Background: Individuals with chronic obstructive pulmonary disease (COPD) are disproportionately affected by social determinants of health that have been associated with worse respiratory outcomes. This study evaluates the association of perceived stress with respiratory outcomes and distinct biological mechanisms among former smokers with COPD. Methods: Participants were assessed in an observational study at baseline, 3-months, and 6-months. Questionnaires assessed perceived stress (Perceived Stress Scale, [PSS]), respiratory symptoms, and incidence of COPD exacerbations. Generalized linear mixed models evaluated the association of PSS score with COPD outcomes and biomarkers of platelet activation (urine 11-dehydro-thromboxane B2 [11dTxB2]), oxidative stress (urine thiobarbituric acid reactive substances [TBARS], 8-hydroxydeoxyguanosine, and 8-isoprostane), and inflammation. Results: Among 99 participants, the median PSS score was 13 (interquartile range 8-18) across all visits. Compared with low perceived stress (PSS 0-13), moderate (PSS 14-26) and high perceived stress (PSS 27-40) were associated with worse respiratory health status and respiratory-related quality of life, with point estimates for high perceived stress exceeding clinically important differences. Only high PSS was associated with increased moderate/severe exacerbations (odds ratio 4.15, 95% confidence interval [CI]: 1.28-13.47). Compared to low stress, high stress was associated with lower TBARS ((i=-25.5%, 95%CI:-43.8--1.2%) and higher 8-isoprostane ((i=40.1%, 95%CI: 11.5-76.0%). Among individuals with mild-moderate COPD, compared to low stress, moderate ((i=20.1%, 95%CI: 3.1-40.0%) and high ((i=52.9%, 95%CI: 22.1-91.6%) stress were associated with higher 11dTxB2. Conclusion: Among former smokers with COPD, higher perceived stress is associated with worse respiratory outcomes. Platelet activation and oxidative stress may be biological pathways through which perceived stress plays a role in COPD.

ABSTRACT Treatment outcomes for Mycobacteroides abscessus ( Mab , also known as Mycobacterium abscessus ) disease are still unsatisfactory, mainly due to issues with drug toxicity, tolerability, and efficacy. Treating Mab disease is challenging due to its high baseline antibiotic resistance, initial requirement for intravenous therapy, and poor medication tolerance. Omadacycline, a new tetracycline, is active against Mab . Since any new antibiotic effective against Mab is expected to be used in combination with other antibiotics, we evaluated the efficacy of two triple-drug combinations comprising omadacycline, omadacycline + amikacin + imipenem, and omadacycline + clofazimine + linezolid against two contemporary Mab clinical isolates in a mouse model of Mab lung disease. Antibiotic administration was initiated 1-week post-infection and was given daily, with Mab burden in the lungs at treatment completion serving as the endpoint. Omadacycline alone moderately reduced Mab levels and maintained better health in mice compared to untreated ones, which typically suffered from the infection. The omadacycline + clofazimine + linezolid combination showed immediate bactericidal activity and enhanced efficacy over 6 weeks, particularly against the more resistant strain (M9507). However, the clofazimine + linezolid combination lacked early bactericidal activity. When combined with amikacin and imipenem, omadacycline did not improve the regimen’s effectiveness over 4 weeks of treatment. Our study showed that omadacycline + clofazimine + linezolid exhibited significant bactericidal activity over an extended treatment duration. However, adding omadacycline to amikacin and imipenem did not improve regimen effectiveness against the evaluated clinical isolates within 4 weeks. Further research in Mab disease patients is needed to determine the most effective omadacycline-containing regimen. IMPORTANCE Mycobacteroides abscessus is a common environmental bacterium that causes infections in people with compromised lung function, including those with bronchiectasis, cystic fibrosis, chronic obstructive pulmonary disease, and weakened immune systems, especially among older individuals. Treating M. abscessus disease is challenging due to the limited effectiveness and toxicity of current antibiotics, which often require prolonged use. Omadacycline, a new antibiotic, shows promise against M. abscessus . Using a mouse model that mimics M. abscessus disease in humans, we studied the effectiveness of including omadacycline with recommended antibiotics. Adding omadacycline to clofazimine and linezolid significantly improved treatment outcomes, rapidly clearing the bacteria from the lungs and maintaining effectiveness throughout. This oral combination is convenient for patients. However, adding omadacycline to amikacin and imipenem did not improve treatment effectiveness within 4 weeks. Further study with M. abscessus patients is necessary to optimize omadacycline-based treatment strategies for this disease.

