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Bronchodilator responsiveness (BDR) in obstructive lung disease varies over time and may be associated with distinct clinical features.Is consistent BDR over time (always present) differentially associated with obstructive lung disease features relative to inconsistent (sometimes present) or never (never present) BDR in tobacco-exposed people with or without COPD?We retrospectively analyzed data from 2,269 tobacco-exposed participants in the Subpopulations and Intermediate Outcome Measures in COPD Study with or without COPD. We used various BDR definitions: change of ≥ 200 mL and ≥ 12% in FEVBoth consistent and inconsistent ATS-BDR were associated with asthma history and greater small airways disease (%parametric response mapping functional small airways disease) relative to never ATS-BDR in participants with GOLD stage 0 disease and the entire cohort. We observed similar findings using FEVDemonstration of BDR, even once, describes an obstructive lung disease phenotype with a history of asthma and greater small airways disease. Consistent demonstration of BDR indicated a high risk of lung function decline over time in the entire cohort and was associated with higher risk of progression to COPD in patients with GOLD stage 0 disease.

Aims The aim is to evaluate associations of lung function impairment with risk of incident heart failure (HF). Methods and results Data were pooled across eight US population-based cohorts that enrolled participants from 1987 to 2004. Participants with self-reported baseline cardiovascular disease were excluded. Spirometry was used to define obstructive [forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) Conclusion Lung function impairment was associated with increased risk of incident HF, and particularly incident HFpEF, independent of and to a similar extent as major known cardiovascular risk factors.

Background Small airways are known to be affected early in the course of chronic obstructive pulmonary disease (COPD); however, traditional spirometric indices may not accurately identify small airways disease. Research Question Can FEV3/FEV6 identify early airflow abnormalities and predict future clinically important respiratory-related outcomes, including development of COPD? Study Design and Methods We included eight hundred thirty-two current and former smokers with post-bronchodilator FEV1/FVC ≥0.7 from the SPIROMICS cohort. Participants were classified as having a reduced pre-bronchodilator FEV3/FEV6 based on lower limit of normal (LLN) values. Repeatability analysis was performed for FEV3 and FEV6. Regression modeling was used to evaluate the relationship between baseline FEV3/FEV6 and outcome measures including functional small airways disease on thoracic imaging and respiratory exacerbations. Interval censored analysis was used to assess progression to COPD. Results FEV3/FEV6 Interpretation FEV3/FEV6 is a routinely available and repeatable spirometric index which can be useful in the evaluation of early airflow obstruction in current and former smokers without COPD. A reduced FEV3/FEV6 can identify those at risk for future development of COPD and respiratory exacerbations.

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults at risk for coronavirus disease 2019 (COVID-19) comprising 14 established United States (US) prospective cohort studies. For decades, C4R cohorts have collected extensive data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R will link this pre-COVID phenotyping to information on SARS-CoV-2 infection and acute and post-acute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and broadly reflects the racial, ethnic, socioeconomic, and geographic diversity of the US. C4R is ascertaining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations, and high-quality events surveillance. Extensive pre-pandemic data minimize referral, survival, and recall bias. Data are being harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these will be pooled and shared widely to expedite collaboration and scientific findings. This unique resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including post-acute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term trajectories of health and aging.

Rationale: Individuals with Chronic Obstructive Pulmonary Disease (COPD) have a high prevalence of depression, which is associated with increased COPD hospitalizations and readmissions. Objectives:...

