cord-000285-7p3b6tyf	2010	The primary goals of the study are: (i) to investigate both the acute and the long-term health consequences of varying severity and aetiology of clinically significant viral respiratory tract infections on the outcomes of allergic rhinitis (AR) and early childhood asthma; and (ii) to identify the potentially modifiable factors that define children who are at greatest risk of developing asthma following infant respiratory viral infection. Thus, we designed the prospective TCRI to establish a base for the evaluation of both the risks and benefits of documented significant infant viral respiratory infection of varying severity and aetiology and other environmental exposures on childhood atopy outcomes and to establish a biospecimen repository for analyses including biomarker testing and genotyping. The TCRI is a prospective cohort of mother-infant dyads enrolled in a longitudinal investigation of the relationship of infant viral respiratory infection severity and aetiology and the interaction of other risk factors on the development of childhood asthma and allergic diseases.
cord-010078-8lkkez3n	2010	Both modes of imaging discriminate early malignant lesions from non-specifi c infl ammation, aid in selecting appropriate sites for biopsy and better delineate tumor margins for more precise staging, but are of little value at present in clinical practice since most patients with malignant pleural effusions have extensive pleural involvement that is easy to diagnose with white light pleuroscopy For pleuroscopic guided pleural biopsies, specimens obtained with the rigid forceps are larger than those with the fl ex-rigid pleuroscope since they are limited by size of the fl exible forceps, which in turn depends on the diameter of the working channel. In the United Kingdom, a thrombosis group has been formed to promote awareness among parliamentarians about the risk and management of VTE; to increase knowledge of its causes, effects, and treatments; and to monitor the implementation of government initiatives and other researches being and this program has corrected the wrong perception that PTE is a rare disease in China Pulmonary hypertension (PH) is a common complication of chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD) or interstitial lung diseases (ILD).
cord-015893-e0fofgxq	2011	Sulfur dioxide, nitrogen dioxide, ozone, and particulate matter in air pollution may • exacerbate asthma, and patients should be cautioned to stay indoors when levels of these irritants are high. A study of children aged 6-8 years with asthma concluded that an asthma exacerbation was of a greater severity if a viral infection was present as opposed to a nonviral illness (7) . Inhaled corticosteroids and leukotriene receptor antagonists (LTRAs) are well known to control the number of wheezing exacerbations in school-age children with chronic persistent asthma, an effect that appears to encompass those episodes caused by viral illness. Viral respiratory infections, and to a lesser extent air pollution, are common triggers of exacerbations and may interact with individuals to affect the development of some forms of asthma. By understanding and anticipating respiratory viral infections and air pollution as important causes of asthma, the health care provider can provide superior care for those who suffer from this chronic disease.
cord-016009-qa7bcsbu	2019	Disease that restricts airflow through either inflammation of the lining of the bronchial tubes or destruction of alveoli Increased risk of emphysema if genetic variant of alpha-1 antitrypsin deficiency and smoking or exposed to high levels of air pollution [11] Bronchiectasis A disorder of the airways that leads to airway dilation and destruction, chronic sputum production, and a tendency toward recurrent infection [39] Bronchiolitis Airway injury that can be caused by infections, irritants, toxic fumes, drug exposures, pneumonitis (typically viral), organ transplants, connective tissue disorders, vasculitis, or other insults [40] Dyspnea Shortness of breath or difficulty breathing [11] Emphysema Thinning and destruction of the alveoli, resulting in decreased oxygen transfer into the bloodstream and shortness of breath.
cord-016173-ro7nhody	2014	Although most clinical practices use symptom-based, guideline-directed assessments to decide on medication use, recent data from a randomized controlled trial suggest lower rates of exacerbation, improved quality of life, and reduced neonatal hospitalization when management decisions were based on measurements of exhaled nitric oxide in pregnancy [ 10 ] . Changes in physiology and immunity associated with pregnancy may increase the risk of infection and severe outcomes in the pregnant women. In addition, infl uenza infection during pregnancy increases the risk of adverse fetal outcomes. Pregnant women are at increased risk for morbidity (including cardiorespiratory complications) and mortality from infl uenza compared with nonpregnant controls [ 43 -46 ] that is more pronounced in the second and third trimester of pregnancy [ 47 ] . In view of potential severe maternal disease from infl uenza and adverse fetal outcomes, benefi ts of treatment with antivirals likely outweigh the potential risks to the fetus.
cord-016783-8x05oh5q	2010	Evidence indicates that environmental factors acting early in life, including respiratory viral infections, exposure to pets and microbial products, day-care attendance, breast feeding, and exposure to allergens, tobacco smoke and other pollutants, are key events for establishment of sensitization and development of chronic, persistent symptoms of allergic diseases [1] . Evidence indicates that environmental factors acting early in life, including respiratory viral infections, exposure to pets and microbial products, day-care attendance, breast feeding, and exposure to allergens, tobacco smoke and other pollutants, are key events for establishment of sensitization and development of chronic, persistent symptoms of allergic diseases [1] . The relationship of exposure to microbial agents (endotoxin, fungal agents, and other microbial contaminants) early in life (3 months of age) and the development of atopic sensitization and physician-diagnosed asthma and wheeze in the first 4 years of life, in children of atopic mothers, was investigated in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study.
cord-016931-il8o0fps	2008	Eine detaillierte Besprechung aller in Tab. 3.1 aufgeführten allergischen Erkrankungen würde den zur Die diagnostische Abklärung erfolgt durch Bestimmung des spezifischen IgE gegenüber Insektengiftbestandteilen (Phospholipase, Melittin etc.) und durch einen Hauttest in Verbindung mit der Anamnese. Heute lässt sich die Rhinitis als Entzündung der nasalen Mukosa definieren, die einhergeht: ▬ klinisch mit Hypersekretion, Niesreiz sowie nasaler Kongestion, ▬ immunologisch auf dem Boden IgE-vermittelter Mechanismen gegenüber Allergenen mit lokaler Sekretion von Zytokinen, eosinophilem kationischem Protein (ECP) und anderen Mediatoren, ▬ histologisch mit einer Infiltration vor allem durch eosinophile Granulozyten und ▬ immunhistologisch mit einer Anreicherung aktivierter T-Lymphozyten und degranulierter eosinophiler Granulozyten. Sie gilt als die klassische allergische Immunreaktion bei Rhinitis allergica, allergischem Asthma bronchiale und atopischer Dermatitis, bildet aber auch eine Komponente der immunologischen Reaktion bei der allergischen bronchopulmonalen Aspergillose. Ausgangspunkt einer immunologischen Reaktion, wie auch der im Rahmen allergischer Erkrankungen, ist die Interaktion des Antigens/Allergens mit APC und einem genetisch definierten, spezifischen T-Zellklon.
cord-017412-1avevzya	2010	Lower airway infections by bacteria, viruses, or fungi are among the most prevalent causes of transmissible disease in humans, with two to three million community-acquired (non-hospital-acquired) cases per year in the United States (Segreti et al., 2005) . Those with physically compromised airways or immune system deficiencies are subject to chronic microbial colonization of their airways and to high-frequency episodes of viral, bacterial, or fungal lower respiratory infections. Many associations with asthma have been detected including exposure to cigarette smoke (Thomson et al., 2004) , caesarean section birth relative to natural birth (Thavagnanam et al., 2008) , early viral respiratory infections (Gold and Wright, 2005; Harju et al., 2006) , early in life antibiotic use (Marra et al., 2006) , and living in the US (Gold and Wright, 2005) . Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations
cord-017789-rhoisec4	2020	Nachdem Th2-Zellen (neben den ILC2-Zellen) als hauptverantwortlich für die Bildung von Th2-Zytokinen angesehen werden, ist es sehr wahrscheinlich, dass der PGE2-EP2-Signalweg eine hemmende Wirkung auf die Th2-Zellproliferation hat und dadurch die allergische Sensibilisierung unterdrücken kann. Somit zeigt sich wiederum (wie bei den Untersuchungen bezüglich Remodeling), dass eine mangelnde Hochregulierung von COX-1 und COX-2 sowie fehlende Vermehrung von PGE2 unter inflammatorischen Bedingungen an der Entwicklung einer chronischen eosinophilen Rhinosinusitis mit Polypen sowohl mit als auch ohne Aspirin-Intoleranz beteiligt sind. Somit offenbart auch diese Studie, dass PGE2 eine protektive Wirkung auf die Lunge hat und als endogener Mediator die überschießende ILC2-Aktivierung der allergischen Inflammation "beruhigen" und gegensteuern kann. 2013): ILC2s sind dafür bekannt, dass sie nach Aktivierung durch die Atemwegsepithel-Zytokine IL-25, IL-33 und TSLP die Zytokine IL-13 und IL-5 freisetzen, aber auch antigenunabhängig als Antwort auf das Mastzellenprodukt Prostaglandin D2 (PGD2) und dadurch bei der Pathogenese von allergischen Erkrankungen eine Schlüsselrolle einnehmen.
