if adequate ventilation is not secured in the room, the number of persons should be limited to avoid overcrowding, which may be a factor in clusters of infected individuals. the ventilation rates needed to prevent sars-cov- transmission have not been reported; thus, opening windows has also been recommended. however, it was difficult to recommend the specific methods because the conditions of the rooms (e.g., the number of windows, and the width and direction of the windows) are different. in the expert meeting on novel coronavirus disease control on may , a "new lifestyle" for the long-term fight against covid- was suggested, comprising three basic measures: social distancing, wearing face masks, and washing hands [ ] . since the middle of april, researchers on building hygiene have collected recent scientific findings and discussed the ventilation measures towards summer [ ] . during the rainy season and summer, opening the windows may create a poor indoor environment with insufficient air-conditioner cooling and dehumidification, resulting in increased risks of heatstroke, insomnia, and allergies owing to mold and mites. after discussions, the researchers produced a document titled "indoor environmental measures in summer against covid- : the suggestion from the researchers on building hygiene" on may , and provided it to the expert meeting members on novel coronavirus disease control and headquarters of the mhlw [ ] . from the present evidence, it is difficult to indicate specific standard values, such as ventilation rates. thus, ventilation and air-conditioning measures recommended under some conditions were shown, see table . on may , , the ministry of the environment and the mhlw served local governments a notice of "action for prevention of heatstroke in ," which requested that they take action to prevent heatstroke under the spread of covid- [ ] . the headquarters of covid- prevention in the mhlw considered expert opinions, scientific literature, international standards, and laws and regulations in japan in the search for effective methods, and published a document titled "ventilation for improving "closed spaces with poor ventilation" with prevention of heatstroke" on june , [ ] . in addition, it published the document titled "methods of ventilation for improving "closed spaces with poor ventilation" with prevention of heatstroke for owners using air-conditioning system without ventilation in commercial facilities" on june , [ ] . the document shows points to remember while opening windows for ventilation, in using air cleaners, and so on. furthermore, in the "q&a for the public," information was provided on home air conditioners and ventilation during the hottest season. it was indicated that air conditioners should be used to prevent heatstroke, but that general air conditioners do not have a ventilatory function; thus, the whole air of a room should be ventilated twice or more per hour and the use of a -h mechanical ventilation system is effective. the society of heating, air-conditioning and sanitary engineering of japan started a special committee against covid- and published a document titled "is covid- spread by air-conditioning or ventilation?-experts' opinions" on june , . in the document, the relationship between airconditioning or ventilation and the risk of infection, the possibility of the spread of covid- through air conditioners, the infection risk by inadequate ventilation and filters, and the prevention of heatstroke with infection control are discussed and the following remarks were obtained [ ] : in japanese buildings, which are designed and managed in accordance with the law for maintenance of sanitation in buildings, considering the performance of ventilation and filters, the risk of the spread of covid- in a room through airconditioning systems is believed to be very low. however, in the case of buildings without the general-performance filters in air conditioners, commercial package-type air conditioners, or a fan coil unit (i.e., fcu), another ventilation method should be added. securing ventilation rates per person may prevent droplet infection through airflow. in hospitals and clinics where individuals can wear face masks all the time, the droplet from infected individuals can be prevented. when adequate ventilation rates are secured, it is necessary to use air conditioners to prevent heatstroke in summer. in hospitals and clinics where individuals are believed to be infected, the airflow from air conditioners should not be directed to any person. considering the fact that in a poorly ventilated room, an individual was infected when spending time with an infected person for less than an hour, not intermittent but continuous ventilation is desirable. in cases where natural ventilation is available, it is desirable to secure ventilation rates by opening the windows and so on if an adequate room temperature is secured. however, in the buildings designed and managed in accordance with the law for maintenance of sanitation in buildings, natural ventilation may cause a bad influence on air balance and may be beyond the standards of the law. thus, it is desirable to consult experts. an industry-classified guideline for the prevention of the spread of covid- was made based on the proposal by the experts' meeting on may , . as of writing this article, approximately guidelines were available on the website of the cabinet secretariat of the japanese government [ ] . the items concerning building environments are cleaning, disinfection, ventilation, room density, etc., and guidelines are shown according to the characteristics of each industry. regarding ventilation, the specific rates or times are not indicated because of the various conditions of ventilation systems or windows. since pneumonia caused by sars-cov- was confirmed in december , the mechanism of infection in an indoor environment has not been clarified. it is important to understand infection mechanism through various studies such as investigation of infection cluster spaces and experiments on the relationship between such environmental factors as temperature and humidity and the infectiousness of the virus. based on these studies, further adequate strategy for the infection risk management in an indoor environment is required. in environmental stabilities of sars-cov- , this virus can persist on the fomite surfaces, such as plastic or metal, between and days in an indoor environment such as a building. sars-cov- in aerosols is also stable for at least several hours if the virus is produced within small-particle aerosols. sars-cov- is mainly transmitted between humans through close contact and respiratory droplets, including fomite transmission. however, close-contact aerosol transmission through smaller aerosolized particles is likely to be combined with respiratory droplet and contact transmission in a confined, crowded, and poorly ventilated indoor environment, as some cluster cases have suggested. therefore, adequate preventive measures to control indoor environmental quality are required. the risk of closecontact aerosol transmission can be reduced sufficiently by taking measures such as ensuring adequate ventilation in accordance with the number of individuals in a room and wearing masks to reduce the aerosols emitted into the indoor air. filtration and uvgi systems have also been developed. however, indoor environmental quality control measures such as ventilation alone cannot prevent exposure from an infected person at a short distance or through environmental surfaces; thus, adequate preventive measures against respiratory droplet and contact transmission, such as disinfection of fomites, hand hygiene, uncrowded spacing, and the wearing of masks, must be taken at appropriate times and places. in japan, epidemiological links to confirmed covid- cases showed that clusters of cases occurred in fitness gyms, a restaurant boat on a river, and a club with live music in february . based on these findings, the expert panel for covid- focused on the " cs," namely, "closed spaces with poor ventilation," "crowded spaces with many people," and "close contact." in addition, the mhlw has recommended adequate ventilation in all closed spaces in accordance with the existing standard of the law for maintenance of sanitation in buildings. although specific ventilation standards for the control of sars-cov- transmission cannot be derived from the existing scientific evidence, covid- has caused serious global damage to public health, community, and the social economy. the united nations conference on environment and development adopted the rio declaration on environment and development in [ ] . table recommendations on the ventilation and air-conditioning measures to prevent covid- infection every indoor space • enough ventilation is necessary to prevent covid- infection. • opening windows is effective for ventilation and opening them wide and for a longer time is desirable. • in summer, air conditioners are necessary to prevent health risks such as heatstroke, etc. • general air conditioners do not function as ventilators, so mechanical ventilation and opening windows are necessary. • when opening windows, it is necessary to prevent harmful insects and animals from coming in. spaces in which air conditioning and ventilation systems are installed • it is necessary to check the systems and to confirm enough ventilation rates are secured. • it is necessary to limit the number of persons in a room or shorten the time they are inside secure enough ventilation rates per person. • it is necessary to investigate what the building is used for, how often it is used, what kind of airconditioning and ventilation system is used in the building when taking such measures as the better control of air-conditioning and ventilation systems, or the use of air cleaners, and the use of humidifiers in winter. principle states: "in order to protect the environment, the precautionary approach shall be widely applied by states according to their capabilities. where there are threats of serious or irreversible damage, lack of full scientific certainty shall not be used as a reason for postponing cost-effective measures to prevent environmental degradation." this principle was also applied to the threats to human health in the public health domain [ ] [ ] [ ] . based on principle , the implementation of practical precautionary measures that took into account technical feasibility, adequate control measures and strategies, and social, economic, and cultural conditions is essential to protect the public from sars-cov- transmission. however, the implementation of an approach based on the precautionary principle should start with a scientific evaluation, as complete as possible, and where possible, identifying at each stage the degree of scientific uncertainty [ ] . therefore, further research and evaluation are required to evaluate the effect and role of indoor environmental quality control, especially ventilation. in this paper, we summarize the effect and role of environmental factors in buildings, spatial dynamics, building operational factors, and a strategy to prevent sars-cov- transmission in a building environment. most transmission has occurred in indoor environments in a closed space, especially inside a building. although ventilation based on the existing regulation has been recommended by the mhlw as one of the initial political actions to prevent the spread of this novel infectious disease, the specific standard has not been recommended. to protect public health from sars-cov- transmission, further research on infection dynamics and the mode of infection in sars-cov- transmission in closed spaces, investigations on indoor environments in the infected cluster spaces, experiments on the influences of indoor environmental conditions on covid- infection, and the effects of ventilation are urgently required. in addition, the development of control measures, guidelines, and strategies to maintain indoor environmental quality at an adequate level are required. a new 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characterization of expiration air jets and droplet size distributions immediately at the mouth opening size distribution and sites of origin of droplets expelled from the human respiratory tract during expiratory activities airborne spread of expiratory droplet nuclei between the occupants of indoor environments: a review ashrae position document on airborne infectious diseases hvac filtration for controlling infectious airborne disease transmission in indoor environments: predicting risk reductions and operational costs the history of ultraviolet germicidal irradiation for air disinfection guidelines for environmental infection control in health-care facilities ashrae. ashrae position document on infectious aerosols the application of ultraviolet germicidal irradiation to control transmission of airborne disease: bioterrorism countermeasure inactivation of virus-containing aerosols by ultraviolet germicidal irradiation inactivation of airborne viruses by ultraviolet irradiation filtration of airborne microorganisms: modeling and prediction immune building systems technology effectiveness of germicidal uv radiation for reducing fungal contamination within air-handling units effect of ultraviolet germicidal lights installed in office ventilation systems on workers' health and wellbeing: double-blind multiple crossover trial tokyo: national task force for covid- outbreak in japan, prime minister of japan and his cabinet national task force for covid- outbreak in japan. epidemiology of covid- outbreak in japan tokyo: national task force for covid- outbreak in japan, prime minister of japan and his cabinet ventilation to improve "closed spaces with poor ventilation" in commercial facilities measures to prevent the large-scale spread of covid- in workplaces maintenance of air-conditioning and ventilation systems in specific buildings methods of ventilation for improving "closed spaces with poor ventilation hospital ventilation and risk for tuberculous infection in canadian health care workers. canadian collaborative group in nosocomial transmission of tb environmental factors relating to a mass outbreak of tuberculosis in a junior high school in association with tuberculous group infection in cram school: effect of ventilation on the infection risk measles outbreak in a pediatric practice: airborne transmission in an office setting emncdc. analysis of the response to the novel coronavirus disease (covid- ) and recommendations tokyo: ministry of health, labour and welfare ventilation for improving "closed spaces with poor ventilation" with prevention of heatstroke methods of ventilation for improving "closed spaces with poor ventilation" with prevention of heatstroke for owners using air-conditioning system without ventilation in commercial facilities tokyo: society of heating, air-conditioning and sanitary engineers of japan covid- information and resources. tokyo: cabinet secretariat united nations the precautionary principle also applies to public health actions the precautionary principle, public health, and public health nursing the precautionary principle: protecting public health, the environment and the future of our children. copenhagen: world health organization regional office for europe communication from the commission on the precautionary principle. brussels: commission of the european communities not applicable. the six authors are justifiably credited with authorship, according to the authorship criteria. in detail: ka-conception, design, acquisition, and interpretation of data, drafting of the manuscript, critical revision of the manuscript, final approval is given; uy and mh-conception, acquisition, and interpretation of data, drafting of the manuscript, critical revision of the manuscript, final approval given; nk, hk, and mo-acquisition and interpretation of data, drafting of the manuscript, critical revision of the manuscript, final approval given. no funder supported this work. ethics approval and consent to participate not applicable. not applicable. the authors declare that they have no competing interests. springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. key: cord- -poh te j authors: leder, k.; newman, d. title: respiratory infections during air travel date: - - journal: intern med j doi: . /j. - . . .x sha: doc_id: cord_uid: poh te j an increasing number of individuals undertake air travel annually. issues regarding cabin air quality and the potential risks of transmission of respiratory infections during flight have been investigated and debated previously, but, with the advent of severe acute respiratory syndrome and influenza outbreaks, these issues have recently taken on heightened importance. anecdotally, many people complain of respiratory symptoms following air travel. however, studies of ventilation systems and patient outcomes indicate the spread of pathogens during flight occurs rarely. in the present review, aspects of the aircraft cabin environment that affect the likelihood of transmission of respiratory pathogens on airplanes are outlined briefly and evidence for the occurrence of outbreaks of respiratory illness among airline passengers are reviewed. (intern med j ; : – ) approximately . × people undertake air travel annually. up to half the travelling population experience a health problem related to overseas travel, and approximately % require medical attention. a recent review of admissions to an australian tertiary care hospital following travel showed respiratory tract infections to be the second commonest cause of illness after gastrointestinal infections and the second most common cause of fever behind malaria. travel on commercial aircraft might be a high-risk environment for transmission of infectious diseases. confined space, limited ventilation, prolonged exposure times and recirculating air, all common to air travel, are demonstrated risk factors for the transmission of upper respiratory tract infections in other settings and create the potential for the spread of respiratory pathogens during flight. the debate regarding infectious disease transmission and air travel has centred on whether cabin ventilation systems, particularly those that involve the now-standard % recirculated air, contribute to the transmission of airborne diseases. the two main transmission routes for respiratory infections are by droplet spread and by the airborne route. droplet spread involves relatively large droplets containing organisms that settle out of the air quickly. it requires direct contact of droplets produced by coughing, sneezing or talking onto the mucous membranes of recipients for transmission, necessitating contact at close range (usually within m). the common cold is an example of an infection spread predominantly by this route. airborne transmission involves dissemination of tiny suspensions of microbial particles (droplet nuclei) that can remain suspended in the air for prolonged periods. droplet nuclei are usually - µm in size, can disperse widely and rapidly in closed environments with a recirculation ventilation system and can easily be drawn into the bronchioles of recipients' respiratory tracts. transmission by this route can lead to infections in a large number of people. tuberculosis (tb) and smallpox can spread in this way. some infections, such as influenza and measles, can be spread by both routes, but are predominantly spread by the indirect airborne route. severe acute respiratory syndrome (sars) is predominantly spread by droplets, but airborne transmission and transmission by contact with contaminated fomites can also occur. anecdotally, many people complain of respiratory symptoms following air travel that could be from acquisition of infection, but could alternatively be associated with other factors inherent in flight, such as lowered barometric pressure, hypoxia and low humidity. , breathing low-humidity air for prolonged periods, for example, can result in dry mucous membranes of the nose and throat, which can lead to respiratory tract irritation. the recent advent of sars brought the issue of potential transmission of infections on board aircraft back into the limelight. thus, it is timely to review the potential role of air travel in the spread of respiratory infections. aspects of the aircraft cabin environment that influence the potential transmission of respiratory pathogens on airplanes will be outlined here and then the internal medicine journal ; : - evidence for the occurrence of outbreaks of respiratory illness among airline passengers will be reviewed. most passenger-carrying aircraft have pressurized cabins that allow the cabin to be ventilated and maintained at a desired cabin air pressure, as well as enabling control of the temperature, relative humidity and air flow volume. cabin air is derived largely from cabin pressurization systems, which generally result in a cabin altitude of - feet at an aircraft altitude of - feet. air at this altitude contains very few microbiological agents. it enters the engine of the aircraft and is compressed to very high pressures (approximately kpa) and heated to very high temperatures (more than °c). any residual microbiological agents in the ambient air will be destroyed at such high temperatures. a proportion of this hot compressed air is used for cabin pressurization purposes. it is sent to the conditioning system and is passed through a series of heat exchangers and refrigeration systems. the air released is dry (relative humidity of approximately %), sterile and free of dust. it is also much cooler and at a lower pressure. the conditioned air then enters a mixing manifold, where it is combined with an equal quantity of filtered recirculated air. the typical mix of conditioned air and recirculated air in a modern jet transport aircraft is : . older commercial aircraft were generally ventilated with % fresh air. however, the introduction of air recirculation systems arose from the requirement during the s to reduce aircraft operating costs. use of a recirculation system means filtration of the air is required. the recirculation system draws air from the aircraft cabin by a series of fans, and this air is passed through high-efficiency particulate air (hepa)-type filters. these filters are similar to those used in hospital operating theatres and sterile wards, and are several orders of magnitude more efficient at removing particulate material than filters used in buildings. hepa-type filters are rated using . -µm sized particles. most bacteria have diameters of approximately µm, so will be removed. viruses are usually . - . µm in size, but generally form clumps or attach to larger dust particles so are also usually trapped in the filters. thus, the use of hepa-type filters in aircraft cabin pressurization systems means that . % of bacteria and viruses produced by aircraft passengers are removed from cabin air. , because both air from outside the aircraft and recirculated air are free of microbial agents, the cabin air is essentially sterile. it has a relative humidity of - % and a temperature of - °c. relative humidity can influence microorganism numbers: a low relative humidity will generally be beneficial for viral growth, as relative humidity and survival are inversely related for viruses, but bacteria will not thrive in a low relative humidity environment. air then enters the distribution pipework for delivery to the cabin. cabin air is taken from below the floor of the aircraft to the overhead cabin ventilation system, which runs the length of the cabin. the ventilation system is usually designed so that air entering the cabin at a given seat row is exhausted at the same seat row. this limits the amount of air flowing in the fore and aft directions (i.e. towards the front and back of the aircraft, respectively), which also helps minimize infection risk. with modern cabin pressurization systems, the cabin air is completely exchanged at least times per hour, compared with air exchanges per hour in a typical office building and exchanges per hour in most homes. this high air exchange rate further reduces the likelihood of transmission of infections. flights can last h or more, during which people sit in close proximity to each other. even if the supplied cabin air is sterile, microbial contaminants can be introduced by passengers. it has been demonstrated that passengers' respiratory tract flora can be isolated from cabin surfaces and air, indicating a potential for transmission of diseases spread by respiratory droplets. however, there is a common misconception among the travelling public that if one person on board an aircraft has an infection, then all other passengers are at risk. because air flow is generally from top to bottom, with little if any front to back flow, and because respiratory pathogens are diluted by frequent air exchanges, passengers at most risk are those in close proximity to the infected passenger, with minimal risk for others. the relative infectiousness of the ill passenger will thus be an important factor in the risk of transmission. only one study has assessed the role of air recirculation as a predictor of postflight upper respiratory tract infections. in this study, the rate of respiratory symptoms after air travel was assessed among passengers on airplanes that did and did not recirculate air. the study found the reported rates of a cold and/or runny nose were similar, suggesting that aircraft cabin air recirculation does not increase the risk for upper respiratory symptoms. a few studies have examined microbial contaminants in cabin air and have found no evidence for increased disease transmission on board commercial aircraft than if equivalent time had been spent on any other form of public transport or in other public places. , one study assessing the health risks of air pollutants, including bacteria and fungi, found that levels of organisms measured in the airline cabin were lower than that required to pose a risk of illness. a recent study found bacterial and fungal counts in aircraft to be a log concentration below that found on city buses, in shopping malls and in the outside air. another study found only very low levels of viable organisms during regular checks of cultures from cabin air. thus, the risk of disease transmission as a result of microbial concentrations in cabin air is considered to be low. however, there are no requirements for airlines to monitor cabin air quality, and whether the few studies that have been performed can be generalized to the thousands of flights undertaken by world airlines every year is unknown. considering the large number of flights undertaken, the following reports of outbreaks of illness, which were compiled after an extensive review of published reports, highlight how relatively infrequently epidemics occur. nevertheless, the actual rate of transmission of respiratory infections during air travel is very difficult to measure. accurate epidemiological studies and public health surveys of disease transmission on aircraft are almost impossible to perform, as they involve collecting data from millions of passengers worldwide. as well as problems with the follow up of those potentially exposed, there are difficulties with the detection of infectious cases, proving the source of infection and generalizing results of one outbreak to other circumstances. the speed of air travel is such that infected passengers might arrive at their destination before the end of the incubation period and might therefore spread disease before symptoms develop. even differentiating the risk associated with the cabin environment from contact in the terminal prior to boarding can be difficult. in addition, many infections are associated with a low attack rate and some have long incubation periods, thereby further reducing the reliability of study results. thus, it is not possible to calculate the exact incidence of passenger illness in-flight or postflight. the survival and transmission of influenza virus in infectious droplets is facilitated by the low humidity of cabin air. aircrew have been found to have a high rate of influenza-like illnesses; one study showed a % attack rate over a -month period in unvaccinated individuals. in addition, outbreaks of influenza transmission during travel have been described. a well-known example of the possible adverse health effects of air travel is a report documenting influenza transmission on board an aircraft. in , an alaskan passenger jet suffered engine failure during take-off. the aborted departure resulted in a -h ground delay. all passengers remained on board the aircraft during this delay, throughout which time the cabin ventilation system was turned off. the apparent index case developed symptoms while on board. within h, % of the passengers and % of the crew had contracted influenza. largely as a result of this outbreak, it is now recommended that, in the case of ground delays of more than min, adequate aircraft ventilation must be supplied. an outbreak of an influenza-like illness in military personnel has also been described. the symptoms were those of a respiratory illness characterized by fever, cough, sore throat and myalgia, and influenza virus was recovered from some symptomatic patients. the majority of patients ( %) had recently completed a series of commercial aircraft flights, and the authors concluded that air travel played a role in the transmission of disease among the infected persons. a recent report described another possible influenza outbreak related to air travel. a person with an influenza-like illness boarded a -seat passenger jet aircraft for a flight lasting just under . h. over the next - days, other passengers developed similar illnesses. most of those affected were sitting close to him, the exceptions being someone who had walked up and down the aisles collecting money for a raffle, and the index case's supervisor who assessed him prior to boarding the flight. air had been circulated and filtered on the aircraft in a routine manner. it was suspected that transmission occurred via droplets to those sitting near him, as he coughed and sneezed throughout the flight. tuberculosis tb transmission has been documented on commercial aircraft from both crew and passengers, and a high level of attention has been given to the potential spread of tb during air travel. however, documented cases of travel on aircraft by individuals with active tb have occurred infrequently. transmission of tb has also been reported during train, bus and ship travel. between and , the centers for disease control and prevention (cdc; atlanta, ga, usa) conducted six investigations into cases of active tb in a crewmember and five passengers in separate events. these investigations focused on the potential exposure of more than passengers and crew on flights involving nine different aircraft types. each of these investigations involved a highly infectious index case. of the six investigations, only two produced evidence of possible tb transmission. , one report involved the transmission of infectious multidrug-resistant tb from an infected passenger to six other passengers travelling on the same two commercial aircraft flights within the usa. several factors were identified as being contributory to transmission of disease. these were proximity of the subsequently infected passengers to the index case (mainly within two rows), the level of infectiveness of the index case and the relatively long duration of exposure. neither the cabin air in general nor the cabin ventilation system in particular was considered to have contributed to transmission. this suggests that air travel itself does not carry a greater risk of transmission than activities in other confined spaces. none of the individuals thought to be infected during flight subsequently developed active tb. the second report involved a retrospective cohort study after a crew member was found to be infected with tb. positive tuberculin skin test rates were found to be greater in crew members who flew with the infected individual during their highly infectious period, compared with crew members who were exposed during less infective periods ( . and . %, respectively) and with unexposed crew ( . %). the risk of infection also correlated to hours of exposure to the index case. the authors concluded that crew-to-crew transmission of tb had probably occurred. transmission to passengers could not be excluded: % of frequent flyer passengers returned a positive tuberculin skin test and flew during the index case's highly infectious period. since these six cdc investigations, another two instances of possible tb transmission have been reported. wang investigated the risk of tb transmission from a person with highly infectious pulmonary tb to fellow passengers and crew members on a -h commercial flight. nine contacts developed a tuberculin skin test conversion, three of whom reported no other risk factors for positive reactions. although none of the three contacts had sat in the same section of the plane as the index patient, the authors concluded that the clustering of tuberculin skin test conversions among passengers demonstrated the possible risk of tb transmission during air travel. a second contact investigation of passengers who travelled on flights with an individual with pulmonary tb showed that five of contacts ( %) had a tuberculin skin test conversion. this indicated possible recent contact with tb, but only two of the five passengers had no other identified risk factors for infection. other aircraft-related contact investigations for tb have produced inconclusive findings. moore et al. examined the likelihood of transmission from a highly infectious passenger with pulmonary and pharyngeal tb on two commercial aircraft flights, each approximately . h in duration. all five passengers who subsequently tested positive for tb had identifiable risk factors and were seated throughout the aircraft (at least five rows away from the index case). the authors acknowledged that tb transmission could not be excluded but felt that the likelihood was low. in a second investigation of crew and passengers who had travelled with a person with highly infectious tb on two long flights, four people had a skin test conversion, but again all had at least one other risk factor for a positive result, thus casting doubt that tb transmission during the flights had occurred. several other investigations have found no evidence of tb transmission to passengers or crew members after passengers with active disease travelled on flights ranging in duration from min to h. , , interpretation of these investigations is limited, however, because of low response rates and because screening of passengers from countries with a high prevalence of tb and/or where bacillus calmette-guerin vaccination is common makes interpretation of skin testing and the significance of inflight contact very difficult. thus, the overall risk of tb transmission during flight is low, but it increases with proximity and duration of exposure to the source patient. no definitive statistics linking active tb to airline travel exist, but the overall public health importance is minor. the world health organization (who) has recently published guidelines for the prevention and control of tb during air travel. these guidelines recommend tracing and informing passengers and crew members if they have been on a flight lasting more than h with a highly infectious person, if they have been sitting close to the infected individual and if less than months has elapsed between the flight and case notification to health authorities. they also recommend maximum efficiency air filters, keeping ground delays to a minimum and denying boarding to individuals with active tb. severe acute respiratory syndrome sars and travel are intricately linked, as it was an american businessman travelling from china via hong kong who exported the disease to vietnam. the sars virus is spread predominantly by contact with respiratory droplets from an index case or by direct contact with contaminated hands or objects, although airborne transmission also occurs. the speed with which sars spread around the world was no doubt facilitated by air travel, but this does not imply that transmission occurred on board aircraft. however, presumed in-flight transmission of sars has been reported. , , a doctor who had had contact with a sars patient in singapore flew from new york to germany while feeling unwell. his wife and mother-in-law, who were incubating sars, were also on the flight. the airline was alerted to the possibility of sars and the doctor and his family were isolated at the back of the plane. a previously well flight attendant had brief contact with them while serving and picking up their food trays. four days later, the flight attendant developed a fever and was subsequently diagnosed with probable sars. no other crew members or unrelated passengers contracted sars. passenger-to-passenger transmission of sars has also been indicated. in a recent study, passengers and crew members were interviewed at least days after travel if they had been on one of three flights lasting . - . h that had transported a patient or patients with sars. one of the flights carrying one symptomatic patient with sars and others was associated with potential transmission of sars to people. illness was related to the physical proximity to the index case, with eight of people seated in the three rows in front of the index patient developing illness compared with of people seated elsewhere (relative risk: . ). in contrast, another flight carrying four symptomatic patients with sars and others resulted in transmission to at most one other person, and a third flight carrying a person with presymptomatic sars resulted in no documented spread of infection to the others on the flight. this suggests that the stage of the illness and size of aircraft might influence transmission. in addition, poorly characterized host factors might predispose certain patients to transmitting the virus to large numbers of people, making them so-called 'super-spreaders' of infection. another recent review examined data from flights to singapore with patients with sars on board in order to assess the risk of in-flight transmission. transmission occurred in only one of the three flights with symptomatic patients with sars on board, and the incidence was estimated to be one in passengers. thus, the authors concluded that the risk of transmission of sars appears to be very low, although they also noted that it might be increased with super-spreaders on board. subsequent analysis of approximately flights in which a symptomatic probable sars case was among the passengers or crew found that cases on four of these flights were associated with possible transmission on board. who acknowledged that air travellers 'within two rows of an infected person could be in danger', although the above study suggests the risk extends to (at least) three rows in front of the index case. the greater concentration of illness in people sitting in front of the index case than behind suggests a role of coughing in transmission, possibly with a combination of airborne and droplet spread. the initiation of screening procedures to detect people with fever prior to boarding during the sars outbreak was appropriate and presumably further reduced the risk of in-flight transmission. additional precautions recommended by who for patients who became febrile during flight included isolation of the case (as best as possible) from other passengers, initiation of protective masks to be worn by crew and strict adherence to personal hygiene and infection control measures for those caring for the case. systematic studies to determine the exact risk of inflight transmission are almost impossible to perform. although the media dramatized cases of sars transmission on airplanes, the fact that sars is associated predominantly with droplet spread makes the risk of mass infection on aircraft unlikely. nevertheless, the potential for airborne transmission and super-spreaders means the risk cannot be altogether discounted. other pathogens with the potential for respiratory transmission during air travel are the common cold, measles, smallpox and meningococcal infection. two published reports have suggested that measles has been transmitted on board international and domestic flights. , only passengers seated within a few rows from the ill individuals were infected. smallpox has now been eradicated, but transmission of smallpox on aircraft has been described. transmission of meningococcal infection (spread by direct contact with respiratory secretions) has been studied during air travel, but no cases of secondary disease among contacts have been reported. nevertheless, because of the perceived potential risk, passengers seated next to a patient with meningococcal infection for flights lasting h or more are considered to be at high risk and antimicrobial prophylaxis is recommended. although concern has been raised about air quality and spread of respiratory pathogens on aircraft, studies of ventilation systems and patient outcomes have suggested the dissemination of pathogens occurs rarely. this is because outside air entering the cabin at altitude is essentially sterile, heating/cooling further reduces microbial risks, hepa filters remove microorganisms from recirculated air and the low humidity, high airflow rates, laminar airflow pattern and frequent air exchanges incorporated into the cabin ventilation and pressurization systems further minimize microbial contamination on board aircraft. when transmission does occur, it is more likely with pathogens spread predominantly by the airborne route, but it requires close exposure to an infected individual, in which case transmission would be likely to occur regardless of the mode of transportation. individuals with significant communicable illness, particularly respiratory infections, should postpone commercial air travel to prevent transmission to others, although the overall risk is very low. screening procedures to detect febrile persons boarding flights during known outbreaks further reduce risks. impact of travel-related health impairments fever in returned travelers: review of hospital admissions for a -year period aircraft cabin air recirculation and symptoms of the common cold transmission of the severe acute respiratory syndrome on aircraft cabin air quality: an overview air quality on long flights health issues of air travel concentrations of selected contaminants in cabin air of airbus aircrafts the microbiological composition of airliner cabin air dissemination of human pathogens by airline travel the possible effects on health, comfort and safety of aircraft cabin environments comfort and health in commercial aircraft: a literature review airliner cabin environment: contaminant measurements, health risks and mitigation options trains, travel, and the tubercle impact of influenza vaccination on civilian aircrew illness and absenteeism an outbreak of influenza aboard a commercial airliner an outbreak of influenza a/taiwan/ / (h n ) infections at a naval base and its association with airplane travel influenza outbreak related to air travel a train passenger with pulmonary tuberculosis: evidence of limited transmission during travel exposure of passengers and flight crew to mycobacterium tuberculosis on commercial aircraft, - tuberculosis and air travel: guidelines for prevention and control transmission of multidrug-resistant mycobacterium tuberculosis during a long airplane flight transmission of mycobacterium tuberculosis associated with air travel two-step tuberculin testing of passengers and crew on a commercial airplane tuberculosis risk after exposure on airplanes a passenger with pulmonary/ laryngeal tuberculosis: no evidence of transmission on two short flights a case of infectious tuberculosis on two long-haul aircraft flights: contact investigation exposure to mycobacterium tuberculosis during air travel tuberculosis on the flight deck confronting the new challenge in travel medicine: sars in-flight transmission of severe acute respiratory syndrome (sars): a case report sars and occupational health in the air low risk of transmission of severe acute respiratory syndrome on airplanes: the singapore experience world health organization. summary of sars and air travel. geneva: world health organization imported measles in the united states interstate importation of measles following transmission in an airport -california disease transmission by aircraft exposure to patients with meningococcal disease on aircrafts -united states key: cord- - dp zkus authors: nwanaji-enwerem, jamaji c.; allen, joseph g.; beamer, paloma i. title: another invisible enemy indoors: covid- , human health, the home, and united states indoor air policy date: - - journal: j expo sci environ epidemiol doi: . /s - - -x sha: doc_id: cord_uid: dp zkus after the emergence of the respiratory virus sars-cov- (covid- ), many exposure and environmental health scientists promptly recognized the potentially catastrophic public health ramifications of concurrent infectious and air pollution-mediated disease. nevertheless, much of this attention has been focused on outdoor interactions. each year, . million people worldwide prematurely die from illnesses attributable to indoor air. hence, poor household indoor air quality is a long-standing public health issue with even greater relevance now that many individuals are spending more time at home. at present, the environmental protection agency does not regulate indoor air, and state-level legislation has resulted in a patchwork of national coverage. here, we describe common sources of indoor air pollution, the health impacts of indoor pollutants, and populations disparately impacted by covid- and poor indoor air quality. furthermore, we detail the need for better legislation that promotes the integrity of the indoor air environment, and what individuals can do to personally protect themselves as we await more comprehensive indoor air legislation. following the emergence of the novel respiratory virus sars-cov- (covid- ), many environmental health experts quickly identified the potentially disastrous public health ramifications of concurrent infectious and air pollution-mediated disease [ ] . however, much of this discussion has focused on the outdoors. annually, . million people worldwide prematurely die from illnesses attributable to household air pollution [ ] . in the united states, radon, a major indoor air pollutant, is the second leading cause of lung cancer and is responsible for , - , deaths each year [ ] . although stay-at-home orders and remote working/learning have increased the relevance of home indoor exposures to all persons, there are still certain vulnerable populations that bear a disparate burden of avoiding the virus outdoors and being exposed to nontrivial pollutants indoors. these populations include children, the elderly, individuals with preexisting conditions, native american tribal nations, and households of low socioeconomic status-particularly those in multifamily buildings [ ] [ ] [ ] [ ] . to be explicit, this is not a call for ignoring social distancing and other public health orders. rather, similar to efforts drawing attention to increases in domestic abuse and the mental health consequences of isolation [ , ] , it is an opportunity to name poor household indoor air quality as a long-standing public health issue with increased relevance during the present pandemic. one common misconception is that the indoor air environment is simply a reflection of the outdoor milieu; however, this is not always the case. outdoor air pollution penetrates indoors, and because americans spend a majority of their times indoors (> %), the majority of exposure to outdoor air pollution occurs indoors. nevertheless, there are distinct, important sources of indoor air pollution [ ] . fireplaces, kitchens, furniture, wall insulation, and personal care products, are just some noteworthy sources of indoor pollutants. household cleaning products are a particularly relevant source of indoor pollution at this juncture in time given that many people may be cleaning more frequently and with stronger disinfectants to reduce rates of viral infection. furthermore, efforts to make homes airtight to improve energy efficiency have created buildings with reduced outdoor ventilation rates resulting in the buildup of indoor pollutants to harmful levels that would be otherwise unacceptable outdoors [ , ] . importantly, the toxicity of indoor air extends beyond the health effects of individual pollutants. the reactive chemistry of pollutants can be an additional source of harmful indoor chemicals including secondary ozonides, oxygenated volatile organic compounds, and hydroxyl radicals [ ] . finally, the microbiota of the indoor environment is becoming an ever-more appreciated contributor to indoor air quality [ , ] . existing studies demonstrate that indoor air microbiomes are quite diverse, and can have meaningful impacts on human health [ ] . although individuals are primarily concerned with the burden of covid- in their indoor air, aerosolized covid- does not exist in isolation. hence, recognition of all airborne microorganisms and how the indoor air microbiome may interact with many of the aforementioned chemical exposures is important for building a more comprehensive understanding of indoor air quality. in contrast to the outdoors where federal mandates like the clean air act of have been passed to maintain air quality, direct top-level legislation for indoor air quality has been lacking. the environmental protection agency (epa) indoor air quality program was slated to be cut in the federal budget, and at present the epa does not regulate indoor air [ ] . some may point to the u.s. housing act ( ), the safe water drinking act ( ), the residential lead hazard reduction act ( ), and the updated toxic substances control act (tsca) ( ) as examples of legislation addressing the indoor environment. however, these measures are indirect in that they limit the introduction of harmful substances that are brought indoors, but do not regulate the indoor environment itself. they have also demonstrated weaknesses in effectiveness. for instance, despite the tsca, the epa still identified the need to offer a final ruling, "that any discontinued uses of asbestos cannot reenter the marketplace without epa review," in april of [ ] . this ruling is particularly concerning as it opens the door for the epa to reconsider uses of asbestos and could result in the reintroduction of asbestos to the marketplace. in lieu of federal indoor air mandates, some states have offered legislation to control the air in schools and other buildings. still, efforts directed at private homes remain limited. moreover, these state-level policies leave a patchwork of national coverage [ ] . the existing discrepancy in the frameworks for regulating outdoor and indoor air can be partially explained by the perception of outdoor air as a shared public good, but indoor air as a discrete personal resource with non-communal impacts [ ] . yet, covid- demonstrates how this logic easily falls apart. the main premise for social distancing and stay-at-home orders is to safeguard the individual and society at-large from peaks in infection that would overwhelm the nation's healthcare system. nevertheless, one can imagine a young boy already living with severe asthma who now has to spend all of his day in a dilapidated urban project apartment. after being exposed to mold and secondhand smoke from his neighbors, he too finds himself rushed to a hospital. in this common scenario, society fails to gain the full benefits of stay-at-home orders because the healthcare system is utilized regardless, and those most at-risk for covid- complications are also placed at greater risk of exposure. still, as we push for broader pieces of legislation to protect our indoor air, what can that young boy do to potentially mitigate the impacts of harmful indoor air on his health? what can other individuals do to protect themselves and their loved ones during these times of home isolation and beyond? when entering the home, remove shoes at the door to avoid tracking harmful particles inside. if someone in your household has covid- or is a healthcare worker, consider using a highefficiency particulate air (hepa) purifier in the home. even though these purifiers are not completely protective against the virus (hepa filters remove particles of . μm and a coronavirus is~ . μm), they can help remove other pollutants and larger viral/microbiome agglomerates from the air. if it is safe to do so, opening up windows can improve indoor air circulation and dilute indoor contaminants. if cooking, make sure the kitchen remains well-ventilated to avoid harmful exposures to fumes and particulate matter. finally when cleaning, avoid the overuse of chemicals and air fresheners that may simply be contributing additional hazardous substances to the air. although there will be limits (e.g., financial, logistical, safety) to the extent to which individuals can fully implement these and similar protective measures in their personal lives, we hope for these suggestions to be a helpful starting place. by continuing to raise awareness-togetherwe can help actualize a future where fewer people succumb to indoor air-related disease. conflict of interest the authors declare that they have no conflict of interest. publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. air pollution, racial disparities and covid- mortality radon-induced lung cancer deaths may be overestimated due to failure to account for confounding by exposure to diesel engine exhaust in beir vi miner studies moving environmental justice indoors: understanding structural influences on residential exposure patterns in low-income communities state clean indoor air laws and smoking among adults with poor mental health perception, culture, and science: a framework to identify in-home heating options to improve indoor air quality in the navajo nation prediction model for air particulate matter levels in the households of elderly individuals in hong kong impact of social distancing on mental health during the covid- pandemic: an urgent discussion danger in danger: interpersonal violence during covid- quarantine introduction to indoor air quality. us epa home energy efficiency and radon related risk of lung cancer: modelling study home energy efficiency and radon: an observational study indoor chemistry microbiota of the indoor environment: a meta-analysis indoor-air microbiome in an urban subway network: diversity and dynamics farm-like indoor microbiota in non-farm homes protects children from asthma development important epa programs put at risk by fy budget proposal. environ prot netw epa actions to protect the public from exposure to asbestos. us epa eli's database of state indoor air quality laws-search page | environmental law institute linking public health, housing, and indoor environmental policy: successes and challenges at local and federal agencies in the united states key: cord- -j cf vzs authors: sattar, syed a. title: indoor air as a vehicle for human pathogens: introduction, objectives, and expectation of outcome date: - - journal: am j infect control doi: . /j.ajic. . . sha: doc_id: cord_uid: j cf vzs airborne spread of pathogens can be rapid, widespread, and difficult to prevent. in this international workshop, a panel of experts will expound on the following: ( ) the potential for indoor air to spread a wide range of human pathogens, plus engineering controls to reduce the risk for exposure to airborne infectious agents; ( ) the behavior of aerosolized infectious agents indoors and the use of emerging air decontamination technologies; ( ) a survey of quantitative methods to recover infectious agents and their surrogates from indoor air with regard to survival and inactivation of airborne pathogens; ( ) mathematical models to predict the movement of pathogens indoors and the use of such information to optimize the benefits of air decontamination technologies; and ( ) synergy between different infectious agents, such as legionellae and fungi, in the built environment predisposing to possible transmission-related health impacts of aerosolized biofilm-based opportunistic pathogens. after the presentations, the panel will address a set of preformulated questions on selection criteria for surrogate microbes to study the survival and inactivation of airborne human pathogens, desirable features of technologies for microbial decontamination of indoor air, knowledge gaps, and research needs. it is anticipated that the deliberations of the workshop will provide the attendees with an update on the significance of indoor air as a vehicle for transmitting human pathogens with a brief on what is currently being done to mitigate the risks from airborne infectious agents. i welcome you all to this multinational workshop! this workshop was conceived over a year ago, and the organizing committee ( table ) formally requested that astm international (www.astm.org/) hold the event under its auspices. astm's committee e , which deals with pesticides, antimicrobials, and alternative control agents, approved the proposal in april . mounting recognition of indoor air as a vehicle for infectious agents is leading government regulators, such as the u.s. environmental protection agency, to refine and update their guidelines, researchers to develop better means of studying airborne pathogens, and civil engineers and architects to find innovative means of making indoor air safer while keeping energy conservation in mind. although comprehensive guidelines and standardized means are available to study chemical pollutants in indoor air, there remains a general lack of suitable experimental facilities and standardized protocols to quantitatively assess the survival of pathogens in indoor air and to document their removal and inactivation by physical and chemical means. this workshop will address these issues, among others. the workshop's specific objectives, therefore, are as follows: the deliberations will also focus on the development of standards for assessing indoor air decontamination technologies and government regulations for registration of products to be marketed. as noted, this workshop has been organized under the auspices and with the support of astm international. the city university of new york and the university of ottawa (canada) are the academic sponsors of the workshop, and financial support has been provided by rb (montvale, nj) and microbac (sterling, va). these companies are also funding publication of the workshop proceedings. we gratefully acknowledge their generous support. the organizing committee has put together an outstanding group of speakers who will offer a comprehensive yet balanced perspective on the key issues. table lists the topics to be covered, along with the names and affiliations of the presenters. elsevier (www.elsevier.com) has agreed to publish the proceedings of the workshop after peer review. elsevier will also provide a preview of the proceedings, including the abstracts for each presentation, for release during the conference of the association for professionals in infection control and epidemiology. the workshop proceedings will also contain a summary of the concluding discussions. potential members of the audience include researchers in aerobiology, makers of air purification technologies, contract laboratories that assess air decontaminants, government regulators dealing with indoor air quality, and members of standards-setting organizations, such astm international (www.astm.org) and american society of heating, refrigerating, and air-conditioning engineers (www.ashrae.org). table is a glossary of the common terms used throughout this workshop's presentations. this is included in an attempt to create a level playing field while facilitating the understanding of the subject matter by experts in fields other than environmental microbiology. however, the emphasis here is on working definitions, recognizing that efforts are needed to develop a more comprehensive glossary for broader applications in this area. aerobiology, the study of living organisms and their components in air, became a full-fledged scientific discipline in . this was followed in by the founding of the international association of aerobiology (https://sites.google.com/site/ aerobiologyinternational/). the initial focus of this group was the study and movement of pollen, but microbes and other life forms were soon added to the mix with a corresponding broadening of the organization's scope (fig ) . the microbiologic quality of indoor air comes under the rubric of aerobiology (fig ) . this workshop will focus only on indoor air as a vehicle for human pathogens. indoor air quality exposure of humans to indoor air and its contents coincided with cave dwelling > , years ago. sharing of the human habitat with domesticated animals, such as cattle, dogs, and pigs, facilitated the rise of zoonotic infections, including airborne infections (eg, measles). exposure to pathogens of humans and animals via the agency of indoor air continues to this day. although the focus here is on indoor air, indoor air is not entirely immune to what goes on outdoors. the air from outside an edifice affects the air indoors and vice versa. in fact, the use of fossil fuels for heating the indoors contributes directly and indirectly to overall climate change. an early consequence of energy conservation was sealed buildings and houses, which eventually gave rise to sick building or tight building syndrome as a result of the trapping of airborne pollutants and higher levels of moisture inside. humans and animals are the main contributors of microbeladen particles indoors. in fact, individuals leave their own personal microbial footprint as a part of the indoor microbiome. aerosolization of microbes from biofilms and resuspension of dust are the other principal contributors to the microbial content of indoor air (fig ) . although the route by which airborne pathogens cause infections varies between microorganisms, improvements in the quality, quantity, and movement of indoor air can mitigate the airborne spread of many human pathogens by preventing pathogen this phenomenon is especially relevant in aerobiology because a host is often exposed to potentially harmful biologic, chemical, or physical agents simultaneously or sequentially. droplet nuclei airborne particles derived from larger droplets after loss of water such droplets are crucial for the spread of infectious agents by air as their relatively small size ( . - . μm) allows for their stability in air while also permitting their retention on inhalation. indoor air quality quality of the air within buildings and other enclosures, with particular reference to the health and comfort of the occupants the overall quality of indoor air is dependent on a mix of a variety of factors that may be site and time sensitive. the capacity of a microbe to infect a given host depends not only on its biology but also on the general health status of the host and the portal of entry into the host. a microbe capable of causing localized or generalized damage to the host please see "infectious agent." the totality of microorganisms and their collective genetic material present in or on the human body or in another environment a certain proportion of the microbes found in a microbiome may not be culturable but detected and identified via their genomes only. this term is now preferred over microflora. opportunistic pathogen a microbial pathogen capable of infecting hosts whose natural defenses are compromised because of advanced age, immunosuppression, or other underlying causes the number, variety, and health significance of such pathogens is on the rise in conjunction with the rising numbers of those debilitated by acquired or induced immunosuppression. pathogen (microbial) any microbe capable of causing damage to the host even an otherwise innocuous microbe can become pathogenic depending on the general resistance of the host or the microbe's entry into normally sterile areas of the body where it can become an opportunistic pathogen. perikairots environment-based opportunistic pathogens biofilm-based microbes such as legionellae and environmental mycobacteria can infect those debilitated because of age or underlying medical conditions. resident microbiota a mix of microbes normally found in or on the host many members of the resident microbiota from skin and mucous surfaces are frequently found in indoor air. particles small enough to access the alveolar space during normal breathing such particles may or may not contain viable microbes. surrogate microbe a microbe that resembles ≥ type of pathogens but is safer and easier to work with in the laboratory; also called a simulant the use of such microbes is crucial in many aspects of microbiology, in general. the body's automatic inhalation and exhalation process at rest in addition to coughing and sneezing, tidal breathing can release infectious agents into the air. transient microbiota microbes temporarily acquired by a host during normal contact with the environment inhalation and reducing the microbial load on environmental surfaces. indoor air is arguably the fastest and most highly efficient means of pathogen spread in a given setting. as depicted in figure , indoor air is a complex and dynamic mixture of numerous components in a constant state of flux influenced by many factors both indoors and outdoors. the quality of indoor air represents the outcome of the unique mix of components in a given setting that, in themselves, change temporally. one major challenge in preventing and controlling the airborne spread of infection is the presence of possibly multiple and mobile sources of pathogens at a given location and time. one or more infected or colonized persons or pets may contaminate the air in their immediate vicinity with exposure of those nearby without the air having reached any available means of pathogen decontamination. certain factors that influence indoor air quality may fall under the categories of chemical and physical. for example, smoke from burning wood for cooking fuel is, of course, chemical in nature, but respirable particles in the smoke are the primary means of lung irritation and potential damage leading to cardiopulmonary syndromes, including lung cancer (http://www.who.int/mediacentre/ factsheets/fs /en/). the study of indoor air quality received a major boost as a consequence of the severe acute respiratory syndrome outbreak in and the anthrax scares in the united states in . it also spawned much interest in the development, assessment, and application of technologies to decontaminate indoor air. as shown in figure , particles > μm in diameter entering the air may rapidly fall out of the air because of their mass under prevailing environmental conditions, particularly temperature and relative humidity, whereas smaller particles can not only remain airborne for extended periods but can also be transported readily indoors by air currents over considerable distances. respirable particles fall in the range of . - . μm in diameter, whereas smaller particles are generally exhaled because of the aerodynamics of breathing. the actual site of retention of the inhaled particles depends on their nominal size. it is noteworthy here that persons with respiratory infections breathe out pathogen-laden particles during tidal breathing. a human adult at rest breathes in an average of , l of air per day. in any given setting, one may choose not to drink the water or eat the food that is available but generally has little choice in breathing the same air as everyone else. this makes air an environmental equalizer-conferring on it the unique potential to parse out evenly whatever it may contain. further, infectious agents entering indoor air mix rapidly with no perceptible color or smell. although the potential of air to spread respiratory pathogens is well recognized, its ability to transmit enteric pathogens is not as well appreciated. airborne particles containing enteric pathogens may be retained in the tonsillar region and swallowed for relocation to the gastrointestinal tract with subsequent replication there. ijaz et al have provided a comprehensive list of human pathogens known or suspected to spread via indoor air. the following are the main topics to be covered during the workshop. despite the recognized significance of indoor air as a vehicle for human pathogens, there are major gaps in our understanding of how well these pathogens remain viable under different environmental conditions. such information is crucial to assessing the potential of a given pathogen to spread by air. construction of an aerobiology chamber (approximately m ) will be described, and data from use of the chamber to test airborne survival of staphylococcus aureus, klebsiella pneumoniae, and acinetobacter baumannii will be presented. many technologies claiming microbial decontamination of indoor air are on the market, but without proper validation of their claims. information will be presented on ways to test such technologies using standardized protocols for registration and marketing purposes. because they may not be readily available and generally are unsafe and difficult to culture in the laboratory, it is rarely possible to use actual field strains of human pathogens in testing. this necessitates the use of surrogate microbes to generate data predictive of the behavior of pathogens. however, certain surrogates that are used commonly and recommended by regulatory agencies and standardssetting organizations alike are inherently unsuitable for experimental work in aerobiology. for example, k pneumoniae, frequently used as a surrogate for airborne gram-negative bacilli, does not survive aerosolization well because it is relatively fragile and unstable in air. therefore, data generated with k pneumoniae likely will not be predictive of the behavior of actual human pathogens. this workshop will identify more suitable surrogates with supporting data. can microbial decontamination of indoor air reduce the risk for pathogen contamination of environmental surfaces? data will be presented to demonstrate that reductions in the levels of airborne microbes can indeed lead to corresponding reductions in the microbial contamination of environmental surfaces in a given setting. the use of integrated models could help analyze outbreaks, evaluate the relative importance of hygiene and infection prevention and control for policymakers, and provide guidance in environmental design for greater occupant safety and comfort. these will be illustrated using some recent examples, including severe acute respiratory syndrome, influenza, and middle east respiratory syndrome. quantitative recovery of viable microbes from air is vital in aerobiologic studies. an update will be given on available methods, including their strengths and limitations. experimentation with airborne microbes is generally quite labor intensive and costly and requires special biosafety precautions. mathematical models can assist greatly in optimizing aerobiology chamber design and in predicting the influence of furniture and other objects on the movement of microbes. data will be presented with specific reference to a chamber that fully conforms to guidance from the u.s. environmental protection agency. biofilms are not only common in the built environment, but they can be common sources of airborne pathogens. such biofilms often contain several microbial species having complex interactions between them. this will be illustrated with the example of how fungi and legionellae coexist with potential risks to human health. product performance test guidelines: ocspp . : air sanitizers-efficacy data recommendations decontamination of indoor air to reduce the risk of airborne infections: studies on survival and inactivation of airborne pathogens using an aerobiology chamber airborne spread of infectious agents in the indoor environment world health organization. who guidelines for indoor air quality: selected pollutants origins of major human infectious diseases domesticated animals and human infectious diseases of zoonotic origins: domestication time matters ventilation rates and health: multidisciplinary review of the scientific literature humans differ in their personal microbial cloud the role of super-spreaders in infectious disease secondary aerosolization of viable bacillus anthracis spores in a contaminated us senate office influenza virus in human exhaled breath: an observational study how much air do we breathe? concentration, size distribution, and infectivity of airborne particles carrying swine viruses generic aspects of airborne spread of human pathogens indoors and emerging air-decontamination technologies key: cord- -ialg d e authors: cori, liliana; donzelli, gabriele; gorini, francesca; bianchi, fabrizio; curzio, olivia title: risk perception of air pollution: a systematic review focused on particulate matter exposure date: - - journal: int j environ res public health doi: . /ijerph sha: doc_id: cord_uid: ialg d e the adverse health effects of exposure to air pollutants, notably to particulate matter (pm), are well-known, as well as the association with measured or estimated concentration levels. the role of perception can be relevant in exploring effects and pollution control actions. the purpose of this study was to explore studies that analyse people’s perception, together with the measurement of air pollution, in order to elucidate the relationship between them. we conducted a systematic review in accordance with the preferred reporting items for systematic reviews and meta-analyses (prisma) guidelines. in march , pubmed, embase, and scopus databases were explored in an attempt to search for studies published from to . the review included studies, most of which were conducted in china (n = ) and the united states (n = ) and published over the last four years (n = ). three studies were multicenter investigations, while five articles were based on a national-level survey. the air quality (aq) was assessed by monitoring stations (n = ) or dispersion models (n = ). many studies were population questionnaire-based, air monitoring and time-series studies, and web-based investigations. a direct association between exposure and perception emerged in studies. this systematic review has shown that most of the studies establish a relationship between risk perception measurement. a broad spectrum of concepts and notions related to perception also emerged, which is undoubtedly an indicator of the wealth of available knowledge and is promising for future research. this systematic review is dedicated to clarifying the role of the perception of risk of air pollution, due to its relevance in the environmental and health field. the goal is to explore studies that analyse people's perception, together with the measurement of air pollution, in order to elucidate the relationship between them. the focus is on particulate matter (pm) as its negative health effects have been demonstrated and quantified. social, cultural, and contextual factors can influence people's perception and the impacts on behavior, agency, self-efficacy, and the relationship with measured pollution should be clarified. this knowledge could be crucial to complementing studies on the health to estimate the relative risk of mortality attributable to pm. in particular, long-term exposure to pm . was estimated to have caused . million deaths in , corresponding to . % of the total global mortality and making pm . the fifth-ranking mortality risk factor [ ] . for pm and pm . , concentration-response risk functions have been developed and proposed for health impact assessments. many studies have included recommendations for actions and explorations of policy implications and the economic impact of pm reductions. green energy policy in europe includes air pollutant emission reduction in the motivation for reduction. moreover, the international agreements addressing climate change consider pm in their reduction plans [ ] . in several asian cities, outdoor pm air pollution is increasing. in india, outdoor air pollution was responsible for more than , deaths in . to deal with these health effects, several countries have launched large-scale policies, such as china [ , ] and india; in other countries like thailand, there is a growing demand for policies to address the issue of polluted air [ ] . although in many countries there are no specific laws or protection rules, who guidelines are taken into consideration [ ] . in china, to address the severe air pollution, the action plan on prevention and control of air pollution established a reduction of the pm . concentration in beijing, nanjing, and guangzhou cities by %, %, and %, respectively, between and . after this, several plans and specific measures were implemented [ ] . in the eu and us, air protection policies are similar and the reduction of air pollution is a central element. in the us, air quality (aq) is a federal matter and the relevant policies apply to the whole country. in the eu, aq policy is based on standards issued by the european commission and national implementations, where member states determine the best way to achieve them within each country. in addition, in the us, air pollution management is implemented through a combination of the aq standard and the emission standard strategies, whereas in the eu, emission standards, emission taxation, and cost-benefit analysis are used [ ] . in , the european commission adopted a clean air policy package for europe in order to set new objectives for eu air policy and reduce the negative health impacts of air pollution, such as respiratory diseases and premature death, by almost % by [ ] . the present systematic review was developed according to the preferred reporting items for systematic reviews and meta-analyses (prisma) statement [ ] . this systematic review was performed by searching three different electronic databases, embase, scopus, and pubmed. upon completing the search, a combination of medical subject headings (mesh) and non-mesh keywords was used. specifically, the keywords air pollution, particulate matter, pm , pm . , risk perception, perception, and health were adopted in the following search query: (air and pollution or (particulate and matter) or pm or pm . ) and (risk and perception or perception) and health. only studies written in english were included and reviews, letters to the editor, and abstracts were excluded. the first search of the three databases was conducted without any time limitations. few articles were published before , so the search was limited to those published from january to march . the following inclusion criteria were adopted: i. perception concerns, exclusively pm exposure; if exposure refers to several pollutants or environmental matrices, pm should be specifically mentioned; ii. pm levels are always measured, both directly and indirectly, and exposure refers to the specific population; iii. pm measurement is only conducted outdoors; iv. pm can also be included in an air quality index, aqi, while perception must always be measured, both directly and indirectly; v. perception can be evaluated via quantitative or qualitative methods. after removing duplicates, three researchers, who are the authors of the paper (l.c., g.d., and o.c.), independently evaluated titles and abstracts according to the eligibility criteria. the articles simultaneously selected by the three reviewers were employed in the next phase, i.e., the full text was read. the researchers thoroughly read the articles selected in the first phase in equal proportion. the reviewers individually decided to accept or reject the articles read. in cases of doubt among the three reviewers, the other two authors (f.g. and f.b.) examined the papers in order to achieve a final decision about their eligibility. all of the relevant data were extracted, including the author(s) name(s), publication date, title, study area, study design, age group(s) of participants, sample study, environmental exposure assessment methods, and main results. more specifically, the following information was taken into consideration: the methodology; the number and characteristics of the subjects involved in the research; how pm was measured; whether specific devices were tested; how risk perception was assessed; and which tools were used. these relevant data were included in table form to obtain a synthetic framework of all articles read in full by reviewers. this table format enabled the authors to complete a cursory overview of the materials selected in the first phase. to be able to analyse the perception, the main methodological issue is the extent of the concept. "perception" and "risk perception" were included in the search to be able to capture a wider variety of research in terms of methods, populations, and issues included. the perception linked to aq measurement is intended to gather information about understanding and knowledge of the issue, psychological reactions, the capacity or availability to act as a consequence of this knowledge, and the response to public policies. suggestions and recommendations for actions are generally presented as practical results of these studies. to systematically examine the articles selected, the explored dimensions of perception (understanding/sensorial perception; reactions/psychological consequences; reactions/physical consequences; behaviors) were categorized by features (awareness; belief; knowledge; concern; risk perception; worry; fear; outrage; familiarity; trust; annoyance; anxiety; life quality change; self-reported health symptoms; avoidance of the problem; search for information; exposure reduction; proactivity; request for action; and acceptance). this means that in each article, one or more of those features are explicitly searched as a tool for the analysis or are assumed in the concept. the prisma flow diagram in figure depicts the article selection process we followed for including studies in this review. we started by searching the three databases mentioned in the methods section and identifying articles. from these first records, we removed duplicates, leaving for further review. we reduced the number of included studies to after screening the titles and abstracts and applying the following exclusion criteria: studies where the main exposures referred to tobacco smoke, indoor settings, specific pollutants originating from industries, or other anthropogenic sources such as caves and mines; • studies evaluating health outcomes related to air pollution, but not to perception or risk perception; • generic studies, editorials, or abstracts in proceedings of conferences. • studies where the main exposures referred to tobacco smoke, indoor settings, specific pollutants originating from industries, or other anthropogenic sources such as caves and mines; • studies evaluating health outcomes related to air pollution, but not to perception or risk perception; • generic studies, editorials, or abstracts in proceedings of conferences. the remaining articles underwent a full-text evaluation, bringing the total number down to published articles that met our inclusion criteria. by the end of the identification process, we had removed about two-thirds of the reports from the amount we initially identified for this current study because it was impossible to know from the titles and abstracts alone whether or not they included the following criteria: presence of indoor air pollution; • presence of other pollutants. table summarizes the main characteristics of the studies included in this review in reverse order of publication date. the remaining articles underwent a full-text evaluation, bringing the total number down to published articles that met our inclusion criteria. by the end of the identification process, we had removed about two-thirds of the reports from the amount we initially identified for this current study because it was impossible to know from the titles and abstracts alone whether or not they included the following criteria: presence of indoor air pollution; • presence of other pollutants. table summarizes the main characteristics of the studies included in this review in reverse order of publication date. survey by a self-administered questionnaire used to collect data on socio-demographic, aq perception and respiratory health symptoms among university students. measurements of traffic-related air pollutants conducted at three sampling sites in university south campus. significant associations between each level of traffic-related air pollutants and aq perception and respiratory health symptoms (p < . ). d. dong, [ ] china (nationwide) n/a web based time series study by the baidu index to explore the relationship between actual level of air pollution and residents' concern about air pollution. on the basis of daily data of days in shanghai, a vector autoregression (var) model was built for empirical analysis. aq measured by the aqi reported by environmental monitoring stations. daily aqi data to measure air pollution level in shanghai freely available from the website of the china aq online monitoring and analysis platform. local residents perceived deprivation of aq and expressed their concern on air pollution within the day the aq index rose. decline of aq in another towns, such as beijing, raised the concern of shanghai residents about local aq. rising concern in shanghai had a beneficial impact on aq improvement. no relationship between pollution perception and health concern, nor with air pollution exposure. pollution perception associated with age, sex, respiratory problems, aq alert knowledge. health concern associated with age, sex, aq alert knowledge, o exposure and poverty. y. lu, [ ] china (nationwide) n/a time series cross-correlation analysis. baidu search index to analyze the patterns of public concern about haze from to , and the dynamic relationship between public concern and aq data. pm . concentration data before july from us embassy and from - to - - from a data integration platform (real-time data of pm . from us embassy). public concern investigated via web. according to annual data, slight decrease of the weak correlation of public concern and aq. removing the annual trend component of time-series, the public concern resulted more sensitive to the short term fluctuation of aq (lag), even as pollution decreased. cross-sectional study by questionnaire to evaluate relationships between concern on health effects of air pollution and personal and environmental factors. participants recruited to fill an online questionnaire on travel and physical activity behaviour, perceptions, attitudes on active mobility and the environment, and socio-demographic factors. air pollution at the residence from europe-wide no and pm . maps with a -m resolution and available for year . the no and pm . models explained . % and . % of spatial variation respectively. the european main road network was used to determine the distance of each residence to the nearest primary road. mean modelled air pollution and mean level of concern per city well correlated for no (r = . ), less for pm . (r = . ). in regression model, sex, children in the household, physical activity and no at the home address significantly correlated to individual concern over health effects of air pollution. no but not pm . at the home address associated with concern over health effects of air pollution. great differences in health perception levels, average daily pm . exposure (add), public acceptance levels, willingness to pay and to accept compensation for air pollution before, during, and after the yog. during the yog, public exposed to pm . lower concentrations most accepted risks posed by haze. after yog, residents more sensitive to haze and demanded higher aq. a greater willingness to pay for risk reduction and to accept compensation for health-related losses. f. gany, [ ] new york city, usa taxi drivers aged and older survey by interview to assess taxi drivers' knowledge, attitudes, and beliefs (kab) about air pollution compared with direct measures of exposures. one hundred drivers completed an air pollution kab questionnaire, and seven taxicabs participated in preliminary in-cab air sampling. roadside and in-vehicle levels of pm . and black carbon (bc) were continuously measured over a single shift on each subject, and exposures compared with central site monitoring. two aerosol monitors, a personal mie dataram and a microaethalometer, to measure fine pm and bc levels, respectively, inside new york city taxi cabs. even with general knowledge about the risks associated with occupational exposure to air pollution, taxi drivers did not consider their exposure and/or potential related risks to their health as priorities in the context of other health concerns. four non-urban regions of denmark: anholt, keldsnor, lindet, sundeved men and women aged and older cross-sectional study to assess environmental conditions and health of residents living nearby agricultural land and animal production facilities. residents invited via mail by answering a printed questionnaire or an online version. exposure assessment to atmospheric pollutants. the concentrations of all pollutants, except for ammonia, were calculated using the integrated multiscale air pollution model system (thor). annoyance is associated with air pollutants and noise. relationship between perceived smog intensity, risk perception and behaviour change (concern behaviours), enhanced in case of negative experience or harmful health experiences (preventive actions). higher level of awareness and risk perception for women. questionnaire survey, investigating how public perceptions of air pollution, risk beliefs and self reported actions limit personal exposure to air pollution across cities. analysis to quantify association between individual variables and self-protective and information-seeking actions due to bad aq. air pollution concentrations obtained from the local and regional environmental agencies. significant differences in subjective evaluation of local aq, according to annoyance, physical symptoms and distress due to air pollution. small differences in levels of self-reported attention to aq, perceived severity and controllability beliefs. self-reported attention to aq levels and worry about health effects of air pollution were the most associated variables with avoid polluted streets, information seeking, change leisure activities and use face-masks. z. tao message volume in sina weibo indicative of true particle pollution levels; the messages contain rich details including perceptions, behaviors, and self-reported health effects. social media data improve existing air pollution surveillance data, especially perception and health-related data that traditionally requires expensive surveys or interview. most informants perceived industrial pollution as posing considerable risk to themselves and the community. three occupational groups (industrial, commerce and service, farmers) perceived differently in relation to socio-economic factors. no consistent or significant correlations were found between annoyance and pm . exposure. large variations in levels of air pollution annoyance, with the highest in traffic; significant determinants: city, self-reported symptoms, downtown residence and gender. some associations with measured pollution emerged analysing specific correlation considering single cities, traffic, downtown living, work. the articles included in this systematic review concern studies carried out in china (n = ), the usa (n = ), greece (n = ), south korea (n = ), the uk (n = ), italy (n = ), spain (n = ), switzerland (n = ), austria (n = ), bangladesh (n = ), belgium (n = ), brazil (n = ), the czech republic (n = ), denmark (n = ), estonia (n = ), finland (n = ), germany (n = ), india (n = ), japan (n = ), kenya (n = ), malaysia (n = ), pakistan (n = ), sweden (n = ), taiwan (n = ) thailand (n = ), and the netherlands (n = ). figure shows the geographical distribution of surveyed countries. the articles included in this systematic review concern studies carried out in china (n = ), the usa (n = ), greece (n = ), south korea (n = ), the uk (n = ), italy (n = ), spain (n = ), switzerland (n = ), austria (n = ), bangladesh (n = ), belgium (n = ), brazil (n = ), the czech republic (n = ), denmark (n = ), estonia (n = ), finland (n = ), germany (n = ), india (n = ), japan (n = ), kenya (n = ), malaysia (n = ), pakistan (n = ), sweden (n = ), taiwan (n = ) thailand (n = ), and the netherlands (n = ). figure shows the geographical distribution of surveyed countries. three articles are multicenter studies, two are surveys performed in seven countries [ , ] , and the remaining are surveys performed in six countries [ ] . six studies were based on a national-level [ , , , , , ] , three on multi-province [ , , ] , and seven on multiple-city surveys [ , , , , , , ] . looking at the timeline distribution of the articles, figure shows that research has increased over the last four years, during which time over % of the studies were published. as indicated in the caption for figure , the year includes only the first three months of the year. the red vertical line in figure indicates the date iarc announced that pm is classified as a carcinogenic to humans (group ) [ ] . three articles are multicenter studies, two are surveys performed in seven countries [ , ] , and the remaining are surveys performed in six countries [ ] . six studies were based on a national-level [ , , , , , ] , three on multi-province [ , , ] , and seven on multiple-city surveys [ , , , , , , ] . looking at the timeline distribution of the articles, figure shows that research has increased over the last four years, during which time over % of the studies were published. as indicated in the caption for figure , the year includes only the first three months of the year. the red vertical line in figure indicates the date iarc announced that pm is classified as a carcinogenic to humans (group ) [ ] . not all studies considered the same type of pm and not all used the same methods for assessing exposure. specifically, studies only considered pm . as an indicator of exposure to pm; studies only considered pm ; study considered pm , suspended particulate matter (spt), and total suspended particles (tsp); studies considered particle number counters (pncs); and studies considered pm . and pm . nine of the studies that considered both pm . and pm evaluated the association between pollution and survey responses using aqi, which is a six-category classification of ambient aq for six major pollutants: carbon monoxide, ground-level ozone, nitrogen dioxide, pm . and pm , and sulfur dioxide. regarding pm exposure assessment, the majority of studies (n = ) used aq data from official monitoring stations, while seven studies used aq models such as the moderate resolution imaging spectroradiometer (modis) aerosol optical depth (aod). only seven studies directly measured pm air concentrations (see table , column "exposure assessment"). two studies considered low pm level chronic exposure [ , ] . the studies selected presented multiple designs, populations involved, and procedures. many studies were questionnaire-based and air monitoring population studies, time series, and web-based studies. sample sizes in general population studies ranged from adult participants in community-based interviews, focus group discussions, and a community forum in kenya [ ] , to , respondents, to a standardized state-based telephone survey [ ] , involving a total of , participants. six of the studies selected were not ad hoc studies, but part of major survey studies [ , , , , , ] and most of them concerned the adult population. among the exceptions is the study of bergstra and colleagues [ ] . in this research, a cross-sectional questionnaire study was conducted for both children ( ± years) and adults ( years and above) living in the direct vicinity not all studies considered the same type of pm and not all used the same methods for assessing exposure. specifically, studies only considered pm . as an indicator of exposure to pm; studies only considered pm ; study considered pm , suspended particulate matter (spt), and total suspended particles (tsp); studies considered particle number counters (pncs); and studies considered pm . and pm . nine of the studies that considered both pm . and pm evaluated the association between pollution and survey responses using aqi, which is a six-category classification of ambient aq for six major pollutants: carbon monoxide, ground-level ozone, nitrogen dioxide, pm . and pm , and sulfur dioxide. regarding pm exposure assessment, the majority of studies (n = ) used aq data from official monitoring stations, while seven studies used aq models such as the moderate resolution imaging spectroradiometer (modis) aerosol optical depth (aod). only seven studies directly measured pm air concentrations (see table , column "exposure assessment"). two studies considered low pm level chronic exposure [ , ] . the studies selected presented multiple designs, populations involved, and procedures. many studies were questionnaire-based and air monitoring population studies, time series, and web-based studies. sample sizes in general population studies ranged from adult participants in community-based interviews, focus group discussions, and a community forum in kenya [ ] , to , respondents, to a standardized state-based telephone survey [ ] , involving a total of , participants. six of the studies selected were not ad hoc studies, but part of major survey studies [ , , , , , ] and most of them concerned the adult population. among the exceptions is the study of bergstra and colleagues [ ] . in this research, a cross-sectional questionnaire study was conducted for both children ( ± years) and adults ( years and above) living in the direct vicinity of an area with heavy industry. parents were asked to answer questions about the health of their children, with a particular focus on respiratory symptoms. among the exceptions, a chinese survey performed on parents years old or older with children between and years old can also be mentioned [ ] . some research has focused on specific groups: gany and colleagues ( ) [ ] recruited taxi drivers for an air-monitoring study in - . another study in employed ethnographic field methods and semi-structured interviews to ask community members to identify salient risks from industrial pollution and examine whether and how perceptions differed across occupational groups (industrial workers, commercial and service sector workers, and farmers) in a futian community [ ] . a study in malaysia included university students [ ] and in a leipzig university study, a collective of cyclists wore a unique combination of sensors that measured the particle number counts (pnc), noise, humidity, temperature, and geolocation [ ] . five studies investigated neighborhood vulnerability. in hong kong, a mixed-methods approach was applied to estimate neighborhood-based environmental vulnerability based on objective environmental measures and subjective environmental understanding from a local population [ ] . in wisconsin, the associations between low-level chronic exposure pm . and cardiopulmonary health and the potential mediating or modifying effects of adverse neighborhood perceptions were examined [ ] . in nairobi, the authors made a case for participatory approaches in aq studies, especially including those living in poor neighborhoods who may be particularly at risk from this trend [ ] . in chicago, the community adult health study studied the impact of individual, social, and built environmental factors on health and disparities in health [ ] . in seoul, korea, , subjects aged > years rated the outdoor aq in the neighborhood [ ] . studies using big data from the internet were typical of asian countries and we selected five of them: google trends for seven asian megacities [ ] ; an internet search engine, baidu [ , ] ; and posts analysed on weibo (a popular microblogging system) in china [ , ] . as for the procedures of the studies included in the systematic review, field studies [ , , , ] , telephone survey studies [ , , , , , ] , on-line surveys [ , , , ] , and mixed procedure studies [ ] were found. in the context of field studies, face-to-face interviews were the fundamental, but sometimes not unique, method employed to collect the data of interest to be related to the objective levels of pollution [ , , , , [ ] [ ] [ ] ] . considering mixed procedures and methods, we can mention maleki's study ( ) [ ] ; in this work, the protocol included in-person, audio-computer-assisted interviews; self-administered questionnaires; a physical examination; and biosample collection. to be able to systematically analyse the articles selected, the explored dimensions of perception were categorized by features. the results of this analysis, presented in table , showed that for "understanding" ( ) , most of the articles focused on awareness ( ); for "reactions/psychological" ( ), more represented risk perception ( ); for "reactions/physical" ( ) , the declared symptoms were most represented ( ); and for "behaviours" ( ) , exposure reduction ( ) and search for information ( ) were the most represented. table . recurrence of dimensions and features related to risk perception in the selected articles. understanding/sensorial perception (n = ) awareness = acknowledgement of the existence of a problem belief = opinion to be exposed knowledge = capacity to understand the existence of a problem reactions/psychological consequences (n = ) concern = apprehension risk perception = there is a risk for health (for me-for others) worry = it is more that concern, linked to a depressive mood the details are shown in table , in lines of the table including each of the features. the studies examining understanding ( ) included risk perception in cases, symptoms in cases, search for information in cases, and exposure reduction in cases. among the studies investigating psychological reactions ( ) , awareness was included in , symptoms in , search for information in , and exposure reduction in cases. the studies investigating physical reactions ( ) also explored awareness in cases, risk perception in cases, search for information in cases, and exposure reduction in cases. the studies analysing behaviors ( ) also explored awareness in cases, risk perception was considered in cases, and symptoms were considered in cases. the results in terms of the association of perception, intended in the broad sense, included the features examined, with measured pollution as the main outcome of this review. to examine the results in brief, see table . table . association between perception and measured air pollution. the number of articles for each kind of association is shown, with the references. further details for each article are in table . association a direct association between air pollution and perception is established, with a specific role of symptoms, behavior, socioeconomic factors, and information/communication in only two cases, the link with air pollution was not evaluated at all: in one case [ ] , features of perception, focusing on behaviors and socioeconomic analysis, were described and in the second case [ ] , the pm level measured in hong kong was used to build the scenarios for the questionnaire, only focusing on public awareness [ ] . in five articles, measured pollution was not correlated with perception [ , , , , ] . in the study by ueberham et al. [ ] , cyclists were not aware of a risk posed by air pollution. in the study of reames and bravo [ ] , no association between pollution perception and air pollution exposure was observed and the findings supported the neighborhood stigma theory [ ] . physical conditions are worse in minority communities, but a disadvantaged social composition seems to independently contribute to negative perceptions of these communities. perceptions of neighborhoods affect residents, also transcending the effects of objective conditions [ ] . gany et al. [ ] carried out air monitoring in new york city taxi cabs and at roadside taxi stands, combined with a survey of taxi drivers' knowledge related to air pollution and the associated health risks. semenza et al. [ ] measured aq and meteorological conditions in portland, or and houston, tx and subjects were interviewed by telephone about their perception and response. in brody et al. [ ] , the perception of local aq was different in dallas and houston and was not driven by actual readings from air monitoring stations. an indirect influence of air pollution on perception was reported by li et al. [ ] , in favor of the relation between awareness and risk perception and symptoms, and by orru et al. [ ] , for which the effect of perceived exposure on symptoms and the effect of perceived exposure on disease were mediated by health risk perception. in nine papers, aq had a scarce influence on perception. in huang et al. [ ] , the main linkage was with behavioral changes as a pre-post survey of the youth olympics showed that awareness and concern grew over time. in huang et al. [ ] , perception was boosted by previous negative experiences with pollution. experience was also crucial in chen et al. [ ] and guo et al. [ ] , where the influence of socio-economic factors was a relevant element for explaining differences in perception. in king et al. [ ] , the stigma theory was utilized for explaining the linkages among awareness, risk perception, and socio-economic factors. socioeconomic factors were also relevant in kim et al. [ ] , where the declared symptoms were not explicitly correlated with perception or pollution and in johnson et al. [ ] and rotko et al. [ ] , where symptoms were included and relevant. the study by pantavou et al. ( and [ , ] established a direct link between symptoms and perception. the consideration of symptoms is crucial because their linkage with perception has been widely reported in the literature. let us consider this aspect in the following articles, where a direct association between perception and measured pollution was identified, adding several further specific features. symptoms were a significant additional element in misra et al. [ ] , where the circulation of information on the web was examined; in particular, the search for "cough" and "asthma", together with "air pollution", related to pollution measurement; zakaria et al. [ ] used a self-administered questionnaire in selangor, malaysia and nikolopoulou et al. [ ] employed a questionnaire-guide in san diego, california to interview university students; bergstra et al. [ ] examined adults and children in an industrial area in the netherlands; malecki et al. [ ] considered the linkage with low-level exposure in wisconsin, usa, selecting a number of questions within a wider survey; dons et al. [ ] developed a cross-sectional questionnaire study in seven european cities; and pantavou et al. [ ] undertook a field study in athens, associating citizen perception, behaviors, and symptoms with air pollution and dust. in mirabelli et al. [ ] , symptoms and information were investigated as a distinctive explanation because the article examined the diffusion of air pollution alerts. there were several interesting observations-in particular, that the received information declared by interviewees is a central element in perception, but it frequently does not correspond to real circulating information (i.e., % of citizens living in an area without aq alerts reported being aware of the alerts). apart from this cue, the analysis strictly correlated referred symptoms with a high perception and pollution awareness. in ban et al. [ ] , in nanjing, china and in wen et al. [ ] , in six states in the usa, together with air pollution perception, symptoms and behaviors were considered to elucidate the consequences of individual behavioral change in terms of coping with smog pollution in the first article [ ] and the consequences of alerts in the second [ ] , several research papers have dealt with the issue of risk communication and alerts and their effects on the population's risk perception [ , , , , ] . in mirabelli et al. [ ] , knowledge of pollution and symptoms of related illnesses were more significant in areas where information about aqi was measured and disseminated. additionally, in reames et al. [ ] , pollution perception and health concerns were associated with air quality alert knowledge. the study of wen et al. [ ] showed that media alerts on air quality are a very important factor related to changes in outdoor activity. in brody et al. [ ] , the authors sought to improve understanding of the major factors shaping public perceptions of air quality, concluding that perceptions appear to be influenced by the setting (urban vs. rural); state identification; and socioeconomic characteristics, such as age, race, political identification, and access to information. in the study of semenza et al. [ ] , people changed behaviors when the air quality was worse, but this does not correspond with what is measured by control units. in dong et al. [ ] , aq and perception were associated with information in the explanation because the analysis was conducted by baidu web information dissemination and people searched for information as a reaction to the growing level of pollution. in tilt et al. [ ] , aq and perception were associated with socioeconomic factors in the elucidation of the relationship. the study was conducted in an industrial district in china, where the people expressed concern about air and water pollution; the analysis showed the differences among industrial workers, farmers, and workers in the commercial sectors, offering an interpretation of the different points of view of the local population. a direct association between perception and pollution has been established in a qualitative research study in a suburb in nairobi, kenya [ ] and in a study using telephone questions and face-to-face interviews aimed at monitoring the evolution of perceived annoyance over time, related to pm in the environment [ ] . furthermore, pu et al. [ ] looked at the perceived risk and satisfaction of aq in chinese provinces; lu et al. [ ] , wang et al. [ ] , and tao et al. [ ] used big data; lu et al. ( ) [ ] employed baidu to analyse the patterns of public concern about haze and the relationship between public concern and aq data provided by monitoring stations; wang et al. [ ] and tao et al. [ ] used weibo to examine the content and quantity of messages referred to aq and to construct an "air discussion index", respectively, to characterize the relationship between pm . and social media posts; cantuaria et al. [ ] developed a cross-sectional study to assess the environmental conditions, annoyance, and health of rural residents in denmark; and cisneros et al. [ ] studied california residents to understand their sources of aq information, perceptions of aq, and behaviors related to aq. the main finding of the present systematic review is that articles out of established a relationship between perception and measured pollution, even if indirect or moderate, showing a variety of methodologies and population samples (table ) . regarding population samples, it must be underlined that the majority of the articles included in the systematic review did not consider the young population, when it is an integral part of the population, so this could be surveyed in the future. given children's vulnerability to the effects of air pollution [ ] , it is vital to understand how children perceive their environment. if perception surveys are performed in schools and followed by environmental and health education interventions, we could also achieve the goal of raising awareness among younger generations [ , ] . the distribution over time shows a substantial growth of publications on this topic in the last years, with publications between and ( figure ); among them, the studies from china have acquired growing importance, with nine publications, while five studies were from the usa (figure ). this is due to an increased concern for air pollution and the implementation of control policies to be monitored and reinforced with ancillary studies. two studies developed in china, at the national level [ ] , and in four chinese megacities [ ] used data collected by the usa embassy, mentioning the growing attention towards air pollution by the chinese population that apparently the usa was boosting, offering air quality data. as a whole, the results confirm the knowledge acquired on the relationship between air pollution and perception; in particular, that encompassed by the seminal article of karen bickerstaff [ ] , which analyzes the developments in two main disciplinary directions. first, consolidation of the socio-cultural perspective, with the contribution of anthropology, geography, and sociology, and second, a convergence between the cultural and psychological approaches. most of the theories that maintain their validity and inform the research had already been presented [ ] . bickerstaff concluded, in particular, that the perception of risk is multi-dimensional and influenced by complex social, political, and cultural processes and that to understand how people frame the risk, it is crucial to address behavioral changes and communication. this analysis is largely valid today, with some additional elements reflected in the articles examined in this systematic review. the diffusion of studies examining human bodies at a very sophisticated and intimate level, such as the human biomonitoring of blood, breast milk, and other specimens, or genetic tests, has led people to perceive pollution of the body and in the body in a more direct way, with relevant ethical implications [ ] . the exploration of the perception of pollution in the body is a growing field of research that has developed from the experience gained and from the continuous attention to the issues of risk communication [ , [ ] [ ] [ ] . the choice of features to summarize the different components of perception was useful for observing the frequency in the recurrences of awareness, risk perception, self-reported symptoms, and search for information, which are representative of the main conceptual areas of interest of those studies. it is also interesting to highlight that some of them were scarcely considered, such as outrage and fear, widely examined in psychological and sociological studies, but included in only one study each [ , ] ; anxiety was considered in two studies [ , ] and request for actions from public authorities was considered in three cases [ , , ]. an increasing number of studies are interpreting risk perception as a health modifier and it can be considered among the psychosocial determinants of health [ ] [ ] [ ] . the term "social determinants" often evokes factors such as health-related features of neighborhoods, pointing to socioeconomic factors such as income, wealth, and education as the fundamental causes of a wide range of health outcomes [ ] . most of the studies examined in this systematic review included health considerations as self-reported symptoms, subject to personal judgement, and the linkage between perception and health symptoms was documented. this is relevant to supporting the hypothesis that risk perception plays a role as a health determinant or health effect modifier. it is interesting to note that the measured pm pollution and the short-and long-term health effects were not relevant in the studies analysed in the present review. however, we wish to emphasize that in , iarc released news about the identification of pm as a carcinogenic for humans [ ] . this assessment defined a step forward for scientific knowledge and the weight of air pollution within the burden of diseases became clearer, as well as its role in the distal determinants of health [ ] . in the same period, there was a turning point in china in terms of the implementation of policies to protect the health of citizens from air pollution and there was a significant improvement in studies on health and air pollution [ , ] . the use of search engine data and social media is changing the ways in which researchers investigate public opinion. consequently, traditional survey research may play a less dominant role [ ] . a recent review of the public's use of big data from web searches shows that the use of google trends has increased dramatically in the last decade. in the process, the focus of research has shifted to forecasting changes. in contrast, in the past, the focus was merely on describing and diagnosing research trends, such as surveillance and monitoring [ ] . one of the most recent applications of big data for the social sciences focused on an investigation of the phenomenon of vaccine hesitancy. some studies have concluded that monitoring new media could be useful for detecting early signals of decreasing vaccine hesitancy and planning and targeting effective information campaigns [ , ] . this systematic review identified only five articles that studied perceived pollution using big data in the past five years. three of them investigated perceived pollution using big data from web searches; namely, one of them used google trends [ ] and the other two, the baidu index [ , ] . although we found a correlation between the aq level and perceived pollution in these three articles, we noticed that each study used different search terms, namely, "air pollution", "cough", and "asthma" [ ] ; "shanghai air quality" [ ] ; and "haze" [ ] . the other two articles collected messages from sina weibo, which is the most popular microblogging service in china. both studies show that social media may be a useful proxy for measuring pollution, mainly when traditional measurement stations are unavailable, censored, or misreported [ , ] . although these studies show promising results, several limitations should be considered, suggesting that we cannot completely abandon the research method of a questionnaire survey. in this regard, one of the main limitations is that big data can only provide an active collective public response compared to questionnaire surveys, which directly indicate public concern based on individual responses. concerning chinese studies, we should consider the effect of government censorship on using social media for informatics in china. the disintermediation of communication, which has been growing exponentially in recent years, represents a relevant change in the circulation of information, with a potential relevant impact on risk perception and consequently, on health [ , ] . it is reflected in the studies examined here, with growing attention being placed on big data utilization and the continuous attention given to the utilization of results, the role of citizens, and the importance to inform and involve people to foster prevention and reduce environmental pollution. in fact, it is clearly conceptualized by the scientific community and decision makers that the only way of managing complex problems in the environment and health domain is sharing responsibility and action to improve the quality and durability of decisions and actions. in particular, it is of utmost importance to gather information about risk perception to plan risk governance actions, including health literacy programs and communication and engagement activities, to be able to dialogue with different social actors and contribute to prevention and protection [ , ] . to the best of our knowledge, this is the first systematic review investigating the relationship between ambient particulate matter levels and perceived pollution. in drafting this paper, we followed the prisma guidelines, which is one of the most appropriate tools for conducting systematic reviews. we searched three different databases to identify the highest possible number of studies and selected an extended timeframe, which allowed us to gather a significant proportion of the papers on this topic. all of the steps in the process, starting from the selection of abstracts to data extraction, were performed by three authors and not by the usual two, who have frequently consulted with each other when clarifying doubts. as for the scope of this systematic review, we are aware of the study's limitations, mainly regarding the capability to gather all published articles on this issue. specifically, two such limitations were the exclusion of some scientific databases and the selection of keywords. moreover, we are aware that our decision not to consider scientific papers from gray literature may represent a limit of completeness, although, on the other hand, we believe the higher qualitative reliability of the review is reasonable and not negligible [ , ] . however, these types of limitations are inherent in all systematic reviews with similar objectives of producing new knowledge in an appropriate time period with only a few summarized articles. regardless of the stated limitations, we believe that our work will be of interest to readers and may provide useful information for developing future lines of research focused on the investigation of social media and web search engines as predictors of air pollution peak episodes. the results of this systematic review reinforce the hypothesis that aq has an important influence on risk perception, through both indirect and direct links. there is a tendency to consider a wide spectrum of concepts and factors connected with perception, for example, behavioural changes, boosted by previous negative experiences with pollution. experience is a key element of cognition and awareness, which can be influenced by socio-economic factors to explain differences in perception. in most articles, a direct association of perception with measured pollution was identified, with several specific features. unlike other types of environmental determinants, the impacts of air pollution, particularly pm, on the health of people and communities have been extensively studied, to the point of identifying a dose-response relationship. it is therefore possible to define the level of exposure of different populations and to take harm limitation measures. these measures will depend both on the actions taken by policy makers and on the willingness of people to contribute by changing personal and collective habits. from the point of view of epidemiological research, it is very interesting to understand whether and how much people are aware of the pollution that surrounds them and how it can affect their state of health. this is relevant for interpreting the existing data and for perspectives in terms of risk reduction, i.e., primary prevention. most of the studies examined in this systematic review include recommendations for actions and explorations of policy implications of air quality improvements. the public acceptance of mitigation policies constitutes a crucial factor for their success, necessitating ancillary actions such as health literacy programs, awareness raising campaigns, and public participation activities. the perception of people regarding exposure to air pollution and personal health is critical for evaluating the responses of communities and the acceptability of related policies. to conclude, this review may call for new studies that consider the younger segment of the population and that use big data as a source of knowledge, without renouncing the more classic methodologies of investigations. in addition, the analysis of the perception of risk as a determinant of health should be addressed. moreover, this topic should be examined in the context of the current covid- emergency and the research on the role of air pollution in the spread of the epidemic. risk perception 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perception of risk human biomonitoring data interpretation and ethics; obstacles or surmountable challenges? environ. health priority persistent contaminants in people dwelling in critical areas of campania region, italy (sebiorec biomonitoring study) biomonitoring studies: bioaccumulation of polychlorinated biphenyls and heavy metals. in human health in areas with industrial contamination; who regional office for risk communication and the role of knowledge broker, experiences in italy impact of knowledge and misconceptions on benefit and risk perception of ccs public perceptions of environmental public health risks in the united states understanding an environmental health risk: investigating asthma risk perception in ontario youth sport the social determinants of health: it's time to consider the causes of the causes distal and proximal factors of health behaviors and their associations with health in children and adolescents social media in public opinion researchexecutive summary of the aapor task force on emerging technologies in public opinion research ten years of research change using google trends: from the perspective of big data utilizations and applications the web and public confidence in mmr vaccination in italy misinformation on vaccination: a quantitative analysis of youtube videos changing roles for primary-care physicians: addressing challenges and opportunities health science commu nication strategies used by researchers with the public in the digital and social media ecosystem: a systematic scoping review protocol definition of a systematic review used in overviews of systematic reviews, meta-epidemiological studies and textbooks the authors thank maria cristina imiotti and rosanna panini for their technical support. the authors declare no conflict of interest. key: cord- -zueqafmn authors: mallet, marc daniel title: meteorological normalisation of pm( ) using machine learning reveals distinct increases of nearby source emissions in the australian mining town of moranbah date: - - journal: atmos pollut res doi: . /j.apr. . . sha: doc_id: cord_uid: zueqafmn the impacts of poor air quality on human health are becoming more apparent. businesses and governments are implementing technologies and policies in order to improve air quality. despite this the pm( ) air quality in the mining town of moranbah, australia, has worsened since measurements commenced in . the annual average pm( ) concentrations during , , and have all exceeded the australian national environmental protection measure's standard, and there has been an increase in the frequency of exceedances of the daily standard. the average annual increase in pm( ) was . [formula: see text] . μg [formula: see text] between and and has been . [formula: see text] . μg [formula: see text] since . the cause of this has not previously been established. here, two machine learning algorithms (gradient boosted regression and random forest) have been implemented to model and then meteorologically normalise pm( ) mass concentrations measured in moranbah. the best performing model, using the random forest algorithm, was able to explain % of the variance in pm( ) using a range of meteorological, environmental and temporal variables as predictors. an increasing trend after normalising for these factors was found of . [formula: see text] . μg [formula: see text] since and . [formula: see text] . μg [formula: see text] since . these results indicate that more than half of the increase in pm( ) is due to a rise in local emissions in the region. the remainder of the rise in pm( ) was found to be due to a decrease of soil water content in the surrounding region, which can facilitate higher dust emissions. whether the presence of open-cut coal mines exacerbated the role of soil water content is unclear. although fires can have drastic effects on the local air quality, changes in fire patterns are not responsible for the rising trend. pm( ) composition measurements or more detailed data relating to local sources is still needed to better isolate these emissions. nonetheless, this study highlights the need and potential for action by industry and government to improve the air quality and reduce health risks for the nearby population. ods are yet to be realised in australia and across the southern hemisphere (rybarczyk and zalakeviciute, ) . ensemble machine learning methods, such as random forests (breiman, ) or gradient boosted regression (fre- und and schapire, , friedman, ) , use a range of predictor variables and an ensemble of decision trees to make predictions. they offer a consider- able advantage over other machine learning methods such as neural networks because the relationships between the predictor variables and the predicted variable can be fully interpreted (fuller and font, ) . furthermore, both numeric and categorical predictor variables can be used, which allows com- plex systems such as regional synoptic conditions or air mass origins to be residents of moranbah have reportedly been concerned with the high levels of dust appearing in households but, to date, a comprehensive investi- gation of trends and drivers of air quality in the township has not been done. the objective of this study is to exploit the recent advances in machine learn- ing to investigate the trends in pm in moranbah and assess the impact of changes in local industrial actions on air quality using open-access datasets and techniques. the primary intent of this study is therefore to provide lo- cal and state governments, as well as industry, a starting point to assess how changes in industrial development, residential growth or modes of employ- ment might influence the air quality to inform future policies or procedures. the secondary intent is to establish a methodology for this meteorological normalisation that accounts for the influence of nearby fires, which are an important source of particulate matter in the australian dry season, as well as other environmental factors such as soil water content. this study will therefore provide an updated meteorological normalisation technique that can then be applied to the numerous datasets of long-term monitoring of air quality across australia. a k-means clustering analysis was then applied to each -hourly trajectories using the openair r-package (carslaw and ropkins, ) (see figure ). this was done using both the euclidean distance and the angular distance the random forest modelling was performed using the rmweather r pack- forest machine learning techniques is that the partial dependencies between the predictor variables and predictant can be investigated. this is done by randomly sampling all but one of the predictor variables, one at a time. exploiting this allows for the influence of each predictor variables on pm to be isolated. ). it is difficult to identify the reason that the random forest algorithm outperformed the gradient boosted regression in this study. even though a wide range of hyper parameters were tested with both models, the random forest models were able to explain more than % more of the variance in pm than the gradient boosted regression. one possible reason is that the random forest models were less prone to over-fitting than the gradient boosted regression for this data set. the optimal random forest model (r = . , rmse = . ) was given it was also computationally much faster than a much higher number of trees. the optimal random forest model and gradient boosted regression model for. this partial dependence gives an indication of the meteorologically nor- malised trend which will be discussed later. temperature was an important predictor variable on the predicted pm . there are many ways that temperature can influence air quality from changes indicates that winds from the north-east and south are responsible for the highest pm concentrations. this will discussed further in the next section. the air mass backwards trajectory was not an influential variable on the predicted pm , giving strong evidence that local, rather than regional or the scope of this study was to explore the alarming increase in pm to above safe levels in moranbah. beyond the local and regional area surround- all raw data are available from free, publicly available, sources that are outlined in the methods. all code that is used to load, clean, analyse and visualise data, as well as the prepared dataset used for gradient boosted regression and random forest modelling, is available on the public github repository, https://github.com/marc-mallet/moranbah p m . towards the development of a low cost airborne sensing system to monitor dust particles after blasting at open-pit mine sites can land use intensification in the mallee, australia increase the supply of soluble iron to the southern ocean? scientific reports unprecedented smoke-related health burden associated with the - bushfires in eastern australia random forests air pollution and health. the lancet deweather: remove the influence of weather on air qual- ity data openair -an r package for air qual- ity data analysis. environmental modelling software - copernicus climate change service (c s): era : fifth gen- eration of ecmwf atmospheric reanalyses of the global climate source apportionment of pm . and pm aerosols in brisbane (australia) by receptor modelling apportionment of sources of fine and coarse particles in four major australian cities by positive matrix factorisation influence of the october dust storm on the air quality of four australian cities mortality and mor- bidity in populations in the vicinity of coal mining: a systematic review. bmc public health a review on the importance of metals and metalloids in atmospheric dust and aerosol from mining operations emission factors of trace gases and particles from tropical savanna fires in australia a desicion-theoretic generalization of on- line learning and an application to boosting greedy function approximation: a gradient boosting machine keeping air pollution policies on track effect of moisture on fine dust emission from tillage operations on agricultural soils sentinel hotspot characteristics of hazardous airborne dust around an indian surface coal mining area. environmental monitoring and using meteorological normalisation to detect interventions in air quality time series. science of the total envi- ronment ran- dom forest meteorological normalisation models for swiss pm trend anal- ysis marine aerosol at southern mid-latitudes gbm: generalized boosted regression models organic aerosol formation from the oxidation of biogenic hydrocarbons char- acterisation of the impact of open biomass burning on urban air quality in brisbane air pollution emis- sions - from australian coal mining: implications for public and occupational health splitr: use the hysplit model from inside r long- term trends in pm . mass and particle number concentrations in urban air: the impacts of mitigation measures and extreme events due to chang- ing climates evalu- ation of interventions to reduce air pollution from biomass smoke on mor- tality in launceston, australia: retrospective analysis of daily mortality the ncep/ncar -year reanalysis project when smoke comes to town: the impact of biomass burning smoke on air quality quantification of secondary organic aerosol in an australian urban location journal of occupational and environmental medicine/american college of ambient partic- ulate air pollution and daily mortality in cities a bagging-gbdt ensemble learning model for city air pollutant concentration prediction biomass burning emissions in north australia during the early dry season: an overview of the safired campaign biomass burning emissions over northern australia constrained by aerosol measurements: i-modelling the distribution of hourly emissions. atmospheric environ- ment the ambient aerosol characterization during the pre- scribed bushfire season in brisbane diurnal variation of pm concentrations and its spatial distribution in the south east queens- land airshed effects of bushfire smoke on daily mortality and hospital admissions in sydney australian government depart- ment of the environment and energy coal mine dust lung disease in the modern era origin, transport and depo- sition of aerosol iron to australian coastal waters. atmospheric environ- ment mining developments and social impacts on communities: bowen basin case studies queensland government statistician's office. url: www.qgso.qld.gov queensland gov- ernment air quality monitoring r: a language and environment for statistical comput- ing size-resolved mass and chemical properties of dust aerosols from australia's lake eyre basin impact of smoke from biomass burning on air qual- ity in rural communities in southern australia characterization of par- ticulate emissions from australian open-cut coal mines: toward improved emission estimates health effects of particulate air pollution: a review of epidemiological evidence machine learning approaches for outdoor air quality modelling: a systematic review bomrang: fetch australian government bureau of meteorology data in r analysis and interpretation of particulate matter-pm , pm . and pm emissions from the hetero- geneous traffic near an urban roadway noaa's hysplit atmospheric transport and dispersion modeling system assessing the impact of clean air action on air quality trends in beijing using a machine learning technique changing supersites: assessing the impact of the southern uk emep supersite relocation on measured atmospheric composition severe air pollution events not avoided by reduced anthropogenic activities during covid- conservation and recycling homelessness in rural and regional queensland mining communities. parity who air quality guidelines for particulate matter, ozone, nitrogen dioxide and sulfur dioxide: global update : summary of risk assessment welcome to the tidyverse extending the kolmogorov-zurbenko fil- ter: application to ozone, particulate matter, and meteorological trends meteorologically adjusted urban air quality trends in the southwestern united states ranger: a fast implementation of random forests for high dimensional data in c++ and r testing and dating of structural changes in practice significant changes in chemistry of fine particles in wintertime beijing from to : impact of clean air actions. environmental science & technology . for "meteorological normalisation of pm using machine learning reveals distinct increases of nearby source emissions in a mining town" by mallet, : • pm concentrations are rising by . ug/m^ per year in moranbah, australia • machine learning methods can account for the influence of meteorology on air quality • meteorologically normalised pm shows rising source emissions from mining activity and drying soil this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. j o u r n a l p r e -p r o o f declaration of interests ☐ the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.☒the authors declare the following financial interests/personal relationships which may be considered as potential competing interests:the author has family members that live in the town that is the focus of this study and employed in local industry. these personal relationships did not influence the analyses or discussion presented in this study in any way. key: cord- -cz f ca authors: heederik, dick j.j.; smit, lidwien a.m.; vermeulen, roel c.h. title: go slow to go fast: a plea for sustained scientific rigor in air pollution research during the covid- pandemic date: - - journal: eur respir j doi: . / . - sha: doc_id: cord_uid: cz f ca present studies on the role of air pollution and covid- spread and prognosis in patients do not fulfill quality criteria and are at present not sufficiently informative. the second study used european data and, based on simple correlation analyses, associated long term (jan-feb ) exposure to nitrogen oxides (nox) in the troposphere (resolution ~ * . km), assessed using satellite data, and absolute numbers of covid- -related deaths. [ ] the study made use of data from administrative regions in france, germany, italy and spain. in this analysis no standardization or adjustments to basic variables as population size and age distributions were made. the result, which was strongly driven by a few data points from italy and spain, was interpreted as an association between nox levels and fatal covid- case counts. the third and smallest study associated levels of no x and ozone between and obtained from monitoring stations across england with covid- mortality in a mere different english regions. [ ] positive associations were seen between levels of nitrogen dioxide and nitrogen oxide and increased covid- mortality and reported number of cases, without adjustment for population size, age distribution or other confounding variables. a negative association was observed with ozone levels. the authors concluded that their study provided a useful framework to guide health policy in countries affected by the pandemic. all three so-called ecological studies rely on aggregate data, which can suffer from the well-known problem of ecological fallacy, where a misjudgment in interpretation occurs as inferences about individuals are reasoned from the group to which the individual belongs. [ ] the study design is prone to potential confounding as on an aggregate level, many factors may vary and even co-vary between geographical entities. given the number of groups (i.e. counties) involved in the first study, and the higher quality of exposure assessment, ecological biases are clearly less likely than in the second and third study. the first study is also methodologically stronger because it is adjusted for a range of confounders at the county level, while in the two other studies, no adjustment for confounding factors was considered. however, a major issue, mostly ignored in these studies, resides in the complexity of a potential association between air pollution and covid- morbidity and mortality. in particular, the effect of air pollution on the spread of sars-cov- infection and on covid- prognosis should be distinguished. the dynamics of an epidemic are dependent on transmissibility, contact rates and duration of infectiousness summarized in the basic reproduction number or r . this factor may differ between geographical regions and over time. changes in r can occur over time as a result of the natural history of the epidemic and infection control measures being implemented, as is shown by the leveling off of epidemic curves in many countries where physical distancing is practiced. in particular, the reproduction number can be high in early stages of an epidemic when disease recognition and control measures are less adequate. whether air pollution affects the spread of an infectious disease, depends on whether the factors that determine the reproduction number; transmissibility, contact rates and duration of infectiousness, are influenced by air pollution. theoretically one can imagine that each of these variables can be influenced by air pollution, by changing host susceptibility, mobility and contact patterns and severity and duration of the infection. to explore whether air pollution influences r , high resolution temporal and spatial data are required, preferably supported by virus sequencing data. this far exceeds the granularity of the data used in air pollution studies and most infectious disease outbreak studies. in particular the two ecological studies which crudely correlate reported numbers of covid- cases or mortality to regional air pollution levels ignored the time of introduction of covid- in the different areas, did not take into account disease dynamics in any way, and ignored basic epidemiologic principles by using inadequate measures of disease frequency. [ ] to study the effect of air pollution on the spread of the pandemic in ongoing studies requires knowledge about the time of the virus introduction in the study area(s) and the dynamics of the pandemic in the study area(s). when comparing different study areas, the local outbreak size needs to be accounted for. the authors of the us study seem well aware of their study's limitations related to outbreak dynamics and acknowledged that using total population size in a county as a proxy for the local size of the outbreak in a given county, may result in unmeasured confounding through partial adjustment for outbreak size. [ ] the updated study probably better adjusted for outbreak dynamics by including days since first covid- case reported and days since issuance of stay-at-home order for each state, resulting in a considerably smaller regression coefficient for pm . and covid- mortality. the fact that the epidemic had spread more evenly across the country, also to less urbanized areas, from almost % of counties with covid- deaths to almost % might also have contributed to a weaker association for pm . . a separate us study, associating covid- fatality rates and mortality to pm . in a three pollutant model (pm . adjusted for and no x ), showed a null association for pm , with covid- fatality rates and a marginally significant association with mortality. [ ] the use of the case fatality rate instead of covid- mortality, and adjustments for epidemic timing of introduction and spread of covid- by adjusting for the time the st and th covid- case occurred, probably explains the marked difference in results for pm . with the other us study. the authors also indicate that control for spatial trends in exposure and residual autocorrelation in exposure between counties may also have contributed to the observed difference in pm . study results. the same study found positive and statistically significant associations for no x . however, it was concluded that no x air pollution level may act as a surrogate for urbanicity, despite of adjustment for population density. these studies together highlights that uncovering the effect of air pollution on the spread of sars-cov- represents an enormous challenge that will require multidisciplinary collaboration and highquality data. other approaches, among which air pollution time series studies need to be explored when the appropriate covid- data to perform such analyses become available. such approaches should also consider the effect of changes in air pollution levels. however, changes in air pollution also occurred after introduction of measures to mitigate the impact of the pandemic. here confounding still plays a major role as many additional factors changed at the same time (e.g. physical activity, stress, social economics, medical care visits) introducing other challenges in the data analyses. in the meantime, multiple other studies have been published, many of which can be found in a useful study repository. [ ] however, many of these studies did not take into account covid- outbreak dynamics. this leads to similar biases are described here. the effect of air pollution on disease prognosis can be studied using more conventional approaches after covid- infection. for instance by following up in time confirmed patients in different regions with different levels of air pollution. however, even this type of study might be complicated by confounding: for instance disease severity and testing policies can differ by treatment center, and the fact that quality of care delivered by health care systems may differently vary across regions depending on the size of the local outbreak. these scenarios are more classical examples of confounding for which a range of solutions may be considered. the use of test-negative designs has been proposed in which risk factors are compared between subjects that test positive or negative to sars-cov- . [ ] such designs can eliminate some of the aforementioned concerns (access to testing etc.), but has other limitations, mainly related to shared risk factors for being tested regardless of the outcome (e.g. presence of respiratory disease). we certainly do not want to argue that air pollution does not play a role in the covid- pandemic. there is previous evidence from the sars coronavirus epidemic [ ] (albeit that this study suffers from the same ecological problem as the current studies), similarities with a possible smoking contribution to the pandemic [ ] , mechanistic evidence involving the angiotensin-converting enzyme (ace- ) receptor in covid- pathology that could be influenced by air pollution [ ] , and the fact that air pollution has previously been causally linked to risk of pneumonia and other comorbidities that contribute to covid- deaths. [ ] however, determining if there is a causal effect and obtaining an accurate estimate of the effect requires rigorous and time consuming research. a final major point of criticism that we wish to make is that one of the aforementioned papers was accepted for publication after a -day review period [ ] , while the other papers made headlines before the peer-review process based on preprint manuscripts. [ , , ] it is important to ask why is this the way covid- air pollution research is being reviewed and communicated? research in this field may be of relevance for the spread of infectious disease and disease prognosis, but outcomes from air pollution research are unlikely to lead to changes in the implementation of pandemic control measures and in the clinical care of patients. instead, air pollution and infectious disease epidemiology research will have an impact in the longer term, as to fully understand etiology and cocontributing factors. thus, there seems little reason to abandon the rigorous peer review process and expedite manuscript publication for covid- air pollution studies. study quality is of great importance and all stakeholders, including the scientific community, policy makers and the general public, are served best by well-conducted and thoroughly appraised studies on air pollution and covid- . we need to avoid creating myths that are diverting political and scientific attention from other urgent and actionable questions. the sentence go slow to go fast is used in industry to combat the short-sighted fixation on speed while sacrificing product quality and hence utility. in the case where research does not have immediate impact on clinical and societal interventions related to the current pandemic, we may want to adopt this philosophy. air pollution researchers and scientific journal editors have an important role in maintaining calm scientific rigor during this tumultuous time. of the global burden of disease project for lower respiratory infections, estimates of the global, regional, and national morbidity, mortality, and aetiologies of lower respiratory infections in countries, - : a systematic analysis for the global burden of disease study ers/ats workshop report on respiratory health effects of household air pollution exposure to air pollution and covid- mortality in the united states medrxiv assessing nitrogen dioxide (no ) levels as a contributing factor to coronavirus (covid- ) fatality links between air pollution and covid- in england. medrxiv air pollution linked to far higher covid- death rates, study finds air pollution may be 'key contributor' to covid- deaths -study, in the guardian exposure to air pollution and covid- mortality in the united states: a nationwide cross-sectional study medrxiv the ecological fallacy strikes back accurate statistics on covid- are essential for policy guidance and decisions urban air pollution may enhance covid- case-fatality and mortality rates in the united states covid- and air pollution analysis proposals for test-negative design and matched case-control studies during widespread testing of symptomatic persons for sars-cov- air pollution and case fatality of sars in the people's republic of china: an ecologic study. environ health clinical characteristics of coronavirus disease in china acute and subchronic exposure to air particulate matter induces expression of angiotensin and bradykinin-related genes in the lungs and heart: angiotensin-ii type-i receptor as a molecular target of particulate matter exposure ambient particulate air pollution and acute lower respiratory infections: a systematic review and implications for estimating the global burden of disease we thank calvin ge for proof-reading and editing the editorial and marc chadeau-hyam for his critical and constructive comments. key: cord- - lgn u authors: liu, tiantian; guo, yubing; wang, mei; hao, xiaotang; he, shicong; zhou, rong title: design of an air isolation and purification (aip) deskfor medical use and characterization of its efficacy in ambient air isolation and purification date: - - journal: biosaf health doi: . /j.bsheal. . . sha: doc_id: cord_uid: lgn u the incidences of nosocomial infections (nis) are increasing throughout the world, especially for those airborne diseases caused by pathogens or air particulates that float in air. in this study, we designed and manufactured a desk for clinic consultation room air purification and air isolation between doctor and patient. the air isolation and purification (aip) desk has a high efficiency particulate air (hepa) filter on the tope and several primary efficiency filters on the sides for air purification. the air circulating between inlet and outlet forms a wind-curtain between doctor and patient. the computational fluid dynamics (cfd) model was used to calculate the speed of the air flow and the angle of sampler. we tested the air purification function of the aip desk in rooms sized about . × . × . m (l × w × h) and found that the aip desk could significantly remove the tested air pollutants like smoke particulates and microorganisms like staphylococcus albus (s. albus)and human adenovirus type (hadv- ). the wind-curtain can significantly block the exhale air of patient being transmitted to the respiratory area of doctor setting in the opposite of aip desk. thus, the aip desk can be used in hospital setting to reduce the risk of nis and protect both doctors and patients. j o u r n a l p r e -p r o o f nosocomial infections (nis), also called hospital-acquired infections, occur during hospitalization or after hospital discharge [ ] . in developed countries, nis affect - % of general hospitalized patients and up to % or more of intensive care patients [ ] . studies have indicated that this common complication currently affecting inpatients is a major biosecurity concern for patients and health care professionals worldwide [ ] [ ] [ ] [ ] . nis are usually caused by multidrug-resistant pathogens, and their appearance will result in extra healthcare costs to patients in terms of prolonged hospital stay and treatments, potential disability, or even death [ ] [ ] [ ] . respiratory viruses are one of the main pathogens that cause hospital-acquired infections [ , ] . for example, the severe acute respiratory syndrome coronavirus (sars-cov) was quickly transmitted within medical staffs, patients and visitors, caused severe additional suffering in china in [ ] . the middle east respiratory syndrome coronavirus (mers-cov) spread rapidly around the world, since the first case was confirmed in saudi arabia in june . it is now found in countries and regions, where it has a serious impact and causes huge financial losses [ ] [ ] [ ] [ ] . in order to prevent and control nis, it is vital for hospitals to take necessary procedures to isolate sources of infections and transmissions to ensure the quality of medical care and protection of vulnerable patients and medical personnel. hand hygiene and personal protective equipment (ppe) are necessary straight forwards ways to prevent nis and protect medical personnel. air purifiers and central ventilation systems are further environmental preventative measures that may be employed. while proper ventilation can significantly reduce the amount of particulate matter and aerosols in air, limited space in some older hospital buildings render it impossible to install a central air supply system. purification efficiency is also limited [ , ] . furthermore, critically ill patients in traditional intensive care units (icus) are more susceptible to be infected via nis as compared to patients in general [ ] . we recently designed an air isolation and purification (aip) desk integrated air isolation and air filtration/purification functions for the purpose of reducing hospital nis. computational fluid dynamics (cfd) model which usually used to assess the effectiveness of hospital ultraviolet germicidal irradiation devices and ventilation systems for the purpose of infection control [ ] [ ] [ ] was adopted in the aip desk. in this study, we used cfd simulation technology to determine the angle of sampler and the air supply speed of the aip desk.cigarette smoke, aerosolized bacteria j o u r n a l p r e -p r o o f staphylococcus albus (s. albus) and human adenovirus type (hadv- ) were used to examine the purification efficiency of the aip desk. hadv- is a stock of our laboratory. adenoviruses were cultured in adenocarcinoma human alveolar basal epithelial cells (a ) that were obtained from the american type culture collection (manassas, va, usa) and subsequently maintained in our lab. a cells were cultured in dulbecco's modified eagle's medium (dmem) containing μg/ml streptomycin and % fetal bovine serum (invitrogen, carlsbad, ca, usa). all cells were frozen using a bioflash drive commercial freezing kit (fibulas, new york, ny. usa). hadv- was purified using standard cscl density gradient centrifugation. abi real-time pcr instrument were used to test the copies of virus (thermofisher, ma,usa). the aip desk was independently designed and developed by our team, and manufactured by guangzhou angel biosafety co., ltd. the desk is . x . x . m j o u r n a l p r e -p r o o f system contains primary efficiency filters on sides and a high efficiency particulate air (hepa) filter on the top of the aip desk. a fan is installed at the position indicated in fig. a , and functions to drive air through the air ducts in the aip desk. upon the fan turned on, negative pressure is formed near the air inlets and sucks the surrounding air to pass through the air-ducts and filters; thereby physically remove pathogenic microorganism-containing aerosols and dust particulates in the adsorbed air. the filtered air then comes out of the air outlets and forms a wind-curtain barrier in front of patient and doctor; therefore, to block patient's exhale air to be transmitted over to doctor's respiratory area ( two rooms with dimensions of . × . × . m (l× w × h) in our laboratory were used to conduct the experiment. the aip desk was placed in the experimental room ( fig a and a ), and another room having a regular clinic desk served as control room. according to the five-point layout method [ , ] , five sampling sites (a, b, c, d and e) as indicated in fig b and b were selected. all the sampling sites were more than m away from the wall, and were approximately m high from the ground, which simulate the height of the patient's/doctor's mouth positions while sitting at each long side of the desk. the hydraulic diameter between the doctor's and the patient's mouths is . cm. to facilitate the mesh division and ensure the quality of the mesh, the small air outlets of the air supply port were merged into one large air outlet, so the air supply area was simulated. it was larger than the data on the computer-aided design drawings but had little effect on the simulation results. there are air outlet ports ( . × . background conditions within the test rooms were established by calibration of the ambient temperature to °c, relative humidity to % ± and total particulates concentrations to × particulates/l. a smoke generator was placed in the middle of the room and the test cigarette was then ignited. the cigarette was stopped when the initial concentration of smoke particulate reached . ± . mg/m . a standard ceiling fan was used to stir the air for min to evenly mix the particulate contaminates with air in the test room. after the ceiling fan was turned off for min, the concentration of particulates was measured using a laser dust particulate counter. the air purification desk was then turned on and allowed to run for min, followed by measurement of the particulate concentration at the sites indicated ( fig b ) . the procedure was repeated times in each gear. identical procedure was performed in the control room having a standard clinic desk. similarly, in the s. albus and hadv- experiments, after calibrating the background conditions, an aerosol generator was used to generate the tested bacterial and viral aerosols for min at the maximum atomization rate of . ml/min. fan stirring was continued for min after the mimic contamination phase was stopped, and the mixture was allowed to stand for min. bacterial sampling was performed at site e ( fig b ) using a six-stage sampler with a sampling time of min, while viruses were sampled at site e using a virus sampler for min. the air purification desk was then turned on for , and min respectively at each gear. bacterial and j o u r n a l p r e -p r o o f viral samples were collected at each of the remaining sampling sites ( fig. b and b , fig. c and c ). these procedures were repeated in the control room. the plates for s. albus collection were placed in an incubator and incubated at °c for h, then colonies formed were counted and the number of growing colonies (cfu/m ) were calculated. the gel membranes for hadv- collection were respectively filled into virus culture solution, dissolved, mixed, and stored at °c.an abc nucleic acid extraction kit (guangzhou hexin technology co., ltd.) was used for nucleic acid extraction of the samples. the number of viral genome copies was determined by real-time quantitative pcr (q-pcr) using a universal adenovirus q-pcr kit (guangzhou hexin health co., ltd.) on applied biosystems real-time pcr system. the sample to be tested was placed in the test room and the background conditions in hospital clinic setting, the testing room was with an aip desk while the control room has a regular clinic desk. doors and windows were opened for h to balance the air of the two rooms with the outside environment. then doors and windows were closed, and ventilation system was turned off for h to stabilize the air for detection of temperature and humidity. the mass concentration of dust particulates was measured, and the data collected were used as the initial concentration. the aip desk was then turned on and data were recorded following the above-mentioned experimental procedure. sampling was performed every min for h, with the sampling head being placed in position a, b, c, d and e ( fig. c and c ). calculation formula used in this study is: blocking rate: e'= (c '-c ') / c ' note: c 'is the average concentration at the initial point, and c ' is the average concentration at each point around. we used spss . (ibm, armonk, ny) for statistical analysis of the data and plotted the graphs using graphpad prism (graphpad software, san diego, ca). p＜ . was considered statistically significant. the air applying angle θ was set at ° and the air distribution speed at m/s where the supplying airflow formed a relatively complete wind-curtain, showed as dark blue in fig. a . study results indicated that patient's exhale air is blocked by the cold air flow emitted from the air outlet on the surface of the aip desk, thus unable to cross over to the doctor's breathing area. the airflow around the doctor is not directly affected by the wind-curtain, and its thermal plume can develop normally. thus, the wind-curtain from the aip desk can block the airflow exchange between the patient and the doctor; thus, reduce the risk of aerosol infection of doctors. the entrainment effect of the wind-curtain and the thermal plume of the human body is reflected in the simulation (fig b) . results indicated that when the air supply speed is at m/s, and the air supply angle is °, the entrainment of the wind-curtain j o u r n a l p r e -p r o o f and human thermal plumes reached a better effect in the simulation. the suction effect generated by the wind-curtain plays a vital role in blocking the air transmission. the patient's exhale air will be drawn into the wind-curtain, then follow the air flow of the wind-curtain to the inlet of the desk for filtration and purification. thereby the patient's exhale air was surrounded and controlled by the wind-curtain. the air purification efficacy of the aip desk in a contaminated room was assessed using cigarette smoke to simulate particulate pollution. the average values for five sampling sites in both the test and control rooms are shown in figure . the number of ≥ . μm particulates remained high throughout the experiment in the control group. however, with the presence of the aip desk, the numbers of smoke particulates dropped rapidly from the first min of the aip operation, then almost . % particulates have been removed when the aip desk run for min. the concentration of smoke particulates continued to decline until after min when the target level was achieved. this was observed in all three gears/air flow speeds of the aip desk ( fig a and b) . the results showed a significant difference between the control and the three experimental groups (p< . ). there were no significant differences in smoke particulate elimination among the high, medium and low gear settings of the aip desk. taken together, these data indicate that the purification desk has a high efficacy against particulate contamination in air. air purification efficacy of the aip desk was assessed in a room contaminated with aerosol pathogens, s. albus or hadv- . results for s. albus removal showed a significant difference between the control and all the three experimental groups when aip desk was run for and min respectively (p< . ) (fig a) . there was no difference in purification efficiency among the groups with three different gears. no bacteria remained detectable in air after aip desk was run for min in all the low, medium and high gears. as to the removal of hadv- , results showed a significant difference between the control and all the three experimental groups when aip desk was run for and min respectively (p< . ) (fig. b) . there was no difference in purification efficiency among the groups with three different gears. no virus remained detectable j o u r n a l p r e -p r o o f in air after aip desk was run for min in all the low, medium and high gears. thus, the aip desk has extremely high purification efficacy against airborne pathogens. cigarette smoke was used to simulate particulate contamination in patient's seating area and efficacy of the air wind-curtain in blocking these smoke particulates (patient's side) escaping to other side (doctor's side) was assessed. results showed that the presence of the wind-curtain could significantly block the smoke particulates penetrating from the patient area to the doctor area (table ) . when the aip desk is set at the low gear and run for min, the average blockingefficacy is . %;when set at the high gear, the average blockingefficacy is . %. approximately . % of the smoke particulates will be blocked when the aip desk was run for min at the high gear. table shows the results of hadv- blocking efficiency of the aip desk. when used even at low air-flow gear, the hadv- blocking rate reached % when aip desk was run for or min respectively (table ) , which means that hadv- did not flow over to other side of the air-wind-curtain. hadv- was not detected at all the sampling sites in the room, indicating that the isolation efficacy of the aip desk is very good for removal of the virus. thus, the wind-curtain formed by aip desk can effectively block smoke particulates and the aerosol pathogen from the patient's area to the doctor's area. to assess the efficacy of the aip desk in a clinical setting, we placed it in a functioning clinic consultation room. fig. showed the purification curve for experimentally contaminated smoke particulates. results indicated that the number of particulates ( . - . μm and . - . μm) were decreased significantly (fig a, b, c and d) after the aip desk was run for min at all three low, medium and high gears. moreover, we found no difference in detected particulate concentration (data not shown) in all five sampling sites (fig c ) , demonstrating that the air purification efficacy is high in the clinical setting. prevention of nis is of vital importance for protection of both healthcare j o u r n a l p r e -p r o o f personnel and vulnerable patients, especial during the outbreak of infectious diseases, for example the currently on-going covid- pandemics. the suddenness and rapid spread of the epidemics might result in insufficient ppe supply or ppe did not meet medical use standards. medical personnel's unfamiliarity and irregularity with ppe operation, intensively increased workload make the implementation and monitoring of traditional disinfection and sterilization methods more difficulty [ ] . in the study of mcmichael et al ( ) for epidemiology of covid- in washington, a total of patients were confirmed, of which were paramedics [ ] . some other studies have shown that respiratory viruses and some pathogens can be transmitted through droplets [ ] [ ] [ ] .therefore, development of novel technologies that can be applied in the clinic environment may represent a cost-effective means of reducing transmission of diseases. in this study, we have described and tested a novel air isolation and purification (aip) desk which we designed and manufactured by guangzhou angel biosafety co., ltd. concept of cdf model [ ] [ ] [ ] was adopted in our design and we found that setting with air supply speed at approximately m/s and the air supply angle θ at ° gives the best droplet isolation efficacy ofthe aip desk. we found that the aip desk has a high purification effect following ambient air contamination by cigarette smoke, s. albus and hadv- . the air purification efficiency of the experimental groups (with an aip desk) at all three wind speeds was consistently higher than that of the control group (with a standard medical consultation desk). apparently, the aip desk provides efficient air purification within the clinic consultation room and additionally protects healthcare personnel by means of a wind-curtain that separates them from patients. hadv- is a dna virus that causes respiratory diseases. it occurs mostly in children and can be fatal; therefore, it is meaningful to use it as test pathogen to detect the purification efficiency of our aip desk. moreover, in our laboratory, we have had the defective hadv , which will not cause human infection during the experiment and j o u r n a l p r e -p r o o f endanger the life and health of the experimental staff. the virus needs to be wrapped into particulates before spreading to the air [ ] . the results of our experiments show that the use of the aip desk can reduce the viral particulates in the air, and therefore reduce the time of the virus floating in the air. in addition, some studies have indicated that m distance between people can effectively reduce the spread of droplets [ ] . by using the aip desk, we can shorten, when it is necessary, the distance between patient and medical staff due to the existence of the protective wind-curtain generated by the aip. studies have shown that activities of on-site personnel during dynamic experiments have an impact on the concentration of pathogens collected and the concentration of respirable particulate matter, with more active people having a greater impact. mechanisms to reduce the impact of the environment and personnel mobility will be the key improvement goal for dynamic purification equipment such as medical isolation clinics [ ] . there are limitations on our experimental tests of the designed aip desk because we only used smoke particulates, s. albus, and viruses to simulate the isolation of patient droplets. we did not truly test the isolation of patient droplets and the protection of medical personnel. related experiments have been planned as our next step research. the use of medical isolation clinics has played an important role in protecting medical personnel and reduce nis [ ] . our aip desk provides a new idea and method for future elimination of nis risk. the medial equipment will fill the gap in dynamic medical air purification and provide technical support for dynamic air disinfection. application of the aip desk will enhance the control of airborne infectious disease, decrease the risk of nis and the improvement to the safety of healthcare personnel. nosocomial infections (nis) have always been an issue impacting public health. as far as covid- epidemic in is concerned, there are , medical staff confirmed infected and at least medical staff died in china. nis are attracting more and more attention, but there have been no effective ways to prevent or reduce it. currently, disinfection of clinic rooms depends only on additional air purifiers or ultraviolet lamps, which is not only expensive and but also achieve only static disinfection. we designed and manufactured an air isolation and purification desk (aip desk) that integrates all the air isolation, filtration and purification functions into one equipment. test results indicated that this desk can effectively reduce and remove particulate matter and pathogens in ambient air. the air circulating between inlet and outlet of aip desk formed a wind-curtain that isolates patient's exhale air from doctor's respiratory area. the aip desk can significantly reduce the risk of cross infection in the hospital, and thus effectively protecting patients and medical staff. journal pre-proof health-care-associated infection in africa: a systematic review portable ultraviolet light 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authors declare that there are no conflicts of interest. tiantian liu,: do the experiment , data analysis and write the paper; yubing guo,mei wang, xiaotang hao, shicong he: do the exprement; rong zhou: design the experiment and data analysis. key: cord- - pyx r authors: grout, andrea; howard, natasha; coker, richard; speakman, elizabeth m title: guidelines, law, and governance: disconnects in the global control of airline-associated infectious diseases date: - - journal: lancet infect dis doi: . /s - ( ) - sha: doc_id: cord_uid: pyx r international air travel is increasingly affecting the epidemiology of infectious diseases. a particular public health, economic, and political concern is the role of air travel in bringing infectious passengers or vectors to previously non-endemic areas. yet, little research has been done to investigate either the infection risks associated with air travel or the empirical evidence for the effectiveness of infection control measures on aircraft and at borders. we briefly review the interface between international and national legislation, policy, and guidelines in the context of existing infection risks and possible scenarios. we have found that public health guidance and legislation, which airlines are required to follow, are often contradictory and confusing. infection control measures for air travel need to be underpinned by coherent and enforceable national and international legislation that is based on solid epidemiological evidence. we recommend further research investment into more effective on-board vector control, health screening, and risk communications strategies, and the development of enforceable and harmonised international legislation. low air fares and a multitude of social and economic factors have resulted in increased air travel. the number of journeys taken by passengers each year has grown from approximately million in to more than · billion in . the epidemiology of infectious diseases associated with air travel and the challenges of infection control are important public health concerns, yet they are scarcely discussed in the literature. aircraft can now travel to almost any part of the world within h, and can enable spread of infection either by inflight infection transmission or by transporting infectious passengers or vectors-eg, malaria-infected mosquitoes-from endemic to non-endemic regions, thus putting populations in destination countries at risk. the combination of rising passenger numbers, new travel destinations, and on-board transmission events can influence transmission patterns of several imported diseases, including severe acute respiratory syndrome (sars), middle east respiratory syndrome (mers), and ebola virus disease. for example, the ongoing transmission of zika virus disease is believed to have been introduced to the americas by air travel. management of these risks requires knowledge of the dynamics of infectious disease transmission and the potential effectiveness of control measures, suggesting that frontline employees (eg, airline staff) would need appropriate training to handle suspected disease cases. as a result of experiences with sars, the international air transport association (iata) issued the emergency response plan and action checklist, which consists of guidelines and best practices for aircrews during public health emergencies. to reduce the risk of on-board disease transmission, the us centers for disease control and prevention (cdc) provides cabin crews with information on general infection control measures and guidelines to identify ill and potentially infectious passengers. passengers with certain conditions-for example, someone recovering from measles-might require medical clearance; however, guidelines for these conditions vary between countries and can be subject to individual airline policy. the effectiveness of infectious disease response strategies largely depends on prompt identification of cases. current measures, such as entry and exit screening, isolation, quarantine, and travel health information might not be feasible or sufficient to control infectious disease transmission. for example, the value of entry screening measures has been questioned, , while an evaluation of border entry screening measures in several countries concluded that a combination of communication methods (eg, in the form of pre-flight health information, in-flight videos, and clinical guidance) for passengers and clinicians might be a more effective strategy for global infectious disease control. collectively, the unique dynamics and interactions at play in an aircraft environment require a distinct response to infectious disease control. in this personal view, we consider the disconnects between global health law, national jurisdictions, organisational guidelines, and aircrew compliance by discussing existing risks and presenting two infection scenarios based on current airline practice. although the risk of disease transmission exists whenever people congregate in confined spaces, aircraft are unique in having individuals from often diverse geographical regions, with differing population immunity and exposure risks, interacting with aircrews and each other. infection can occur via direct transmission through contact with skin, blood, or other bodily fluids (eg, ebola virus), or via indirect transmission without person-to-person contact. indirect transmission on an airplane can occur through infectious droplets (eg, influenza virus), through contaminated surfaces or objects (eg, meticillin-resistant staphylococcus aureus), or long-distance air travel in particular exposes passengers to several factors that could affect disease transmission. the transmission characteristics of a pathogen, ambient climatic conditions, time spent on board, and aircraft type can affect quantification of the general transmission risk. absolute figures for the risk of in-flight disease transmission are therefore not readily available and the evidence base is inadequate. mangili and gendreau reported in-flight transmission of influenza, sars, tuberculosis, measles, smallpox, and other pathogens. on a h flight from hong kong to beijing in , of passengers were infected with the sars virus by a single ill passenger, while modelling has demonstrated the possibility of in-flight transmission of mers coronavirus. protective measures are in place in modern aircraft, but these measures are not necessarily as robust as assumed. for example, commercial aircraft use highefficiency particulate air (hepa) filters to restrict exposure to small airborne particles. however, there are no regulations requiring that hepa filters be in place, and little testing has taken place to assess the effectiveness of these filters. in , ebola virus disease was brought to the usa, the uk, and nigeria by undiagnosed infected people aboard aircraft. brownstein and colleagues demonstrated the effect of air travel on the global spread of seasonal influenza, noting that decreased air traffic following the terrorist attacks of sept , , was associated with a delayed influenza season. maloney and cetron documented the air-travel-associated transmission of meningococcal disease. global air travel could spur the spread of epidemics by bringing viruses and parasites to new areas. infected mosquitoes on intercontinental flights are believed to have contributed to the global spread of malaria. , west nile virus is widely suspected to have been spread to the usa by an infected mosquito carried by plane. similarly, the introduction of zika virus to the americas coincided with an upsurge of air travel to brazil from endemic countries in . management of the risk of transporting infected passengers requires knowledge of transmission dynamics and the potential effectiveness of airport entry and exit screening measures, the ability to appropriately isolate or quarantine individual passengers on an aircraft, and adequately trained aircrew who are able to identify signs of infection and take appropriate measures. for example, who maintains that the risk of vector-borne diseases being transmitted aboard aircraft is low, but recommends aircraft disinsection (a public health measure involving insecticide treatment of aircraft interiors and holds), stating that "there have been frequent instances of insects of public health importance being introduced from one country to another, with occasional dire consequences". however, the effectiveness of disinsection is unclear. minimisation of the risk of inadvertently carrying insect vectors requires consistent use of effective control measures, including insecticides that are safe for frequent aircrew and passenger exposure. public health measures for international air travel include a range of national and international legislative tools, policies, and guidelines. globally, countries signed the legally binding international health regulations (ihrs), with the aim of controlling global disease spread. however, the only ihr provision relating to air travel is the requirement that all chief pilots provide a brief aircraft general declaration on passenger health to ground staff before disembarkation. the international civil aviation organization (icao) and iata coordinate with who and provide recommendations, but specific controls are left to the discretion of individual countries. national guidance and legislation are uncoordinated across countries, and-with no strong evidence underpinning control measures-they are often inconsistent. following the sars epidemic, iata recommended that all air carriers create an emergency response plan for public health emergencies, but these are only guidelines and legislative powers lie with national authorities. airlines face conflicting obligations, since they must comply with infectious disease controls in both origin and destination countries. airlines owe a duty of care to three different groupspassengers, aircrew, and destination country populations-and these duties sometimes conflict. for example, the us environmental protection agency prohibits usage of some insecticides because of potential risks to aircrew, whereas national laws in australia and new zealand require usage of these insecticides. us airlines flying to these countries must purchase insecticides at stopovers, and airline