key: cord-0005687-eo3vf9v3 authors: Hui, David S.; Chow, Benny K.; Chu, Leo C.Y.; Ng, Susanna S.; Hall, Stephen D.; Gin, Tony; Chan, Matthew T.V. title: Exhaled Air and Aerosolized Droplet Dispersion During Application of a Jet Nebulizer date: 2015-12-16 journal: Chest DOI: 10.1378/chest.08-1998 sha: 110f1d8e7cfc045022c195d0025270b51e027d15 doc_id: 5687 cord_uid: eo3vf9v3 BACKGROUND: As part of our influenza pandemic preparedness, we studied the dispersion distances of exhaled air and aerosolized droplets during application of a jet nebulizer to a human patient simulator (HPS) programmed at normal lung condition and different severities of lung injury. METHODS: The experiments were conducted in a hospital isolation room with a pressure of − 5 Pa. Airflow was marked with intrapulmonary smoke. The jet nebulizer was driven by air at a constant flow rate of 6 L/min, with the mask reservoir filled with sterile water and attached to the HPS via a nebulizer mask. The exhaled leakage jet plume was revealed by a laser light sheet and images captured by high-definition video. Smoke concentration in the plume was estimated from the light scattered by smoke and droplet particles. FINDINGS: The maximum dispersion distance of smoke particles through the nebulizer side vent was 0.45 m lateral to the HPS at normal lung condition (oxygen consumption, 200 mL/min; lung compliance, 70 mL/cm H(2)O), but it increased to 0.54 m in mild lung injury (oxygen consumption, 300 mL/min; lung compliance, 35 mL/cm H(2)O), and beyond 0.8 m in severe lung injury (oxygen consumption, 500 mL/min; lung compliance, 10 mL/cm H(2)O). More extensive leakage through the side vents of the nebulizer mask was noted with more severe lung injury. INTERPRETATION: Health-care workers should take extra protective precaution within at least 0.8 m from patients with febrile respiratory illness of unknown etiology receiving treatment via a jet nebulizer even in an isolation room with negative pressure. Table I Visualization of airflow around the nebulizer mask was facilitated by marking air with smoke particles produced by a smoke generator (M-6000, NI9; DS Electronics; Sydney, Australia) as in our previous studies. The oil-based smoke particles, measured < Ium in diameter, are known to follow the airflow pattern precisely with negligible slip. 18 The smoke was introduced continuously to the right main bronchus of the HPS. It mixed with alveolar gas and was then exhaled through the airway. Sections through the leakage jet plume were then revealed by a thin laser light sheet created by a diode-pumped solid stated laser device (OEM UGll-800mW; Lambdapro Technologies; Beijing. China), with custom cylindrical optics for two-dimensional laser light sheet generatton.v-" The experiments were recorded with a digital video camcorder (Sony High-Definition, HDR-SR8E; Sony; Tokyo, Japan; ClearVid CMOS Sensor, Carl ZeissVario-Sonnar 1'* Lens; Carl Zeiss GmbH; [ena, Germany), with optical resolution of 1,440X 1,080 pixels per video frame. 'I1le laser light sheet (green; wavelength, 532 nm; continuous-wave mode) was adjusted to encompass the hugest Oxygen consumption, mUmin Lung compliance, mUcm HzO Respiratory rate, breaths/min t Tidal volume, mLf MATERIALS AND METHODS breathing, suggesting that aerosols may playa role in the transmission of influenza. There is a strong association between ventilation, environmental air movements, and the airborne transmission of infectious diseases such as measles, tuberculosis, chickenpox, influenza, smallpox, and severe acute respiratory syndrome (SARS).4 Since respiratory therapy may generate infective aerosols, there is potential risk that treatment may result in a superspreading event among patients and health-care workers in close contact. The use of a jet nebulizer driven by air at 6 Umin for the administration of aerosolized salbutamol in an index patient had probably enhanced the spread of SARS, leading to a major nosocomial outbreak in our hospital in 2003. 5--7 We have reported the dispersion distances of exhaled air, as marked by smoke particles, during application of oxygen therapy via a simple mask and during noninvasive positive pressure ventilation (NPPV).Il-1O As part of our influenza pandemic preparedness, we studied dispersion distances of exhaled air and aerosolized droplets during application of a jet nebulizer to a human patient simulator (HPS) programmed to breathe at normal lung condition and at different degrees of lung injury. We hypothesized that as lung compliance deteriorated with worsening lung injury, there would be more extensive leakage through the side vents of the jet nebulizer. The experiments were conducted in an isolation room