cord-018537-t1gi76nc	2013	Während im Säuglingsalter häufig vor allem virale Auslöser zu einmaligen obstruktiven Bronchitiden oder Bronchiolitiden führen, ist bei rezidivierenden Formen in jedem Alter, insbesondere beim Vorliegen von multiplen Auslösern, an ein frühkindliches Asthma bronchiale zu denken. Lebensjahr bei Kleinkindern verwendet, die eine akute virale Infektion der unteren Atemwege mit obstruktiver Symptomatik (auch wenn vorwiegend Pfeifen/Giemen vorliegt) erleiden, Dies wird in unseren Regionen als »virusinduziertes Wheezing«, »wheezy bronchitis« oder eben als obstruktive Bronchitis klassifiziert. Speziell bei Frühgeborenen und sehr jungen Säuglingen (<3 Monate) kann es ihm Rahmen von RSV-Infektionen zu zentralen Apnoen mit Bradykardien kommen, die vermutlich als Folge einer direkten Störung des Atemzentrums durch das Virus entstehen. Asthmaentwicklung Obwohl die »Huhn und Ei-Frage« nicht vollständig klar ist, nimmt man heute aufgrund von Erkenntnissen an großen Geburtskohorten an, dass frühe Virusinfektionen eher nur bei Kindern mit gewissen prädisponierenden Faktoren eine nachfolgenden Störung der Immunentwicklung und Allergie beeinflussen oder gar induzieren können (two hit hypothesis).
cord-019347-tj3ye1mx	2010	Method:Case Report:A 15y/o w/f athlete presented with a two month history of recurrent hives and angioedema which she associated with ingestion of Halloween candy .One week before evaluation she had hives with Coconut as well.Her history was othewise unremarkable except for recurrent UTI''S, annual sinusitis, pneumonia in 1998 as well as migraines.She denied sexual activity.Her physical exam was normal.Results:An evaluation for autoimmune disease revealed normal ESR, ANA, DSDNA, mono and hepatitis serology as well as lyme titers however her CH50 was low17u/ml(normal 26-58U/ml)and evaluation of complement revealed c4 14mg/dl(normal 16-47mg//dl)and c2 <1.3mg/dl(normal 1.6-3.5mg/dl)with normal c3, c5-c9.Her father had nor-malc4 but c2 was 1.4mg/dl (normal 1.6-3.5mg/dl)Her sister had c2 of 1.5mg/dl and normal c4 and her mother had normal c2 and c4.Her workup included positive prick skin test to ragweed, ash and grass and she was started on Rhinocort and Clarinex seasonally.She has been followed for one year with resolution of hives and is asymptomatic.Her diagnosis had been confirmed by a pediatric rheumatologist.Conclusion;We present an atypical case of C2 complement deficiency in an currently asymptomatic individual.
cord-021905-fjcks7w4	2009	The level of cat allergen that is required to induce asthma symptoms is not well defined, so strict avoidance and proper cleaning after an animal has been removed from the household are key to preventing morbidity. Accordingly, improper setting of the central air humidifier (commonly part of a home''s central heating and air-conditioning unit) may worsen asthma control; while dehumidifiers set to keep humidity levels lower than 50% may be beneficial in reducing asthma symptoms from house-dust mite exposure. Similar to the aforementioned avoidance measures for pollen-sensitive asthmatic individuals, asthma symptoms from exposure to mold spores may be minimized by staying indoors as much as possible (especially during peak spore concentrations) and keeping home and automobile windows closed. Other important outdoor asthma triggers include exposure to vehicle traffic (especially diesel exhaust), which might exacerbate preexisting allergic conditions by enhancing airway responses to allergen, a potential compounding effect.
cord-022050-h24f0fpd	2009	• Hypercapnic chronic obstructive pulmonary disease (COPD) patients should be treated with noninvasive ventilation and supplemental oxygen sufficient to overcome hypoxemia but avoid hyperoxia. Uncontrolled oxygen administration may precipitate acute hypercapnia in patients with acute COPD exacerbations as a result of relaxing hypoxic vasoconstriction, thereby allowing increased perfusion to regions with reduced alveolar ventilation. Most commonly, patients with severe asthma have a history of previous hospitalizations for asthma (some that may be near fatal), low socioeconomic status, female gender, obesity, nighttime symptoms, FEV 1 less than 60% with optimal treatment, continual symptoms, reduced quality of life, use of oral or systemic steroids in the past 12 months, use of more than canister of SABA per month, elevated residual volume-tototal lung capacity (RV:TLC) ratio on pulmonary function testing, and a peak expiratory flow rate variability of more than 30% (i.e., variability-(bestworst)/best reading). Non-invasive positive pressure ventilation for treatment of respiratory failure due to exacerbations of chronic obstructive pulmonary disease.
cord-022155-9759i9wr	2018	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. 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. 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 assertion from the BASE study of the association of SBS with the increasing difference in concentration of CO 2 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.
cord-022467-j2trahab	2009	A recent clinical trial that included children over age 12 years and used a fixedcombination homeopathic remedy for a mean 4.1 days of treatment reported that 81.5% reported subjective feelings of being symptom free or significantly improved without complaint of any adverse side effects. 4 A randomized, double-blind, placebocontrolled study from Great Britain of 170 children with a starting median age of 4.2 years in the experimental group and 3.6 years in the placebo group concluded that individually prescribed homeopathic remedies seem to be ineffective in reducing symptoms or decreasing the use of antibiotics in pediatric patients with URI. 414 In a nonrandomized clinical trial involving 30 children ages 3 months to 8 years with chronic diarrhea of 2 to 4 months'' duration that was unresponsive to Western medicine and TCM, individualized acupuncture treatment eliminated symptoms and normalized stools.
cord-022527-a0x6lws3	2012	The role of the eosinophils as key players in the pathophysiology of asthma has been debated, despite evidence that the cells are present and activated in the airway lumen and tissue 1 of patients with current asthma; are increased in number when asthma is uncontrolled 2 or severe 3 and decreased when asthma is controlled 4 ; and treatment strategies that aim to control airway eosinophilia are significantly more effective and less expensive in improving asthma control 5,6 and decreasing asthma exacerbations compared to guideline-based clinical strategies. 11 Since allergic asthma is primarily a T-helper type 2 (T h 2)-mediated disease, it is not surprising that cytokines driving eosinophilia are T h 2 cell products: specifically, granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and interleukin-5 (IL-5), which signal through specific high-affinity cell-surface receptors linked to a common b-chaindall of which can act as eosinophil growth factors that promote formation of eosinophil/basophil (Eo/B) colony-forming units (CFU) in functional assays.
cord-022650-phsr10jp	2018	0685 | Skin prick test reactivity to aeroallergens in adult allergy clinic in a tertiary hospital: a 12-year retrospective study Results: Five different human sera were screened for specific IgE level against 29 different allergen sources using test methods of three different suppliers. Conclusion: This multicenter prospective study confirmed that stepwise single-dose OFC to egg will help to clarify the severity of egg allergy, and will contribute to improved food allergy manageMethod: The study design was a retrospective cohort study extracting data from the electronic chart of children older than 4 years who visited our out-patient clinic for egg or milk allergy and who underwent an oral food challenge test (OFC) twice within 24 months between November 2013 and December 2017. Results: In the base case analysis, using Italy clinical practice patients with moderate-to severe allergic rhino-conjunctivitis (SS ranging from 6 to 15 points) and a mean age at entry of 21 years, both SCIT and SLIT were associated with increased cost but superior efficacy compared to pharmacotherapy alone.
cord-022653-qa1uph35	2017	0206 | G protein coupled receptor kinase 2 (GRK2) regulates endothelial permeability induced by Bradykinin 0208 | Pharmacokinetics (PK) and pharmacodynamics (PD) of c1 esterase inhibitor of chronic urticaria challenges most commonly identified were the following: time of onset of disease; frequency/duration of and provoking factors for wheals; diurnal variation; occurrence in relation to weekends, holidays, and foreign travel; shape, size, and distribution of wheals; associated angioedema; associated subjective symptoms of lesions; family and personal history regarding urticaria, atopy; previous or current allergies, infections, internal diseases, or other possible causes; psychosomatic and psychiatric diseases; surgical implantations and events during surgery; gastric/ intestinal problems; induction by physical agents or exercise; use of drugs; food allergies; relationship to the menstrual cycle; smoking habits; type of work, hobbies; stress; quality of life and emotional impact; previous therapy and response to therapy, and previous diagnostic procedures/results.
