Understanding the particle size distribution in the air and patterns of environmental contamination of SARS-CoV-2 is essential for infection prevention policies. Here we screen surface and air samples from hospital rooms of COVID-19 patients for SARS-CoV-2 RNA. Environmental sampling is conducted in three airborne infection isolation rooms (AIIRs) in the ICU and 27 AIIRs in the general ward. 245 surface samples are collected. 56.7% of rooms have at least one environmental surface contaminated. High touch surface contamination is shown in ten (66.7%) out of 15 patients in the first week of illness, and three (20%) beyond the first week of illness (p = 0.01, χ test). Air sampling is performed in three of the 27 AIIRs in the general ward, and detects SARS-CoV-2 PCR-positive particles of sizes >4 µm and 1-4 µm in two rooms, despite these rooms having 12 air changes per hour. This warrants further study of the airborne transmission potential of SARS-CoV-2.

The association between long-term exposure to ambient air pollution and respiratory symptoms was investigated in a cross-sectional study in random population samples of adults (aged 18 to 60 yr, n = 9,651) at eight study sites in Switzerland. Information on respiratory symptoms was obtained with an extended version of the European Community Respiratory Health Survey questionnaire. The impact of annual mean concentrations of air pollutants was analyzed separately for never-, former, and current smokers. After controlling for age, body mass index, gender, parental asthma, parental atopy, low education, and foreign citizenship, we found positive associations between annual mean concentrations of NO2, total suspended particulates, and particulates of less than 10 micrometers in aerodynamic diameter (PM10) and reported prevalences of chronic phlegm production, chronic cough or phlegm production, breathlessness at rest during the day, breathlessness during the day or at night, and dyspnea on exertion. We found no associations with wheezing without cold, current asthma, chest tightness, or chronic cough. Among never-smokers, the odds ratio (95% confidence interval) for a 10 micrograms/ m3 increase in the annual mean concentration of PM10 was 1. 35 (1.11 to 1.65) for chronic phlegm production, 1.27 (1.08 to 1.50) for chronic cough or phlegm production, 1.48 (1.23 to 1.78) for breathlessness during the day, 1.33 (1.14 to 1.55) for breathlessness during the day or at night, and 1.32 (1.18 to 1.46) for dyspnea on exertion. No associations were found with annual mean concentrations of O3. Similar associations were also found for former and current smokers, except for chronic phlegm production. The observed associations remained stable when further control was applied for environmental tobacco smoke exposure, past and current occupational exposures, atopy, and early childhood respiratory infections when restricting the analysis to long-term residents and to non- alpine areas, and when excluding subjects with physician-diagnosed asthma. The high correlation between the pollutants makes it difficult to sort out the effect of one single pollutant. This study provides further evidence that long-term exposure to air pollution of rather low levels is associated with higher prevalences of respiratory symptoms in adults.

RATIONALE:Nearly 60% of U.S. children live in counties with particulate matter less than or equal to 2.5 μm in aerodynamic diameter (PM) concentrations above air quality standards. Understanding the relationship between ambient air pollution exposure and health outcomes informs actions to reduce exposure and disease risk. OBJECTIVES:To evaluate the association between ambient PM levels and healthcare encounters for acute lower respiratory infection (ALRI). METHODS:Using an observational case-crossover design, subjects (n = 146,397) were studied if they had an ALRI diagnosis and resided on Utah's Wasatch Front. PM air pollution concentrations were measured using community-based air quality monitors between 1999 and 2016. Odds ratios for ALRI healthcare encounters were calculated after stratification by ages 0-2, 3-17, and 18 or more years. MEASUREMENTS AND MAIN RESULTS:Approximately 77% (n = 112,467) of subjects were 0-2 years of age. The odds of ALRI encounter for these young children increased within 1 week of elevated PM and peaked after 3 weeks with a cumulative 28-day odds ratio of 1.15 per +10 μg/m (95% confidence interval, 1.12-1.19). ALRI encounters with diagnosed and laboratory-confirmed respiratory syncytial virus and influenza increased following elevated ambient PM levels. Similar elevated odds for ALRI were also observed for older children, although the number of events and precision of estimates were much lower. CONCLUSIONS:In this large sample of urban/suburban patients, short-term exposure to elevated PM air pollution was associated with greater healthcare use for ALRI in young children, older children, and adults. Further exploration is needed of causal interactions between PM and ALRI.

