Air Pollution Exposure and Interstitial Lung Features in SPIROMICS Participants with COPD.

RATIONALE: It is unknown whether air pollution is associated with radiographic features of interstitial lung disease in individuals with chronic obstructive pulmonary disease (COPD). OBJECTIVES: To determine whether air pollution increases prevalence of interstitial lung abnormalities (ILA) or percent high-attenuation area (HAA) on computed tomography (CT) in individuals with a heavy smoking history and COPD. METHODS: We performed a cross-sectional study of SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study), focused on current or former smokers with COPD. 10-year exposure to particulate matter < 2.5 µm (PM2.5), nitrogen oxides (NOx), nitrogen dioxide (NO2), and ozone (O3) prior to enrollment CTs (completed between 2010-2015) were estimated with validated spatiotemporal models at residential addresses. We applied adjusted multivariable modified Poisson regression and linear regression to investigate associations between pollution exposure and relative risk of ILA or increased percent HAA (between -600 and -250 Hounsfield units) respectively. We assessed for effect modification by MUC5B-promoter polymorphism (GT/TT vs GG at rs3705950), smoking status, sex, and percent emphysema. RESULTS: Among 1272 participants with COPD assessed for HAA, 424 were current smokers, 249 were carriers of the variant MUC5B allele (GT/TT). 519 participants were assessed for ILA. We found no association between pollution exposure and ILA or HAA. Associations between pollutant exposures and risk of ILA were modified by the presence of MUC5B polymorphism (p-value interaction term for NOx = 0.04 and PM2.5 = 0.05) and smoking status (p-value interaction term for NOx = 0.05, NO2 = 0.01, and O3 = 0.05). With higher exposure to NOx and PM2.5, MUC5B variant carriers had increased risk of ILA (Relative Risk [RR] per 26ppb NOx 2.41; 95% Confidence Interval [CI] 0.97 to 6.0) and RR per 4 µg·m-3 PM2.5 1.43; 95% CI 0.93 to 2.2). With higher exposure to NO2, former smokers had increased risk of ILA (RR per 10ppb 1.64; 95% CI 1.0 to 2.7). CONCLUSIONS: Exposure to ambient air pollution was not associated with interstitial features on CT in this population of heavy smokers with COPD. MUC5B modified the association between pollution and ILA, suggesting that gene-environment interactions may influence prevalence of interstitial lung features in COPD.

Airway tree caliber heterogeneity and airflow obstruction among older adults.

Smaller mean airway tree caliber is associated with airflow obstruction and chronic obstructive pulmonary disease (COPD). We investigated whether airway tree caliber heterogeneity was associated with airflow obstruction and COPD. Two community-based cohorts (MESA Lung, CanCOLD) and a longitudinal case-control study of COPD (SPIROMICS) performed spirometry and computed tomography measurements of airway lumen diameters at standard anatomical locations (trachea-to-subsegments) and total lung volume. Percent-predicted airway lumen diameters were calculated using sex-specific reference equations accounting for age, height, and lung volume. The association of airway tree caliber heterogeneity, quantified as the standard deviation (SD) of percent-predicted airway lumen diameters, with baseline forced expired volume in 1-second (FEV1), FEV1/forced vital capacity (FEV1/FVC) and COPD, as well as longitudinal spirometry, were assessed using regression models adjusted for age, sex, height, race-ethnicity, and mean airway tree caliber. Among 2,505 MESA Lung participants (means ± SD age: 69 ± 9 yr; 53% female, mean airway tree caliber: 99 ± 10% predicted, airway tree caliber heterogeneity: 14 ± 5%; median follow-up: 6.1 yr), participants in the highest quartile of airway tree caliber heterogeneity exhibited lower FEV1 (adjusted mean difference: -125 mL, 95%CI: -171,-79), lower FEV1/FVC (adjusted mean difference: -0.01, 95%CI: -0.02,-0.01), and higher odds of COPD (adjusted odds ratio: 1.42, 95%CI: 1.01-2.02) when compared with the lowest quartile, whereas longitudinal changes in FEV1 and FEV1/FVC did not differ significantly. Observations in CanCOLD and SPIROMICS were consistent. Among older adults, airway tree caliber heterogeneity was associated with airflow obstruction and COPD at baseline but was not associated with longitudinal changes in spirometry.NEW & NOTEWORTHY In this study, by leveraging two community-based samples and a case-control study of heavy smokers, we show that among older adults, airway tree caliber heterogeneity quantified by CT is associated with airflow obstruction and COPD independent of age, sex, height, race-ethnicity, and dysanapsis. These observations suggest that airway tree caliber heterogeneity is a structural trait associated with low baseline lung function and normal decline trajectory that is relevant to COPD.