cord-022658-mq91h15t	2008	Patients with rhinitis or asthma caused by allergens for which the clinical efficacy and safety of SIT have been documented by placebo-controlled, doubleblind studies, and those requiring daily pharmacotherapy for longer periods (e.g., preventive treatment during a pollen season or perennially) are candidates for SIT. in most cases when significant airway comorbidity is present (asthma, chronic sinusitis, nasal polyps, or otitis media with effusion) when the diagnosis is in question or special diagnostic testing is required when occupational rhinitis is suspected, to distinguish between clear-cut allergic reactions and toxic or nonallergic reactions when poor symptom control necessitates a consultation for environmental control measures, pharmacotherapy, or specific immunotherapy when medication side-effects are intolerable when rhinitis is only part of a complex series of mucosal allergies.
cord-023239-06a03o14	2016	The basics of inhaler technique / device / adherence / allergen exposure are all being maintained A retrospective analysis of follow-up of children with difficult asthma for up to six years revealed that those in whom underlying modifiable factors were identified and addressed had an improvement in lung function and reduction in exacerbations over time, while being able to reduce maintenance dose of inhaled steroids such that the majority fell below the threshold for problematic severe asthma 4 . Long-term follow up of children investigated in infancy and reassessed in later childhood have so far showed that reduced baseline lung function in symptomatic infants was significantly associated with subsequent respiratory morbidity as well as with the need of anti-asthma medication at the age of 3 years.
cord-023288-sqr33y72	2008	Results Data indicate splice variant expression in dendritic cells from asthmatic patients is influenced by asthma severity. Methods Randomized controlled trials (RCTs) of GORD treatment in adults or children that reported asthma health outcomes and had symptomatic GORD were included and assessed in accordance with the standard Cochrane systematic review process. Results 11 male (44%) and 14 female (56%) patients with moderate to severe persistent asthma (mean age 44 years, SD = 11) participated. Methods A comprehensive range of intracellular T-cell and monocyte proand anti-inflammatory cytokines/chemokines was investigated in peripheral blood from 5 OSA patients and 5 aged-matched control subjects (with no evidence of sleep problems) using multiparameter flow cytometry. Methods Following completion of a 12-month exercise study, which included a supervised program (Intervention, n = 18) and control group (Control, n = 17), COPD subjects [mean age (SD): 66 (8); mean FEV1 (% predicted) = 56% (19)] were asked to complete a questionnaire.
cord-023303-fxus38mp	2008	Results Data indicate splice variant expression in dendritic cells from asthmatic patients is influenced by asthma severity. Methods Randomized controlled trials (RCTs) of GORD treatment in adults or children that reported asthma health outcomes and had symptomatic GORD were included and assessed in accordance with the standard Cochrane systematic review process. Results 11 male (44%) and 14 female (56%) patients with moderate to severe persistent asthma (mean age 44 years, SD = 11) participated. Methods A comprehensive range of intracellular T-cell and monocyte proand anti-inflammatory cytokines/chemokines was investigated in peripheral blood from 5 OSA patients and 5 aged-matched control subjects (with no evidence of sleep problems) using multiparameter flow cytometry. Methods Following completion of a 12-month exercise study, which included a supervised program (Intervention, n = 18) and control group (Control, n = 17), COPD subjects [mean age (SD): 66 (8); mean FEV1 (% predicted) = 56% (19)] were asked to complete a questionnaire.
cord-023308-af5nihyi	2008	Results Data indicate splice variant expression in dendritic cells from asthmatic patients is influenced by asthma severity. Methods Randomized controlled trials (RCTs) of GORD treatment in adults or children that reported asthma health outcomes and had symptomatic GORD were included and assessed in accordance with the standard Cochrane systematic review process. Results 11 male (44%) and 14 female (56%) patients with moderate to severe persistent asthma (mean age 44 years, SD = 11) participated. Methods A comprehensive range of intracellular T-cell and monocyte proand anti-inflammatory cytokines/chemokines was investigated in peripheral blood from 5 OSA patients and 5 aged-matched control subjects (with no evidence of sleep problems) using multiparameter flow cytometry. Methods Following completion of a 12-month exercise study, which included a supervised program (Intervention, n = 18) and control group (Control, n = 17), COPD subjects [mean age (SD): 66 (8); mean FEV1 (% predicted) = 56% (19)] were asked to complete a questionnaire.
cord-023331-jrvmgnu3	2008	Results Data indicate splice variant expression in dendritic cells from asthmatic patients is influenced by asthma severity. Methods Randomized controlled trials (RCTs) of GORD treatment in adults or children that reported asthma health outcomes and had symptomatic GORD were included and assessed in accordance with the standard Cochrane systematic review process. Results 11 male (44%) and 14 female (56%) patients with moderate to severe persistent asthma (mean age 44 years, SD = 11) participated. Methods A comprehensive range of intracellular T-cell and monocyte proand anti-inflammatory cytokines/chemokines was investigated in peripheral blood from 5 OSA patients and 5 aged-matched control subjects (with no evidence of sleep problems) using multiparameter flow cytometry. Methods Following completion of a 12-month exercise study, which included a supervised program (Intervention, n = 18) and control group (Control, n = 17), COPD subjects [mean age (SD): 66 (8); mean FEV1 (% predicted) = 56% (19)] were asked to complete a questionnaire.
cord-023713-daz2vokz	2013	A systematic review and metaanalysis of the longitudinal studies relating maternal vitamin D status during pregnancy to childhood outcomes concluded that high maternal dietary vitamin D intake is associated with a reduced risk of children wheezing up to the age of 5 years (OR = 0.56; 95% CI, 0.42 to 0.73). The Dutch Prevention and Incidence of Asthma and Mite allergy (PIAMA) birth cohort study related symptom data prospectively collected annually from 3863 children up to the age of 8 years to land-use regression estimates of individual NO 2 , PM 2.5 , and soot exposures at their birth addresses. 327 A systematic review and meta-analysis of prospective birth cohort studies evaluating the effects of allergen (i.e., HDM or dietary) avoidance during pregnancy concluded that early-life allergen avoidance in isolation does not reduce the likelihood of asthma in children at age 5 years (OR = 1.22; 95% CI, 0.83 to 1.78).
cord-252012-hdjbxah8	2010	Traditionally associated with acute respiratory illness (ARI) or symptoms of the "common cold," the respiratory viruses implicated in asthma exacerbations predominantly possess RNA genomes with a distinct genome organization (positive [1] or negative [À] sense), virus particle (virion) morphology (enveloped or nonenveloped), host cell receptor interaction, and well-defined annual or seasonal prevalence. These "newly identified viruses" (NIVs) including human metapneumovirus (HMPV; described pre-SARS), the human rhinovirus (HRV) species C (HRV-Cs), human coronaviruses (HCoVs)-NL63 and -HKU1, human bocavirus (HBoV), and the KI and WU polyomaviruses (KIPyV and WUPyV) are now the focus of intense research, and their involvement in asthma exacerbations is slowly beginning to be determined. 34 In a retrospective study of clinical samples taken over a 20-year period from young children (median age 14.5 months), the percentage of lower respiratory tract illness (LRTI; including asthma exacerbations and bronchiolitis) associated with any HCoV, HCoV-NL63, or HCoV-OC43 was estimated to be 4.6%, 2.6%, and 1.9%, respectively.
cord-252769-fe50u028	2008	Animal research is difficult to extrapolate to man but suggests RSV can induce allergic sensitisation 28 , increase bronchial and interleukin (IL)-13 hyperresponsiveness, and rão, na maioria dos casos, consequências remotas, embora algumas vezes descrevam sibilâncias que irão desaparecer aos 3 -5 anos e só raramente se prolongam, instalando -se ou não uma asma. This phenomenon has been put to the test in inhalatory challenge tests which could bring on asthma episodes or exacerbations in children and adults 82, 102 , but, to test this seeming paradox, it is not necessary to resort to these arguments as in a German study 82 , the degree of early life exposure to domestic endotoxins was in direct correla-Infecção na modulaçâo da asma J Pinto Mendes fende um efeito daquelas células na supressão simultânea das respostas Th 1 e Th 2 .