Ambient air pollution exposure has been linked to mortality from chronic cardiorespiratory diseases, while evidence on respiratory infections remains more limited. We examined the association between long-term exposure to air pollution and pneumonia-related mortality in adults in a pool of eight European cohorts. Within the multicenter project ELAPSE (Effects of Low-Level Air Pollution: A Study in Europe), we pooled data from eight cohorts among six European countries. Annual mean residential concentrations in 2010 for fine particulate matter, nitrogen dioxide (NO), black carbon (BC), and ozone were estimated using Europe-wide hybrid land-use regression models. We applied stratified Cox proportional hazard models to investigate the associations between air pollution and pneumonia, influenza, and acute lower respiratory infections (ALRI) mortality. Of 325,367 participants, 712 died from pneumonia and influenza combined, 682 from pneumonia, and 695 from ALRI during a mean follow-up of 19.5 years. NO and BC were associated with 10-12% increases in pneumonia and influenza combined mortality, but 95% confidence intervals included unity (hazard ratios, 1.12 [0.99-1.26] per 10 μg/m for NO; 1.10 [0.97-1.24] per 0.5 10m for BC). Associations with pneumonia and ALRI mortality were almost identical. We detected effect modification suggesting stronger associations with NO or BC in overweight, employed, or currently smoking participants compared with normal weight, unemployed, or nonsmoking participants. Long-term exposure to combustion-related air pollutants NO and BC may be associated with mortality from lower respiratory infections, but larger studies are needed to estimate these associations more precisely.

(the pneumococcus) is the leading cause of pneumonia and bacterial meningitis. A number of recent studies indicate an association between the incidence of pneumococcal disease and exposure to air pollution. Although the epidemiological evidence is substantial, the underlying mechanisms by which the various components of air pollution (particulate matter and gases such as NO and SO) can increase susceptibility to pneumococcal infection are less well understood. In this review, we summarize the various effects air pollution components have on pneumococcal pathogenesis and transmission; exposure to air pollution can enhance host susceptibility to pneumococcal colonization by impairing the mucociliary activity of the airway mucosa, reducing the function and production of key antimicrobial peptides, and upregulating an important pneumococcal adherence factor on respiratory epithelial cells. Air pollutant exposure can also impair the phagocytic killing ability of macrophages, permitting increased replication of . In addition, particulate matter has been shown to activate various extra- and intracellular receptors of airway epithelial cells, which may lead to increased proinflammatory cytokine production. This increases recruitment of innate immune cells, including macrophages and neutrophils. The inflammatory response that ensues may result in significant tissue damage, thereby increasing susceptibility to invasive disease, because it allows access to the underlying tissues and blood. This review provides an in-depth understanding of the interaction between air pollution and the pneumococcus, which has the potential to aid the development of novel treatments or alternative strategies to prevent disease, especially in areas with high concentrations of air pollution.

BACKGROUND:Exposure to household air pollution is a risk factor for severe pneumonia. The effect of replacing biomass cookstoves with liquefied petroleum gas (LPG) cookstoves on the incidence of severe infant pneumonia is uncertain. METHODS:We conducted a randomized, controlled trial involving pregnant women 18 to 34 years of age and between 9 to less than 20 weeks' gestation in India, Guatemala, Peru, and Rwanda from May 2018 through September 2021. The women were assigned to cook with unvented LPG stoves and fuel (intervention group) or to continue cooking with biomass fuel (control group). In each trial group, we monitored adherence to the use of the assigned cookstove and measured 24-hour personal exposure to fine particulate matter (particles with an aerodynamic diameter of ≤2.5 μm [PM]) in the women and their offspring. The trial had four primary outcomes; the primary outcome for which data are presented in the current report was severe pneumonia in the first year of life, as identified through facility surveillance or on verbal autopsy. RESULTS:Among 3200 pregnant women who had undergone randomization, 3195 remained eligible and gave birth to 3061 infants (1536 in the intervention group and 1525 in the control group). High uptake of the intervention led to a reduction in personal exposure to PM among the children, with a median exposure of 24.2 μg per cubic meter (interquartile range, 17.8 to 36.4) in the intervention group and 66.0 μg per cubic meter (interquartile range, 35.2 to 132.0) in the control group. A total of 175 episodes of severe pneumonia were identified during the first year of life, with an incidence of 5.67 cases per 100 child-years (95% confidence interval [CI], 4.55 to 7.07) in the intervention group and 6.06 cases per 100 child-years (95% CI, 4.81 to 7.62) in the control group (incidence rate ratio, 0.96; 98.75% CI, 0.64 to 1.44; P = 0.81). No severe adverse events were reported to be associated with the intervention, as determined by the trial investigators. CONCLUSIONS:The incidence of severe pneumonia among infants did not differ significantly between those whose mothers were assigned to cook with LPG stoves and fuel and those whose mothers were assigned to continue cooking with biomass stoves. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; HAPIN ClinicalTrials.gov number, NCT02944682.).