Abstract Background Anemia is a prevalent comorbidity in COPD associated with increased morbidity. However, the significance of longitudinal anemia status and variation in anemia status trends over time in COPD are not known. Furthermore, individuals with COPD and smoking history often have multiple comorbidities, in particular cardiovascular disease. The objective of this study was to evaluate the association between longitudinal anemia status and COPD outcomes, accounting for comorbid cardiovascular disease. Methods Serial hemoglobin measures and clinical outcomes were obtained in former smokers with moderate to severe COPD from two clinical studies over a 6-to-9-month period. In the first analysis, the association between repeated measures of time-varying anemia status and outcomes was assessed by generalized estimating equations adjusted for covariates including cardiovascular disease. In the second analysis, each participant’s anemia risk profile during the study period was characterized as high versus low anemia risk-growth rate. Mean differences in the progression of COPD outcomes over time between the two groups were assessed using a generalized linear mixed model. Effect modification by baseline coronary artery calcium (CAC) burden was explored. Results There were 159 individuals with mean age of 66.5 years (± 8.3) and mean FEV1% predicted of 51.4% (± 17.0), of which 41% were ever-anemic during the study period. Repeated measures of anemia status were associated with higher St. George’s Respiratory Questionnaire (SGRQ) scores (β 2.5, 95% CI: 0.1,4.8, p = 0.04), lower 6-minute walk distance (6MWD) (β -38.6, 95% CI: -67.7,-7.4, p = 0.02), and higher rate of moderate-to-severe exacerbations over the prospective follow-up period (IRR 1.8, 95% CI: 1.1,2.8, p = 0.02). There was effect modification by CAC burden such that with higher burden the mean difference in COPD outcome by anemia status was greater for a subset of symptom scores. Participants with profiles of increasing anemia risk had higher estimated rates of decline in the FEV1% predicted and 6MWD and increase in SGRQ scores compared to those with stable or decreasing anemia risk. Conclusions Longitudinal anemia status trends may be predictive of COPD disease trajectory. Anemia status by repeated measures analysis is associated with COPD morbidity with potentially stronger associations in the setting of high CAC burden.

Background: Omega - 3 polyunsaturated fatty acids (PUFAs) have been associated with systemic anti - inflammatory responses. Dietary intake of omega - 3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has also been associated with lower chronic obstructive pulmonary disease (COPD) morbidity using self - report food frequency questionnaires. Objective: The objective of this study was to investigate the relationship between measured PUFA intake using plasma EPA+DHA levels and COPD morbidity. Methods: Former smokers with moderate - to - severe COPD living in low - income communities were enrolled in a 6 - month prospective cohort study. Participants completed standardized questionnaires, spirometry, and plasma samples at 3 - month intervals. Total plasma PUFAs were analyzed using gas chromatography/mass spectrometry for DHA and EPA concentrations. Linear or logistic mixed model regression was used to evaluate EPA+DHA's and COPD morbidity's association, accounting for demographics, lung function, pack years, comorbidities, and neighborhood poverty. Results: A total of 133 plasma EPA+DHA samples from 57 participants were available. Participants exhibited average plasma EPA and DHA levels of 14.7 +/- 7.3 mu g/mL and 40.2 +/- 17.2 mu g/mL, respectively, across the 3 clinic visits. Each standard deviation increase in EPA+DHA levels was associated with 2.7 points lower St George's Respiratory Questionnaire score (95% confidence interval [CI] - 5.2, - 0.2) and lower odds of moderate exacerbation (odds ratio 0.4; 95% CI 0.2, 0.9), but lacked significant association with the COPD Assessment Test score (95% CI - 2.4, 0.8), modified Medical Research Council dyspnea scale (95% CI - 02, 0.2), or severe exacerbations (95% CI 0.3, 1.4). Conclusion: Plasma EPA+DHA levels are associated with better respiratory - specific quality of life and lower odds of moderate exacerbations in patients with moderate - to - severe COPD. Further research is warranted to investigate the efficacy of an omega - 3 dietary intervention in the management of COPD morbidities.