cord-254766-585iu5ey	2008	This review summarizes the evidence associated with factors that may contribute to the development or exacerbation of asthma including age, host factors, genetic polymorphisms, altered immune responses, and aspects of viral antigen expression. These observations suggest that respiratory viral infections lead to a prolonged period of increased antigen presentation in the airways resulting in de novo and memory T-cell responses not only to the virus but also to unrelated antigens including allergens. In addition to studies of primary infections, models studying the interactions between respiratory viral infections and allergen sensitization are essential in understanding the mechanisms of virus induced asthma exacerbations. These studies show that the immune responses to allergen sensitization and respiratory viral infections interact to cause persistent inflammation and AHR, symptomatic of the asthmatic response (Fig. 2) [53] . Recurrent respiratory syncytial virus infections in allergen sensitized mice lead to persistent airway inflammation and hyperresponsiveness
cord-257244-gryp0khc	2017	Despite these important associations, the use of antiinfectives (antibiotics, antivirals, antifungals, vaccines) that specifically target known pathogens, or drugs that are based on or exploit microbe-host receptor interactions (toll-like receptor agonists, bacterial lysates) or are immunomodulators (vitamin D), and/or may work in part by altering our associated microbiology (probiotics) are, with the exception of severe asthma, seldom considered in asthma treatment, prevention and guidelines. Overall, antibiotic use is associated with asthma risk rather than protection at most stages of human development, including pregnancy, 10, 11 early life 12 and childhood, 13 although why this is so is a subject widely debated. 10 In retrospective studies, the association between antibiotic use and increased risk of asthma or wheezing in children is further confused due to the potential of reverse causation. Inhibiting virus replication through interfering with viral enzymes active within cells poses additional problems in drug discovery; however, several useful inhibitors for respiratory tract viruses have found their way into phase I/II clinical trials.
cord-258093-6fn8ei9f	2011	The aging lung Large, longitudinal, and more complete studies to determine the effects of aging on the function of the respiratory system Improved knowledge about lung structure-function relationships in older age using techniques of imaging and measures of lung function not requiring effort (eg, high-resolution computed tomographic scanning and forced oscillation) Improved assessment of lung processes underlying airflow limitation attributable to aging versus COPD or asthma, especially in asthmatic patients who smoke Studies to examine the effects of aging in ethnic groups and the role of gender Epidemiology, effect, diagnosis, and management Determine the true prevalence and cost of asthma in the older population Develop a uniform definition of asthma to be applied to health care records that will distinguish asthma from COPD and mixed asthma/COPD Evaluate evidence-based treatment algorithms for older asthmatic patients, such as those developed by the National Heart, Lung, and Blood Institute and Global Initiative For Asthma guidelines 7 Assess the effect of asthma treatment, including direct medical costs of care, indirect costs of care, and value of treatment in improving quality of life 8, 9 Assess the effect of comorbid conditions, especially COPD and congestive heart failure, on asthma 9 Characterize phenotypes of elderly asthma with regard to responses to therapy and long-term outcomes based on age of onset, duration of disease, and environmental triggers Develop algorithms for electronic medical record systems that are asthma-specific Evaluate effects of current asthma medications in older patients compared with younger patients Identify pharmacogenetic determinants of response to asthma medications in older adults Identify simpler and safer drug delivery systems and schedules for older adults Develop simple methods to differentiate COPD from asthma exacerbations in older adults
cord-260472-xvvfguht	2007	The association between upper respiratory viral infections and asthma exacerbations in children was demonstrated almost three decades ago using virus cultures and serological techniques [5] . Abbreviations: RTePCR, reverse transcriptionepolymerase chain reaction; RV, rhinovirus; PIV, parainfluenza virus; RSV, respiratory syncytial virus; MPV, human metapneumovirus; ICAM-1, intracellular adhesion molecule-1; IFN-b, interferon-beta; NGF, nerve growth factor; SP, substance P; NK1, neurokinin 1 receptor; MBL, mannose-binding lectin; LABA, long-acting b 2 agonists. In the human respiratory tract, all the above agents are able to produce a spectrum of clinical acute infection phenotypes, ranging from the common cold, croup and acute bronchiolitis, to pneumonia, although each virus has increased propensity for a particular clinical disease (e.g. parainfluenza for croup, RSV for severe bronchiolitis, influenza for pneumonia) [21, 22] . Rhinovirus is the key virus accounting for the majority of exacerbations both in children and adults and thus the effective treatment or prevention of that infection would be a major asset in asthma therapy.
cord-263556-y8vx4ie2	2017	Based on our previous findings, 8, 9 we hypothesized that in children with high rhinovirus genome load, the effect of OCS is likely to last beyond 12 months by reducing the need for initiation of long-term asthma control medication. Second, in the placebo group, asthma risk was high: regular asthma control medication was initiated to all children with high rhinovirus genome load during the subsequent 14 months after the first acute rhinovirus-induced wheezing episode. No difference was found in overall analysis F I G U R E 3 The time to initiation of asthma control medication in children randomized to receive prednisolone or placebo for the first rhinovirus-induced wheezing episode. 9 In summary, early systemic short-course prednisolone treatment may be beneficial in reducing the risk for asthma control medication during the first 5 years in first-time wheezing preschool children whose episode was severe and associated with high rhinovirus genome load.
cord-267835-ic0oqqln	1996	There is a need to examine further the proper role, if any, of antibiotics in such situations, to determine the optimum dose and course length of oral steroid therapy, and to continue validating the use of self-management plans in acute asthma management. Thus, there is a need to examine further GPs'' ideas regarding current management of acute asthma attacks in general practice, with particular reference to those associated with respiratory tract infection. This study aimed to examine the reported usage of oral steroids and antibiotics in asthma attacks associated with respiratory tract infection managed in general practice, and the timing of follow-up consultations using a postal scenario-based questionnaire sent to all GP principals in one health district. The results show that most GPs would prescribe oral steroids when faced with an acute asthma attack associated with respiratory tract infection and managed within a general practice setting.
cord-269554-fzu6dy4e	2020	Univariate analysis of COVID-19 outcomes revealed that asthma was significantly associated with higher rate of endotracheal intubation (40.3% vs 27.8%, p = 0.036), mechanical ventilation (both invasive and non-invasive) (70.7% vs 52.2%, p = 0.039), and longer hospital length of stay (15.14 ± 12.48 days vs 11.51 ± 10.58 days, p = 0.015). Asthma was not associated with a higher rate of Intensive Care Unit (ICU) admission (22.2% vs 14.9%, p = 0.12), acute respiratory distress syndrome (37.5% vs 30.9%, p = 0.27), or death (9.7% vs 13.5%, p = 0.45) among COVID-19 patients. On comparison to non-asthmatic obese patients, obese asthmatic patients were more likely to develop sepsis (25.9% vs 14.2%, p = 0.042), had higher risk of ICU admission (48.1% vs 33.2%, p = 0.042), and required prolonged intubation (2.73 ± 3.63 days vs 1.38 ± 2.07, p = 0.032).Impact of asthma comorbidity on COVID-19 outcomes
cord-270647-vn4kirrx	2018	OBJECTIVES: To describe the virome and bacteriome present in the upper respiratory tract of hospitalized children with a clinical diagnosis of asthma and pneumonia during an acute exacerbation and an acute respiratory illness ARI episode respectively. Both groups differ with respect to the associated virus and bacteria: while asthma exacerbations have been associated to a specific rhinovirus infection, pneumonia can be related to a wide range of bacterial, fungal and viral agents, with a high prevalence of Respiratory Syncytial Virus (RSV) [2, 7] . Here we describe the virome and bacteriome present in the Upper Respiratory Tract of hospitalized children clinically diagnosed with asthma and pneumonia, during an acute exacerbation and an ARI episode respectively, at the National Institute of Respiratory Diseases (INER, Mexico City) during 2014 and 2015 winter seasons. Prevalence of respiratory viral infection in children hospitalized for acute lower respiratory tract diseases, and association of rhinovirus and influenza virus with asthma exacerbations
cord-270834-b625s54s	2020	title: COVID-19 severity in hospitalized patients with asthma: A matched cohort study We matched 80 asthma inpatients with COVID-19 to 323 comparators ( Table I) . In the fully adjusted model, the risk of ICU admission was lower among asthma patients than 116 comparators (adjusted hazard ratio [aHR] 0.52, 95%CI:0.30-0.90) ( Table II) . In the fully 118 adjusted model, the risk of mechanical ventilation was lower among asthma patients than 119 comparators (aHR 0.42, 95%CI: 0.21-0.81). In this matched cohort study of MGH inpatients with COVID-19, we identified that asthma 126 patients were less likely to require ICU admission and mechanical ventilation but were not at 127 increased risk for death. Although current research specifically assessing asthma and COVID-19 remains limited, recent 133 reports suggest that asthma is not overrepresented among severe COVID-19 cases and may not 134 be associated with an increased risk of hospitalization or death.
