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: MESA (Multi-Ethnic Study of Atherosclerosis) 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) (2000-2002). Percentage emphysema, defined as percentage of lung pixels below -950 Hounsfield units, was assessed up to five times per participant via cardiac CT scan (2000-2007) and equivalent regions on lung CT scan (2010-2018). Long-term outdoor air pollutant concentrations (particulate matter with an aerodynamic diameter ⩽2.5 µm, oxides of nitrogen, and ozone) were estimated at the residential address with validated spatiotemporal 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. Measurements and Main Results: Among 6,793 participants (mean ± SD age, 62 ± 10 yr), baseline airway tree caliber was 3.95 ± 1.1 mm and median (interquartile range) of percentage emphysema was 2.88 (1.21-5.68). In adjusted analyses, 10-year emphysema progression rate was 0.75 percentage points (95% confidence interval, 0.54-0.96%) higher in the smallest compared with 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 the mechanisms of airway-alveolar homeostasis and air pollutant deposition is needed.

Estimating ambient air pollutant concentrations outside and inside homes in the Subpopulations and Intermediate outcomes in COPD air pollution (SPIROMICS air) cohort.

BACKGROUND: Valid, high-resolution estimates of population-level exposure to air pollutants are necessary for accurate estimation of the association between air pollution and the occurrence or exacerbation of adverse health outcomes such as Chronic Obstructive Pulmonary Disease (COPD). OBJECTIVES: We produced fine-scale individual-level estimates of ambient concentrations of multiple air pollutants (fine particulate matter [PM2.5], NOX, NO2, and O3) at residences of participants in the Subpopulations and Intermediate Outcomes in COPD Air Pollution (SPIROMICS Air) study, located in seven regions in the US. For PM2.5, we additionally integrated modeled estimates of particulate infiltration based on home characteristics and measured total indoor concentrations to provide comprehensive estimates of exposure levels. METHODS: To estimate ambient concentrations, we used a hierarchical high-resolution spatiotemporal model that integrates hundreds of geographic covariates and pollutant measurements from regulatory and study-specific monitors, including ones located at participant residences. We modeled infiltration efficiency based on data on house characteristics, home heating and cooling practices, indoor smoke and combustion sources, meteorological factors, and paired indoor-outdoor pollutant measurements, among other indicators. RESULTS: Cross-validated prediction accuracy (R2) for models of ambient concentrations was above 0.80 for most regions and pollutants. Particulate matter infiltration efficiency varied by region, from 0.51 in Winston-Salem to 0.72 in Los Angeles, and ambient-source particles constituted a substantial fraction of total indoor PM2.5. CONCLUSION: Leveraging well-validated fine-scale approaches for estimating outdoor, ambient-source indoor, and total indoor pollutant concentrations, we can provide comprehensive estimates of short and long-term exposure levels for cohorts undergoing follow-up in multiple different regions.

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.

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.

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.

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.

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.

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.

Idiopathic pulmonary fibrosis: unmasking cryptogenic environmental factors.

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease of unknown origin that is associated with high morbidity and mortality. In this perspective, we briefly review the current understanding of the pathophysiology of IPF and the importance of environmental triggers as a precipitant of disease. We discuss occult intrinsic and extrinsic environmental factors that affect the lung microenvironment and may contribute to the development and progression of disease. The clinical implications of this framework need to be further elucidated, because prompt identification and elimination of occult exposures may represent a novel treatment modality.

Ambient air pollution and pulmonary vascular volume on computed tomography: the MESA Air Pollution and Lung cohort studies.