that measured 2.8 X 4.22 X 2.4 m, with 12 air exchanges per hour (Fig 1) . This is one ofthe 36, double-door, negative pressure (-5 Pa) isolation rooms specifically constructed on the top floor ofthe hospital after the major outbreak of SARS5 to facilitate management of patients with highly infectious diseases. The experimental design and method of data analysis have been described in details in our previous studies 8-10 on exhaled air dispersion related to NPPV and Simple oxygen mask. In this study, we examined the extent of exhaled air leakage through the side vents of the jet nebulizer (Salter Labs; Arvin, CAl attached to a high-fidelity HPS (HPS 6.1; Medical Education Technologies Inc.; Sarasota, FL). The jet nebulizer had a built-in air pump driven by a constant flow of air at 6 Umin for the purpose of the study. The nebulizer reservoir was filled with sterile water. The HPS contains a realistic airway and a lung model that undergoes gas exchange (ie, it removes oxygen and adds carbon dioxide to the system). Lung compliance and airway resistance also respond in a realistic manner to relevant challenges. In addition, the HPS produces an airflow pattern that is close to the in vivo human situation, and has been applied in previous studiesI 1-15 to simulate human respiration. The simulator represented a 70-kg adult male sitting on a 45°-inclined hospital bed. In this study, we programmed lung compliance and oxygen consumption of the HPS to mimic three different lung conditions: normal, mild lung injury, and severe lung injury ( Table l)yu7 cross-section of the entire leakage jet plume through the nebulizer side vents alongthe coronal plane lateralto the HPS. nus allowed us to investigate the regions directly above and lateralto the mask and the patient. All leakage jet plume images revealed by the laser light sheet were captured by the high-definition video camera positioned at the end of the bed directIy opposite to the HPS.Smoke concentration in the plumewasestimatedfromthe lightscatteredby smoke particles (Fig 2) .8-10 We estimated normalized smoke concentration in the mask leakage air from the light scattered by the particles. In short, the thin laser light sheet of near-constant intensityilluminated smoke particle markers in the mask airflow leakage. Smoke particles scattered laser light perpendicular to the light sheet, and thiswas collected and integrated by the complementary metal oxide semiconductor (CMOS)video camera element and lens. s -IO This analysis was based on scattered light intensity being proportional to particle concentration under the special conditionsof constant intensity laser light sheet illumination and monodisperse, small (submicrometer) particles.IS The motion video of several breathing cycles for a given lung model setting was captured to a computer and individualframes extractedas gray scalebitmaps for intensityanalysis. Frames were extracted at times corresponding to the beginning of inspiration to generate an ensemble averagefor the correspondinginstant of the respiratorycycle. s-IO The largest spread of contours from the nebulizer mask was chosen, and this was found to be at approximately the mid-time of the respiratory cycle. All gray scale frames were read into a program specifically developed for this study (MathCad 8.0; Mathsoft; Cambridge, MA),19 along with background intensity images taken with the laser switched off. The background intensity image was subtracted from each frame pixel by pixel to remove any stray FIGURE 2. A jet nebulizer was attached to a high-fidelity HPS with a laser Iiliht sheet shining from the left side of the simulator at the coronal plane. The simulator represented a 70-kg adult man sitting on a 45°-inclinedhospital bed and was programmed to breathe spontaneously. 650 background light. and the pixel intensity values were averaged over all frames to determine the ensemble averaged intensity. The resulting image was the total intensity of light scattered perpendicular to the light sheet by the smoke particles and was directIy proportional to smoke concentration. The imagewas normalized against the highest intensity found within the leakage jet plume to generate nonnalizedparticleconcentration contours. S -IO The leakagejet plume consistsof a combinationof pulmonary smoke and the aerosolized medication. The leakage plume of "unused" aerosolized medications from the jet nebulizer should also be considered as infective because it mixeswith the exhaled air before it escapes through the side vents of the nebulizer mask. As the smoke particles mark air that originates from the HPS airways, before leaking from the mask, the concentration contours effectively represent the