BACKGROUND:Exposure to ambient particulate matter (PM) is associated with a number of adverse health outcomes, but potential mechanisms are largely unknown. Metabolomics represents a powerful approach to study global metabolic changes in response to environmental exposures. We therefore conducted this study to investigate changes in serum metabolites in response to the reduction of PM exposure among healthy college students. METHODS:We conducted a randomized, double-blind crossover trial in 55 healthy college students in Shanghai, China. Real and sham air purifiers were placed in participants' dormitories in random order for 9 days with a 12-day washout period. Serum metabolites were quantified by using gas chromatography-mass spectrometry and ultrahigh performance liquid chromatography-mass spectrometry. Between-treatment differences in metabolites were examined using orthogonal partial least square-discriminant analysis and mixed-effect models. Secondary outcomes include blood pressure, corticotropin-releasing hormone, adrenocorticotropic hormone, insulin resistance, and biomarkers of oxidative stress and inflammation. RESULTS:The average personal exposure to PMs with aerodynamic diameters ≤2.5 μm was 24.3 μg/m during the real purification and 53.1 μg/m during the sham purification. Metabolomics analysis showed that higher exposure to PMs with aerodynamic diameters ≤2.5 μm led to significant increases in cortisol, cortisone, epinephrine, and norepinephrine. Between-treatment differences were also observed for glucose, amino acids, fatty acids, and lipids. We found significantly higher blood pressure, hormones, insulin resistance, and biomarkers of oxidative stress and inflammation among individuals exposed to higher PMs with aerodynamic diameters ≤2.5 μm. CONCLUSIONS:This study suggests that higher PM may induce metabolic alterations that are consistent with activations of the hypothalamus-pituitary-adrenal and sympathetic-adrenal-medullary axes, adding potential mechanistic insights into the adverse health outcomes associated with PM. Furthermore, our study demonstrated short-term reductions in stress hormone following indoor air purification. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT02712333.

BACKGROUND:Air pollution from road traffic is a serious health hazard, and people with preexisting respiratory disease may be at increased risk. We investigated the effects of short-term exposure to diesel traffic in people with asthma in an urban, roadside environment. METHODS:We recruited 60 adults with either mild or moderate asthma to participate in a randomized, crossover study. Each participant walked for 2 hours along a London street (Oxford Street) and, on a separate occasion, through a nearby park (Hyde Park). We performed detailed real-time exposure, physiological, and immunologic measurements. RESULTS:Participants had significantly higher exposures to fine particles (<2.5 microm in aerodynamic diameter), ultrafine particles, elemental carbon, and nitrogen dioxide on Oxford Street than in Hyde Park. Walking for 2 hours on Oxford Street induced asymptomatic but consistent reductions in the forced expiratory volume in 1 second (FEV1) (up to 6.1%) and forced vital capacity (FVC) (up to 5.4%) that were significantly larger than the reductions in FEV1 and FVC after exposure in Hyde Park (P=0.04 and P=0.01, respectively, for the overall effect of exposure, and P<0.005 at some time points). The effects were greater in subjects with moderate asthma than in those with mild asthma. These changes were accompanied by increases in biomarkers of neutrophilic inflammation (sputum myeloperoxidase, 4.24 ng per milliliter after exposure in Hyde Park vs. 24.5 ng per milliliter after exposure on Oxford Street; P=0.05) and airway acidification (maximum decrease in pH, 0.04% after exposure in Hyde Park and 1.9% after exposure on Oxford Street; P=0.003). The changes were associated most consistently with exposures to ultrafine particles and elemental carbon. CONCLUSIONS:Our observations serve as a demonstration and explanation of the epidemiologic evidence that associates the degree of traffic exposure with lung function in asthma.