A generalized case-cohort design has been used when measuring exposures is expensive and events are not rare in the full cohort. This design collects expensive exposure information from a (stratified) randomly selected subset from the full cohort, called the subcohort, and a fraction of cases outside the subcohort. For the full cohort study with competing risks, He et al. [11] studied the non-stratified proportional subdistribution hazards model with covariate-dependent censoring to directly evaluate covariate effects on the cumulative incidence function. In this paper, we propose a stratified proportional subdistribution hazards model with covariate-adjusted censoring weights for competing risks data under the generalized case-cohort design. We consider a general class of weight functions to account for the generalized case-cohort design. Then, we derive the optimal weight function which minimizes the asymptotic variance of parameter estimates within the general class of weight functions. The proposed estimator is shown to be consistent and asymptotically normally distributed. The simulation studies show (i) the proposed estimator with covariate-adjusted weight is unbiased when the censoring distribution depends on covariates; and (ii) the proposed estimator with the optimal weight function gains parameter estimation efficiency. We apply the proposed method to stem cell transplantation and diabetes data sets. Competing risks data, Covariate-adjusted weight function, Optimal weight function, Stratified generalized case-cohort design.

Introduction: Medication non-adherence increases the risk of hospitalization and mortality in older adults. Evidence from previous studies was not conclusive due to small sample size or lack of adjustment for potential confounders. This study aims to investigate the prevalence and predictors of medication non-adherence in older adults, considering both individual-level and neighborhood-level factors. Methods: We studied participants (aged 66-90 years) who were on at least one medication at visit 5 (2011-2013) of the ARIC Study. Potential predictors included demographic factors, individual-level and neighborhood-level socioeconomic factors, behavioral factors, depressive symptoms, and cognitive function. We estimated the prevalence of self-reported medication adherence using the Morisky Green Levine medication adherence questionnaire and considered intermediate and low as medication non-adherence. We used multivariable logistic regression to identify independent predictors of medication non-adherence, further adjusting for race-center, insurance types, comorbidities, and number of medications. Results: Among 5304 participants (mean age of 75.5 [SD 5.1] years, 21.6% Black, and 58.2% female), 2.3% and 37.1% reported low and intermediate medication adherence, respectively. After adjustment, age 66-74 (odds ratio [OR]= 1.23 [95% CI, 1.10-1.38]), current drinker (1.31 [1.10-1.55]), lack of physical activity (PA) (1.18 [1.01-1.37] for intermediate PA; 1.38 [1.21-1.58] for low PA), and depressive symptoms (2.30 [1.82-2.91]) were significant predictors of medication non-adherence ( Table ). Education and ADI were not associated with medication non-adherence. Conclusions: We found that almost 40% of older adults have medication non-adherence. Unhealthy lifestyle factors and depressive symptoms were associated with medication non-adherence. Education and neighborhood-level SES were not. Depression is an important modifiable factor to improve medication adherence in older adults.

RATIONALE: Individuals with chronic obstructive pulmonary disease (COPD) have a high prevalence of depression, which is associated with increased COPD hospitalizations and readmissions. OBJECTIVES: Examine the impact of depressive symptoms compared with FEV(1)% on COPD morbidity. METHODS: Using longitudinal data from individuals with COPD in the Subpopulations and Intermediate Outcome Measures in COPD Study, longitudinal growth analysis was performed to assess COPD morbidity by assessing differences in baseline 6-minute walk distance and patient reported outcomes (PROs) and their rate of change over time explained by depressive symptoms or lung function, as measured by Hospital Anxiety and Depression Scale or FEV(1)% respectively. PROs consisted of in-person completion of St. George's Respiratory Questionnaire, COPD Assessment Test, Functional Assessment of Chronic Illness Therapy Fatigue, and Modified Medical Research Council Dyspnea Scale measures. RESULTS: Of the individuals analyzed (n = 1,830), 43% were female, 81% Caucasian with mean ± SD age of 65.1 ± 8.1, and 52.7 ± 27.5 pack-years smoking. Mean ± SD FEV(1)% was 60.9 ± 23.0% and 20% had clinically significant depressive symptoms. Adjusted models showed higher Hospital Anxiety and Depression Scale scores and lower FEV(1)% each were associated with worse PROs at baseline (P ⩽ 0.001). Depression accounted for more baseline variance in St. George's Respiratory Questionnaire, COPD Assessment Test, and Functional Assessment of Chronic Illness Therapy Fatigue than FEV(1)%, explaining 30–67% of heterogeneity. FEV(1)% accounted for more baseline variance in Modified Medical Research Council Dyspnea Scale and 6-minute walk distance than depression, explaining 16–32% of heterogeneity. Depressive symptoms accounted for 3–17% variance in change over time in PROs. In contrast, FEV(1)% accounted for 1–4% variance over time in PROs. CONCLUSIONS: Depression is more strongly associated with many PROs at baseline and their change over time compared with FEV(1)%. Recognizing and incorporating the impact of depressive symptoms into individualized care may improve COPD outcomes.

