Woodruff, Prescott G.

Importance People who smoked cigarettes may experience respiratory symptoms without spirometric airflow obstruction. These individuals are typically excluded from chronic obstructive pulmonary disease (COPD) trials and lack evidence-based therapies. Objective To define the natural history of persons with tobacco exposure and preserved spirometry (TEPS) and symptoms (symptomatic TEPS). Design, Setting, and Participants SPIROMICS II was an extension of SPIROMICS I, a multicenter study of persons aged 40 to 80 years who smoked cigarettes (>20 pack-years) with or without COPD and controls without tobacco exposure or airflow obstruction. Participants were enrolled in SPIROMICS I and II from November 10, 2010, through July 31, 2015, and followed up through July 31, 2021. Exposures Participants in SPIROMICS I underwent spirometry, 6-minute walk distance testing, assessment of respiratory symptoms, and computed tomography of the chest at yearly visits for 3 to 4 years. Participants in SPIROMICS II had 1 additional in-person visit 5 to 7 years after enrollment in SPIROMICS I. Respiratory symptoms were assessed with the COPD Assessment Test (range, 0 to 40; higher scores indicate more severe symptoms). Participants with symptomatic TEPS had normal spirometry (postbronchodilator ratio of forced expiratory volume in the first second [FEV 1 ] to forced vital capacity >0.70) and COPD Assessment Test scores of 10 or greater. Participants with asymptomatic TEPS had normal spirometry and COPD Assessment Test scores of less than 10. Patient-reported respiratory symptoms and exacerbations were assessed every 4 months via phone calls. Main Outcomes and Measures The primary outcome was assessment for accelerated decline in lung function (FEV 1 ) in participants with symptomatic TEPS vs asymptomatic TEPS. Secondary outcomes included development of COPD defined by spirometry, respiratory symptoms, rates of respiratory exacerbations, and progression of computed tomographic–defined airway wall thickening or emphysema. Results Of 1397 study participants, 226 had symptomatic TEPS (mean age, 60.1 [SD, 9.8] years; 134 were women [59%]) and 269 had asymptomatic TEPS (mean age, 63.1 [SD, 9.1] years; 134 were women [50%]). At a median follow-up of 5.76 years, the decline in FEV 1 was −31.3 mL/y for participants with symptomatic TEPS vs −38.8 mL/y for those with asymptomatic TEPS (between-group difference, −7.5 mL/y [95% CI, −16.6 to 1.6 mL/y]). The cumulative incidence of COPD was 33.0% among participants with symptomatic TEPS vs 31.6% among those with asymptomatic TEPS (hazard ratio, 1.05 [95% CI, 0.76 to 1.46]). Participants with symptomatic TEPS had significantly more respiratory exacerbations than those with asymptomatic TEPS (0.23 vs 0.08 exacerbations per person-year, respectively; rate ratio, 2.38 [95% CI, 1.71 to 3.31], P < .001). Conclusions and Relevance Participants with symptomatic TEPS did not have accelerated rates of decline in FEV 1 or increased incidence of COPD vs those with asymptomatic TEPS, but participants with symptomatic TEPS did experience significantly more respiratory exacerbations over a median follow-up of 5.8 years.

Background: Adults with cardiovascular co-morbidities and risk factors are at greater risk of severe COVID-19. These same risk factors may also be associated with an attenuated antibody response to COVID-19 vaccines, although studies in diverse, U.S. population-based cohorts have been limited. Methods: The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) conducted a serosurvey for SARS-CoV-2 antibodies via dried blood spot (DBS) in 14 U.S. cohorts. IgG antibodies to SARS-CoV-2 spike subunit 1 (S1) and nucleocapsid (N) were measured from DBS using a semi-quantitative microsphere immunoassay and reported as median fluorescence intensity (MFI). Multivariable adjusted linear models regressed log-transformed anti-S1 MFI on age, sex, race/ethnicity, education attainment, self-reported diabetes, hypertension, cardiovascular disease (CVD), chronic kidney disease, smoking history, body mass index (BMI), asthma, obstructive lung diseases, DBS batch, anti-N MFI, vaccine type, time between vaccine and DBS, and vaccine dose at time of DBS collection. Results are presented as the percent difference in anti-S1 MFI compared with a reference group. Results: There were 6614 vaccinated participants prior to booster regimens and DBS collection (April 2021-July 2022) with 50%, 48%, and 2% of the cohort who received BNT162b2, mRNA-1273, or other vaccines, respectively. The mean (SD) time between vaccination and DBS was 3.8 (1.8) months. Over 10% of the cohort had self-reported a history of diabetes, 55% had hypertension, and 74% had a BMI>25 kg/m 2 . Anti-S1 MFI decreased as the time between vaccine dose and DBS collection increased. Diabetes was associated with a 16.1% lower anti-S1 MFI (95%CI:-22.4,-9.5) whereas neither hypertension (-3.8%;95%CI:-9.3,2.1), nor cardiovascular disease history (-5.3%;95%CI:-16.3,7.4) were associated with anti-S1 MFI. Former and current smoking history were each associated with a lower anti-S1 MFI: (-6.6%;95%CI:-12.1,-0.8) and (-16.1%;95%CI:-24.7,-6.6), respectively. Participants with a BMI 25-29.9 kg/m 2 had a 7.6% higher anti-S1 MFI (95%CI:0.3,15.4) whereas those with a BMI of 30-35 kg/m 2 and >35 kg/m 2 had 6.2% (95%CI:-2.4,15.5) higher and 8.9% lower (95%CI:-17.6,0.7) MFI levels, respectively. Older age and male sex were each associated with a lower anti-S1 MFI and mRNA-1273 vaccine, Asian subgroup, higher anti-N titer, and prior COVID-19 infection were each associated with higher anti-S1 MFI. Chronic kidney disease, education attainment, and lung disease were not associated with anti-S1 MFI. Conclusions: Several traditional cardiovascular disease risk factors were associated with diminished humoral responses to the initial COVID-19 vaccine regimens in a diverse U.S. population-based cohort and may have implications on strategies to improve vaccine responses.