Background: Low socioeconomic status (SES) has been associated with worse clinical outcomes in chronic obstructive pulmonary disease (COPD).Food insecurity is more common among individuals with low SES and has been associated with poor outcomes in other chronic illnesses, but its impact on COPD has not been studied.Methods: Former smokers with spirometry-confirmed COPD were recruited from low-income areas of Baltimore, Maryland and followed for 9 months as part of a cohort study of diet and indoor air pollution.Food insecurity and respiratory outcomes, including COPD exacerbations and patient-reported outcomes, were assessed at regular intervals.The association between food insecurity and COPD outcomes was analyzed using generalized linear mixed models.Additional analyses examined the association of COPD morbidity with sub-domains of food insecurity and the association of food insecurity with measures of psychological wellbeing.Results: Ninety-nine participants had available data on food insecurity and COPD outcomes.26.3% of participants were food insecure at one or more times during the study.After adjusting for individual SES, neighborhood poverty, and low healthy food access, food insecurity was associated with higher incidence rate of moderate and severe exacerbations, worse dyspnea, COPD health status, and respiratory-specific quality of life.Sub-domains of food insecurity were independently associated with worse patient-reported outcomes.Food insecurity was additionally associated with higher perceived stress.Discussion: Among former smokers with COPD, food insecurity was associated with higher incidence of exacerbations, worse patient-reported outcomes, and higher perceived stress.Subdomains of food insecurity were independently associated with worse patient-reported outcomes.

Mycobacteroides abscessus (Mab, also known as Mycobacterium abscessus) causes opportunistic pulmonary and soft tissue infections that are difficult to cure with existing treatments. Omadacycline, a new tetracycline antibiotic, exhibits potent in vitro and in vivo activity against Mab. As regimens containing multiple antibiotics are required to produce a durable cure for Mab disease, we assessed efficacies of three three-drug combinations in a pre-clinical mouse model of pulmonary Mab disease to identify companion drugs with which omadacycline exhibits the highest efficacy. Additionally, we assessed the susceptibility of Mab recovered from mouse lungs after four weeks of exposure to the three triple-drug regimens. Among the three-drug regimens, omadacycline + imipenem + amikacin produced the largest reduction in Mab burden, whereas omadacycline + imipenem + linezolid exhibited the most effective early bactericidal activity. Omadacycline + linezolid + clofazimine, a regimen that can be administered orally, lacked early bactericidal activity but produced a gradual reduction in the lung Mab burden over time. The robust efficacy exhibited by these three regimens in the mouse model supports their further evaluation in patients with Mab lung disease. As we were unable to isolate drug-resistant Mab mutants at the completion of four weeks of treatment, these triple-drug combinations show promise of producing durable cure and minimizing selection of resistant mutants.

Mycobacteroides abscessus is an opportunistic pathogen in people with structural lung conditions such as bronchiectasis, chronic obstructive pulmonary disease, and cystic fibrosis. Pulmonary M. abscessus infection causes progressive symptomatic and functional decline as well as diminished lung function and is often incurable with existing antibiotics. We investigated the efficacy of a new tetracycline, omadacycline, in combination with existing antibiotics recommended to treat this indication, in a mouse model of M. abscessus lung disease. Amikacin, azithromycin, bedaquiline, biapenem, cefoxitin, clofazimine, imipenem, linezolid, and rifabutin were selected as companions to omadacycline. M. abscessus burden in the lungs of mice over a 4-week treatment duration was considered the endpoint. Omadacycline in combination with linezolid, imipenem, cefoxitin, biapenem, or rifabutin exhibited early bactericidal activity compared to any single drug. Using three M. abscessus isolates, we also determined the in vitro frequency of spontaneous resistance against omadacycline to be between 1.9 x 10(-10) and 6.2 x 10(-10) and the frequency of persistence against omadacycline to be between 5.3 x 10(-6) and 1.3 x 10(-5). Based on these findings, the combination of omadacycline and select drugs that are included in the recent treatment guidelines may exhibit improved potency to treat M. abscessus lung disease. IMPORTANCE M. abscessus disease incidence is increasing in the United States. This disease is difficult to cure with existing antibiotics. In this study, we describe the efficacy of a new tetracycline antibiotic, omadacycline, in combination with an existing antibiotic to treat this disease. A mouse model of M. abscessus lung disease was used to assess the efficacies of these experimental treatment regimens. Omadacycline in combination with select existing antibiotics exhibited bactericidal activity during the early phase of treatment.