Rationale: Ambient air pollution exposure is associated with respiratory morbidity among individuals with chronic obstructive pulmonary disease (COPD), particularly among those with concomitant obesity. Although people with COPD report high incidence of poor sleep quality, no studies have evaluated the association between air pollution exposure, obesity, and sleep disturbances in COPD. Methods: We analyzed data collected from current and former smokers with COPD enrolled in the Subpopulations and Intermediate Outcome Measures in COPD -Air Pollution ancillary study (SPIROMICS AIR). Socio-demographics and anthropometric measurements were collected, and 1-year mean historical ambient particulate matter (PM(2.5)) and ozone concentrations at participants’ residences were estimated by cohort-specific spatiotemporal modeling. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI), and regression models were constructed to determine the association of 1-year PM(2.5 )(1Yr-PM(2.5)) and 1-year ozone (1Yr-ozone) with the PSQI score, and whether obesity modified the association. Results: In 1308 participants (age: 65.8±7.8 years, 42% women), results of regression analyses suggest that each 10µg/m(3) increase in 1Yr-PM(2.5 )was associated with a 2.1-point increase in PSQI (P=0.03). Obesity modified the association between 1Yr-PM(2.5) and PSQI (P=0.03). In obese and overweight participants, a 10µg/m(3) increase in 1Yr-PM(2.5) was associated with a higher PSQI (4.0 points, P

Potentially inappropriate medication (PIM) use is an important public health problem, particularly among older adults who may need multiple pharmacologic therapies for various chronic conditions. As socioeconomic status (SES) affects the quality of healthcare that individuals receive, SES may be associated with the use of PIM in older adults. This study aimed to determine whether low SES is associated with increased use of PIM.We studied 4927 participants (aged 66-90 years) who were on at least one medication at visit five (2011-2013) of the Atherosclerosis Risk in Communities Study. We created a cumulative SES score categorized as high (7-9), middle (3-6), and low (0-2) based on education, income, and area deprivation index. We use multivariable logistic regression to examine the associations between SES and use of two or more PIM for older adults, defined by the 2019 Beers Criteria.A total of 31.0% and 6.9% of the participants used one or more PIM and two or more PIM, respectively. After adjusting for demographic characteristics and insurance type, low cumulative SES score was associated with significantly greater use of two or more PIM (odds ratio [OR] = 1.83 [95% confidence interval (CI) 1.18-2.86]), as was middle cumulative SES score (OR = 1.40 [95% CI 1.06-1.83]), compared to high cumulative SES score. The results remained significant after further adjusting for comorbidities and medication burden for low cumulative SES score (OR = 1.66 [95%CI 1.02-2.71]).We found that lower SES was associated with greater use of PIM among older adults independent of their medication burden and comorbidities, suggesting socioeconomic disparities in quality of medication management. Focused efforts targeting older adults with low SES to reduce PIM use may be needed to prevent adverse drug events.