unions have raised serious concerns about the "inconsistent and inappropriate application", toxicity, and potential adverse health effects of these agents. other airlines have reported difficulties in aircraft storage of aerosol insecticides that were either banned or prohibited from import in some destination countries. additionally, doubt exists as to the effectiveness of disinsection, with research identifying increasing resistance of mosquitos to insecticides. although the icao encouraged more research into non-chemical disinsection procedures in , procedures have not changed and airplane disinsection policies and implementation remain inconsistent worldwide. airlines and national authorities can refuse to transport passengers they consider to be a health risk. the us air carrier access act states that carriage can be refused www.thelancet.com/infection vol april e personal view where a passenger presents with a disease that "is both readily transmitted in the course of a flight and which has serious health consequences (eg, sars, but not aids or a cold)". this rule applies to all flights of us carriers and flights to or from the usa, but it clearly requires any disease to be diagnosed before the flight. considerable debate continues about the effectiveness and practicality of screening passengers at entry, exit, or both. further research must be prioritised before national and international legislation can take a consistent, evidence-informed approach to screening, because flight duration and pathogen transmission dynamics are just two important factors that challenge one-size-fits-all recommendations. enforcement of national laws is highly variable, with non-compliance carrying financial penalties and criminal sanctions in some countries, but little evidence of enforcement in others. countries are signatories to the montreal convention, which imposes obligations to protect passengers. however, although this convention enables compensation claims to be made, proving an airline's liability for a passenger contracting an infectious disease during the flight can be challenging evidentially. even if transmission time can be proven, airlines can defend the extent to which they should have been expected to identify the risk. they can argue that liability should lie with the infectious passenger who took the flight without notifying the airline or health authorities. although industrial injury claims have been brought on behalf of aircrew for alleged adverse reactions to constant insecticide exposure in aircraft, these claims have been defended on the basis that airlines were following who guidelines. , the montreal convention does not apply to individuals in a destination country who could become infected by a passenger or imported vector. although regulatory liability might still exist and personal litigation against an airline could be undertaken, proving causal transmission will again be very difficult, particularly if the disease in question did not become symptomatic until some time after the flight had landed. two hypothetical scenarios are provided to show the potential occurrence and wider implications of disease transmission on aircraft. ebola is an infectious and often fatal disease marked by fever, nausea, vomiting, and-less frequentlyhaemor rhaging, and spread through infected bodily fluids. on a flight from frankfurt to washington, dc, a -year-old passenger started complaining of a severe headache, abdominal pain, nausea, and sweating. he recalled no specific symptoms before boarding, but claimed he had been feeling generally unwell since his arrival from abuja, an interim stopover on his itinerary that had originated in kampala days earlier. about h into the flight, his symptoms worsened and the cabin supervisor requested medical assistance. as there was no doctor on board, a nurse examined the passenger and, suspecting he might be infectious, advised the crew to "isolate him as a precautionary measure". the passenger was taken to a seat near the galley and looked after by two crew members for the remainder of the flight. meanwhile, he had violent bouts of vomiting and became increasingly disoriented. the cabin supervisor notified the chief pilot of a sick passenger, but did not communicate the severity of his condition. the pilot assumed the situation was controlled and did not contact us health authorities. upon landing, the passenger's condition had deteriorated and an ambulance was requested. after h, the passenger was determined to be positive for ebola virus. this scenario demonstrates an absence of communication between crew members and between aircrew and ground staff in the destination country. this miscommunication delayed notification of a potentially severe health risk from infected bodily fluids, such as vomit; moreover, an ambulance with infection control facilities should have been requested while the plane was airborne. this represents non-compliance with iata guidance and a potential criminal breach of us health and quarantine laws. us laws are enforceable against both individuals and organisations, with penalties including fines and imprisonment. , vector-borne diseases (eg, malaria, yellow fever, and zika virus) are transmitted by mosquitoes or other vectors to human beings, and contribute to a substantial proportion of the global infectious disease burden. mosquito ecology suggests that aircraft are associated with a higher risk of introducing a live infected mosquito than are sea or road transport. following national requirements, disinsection was carried out by aircrew during descent into mumbai airport. the flight had originated in london. a passenger who regularly travelled on this route objected to being sprayed with insecticide, pointing to potentially dangerous adverse health effects. he added that, having travelled with different airlines, he had not witnessed any in-flight spraying for years. on the return flight, several passengers complained about the presence of mosquitoes in the cabin before take-off. the aircraft had been parked on the apron of mumbai airport, with cabin and cargo doors open during baggage loading and passenger embarkation. passengers demanded protection from mosquitoes and wondered why spraying was done upon entering india, but not upon departure. this scenario reflects inconsistencies in, and in adequate monitoring of, disinsection policy. indian national law requires disinsection on inbound flights, but india is itself personal view a reservoir of vector-borne diseases. guidance from who and iata uses permissive rather than mandatory language on disinsection, and thus national policies determine whether countries choose to implement disinsection consistently for all arriving aircraft or only require the process on selected aircraft. policies are not always clear, and it is necessary to balance the fears of health risks from both insecticides and mosquitoes. to be effective, infection control measures for air travel need to be underpinned by coherent and enforceable national and international legislation that is based on solid epidemiological evidence. since aircrew are not infectious disease specialists and would not normally have medical training, recognition of potential disease cases and adequate communication of an in-flight illness remains challenging and ad hoc. the dynamics of existing, emerging, and re-emerging infectious pathogens mean that infectious diseases will always challenge control efforts as pathogens exploit novel evolutionary niches. incoherent guidelines and inconsistently applied laws unnecessarily hinder disease control efforts, and the evidence base underpinning control measures for airlineassociated infectious diseases needs to be strengthened considerably. public health involves balancing the rights of the majority against those of the individual, and issues related to air travel require particular review and improvement by the global health community. first, a systematic review should be done to appraise the evidence supporting control measures for transmission of infectious diseases via air travel. second, airlines and the global health community need to invest in research to identify better, non-toxic insecticides, or non-chemical means to control insect vectors. third, additional research and investment into airport health screening measures is required to better identify infectious passengers. disease transmission can be minimised if passengers take appropriate precautions before or during a flight, or refrain from flying altogether when ill. current education and communication strategies (and refund policies for missed flights) therefore warrant improvement. fourth, these measures cannot be implemented in the absence of enforceable and harmonised international legislation and governance. achieving this goal will be a major challenge, but a starting point could be for international or regional bodies-such as who or the european union-to produce model legislation or standards for the guidance of member states. close consultation with iata and icao would be required to develop such legislation or guidance. enforceability might be encouraged by treating this as a security issue, similar to ensuring the mechanical safety of aircraft. in the context of regular global air travel and evidence of dangerous non-endemic diseases appearing in new, vulnerable populations, the risks of airline-associated infection are growing. potential costs or inconvenience to passengers and aircrews might arguably be a lesser evil than transmission of potentially fatal infections to vulnerable populations. however, without concerted efforts from the global health community, the threat can be expected to worsen. ag developed the scenarios and drafted the manuscript with ems, who wrote on legal aspects. nh contributed to writing and interpretation. rc provided interpretation and critical review. all authors approved the version for submission. we declare no competing interests. air transport, passengers carried: international civil aviation organization, civil aviation statistics of the world and icao staff estimates transmission of infectious diseases during commercial air travel infectious risks of air travel zika virus in the americas: early epidemiological and genetic findings emergency response plan: a template for air carriers infection control guidelines for cabin crew members on commercial aircraft mode of travel: health considerations entry and exit screening of airline travellers during the a (h n ) 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international flights cfr part : nondiscrimination on the basis of disability in air travel; final rule entry screening for severe acute respiratory syndrome (sars) or influenza: policy evaluation convention for the unification of certain rules for international carriage by air. montreal: international civil aviation organization preventing airline liability for spread of communicable diseases air quality in airplane cabins and similar enclosed spaces qantas steward with parkinson's to sue over pesticide link us code § : quarantine regulations governing civil air navigation and civil aircraft us code § : penalties for violation of quarantine laws vector-borne diseases: overview evidence in australia for a case of airport dengue key: cord- -z b b authors: lim, taesub; cho, jinkyun; kim, byungseon sean title: predictions and measurements of the stack effect on indoor airborne virus transmission in a high-rise hospital building date: - - journal: build environ doi: . /j.buildenv. . . sha: doc_id: cord_uid: z b b as the viral diseases such as severe acute respiratory syndrome (sars) and influenza a (h n ) occur in many countries recently, the epidemic of those influenza viruses causes many human casualties. moreover, the second infection from infected patients particularly within general hospitals frequently takes places due to improperly hospitalized and/or quarantined patients. accordingly, it becomes a great concern to accommodate safer ventilation system in general hospital wards against such airborne transmitted viruses. it is also a recent trend that many urban general hospitals are designed and constructed as high-rises. if a virus is transmitted through uncontrolled air movement within a hospital and then infected other patients or healthy visitors, it might be impossible to control the spread of the disease. thus research has been preceded scrutinizing stack effect on the indoor airborne virus transmission in large hospitals by conducting both the field measurement and numerical analysis according to the outdoor temperature and the releasing vertical points of the tracer gas assumed as a viral contaminant. in the field measurement of a high-rise hospital, the indoor airflow was affected by the stack effect of vertical chute of the building. the numerical simulation was verified by comparing its prediction results and the field measurement data. in result, very high possibility has witnessed that the airborne contaminant emitted from the infected patients in the lower floors could be transported to the higher floors through the airflow driven by the stack effect. the spread of diseases from infected patients within hospitals causes many human casualties. if a virus were to be transmitted through uncontrolled air movement within a hospital and were then to infect other patients or healthy visitors, it would be impossible to contain the spread of the disease [ ] . a pressure difference occurs in buildings due to different densities of outside and inside air that arise from temperature variation. because the exterior of a building is cold and building interiors are warm during wintertime, the pressure above the ground surface is lower inside the building and airflows into the lower section of the building due to such pressure difference. the inflow air travels up the vertical shafts such as elevators to move to the higher section of the building and then flows outside. until now, research on the stack effect has mainly focused on high-rise apartments that were built from around the year . many of the relevant studies have made significant progress, and solutions to various problems are steadily being published [ ] , even studies on concrete construction methods for strengthening the air-tightness of building interiors, such as using revolving doors and windbreak rooms. although research on the stack effect has been generally limited to high-rise apartments, there is a high probability that such research will also be carried out on high-rise hospital buildings. unlike in high-rise apartments, however, the changes in airflows due to the stack effect could cause serious problems in high-rise hospitals by allowing airborne viruses to spread. because the traffic volume of residents in high-rise apartments is small, the stack effect can be reduced by installing features such as windbreak rooms or revolving doors. however, in hospitals where numerous outpatients and hospitalized patients, their families, doctors, nurses and students are constantly moving in and out, such measures do not render any significant results. in this environment, there is a high possibility that infectious airborne viruses could spread out to the entire hospital via vertical routes of elevators or staircases through the stack effect. currently, however, only studies on the possibility of the stack effect in high-rise hospitals have been published and there have been no detailed reports based on field measurements. only a few analyses of the impact of the stack effect on the spread of airborne infectious disease have been conducted. major studies that have been carried out so far dealing with the stack effect are as follows. jo et al. [ ] measured the distribution of pressure differences between floors or spaces in highrise apartments during winter using a network airflow model, which was also used to analyze the stack effect in various architectural alternatives. to prevent the stack effect, tamblyn [ , ] introduced a mechanical ventilation system, and to separate the spaces (between apartment unit doors and elevator halls) where stack pressure significantly occurs due to the increased air-tightness, jacques [ ] and jo et al. [ ] each proposed vestibules and air-lock doors. however, lovatt and wilson [ ] published research results that demonstrated that it is not desirable to use a mechanical ventilation system because it could produce unexpected problems in the building, and if improvement in the level of air-tightness does not occur throughout the building, it could instead strengthen the stack effect. major studies analyzing how airborne viruses spread have also been carried out (rice et al. [ ] ; bjorn and nielsen [ ] ; huang and tsao [ ] ; qian et al. [ ] ; rui et al. [ ] ), mostly on smaller spaces such as surgery rooms or isolation rooms, rather than on the entire hospital, focusing on the diffusion analysis of viral pathogens. in around , when sars, with its threat of causing the corona virus, broke out in locations such as hong kong and north america, several studies were published that dealt with infection route analysis (li et al. [ ] ; yu et al. [ ] ; lim et al. [ , ] ). by analyzing actual cases where pathogens spread quickly, these studies derived the conclusion that pathogens can spread through the air. studies on the spread of viral pathogens and contaminants generally assume that the breathed air exhaled from patients is the source of contaminants or pathogens and their diffusion is therefore analyzed. considering the breathed air, hayashi et al. [ ] reported that the breathing volume of an adult under normal conditions was l/min based on . met of activity during sleep (convective heat transfer . w/person), and the volume of exhaled air under normal conditions was . l/min. bjorn and nielsen [ ] proposed a human body model for breathing, in which adults breathed about ten times a minute and produced l/ min of breathed air. they also reported that the convective heat transfer of the human body was w. haselton and sperandio [ ] carried out a study on heat exchange from convection between nose and air. it was shown that, in the case of an adult, the openings for nose and mouth were on average about . m in diameter, and during breathing, the temperature of exhaled air was c for the nose and c for the mouth. using these research results, qian et al. [ ] prepared actual mannequins and assumed the average speed of exhaled air to be . m/s at c. they then carried out tests on pathogen diffusion and cfd analysis. however, because the virus included in the exhaled air is eventually mixed together with sprays, they could not calculate the number of pathogens discharged from the exhaled air of individual patients. because of this, in the case of studies that examined the spread of airborne pathogens as a network model, the number of pathogens included in the exhaled air were analyzed by assuming the number as a specific value (cfu/ m ), whereas studies that used the cfd modeling assumed tracer gases such as co , sf or n o as the pathogen and comparatively analyzed the infection route and its likelihood. lim et al. [ ] also suggested that analysis of airborne pathogens was possible using tracer gas. since viruses are heavier than gas but are very small compared to solid particles, they are more likely to float on air, similarly to gas, than germs with larger and heavier particles. because of these characteristics, li et al. [ ] and yu et al. [ ] used n o, which is slightly heavier than air, to simulate viruses in their studies and analyzed its diffusion route. it is judged, therefore, that if a method of differentiating danger levels according to the concentration of tracer gas was additionally presented, it could somewhat supplement the ambiguities in analyzing diffusion using tracer gas. the purpose of this paper is to analyze the diffusion path of contaminated air from patients infected with an airborne virus in high-rise hospitals, focusing on the stack effect, and to provide some engineering controls and architectural design plans for minimizing the vertical diffusion of pathogens into the entire hospital space. by comparing between field measurements and network mathematical model, this study tries to predict the stack effect on indoor airborne virus transmission. the study process is described below: . a sample high-rise hospital was selected, and pressure difference measurements related to the stack effect were carried out for the entire building in order to examine general airflow patterns. . by comparing the field measurements and the simulation prediction values, the reliability of the simulation program was compared. . the infection path was analyzed following the location of patients in each floor and the stack effect was proven to be one of the main factors causing the spread of viruses. because the field measurements were taken from an actual hospital in operation, there were many limitations. because we carried out measurements during early morning hours, we had complete control over public areas, such as elevator halls and hallways, but for measuring rooms that required privacy, we carried out measurements only in those rooms where we obtained the consent of both the patients residing in those rooms and their doctors. the field measurement of tracer gas was not carried out because we did not get permission from the hospital administrators, and hence we carried out simulations instead. in future follow-up studies, we plan to build a miniature model and conduct mock-up tests using tracer gas. several multicompartment flow models have been developed, i.e. contamw [ ] and comis [ ] flow rates. the commonly used network model has been found to be appropriate for this study, where calculation process is reasonable. contanw was employed to simulate both airflow and concentration. the results will be very useful for exposure assessment and control strategy planning. the evaluation of how infectious pollutants spread due to changes in indoor airflow will focus purely on stack effect, and any effect from wind will accordingly be excluded from consideration. for health risk assessment, after obtaining the concentration profile, detailed exposure modeling can be advanced, if necessary. it would be more meaningful to estimate a long-term exposure because there are some external factors which vary significantly with time. there are three main factors that affect indoor airflow in highrise buildings during cold winter season: stack effect, wind speed/direction and air balance of hvac system (supply and return air volumes). the stack effect occurs when the air inside the building is either more or less dense than the outside air because of the temperature difference. if the air inside the building, which has a high opening in one and low opening in another, is warmer than the outside air like winter, this warmer air will float out the top opening, being replaced with cooler air from outside. the pressure distribution for inside and outside the building arising from stack effect can be shown as in fig. . here, a section exists where the air pressures outside and inside the building become the same, which is called a neutral pressure level (npl). accordingly during winter season, infiltration occurs in sections below the npl while exfiltration occurs in sections above it. in such situation, the pressure difference dp s is the difference between outside pressure p s(o) and inside pressure p s(i) for any random height h. stack effect can be calculated from the following relation [ ] : the pressure difference dp s arising from stack effect can thus be shown as a function of vertical distance from the npl and difference between the outside and inside average air densities of a building, or a function of distance from the npl, outside air density, and absolute temperature of inside and outside air. it can be seen that greater inside and outside temperature difference and greater building height correlate with greater pressure difference due to stack effect. it can also be seen that pressure difference at the npl is zero, and during wintertime, pressure difference below the npl has a positive (þ) value while pressure difference above the npl has a negative (À) value. the rate at which air flows depends on several factors, the inside and outside air temperatures, the area of the openings, and the height difference between the top and bottom openings, the draft or draught flow rate induced by the stack effect can be calculated with equation ( ) [ ]. the wind pressure created in a building can be shown as a function of variables such as air density, the direction and wind speed. equation ( ) [ ] shows how the wind pressure is calculated. because wind pressure at the side of building can differ according to the side receiving the wind, the direction of the wind can distort the pressure difference profile on traditional stack effect shown in fig. . in other words, when wind blows on a building with stack effect, the wind pressure applies not evenly to all sides of the building but differently according to where the building side is located in relation to the wind direction, and thus the pressure difference between inside and outside the building differs for each side of the building. for example, in fig. when there is no wind, the pressure distribution between floors has a fixed pressure difference profile between floors arising from stack effect, with the npl being at the center point. when there is wind, however, as shown is fig. , the side of the building receiving the wind has high pressure while the opposite side has low pressure, and thus many pressure areas form in the building. accordingly, in the low floors, if the wind pressure is high, it aggravates the pressure difference from stack effect and increases infiltration through openings. at the opposite side of the building, however, while infiltration could still occur through stack effect, the low pressure caused by the wind could also cancel the pressure difference, thus eliminating infiltration, or reverse the pressure difference, thus causing airflow to go out from the building. in contrast, while inside building pressure is normally higher than outside pressure in high floors due to stack effect and airflow that go out of the building through openings, wind could apply enough pressure to cancel out the pressure difference, thus canceling airflow, or even reverse such pressure difference and cause infiltration. in conclusion, while wind pressure could enhance stack effect, it could also cancel out of reverse the effect, and thus has the potential to cause indoor airflow to change patterns and move in various directions. indoor air balance can show various patterns according to the difference between the supply and return air volumes of hvac or mechanical ventilation systems. in general, supply air volume is more than return air volume because of individual exhaust. spaces with greater supply air volume have higher pressure in comparison to other spaces, and in order to find a pressure equilibrium point, the surplus air is made to go out through the openings or find low pressure spaces to flow to. thus having greater supply of air volume is positive in that it can not only supply fresh air and dilute pollutants, thus lowering their exposure concentration, but it can also make controlling indoor airflow difficult, and in the worst scenario, the airflow to low pressure spaces could further aggravate the spread of pollutants. in this paper, because the main focus is on the observation of pathogen transmission within the hospital due to factors related to stack effect only, we eliminated factors for wind speed/direction and indoor air balance of hvac system. we assumed there was no wind and set the boundary condition for indoor air balance based on the hvac operating and design data of the subject hospital. field measurements were conducted on two buildings during the cold season to obtain the actual pressure distribution profiles and to verify the problems caused by stack effect. in order to identify the existence and degree of the stack effect in high-rise hospitals, s-hospital, one of the recently constructed high-rise hospitals, was selected as the study subject. fig. shows the test hospital's current state in detail, and the measurement locations for its wards are marked. the measurement details and instruments are shown in table . to prepare for the field measurements of the hospital building, the building's airflow paths were examined through a previous on-site survey. to ensure the accuracy of experiment, the first round of measurements was carried out on march , and the second round was carried out on april . the measurements were carried out between and am, when the elevator operation could be controlled and the outside temperature was low. as shown in fig. , for the test hospital, for each building, there is a central core with two elevator halls, ward units surrounding the core, and the connecting corridor. in the typical floor plan, each floor is separated by exterior walls, ward unit boundaries including entrance doors, and vertical shaft walls including elevator doors. the pressure differences across these building components are measured to obtain the pressure distribution profiles. absolute pressures of the essential zones were measured. the absolute pressure was measured at the floor surface of the zones on each floor simultaneously by using absolute pressure barometers going down from the top floor to the basement floor of the building. in measuring the pressure in the elevator hall, the measurements were taken with the elevator doors closed by using distal micro nanometer. air flow through large openings is usually bidirectional. since the elevator doors and ward doors are closed, the opening is not large. during the initial measurement, the bi-directional flow of the door was checked. there was no occurrence of bidirectional flow phenomena. furthermore, to measure the airflow and direction when the elevator doors were open, only one elevator was used to conduct the experiment for each floor, and airflow was measured from the center using an anemometer after the elevator door opened. field measurements were carried out at dawn in cold weather and stable conditions to minimize other influences such as wind, elevator use by residents, and opening of doors. of the two, the first elevator hall was selected, which was used frequently by visitors, and the pressure difference at its elevator doors was measured. the first elevator hall had eight elevators, but because not all elevators could be measured, only one representative elevator was chosen. to do this, the pressure difference at each elevator door needed to stay the same. fig. shows the pressure difference measurements of elevator doors up to the th floor while all eight elevators were stationed at the third basement floor. the pressure difference at the elevator doors ranged from . pa (minimum) to . pa (maximum), showing a difference of less than pa between the doors. accordingly, the eighth elevator door was selected and the pressure difference at the door was measured for all floors. pressure difference was also measured at the doors and windows of selected wardrooms, and the elevator shaft and hall temperatures were also measured. in addition, after measuring the pressure difference and temperatures, one elevator from among the eight stationed in the third basement floor was brought up to the floor being measured, and the air flow direction and wind speed from the elevator were measured when its door opened. this measurement process was repeated ten times. however, as the pressure difference at the ward doors and windows could affect the condition of hospitalized patients, measurements of select wardrooms on the first, third, sixth, ninth, th, th, and th floors were carried out twice with the consent from the hospital's personnel. the temperature measurement results are shown in fig. , which lists the average inside and outside temperatures and the highest and lowest temperatures for each floor. because the measurements were performed early in the morning, temperature measurements were stable without any noticeable deviations between measurements. the average outside temperature was . c, with the temperature distribution ranging from the lowest temperature of . c and the highest temperature of . c. the temperature inside the elevator shaft differed for each floor: c in the first basement floor, and c in the th floor. although there were slight variations according to whether or not the floor had a door connected to the outside, the temperature generally increased with the increase in floor height of the building. the temperature inside the core (elevator hall) was c in the second basement floor, rising to an average of . c with the increase in floor height of each floor and was c in the th floor. in particular, when the temperature curves in the elevator shaft were compared with those of the core, there was no significant difference in the lower section of the building, but the core temperature was higher, and in the upper section of the building, the elevator shaft temperature was higher. fig. (a) shows the measurements of pressure difference at the elevator doors and ward doors and windows connected to the outside air for each floor, and fig. (b) shows the air flow direction and wind speed entering and exiting the elevator and the core when the elevator door opens on each floor. fig. (a) actually shows a typical pressure difference profile due to the stack effect. the npl without any pressure difference forms in the central part of the building between the eighth and th floors. regarding pressure difference at the elevator doors (elevator shaft pressure e hall pressure), the difference was shown to be minimal at less than pa in the first basement floor and second floor because there were no doors connecting these floors to the outside. on the first floor where there was an entrance, the average pressure difference was À . pa. from the first floor to the fifth floor, the pressure difference between the floors was fairly even at À pa, and in the th floor, the average pressure difference was high at . pa. in particular, the pressure difference between the first floor and the fifth floor was low compared to that in the th floor and the difference was not large between the floors. this is because, in the first floor, the inflow of outside air was comparatively higher than in other floors due to its wide surface area and windows connecting to the outside, while in the fifth floor, the pressure did not significantly differ from that in the first floor due to the effect of an atrium that was vertically connected from the first floor to the fourth floor. unlike the pressure difference at the elevator doors, there was no significant pressure difference at the divided doors and windows in locations such as consulting rooms and wardrooms. this was because the pressure difference due to the stack effect was dispersed by many rooms surrounding the outer walls, and that dispersed pressure was collecting in the elevator area at the center of the building. in addition, because the floor surface and outer surface areas were wide from the first to the fifth floors, the pressure difference at each door and window in those floors became very small. due to these reasons, the pressure differences at the doors and windows in the first floor were À . pa and À . pa, respectively. in contrast, in wards on the sixth floor or higher, because the floor surface and outer surface area became comparatively smaller with smaller wardrooms divided with interior walls into rooms for five people or two people, the pressure difference at the ward doors and windows was greater than in the lower section of the building. thus, in the th floor, the pressure differences at ward doors and windows were . pa and . pa, respectively. in particular, the values significantly differed for the doors and the windows because the pressure difference for the windows was smaller due to the smaller wardrooms, while the pressure difference for the doors was greater due to the fact that the pressure concentrated in the elevator halls from the stack effect was distributed to each of the wardrooms. fig. (b) shows the airflow direction and wind speed when the elevator doors are opened. negative values show airflow from the core to the elevator shaft while positive values show it moving from the elevator shaft to the core. the airflow direction and wind speed for each floor were shown to be determined according to the pressure difference in relation to the npl. when the elevator door was opened in the first floor of the building, the inside air flow was shown to flow into the elevator at a wind speed of . m/s. once in the upper section of the building, however, above the npl, the wind speed was shown to steadily increase and, in the th floor, the airflow was measured flowing out of the elevator at a wind speed of . m/s. even though the time of measurement was in april when the inside and outside temperature difference was comparatively smaller than in december, in the upper section of the building, an air flow with unpleasantly high wind speed was flowing out from the elevator shaft when the elevator doors were opened. as shown in fig. (b) , the airflow direction and wind speed profiles for when the elevators in each floor were opened support the argument that the stack effect does occur at the hospital being measured. in multi-zone buildings, especially in high-rise buildings, airflows through exterior walls, openings and adjacent spaces are affected by the resistance of leakage areas depending on the part of building, opening area, etc. therefore, a network model method is suitable for predicting the pressure distribution to analyze the impact of stack effect in high-rise buildings. in this study, con-tamw is used. the airflow calculations in contamw are based on equations ( )e( ) [ ] . the air flow rate from zone x to zone y, q x,y is some function of the pressure drop along the flow path, p x ep y : the mass of air, m x , in zone x is given by the ideal gas law: for a transient solution the principle of conservation of mass states is shown in equation ( ) vm x vt the reliability of a multi-zone airflow simulation program for evaluating the vertical spread of airborne pathogens was simulated. in order to interpret the air movements measured in the test hospital, the task of simplifying complex interior spaces by dividing them into zones is necessary. fig. shows simplified computer modeling of the complex floors or surface areas for contamw simulation. in the case of the building's lower section, the areas used for consulting and administrative duties were set as a large zone, and in the case of the ward section, the areas used as patients' rooms were set as another large zone. the elevator halls and the hallways, the washrooms, and vertical shafts (stairways and elevators) were set as separate zones, and the vertical shafts of different floors, which affect the air flow between floors, were then connected. to obtain a stable state interpretation, the calculation conditions were, as much as possible, set at the same values as the real measurements. accordingly, the outside temperature was set at the average temperature of field measurements at . c, and the inside temperature was also set at the average temperature of field measurements at c (average of inside temperatures that were actually measured). numerous input data must be supplied in the contamw to define a building. air leakage is one of the influential factors of pressure distribution. therefore, the air leakages of essential components on major airflow paths were measured for airflow simulations. for components whose air leakages were not measured, published data [ ] were used as input for the simulation model. the basic input values on infiltration are as shown in table , and the supply air and return air volumes for each floor are as shown in table . the examination of data from the building management showed that the supply and return air volumes at night were being operated at % of their maximum levels, and the supply air volume was about % greater than the return air volume. at night, with the exception of the emergency room on the first floor, the consulting rooms and office rooms were located from the first floor to the fifth floor, and only a minimum ventilation system was operating in order to maintain the inside temperature. from the results of field measurements, it is judged that the supply and return air volumes did not exert any noticeable influence on the pressure difference profiles due to the stack effect that occurs in the test hospital. the assumed input data were checked through numerous simulations to obtain agreement between the simulated and the measured pressure distributions. since stack effect problems on typical floors occur mostly around the core area, input data were checked by matching the pressure differences mainly across the elevator doors and ward entrance doors. the initial simulations results did not match the measurement results well. it is assumed that the simulated values deviated from the measured values because the air leakage data of exterior walls of test building was not being estimated accurately and lobbies and basement floors had numerous doorways connected to the outdoor air. therefore, the air leakage data were modified for the exterior walls, entrance doors located on lobbies and basement floors, and orifice area on the top of the elevator shafts, which is connected to the elevator machine room. the leakage data for the elevator, stairwell, and residential entrance doors, however, were not adjusted because they were based on tested values. when the elevator doors are operating under normal conditions, the initial simulation estimates that were used to analyze the air movements in the test hospital showed that the pressure differences in the first and second basement floors were about pa greater than the actual pressure difference measurements. because of these differences between the simulation estimates and the field measurements of the pressure differences in the first and second basement floors, in the th floor, the simulation estimate was about pa higher than the field measurement. this shows that the input data in the connecting area, such as between the basement parking lot and the elevators, is probably incorrect. accordingly, the input data for other floors were fixed and those for the basement were revised. the revision was carried out in the process of changing the air-tightness of the surface area and the infiltration volume data for the doors at the basement parking lot. also, with the revision, the pressure difference in the first and second basement floors was compared with the field measurements and was reduced to less than pa. as the basement floors were revised, the gap between simulation and actual values for the th floor also naturally decreased. the differences between field measurements and estimates for elevator doors and ward entrance doors in all floors were less than pa and . pa, respectively, which showed the reliability of the simulation. fig. compares the pressure differences across elevator doors and ward entrance doors, obtained by measurement and simulation. this figure shows that, in general, the simulation results match the measurement results well, except for a few floors. based on the test hospital's contamw input variables that were confirmed to be reliable, various proposals for analyzing the infectious airborne virus were made and applied, thus enabling diverse simulation tests. the airflow pattern changes due to outside air temperature in various spaces were identified for each floor, and the influence of the stack effect on the vertical spread of airborne viruses was analyzed. the calculation conditions were the same as the simulation verification conditions discussed above except for the outside temperature. for the basic outside air temperature, À c was selected based on the seoul region's tac . %, and the temperature was then changed sequentially to À c, c, c, and c, and analyzed as stable states. also, in order to analyze only the consequence of the stack effect, it was assumed that there was no wind outside the building. the spread of the airborne virus was calculated and interpreted by assuming the volume of air breathed by infected patients. n o was chosen as the tracer gas for tracing the spread of the airborne virus that originated from breathed air emitted from infected patients and released from the breathing area of a sitting human to simulate the coughing or sneezing of a sick patient. it is present in the atmosphere with variable background levels fluctuating around . ppm. however, the fluctuations are slow and the test results can be background corrected [ ] . and we assumed that the tracer gas originated at second floor, fourth floor and seventh floor. fig. shows the indoor airborne virus transmission path. . . the effect of pressure difference caused by outside air temperature fig. shows the changes in pressure difference due to outside air temperature for each floor. examining the pressure difference at the elevator doors when the outside temperature was À c (because first and second basement floors did not have outside walls), the pressure difference was less than À pa, but for the first floor with entrance doors, it was À . pa due to the high pressure in the elevator halls. for the second, third, and fourth floors, the pressure difference did not change significantly from that of the first floor because the floors were vertically connected to the first floor through the void. from the fifth floor onwards, the pressure difference increased from pa to pa for each floor, and it was . pa in the st floor. examining the pressure difference at the doors of various rooms and wardrooms, it was À . pa for the first floor and steadily increased with the increase in the height of the floors, reaching . pa for the th floor. the pressure difference at the windows showed the same pattern, and the fluctuations stayed within ae pa. it was also shown that a lower outside temperature led to a wider pressure difference profile than that of the stack effect because of the increase in the temperature gap with the inside temperature. this means that the stack effect became more pronounced and increased the air inflow and outflow volumes between spaces. when the rate of change in pressure difference was compared to the rate of change in outside temperature, an increase in the outside temperature from À c to À c showed about % decrease in the pressure difference due to the stack effect, an increase from À c to c showed a . %, an increase from À c to c showed a . % decrease, and an increase from À c to c showed a . % decrease. the investigation is focused on the passive tracer gas concentration field and infection risks. some of the results are compared with the earlier on-site measurements [ ] . considering that the sizes of human-generated aerosols typically range from to mm, using a tracer gas to represent their aerodynamic behaviors by neglecting the gravity effect on the aerosols can reasonably give meaningful results, especially for those fine droplets. the aerosols' movement modeling, which can more accurately capture the dispersion characteristics of sneezed/coughed virus-containing droplets, will be studied and reported in a separate paper [ ] . based on the knowledge of infection dose (the number of organisms required to cause infection), the risk of airborne infection and ventilation rate per person can be correlated by wellseriley equation [ ] . the quantum, q, represents the generation rate of infectious doses. exposure to one quantum gives an average infection probability of ( À e À ). the wellseriley equation is set up on the assumption of a well-mixed and steady-state condition. we can get the concentration of infectious particles at a certain point, which allows derivation of spatial distribution of infection risk. it does not require the assumption of well-mixed conditions. the spatial variance of infection probability is similar to the distribution of mass fraction of the tracer gas and a high concentration denotes a high risk [ ] . fig. shows the tracer gas concentration for each floor according to the outside temperature and the floors where the tracer gas originated (second floor, fourth floor, seventh floor). the overall concentration range was weak at less than . e- , but because this concentration represents the average concentration for the entire space, a comparative analysis is needed. the tracer gas, which represents the spread of airborne viruses, rose through the elevator halls and was detected in the upper section of the building, but it was not detected in the lower section of the building below the npl. within the upper section, the concentration increased as floor heights increased. examining the concentration according to where the tracer gas originated from, when the outside temperature was À c, the second floor showed about % higher concentration than that of the fourth and seventh floors. this was because the air inflow was much greater in the first and second floors, whereby the inflowing air was rising to the upper parts through the elevator shafts. the tracer gas originating from the fourth and seventh floors was also detected in the upper floors, but investigating the pressure difference profile due to the stack effect, because the volume of air moving up to the upper floors through the fourth and seventh floors is rather small, only a small amount of gas is detected. in the upper floors above the npl, when the tracer gas is released it does not spread toward the elevator halls but rather moves toward the windows facing outside air, thus limiting the gas from being detected throughout the floor. looking at these results, it is judged that controlling the outside air flowing in through openings and entrances on the first and second floors will play an important role in blocking the spread of infectious viruses due to the stack effect. fig. shows the tracer gas concentration profile over the height of the hospital building, when the gas is released from the second floor and the outside temperature is set at À c, c, and c. in the figure, looking at the concentration distribution for each floor when the temperature was À c, the concentration detected in the upper floors was about % higher than when the temperature was þ c. this was in-line with the above assumption that the outside temperature affected the concentration of tracer gas detected in the upper floors. at a time when epidemics such as h n are spreading throughout the world, the general hospital is a place of battle with biological pathogens and, in certain cases, can become the most dangerous place from where infectious disease can spread. this paper has used previous studies as a basis and proved through on-site measurements and multizone airflow simulations the possibility of infectious airborne viruses spreading through the stack effect in large, high-rise hospitals. also, by analyzing the influence of the stack effect regarding vertical spread of gas to the entire hospital space, the paper presented basic data for ventilation planning for high-rise hospitals. the results of this research are as follows: ( ) the pressure difference pattern for each floor of the test hospital shows a typical stack effect, and in the process of comparing field measurements with the contamw estimates, the estimate values were checked based on the actual values in order to obtain reliability. investigating the air inflow pattern due to pressure difference and using the npl as the standard, in the lower section of the building the outside air flowed in through openings and cracks, such as entrances and windows, and moved to the core, where it rose to the upper floors through elevator shafts and staircases, and then flowed out again through the upper floor openings and cracks, such as ward room windows. ( ) the elevator shaft and core temperatures rose as floor heights increased, and when the elevator doors opened, the air flow direction flowed into the elevator shafts in the lower floors whereas it flowed out from the core in the upper floors. the wind speed when the elevator doors opened was about m/s on the th floor, causing an unpleasant experience for the people using the elevator halls. examining the changes in the pressure difference profile in each of the spaces due to changes in the outside temperature, when the outside temperature decreased, the overall pattern did not change, but the pressure difference changed dramatically. each c decrease in outside temperature caused about % increase in pressure difference. also, when tracer gas representing infectious airborne viruses was released from designated floors, the current movement pattern due to the stack effect caused the gas to be detected in the upper floors but not in the lower floors. as the floor where the tracer gas was released reduced in height, or as the outside temperature reduced, the concentration detected in the upper floors increased, and this concentration level increased in the higher floors. when all the results of the study are considered together, in order to minimize the spread of air flow movement due to the stack effect, the existing construction method should continue to be used but an additional plan for the frequently used entrances of the hospital to be made more airtight is required. moreover, a zoning plan could be considered where the wardrooms for patients with a possible infectious disease are placed in the upper floors above the npl. the influence of ward ventilation on hospital cross infection by varying the location of supply and exhaust air diffuser using cfd characteristics of pressure distribution and solution to the problems caused by stack effect in high-rise residential buildings coping with air pressure problems in tall buildings hvac system effects for tall buildings controlling stack pressure in high-rise buildings by compartmenting the building stack effect in tall buildings an evaluation of hospital special-ventilation-room pressures dispersal of exhaled air and personal exposure in displacement ventilated rooms tracer gas concentration profile over the height of the hospital building the influence of air motion on bacteria removal in negative pressure isolation rooms dispersion of exhalation pollutants in a two-bed hospital ward with a downward ventilation system study on biological contaminant control strategies under different ventilation models in hospital operating room multi-zone modeling of probable sars virus transmission by airflow between flats in block e temporal-spatial analysis of severe acute respiratory syndrome among hospital inpatients the prediction of infection risk of indoor airborne transmission of diseases in high-rise hospital: tracer gas simulation cfd analysis on characteristics of contaminated indoor air ventilation and its application in the evaluation of the effects of contaminant inhalation by a human occupant convective exchange between the nose and the atmosphere building and fire research laboratory, national institute of standards and technology comis-an international multizone air flow and contaminant transport model, lbnl- . environmental energy technologies division smoke movement and control in high-rise buildings. national fire protection association american society of heating, refrigerating and air-conditioning engineers using n o as tracer gas on-site quantification of re-entry ratio of ventilation exhausts in multi-family residential buildings and implications the airborne transmission of infection between flats in high-rise residential buildings: tracer gas simulation airborne spread of measles in a suburban elementary school key: cord- - uiq at authors: wang, junfeng; xu, xiaoya; wang, shimeng; he, shutong; li, xiao; he, pan title: heterogeneous effects of covid- lockdown measures on air quality in northern china date: - - journal: appl energy doi: . /j.apenergy. . sha: doc_id: cord_uid: uiq at in response to the spread of covid- , china implemented a series of control measures. the causal effect of these control measures on air quality is an important consideration for extreme air pollution control in china. here, we established a difference-in-differences model to quantitatively estimate the lockdown effect on air quality in the beijing-tianjin-hebei (bth) region. we found that the lockdown measures did have an obvious effect on air quality. the air quality index (aqi) was reduced by . %, the concentration of no( ), pm , pm . , and co were reduced by . %, . %, . %, and . % respectively. at the same time, we further explored the heterogeneous effects of travel restrictions and the control measure intensity on air quality. we found that the traffic restrictions, especially the restriction of intra-city travel intensity (ti), exhibited a significant heterogeneous effect on no( ) with a decrease of approximately . %, and every one-unit increase in control measures intensity reduced the concentration of air pollutants by approximately – %. this study not only provides a natural, experimental basis for control measures on air quality but also indicates an important direction for future control strategies. importantly, determining the estimated effect helps formulate accurate and effective intervention measures on the differentiated level of air pollution, especially on extreme air pollution. coronavirus disease (covid- ) spread internationally and triggered a global public health crisis [ ] . in china, it was initially identified in wuhan in december , then quickly spread around china and became a global infectious disease [ ] . china has taken a series of control measures to prevent upgrades in the epidemic spread [ ] . the chinese government implemented full lockdown for the serious epidemic in wuhan, carried out comprehensive prevention and control measures according to the risk level in other regions, closed public places, strengthened the prevention and control of public service facilities, cancelled or delayed all kinds of public gatherings, and implemented telecommuting and teaching. there is no doubt that there was a huge economic cost of implementing these restrictions [ , ] . on the one hand, the epidemic has spread rapidly around the world, directly harmful to the capital markets. on the other hand, to control the spread of the epidemic, countries have taken measures such as controlling production activities, which will also harm social and economic operation [ ] . in addition, the epidemic is also damaging energy supplies in the energy sector, such as the electricity sector [ ] . nevertheless, there have been unintended environmental benefits, resulting in a drop in carbon emissions and air pollutant concentrations, especially no , during the spring festival [ , ] . reduced economic activity and traffic restrictions have led directly to changes in china's energy consumption, thereby preventing environmental pollution [ ] . pollution levels in china dropped sharply in a matter of days because of the restrictions on human activities and traffic [ ] . the reduction in no pollution was first apparent in wuhan and then spread across the rest of the country, and no emissions were reduced by approximately % during the covid- outbreak (nasa, ) . the concentration of major pollutants on the ground also dropped significantly in most parts of china [ , ] . a range of air pollution concentration monitoring data provided evidence of declining air pollution during the covid- outbreak, but the evidence was insufficient to show how and to what extent lockdown measures affected air quality during the covid- outbreak. chauhan and singh [ ] found that pm . in big cities such as beijing and shanghai decreased by approximately % by comparing the pm . data of ground stations during - with that of the past three years, wherein the decrease of pm . for different months was related to the implementation of urban lockdowns. mahato et al. [ ] compared air pollutant concentrations before and during the lockdown in delhi (india) and found the average concentration of pm and pm . decreased by % and %, respectively, followed by decreases in the no and co levels of . % and . %, respectively. tobias et al. [ ] assessed the change in average air pollutant concentrations before and during the control measures in barcelona (spain) and found that the most significant reductions were % and % for black carbon (bc) and no , respectively, which was mainly related to the reduction in traffic emissions. several studies have been carried out on the control measure mechanisms for air quality during the covid- outbreak. most of the studies were carried out by simulating the correlation between different control measures and air quality. wang et al. [ ] simulated three different emissions cases during the control period using the community multiscale air quality (cmaq) model and found that the reduction of anthropogenic emissions, mainly traffic and industrial emissions, contributed to the reduction in pm . concentrations by - %. li et al. [ ] studied the correlation between human and industrial activities and air pollution in the yangtze river delta region of china through photochemical modelling and found that the concentrations of pm . , no , and so decreased by . %, . %, and . % year-on-year during the lockdown level i response, respectively. the level ii response period saw reductions of . %, . %, and . %, respectively. several empirical studies have been carried out on the effect of lockdown control measures on air quality. bao and zhang [ ] used the least square dummy variable (lsdv) model to study the changes in air pollutant concentrations in cities across northern china. the air quality index (aqi) decreased by . % on average, and the concentrations of the five air pollutants (so , pm . , pm , no , and co) decreased by . %, . %, . %, . %, and . %, respectively. since the covid- lockdown was an external intervention, its effect can be more quantitatively identified by using quasi-experimental methods. he et al. [ ] used two groups of difference in differences (did) models to quantify the effect of control measures. compared with non-controlled cities, weekly aqi and pm . in controlled cities decreased by . points ( %) and . g/m ( %), respectively. meanwhile, compared with the same period in , the aqi dropped by . points ( %) and pm . fell by . points ( %). the beijing-tianjin-hebei (bth) region is one of the major economic zones in northern china. air pollution in this region has always been a huge concern, especially in winter [ ] . when meteorological conditions are unfavourable, air pollution usually becomes more serious than in other areas due to the unique topography [ ] . since the implementation of the control policy on january, , almost all industries except power plants and large-scale enterprises were closed, and traffic was also restricted. this should have resulted in a significant improvement in air quality. however, regional heavy air pollution was still present after the implementation of extreme control measures [ ] . the objectives of this study are to (i) explore the causal effect of covid- lockdown measures; (ii) quantitatively estimate the heterogeneous improvements in air pollutant concentrations due to comprehensive lockdown measures; (iii) identify classified control strategies for facing differentiated levels of air pollutants and extreme air pollution. our study chose data including daily air pollutant concentrations and weather conditions in the bth region and designed a did model to quantitatively identify the effect of control measures on air pollution during the covid- outbreak. in addition, we innovatively studied the causal relationship between traffic restrictions and the intensity of control measures on air pollutants. specifically, we used the population migration index from baidu maps to estimate the effect of travel restrictions on air pollution reduction. moreover, we used the implementation stringency index of control measures collected by the oxford covid- government response tracker (oxcgrt) to explore the relationship between control intensity and air pollution reduction. the remainder of this paper is structured as follows. section introduces the empirical strategy. section reveals the effects of control measures on air pollution during the covid- outbreak. section discusses the heterogeneity of the effects, the role of travel restrictions, and the intensity of the measures. section presents the discussion on the implications of measures for air pollution control and section concludes this study. first, we used lsdv estimation strategies to observe the effect of the spring festival and the covid- control measures on air quality. our main model is a city fixed effect panel data model, as follows: , lnp it = +α corona + α holiday + α other holidays + w it + x it + i + t + ε it ( ) where is the dependent variable and is the logarithm of the daily mean air pollutant lnp it concentration (aqi, pm . , pm , so , no , co) in city i on day t; "corona" was set as if it was a day during the initial covid- outbreak ( . did models have been widely used to evaluate the causal effect of government regulations on the atmospheric and separate policy influences from other influencing factors [ ] . these models can eliminate uncontrollable and unpredictable factors in the periods before and after the regulation implementation [ ] . as the covid- controls coincided with china's spring festival, which changed people's production and consumption activities and affected air pollution [ ] . to separate the effect of the spring festival holiday, we chose the air pollution data in as the experimental group and the same period in as the control group. since the spring festival in was extended to february, , we sourced data days before and after the start of the spring festival in ( . . - . here, heterogeneous effects of travel restrictions and the control measure intensity on air quality were explored in our study. no emissions from fossil fuel combustion, especially traffic pollution, are the main source of no emissions [ , ] . traffic restrictions during the covid- outbreak provided an opportunity to better establish the relationship between travel restrictions and air pollution. we collated the intra-city travel intensity (ti) and move-in (mi) and move-out (mo) indices in the bth region during the spring festival in and from baidu maps. these parameters used baidu maps positioning data to reflect domestic spring festival migration and to realize the visualization of the scale of population migration during the spring festival travel rush. to quantitatively demonstrate the effect of travel restrictions on the pollutant concentrations, especially the concentration of no , we incorporated the mi, mo, and ti into the explanatory model as an independent variable: restrictions in the bth region during covid- reduced air pollutant concentrations, but the relationship between specific measures and pollutant concentrations has received little attention. oxcgrt collected information on several different common policy responses by governments to the covid- pandemic . we chose policy indicators including school closures, workplace closures, cancelled public events, restrictions on gatherings, public transport closures, stay at home requirements, restrictions on internal movement, and international travel controls. the indicators were combined to reflect the overall co ntrol intensity of covid- control measures, and replaced covid- control in the explanatory model to quantitatively reflect the intensity's influence on air pollutant concentrations: to choose the valid model, we employed the hausman test and confirmed the correct use of fixed effects in these panels (equation , equation and equation ). the dependent variables in all the four equations are logarithmic processed in order to avoid possible heteroscedasticity and reduce data fluctuations. and the relative changes can be interpreted more easily [ , ] . air quality data was taken from the national urban air quality real-time release platform of china's environmental monitoring station. the data set included hourly readings of the aqi, pm . , pm , so , no , and co from air quality monitoring stations, covering all of china's prefecture-level cities. we folded the data set into prefecture-level cities according to the site locations and collected daily pollutant concentration data (aqi, pm . , pm , so , no , co) from cities from . . to . . in the bth region. meteorological data was sourced from china's daily surface meteorological data provided by the national meteorological information center, which collects meteorological records from surface meteorological stations . we used the same method as for the air quality data to collapse the site data into city-level datasets. daily meteorological data (daily mean temperature, daily mean relative humidity, daily mean wind speed, and daily precipitation (accumulated over h)) for cities in the bth region were collected. we matched the meteorological data and air quality data based on the geographical coordinates of the stations and prefecture-level cities, following the procedures employed in a previous study by fan et al. [ ] . for prefecture-level cities with urban monitoring stations, we used the averaged data from air quality monitoring stations located in the same city, while for cities without monitoring stations, we matched the stations within a radius of km to the geometric centre of each city and calculated their daily means. table presents the summary statistics of our key variables. we start by presenting changes in air quality in the bth region during the spring festival in and ( figure ) . the air quality levels before the spring festival in and were approximately equal, indicating that the parallel trend assumption may hold. with the implementation of covid- control measures in , the concentration of no in the spring festival was significantly lower than in , with little difference in the concentration of other pollutants. aqi, pm . , pm , and so were lower over approximately days than in , and the co values overlapped with the results. this result indicated that the air quality of the control city slightly improved, although a delay effect could have occurred. however, it is worth noting that during the spring festival, the concentration of pollutants in was higher than that in , rising first and then falling, which may have been due to the influence of adverse meteorological factors in . compared with the previous spring festival periods, the bth region in experienced higher relative humidity and temperature, which facilitated multiphase reactions for aerosol formation and growth. low wind and little precipitation were also favorable for haze formation [ , ] . these meteorological conditions may obscure the true impact of the covid- control measures. so to better understand the effect of covid- control measures as opposed to exceptional weather conditions, meteorological variables were controlled in the model. first, we carried out a regression using the model in equation on the factors affecting air pollutant concentrations from . . to . . (table ) . we found that the implementation of control measures significantly reduced air pollutant concentrations indicating that they improved air quality. the aqi decreased by . %, no decreased by . %, followed by pm . , so , pm , and co which decreased by . %, . %, . %, and . %, respectively. the spring festival and other holidays had little or no significant effect on air pollutant concentrations except the no and co. however, the meteorological factors showed strong explanatory power. the time variables (year and month) represents the long-term time trend due to the annual or the monthly variation of air pollutants [ ] , also exhibited a significant effect on air pollutant concentrations. the constants are all statistically significant, indicating that it well balanced the error terms not accounted for by other terms in the model， and guarantees that the residuals have a mean of zero. we used the did model (eq. ) to separate control measures during the covid- outbreak from the spring festival effect and quantitatively identify the net effect of control measures on air quality. we set the air pollutant concentrations in as a control group (where no control measures were implemented), and the air pollutant concentrations in as the experimental group. the results of the did analyses (table ) demonstrated that the control measures improved the air quality compared with the same period in . the aqi decreased by . %, no decreased by . %, followed by pm , pm . , and co which decreased by . %, . %, and . %, respectively. however, there was no significant effect observed for so , which is similar to previous researches in areas where the concentration level of so was low [ , ] . moreover, the emission of so was mainly related to activities such as coal heating and the demand for heating did not decrease during the covid- outbreak [ ] . . . test on parallel trend assumption did models require that the experimental and control groups exhibit the same development trend over time [ ] , so we examined the parallel trend assumption to determine whether the pollutant concentration trend was parallel before the policy implementation in the control and treatment group firstly, it can be seen that the trends of air pollutants before intervention were basically the same in the control group ( ) and the experimental group ( ) before the implementation in section . (fig. ) . therefore, the parallel trend assumption in this study may be right. in order to better demonstrate the policy impact, we also drew the residual graph of the estimated results of model eq.( )，fig. shows the time trends days before and after the spring festival of residuals of air quality after eliminating the effects of weather and possible confounding factors. it can be seen that the residuals of both the control group and the experimental group are standardized to a mean of zero [ ] . the further counterfactual analysis is carried out by using the following model (eq. ) to test the parallel trend assumption more strictly [ ] . specifically, we added the interaction terms between the grouping variable treat and the time trend of the days before the implementation of the control measures to verify the parallel trend of the days before the implementation of the control measures. the beginning of the control measures and the next days were also added to prevent complete collinearity. if the interaction terms of the days before the implementation of the control measures have no significant influence on the explanatory variable, the parallel trend assumption is satisfied. where d represents the days from the implementation of the control measure, trend represents the time trend ， represents a series of estimated coefficients for the days δ before the initiation of the control measures, reflecting the difference in pollutant indicators between the control group and the experimental group as compared to the time before the control measures were implemented. table shows the estimated results of model . it can be seen that most of the estimates for the days before the start of the control measures are around zero, and most of the coefficients are not statistically significant. further, figure shows the trend of the estimated coefficients of aqi. we found that the estimated coefficients mostly near the zero value before the implementation of measures, and there is no clear trend. despite an abnormal down and days before the start of the measures, but then becomes zero value quickly. these results show that the experimental group and control group before the implementation of control measures have the same trend [ ] . we provide additional evidence to demonstrate that our empirical results were robust. first, we assessed whether our findings remained true if the sample window width was changed. the original sample window in this study involved the days before and after the spring festival. we dropped - days at the head and the tail, separately, and re-estimated our model. our results are reported in table . the directions and magnitudes of coefficients were comparable to our previous findings (i.e., consistent with table ). subsequently, considering beijing and tianjin tightened control measures during the covid- outbreak, we further estimated the robustness of our results by removing beijing and tianjin to prevent megacities from interfering with the results. table shows the effects of the other cities alone. all of the findings were robust to this change (i.e., consistent with table ), suggesting that our results were not dominated by the megacities that were most affected by the virus. we first investigated the change in mi, mo, and ti in the bth region during the spring festival in and (fig. ) . before the spring festival, the travel intensity and scale of migration in and were similar, while after the implementation of the regulations in , the travel intensity and migration scale decreased significantly compared with the same period in . table shows the empirical results of model . we take the logarithms on the pollutants as the outcomes. it can be seen that the intra-city ti and mi and mo indices demonstrated a significant, positive influence on the no concentration; one-unit increase in ti in cities increased the no concentration by . %. however, there was no significant effect on the aqi, pm . , pm , and co concentrations. the ti also had a positive effect on the so concentrations, but the effects of mi and mo were negative. note：*,**,*** indicate significance at %, %, and % levels, respectively. table shows the empirical results of model . the restriction measures displayed a significant, negative effect on the air pollutant concentrations, and for every one-unit increase in the intensity of the control measures, the air pollutant concentration decreased by - %, indicating that the implementation of the restriction measures played a crucial role in improving the atmospheric environment. note：*,**,*** indicate significance at the %, %, and % levels, respectively. china has taken a series of extreme control measures such as factories closures and traffic restrictions in response to the covid- outbreak. however, heavy air pollution was still observed in the bth region during a period of unfavourable weather conditions. human perception on the effectiveness of atmospheric pollution prevention and control measures varied. a scientific, empirical study was needed to quantitatively identify the causal effect of regulatory measures on air quality during the covid- outbreak. firstly, the model and estimated result in this study provided an important natural experiment to explore the causal effect of lockdown measures on air quality. here, real-time monitoring data from china's air pollution monitoring stations were used to demonstrate air pollutant concentration trends before and after the covid- outbreak, and a did model was used to estimate the causal effect of the implementation of lockdown measures on air quality, controlling for the interference of meteorological, vacation, and other important factors. the implementation of control measures reduced air pollution, which provided empirical evidence on the identification of the causal effect of lockdown measures on air quality during the covid- outbreak. two findings of this study are important for future air pollution control. first, we found that the traffic restrictions, especially the restriction of intra-city ti, were important for no pollution control in high-population-density urban regions. this points towards an important direction for future control strategies of no pollution. future controls on no pollution should focus on the control of traffic activities, especially the control of intra-city ti. as traffic restrictions were gradually lifted at the end of february, anti-epidemic measures on public transportations (e.g., bus and subway) are still strict. this may lead to the increasing use of private cars [ ] . thus calling for a green and safe return towards urban daily traveling is a major concern for the government. as individual mobility modes, walking and cycling are desirable under this circumstance. non-motorised transportation infrastructure for walking and cycling should be continually improved, which will deliver a double benefit to both epidemic prevention and air quality in the long run. in addition, an intra-city ti index system could be established through real-time monitoring of big data systems to achieve accurate control. at the same time, appropriate regulation and incentive mechanisms can be established to reduce the intensity of intra-city travel, such as traffic restrictions of tail numbers, oil price increases, public transportation subsidies, and so on [ , ] . secondly, our study quantified the improvement of air pollution with a differentiated intensity of control measures in the bth region. we have made a pioneering quantification of the control measures and found that the intensity of control measures had a significant effect on air pollution. it has important significance for the formulation of accurate and effective socio-economic measures. as a densely populated area with severe air pollution in china, the bth region has a huge scale of economic activities and energy consumption [ ] . the economic cost will be huge if population mobility and industrial activities are unreasonably restricted, so it is important to establish appropriate, flexible, and sustainable measures for air pollution control. based on our results, it would be helpful to improve the effectiveness of air pollution control by establishing refined and intelligent hierarchical control measures for economic and social activities and policies for energy conservation and emission reduction [ ] . for further control of air pollution in the bth region, classified control measures could be established according to the causal effect of lockdown measures on air pollution concentration and emission reduction targets, and different means combinations and implementation methods could be carried out to adapt to the classification system of different pollutant levels. finally, this study also investigated the experimental significance of control measures for the reduction of extreme air pollution. the covid- outbreak is a special public health event due to its particularity and uncertainty and provides an extremely rare natural experiment in the control of social and economic activities affecting air pollution. there are massive pollution outbreak events in northern china, especially in the bth region, such as winter fog haze pollution. extreme air pollution harms human health and the social economy, especially in densely populated and economically developed urban agglomerations [ , ] . therefore, highintensity restrictions on population, traffic, and economic activities should be taken to reduce its harm to deal with extreme urban pollution. for example, when an extreme air pollution event occurs, the teleworking and online-education system developed during the covid- lockdown will immediately be used. our research has provided important evidence for contingency planning on integrated socio-economic control measures in extreme pollution situations. determining the causal effect of control measures on air pollution during the covid- outbreak is an important issue. here, we quantitatively identified the causal effect of lockdown measures on air quality in the bth region by building a did model. we not only found that lockdown measures had a significant positive effect on air quality, but also discovered the heterogeneous effects of lockdown measures. as was expected, the implementation of control measures reduced the aqi decreased by . %, no decreased by . %, followed by pm , pm . , and co which decreased by . %, . %, and . %, respectively. further study showed that traffic restrictions, especially the restriction of intra-city travel intensity (ti), had a significant and heterogeneous effect on no with a concentration decrease of approximately . %. moreover, we conducted a study on the intensity of the control measures and found that every one-unit increase in the intensity of control reduced the air pollutant concentration by approximately - %. our study focuses on air pollution reduction caused by the suspension of human-related energy activities during the covid- lockdown. these findings had important implications for reducing air pollution, and would help policymakers to implement differentiated management policies for different air pollution situations [ ] . we found that the management of traffic activities was important for no pollution control in high-population-density urban regions, especially the intra-city travel intensity (ti). thus the safe individual mobility should be promoted to make an environmentally friendly recovery. and big data and artificial intelligence can be used to accurately achieve air pollution control. moreover, high-intensity restrictions on population, traffic, and economic activity are important to deal with extreme air pollution in cities. this study provides important evidence for developing emergency plans for comprehensive social and economic control measures in extreme pollution situations by estimating the differentiated effects on air pollution reduction induced by different highintensity control measures. based on above findings, we highlighted the importance of green commuting and intelligent hierarchical control measures for both energy conservation and emission reduction, which is conducive to the future green recovery of transport and energy system. moreover, china is the country with the earliest outbreak of covid- and the most drastic quarantine measures. the heterogeneous effects of covid- lockdown on air quality in northern china have reference significance from international perspectives. it is necessary to point out two areas for further study. although there was an unprecedented improvement in air quality as a result of the control measures, air pollution during the lockdown maintained a high level. other sources of air pollution such as coal-fired winter heating systems and adverse meteorological factors may have contributed to air pollutant concentrations [ , ] . secondly, the positive effect on air quality was temporary, as studies have found that the control measures during the covid- outbreak have only improved china's air quality in the short term. however, massive energy use and industrial activity may lead to higher air pollution levels when the covid- outbreak control measures are removed over the long term [ ] . a significant challenge remains to maintain this improvement in air quality. finally, since air pollution occurs in line with human activities, prevention, and control of air pollution is a long-term battle. although the extreme control measures of public emergencies such as the covid- outbreak have demonstrated an improvement in air quality, they caused significant damage to society and the economy. therefore, the formulation of sustainable development measures that consider economic, social, and environmental aspects is the key to the long-term control of air pollution in the bth region [ , ] . a novel coronavirus outbreak of global health concern clinical 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chinese cities on-road emission measurements of reactive nitrogen compounds from heavy-duty diesel trucks in china short-and intermediate-term exposure to no and mortality: a multi-county analysis in china impact of energy saving and emission reduction policy on urban sustainable development: empirical evidence from china evaluation of the impact of bus rapid transit on air pollution in mexico city winter heating, air quality, and mortality in china unexpected air pollution with marked emission reductions during the covid- outbreak in china severe air pollution events not avoided by reduced anthropogenic activities during covid- outbreak quantifying the air pollutants emission reduction during the olympic games in beijing spatial correlation analysis of energy consumption and air pollution in beijing-tianjin-hebei region do ship emission control areas in china reduce sulfur dioxide concentrations in local air? a study on causal effect using the difference-indifference model apec blue" endeavor: causal effects of air pollution regulation on air quality in china emission reduction and energy-intensity enhancement: the expected and unexpected consequences of china's coal consumption constraint policy does energy transition improve air quality? evidence derived from china's winter clean heating pilot (wchp) project the relationship between trends in covid- prevalence and traffic levels in south korea the effect of driving restrictions on air quality in mexico city the effect of beijing's driving restrictions on pollution and economic activity the effect of environmental regulation on air quality: a study of new ambient air quality standards in china the regional impacts of cooking and heating emissions on ambient air quality and disease burden in china the heterogeneous effects of socioeconomic determinants on pm . concentrations using a two-step panel quantile regression evidence on the impact of sustained exposure to air pollution on life expectancy from china's huai river policy new evidence on the impact of sustained exposure to air pollution on life expectancy from china's huai river policy a preliminary assessment of the impact of covid- on environment -a case study of china effects of environmental policy on public risk perceptions of haze in tianjin city: a difference-in-differences analysis key: cord- -z l vdsr authors: río, francisco garcía; clau, luis borderías; macario, ciro casanova; celli, bartolomé r.; sanglás, joan escarrabill; mangado, nicolás gonzález; torrent, josep roca; romero, fernando uresandi title: air travel and respiratory disease date: - - journal: archivos de bronconeumología ((english edition)) doi: . /s - ( ) - sha: doc_id: cord_uid: z l vdsr nan in recent years there has been a progressive rise in the number of people who travel by air. according to data from the international civil aviation organization, million people traveled by air in and, despite problems related to security restrictions and severe acute respiratory syndrome (sars), it is anticipated that the number of passengers will increase annually by . % until . more than million air traffic operations were handled during in airports managed by the spanish aviation authority (aeropuertos españoles y navegación aérea, aena), representing travel by million passengers. those figures correspond to a % increase in the number of passengers since , with an annual increase of %. in addition, advances in the monitoring and treatment of many chronic respiratory diseases have allowed changes in the lifestyle of patients. thus, patients are now able to consider leisure and professional activities that were not possible some years ago. although adverse respiratory events as a result of air travel are not common, this form of transport does present potential risks. data from airline companies forming part of the international air transport association (iata) show that between and there were deaths in flight, corresponding to . deaths per million passengers or . deaths per million takeoffs. respiratory complications represented the third highest known cause of death ( %) after cardiac causes ( %) and deaths due to cancer ( %). in addition, it was noteworthy that while there was prior knowledge of the presence of heart disease in only % of deaths due to cardiac events, there was prior knowledge in % of those due to respiratory disease, suggesting that there are problems in the assessment of patients prior to the flight or in