Airway Tree Caliber and Susceptibility to Pollution-associated Emphysema: MESA Air and Lung Studies.

RATIONALE: Airway tree morphology varies in the general population and may modify the distribution and uptake of inhaled pollutants. OBJECTIVES: We hypothesized that smaller airway caliber would be associated with emphysema progression and would increase susceptibility to air pollutant-associated emphysema progression. METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) is a general population cohort of adults 45-84 years old from six U.S. communities. Airway tree caliber was quantified as the mean of airway lumen diameters measured from baseline cardiac computed tomography (CT) (2000-02). Percent emphysema, defined as percentage of lung pixels below -950 Hounsfield units, was assessed up to 5 times per participant via cardiac CT scan (2000-07) and equivalent regions on lung CT scan (2010-18). Long-term outdoor air pollutant concentrations (PM2.5, NOx, O3) were estimated at residential address with validated spatio-temporal models. Linear mixed models estimated the association between airway tree caliber and emphysema progression; modification of pollutant-associated emphysema progression was assessed using multiplicative interaction terms. MAIN RESULTS: Among 6,793 participants (mean±SD age: 62±10 years), baseline airway tree caliber was 3.95±1.1 mm and median (interquartile range) of percent emphysema was 2.88 (1.21-5.68). In adjusted analyses, 10-year emphysema progression rate was 0.75 percentage points (95%CI 0.54-0.96%) higher in the smallest compared to largest airway tree caliber quartile. Airway tree caliber also modified air pollutant-associated emphysema progression. CONCLUSIONS: Smaller airway tree caliber was associated with accelerated emphysema progression and modified air pollutant-associated emphysema progression. A better understanding of mechanisms of airway-alveolar homeostasis and air pollutant deposition are needed.

Blood Pressure Effect of Traffic-Related Air Pollution : A Crossover Trial of In-Vehicle Filtration.

BACKGROUND: Ambient air pollution, including traffic-related air pollution (TRAP), increases cardiovascular disease risk, possibly through vascular alterations. Limited information exists about in-vehicle TRAP exposure and vascular changes. OBJECTIVE: To determine via particle filtration the effect of on-roadway TRAP exposure on blood pressure and retinal vasculature. DESIGN: Randomized crossover trial. (ClinicalTrials.gov: NCT05454930). SETTING: In-vehicle scripted commutes driven through traffic in Seattle, Washington, during 2014 to 2016. PARTICIPANTS: Normotensive persons aged 22 to 45 years (n = 16). INTERVENTION: On 2 days, on-road air was entrained into the vehicle. On another day, the vehicle was equipped with high-efficiency particulate air (HEPA) filtration. Participants were blinded to the exposure and were randomly assigned to the sequence. MEASUREMENTS: Fourteen 3-minute periods of blood pressure were recorded before, during, and up to 24 hours after a drive. Image-based central retinal arteriolar equivalents (CRAEs) were measured before and after. Brachial artery diameter and gene expression were also measured and will be reported separately. RESULTS: Mean age was 29.7 years, predrive systolic blood pressure was 122.7 mm Hg, predrive diastolic blood pressure was 70.8 mm Hg, and drive duration was 122.3 minutes (IQR, 4 minutes). Filtration reduced particle count by 86%. Among persons with complete data (n = 13), at 1 hour, mean diastolic blood pressure, adjusted for predrive levels, order, and carryover, was 4.7 mm Hg higher (95% CI, 0.9 to 8.4 mm Hg) for unfiltered drives compared with filtered drives, and mean adjusted systolic blood pressure was 4.5 mm Hg higher (CI, -1.2 to 10.2 mm Hg). At 24 hours, adjusted mean diastolic blood pressure (unfiltered) was 3.8 mm Hg higher (CI, 0.02 to 7.5 mm Hg) and adjusted mean systolic blood pressure was 1.1 mm Hg higher (CI, -4.6 to 6.8 mm Hg). Adjusted mean CRAE (unfiltered) was 2.7 µm wider (CI, -1.5 to 6.8 µm). LIMITATIONS: Imprecise estimates due to small sample size; seasonal imbalance by exposure order. CONCLUSION: Filtration of TRAP may mitigate its adverse effects on blood pressure rapidly and at 24 hours. Validation is required in larger samples and different settings. PRIMARY FUNDING SOURCE: U.S. Environmental Protection Agency and National Institutes of Health.