The case-cohort design, among many two-phase sampling designs, substantially reduces the cost of an epidemiological study by selecting more informative participants within the full cohort for expensive variable measurements. Despite their benefits, additive hazards models, which estimate hazard differences, have rarely been used for the analysis of case-cohort studies due to the lack of software and application examples. In this paper, we describe a newly developed estimation method that fits the additive hazards models to general two-phase sampling studies along with the R package addhazard that implements it. It allows for missing covariates among cases, cohort stratification, robust variances, and the incorporation of auxiliary information from the full cohort to enhance inference precision. We demonstrate the use of this tool to estimate the association of the risk of coronary heart disease (CHD) with biomarkers high-sensitivity C-reactive protein (hs-CRP) and Lipoprotein-associated phospholipase A2 (Lp-PLA2) by analyzing the Atherosclerosis Risk in Communities Study, which adopted a two-phase sampling design for studying these two biomarkers. We show that the use of auxiliary variables from the full cohort based on calibration techniques improves the precision of the hazard difference being estimated. We observe a synergistic effect of the two biomarkers among participants with lower LDL cholesterol (LDL-C): the CHD hazard rate attributable to the combined action of high hs-CRP and high Lp-PLA2 exceeded the sum of the CHD hazard rate attributable to each one independently by 11.58 (95% CI 2.16–21.01) cases per 1000 person-years. With higher LDL-C, we observe the CHD hazard rate attributable to the combined action of high hs-CRP and medium Lp-PLA2 was less than the sum of their individual effects by 13.42 (95% CI 2.44–24.40) cases per 1000 person-years. This demonstration serves the dual purposes of illustrating analysis techniques and providing insights about the utility of hs-CRP and Lp-PLA2 for identifying the high-risk population of CHD that the traditional risk factors such as the LDL-C may miss. Epidemiologists are encouraged to use this new tool to analyze other case-cohort studies and incorporate auxiliary variables embedded in the full cohort in their analysis.

ARIC (Atherosclerosis Risk In Communities) initiated community-based surveillance in 1987 for myocardial infarction and coronary heart disease (CHD) incidence and mortality and created a prospective cohort of 15,792 Black and White adults ages 45 to 64 years. The primary aims were to improve understanding of the decline in CHD mortality and identify determinants of subclinical atherosclerosis and CHD in Black and White middle-age adults. ARIC has examined areas including health disparities, genomics, heart failure, and prevention, producing more than 2,300 publications. Results have had strong clinical impact and demonstrate the importance of population-based research in the spectrum of biomedical research to improve health.

Rationale: The relative roles of mucus plugs and emphysema in mechanisms of airflow limitation and hypoxemia in smokers with chronic obstructive pulmonary disease (COPD) are uncertain.Objectives: T...

Objective To characterize the longitudinal relationships between blood pressure measured over 24 years and arterial stiffness in late life measured as pulse wave velocity (PWV). Methods Carotid--femoral (cf) and femoral--ankle (fa) PWV were measured in 4166 adults at the visit 5 Atherosclerosis Risk in Communities study cohort examination (2011-2013). Participants were categorized into tertiles of PWV measurements. Blood pressure measurements were made at baseline (1987-1989), three subsequent triennial examinations, and visit 5. Results Partial correlation coefficients between visit 5 cfPWV and SBP ranged from 0.13 for visit 1 SBP to 0.32 for visit 5 SBP. For visit 5 faPWV, correlations were ∼0 for visits 1 to 4 SBP, but was 0.20 for visit 5 SBP. Over 24 years of follow-up, those with higher average SBP were more likely to fall in the middle and upper tertiles of visit 5 cfPWV. Average pulse pressure and mean arterial pressure over 24 years had similar but weaker associations with cfPWV tertiles. DBP had no clear association with cfPWV. Blood pressure measurements were positively associated with faPWV tertiles only cross-sectionally at visit 5. Conclusion Adult life-course measures of SBP, more so than mean arterial and pulse pressure, were associated with later life central arterial stiffness. By contrast, only contemporaneous measures of blood pressure were associated with peripheral arterial stiffness. Although arterial stiffness was only measured at later life, these results are consistent with the notion that elevated blood pressure over time is involved in the pathogenesis of arterial stiffening.