cord-271790-3s8o774l	2008	Animal research is difficult to extrapolate to man but suggests RSV can induce allergic sensitisation 28 , increase bronchial and interleukin (IL)-13 hyperresponsiveness, and rão, na maioria dos casos, consequências remotas, embora algumas vezes descrevam sibilâncias que irão desaparecer aos 3 -5 anos e só raramente se prolongam, instalando -se ou não uma asma. If viral infection in acute asthma, particularly RV -the most studied -is associated with neutrophilic inflammation, cellular lysis and production of interferons (IFNs) 46 and if the environment is rich in IL-4, the production of IL-5, RANTES (Regulated upon Activated T cell Expressed and Selected), eotaxin, eosinophilic infiltration and IgE production 47 generally occur. While children at risk at allergic asthma have long been told to avoid contact with these animals, it is concluded that prolonged early life exposure to Feld-1 induces a form of immune tolerance specific to that allergen 89 .
cord-272742-q37xxkja	2020	key: cord-272742-q37xxkja authors: Mei‐Zahav, Meir; Amirav, Israel title: Aerosol treatments for childhood asthma in the era of COVID‐19 cord_uid: q37xxkja To the Editor, About 10% of children in the United States have asthma and aerosols are the cornerstone of treatment of asthma. Nebulizers (wet or jet) are one of the commonly used aerosol-generating medical devices and generate small particles that can spread to a larger distance than a normal breath. In conclusion, given that MDI/VHC has been shown to be as effective in numerous clinical situations, switching from nebulization to MDI/VHC treatment should be another important step that pediatricians can take in reducing COVID-19 spread, particularly among health caregivers. Meir Mei-Zahav MD 1, 2 Israel Amirav MD 2,3,4 1 Factors involved in the aerosol transmission of infection and control of ventilation in healthcare premises Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma Paediatric asthma and COVID-19
cord-280210-6xivdgvt	2020	So I try to keep up with epidemiology, even though at this writing, in May 2020, more than 10,000 scientific or medical articles have already appeared on this novel coronavirus, SARS-CoV-2, that causes the disease COVID-19. So, against all odds, I will start with thoughts on infections and epidemics, on our primal fear of contagion, and on quarantine or "social distancing." Then, I will address four questions I have received that are relevant to athletes. Now is the time to read John Barry''s "The Great Influenza," on the deadliest plague in history, the influenza pandemic from early 1918 to early 1920 that killed up to 100 million people worldwide. Early in the acquired immune deficiency syndrome panic, a Boston neurosurgeon called for Massachusetts to quarantine "irresponsible" carriers of human immunodeficiency virus on Penikese Island. Question 3: If athletes test positive for the antibody, are they immune to this Coronavirus?
cord-280859-3ff72mlq	2019	Nasopharyngeal mucosa cell samples were collected from the participants and examined by reverse transcription‐polymerase chain reaction to detect rhinovirus (RV), respiratory syncytial virus (RSV), enterovirus (EV), parainfluenza virus (PIV), Mycoplasma pneumoniae, and others. The median age and house-dust mite IgE levels at admission were significantly higher in the single infection group than those in the superinfection group (P < .001), whereas there were no significant differences in body temperature, SpO 2 , duration of hospitalization, serum levels of CRP, intensity of asthma exacerbation, and bronchial asthma severity between the two groups. The detection frequency of RV and RSV in our study was consistent with that in previous reports on the relationship between causative viruses and exacerbation in asthmatic patients, suggesting that our study illustrates the actual virus prevalence associated with asthma exacerbation. In conclusion, our three-season analysis on the prevalence of causative pathogens in hospitalized children with asthma exacerbation revealed that RV and RSV were most frequently detected.
cord-281844-c0uhcatg	2014	Abstract Objective To review the available literature on the association between acute viral respiratory tract infection and the onset of asthma exacerbations, identifying the most prevalent viruses, detection methods, as well as preventive and therapeutic aspects. Studies using reverse transcriptase polymerase chain reaction (RT-PCR) as the detection technique, isolated or combined with traditional methods, observed positivity for respiratory viruses in up to 92.2% of episodes of acute asthma exacerbation in children. Several authors have performed studies aiming to detect viruses in respiratory secretions of exacerbated asthma patients, showing a prevalence of viral identification that varies with several factors, such as patient age, time of the year, method of sample collection, and method of viral detection. The use of viral detection techniques with high sensitivity and specificity has increased the identification of some respiratory viruses in children with asthma exacerbation.
cord-283870-b9hvcrd1	2017	23 Finally, the use of inhaled IFN-b at the time of an upper respiratory infection reduces the airway viral load and improves clinical symptoms in patients with asthma. 50 ICS but under poor control, 50 Pauwels et al showed that highdose budesonide further reduced severe asthma exacerbations, that is, need for systemic corticosteroids, by nearly 50% compared with treatment with low-dose ICS in adults. In 2 replicate trials with a total of 912 adult patients with severe asthma and using ICS/LABA, adding tiotropium, 5 mcg, increased the time to first exacerbation by 56 days over placebo, and reduced exacerbations by 21% ( Figure 5 ). Two anti-IL-5 monoclonal antibodies, mepolizumab and reslizumab, are approved as maintenance therapy for patients with uncontrolled, persistent eosinophilic asthma with an exacerbation phenotype despite high-dose ICS.
cord-284313-rg3krh7d	2007	Abstract Background:This study examined the contribution of airway inflammation to the delayed lung function recovery that occurs in some people following virus-induced asthma exacerbations. In contrast, during exacerbation, subjects with persistent airway obstruction showed no differences in inflammatory cell counts compared to stable subjects with asthma, nor did cell counts change postexacerbation. Table 3 indicates that during the exacerbation the CCQ was elevated in both the airwayrecovery and the persistent-airway-obstruction groups; then, at 4 to 6 weeks postexacerbation, a similar improvement in virus symptoms was seen in both groups (percentage change in CCQ) [Fig 1] . The poor lung function (percent predicted FEV 1 ) observed during the acute episode significantly improved in the airway-recovery group, with values returning to levels of stable asthma patients postexacerbation. 11 Conversely, patients in the persistent-airway-obstruction group showed a lower airway inflammatory profile during exacerbations similar to those with stable asthma (Fig 2) , and this did not change significantly postexacerbation (Table 4 ).
cord-286328-ap0wfjhq	2012	CONCLUSIONS & CLINICAL RELEVANCE: We conclude that, in children with asthma, naturally-occurring viral infections apparently induce a robust innate immune response including expression of specific chemokines, IFNs and IFN-responsive genes. To further examine the innate immune response to viral infection in children with asthma, we measured nasal aspirate cytokine levels in 16 asthmatic children before and after upper respiratory tract infections. We also examined the effects of upper respiratory tract infection on mRNA levels of selected markers of viral infection, including IFNs. Finally, we evaluated a new method of virus detection using a single polymerase chain reaction-ligation detection reaction (PCR-LDR) multiplex assay. We performed home measurements of respiratory symptoms and collected nasal secretions (for detection of viral RNA by PCR and host biomarkers by PCR and ELISA) on 3 days during a week when children were healthy (not reporting upper respiratory tract infection or asthma symptoms), and again during a week when they experienced cold or flu-like symptoms.
cord-288344-8dar2p3j	2020	title: The rescue intervention strategy for asthma patients under severe air pollution: a protocol for a single-centre prospective randomized controlled trial Therefore, we hypothesize that the rescue intervention strategy of budesonide/formoterol plus original treatments under severe pollution may reduce the risk of asthma exacerbations caused by air pollution before patients have symptoms. When the air quality index (AQI) reported by the air pollution monitoring station for the study is no less than 200, participants in the RIS group will receive budesonide/formoterol (160 μg/4.5 μg/dose, 1 dose/time, b.i.d.) plus original treatments until the end of severe pollution (AQI < 200). This singlecentre, prospective, randomized and standard treatment parallel control clinical trial aimed to determine whether the rescue intervention strategy will reduce the risk of air pollution-related asthma exacerbations. This is a single-centre, prospective, randomized and standard treatment parallel control study aimed at decreasing the risk of asthma exacerbations under severe air pollution with a novel rescue intervention strategy.
cord-289697-g24xib4l	2005	In addition to viral infections, RTIs with atypical organisms, such as Mycoplasma pneumoniae and Chlamydia pneumoniae, precipitate a significant proportion of acute episodes of wheezing, contribute to the severity and persistence of asthma, and may serve as the initial insult that leads to development of asthma [17] [18] [19] . The time course of influenza-induced asthma exacerbations was examined retrospectively in 20 asthmatic children 8 to 12 years of age with acute respiratory symptoms [28] . Respiratory syncytial virus (RSV) infects almost 100% of children by 2 years of age and is the most common cause of bronchiolitis and pneumonia in infants [34] . Thus, despite the efficacy of inhaled corticosteroids in the control of asthma and reduction of exacerbations, patients continue to experience exacerbations, particularly in the setting of viral RTIs. Several treatment approaches have been investigated in an attempt to reduce the morbidity associated with wheezing associated with RTIs. Brunette et al [98] examined the effect of a short course of oral corticosteroid administered in an unblinded manner at onset of URI symptoms in a group of children with histories of recurrent wheezing in the setting of viral infections.