probability of encountering exhaled air and the aerosolizedmedication around the patient that has come from within the mask and/or the patient's respiratory system. The smoke concentration contours are made up of data collected from 10 breaths. A contour value of 1 indicates a region that consistsentirelyof air exhaled by the patient, where there is a veryhighchance of exposure to the exhaled air, such as at the mask exhaust vents.A valuenear 0 indicates no measurable air leabgein the regionand a smallchanceof exposure to the exhaled air. 8 -10 The study received nonionizing radiation and biologicallchemical safety approval bythe Chinese University of Hong Kong. As the exhalation smoke jet was noted to leak through the side vents of the nebulizer mask, we therefore presented the lateral distances of air particle dispersion with reference to the coronal plane (Fig 3, top left) . The dispersion distances increased with worsening lung injury. At normal lung condition (oxygen consumption, 200 mUmin; lung compliance, 70 mUcm H 2 0 ), the average respiratory rate was 12 breaths/min and tidal volume was 700 mL. The maximum dispersion distance of smoke particles, defined as the boundary with a region encountering < 5% concentration of exhaled smoke particles (light blue contour), was 0.45 m, whereas the dispersion distance of a high concentration of smoke particles (white and red zone and above) was 0.2 m (Fig 3, top right) . In mild lung injury (oxygenconsumption, 300 mUmin; lung compliance, 35 mUcm H 2 0 ; respiratory rate, 25 breaths/ min; tidal volume, 300 mL), the maximum dispersion distance of a low concentration of smoke particles increased to 0.54 m, whereas that of a high concentration was 0.15 m (Fig 3, bottom left) . In severe lung injury (oxygen consumption, 500 mUmin; lung compliance, 10 mUcm H 2 0 ; respiratory rate, 40 breaths/min; tidal volume, 150 mL), a larger and more diffuse exhalation jet leaked through the side vents of the nebulizer mask was noted, probably due to its gravitational effect. Although the exhalation distance of a high concentration of smoke particles (eg, red zone on scale) was < 0.1 m, the maximum dispersion distance extended beyond Original Research The white color code and the red color code represented regions consisting of 100% and 70%, respectively, of smoke particles, whereas the background of the isolation room (deep blue code) was free of smoke particles. Bottom lett: The simulator was programmed to mimic mild lung injury with oxygen consumption of 300 mUmin, lung compliance of 35 mUcm H 20, respiratory rate of 25 breaths/min, and tidal volume of 300 mL. The maximum exhalation distance of a lowconcentration of smokeparticles iJicreased to 0.54 m, whereasthat of a high concentration was 0.15 m. Bottom right: The simulator was programmed to mimic severelung injurywith oxygen consumption of 500 mUmin, l~compliance of 10 mUcm H 2 0 , respiratory rate of 40 breaths/min, and tidal volume of 150 mL. Although the exhalation distance of a high concentration of smoke particles (red zone) was < 0.1 m, that of a low concentration of smoke particles was noted to extendbeyond0.8 m as a result of more extensive leakage throughthe nebulizersideventsof the nebulizermask, with a projectile shape due to gravitational effect. 0.8 m due to more extensive leakage through the nebulizer side vents (Fig 3, bottom right) . DISCUSSION With an extremely fine smoke particle tracer in order to demonstrate the maximum distribution of exhaled air, this study investigated the dispersion distances of exhaled air particles during application of a jet nebulizer under normal lung condition vs www.chestjoumal.org different degrees of lung injury in our hospital isolation room with negative pressure. Using laser smoke visualizationmethods, we have shown that the maximum dispersion distance of a low concentration of air particles increased from 0.45 m at normal lung condition to 0.54 m and beyond 0.8 m during mild and severe lung injury, respectively. Interestingly, the dispersion of high-concentration smoke particles was reduced with worsening lung injury. These data suggest that the dispersion of exhaled air during application of jet nebulizer is determined by both the CHEST /135/3/ MARCH, 2009 expiratory effort and the leakage of "unused" aerosolized droplets through the exhalation ports of the jet nebulizer. In this regard, exhaled air from the lungs contained high concentration of smoke particles and was dispersed according to expiratory flow. Therefore, the dispersion distance of high-concentration smoke particles was significantly reduced by > 40% as the tidal volume was decreased from 700 to 150 mL. In contrast, the extent of leakage