Rationale: African American individuals have worse outcomes in chronic obstructive pulmonary disease (COPD). Objectives: To assess whether race-specific approaches for estimating lung function contribute to racial inequities by failing to recognize pathological decrements and considering them normal. Methods: In a cohort with and at risk for COPD, we assessed whether lung function prediction equations applied in a race-specific versus universal manner better modeled the relationship between FEV1, FVC, and other COPD outcomes, including the COPD Assessment Test, St. George's Respiratory Questionnaire, computed tomography percent emphysema, airway wall thickness, and 6-minute-walk test. We related these outcomes to differences in FEV1 using multiple linear regression and compared predictive performance between fitted models using root mean squared error and Alpaydin's paired F test. Measurements and Main Results: Using race-specific equations, African American individuals were calculated to have better lung function than non-Hispanic White individuals (FEV1, 76.8% vs. 71.8% predicted; P = 0.02). Using universally applied equations, African American individuals were calculated to have worse lung function. Using Hankinson's Non-Hispanic White equation, FEV1 was 64.7% versus 71.8% (P

Background: Excess body mass index (BMI) and weight gain are well-known risk factors for diabetes. Nevertheless, the associations of BMI and weight gain in young adulthood with subsequent diabetes in African Americans, and the standardized effects of these weight variables have not been well studied. Methods: We studied 12,672 white and African American men and women 45–64 years of age (i.e., during mid-adulthood) who participated in the Atherosclerosis Risk in Communities Study visit 1 (1987–1989), and were reexamined at three follow-up examinations. Associations between recalled BMI at age 25 (i.e., during young adulthood) and subsequent weight change with incident diabetes at ages 45 and above (i.e., during mid-adulthood to older adulthood) were examined using Cox proportional hazard models. Results: Over the 9-year follow-up, we identified 1,501 cases of incident diabetes. The incidence rates were higher among African Americans (men: 24.5 and women: 26.3 per 1,000 person-years) compared to whites (men: 16.3 and women: 10.5 per 1,000 person years). Compared to normal-weight individuals at age 25, those who were overweight or obese and those who gained more weight after age 25 had a higher risk of developing diabetes later in all four race-sex groups with the highest risk in African Americans. In the race-sex groups combined, the mutually adjusted hazard ratio for BMI at age 25 and percent weight change were 1.97 (1.79–2.17) and 2.89 (2.59–3.11), respectively, comparing the 85th to the 15th percentiles of the exposures. Conclusions: African Americans were at higher risk of diabetes than whites. Both higher BMI at age 25 and subsequent weight gain were independently associated with higher risk for diabetes in all the race-sex groups; however, overall weight gain was more potent than BMI.

Author(s): Cooper, Christopher B; Paine, Robert; Curtis, Jeffrey L; Kanner, Richard E; Martinez, Carlos H; Meldrum, Catherine A; Bowler, Russell; O'Neal, Wanda; Hoffman, Eric A; Couper, David; Quibrera, Miguel; Criner, Gerald; Dransfield, Mark T; Han, MeiLan K; Hansel, Nadia N; Krishnan, Jerry A; Lazarus, Stephen C; Peters, Stephen P; Barr, R Graham; Martinez, Fernando J; Woodruff, Prescott G; SPIROMICS investigators | Abstract: RationaleSome COPD patients develop extreme breathlessness, decreased exercise capacity and poor health status yet respiratory disability is poorly characterized as a distinct phenotype.ObjectiveTo define respiratory disability in COPD based on available functional measures and to determine associations with risk for exacerbations and death.MethodsWe analyzed baseline data from a multi-center observational study (SPIROMICS). This analysis includes 2332 participants (472 with severe COPD, 991 with mild/moderate COPD, 726 smokers without airflow obstruction and 143 non-smoking controls).MeasurementsWe defined respiratory disability by ≥4 of 7 criteria: mMRC dyspnea scale ≥3; Veterans Specific Activity Questionnaire l5; 6-minute walking distance l250 m; St George's Respiratory Questionnaire activity domain g60; COPD Assessment Test g20; fatigue (FACIT-F Trial Outcome Index) l50; SF-12 l20.ResultsUsing these criteria, respiratory disability was identified in 315 (13.5%) participants (52.1% female). Frequencies were severe COPD 34.5%; mild-moderate COPD 11.2%; smokers without obstruction 5.2% and never-smokers 2.1%. Compared with others, participants with disability had more emphysema (13.2 vs. 6.6%) and air-trapping (37.0 vs. 21.6%) on HRCT (Pl0.0001). Using principal components analysis to derive a disability score, two factors explained 71% of variance, and a cut point -1.0 reliably identified disability. This disability score independently predicted future exacerbations (s=0.34; CI 0.12, 0.64; P=0.003) and death (HR 2.97; CI 1.54, 5.75; P=0.001). Thus, participants with disability by this criterion had almost three times greater mortality compared to those without disability.ConclusionOur novel SPIROMICS respiratory disability score in COPD was associated with worse airflow obstruction as well as airway wall thickening, lung parenchymal destruction and certain inflammatory biomarkers. The disability score also proved to be an independent predictor of future exacerbations and death. These findings validate disability as an important phenotype in the spectrum of COPD.