BACKGROUND: Air pollution alters small pulmonary vessels in animal models. We hypothesised that long-term ambient air pollution exposure would be associated with differences in pulmonary vascular volumes in a population-based study. METHODS: The Multi-Ethnic Study of Atherosclerosis recruited adults in six US cities. Personalised long-term exposures to ambient black carbon, nitrogen dioxide (NO2), oxides of nitrogen (NO x ), particulate matter with a 50% cut-off aerodynamic diameter of <2.5 µm (PM2.5) and ozone were estimated using spatiotemporal models. In 2010-2012, total pulmonary vascular volume was measured as the volume of detectable pulmonary arteries and veins, including vessel walls and luminal blood volume, on noncontrast chest computed tomography (TPVVCT). Peripheral TPVVCT was limited to the peripheral 2 cm to isolate smaller vessels. Linear regression adjusted for demographics, anthropometrics, smoking, second-hand smoke, renal function and scanner manufacturer. RESULTS: The mean±sd age of the 3023 participants was 69.3±9.3 years; 46% were never-smokers. Mean exposures were 0.80 µg·m-3 black carbon, 14.6 ppb NO2 and 11.0 µg·m-3 ambient PM2.5. Mean±sd peripheral TPVVCT was 79.2±18.2 cm3 and TPVVCT was 129.3±35.1 cm3. Greater black carbon exposure was associated with a larger peripheral TPVVCT, including after adjustment for city (mean difference 0.41 (95% CI 0.03-0.79) cm3 per interquartile range; p=0.036). Associations for peripheral TPVVCT with NO2 were similar but nonsignificant after city adjustment, while those for PM2.5 were of similar magnitude but nonsignificant after full adjustment. There were no associations for NO x or ozone, or between any pollutant and TPVVCT. CONCLUSIONS: Long-term black carbon exposure was associated with a larger peripheral TPVVCT, suggesting diesel exhaust may contribute to remodelling of small pulmonary vessels in the general population.

Severe Silicosis in Engineered Stone Fabrication Workers - California, Colorado, Texas, and Washington, 2017-2019.

Silicosis is an incurable occupational lung disease caused by inhaling particles of respirable crystalline silica. These particles trigger inflammation and fibrosis in the lungs, leading to progressive, irreversible, and potentially disabling disease. Silica exposure is also associated with increased risk for lung infection (notably, tuberculosis), lung cancer, emphysema, autoimmune diseases, and kidney disease (1). Because quartz, a type of crystalline silica, is commonly found in stone, workers who cut, polish, or grind stone materials can be exposed to silica dust. Recently, silicosis outbreaks have been reported in several countries among workers who cut and finish stone slabs for countertops, a process known as stone fabrication (2-5). Most worked with engineered stone, a manufactured, quartz-based composite material that can contain >90% crystalline silica (6). This report describes 18 cases of silicosis, including the first two fatalities reported in the United States, among workers in the stone fabrication industry in California, Colorado, Texas, and Washington. Several patients had severe progressive disease, and some had associated autoimmune diseases and latent tuberculosis infection. Cases were identified through independent investigations in each state and confirmed based on computed tomography (CT) scan of the chest or lung biopsy findings. Silica dust exposure reduction and effective regulatory enforcement, along with enhanced workplace medical and public health surveillance, are urgently needed to address the emerging public health threat of silicosis in the stone fabrication industry.

Occupational Exposures and Subclinical Interstitial Lung Disease. The MESA (Multi-Ethnic Study of Atherosclerosis) Air and Lung Studies.

RATIONALE: The impact of a broad range of occupational exposures on subclinical interstitial lung disease (ILD) has not been studied. OBJECTIVES: To determine whether occupational exposures to vapors, gas, dust, and fumes (VGDF) are associated with high-attenuation areas (HAA) and interstitial lung abnormalities (ILA), which are quantitative and qualitative computed tomography (CT)-based measurements of subclinical ILD, respectively. METHODS: We performed analyses of participants enrolled in MESA (Multi-Ethnic Study of Atherosclerosis), a population-based cohort aged 45-84 years at recruitment. HAA was measured at baseline and on serial cardiac CT scans in 5,702 participants. ILA was ascertained in a subset of 2,312 participants who underwent full-lung CT scanning at 10-year follow-up. Occupational exposures were assessed by self-reported VGDF exposure and by job-exposure matrix (JEM). Linear mixed models and logistic regression were used to determine whether occupational exposures were associated with log-transformed HAA and ILA. Models were adjusted for age, sex, race/ethnicity, education, employment status, tobacco use, and scanner technology. MEASUREMENTS AND MAIN RESULTS: Each JEM score increment in VGDF exposure was associated with 2.64% greater HAA (95% confidence interval [CI], 1.23-4.19%). Self-reported vapors/gas exposure was associated with an increased odds of ILA among those currently employed (1.76-fold; 95% CI, 1.09-2.84) and those less than 65 years old (1.97-fold; 95% CI, 1.16-3.35). There was no consistent evidence that occupational exposures were associated with progression of HAA over the follow-up period. CONCLUSIONS: JEM-assigned and self-reported exposures to VGDF were associated with measurements of subclinical ILD in community-dwelling adults.