their in-flight care. aside from fatal events, respiratory symptoms are responsible for a good proportion of the emergencies that occur on board aircraft. analysis of all cases in which the first-aid kit was used on commercial aircraft belonging to the iata between august and july showed that chest pain and dyspnea were of the most common causes, along with loss of consciousness. , likewise, % of passengers who required medical assistance had a known medical condition associated with the episode that occurred on board the aircraft, further indicating the importance of careful assessment prior to flight. along similar lines, a service offering the assistance of experts by radio during in-flight emergencies received calls in , of which % corresponded to respiratory problems. , thus, respiratory problems may represent up to % of in-flight emergencies. in response to this situation, various guidelines and recommendations have been prepared by scientific societies or the airline companies themselves. , [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] however, little scientific information supported by a high level of evidence is available in this field, meaning that the majority of the recommendations are based solely upon expert consensus. in fact, in recent years, conflicting results have been reported using the regimens recommended in previous guidelines. furthermore, there is a local problem generated by differences in the legislation and the wide range of criteria, resources, and attitudes of the different airline companies. the aim of these guidelines is to define assessment protocols for patients with chronic respiratory disease intending to travel by plane that are adapted to the situation in spain and the most recent available data. in addition, the guidelines aim to establish specific recommendations for the most common respiratory diseases. extensive information is available on respiratory physiology during air travel in both healthy individuals and patients. , - , - some of those detailed reviews of francisco garcía río a (coordinator), luis borderías clau, b ciro casanova macario, c bartolomé r. celli environmental conditions and their control are published by the airlines themselves and are available on the internet. , it is worth remembering that the atmosphere surrounding the earth's crust is made up of different layers or strata: the troposphere, the stratosphere, the mesosphere, the thermosphere, and the exosphere. the layer closest to the earth is the troposphere, which extends from sea level to m ( feet) at the poles and to m ( feet) at the equator (appendix ). today's commercial aircraft fly within this zone. atmospheric pressure depends on the column of air above the measurement point; consequently, the higher the altitude, the lower the pressure. since the reduction in atmospheric pressure is logarithmic (figure ), at lower levels small changes in altitude produce substantial changes in pressure. thus, at m ( feet) the atmospheric pressure is less than half that at sea level. the composition of the troposphere is constant and contains approximately % nitrogen and % oxygen. since the partial pressure of a gas is a function of its concentration and the total pressure, oxygen tension is directly dependent upon altitude and drops exponentially as altitude increases ( figure ). this hypoxia is the cause of the limitations and risks faced by mountaineers and also of acclimatization problems in high-altitude populations. in addition, adaptation to this type of environment is affected by the amount of exercise that is performed. in terms of the physiologic response of the human body, the atmosphere can be divided into zones: the physiologic zone, the physiologically deficient zone, and the zone equivalent to space. the physiologic zone is where the human body is well adapted and where the oxygen level is sufficient to maintain normal processes. this zone extends from sea level to an altitude of m. nevertheless, rapid changes in altitude within this zone can cause minor problems due to the expansion of gases trapped within the body. the physiologically deficient zone extends from to m. in that zone, the reduction in barometric pressure causes a critical environmental hypoxia, necessitating the use of supplementary oxygen at higher altitudes. from a physiologic point of view, space begins at an altitude of m. in this zone, the low ambient pressure means that humans are unable to survive even with supplementary oxygen and they require pressurized suits. above m the barometric pressure is lower than the vapor pressure of water at ºc and body fluids evaporate. commercial aircraft generally fly at an altitude of around to m ( - feet). , , if the internal pressure of the aircraft were to be directly dependent upon the external atmospheric pressure the environment would be incompatible with life. consequently, aircraft must be pressurized, that is, have elevated pressure compared with that of the external environment. to achieve this, they take ambient air and compress it. since the gas heats up in this process, it must subsequently be cooled. the pressure is controlled according to the quantity of air injected and through the use of escape valves set to the desired pressure. to support the pressure difference, the structure of the aircraft must be reinforced and that increases its weight. as a result of both the increased weight and the additional energy required to compress the air, cabin pressurization increases aircraft fuel consumption and thereby decreases their independence. the pressurization system used by commercial aircraft is known as isobaric. initially, as the aircraft climbs in altitude, it maintains the same ambient pressure as its environment, and then, from a certain altitude, it maintains a constant (isobaric) pressure, irrespective of changes in altitude. many military aircraft employ a different system known as differential-isobaric pressurization, which imposes fewer structural requirements and thereby saves weight. due to the technical limitations mentioned and the cost, aircraft pressure is not maintained at that of sea level but rather at an intermediate pressure; that pressure depends on the type of aircraft but is usually approximately equivalent to that of an altitude of m. altitude, the atmospheric oxygen tension is equivalent to breathing . % oxygen at sea level. although international legislation establishes that minimum cabin pressure should correspond to an altitude of m ( feet), the pressure does not remain constant throughout a flight. in a large series of measurements performed during commercial flights, it was determined that the conditions within aircraft cabins usually correspond to an altitude of to m ( - feet) above sea level. , , survival in the event of a sudden reduction in cabin pressure necessitates the use of oxygen masks (obligatory equipment on commercial flights). it is also important to note that at an altitude of m a person will lose consciousness in to seconds. the degree of pressurization also depends on the type of plane. the old concorde was pressurized at a comfortable level corresponding to an altitude of m ( feet). the current tendency for new models of aircraft, whether manufactured by boeing or airbus, is to pressurize at this more comfortable, safer pressure. however, the new airbus is expected to carry around passengers with a cabin pressure equivalent to an altitude of more then m ( feet) for up to hours. in addition to the difficulties caused by changes in barometric pressure, the external environment presents additional problems for commercial flights. the concentration of ozone, which is very low at sea level, increases with altitude and peaks in the stratosphere. ozone, which is important to filter ultraviolet radiation, is toxic to the respiratory system, even at concentrations below part per million (ppm), which can be reached at some common flight altitudes. to manage this problem, planes have catalytic ozone converters installed to reduce the concentration of the gas. the regulations of the federal aviation administration establish a maximum mean concentration of . ppm and a maximum peak concentration of . ppm. the temperature falls by approximately ºc for every m increase in altitude, necessitating warming of the air inside the cabin. this air normally has a low humidity ( %), which can cause problems for some individuals. most commercial aircraft recirculate approximately % of the air to improve humidity and energy efficiency. the air must be filtered to retain particles smaller than . µm in diameter using highefficiency particulate air (hepa) filters similar to those used in hospital operating theaters. in addition to particles in suspension, this system is considered effective for the retention of bacteria, fungi, and even viruses released during speech, coughing, or sneezing ( figure ). the air is renewed to times per hour, although this may vary according to the model and the zone of the plane. the cabin ventilation system generates transverse airflow and is able to renew the air more effectively than in buildings with air conditioning. complex electronic systems with sensors located throughout the cabin control the temperature and regulate valves in order to maintain a temperature that is as homogeneous as possible. finally, it is worth mentioning that the carbon dioxide content of this filtered and conditioned air is usually very low ( ppm). the partial pressure of inspired oxygen (pio ) is a function of the atmospheric pressure and the vapor pressure of water. as the vapor pressure of water at the same body temperature remains stable with altitude, pio will decrease with altitude (hypobaric hypoxia). breathing ambient air at m ( feet) is equivalent to breathing . % oxygen at sea level, meaning pio falls from mm hg at sea level to mm hg at m. , in healthy subjects, this can represent a reduction in pao from to mm hg, , , which is usually well tolerated and does not produce symptoms. however, in patients with chronic respiratory diseases and some degree of baseline hypoxemia, the reduction in pio during the flight can cause more marked reductions in oxyhemoglobin saturation. [ ] [ ] [ ] acute exposure to a hypobaric environment triggers hyperventilation, which is essentially induced by stimulation of peripheral chemoreceptors and is usually mediated by an increase in tidal volume. it also generates an increase in cardiac output to compensate for the residual systemic hypoxia. this increase is mainly mediated by tachycardia and is usually proportional to the drop in oxygen saturation. the increased pulmonary perfusion caused by the rise in cardiac output is associated with hypoxic vasoconstriction of the pulmonary artery and increased systolic pulmonary pressure. as a consequence of the increase in pulmonary vascular resistance, there is a redistribution of pulmonary blood flow and an increase in perfusion of certain areas of the lungs compared with the situation at sea level. altitude is also associated with limitation of oxygen diffusion from the atmosphere into the pulmonary capillaries as a consequence of the interaction of various factors. both the reduced pio and the reduction in affinity of hemoglobin for oxygen in conditions of low pao lead to a more marked drop in the oxygen content of the pulmonary capillaries than at sea level. finally, the transit time of blood through the pulmonary capillaries is shortened due to the tachycardia caused by the altitude and this limits the time available to establish an adequate oxygen equilibrium. the net result is an increase in the alveolar-arterial oxygen difference. , , in addition, the oxyhemoglobin saturation is significantly reduced during physical exercise in a hypobaric environment. exercise at high altitudes also increases the alveolar-arterial oxygen difference in subjects who normally reside at sea level, while it does not affect those native to high altitudes. studies performed using the multiple inert gas elimination technique have shown that hypobaric hypoxia is associated with a greater heterogeneity in the ventilation-perfusion ratio and a limitation of diffusion that together worsen hypoxemia as exercise intensity increases. limited diffusion secondary to reduced pio appears to exert the greatest influence on blood gas alterations during exercise in a hypobaric environment. additionally, the interstitial edema caused by extravasation of fluids into the extravascular space appears to potentiate the ventilation-perfusion imbalance. the changes described have few consequences in healthy subjects, who might only note a slight increase in tidal volume and heart rate. however, hypobaric hypoxia represents a risk for some patients with chronic respiratory disease, in whom it can aggravate preexisting hypoxemia and favor the development of cardiovascular complications. in fact, it is recognized that hypoxia reduces the ischemic threshold in men with exerciseinduced ischemic heart disease as well as favoring some atrial arrhythmias and being associated with ectopic ventricular beats as a result of increased sympathetic activity. with increasing altitude, barometric pressure is reduced and gases expand if they are trapped in the body, unable to escape. this phenomenon is explained by boyle's law, which establishes that the volume of a gas is inversely proportional to the pressure: although the expansion of the trapped gases is limited, it occurs rapidly, and in healthy subjects can cause discomfort in organs such as the ear, paranasal sinuses, teeth, and gastrointestinal system. in patients with respiratory diseases, and even in young, apparently healthy individuals with small apical bullae, the phenomenon can generate more serious problems. [ ] [ ] [ ] [ ] ears. air trapping can occur in the ears due to partial or complete obstruction of the eustachian tube, which normally equalizes air in the middle ear with the outside. this can occur both during ascent and descent and is also one of the main problems associated with underwater diving. it can be the result of a chronic intrinsic or acquired obstruction or an acute process caused by an infection or allergic reaction. with increasing altitude, the air expands and exerts a pressure on the tympanic membrane, which expands outward. when a pressure increase of to mm hg is reached, a small bubble of air is expelled into the nostrils and is sometimes accompanied by a small noise. upon descent, the reverse situation occurs. the external pressure increases and the tympanic membrane is pressed inwards. it is much more likely for obstruction to occur in this situation since the eustachian tube functions less effectively in this direction. this air block can produce sounds, nausea, and pain in the ears that is sometimes very intense, particularly if the finally phase of the descent occurs very rapidly. a useful maneuver to prevent this obstruction involves repeated swallowing of saliva. consumption of liquids or food can also help. if the condition persists, gentle valsalva maneuvers are recommended. paranasal sinuses. the paranasal sinuses can present similar problems to those experienced in the ear. in this case, the obstruction may be due to chronic lesions such as polyps or to acute problems such as mucus generated in response to infections or allergies. in general, the problem appears during descent and in % of cases affects the frontal sinuses. the pain can become very intense. [ ] [ ] [ ] [ ] barodontalgia. some subjects may experience dental pain, mainly during ascent to between and m. it was initially thought that small pockets of air trapped during dental restoration or other manipulations were the cause of the problem. however, it has not been possible to confirm that hypothesis, despite the association of symptoms with different types of dental complaints. gastrointestinal tract. the gastrointestinal tract usually contains some quantity of gas, and consequently, gastrointestinal discomfort is common during air travel. nevertheless, such problems are of minor significance at the cabin pressures reached during commercial air travel. lungs. in healthy subjects without structural abnormalities there are usually no problems of this type associated with the lungs since pulmonary gas pressure is rapidly equalized with the ambient pressure. nevertheless, some young, apparently healthy subjects may have apical bullae, which can burst during ascent and cause a pneumothorax. in some cases this may be a tension pneumothorax and become serious. given that the gas in the body cavities is saturated with water vapor, the expansion caused by increased altitude is greater than that calculated according to boyle's law. given that body temperature remains constant, in the case of bullae or closed pneumothorax the increase in volume can be calculated with the following formula: ∆volume= pressure of gas at sea level-water vapor pressure if it is assumed that the gas pressure is mm hg at sea level and mm hg at an altitude of m, and that water vapor pressure remains constant at mm hg, it can be estimated that the volume of trapped gas will increase by . % during ascent. the problem is much more severe in patients with chronic obstructive pulmonary disease (copd), since those patients usually have regions of emphysema that are poorly connected with the exterior or separated from it and can cause rupture and pneumothorax, in addition to the problems generated by hypoxia. airline companies usually recommend that individuals do not fly within weeks of the resolution of a spontaneous pneumothorax, although the scientific evidence supporting this recommendation is very limited. if the pneumothorax has been treated surgically or by pleurodesis with talc it is highly unlikely that there will be a relapse during flight. diving and flight. a particular problem may occur following scuba diving activities. dissolved nitrogen can accumulate in the tissues (residual nitrogen) during scuba diving, particularly when diving is deep and repeated. during ascent, that nitrogen may be released and give rise to symptoms of decompression, which in some cases can be severe. in general, it is recommended that individuals do not fly within hours following scuba diving, and that they abstain longer periods if diving required decompression breaks. tables and computer programs are available that can help determine the amount of residual nitrogen and the recommended delay before flying. [ ] [ ] [ ] [ ] as mentioned, cabin humidity is usually less than % to %. this can cause skin dryness and discomfort in the eyes, mouth, and nostrils. the dehydration caused by a long flight can also be significant in patients with bronchiectasis. if nasal irritation is particularly acute, use of a hypertonic saline spray is recommended. prolonged immobility, particularly in a sitting position, contributes to the accumulation of blood in the legs, and this can cause swelling, tightness, and discomfort in the lower limbs. in turn, immobility can favor the development of deep vein thrombosis (dvt). for some subjects, the aircraft environment and the flight itself can trigger increased anxiety, which can lead to an exaggerated perception of some respiratory symptoms or contribute to the deterioration of an existing respiratory condition. it is difficult to establish definitive guidelines based on currently available information. in fact, a wide variety of procedures are used for the assessment of patients with respiratory disease. in a review of in-flight requests for oxygen, information on oximetry or spirometry results were only available in % of cases. furthermore, a survey of specialists in respiratory medicine in england and wales revealed that they followed highly diverse criteria in prescribing use of oxygen in flight. in any case, to establish a medical opinion on risk in air travel, the type, reversibility, and degree of functional impairment caused by the disease must be assessed along with the tolerance of the patient for the predicted flight altitude and the length of exposure. although all patients with chronic respiratory disease may benefit from a clinical assessment prior to undertaking air travel, such assessment should be considered obligatory in those situations shown in table . the following procedures should be considered in this preliminary examination: -medical history, in which special attention should be paid to recognizing all cardiorespiratory disease, with particular interest in comorbidity that could be worsened with hypoxemia (cerebrovascular disease, ischemic heart disease, heart failure). it is also important to assess dyspnea and other respiratory symptoms and compile previous experiences of the patient on other flights. -measurement of oxyhemoglobin saturation by pulse oximetry (spo ) or arterial blood gas analysis, following a period of rest sufficient to guarantee stability of the recordings. in the case of clinical suspicion of hypercapnia, blood gas analysis should obviously be performed. -forced spirometry , and single-breath determination of the diffusing capacity of the lung for carbon monoxide (dlco). -walk test. the medical departments of some airlines propose walking for m as a way to assess tolerance of flight conditions. in such a test, the aim is to verify that the patient is capable of walking m without limitation due to dyspnea. although it is a crude procedure that has not been sufficiently validated, it allows an estimate to be made of the cardiorespiratory reserve by assessing the increase in ventilation and cardiac output in response to exercise. in principle, there is no reason to use a m walk test in place of the minute walk test, which is commonly used in many patients with respiratory disease and is well standardized. criteria for concern should be the inability of the patient to continue walking for minutes, a distance covered of less than m, or the development of severe dyspnea (score of more than on the borg scale). garcÍa pressure of gas at m-water vapor pressure -incremental cardiorespiratory exercise test. the incremental exercise test is not recommended for the systematic assessment of all patients, although it could be useful if the results of simulated altitude-induced hypoxia were unclear. it has been confirmed that a peak oxygen consumption (vo max) greater than . ml/min/kg in patients with moderate or severe copd is associated with a pao of greater than mm hg during the flight. that relationship between vo max and pao was confirmed in the first and fourth hour of flight in a study involving patients with severe copd. in fact, in a multivariate analysis, pao at sea level and vo max were selected as independent predictors of pao during the first hour of flight. however, in the fourth hour the only independent variable associated with vo max was pao . identification of at-risk patients. the information collected in the aforementioned procedures should allow identification of patients who should not fly (table ) along with those in whom the hypoxemia in flight could prove dangerous. in general, it is accepted that patients with acute respiratory failure should not fly. this should also apply to patients with sputum-positive tuberculosis. in the case of patients who are negative for the human immunodeficiency virus (hiv), it would be necessary to have taken antituberculosis treatment for at least weeks. in hiv-positive patients, negative sputum stains or a negative sputum culture are required during the course of the treatment. passengers with respiratory symptoms who come from areas of local transmission of sars should also be prohibited from flying, as should contacts of probable or confirmed cases of sars who have been exposed within the last days. patients with undrained pneumothorax, subcutaneous or mediastinal emphysema, or a pulmonary contusion, or who have undergone a major thoracic surgical procedure in the last weeks are also considered to have a respiratory contraindication for air travel. most current guidelines only consider the results of pulse oximetry or baseline arterial blood gas analysis in screening for patients at risk of developing severe hypoxemia. , [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] in fact, pao greater than mm hg or spo above % are usually considered acceptable for air travel in the majority of cases. , however, in recent years it has been shown that screening based on pao or spo alone are insufficient. for instance, a study was performed in which in-flight hypoxemia was assessed in a group of patients with copd who had a resting pao of more than mmhg, without hypercapnia, and a forced expiratory volume in second (fev ) less than % of reference. in % of the patients, pao was less than mm hg at an altitude of m and % had a pao of less than mm hg. what was even more noteworthy in that study was that % of the patients had a pao less than mm hg when they undertook lowintensity exercise similar to that necessary to walk along the aisle of the cabin or to go to the bathroom. similar findings have been obtained in patients with interstitial disease. figure shows a proposed algorithm for patient assessment. in those patients who receive home oxygen therapy, it is recommended that the oxygen flow be increased during the flight, usually by to l/min. in other patients, in-flight hypoxemia should be estimated if they have a pao less than mm hg or an spo less than %, if the forced vital capacity (fvc) or dlco is less than % of reference, or if other risk factors are present ( table ) . based on the level of hypoxemia during air travel in healthy subjects, a pao of more than to mm hg has been arbitrarily considered acceptable. [ ] [ ] [ ] [ ] [ ] consequently, it is important to estimate the pao during the flight, since below mm hg provision of supplementary oxygen during the flight is recommended. pao at altitude can be estimated in ways: through the use of prediction equations or with a hypoxia-altitude simulation (hypoxic challenge) test. absolute acute respiratory failure sputum-positive tuberculosis passengers from areas with recent local outbreaks of severe acute respiratory syndrome (sars) with respiratory symptoms contacts of probable or confirmed cases of sars who have been exposed in the last days undrained pneumothorax thoracic surgery within the last weeks lung contusion subcutaneous or mediastinal emphysema relative resolution of a spontaneous pneumothorax in the last weeks major thoracic surgery within the last weeks scuba diving in the last hours (table ) . , [ ] [ ] [ ] [ ] [ ] [ ] [ ] some of them allow pao to be determined for any given altitude based on values obtained at sea level ( figure ). , in most cases, the equations were established for patients with copd and the measurements of pao at altitude were performed in hypobaric chambers or following altitude simulation via respiration with a fraction of inspired oxygen (fio ) of %. the accuracy improves when measurements of fev , or fev /fvc are included. in addition, greater accuracy is obtained when they are applied to copd patients with an fev less than % of reference. despite the simplicity of equations to estimate in-flight hypoxia and their widespread availability, they also have drawbacks. the most important is the consequence of their very large % confidence interval, which is ± . mm hg, mainly due to the use of very small samples in their calculation. it is notable that in patients with severe copd differences have been detected between the actual pao during the flight and that estimated in the equation of gong et al of - ± mm hg (range, - to mm hg). in almost all cases, patient series used to develop the equations have involved healthy men or men with copd, meaning that accurate information on women is lacking. nor have flight duration and cabin conditions been considered. in addition, the equations have not been validated with another hypoxia test repeated after the test used to generate them. it is possible that equations that include fev underestimate the severity of hypoxemia triggered by altitude in hypercapnic patients, since some authors have demonstrated that pao at altitude is inversely proportional to paco at sea level. in the same way, equations that use fev or fev /fvc in healthy subjects probably overestimate pao at altitude. it is also likely that the cause of the hypoxemia should be taken into account. for instance, hypoxemia as a result of shunt is affected very little by altitude, while that caused by ventilation-perfusion imbalance is highly dependent upon pio . , recently, a specific prediction equation that includes dlco was developed for patients with restrictive disease. another equation relevant to patients with copd or interstitial disease has also been proposed. in addition, in recent years models have incorporated paco , both for healthy subjects and patients with copd. in the light of available data, the equation published by muhm would be the most recommendable in healthy subjects and patients with copd, while that of christensen et al would be advisable for patients with restrictive disease. hypoxia-altitude simulation test. although hypobaric hypoxia is the ideal method to estimate the degree of hypoxemia during a commercial flight, it can not be used in ordinary clinical practice due to the limited availability of hypobaric chambers (appendix ). as an alternative, it is recommended to resort to the isobaric hypoxia-altitude simulation (hypoxic challenge) test, initially described by gong et al. this test assumes that respiration of a hypoxic gas mixture at sea level (normobaric hypoxia) simulates the hypobaric hypoxia characteristic of higher altitude. the maximum altitude corresponding to cabin pressure ( m) can be simulated by respiration of a mixture of % oxygen in nitrogen. no specific preparation is required for the test. it is recommended that the test be performed without interruption of the patient's usual medication, attempting to avoid changes in the dose or intervals of the medication. once patients are seated, they can be made to breathe a hypoxic gas mixture using a douglas bag, a plethysmography chamber, or a venturi mask. the most traditional and simple method is to ask the subject to breathe the gas mixture contained in a to l douglas bag, which is filled with % oxygen and nitrogen as a carrier using pressurized cylinders. in this case, the patients can breath through a mouthpiece with a nose clip, or through a face mask with a valve to prevent rebreathing. , the second option involves filling a sealed plethysmography chamber with a gas mixture ( % oxygen in nitrogen) that can be kept constant by introducing oxygen or nitrogen through a port. this procedure has the advantage of not requiring a mask or mouthpiece and also allowing titration of the oxygen flow required to correct the hypoxemia by administration of oxygen through nasal prongs within the hypoxic environment of the chamber. however, while the patient remains in the chamber it is not possible to obtain samples of arterial blood and monitoring is therefore limited to spo . as a third possibility, a venturi mask can be used in which oxygen is replaced with nitrogen as the carrier gas. it has been confirmed with various devices that a venturi system at % generates an fio of %, while % produces an fio of %, both in healthy subjects and patients with copd. however, it must be remembered that not all commercial models based on the venturi principle are able to administer oxygen with an error of less than %, as claimed in their specifications. in addition, the fio can be reduced if the inspiratory flow of the patient exceeds the total flow generated by the apparatus. although its role is more limited, the dead space inside the mask also affects the concentration of oxygen provided. it is also necessary to consider that nitrogen is % less dense than oxygen, meaning that the carryover capacity for air through the venturi system is lower than that of oxygen, thereby making the fio achieved less accurate. thus, it appears reasonable to suggest that if this system is used to administer the hypoxic gas mixture then fio should be monitored simultaneously. during the test, the patient will be asked to breathe at tidal volume and the test will be ended after minutes , or when a stable situation is achieved, defined as the absence of variability in spo (± %) or heart rate (± beats per minute) for at least minutes. it is recommended that spo be monitored continuously and that arterial blood gas analysis be performed at the beginning and end of the test. in terms of pulse oximetry, it should not be forgotten that true oxygenation can be slightly overestimated in smokers, given that the technique does not discriminate between oxyhemoglobin and carboxyhemoglobin. furthermore, most pulse oximeters display a certain degree of inaccuracy and variability in the saturation range between % and %. therefore, spo should only be used to monitor the test, while interpretation of the test results should be based on pao . in both healthy subjects and patients with copd, the hypoxic challenge test provides a measure comparable to that obtained by simulating the same altitude in a hypobaric chamber. the relationship between isobaric hypoxia and hypobaric hypoxia appears not to be affected by the age or the sex of the subjects. in turn, it has also been demonstrated that there is a good correlation between the pao obtained during simulation of altitude-induced hypoxia and that determined during flight, although this correlation is weakened when the interval between the measurements is longer than months. in terms of safety, the tolerance of hypoxic challenge is good and only mild side effects such as tachycardia, dyspnea, vertigo or nausea, headache, and sleepiness have been described. hypoxic challenge offers certain advantages over prediction equations. it provides a more accurate assessment of the individual's response to hypoxia. in addition, it allows assessment of the possible effects of hypoxia, such as symptoms or electrocardiographic (ecg) abnormalities. although initial studies involved continuous ecg monitoring, , few arrhythmias related to hypoxia were identified and all of them were benign; consequently, systematic ecg monitoring is not recommended. however, it may be considered on an individual basis in patients with cardiovascular comorbidity. despite these considerations, hypoxic challenge is a procedure that also presents limitations. it does not reproduce cabin conditions of pressure or air density. however, in order for reduced air density or flow turbulence to generate an increase in fev or a reduction in work of breathing, altitudes of more than m are required, suggesting that these factors will have little influence. in addition, the potential beneficial effect of the reduced air density will never be greater than the negative effect caused by the reduction in pio , the increase in lung elasticity and air trapping, and the poor distribution of ventilation. , the length of the flight is also not taken into account during hypoxic challenge. however, changes in arterial blood gases during a flight lasting hours have recently been analyzed in patients with copd. it has been demonstrated that when patients remain seated pao falls until cruising altitude is reached and then remains stable for the rest of the flight. there is less consensus regarding the application of these recommendations in children with respiratory diseases. little information is available on physiologic changes at altitude in children. in addition, the spectrum of disease can be very broad. in premature babies with acute viral respiratory infection there is a greater risk of apnea due to immaturity of the breathing pattern. in that case, environmental hypoxia can increase the risk of apnea and it is therefore recommended that infants do not fly until months after the date for full-term birth. on the other hand, some children with cystic fibrosis are better adapted to a hypoxic environment, probably through changes in the dissociation characteristics of hemoglobin. as a result, the current recommendation considers that children with an fev less than % of reference for cystic fibrosis or other chronic lung disease should undergo a hypoxic challenge test and that if spo is less than % during the test then provision of oxygen during the flight should be prescribed. , the most recommendable route for administration of the hypoxic gas mixture in children is breathing in a plethysmography chamber. supplementary oxygen is recommended during air travel for patients who have an estimated in-flight pao of less then mm hg obtained with prediction equations or, preferably, a hypoxic challenge test ( figure ). , the criteria on which this cutoff is based are arbitrary. since healthy individuals can reach a pao of to mm hg at cabin altitude, mm hg was considered to represent the lower limit for a clinically acceptable pao . therefore, that cutoff is based on expert consensus and does not have scientific support. patients with an estimated pao greater than mm hg could fly without a requirement for supplementary oxygen. finally, the group of patients with an estimated pao between and mm hg should be assessed on an individual basis. in this case, if there is serious deterioration of resting lung function, marked exercise limitation in either the walk test or the incremental cardiorespiratory exercise test, or comorbidity, provision of oxygen during the flight could also be recommended ( figure ). oxygen is usually provided during the flight through nasal prongs. in patients with severe copd subjected to conditions of hypobaric hypoxia similar to those in the cabin of a commercial aircraft, it has been shown that provision of oxygen through nasal prongs at a rate of l/min produces a greater increase in pao than when administered using a venturi mask at % or %. in fact, ventimask systems may favor dilution of ambient air at relatively low flow rates. an oxygen flow of l/min appears sufficient to correct the hypoxemia in most cases. it has been confirmed that provision of oxygen through nasal prongs at l/min in healthy subjects and patients with obstructive or restrictive disease who breathe an ambient fio of % achieves an spo similar to that recorded when they breathe at an fio of %. in restrictive diseases, a flow rate of l/min also appears to be sufficient to maintain adequate oxygenation during the flight, although when the patient moves about the aircraft it may be advisable to increase the flow to l/min, so long as an extension is available. finally, provision of supplementary oxygen should be considered a safe and effective procedure for the management of many patients with chronic respiratory diseases who undertake a journey by air. , , for example, it has recently been described that provision of oxygen during flights of up to km allowed a group of patients with severe lung disease to reach their destinations satisfactorily. in that study, only a few episodes of near fainting were observed due to insufficient oxygenation when going to the bathroom without supplementary oxygen. consultation prior to air travel. however, the response of physicians cannot currently be clear and robust, since there is insufficient scientific evidence and many elements remain to be clarified. in general, the first recommendation for a patient with copd and hypoxemia would be to avoid air travel and look for other means of transport. this indication might have been valid some years ago but it is currently insufficient for many patients, since it may affect their quality of life and in some cases their work. in fact, a small survey performed in the united states of america on patients with severe copd showed that each year approximately in traveled by air. however, those results cannot be extrapolated to spain, where the proportion is likely to be lower. as for other diseases, it is accepted that patients with copd should maintain a pao of more than mm hg during a flight. , , with this threshold, no problems have been observed in studies involving hypoxic challenge and it seems reasonable given the clinical experience accumulated in patients with copd treated by continuous home oxygen therapy. however, this level is arbitrary and no studies have analyzed its possible consequences in periods of time closer to those of flights, although flight duration appears to have less effect than the altitude reached. despite the potential impact of copd, few studies have addressed the problem of hypoxemia at high altitude during air travel in this setting. furthermore, the studies performed have involved small samples of patients without severe hypoxemia, the majority eucapnic, and without significant cardiovascular comorbidity. , , , , the results of those studies indicate that patients can have reductions in pao of up to mm hg when they reach an in-flight altitude of m ( feet). this situation is not uncommon in normal flights, and although the incidence of medical problems appears minimal in the general population, , the same is not true of copd patients, in whom symptoms and the requirement for in-flight medical assistance are more common. nevertheless, these events do not normally appear to be particularly serious, and when they are, they are usually cardiovascular in origin. , although the interpretation of these data may be erroneous due to the limitations of their collection, it is also possible that the tolerance of hypoxemia in patients with copd (without other factors that could alter oxygen transport such as heart disease or anemia) is greater than might be expected. according to current knowledge, it could be recommended that all patients with moderate or severe copd who wish to travel by air should be clinically assessed, with attention to the following elements: ) ruling out the presence of exacerbation or that the patient is in an early phase of recovery from an exacerbation, ) identifying the treatment being taken, and ) reducing comorbidity. once clinical stability has been confirmed and treatment optimized, arterial blood gas analysis and spirometry should be performed in the days prior to flying. the values obtained for pao must be adjusted to sea level; in some regions of spain that may imply an increase of up to mm hg. in order to simplify the assessment, the following algorithm could be recommended in response to the presence of hypoxemia ( figure ): . pao > mm hg. in general, patients with this pao will not present severe hypobaric hypoxemia, making systematic estimation of in-flight pao unnecessary. nevertheless, the presence of symptoms (dyspnea or chest pain) during previous flights should be assessed, and if they are present, oxygen support at low flow rates ( - l/min) should be recommended. it also seems wise to extend that treatment option to those cases and in which the in-flight cabin pressure corresponds to an altitude of greater than m ( feet) and the patient has very severe copd (fev ≤ %), where limitations may be present in the mechanisms of compensation for hypoxemia, or diseases that alter oxygen transport. . pao = - mm hg. an estimate of in-flight pao should be made using a prediction equation or, preferably, hypoxic challenge. prescription of oxygen at low flow rates is recommended in the following situations: -estimated in-flight pao less than mm hg -flights in which the cabin pressure corresponds to an altitude greater than m ( feet) -presence of cardiovascular comorbidity and/or anemia . pao < mm hg. patients in this situation usually already receive continuous home oxygen therapy. the goal would be maintenance of the same oxygen levels during the flight, necessitating an increase of to . l/min over the patient's usual oxygen support. such treatment should not normally create problems in eucapnic copd patients, in whom a tendency toward hypocapnia due to hyperventilation has been observed. however, in the presence of hypercapnia, prior assessment of variations in gas exchange following increased oxygen support should be undertaken. it is important to mention that patients who are not receiving continuous home oxygen therapy have a lower sense of the severity of the disease and a substantial proportion may not consult their doctor prior to undertaking air travel. thus, improved treatment education should be developed for this patient population. alongside preflight planning based on pao , other general measures to prevent deterioration of hypoxemia include the following: -avoid excessive physical effort: do not carry weight and reserve a seat close to the bathroom. however, this should not be a contraindication for the necessary movement of the lower limbs to prevent dvt -avoid sleep -do not eat large meals it is advisable for airline companies to have trained staff available who are able to monitor spo in patients who require oxygen during the flight (spo between % and % could be acceptable). in addition, they might be able help to detect abnormalities in heart rhythm, which although rare, show a high between-individual variability. this monitoring is essential if the patient has to travel urgently whilst clinically unstable. while awaiting new studies that improve upon the substantial limitations in our understanding, the overall message is that all patients with copd should be assessed by their pneumologist prior to air travel. supplementary oxygen should be provided for those patients whose estimated in-flight pao is less than mm hg, taking particular care with those who have cardiovascular comorbidity. commercial flights represent a favorable environment for the spread of pathogens transported by passengers or flight personnel, as was shown during the recent outbreak of sars. few studies or data are available on this topic and it is difficult to quantify the global repercussions, which may be underestimated, since almost all of the diseases involved have incubation periods that are shorter than the length of the trip, some of the diseases are treated as trivial processes, and the studies that have been performed have included a significant proportion of passengers who could not be located. the international health regulations adopted worldwide in to limit the spread of disease are in the process of revision. , recently, the world health organization (who) published guidelines on infectious diseases and air travel. risk factors. the respiratory infections that have been the object of the greatest interest are pulmonary tuberculosis, sars, and infections caused by the influenza virus. since the microorganisms responsible for those infections are mainly transmitted through the air, the risk of transmission during flights is affected by duration, the proximity of the index case, and the cabin ventilation, in addition to the pathogenic characteristics, the epidemiology of the infection in each region, and the immune status of the subject. the use of appropriate filters and correct recirculation of air in the plane reduces the risk of infection. although the safety of hepa filters in protection against viruses has been questioned, a more serious concern is the absence of legislation obliging their use in most countries. hepa filters were found not to be used on % of flights carrying more than passengers in the usa, and that figure is considerably higher in small planes that undertake local flights. based on the cases analyzed and studies involving mathematical models, individuals seated in either of the rows of seats closest to the affected passenger are at the highest risk for transmission of mycobacterium tuberculosis and if ventilation is doubled, the risk is reduced by half. the probability of transmission is also reduced to almost zero in passengers seated rows from the zone of infection. , however, this "safe distance" does not apply in the case of a patient with sars, who could infect any other healthy passenger seated in the next rows. studies performed by the who have failed to demonstrate that air recirculation by itself facilitates transmission of infectious disease on board aircraft. however, it should be confirmed that the cabin ventilation system functions correctly and continuously while passengers are on board, independently of whether or not the plane is in flight or held on the runway, as inadequate functioning clinical calls have recently been made in scientific journals and in the general media for serious consideration to be given to regulations on the use of hepa filters and for an increase in the number of checks made on aircraft by the authorities. , tuberculosis. a third of the world's population is infected by m tuberculosis, and consequently, it is the most extensively studied model of transmission during air travel. evidence is available that transmission from smear-positive individuals is more common during long flights (longer than hours) and can affect both the passengers and crew members. seven episodes of possible tuberculosis transmission during airplane journeys have been studied, of the episodes corresponding to strains resistant to isoniazid and rifampicin. possible transmission of the infections (mantoux conversion) to other passengers or crew members could only be established in of the episodes, although it was not possible to demonstrate development of the disease as a result of exposure during a commercial flight in any of the cases. , in the remainder, the studies found no evidence of transmission, were inconclusive, , or the likelihood of transmission was considered very low. in all of the cases, the index patient had substantial radiographic involvement and sputum stains revealed acid-fast bacilli with positive sputum cultures. despite the fact that acquisition of the disease and possibly transmission of the infection is less likely than in other modes of transport, a great deal of anxiety has been generated among the public, health authorities, and airline companies, and consequently, the who has published guidelines with a protocol that ends with a series of recommendations for passengers, physicians, health authorities, and airlines (appendix ). severe acute respiratory syndrome. the epidemic outbreak of sars, for which the causative agent is a coronavirus, is the most recent and representative example of a disease transmitted by a very small number of travelers to other countries and continents within a few weeks. studies showed that in of the flights investigated for carrying patients infected with the sars virus transmission of the virus to other passengers was likely to have occurred. . - the majority of the patients who were infected had been seated in the rows closest to the index case, although at least in flight lasting hours (hong kong-beijing) an outbreak occurred that affected a high percentage of passengers seated up to rows from the index case and subsequently in more than secondary cases. possible explanations for that outbreak have been sought, and although no conclusive results have been obtained, it has been suggested to have occurred mainly through aerial transmission from a direct or indirect contact, that some of the passengers were infected prior to the flight, or that it occurred as a result of defective cabin ventilation. the cabin crew may have an increased risk of acquiring the disease due to their movement through the aircraft. the who developed a series of recommendations and guidelines, which included a series of measures that should be followed by all countries (appendix ) . , once those measures were put into practice, no new cases of long-distance propagation of the disease were identified. influenza. epidemic infection with the influenza a virus appears between the months of october and april in the northern hemisphere and between may and september in the southern hemisphere. in a recent study undertaken in switzerland, almost % of passengers who suffered fever during a journey to subtropical or tropical regions had a significant antibody titer against influenza viruses when they returned and in more than % it was possible to demonstrate a seroconversion of more than times the initial titer. the most common pathogens in fever episodes outside the periods of local epidemic were influenza viruses. that source may be the cause of some of the limited outbreaks that occur during the nonepidemic period. , other viruses such as influenza b and parainfluenza also have demonstrated pathogenic capacity. , as in conventional epidemic outbreaks, a series of risk factors affect acquisition of infection, such as age over years, presentation of comorbid conditions, and close contact with the index case, meaning that tourism in groups can facilitate infection. nevertheless, only studies have reported infection during air travel. , , the passengers seated in the rows closest to the index case were the most often affected, although given the high infectiousness of the virus, between % and % of the passengers was possible in flights lasting longer than hours and up to % of secondary familial contacts developed the disease. suspension or failure of the ventilation system favors disease transmission, as demonstrated in a flight in which an individual with flu infected % of the passengers. some countries recommend flu vaccination for those passengers undertaking journeys to the southern hemisphere during the summer and who were not vaccinated during the previous year. some microorganisms that do not produce respiratory symptoms, or at least are not associated with respiratory conditions as the principal symptoms, are nevertheless transmitted through the airways. among them, meningococcus and measles virus are the most noteworthy as a result of their infectiousness, morbidity and mortality. between and , cases were studied of patients with meningococcal disease who had traveled by plane during the infectious period without evidence of a single secondary case. nevertheless, given the severity of the disease, it is advised that individuals seated near the index case begin prophylactic treatment in the hours following the case being reported, so long as less than days have elapsed since the contact. , the measles virus is highly contagious, with up to % of exposed individuals developing the disease, and cases have been described of transmission during air travel. [ ] [ ] [ ] [ ] currently, the vaccination schedule in the different autonomous communities of spain includes vaccination against meningococcus from the age of years and measles from months, making the risk of transmission of those diseases presumably minimal, although individuals without antibodies or those from other countries who have not been vaccinated could be affected. no epidemic outbreaks have been reported for the virus that causes the common cold, but this absence is presumably due to the high frequency of the disease and the difficulties associated with investigating it. one study found no evidence that the air recirculation system in the cabin aided appearance of symptoms of infection in the upper airways. there is currently a great deal of concern regarding spread of the avian flu virus (h n ). this virus has a shorter incubation period and is more contagious than the sars virus. the usa has prepared a national plan to prevent the spread of outbreaks through the establishment of a series of specific health measures in airports. in addition to an increase in the number of health care workers, medical consulting rooms have been built that allow the health of passengers to be assessed and isolation rooms created to establish a quarantine area in international airports. those facilities are in permanent contact with the centers for disease control and prevention (cdc) and have access to passenger information for all flights in order to identify contacts of a possible index case. to date, the benefits of such a strategy have not been demonstrated and it is quite unlikely that it would prevent or slow an epidemic caused by introduction of the influenza or sars virus. detection of individuals with the disease exclusively in the destination airport would only have consequences for the detection of individuals who developed the clinical features during the flight and of contacts, thereby making the sensitivity low. most experts are in favor of strategies similar to those followed in the sars outbreak, including monitoring to detect individuals with symptoms in the departure airport, in an effort to prevent individuals with the disease from boarding the flight. [ ] [ ] [ ] [ ] if a case of infection with the avian influenza virus is confirmed, isolation measures similar to those followed for patients and contacts with sars must be established, treatment with neuraminidase inhibitors should be initiated immediately, and in contacts, prophylactic measures with those drugs should be started during the first hours. if a specific vaccine is available it should be immediately administered to contacts. the who has established a global plan in which these elements are considered. , recently, a series of recommendations and considerations were prepared on the management of exposure to an infectious disease during commercial air travel : -although passenger transport companies can refuse to transport individuals with a disease, they cannot undertake systematic examination in an effort to identify ill passengers. -early diagnosis is necessary to establish measures for the other passengers. -governments have the legal authority, in accordance with international law, to establish controls on passengers with transmissible diseases for which declaration is obligatory. -the authorities may establish measures to quarantine passengers who arrive at their airports. -physicians must identify those subjects who are not in a good enough state of health to travel by air and inform them of how a flight might affect their health. -prevention is the best course of action and postponement of the journey should be advised. -hand washing reduces the risk of transmission of contagious diseases and should be performed as a matter of course during travel and always prior to eating. -the mouth and nose should be covered in the event of sneezing or coughing and hands should be washed afterwards to protect others. -in the case of a passenger with suspected sars during the flight, a us national institute for occupational safety and health n mask should be provided and an isolation zone established in the aircraft. survival and quality of life have improved in patients with cystic fibrosis, making it not uncommon for them to want to go on holidays and even undertake work that may involve air travel. few studies have assessed the effects of commercial flights on patients with cystic fibrosis. there is some disagreement regarding estimation of the level of hypoxemia in those patients. although in a study performed in a small group of patients aged between and years, hypoxic challenge predicted with a high level of sensitivity and specificity the development of desaturation during the flight, later studies have not confirmed those findings. a study undertaken by the same group that contained a larger number of subjects and involved longer flights ( - hours) contradicted the earlier findings and showed that an fev less than % of reference better identified patients who desaturated than did the results of hypoxic challenge. only a small percentage of the patients who displayed reductions in spo to below % presented symptoms and required oxygen supplementation. however, it should be noted that the patients included in those studies were stable, had disease that was not very advanced, and were younger than other groups of patients with cardiac or respiratory diseases for whom reduction of pao to below mm hg necessitates the implementation of oxygen therapy during the flight. this would explain the greater tolerance of hypoxia seen in patients with cystic fibrosis, confirmed both in acute exposure in hypobaric chambers and during time at altitude. in addition, in patients with cystic fibrosis, the results of hypoxic challenge are particularly variable over time and can change within a few weeks. , consequently, the decision to have a cystic fibrosis patient use oxygen therapy during a flight should not be based exclusively on hypoxic challenge tests but also on clinical parameters and the degree of bronchial obstruction. other recommendations to consider in patients with cystic fibrosis who intend to travel by air are summarized in table . some authors have described an increase in exacerbations following a holiday, , related to poorer management of the disease. correct compliance with treatment and, in particular, physiotherapy improves the conditions in which the return flight is undertaken and reduces the likelihood of complications. the estimated incidence of venous thromboembolic disease (vtd) in the general population is per person-years. the pathogenesis of dvt was first described by virchow in , and the description remains valid today. it is based on a triad formed by stasis of venous blood flow, damage to the vascular endothelium, and hypercoagulability. these circumstances coincide in acquired-transient or persistent-or congenital conditions defined as risk factors, present in approximately % of patients with vtd. extended journeys have been associated with an increased incidence of vtd and have been included in the list of risk factors. , in , the term "economy class syndrome" was coined following the description of cases of vtd after flights in economy class. the aim was to highlight that the limited space within which to stretch the legs during an extended period of time reduces venous return and favors stasis of venous blood flow. this situation is not exclusive to air travel in economy class. it has also been described in business class and in other forms of travel, such as cars and buses, involving long periods of time with the lower limbs flexed and at rest. apart from venous stasis, there is a lack of agreement regarding other factors associated with air travel that could contribute to dvt such as dehydration, favored by the low humidity of the cabin and in some cases increased by the diuretic effect of coffee or alcoholic drinks, and the hypobaric hypoxia associated with pressurized cabins. dehydration could predispose to dvt as a result of hemoconcentration and blood hyperviscosity, although this hypothesis has not been confirmed. it has been observed in experimental studies that hypobaric hypoxia favors activation of clotting , and reduces physiologic fibrinolytic activity of endothelial cells ; however, those results have not been reproduced in subsequent studies. incidence and risk of vtd. studies addressing the incidence and risk of thrombosis associated with long-distance flights have employed a variety of different methods and yielded disparate results. for passengers with a high risk of thrombosis due to the presence of additional risk factors the incidence of vtd appears to be high, from % to %. , in patients at low or moderate risk the incidence drops to between % and %. , most of the vtd events that were identified were asymptomatic dvt that exclusively affected the venous territory of the calf, although the screening method used in almost all of the studies involved venous compression ultrasound with or without doppler, raising questions over the results due to the limited sensitivity of the technique for distal clots. the influence of other individual risk factors appears to be decisive in generating dvt. the incidence of pulmonary embolism has been assessed in cohort studies. [ ] [ ] [ ] according to data collected in paris airports between and , the incidence of this entity has increased. significant differences have been described in incidence rates according to distance traveled, ranging from . per passengers for distances of less than km to . cases per passengers in flights of more than km. differences were also seen according to distance traveled in a study performed at madrid barajas airport. in flights lasting more than hours the incidence of pulmonary embolism was . per passengers and in flights lasting to hours it was . per passengers, while no cases were observed in flights lasting less than hours. consequently, hours has been considered the cutoff for recommending general measures for the periodic movement of the limbs. the relative risk of vtd is difficult to establish due to the heterogeneity of the studies. , , considering only air travel, the risk is not clear (odds ratio, . ), and consequently, it could not be considered as an independent risk factor. however, in passengers with additional risk factors for thrombosis, the odds ratio increased in all studies to represent a -fold to -fold higher risk of vtd. recently, it has been demonstrated that the immobility during a flight lasting more than hours increases the levels of certain markers of clotting in subjects without risk factors for thrombosis, but it remains to be established whether this represents an increased risk of vtd. prophylactic measures. patients must be assessed individually and the presence of other risk factors for venous thrombosis identified (table ) in order to adopt prophylactic interventions. classification of the risk as moderate or high in these circumstances is not well established. it seems reasonable to extrapolate the impact of each of these factors on vtd. general measures. adequate hydration, regular movement of the lower limbs, and avoiding keeping the legs bent for long periods of time are the measures recommended by most experts. these measure are recommended for general application in flights lasting more than hours. drink lots of liquids to avoid noxious effects of the dry cabin air on the secretions and mucosa of the airway if the patient uses a nebulizer, some airlines allow the patient's own nebulizer to be used or provide one for long-haul journeys if possible, physiotherapy exercises should be performed during stopovers on long journeys compression stockings. in passengers at high risk of thrombosis, compression stockings, generally knee length and with a pressure of to mm hg have proven to be effective in reducing the incidence of vtd; [ ] [ ] [ ] ; no adverse effects are associated with their use and they are well tolerated. prophylactic drug treatment. the use of acetylsalicylic acid and low molecular weight heparins has been tested in passengers at high risk of thrombosis. a dose of mg acetylsalicylic acid for days proved to be ineffective and caused gastrointestinal discomfort in % of subjects. in contrast, a single dose of enoxaparin, both at a therapeutic weight-adjusted dose and as a high-risk prophylactic dose, administered to hours prior to the flight reduced the incidence of dvt without side effects. the general conclusions on vtd and air travel are summarized in table . few studies have addressed the effects of air travel on patients with respiratory diseases who present respiratory failure or severe abnormalities in control of ventilation. issues that must be taken into account in relation to air travel in such patients, in addition to the characteristics and length of the flight, are the following: ) the total length of the journey (flight time plus predicted waiting time and risk of unexpected delays), ) travel from the airport to the final destination, ) logistic aspects such as provision of oxygen or the feasibility of charging the batteries of the apparatus or a wheelchair during the flight and at the destination, and ) the altitude of the destination point and the length of time the individual will remain there. most patients can travel despite limitations, so long as the journey is sufficiently prepared and no elements are left to chance. in general, an increase in oxygen flow of to l is recommended in patients who receive home oxygen therapy. it is also essential to know the conditions of each airline company prior to embarking upon a journey, both in terms of the transport and provision of oxygen and in relation to the accessories required by the patient (wheelchair, ventilator) and the requirement to travel with an escort. some companies allow the passenger to carry small oxygen bottles (a maximum of bottles less than . m long and mm in diameter), but other companies do not accept transport of oxygen, although they allow the use of some oxygen concentrators, according to very strict regulations, so long as the user has sufficient batteries available to last the entire duration of the flight. cases have been described of patients with kyphoscoliosis or neuromuscular diseases in whom long air journeys generated right heart failure, presumably linked to the hypoxia maintained during the flight. from a theoretical point of view, in patients with nonhypercapnic restrictive disease (caused by involvement of the parenchyma), who present a risk of hypoxia during the flight, oxygen would be indicated to reduce the impact of hypoxemia on pulmonary hypertension. in patients with restrictive diseases who use mechanical ventilation (for extrapulmonary involvement), it is recommendable that they carry the apparatus with them during the flight, even if they only use it at night. clearly, patients with continuous ventilation should carefully assess the journey since they will need to use the ventilator throughout the travel period, including during airport transfers. from a logistic perspective, it is very important to confirm the hand luggage that the patient can carry, especially in relation to wheelchairs, the ventilator, and the spare battery. in the case of patients with severe disability, most airlines require the presence of an escort and consider that person can take responsibility for there are few reports in the literature on the impact of air travel in patients with sleep apnea-hypopnea syndrome (sahs). some complications have been associated with long journeys followed by a period at altitude. all patients with sahs should avoid consumption of alcohol immediately before and during the flight. patients in a severe condition should employ continuous positive airway pressure (cpap) during long flights. to this end, they should have a dry cell battery available for use as an energy source for the equipment. although the low humidity of the air in aircraft cabins may favor the development of bronchospasm due to loss of water from the bronchial mucosa, asthma attacks during air travel are thought to be rare. in addition, it is sometimes difficult to differentiate them from dyspnea due to hyperventilation or panic. more recently, a higher incidence of episodes of bronchospasm requiring treatment during flight has been described. patients with controlled asthma and no respiratory failure do not present problems for air travel, although they should ensure that they have their medication to hand. patients with severe asthma with frequent exacerbations and serious attacks should ensure that the disease is well controlled prior to the day of the flight. since , the emergency medication in most aircraft includes bronchodilators, both in pressurized cartridges and for injection. however, in case of an attack, patients are recommended to take their normal rescue medication. patients with primary tumors or metastases can generally fly safely. nevertheless, it may be necessary to consider measures to alleviate hypoxemia or pain. pneumothorax is a contraindication for air travel. a patient will only be allowed to fly when the lung has been completely reinflated. the patient should not be allowed to fly until hours after pleural drainage has been withdrawn and with a radiograph performed hours after completion of drainage to confirm resolution of the pneumothorax. optionally, some airline companies may accept transport of a passenger with a pleural drain. in that case, since it is difficult to guarantee continuous aspiration during the flight, it is recommended that a heimlich valve be used. in exceptional cases it may be necessary to evacuate a pneumothorax during the flight. this should only be done by trained staff and when the cabin pressure corresponds to sea level. simple rib fractures do not usually present problems during the flight, particularly when there is no lung damage or prior pulmonary disease. the main problem associated with such fractures is pain, which can reduce ventilation. therefore, it is important that adequate analgesia is guaranteed during the flight. multiple fractures may cause thoracic instability and, in that case, the requirement for specialized transport should be considered. flights should be postponed in all patients with acute respiratory failure due to lung contusion until lung function returns to normal. , likewise, mediastinal or subcutaneous emphysema constitutes a contraindication for travel on commercial flights. in any of those situations, if air travel is essential an air ambulance is required. although individual assessment is necessary, as a general rule patients are advised not to fly until at least weeks after the operation. patients with respiratory diseases who require oxygen on board or some form of health care during the flight are the association between venous thromboembolic disease (vtd) and air travel is weak. the clearest risk is for presentation of asymptomatic deep vein thrombosis (dvt) restricted to the calf area. symptomatic episodes of vtd, including fatal pulmonary thromboembolism, are rare. the risk is increased in journeys lasting more than hours in patients with additional risk factors. regular movement of the legs and hydration should be a general recommendation. in passengers with other risk factors for venous thromboembolism, the decision to implement other prophylactic measures should be made on an individual basis. knee-length compression stockings are effective and reduce the incidence of dvt. low molecular weight heparins are effective in patients at high risk of thrombosis. in general, a single high-risk prophylactic dose of low molecular weight heparin appears to be sufficient but should be assessed on an individual basis. aspirin is ineffective and should not be recommended. considered as ill patients who require medical authorization (medical fitness for air travel [meda] case). all patients who report such a condition must be informed when making the reservation of the process that needs to be followed in order to obtain medical authorization, of the limitation and requirements that exist, of the number of escorts required, and of the cost of the service requested. in turn, they must complete the incad/medif form provided by the company (appendix ), based on iata recommendations, and send it by fax to the medical department of the airline company to receive authorization and initiate the corresponding procedures. oxygen is normally supplied through a mask, although patients may use their own nasal prongs. three sources of oxygen can be used in aircraft. if cabin pressure is lost, passengers may receive oxygen through masks located above their seats. however, this oxygen source, which has a limited duration, cannot be used for provision of supplementary oxygen to sick patients during the flight. the most common practice is to use cylinders with a capacity of cubic feet. at a flow rate of l/min, those cylinders can provide oxygen for hours, , making it important to estimate the number of cylinders that the patient will need based on the flow prescribed and the length of the journey. recently, the american department of transportation approved the use of portable oxygen concentrators, which can be used during takeoff and landing and while moving inside the cabin. this equipment can also help the patient while moving inside the plane and in the terminal. to date, the only approved models are manufactured by inogen (www.inogen.net) and airsep (www.airsep.com). it should be noted that most companies do not allow the use of liquid oxygen on board. if the patient wishes to transport a portable liquid oxygen system it must be checked in empty and filled on arrival at the destination. in general, in-flight oxygen is administered at flow rates of or l/min, and exceptionally, at l/min. the medical department of the airline company may require that the patient be accompanied by an escort trained in the used of the oxygen therapy system. in most cases, provision of oxygen during the flight is a service paid for by the passenger. as a guide, from january the spanish airline iberia charges € per flight and requires at least hours notice prior to departure of the flight or hours in the case of emergencies. in more exceptional cases, some companies may insist that a second seat is purchased for the oxygen source. previous experiences of travel with patients requiring oxygen therapy or mechanical ventilation show that the main problems arise during transfer of the patients. in general, most companies only provide oxygen during the period of time inside the plane or during transfer between planes of the same company. if oxygen is required during boarding or while waiting in the airport, the passenger should inform the medical services of the company to organize specialized transport, such as ambulance transfer to the plane. transport with oxygen during the flight does not represent an exceptional situation. data from the airline iberia indicate that persons require supplementary oxygen in flight each year. it is also possible to use cpap equipment or ventilators during flights. in that case, patients should carry their own equipment, since it is not provided by airlines. it is important to mention that, since the great majority of commercial aircraft do not have plug sockets in the cabin, the patient should carry a dry cell battery to independently power the equipment. permission to use cpap or a ventilator on board must also be requested when making the reservation and requires authorization by the medical department of the company. in general, an escort is not required for the use of cpap, obtain a report of the clinical condition of the patient that includes the most recent functional assessment and treatment. this is essential if the stay is for a number of weeks and the destination does not have the usual health care resources. in countries in which smoking is still allowed inside the aircraft, the patient must be seated in a nonsmoking area. avoid excessive alcohol consumption prior to and during the flight, especially in cases of apnea-hypopnea syndrome and risk of venous thromboembolic disease. move around during long flights, unless oxygen is required. if oxygen is required, it should be used if possible while moving inside the plane (with an extension to allow movement). prophylactic measures should be taken to reduce the risk of thromboembolism. carry required medication, especially rescue inhalers, in hand luggage. if medication is checked with baggage, ensure that it is not affected by the extreme conditions in the hold. use spacer chambers rather than nebulizers. if continuous positive airway pressure is required on a long-haul flight, carry a dry cell battery, which must be switched off prior to landing. patients who require a ventilator must be able to tolerate temporary disconnection of the apparatus during takeoff and landing. the requirement for oxygen or any other form of medical assistance must be indicated when the reservation is made, at least hours. prior to departure. if necessary, assistance must be organized with the medical department of the company to transfer the patient within the airport. whereas mechanical ventilation usually demands the presence of an assistant trained in its use. patients who are completely dependent on a ventilator and cannot tolerate temporary disconnection of the equipment during takeoff and landing, or in the event of other occurrences, cannot fly in commercial aircraft. in such cases, the use of air ambulances is necessary. nevertheless, there is a marked diversity in the regulations, availability, cost, and ease of oxygen provision during air travel, making it advisable for patients or their representatives to determine the criteria established by the company with which they intend to fly. this information can be obtained directly from travel agencies, when making a reservation, or via the webpage of the british lung foundation. finally, all patients with respiratory diseases who intend to fly are advised to consider certain general recommendations ( table ) and even to access specific information sources for patients. [ ] [ ] [ ] . individuals with tuberculosis (tb) with the possibility of between-individual transfer, such as sputum-positive patients, must postpone their journey until they are no longer a potential source of transmission. . if the history of a patient with tb who could transmit the disease shows that he or she has recently undertaken a journey by air (eg, within the last months), the physician should immediately inform the health authorities in the declaration of the tb case. . the health authorities should immediately contact the airline company if the person has undertaken a journey lasting at least hours in a commercial aircraft during the last months. for the airline companies . airline companies should work closely with health authorities in the provision of information to passengers and flight crew who may have been exposed to mycobacterium tuberculosis as well as in the identification of those passengers who should be informed. airline companies should cooperate closely with health authorities in the provision of information to passengers and flight crew who may have been exposed to m tuberculosis as well as in the identification of those passengers who should be informed. airline companies should require the home and work addresses and telephone numbers of passengers so that they can be informed in the event of potential health risks (exposure to m tuberculosis or other infectious diseases, exposure to toxins, etc). airline companies should ensure that all crew receive appropriate training in first aid and the use of universal precautions regarding exposure to biologic fluids. all aircraft must be equipped with emergency medical supplies (including gloves, masks containing high efficiency particulate air [hepa] filters, and biohazard bags). . airline companies must have prearranged access to physicians with experience in transmissible disease who are available for subsequent consultation by health authorities. records of all diseases and medical emergencies must be kept for at least years. . long delays should be reduced to a minimum and hepa filters should be installed and maintained at maximum efficiency ( . % at . µm). centro travel by air: health considerations flying with respiratory disease inflight deaths during commercial air travel. how big a problem? utilization of emergency kits by air carriers. oklahoma city: faa civil aeromedical institute response capability during civil air carrier inflight medical emergencies. oklahoma city: faa civil aeromedical institute british thoracic society standards for care committee. managing passengers with respiratory disease planning air travel: british thoracic society recommendations expert care, everywhere managing passengers with respiratory disease planning air travel: british thoracic society recommendations standards for the diagnosis and care of patients with chronic obstructive pulmonary disease the canadian thoracic society standards committee. recommendations for 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flight: the need for more rational guidelines recomendación separ sobre gasometría arterial recomendaciones separ ats/ers task force: standardisation of lung function testing. standardization of spirometry ats/ers task force: standardisation of lung function testing. standardisation of the single-breath determination of carbon monoxide uptake in the lung ats statement: guidelines for the sixminute walk test development of severe hypoxaemia in copd patients at m ( ft) altitude reevaluation of birth weights at high altitude hypoxia-altitude simulation test. evaluation of patients with chronic airway obstruction hypoxaemia during altitude exposure. a meta-analysis of chronic obstructive pulmonary disease hypoxia-altitude simulation test hypoxaemia during aeromedical evacuation the preflight evaluation. a comparison of the hypoxia inhalation test with hypobaric exposure predicted arterial oxygenation at commercial aircraft cabin altitudes effect of hypobaric hypoxia on blood gases in patients with restrictive lung disease effect of simulated commercial flight on oxygenation in patients with interstitial lung disease and chronic obstructive pulmonary disease detection and correction of hypoxemia associated with air travel air transportation of patients with acute respiratory failure: theory ventilationperfusion inequality in chronic obstructive pulmonary disease assessment of oxygen supplementation during air travel an air-entrainment device for preparing precision gas mixtures the effect of carbon monoxide inhalation on pulse oximetry and transcutaneous po accuracy of oxyhemoglobin saturation monitors during simulated altitude exposure of men with chronic obstructive pulmonary disease is normobaric simulation of hypobaric hypoxia accurate in chronic airflow limitation? pulmonary mechanics at altitude in normal and obstructive lung disease patients changes in lung volume, lung density, and distribution of ventilation during hypobaric decompression predicting hypoxaemia during flights in children with cystic fibrosis oxygen supplementation during air travel in patients with chronic obstructive pulmonary disease the accuracy of venturi masks at altitude the safety of air transportation of patients with advanced lung disease. experience with patients requiring lung transplantation or pulmonary tromboendarterectomy preflight medical screenings of patients. analysis of health and flight characteristics air travel in patients with chronic obstructive pulmonary disease altituderelated hypoxia: risk assessment and management for passengers on commercial aircraft short-term adaptation to moderate altitude kardiopulmonale belastung von flagpassagierien mit obstruktiven ventilationsstorungen prevalence of in-flight medical emergencies on commercial airlines hemodynamic effects of altitude exposure and oxygen administration in chronic obstructive pulmonary disease transmission of multidrug resistant mycobacterium tuberculosis during a long airplane flight revision of the international health regulations international infectious disease law. revision of the world health organization's international health regulations geneve: who using a mathematical model to evaluate the efficacy of tb control measures aviation safety: more research needed on the effects of air quality on airliner cabin occupants estimation of tuberculosis risk on a commercial airliner transmission of infectious diseases during commercial air travel transmission of severe acute respiratory syndrome on aircraft an outbreak of influenza aboard a commercial airline ticket to ride: spreading germs a mile high transmission of mycobacterium tuberculosis associated with air travel exposure to mycobacterium tuberculosis during air travel exposure of passengers and flight crew to mycobacterium tuberculosis on commercial aircraft, - tuberculosis risk after exposure on airplanes a passenger with pulmonary/laryngeal tuberculosis: no evidence of transmission on two short flight tuberculosis and air travel. guidelines for prevention and control. who/tb . . geneve: world health organization update . -more than cases reported globally, situation in taiwan, date on in-flight transmission, report on henan province, china consensus document on the epidemiology of severe acute respiratory syndrome (sars). who/cds/csr/gar/ who recommended measures for persons undertaking international travel from areas affected by severe acute respiratory syndrome (sars) world health organization. summary of sars and air travel in flight transmission of severe acute respiratory syndrome virus (sars): a case report influenza virus infection in travelers to tropical and subtropical countries an outbreak of influenza a/taiwan / (h n ) infections at a naval base and its association with airplane travel an outbreak of influenza a caused by imported virus en united states mixed outbreak of parainfluenza type and influenza b associated with tourism and air travel influenza outbreak related to air travel specific recommendations for vaccination and disease prevention: influenza exposure to patients with meningococcal disease on aircraft -united states imported measles in the united states low risk of measles transmission after exposure on an international airline light epidemiological notes and reports. interstate importation of measles following transmission in an airport-california multistate investigation of measles among adoptees from china aircraft cabin air recirculation and symptoms of the common cold triple airport quarantine stations. health program aims to prevent infectious diseases from entering country.washington post staff writer entry screening for severe acute respiratory syndrome (sars) or influenza: policy evaluation are we ready for pandemic influenza? h n influenza pandemic: contingency plans global task force for influenza will it be the next pandemic influenza. are we really? aviar influenza. a new pandemic threat? who global influenza preparedness plan. the role of who and recommendations for national measures before and during pandemics prediction of hipoxaemia at high altitude in children with cystic fibrosis respiratory function and blood gas variables in cystic fibrosis patients during reduced environmental pressure lung function in adults with cystic fibrosis at altitude: impact on air travel flying cystic fibrosis: getting there and back safely exacerbations of cystic fibrosis after holidays at high altitude-a cautionary tale intensified physiotherapy improves fitness to fly in cystic fibrosis patients the epidemiology of venous thromboembolism relative impact of risk factors for deep vein thrombosis and pulmonary embolism: a population-based study an epidemiologic study of risk factors for deep vein thrombosis in medical outpatients: the sirius study guía para el diagnóstico, tratamiento y seguimiento de la tromboembolia pulmonar thrombosis of the deep leg veins due to prolonged sitting pulmonary thromboembolism after travel síndrome del pasajero de clase económica the best study -a prospective study to compare business class versus economy class air travel as a cause of thrombosis travel as a risk factor for venous thromboembolic disease: a case-control study association between acute hypobaric hypoxia and activation of coagulation in human beings changes of biochemical markers and functional tests for clot formation during long-haul flights is mild normobaric hypoxia a risk factor for venous thromboembolism? venous thromboembolism from air travel: the lonflit study venous thrombosis after long-haul flights frequency of venous thromboembolism in low to moderate risk long distance air travellers: the new zealand air traveller's thrombosis (nzatt) study venous thromboembolism in passengers following a -h flight: a case-control study thromboembolic syndrome from prolonged sitting and flights of long duration experience of the emergency medical service of the paris airports severe pulmonary embolism associated with air travel incidence of air travel-related pulmonary embolism at the madrid-barajas airport prevention of venous thromboembolism long-haul flights and deep vein thrombosis: a significant risk only when additional factors are also present activation of coagulation system during air travel: a crossover study prevention of edema, flight microangiopathy and venous thrombosis in long flights with elastic stockings. a randomised trial: the lonflit concorde edema-ssl study prevention of venous thrombosis with elastic stockings during long-haul flights: the lonflit jap study venous thrombosis from air travel: the lonflit study -prevention with aspirin vs low-molecularweight heparin (lmwh) in high-risk subjects: a randomised trial prevention of flight venous trombosis in high risk subjects with stockings or one-dose enoxaparin