cord-293678-jfjc7wjb	2020	title: SEVERE ASTHMA DURING THE COVID-19 PANDEMIC: CLINICAL OBSERVATIONS It is 110 estimated that the global economic burden of asthma is between 1.5 and 3 billion euros 111 annually, and higher costs are associated with greater disease severity (5). Severe asthma affects 3.9% of asthmatic patients (5). It is defined as an inflammatory 113 chronic respiratory disease that remains uncontrolled despite optimal therapy and 114 treatment of contributing factors, or which worsens when high-dose treatment is 115 decreased (6). Around 50% of patients with severe asthma experience uncontrolled or 116 partially controlled symptoms despite maximal treatment (5). The aim of this study is to determine the prevalence and characterization of COVID-19 120 infection among patients with severe asthma according to ERS/ATS criteria who 121 presented to our allergy department during the COVID-19 pandemic. ATS guidelines on definition, evaluation and treatment of 219 severe asthma
cord-295575-zgta5ah8	2019	The purpose of this literature review was to specifically examine asthma outcomes related to environmental exposures to microbial products, pertaining to endotoxin from bacteria-(1,3)-β-D-glucan and ergosterol from fungus, and common viruses associated with worsening asthma morbidity (rhinovirus, respiratory syncytial virus (RSV), enterovirus, and the influenza virus) during infancy, and to assess the risk of asthma development later in childhood [15] [16] [17] [18] (see Table 1 ). conducted a prospective longitudinal study examining whether early exposure to microbial products in dust was associated with allergy and asthma later in childhood for children in suburban areas using the following three birth cohort studies for children born between 1996 and 1999: [24••] , dust samples were collected from children''s mattresses, bedroom floors, and living room floors; and showed no association between endotoxin nor the fungal membrane lipid ergosterol in the development of asthma with exposure from birth to 7 years of age.
cord-299672-dq1y1gkc	2010	Conclusions Respiratory viral infections are commonly found in children with asthma exacerbation, with HRV being the most important pathogen in our patients. Our primary outcome was the difference in detection rate for any respiratory pathogen between children with asthma with acute exacerbation and controls (ie, stable asthma). Secondary outcomes consisted of differences in the clinical severity of asthma exacerbation, lung function parameters, and fractional exhaled nitric oxide concentration (FeNO) in relation to patients with different respiratory pathogens. HRV infection was associated with asthma exacerbation in the children, which is consistent with FeNO was the only parameter that differed between patients with and without HRV, being signifi cantly lower in the former group ( P 5 .018). Identifi cation of viral and atypical bacterial pathogens in children hospitalized with acute respiratory infections in Hong Kong by multiplex PCR assays
cord-300311-eah49b3g	2007	Other studies are often based on selected populations with existing symptoms or complications, reflecting only the worst of the spectrum of disease caused by acute respiratory infections [9, [14] [15] [16] [17] ] and thus disregarding their often self-limiting nature. The availability of effective vaccines against the key viruses involved in asthma exacerbations thus could play an important role in its prevention. However, because of a lack of clinical effectiveness, the natural antigenic variations of the influenza virus, and the low average incidence of influenza, cost-effectiveness in children and adults with asthma will not be easily achieved if vaccination has to be delivered annually. Community study of role of viral infections in exacerbations of asthma in 9-11 year old children Effectiveness of influenza vaccine for the prevention of asthma exacerbations Influenza vaccination in patients with asthma: effect on the frequency of upper respiratory tract infections and exacerbations
cord-301022-0q2ertja	2011	38 However, dietary antigen avoidance has not proved to be effective in most studies and a 2008 review in Pediatrics states, "for infants at high risk of developing atopic disease, there is evidence that exclusive breastfeeding for at least 4 months compared with feeding intact cow milk protein formula decreases the cumulative incidence of atopic dermatitis and cow milk allergy in the first 2 years of life." 39 Beyond this, whether exposure to antigenic foods early in life promotes sensitization or tolerance is unclear. Although preventing allergy through environmental control has shown mixed results, two controlled studies have shown that treating young children who have atopic dermatitis with antihistamines decreases the risk of developing asthma. 101 This phenotype is also associated with early sensitization to food or inhalant allergens 102 and reduced lung function at age 6 years (compared with children with no history of wheezing with lower respiratory illnesses).
cord-303606-ypkia5x1	2011	We performed a prospective cohort study from September 2003 to December 2004 to delineate attributing the effect of different respiratory viral infections including newly discovered ones to asthma exacerbations in children in Hong Kong. Plausible explanations for much lower virus detection rate than previously reported include improved personal hygiene and precautionary measures taken during respiratory tract infections in the immediate post-severe acute respiratory syndrome period together with a significant contribution of other adverse factors like environmental air pollution. Plausible explanations for much lower virus detection rate than previously reported include improved personal hygiene and precautionary measures taken during respiratory tract infections in the immediate post-severe acute respiratory syndrome period together with a significant contribution of other adverse factors like environmental air pollution. Thus, we carried out a prospective study to delineate the current role of different viral respiratory tract infections including newly discovered respiratory viruses in asthma exacerbation in children in our locality.
cord-304549-e8q8mck4	2005	Abnormal signaling between the epithelium, which is in contact with the environment, and the underlying (myo)fibroblasts and dendritic cells indicating reactivation of the epithelial mesenchymal trophic unit, which is involved in fetal lung development and branching, provide a basis for asthma that encapsulates both T(H)2 polarization and airway wall remodeling. Asthma is a complex disorder involving a combination of genetic and environmental interactions that culminate in a specific type of inflammation involving mast cells, eosinophils, and macrophages and polarization of T cell-mediated immunity toward enhanced production of cytokines encoded in a cluster on the long arm of chromosome 5. Two fundamental approaches are being used to discover susceptibility genes in asthma and atopy: linkage analysis with functional cloning and association analysis for mutations of "candidate" genes thought to be involved in disease pathogenesis. 55 In susceptible mice genetic linkage has shown that ozone-induced lung inflammation is directed by genes encoded on chromosome 17, including the strong candidate TNF-α, a pleiotropic cytokine generated during oxidant-induced cell injury.
cord-305838-i0ck2oo0	2020	Home measurement of peak expiratory flow (PEF) using an inexpensive portable handheld device is already a guideline-recommended option to facilitate patient self-management in asthma and in the diagnosis of occupational asthma, but its role is less well defined in COPD. 37 Electronic portable spirometers have been studied and found to be comparable to conventional laboratory spirometry in several chronic respiratory conditions, such as asthma and COPD, cystic fibrosis, idiopathic pulmonary fibrosis, and post-lung and hematopoietic stem cell transplant monitoring. Oscillometry is emerging as an alternative form of pulmonary function testing that offers some advantages over conventional PFTs. 54 It has been shown to be more sensitive than spirometry in early diagnosis of COPD, 55, 56 to correlate better with respiratory symptoms and asthma control 57,58 as well as in identifying spirometrically silent episodes of biopsy-proven acute graft rejection following lung transplant.
cord-307202-iz1bo218	2014	Current asthma management involves a step-up and step-down approach based on asthma control with a large degree of heterogeneity in responses to the main drug classes currently in use: β(2)-adrenergic receptor agonists, corticosteroids, and leukotriene modifiers. Human studies have identified elevated numbers of cells expressing IL13 mRNA in the bronchial tissue of atopic and nonatopic asthmatic subjects [50] ; administration of recombinant IL13 in mouse lungs resulted in an increase in airway mucus secretion, development of subepithelial fibrosis, airway hyper-responsiveness (AHR), and eosinophilic airway inflammation-that is, several key features of the human disease [51] . While methods of stratifying asthma patients to specific treatments based on nongenetic factors such as clinical outcomes, cellular measures, or protein biomarkers have shown some success, a large body of work has investigated the potential of genetic markers as predictors of patient responses to existing therapies, i.e., pharmacogenetics.
cord-308169-a0ft6wdy	2013	A recently published consensus statement on severe asthma broadened the concept of ''difficult asthma'' to reflect the situation in less developed countries, where access to medications and appropriate care is a major issue, by defining three different patient groups including un(der)treated symptomatic patients, patients with low treatment adherence or unconventional therapies, and those remaining symptomatic despite high doses of anti-asthmatic therapies (13, 14) . Other similar initiatives included the EU-sponsored Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) consortium that has published a consensus-based systematic algorithm approach to differentiate between ''problematic'', ''difficult'' and ''severe refractory'' asthma in the evaluation of patients with chronic severe asthma symptoms for use in clinical research and specialized care (73) . These treatment options for patients with severe asthma who remain symptomatic despite adhering to standard medical care include novel anti-inflammatory drugs that have been shown in preliminary studies to be effective in treating airway inflammation in asthma and so warrant further investigation (32, (83) (84) (85) (86) , and other novel approaches such as bronchial thermoplasty (87) .