Public health policy decisions in the United States have resulted in 62.4% of the population having access to fluoridated water. The purpose of this study was to examine the association between community water fluoridation and osteosarcoma. A secondary data analysis was performed with data collected from 2 separate but linked studies. Patients for phase 1 and phase 2 were selected from US hospitals via a matched case-control study design. For both phases, cases included patients diagnosed with osteosarcoma, and controls were patients diagnosed with other bone tumors or nonneoplastic conditions. In phase 1, cases ( n = 209) and controls ( n = 440) were patients of record in the participating orthopedic departments from 1989 to 1993. In phase 2, cases ( n = 108) and controls ( n = 296) were incident patients who were identified and treated by orthopedic physicians from 1994 to 2000. This analysis included all patients who met eligibility criteria on whom we had complete data on covariates, exposures, and outcome. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% CIs for the association of community water fluoridation with osteosarcoma. A modestly significant interaction existed between fluoridation living status and bottled water use ( P = 0.047). The adjusted OR for osteosarcoma and ever having lived in a fluoridated area for nonbottled water drinkers was 0.51 (95% CI, 0.31 to 0.84; P = 0.008). In the same comparison, the adjusted OR for bottled water drinkers was 1.86 (95% CI, 0.54 to 6.41; P = 0.326). Findings from this study demonstrated that community water fluoridation is not associated with an increased risk for osteosarcoma.

Background The relationship between 25-hydroxyvitamin D (25-OH-vitamin D) and COPD outcomes remains unclear. Using the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), we determined associations among baseline 25-OH-vitamin D and cross-sectional and longitudinal lung function and COPD exacerbations. Methods Serum 25-OH-vitamin D level was measured in stored samples from 1,609 SPIROMICS participants with COPD. 25-OH-vitamin D levels were modeled continuously and dichotomized as deficient ( Results Vitamin D deficiency was present in 21% of the cohort and was more prevalent in the younger, active smokers, and blacks. Vitamin D deficiency was independently associated with lower % predicted FEV1 (by 4.11%) at enrollment (95% CI, –6.90% to –1.34% predicted FEV1; P = .004), 1.27% predicted greater rate of FEV1 decline after 1 year (95% CI, –2.32% to –0.22% predicted/y; P = .02), and higher odds of any COPD exacerbation in the prior year (OR, 1.32; 95% CI, 1.00-1.74; P = .049). Each 10-ng/mL decrease in 25-OH-vitamin D was associated with lower baseline lung function (–1.04% predicted; 95% CI, –1.96% to –0.12% predicted; P = .03) and increased odds of any exacerbation in the year before enrollment (OR, 1.11; 95% CI, 1.01-1.22; P = .04). Conclusions Vitamin D deficiency is associated with worse cross-sectional and longitudinal lung function and increased odds of prior COPD exacerbations. These findings identify 25-OH-vitamin D levels as a potentially useful marker of adverse COPD-related outcomes.

Rationale: The role of PI (protease inhibitor) type Z heterozygotes and additional rare variant genotypes in the gene encoding alpha-1 antitrypsin, SERPINA1 (serpin peptidase inhibitor, clade A, me...