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 mu g/m(3) 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 mu m 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.

BACKGROUND:Indoor pollutants have been associated with worse clinical outcomes in chronic obstructive pulmonary disease (COPD). Elevated biomarkers are associated with ambient pollution exposure, however the association with indoor pollution remains unclear. METHODS:Former smokers with spirometry-confirmed COPD were randomized to portable air cleaner or placebo. Indoor particulate matter (PM2.5, PM10, and ultrafine particles [UFP; PM<0.1]) and biomarkers were measured longitudinally at pre-specified intervals and course PM fraction (PM10-2.5) was calculated. Biomarkers were categorized based on associations with biologic mechanisms: inflammation (white blood cell count, interleukin [IL]-6, IL-8, IL-1β, tumor necrosis factor-α, interferon-γ, serum amyloid A), platelet activation (P-selectin, CD40 ligand [CD40L], 11-dehdydro-thromboxane-B2 [11dTxB2]), endothelial dysfunction (Vascular Cell Adhesion Molecule [VCAM]-1, Intercellular Adhesion Molecule [ICAM]-1), and oxidative stress (thiobarbituric acid reactive substances [TBARS], 8-hydroxydeoxyguanosine, 8-isoprostane). Associations between PM concentrations and each biomarker were analyzed using multivariable linear mixed models. An intention-to-treat analysis was performed to evaluate the air cleaner intervention on the biomarker levels longitudinally. RESULTS:Fifty-eight participants were randomized to each group. Finer PM was more strongly associated with higher IL-8 (mean difference per doubling: UFP 13.9% [p = 0.02], PM2.5 6.8% [p = 0.002], PM10-2.5 5.0% [p = 0.02]) while interferon-γ was associated with UFP and IL-1β with PM10-2.5. UFP and PM2.5 were associated with elevated levels of the oxidative stress biomarkers TBARS and 8-isoprostane respectively. For platelet activation markers, UFP was associated with higher 11dTxB2 while PM2.5 was associated with higher P-selectin and CD40L. Pollutants were not associated with biomarkers of endothelial dysfunction. In intention-to-treat analysis there was no association of the air cleaner intervention with any of the biomarkers. DISCUSSION:Among former smokers with COPD, elevated levels of indoor air pollutants, particularly ultrafine particles (PM<0.1), were associated with elevated biomarkers of inflammation, platelet activation, and oxidative stress. However, an air cleaner intervention that reduced PM did not significantly reduce biomarker levels.

of the initiation rate and the point in the titration curve in which propofol was started would be of interest for future analyses (2). We commend the authors for exploring a provocative and complex topic with a strong, multilayered statistical approach. The post hoc analyses should be interpreted prudently, but it is plausible the dose makes a difference in combination sedative therapy (12). Future work should factor heterogeneity of treatment effect for age into the trial design a priori and explore the pharmacokinetics–pharmacodynamic and safety profiles of sedative and analgesic combinations so commonly used in clinical practice (13–15).

Background: Chronic Obstructive Pulmonary Disease (COPD) affects ~16 million U.S. adults. Phthalates, synthetic chemicals in consumer products, may adversely impact pulmonary function and airway inflammation; however, their role on COPD morbidity risk remains unknown.Objective: We examined cross-sectional associations between phthalate exposures and respiratory morbidity in a pilot study of 40 COPD patients who were former smokers.METHODSWe quantified 11 urinary phthalate biomarkers in samples collected at baseline in a prospective cohort study in Baltimore, Maryland. COPD baseline morbidity measures included: health status and quality of life measures (CAT: COPD Assessment Test, CCQ: Clinical COPD Questionnaire, SGRQ: St. George’s Respiratory Questionnaire; mMRC: Modified Medical Research Council Dyspnea Scale), lung function, and exacerbations (12-month retrospective and 9-months prospective). To examine associations between morbidity measures and phthalate exposures, we used multivariable linear, logistic, and Poisson regression for continuous, binary, and count outcomes, respectively, adjusting for age, sex, race/ethnicity, education, and smoking pack-years.Results: Mono-n-butyl phthalate (MBP) concentrations were associated with increased CAT (β, 2.41;95% CI, 0.31-4.51), mMRC (β, 0.33;95% CI 0.11-0.55), and SGRQ (β, 7.43;95% CI 2.70-12.2) scores at baseline. Monobenzyl phthalate (MBzP) was also significantly associated with CCQ and SGRQ scores at baseline. Concentrations of the molar sum of Di(2-ethylhexyl) phthalate (DEHP) were associated with higher risk of exacerbations in the prior 12 months at baseline (odds ratio, OR=3.69; CI 1.14, 11.96 and OR = 7.10;95% CI 1.60, 31.45 for severe and moderate, respectively) and in the prospective follow-up period (incidence rate ratio, IRR=1.73;95% CI 1.11, 2.70 and IRR=1.56;95% CI 1.02, 2.38, for moderate and severe exacerbations, respectively). MEP concentrations were inversely associated with exacerbations.Conclusion: We observed suggestive evidence that exposure to select phthalates may increase morbidity risk among COPD patients. Findings warrant replication in larger studies given widespread phthalate exposures and potential implications for COPD patients.