Indoor Pollution and Lung Function Decline in Current and Former Smokers: SPIROMICS AIR.

Rationale: Indoor pollutants have been associated with chronic obstructive pulmonary disease morbidity, but it is unclear whether they contribute to disease progression. Objectives: We aimed to determine whether indoor particulate matter (PM) and nitrogen dioxide (NO2) are associated with lung function decline among current and former smokers. Methods: Of the 2,382 subjects with a history of smoking in SPIROMICS AIR, 1,208 participants had complete information to estimate indoor PM and NO2, using individual-based prediction models, in relation to measured spirometry at two or more clinic visits. We used a three-way interaction model between time, pollutant, and smoking status and assessed the indoor pollutant-associated difference in FEV1 decline separately using a generalized linear mixed model. Measurements and Main Results: Participants had an average rate of FEV1 decline of 60.3 ml/yr for those currently smoking compared with 35.2 ml/yr for those who quit. The association of indoor PM with FEV1 decline differed by smoking status. Among former smokers, every 10 µg/m3 increase in estimated indoor PM was associated with an additional 10 ml/yr decline in FEV1 (P = 0.044). Among current smokers, FEV1 decline did not differ by indoor PM. The results of indoor NO2 suggest trends similar to those for PM ⩽2.5 µm in aerodynamic diameter. Conclusions: Former smokers with chronic obstructive pulmonary disease who live in homes with high estimated PM have accelerated lung function loss, and those in homes with low PM have lung function loss similar to normal aging. In-home PM exposure may contribute to variability in lung function decline in people who quit smoking and may be a modifiable exposure.

Associations Between Insurance, Race and Ethnicity, and COVID-19 Hospitalization, Beyond Underlying Health Conditions: A Retrospective Cohort Study.

Introduction: : People of lower socioeconomic position (SEP) and people of color (POC) experience higher risks of severe COVID-19, but understanding of these associations beyond the effect of underlying health conditions (UHCs) is limited. Moreover, few studies have focused on young adults, who have had the highest incidence of COVID-19 during much of the pandemic. Methods: : We conducted a retrospective cohort study using electronic health record data from the University of Washington Medicine healthcare system. Our study population included individuals aged 18-39 years who tested positive for SARS-CoV-2 from February 2020 to March 2021. Using regression modeling, we estimated adjusted risk ratios (aRRs) and differences (aRDs) of COVID-19 hospitalization by SEP (using health insurance as a proxy) and race and ethnicity. We adjusted for any UHC to examine these associations beyond the effect of UHCs. Results: Among 3,101 individuals, the uninsured/publicly insured had a 1.9-fold higher risk of hospitalization (aRR [95% CI]=1.9 [1.0, 3.6]) and 9 additional hospitalizations per 1,000 SARS-CoV-2 positive persons (aRD [95% CI]=9 [-1, 20]) compared to the privately insured. Hispanic or Latine, non-Hispanic (NH) Asian, NH Black, and NH Native Hawaiian or Pacific Islander patients had a 1.5-, 2.7-, 1.4-, and 2.1-fold-higher risk of hospitalization (aRR [95% CI]=1.5 [0.7, 3.1]; 2.7 [1.1, 6.5]; 1.4 [0.6, 3.3]; 2.1 [0.5, 9.1]), respectively, compared to NH White patients. Conclusions: Though they should be interpreted with caution given low precision, our findings suggest the increased risk of COVID-19 hospitalization among young adults of lower SEP and young adults of color may be driven by forces other than UHCs, including social determinants of health.

The Emerging Spectrum of Respiratory Diseases in the U.S. Cannabis Industry.