Air pollution and subclinical interstitial lung disease: the Multi-Ethnic Study of Atherosclerosis (MESA) air-lung study.

We studied whether ambient air pollution is associated with interstitial lung abnormalities (ILAs) and high attenuation areas (HAAs), which are qualitative and quantitative measurements of subclinical interstitial lung disease (ILD) on computed tomography (CT).We performed analyses of community-based dwellers enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA) study. We used cohort-specific spatio-temporal models to estimate ambient pollution (fine particulate matter (PM2.5), nitrogen oxides (NOx), nitrogen dioxide (NO2) and ozone (O3)) at each home. A total of 5495 participants underwent serial assessment of HAAs by cardiac CT; 2671 participants were assessed for ILAs using full lung CT at the 10-year follow-up. We used multivariable logistic regression and linear mixed models adjusted for age, sex, ethnicity, education, tobacco use, scanner technology and study site.The odds of ILAs increased 1.77-fold per 40 ppb increment in NOx (95% CI 1.06 to 2.95, p = 0.03). There was an overall trend towards an association between higher exposure to NOx and greater progression of HAAs (0.45% annual increase in HAAs per 40 ppb increment in NOx; 95% CI -0.02 to 0.92, p = 0.06). Associations of ambient fine particulate matter (PM2.5), NOx and NO2 concentrations with progression of HAAs varied by race/ethnicity (p = 0.002, 0.007, 0.04, respectively, for interaction) and were strongest among non-Hispanic white people.We conclude that ambient air pollution exposures were associated with subclinical ILD.

Cystic Fibrosis is Associated with Adverse Neonatal Outcomes in Washington State, 1996-2013.

OBJECTIVE: To determine whether cystic fibrosis (CF) is associated with adverse neonatal outcomes in a recent birth cohort in the US. STUDY DESIGN: A retrospective matched cohort study of infants born in Washington State from 1996 to 2013 was identified through birth certificate data and linked to statewide hospital discharge data. Infants with CF were identified by hospitalization (through age 5 years) in which a CF-specific International Classification of Diseases, Ninth Revision code was recorded. "Unexposed" infants lacked CF-related International Classification of Diseases, Ninth Revision codes and were randomly selected among births, frequency-matched to "exposed" infants on birth year. Associations of CF with adverse neonatal outcomes (low birth weight [LBW], small for gestational age [SGA], preterm birth, and infant mortality) were estimated through Poisson regression. We performed extreme value imputation to address possible ascertainment bias. RESULTS: We identified 170 infants with CF and 3400 unexposed infants. CF was associated with increased relative risk (95% CI) of 3.5 (2.5-4.9), 1.6 (1.1-2.4), 3.0 (2.2-4.0), and 6.8 (1.7-26.5) for LBW, SGA, preterm birth, and infant death, respectively. The estimated relative risks were similar among infants born from 2006 to 2013, except SGA was no longer associated with CF diagnosis. Results were robust to extreme value imputation and exclusion of infants with meconium ileus. CONCLUSIONS: Observed associations of CF with LBW, preterm birth, and infant death are unlikely to be due to ascertainment bias. Further work is needed to determine how to prevent these adverse neonatal outcomes.

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.