Rational:Poor indoor air quality has been associated with worse chronic obstructive pulmonary disease (COPD) morbidity. In-home portable air cleaners reduce indoor pollutants and could improve respiratory health. Factors associated with air cleaner adherence among adults with COPD remains unknown. Methods:In a 6-month trial of former smokers with COPD, participants (n=116) received active or sham portable air cleaners. Air cleaner adherence was measured by electronic monitors. Potential baseline predictors of adherence included individual factors (demographics, socioeconomic status, smoking history, psychological well-being), COPD disease severity, and housing characteristics. Time and season were also considered. Stepwise logistic regression and longitudinal fixed effect analysis were performed to assess independent predictors of adherence. Results:A total of 109 participants had an objective measure of adherence, and 76.1% used at least 1 air cleaner 80% of the time (defined a priori as adherent). Higher annual household income ≥$35,000 (odds ratio [OR]=4.4, 95% confidence interval [CI], 1.1-18.0) and use of heat pump/electricity (versus gas) for heating (OR=6.1, 95%CI, 1.7-22.4) were associated with higher odds of adherence. Further, poor quality of life (St George's Respiratory Questionnaire, per 10-point increase) and prior year exacerbations were associated with lower odds of adherence (OR=0.65, 95%CI, 0.4-1.0) and (OR=0.26, 95%CI, 0.1-0.9), respectively. Adherence was highest during the first month and lower during winter compared to other seasons. Conclusion:These findings suggest that cold weather season, use of gas for home heating, and lower annual income negatively impact adherence. Poor quality of life and worse disease control may also decrease adherence. Addressing factors associated with air cleaner adherence should be considered when designing future environmental studies.

BACKGROUND:Neighborhood poverty has been associated with poor health outcomes. Previous studies have also identified adverse respiratory effects of long-term ambient ozone. Factors associated with neighborhood poverty may accentuate the adverse impact of ozone on respiratory health. OBJECTIVES:To evaluate whether neighborhood poverty modifies the association between ambient ozone exposure and respiratory morbidity including symptoms, exacerbation risk, and radiologic parameters, among participants of the SPIROMICS AIR cohort study. METHODS:Spatiotemporal models incorporating cohort-specific monitoring estimated 10-year average outdoor ozone concentrations at participants' homes. Adjusted regression models were used to determine the association of ozone exposure with respiratory outcomes, accounting for demographic factors, education, individual income, body mass index (BMI), and study site. Neighborhood poverty rate was defined by percentage of families living below federal poverty level per census tract. Interaction terms for neighborhood poverty rate with ozone were included in covariate-adjusted models to evaluate for effect modification. RESULTS:1874 participants were included in the analysis, with mean (± SD) age 64 (± 8.8) years and FEV1 (forced expiratory volume in one second) 74.7% (±25.8) predicted. Participants resided in neighborhoods with mean poverty rate of 9.9% (±10.3) of families below the federal poverty level and mean 10-year ambient ozone concentration of 24.7 (±5.2) ppb. There was an interaction between neighborhood poverty rate and ozone concentration for numerous respiratory outcomes, including COPD Assessment Test score, modified Medical Research Council Dyspnea Scale, six-minute walk test, and odds of COPD exacerbation in the year prior to enrollment, such that adverse effects of ozone were greater among participants in higher poverty neighborhoods. CONCLUSION:Individuals with COPD in high poverty neighborhoods have higher susceptibility to adverse respiratory effects of ambient ozone exposure, after adjusting for individual factors. These findings highlight the interaction between exposures associated with poverty and their effect on respiratory health.