While the cannabis industry is one of the fastest growing job markets in the United States and globally, relatively little is known about the occupational hazards that cannabis production workers face. Based on the closely related hemp industry and preliminary studies from recreational cannabis grow facilities, there is concern for significant respiratory exposures to bioaerosols containing microbial and plant allergens, chemicals such as pesticides, volatile organic compounds, and other irritant gases. Components of the cannabis plant have also recently been identified as allergenic and capable of inducing an immunoglobulin E-mediated response. Accumulating evidence indicates a spectrum of work-related respiratory diseases, particularly asthma and other allergic diseases. Disentangling causal relationships is difficult given the heterogeneity of mixed exposures, diagnostic challenges, and confounding by personal cannabis use. Despite and because of these uncertainties, better regulatory guidance and exposure controls need to be defined in order to reduce the risk of work-related disease.

Association between any underlying health condition and COVID-19-associated hospitalization by age group, Washington State, 2020-2021: a retrospective cohort study.

BACKGROUND: Presence of at least one underlying health condition (UHC) is positively associated with severe COVID-19, but there is limited research examining this association by age group, particularly among young adults. METHODS: We examined age-stratified associations between any UHC and COVID-19-associated hospitalization using a retrospective cohort study of electronic health record data from the University of Washington Medicine healthcare system for adult patients with a positive SARS-CoV-2 test from February 29, 2020, to March 13, 2021. Any UHC was defined as documented diagnosis of at least one UHC identified by the CDC as a potential risk factor for severe COVID-19. Adjusting for sex, age, race and ethnicity, and health insurance, we estimated risk ratios (aRRs) and risk differences (aRDs), overall and by age group (18-39, 40-64, and 65 + years). RESULTS: Among patients aged 18-39 (N = 3,249), 40-64 (N = 2,840), 65 + years (N = 1,363), and overall (N = 7,452), 57.5%, 79.4%, 89.4%, and 71.7% had at least one UHC, respectively. Overall, 4.4% of patients experienced COVID-19-associated hospitalization. For all age groups, the risk of COVID-19-associated hospitalization was greater for patients with any UHC vs. those without (18-39: 2.2% vs. 0.4%; 40-64: 5.6% vs. 0.3%; 65 + : 12.2% vs. 2.8%; overall: 5.9% vs. 0.6%). The aRR comparing patients with vs. those without UHCs was notably higher for patients aged 40-64 years (aRR [95% CI] for 18-39: 4.3 [1.8, 10.0]; 40-64: 12.9 [3.2, 52.5]; 65 + : 3.1 [1.2, 8.2]; overall: 5.3 [3.0, 9.6]). The aRDs increased across age groups (aRD [95% CI] per 1,000 SARS-CoV-2-positive persons for 18-39: 10 [2, 18]; 40-64: 43 [33, 54]; 65 + : 84 [51, 116]; overall: 28 [21, 35]). CONCLUSIONS: Individuals with UHCs are at significantly increased risk of COVID-19-associated hospitalization regardless of age. Our findings support the prevention of severe COVID-19 in adults with UHCs in all age groups and in older adults aged 65 + years as ongoing local public health priorities.

A Cross Sectional Study of Respiratory and Allergy Status in Dairy Workers.

INTRODUCTION: Workers on dairy farms face exposures to organic dusts and endotoxin. At the same time, a number of studies of farmers have reported a lower prevalence of asthma in farmworkers compared to persons without farm contact. The "hygiene hypothesis" suggests that early life exposures on farms could be protective against allergic disease and asthma. Such protective relationships are less well studied in adult farm workers. METHODS: A cross-sectional analysis of respiratory function and allergy status was performed in a sample of dairy farm workers (n = 42) and community controls (n = 40). Measures of respiratory status (spirometry, exhaled nitric oxide FeNO, self-reported symptoms) and levels of total and bovine-specific IgE were compared between the groups. RESULTS: Prevalence of self-reported asthma and most respiratory symptoms was similar in the two groups, with the exception of increased report of dyspnea among dairy workers. In the dairy workers, level of lung function was not reduced and FeNO was not increased. In unadjusted and adjusted models, dairy work was not associated with reduced lung function or increased airway inflammation. Mean IgE levels did not differ significantly between workers and controls, but elevated bovine-specific IgE was detected only among dairy workers, with an apparent association between elevated bovine IgE and increased FeNO. CONCLUSION: While dairy workers did not demonstrate increased asthma prevalence compared to controls, sensitization to bovine antigen in several workers appeared to be associated with airway inflammation. Occupational health programs for dairy workers should consider the risk of animal allergy as part of respiratory health protection efforts.