ofaerosolized droplets was inversely proportional to the tidal volume. Although aerosol deposition within the simulated patient does not model deposition within a real lung, much of the aerosolized medication was deposited within the simulated patient during inspiration, and the amount of leakage was therefore less in normal lung condition than in the severe lung injury model. Although the leakage of aerosolized droplets carried only small amount of exhaled smoke particles, these were responsible for dispersing Iowconcentration smoke particles to a longer distance in severe lung injury. These findings have important clinical implications to the hea1th-care workers who often manage patients with respiratory failure and febrile illness of unknown etiology at a close distance. It is important to provide adequate respiratory protection for health-care workers in addition to applying standard, contact, and droplet precautions in order to prevent nosocomial infections. The jet nebulizer is an aerosol-generating device commonly used to deliver aerosolized bronchodilation to patients with airway diseases and pneumonia. It was implicated as the cause of a major hospital outbreak of SARS in 2003.5--7 While the major routes for transmission of SARS were related to infected droplets and fomites, as is usually the case in viral pneumonia,20 there was evidence that SARS might have spread by airborne transmission. 21 -24 It was not entirely clear if different modalities of respiratory support had contributed to the nosocomial outbreaks of SARS through generation of infective aerosols. Our previous studies 9 • 10 have shown that the maximum exhaled air dispersion distances from patients receiving oxygen via a Hudson mask and during NPPV were 0.4 m and 0.45 m, respectively. A case-control study25 involving 124 medical wards in 26 hospitals in Guangzhou and Hong Kong has identified SARS patients requiring oxygentherapy or NPPVas independent risk factors for superspreading nosocomial outbreaks of SARS. Our previous study9 has shown an exhaled air dispersion distance of 0.22 m from the simple oxygen mask when oxygen was delivered at 6 Umin to the HPS with mild lung injury. The current study has shown that the jet nebulizer system driven by air at 6 Umin can extend the dispersion distance much further, especially in the presence of more severe lung injury ( Table 2) . Apart from aerosol-generating procedures, environmental factors such as medical ward airflow and ventilation play a significant role in the aerosol transmission of infection in health-care premises." A recent review4 has demonstrated a strong association between ventilation, air movements in buildings, and the transmission/spread of infectious diseases such as measles, tuberculosis, influenza, and SARS, but there are insufficient data to specify and quantify the minimum ventilation requirements in hospitals and isolation rooms in relation to spread of infectious diseases via the airborne route. In a stud y 27 of the dispersion characteristics of polydispersed droplets in a general hospital ward equipped with ceilingmixing type ventilation system, the small droplets or droplet nuclei (initial size S 45 J.Lm) behaved as airborne transmittable particles (staying airborne for > 360 s) and the dispersions were strongly affected by the ward ventilation airflow pattern. The expiratory droplets exhibited an initial rapid dispersion followed by slower dispersion in the subsequent stage. In contrast, large droplets (with initial size This study has applied smoke particles as markers for exhaled air in the HPS model because there is no safe and reliable marker that can be introduced into human lungs for study.8-10 The inertia and weight of larger droplets in an air droplet two-phase flow would certainly cause them to have less horizontal dispersion than the continuous air carrier phase in which they travel. However, evaporation of water content in some respiratory droplets during the jet nebulizer therapy would produce droplet nuclei suspended in air, whereas the larger droplets would fall to the ground in a trajectory pathway due to gravitational effects. A droplet nucleus is the airborne residue of a potentially infectious aerosol from which most of the liquid has evaporated and may have diameter < 10~m.4.26 Asthe smoke particles in this study mark the continuous air phase, our data contours are referring to exhaled air and droplet nuclei (including the aerosolized medication) rather than the risk of large droplet transmission.sJ? However, we could not capture the full air-dispersion distance in severe lung injury because we were unable to position the laser team far away from the HPS due to the small