travel techonology-dependent patients with respiratory disease oxygen and air travel cor pulmonale presenting in a patient with congenital kyphoscoliosis following intercontinental air travel assisted ventilation at home. . oxford: medical publications emergencies in the air responding to medical events during commercial airline flights viajar con oxígeno. reflexiones a propósito de la primera reunión internacional de pacientes con déficit de alfa- antitripsina a comparative analysis of arranging in-flight oxygen aboard commercial air carriers air travel with a lung condition safe flying for people with lung disease medical guidelines for airline passengers the authors would like to thank dr fernando merelo de barberá, head of aerospace medicine at iberia, and dr francisco ríos tejada, head of the department of aerospace medicine at the aerospace medicine training center, for advice on preparation of the manuscript. . establish a screening system organized by the authorities in the affected regions in which all passengers are assessed by health workers at the point of departure. in case of suspicion during the flight, isolation measures should be taken for subjects who are suspected to carry the disease (provision of an exclusive bathroom, covering the mouth and nostrils of the patient with an appropriately protective mask) and the health authorities at the destination point should be informed about the suspicion. . management of contacts. contacts are considered as all individuals seated in the rows closest to the index case and all those who have had close contact with the index case prior to or during the journey. if the affected individual is a member of the cabin crew, all passengers are considered contacts. it is obligatory for the health authorities to identify and locate the whereabouts of those individuals for the following days and to contact the health authorities immediately if they develop any symptoms. . the aircraft should be disinfected according to world health organization guidelines. key: cord- -e lf ddk authors: arafat, s. m. yasir; tripathy, sarvodaya; kar, sujita kumar; kabir, russell title: climate and clean air responses to covid- : a comment date: - - journal: int j public health doi: . /s - - - sha: doc_id: cord_uid: e lf ddk nan administration (nasa) and the european space agency (esa) had released images suggesting an improvement of the environmental quality and reduction of the emission of no up to % post-lockdown in china (muhammad et al. ) . similar changes were also observed in other countries like france, italy, spain, and the usa. it was claimed on the basis of the satellite images of the countries before and after lockdown. fresh images from nasa showed a rebound of no level in china with the ending of lockdowns and resuming of the economic activities (nasa earth observatory ). another study conducted in são paulo, brazil showed a drastic reduction in nitric oxide, no , and carbon monoxide concentrations during the lockdown phase. in the same study, they also found about a % increase in ozone concentrations in the urban areas that were attributable to a decrease in traffic (nakada and urban ). however, most of the studies used satellite images to measures the air pollution level in these countries, but no actual scale measurement of air pollution has been done so far globally, to check and compare the air pollution level during, before, and after the lockdown period. it is also imperative to find out how indoor air quality has changed during this lockdown as people are staying at home longer than usual. who states that the bad quality of the air is associated with the death of about million people which is more than road traffic accident-related deaths. nine out of individuals breathe air containing pollutants. most of the deaths related to air pollution are due to non-communicable diseases such as % of brain stroke-related deaths, % heart disease-related deaths, % of lung diseases and lung cancer-related deaths are attributed to air pollution (world health organization ). a call for comments has been made in regard to the climate and clean air responses to covid- so that the proper attention could be warranted to sustain the improved air quality during the busy days of life (agrawala et al. ) . as lockdown was found to be an effective strategy to control all forms of pollutions, including air pollution, there is a need to think about the periodic implementation of lockdown in an organized fashion to maintain the fresh air quality. now, this is the time to think about making the world more liveable by making it pollution-free. so far as the air pollution is concerned, the current covid- related lockdown has been proved to be a blessing in disguise. however, country-specific, as well as culturespecific, strategies should be considered as there are strong chances of failure of universal strategies without considering the local factors. for example, measures like alternative energy sources, policies to manage economic challenges, lifestyle modifications, utilizing the natural resources can be implemented, based on the needs. all the countries should develop the air pollution surveillance system to measure, monitor, and regulate the air quality level (kutlar joss et al. ) . also, there is a need to create international pressure to raise the political will in the low-and middle-income countries. more research and funds should make ready aiming at the reduction of environmental pollution. funding none. conflict of interest none. ethical approval not applicable. informed consent not applicable. call for comments: climate and clean air responses to covid- iqair (nd) world's most polluted cities in time to harmonize national ambient air quality standards covid- pandemic and environmental pollution: a blessing in disguise? covid- pandemic: impacts on the air quality during the partial lockdown in são paulo state gen-dioxide-levels-rebound-in-china?utm_source=card_ &utm_ campaign=home the new indian express ( ) air pollution levels in delhi drop by % post-lockdown air pollution. world health organization key: cord- - s npse authors: du, sean quan; yuan, weiming title: mathematical modeling of interaction between innate and adaptive immune responses in covid‐ and implications for viral pathogenesis date: - - journal: j med virol doi: . /jmv. sha: doc_id: cord_uid: s npse we have applied mathematical modeling to investigate the infections of the ongoing coronavirus disease‐ (covid‐ ) pandemic caused by sars‐cov‐ virus. we first validated our model using the well‐studied influenza viruses and then compared the pathogenesis processes between the two viruses. the interaction between host innate and adaptive immune responses was found to be a potential cause for the higher severity and mortality in covid‐ patients. specifically, the timing mismatch between the two immune responses has a major impact on disease progression. the adaptive immune response of the covid‐ patients is more likely to come before the peak of viral load, while the opposite is true for influenza patients. this difference in timing causes delayed depletion of vulnerable epithelial cells in the lungs in covid‐ patients while enhancing viral clearance in influenza patients. stronger adaptive immunity in covid‐ patients can potentially lead to longer recovery time and more severe secondary complications. based on our analysis, delaying the onset of adaptive immune responses during the early phase of infections may be a potential treatment option for high‐risk covid‐ patients. suppressing the adaptive immune response temporarily and avoiding its interference with the innate immune response may allow the innate immunity to more efficiently clear the virus. vere illness tend to have severe pneumonia, sometimes acute respiratory distress, which could lead to multiple organ failures and death. the hospital stay can be weeks for such patients. [ ] [ ] [ ] [ ] there is no proven cure or antiviral drugs available yet. the influenza virus typically binds to the sialic acid receptors on the surface of epithelial cells in the upper respiratory tracks and the upper divisions of bronchi. in very severe, and often fatal cases of influenza, the infection will spread to the lower lungs. , similarly, the sars-cov- virus binds to the angiotensin-converting enzyme (ace ) receptors on the surface epithelial cells. these cells with ace expression are hence vulnerable to virus attack and are called target cells in mathematical models. the density of the target cells has been found to vary significantly in different regions of the respiratory tracks, with the highest in the lungs, followed by the nose, and lastly, the trachea/bronchi tissues. [ ] [ ] [ ] as such pneumonia is relatively common among covid- patients. the incubation time for influenza is typically hours or less. the eclipse phase is reported to be around hours, with viral load peaks around to days postinfection (dpi). the infection typically resolves in to days. in typical influenza patients, the adaptive immune responses (airs) including pathogen-specific antibodies (abs) and cd + cytotoxic t lymphocytes (ctl) are first observed around dpi, peaking around dpi. the mean incubation period for covid- patients is estimated to be days, with a range distribution of days. , the median time from symptoms to discharge from the hospital was about days, whereas the median time to death was days. in this paper, we used mathematical modeling to investigate the dynamics of the viral infection/replication inside a human host, in particular, the influenza and the sars-cov- virus, as well as the interactions of target cells with the innate and airs. our model suggests that most of the differences between the two types of infections can potentially be attributed to the timing mismatch between the two immune responses. more specifically, influenza is a very acute infection; all vulnerable cells are completely depleted and viruses are more or less cleared by the innate immune response, before the adaptive immune response (air), which has a transient nature, reaches a significant level. the arrival of air may seem futile but it helps to completely clear the remaining viruses. on the other hand, the peak level of the air of the covid- patients is more likely to come before the number of infected cells reaches its peak, due to the slower disease progression outlined above. as such the air helps to eliminate more viruses in the rapid growth phase and slow down the infection and depletion of vulnerable epithelial cells in the lungs of covid- patients. a strong air, in this case, may be bad for the patients, as the disease progression is extended longer while a weaker air can be beneficial for the patients due to the rapid depletion of the target cells. one recent observation puzzling for many is the apparent resurgence of the disease for some "cured" patients. based on our theory and modeling, this phenomenon can be explained by that of a strong interaction of innate and airs in a host, which can sometimes create double peaks in viral load, separated by weeks. in the second part of our study, we applied our modeling to the current bedside treatment regimen. antiviral drugs and immunosuppressive drugs have been evaluated as potential treatments for high-risk patients. we proposed an immune-suppressing treatment based on the leanings of our modeling study, which is to apply immunosuppressive drugs during the early phase of infection to reduce the airs to a level low enough not to interfere with the innate immune response. once the vulnerable cells are depleted, the drug should be removed to let the air run its course to clear the remaining virus. this new approach can potentially lead to fast and complete recovery. this counter-intuitive approach aims to mimic the excellent job human immune systems have done with the influenza infection. further studies on immune responses of covid- patients and validation of our core assumptions and theory are needed before this can be applied in real patients' situations. mathematical models have been developed to understand the dynamics of viral infections. [ ] [ ] [ ] [ ] [ ] most of them fall into the category of the target cell-limited model with some variations. the simplest version includes three species: uninfected susceptible target cells (t), which in our case is the surface epithelial cells with ace receptors, located at the respiratory tracks including lungs, nasal and trachea/ bronchial tissues, infected virus-producing cells (i), and the virus particles (v). they can be described by the following set of differential equations: the ability of a virus to grow the infection or to be cleared is determined by the basic reproductive ratio r: where r represents the number of infected cells newly generated by one infected cell. with r> the infection grows, while with r< infected cells decrease and the virus is cleared out. here it is important to note that t is a variable. when the target cells are depleted, t goes down, and so does r. this is a very simple yet critically important concept for understanding the virus clearance. complete depletion of the target cells, namely = t , leads to = r , hence achieving the best virus clearing ability. r is the native ( ). in their experiment, the authors found that the viral load peaked at to dpi. the level of + cd cells and igm data shows a very narrow peak at about days dpi, while the level of igg antibody shows a relatively broad peak lasting well over days. we seek to mimic these temporal profiles, using Δ ( ′) t e as an example: , . with such a profile, we can choose the peak position ′ t c , and the rising and falling width w r and w f in our simulation to see the effects of these parameters on the viral infection dynamics. our main assumption is that the air is a short term effect, which assumes that the virus is successfully cleared timely and the patient survived. as such, it is not our goal to develop a detailed model for airs, but rather to understand the necessary conditions that are needed for a successful outcome for the patients. other components like iga, cd + t cells, and a number of other components of the air could also play important roles here. to analyze the effect of antiviral drugs that either block infection ϵ k and/or production of viral particles ϵ p , the target cell-limited model is modified as follows: refers to a drug that is % effective. with the action of the drug, the reproduction number r is revised as follows: finally, we want to add another component to describe the effect of a drug that suppresses the innate immune response, for reasons that will be discussed in the section of treatments by immunosuppressive drugs. equations ( ), ( ), and ( ) are changed to the following: c describes no effect of immunesuppressing drugs while δ ϵ = , c refers to complete suppression. mathematical models of influenza infections have been studied extensively, , - our interest is to use it as a starting point before we embark on more challenging work on sars-cov- infections. we have carefully evaluated the parameter values tabulated by beauchemin et al and decided to use the values shown in table . the choice of the parameters is based on cross-checking multiple sources, and testing many simulation runs with variations of parameters to ensure that the output agrees with what is known about influenza infections. it is not our intent to fit the model to any specific set of data, but rather to be able to reproduce the general features of the influenza infections. the result is shown at figure . with these parameters, the infected cell count peaks at . dpi; viral load peaks at . dpi, and and the r is about . γτ , which describes an exponential growth rate (shown in appendix) is . . as we should expect, the target cells are depleted shortly following the peak of the infected cells, after which the virus count decays exponentially. the situation with regard to the decay portion is more complicated, and the consideration of the air is warranted if one is to understand it beyond dpi. table shows the parameters for the three components we considered in equations ( ). these values are chosen so that the temporal profiles resemble what was presented by miao et al the choice of the peak time is based on beauchemin et al we should clarify that the temporal profiles are not completely the same as in reference, as some other literature has shown broader profiles. we have done sensitivity analysis by doing multiple simulations, and find that as long as the width is not too narrow, the results are not sensitive to the width or shape of the peak. on the other hand, the location of the peak time is very important for the complete clearing of the virus. the result is shown in figure . in figure , we included the same graph for virus count without the air, as shown in figure as long as the native r is greater than , this pattern is the universal behavior of the equations ( ), namely, a rapid exponential rise followed by an exponential decay, then eventually reaching an equilibrium at a low level of infection. changing parameters in table will change the time scale, the peak/trough levels and locations of virus count etc., but the general pattern is the same. when the air is included, the virus clears out much faster. by day , the virus is completely gone. mathematically virus and infected cells count never actually go to zero. however, we know that the infected cell count has to be an integer. therefore when this number is below , one can safely consider it game-over for the virus. in our modeling, we set this cutoff to be . infected cell to be conservative. the temporal profile of the three components of the air are also shown in figure so that the readers can see their peak positions as compared to the actual virus counts over time. after the air becomes active, the decay of virus count becomes much faster. we also tried to vary the parameters around what is listed in due to the lack of experimental data, the discussions below are based on our best assumptions and observations. when shifting gears from the influenza virus to the novel corona virus, the most important difference we noticed is the difference in the pace of infection progression. multiple reports suggested that the viral counts of sars-cov- do not reach a peak until to weeks postinoculation. [ ] [ ] [ ] here we will make a bold assumption that, if without the air, the peak time is around to days, if not more. as most of the severe cases result in pneumonia and the lungs are significantly larger than the nose, t is estimated to be higher by a factor of . table lists the only two parameters that are changed from tables and , together with the three dependent variables as outputs from the model. here we aimed to have a peak time for infected cells at around dpi if considering the effect of innate immune response only. together with a times increase of t , these constraints essentially limited our choice for the only other variable to a very narrow range. the result is shown in figure . as we can see in figure , the curve of virus count for an innate immune response only (no air) is similar to that of influenza infec- our initial choice of air activity of . is purely artificial at this point, so we want to explore the effect of different levels of air activity. the result is shown in figure . as we can see, with the air activity level of . - . , the virus count reaches a high level, and then the growth is slowed with the activation of the air at around dpi. after the effect of the air wanes, the virus count continues its ascent, reaching its peak at a later date. at a higher air activity level, we start to see an apparent drop in virus count after the onset of air, reaching a trough then rising to its peak at a much later day. overall, an increase in the air activity tends to increase the duration of viral activity extensively in this case. this is because early activation of the air helps to reduce infection and depletion of target cells before it reaches a peak level, which saves a large number of uninfected target cells for later infection. when the effect of the air wanes, the virus takes control again when the effective r rises above . whether the virus count grows or drops during the peak air activity is dependent on how strong the air effect is, and whether the effective reproductive ratio r at the time is greater or less in figure with the air activity level greater or equal to . offers a ready explanation for some perplexing clinical observations that some patients can appear to be recovered, but have the virus level resurges at a later time. what's even more interesting is when we shift the day that the air activity peaks, as shown in figure . to show the air effect on viral replication in a more pronounced fashion, we fix the air activity level at . , and vary the day of its peak with additional simulations, we have found that if the air peak is after the viral peak, a higher level of air activity always helps to clear the virus faster. contrarily, if the air peaks before the viral peak, higher air activity can increase the duration of viral activity. we also found that if the air level is low enough, for example below . , its effect becomes negligible and the virus replication and clearing process is in essence, our modeling aims to explore potential means to manage the covid- infections so that it can be similar to influenza infections. when the virus can be quickly and completely cleared, the air should be transient, similar to the influenza infections. our modeling then establishes that one of the requirements is that the peak of air needs to come after the peak of infected cells, or equivalently, the peak of viral load. this can be viewed as a necessary condition for fast and complete clearing of virus. to achieve rapid clearing of the virus, it is also desirable to have the target cells more or less completely depleted. in reality, when the virus cannot be cleared timely, it is likely that the air will also be extended longer, so the conclusions from our modeling related to the later stage development may need to be modified. when searching for a cure for covid- patients, an effective antiviral drug is highly anticipated, so we decided to model the effect of the antiviral drug on the corona virus infection. we started our base case with a peak of the air at dpi, and air activity level of . , as shown before. from equations ( ), the expression for r is revised as follows: here r is the native reproductive ratio; t t is the percentage of the target cells that are not depleted. the first two brackets show the effect of the antiviral drugs on the reproductive ratio r, which shows that the drug has an equivalent effect regardless of whether it is acting on k or p. next, we tried to simulate the effect of an antiviral f i g u r e effect of adaptive immuneresponse (air) peak day on viral dynamics: data shows the viral load over time when the day of air peak is changed from to days drug with % efficacy on k, namely, ϵ = . k , taken for days consecutively. taking this drug for a longer time does not necessarily make it more beneficial in this particular scenario. as a comparison, the base scenario is also included with a native r of . , and air activity of . peaking at dpi. the base scenario is shown as a blue line in figure . when the drug is applied, the effective r is reduced to . , according to the formula above, not considering the effect of target cell depletion. similar to the air effects shown in figure , figure shows that additional drug-induced antiviral activity has a pronounced effect on the duration of viral activity within the host for the three scenarios when the antiviral drug is started on dpi, dpi, or dpi. during the days when the antiviral drug is effective, the virus growth rate is reduced. after the drug is removed, the virus either resumes its growth or remains at a plateau. in all three scenarios, the duration of virus activity is extended substantially, which can lead to detrimental consequences for the patients. on the other hand, if the drug is started or dpi, after the peak of infected cells, the effect of the antiviral drug is to speed up the virus clearing, which is beneficial for the patient. in figure , the depletion of target cells is also shown for the scenario of the drug started at dpi. as we can see, the depletion is not complete ( % target cells remain), which explains why the decay is slow even with the additional drug activity. the situation is very different if the antiviral drug efficacy is raised to %, namely, ϵ = . k . when the drug is applied, the effective r becomes . , which leads to virus clearance. we ran the same set of scenarios as above and the results are shown in figure . the blue line again shows the base scenario with no drug applied. if the drug is applied early, as shown for the scenario with a start date of dpi, the infection can be stopped completely before it makes any real progress. when the drug is started at or dpi, double peaks of viral count are observed. the reason is that when the drug is stopped, r jumps back to , so that virus resumes its rapid growth until the target cells are depleted, causing a second peak in virus count. therefore if the drug is stopped before the virus is cleared out completely, the infection will resurge. this is similar to what we have seen in figure with the transient antiviral activity of strong air, except the peaktrough-peak curve is smoother there. when the drug is applied after the viral peak is reached, it has a small but positive effect of faster recovery, similar to the scenario shown in figure . the level of target cell depletion is also shown for the scenario of the drug started at dpi. at the first peak of viral load, less than % of the target cells are depleted by the infection. this is why a second exponential growth starts after the drug is removed. to avoid this kind of unwanted effect, the antiviral drug needs to be maintained until the virus is completely cleared. in the appendix, we showed the relationship between the duration the drug needs to be administered, and the time the drug is started. the simple rule of thumb is that the later the drug is started, the longer it is required to be applied to ensure complete clearing of the virus. it is interesting to note that γ-immunoglobulin has been widely used to treat covid- patients in china. in a way, injection of γ-immunoglobulin can be modeled similarly as antiviral drugs f i g u r e effect of antiviral drug on viral dynamics: the drug is assumed to be % effective on k, and applied to a host with r of . for days consecutively with various starting dates; viral counts to the left with exponential scale; target cell ∕ t t is shown for the scenario of the drug applied at dpi, to the right with linear scale du and yuan | (assuming that it is able to deliver some antiviral function). it will be interesting to know if some researchers have compiled data to correlate the efficacy of this treatment with the timing of the injections. our theory predicts that if the γ-immunoglobulin is used early on, it will most likely delay the depletion of target cells so the duration of the disease will be extended for the patients, hence with poor prognosis. on the other hand, if it is applied after the peak of infected cells, it should be helpful to some extent. in summary, for an antiviral drug to be useful, the drug needs to be effective enough so that the effective reproductive ratio r falls below (see equation ( ) for the factors affecting r). under such a condition, it is desirable to apply it early on and must be maintained until the viral load is completely cleared (in the appendix we provide an estimate for the duration of the regimen). when a drug cannot meet this criterion, applying it before the target cells are fully depleted is typically not beneficial to the patient, and likely will make things worse for the patients. this should have some significant implications for drug companies when they design the clinical trials. at this point, as we do not know much about the potential level of the air, r , and the efficacy of the antiviral drug, it is difficult to identify a risk-free way of applying the antiviral drug. a prudent approach is to measure the viral loads frequently post-drug administration. if the viral load does not drop rapidly shortly after, it may indicate that the effective r is not below , and the drug should be stopped. if the drug is known to be effective but not effective enough to cause r to go below , it might still be useful to apply it after a large percentage of the target cells have been depleted. as a safety measure, it may be desirable to continue the regimen for a few more days after the viral load drops below the detection limit to ensure complete clearance. currently, there is already a class of drugs called immunosuppressive drugs (drugs to suppress airs). a large body of research has been done on the effects of the drugs on different parts of immune response. , the goal of investigating immunosuppressive drugs is to explore their possible applications in covid- disease management. immunosuppressants such as corticosteroids have been applied to sars and covid- patients, with positive results. , from the previous discussions, we propose a potential treatment plan by applying immunosuppressive drugs as soon as an infection is detected in the lungs, and remove the drug as soon as the target cells are fully depleted. this approach is simple and only requires the immunosuppressive drugs to be able to reduce the air activity to a level low enough not to interfere with the innate immunity. from the discussions around figure , this approach should clear out the virus quickly if the air activity level is below . . if the drug effect is not removed quickly, and the air does not rise after the drug is removed, the patients may not be able to completely clear the residue level of the virus. we projected that a short regimen of antiviral drugs to days after the peak of virus counts may help to completely clear the remaining low level of virus load. the purpose of the antiviral drug f i g u r e effect of antiviral drug on viral dynamics: the drug is assumed to be % effective on k, and is applied for days consecutively with various starting dates; viral counts to the left with exponential scale; target cell ∕ t t is for drug started on dpi only, shown with linear scale to the right regimen is to mimic the effect of the air in patients with influenza infections. if the drug effect can be removed immediately after the peak infection, so that the air level increases after the drug is removed, we then have a situation that the air peaks after the target cells are depleted. the discussions around figure established that with this scenario, the virus can always be cleared completely, regardless of the level of the air. with this approach, the novel coronavirus infections are essentially reduced to influenza-like infections in adults, except with slower disease progression. one possible concern with our proposed approach is that the immunosuppressive drugs may inevitably have some limited side effects on the innate immune response, in addition to the intended effect on the air. this is considered by equations ( ), which gives us the following (see appendix): to address this possible concern, we did some simulations with the following: the immunosuppressive drug is assumed to have either a % or % effect on ϵ δ , the drug with % effect on ϵ δ is applied from dpi up to dpi, while the second drug is applied from dpi up to dpi. the choice to apply the drug from dpi is merely to simplify our simulation, and may not be necessary, as our main goal is to suppress the air. the air peak day is assumed to be the same as the base scenario at dpi, and the air activity level is reduced to . . the same base scenario without drug is also shown as the blue line in figure . with both scenarios, we observed a big reduction of the duration of viral activity. not only the date of viral peak is moved from to dpi, but the decay from the peak is also much faster. this rapid decay is beneficial for the patients as well, and it's due to the complete depletion of the target cells. the overall virus replication curve with the immunosuppressive drug resembles closely the curve for adult influenza infections (shown in figure ) except with a longer time scale. when compared to the base scenario with air (the blue line in figure ), we find that the maximum viral load is increased by a factor of . - . . however, if we compare it to the base scenario of innate response alone without air, the maximum viral load varies by less than %. in summary, we think that the benefit of shortening the disease duration outweighs the cost of increased viral load for a short period. we see multiple potential advantages of this novel approach. there are a number of well-studied, fda-approved drug f i g u r e effect of immunosuppressive drug on viral dynamics: the drug is assumed to be or % effective so ϵ δ = . or . ; drug is applied from dpi until or dpi (with the end day shown on legend); viral counts shown to the left with exponential scale; target cell ∕ t t is shown for dpi for both % and % drugs, with linear scale to the right du and yuan | candidates to choose from. animal models can help to define the range for the main parameters quickly. finally, as long as the drug is applied for enough days so that the suppression of the air is beyond the peak of virus load, this approach always resulted in a quick clearance of the virus. removing the drug in time should enable the air to be fully stimulated, so the patient most likely can have antibody-based immunity for the virus in the near future, as in the case of patients recovered from influenza infections. in our discussion so far, we have assumed that the drug effect is immediate, namely, the drug effect shows up immediately after its application and the effect goes away immediately after the drug is removed. this is clearly not realistic, so one of the key considerations when selecting the right immunosuppressive drugs is its pharmacokinetics; a drug with short elimination and absorption half time is more desirable, considering the time-sensitive nature of the effect. in a recent study by wang et al, the authors reviewed the effect of a low-dose and short-term application of corticosteroid to covid- patients at an early stage, and found some clear benefits of for the patients as compared to the patients without the treatment, including the shortening the disease course. this is consistent with our findings. in their study, the drug corticosteroid was applied for days or more, which according to our theory, might be a little too long for optimal results, considering its half time of to days. previous studies have investigated the rna expression of ace in human tissues. two more recent studies have shown that the percentage of epithelial cells with ace receptors in bronchial is much lower than in turbinate and lung tissues ( . % vs - %). , considering the difference in surface area between the lungs and the nasal cavity, [ ] [ ] [ ] we arrived at a rough estimate of as the ratio of target cells in these two organs. a quick simulation using the much lower t suggests that the peak of infected cells is changed from to dpi in the nose with the innate immune response alone. if infection is localized at the nasal cavity only, it is then much more likely for the peak of the air to come after the peak of infected cells. in this case, most likely the infection will resolve itself just like influenza infections, except the disease may take a few more days. this may explain why a lot of people do not develop severe symptoms or remain asymptomatic if the infection is localized in the nasal area without reaching and propagating in the lungs. if our analysis can be verified clinically, methods and techniques (for example antiviral nasal sprays) to enhance trachea/ bronchial tubes as a barrier to stop the spread of the virus from upper respiratory tracks to the lungs can be effective in reducing the percentage of patients with pneumonia. another important parameter we have not discussed is the cell regeneration rate, τ d , of the epithelial cells. in table , we have listed it as . × − , which corresponds to − day − for d. this is based on a study by rawlins and hogan on the half-life of epithelial cells in the mouse lung. this parameter, if it is higher, will make the depletion of the target cells more difficult. this is because as the target cells are depleted, new target cells are generated. the higher the regeneration rate, the more new target cells are available for viruses to infect and stay alive. our simulation results remain essentially the same if this parameter is lower or increased by no more than a factor of . beyond that, depletion of the target cells becomes substantially more difficult to achieve. thereby, clearing the virus also becomes harder to accomplish. could this be the reason for the observed higher severity rate among older patients? we reason that this is not likely, as the cell regeneration rate should be higher for younger patients, while older people are known to have more difficulty repairing lung damage. in this article, we have applied the target cell-limited model to study the novel corona virus infections mostly in human lungs. through comparison between sars-cov- and influenza viruses, and by analyzing the interactions among various players (target cells, innate and airs, and different types of drugs), we propose that the main reason for the higher probability of severe symptoms, prolonged hospital stays, and even fatal outcomes for covid- patients , may be that the peak of infected cells and virus counts often comes after the peak of the air in these patients. this mismatch of timing and the resulted interference with innate immunity by adaptive immunity, leads to incomplete depletion of the target cells, thus providing uninfected target cells for continued infection. prolonged infection can induce overactive immune responses, secondary complications, and sometimes fatal outcomes. we also discussed the prospects of antiviral drugs and immunosuppressive drugs in combating covid- infections. our proposal to apply immunosuppressive drugs at an early stage to reduce the interference from adaptive immunity so that the innate immunity and the depletion of target cells can together achieve fast elimination of the virus seems to be unconventional. however, it is particularly interesting to note that, as we were working on our mathematical modeling, the recent study by wang et al demonstrated that an early stage low-dose and short-term application of corticosteroid treatment in patients with severe covid- pneumonia was beneficial and essentially validated our findings. we envision that new insights from our analysis and modeling will encourage more work in this direction. clinical features of patients infected with novel coronavirus in wuhan clinical characteristics of hospitalized patients with novel coronavirus-infected pneumonia in wuhan, china epidemiological and clinical 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therapy effects of antirejection drugs on innate immune cells after kidney transplantation immunobiology: the immune system in health and disease early, low-dose and short-term application of corticosteroid treatment in patients with severe covid- pneumonia: single-center experience from wuhan, china. medrxiv description and clinical treatment of an early outbreak of severe acute respiratory syndrome (sars) in guangzhou, pr china histology a text & atlas anatomical and histological factors affecting intranasal drug and vaccine delivery ciliated epithelial cell lifespan in the mouse trachea and lung regeneration of the aging lung: a mini-review the authors would like to express their appreciation for professor yong-zhong qian for some productive discussions. weiming yuan is supported by the nih grant (r ai ) and partially supported by nih grant p ca to the university of southern california norris comprehensive cancer center from the national cancer center. the authors declare that there are no conflict of interests. http://orcid.org/ - - - solving the above equation, we find the following:the time it takes for the infected cells to reach the peak, t r , is as follows, assuming complete depletion of the target cells: notice that here we used i max and i min , because to clear virus completely we need to get to a level lower than the initial level of infected cells. immediately we can see that when = r , we have the lowest t c , which means the fastest clearing of virus. if we assume that, the above result can be further simplified: key: cord- -ar cnsa authors: rouadi, philip w.; idriss, samar a.; naclerio, robert m.; peden, david b.; ansotegui, ignacio j.; canonica, giorgio walter; gonzalez-diaz, sandra nora; rosario filho, nelson a.; ivancevich, juan carlos; hellings, peter w.; murrieta-aguttes, margarita; zaitoun, fares h.; irani, carla; karam, marilyn r.; bousquet, jean title: immunopathological features of air pollution and its impact on inflammatory airway diseases (iad) date: - - journal: world allergy organ j doi: . /j.waojou. . sha: doc_id: cord_uid: ar cnsa air pollution causes significant morbidity and mortality in patients with inflammatory airway diseases (iad) such as allergic rhinitis (ar), chronic rhinosinusitis (crs), asthma, and chronic obstructive pulmonary disease (copd). oxidative stress in patients with iad can induce eosinophilic inflammation in the airways, augment atopic allergic sensitization, and increase susceptibility to infection. we reviewed emerging data depicting the involvement of oxidative stress in iad patients. we evaluated biomarkers, outcome measures and immunopathological alterations across the airway mucosal barrier following exposure, particularly when accentuated by an infectious insult. the presence in the air of one or more natural or anthropogenic substances at a concentration, or location, for a duration, above their natural levels with the potential to cause an adverse health effect defines air pollution. indoor air pollution refers to chemical, biological, and physical exposure of air pollutants in homes, schools, and workplaces. similar to indoor air pollution, ambient (outdoor) air pollution can result from chemical substances or biologically derived contaminants modified by climate change or human activity such as bioaerosols and aeroallergens. air quality guidelines endorsed by the world health organization (who) aim to provide clean air in and around the home. air pollution reduced life expectancy in by year and months on average worldwide. who has linked . million deaths globally in to household cooking using coal, wood and biomass stoves. outdoor air pollution in the same year caused an estimated . million deaths. in inflammatory airway disease (iad) patients an estimated - % increased risk in asthma-related mortality was commensurate with a rise in ambient pollutant concentrations such as no , pm . , or ozone when computed few days prior to asthma death. similar but smaller increments in chronic obstructive pulmonary disease (copd)-related mortality were attributed to pollution and ranged from . % to . %. in the respiratory tract, air pollution can impact wellness in healthy people and patients with iad, irrespective of their atopic status. hence, the airway mucosal barrier may be disrupted by immunopathological mechanisms resulting from effects of pollution and iad. the co-occurrence of iad phenotypes (allergic rhinitis, and chronic rhinosinusitis, copd and asthma) within an individual increases the likelihood of pollutant induced exacerbation of disease or infection. we reviewed the following iads in relation to air pollution. allergic rhinitis (ar), is an ige mediated inflammatory disease generated by a spectrum of outdoor aeroallergens like pollens or indoor aeroallergens such as dust mites, cockroaches, cat allergens, or molds. crs represents multiple overlapping rhinosinusitis phenotypes with different endotypes. asthma is characterized by chronic atopic or non-atopic inflammation of the airway with superimposed episodes of acute exacerbations. the majority of exacerbations are triggered by respiratory viral infections, most commonly human rhinovirus. , other triggers include allergens and atmospheric pollutants. , copd, another chronic inflammatory airway disease, is characterized by airflow limitation and cough. acute exacerbation of copd, like in the upper airway, can be triggered by infection and inhalation of irritants. , chemical pollutants are health-damaging atmospheric aerosol and non-aerosol particles originating from a variety of natural (eg, volcanic eruptions) or anthropogenic sources (eg, biomass burning, fossil fuel combustion, or traffic related particles). primary pollutants such as particulate matter (pm) and volatile organic compounds are aerosol particles directly emitted as solid or liquid droplets in the air. in the atmosphere, natural gasto-particle conversion can culminate in secondary chemical pollutant particles like are ozone and pm. particularte matter (pm) is a mixture of solid and liquid particles suspended in indoor and outdoor air. their source, size, classification, and airway distribution patterns are well described. [ ] [ ] [ ] various human indoor activities cause resuspension and deposition of particles in indoor air, a process governed primarily by the effective size of the particle. this can range from hours for pm to several months for -mm particulate pollutants. pm . broadly represents around % of the total mass of pm and can be inhaled more deeply into the lungs, with a portion depositing in the alveoli and entering the pulmonary and systemic circulation. the submicron pm family, ultrafine particles and nanoparticles, due to their small size, have a relatively large surface area allowing a greater proportion of compounds to be displayed at the surface such as metals and organic compounds. , they cannot be taken by macrophages and can escape phagocytosis. when retained in the lungs, the ensuing inflammation can result in asthma and lung fibrosis; , yet they can allocate to distant organs through systemic circulation resulting in different toxicological phenotypes such as diabetes and heart disease. [ ] [ ] [ ] the adverse health effects of pm are not uniform since pm is not a single entity; rather its constituents and their proportion in ambient air can change from one geographical location to another depending on the type of emissions inherent to each area. volatile organic compounds (vocs) and formaldehyde vocs are primary pollutants located mainly indoors and include benzene, toluene, xylenes, terpenes, and polycyclic aromatic hydrocarbons. they produce a secondary pollutant, formaldehyde, by an indoor chemical reaction between ozone or nitrogen oxide and terpene. formaldehyde appears to be associated with a higher risk of nasopharyngeal carcinoma and leukemia. the primary domestic, - microbial, and socio-cultural sources of vocs , are well elaborated. diesel exhaust represents the most important local contributor to ambient air pollution and has been classified by who as carcinogenic to humans. it is a complex mixture of chemicals and metals stratified into fractions: a solid fraction (made of a soot of carbon core, metals, and their oxides), a gaseous fraction (made of nitrogen, oxygen, and polycyclic aromatic hydrocarbons -pahs), and a liquid fraction where pahs can adsorb into soot or water droplets. , ultrafine particles, nitrogen oxide, and pm (in the range of . mm) can be produced also by internal combustion of diesel engines. metal elements include chromium, magnesium, zinc, and lead and are associated with engine emissions and abrasion of tires and brake pads. vanadium and nickel are tracers of long-range transport from the use of heavy fuel oil. the relatively large surface area of diesel exhaust particles (deps) permits many of these chemicals and metals to attach to its core. thus, most of the deleterious effects of deps are due to chemicals that are adsorbed onto their surface. ozone and nitrogen oxide (nox) to date, ozone is considered the most damaging air pollutant in terms of adverse effects on human health, vegetation, and crops. [ ] [ ] [ ] [ ] [ ] [ ] it produces short-and long-term effects on cardiorespiratory function. recent evidence suggests there is no threshold concentration below which there are no effects on health. ground-level ozone is formed in the atmosphere by a complex reaction of its precursors, nitrogen oxide (nox), carbon monoxide, and volatile organic compounds in the presence of sunlight. background ozone concentrations are strongly correlated with the increased global nox emissions derived from human-generated fossil fuel combustion and biomass burning. tobacco smoke (tbs) tobaco smoke (tbs) emits a wide range of gases, aerosolized liquids, and fine particulate matter including voc and formaldehyde, nitrogen oxide, pm . , and nicotine. , tbs is estimated to cause approximately , excess deaths per year, and it can contribute to % of all cancer deaths. among other actions, tbs can induce dna damage, change in sputum (mucin) quality, and depressed antioxidant and antimicrobial activity in smokers and among copd patients. , household dust household dust represents a convenient means to sample respiratory exposure to pollutants. in one study, the respirable fraction of dust constituted less than % of the total weight of dust surrounding us, and on scan electron microscopy consisted of large flakes (> mm diameter) to which are adherent smaller particles. the median aerodynamic diameter of respirable dust particles allows their deposition both in the nose and lungs. the chemical composition of these flakes suggests household dust might be an important carrier vehicle of organic pollutants into the airways in addition to its intrinsic risk of oxidative stress. allergens can pollute indoor and outdoor air and exacerbate ar and asthma. indoor allergenic pollutants can be derived from skin scales of pets (eg, cats, dogs), urine of rodents (eg, mice), molds, or from fecal material of arthropods such as house dust mites and cockroaches. outdoor allergens are aeroallergens originating from grasses, trees, weeds, or molds. outdoor pollen also modulates indoor aeroallergen concentration. the concentration of aeroallergens in the indoor environment is governed by complex bioaerosol dynamics. for example, airborne cat allergen (fel d ) is mostly associated with large particles (> mm), but around / of fel d are carried on particles less than micra in diameter. thus fel d can be deposited in the alveoli but most importantly suspended for several days in the air favoring distribution of the allergen in the environment. [ ] [ ] [ ] also, the groups of mite allergens listed in the who nomenclature of allergens are composed of particles ranging in diameter from to mm. hence, they can become airborne upon disturbance and can be carried on house dust that becomes a vector for exposure. how dust mite allergen particles can induce and volume , no. , month trigger asthma in lower airways remains to be determined. the diversity and functioning of the normal microbiome are crucial for maintaining the health of the host. while the effects of pm on human health are well established, the impact of infectious particles on bacterial ecosystems has been overlooked. in vitro studies suggest black carbon, a major component of pm, is strongly implicated in predisposition to respiratory infectious diseases, , and induces structural and functional changes in the biofilms of both streptococcus pneumonia and staphylococcus aureus. this is manifested by increase in biofilm thickness and tolerance to degradation by proteolytic enzymes, thereby promoting colonization of the respiratory tract. similarly, evidence suggests indoor and outdoor dust modifies microbial growth, virulence, and biofilm formation of opportunistic pathogens. by exposing opportunistic bacteria (pseudomonas aeruginosa, escherichia coli, and enterococcus faecalis) to progressively increasing concentrations of indoor and outdoor dust, a differential growth pattern of pathogens was noted. this was commensurate with increased biofilm formation and sensitivity to oxidative stress following hydrogen peroxide challenge. consequently, the detrimental impact of particulate pollutants on human health is not only due to direct effects on the host but also may involve the effect on bacterial behavior in the host. oxidative stress is a disproportionate generation of free radicals beyond the body antioxidant capacity. it translates into a non-ige mediated th airway inflammation following exposure to a pollutant. in brief, reactive oxygen species (ros), generated naturally as by-product of cell growth and metabolism, can be produced following pollutant exposure. , ros include oxygen radicals (eg, superoxide, hydroxyl, hydroperoxyl) and certain non-radicals (eg, h o , ozone, singlet oxygen) that are easily converted into radicals. ros have a pivotal role in cell signaling in the oxidation/reduction cascades following exposure and ultimately generation of anti-oxidant mechanisms thru nrf- , activator protein , and nuclear factor-kappa b. [ ] [ ] [ ] [ ] antioxidants are scavengers of ros and can be enzymatic or non-enzymatic systems, constitutive or de novo synthesized by activated gene expression, according to ros load. the inflammatory phase of oxidative stress involves cytokines-and chemokines-mediated activation and recruitment of inflammatory cells secondary to direct effect of pollutants on airway epithelial cells. this can propagate oxidative stress further and augment the inflammatory response and tissue damage. alternatively, ros can contribute directly to cell injury and apoptosis by disrupting cellular and nuclear membranes in the epithelial barrier wall and altering the function of cellular enzymes. , a different mechanism by which environmental pollution can trigger disease in the nose is via a neurogenic mechanism. another component of oxidative pathway is the exposure-driven adjuvant effect on atopy where environmental pollution acts as an exacerbating factor for allergic airway disease by enhancement of allergic airway hypersensitivity in atopic individuals. the evidence emerges from experimental protocols involving inhalation of pollutants and allergen challenge which show pollutants can act synergistically to heighten the allergic response with increased expression of th inflammatory biomarkers. , this is in contrast to healthy individuals which express either th or a mixed th /th profile in controlled exposure studies. epidemiological studies suggest pollution modulates ar, [ ] [ ] [ ] [ ] [ ] [ ] [ ] rhinosinusitis, and asthma. , other studies suggest a positive association between exposure and prevalence of ar and asthma , [ ] [ ] [ ] [ ] in children and adults predominately in reports on short-term exposure and residential proximity studies to sources of traffic pollution. , however, other long-term exposure studies provided evidence to the contrary. [ ] [ ] [ ] this could be due to differences in study design, methods of exposure assessment, and complex nature of studied pollutants. inin-vivovivo studies in both human and animal models suggest pollutant exposure induces inflammatory changes in normal, chronically diseased and allergic nasal and sinonasal tissues ( table ). the cytokine profile of affected tissues suggests activation of the oxidative inflammatory pathways. [ ] [ ] [ ] moreover, there is compelling evidence for involvement of oxidative stress inflammatory pathways following pollutant exposure in the pathogenesis of rhinitis, crs, and asthma irrespective of atopic status. this stems from an abundance of literature on oxidative stress biomarkers studied under natural or experimental allergen exposure both in seasonal and perennial ar described in table . in fact, dust mite or ragweed allergic patients exposed to diesel exhaust particlesdeps in climate chamber expressed higher nasal symptom scores following dust mite or ragweed challenge, respectively, when compared to nonexposed but allergen-challenged patients. , also in the lower airways, short-term natural increase in ambient air ozone was associated with deteriorating lungh function tests in atopic asthmatics despite use of proper asthma controller therapy. similarly, an ozone exposure protocol revealed atopic asthmatics expressed depressed spirometry testing results compared to healthy volunteers. along with this, climate chamber studies revealed (ozone) exposure of healthy or allergic asthmatics induces a neutrophilic or a mixed neutrophilic and eosinophilic inflammatory profile in the lower airways, respectively. furthermore, gene expression profiles of sputum cells recovered from healthy volunteers and allergic asthmatic patients also confirmed significant difference in inflammatory response to ozone exposure. analysis of biomarkers activity greatly improved our understanding of cascade and signal pathways involved in atopic and non-atopic phenotypes of airway disease following exposure. although most oxidative stress biomarkers require tissue specimen collection, some studies suggest an analysis of biomarkers can be determined non-invasively in exhaled breath condensates or blood. [ ] [ ] [ ] [ ] [ ] [ ] natural allergen exposure reverses oxidative and antioxidative status compared to asymptomatic period, with a persistent oxidative state outside pollination season in allergic patients when compared to healthy controls. ar and asthma comorbidity in children does not seem to augment oxidative stress markers compared to ar alone, although adult patients with seasonal ar and asthma manifest an exaggerated stress response during natural allergen exposure compared to ar alone. clinically, oxidative stress correlates with nasal symptom scores in children with perennial ar and can predict ar severity independent of total ige. additionally, ros status does not correlate with atopic skin sensitization in children with perennial ar. furthermore, dust mite challenge in asthmatics or sensitized mice resulted in oxidative damage to nucleic acids as well as lipids and proteins and subsequently triggered dna repair pathways. further blockage of dna repair proteins resulted in increased production of dna double-strand breaks and cell apoptotic enzymes suggesting importance of dna repair in suppressing airway inflammation. endogenous antioxidant response in atopic respiratory diseases is complex and oxidative stress response to anti-inflammatory drugs isare poorly understood. antioxidant enzymes mostly studied in atopic respiratory diseases include heme oxygenase and , , nadph oxidases, catalase, , superoxide dismutase, , , dual oxidases and (in crs patients), paraoxonase, and glutathione peroxidase. , antioxidant activity can also be measured by serum thiol-sh and total antioxidant status ( table ). in this respect, evidence suggests oxidative stress decreases antioxidant enzyme activity or total antioxidant status in atopic children , , or in human in vitro controlled exposure studies, whereas other studies present evidence to the contrary. for example, heme oxygenase antioxidant (iso)enzyme- activity was preferentially increased in a human in vitro model of perennial ar, and upregulated in a human exposure model of copd aggravated by infection; ; also dual oxidase antioxidant (iso) enzymes showed preferential upregulation in different phenotypes and endotypes of crs. , contrary to this, antioxidant enzymes can be downregulated in asthma and rhinitis irrespective of atopic status, and in vitro animal exposure models challenged by an infectious insult. importantly, genetic polymorphism in antioxidant/ detoxifying genes like gstm and gstp can alter oxidative stress response in patients with copd and those with ar following exposure. , exogenous (dietary) antioxidants are scavengers of oxygen free radicals and can act on different levels of defensive antioxidation pathways. , epidemiologic, in vivo , and in vitro studies suggest a beneficial role of exogenous antioxidants in patients with iad or in controlled exposure studies of healthy sinonasal epithelial cells. however, lack of clinical trials data clearly supporting their efficacy, in addition to their potential role in skewing th /th balance towards a th -type immunity as suggested in vitro, renders their indication restricted to special situations such as over exposure to environmental pollutants, among others. nacetylcysteine maintains a potent antioxidant effect in in vitro studies or in ovalbuminsensitized rats by downregulating tumor necrosis factor-alpha in recruited inflammatory cells. along these lines, intranasal steroids can exhibit an exogenous antioxidant regulatory role in seasonal ar by decreasing exhaled breath condensates of leukotriene b and -isoprostane, although no effect was seen on exhaled carbon monoxide and nitrogen oxide. in another study involving children with ar and asthma, no effect of topical nasal steroid therapy was noted on measured lipid peroxidation oxidative stress biomarkers and antioxidant enzymes. data on potential antioxidant effect of inhaled steroids in adult asthmatics is scarce. epidemiological studies suggested prior intake of oral or inhaled steroids in adult asthmatic patients had no effect on asthma control, as measured by clinical symptoms and fev testing, with pm and ozone exposure. other similar studies noted increased consumption of asthma controller therapy (bronchodilators, inhaled corticosteroids, or both) with pm or no exposure in adults. moreover, in children inhaled steroid therapy downregulated induced expression of heme oxygenase- in non-smoking patients with bronchiectasis but had no effect on exhaled carbon monoxide. furthermore, desloratadine can exert an antioxidant effect in children with perennial ar by increasing antioxidant enzyme activities (catalase and superoxide dismutase) and decreasing lipid peroxidation marker (malonaldehyde) although no effect was seen on total antioxidant status. when compared to placebo, fexofenadine improved nasal symptom scores in ragweed ar patients following ragweed challenge and dep controlled exposure. the majority of controlled human exposure studies to ambient pollutants have been conducted in climate chambers on healthy individuals. [ ] [ ] [ ] [ ] for example, relative to clean air, mixtures of vocs increased ratings of nasal irritation, odor intensity and cognitive symptoms (memory loss, dizziness), and a two-fold increase in polymorphonuclear cells in nasal lavage immediately following exposure. similar studies using different pollutants showed no detectable effects on nasal symptom scores or markers of nasal inflammation. , additionally, healthy subjects exposed to room air, nanoparticles, or o /terpene showed no significant changes in inflammatory biomarkers in blood, sputum or nasal secretions and pulmonary function tests. however, only nanoparticles exposure increased significantly high frequency variability in heart rate, thereby indicating a shift in autonomic balance to a more parasympathetic tone. low level ozone exposure in healthy subjects resulted in increased sputum production of airway inflammatory cells such as neutrophils, monocytes, and dendritic cells, and modification of cell surface phenotypes of antigen presenting cells. using a similar protocol the reported decrement in lung spirometry testing (fev ) of healthy subjects was associated with increased neutrophilic airway inflammation following exposure; the latter likely being more pronounced in healthy individuals with gstm null genotype. more importantly, comparing healthy controls to atopic asthmatics, exposure to high levels of ultrafine particles in a climate chamber was associated with a small but significant fall in arterial oxygen saturation, a fall in forced expired volume over s (fev ) the morning after exposure, and a transient slight decrease in low frequency (sympathetic) power during quiet rest. these controversial results can be related partly to the nature and concentration of the investigated pollutant or its experimental duration of exposure keeping in mind brief exposure to a single pollutant in a climate chamber does not reflect chronic exposure to multiple pollutants in real life. controlled exposure studies in atopic patients involving allergen challenge revealed more consistent results. for example, dust mite allergic patients reported worsening nasal symptom scores following intranasal dust mite challenge and dep exposure commensurate with increased histamine levels in nasal washes, all suggestive of induced mast-cell degranulation. similarly, controlled exposure studies in ragweed allergic patients challenged with dep and ragweed outside their pollen season reported higher total nasal symptoms scores or increased levels of specific ige and expression of th inflammatory cytokines, when compared to ragweed challenged alone. taken together, controlled airway exposure studies to ambient pollutants in healthy individuals show small but significant negative health effects whereas exposure studies in allergic patients support the role of pollutants in increasing atopic airway hypersensitivity. large scale translational studies are needed to correlate the bio-cellular toxic effects of pollution with epidemiological studies. signal and cascade pathways triggered across the airway mucosal barrier at first encounter of pollutants are complex (see fig. ). airway mucosal cells can recognize pollutants through an epithelial toll-like receptors (tlr)-mediated mechanism either directly or indirectly by the intermediary of pattern recognition receptors (see below). more precisely, pollutants such as pm, cigarette smoke, and ozone can present themselves directly to subclasses of surface tlrs, namely tlr and tlr , which can serve as ligands for these pollutants. alternatively, pollutants can be bound to pattern recognition receptors, a collective conglomerate of receptors which encompasses tlrs and normally can recognize conserved molecular structures derived from microbial agents or released by damaged nonmicrobial cells. once triggered, pattern recognition receptors and tlrs attract antigen presenting cells and leukocytes to the site of inflammation resulting in priming of the airway to subsequent mucosal infectious insults. afterwards, when eventuated by an infectious challenge, alveolar macrophages mount a heightened inflammatory response aimed at containing and clearing bacteria while producing minimal collateral tissue damage. , the immunological "storm" resulting from co-exposure and infection is studied in different clinical models of respiratory cells and also in patients with iad such as copd ( table ) . another signal pathway is mediated by submucosal innate lymphoid cells (ilcs) which can differentiate into adaptive subsets. ilc s relates to immune reactions in crs without nasal polyps, copd, and some viral and bacterial infections; whereas ilc s becomes important in regulating type immunity and some helminthic and viral infections. , other immunologic and antimicrobial responses to pollutant exposure modulate expression of host defense peptides and antiviral mechanisms, impair mucus production crucial for capturing pollutants or weaken tight junctions essential for the epithelial airway defense barrier. , epidemiological studies suggest indoor and outdoor air pollution increase the risk of respiratory tract infections in both pediatric - and adult populations. , , , for example, morbidity of the recent covid- pandemic disease has been linked partly to air pollution. [ ] [ ] [ ] [ ] also, air pollution can aggravate the severity of asthma caused by respiratory viral infections. moreover, in vitro studies suggest air pollution may suppress innate and adaptive immunity and increases susceptibility to bacterial and viral respiratory infections in both human and animal clinical models, following short-or long-term exposure (see table ). for example, in the upper airways diesel exhaust exposure increased the number of human nasal epithelial cells infected by influenza a virus in vitro the proposed mechanism was enhancement of virus attachment and entry into respiratory cells mediated by radical oxygen species, despite increased antiviral interferon-dependent signaling and interferon-stimulated gene expression by dep exposure. also, in vitro rrhinovirus (rv) infectivity following nitrogen oxide and ozone exposure in human respiratory epithelial cells loss of low-level dep-exposed mdmf along their differentiation into macrophages likely due to dysfunctional (loss of mitochondrial membrane electrical potential and lysosomal function) and phenotypic (tlrmediated reduction in cd and cd surface marker expression) structural changes in mdmf of healthy exposed individuals. this can likely contribute to inflammation in copd by decreased mdmf proinflammatory cytokines (cxcl ) production. resulted in increased icam receptor expression (receptor for rv ) and pro-inflammatory il- cytokine production. in another combined human and animal model, activated nasal airway microbial proteins at the surface mucosal liquid, which include lysozyme, human cathelicidin antimicrobial peptide, and human b defensins, were attenuated following (pm) exposure and staphylococcus aureus infection. the ensuing impaired bacterial killing resulted from adsorption and electrostatic interactions between either pollutant or bacteria with activated microbial proteins leading to the depletion of the latter. the literature on the lower airways exceeds that on the upper airways. in this respect, susceptibility to infections following exposure was examined at several stages of immunological alterations triggered in host cells. starting with the epithelial barrier level, an initial in vivo pm exposure of bronchial epithelial cells in mice followed by experimental infection with pseudomonas aeruginosa resulted in decreased levels of an epithelial ciliary marker (b tubulin) and a non-ciliary epithelial (clara cells) marker, and their gene expression/transcription regulator, all suggesting airway remodeling is a contributing factor to the impaired bacterial clearance. furthermore, an initial infection with pseudomonas aeruginosa induced an epithelial antimicrobial peptide human beta defensin ; but as the model was pre-exposed to pm, induction of human beta defensin was suppressed and a cell senescence biomarker (sa-b-gal) was upregulated in an ros-dependent process. also, in an in vitro human model, a pm-enhanced susceptibility to streptococcus pneumoniae infection was heightened by increased bacterial adhesion and penetration into bronchial epithelial cells. this was mediated by a receptor for platelet-activating factor, a putative receptor for pm-stimulated pneumococcal adhesion to airway cells. on a submucosal level, macrophages and monocytes play a central role in phagocytosis. the study of immunopathological alterations in phagocytosis has shown inconsistent results. for example, in an exposure (pm)-infectious animal model, impaired streptococcus pneumoniae clearance and phagocytosis resulted from decreased macrophages internalization of bacteria, although increased binding of microbe to surface of macrophages was reported. in a similar model increased susceptibility to staphylococcus aureus infection resulted from depressed phagocytosis index and abnormal natural killer cell response. also, in another animal exposure model increased infectivity to listeria monocytogenes resulted from decreased ros-induced nitric oxide production by alveolar macrophages. in contrast, natural (chronic) pm exposure of human bronchoalveolar lavage fluid decreased macrophage cytokine (cxcl ) release and downregulated induced phagosomal oxidative burst. per contra, no impairment in macrophage redox potential, proteolysis or phagocytosis was observed likely due to the experimental chronicity of exposure. additionally, in an analogous model using high levels of the same pollutant (pm), the impaired antimicrobial defense resulted from defective macrophage activation of t cells by class ii þ major histocompatibility complex and subsequent decrease in interferon-g production, but unaltered phagocytic activity. interestingly, no increase of neutrophils and tnf-a levels was observed in bronchoalveolar lavage following exposure and infection suggesting acute exposure to relatively high level of pm does not trigger a classic or sustained inflammatory response. besides suggesting interference with innate immunity, exposure studies suggest further alterations in adaptive immunity as evidenced by immunopathological relationships between antigen presenting cell cytokines, the corresponding sensitized t cells subsets, and recruited neutrophils (see table ). as such, a listeria monocytogenes-mediated suppression of macrophages immune response upon low dose dep exposure manifested as "dysfunctional" production of macrophages-derived cytokines. this was associated with downregulation of innate protective cytokines (e.g. il- b, tumor necrosis factor-a, il- , il- and interferon-g), suppression of adaptive cd and cd t cell immune response, and upregulation of macrophage bactericidal anti-inflammatory cytokines (il- and il- ). other examples of altered cytokine release include the pro-inflammatory besides the role of cytokines in fine tuning extent of inflammation in these models, t cell subsets like t cytotoxic (cd þ ) and regulatory t cells (treg) in addition to neutrophils have been studied. dep exposure in rats increased susceptibility to listeria monocytogenes infection by attenuating t cell mediated immunity, namely cd þ t helper lymphocytes and cd þ t cytotoxic cells; pm exposure in neonatal mice resulted in depression of adaptive response to influenza virus a infection and by an increased expression in treg cells and il- in lung tissues. interestingly, the induced immunosuppressive effect was reversed by treg depletion and restored by either treg transfer or recombinant il- treatment. furthermore, airway neutrophilia, which is instrumental in bacterial clearance, has been studied in inin-vitrovitro infectious exposure model in relationship to th and th proinflammatory cytokine release. the concomitant increase in bronchoalveolar lavage fluid il- with airway neutrophilia, and their attenuation in il- "knock out" mice following exposure and infection suggested the importance of il- in inducing neutrophil-mediated airway inflammation. also, decreased induction of il- a-mediated airway neutrophilia following exposure and infection in il- r mice compared with wild-type controls also suggests il- signaling is required in il- aexacerbated neutrophilia. moreover, in an in vivo exposure-infectious animal model modulated by interferon-g priming to mimic viral infection, an impaired pm-mediated bacterial phagocytosis correlated with activation of genes encoding neutrophil-recruiting chemokines and increased histopathology suggestive of severe pneumonia. still, in an animal in vivo model, exposure followed by lps infection induced cytokine changes in the lung suggestive of a th /th imbalance and manifested by increased expression of il- among others, and a concordant decrease in ifn-g expression. the infectious-exposure model is an attractive tool to explore immunopathological alterations in copd patients or in laboratory cells exposed to secondhand smoking. in a mice model, weeks secondhand smoking pre-exposure was followed by infection with non-typeable haemophilus influenza which is a pathogen commonly implicated in acute exacerbation of copd. the model revealed increased number of immune cell infiltrates except for macrophages, and a suppressed induction of a robust adaptive immune response manifested as decreased ifn-g. also, a downregulated t cell adaptive response manifested by decreased bacterial clearance and diminished efficiency of specific antibody subclass switching, both mitigated by anti-viral vaccination. in a similar animal model examining the immunological effect of antibiotic therapy, cigarette smoke exposure followed by streptococcus pneumoniae infection resulted in recruitment of macrophages and monocytes in lung tissue and alveolar fluid reportedly to confine infection to the lung; also a decreased number of neutrophils but a differential increase in neutrophil-mediated antimicrobial peptide, myeloperoxidase. antibiotic therapy had no effect on mice survival rate but reduced lung injury and induced a differential change of cytokine levels in bronchoalveolar lavage fluid most importantly downregulation of th and th inflammatory cytokines. human in-vitro pre-exposure and infectious models are designed to mimic acute exacerbations in stable but exposed copd patients. dep exposure followed by non-typeable haemophilus influenza infection did not compromise mucosal barrier function in copd or healthy patients. however, epithelial endoplasmic reticulum activity was markedly disrupted in copd patients, manifested by depressed gene expression of the integrated stress response markers in an ros-mediated process. in another model, macrophages differentiating from locally recruited monocytes in lungs of copd patients were pre-exposed to low level dep and subsequently challenged with tlr agonists or heat killed e.coli. this resulted in structural and functional changes in innate and adaptive immune system consisting of mitochondrial and lysosomal dysfunction in macrophages, decreased expression of their surface recognition markers, loss of macrophage differentiation, and reduction in proinflammatory cytokine production (e.g.il- ). the majority of exposure-infection human and animal models have examined immunological alterations following long-term (weeks) and lowdose pre-exposure periods which best mimics real-life outdoor pollutant exposure or indoor secondhand smoking relevant to copd. nevertheless, other models which studied brief and short-term (hours to days) exposure periods have yielded mixed results. for example, one-week diesel exhaust pre-exposure of mice in vivo decreased pseudomonas aeruginosa clearance from bronchial epithelial cells, whereas in the same model a six-months pre-exposure did not. also, in an in vivo model, mice were pre-exposed to pm for day (short term) or weeks (long term), later infection with influenza virus a and survival rate was assessed over the ensuing days following contamination. short-term exposure improved mice survival rate and triggered a robust immune response whereas long-term exposure did not, reportedly mediated by macrophage cytokine gene expression regulator kdm a. to model secondhand smoking exposure or for recent initiation of active smoking, mice were exposed to brief ( h per day for days) low dose of side stream cigarette smoke or to prolonged ( . weeks) high dose cigarette smoke, respectively, and later inoculated with streptococcus pneumonia. surprisingly, brief exposure did not show significant survival benefit whereas prolonged exposure in mice did, reportedly due to diminished propagation of bacteria into the systemic circulation during chronic exposure. finally, in a mice model examining only chronic secondhand smoking exposure and its impact on non-typeable haemophilus influenza antimicrobial response, weeks secondhand smoking preexposure, theoretically mimicking mainstream smoking, compromised the ability of host t cellmediated adaptive immune system to mount an effective response against non-typeable haemophilus influenza infection. taken together, these models suggest exposure impairs innate and adaptive immunity against airway microbial infections. limitations inherent to the design of these models compel a careful interpretation of results taking into consideration the response to infectivity of animal host cells, the duration and intensity , , , of pollutant pre-exposure, and the nature of microbial agents used for contamination. we reviewed evidence for the involvement of oxidative stress pathways and their nature in healthy individuals and patients with inflammatory airway diseases following exposure to a spectrum of important chemical, allergic and infectious air contaminants. when comparing exposure clinical models in patients with ar, crs, and allergic asthma, the signal and cascade pathways can generate important oxidative and anti-oxidative markers and induce specific changes in adaptive and innate immune system. thus, exposure can amplify the inflammatory process in 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diesel exhaust particle exposure in vitro alters monocyte differentiation and function biochemical and biophysical research communications down-regulating pulmonary macrophage kdm a and mediates histones modi fi cation in il- and ifn-b promoter regions cigarette smoke-mediated inflammatory and oxidative responses are strain-dependent in mice the importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: current state a review of the epidemiological evidence for the ' antioxidant hypothesis human and animal research not applicable. not applicable.availability of data and materials not applicable. we attest that all authors contributed significantly to the creation of this manuscript.-philip rouadi and samar idriss initiated the work, contributed substantially to the conception and design of the study, the acquisition, analysis, and interpretation of data. -philip rouadi supervised the manuscript.ethics committee approval not applicable. all authors agreed to the publication of this work. the authors have nothing to declare relative to this paper. key: cord- -ug uew authors: crema, e. title: the sars-cov- outbreak around the amazon rainforest: the relevance of the airborne transmission date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: ug uew background this paper presents a global analysis of the sars-cov- outbreak in brazil. amazonian states have a much higher contamination rate than the southern and southeastern states. so far, no explanation has been provided for this striking difference that can shed light on the airborne transmission of the virus. minimizing airborne transmission, health authorities recommend two meters as a safe distance. however, recent experiments reveal that this can be the main form of contagion. there is a lack of theoretical explanation on how airborne transmission works. methods to investigate the spread of sars-cov- in different macro environments, we analyzed the daily official data on the evolution of covid- in brazil. we compared our epidemiologic results obtained in states with very different climatic characteristics, and that had adopted, almost simultaneously, similar social isolation measures. to understand the virus spread, it was necessary to calculate theoretically the movement and behavior in the air of saliva droplets. findings the transmission of sars-cov- is much faster in the amazon rainforest region. our theoretical calculations explain and support the empirical results observed in recent experiments that demonstrate the relevance of aerial transmission of the coronavirus. interpretation an onset of collective immunity may have been achieved with a contamination rate of about % of the amazonian population. if confirmed, this result will have an essential impact on the management of the pandemic across the planet. the airborne transmission played a decisive role in the striking difference in the evolution of the pandemic among brazilian regions. air humidity is the most important climatic factor in viral spreading, while usual ambient temperatures do not have strong influence. there is no safe indoor distance for the coronavirus transmission. so, mask and eye protection are essential. the ray of light that runs through a dark room reveals the existence of numerous small grains of dust that can float in the air for a long time. since antiquity, this phenomenon was already known. a famous observation of this effect is documented in lucretius's poem de rerum natura, written around bc. in addition to the empirical description of the phenomenon, and following the tradition of democritus and epicurus, lucretius also proposed an atomistic explanation for the support of particles in the air, according to which their weight would be compensated by the collisions of air atoms. however, the behavior of tiny bodies immersed in fluids was only understood from the th century on owing to the works of robert brown, george gabriel stokes, and finally with einstein's famous work of , on the movement of small particles in suspension within liquids at rest. currently, this phenomenon has gained tragic relevance due to the uncontrolled dispersion of the covid- throughout the planet, since airborne transmission is one of the forms of viral contamination, as well as the direct reception of drops exhaled by a contaminated person and the contact with infected surfaces. there is still no consensus among researchers as to which of these forms of contagion is the most important in the case of the coronavirus. despite being the third outbreak of this virus in less than two decades, existing research had not yet fully understood its transmission mechanisms. a similar situation occurred with the influenza virus. while some important books and works drew attention to the relevance of the transmission by aerosols (droplets), [ ] [ ] [ ] other authors argued that short-distance transmission by drops would be the main means of infection, , and this latter position prevailed for a long time among health authorities who practically ignored airborne transmission. , at the end of march , the world health organization (who) released a bulletin stating that there was insufficient scientific evidence that sars-cov- was significantly airborne transmitted. a few months ago, at the beginning of the current pandemic, several governments and the most important health authorities on the planet recommended that only hand washing and a distance of two meters between people would be safe protection procedures and that the use of masks was unnecessary throughout the population. however, with the rapid spread of the coronavirus in countries and in the world, the deadly reality has imposed itself and forced the planetary health authorities to reverse this directive, saving thousands of lives by requiring the use of masks in several countries. from a scientific point of view, this late change in positioning was the authorities' recognition that air transmission of sars-cov- is an unquestionable fact. nevertheless, it remains to be understood how this process takes place. in this article we will clarify the physical processes involved in this means of contamination and explain theoretically the results of recent epidemiologic experiments. besides, we will discuss some recent relevant epidemiologic papers and analyze the sars-cov- outbreak around the amazon rainforest that may help to understand the relevance of the long-range viral airborne transmission. finally, we will show that there are still some important recommendations that health authorities should indicate to reduce viral transmissibility. the airborne transmission of the coronavirus is now experimentally well demonstrated by important works published during the last months. a relevant study issued in the journal nature revealed the existence of the rna of the sars-cov- in aerosols collected from the air of several closed environments and open places of two hospitals in wuhan dedicated only to patients infected with covid- ( ) . another paper analyzed the air at the nebraska hospital center and also found the sars-cov- in most environments occupied by patients with mild and moderate infections. in these two studies it was not possible to confirm if these viruses were active. however, this doubt was finally resolved by a study published in the new england journal of medicine, where the presence of active sars-cov- in droplets was observed more than three hours after they were artificially produced in the laboratory ( % of relative humidity and temperatures between - ºc). now, it is certain that under normal day-to-day conditions sars-cov- remains active for hours in the droplets suspended in the air. extensive study published in the lancet journal, analyzing empirical data from countries on continents, concluded that the probability of infection by sars-cov- decreases by · % when using a protection for the eyes. that is, the risk of contagion through the eyes is very high and continues to be minimized by health authorities, including the who, as had happened in the case of masks. this may be a new mistake in combating the pandemic. on the other hand, further experiments visualized the production of saliva droplets during a person's normal speech, breathing, sneeze and cough. [ ] [ ] [ ] thousands of drops were exhaled and their dispersion in the air was video recorded. they used a laser beam technique of high resolution that was able to identify even submicron droplets. in the video from kyoto university, one can watch the movement of these drops, revealing all rights reserved. no reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in the copyright holder for this this version posted august , . . https://doi.org/ . / . . . doi: medrxiv preprint that while the larger ones fall rapidly and settle on the ground and furniture, there are hundreds of micro droplets that remain suspended in the air several hours after being exhaled. and, most seriously, these small drops disperse rapidly and, a few minutes after their production, occupy the entire environment, covering distances greater than eight meters. besides these experiments, there were several empirical situations that put in another new and very relevant epidemiological event has occurred in the current covid- pandemic in brazil: the amazonian states that house the forest have presented contamination rates higher than %, while in southern states this rate has been less than %. to understand this striking difference, we analyzed the official primary data on the pandemic released daily by all states of the country. we will use the number of deaths as an analysis parameter because there is a huge underestimation of the number of cases of the disease due to the extremely low number of tests performed by the brazilian government. it should be kept in mind that the number of deaths is also undervalued. one all rights reserved. no reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in the copyright holder for this this version posted august , . perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in the copyright holder for this this version posted august , . . https://doi.org/ . / . . . doi: medrxiv preprint % and %, respectively. in other cities near the rainforest this percentage attained % to %. therefore, the contamination rate that could have produced the interruption of the spread of the epidemic observed in fig. was only of the order of %. if confirmed by further studies, this result will have an extraordinary impact on the management of the pandemic on the planet. the striking difference observed between the north and south regions could not be explained by the issue of social isolation, since both adopted, almost simultaneously, similar isolation measures. nor is it due to the greater poverty in the northern region, as the southern states also have a large number of inhabitants living in precarious dwellings, including thousands of slums, which would facilitate the rapid spread of the virus. a possible difference in health care system between regions could also not be claimed as an explanation of this phenomenon, as it would not justify the sudden drop in the number of deaths. so, the remarkable disparity in the evolution of the contamination in these regions needs to be deeply investigated. a factor that can play an important role in the spread of sars-cov- is the climate. during the months investigated in this work, in the regions surrounding the forest, the average temperatures were always above ºc and the average relative humidity, above %. in southern states, average temperatures and average relative humidity were not higher than ºc and %, respectively. therefore, there is no direct relationship between high ambient temperature and decreased transmissibility. on the other hand, some studies showed that, in general, in environments with relative humidity above %, approximately, the drops absorb more than evaporate water into the air. , so, we believe that the airborne transmission of the sars-cov- , facilitated by the high humidity of the air, could be a primary factor in the development of the epidemic in brazil. our hypothesis is confirmed by other studies conducted in some cities in brazil at the beginning of the pandemic, although these studies use the number of cases as an analysis variable. , to better understand this relationship, it is interesting to know the amount of water vapor that actually exists in the atmosphere, that is, its absolute humidity. one kilo of air with relative humidity %, at ºc, contains approximately g of water in the form of vapor, while at a relative humidity of %, at ºc, the amount of water is only g. that is, the process of water evaporation/absorption is very complex in the amazonian weather conditions, and, on average, the drops expelled by an infected person all rights reserved. no reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in the copyright holder for this this version posted august , . . https://doi.org/ . / . . . doi: medrxiv preprint will absorb water from the atmosphere, allowing the viruses to survive much longer in suspension or deposited on surfaces. a similar situation has occurred in abattoirs in france, germany, and the usa that have become huge poles of contamination. the dominant explanation for this phenomenon has been the airborne transmission facilitated by the low temperature of these environments. we agree that the aerial contagion was responsible for the spread of the virus in the abattoirs. however, the pandemic evolution in brazil, middle east, europe, china, and usa has demonstrated that habitual temperatures seem to have little influence on the survival of the virus in the external environment. therefore, we believe that also in the abattoirs the most important factor was the very high humidity of the air during a coughing, sneezing, or speech, thousands of drops of saliva and secretions from the pulmonary tract are expelled with high speeds and penetrate more than two meters into ambient air. these drops have diameters between fractions of micrometers up to fractions of centimeters. [ ] [ ] [ ] [ ] depending on their composition and air humidity, they can evaporate or absorb water from the environment, and this process is fundamental to the survival of the virus. after the evaporation or growth of the drop, its equilibrium size will define its dynamics and the progression of the epidemic. the smaller droplets (diameter< µm) are responsible for the airborne transmission that has been recently recognized by numerous researchers as decisive in the spread of the sars-cov- and the who asks that it be better studied. in an attempt to contribute to this all rights reserved. no reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in the copyright holder for this this version posted august , . . https://doi.org/ . / . . . doi: medrxiv preprint scientific effort, this work will also investigate the movement of these droplets to demonstrate how airborne transmission is physically possible. two situations will be considered: they fall into the air at rest; and under action of a vertical airflow upwards which can be produced by an air conditioning system and/or air renewal. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in the copyright holder for this this version posted august , . . https://doi.org/ . / . . . doi: medrxiv preprint epidemiological implications of this expression, we will calculate the fall of drops of human saliva in the air at a pressure of mmhg and a temperature of º c. table shows the values of the time constant τ calculated for drops of radius ranging from · µm to µm. on the other hand, fig. shows the dynamics of two drops, of radii · µm and · µm, where are shown the variations of their velocities with time. we observed that the drops start to fall from rest, increase their velocities, and in a few microseconds acquire extremely small constant velocities, vlim. for example, in this ideal situation, with stationary air, a drop of radius · µm falls with speed · µm/s, and a drop of radius · µm falls with speed µm/s, approximately. evidently, these values are negligible when compared to the speeds of the random air currents that exist in real environments, which are in the order of cm/s, according the measurements by matthews et al. these internal currents are produced by local all rights reserved. no reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in the copyright holder for this this version posted august , . . https://doi.org/ . / . . . doi: medrxiv preprint differences in temperature and pressure, by the movement of objects or people around the environment, and statistical variation of the pressure. it means that the movement of small suspended particles will be governed by these air currents and they can be dragged until meters or more in minutes. so, these currents are responsible for the movement of dust grains observed by lucretius, and also for the fluctuation and movement of micro drops filmed in the experiments described above. it is important to remember that the coronavirus has a more or less spherical shape with a diameter of the order of nanometers, that is, the drops we dealt with in this work can carry from hundreds to millions of viruses. the last column of table shows the time, ttot, that the drops take to reach the ground starting from a height of · meters. even considering the air at rest, it shows that drops of diameters · µm, · µm, and · µm would remain suspended for several hours in the air. however, the air currents in indoor environments are even more important when they have an air renewal and/or conditioning system that creates a continuous flow of air in a more or less fixed direction. we will evaluate this phenomenon in the case of an aspiration system placed on the ceiling of the environment, producing an airflow in the vertically upward direction, with speed v. the diagram on the side shows the forces acting on it. in this case, the viscous friction force of the air passing through the droplet can compensate for and/or overcome the weight force, causing it to remain stopped and/or be aspirated towards the ceiling. let's consider the equilibrium limit case, when friction exactly compensates for the weight of the droplet and it stays at rest at a certain height of the ground. disregarding langevin's force, the speed of air that holds a drop at rest can be easily calculated for its different sizes. figure shows the air velocity necessary to balance drops of different radii, where we observe that they are very small velocities, of a few mm/s, even for the largest drops considered. that is, if the air conditioning system is not well dimensioned, it eliminates the smallest drops, but it can keep larger drops in suspension and/or drastically decrease its fall times, precisely the drops that have a greater potential for infection because they can carry a greater amount of viruses. for example, a continuous vertical flow of air with a speed of only mm/s, approximately, keeps drops of diameter µm suspended at rest for an unlimited time. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in the copyright holder for this this version posted august , . . finally, we must discuss the effect of heating systems placed on the ground, as they also create an upward airflow and can keep contaminated droplets floating in the air for a long time, increasing the risk of contamination. perhaps, this may be one of the factors that increase the spread of viral epidemics during the winter. it is now experimentally and theoretically demonstrated that airborne contagion by sars-cov- can occur long after an infected person has spoken, coughed, or sneezed in an environment. these scientific results call into question one of the main recommendations of health authorities to contain the outbreak: the distance of m to m between people would be a safe method of prevention. this indication is based only on old studies about the direct transmission by larger drops, dangerously ignoring the contamination by the virus airborne in droplets that remain suspended in the air for several hours, and even days after the environment has been visited by an infected person. this recommendation created in the population the false idea that, by staying two meters from each other, it is not necessary to use a mask or other protections. even the highest leaders of the who conduct daily interviews without a mask. all rights reserved. no reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in the copyright holder for this this version posted august , . . therefore, an important warning must be made: the distance of two meters is not safe for those who do not wear a mask and, if we consider the infection by the eyes, the distance of two meters is not safe even for those wearing a mask. the very high sars-cov- transmission rates in amazonian states in brazil and many abattoirs around the world provide empirical corroboration of the relevance of the airborne way of contagion. these two environments have high air humidity that allows viruses to survive much longer in droplets in suspension or deposited on surfaces. therefore, air humidity seems to be the major climatic factor in the development of the covid- epidemic. on the other hand, apparently, there is no direct relationship between high ambient temperature and decreased transmissibility. besides, the collective immunity in amazonian states may have been achieved with a contamination rate of around % of the population, much lower than predict conventional statistical studies, and which would have an extraordinary impact on pandemic management across the planet. the argument that the wind disperses the drops has made people feel more protected in open places. however, the same wind that can disperse the drops can also carry them and project them on passersby, whether on the beach, on the street, in the elevator, at home, or on public transport. so, in addition to the mask the use of eye protection should also be recommended. it should not be forgotten that drops in suspension can also be deposited on our face, hair, and clothes. finally, another important alert about air conditioning and heating systems comes from our calculations: if they are poorly positioned and/or sized, they can work as a dangerous spreader of viruses. nature des choses (Éditions gallimard, essais folio influenza virus" in douglas and bennett's principles and practice of infectious diseases airborne transmission of sars-cov- : the world should face the reality who writing group: nonpharmaceutical interventions for pandemic influenza, international measures transmission of influenza a in human beings public health agency of canada canadian pandemic influenza plan (appendix f) department of health and human services pandemic influenza plan aerodynamic analysis of sars-cov- in two wuhan hospitals aerosol and surface stability of sars-cov- as compared with sars-cov- physical distancing, face masks, and eye protection to prevent person-to-person transmission of sars-cov- and covid- the airborne lifetime of small speech droplets and their potential importance in sars-cov- transmission toward understanding the risk of secondary airborne infection: emission of respirable pathogens environmental transmission of sars at amoy gardens extensive viable middle east respiratory syndrome (mers) coronavirus contamination in air and surrounding environment in mers isolation wards covid- outbreak associated with air conditioning in restaurant identifying airborne transmission as the dominant route for the spread of covid- mechanistic insights into the effect of humidity on airborne influenza virus survival, transmission and incidence absolute humidity modulates influenza survival, transmission, and seasonality evidence that high temperatures and intermediate relative humidity might favor the spread of covid- in tropical climate: a case study for the most affected brazilian cities association between climate variables and global transmission of sars-cov- survival characteristics of airborne human coronavirus e dilution of respiratory solutes in exhaled condensates toward understanding the risk of secondary airborne infection: emission of respirable pathogens atmospheric science, an introductory survey it is time to address airborne transmission of covid- air velocities inside domestic environments: an important parameter in the study of indoor air quality and climate key: cord- -egbahelm authors: benmarhnia, tarik title: linkages between air pollution and the health burden from covid- : methodological challenges and opportunities date: - - journal: am j epidemiol doi: . /aje/kwaa sha: doc_id: cord_uid: egbahelm the covid- pandemic revealed and exacerbated existing social and economic health disparities and actionable epidemiological evidence is needed to identify potential vulnerability factors to help inform targeted responses. in this commentary, methodological challenges and opportunities regarding the links between air pollution and covid- are discussed with a focus on: i) the role of differential exposure to air pollution across populations and explain spatio-temporal variability of the epidemic spread and resultant mortality; ii) the indirect impacts of interventions treated as natural experiments to control covid- person-to-person spread on air pollution and population health. i first discuss the potential mechanisms between exposure to air pollution and covid- and the opportunity to clearly formulate causal questions of interest through the target trial framework. then, i discuss challenges regarding the use of quasi-experimental designs that capitalize on the differential timing of covid- policies including the selection of control groups and potential violations of the common shock assumption. finally, i discuss environmental justice implications of this many-headed beast of a crisis. in this commentary, i will describe some methodological challenges and opportunities regarding these two types of questions based on the literature (some peer reviewed, some not yet) that is available to date. i will focus on etiological questions, keeping in mind that methodological challenges regarding availability, exhaustiveness and validity of data are definitely an underlying issue ( ) . finally, i will briefly discuss other related topics including environmental justice implications of this many-headed beast of a crisis. mechanisms through which acute exposure to air pollutants, such as fine particles, may impact respiratory health are well documented and include pulmonary inflammation that may reduce lung function through bronchoconstriction or an alteration of the pulmonary immune system ( , ) . in parallel, chronic exposure to fine particle pollution notably exacerbates chronic inflammation with cellular proliferation and extracellular matrix reorganization ( ) and also weakens pulmonary immune response ( ) . several toxicological studies have described such mechanisms ( , ) and a vast body of epidemiological evidence confirms the role of acute and chronic exposure to various air pollutants on respiratory hospital admissions, e.g. chronic obstructive pulmonary disease (copd) ( ) or asthma exacerbation ( ) . furthermore, several papers reported that exposure to air pollution exacerbates the severity of various respiratory infections ( ) such as influenza ( ) and possibly another coronavirus infection the sars ( ) . a recent study found that chronic exposure to pm . and ozone increases the risk of acute respiratory distress syndrome among older adults in the us ( ) . based on this background knowledge, it is conceivable to suggest that exposure to air pollution may influence the variability in the severity of covid- symptoms or contribute to explaining it is also important to re-emphasize that effect modification is differing levels of air pollution. scale dependent and that for such type of public health prioritization efforts, the additive scale has been shown to be preferable ( ) . another potential approach to better understand the air pollution link for covid- symptoms severity would be to focus on alternative outcomes, such as spatio-temporal changes infection fatality rates instead of counts of covid- cases or deaths. this design would better capture how exposure to air pollutants influence variability in symptoms severity or if the probability of dying from covid- in a given population (with detailed information regarding covid- cases and time in the denominator) is influenced by air pollution levels. of course, getting accurate statistics and accurate numerators and denominators to estimates population attack or infection fatality rates can be an extremely challenging task ( ), but hopefully such surveillance data collection will be improving with time. in this context, the target trial framework ( , ) can be particularly useful when designing a research question regarding the links between exposure to air pollution and covid- . the benefits of using the target trial framework to clarify assumptions, causal contrasts and actionable implications has been demonstrated for other topics ( ) ( ) ( ) ( ) by clearly specifying the hypothetical manipulation that is intended in the first place. in this pandemic context with limited available data and time-sensitive actionable evidence ( ) , dedicating a preliminary phase to clearly identifying the intended hypothetical manipulation and how targeted actions based on background air pollution levels would maximize potential benefits, may be valuable. and the target trial framework can be a suitable tool. the policies ( ) . for instance, it may be challenging to identify an appropriate control group that would have a parallel trend for the outcome of interest given that the timing and intensity of policies are strongly correlated with the spatio-temporal variation of the spread of the disease. indeed, jurisdictions that may first undertake actions to control covid- person-to-person spread may also suffer from earlier and higher rates which motivates such policies. given the known timing of the disease incubation period and lagged effects ( , ) , it is likely to initially observe an increase in the counted cases after the implementation of the policy of interest. this highlights the importance of accounting for both pre-trends and lagged expected effects when designing a study to evaluate the health impact of such policies. it has also been shown that anticipation behaviors may take place where people took social distancing precautions before any official restrictions were in place ( ) . several jurisdictions also implemented various policies at the same time and local communities or institutions such as universities may have implemented additional non-official preventive measures. this could potentially lead to violations of the common shock assumption. furthermore, some spillover effects are expected where the covid- responses may lead to drastic population mobility ( ) or where abatement in traffic emissions may impact other jurisdictions across administrative borders. given these potential challenges, it is particularly important to design an appropriate identification strategy and adopt various sensitivity analyses and falsification tests. finally, it is also important to emphasize that exposure to air pollution is not random and may intersect with other social determinants of health. indeed, differential exposure and susceptibility where socio-economic and race/ethnic minorities bear disproportionate burden from air pollution are well documented ( ) ( ) ( ) ( ) . such environmental justice issues are critical and may contribute to explain the reported differential impacts of covid- on race/ethnic communities in the us occupational health ( , ) can also provide critical actionable evidence by identifying highrisk workers given that some workplace conditions (e.g. health care providers and caregivers; water and wastewater sector; construction workers…) may increase severity of health outcomes or interact with other risks such as extreme heat ( ) . at the same time, other challenges include the capability to manage compound risks regarding extreme weather events such as extreme heat ( ) . considering the double jeopardy that some communities may face regarding covid- and the disproportionate burden they face during extreme weather events as well as conflicts between covid- preventive actions and 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or pollution? a review of theory and evidence from longitudinal environmental justice studies trump orders agencies cut environment reviews, citing 'economic emergency'. the guardian, the covid- pandemic: a moment for exposure science occupational risks for covid- infection working from home in the time of covid- : how to best preserve occupational health? heat warning and public and workers' health at the time of covid- pandemic protect the vulnerable from extreme heat during the covid- pandemic key: cord- -qkhfp l authors: steiner, daniel j.; cognetti, john s.; luta, ethan p.; klose, alanna m.; bucukovski, joseph; bryan, michael r.; schmuke, jon j.; nguyen-contant, phuong; sangster, mark y.; topham, david j.; miller, benjamin l. title: array-based analysis of sars-cov- , other coronaviruses, and influenza antibodies in convalescent covid- patients date: - - journal: biorxiv doi: . / . . . sha: doc_id: cord_uid: qkhfp l detection of antibodies to upper respiratory pathogens is critical to surveillance, assessment of the immune status of individuals, vaccine development, and basic biology. the urgent need for antibody detection tools has proven particularly acute in the covid- era. we report a multiplex label-free antigen microarray on the arrayed imaging reflectometry (air) platform for detection of antibodies to sars-cov- , sars-cov- , mers, three circulating coronavirus strains (hku , e, oc ) and three strains of influenza. we find that the array is readily able to distinguish uninfected from convalescent covid- subjects, and provides quantitative information about total ig, as well as igg- and igm-specific responses. what they do not provide, however, is a broader understanding of the human immune response to sars-cov- infection, or illuminate potential relationships between covid- infection and previous infections (and immunity to) other respiratory viruses including circulating coronaviruses that cause the common cold. to address these goals, multiplex analytical techniques are required. a bead-based multiplex immunoassay for six coronaviruses infecting humans (pre-sars-cov- ) has been reported, and more recently a -plex assay on the quanterix platform focused on sars-cov- antigens has been described. despite these advances, there remains a significant need for analytical methods able to rapidly quantify antibodies not only to sars-cov- , but also to other coronaviruses, and other pathogenic viruses. most importantly, these must be able to discriminate among responses to different closely related viruses and different antigens from the same virus. to address this need, we have developed a prototype -plex array on the arrayed imaging reflectometry (air) platform. air is a label-free multiplex sensor method in which the surface chemistry and deposition of capture molecules to form a microarray on a silicon chip are carefully controlled such that s-polarized hene laser light at a . º incident angle to the chip undergoes total destructive interference within the surface film. binding to any probe spot on the array degrades the antireflective condition in proportion to the amount of material bound, yielding an increase in the reflected light as observed by a ccd camera. by comparing the intensity of the reflected light to an experimentally validated model, the thickness change for each spot, and therefore the quantity of each analyte in the sample, may be precisely and sensitively determined. we have previously reported the utility of influenza antigen arrays fabricated on the air platform for assessment of anti-influenza antibodies in human, animal, and avian serum, , both as a tool for viral surveillance and for assessment of the efficacy of a candidate vaccine. we have also demonstrated that air is scalable at least to -plex assays, used for discriminating different influenza virus serotypes. , we therefore anticipated that the platform would be useful as a way to quantify anti-sars-cov- antibodies, antibodies to other coronaviruses including circulating ("common cold") strains, and other respiratory pathogens including influenza. here, we discuss the development and testing of a mixed coronavirus / influenza antigen panel on air, and its application to analyzing the coronavirus antibody profile of a cohort of convalescent covid- patients and subjects of unknown disease status. material sources: for air assays, sars-cov- , sars-cov, mers, and influenza type a and b antigens were obtained from sino biological, inc., and are described in more detail below. most antigens were supplied as lyophilized material and reconstituted at the recommended concentrations using -mΩ water, while the remaining antigens were supplied frozen on dry ice. pbs-et was prepared as phosphate buffer ( mm monobasic sodium phosphate, mm dibasic sodium phosphate, mm nacl) with . % w/v tween- and mm edta. aminereactive substrates for fabrication of air arrays were provided by adarza biosystems, inc. for elisa assays, sars-cov- full-length spike and rbd were produced in-house using a mammalian expression system, , as was influenza a/h n /california hemagglutinin. hcov- e and hcov-oc spike proteins (baculovirus-expressed) were obtained from sino biological. tetanus toxoid (ttd) was obtained from calbiochem. antigen probe formulation: prior to microarray fabrication, antigens were buffer-exchanged and concentrated using amicon centrifugation filters (emd millipore) into phosphate buffer at ph . and ph . prior to use. during development, several printing concentrations and/or solution ph values of each antigen were tested, along with sugar additives (glycerol, trehalose) in order to optimize spot uniformity and morphology as well as initial probe thickness. preparation of arrays: arrays were printed on amine-reactive silicon oxide substrates (adarza biosystems, inc.) using a scienion sx piezoelectric microarrayer (scienion, a.g.) with spot volumes of approximately pl. six spots were printed for each antigen, the final layout of which is shown in figure . the number of spots arrayed was not critical to robust analytical performance or statistical analysis. each spot consists of approximately pixels when imaged by the ccd in an air chip reader (adarza biosystems, inc.), with each pixel representing a discrete interrogation of a unique probe surface region. therefore, averaging these pixel values together produces an inherently reliable measure of analyte-to-probe response. dilutions of polyclonal anti-fluorescein (anti-fitc, rockland inc.), were printed as negative intra-array controls. after printing, chips were mounted onto adhesive strips at appropriate spacing for -well plates, and then placed into mm sodium acetate buffer (ph ) for minutes. next, a . % bsa solution was added to each well resulting in a final bsa concentration of . % to passivate the remaining amine-reactive surface functionality. after blocking for minutes, the chips were transferred to new wells containing % fetal bovine serum (gibco) in pbs-et as a secondary block, and incubated for min. this step was required to reduce nonspecific binding from human serum at the assay endpoint. the chips were then rinsed briefly ( min) in new wells containing pbs-et, then transferred to wells containing microarray stabilizer solution (surmodics ivd). after a -minute incubation, the chips were dried at °c in an oven for min. this last step renders the sensors shelf-stable, until use in assays performed later. igm, or % fbs as a negative control. each of these conditions was produced in duplicate. secondary antibodies were diluted to μg/ml for both goat α-higg (jackson immunoresearch) and rabbit α-higm (rockland, inc.) in adarza diluent. after one hour of incubation with secondary antibodies at room temperature, chips were washed twice for minutes in pbs-et, then rinsed with water and dried with nitrogen as before. data analysis: air images were analyzed using the adarza ziva data analysis tool. probe spots with major defects or debris were manually flagged and eliminated, and minor defects in spot quality were automatically identified and excluded from the median intensity measurement. the median intensity values were converted to median thickness values using a best-fit line to an experimentally derived reflectance model. then, the median thickness values were further processed in microsoft excel as described below, and are referred to simply as "thickness" hereafter. while anti-fitc spots were designed to serve as an intra-chip normalizer, these were not used as such due to the unexpected presence of anti-goat igg antibodies in some single donor human serum samples. therefore, the blank area served an intra-chip normalizer to mitigate any variation in the reactivity of the surface chemistry between air chips. the thickness of the blank area was subtracted from the thickness of each probe spot to produce "normalized thickness" values for each probe spot. all of the normalized thickness values across replicate chips (n= ) were averaged together (maximum of n= probe spots) for each antigen, and the standard deviation was calculated. the average thickness for each antigen in the fetal bovine serum (fbs) control was subtracted from the average thickness obtained for each antigen in each subject sample to produce the "normalized thickness change (Δ thickness)." in the case of the polyclonal antibody titration, the control chip was incubated in a matrix of fbs and pnhs. elisa assay: serum igg titers specific for sars-cov- proteins and selected non-coronavirus proteins were determined by elisa as described previously. human serum standards were used to assign weight-based concentrations of antigen-specific igg as previously described, with the limit of assay sensitivity set at . μg/ml for all antigens. , results: . this is as expected given the prevalence of these viruses in the general population. addition of an anti-sars-cov- polyclonal antibody raised against the sars-cov- spike protein receptor binding domain (rbd) at μg/ml produced a strong signal on all three rbdcontaining antigens (s + s ecd, s , and rbd). overall response to the polyclonal antibody was well-behaved, and titrated to zero as expected ( figure c and d) . quantitative data are presented in Ångstroms of build. at the highest concentrations, significant cross-reactive binding to the hcov- e spike protein was observed, as well as some binding to the hcov-oc spike protein and mers s . calculated limits of detection for these data were . ng/ml (sars-cov- s + s ecd), . ng/ml (sars-cov- s ), and . ng/ml (sars-cov- rbd). however, these should be viewed as provisional, and subject to optimization. response of a commercial anti-sars-cov- rabbit polyclonal antibody (pab) on the array. (a) array exposed to array exposed to % fbs + % pnhs; (b) array exposed to μg/ml anti-sars-cov- pab in % fbs + % pnhs. strong responses to sars-cov- s +s ecd, s , and rbd are observed, as well as smaller cross-reactive responses to hcov- e, hcov-oc , and mers spike proteins; (c) quantitative data for the titration. convalescent serum array responses were compared to an elisa assay ( figure ). as elisa values were all igg-specific, and air data discussed thus far (obtained in a "label-free" mode) was a combination of igg and igm-specific responses, these results would not be expected to match precisely. differences in the expression system used for antigen production (baculovirus for commercial antigens used in air; hek t cells used for antigens used in the elisa assays) could also lead to differences. however, overall trends for sars-cov- antigens correlate well, as shown in figure . to provide further detail with regard to the response, air assays were run using secondary anti-igg and anti-igm antibodies to determine class-specific responses for a subset of samples ( figure ). was the case with assays run using the laboratory air assay, analysis using the ziva system readily discriminated between negative and convalescent samples (figure ). three putative convalescent covid- samples gave responses on all sars-cov- antigens that were below the threshold for a positive response (two standard deviations above the average of the negative samples). this is analogous to the air and elisa results obtained for sample hd , as described above. the remaining convalescent samples gave strong responses on at least one sars-cov- antigen, with many responding strongly to both rbd and s ( figure ). with at least one sars-cov- antigen response above threshold. health and disease result from many factors, including the overall landscape of a person's immune system. as such, methods for profiling antigen-specific antibody titers to a range of diseases in addition to the disease of primary current interest are of utility when studying the disease. to that end, we have presented preliminary data on a -plex array on the air platform, developed in response to the need to study sars-cov- but incorporating antigens for other coronaviruses and influenza. responses to sars-cov- antigens on the array effectively discriminated between serum samples from uninfected and covid- convalescent subjects, with generally good correlation to elisa data. follow-up assays demonstrated that exposure of the arrays to anti-igg and anti-igm antibodies enabled discrimination of antibody isotype. an important aspect of this work is the ability to evaluate anti-sars-cov- immunity in the context of the individual's overall immune landscape. because available chip real estate allows for substantial expansion of the multiplex capability of the array, in ongoing efforts we will add additional antigens for other strains of influenza (by analogy to our previous work ), as well as other upper respiratory infections such as respiratory syncytial virus and metapneumovirus. other coronavirus antigens including nucleocapsid (n) are also likely candidates for addition to the array, as they are known to produce an immune response (as seen in the elisa results, for example). thus, the flexibility of the air platform will prove useful not only in the current pandemic, but as other viruses inevitably emerge. report from the american society for microbiology covid- international summit targets of t cell responses to sars-cov- coronavirus in humans with covid- disease and unexposed individuals anti-sars-cov- virus antibody levels in convalescent plasma of six donors who have recovered from covid- serology assays to manage covid- developing antibody tests for sars-cov- " the lancet sars-cov- seroconversion in humans: a detailed protocol for a serological assay, antigen production, and test setup diagnostic value and dynamic variance of serum antibody in coronavirus disease development and clinical application of a rapid igm-igg combined antibody test for sars-cov- infection diagnosis profiling early humoral response to diagnose novel coronavirus disease (covid- ) test performance evaluation of sars-cov- serological assays development and evaluation of a multiplexed immunoassay for simultaneous detection of serum igg antibodies to six human coronaviruses ultra-sensitive high-resolution profiling of anti-sars-cov- antibodies for detecting early seroconversion in covid- patients a theoretical and experimental analysis of arrayed imaging reflectometry as a sensitive proteomics technique validation of arrayed imaging reflectometry biosensor response for protein-antibody interactions: cross-correlation of label-free, arrayed sensing of immune response to influenza antigens a multiplex label-free approach to avian influenza surveillance and serology crowd on a chip: label-free human monoclonal antibody arrays for serotyping influenza characterizing emerging canine h influenza viruses sars-cov- seroconversion in humans: a detailed protocol for a serological assay, antigen production, and test setup a serological assay to detect sars_cov- seroconversion in humans investigation of non-nucleophilic additives for reduction of morphological anomalies in protein arrays memory b cell expansion by seasonal influenza virus infection reflects early-life imprinting and adaptation to the infecting virus assignment of weight-based antibody units to a human antipneumococcal standard reference serum, lot -s statistical method for determining and comparing limits of detection of bioassays we thank alicia papalia for assistance with human samples, and florian krammer for the generous donation of plasmids for sars-cov- antigen production (s + s ecd and rbd). key: cord- - u authors: raciti, loredana; calabrò, rocco salvatore title: can volcanic trace elements facilitate covid- diffusion? a hypothesis stemming from the mount etna area, sicily date: - - journal: med hypotheses doi: . /j.mehy. . sha: doc_id: cord_uid: u in december , severe cases of pneumonia of unknown aetiology were reported in wuhan city, in china. lately, the pneumonia was related to the severe acute respiratory syndrome coronavirus- (sars-cov- ), and the diseases was termed coronavirus disease- (covid- ). at the end of january , the infection spread all over italy, but with high infection rates and mortality in the northern part, especially in lombardy, the most industrialized and polluted region of the country. it is noteworthy that a strong association between severe viral respiratory disease and air pollution has been described. air pollutant could be solid particles, liquid droplets, or gases and can be of natural origin (such as ash from a volcanic eruption) or released from motor vehicle depletes (carbon monoxide gas) or factories (sulfur dioxide). volcanic eruptions release large amounts of sulphuric acid, hydrogen sulfide, and hydrochloric acid into the atmosphere. pulmunary diseases spread by means of small droplets in the breath, also called aerosols, and air pollution may facilitate the outside survival of viruses. we suppose that ash and gases emitted from the mount etna contributed to air pollution, potentially favouring the major contagion of covid- in the eastern flank of the mountain, as in catania city. in fact, ash and gases (with regard to radon) are usually particularly intense in winter, with a reduction of emission of specific metals with warmer weather. this is the first paper that elaborates the hypothesis of a potential role of volcanic gases and heavy metals-related air pollution, combined to specific climatic conditions and regional topography, in favouring severe covid- diffusion in sicily. clinical and epidemiological studies are needed to support the hypothesis and plan the due prevention and awareness-raising campaigns. mount etna is the highest active volcano in europe, and it is located on the east coast of sicily, between the cities of messina and catania. the etna covers an area of , km with a basal circumference of km ( figure ) [ ] . during the uprising of the volcanic eruptive plume, soluble ash fraction and solid particles are emitted [ ] . these latter include gases trapped in the volcanic rocks, dissolved or dissociated gases in magma and lava or ashes, or gases emanating directly from lava or indirectly through ground water heated by the volcanic action. volcanoes may discharge flows of ash and gas up to kilometres away, with the generation of cloud columns - km high and blasting about km-wide chunk off the tip of the volcano [ , ] . in volcanic areas, the emissions and deposits of volcanogenic elements are key factors for geochemical mobility of trace elements (tes), and their distribution in the environment might impair animals and human health. among all the volcano elements, metals represent the main natural source [ , ] . fine particulate matter with an aerodynamic diameter of . m or less (pm . ), m or less (pm ) are sulfur dioxide (so ), nitrogen dioxide (no ), carbon monoxide (co) and ozone (o ) that affect airways through inhalation and exacerbate the susceptibility to and severity of respiratory virus infections [ ] [ ] [ ] . moreover, trace elements deposit in soil and plants representing a high risk of ingestion of metals by the population with serious toxic effects for public health [ ] . when added to other environmental toxicants, such as herbicides, pesticides and industrial emissions, heavy metals are associated with an increased risk of neurodegenerative diseases [ ] [ ] [ ] [ ] . a recent study evaluating the level of tes in scalp hair of school-children living around the mount etna area, showed a high level of metals and nickels [ ] . moreover, areas of different flank present different susceptibility to neurodegenerative diseases, being eastern to southern flank more exposed than western one [ ] . heavy metals have been dosed in the groundwater of the etna (used for water plants or to drink), especially in the eastern and southern sectors of the volcano, and they are believed to contribute to intoxication of public health and to pulmonary or neurodegenerative diseases [ , , ] . moreover, food, especially, fishes are highly concentrate of several metals [ , ] , and this is likely related to gases emitted by the etna mountain [ ] [ ] [ ] , that blow from the eastern to the southern of the volcano, most of the time westerly to north-westerly trade winds, emitting about % of the global volcanic heavy metals, including radon [ ] . radon ( rn) is a noble gas, invisible, odorless, tasteless, and short-lived decay product of uranium ( u), whose high activity concentration in radon emissions at the topographic surface is produced by convective flow of gases that facilitate the transport of radon from greater depth within soils ( ) ( ) . the collapsing flanks are bordered by numerous active faults [ ] that cross urban areas, and are likely the locations of high soil degassing and elevated radon activities [ ] . in the areas of strong degassing, particularly in the east and south-west flanks of the volcano, due to continuous tectonic deformations and gravitational collapses [ ] [ ] , radon activity was up to , bq/m [ ] . in sicily radon has been highly related with lung cancer ( ) ( ) , and could favour pulmonary infections, as well as other elements do [ ] . in december , severe cases of pneumonia of unknown aetiology were reported in wuhan city, in china. lately, the pneumonia was related to the severe acute respiratory syndrome coronavirus- (sars-cov- ), previously named novel coronavirus ( -ncov), and the diseases was termed coronavirus disease- (covid- ) [ ] [ ] . at the end of january , after the first case in codogno, the infection spread all over italy, but with high infection rates and mortality in the northern part, especially in lombardy, the most industrialized and polluted region of the country. it is noteworthy that a strong association between severe viral respiratory disease and air pollution has been described [ ] . air pollutant could be solid particles, liquid droplets, or gases. a pollutant can be of natural origin or man-made and classified as primary or secondary, based on natural origin (such as ash from a volcanic eruption: primary) or released from motor vehicle depletes (carbon monoxide gas) or factories (sulfur dioxide) [ ] [ ] . the inhalable fraction of particles in the air that can enter the nose or mouth depends on external wind speed and direction, as well as on the particle-size distribution by aerodynamic diameter [ ] [ ] [ ] . two alternative size-selective criteria, often used in atmospheric monitoring, are pm and pm . . pm is defined by iso as "particles which pass through a size-selective inlet with a % efficiency cut-off at μm aerodynamic diameter (defined as "thoracic convention"), whereas pm . as "particles which pass through a size-selective inlet with a % efficiency cut-off at . μm aerodynamic diameter"; these latter correspond to the "high-risk respirable convention" [ ] . then, particles with a diameter smaller than μm can enter the bronchi, while the ones with an effective diameter smaller than . μm can enter as far as the gas exchange region in the lungs [ ] , because of prolonged permanence in the air than heavier particles, bypassing the nose and throat. high concentrations of pm . particles characterize the air of hubei region in china, as well as the po valley (italy), revealing the possible correlation between the major distribution of covid- and the concentration of pollutants [ ] . in fact, pollution insult decreases airway ciliary activity, and increases excessive mucus production, exposing to progressive and chronic inflammation of the respiratory airways with severe respiratory diseases after viral infections. several factors contribute to individual reactions to air pollutants: the type of pollutant a person is exposed to, the degree of exposure, and the individual's health status and genetics [ ] . to this end, air pollution is a significant risk factor for viral respiratory infections, heart disease, chronic obstructive pulmonary disease, stroke and lung cancer [ ] [ ] . origin of pollutant could be volcanoes emissions. volcanic eruptions release large amounts of sulphuric acid, hydrogen sulfide, and hydrochloric acid into the atmosphere. these gases react with other atmospheric particles to form aerosols and eventually return to earth as acid rain, having a number of adverse effects on the environment and human life [ ] . pulmunary diseases spread by means of small droplets in the breath, also called aerosols [ ] , and air pollution may facilitate the outside survival of viruses. on the other hand, heavy metals origin from geologic cycle (e.g. erosion, volcanic activity, windblown dust, etc.) and other industrial or artificial activities (industrialization, fuel combustion, roadway traffic, etc.). indeed, metals accumulate in aquatic and terrestrial systems with biomagnification in food chain, after being conveyed by air further contributing to air pollution. [ ] . another active and very dangerous asian volcano is the taal, on the island of luzon, philippines. in december , an alert level to four due to an explosive eruption was raised and a "total evacuation" order to population living within -kilometer around the volcano was done for the high risk of toxicity of volcanic ash (that could travel hundreds of kilometres an hour), toxic gases emitted from the eruption, and mud flows caused by ash mixing with water vapour in the atmosphere. a column of ash raised up as it erupts on january shower down on the south-west sector of the volcano [ ] . then, volcanoes gases and heavy metals could contribute to air pollution of the china. as well as in china, we suppose that ash and gases emitted from the mount etna contributed to air pollution, potentially favouring the major contagion in the eastern flank of the mountain, as in catania. moreover, the reduction in number of contagion and virulence in the last month would be justified by the interaction of several factors, as social distances and lockdown, and environmental issues, including a warmer climatic season and concentration of gases emitted. in fact, ash and gases are usually particularly intense in winter, with a reduction of emission of specific metals with warmer weather [ ] . in particular, radon concentration is generally lower in summer, when air temperature is higher. a negative correlation between radon concentration and air temperature has been found with consequent lowering of indoor radon concentration. on the other hand, no seasonal cyclicity due to meteorological parameters was found. then, active faults ( - m) and volcanic substrates could be an alternative explanation of radon and other pollution elements variation [ ] . based on all this information, our hypothesis is that the volcano ash/gas together with climatic conditions may have promoted a longer persistence of the viral particles in the air, mleading to a higher prevalence of covid- in the eastern to southern part of sicily. air pollution has been suggested as cofactor of the spread of covid- in industrial cities, in an attempt to explain the major incidence of the virus infection in the north of italy, especially in the po valley. the main involved italian cities are, indeed, lodi, cremona and bergamo, defined as the "industrial triangle" which is characterized by a high density of factories, traffic and intensive agriculture with the highest pollution levels [ ] . in sicily, the highest incidence of infection was in catania, followed by messina and palermo, although this latter city is the biggest sicilian one (see fig and ) . because of its altitude and geographical position of mount etna, the volcano displays a role in the exposure of the flanks to the dominant winds: most of the rainfall is on the eastern flank, as the volcano itself induces condensation of wet air masses coming from the ionian sea, where catania is [ ] . gases blow from eastern to the southern due to the westerly to north-westerly trade winds [ ] . in fact, quantitative of heavy metals is more representative in the ground waters in the eastern and southern sectors of the volcano. the presence of tes in the water is the results of degassing of magmatic volatiles, such as radon, by the known faults or faults that are not clearly visible at the surface ( , ) . due to direction of gas emissions, we should expect (how it is actually) a lower incidence of infectious in the western flank of the volcano (palermo, trapani, etc) than the eastern or southern (messina and catania), as demonstrated by prevalence data in figure and . on the other hand, the reduction of specific and dangerous gases emitted with warmer weather, reveals a potential correlation between the distribution of severe covid- in sicily and the metals diffusion resulting from a combination of volcano emissions, locally climatic conditions, population genetic predispositions and regional topography. this is the first paper that elaborates the hypothesis of a potential role of volcanic gases and heavy metals-related air pollution, combined to specific climatic conditions and regional topography, in favouring severe covid- diffusion in sicily. the idea stems from the fact that tes likely lead to a major susceptibility of respiratory system to infection. based on the frontera hypothesis, heavy metal air pollutants combined to climatic conditions prolonged the permanence of the virus in the air, as well as the susceptibility to pulmonary virus infection. in biancavilla, town located in in eastern sicily, a relation between a higher risk of mesothelioma, as well as chronic obstructive pulmonary disease, and asbestiform fiber used in the local building industry (fluoro-edenite) was found. then, preventive manoeuvres were done, such as covering with asphalt of roads previously paved with local soil materials, and removal of sources of dust in the urban area [ ] [ ] . moreover, a recent environmental survey showed the presence of both c. neoformans and c. gattii species complexes in the environment. in particular, these species were previously recovered from messina (northeast sicily) in several samples of bird excreta, as well as in eucalyptus camaldulensis, prunus dulcis (almond), and ceratonia siliqua (carob) [ ] [ ] [ ] . in , trovato et al found that c. neoformans and c. gattii species colonize olive trees, samples from olive trees collected from different sites in eastern sicily around mount etna, as well as carob trees [ , ] . assays showed that volcanic soil is a suitable substrate for the growth of c. neoformans and c. gattii species for the characteristics of the soil rich in iron and copper, potassium, phosphorus and magnesium, but poor of nitrogen and calcium [ ] . therefore, the blastospores and basidiospores producted by cryptococcal yeasts represent a potential source of infection since soil aerosols could transfer small cells and spores (and potentially virus particles) in pulmonary alveoli of humans and animals causing the onset of the infection [ ] . pulmunary diseases caused by tes were also demonstrated by censi et al. [ ] . it is noteworthy that two rare pulmonary diseases, i.e. dendriform pulmonary ossification and pulmonary microlithiasis were related to inhalation of atmospheric particles released by industrial practices or hydrocarbon combustion [ ] . one possible cause of these pathologies is the disposal of metal dust with large affinity to phosphate precipitation, such as lanthanides (yln), produced during the manufacture of mirrors, optical lenses, and certain electronic [ , ] . lanthanides can crystallize in interstitial lung spaces and it could be diagnosed by broncho-alveolar lavage fluid dosing yln content. pulmunary characteristics are phosphatic microcrysts in intraaveolar areas of the lungs [ ] . the microcrysts may precipitate with yln-phosphates and progress to pulmonary fibrosis due to dissolution of atmospheric particles [ ] . due to the increasing utilization of yln for agricultural and industrial applications, the measurement of yln fractionation in lung fluid has the potential to be a viable tracer of human exposure to heavy fluxes of fine particulates enriched in heavy metals pollutants. based on these information, we could hypothesize that volcanic trace elements might play an important role in the predisposition and development of viral infection, as covid- , and thus prevention of respiratory diseases due to pollutions is fundamental. because of the underestimation of volcanic gases emitted, we would like to encourage an accurate surveillance of the level of heavy metals and air pollution in the predisposed areas. our hypothesis may imply a higher level of attention to the risk of infection spread in sicily. it would be very important to carry out a clinical and epidemiological survey to identify heavy metals in soils and water, especially in the exposed flank areas of the volcanoes, reducing the usage and consumption of products with the higher levels of tes. further epidemiological and ecological surveys to confirm our hypothesis should be carried out. the authors state neither conflict of interest nor financial support. lava flow hazards at mount etna: constraints imposed by eruptive history and numerical simulations tephra fallout of etna flank eruption: analysis of the deposit and plume dispersion endogenous magma degassing and storage at mount etna eruptive and diffuse emissions of carbon dioxide from etna volcano air pollution and respiratory viral infection so emissions at mt. etna with particular reference to the period - 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". recognition, evaluation, control. news and views from diamond environmental limited earth observation data group arpa lombardia: air pollutants monitoring fundamentals of air pollution global seasonal influenza-associated mortality collaborator network three active volcanoes in china and their hazards three active volcanoes in china and their hazards three active volcanoes in china and their hazards preliminary indoor radon measurements near faults crossing urban areas of mt. etna volcano (italy). front public health regional air pollution persistence links to covid- infection zoning atmospheric sources ad sinks of volcanogenic elements in a basaltic volcano natural and anthropogenicfactors affecting groundwater quality of an active volcano adverse health effects of fluoro-edenitic fibers: epidemiological evidence and public health priorities mortality from chronic obstructive pulmonary disease and pleural mesothelioma in an area contaminated by natural fiber (fluoro-edenite) serotyping of cryptococcus neoformans isolates from environmental and clinical sources in extreme southern italy (calabria and sicily, central mediterranean area) molecular subtyping of clinical and environmental strains of cryptococcus neoformans variety neoformans serotype a isolated from southern italy cryptococcus neoformans/ cryptococcus gattii species complex in southern italy: an overview on the environmental di?usion of serotypes, genotypes and mating-types cryptococcus neoformans and cryptococcus gattii species complex isolates on the slopes of mount etna environmental distribution of cryptococcus neoformans and c. gattii around the mediterranean basin rare earth elements distribution in grapevine varieties grown on volcanic soils: an example from mount etna yttrium and lanthanides in human lung fluids, probing the exposure to atmospheric fallout inhalation of hydrocarbon combustion products as a cause of dendriform pulmonary ossification long-term occupational risk of rare-earth pneumoconiosis. a case report as investigated by neutron activation analysis dissolution of functional materials and rare earth oxides into pseudo alveolar fluid dendriform pulmonary ossification in patient with rare earth pneumoconiosis report of two cases with unique findings fig. . shows the location of mount etna, with images of its eruptions valle bove ; c: etna view landing to catania airport; d: etna view from giarre, a city in the eastern flank of the mountain; e: strombolian etna eruption with high km of ash emission weekly reported numbers of positive cases for covid- in sicily, evaluated per single province *legend: decreto "zone rosse": national decree where "red zones" where closed without any possibility to go to or to travel from all these individualized areas (lumbardy); decreto #iorestoacasa": national decree with any limitations to go out, unless strictly necessary and to keep social distances (quarantine effort); decreto "chiudi italia": all commercial activities were suspended key: cord- - cto y authors: kruizinga, matthijs d.; essers, esmée; stuurman, f. e.; zhuparris, ahnjili; van eik, nellie; janssens, hettie m.; groothuis, iris; sprij, arwen j.; nuijsink, marianne; cohen, adam f.; driessen, gertjan j. a. title: technical validity and usability of a novel smartphone‐connected spirometry device for pediatric patients with asthma and cystic fibrosis date: - - journal: pediatr pulmonol doi: . /ppul. sha: doc_id: cord_uid: cto y background: diagnosis and follow‐up of respiratory diseases traditionally rely on pulmonary function tests (pfts), which are currently performed in hospitals and require trained personnel. smartphone‐connected spirometers, like the air next spirometer, have been developed to aid in the home monitoring of patients with pulmonary disease. the aim of this study was to investigate the technical validity and usability of the air next spirometer in pediatric patients. methods: device variability was tested with a calibrated syringe. about subjects, aged to , were included in a prospective cohort study. fifty‐eight subjects performed conventional spirometry and subsequent air next spirometry. the bias and the limits of agreement between the measurements were calculated. furthermore, subjects used the device for days at home and completed a subject‐satisfaction questionnaire at the end of the study period. results: interdevice variability was . % and intradevice variability was . %. the average difference between the air next and conventional spirometry was ml for forced expiratory volume in second (fev ) and ml for forced vital capacity (fvc). the limits of agreement were − ml and + ml for fev and − ml and + ml for fvc. about % of fev measurements and % of fvc measurements at home were acceptable and reproducible according to american thoracic society/european respiratory society criteria. parents scored difficulty, usefulness, and reliability of the device . , . , and . out of , respectively. conclusion: the air next device shows validity for the measurement of fev and fvc in a pediatric patient population. diagnosis and longitudinal follow-up of pulmonary diseases have relied on pulmonary function tests (pfts) since the nineteenth century. traditionally conducted in the clinic, spirometry can be a difficult technique, and the accuracy and repeatability depend on many factors such as equipment, patient effort, and supervision and encouragement of a technician. nevertheless, a single pft is no more than a snapshot of disease activity, and is unable to capture the variability of symptoms in chronic pulmonary disease. longitudinal data on a regular basis regarding pulmonary health could be very valuable for patients, clinicians, and clinical researchers, and this could be obtained by performing pfts at the patients' home. an increase in readily available objective longitudinal data could be particularly useful in pediatrics, as children often find it difficult to perceive and express the severity of their symptoms. , researchers have investigated the clinical value of home-based measurements of several devices for pediatric asthma and cystic fibrosis (cf). while pulmonary outcomes were correlated to disease activity, the devices appeared to offer little benefit for clinical practice in terms of reduced admission rates, better disease control, or slower decline in pulmonary function. [ ] [ ] [ ] since then, improvements in technology have allowed for the development of devices for measurement of complete flow-volume curves at relatively low cost. an example is the air next spirometer, a bluetooth connected device, allowing patients to perform spirometry tests with a smartphone. use of the device has been reported in adult patients, but not yet in the pediatric population. , before implementation in pediatric clinical care or clinical trials, a comprehensive technical validation of the device must be performed, consisting of the assessment of intraand interdevice variability, comparison with conventional spirometry, as well as the assessment of usability for pediatric patients. the aim of this study is to determine the agreement between the air next spirometer and conventional spirometry and to evaluate the usability of the device for children and parents when used at home. this analysis was part of a study investigating a novel homemonitoring platform (chdr more) in pediatrics. during this study, pediatric patients with controlled asthma (n = ), uncontrolled asthma (n = ), and cf (n = ) were recruited from the outpatient clinic of the hospitals. all children were aged between and years. asthma control was defined using the global initiative for asthma criteria and asthma control questionnaire (cutoff > . points). , children and parents were given a -minute training and practice session and were asked to perform pfts once daily with the mobile device for a duration of days. when logistically feasible, children visited the hospital to perform a conventional spirometry test at the outpatient clinic at the beginning or end of the study period and performed an air next spirometry test during the same visit. the sequence of tests was chosen based on preference for each patient. the air next device cannot be manually calibrated. we used a calibrated syringe (viasys, conshohocken, pa) with a capacity of ml to evaluate accuracy and the inter-and intradevice variability. the syringe was used to push the complete capacity through an air next device times per device on devices with a single turbine. in addition, the syringe was used on different turbines with a single air next device. ats and ers acceptability guidelines were used to judge and grade pft quality (grade a-f from best to worst). spirometry maneuvers were acceptable if the start was rapid and without hesitation, the | course of the expiratory maneuver was continuous, without any artefacts or evidence of coughing in the first second and if the end of the maneuver did not show early or abrupt interruption. the difference between the best two acceptable fvc and fev should have been less than ml. at least three maneuvers were performed per spirometry session. when it was difficult to obtain reproducible maneuvers during supervised measurements, a maximum of maneuvers per patient were performed and the usable maneuvers were used. for home use, subjects were instructed to perform three maneuvers per session and were able to perform two additional measurements when appropriate (for example, mistiming of the forced exhalation or application errors). subjects were not asked to self-grade repeatability during the study period. at the end of the study period, a questionnaire regarding user experience was completed. parents and participants were asked to give their opinion about the reliability of the device, the difficulty of using the device, and whether they found the use of the device to be useful or tedious on a -point likert scale. baseline characteristics were summarized. inter-, intra-, and turbine variability were calculated and expressed as a coefficient of variability (cv). concordance between air next spirometry and conventional spirometry was assessed using the methods described by altman and bland. the mean differences between methods and the % limits of agreement were calculated for fev , fvc, pef, and fev / fvc ratio. for fev and fvc, acceptable bias was no more than ml. for pef and fev /fvc ratio, the acceptable average bias was ml/s and %, respectively. , pearson correlation coefficients between the two methods were calculated. spirometry measurements at home were graded for quality and the number of maneuvers assigned to each grade were summarized descriptively. a mean grade per subject was calculated. the average mean grades of the three study groups were compared via a one-way analysis of variance test and pairs were compared with tukey's range test to adjust for multiple comparisons. usability was evaluated by analyzing the end-of-study questionnaire completed by subjects and their parents. r version . . was used for statistical analysis and visualization. promasys software (omnicomm, lauderdale, fl) was used for data management. a total of subjects were included in the main study. the average age was years (range, - ). subjects had performed an average of (sd ) hospital-based pfts before the study. other baseline characteristics are displayed in table . of measurements in devices, the average bias from the calibrated ml was − ml (range, − to ml). the average intradevice cv was . % (range, . %- . %). furthermore, the average interdevice cv was . %. average turbine bias was − ml and turbine cv was . %. about % of measurements with the calibrated syringe exceeded the % accuracy threshold advised by ats standards. fifty-eight subjects were able to perform hospital and air next pfts subsequently. when comparing output between the two methods, there was one extreme outlier, most likely due to a technical defect resulting in a blockage of the outflow of the air next turbine, which was excluded from the statistical analysis. figure shows the limits of agreement and correlation between the air next and conventional spirometry of the several parameters. for fev , the average bias was ml and the % limits of agreement were − and + ml. there was still a good correlation between the two methods for both pef (r = . , p < . )) and fev /fvc ratio (r = . , p < . ). there was no proportional bias for any of the parameters. there was a correlation (r = −. , p = . for fev and r = −. , p = . for fvc) between the absolute difference in fev and fvc (expressed in % of predicted fev and fvc) and age ( figure s ), but not between the absolute difference and previous spirometry experience, expressed as the amount of pfts performed in the past ( figure s ). there was no statistically significant difference in absolute bias for fev between the three groups (p = . ; figure s ). when the absolute difference between the two methods was expressed as a percentage of the predicted fev and fvc, the mean bias was . % (sd %) of predicted fev and . % (sd . %) of predicted fvc. the bias of fev of subjects who performed the comparison at the end of the study period was slightly higher ( % of predicted, p = . ) compared to subjects who performed the comparison at the beginning of the study period ( figure s ). a total of spirometry measurements were performed with the air next device during the course of the study, resulting in an average compliance of %. the curves of sessions were available for analysis. when graded according to the ats/ers criteria, % of the fev measurements were considered acceptable and reproducible, as well as % of the fvc measurements. a significant number of sessions were grade e, meaning they did not produce more than one acceptable maneuver or that the reproducibility was too low. about % of measurements were neither acceptable nor usable for both fev and fvc. summarized grades are listed in figure a ,b. there was a statistically significant difference on average grade between cf patients and patients with uncontrolled asthma (fev , p = . ; figure c and fvc, p = . ; figure d ). age and average grade were not correlated ( figure s ). day-to-day cv of acceptable trials (grade a-c) was . % (sd . %) for fev and . % (sd . %) for fvc. sixty-nine ( %) subjects completed the end-of-study questionnaire. in general, parents found the use of the spirometry device to be acceptable. when asked to score their agreement with the statement "i found the use of the spirometer to be tedious," the average score was . out of (sd . ). furthermore, parents scored the difficulty . out of (sd . ), usefulness . out of (sd . ) and the perceived reliability . out of (sd . ). summarized results are displayed in figure s . the current study investigates the technical validity and user experience of the air next spirometer for pediatric patients. air next spirometer output was compared with the gold standard: conventional spirometry in the clinic. subjects and their parents also completed a questionnaire regarding the usability of the device. f i g u r e ers/ats grades for measurements performed at home. all spirometry sessions were graded according to ats/ers guidelines for fev and fvc separately. grade a-e represent sessions with acceptable maneuvers but with varying repeatability. grade u includes session with usable but not with acceptable maneuvers and grade f is reserved for session without acceptable or usable maneuvers. a, proportion of spirometry sessions that were awarded each grade for fev . b, proportion of spirometry sessions that were awarded each grade for fvc. c, boxplot of average fev grade per study group. dots represent individual averages. there was a statistically significant difference between the cf and uncontrolled asthma group (p = . ). d, boxplot of average fvc grade per study group. dots represent individual averages. there was a statistically significant difference between the cf and uncontrolled asthma group (p = . this study has some limitations, one of which is that not all of the participants could be included in the validation group. this is mainly due to logistical reasons and the fact that the comparison was part of a secondary analysis of a clinical study. however, there were no large differences in baseline characteristics between the complete cohort and the validation cohort ( table ). the nonrandomized order of tests may have influenced the results through spirometry-induced bronchoconstriction. however, we did not diagnose this condition in any of the included subjects. the curves of spirometry sessions were unavailable for review due to application connectivity errors. however, this issue occurred at random and, therefore, did not impact our overall conclusions. although we found no correlation between the absolute bias and previous spirometry experience when comparing conventional spirometry to the air next, the proportion of highly the air next will be performed to determine the objectivity and reproducibility of longitudinal unsupervised measurements. the air next spirometer is technically valid for the measurement of contributions to vital statistics, obtained by means of a pneumatic apparatus for valuing the respiratory powers with relation to health poor perception of 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an official american thoracic society and european respiratory society technical statement measurement in medicine: the analysis of method comparison studies primary care spirometry asthma outcomes: pulmonary physiology validation of the portable air-smart spirometer technical and functional assessment of office spirometers: a multicenter comparative study assessment of accuracy and applicability of a new electronic peak flow meter and asthma monitor comparison of a handheld turbine spirometer to conventional spirometry in children with cystic fibrosis recommendations for a standardized pulmonary function report. an official american thoracic society technical statement determinants of correct inhalation technique in children attending a hospital-based asthma clinic a virtual asthma clinic for children: fewer routine outpatient visits, same asthma control the future of clinical trial design: the transition from hard endpoints to value-based endpoints spirometry-induced bronchial obstruction technical validity and usability of a novel smartphoneconnected spirometry device for pediatric patients with asthma and cystic fibrosis the authors would like to thank mohamed chouchouh el khattabi for performing the variability assessments, the pulmonary function technicians for performing the conventional pulmonary function tests, and the clinical trial assistants and other support staff at the kruizinga et al. centre for human drug research. the study was funded by the centre for human drug research. this was an investigator-initiated study by the centre for human drug research, an independent clinical research foundation in leiden, the netherlands. the authors declare that there are no conflict of interests. mk conducted and designed the study, analyzed the data, and wrote the manuscript; ee conducted the study, analyzed the data, and reviewed the manuscript; ne performed measurements and reviewed the manuscript; hj, ig, as, and mn recruited patients and reviewed the manuscript; az supported data analysis; fs and ac designed the study and reviewed the manuscript; and gjd designed the study, supervised study conduct, and reviewed the manuscript. all data is available from the corresponding author upon reasonable request. http://orcid.org/ - - - key: cord- -g fuax p authors: haig, c.w.; mackay, w.g.; walker, j.t.; williams, c. title: bioaerosol sampling: sampling mechanisms, bioefficiency and field studies date: - - journal: j hosp infect doi: . /j.jhin. . . sha: doc_id: cord_uid: g fuax p investigations into the suspected airborne transmission of pathogens in healthcare environments have posed a challenge to researchers for more than a century. with each pathogen demonstrating a unique response to environmental conditions and the mechanical stresses it experiences, the choice of sampling device is not obvious. our aim was to review bioaerosol sampling, sampling equipment, and methodology. a comprehensive literature search was performed, using electronic databases to retrieve english language papers on bioaerosol sampling. the review describes the mechanisms of popular bioaerosol sampling devices such as impingers, cyclones, impactors, and filters, explaining both their strengths and weaknesses, and the consequences for microbial bioefficiency. numerous successful studies are described that point to best practice in bioaerosol sampling, from the use of small personal samplers to monitor workers' pathogen exposure through to large static samplers collecting airborne microbes in various healthcare settings. of primary importance is the requirement that studies should commence by determining the bioefficiency of the chosen sampler and the pathogen under investigation within laboratory conditions. from such foundations, sampling for bioaerosol material in the complexity of the field holds greater certainty of successful capture of low-concentration airborne pathogens. from the laboratory to use in the field, this review enables the investigator to make informed decisions about the choice of bioaerosol sampler and its application. recent outbreaks such as severe acute respiratory syndrome (sars), h n influenza, and the h n avian influenza pandemic have raised concerns among infection control teams about the importance of the aerosol transmission of pathogens and have been an impetus to investigate the transmission dynamics of bioaerosols including influenza. e studies of suspected airborne transmission routes of various pathogens have been undertaken with differing degrees of success. bioaerosol material is derived from biological origins, including aerial suspensions of bacteria, viruses, fungi, enzymes, and pollen. the size range varies from submicron-sized viral particles to fungal spores and pollen grains up to mm in diameter. if carried by a favourable air flow, bioaerosol material may be distributed over large distances with potentially fatal results. for example, a community-wide outbreak of legionnaires' disease, which resulted in fatalities, had an outbreak source in industrial cooling towers km from the affected community. however, bioaerosols may be relatively delicate structures susceptible to damage due to environmental conditions, such as desiccation. there are several different types of bioaerosol sampler available to investigators, which broadly fall into four categories including impingers, cyclones, impactors, and filters ( figure ). impingers and cyclones collect airborne particles into a liquid collection medium, whereas impactors collect particles on to solid/semi-solid mediums and filters trap bioaerosol material on fine fibres or porous membrane surfaces. the mechanisms of each collection method and their associated benefits/drawbacks are discussed in detail in the subsequent section. this paper constitutes a review of bioaerosol sampling mechanisms and seeks to address practical issues such as choosing a bioaerosol sampling device, bioefficiency, and operational considerations. a comprehensive literature search was performed, using electronic databases to retrieve english language papers on bioaerosol sampling within hospitals and the wider environment. the databases searched were science direct, medline (web of science), proquest, and taylor & francis online. the primary search criterion was bioaerosol with secondary search criteria being sampling, hospital, pathogen, infection, environment, cyclone, impactor, impinger, and aerosol. the final search was on january th, . initially papers were included from to present day; however, having received expert advice, the search was revised to included papers from onwards. patents and foreign language papers were excluded from the literature review. the search yielded publications, of which were included in the review. the software programme endnote was used for reference management. bioaerosols may be collected using passive or active sampling systems as described in the following sections, with active sampling devices involving a mechanical component. , passive sampling passive sampling is arguably the most readily available, economic, and unobtrusive method of bioaerosol sampling and relies on particles settling by means of gravity, on a collection substrate housed in a settle plate. the collected particles are usually quantified in terms of the number of colony-forming units (cfu) within the area of the settling plates for the duration of a specified time-period (for example in units of cfu/m /h). as no mechanical aids, such as a pump, are required, passive sampling has the benefit of not disturbing the surrounding air. the settling velocity of a particle describes the speed of the particle as it descends in still air and is dependent on particle size and density. smaller, lighter particles will remain airborne for longer than larger, denser particles; and if the air speed exceeds the settling velocity the particle will remain suspended indefinitely. in addition, as airflow, even within an enclosed room, will be driven by subtle variations in temperature, the source volume of air for the passively collected sample will be unknown. the combination of these factors has allowed passive sampling to be regarded as both quantitatively and qualitatively inaccurate, and as a subordinate collection method to active sampling. however, this is an oversimplification to the invariably complex nature of bioaerosol sampling. if the area of interest is the dust contamination of surfaces, for example wounds or surgical instruments, then the assessment of the microbial fallout, as opposed to particles remaining suspended in the air, is the imperative. substantial effort has been made to standardize the use of settle plates in the investigation of microbial surface contamination, with consideration given to plate size, position, and length of exposure. the / / scheme refers to the positioning of mm diameter petri dishes at a height of m above floor level, m from a wall, and with an exposure time of h. this standardized method also allows for description of the microbial contamination of the surrounding atmosphere through the use of an index of microbial air contamination (ima). more recently an investigation into contamination in modern operating theatres (ots) with turbulent airflows suggested that the ima value could lead to an underestimation of the risk. in a study which compared air and surface sampling for aspergillus sp. using contact plates within a hospital ward, a significant difference between the collection of airborne and surface spores was noted, with aspergillus accounting for > % of the fungi isolated in the air but < % of fungi isolated from surfaces. this study underlined the need to be aware of the fact that pathogens which have settled on to a surface (subsequently collected on a contact plate) or settle plate may not give an accurate reflection of the suspended airborne concentrations of that pathogen. another study concluded that although settle plates could demonstrate a close correlation with bioaerosol collection undertaken by active samplers, there were exceptions, with settle plates shown to be less sensitive to the collection of fungal spores. to countermand this deficiency an increase of the exposure time of settle plates from to h was proposed. by contrast, using a min settle plate exposure time, a study in post-flood central thailand demonstrated that settle plates can be used as an alternative to active sampling systems. the study did, however, acknowledge that the higher than average fungal bioaerosol presence may have limited the generalizability of their findings. surface sampling in intensive care units has been undertaken using tryptic soy agar contact plates accompanied by air sampling using a sampl'air lite (aes chemunex, bruz, france). the total viable count of collected microbes varied between the surface and air sampling methods, which suggested that the source of the contamination may be different. surface contamination is especially influenced by human activity such as touch. surface and air sampling both concluded that the bed areas were consistently highly contaminated. the effectiveness of nitrocellulose membranes as an alternative to replication detection and organism counting (rodac) plates for surface sampling has been demonstrated. the membranes have the advantage of being more effective at removing microbes, while also enabling samples to be taken from curved surfaces. passive sampling can also be used to describe more unusual methods of collection of bioaerosol material such as solid phase microextraction (spme). microbial volatile organic compounds (mvoc) have been successfully collected using an mm stableflex carboxen/polydimethylsiloxane fibre contained in a commercial housing. active sampling cannot be discussed without reference to a particle's mass and inertia. the mass of a particle is equal to its volume multiplied by its density, so it is possible for two particles to have the same mass but differing volumes and densities. if, however, two particles have the same density but differ in volume, then the larger particle will have a greater mass than the smaller particle. the inertia of a particle can be described as follows: consider two particles with differing masses being carried by an air flow inside a pipe. on reaching a bend in the pipe, the particle with the smaller mass will be able to travel along the airflow streamline and continue beyond the bend, whereas the particle with the larger mass will be unable to turn as quickly and will hit the wall and potentially become attached (figure ). when a particle collides with a wall because its mass is too great to allow it to travel with the airflow, the collision is known as inertial impaction. if particles of varying size all have the same density then the larger particles will succumb more readily than the smaller particles to inertial impaction, hitting the wall at a bend in the pipe. hence the smaller particles will be collected in the sampling devices but the larger ones will not. there are several active sampling devices including impingers, cyclones, and impactors, which will be discussed in detail later. however, all active bioaerosol sampling systems consist of five fundamental elements which are necessary to undertake accurate sampling: . inlet to the sampling device . transport of the air sample through the device . particle size selection (not always present) . collecting medium . pump and calibrated flow monitoring. first, the design of the inlet combined with the air flow rate is essential in the collection of a representative sample that correctly reflects the concentration and size distribution of the airborne particles. in a moving air stream, such as a ventilation duct, this is achieved by isokinetic sampling. this method considers the ratio of duct and sampling probe diameters, air flows, and inlet orientation to the air stream to ensure successful capture of particles regardless of size or inertia, thus providing a representative sample. sampling in still air is also affected by particle inertia, with larger particles being susceptible to evading probe collection; as the particle nears the inlet its velocity increases, thus increasing its stopping distance which may permit the particle to bypass the probe, distorting the concentration in the sample collected. the situation in still air is more straightforward but the probe inlet must be positioned horizontally to prevent an over/underestimation sampling bias. air streamline figure . inertial impaction in a pipe. once the air sample is within the device, the sample path should be as straight and direct as possible in order to minimize losses in the conducting tubing. where this is not possible, for example in a cascade impactor, particle loss will occur through inertial impaction on the bends between collection stages. in devices with sampling probes, particle loss may also occur in the probe head or flexible connective tubing, as particles will be lodged on to the side wall and will not reach the sampling medium. examples of this include liquid-based bioaerosol samplers, which also experience collection losses through evaporation of the collecting liquid and adhesion of the particles to the device walls. when this occurs the particles do not enter the collection liquid and the sampling process may therefore yield lower or false-negative results. regardless of the mechanism of particle loss, predicting the quantity of losses is problematic, as much depends on the interaction of the air/liquid flows, particle inertia and the design of the sampler. an estimation of losses can be achieved through appropriate laboratory validation, which is discussed in more detail below. identification of particle size selection is not always available in a sampling device; however, there are several ways of selecting by particle size, either by using a pre-classifying cyclone or a series of impaction plates. collection of the bioaerosol samples is normally on to agar or a filter or into liquid, with liquid collection placing less stress on the bioaerosol particles as they are not dried out and are more likely to maintain their viability than the other two methods. calibrated flow monitoring and the pump are crucial to the collection procedure as they ensure that the sampling device operates with an accurate air flow rate. each device will have an optimum speed at which the air flow should pass through the inlet and subsequent tubing to ensure that the bioaerosol particles will be collected with maximum efficiency. bioaerosol samplers vary considerably in size from large static samplers to smaller, portable personal samplers. large static samplers operate with higher flow rates of about . e l/min, allowing them to collect larger volumes of air more rapidly than personal samplers operating at about e l/min. e impingers impingers operate by channelling particle-laden air flow through nozzles that exit into a chamber containing liquid (example shown in figure a ). as the particles exit the nozzles in a jet of air they enter the collection chamber ( figure ). the distance from the nozzle outlet to the surface of the liquid along with the air flow rate influences the diameter of the particles that will be collected. collection on to liquid prevents desiccation of the collected particles; however, shear forces in the jet in conjunction with the turbulence caused by the air being forced into the chamber may result in loss of viability. this bioefficiency (the ability of the sampling device to maintain the viability of the bioaerosol during and after sampling) may also be reduced through evaporation, re-aerosolization (loss of previously collected particles) and adherence of particles to the internal walls of the collection chamber. , e bioaerosol impingers that are widely used include the all-glass impinger (ace glass inc., vineland, nj, usa), the bio-sampler (skc inc., covington, ga, usa) and the multistage liquid impinger (burkard manufacturing co. ltd, rickmansworth, uk) among others. , e cyclones in a cyclone sampler (figure b) the particle-laden air is forced by the shape of the collection chamber into a spiral, swirling flow ( figure ). within this airflow, particles experience a centrifugal force proportional to their diameter, density, and speed. this centrifugal force carries particles with sufficient inertia towards the cyclone wall where they are separated from the air flow into a liquid. this generally means that larger particles are more likely to be collected than smaller particles, and, as with all samplers, a calibrated airflow is essential to maintain the correct collection efficiency. on reaching the bottom of the cyclone, the air flow reverses its direction and carries the smaller, uncollected particles out of the cyclone through a vortex finder positioned in the cyclone roof. to increase the bioefficiency, a film of liquid is injected near to the cyclone's inlet, resulting in wetting of the cyclone walls; the liquid is then collected at the base of the cyclone for analysis. , collecting the particles on a liquid film maintains their viability but shear forces may still reduce bioefficiency. collection losses may again arise from evaporation of the collection liquid, resulting in the re-aerosolization of liquid air streamline previously collected material or through liquid carryover where the liquid injected into the cyclone travels over the cyclone roof and vortex finder wall before escaping from the system, carrying with it collected particles. , cyclones vary considerably in size and airflow rate, with both the cyclone geometry and the airflow