Ambient Air Pollution and Stroke: An Updated Review.

Despite recent advances in treatment and prevention, stroke remains a leading cause of morbidity and mortality. There is a critical need to identify novel modifiable risk factors for disease, including environmental agents. A body of evidence has accumulated suggesting that elevated levels of ambient air pollutants may not only trigger cerebrovascular events in susceptible people (short-term exposures) but also increase the risk of future events (long-term average exposures). This review assesses the updated evidence for both short and long-term exposure to ambient air pollution as a risk factor for stroke incidence and outcomes. It discusses the potential pathophysiologic mechanisms and makes recommendations to mitigate exposure on a personal and community level. The evidence indicates that reduction in air pollutant concentrations represent a significant population-level opportunity to reduce risk of cerebrovascular disease.

Successful Treatment of Prolonged, Severe Coronavirus Disease 2019 Lower Respiratory Tract Disease in a B cell Acute Lymphoblastic Leukemia Patient With an Extended Course of Remdesivir and Nirmatrelvir/Ritonavir.

A patient with B-cell acute lymphoblastic leukemia (ALL) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had persistent, progressive pneumonia with viremia after 5 months of infection despite monoclonal antibodies, intravenous (IV) remdesivir and prolonged oral steroids. Twenty days of nirmatrelvir/ritonavir and 10 days of IV remdesivir led to full recovery.

Black carbon content in airway macrophages is associated with increased severe exacerbations and worse COPD morbidity in SPIROMICS.

BACKGROUND: Airway macrophages (AM), crucial for the immune response in chronic obstructive pulmonary disease (COPD), are exposed to environmental particulate matter (PM), which they retain in their cytoplasm as black carbon (BC). However, whether AM BC accurately reflects environmental PM2.5 exposure, and can serve as a biomarker of COPD outcomes, is unknown. METHODS: We analyzed induced sputum from participants at 7 of 12 sites SPIROMICS sites for AM BC content, which we related to exposures and to lung function and respiratory outcomes. Models were adjusted for batch (first vs. second), age, race (white vs. non-white), income (<$35,000, $35,000~$74,999, ≥$75,000, decline to answer), BMI, and use of long-acting beta-agonist/long-acting muscarinic antagonists, with sensitivity analysis performed with inclusion of urinary cotinine and lung function as covariates. RESULTS: Of 324 participants, 143 were current smokers and 201 had spirometric-confirmed COPD. Modeled indoor fine (< 2.5 µm in aerodynamic diameter) particulate matter (PM2.5) and urinary cotinine were associated with higher AM BC. Other assessed indoor and ambient pollutant exposures were not associated with higher AM BC. Higher AM BC was associated with worse lung function and odds of severe exacerbation, as well as worse functional status, respiratory symptoms and quality of life. CONCLUSION: Indoor PM2.5 and cigarette smoke exposure may lead to increased AM BC deposition. Black carbon content in AMs is associated with worse COPD morbidity in current and former smokers, which remained after sensitivity analysis adjusting for cigarette smoke burden. Airway macrophage BC, which may alter macrophage function, could serve as a predictor of experiencing worse respiratory symptoms and impaired lung function.

Demographic, exposure and clinical characteristics in a multinational registry of engineered stone workers with silicosis.