RATIONALE:Acute respiratory effects of low-level ozone exposure are not well defined in older adults. OBJECTIVES:MOSES (The Multicenter Ozone Study in Older Subjects), although primarily focused on acute cardiovascular effects, provided an opportunity to assess respiratory responses to low concentrations of ozone in older healthy adults. METHODS:We performed a randomized crossover, controlled exposure study of 87 healthy adults (59.9 ± 4.5 yr old; 60% female) to 0, 70, and 120 ppb ozone for 3 hours with intermittent exercise. Outcome measures included spirometry, sputum markers of airway inflammation, and plasma club cell protein-16 (CC16), a marker of airway epithelial injury. The effects of ozone exposure on these outcomes were evaluated with mixed-effect linear models. A P value less than 0.01 was chosen a priori to define statistical significance. MEASUREMENTS AND MAIN RESULTS:The mean (95% confidence interval) FEV and FVC increased from preexposure values by 2.7% (2.0-3.4) and 2.1% (1.3-2.9), respectively, 15 minutes after exposure to filtered air (0 ppb). Exposure to ozone reduced these increases in a concentration-dependent manner. After 120-ppb exposure, FEV and FVC decreased by 1.7% (1.1-2.3) and 0.8% (0.3-1.3), respectively. A similar concentration-dependent pattern was still discernible 22 hours after exposure. At 4 hours after exposure, plasma CC16 increased from preexposure levels in an ozone concentration-dependent manner. Sputum neutrophils obtained 22 hours after exposure showed a marginally significant increase in a concentration-dependent manner (P = 0.012), but proinflammatory cytokines (IL-6, IL-8, and tumor necrosis factor-α) were not significantly affected. CONCLUSIONS:Exposure to ozone at near ambient levels induced lung function effects, airway injury, and airway inflammation in older healthy adults. Clinical trial registered with www.clinicaltrials.gov (NCT01487005).

Air pollution is responsible for the premature death of about 7 million people every year. Ozone (O) and nitrogen dioxide (NO) are the key gaseous pollutants in the troposphere, which predominantly result from combustion processes. Their inhalation leads to reactions with constituents in the airway surface fluids (ASF) of the respiratory tract and/or lungs. ASF contain small molecular-weight antioxidants, which protect the underlying epithelial cells against oxidative damage. When this defense system is overwhelmed, proteins and lipids present on cell surfaces or within the ASF become vulnerable to attack. The resulting highly reactive protein and lipid oxidation products could subsequently damage the epithelial cells through secondary reactions, thereby causing inflammation. While reactions of NO with biological molecules are considered to proceed through radical pathways, the biological effect of O is attributed to its high reactivity with π systems. Because O and NO always coexist in the polluted ambient atmosphere, synergistic effects resulting from in situ formed strongly oxidizing nitrate radicals (NO) may also require consideration. For example, in vitro product studies revealed that phenylalanine, which is inert not only to oxidants produced through biochemical processes, but also to NO or O in isolation, is damaged by NO. The reaction is initiated by oxidation of the aromatic ring and, depending on the availability of NO, leads to formation of nitrophenylalanine or β-nitrooxyphenylalanine, which could serve as marker for NO-induced oxidative damage in peptides. More easily oxidizable aromatic amino acids are directly attacked by NO and are converted to the same products independent of whether O is also present. Remarkably, NO-induced oxidative damage in peptides occurs not only through the well-established radical oxidation of peptide side chains, but also through an unprecedented fragmentation/rearrangement of the peptide backbone. This process is initiated by a nonradical N-nitrosation of a peptide bond involving the dimer of NO, i.e., NO, and contracts the peptide chain in the N → C direction by expelling one amino acid residue with simultaneous fusion of the remaining molecular termini, thereby forming a new peptide bond. This peptide cleavage could potentially be highly relevant for peptide segments with "nonvulnerable" side chains closer to the terminus that are not tied up in complex secondary and tertiary structures and therefore accessible for environmental oxidants. Likewise, NO reacts with cholesterol at the C═C moiety through an ionic mechanism, which leads to formation of 6-nitrocholesterol in the presence of moisture. Contrary to common belief, this clearly shows that ionic chemistry, in particular nitrosation reactions by intermediately formed NO, requires consideration when assessing NO toxicity. This conclusion is supported by recent work by Colussi et al. (Enami, S.; Hoffmann, M. R.; Colussi, A. J. Absorption of inhaled NO. J. Phys. Chem. B. 2009, 113, 7977-7981), who showed that anions in the airway surfaces fluids mediate NO absorption by catalyzing its hydrolytic disproportionation into NO/HNO and NO. These findings could be the key to our understanding why NO, despite its low water solubility, has such pronounced biological effects in vivo.