rate affecting the collecting efficiency. depending on the scale of the cyclone they can be used for collecting large volumes of air while operating at high flow rates or as miniature cyclones that can be worn on a person's clothing in potentially hazardous environments, with the collected material being analysed at the end of each day to assess exposure. cyclones are also frequently used as pre-classifiers, removing larger particles from an airflow before further size classification by other types of sampler. cyclones that are widely used include the coriolis Ò m (bertin technologies, saint quentin en yvelines, france), sass (research international, inc., monroe, wa, usa), burkard cyclone sampler (burkard manufacturing co. ltd, uk) along with several other cyclones specifically designed for bioaerosol sampling. , , e impactors in common with cyclones, impactors use the inertia of a particle to facilitate collection. the air sample is passed through an array of nozzles that channel a jet of particle-laden air across a gap towards an agar culture plate, which lies perpendicular to the nozzle outlet. the air flow of the jet will follow a set of curves known as streamlines through the sampler; these curves lie tangentially to the velocity vectors of the flow. the plate deflects the streamlines by , with the air flowing past the plate and through the passageway between the plate and the device walls ( figure ). the particles with sufficiently low inertia will be carried by the streamlines and escape capture. however, particles with higher inertia will be unable to follow the curve of the streamlines, and, under the influence of the centrifugal force, will impact on the agar plate. the collection efficiency of an impactor is therefore primarily dependent on the diameter and density of the particle and the diameter of the nozzle, along with the air velocity of the jet (hence the need to calibrate the air flow through the device). the efficiency of an impactor should have a sharp cutoff curve, with the ideal impactor acting like a sieve, with all particles above a certain size, known as the cut-off size, being captured by the agar plate. this feature makes impactors highly suitable as particle size classifiers, with particles greater than a given size being separated from the air flow, while smaller particles remain airborne. a single-stage impactor has one cut-off size, so only requires one set of nozzles and an agar plate (see example in figure c ). cascade impactors can be used to gain information on the particle size distribution of an aerosol, with the particle-laden air flow being passed through successive tiers of nozzles and impaction plates. each tier, known as a stage, will collect particles of a specific size with the smaller particles remaining airborne and passing on to the next stage. at each subsequent stage, the nozzle diameter will become progressively smaller, hence the jet velocity increases, and the particle cut-off size is reduced. finally the air flow will pass through a filter to allow remaining small particles to be captured. by weighing the impaction plates from each stage and the filter, before and after sampling, the fraction of the total mass in each particle size range can be established. after cultivation the number of cfu should be enumerated and the counts corrected by positive-hole correction method, which accounts for deposition of multiple bioaerosol particles at the same deposition area. e in practice, each stage in a cascade impactor will not behave entirely like a sieve, and some particles will be deposited in the passageways between the stages or may bounce off the impaction plates and avoid capture. the airflow over the impaction plates may also be disturbed by the build-up of deposited particles, leading to altered collection efficiencies; however, this can be overcome by the use of multi-jet impactors with > nozzles. the bioefficiency of impactors is air streamlines collection substrate reduced due to the shear forces on the bioaerosol particles within the jet and on impaction with the agar plates. the microbial species under investigation along with jet velocity and jet-to-plate distance have been found to play an important role in the enumeration of bioaerosols. desiccation of the pathogen will also reduce bioefficiency, which can be overcome by mineral-oil-spread agar plates. despite the drawback of reduced viability, impactors are frequently used in sampling for many airborne pathogens. , , virtual impactors also use the centrifugal force and inertia to separate particles depending on their diameter. however, virtual impactors do not collect on to an agar plate but instead have a collection probe operating with a minor flow. this works by particles entering the impactor and being carried by the major flow around a bend ( figure ). the smaller particles are able to follow the streamlines around the curve while the particles larger than the cut-off diameter of the apparatus have sufficient inertia to carry them into the collection probe. the minor flow in the collection probe carries these larger particles on to a collection filter. likewise the smaller particles are collected on a filter in a separate part of the device. virtual impactors usually have only one or two stages, as each separation stage requires control of both the major and minor flow rates. the use of a collection probe rather than an agar plate avoids issues of particle bounce and deposition build-up; however, virtual impactors suffer collection losses near to the size of the cut-off diameter at the inlet of the probe. a useful feature of these devices is that the airflow in effect concentrates the particles larger than the cut-off size into a smaller volume of air, making virtual impactors useful as particle concentrators. slit impactors operate using the same principles of centrifugal force and particle inertia as described with regard to other impactors. rotating agar plates are especially useful as they provide a record of bioaerosol concentration over a specified time-period to enable certain activities to be monitored. bioaerosol particles enter the apparatus through a slit, causing the particles to impact on the slowly rotating agar plate below. the smallest particles will escape capture by following the streamlines of the air flows over the plates through the passageways to the outlet. impactors may also take the form of sticky plastic rods, such as rotorods (ted brown associates, los altos hills, ca, usa), or sticky glass plates where the airflow rate through the device can be adjusted in order to vary the collected particle size diameter, for example versatrap spore trap cassette (skc, inc.). examples of impactors include various single-stage and multi-stage anderson impactors, aerotech n- impactor (aerotech laboratories, coventry, uk), air test omega (lcb, la salle, france), air samplair mas- (merck, lyon, france), and bioimpactor - (aes), biostage impactor (skc, inc.) among many others. , e filters personal samplers are small, portable devices that are attached to workers' clothing to provide a representative sample of the exposure of the individual to hazardous aerosol. as with larger devices, personal samplers require a pump to draw air through the device, with a sample head, foam, or cyclone being used as pre-selectors for particle size. the bioaerosol particles are collected on to filters from where they can be transferred on to plates or dissolved into a liquid solution for culturing, or examined by microscopy (e.g. immunofluorescence). sampling by filtration is commonplace in aerosol collection but less popular for the collection of bioaerosol particles due to the loss of bioefficiency through desiccation of the pathogen; however, there have been notable successes with filter collection of bioaerosols. , fibrous filters consist of layers of fine fibres with relatively substantial gaps between the fibres that allow the filter to be between % and % air. as particles pass through the filter they are captured by the fibres. membrane filters have a complex pore-like structure and a porosity of about e % less than fibrous filters. as particle-laden air enters the membrane filter, the particles are deposited on the pore structures, with the benefit that particles much smaller than the pore diameters may be successfully captured. personal samplers with various filters include the inhalable gsp samplers (cis; bgi, inc., waltham, ma, usa) used with teflon and polycarbonate filters, pas- sampling heads containing polytetrafluoroethylene (ptfe) filters (millipore, merck, france) and the button aerosol sampler containing gelatin filters (skc, inc.). , , other bioaerosol sampling techniques less widely used bioaerosol sampling techniques include electrostatic precipitation and condensation techniques. on entering the inlet of an electrostatic precipitator, the bioaerosol particles are electrically charged at the inlet before progressing through an electric field, where they are separated from the air flow and deposited on to charged plates. although there is active research into the natural charge on bioaerosol particles and the efficiency and design of electrostatic precipitators, there is concern that the electric field undermines air streamlines collection probe figure . particle-laden airflow in a virtual impactor. the viability of microbes and that more extensive investigations are required into this sampling technique. , e sampling of bioaerosol through condensation techniques involves the air sample being processed through a humidifier. subsequently the warm, humid air is rapidly cooled with the bioaerosol particles acting as condensation nuclei. although this method can be used effectively to amplify small microbes, hence improving their chances of detection, the system is complex to use and heat transfer to the microbes may result in a loss of viability. , , choosing the bioaerosol sampler considerations when choosing a bioaerosol sampler include the type and size of micro-organisms under investigation, the environment where the sampling is to be undertaken, and cost. other factors, more specific to active samplers, should include ease of cleaning/disinfection and precautions that need to be implemented to prevent exhaust air from contaminating the sampling environment. manufacturers' websites usually provide information regarding the suitability and cost of their devices; however, more revealing is the practical use made of bioaerosol samplers by investigators in the field. sampling for airborne pathogens that may pose a health risk is not limited to healthcare environments. wastewater treatment plants (wwtps), farms and slaughterhouses, public and residential buildings, compost facilities and the general outdoor environment have all been the focus for bioaerosol studies and much can be learned from such research. , , , , , e if the research is focused on an individual's risk of exposure to harmful airborne microbes, then the obvious choice of device is the personal sampler. these samplers can be worn on the person's clothing and have proven successful in capturing fungi, bacteria, and even viruses. , , , one notable study investigated the potential for workers at a danish wwtp to be exposed to aerosolized noroviruses (novs), adenoviruses (advs), endotoxins, moulds, and bacteria. this is consistent with previous studies reporting increased occurrence of gastrointestinal illness among wwtp workers compared with control groups. , the study used inhalable gsp samplers (cis; bgi, inc.) to monitor the exposure of sixteen workers. teflon filters were fitted to the gsp samplers to allow endotoxin capture, whereas polycarbonate filters were successfully used for bacteria, mould, and virus collection. this study was the first to detect viruses, specifically norovirus gi, using gsp samplers. the exposure risk experienced by workers in a slaughter house was also undertaken with the wearing of personal samplers. the samplers consisted of pas- sampling heads containing mm pore size polytetrafluoroethylene (ptfe) filters (merck millipore sas, molsheim, france) attached in the breathing zone and were connected to portable sampling pumps (gilian , sensidyne, inc., st petersburg, fl, usa). the ptfe filters successfully captured wu polyomavirus and human papillomavirus along with other pathogens. one drawback of this study, which was focused on analysing the inhaled breath of the workers, was that it became apparent that the filters were also sampling exhaled breath. this would have been overcome by the use of larger static samplers placed away from workers' immediate environment that were able to sample a bulk background air volume. on occasion, using more than one type of sampler may be necessary to overcome specific sampler limitations. personal samplers have also been used as static samplers in a variety of situations. gelatin filters ( mm pore size) fitted to a button inhalable aerosol sampler (skc, inc.) have successfully captured influenza a virus (h n ) nucleotides, dermatophagoides allergens (der f and der p ), and bacillus subtilis in a laboratory setting; whereas other studies have used gelatin filters with iom personal samplers (skc, inc.) to successfully capture airborne legionellae from a wwtp and shower rooms in nursing homes and methanobrevibacter species and saccharopolyspora rectivirgula (causative agents of farmer's lung) in a dairy barn. , however, gelatin filters were noted to perform poorly in high-humidity environments, as they dissolved when sampling in a shower room for > min. gelatin filters fitted to iom samplers have been shown to have good efficiency in capturing total and viable legionellae but perform very poorly in capturing culturable samples. midget impingers (skc, inc.) have been successfully used to assess the effectiveness of a selection of surgical face masks against aerosolized influenza. having undertaken field work, it may be possible to correlate field data to laboratory results to assess the potential risk to workers' health of exposure to other degrees of contamination. a study investigating organic dust toxic syndrome (odts) in a seed handling factory used gsp inhalable samplers attached to workers' clothing to collect bioaerosol samples during h shifts. in the laboratory it was determined that a rotating drum (hse rotating drum dustiness tester, j.s. holdings, hertfordshire, stevenage, uk) containing contaminated dust could successfully aerosolize bacteria and fungi. by comparing results with the samples collected by the personal samplers, it was possible to calculate the concentration of airborne microbes to which the workers would be exposed from the tested dust. one major limitation with personal samplers is their relatively low flow rate, which can be as low as l/min. , , , therefore longer sampling times are more appropriate to sample a significant volume of air and this may lead to loss of bioefficiency through desiccation of the pathogen, however the loss of bioefficiency is dependent not only on sampling time, but also the microbial species and relative humidity. , in comparison with personal samplers larger static samplers, with their associated higher flow rates, enable the capture of larger, more representative air samples over the same time interval. their associated flows rates vary considerably from about . l/min for the biosampler (skc, inc.) and the agi- (ace glass, inc.) through l/min for the coriolis cyclone (bertin technologies) and the mas- /a (merck), to l/min for a described impactor. , , larger samplers have been used extensively in healthcare environments and in other indoor and outdoor environments to successfully capture viruses, bacteria, and spores. , e investigating the aerial transmission dynamics of influenza gained impetus during the recent h n avian influenza pandemic; however, prior to this and during the h n pandemic, work was undertaken to assess the risk to healthcare workers carrying out aerosol-generating procedures (agps) on h n positive patients. e using glass may three-stage impingers (produced at health protection agency, porton down, uk), air was sampled m from the head of the h n -positive patient while agps were being undertaken. the impinger operated at l/min for min intervals and classified the particles into three aerodynamic size ranges (> . mm, e . mm and . e mm) to assess the respiratory fraction. the air was collected into ml of phosphate-buffered saline and samples analysed using quantitative reverse transcriptionepolymerase chain reaction. the study showed that the may three-stage impinger proved successful in capturing h n rna. other studies have used larger static samplers to investigate airborne microbial concentration in operating theatres and recovery rooms, the aerial spread of mrsa in hospitals and residential environments, along with investigations undertaken in non-healthcare environments. , , , , , , determining the bioefficiency the most important aspect of bioaerosol sampling for the user to understand is bioefficiency. the bioefficiency of the sampling device is affected by the mechanical stress and desiccation experienced by the pathogen and will vary with the type of sampling device chosen, the sampling time, the type of pathogen under investigation and environmental conditions. , many studies have compared the effectiveness of various samplers but unless previous studies have examined the pathogen that you wish to investigate then such studies are of limited use in providing information on bioefficiency. e , , , , , it is therefore necessary to test the sampler/pathogen combination in a laboratory, preferably at a similar humidity to that which is expected in the field. this can be undertaken by spiking the sampler with a known concentration of the pathogen and then assessing the concentration collected. however, earlier studies used various other methods, such as using two samplers in tandem or parallel, to assess sampling efficiency. surrogate viruses may be used to limit the hazard when investigating high-risk pathogens, but it should be borne in mind that each pathogen responds uniquely to the conditions experienced. the time-interval during which the sampler will operate should also be replicated during laboratory testing in order to identify any operational issues or time-related loss of bioefficiency. during such bioefficiency tests, inherent variations in performance of the sampler may also become evident over different particle size ranges. with the limitations of different sampling devices being widely acknowledged and variation in collection efficiency between such devices being noted, establishing the bioefficiency of your chosen sampler against the target microbe in itself provides a valuable contribution to the field of bioaerosol sampling. , if the target microbe is unknown and a general assessment of bioaerosol particles present in an environment is sought, then the use of different types of sampling devices will mitigate the limitations of individual samplers, making a comprehensive study more likely. finally this is also a good opportunity to test the storage, enumeration and identification procedure, be that through cultivation and visual enumeration of the cfu, various pcr techniques, metagenomics, mass spectrometry, epifluorescence microscopy, matrix-assisted laser desorption/ionization mass spectrometry or other means. , , , , , , , these enumeration and identification methods, along with their advantages and limitations, have recently been discussed and are not repeated here; however, it should be noted that quantification of the pathogens captured by active samplers is normally expressed per cubic metre of air, which provides another reason to determine accurately the air flow rate of the device and the sampling time-period. , , , bioaerosol sampling out in the field the statistical analysis relating to bioaerosol sampling varies considerably depending on the nature of the study, and an investigator would do well to consult a statistician when designing any study. , , errors arising from bioaerosol sampling are typically threefold: random error of samples containing a finite number of discrete particles; errors due to non-uniformity of the bioaerosol distribution in the atmosphere; and errors due to sampling techniques. the sampling period will be influenced by factors that include the operational limitations of the sampling devices, such as the rate of evaporation of the collecting liquid, or the amount of time one has access to a site. however, even with such matters taken into consideration, the sampling timeperiods used by investigators varied widely, from as low as min to several hours. , the longer the sampling period the greater the volume of air being collected, thus the higher probability of capturing airborne pathogens, as long as the bioefficiency of the sampler does not deteriorate with time. when using samplers with differing flow rates concurrently, it may be preferable to calculate the sampling time of each device so that the volume of air captured is the same. if short sampling periods are most suited to the device being used, then repeating the sampling in triplicate should be considered. the overall length of the study may span from one day to a couple of years. new techniques such as lightinduced fluorescence (lif) methodologies are being implemented in real-time online biological particle sensors, enabling continuous on-site detection of bioaerosol counts. the height of the sampling device above floor level within an indoor environment is also important if the investigation is collecting samples from the breathing zone of patients. , if a more general bioaerosol sampling regime is undertaken, then sampling at different heights within a room and at several spatial locations will provide good sampling coverage. once the samples have been taken, they should be transported and stored in conditions that preserve their efficacy until cultivation and/or identification can be undertaken. having previously undertaken a bioefficiency study, the investigator is in a strong position to estimate with reasonable accuracy the concentration of the target bioaerosol in the sampled environment. combining this information with the genus of the captured microbe, the particle size range (informing on the penetration of the respiratory system), and the health effects on the human or animal population, conclusions can be made regarding bioaerosol concentration and health risk. presently there is no international consensus on the acceptable exposure limits of bioaerosol concentration, with a recent review drawing attention to this research deficit. a lack of bioaerosol studies targeting viruses and archea has also been identified, further limiting our understanding of the impact of airborne microbes on human health. several of the studies discussed in this review were based in bioaerosol-emitting facilities, such as wwtp and compost facilities, where the exposure to harmful microbes is a cause for concern for occupational safety reasons and for risk to health of the population in the surrounding area. in such cases the task for current research is to establish suitable doseeresponse relationships to enable health-based exposure limits for bioaerosols to be derived. such exposure limits would be designed to protect the general population from the ill effects of long-term exposure to bioaerosols. the situation for healthcare studies is quite different with a wide array of 'at risk' groups needing to be considered, making the derivation of health-based exposure limits challenging. the staff, patients or their visitors may be the source of the bioaerosol health risk, such as with sars virus, respiratory syncytial virus, influenza, measles, mumps, or rubella viruses. their stay in hospital may be brief and may not be contained to one ward, making it difficult to trace the source of an outbreak. the wider environment may also be a source of harmful bioaerosols, such as an increased risk of airborne aspergillus during construction activities or the risk of legionella bacteria in hvac (heating, ventilation, and air conditioning) or water systems. to gain a greater understanding of the transmission dynamics of certain airborne diseases and to increase hygiene standards through improved infection control, bioaerosol sampling studies have frequently focused on healthcare environments. bioaerosol sampling in operating theatres (ots) is motivated by the need to reduce the incidence of surgical-site infections. with the inclusion of high-efficiency particulate air (hepa) filters within ots, cleanroom technology standards have frequently been applied to these healthcare settings with the airborne particulate count being monitored. with the observations that bioaerosol sampling is time consuming, requires trained personnel and that results are not instantaneous, interest has grown in the correlation between microbiological and dust contamination, to the extent that it has been suggested that microbial sampling should be limited to epidemics, validation of protocols, or changes to the ot environment that may affect microbial content. further investigations have been unable to establish a relationship between dust particles and microbes in ots, although a relationship between the number of airborne microbes and human activity was confirmed. this relationship between increased airborne bacterial concentration and human activity is widely accepted. , approximately e % of human skin debris carries bacteria and skin shedding increases with physical activity, with millions of particles being shed per person each day. in addition to measuring the dust count using a light-scattering particle analyser, bioaerosol sampling was undertaken using both passive and active sampling. settle plates with a mm diameter were placed at strategic locations, m above floor level, throughout the ot and left exposed during surgical operations. the active sampling was undertaken using a single stage slip-type impactor operating at l/min for duration of min, with samples taken during operations. the study did observe an increased concentration of dust particles > mm during conventional surgery as opposed to scope procedures. an inverse relationship between dust and bacterial concentration was reported. as the ot door opened into the anaesthetic room, the turbulent airflow resulting from the pressure differential between the two rooms in effect removed dust from the ot. however, the bacterial concentration increased and it was proposed that this may be due to increased movement of the staff. this highlights the need for the investigator to be aware of airflow in and between areas under investigation, in addition to patterns of human activity. over a three-year sampling period, a study of surface and airborne microbial contamination was conducted in ots. both passive and active sampling was conducted during the commissioning of ots, during major renovations and surgical activities, as well as in adjacent corridors. passive sampling was undertaken using mm diameter settle plates using the / / scheme (explained in the section on 'passive sampling') with tryptic soy agar used for the total aerobic bacterial count, whereas sabouraud dextrose agar with chloramphenicol was used for fungal isolation. active sampling of airborne contamination was carried out using a duosas sampler (pbi international, milan, italy) operating at l/min. the study found a moderately strong correlation between the active and passive sampling methods, with the discrepancy between the two techniques being attributed to the relatively short sampling period and limited spatial collection zone of the active sampler compared with the longer exposure time of the settle plates. the investigation also concluded that bioaerosol sampling could be used for the evaluation of the ventilation and air conditioning system within the ot. comparing the results from sampling during different surgical procedures also had the potential to inform improved surgical hygiene practice. correlation between active and passive sampling was also described during a study comparing different ventilation regimes in ots. using a surface air system sampler (sas, international pbi, milan, italy) operating at l/min and settle plates, both with tryptic soy agar, the study showed that unidirectional airflows within ots did not guarantee low counts of airborne bacteria. the study also confirmed that an increased number of people and door openings in an ot influenced an increase in bacterial count. a year-long monitoring of airborne microbial contamination in ots and surrounding areas has also been studied using mixed effect models to assess the influence of air temperature, relative humidity, number of people in a space and different sampling locations on levels of co , suspended particulate matter, and airborne bacteria. bioaerosol sampling was undertaken using an andersen one-stage viable impactor (n ; andersen samplers, atlanta, ga, usa), with tryptic soy agar. the sampling period was min, with duplicate samples taken at a height of . e . m from floor level to represent the breathing zone of healthcare workers. in concurrence with a previous study, bacillus spp., micrococcus spp., and staphylococcus spp. bacteria were frequently found in the operating theatre area. the study found a positive correlation between airborne bacterial concentration and suspended particulate matter (pm and pm . ). a positive correlation was also found between the number of people in a room and co concentrations, but, when temperature, relative humidity and sampling location were accounted for, no significant correlation was found between the number of people and bacterial concentrations. one exception was the postoperative recovery room where there were a greater number of people, higher co levels, and higher concentrations of bacteria. caution should be exercised when investigating the relationship between the number of human occupants and the concentration of airborne microbes. although a correlation has been noted within one room of this investigation and in previous studies mentioned in this section, a study carried out in an environmental chamber suggested that outdoor air had a greater influence on the bioaerosol composition. airborne viral and bacterial concentrations were monitored in the outpatient area of a paediatric unit and in the paediatric emergency room twice a week for one year. the sampled air was filtered through a closed face, threepiece disposable, plastic cassette containing a . mm polytetrafluoroethylene filter and operating at l/min. the air within the outpatient area was sampled for h a day whereas the air in the emergency room was monitored during h periods. in both cases, the bioaerosol sampler was positioned in the breathing zone between . and . m above floor height. during the course of the study, filter samples were taken and airborne adenovirus and mycoplasma pneumoniae were detected in both monitored areas, with greatest prevalence found in the outpatient area. the negative control was the use of filters with no air flow passing though the sampling device. no adenovirus and m. pneumoniae was found on the negative controls. the study did, however, passive sampling e settle plates e consider using the : : scheme with mm plates e surface sampling e consider using membranes (e.g. nitrocellulose) as an alternative to contact plates on curved surfaces e surface and aerial contamination may have different sources e results from passive and active samplers should not be assumed comparable active sampling e impactors e collection on to agar plates e collection efficiency highly dependent on particle size (should be sieve-like in performance) e ideal as a particle size classifier e loss of bioefficiency: shear forces, desiccation, particle bounce, and deposition build-up e virtual impactors e collection into liquid, thus minimizing risk of desiccation e collection efficiency dependent on particle size e useful as particle concentrators e slit impactors e collection on to agar plates e loss of bioefficiency: shear forces, desiccation, particle bounce, and deposition build-up e records variation in bioaerosol concentration over a specified time-period e impingers e collection into liquid, thus minimizing risk of desiccation e loss of bioefficiency: shear forces, re-aerosolization, evaporation, adherence to device walls e collection efficiency dependent on particle size e cyclones (wetted) e collection into liquid, thus minimizing risk of desiccation e loss of bioefficiency: shear forces, liquid carryover, evaporation, adherence to device walls e may be used as pre-classifiers for particle size e collection efficiency dependent on particle size e vary considerably in size and airflow rate e filters e small, portable personal samplers e loss of bioefficiency: desiccation e collection efficiency dependent on particle size (sample head, foam, or cyclone being used as pre-selectors) in the laboratory e calibrate the flow rate of the active sampler e ensures the maximum collection efficiency e influences the size of particles collected e determine the bioefficiency of the sampler against the target pathogen e test in air conditions expected in the field (relative humidity and temperature) e spike sampler with known concentration of the target pathogen e each type of pathogen has a unique response to conditions experienced e surrogate viruses may be used in place of hazardous pathogens; however, response may differ from target pathogen e check that bioefficiency is maintained throughout planned sampling time e determine errors in numeration when sampling from a known, repeatable concentration of the target pathogen e ensure that the sampler exhaust is not a source of pathogen contamination to the environment e test the storage, enumeration, and identification procedure in the field e position of the inlet sampler e avoid strong airflows around the inlet of the sampler e if using an inlet nozzle, position horizontally e ensure that the sample position is beyond the range of droplet fallout from a source (e.g. coughing/vomiting patient) e aerial microbial concentration e expect non-uniformed concentration in the area studied (expect associated sampling errors) e consider taking samples at various locations in the area studied e note human/animal activity and number of humans/ animals present, as this may influence concentration of certain microbes e be aware of airflow patterns due to hvac (heating ventilation and air conditioning) and natural ventilation e note air quality: relative humidity, temperature (also consider co and particle dust count) e there may be seasonal variation in concentration of the target pathogen e active samplers: quantification of pathogens e expressed as enumeration per cubic meters of air e need to know the collection time and flow rate of the sampler notice evidence of seasonal variation in this taiwanese hospital, with airborne adenovirus peaking in the summer months, whereas m. pneumoniae detection rates increased in the autumn and winter. identifying peaks in bioaerosol contamination during certain months allows for ventilation rates in affected areas to be increased to reduce the risk to patient health. effective ventilation and controlled airflow patterns within wards alongside improvements in hygiene and operational procedures are arguably the strongest defence against high concentrations of airborne microbial contamination. , , , these hospital-based bioaerosol investigations highlight many of the issues facing the bioaerosol researcher. the methodologies applied differ between research teams. sampling devices vary with regards to their collection efficiency. concentrations of airborne pathogens are influenced by airflows within the hospital building and seasonal variation. the influence and correlation between human activity, air quality (humidity, temperature, co concentration) and dust particle count on bioaerosol concentration is uncertain, with contradictory results being presented. the transmission dynamics of some pathogens are not fully understood and an airborne component to transmission should not be overlooked. even with a good understanding of the concentrations of bioaerosols in an environment, the health-based exposure limits for a diverse group of patients and staff may not be known. yet such research can inform on appropriate ventilation rates to maintain good air quality, assess the bioaerosol risk to patients and staff, gain a greater understanding of the transmission dynamics of pathogens, and suggest improvements to hygiene procedures. amid all the uncertainties and difficulties of bioaerosol research, the goal remains to gain a greater understanding of airborne pathogens and to provide safe healthcare environments for our patients and staff. a summary of the key points in bioaerosol sampling is presented in box . a wide variety of bioaerosol samplers have been used to investigate airborne pathogens in healthcare facilities and other environments. we have described the underlying principles behind bioaerosol sampling devices along with benefits and disadvantages of various designs. examples of bioaerosol sampling have been given to point to best practice and to highlight the wide array of devices used and pathogens captured. due to the unique response of each variety of pathogen to environmental conditions and the stresses experienced in differing sampling devices, the investigator should commence studies by determining the bioefficiency of the chosen sampler and the pathogen under investigation within laboratory conditions. from such foundations, sampling for bioaerosol material in the complexity of the field holds greater certainty of successful capture of low-concentration airborne pathogens. avian influenza h n transmission in households, indonesia airborne transmission of influenza a/h n virus between ferrets influenza aerosols in uk hospitals during the h n ( ) pandemic e the risk of aerosol generation during medical procedures roles of sunlight and natural ventilation for controlling infection: historical and current perspectives a community-wide outbreak of legionnaires' disease linked to industrial cooling towers e how far can contaminated aerosols spread? the development of a bioaerosol sampler for the detection of enzymes in industry bioaerosol evaluation in indoor environments iso - : . cleanrooms and associated controlled environments e biocontamination control e part : general principles and methods aerosol technology environmental control of microbial contamination in the operating room the index of microbial air contamination operating theatre ventilation systems and microbial air contamination in total joint replacement surgery: results of the gisio-ischia study prospective survey of indoor fungal contamination in hospital during a period of building construction microbial air monitoring in operating theatres: experience at the university hospital of parma post-flood measurement of fungal bio-aerosol in a resourcelimited hospital: can the settle plate method be used? healthcare environments and spatial variability of healthcare associated infection risk: cross-sectional surveys comparative efficiency of nitrocellulose membranes versus rodac plates in microbial sampling on surfaces prediction of mold contamination from microbial volatile organic compound profiles using solid phase microextraction and gas chromatography/mass spectrometry physical and chemical properties of aerosols. london: blackie academic & professional investigation of inherent and latent internal losses in liquid-based bioaerosol samplers evaluation of sampling techniques for detection and quantification of airborne legionellae at biological aeration basins and shower rooms bioaerosol sampling with a wetted wall cyclone: cell culturability and dna integrity of escherichia coli bacteria metagenomic detection of viruses in aerosol samples from workers in animal slaughterhouses the impact of sampler selection on characterizing the indoor microbiome effect of sampling time on the collection efficiency of all-glass impingers long-term sampling of airborne bacteria and fungi into a nonevaporating liquid collection of airborne microorganism into liquid by bubbling through porous medium influence of storage on the fungal concentration determination of impinger and filter samples rapid quantification of bioaerosols containing l. pneumophila by coriolis Ò m air sampler and chemiluminescence antibody microarrays sampling port for real-time analysis of bioaerosol in whole body exposure system for animal aerosol model development reverse-flow centrifugal separators in parallel: performance and flow pattern the cyclone scrubber e a high efficiency wet separator the development of sampling methods for the assessment of indoor bioaerosols development of a biosensor for airborne proteases an improved wetted wall bioaerosol sampling cyclone a direct approach to the design of cyclones for aerosol-monitoring applications computational fluid dynamics (cfd) and empirical modelling of the performance of a number of cyclone samplers use of a culture-independent approach to characterize aerosolized bacteria near an open-freestall dairy operation correlation between olea europaea and parietaria judaica pollen counts and quantification of their major allergens ole e and par j -par j field evaluation of a personal, bioaerosol cyclone sampler wetted wall cyclones for bioaerosol sampling chamber evaluation of a personal, bioaerosol cyclone sampler development of a personal bioaerosol sampler based on a conical cyclone with recirculating liquid film new sampler for the collection, sizing, and enumeration of viable airborne particles positive-hole correction of multiple-jet impactors for collecting viable microorganisms inertial samplers: biological perspectives an alternative approach for the correction of bioaerosol data collected with multiple jet impactors effect of physical and biological parameters on enumeration of bioaerosols by portable microbial impactors enhancing bioaerosol sampling by andersen impactors using mineral-oil-spread agar plate reduction and characterization of bioaerosols in a wastewater treatment station via ventilation critical working tasks and determinants of exposure to bioaerosols and mvoc at composting facilities aerosol measurement: principle, techniques and applications review of bioaerosols in indoor environment with special reference to sampling, analysis and control mechanisms prediction of mold contamination from microbial volatile organic compound profiles using head space gas chromatography/mass spectrometry effects of condensational growth on culturability of airborne bacteria: implications for sampling and control of bioaerosols comparison of two biological aerosol sampling methods differences in detection frequency as a bioaerosol data criterion for evaluating suspect fungal contamination comparative performance of impactor air samplers for quantification of fungal contamination a comparison of the efficiencies of a portable biostage impactor and a reuter centrifugal sampler (rcs) high flow for measuring airborne bacteria and fungi concentrations exposure to airborne noroviruses and other bioaerosol components at a wastewater treatment plant in denmark use of gelatin filter and biosampler in detecting airborne h n nucleotides, bacteria and allergens charge levels and gram (ae) fractions of environmental bacterial aerosols collection of airborne microorganisms by a new electrostatic precipitator design and development of an electrostatic sampler for bioaerosols with high concentration rate influence of secondary flows on the collection efficiency of a cylindrical electrostatic precipitator development and evaluation of a novel bioaerosol amplification unit (bau) for improved viral aerosol collection the efficient method for simultaneous monitoring of the culturable as well as nonculturable airborne microorganisms airborne enteric coliphages and bacteria in sewage treatment plants microorganisms in bioaerosol emissions from wastewater treatment plants during summer at a mediterranean site reducing bioaerosol dispersion from wastewater treatment and its land application: a review and analysis relationship between airborne detection of influenza a virus and the number of infected pigs the potential for community exposures to pathogens from an urban dairy food animal transport: a potential source of community exposures to health hazards from industrial farming (cafos) bioaerosols from municipal and animal wastes: background and contemporary issues airborne bacteria and carcass contamination in slaughterhouses distribution and identification of culturable airborne microorganisms in a swiss milk processing facility human occupancy as a source of indoor airborne bacteria / )-b-d-glucan, fungi, and dust mite allergens in flood-affected homes of new orleans evaluation of respiratory symptoms and their possible association with residential indoor bioaerosol concentrations and other environmental influences / )-b-d glucan, and endotoxin from flood-affected materials collected in new orleans homes characterization of seasonal indoor and outdoor bioaerosols in the arid environment of el paso. texas isolation of staphylococcus aureus and antibiotic-resistant staphylococcus aureus from residential indoor bioaerosols indoor and outdoor bioaerosol levels at recreation facilities, elementary schools, and homes sampling for indoor fungi autocorrelation and variability of indoor air quality measurements environmental assessment of aerosols, bioaerosols, and airborne endotoxins in a machining plant bioaerosol concentrations in noncompliant, compliant, and intervention homes in the midwest exposure to culturable airborne bioaerosols during noodle manufacturing in central taiwan workplace exposure to bioaerosols in pet shops, pet clinics, and flower gardens characterizations and relationships between outdoor and indoor bioaerosols in an office building bioaerosol emissions from open window composting facilities: emission characterisation and dispersion modelling improvements presence of legionella and free-living amoebae in composts and bioaerosols from composting facilities spatial variations in airborne microorganism and endotoxin concentrations at green waste composting facilities evaluating the quality of bioaerosol risk assessments for composting facilities in england and wales particle size distribution of airborne aspergillus fumigatus spores emitted from compost using membrane filtration sorting and recycling of domestic waste. review of occupational health problems and their possible causes ambient influenza and avian influenza virus during dust storm days and background days. environ personal sampler for monitoring of viable viruses; modelling of outdoor sampling conditions culturable airborne fungi in outdoor environments in beijing evaluation of four bioaerosol samplers in the outdoor environment london plane tree bioaerosol exposure and allergic sensitization in the adaptation of existing personal inhalable aerosol samplers for bioaerosol sampling performance characteristics of the button personal inhalable aerosol sampler health effects among workers in sewage treatment plants work related symptoms among sewage workers: a nationwide survey in sweden characterization of bioaerosols from dairy barns: reconstructing the puzzle of occupational respiratory diseases by using molecular approaches effectiveness of surgical masks against influenza bioaerosols microbial diversity in bioaerosol samples causing odts compared to reference bioaerosol samples as measured using illumina sequencing and maldi-tof effect of sampling time and air humidity on the bioefficiency of filter samplers for bioaerosol collection air quality monitoring of the post-operative recovery room and locations surrounding operating theatres in a medical centre in taiwan surveillance of airborne adenovirus and mycoplasma pneumoniae in a hospital paediatric department indoor air quality varies with ventilation types and working areas in hospitals collection efficiencies of aerosol samplers for virus-containing aerosols air and surface contamination patterns of meticillin-resistant staphylococcus aureus on eight acute hospital wards change in environmental bacterial flora in a new hospital building comparison of the collecting efficiency of microbiological air samplers a slit sampler for collecting and counting air-borne bacteria methods for sampling of airborne viruses the performance of the biotest rcs centrifugal air sampler airborne viable, non-viable, and allergenic fungi in a rural agricultural area of india: a -year study at five outdoor sampling stations on-line monitoring of airborne bioaerosols released from a composting/green waste site ventilation and transport; bioaerosols in healthcare environments non-culturable bioaerosols in indoor settings: impact on health and molecular approaches for detection evaluation of exposureeresponse relationships for health effects of microbial bioaerosols e a systematic review environmental controls in operating theatres risk factors for particulate and microbial contamination of air in operating theatres reduction of skin bacteria in theatre air with comfortable, non-woven disposable clothing for operating-theatre staff behaviours and rituals in the operating theatre chamber bioaerosol study: outdoor air and human occupants as sources of indoor airborne microbes the control by ventilation of airborne bacterial transfer between hospital patients, and its assessment by means of a particle tracer: ii. ventilation in subdivided isolation units detection of viruses in used ventilation filters from two large public buildings none declared. none. key: cord- -ly fop d authors: faustini, annunziata; davoli, marina title: attributable risk to assess the health impact of air pollution: advances, controversies, state of the art and future needs date: - - journal: int j environ res public health doi: . /ijerph sha: doc_id: cord_uid: ly fop d despite the increased attention given to the health impact assessment of air pollution and to the strategies to control it in both scientific literature and concrete interventions, the results of the implementations, especially those involving traffic, have not always been satisfactory and there is still disagreement about the most appropriate interventions and the methods to assess their effectiveness. this state-of-the-art article reviews the recent interpretation of the concepts that concern the impact assessment, and compares old and new measurements of attributable risk and attributable fraction. it also summarizes the ongoing discussion about the designs and methods for assessing the air pollution impact with particular attention to improvements due to spatio-temporal analysis and other new approaches, such as studying short term effects in cohorts, and the still discussed methods of predicting the values of attributable risk (ar). finally, the study presents the more recent analytic perspectives and the methods for directly assessing the effects of not yet implemented interventions on air quality and health, in accordance with the suggestion in the strategic plan − from the health effect institute. the impact of exposure on public health is assessed by measuring its contribution to the total disease incidence or mortality [ ] . the attributable risk and the attributable fraction are the most important measurements of this impact. the attributable risk (ar) is the rate (proportion) of a health outcome (disease or death) in exposed individuals, which can be attributed to the exposure [ ] . ar assesses how much greater in absolute terms the frequency of an outcome is among the exposed compared with the non-exposed [ ] . it is measured as the difference in the rates of an outcome among unexposed individuals (iu) from the rates among those who have been exposed (ie), according to the formula: ar = ie − iu. this estimate is based on the assumption that all other possible causes of the studied outcome have equal effects in exposed and non-exposed individuals. the concept of ar was first proposed by levin in [ ] in the context of studies on cancer, which were mainly cohort studies where people were assembled on exposure and followed over a defined period of time. in the light of the discussion about the attributable measures by greenland and robins in [ ] , steenland and armstrong in [ ] , rothman [ ] and greenland in [ ] we underline that this ar is very similar to a difference of incidence proportions or average risks, since it uses as denominators the exposed and not-exposed individuals and not the time-persons. the attributable fraction (af) is the proportion of all cases (or overall incidence) that can be attributed to a specific exposure in a population since it combines relative risk and prevalence of exposure. it is measured as ar divided by the incidence risk in the exposed, according to the formula: af = ((ie − iu)/ie). thus giving an estimate of the proportion of cases that would not have occurred if exposure had been totally absent [ , ] . the no-exposure hypothesis is usually defined as counterfactual-i.e., far from the experience-in a causal approach framework, since it postulates that the same population is followed in an identical situation where only the exposure level changes to the reference value of [ ] . this estimate as well as ar is based on the assumptions that ( ) all other possible causes of the studied outcomes have equal effects in the exposed and nonexposed groups, ( ) the studied association is causal. the af, like the ar, uses proportions or risk fractions, but divides the difference estimated in the ar by the proportion of cases among the exposed, thus giving an indication of the magnitude of excess risk from exposure as a proportion of total incidence, unlike ar. to extend this definition to the general population, ar should be theoretically estimated from a life-time follow-up of exposed and non-exposed cohorts in the studied population [ ] . in general, using ar, af and ef similarly in those exposed and in the population as a whole, is not acceptable as it has been pointed out by rothman [ ] and greenland [ ] , essentially because populations are not closed cohorts and causality requires many assumptions relative to biological evidence. attributable fraction has been renamed excess fraction (ef) by greenland and robins [ ] , to resolve the ambiguity introduced by the term "attributable" whose meaning might be either a case in which an exposure played an etiological role (etiological fraction) or a case that would not have occurred, had the exposure not occurred (excess fraction). the difference is important since all excess cases are etiological cases, but not all etiological cases contribute to the fraction attributable to a specific exposure. the authors then proposed three different meanings of attributable fraction: excess fraction, etiologic fraction and incidence-density fraction, that uses the rate per person-years per year. these definitions should be chosen and estimated according to the questions of the research and to their relevance to public health, as discussed below. if the essential question is "whether" the outcome occurs by time t due to an exposure, and if then the public health objective is to control the dangerous exposure overall, then the excess fraction is an adequate estimate of an attributable fraction. if the essential question is "when" the exposure occurs, and the public health objective is identifying the specific age and condition when preventing or reducing exposure, the excess fraction could adequately represent the af, on the condition that hypotheses about periods or conditions of vulnerability are made explicit. if the essential question is "whether the exposure caused the outcome", attributable fraction (af) by itself is not an appropriate estimate, because according to the traditional definition, the af measures only the excess cases that could in total be much fewer than the etiological cases, because they are related only to the studied exposure. we would like to point out here that excess fraction could be an etiological fraction (ef) and therefore, the proportion by which the incidence rate of the outcome in the population would be reduced on condition that the exposure was eliminated; in the above first and second cases, it is also required that ( ) a causal (etiological) relationship between the studied exposure and the effect was assessed, and ( ) the many biological assumptions about a causal relationship were respected. ar has been used in the literature to mean various concepts and measures. these other measures include the population attributable risk (par), the population excess rate (per), and the rate difference (rd), but none of them can be considered entirely equivalent to af. their definitions follow according to the last dictionary, [ ] to lead to a better understanding in the literature, and to review briefly the possible pitfalls connected to the concept of causality [ , ] . the population attributable risk (par) helps determine which exposures are most important in a specific community and is calculated as the incidence of a disease in the total population, minus the incidence in the group of those unexposed to a specific risk factor (it − iu), thus giving the risk attributable to that risk factor in the population. par is often used instead of af. it is measured as: par = ((it − iu)/(it × ), where "it" is the incidence rate for the total population, iu is the incidence rate among the unexposed, or par = (((pe(ie − iu)/(pt × it) × ), where pe is the number of people exposed, ie is the incidence rate among the exposed, iu is the incidence rate among the unesposed, pt is the number of people in the population, and it is the incidence rate in the population. the population excess rate (per) is very similar to par; it measures the disease associated with exposure to a putative cause in the population, but it is calculated merely as the difference between the rates of disease in the total population and in the nonexposed. per = pt − pu. the rate difference is used as a measurement that is equivalent to the population excess rate, but it is once again calculated as absolute difference between incidence rate in an exposed population group and a non exposed population group, according to the formula: rd = ie − iu. to complete this brief review of the concepts related to the definition of attributable risk we would also like to consider here the definitions of health impact assessment and accountability. the definition of health impact assessment (hia), as published in the gothenburg consensus paper by the who regional office for europe in , is "a combination of procedures or methods by which a policy, program or project may be judged as to the effects it may have on the health of a population [ ] ." impact assessment is an important step in public health epidemiology, and can be seen as related to risk characterization, the last step in risk assessment, as defined by epa [ ] , together with hazard assessment, dose-response assessment and exposure assessment. risk characterization ( ) reports the epidemiological results, including estimates of population exposed with harmful effects, ( ) makes explicit assumptions and uncertainties, and ( ) provides indications for public-health interventions to reduce exposure. the fields in which impact assessment has been applied include studies about the environment where people live, either natural [ ] or man-made (through urban planning or house building [ ] ), their health care systems [ ] , their medical treatments [ ] , but also the clinical prediction models [ ] and the impact of reducing exposure through controlling sources and passing legislation to reduce exposure [ ] . on the other hand, it has long been recognized that health and its determinants are strongly influenced by policies, programs, and projects outside of the health care sector. thus we have the obvious interface between the epidemiological results for the hia and the more complex policy impact assessments (pias), which define formally evidence-based procedures to assess the economic, social, and environmental effects of public policy [ ] . these procedures are not analyzed here, nor are the possible interactions with various levels of pias. we would like just to touch upon the complexity of pias which require many different kinds of expertise. the pia procedures have been incorporated into policy making in the oecd countries and the european commission [ ] . we would instead like to verify here how much of the prediction made many years ago by irvapicciottohas in fact come to pass. she wrote at the time: "a serious appraisal of current methods and practice suggests that much can be done to improve scientific rigor in risk assessment [ ] . accountability which has been termed "evaluating the extent to which air quality regulations improve public health" is part of a broad effort to assess the performance of environmental regulatory policies. the methods for accountability research have been promoted by the health effect institute [ ] . one of the strengths of this approach consists in analyzing the compliance to the most important steps of the chain of effectiveness to add or change regulatory actions. in the case of air pollution, the crucial steps involve emissions, ambient air quality, exposure/dose, human-health response. the health effects of air pollution have been well known to the scientific community since the early th century, when serious epidemics of mortality and respiratory diseases were linked to concurrent extraordinary peaks of air pollution in natural experimental or extraordinary scenarios such as london fog [ ] ; fog in the meuse valley [ ] ; still mill in utah valley [ ] . toward the end of the th century, researchers started to focus their attention on the possible adverse health effects induced by "common" levels of outdoor air pollutants [ , ] . clinicians have also acknowledged the causal role of air pollution on human health since , when the american thoracic society (ats) first defined the concept of an "adverse respiratory effect of air pollution" (ats, ) as "medically significant physiologic or pathologic changes" [ ] . all these scientific contributions provided a fundamental support for the definition of standardized legislation on air quality in the united states (u.s. epa, ) and in europe (european council, ; european parliament and council, ). today's research is exploring the possible effects of air pollution below the current limits of exposure both for short-term exposure-going from aphena in europe and the usa [ ] up to the recent almost worldwide studies [ , ] -and for long-term exposure (e.g., in the netherlands [ ] in europe [ ] , in the usa [ , ] and in china [ ] ). in the late s, two important multicity studies-one in europe (aphea, ) and another in the usa (nmmaps, )-were started with the aim of providing answers to the unresolved uncertainties which had emerged from previous studies about the short-term effects of air pollution which had been carried out mainly in single cities, apart from the milestone air pollution andmortality in six us cities [ ] . we summarize below the essential points of these studies since they are the basis of many subsequent methodological developments right up to today. both aphea and nmmaps were multicity studies which benefited from the following advantages over single-city studies: they involve larger populations and can recruit a larger number of cases, thus increasing the power of association; . they can observe the same relationship under different circumstances, such as seasons, and in different populations thus making causality a more plausible interpretation of any possible association, providing that heterogeneity has been controlled for or assessed; . even a "weak" effect of air pollution on health will constitute an important public health problem, since a unique characteristic of air pollution exposure is its ubiquity for large populations. the most important problems with these studies were recognized by the researchers themselves, i.e., ( ) not having studied other factors potentially responsible for the effects, including air pollutants other than particulate matter (pm), ( ) not having individual measurements of exposure, which could prefigure exposure measurement errors, ( ) having measured mortality that was premature only by a few days, which is an effect of limited public-health impact, ( ) having used different methods to study this association in different cities. to respond to the above problems: . the researchers thereafter proposed a "measurement error model for time-series studies of air pollution and mortality" which was a combination of the berkson model; and the bayesian hierarchical generalized additive model (gam). the berkson model [ ] deals with the relationship between ambient concentration and personal exposure by comparing the two measurements to estimate the error between them. although the berkson error-unlike the misclassification-causes little or no bias in the association, the difference between the average personal exposure and the true ambient level has been identified as an important source of bias in log-linear models [ ] . the bayesian hierarchical generalized additive model was the tool for modeling variability across the studies of the relationship between personal and ambient exposure concentrations. two different approaches were available: a hierarchical multivariate regression with missing predictors for either continuous or categorical data [ ] . . they included gaseous pollutants in subsequent studies on air pollution effects. this innovation was supported by using a hierarchical model to assess exposure-health outcome association which made it possible to estimate the independent effects of multiple pollutants in the presence of measurement error [ ] . they adopted a longer scale of mortality linked to short-term exposure which overcame the mortality displacement [ ] , and helped to introduce the long-term studies. . they took into account the temporal structure of the exposure-response relationship which led to including effects of up to days after exposure peak or harvesting. the distributed lag models played the major role in assessing the new exposure-response relationship of short-term effects [ , ] . later, the study by gasparrini and leone [ ] extended the definition of attributable risk within the framework of distributed lag models. . they revised the frailty hypothesis-which restricted mortality to the frail people-by showing that larger effects occurred in frail people only at shorter time scales [ ] . in parallel, a rich discussion developed about which was the better design, to assess the effects of long-term exposure between time-series and cohort study. the idea that cohort design might have been more appropriate for assessing effects related to long-term exposure was introduced in nmmaps in [ ] . the discussion began with kunzli's observations [ ] about the double action of air pollution on both the long-term underlying diseases and the short term risk of death: the author identified four different combinations: (a) air pollution increases the risks of both underlying diseases, leading to frailty, and of short-term mortality among the frail; (b) air pollution increases the risk of chronic diseases but is unrelated to the timing of death; (c) air pollution is unrelated to chronic diseases but short term exposure increases mortality among the frail; (d) neither underlying chronic disease nor death is related to air pollution exposure. the author concluded that the cohort design was more powerful for studying long-term exposure, as opposed to the time-series approach, because the later captures deaths in categories (a) and (c) only, whereas the cohort design assesses cases in categories a, b and c. hence the impact assessment of air pollution on mortality should be based on cohort studies. this position has been discussed claiming that "lifetime lost due to short air pollution peaks, may not be sufficiently captured in cohort studies because long-term mean concentrations are insensitive to such hidden peaks" [ ] . although no available design could fully assess the contribution of air pollution to life experience, cohort studies might be more powerful for case attribution, if long-term exposure was used, since it also reflects past peak exposures. the spatio-temporal extension of short-term analysis [ ] as well as the studies of the short term effects in cohorts [ , ] contributed important developments in assessing the effects of this sort of cumulative exposure to both short-term and long term exposures: • the first approach overcame the limited capacity of the time-series so as to take account of spatial variation [ ] and the introduction of cox proportional hazards models in spatio-temporal analysis introduced the possibility of estimating results for different geographic levels, such as cities and states; • the second approach included in the short-term assessment the effect due to the sensitivity of some population subgroups, which is itself due to long-term exposure [ , ] . the current situation seems to promise further interesting developments in the methods of dealing with spatial-temporal analysis of short-term health effects. two recent studies show the potential of using the time-series approach in studying numerous areas [ , ] , strengthened by the concentration-response function whose important role has been recognized as a metric for impact assessment in addition to the cause-effect metric [ ] [ ] [ ] (see also below page , the role of dose-response curve). in the above-cited recent multi-area papers [ , ] , the contribution of short-term exposure in increasing mortality emerged as independent of long-term exposure, and a no-threshold linear relationship has been confirmed for the pm-mortality function, with continuous increases starting even at concentrations below those of the current guidelines. it is also worth noting that the authors used the excess fraction to estimate the risk attributable to short-term exposure, thus highlighting the opportunity of regulatory interventions [ , ] . daily increases of µg of pm have been associated, within days, with an additional . % ( % cis, . − . ) of daily mortality, . % ( % ci, . − . ) of cardio-vascular mortality and . % ( % ci, . − . ) of respiratory mortality. the studies of long-term (l-t) effects are characterized by prolonged exposures to air pollution, measured by annual average and by health effects in the exposed population. health effects are usually measured as all-cause and cause-specific mortality, and as diseases diagnosed in health services (hospitals, emergency rooms, medical offices). health effects are also estimated as decreased survival which is measured in terms of either life expectancy or years of life lost (yll). all of these measurements are appropriate for estimating attributable risks or excess fractions, both which are important metrics of risk assessment. the long-term approach led to important methodological improvements after the first studies on mortality [ , [ ] [ ] [ ] , that facilitated estimating ars: . an increasingly accurate assessment of exposure (although not yet at the individual level) ranging from continuous monitoring of pm and pm . components [ ] to models for spatial analysis [ ] up to the current, almost worldwide coverage [ ] ; . a more comprehensive picture of the health effects of air pollution, which include cancer [ , ] , metabolic diseases [ ] , maternal and birth outcomes [ , ] , developmental effects [ ] , cognitive impairment [ ] and central nervous system (cns) diseases [ ] . all these additional diseases have a progression that is consistent with cumulative exposure and progressive mechanisms of damage, such as chronic or degenerative diseases; . an updated definition of "adverse health effects of air pollution" that includes asymptomatic signs of health deterioration, such as biological effects, altered biomarkers and reduced functions [ ] the extension of exposure-lag-response models to allow for the health effects due to the protracted exposures to environmental factors [ ] . the most frequently used approaches for assessing l-t effects were cohort studies and the studies that use functions to link exposure to health effects [ ] . cohort studies had been focused on specific sources that were both noxious to human health and susceptible to reduction, such as traffic density [ ] [ ] [ ] , industrial emissions [ ] and home wood combustion [ ] . or they used cohorts created for different reasons but appropriate for representing population and assuring long prospective follow-ups to assess exposure changes after interventions [ , , [ ] [ ] [ ] . in addition, they also used populations that were resident in defined areas thanks to the availability of wide-ranging administrative and environmental data [ ] [ ] [ ] [ ] [ ] . studies using functions to link long-term exposure to health effects were promoted by the global burden of disease (gbd) for estimating the burden of diseases attributable to ambient pm . in areas with extremely high concentrations of air pollution, but no direct epidemiological evidence [ ] , such as india [ ] . the integrated response function that these studies implemented uses satellite data to assess air pollution and makes deaths data and mortality rates comparable through the use of a standardized method [ ] . this makes it possible to compare attributable risks across countries, where, briefly, the risk function to link exposure to health effects is estimated in each country for different exposures (ambient air pollution, second-hand smoke, active smoking and household solid cooking fuel), and the population attributable fractions (pafs) for each of them are calculated by using worldwide ambient pm . concentrations [ ] . both short-term and long-term studies of air pollution effects contribute to health impact assessment, since both of them give estimates of damage due to increasing noxious exposures, by using population attributable fractions or excess fractions, as the metric of effects. an additional metric called "impact fraction" has also been proposed [ ] for assessing "the potential efficacy, effectiveness, adequacy, and efficiency of planned intervention strategies", in studies that aim to estimate the health gains achievable by potential reductions of air pollutants levels [ ] [ ] [ ] . this approach could contribute increasingly to supporting the political decision to cut back air pollution, but the methods used in estimating the potential benefits should be further enhanced, so that the hei indicates it as the first pointer for accountability in the strategic plan − for understanding the health effects of air pollution, nd mar, : − [ ] . the theoretical concept of these potential effect measures is that they are a special case of attributable fraction that compare the effect of an observed exposure with that of a counterfactual case in which exposure is completely absent. as a matter of fact, different potential conditions of exposure are usually chosen [ ] (possibly on the basis of the knowledge about the available technologies). hence, a current choice of new limits to which air pollution concentrations should be decreased cannot rely on a counterfactual case that would posit zeroing air pollution, nor on a safe tested level, as we know that no threshold exists in the dose-response curve of air-pollution and health effects. finally, the definition of an "acceptable" damage not based on scientific evidences should involve larger social, economic and-political institutions. these studies have been and could be still useful also in revising the methods used to predict the possible beneficial effects of interventions, along the same lines as what the hei did by supporting, in the s, intervention studies on air pollution to test whether the proposed methods were able ( ) to assess the population exposure, ( ) to identify an effective dose of exposure ( ) to identify the best health outcomes (defined as those associated with several pollutants and detectable shortly after exposure change), ( ) to identify the best populations as those which make it possible to assess differences between areas, and to study the effects related to intervention [ ] . other studies help in choosing priorities for the intervention studies on the basis of the observed risk assessments for different exposures (behavioral, environmental, occupational), like those provided by the gbd studies [ ] , or from different sources (industrial, residential, vehicular and multiple sources) with respect to their effects on mortality, morbidity and on changes in pollutant concentrations [ ] . promoting an intervention to reduce air pollution with the purpose of reducing the health effects, requires evidence of a causal relationship between exposure to that pollution and those effects. it also requires estimates of excess fractions for the exposure so as to be able to evaluate to what extent the interventions have met expectations. a no-threshold linear concentration-response (c-r) curve has been assumed to exist by researchers on the basis of a linear relationship of the observed intermediate values in most of the initial studies on air pollution effects. likewise, a further assumption was that a linear relationship of not measured values there could be on both the left curve, i.e., at the lowest levels of pollutants, and the right one, at the highest levels. the assumptions about the lowest levels of pollutants were discussed from the point of view of public health, since the shape of the c-r curve is an important parameter for predicting the benefits of reducing high-level exposure [ , ] . just a bit of evidence of a threshold was found, whereas the two methods of assessing regression linearity (penalized splines and model averaging) were equivalent. the possibility of predicting c-r curves at the highest levels at which to intervene first of all so as to reduce damages, has been discussed most recently by cox [ ] . the author questions the possibility that the observed c-r relationship might be used to predict the effects of an intervention at the highest levels of pm . , because this would imply that the magnitude or the direction of the observed curve was similar to those of the predicted curve after intervention. this assumption could not be necessarily true, since the observed values are fixed, whereas the predicted values are based on changing pollutant levels. additionally, pope, even though he recognized that both the burden of disease attributable to pm . and the benefits of reducing pollution depend upon the observed c-r function, found that pollution abatement may yield greater benefits in relatively clean areas than in highly polluted ones. hence, he concluded that the shape of the c-r function should be further explored to better understand this relationship for more effective abatement of air pollutant effects in the future [ ] . new types of evidence were proposed for estimating air pollutant regulatory strategies on the basis of direct experiments, rather than deriving predictions from observed situations [ ] . the most important feature of this approach-that justifies the use of the term 'causal inference'-is that different areas are analyzed to allow for the assumption that the intervention to reduce exposure in certain areas is assessed at random, as in a hypothetical randomized experiment. thus the researchers "anchored" the exposure assessment to the estimates of the causal consequences of well-defined interventions, and could conclude that the observed health effects, observed after the intervention, had diminished due to a given reduction in concentrations. the new methods were applied by zigler and colleagues to two case studies: • the first one, the "causal" health impact on mortality-among medicare beneficiaries-in areas which exceeded the pm limits, was compared with the mortality rates among medicare beneficiaries in areas where pm limits were not reached. the members of the first group were assumed to be randomly assigned to "treatment", after testing their comparability with the second group (controls) for potential confounders by using the propensity-score method. in other words, this causal approach allows the consideration of mortality rates among controls as the mortality that might have occurred among cases had their area's exposure been below the pm limit. the second case study examined the extent to which sulfur dioxide (so ) affects emissions of so , nitrogen oxides (no(x)), and carbon dioxide (co ). the authors tested a range of scrubber technologies to reduce multiple gaseous pollutants (so , no and co ) in emissions and outdoor pm . concentrations in areas where plants were either equipped with scrubbers or were not so equipped. the causal estimates were supported by applying principal stratification and causal mediation methods to assess the exposure, while a bayesian nonparametric method was used to evaluate whether the effect on pm . was really mediated by reducing gas emissions. scrubber systems (chemical or gas scrubbers) control air pollution by removing particulate matter and/or gases from industrial exhaust streams. propensity scores [ ] , principal stratification [ ] , causal mediation analysis [ ] , spatial hierarchical models [ ] , and bayesian estimation [ ] are the methods that support and allow us to evaluate a causal relationship [ ] . by grounding accountability research in a potential-outcome framework and applying these methods to national data sets, the authors provide additional evidence of the health effects of long-term, large-scale air quality regulations. the experiences briefly presented above remind us of the difficulties of this discussion. if, from a scientific point of view, it is always possible and appropriate to improve on the available knowledge, as was done in developing the first studies on air pollution effects (see above pp. - ), from a public heath point of view, taking a decision on the basis of the contemporaneously available knowledge (as it was done at the end of the th century in both europe and the usa) would be at times desirable or even necessary. epidemiologists have expressed doubts about policy indecision in the face of clear scientific evidences [ , ] . on the other hand, the problems of uncertainty [ ] , verification of hypothesis [ , ] and heterogeneity still affect important studies. uncertainty is due to errors in estimating mean values in a population, especially when parts of it are commuters; uncertainty may have multiple explanatory factors and is currently quantified by montecarlo simulation, a statistical technique requiring many assumptions. interventions implemented to reduce traffic have not achieved the expected results, but the verification of this hypothesis could rely on many factors not considered in carrying out the interventions such as the spatial and temporal variability of a similar "preventive" intervention. heterogeneity, the first recognized in the multicity studies, has been partly explained by the different composition of particulate matter in different areas [ ] , or controlled by using hierarchical bayesian models to combine the city-specific estimates [ ] but the discussion about the assumptions of these models is still open [ , ] . we can but wish for increasingly well-defined research questions, more accountability studies and further improvements in research methods so as to provide more solid answers to the scientific questions and the policy indecision. meanwhile we would like to go back here to what pope and dockery wrote in about the effects of fine particulate air pollution [ ] . "despite important gaps in scientific knowledge and continued reasons for some skepticism, a comprehensive evaluation of the research findings provides persuasive evidence that exposure to fine particulate air pollution has adverse effects on cardiopulmonary health". the accountability studies, as we saw before, arose as an attempt to "evaluate the extent to which air quality regulations improve public health to assess the performance of all environmental regulatory policies" [ ] . we return now to this first mission of accountability, to reconsider its strengths and weaknesses. three fundamental steps were identified in evaluating these regulatory policies, in logical sequence they are as follows: ( ) reducing emissions, ( ) improving ambient air quality, ( ) reducing adverse health effects; we could summarize these steps as the impact of air quality improvement on public health. a few of the most important accountability studies which applied these criteria are reported as follows: . the ban of coal sales in dublin was followed by an important decrease in black smoke concentrations ( %); natural mortality decreased by . %, respiratory mortality by . % and cardiovascular mortality by . % [ ] . reducing the sulfur content in fuel in hong kong was followed by a substantial reduction in seasonal deaths during the first months, followed by a peak death rate in the subsequent cool-season. it seemed that the intervention led to a significant decline in the annual trend of deaths from all causes ( . %; p = . ), respiratory ( . %; p = . ) and cardiovascular ( . %; p = . ) diseases, but not from other causes. the average gain in life expectancy attendant upon the lower pollutant concentration was to days [ ] . some measures to reduce traffic were implemented in more than one situation. the results in these cases are conclusive as regards neither exposures nor health effects. among the initial studies, those carried out in atlanta during the olympic games have produced contradictory results. the first [ ] found promising evidence, as the decreased led to a prolonged reduction in ozone levels and lower rates of childhood asthma events. the other study [ ] instead found that meteorological conditions contributed significantly to the reduction in ozone, emergency department visits did not decrease, and the strategy adopted for the occasion would not be sustainable beyond that exceptional event. in contrast, both the studies carried out in london to assess the impact of the congestion charging scheme (ccs) did not find conclusive results: the first, appearing five years after the introduction of the ccs, showed a modest benefit in air pollution levels and life expectancy. the explanation given was that the greater reductions in air pollution in deprived areas have had only a small impact in counteracting the socioeconomic inequalities in exposure and mortality rates [ ] . the second study, published eight years after the introduction of the ccs, deals with the oxidative potential (op) of pm as a parameter of traffic exposure. it shows a remarkable variation of op between roadside and urban background locations, which was attributed to varying pm components. this result is consistent with the increased vehicle use throughout london in recent years and a decreased number of vehicles entering the ccs [ ] . another well-conducted study evaluates, in several dutch cities, the air quality and health effects of local traffic policies including low emission zones; however, apart from one urban street in the hague where traffic flow and air pollution were drastically reduced, the study did not find that "reductions in air pollution related to abatement policies lead to actual improvements in respiratory function" [ ] . the experience that the world is currently facing thanks to covid- reduces mobility-worldwide and simultaneously-as regards both long distance and local urban traffic, thus offering the framework for a "natural" experiment which the health effect institute also suggested to study [ ] more specifically about the health effects of reducing traffic and long-distance transports. what has emerged until now are few points which, however, support the hypothesis of a natural experiment, such as the reduction of particulate matter in the atmosphere during the pandemic [ ] , the association of air pollutants (pm, no and o ) with an increased risk of covid- infection [ ] and a possible role in transmission of severe covid- infections by air pollutants [ ] . some people would like causal accountability studies to support the more effective political interventions and thus replace traditional assessment which would be based on expensive studies about the exposure-response relationship in estimating the burden of diseases [ ] . but the authors themselves of the causal accountability studies have concluded that their methods are "an important addition to the toolkit and should continue to be further explored, but cannot wholly substitute for accountability assessments that rely on evidence from other scientific methods, including more traditional epidemiology analyses." in general, the impact of the interventions on public health should be maintained both to verify the full achievement of the results and to identify the potential necessary corrections, since the process of accountability involves so many scientific, administrative and political institutions. in addition, it is possible that many interventions together, or in sequence, are needed to reduce pollutants or that they require more time to exert effects on total population health and so on. this is well evidenced in a not very recent paper which anticipated the importance of longer term, wide-ranging actions or events such as the complex changes associated with the reunification of germany [ ] . this approach is also evocative of experiments that respect the natural times for changes. both the kind of accountability that assesses the 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article is an open access article distributed under the terms and conditions of the creative commons attribution (cc by) license acknowledgments: i thank karen christenfeld for the accurate revision of the english text. neither financial nor other relationships might lead to a conflict of interests.note: manuscript has neither been published previously nor is under consideration for publication in another journal. key: cord- -x gd kq authors: kelly, frank j.; mudway, ian s.; fussell, julia c. title: air pollution and asthma: critical targets for effective action date: - - journal: pulm ther doi: . /s - - - sha: doc_id: cord_uid: x gd kq evidence to advocate for cleaner air for people with asthma is not in short supply. we know that air pollution is associated with the development and worsening of the condition and that mitigating interventions can improve respiratory outcomes. we have clear targets, particularly traffic emissions, especially in urban areas, and plenty of potentially effective actions. road traffic must be reduced, and what remains should be cleaner and greener. urban green spaces, safe cycle networks and wider pavements will promote active travel and leisure time exercise. healthcare professionals must ensure people are aware of their air quality, its impact on asthma and the appropriate behaviour to safeguard health. what remains are realistic policies and effective measures, based on the correct scientific evidence, to be taken forth with political courage and investment so that air pollution no longer contributes to the development or worsening of respiratory ill health. we know that air pollution is associated with the development and worsening of asthma and that improving air quality can result in respiratory health gains. the challenge associated with achieving sustained reductions in air pollutants to reduce new-onset asthma and prevent worsening symptoms in those already afflicted should not be considered an intractable one. we have clear targets and a wealth of opportunities to effectively act and make progress. in this review, we discuss a broad array of interventions, targeted to multiple sectors of society, with the aim to bring multiple public