OBJECTIVES: To investigate differences in workplace exposure, demographic and clinical findings in engineered stone (ES) workers from a multinational consortium using the Engineered Stone Silicosis Investigators (ESSI) Global Silicosis Registry. METHODS: With ethics board approval in Israel, Spain, Australia and the USA, ES workers ages 18+ with a physician diagnosis of work-related silicosis were enrolled. Demographic, occupational, radiologic, pulmonary function and silica-related comorbidity data were compared cross-sectionally among countries using analysis of variance, Fisher's exact tests and logistic regression. RESULTS: Among 169 ES workers with silicosis, most were men, with mean age 51.7 (±11.4) years. Mean work tenure in stone fabrication or masonry was 19.9 (±9.8) years. Different methods of case ascertainment explained some inter-country differences, for example, workers in Queensland, Australia with a state-based surveillance program were likely to be identified earlier and with shorter work tenure. Overall, 32.5% of workers had progressive massive fibrosis, the most severe form of dust-related pneumoconiosis, of whom 18.5% reported ≤10 years of work tenure. Lung function impairment including restriction, reduced diffusion capacity and hypoxaemia was common, as was autoimmunity. CONCLUSIONS: Findings from a multinational registry represent a unique effort to compare demographic, exposure and clinical information from ES workers with silicosis, and suggest a substantial emerging population of workers worldwide with severe and irreversible silica-associated diseases. This younger worker population is at high risk for disease progression, multiple comorbidities and severe disability. The ESSI registry provides an ongoing framework for investigating epidemiological trends and developing prospective studies for prevention and treatment of these workers.

Environmental Cadmium and Mortality from Influenza and Pneumonia in U.S. Adults.

BACKGROUND: Environmental cadmium exposure is widespread. In humans, cadmium is poorly excreted, triggers pulmonary inflammation, reduces pulmonary function, and enhances lung injury by respiratory syncytial virus. OBJECTIVES: We examined the association of cadmium burden with mortality related to influenza or pneumonia. METHODS: This prospective analysis of the National Health and Nutrition Examination Survey (NHANES) included 7,173 and 8,678 participants ≥45 years of age enrolled in NHANES-III and NHANES 1999-2006, respectively. Associations were evaluated between cadmium and mortality from influenza or pneumonia during a median follow-up of 17.3 y (NHANES-III, based on creatinine-corrected urine cadmium) and 11.4 y (NHANES 1999-2006, based on blood cadmium). Survey-weighted Cox proportional hazard models were used to compute hazard ratios (HRs) comparing the mortality of individuals at the 80th vs. the 20th percentile of cadmium concentrations. RESULTS: In NHANES-III, after adjustment for sex, race/ethnicity, education, body mass index, serum cholesterol, hypertension, and NHANES phase (or cycle), the HR comparing influenza or pneumonia mortality among participants with creatinine-corrected urinary cadmium in the 80th vs. 20th percentile was 1.15 (95% CI: 1.05, 1.26; p=0.002) in the population as a whole and 1.27 (95% CI: 1.12, 1.43; p=0.002) among never smokers. In NHANES 1999-2006, adjusted HRs for the 80th vs. 20th percentile of blood cadmium were 1.14 (95% CI: 0.96, 1.36; p=0.15) for the overall population and 1.71 (95% CI: 0.95, 3.09; p=0.07) in never smokers. DISCUSSION: Among middle-aged and older adults in the United States, higher cadmium burdens are associated with higher mortality from influenza or pneumonia. This raises the possibility that cadmium may worsen outcomes from COVID-19 infections. https://doi.org/10.1289/EHP7598.

Exposure Assessment Tools for Hypersensitivity Pneumonitis. An Official American Thoracic Society Workshop Report.

This report is based on proceedings from the Exposure Assessment Tools for Hypersensitivity Pneumonitis (HP) Workshop, sponsored by the American Thoracic Society, that took place on May 18, 2019, in Dallas, Texas. The workshop was initiated by members from the Environmental, Occupational, and Population Health and Clinical Problems Assemblies of the American Thoracic Society. Participants included international experts from pulmonary medicine, occupational medicine, radiology, pathology, and exposure science. The meeting objectives were to 1) define currently available tools for exposure assessment in evaluation of HP, 2) describe the evidence base supporting the role for these exposure assessment tools in HP evaluation, 3) identify limitations and barriers to each tool's implementation in clinical practice, 4) determine which exposure assessment tools demonstrate the best performance characteristics and applicability, and 5) identify research needs for improving exposure assessment tools for HP. Specific discussion topics included history-taking and exposure questionnaires, antigen avoidance, environmental assessment, specific inhalational challenge, serum-specific IgG testing, skin testing, lymphocyte proliferation testing, and a multidisciplinary team approach. Priorities for research in this area were identified.