Summary Background Former smokers now outnumber current smokers in many developed countries, and current smokers are smoking fewer cigarettes per day. Some data suggest that lung function decline normalises with smoking cessation; however, mechanistic studies suggest that lung function decline could continue. We hypothesised that former smokers and low-intensity current smokers have accelerated lung function decline compared with never-smokers, including among those without prevalent lung disease. Methods We used data on six US population-based cohorts included in the NHLBI Pooled Cohort Study. We restricted the sample to participants with valid spirometry at two or more exams. Two cohorts recruited younger adults (≥17 years), two recruited middle-aged and older adults (≥45 years), and two recruited only elderly adults (≥65 years) with examinations done between 1983 and 2014. FEV1 decline in sustained former smokers and current smokers was compared to that of never-smokers by use of mixed models adjusted for sociodemographic and anthropometric factors. Differential FEV1 decline was also evaluated according to duration of smoking cessation and cumulative (number of pack-years) and current (number of cigarettes per day) cigarette consumption. Findings 25 352 participants (ages 17–93 years) completed 70 228 valid spirometry exams. Over a median follow-up of 7 years (IQR 3–20), FEV1 decline at the median age (57 years) was 31·01 mL per year (95% CI 30·66–31·37) in sustained never-smokers, 34·97 mL per year (34·36–35·57) in former smokers, and 39·92 mL per year (38·92–40·92) in current smokers. With adjustment, former smokers showed an accelerated FEV1 decline of 1·82 mL per year (95% CI 1·24–2·40) compared to never-smokers, which was approximately 20% of the effect estimate for current smokers (9·21 mL per year; 95% CI 8·35–10·08). Compared to never-smokers, accelerated FEV1 decline was observed in former smokers for decades after smoking cessation and in current smokers with low cumulative cigarette consumption ( Interpretation Former smokers and low-intensity current smokers have accelerated lung function decline compared with never-smokers. These results suggest that all levels of smoking exposure are likely to be associated with lasting and progressive lung damage. Funding National Institutes of Health, National Heart Lung and Blood Institute, and US Environmental Protection Agency.

Chronic obstructive pulmonary disease (COPD) is a common, progressive lung disease that often manifests with psychiatric symptoms. Despite this, patients with COPD are not routinely screened for anxiety and depression, which substantially contribute to COPD-related morbidity.To determine the relationship among COPD symptom severity, exacerbation risk, and clinically significant anxiety and depression symptoms in ever smokers with COPD.We used baseline data from the Subpopulations and Intermediate Outcome Measures In COPD Study (SPIROMICS) cohort to examine ever smokers with COPD across Global Initiative for Obstructive Lung Disease (GOLD) disease severity groups. Multivariable logistic regression models were used to calculate odds ratios for clinically significant anxiety and depression for each GOLD group, which was compared to the control group of ever smokers without COPD. Odds ratios were adjusted for subject demographics, medical comorbidities, and substance use covariates, and comparisons were completed using 2-tailed tests.Of the 2664 subjects studied, 784 (29.4%) had clinically significant anxiety, and 497 (18.7%) had clinically significant depression. In the multivariable analysis, high pulmonary symptom groups, groups B and D, had increased adjusted odds of clinically significant anxiety (group B: adjusted odds ratios [AOR] 1.28, P = 0.03; group D: AOR 1.95, P0.0001) and depression (group B: AOR 2.09, P0.0001; group D: AOR 3.04, P0.0001). GOLD group D, the group with high pulmonary symptoms and high COPD exacerbation risk, had the greatest risk of both anxiety and depression among the GOLD groups.High COPD symptom severity, even in the absence of elevated COPD exacerbation risk, is associated with clinically significant anxiety and depression. Our separate analyses of anxiety and depression symptoms in a large, multisite, national cohort are unique within the literature and have important treatment implications for COPD patients. Our findings also highlight the utility of screening patients with high COPD symptom severity for anxiety and depression.