health benefits, in addition to air quality improvements. asthma is a common and chronic condition of the lung in which inflammation causes the bronchi to swell and narrow the airways, leading to episodic periods of wheezing, shortness of breath, cough and chest tightness. it affects around million people worldwide [ ] . incidence and prevalence are higher in children, however morbidity and mortality are higher in adults [ ] . asthma tends to be a disease of more developed economies where there is some evidence that prevalence may have peaked [ ] . in contrast, rates are increasing in low-and middle-income countries where outcomes are much worst [ , ] . superimposed upon day-to-day symptoms, sufferers experience life-threatening exacerbations lasting from days to weeks, which are caused by a variety of stressors, including respiratory viral infections, allergen exposure and air pollution. there is now consistent evidence that exposure to traffic-related air pollution (trap; particularly nitrogen dioxide [no ]) is associated with an increased risk of developing asthma across the entire life course, and evidence is accumulating for a link between poor indoor air quality and new cases [ , ] . a recent global (incorporating countries and major cities) estimate of the burden of paediatric asthma incidence attributable to ambient no at a spatial resolution fine enough to resolve intra-urban and near-roadway exposure gradients reported that each year million new paediatric asthma cases could be attributable to no pollution; % of these in urban centres (table ) [ ] . the work also estimated that about % of children lived, and % of new asthma cases attributable to no occurred, in areas with annual average no concentrations lower than the world health organisation's annual air quality guideline of lg/m . whilst there is no known cure for asthma, pharmacological intervention significantly improves symptoms [ , ] . unfortunately, however, despite international guidelines, treatment compliance rates ([ %) required to maintain disease control is often poor, even in countries where treatment is readily accessible [ , ] . reducing the onset of asthma and safely controlling symptoms through air pollution mitigation strategies, discussed herein, should therefore be regarded a significant component of the overall armamentarium against this debilitating respiratory condition. the studies selected for inclusion in this review were collected through a search of the pubmed database and grey literature using the following keywords: 'asthma' and 'air pollution' or 'traffic' or 'indoor air' or 'particulate matter (pm)' or 'no ' or 'oxides of nitrogen (no x )' or 'diesel' and 'mitigating' or 'interventions' or 'policy' or 'reducing' or 'action' or 'public awareness'. the information included in this review has been chosen to deliver a broad discussion of interventions, targeted to multiple sectors of society, to reduce the burden of air pollution on the prevalence and severity of asthma. this article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors. data from many parts of the world strongly suggest that policies designed to reduce air pollution can improve respiratory outcomes. in california, reductions in pm . (pm with a diameter \ . lm) and no between and reduced the risk of incident asthma in children by % (fig. ) [ ] . in a swiss cohort of adults, a decline in pm (pm with a diameter \ lm) concentrations from to was associated with a % decrease in the annual rate of decline in forced expiratory volume in s [ ] . a follow-up study found that for every , persons in the community, a further decline in pm from to was associated with fewer people with wheeze or shortness of breath [ ] . in japan, legislation was passed in to limit transportation-related emissions. by , decreases in pm . and no were linked to a lower ( . - . %) prevalence of paediatric asthma [ ] . benefits have also been observed following local air quality interventions associated with factory closures and hosting of olympic games. hospital admissions for childhood asthma fell by half, in association with a significant reduction in pm . , because of a -month closure of a steel mill in the utah valley [ ] . a -day ''alternative transportation strategy'' implemented by the city of atlanta in the summer of brought about a % decrease in peak morning traffic; within weeks of this decrease, there was a % reduction in children seeking medical care and a % decrease in hospitalisations for asthma [ ] . in preparation for the beijing olympics, the chinese government enacted factory emission and travel restrictions that resulted in pollutant concentrations decreasing by up to % [ ] . within months, these reductions were linked to an improvement in lung function among both healthy adults and those with asthma [ ] as well as % fewer asthma-related physician visits [ ] . benefits of improving indoor air quality have also been documented. installing less polluting heating appliances (heat pump, wood pellet burner, flued gas) in homes of children with asthma in new zealand reduced symptoms, days off school, healthcare use and visits to a pharmacist [ ] . australian schools randomly allocated either to retain unflued gas heaters or have replacement flued gas/electric heaters installed reported a significant reduction in breathing difficulties, chest tightness and asthma attacks in the intervention group [ ] . the substantial challenges associated with achieving the sustained reductions in air pollutants necessary to reduce new-onset asthma and to prevent a worsening of symptoms in those already afflicted reflect not only the insidious nature of this environmental insult, but also the wealth and complexity of issues entwined with sub-optimal air quality. europe's car fleets have been transformed to being powered by diesel (emitting more pm and no x than their petrol or hybrid counterparts) [ ] . the powering of light and heavy goods vehicles [ ] , machinery on the ground [ ] and ships in the port area [ ] are also dominated by diesel. schools are invariably sited near busy roads and traffic junctions made worse by the 'school run' that is synonymous with idling engines as parents drop off or wait for their children [ ] . in , schools within london were in areas exceeding the annual mean no eu limit value [ ] . people on low incomes and ethnic minorities tend to be more affected than others by equivalent exposure to air pollutants [ ] and are also exposed to some of the worst outdoor and indoor air quality [ , ] . indoor environments, where most human activities now take place within an enclosed space, are characterised by a chemically diverse and complex air quality [ ] . furthermore, unlike tobacco smoke, healthcare professionals have yet to take effective ownership of the problems that air pollution inflicts on society. on a more optimistic note, and one that this commentary attempts to take, such a challenge should not be regarded as intractable, but one in which there plenty of opportunities and ways, some of which are discussed below, to effectively act and make progress. one of the most significant sources of air pollution in urban areas, where % of the world's population now resides [ ] , is road traffic (exhaust emissions, as well as particles from tyre, brake and road surface wear). it is, as stated earlier, also the source that has repeatedly been shown to cause/worsen asthma. the main traps of concern to health in european cities are pm . (particularly the fraction derived from the tailpipe) and no . in london in the uk, traffic is responsible for around % of no x and % of pm and pm . concentrations at roadside locations [ ] . this is not only due to the significant growth in vehicle numbers, but also to failures of vehicle manufacturers to ensure that they meet emissions limits in realworld driving conditions. across markets, representing approximately % of global diesel vehicle sales, anenberg et al. [ ] reported that over one-half of light-duty and nearly one-third of heavy-duty diesel vehicle emissions are in excess of certification limits. cleaning up the air in heavily populated urban areas to reduce the heavy toll on people with asthma therefore requires a reduction in road traffic as well as a cleaner and greener element to what remains on the road. cleaner fossil-fuelled vehicles require tougher regulations to reduce exhaust emissions, not only for new vehicles, but also afterwards in annual safety/roadworthy tests. commonly cited disincentives aimed at removing the most polluting components of the fleet, i.e. those fuelled by diesel, include levies on fuel, surcharges for parking and the introduction of lowemission zones (lez). however, whilst largescale lezs can deliver improvements in urban air quality, data suggest that, at least in densely populated european cities, more ambitious schemes are required to meet legislative limits and deliver improvements to childhood respiratory health, including asthma symptoms [ ] . the introduction and rigorous evaluation of zones with greater reductions in pollutant concentrations are clearly warranted and may benefit from adjuvant clean air zones that introduce no vehicle idling areas, minimise congestion and support active and low-emission travel through the integration of public transport networks, including park-and-ride schemes. the continued development of new technologies by motor manufacturers in producing vehicles that rely on alternative fuels (electricity, hydrogen) coupled with seamless interfaces with sustainable energy suppliers must also be actively encouraged and incentivised. alternatively fuelled vehicles are not however the sole answer to poor air quality since zero-emission road transport does not currently exist. particulate pollution from road traffic not only includes engine emissions, but also an increasing contribution from brake/tyre wear and road surface abrasions [ ] . it is noteworthy that the potential of non-tailpipe emissions to elicit health effects is largely ignored at the regulatory level despite links with pulmonary toxicity [ ] . to this end, non-tailpipe particulate pollution must be tackled by considering regulation in line with exhaust emissions and innovations in the development of 'safer' tyres, brakes and road surfaces. procurement of appropriate vehicles in the public and commercial sectors is crucially important and nowhere more so than for school buses. data from the usa show that although school bus commutes usually make up only a small part of a child's day, they can contribute up to one-third of a child's -h overall exposure to black carbon during a school day [ ] . moreover, data support the emission reduction benefits of high-efficiency cabin air filtration system [ ] and anti-idling [ ] , as well as health benefits associated with changing fuel from diesel to compressed natural gas [ ] . it should also be stressed that cleaner road transport will not only emerge from the vehicle itself, but also from practices, such improved energy-efficient driving skills that could be introduced through tests and training programmes. for example, a smooth driving style (vs. frequent stopping and starting) ensures that motorists travel steadily at an optimum speed, thereby reducing fuel consumption and in turn air pollution through reduced exhaust emissions, as well as particles emitted from brake and tyre wear [ , ] . the safe and efficient movement of people around towns and cities ultimately necessitates fewer vehicles. this can only be achieved through: ( ) clean, efficient and expanded public transport systems coupled with car share/club schemes and ( ) as much active transport in the form of walking and safe cycling as is feasibly possible. people need to be given more cost-effective and easier alternatives to move through the urban environment, be that on the school run and/or on the commute to work, without necessarily owning a car or taking one out for short journeys. a report by the european court of auditors reveals that commuters in europe are still choosing their cars over public transport, enduring ever-longer journey times into some city centres owing to traffic congestion [ ] . cost, convenience and time-efficiency were all factors cited as challenges in persuading citizens to leave the comfort of their cars for other forms of transport. it is likely however that perception and beliefs also come into play, with car ownership construed to be symbols of success and social status [ ] . the built environment incorporates multiple components that can influence local air quality and in turn ill health. some examples include neighborhood design (walkability, bikeability, connectivity), housing quality, schools, transport facilities (roads, railways, ports, airports), power plants, industrial facilities, accessibility to shops and green space. cities created prior to the introduction of cars tend to be more densely populated and more walkable compared to newer conurbations, which tend to be less populated and more reliant on cars for transport. a vicious circle often ensues in that the mass use of cars in newer cities often goes hand in hand with inadequate public transport, poor infrastructure for active commuting, lack of green space and higher exposures to air pollution. strategies to clean up the air in cities of all ages should focus on the 'cleaner/fewer vehicles' formula already discussed. a cleaner element should be encouraged by not only providing, but also maintaining, adequate charge points for electric vehicles. fewer vehicles will ensue from siting new buildings in locations near essential amenities, thereby reducing the requirement for motorised travel and thus minimising the exposure of vulnerable/disadvantaged groups to inadequate air quality. this could be achieved by locating new homes for essential workers, schools, nurseries and care homes away from roads and avoiding the creation of configurations such as deep street canyons that encourage dangerous concentrations of air pollution to build up [ ] . when air pollution limits are exceeded, local authorities need to act strategically to close or divert roads to reduce the volume of traffic, especially near schools and vulnerable communities. this of course can only be achieved by adequate, accurate and accessible air pollution monitoring programmes. planting trees and the construction of green walls and roofs to create an organic barrier to intercept pm and absorb gaseous pollutants have had mixed results by either improving air quality or in fact worsening it by restricting street ventilation. that the absolute effect of urban greening strategies will depend on factors such street configuration and canopy design means that the appropriate management of urban vegetation (siting, choice of species, maintenance regimes) is critical to maximise potential benefits [ ] . with relevance to asthma, any beneficial and cost-effective to these greening strategies should avoid the use of highly allergenic plants. failure to do so risks marginal gains in air quality being offset by a significant increased risk of exposure to known triggers of asthma exacerbations [ ] . compared to the growth in the volumes of road traffic in the uk over the last years, active transport (walking and cycling) has been on the decline [ ] despite its social, economic and health benefits [ ] [ ] [ ] . well-designed and maintained urban green spaces, coupled with fewer vehicles on the road to permit expanded safe cycle networks, wider pavements and other public areas (as discussed above) will create the much-needed opportunities for active travel. additional mechanisms to promote a step change include mandatory cycle training at schools, cycle-to-work schemes and steps to support cyclists and pedestrians by, for example, providing a choice of routes to avoid highly polluted roads. beyond active transport to reach schools, higher education establishments and workplaces, the provision of pleasant and mixed-activity spaces will also encourage more exercise taken as a form of leisure. a marvellous exemplar is the infamous la ciclovía in bogotá that, every sunday between and hours, hands miles of its usually choking city streets over to over million cyclists, skaters, walkers, runners and other athletes (fig. ) [ ] . this much-loved programme began in as a citizen protest that the city was becoming too car-focused, and now attracts city-dwellers of all ages and social backgrounds who exercise alongside each other through the colourful neighbourhoods of columbia's capital city [ ] . as one of the world's most successful mass recreation events, it has become one of the city's most famous exports. ciclovías have sprung up in numerous south american countries as well as cities in canada and the united states. we need more ciclovías around the world to provide a tangible vision of what a city with more cycle paths and fewer cars might look like, not just for weekly recreation, but also how cities could be designed and run differently. in addition, by truly embracing young children, they can create a generation that look at the street from a completely different perspectiveone that feels like an extension of their driveway and is therefore a safe place for recreation in a dense urban metropolis. promoting physical activity in car-free urban spaces is a double positive for asthmatics in reducing trap, increasing exercise and promoting healthier lifestyles and wellbeing. evolving research suggests that structured exercise routines may help improve some aspects of asthma control. indeed, results from several recent systematic reviews and meta-analyses not only strongly support the safety of structured exercise routines in children and adults with asthma, but also suggest such routines favour improvements in asthma symptoms and quality of life [ ] . up until relatively recently, air pollution was invariably deemed to be solely an outdoor issue, in the general belief that the confines of an inside space, and particularly one's home, offer protection. there are however unique factors which, when combined, have created challenges to indoor living: increased time spent indoors owing to dramatic changes in the lifestyle and working conditions of modern society [ ] ; the transition from natural (wooden floors and woolen carpets) to synthetic (synthetic floor coverings with added stain repellants and flame retardants) materials that have been introduced into indoor spaces [ ] ; the construction of energy-efficient-and with this, airtight-homes that lack inadequate ventilation and promote the buildup of air pollutants [ , ] . in response to these trends and evidence that ill-health, including the severity and/or prevalence of asthma, is heightened by many indoor air pollutants, including no x from gas cooking [ ] , cleaning products [ ] , formaldehyde [ ] , phthalates [ ] , allergens [ ] , mould [ ] and carbon monoxide [ ] , a set of recommendations from experts and young people have recently been published [ ] . this welcome initiative provides wide-ranging advice for government, local authorities, building and child healthcare professions and the public about the changes that are needed ensure that air quality in homes, nurseries and schools does not pose a health risk to children. there is clearly ample evidence to advocate for cleaner air for people with asthma, but since clear and objective scientific assessments are so crucially important to guide the development of evidence-based public health policies, there remains the need for further cross-disciplinary research into the respiratory health effects of air pollution, as well as the effectiveness of mitigation strategies. for example, the independent effects of no and pm are still unclear and need to be deciphered, especially at a time when uptake of electric vehicles is eliminating no emissions, with little of no impact on pm emissions from tyre and brake wear [ ] . another area of uncertainty is the potential of pm from biomass burning to contribute to asthma. this is especially pertinent in the light of the fashionable return of residential wood burning in europe owing to aesthetic appeal and quest to reduce fossil fuel combustion [ ] . research themes applicable to indoor spaces that require greater scientific understanding include the benefits of indoor air filtration, placement of building air intake away from sources of air pollution and vegetative/physical barriers between roadways and homes and schools. such areas of research will benefit from the considerable advances in mobile sensors that can be carried by individuals to monitor personal air pollutant exposure, as well by modeled-based approaches using big data. one such exemplar that is the breathe london: wearables study that provided children and teachers with wearable sensors to carry to and from school to characterise london's school children's exposure to air pollution [ ] . initiatives such as this one, which gathered million measurements, create unique data sets to determine where children may be exposed to elevated concentrations and which forms of transport are more polluting, and to compare air quality within and surrounding schools. validation studies are also reporting coherent epidemiological trends that support the use of smart phone application (app)-sourced data to examine relationships between asthma symptoms and air quality [ , ] . these rapidly evolving technologies will enable estimates of personal air pollution exposures for large populations-currently an elusive goal, but a central one to determine health impacts, evaluate exposure sources, detect susceptible populations and identify intervention opportunities. when individuals, especially vulnerable patients with respiratory problems such as asthma and chronic obstructive pulmonary disease, are exposed to such a well-established and preventable cause of ill health and premature death, our public health and healthcare professionals must have the knowledge to provide sound, evidence-based advice. this requires training about air quality and health risks and being equipped with toolkits to screen and identify at risk populations, raise public awareness, influence behavioural change, help prevent and/or control associated disease and take collective action to bring about positive change. defining patient exposure to air pollution can be difficult since sources and composition vary between communities and within households. one way to open up knowledge and awareness would be for primary healthcare workers to simply pose pertinent questions to patients, alongside those already asked about diet, exercise, smoking and alcohol, and document the answers in medical records [ ] . for indoor air pollution, asking what type of fuel is used for cooking and heating, how the home is ventilated and what sort of cleaning, do-ityourself and personal care products are routinely used may provide important information to help gauge the extent of exposure and advise on lifestyle or products changes that can improve indoor air quality. an understanding of outdoor air pollution exposure requires clinicians to be equipped with reliable local air pollution data supplied by a reputable source, whilst questions to patients should focus on proximity of the household/workplace to urban or industrial environments, commuting practices, occupation and time spent near heavy traffic. additional inquiries to provide a qualitative picture of exposure should focus on outdoor physical exertion (e.g. active transport during commutes, manual work, exercising) and open-ended questions about air pollution in the local community to identify any sources of risk that may otherwise go undetected. such a screening approach will allow clinicians to be better placed to design and discuss individualtailored strategies. recommendations to reduce exposure should always emphasize the importance of avoiding the pollutant source-the most effective intervention. they must also be practical and inexpensive and guard against negative behavioural patterns, such as healthy individuals avoiding outdoor exercise. furthermore, recommendations must avoid advocating the use of inaccurate personal pollution-monitoring devices and any interventions designed to reduce air pollution exposure/the risk of adverse respiratory outcomes that are scientifically unproven. the public must also have access to engaging and high-quality educational materials in primary care and hospital settings. this will go some way in ensuring patients (including low-risk individuals) are better informed on this key issue. as influential members of the community, healthcare workers have a particularly important role to play in advocating for cleaner and safer air on behalf of their patients and thereby advance the global effort to combat the adverse effects of air pollution. a hugely successful analogy is the effective anti-tobacco campaigns that facilitated the smoke-free legislation. the resulting health gains documented worldwide exceeded expectation, including a reduction in childhood and adult hospital admissions for asthma [ ] . outside of clinical settings, approaches to raise awareness of air quality where people, and especially susceptible individuals, congregate (e.g. bus stops, rail stations, shopping areas, etc.) are a crucial as a way of warning of the potential health risks. in an ideal world, people should also regularly check an air quality index (using traditional and social media) or a smart phone app before going to work or school or pursuing leisure activities, prompting them to take action (reduce exposure and/or increase use of inhaled reliever medication) in the event of increased pollution [ ] . alert services accessed via apps are becoming increasingly informative and engaging by providing realtime data and proactively warning registered users of impending pollution events (fig. ) [ , ] . these services also offer tailored advice on how specific groups can reduce emissions by, for example, providing low-pollution journey planners to reduce exposure. the breathe london: wearables study described earlier spans the scientific research/public awareness divide by introducing initiatives such the relatable presentation of collected data to participating school communities, science lessons and surveys/focus groups for children and parents to assess views and perceptions of air pollution [ ] . to recap, we do not have a shortage of evidence to advocate for cleaner air for people with asthma. we know that air pollution is associated with the development and worsening of the condition and, importantly, since we are dealing with an avoidable health risk, mitigating interventions can result in prompt and substantial health gains. we also have a clear target, namely traffic emissions, especially in urban areas, and plenty of potential actions to safeguard the health of people of all ages. this is all good news. a crucial component to what remains is political will, guided by the science, since the recommendations discussed herein would need to be supported by a new clean air act, based upon world health organisation health-based air quality limits, the adequacy of which are currently being revisited. however, deciding upon and executing the necessary policies is a complex challenge when it necessitates among other measures, a reduction in road traffic and a cleaner and greener element to what remains on the road-coupled to a heavy burden of expenditure. policymakers are invariably torn between tightening controls on emissions to enhance health and succumbing to economic pressures not to reduce emissions. several actions in combination must however be taken since multiple measures, each producing a benefit of varying size, are likely to act cumulatively to produce significant change. the response to the coronavirus disease (covid- ) pandemic across the world, in the form of economic rescue packages, has however clearly demonstrated the power of governments and the speed at which they can act when the political will is there and when there is a shared sense of an emergency. we really need to hold onto this, and must guard against voices that may say we need to de-regulate to get the economy going again in a non-sustainable way. in support, findings suggest that the pandemic and, specifically, imposed lockdown measures could result in behavioural changes and thus environmental improvements to benefit those living with asthma. it has clearly given people the opportunity to appreciate how much they depend on exercise in treasured green spaces. there are also glimmers of hope that reduced reliance on the car and increased active travel may emerge. in the uk, an aa-populus poll fig. cityair smartphone app. the app shows: ( ) advice tailored to specific user groups; ( ) air pollution forecast; ( ) low-pollution journey planners survey reported that one-fifth of drivers will use their cars less when restrictions are lifted [ ] . fear of contracting coronavirus on public transport has also led to a boom in cycle-towork schemes, whilst demand for greater mobility and exercise amid lifestyle changes has also boosted bike sales across the uk [ ] . mindset shifts such as these should now be skilfully harnessed with realistic policies and effective measures. in turn, they must be taken forth with political courage and investment so that air pollution no longer contributes to the development or worsening of respiratory ill health. between public health england and imperial college. the views expressed are those of the author(s) and not necessarily those of the nihr, public health england or the department of health and social care. the study was also part supported by the mrc centre for environment and health, which is currently funded by the medical research council (mr/s / , - ). infrastructure support was provided by the nihr imperial biomedical research centre (brc). no rapid service fee was received by the journal for the publication of this article. authorship. all named authors meet the international committee of medical journal editors (icmje) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. disclosures. frank kelly, ian mudway and julia fussell have nothing to disclose. compliance with ethics guidelines. this article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors. data availability. data sharing is not applicable to this article, as no datasets were generated or analysed during the current study. open access. this article is licensed under a creative commons attribution-non-commercial . international license, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the creative commons licence, and indicate if changes were made. the images or other third party material in this article are included in the article's creative commons licence, unless indicated otherwise in a credit line to the material. if material is not included in the article's creative commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. to view a copy of this licence, visit http://creativecommons.org/licenses/bync/ . /. chronic respiratory diseases: asthma. q&a detail epidemiology of asthma in children and adults worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in 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collected using researchkit can smartphone data identify the local environmental drivers of respiratory disease? developing a clinical approach to air pollution and cardiovascular health smoke-free legislation and child health monitoring air pollution: use of early warning systems for public health london air. mobile apps cityair app automobile association (aa) coronavirus: boom time for bikes as virus changes lifestyles funding. this study was funded by the national institute for health research (nihr) health protection research unit in environmental exposures and health, a partnership key: cord- -g zteit authors: park, kyu-tae; hwang, jungho title: filtration and inactivation of aerosolized bacteriophage ms by a cnt air filter fabricated using electro-aerodynamic deposition date: - - journal: carbon doi: . /j.carbon. . . sha: doc_id: cord_uid: g zteit abstract carbon nanotubes (cnts) were coated on a sample of glass fiber air filter medium at atmospheric pressure and room temperature using electro-aerodynamic deposition (ead). in the ead method, cnts (diameter: nm, length: – μm) were aerosolized, electrically charged, and injected through a nozzle. a voltage was applied externally between the ground nozzle and a planar electrode on which the sample was located. the charged cnts were deposited on the sample in a vertically standing posture even at a low flow velocity. before the deposition experiment, a calculation was performed to determine the applied voltage by simulating the electric field, flow field, and particle trajectory. using cnt-coated filter samples, virus aerosol filtration and anti-viral tests were carried out using the aerosol number counting method and the plaque counting method, respectively. for this purpose, bacteriophage ms was aerosolized with an atomizer. the particle filtration efficiency was increased to . % in the most penetration particle size zone ( nm) and the antiviral efficiency of the cnt filter was % when the coating areal density was . × #/cm . the susceptibility constant of virus to cnts was . cm /μg. biological aerosols generally include bacteria, fungi, viruses and their derivatives such as endotoxin, glucans and mycotoxin. exposure has been shown to cause many adverse health effects including allergic, toxic, and infectious responses [ ] [ ] [ ] . aerosol transmission is known to play an important role in observed airborne microbial infections. studies indicate that large scale outbreaks of severe acute respiratory syndrome (sars) were mainly the result of airborne exposure routes [ , ] . viruses are detected in air samples collected from hospital rooms [ , ] and also in human breath [ , ] . a study indicated that there was an approximately % possibility of influenza virus infections in people wearing surgical and n respiratory masks [ ] . therefore, development of efficient air control technology is important in combating inhalation-related diseases. over the years, a large volume of studies have been undertaken to develop air cleaning technologies. among the various air cleaning techniques, filtration is widely applied to remove particles from air streams. however, recent research has demonstrated that some microorganisms are capable of colonizing the air filter surface in heating, ventilating, and air-conditioning systems (hvac) [ ] [ ] [ ] , and the organic or inorganic materials deposited on the filter surface can contribute to microbial growth. air filters contaminated by microorganisms lead to the release of microorganisms from the filter surface [ ] , and the emission of volatile organic http://dx.doi.org/ . /j.carbon. . . - /Ó elsevier ltd. all rights reserved. compounds (vocs) produced by microbial metabolism [ , ] . biologically contaminated filter could pose a significant health hazard through reaerosolizing opportunistic pathogenic or allergenic aerosols [ ] . antimicrobial treatment could be a possible solution to these problems. carbon nanotubes (cnts) have been increasingly used in environmental applications due to their high specific surface area, smooth surface, and adsorption capability [ ] . recently, multi-walled and single-walled cnt filters were developed and found to be effective for multilog microbial removal from contaminated water by physical straining, puncture and depth filtration [ ] [ ] [ ] [ ] . cnts were shown to inactivate the highest percentage of cells both in monocultures and diverse microbial communities of river water and wastewater effluents [ ] [ ] [ ] . a cnt filter was successfully created and utilized to remove biological agents from water with filtration efficiency [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . even though carbon nanotube filters have been extensively studied for water purification, there are only a few reports in the literature on carbon nanotube use for air purification. viswanathan et al. [ ] presented the first investigation of the use of multi-walled carbon nanotubes (mwcnts) as high efficient, airborne particulate filter media. high filtration efficiencies were achieved from films of mwcnts deposited onto cellulose fiber filters. the mwcnt-coated filters exhibited low pressure drops and better filter quality than cellulose filters. park and lee [ ] constructed a metal mwcnt filter in which carbon nanotubes were grown directly on the micron-sized metallic fibers of the air filter using the thermal chemical vapor deposition (cvd) method. the metal mwcnt filter had higher filtration efficiency than conventional filters without a significant decrease in pressure. karwa and tatarcuk [ ] studied an enhancement in aerosol filtration by synthesizing carbon nanostructures including nanofibers within nickel sintered metal microfibrous matrices/filter media. their study showed that carbon nanostructure synthesis led to significant improvement in the performance of filter media with large initial pore size because the pore diameters did not reduce significantly with synthesis. yildiz and bradford [ ] prepared novel filters by drawing aligned cnts sheets and embedding them between polypropylene melt-blown nonwoven fabrics using calendaring. the filters were prepared with an increasing number of cnt sheets. the filtration performance of the novel filters showed that when the number of cnts layers increased, the filtration efficiency increased dramatically, while the pressure drop also increased. guan and yao [ ] investigated the removal efficiencies of cnt filters for a collection of aerosolized biological and non-biological particles. in their preparation of the cnt filters, a predetermined volume of cnt suspension with a certain concentration was uniformly filtered through the membrane support. the removal efficiencies for aerosols and bacteria were shown to increase with increased loadings of cnts regardless of membrane supports and pore size tested. xu and yao [ ] fabricated a single walled carbon nanotube (swcnt) filter with cnt solution, and investigated its anti-bacterial efficacy with cnt loading. their results revealed that particle types and cnt loading had greater effects on anti-bacterial efficacy than other membrane types and pore sizes tested. park et al. [ ] reported that a mwcnt-deposited glass fiber filter showed increased particle filtration efficiency and antibacterial activity. in the fabrication of cnt filters, samples of glass fiber filter media were catalytically activated with iron (fe) nanoparticles generated by the spark discharge method. the catalytically activated filter samples were placed in a thermal cvd reactor in which mwcnt fibers were vertically grown on the activated spots after acetylene (c h ) gas was carried into the reactor. however, the fabrication of a cnt filter using the spark discharge method followed by the cvd process requires time and effort in controlling the operation of a cvd reactor. in addition, the durability of a cnt filter made by the cvd process can be degraded in the high temperature environment associated with the cvd process. in this paper, we suggest an aerosol process of fabricating a cnt filter at atmospheric pressure and temperature using the electro-aerodynamic deposition (ead) method, the details of which were introduced in our previous study [ ] . in the ead method, cnts were aerosolized, electrically charged, and injected through a nozzle, where an external electric field was applied. the charged cnts were vertically deposited on the glass fiber filter media even at a low flow velocity. using cnt coated filter samples, virus aerosol filtration and anti-viral tests were carried out using the aerosol number counting technique and the plaque counting method, respectively. susceptibility has been used to explain the relative importance of various parameters affecting antimicrobial efficacy. yoon et al. [ ] used susceptibility to evaluate the antibacterial effects of silver and copper nanoparticles. kim et al. [ ] applied susceptibility to evaluate the antibacterial effects of corona discharge-generated ions in the air. in this paper, the susceptibility of a virus to cnts was calculated to determine the inactivation efficacy with respect to cnt concentration. materials and methods after compressed air was passed through a clean air supply consisting of an oil trap, diffusion dryer, and high efficiency particulate air (hepa) filter, the particle-free compressed air entered a collison type atomizer ( , tsi inc., usa), which was filled with ml of de-ionized water and ml of % cnt solution. the aerosol flow rate was controlled by a rotameter. dry, clean air at lpm formed a high-velocity jet through an orifice in the atomizer. the pressure drop from this jet drew the cnt solution up through a tube. the solution was then broken up into droplets by the high-velocity air jet. the resultant larger droplets impinged on an impactor, while the smaller droplets made no contact and formed an aerosol that exited through an outlet. the aerosolized cnts were passed through a diffusion dryer for water removal and a neutralizer (soft x-ray charger , hct, korea) to induce a boltzmann charge distribution ( fig. (a) ). the neutralized cnts entered a unipolar charger where a stainless steel needle (wire) electrode, located at the center, was used to generate a corona discharge on its sharp tip (fig. b) . the corona discharge generated air ions, which moved along the electric field to a grounded cylinder (made of duralumin). the amount of charge per particle was controlled by dc voltage supplied from a high voltage power supply. a voltage of À kv was applied to the needle to charge the cnts. details of the charger are described in park et al. [ ] . the electrical current carried by the charged cnts was measured with an aerosol electrometer ( a, tsi, isa) to obtain the average charge number of the cnts, using the following equation: where n p is the average charge number, e is the elementary charge, i is the measured current, q is the flow rate, and n is the number concentration of the charged cnts (fig. b ). an ion trap was used to remove free unattached ions and allow charged particles to pass through the ion trap zone. the ion trap voltage was v [ ] . the charged cnts then entered a cylindrical nozzle (fig. c ) with a length of cm and a diameter of mm, which induced a fully developed flow and minimize the entrance effect at the nozzle (re = ). the nozzle filet had a finite radius of curvature ( mm) at the tip so that the electric field applied to this tip was minimized [ ] . after the charged cnts were ejected from the nozzle, they were guided by electrical force to deposit on a substrate located on an electrode to which a high voltage was applied. the distance between the nozzle and the substrate was mm. a silicon wafer or glass fiber filter medium (fabriano, italy) was used as the substrate. before the deposition experiment, a calculation was performed to determine the voltage applied to the substrate. commercial computational fluid dynamics (cfd) software, fluent, with external user defined function (udf) code was used to simulate the electric field, flow field, and particle charging motion. fluent is a solver software package for various physics and engineering applications and utilizes the finite volume method (fvm). even though fluent does not include an electric field solver, udfs allow for the customization of fluent to fit particular modeling needs. the discrete phase model (dpm) and the laminar model in fluent were used as the particle solver and the flow solver, respectively. first, the continuity equation and navier-stokes equation were solved for the flow velocity. the electric field was then obtained by solving poisson's equation with known particle concentration and particle charge (n p ) values. finally, the particle trajectory was calculated using the following equation: whereũ is the flow velocity, q is the density of air,g is the gravitational constant, d p is the particle diameter,ũ p is the particle velocity, q p is the particle density, c c is the cunningham slip correction factor, and l is the dynamic viscosity of air.f p in eq. ( ) describes the electrostatic forces on a particle (per unit mass) and can be expressed as follows: wheref e is the coulombic force per unit mass that is induced by charges and electric fields,f di is the dipole force per unit mass, andf im is the image force acting on a particle per unit mass [ , ] . simulation details can be found in park et al. [ ] . a scanning mobility particle sizer (smps) system consisting of a differential mobility analyzer (dma, , tsi, usa) and a condensation particle counter (cpc, , tsi, usa) was utilized to evaluate the cnt coating efficiency (fig. c) . aerosol sampling was carried out upstream of the nozzle (i) and also at the air outlet (ii) from undeposited cnts exited. the smps system was operated under a sampling flow rate of . lpm and a scan time of s. after fabrication of the cnt filter using glass fiber filter medium as the substrate, it was necessary to confirm whether the cnts were firmly deposited on the glass fibers. for this purpose, clean air with a face velocity of . m/s was forced to flow through the cnt filter. a smps was located downstream of the cnt filter to measure the number of cnts that detached from the filter. bacteriophage ms (atcc -b ) and escherichia coli strain c (attcc ) were selected as the test virus and host bacteria, respectively. to recover bacterial cells from a freezedried state, ml of tryptic soy broth (tsb) was mixed with the freeze-dried bacterial cells and the mixture was incubated with shaking for h at °c. a total of . ml of the incubated bacterial solution was injected into the ml of tsb. the tsb solution containing the bacteria was used as the host bacterial solution after incubation with shaking for six hours at °c. one milliliter of tsb was injected into the freeze-dried ms virus, and . ml of the viral solution was extracted. the extracted solution was mixed with . ml of the host bacterial solution and ml of soft tryptic soy agar (tsa) containing g/l of agar. the resulting agar solution was poured into a petri dish and incubated overnight at °c. the surface of the agar was scraped off with ml of phosphate buffer solution (pbs), ph . . the solution was centrifuged for min at g, and the supernatant was used as the virus solution in subsequent experiments. prior to filtration testing, the pressure drop across the cnt filter was measured using a differential pressure gauge (magnehelic , dwyer instruments inc., usa) with various face velocities of clean air ranging from . m/s to . m/s. after the pressure drop test, the filtration test was carried out using bacteriophage ms . the experimental setup for the filtration test is shown in fig. d . the system consisted of a test duct with a cross-sectional area of mm · mm and a length of mm, a test particle generation system, and a measurement system. a cnt filter sample was installed in the middle of the test duct. two isokinetic stainless steel sampling probes were placed before and after the filter media for aerosol sampling. aerosolized virus particles were supplied to the test duct by the same procedure used in the supply of aerosolized cnts. the number concentration of the virus particles was measured using an smps before and after the filter. a stream of clean air was delivered to the test duct and mixed with the particle-laden air flow to adjust the flow velocity. the fractional particle filtration efficiency, g f ðd p Þ, was defined using the following equation: where c(d p ) is the number concentration of aerosolized bacteriophage ms of size d p . the filter quality factor was evaluated with various face velocities using following equation: where q f is the quality factor, dp is the pressure drop, and g f is the integrated value of g f ðd p Þ over the particle size d p . the experimental set-up for the antiviral test is also shown in fig. d . to aerosolize the virus particles, . ml of the supernatant was diluted with ml deionized (di) water. the virus particles were aerosolized, and deposited onto each test filter for min in the test duct. a pristine filter and cnt-coated filter were used for comparison. each filter was put into the ml of di water and subjected to sonication for ten minutes with a batch-type sonicator (kmc v, vision scientific, korea) to detach deposited virus particles from the filter. then . ml of the water containing virus particles was mixed with . ml of host bacterial solution and ml of soft tsa. the mixed solution was poured into a petri dish and incubated overnight at °c. the number of plaques that appeared on the plate was counted and the antiviral efficiency was calculated using the following equation: where the numerator is the number of plaque forming units (pfu) on the nutrient agar plate after incubation when the cnt filter was used, and the denominator is the number of plaque forming units on the nutrient agar plate after incubation when the pristine glass fiber filter was used. the susceptibility of virus to cnts was determined by calculating the susceptibility constant z defined by the following equation, where c is the coating areal mass density of cnts (lg/cm ). a higher z value implies higher antiviral activity. moreover, experiments were carried out to compare the viable viral count in the air before and after the filtration, with both pristine and modified filters under the same experimental condition with the filtration test (at face velocity: . m/s). we generated virus with an atomizer and sampled aerosolized virus at both upstream and downstream the test filter. the sampled virus was captured on a sampling filter and cultured for pfu counting. the process depositing of cnts on a glass fiber filter sample required that the cnts were highly charged by the corona charger. when a voltage of À kv was applied to the needle of the charger, the current carried by the charged cnts was measured to estimate their average charge using eq. ( ). with measured values of i (= . · À a), q (= lpm), and n (= . · #/cm ), we determined that the average charge number was , which was in good agreement with the value of obtained from calculation using the classical charging theory [ ] . in the calculation, we assumed that the cnts had a shape factor of . [ ] . the particle diameter calculated with this shape factor was nm, which was very close to nm measured using the smps system. for a given cnt charge number, a calculation was carried out to determine the voltage applied to the substrate. fig. shows the (a) voltage distribution and (b) trajectories of cnts near the substrate, under the electric field. when the applied voltage was less than v, cnt particles would not deposit on the substrate. however, at a potential of v, cnts started to deposit on the substrate and the cnt deposition area decreased. the calculated results were in good agreement with those predicted by the following equation [ ] : where w is the nozzle width, u is the flow velocity at the nozzle, v is the voltage applied to the substrate, h is the distance between the nozzle and the substrate, and w p is the radius of the coated region. cnt deposition experiments were conducted with a si wafer substrate. fig. shows field emission scanning electron microscopy (fe-sem) images of cnts deposited on the substrate. when the charger was not operated, there were no cnts observed on the substrate, regardless of the voltage applied ( fig. (a) ). when charged cnts were flowing toward the substrate where no electric field was applied, several particles were deposited as shown in fig. (b) , which was caused by an image force between the cnts and the substrate (eq. ( )). when the charged cnts were delivered to a substrate of opposite polarity, many of them were successfully deposited on the (fig. (c) ). fig. (d) shows a frontal view of the deposited cnts. note that the cnts were vertically aligned. this phenomenon was due to characteristics of the charged cnts. according to keblinski et al. [ ] , cnts have higher charge concentration on both tube ends than in the central part. therefore, when they landed on the substrate the end of each cnt that was closer to the substrate than the other end was attracted to the substrate, resulting in the standing posture of the tubes. the cnt deposition experiment was also carried out using glass fiber filter medium as the substrate. the cross-sectional size of the filter was mm · mm. fig. shows the size distribution of cnts measured before the nozzle inlet (location i in fig. ) and away from the nozzle outlet (ii), measured with the smps system. the total number concentrations of cnts at locations i and ii were . · #/cm and . · #/ cm , respectively, resulting in a coating efficiency of %. with coating times of min, min, and min, the coating areal densities of fabricated cnt filters were . · #/cm , . · #/cm , and . · #/cm , respectively. fig. shows an fe-sem image of the cnt-coated filter (coating time = min). the cnts were observed to be standing vertically on each filter fiber. experiments were carried out using forced clean air with a face velocity of . m/s in order to determine whether cnts could be detached from the filter. the results in fig. (a) show that no cnts were detached from any of the three filter samples. the pressure drop across each test filter media was also measured at various face velocities of the clean air. the results are summarized in fig. (b) , which shows that cnt deposition did not affect the pressure drop, implying that the change in filter solidity due to the addition of the cnts was negligible. for comparison, the following theoretical prediction of pressure drop was used [ ] : where, u is the face velocity, t is the filter thickness (= . mm), a is the solidity (= . ) , and d f is the diameter of filter fiber (= lm). the calculations were consistent with the data from the pristine test filter. the size distribution of the aerosolized viral particles (bacteriophage ms ) is shown in the inset of fig. . the total concentration and mode diameter were . · #/cm and . nm, respectively. fig. shows the effect of cnt coating on filtration efficiency as a function of particle diameter (g f ðd p Þ). the face velocity was . m/s. the results show that the filtration efficiency was improved overall by the presence of cnts on the glass fiber filter. the overall filtration efficiencies (g f ) were %, . %, %, and . % for the pristine filter and cnt filters with coating areal densities of . · #/cm , . · #/cm , and . · #/cm , respectively. particle sizes of nm and nm were the most abundant penetration particle size for the pristine filter and cnt-coated filter, respectively. the fractional filtration efficiency was % (d p = nm) with the pristine filter, but increased to . % (d p = nm) with the cnt-coated filter (coating areal density: . · #/cm ). for the pristine filter, the fractional filtration efficiency was also determined theoretically using the following equation [ ] : the single fiber (fractional) filtration efficiency e(d p ) is defined as where e diff , e int , and e imp are the filtration efficiencies due to brownian diffusion, interception, and inertial impaction, respectively [ ] . the theoretical results were in good agreement with the experimental data. quality factors were evaluated using eq. ( ) for various face velocities. the quality factor increased with coating areal density for a given face velocity, but decreased with face velocity for a given coating areal density. the best quality factor of . ( % increase compared to the pristine filter) was obtained when the face velocity was . m/s and the coating areal density was . · #/cm . antiviral efficiency fig. shows the results of antiviral testing. as the coating areal density increased, the pfu value decreased exponentially (decay constant = À . cm ). the filter had higher antiviral efficiency with increasing cnt density. the antiviral efficiency was % with a coating areal density of . · #/ cm . the relationship between Àln( À g a ) and c is the z value, which is the slope of the line, was . cm /lg. according to fig. , the viable viral count ratio in the air before and after the filtration for a pristine filter (coating areal density = ) was same as the penetration ratio ( À g f ). however, in case of cnt coated filters, the viable viral count ratio was lower than the penetration ratio and decreased with coating areal density, implicating that the virus could be physically damaged when they passed through the cnt coated filter. fig. (a) shows tem images of viruses sampled from the viral solution which was prepared by filtration of the viruses on the pristine filter and subsequent detachment of the viruses from the pristine filter with sonication in de-ionized water. their shape was close to circular with a diameter of approximately nm, which was consistent with the value measured using the smps as shown in the inset of fig. . fig. (b) and (c) shows tem images of viruses captured on the cnts. fig. (b) and (c) also shows viruses that were detached from the cnts during the sonication process. the morphology of the detached viruses changed to a dumbbelllike or tore shape, clearly seen in fig. (d) . in previous studies [ ] [ ] [ ] [ ] , viruses were completely removed by a depth filtration mechanism, that is, capture by nanotube bundles inside the cnt layer. liu et al. [ ] also reported that the adsorption process of virus on cnts follows the chemical adsorption mechanism and the process may be associated with electronic sharing or electronic exchange of covalent forces in the surface between nanomaterials and virus. the removal rate of virus became higher with the dosage of nanomaterial since the total adsorption effect is boosted as the dosage increases. in this study, fig. shows that mechanical damage due to puncture and straining by cnts can be inferred as one of virus removal mechanisms. in this paper, we introduced a methodology that cnt air filter can be fabricated by coating aerosolized cnts on a filter at atmospheric pressure and room temperature condition. conventionally, wet coating by solution process has been used to deposit any functional materials to a filter, followed by a drying process with heated air flow. cnt air filter also can be fabricated by cnt growth on a filter medium via cvd process [ ] , where a tube furnace need to be used. however, using heated air flow or tube furnace often causes deformation of filter materials. since our methodology does not include any solution process and high temperature treatment on the filter, possible chances of filter deformation are avoided. in this paper, cnt air filter was fabricated in a laboratory scale. if we want to scale up the fabrication process, we need to supply higher amount of cnts, use a nozzle with bigger diameter, and increase the number of nozzles to cover large area deposition, and so on. cnt air filter can be used in a wide range of applications such as automobile air conditioning system, secondary sterilization system, and counter-terrorism mask. this study is the first to report the fabrication of cnt filters at atmospheric pressure and room temperature using electroaerodynamic deposition of aerosolized cnts. cnt filters had better filtration efficiencies for aerosolized bacteriophage ms than medium air filters with a negligible decrease in pressure. the particle filtration efficiency was increased to . % in the most penetration particle size zone ( nm) and the antiviral efficiency of the cnt filter was % when the coating areal density was . · #/cm . the susceptibility constant of virus to cnts was . cm /lg. these cnt filters will be useful for both filtration and inactivation of viral aerosols. review: bioaerosol health effects and exposure assessment: progress and prospects health effects of indoor fungal bioaerosol exposure health effects of indoor-air microorganisms review: detection of airborne sever acute respiratory syndrome (sars) coronavirus and environmental contamination in sars outbreak units evidence of airborne transmission of the severe acute respiratory syndrome virus measurement of airborne influenza virus in a hospital emergency department detection of varicella-zoster virus dna in air samples from hospital rooms influenza virus in human exhaled breath: an observational study exhalation of respiratory viruses by 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carbon-based nanomaterials: implications for river water and waste water effluent on the minimum efficiency and the most penetrating particle size for fibrous filters carbon nanotube blended polyethersulfone membranes for fouling control in water treatment preparation of nanofilter from carbon nanotubes for application in virus removal from water electrochemical carbon nanotube filter performance toward virus removal and inactivation in the presence of natural organic matter electrochemical multiwalled carbon nanotube filter for viral and bacterial removal and inactivation high efficiency fine particulate filtration using carbon nanotube coatings development of cnt-metal-filters by direct growth of carbon nanotubes aerosol filtration enhancement using carbon nanostructures synthesized within a sintered nickel microfibrous matrix aligned carbon nanotube sheet high efficiency particulate air filters use of carbon nanotubes filter in removing bioaerosols effects of single-walled carbon nanotube filter on culturability and diversity of environmental bioaerosols fabrication of a multi-walled carbon nanotube-deposited glass fiber air filter for the enhancement of nano and submicron aerosol particle filtration and additional antibacterial efficacy deposition of charged aerosol particles on a substrate by collimating through an electric field assisted coaxial flow nozzle susceptibility constants of escherichia coli and bacillus subtilis to silver and copper nanoparticles application of air ions for bacterial de-colonization in air filters contaminated by aerosolized bacteria design and evaluation of a unipolar aerosol charger to generate highly charged micron-sized aerosol particles development and performance test of a unipolar diffusion charger for real-time measurements of submicron aerosol particles having a log-normal size distribution numerical investigation of corona plasma region in negative wire-to-duct corona discharge aerosol technology: properties, behavior, and measurement of airborne particle electromechnics of particles charge distribution and stability of charged carbon nanotubes air filtration the removal and inhibitory effect of cnts on model viruses this research is supported by korean ministry of environment as ''the eco-innovation project'' ( - - ). key: cord- -i fjr vw authors: cho, yu sung; hong, seung chan; choi, jeongan; jung, jae hee title: development of an automated wet-cyclone system for rapid, continuous and enriched bioaerosol sampling and its application to real-time detection date: - - journal: sens actuators b chem doi: . /j.snb. . . sha: doc_id: cord_uid: i fjr vw we present a novel bioaerosol sampling system based on a wet-cyclone for real-time and continuous monitoring of airborne microorganisms. the automated and real-time bioaerosol sampler based on wet-cyclone (arbsw) continuously collects bioaerosols in a liquid medium and delivers the samples to a sensing device using a wireless remote control system. based on a high air-to-liquid-flow-rate ratio (∼ . × ( )) and a stable liquid thin film within a wet-cyclone, the system achieved excellent sampling performance as indicated by the high concentration and viability of bioaerosols (> % collection efficiency for > . -μm-diameter particles, > % biological collection efficiency for staphylococcus epidermidis and micrococcus luteus). furthermore, the continuous and real-time sampling performance of the arbsw system under test-bed conditions and during a field test demonstrated that the arbsw is capable of continuously monitoring bioaerosols in real time with high sensitivity. therefore, the arbsw shows promise for continuous real-time monitoring of bioaerosols and will facilitate the management of bioaerosol-related health and environmental issues. concerns over airborne microorganisms, called bioaerosols, have increased due to their adverse effects on the human body and the environment [ ] [ ] [ ] [ ] . bioaerosols, such as pathogenic viruses, bacteria, and fungal spores, are associated with infectious diseases, allergies, and asthma [ , [ ] [ ] [ ] . for example, the middle east respiratory syndrome (mers) and severe acute respiratory syndrome (sars) coronaviruses, which have recently killed hundreds of people in east asia, are transmitted by direct inhalation of contaminated bioaerosols [ ] . therefore, the world health organization (who) recommends that the bioaerosol concentration within indoor air be less than cfu/m air [ , ] . a technique enabling rapid real-time detection of airborne microorganisms would be advantageous for public health research and bioterrorism defense; however, the development of such a system is at an early stage. a major reason for the slow pace of development is the difficulty of determining the concentration and type of bioaerosols in the air stream [ ] [ ] [ ] [ ] [ ] [ ] . bioaerosols are typically detected by first collecting them in a liquid or on a surface and analyzing the collected particles using culture-based techniques, biochemical assays (e.g., polymerase chain reaction (pcr)) and/or enzyme-linked immunosorbent assay (elisa) [ , [ ] [ ] [ ] [ ] . recently, the development of real-time detection systems for microorganisms in liquid medium has made considerable progress [ , [ ] [ ] [ ] ; however, the performance of bioaerosol sampling systems with regard to biological stability, particle collection efficiency, and particle enrichment is still insufficient for use as a real-time system. in addition, integration of the bioaerosol sampling system and the detection system, including rapid and stable sample transfer, would be desirable for continuous real-time monitoring of bioaerosols. the ideal bioaerosol sampler should have the following characteristics: (i) rapid and continuous sampling, (ii) high collection efficiency and stable microbial recovery (e.g., liquid or semi-liquid collection medium), (iii) high particle enrichment, (iv) integration with the detection system (e.g., continuous and consistent sample delivery) and (v) portability and automated operation. tan et al. developed an automated electrostatic sampler that involves collection of bioaerosols in a liquid reservoir and their delivery to sensing devices [ ] . liu et al. and other researchers described an airborne pathogen direct analysis system based on microfluidic enrichment [ ] [ ] [ ] ; however, these systems require prolonged sampling for enrichment. a novel bioaerosol sampling system, the microsampler, based on two-phase fluid control in a microchip can be used with a real-time bioaerosol sensor [ ] ; however, due to the low throughput, adequate sampling is difficult in the presence of bioaerosol concentrations < cfu/m air . a wet-cyclone collects aerosols into a liquid film on the inner wall of the cyclone using the particle centrifugal force and the liquid surface tension. such systems achieve high sampling performance and enable the concentration of samples due to the high flow rate ratio between the incoming air and drainage liquid. considerable research has focused on the development of wet-cyclone bioaerosol samplers [ ] [ ] [ ] [ ] [ ] ; however, these have a large particle cut-off diameter, and a low particle collection efficiency and aerosol-to-liquid transfer rate; furthermore, the twophase flow operation is unstable and few fully integrated bioaerosol sampling systems are capable of continuous real-time sampling. here, the automated and real-time bioaerosol sampler based on wet-cyclone (arbsw) system for continuous real-time monitoring of bioaerosols is presented. the arbsw system continuously collects airborne microorganisms and automatically delivers them to an analytical sensor. the aerosol collection efficiency, particle air-to-liquid transfer efficiency, sample enrichment, and microbial recovery of the arbsw are evaluated. in addition, the arbsw was subjected to sampling sensitivity tests of bioaerosol detection under test-bed conditions, as well as real-time bioaerosol monitoring in a real atmosphere environment. the results demonstrate that the arbsw facilitates continuous bioaerosol monitoring with high sensitivity in real-world environments. standard-size particles and bacteria were used as test aerosols to evaluate the performance of the arbsw system. monodisperse and spherical standard polystyrene-latex (psl) particles ( . , . , , , . , . , . , . , . and . μm in diameter; . g/cm density; duke scientific corp., palo alto, ca, usa) and red fluorescent psl (fpsl) particles ( . , . , . , . and . μm in diameter; . g/cm density; fluoro-max™, thermo scientific, waltham, ma, usa) were used to evaluate the aerosol collection efficiency and air-to-liquid particle transfer efficiency of the arbsw. staphylococcus epidermidis (atcc ) and micrococcus luteus (atcc ) were used as the test airborne microorganisms. these gram-positive bacteria are commonly found in indoor environments and on human skin [ , ] , and are used widely in bioaerosol research [ , [ ] [ ] [ ] . in particular, s. epidermidis is an important opportunistic pathogen and is the most common source of infections on indwelling medical devices [ ] . the bacteria were incubated in nutrient broth (becton dickinson, franklin lakes, nj, usa) at °c for h. upon reaching an optical density at nm of . , bacterial suspensions were harvested by centrifugation ( × g, min), washed three times with sterilized deionized water (sdw) and diluted with ml of sdw. subsequently, a ml aliquot (∼ colony forming units (cfu)/ml) was poured into the nebulizer. figure s (a) shows a schematic diagram of the test aerosol generation. compressed clean air was passed into a six-jet collison nebulizer (bgi inc., waltham, ma, usa) via a mass flow controller (mfc, fc- s; mykrolis corp., billerica, ma, usa) at a flow rate of l/min. to remove moisture and electrical charge from the aerosols, the nebulized particles were sequentially passed through a diffusion dryer and po neutralizer. the test aerosol flow was diluted with an additional clean air flow ( - l/min) in a mixing chamber and inserted into the arbsw system. as shown in figure s (b), the size distribution and number concentration of the test aerosols before and after passing through the arbsw system were measured in real-time using a wide-range particle spectrometer (wps) ( xp; msp corp., shoreview, mn, usa; particle size range nm to μm) and an aerodynamic particle sizer (aps) ( ; tsi inc., st. paul, mn, usa; particle size range . - μm), respectively. figure s (c) shows the schematic diagram of the wet-cyclone module operation. there is one aerosol inlet and three sampling liquid inlets in the side of the wet-cyclone, and the outlets for the exhausted air and hydrosol liquid (including particle sample) are in the upper and bottom side. during operation, the liquid sampling medium (e.g., sdw) was injected at - ml/h through the three ports of the wet-cyclone using a syringe pump (kd ; kd scientific inc., holliston, ma, usa). the liquid drainage flow rate was controlled at - ml/h using a peristaltic pump (t -wx ; longer corp., hebei, china). the liquid sampling medium can be transferred continuously and directly to the particle detection part or storage container array for later processing. figure s (d) shows a schematic diagram of the particle characterization after sample collection. airborne bacterial particles were deposited onto copper transmission electron microscopy (tem) grids (carbon film on a copper mesh; cf -cu; electron microscopy sciences, hatfield, pa, usa) using an electrostatic precipitating nanoparticle collector (model ; hct inc., icheon, republic of korea). a field emission-scanning electron microscope (fe-sem; teneo volumescope, fei, hillsboro, or, usa) was used to visualize the structure and morphology of surface-deposited airborne bacterial particles. to calculate the fpsl particle concentration in the drainage liquid medium, aliquots (∼ μl) from the wet-cyclone outlet were injected into a disposable hemocytometer (dhcn ; incyto, cheonan, republic of korea). next, the fpsl particles were counted using a fluorescence microscope (bx ; olympus, tokyo, japan) with a u-mwg filter set (excitation, - nm; emission, > nm). images of at least nine microscopic fields were captured using a charge-coupled device (ccd) array camera. particles were enumerated using imagej software (national institutes of health, bethesda, md, usa). for the colony counting assay, the collected bacterial suspensions were serially diluted in sdw. aliquots of μl of the suspensions were spread on the surface of nutrient agar (becton dickinson) in petri dishes. colonies were counted after incubating the petri dishes for h at °c. the prototype arbsw system automatically controls the air sampling, liquid supply, liquid drainage flow rate and sample delivery using software based on arduino and matlab. the system can be remotely controlled using the wireless control panel and is × × cm in size. aerosols are entered through the inlet of the arbsw by an air pump and continuously collected in the sampling liquid flow. two peristaltic pumps enable a continuous supply of liquid to the arbsw system and a transfer of liquid to the analytical detection part at the appropriate flow rate. for evaluating the bioaerosol collection efficiency of the arbsw, the number concentrations of the test bioaerosols before and after transmission through the arbsw system were measured using an aps. simultaneously, the drainage liquid was sampled (∼ μl) and the colony number was determined using the colony counting assay. finally, the culturable bioaerosol number concentration (cfu/ml) was determined according to the total liquid volume. the biosampler (skc inc., eighty four, pa, usa) was used for performance evaluation in terms of the relative microbial recovery (%) and sample enrichment ratio of bioaerosol. the biosampler was formed of glass and consisted of three parts: an inlet, a nozzle section with three tangential sonic nozzles and a collection vessel. the collection vessel was filled with a liquid collection medium ( ml). the nozzles of the biosampler create a swirling air flow ( . l/min air of air supply) that maintains microorganism viability by gently moving particles onto the collection surface without re-aerosolization [ , [ ] [ ] [ ] . under the same bioaerosol exposure condition (∼ particles/cm air of total aerosol number concentration (tanc)), we sampled the bioaerosols using the arbsw and biosampler and obtained the culturable bioaerosol number concentration, respectively. finally, we compared the relative microbial recovery (%) and the sample enrichment ratio between the arbsw and biosampler under various sampling times. figure s shows a schematic diagram of the sensitivity test setup to evaluate the real-time sampling responsivity of the arbsw under the abrupt bioaerosol exposure conditions. the s. epidermidis suspension was nebulized for s at -min intervals in a biosafety cabinet. while the arbsw system samples surrounding bioaerosols in a real-time manner, the aps monitors the change of tanc at -min intervals. the real-time colony concentration of sampled particles using arbsw was determined using the colony counting assays and compared with the real-time data of aps. figure s shows a schematic diagram of the real-world field test setup. the temperature, relative humidity and wind speed were monitored using a hot-wire anemometer with thermohygrometer (tes- ; tes electrical electronic corp., taipei, taiwan). the atmospheric particulate matter (pm) concentration and tanc were monitored using an optical particle counter (opc) (model . ; grimm aerosol technik ainring gmbh & co. kg, ainring, germany). the arbsw also sampled the atmospheric bioaerosols continuously and the liquid samples were stored every min. these samples were tested using colony counting assays to obtain the bioaerosol colony concentration. fig. (a) shows the aerosol collection principle of the wet-cyclone module for the arbsw system. the cyclone is a conical device that creates an internal helical air stream and collects aerosols on the inner wall through centrifugal force. in our wet-cyclone module, a stable liquid thin film is formed on the inner wall of the cyclone by centrifugal force and the shear force generated by the high air-flow rate. at the same time, the liquid film slowly and continuously flows down the cyclone according to the balance between the supply and drainage liquid flow for delivering samples. due to the large difference between the air and liquid flow rates, aerosols entering the wet-cyclone are completely collected in the liquid film, rapidly concentrated to a high enrichment ratio and continuously delivered to an analytical sensor. our bioaerosol sampling system has a cut-off diameter of . μm and collection efficiency of > % for aerosols > μm in diameter with high-throughput operation. the cut-off diameter (d ), defined as the diameter of the aerosol having a collection efficiency of %, is expressed as follows [ ] : where μ is the air dynamic viscosity, b is the width of the air inlet, ρ p is the particle density, u a is the air velocity at the inlet, c c is the cunningham slip correction factor calculated using c c = + . reason, we analyzed the air flow and aerosol behavior in the wet-cyclone to optimize the cyclone design parameters using commercial computational fluid dynamics software (fluent . ; ansys inc., canonsburg, pa, usa). the finite volume method was employed to solve the governing equations and the discrete phase model in fluent code was used for particle tracking. figure s shows the optimal cyclone geometry and dimensions and figure s (a) shows the trajectories of aerosols entering the cyclone at the optimal inlet air flow rate of ∼ l/min. the particle collection position gradually lowers with decreasing particle size; all particles ≥ . μm diameter were captured in the liquid film (fig. s (c) ) indicated a cut-off diameter of ∼ . μm. fig. (b) shows photographs of the wet-cyclone module based on the simulation results. for real-time continuous particle sampling with a high concentration ratio, the liquid sampling medium should form a stable film on the wall of the cyclone under the high air flow rate condition. the stable liquid film means that the liquid covers the entire surface of the cyclone wall without being sprayed out of the film, to prevent sampling loss in the cyclone. the drag force of the fluid on the particle is proportional to the cube of the particle size, whereas the force between the particle and the wall is proportional to the particle size. therefore, if fine aerosols directly adhere to the cyclone wall, there is no way to remove the particles, resulting in sampling loss [ ] . the influence of air flow on a liquid film can be expressed by the modified webber number, we m . this can be conceived of as a measure of the relative importance of the inertia of a fluid compared to its surface tension [ ] : where ρ l is the liquid density, t l is the thickness of the liquid film and σ l is the surface tension of the liquid. when we m increases the inertia of the liquid due to the shear force generated at the interface between the liquid film, the air flow overwhelms the surface tension of the film surface and the liquid is separated from the surface and sprayed into the surrounding air stream. to maintain a stable liquid film the we m should be lowered by adjusting the air flow rate and the liquid flow rate. however, reducing the air flow rate to lower we m hampers particle concentration and decreases the collection efficiency of fine aerosols (see eq. ( )). therefore, it is important to optimize the liquid flow inside the cyclone by controlling the liquid supply and drainage flow rates. a numerical analysis was conducted to identify the optimal air flow and liquid flow conditions for the stable film. the volume-of-fluid (vof) model, a two-phase flow model in fluent code, was developed to calculate the hydrodynamics of liquid film formation inside the cyclone under various operating conditions. for the reasons mentioned above, the air flow rate was set at > l/min and the liquid drainage flow rate was limited to ml/h to attain an enrichment ratio of > . within the cyclone the surface of the thin liquid film rapidly evaporates due to the high air flow rate; therefore, if the liquid supply flow rate was lower than or equal to the drainage flow rate, a stable liquid film would not be formed and the liquid would split into multiple streams ( fig. (a) (i); supplied liquid flow rate (q s ) = ml/h, drainage liquid flow rate (q d ) = ml/h). in contrast, if the supply flow rate were larger than the drainage flow rate, the liquid would float inside the cyclone and tend to clog (fig. (a)(iii) ; q s = ml/h, q d = ml/h). the optimal supply and drainage flow rate ratio is around . (fig. (a) (ii); q s = ml/h, q d = . ml/h). the conditions for the formation of a stable liquid film in the real wet-cyclone were optimized using the numerical analysis. fig. (b) shows the optimized operating domains, where stable liquid films are formed at air flow rates of , and l/min. for l/min, the optimal liquid supply-todrainage-flow rate ratio is around . , similar to the numerical analysis result (fig. (c)(ii) ). the optimal ratio slightly increased with an increasing air flow rate due to faster evaporation ( . and . at air flow rates of and l/min, respectively). if the amount of supplied liquid was too low (fig. (c)(i)) or too high (fig. (c)(iii) ) unstable films were formed, similar to the numerical analysis result. these cases are also shown in movie s . we evaluated the aerosol collection performance of the wet-cyclone module at liquid supply flow rates of , , , , and ml/h and sampling air flow rates of , and l/min using standard psl particles (fig. (a) ). the total aerosol collection efficiency (η t ) was defined as the fraction of the total number concentration of the entering pm retained by the wet-cyclone: where, c in and c out represent the aerosol number concentration at the air inlet and outlet, respectively. at a l/min air flow rate (fig. (a ) ), the collection efficiency of aerosols over . μm in diameter was > %, similar to the simulation result. as the air flow rate was increased, the particle collection performance improved due to the increased centrifugal force; the collection efficiency of aerosols > . μm in diameter was ∼ . % at l/ min (fig. (a ) ) and ∼ . % at l/min (fig. (a ) ). however, the liquid supply flow rate had little effect on the aerosol collection performance. the proportion of the input aerosols delivered to the analytical sensor part was also assessed. in eq. ( ), the η t is equal to the sum of the air-to-liquid particle transfer efficiency and the fraction of particles lost to the inner wall of the cyclone. this air-to-liquid particle transfer efficiency (η al ) is defined as the transfer fraction of aerosol in the air to the liquid medium in the cyclone. we measured η al by comparing the total number of fpsl particles collected with that in the liquid drainage medium: where n d is the total number of particles in the liquid drainage medium, n in is the total number of aerosols in the inlet air, c d is the number concentration of particles in the liquid drainage medium and q a is the air flow rate. as shown in fig. (b) , η al increased as the liquid flow rate and air flow rate were increased; however, the particle size had little effect on the η al of the wet-cyclone. these results are related to the uniformity and coverage of liquid film on the inner wall of the wet-cyclone. the higher air and liquid flow rates yield a more uniform liquid film with greater coverage in the wet-cyclone, which can decrease the particle fig. . aerosol sampling performance of the wet-cyclone system. the aerosol collection efficiency of the standard polystyrene latex (psl) particle for the wet-cyclone system with various sampling air flow rates of (a ) l/min, (a ) l/min and (a ) l/min is evaluated at various supplied liquid flow rates of , , , , and ml/h. the aerosol-to-liquid transfer efficiency of the wet-cyclone system is evaluated using fluorescent psl particles under sampling air flow rates of (b ) l/ min, (b ) l/min and (b ) l/min. loss therein. in this study, the optimum flow rates (η al > . %) were determined to be: air, l/min; liquid supply, ml/h; and liquid drainage, ml/h (air-to-liquid enrichment ratio of ∼ . × ). the arbsw system was developed using the above numerical and experimental results and all parts are operated automatically. fig. is a photograph of the arbsw and wireless remote-control panel. the realtime bioaerosol sampling performance of the arbsw system was evaluated using test microorganisms (s. epidermidis and m. luteus). fig. (a) shows the size distributions of the test bioaerosols as unimodal curves. the specific geometric mean diameter (gmd) of s. epidermidis and m. luteus was . ± . μm and . ± . μm, respectively. the gmd is defined as Ʃn j lndj/n, where n j is the number of particles in the j th group, d j is the diameter of an individual particle and n is the total number of particles. the maximum and minimum aerodynamic diameters of s. epidermidis and m. luteus were ∼ . and ∼ . μm, and ∼ . and ∼ . μm, respectively. sem showed that cells of both taxa are spherical (fig. (b) ). the bioaerosol collection efficiency of the arbsw system was initially assessed. the collection efficiency of s. epidermidis and m. luteus was more than % over their entire size range (fig. (c ) ), similar to the standard psl particles. the total collection efficiency of both bioaerosols was > % (fig. (c ) ). next, the microbial recovery of bioaerosols sampled by the arbsw system was assessed. a comparative test was conducted with the conventional verified bioaerosol sampler, called biosampler, which has a collection efficiency of > % for bioaerosol sizes of > . μm and a microbial recovery of > %. according to the biosampler's operational manual, . l/min of air enters ml of sampling liquid in a reservoir and the enrichment of the collected particles is proportional to the sampling time (typically min to reduce the desiccation effect) [ , [ ] [ ] [ ] . in contrast, the arbsw system maintains a high particle enrichment ratio regardless of the sampling time, due to the constant air-to-liquid flow rate ratio (∼ . × ; use of the continuous entered air flow ( l/min) and drainage liquid flow ( ml/h)). therefore, if there is no biological or physical loss in the arbsw system, the concentration of microbes captured by the arbsw during min is theoretically ∼ -fold higher than that of the biosampler under the same environmental conditions. luteus ( ± . cfu/ml) sampled by the arbsw system were ∼ . -and ∼ . -fold higher than those by the biosampler, which were ± . and ± . cfu/ml, respectively. these values correspond to the theoretical predictions. as shown in fig. (e), the relative microbial recovery of s. epidermidis and m. luteus using the arbsw system was ± . % and ± . %, respectively (those of the biosampler were fixed at %), showing that the arbsw system has comparable microbial recovery to the biosampler. it is important that the arbsw system obtains highly concentrated samples consistently and rapidly, so that real-time sensing of bioaerosols can be achieved. we assessed the s. epidermidis colony concentration at sampling times of . , , , and min using the arbsw and biosampler (fig. (f) ). the tanc from the nebulized bacterial medium was kept constant at ∼ particles/cm air . the concentration of the sampled particles was too low to be measured with the bio-sampler when the sampling time was less than min. a concentration of . × cfu/ml was measured for a sampling period of min, and it was observed that the concentration increased proportionally with sampling time. in contrast, the arbsw system yielded a highly enriched sample (∼ . × cfu/ml) irrespective of the sampling time. therefore, the arbsw system is capable of highly enriched sampling of bioaerosols in a short time, with superior microbial recovery compared to a conventional instrument. real-time airborne microorganism monitoring systems should be capable of responding to abrupt changes in bioaerosol concentrations. to evaluate the responsivity of the arbsw system, a test-bed environment that allows for sudden changes in bioaerosol concentration was used, as shown in fig. (a) (details of the experimental setup are in fig. s ). fig. (b) shows the tanc and colony concentration of the bioaerosols at -min intervals during the test. aps showed that the tanc rapidly increased from to . particles/cm air during the first nebulization, and decreased to . particles/cm air after -min of nebulization. after min of nebulization, the tanc was < . particles/ cm air , indicating removal of > % of bioaerosols. the colony concentration increased to . cfu/cm air during the nebulization and decreased to . cfu/cm air within min. after min of nebulization, the concentration was < . cfu/cm air . in the second nebulization, the tanc increased from to . particles/cm air and the colony concentration increased from to . cfu/cm air . thus, the colony concentration results of the arbsw correspond well to the tanc variation measured by aps. additionally, the results demonstrate that the arbsw system is capable of continuous and accurate real-time bioaerosol monitoring, even in the presence of rapid changes in concentration. a field test of the arbsw system was conducted, where real-time monitoring of bioaerosols at a pond was performed at the korea institute of science and technology (kist, seoul, republic of korea) on august , ( : - : ) ( fig. (a) ). fig. (b) shows the variations in atmospheric pm and total culturable bioaerosol concentrations during the field test (details of the experimental setup are in fig. s ). pm and pm . are defined as the mass fractions (μg/m air ) of aerosols with an aerodynamic diameter smaller than and . μm, respectively [ ] . the pm concentration decreased from to μg/m air and the pm . decreased from to μg/m air . during the field test, the tanc also decreased from ∼ . × to ∼ . × particles/m air at a particle size range > . μm (˜ % reduction) (fig. s ) , similar to the trends of pm concentrations (fig. (b) ). the total bioaerosol concentration monitored by the arbsw decreased from to cfu/ m air at a rate similar to those of pm and pm . . these results indicate that the bioaerosol concentration was influenced predominantly by the pm concentration. more environmental monitoring data are shown in the supporting information (fig. s ) . these results demonstrate that the arbsw system can perform continuous and real-time bioaerosol monitoring in real-world environments. the arbsw system enables real-time monitoring of bioaerosols in real environments. this system has superior particle collection and particle transfer efficiency into a liquid medium. compared with a conventional bioaerosol sampler, the arbsw system enables marked particle enrichment and stable microbial recovery. furthermore, the arbsw not only has an excellent sampling performance with rapid responsivity, but is also suitable for the real-time monitoring of bioaerosols in real-world environments. the continuous liquid-based particle sampling used by the arbsw system, when integrated with a real-time particle analysis system (e.g., microfluidic flow cytometer), enables continuous quantitative characterization of airborne microorganisms and facilitates analysis of the physicochemical and biological properties of bioaerosols, for example using markers for specific aptamers or antibodies. j.h.j. conceived the initial idea; 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