Asthma is an inflammatory disease of the airways, and exacerbations of this disease have been associated with high levels of air pollution. The objective of this study was to examine whether ambient air pollution and/or allergen exposure induces inflammatory changes in the upper airways of asthmatics. Sixty patients with intermittent to severe persistent asthma visited the Hospital's Out Patient Clinic every 2 wk for a period of 3 mo, and on each visit a nasal lavage was obtained. Associations between nasal inflammatory parameters and seasonal allergens and/or air pollution exposures were analyzed using linear regression analysis. The study ran from July 3 to October 6, 1995, during which period ozone (8-h mean: 80 micrograms/m3) and PM10 (24-h mean: 40 micrograms/m3) were the major air pollutants; the major aeroallergen was mugwort pollen (24-h mean: 27 pollen grains/m3). Effects on both cellular and soluble markers in nasal lavage were demonstrated for both ozone and mugwort pollen, but not for PM10. Ambient ozone exposure was associated with an increase in neutrophils (112% per 100 micrograms/m3 increase in 8-h average ozone concentration), eosinophils (176%), epithelial cells (55%), IL-8 (22%), and eosinophil cationic protein (ECP) (19%). Increases in environmental mugwort pollen counts were associated with an increase in nasal eosinophils (107% per 100 pollen/m3) and ECP (23%), but not with neutrophils, epithelial cells, or lL-8. This study demonstrated that both ambient ozone and allergen exposure are associated with inflammatory responses in the upper airways of subjects with asthma, although the type of inflammation is qualitatively different.

There is growing evidence that chronic obstructive pulmonary disease (COPD) can be caused and exacerbated by air pollution exposure. To document the impact of short-term air pollution exposure on inflammation markers, proteases, and antiproteases in the lower airways of older adults with and without COPD. Thirty participants (10 ex-smokers with mild to moderate COPD and 20 healthy participants [9 ex-smokers and 11 never-smokers]), with an average age of 60 years, completed this double-blinded, controlled, human crossover exposure study. Each participant was exposed to filtered air (control) and diesel exhaust (DE), in washout-separated 2-hour periods, in a randomly assigned order. Bronchoscopy was performed 24 hours after exposure to collect lavage. Cell counts were performed on blood and airway samples. ELISAs were performed to measure acute inflammatory proteins, matrix proteinases, and antiproteases in the airway and blood samples. In former smokers with COPD, but not in the other participants, exposure to DE increased serum amyloid A (effect estimate, 1.67; 95% confidence interval [CI], 1.21-2.30;  = 0.04) and matrix metalloproteinase 10 (effect estimate, 2.61; 95% CI, 1.38-4.91;  = 0.04) in BAL. Circulating lymphocytes were increased after DE exposure (0.14 [95% CI, 0.05-0.24] cells × 10/L;  = 0.03), irrespective of COPD status. A controlled human crossover study of DE exposure reveals that former smokers with COPD may be susceptible to an inflammatory response compared with ex-smokers without COPD or never-smoking healthy control participants. Clinical trial registered with www.clinicaltrials.gov (NCT02236039).

Low exposure to microbial products, respiratory viral infections and air pollution are major risk factors for allergic asthma, yet the mechanistic links between such conditions and host susceptibility to type 2 allergic disorders remain unclear. Through the use of single-cell RNA sequencing, we characterized lung neutrophils in mice exposed to a pro-allergic low dose of lipopolysaccharide (LPS) or a protective high dose of LPS before exposure to house dust mites. Unlike exposure to a high dose of LPS, exposure to a low dose of LPS instructed recruited neutrophils to upregulate their expression of the chemokine receptor CXCR4 and to release neutrophil extracellular traps. Low-dose LPS-induced neutrophils and neutrophil extracellular traps potentiated the uptake of house dust mites by CD11bLy-6C dendritic cells and type 2 allergic airway inflammation in response to house dust mites. Neutrophil extracellular traps derived from CXCR4 neutrophils were also needed to mediate allergic asthma triggered by infection with influenza virus or exposure to ozone. Our study indicates that apparently unrelated environmental risk factors can shape recruited lung neutrophils to promote the initiation of allergic asthma.