size of the isolation room. When an infected person coughs or sneezes, respiratory droplets are released. In addition to maintaining contact, droplet, and standard precautions among the health-care workers when providing routine care to patients infected with H5Nl influenza, the World Health Organization 28 currently recommends airborne precautions in health-care facilities, including placing patients with suspected and confirmed H5Nl influenza in isolation rooms with at least 12 air exchanges per hour (if available) during aerosol-generating procedures due to the high lethality of the disease and uncertainty about the mode of human-to-human transmission. The negative pressure room will reduce the spread of airborne contamination between rooms. The air-exchange rate and airflow patterns are important factors in the control of airborne virus infection, and good ventilation arrangement may enhance the safety of staff when performing medical treatments within isolation rooms.P? In health-care facilities where negative pressure isolation room is not available, an alternative is to administer bronchodilator to high-risk patients in the form of a metered-dose inhaler via a spacer or in dry powder formulation because these methods have equivalent efficacy to the jet nebulizer in relieving bronchospasm due to acute asthma. [30] [31] [32] [33] [34] In summary, this study has shown that substantial exposure to exhaled air occurs at least within 0.8 m from patients receiving treatment via a jet nebulizer www.chelItjoumal.org in an isolation room with negative pressure. Healthcare workers should take special precautions when caring for patients with febrile respiratory illness requiring treatment via a jet nebulizer. Writing Committee of the Second World Health Organization Consultation on Clinical Aspects of Human Infection with AvianInfluenza A (H5Nl) Virus: update on avian influenza A (H5Nl) virus infection in humans Review of clinical symptoms and spectrum in humans with influenza AlH5Nl infection DeHaan WHo et al. Influenza virus in human exhaled breath: an observational study Role of ventilation in airborne transmission of infectious agents in the built environment: a multidisciplinary systematic review A major outbreak of severe acute respiratory syndrome in Hong Kong Index patient and SARS outbreak in Hong Kong SARS: experience at Prince of Wales Hospital. Hong Kong Airflows around oxygen masks: a potential source of infection? Exhaled air dispersion during oxygendelivery via a simple oxygen mask Non-invasive positive pressure ventilation: an experimental model to assess air and particle dispersion Patient simulation for training basic and advanced clinical skills Bellows-less lung system for the human patient simulator Performance of an oxygen delivery device for weaning potentially infectious critically ill patients 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 Breathing pattern and workload during automatic tube compensation, pressure support and T-piece trials in weaning patients Pulmonary pathophysiology of pneumococcal pneumonia Fluid dynamics of multiphase systems Mathcad 8.0 for Windows. users guide The severe acute respiratory syndrome Evidence of airborne transmission of the severe acute respiratory syndrome virus Detection of airborne severe acute respiratory syndrome (SARS) coronavirus and environmental contamination in SARS outbreak units. I Viral load distribution in SARS outbreak Temporal-spatial analysis of severe acute respiratory syndrome among hospital inpatients Why did outbreaks of severe acute respiratory syndrome occur in some hospital wards but not in others? Factors involved in the aerosol transmission of infection and control of ventilation in healthcare premises Dispersion of expiratory droplets in a general hospital ward with ceiling mixing type mechanical ventilation system Clinical management of human infection with avian influenza A (H5N 1) virus: WHO updated advice 15 Virus diffusion in isolation rooms Inhaled albuterol via jet nebulizer no better than via metered dose inhaler with spacer or drypowder for Rx of severe asthma Randomized trial of salbutamol via metered-dose inhaler with spacer versus nebulizer for acute wheezing in children less than 2 years of age Costs and effectiveness of spacer versus nebulizer in young children with moderate and severe acute asthma A comparison of albuterol administered by metered-dose inhaler and spacer with albuterol by nebulizer in adults presenting to an urban emergency department with acute asthma Nebulizers vs metereddose inhalers with spacers for bronchodilator therapy to treat wheezing in children aged 2 to 24 months in a pediatric emergency department