cord-309421-725u6dau	2020	METHODS: SOURCE is an ongoing phase 3, multicentre, randomized, double-blind, placebo-controlled study to evaluate the effect of tezepelumab 210 mg administered subcutaneously every 4 weeks on OCS dose reduction in adults with OCS-dependent asthma. SOURCE also aims to demonstrate that treatment with tezepelumab in patients with severe asthma is associated with reductions in exacerbation rates and improvements in lung function, asthma control and health-related quality of life, while reducing OCS dose. SOURCE also aims to demonstrate that treatment with tezepelumab in patients with severe asthma is associated with reductions in exacerbation rates and improvements in lung function, asthma control and healthrelated quality of life, while reducing OCS dose. In the phase 2b PATHWAY study (ClinicalTrials.gov identifier: NCT02054130), tezepelumab significantly reduced asthma exacerbations over 52 weeks by up to 71% compared with placebo in patients with severe, uncontrolled asthma, irrespective of baseline biomarker status [24, 26] , and improved lung function, asthma control and patient HRQoL [24] .
cord-312613-1nl7q6cy	2016	Respiratory viral infections, particularly respiratory syncytial virus (RSV) and rhinovirus, are the most importance risk factors for the onset of wheezing in infants and small children. The association between bronchiolitis caused by RSV and the development of recurrent wheezing and/or asthma was first described more than 40 years ago, but it is still unclear whether bronchiolitis causes chronic respiratory symptoms, or if it is a marker for children with a genetic predisposition for developing asthma in the medium or long term. In the Childhood Origins of Asthma (COAST) study, which followed a cohort of 289 newborns with high risk of developing asthma, lower respiratory tract infection associated with rhinovirus was the main risk factor for presenting recurrent wheezing at 3 and 6 years of life, with an odds ratio of 10 for rhinovirus bronchiolitis compared to 2.6 for RSV bronchiolitis. 3 found that 80% of asthma exacerbations in asthmatic children aged 9-11 years were associated with viral respiratory infection, of which two thirds were caused by rhinovirus.
cord-312952-9gbb4own	2020	While the majority of studies indicate that the detection rate of respiratory viruses in patients with asthma and healthy subjects is similar [10] , they have been found to differ with regard to the bacterial composition of the airways [11] . This technique was chosen for the present study, to test the hypothesis that elderly patients with asthma display a different profile of respiratory pathogens in the airways as compared to non-elderly asthmatics, and that this profile may be related to local airway and/or systemic inflammation. This study is the first to use the IS technique to compare detection rates of respiratory pathogens in the airways of elderly and non-elderly patients with asthma. Although the detection rate and profile of respiratory viruses in IS was similar in elderly and non-elderly patients with asthma, the presence of pathogens was associated with some clinical characteristics only in older subjects.
cord-320431-0877trhh	2020	In case of asthma, all these functions are impaired by the already existing allergic immune response that per se weakens the barrier integrity and self-cleaning abilities of the airway epithelium making it more vulnerable to penetration of allergens as well as of infection by bacteria and viruses. Besides this innate "rapid response team, " the polarized epithelium of the human airways is also able to transport and apically release immunoglobulins that carry a J-chain (joining chain) by using its poly Ig receptor (pIgR) (145) (146) (147) that is expressed by all non-stratified epithelial cells (Figure 2) . After contact for example with HDM extracts, representing a major source of asthma associated allergens, TLR4 dependent activation of NFκB and protease induced injuries in airway epithelial cells lead to secretion of chemokines and cytokines like thymic stromal lymphopoietin (TSLP), GM-CSF, IL-25, and IL-33 (211) (212) (213) (214) (215) .
cord-321824-zbo75ki3	2019	Respiratory viruses other than rhinovirus or respiratory syncytial virus, including human metapneumovirus, influenza virus, and human bocavirus, are important pathogens in acute wheezing illness and asthma exacerbations in young children. Whether infection with these viruses in early life is associated with recurrent wheezing and/or asthma is not fully investigated, although there are data to suggest children with human metapneumovirus lower respiratory tract infection may have a higher likelihood of subsequent and recurrent wheezing several years after initial infection. viruses are associated with acute wheezing illness, including rhinovirus (RV), respiratory syncytial virus (RSV), human metapneumovirus (hMPV), influenza virus, parainfluenza virus, adenovirus, human bocavirus (HBoV), 1 coronavirus, and enterovirus ( Table 1) . 17 In another study of children 1 to 14 years of age with hMPV infection, differences in measures of cell-mediated immunity distinguished hMPV from other respiratory viruses, such as RSV and influenza.
cord-323761-9m177ozm	2020	Studies have shown that maternal asthma increases the risk for adverse complications in fetuses and mothers, including SGA (small for gestational age), LBW (low birth weight), congenital malformations (cleft lip or cleft palate), increased perinatal mortality, PB (premature birth), maternal preeclampsia, gestational hypertension, gestational diabetes, prenatal hemorrhage, caesarean section, urinary tract infection, excessive amniotic fluid, and premature rupture of membranes, especially for those patients with severe or uncontrolled asthma during pregnancy [6, 7] . e long-term goals of asthma management are to achieve good symptom control, maintain normal activity levels, and minimize the risk of acute attacks, irreversible damage to lung function, and drug-related adverse effects. Anti-IgE monoclonal antibody omalizumab is as an add-on therapy for the treatment of nonpregnant patients with moderate-to-severe persistent asthma that is inadequately controlled with ICS and has the effect of preventing exacerbation, reducing the frequency of asthmatic symptoms, reducing the frequency of emergency room visit or hospital admission, and reducing the steroid dose.
cord-327610-cm3vkpcn	2020	The pathological role of cellular senescence, especially that involving the silent information regulator 2 homolog sirtuin (SIRT) protein family, has recently been demonstrated in stable and exacerbated chronic respiratory disease states. Thus, SIRT1 activators, including resveratrol, may be effective in targeting CXCL8-induced neutrophilic airway inflammation in virus-induced and steroid-resistant asthma exacerbations [58, 59] . These lines of evidence suggest that activation of SIRT1 may lead to suppression of neutrophilic inflammation, possibly through suppression of CXCL8 and may be an effective therapeutic strategy, especially for steroid-resistant virus-induced asthma exacerbations. These results indicated that SIRT1 activation could be a novel therapeutic strategy for virus-induced asthma exacerbations by regulating MMP-9 expression and suppressing airway neutrophilic inflammation and remodeling. These data suggested that SIRT1 activation may ameliorate IgE-mediated airway inflammation in viral-induced asthma exacerbations, whereas the detailed mechanism by which omalizumab blocks IgE is unclear and requires further study.
cord-328918-nc0a77r6	2020	title: Citrullinated histone H3, a marker of extracellular trap formation, is increased in blood of stable asthma patients In the present study we have evaluated circulating H3cit in stable asthmatics and investigated its relationship with asthma severity, pulmonary function and selected blood and bronchoalveolar lavage (BAL) biomarkers. We have recently reported evidence of a prothrombotic state in asthma which is characterized by enhanced plasma thrombin formation, impaired clot lysis and platelet activation [13] , all of them related to the low-grade systemic inflammation [3] , endothelial injury [14] , elevated exacerbation rate [15] , and likely increased atherosclerotic risk [16, 17] . In the present study we have demonstrated that serum H3cit, a novel biomarker of ETs formation, is increased in stable asthma subjects. Asthma is characterized by increased circulating H3cit likely related to the enhanced lung ETs formation.
cord-332053-df44guu7	2015	The Effect of Viral Infection on Exhaled Nitric Oxide in Children with Acute Asthma Exacerbations Jonathan Malka, MD a,b , Ronina Covar, MD c,d , Anna Faino, MS e , Jennifer Fish, CPNP f , Paige Pickering, BS g , Preveen Ramamoorthy, MD g , Melanie Gleason, PAC b,h , and Joseph D. All patients who presented to the Urgent Care Clinic at National Jewish Health for an acute asthma exacerbation and who had undergone spirometry and FENO measurements within the last 6 months when clinically stable (visit 1) were approached to participate in the study (Figure 1 ). We found FENO levels to be the highest in children with acute asthma exacerbations that were not associated with viral infections [PCR(À)]. B, Change in exhaled nitric oxide levels from baseline, during an exacerbation, and following a course of prednisone in adjusted models.