Rationale: The impact of the COVID-19 pandemic on tobacco use patterns remains incompletely understood. We aimed to examine changes in cigarette smoking patterns over the first 2 years of the COVID-19 pandemic (2020-22) in a large, multiethnic, US community-based sample. Methods: The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) ascertained the impact of the COVID-19 pandemic on participants from 14 longitudinal NIH-funded cohorts via 2 waves of standardized questionnaires conducted 2020-22. The C4R questionnaire collected data on cigarette use patterns for the current and immediate pre-pandemic periods (January-March 2020). These data were used to define pandemic-era smoking initiation, smoking cessation, and changes in smoking intensity. Multivariable logistic regression models were adjusted for centrally harmonized pre-pandemic data on sociodemographic characteristics, remote smoking history, and co-morbidities and pandemic-era psychological health, insomnia, and SARS-CoV-2 infection history ascertained through C4R questionnaires. Multiple imputation by chained equations was used to account for missing covariate data. Results: Of 17179 participants completing C4R questions on pandemic-era smoking behaviors, 1899 (11%) participants reported current smoking in the immediate pre-pandemic period (mean age 70 years, 59% women, 31% African American, 2% Hispanic, 1% Asian, 22% American Indian/Alaskan Native [AIAN]). Of these 181 (10%) self-reported quitting during the pandemic. Among 1718 (90%) who continued smoking, smoking intensity increased in 17% and decreased in 26%. Among 15093 participants who were not smoking prior to March 2020, 135 (0.9%) initiated smoking during the pandemic period, including 120 (89%) with a remote history of smoking and 15 (11%) with no history of smoking. Pandemic-era smoking cessation was associated with older age(80+ years vs <65 years [adjusted odds ratio; 95%CI] 2.1; 1.1-4.0), obesity(vs normal weight 1.6; 1.02-2.6) and history of SARS-CoV-2 infection (2.1; 1.3-3.1). Pandemic-era smoking initiation was associated with concurrent use of cannabis (3.1; 1.9-5.2), e-cigarette (29.6; 14.8-59.2), and/or alcohol (1.8; 1.1-2.9). Compared to non-Hispanic white participants, AIAN participants had lower odds of quitting (0.1; 0.03-0.6) and African American participants had higher odds of increased smoking intensity (2.0; 1.3-3.1). Depressive symptoms were associated with smoking initiation (2.4; 1.3-4.3) and increased smoking intensity (2.6; 1.5-4.5). Conclusion: Greater odds of smoking initiation and/or increased smoking intensity were observed in minoritized groups and participants reporting depressive symptoms. Majority of those who initiated smoking during pandemic-era were relapsers. Smoking cessation programs remain important to improving public health and reducing health disparities.

Abstract Study Objectives Sleep is an important dimension in the care of chronic obstructive pulmonary disease (COPD), but its relevance to exacerbations is unclear. We wanted to assess whether sleep quality as measured by the Pittsburgh Sleep Quality Index (PSQI) is associated with an increased risk of COPD exacerbations and does this differ by socio-environmental exposures. Methods We included 1647 current and former smokers with spirometrically confirmed COPD from the SPIROMICS cohort. We assessed incidence rate ratios for exacerbation using zero-inflated negative binomial regression adjusting for demographics, medical comorbidities, and multiple metrics of disease severity, including respiratory medications, airflow obstruction, and symptom burden. Our final model adjusted for socio-environmental exposures using the Area Deprivation Index, a composite measure of contemporary neighborhood quality, and Adversity–Opportunity Index, a composite measure of individual-level historic and current socioeconomic indicators. We used a pre-determined threshold of 20% missingness to undertake multiple imputation by chained equations. As sensitivity analyses, we repeated models in those with complete data and after controlling for prior exacerbations. As an exploratory analysis, we considered an interaction between socio-environmental condition and sleep quality. Results After adjustment for all co-variates, increasing PSQI scores (range 0–21) were associated with a 5% increased risk for exacerbation per point (p = .001) in the imputed dataset. Sensitivity analyses using complete cases and after controlling for prior exacerbation history were similar. Exploratory analysis suggested less effect among those who lived in poor-quality neighborhoods (p-for-interaction = .035). Conclusions Poor sleep quality may contribute to future exacerbations among patients with COPD. This represents one target for improving disease control. Clinical Trial Registration Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS). ClinicalTrials.gov Identifier# NCT01969344. Registry URL: https://clinicaltrials.gov/ct2/show/.