Rationale: Black adults have worse health outcomes compared with white adults in certain chronic diseases, including chronic obstructive pulmonary disease (COPD). Objectives: To determine to what degree disadvantage by individual and neighborhood socioeconomic status (SES) may contribute to racial disparities in COPD outcomes. Methods: Individual and neighborhood-scale sociodemographic characteristics were determined in 2,649 current or former adult smokers with and without COPD at recruitment into SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study). We assessed whether racial differences in symptom, functional, and imaging outcomes (St. George's Respiratory Questionnaire, COPD Assessment Test score, modified Medical Research Council dyspnea scale, 6-minute-walk test distance, and computed tomography [CT] scan metrics) and severe exacerbation risk were explained by individual or neighborhood SES. Using generalized linear mixed model regression, we compared respiratory outcomes by race, adjusting for confounders and individual-level and neighborhoodlevel descriptors of SES both separately and sequentially. Measurements and Main Results: After adjusting for COPD risk factors, Black participants had significantly worse respiratory symptoms and quality of life (modified Medical Research Council scale, COPD Assessment Test, and St. George's Respiratory Questionnaire), higher risk of severe exacerbations and higher percentage of emphysema, thicker airways (internal perimeter of 10 mm), andmore air trapping on CTmetrics compared with white participants. In addition, the association between Black race and respiratory outcomes was attenuated but remained statistically significant after adjusting for individual-level SES, which explained up to 12- 35% of racial disparities. Further adjustment showed that neighborhood-level SES explained another 26-54% of the racial disparities in respiratory outcomes. Even after accounting for both individual and neighborhood SES factors, Black individuals continued to have increased severe exacerbation risk and persistently worse CT outcomes (emphysema, air trapping, and airway wall thickness). Conclusions: Disadvantages by individual- and neighborhoodlevel SES each partly explain disparities in respiratory outcomes between Black individuals and white individuals. Strategies to narrow the gap in SES disadvantages may help to reduce race-related health disparities in COPD; however, further work is needed to identify additional risk factors contributing to persistent disparities.

Rationale: Racial residential segregation has been associated with worse health outcomes, but the link with chronic obstructive pulmonary disease (COPD) morbidity has not been established.Objectives: To investigate whether racial residential segregation is associated with COPD morbidity among urban Black adults with or at risk of COPD.Methods: Racial residential segregation was assessed using isolation index, based on 2010 decennial census and baseline address, for Black former and current smokers in the multicenter SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study), a study of adults with or at risk for COPD. We tested the association between isolation index and respiratory symptoms, physiologic outcomes, imaging parameters, and exacerbation risk among urban Black residents, adjusting for established COPD risk factors, including smoking. Additional mediation analyses were conducted for factors that could lie on the pathway between segregation and COPD outcomes, including individual and neighborhood socioeconomic status, comorbidity burden, depression/anxiety, and ambient pollution.Measurements and Main Results: Among 515 Black participants, those residing in segregated neighborhoods (i.e., isolation index ⩾0.6) had worse COPD Assessment Test score (β = 2.4; 95% confidence interval [CI], 0.7 to 4.0), dyspnea (modified Medical Research Council scale; β = 0.29; 95% CI, 0.10 to 0.47), quality of life (St. George's Respiratory Questionnaire; β = 6.1; 95% CI, 2.3 to 9.9), and cough and sputum (β = 0.8; 95% CI, 0.1 to 1.5); lower FEV1% predicted (β = -7.3; 95% CI, -10.9 to -3.6); higher rate of any and severe exacerbations; and higher percentage emphysema (β = 2.3; 95% CI, 0.7 to 3.9) and air trapping (β = 3.8; 95% CI, 0.6 to 7.1). Adverse associations attenuated with adjustment for potential mediators but remained robust for several outcomes, including dyspnea, FEV1% predicted, percentage emphysema, and air trapping.Conclusions: Racial residential segregation was adversely associated with COPD morbidity among urban Black participants and supports the hypothesis that racial segregation plays a role in explaining health inequities affecting Black communities.