cord-332298-ig1j5z07	2020	In the last few years, the terminology has further evolved with the term equine asthma (EA) now being recommended to describe horses with chronic respiratory signs ranging in severity from mild to severe that were previously referred as inflammatory airway disease and recurrent airway obstruction, respectively (3) . The future development of new portable and sensitive devices for measuring the lung function of horses (forced oscillation or flow interruption techniques), or the discovery of blood biomarkers for EA would help not only to facilitate the diagnosis of mild and moderate forms of EA in clinical practice, but also to possibly identify new phenotypes for these conditions. Qualitative data were gathered through semi-structured focus group discussions designed to capture current practices and opinions relating to the diagnosis and treatment of lower airway inflammation, as well as familiarity with and views on the most recent ACVIM consensus statement (3), in which the term "mild-moderate equine asthma" was recommended.
cord-332737-iclruwmx	2017	Another recent study concluded that the nasopharyngeal microbiome within the first year of life was a determinant for infection spread to the lower airways and predicted the severity of accompanying inflammatory symptoms, as well as risk for future asthma development. Factors that predict risk in non-asthmatics for developing the "infectious asthma" syndrome include a previous history of self-limited lower respiratory tract illnesses such as acute bronchitis (often with wheezing) and/or pneumonia [35, 38, 39] . A 2013 metaanalysis of 12 randomized, controlled trials (RCTs) of macrolides for the long term management of asthma in both adults and children found positive effects on peak expiratory flow rate (PEFRa measure of pulmonary function), asthma symptoms, asthma quality of life (AQL), and airway hyper responsiveness (AHR), but not on forced expiratory flow rate in 1 s (FEV1) [77] .
cord-333175-klnxnxwm	2020	Currently, the CDC reports that asthma is present in about 17% of hospitalized COVID-19 patients, making it the fourth most prevalent comorbidity behind hypertension, obesity, and diabetes [4] . Obese and diabetic patients have been categorized as high-risk, but there is still limited data regarding the impact of bronchial asthma on COVID-19 outcomes [5] . Univariate analysis of COVID-19 outcomes revealed that asthma was significantly associated with higher rate of endotracheal intubation (40.3% vs 27.8%, p = 0.036), mechanical ventilation (both invasive and non-invasive) (70.7% vs 52.2%, p = 0.039), and longer hospital length of stay (15.14 ± 12.48 days vs 11.51 ± 10.58 days, p = 0.015). Asthma was not associated with a higher rate of Intensive Care Unit (ICU) admission (22.2% vs 14.9%, p = 0.12), acute respiratory distress syndrome (37.5% vs 30.9%, p = 0.27), or death (9.7% vs 13.5%, p = 0.45) among COVID-19 patients.
cord-336562-5qmzne98	2017	The ability to obtain tidal breathing measurements may lead to new insights into changes in chest and abdominal motion in pediatric respiratory disease. 47 Acute viral bronchiolitis, due to RSV and other pathogens, continues to have a major impact worldwide on childhood mortality and hospital admissions, 51 is associated with subsequent asthma and allergy risk, 52 and could be increasing in incidence. 57 Flores et al 58 conducted a randomized clinical trial comparing 3% hypertonic saline to normal saline in previously healthy infants hospitalized with mild-to-moderate acute viral bronchiolitis. Thus, the study does not support the use of nebulized hypertonic saline over normal saline in therapy of hospitalized children with mild-to-moderate acute viral bronchiolitis. Association between trafficrelated air pollution and asthma in preschool children in a national Japanese nested case-control study Changes in lung function measured by spirometry and the forced oscillation technique in cystic fibrosis patients undergoing treatment for respiratory tract exacerbation
cord-339578-eg19rfvi	2017	OBJECTIVE: Our aim was to compare the frequency of asthma development at 6–8 years in children with previous admission for bronchiolitis associated with single versus double or multiple viral infection. CONCLUSIONS: Asthma at 6–8 years is more frequent and severe in those children previously hospitalized with viral coinfection-bronchiolitis compared with those with single infection. Of the 351 children previously admitted with bronchiolitis, with positive viral detection and current age between 6 and 8 years, 244 (52 coinfections and 192 single infections) could be located and agreed to participate in the study. In conclusion, asthma at the age of 6-8 is more frequent and severe in those children previously hospitalized with viral coinfection bronchiolitis compared with those with single infection. Moreover, viral coinfection, allergic rhinitis and older age at admission seem also to be strong independent risk factors for asthma development in children previously hospitalised because of bronchiolitis.
cord-340583-kjrxrk50	2020	Importantly, none of the largest epidemiological studies including children with COVID-19 reported clinical findings or underlying characteristics to help assess whether asthma -or other chronic lung diseases-constitutes a risk factor for SARS-CoV-2 infection or COVID-19 severity. Rather than a risk factor, a recent review of data in adults reported that both asthma and COPD appear to be under-represented in the comorbidities reported for patients with COVID-19, compared with global estimates of prevalence for these conditions in the general population (63) . After an extensive review of the current literature, only two reports included information on asthma as a potential risk factor for COVID-19 infection -but not severity or mortality-in children. However, the largest studies to date have been limited to a description of the number of cases by age group, and so it remains unclear whether childhood asthma -or other pediatric respiratory diseases-are associated with COVID-19 risk or severity.
cord-342464-6vk2oxo5	2012	The hygiene hypothesis posits that repeated exposure to diverse common infections (in particular, with bacteria, food-borne and oro faecal parasites 4 , and hookworms 5 ) and exposure to environmental microbiota during childhood 6, 7 are strongly associated with a healthy maturation of the immune system and with protection from the development of asthma and allergies later in life 8, 9 . Case control studies show a clear link between respiratory virus infection together with allergen exposure in sensitized children 108 and adults 109 in increasing the risk of hospital admissions due to asthma exacerbations. 5. Excessive T H 2 type responses are implicated in the pathogenesis of RSV-mediated bronchiolitis 110 , and increased production of IL-5 by T cells at birth is associated with a greater risk of severe respiratory infection 111 .
cord-346253-0mnsm6s4	2012	HRV are the most common viral agents [33] ; Other respiratory tract viruses detected in children with an asthma exacerbation include RSV, influenza, coronavirus, hMPV, parainfluenza virus, adenovirus, and bocavirus [34] [35] [36] . Beside importance for bone health, vitamin D plays an important role in adequate function of both the innate and adaptive immune systems including development of dendritic cells and regulatory T lymphocytes [151, 152] production of antimicrobial proteins by airway epithelium [153] , modifying the effect of intestinal flora on inflammatory disorders [107] , and modulation of the inflammatory response to viral infections [154] . In a recent study of 48 children from five to 18 years of age, with newly diagnosed asthma, vitamin D supplementation during the northern hemisphere winter months (September to July) prevented declining serum concentrations of 25(OH) D and reduced the risk of asthma exacerbation triggered by acute respiratory tract infections [161] .
cord-346751-x3gd19kq	2020	There is now consistent evidence that exposure to traffic-related air pollution (TRAP; particularly nitrogen dioxide [NO 2 ]) 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 [5, 6] . 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 [35] . 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.
cord-351129-lzzyn570	2020	For allergic patients who have been followed up at an allergy clinic in our region, it is recommended that they (patients with asthma, rhinitis, atopic dermatitis or chronic urticaria) continue to receive maintenance therapy and be in a well-controlled status. It was reported that none of the 140 patients who were hospitalized due to confirmed COVID-19 in Wuhan, China had asthma or other allergic diseases such as AR, atopic dermatitis (AD) and food allergy. The Allergic Rhinitis and its Impact on Asthma (ARIA)-European Academy of Allergology and Clinical Immunology (EAACI) mentioned that patients with common allergic conditions do not develop additional distinct symptoms or seem to be at increased risk of severe disease when infected with COVID-19.
cord-351565-ryjxbqno	2006	In recent years studies employing new sensitive molecular methods of identification for the most common upper respiratory tract viruses (coronavirus and rhinovirus) have demonstrated that viral infections are associated with the majority of asthma exacerbations in children and adults in the community [1, 2] . In this issue of the journal a further detailed study employing experimental rhinovirus infection reports on both these aspects, demonstrating that bronchial hyperreactivity is induced and that IL-8 may play a role in the induction of bronchial hyperreactivity and therefore possibly in exacerbations of asthma [9] . In this study atopic asthmatic subjects were challenged with rhinovirus 16 or placebo and the severity of the cold and asthma symptoms monitored along with bronchial hyperreactivity, pulmonary function, nasal lavage IL-8 levels and peripheral blood lymphocyte and neutrophil counts.