COPD With Lung Cancer Among Older United States Adults: Prevalence, Diagnostic Timeliness, and Association With Earlier Stage Tumors.

Rationale: Chronic obstructive pulmonary disease (COPD) is a common comorbidity among patients with lung cancer, and an important determinant of their outcomes, however, it is commonly underdiagnosed. Objective: Our objective was to estimate the prevalence of COPD among a cohort of U.S. lung cancer patients, the timing of a COPD diagnosis relative to their lung cancer diagnosis, and the association between an earlier diagnosis of COPD and stage of lung cancer, with consideration of patient sociodemographic modifying factors. Methods: We conducted an analysis of the Medicare-linked Surveillance, Epidemiology, and End Results database including patients aged 68+ years who were diagnosed with lung cancer between 2008 to 2017. Exposure: Prevalence of COPD was identified using claims and subclassified based on the timing of its diagnosis relative to the lung cancer diagnostic episode-"preexisting" if diagnosed > 3 months before lung cancer, and "concurrent" if diagnosed around the same time as the lung cancer (+/-3 months). Outcome: The stage of cancer at diagnosis (early versus late) was the outcome. Results: Among 159,542 patients with lung cancer, 73.5% had COPD. Among those with COPD, 34.4% were diagnosed within 3 months of their lung cancer diagnosis and considered to have "concurrent COPD." We observed a positive association between preexisting COPD diagnosis and early-stage lung cancer (prevalence ratio= 1.27; 95% confidence interval= 1.23-1.30), in adjusted models which were stronger for male, non-Hispanic Black, and Hispanic patients. Conclusions: Seven out of 10 patients with lung cancer have COPD, however, many do not receive their COPD diagnosis until around the time of their lung cancer diagnosis. Among these patients, an early COPD diagnosis may improve early detection of lung cancer.

From Invisibility to Inclusion: A Call to Action to Address COPD Disparities in the Lesbian, Gay, Bisexual, Transgender, and Queer+ Community.

COPD is a significant cause of morbidity and mortality both in the United States and worldwide. Lesbian, gay, bisexual, transgender, or queer + (LGBTQ+) individuals (the plus sign indicates inclusion of people who are questioning, intersex, asexual, or who hold other gender/sex/romantic identities not specifically identified) have a higher rate of tobacco smoking, predisposing them to an increased risk of developing COPD. Despite this risk, the burden of COPD in LGBTQ+ individuals is not known. Moreover, there is limited focus on efforts to identify and reduce disease risk in this population. In this perspective, we present the results of a focused literature review of COPD in LGBTQ+ populations. We found only 8 studies that reported the prevalence of COPD in different subgroups of the LGBTQ+ population. All studies found an increased prevalence of COPD in the studied LGBTQ+ sub-groups compared to their heterosexual and/or cisgender counterparts. We propose a 3-pronged call to action to improve the care of LGBTQ+ people with COPD. First, we must improve awareness and education about COPD in the LGBTQ+ community through the effective development and dissemination of educational resources to LGBTQ+ people and their health care providers. Second, we call for prevention and intervention efforts through targeted tobacco cessation initiatives and case-finding via screening spirometry among symptomatic LGBTQ+ smokers. Finally, well-designed cohort studies are required to better characterize the COPD burden among LGBTQ+ populations. With targeted approaches in these 3 areas, we can improve the health of this vulnerable population, historically marginalized by current COPD research efforts.

Longitudinal Follow-Up of Participants With Tobacco Exposure and Preserved Spirometry.

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 [FEV1] 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 (FEV1) 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 FEV1 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 FEV1 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.

HIV-associated lung disease.

Lung disease encompasses acute, infectious processes and chronic, non-infectious processes such as chronic obstructive pulmonary disease, asthma and lung cancer. People living with HIV are at increased risk of both acute and chronic lung diseases. Although the use of effective antiretroviral therapy has diminished the burden of infectious lung disease, people living with HIV experience growing morbidity and mortality from chronic lung diseases. A key risk factor for HIV-associated lung disease is cigarette smoking, which is more prevalent in people living with HIV than in uninfected people. Other risk factors include older age, history of bacterial pneumonia, Pneumocystis pneumonia, pulmonary tuberculosis and immunosuppression. Mechanistic investigations support roles for aberrant innate and adaptive immunity, local and systemic inflammation, oxidative stress, altered lung and gut microbiota, and environmental exposures such as biomass fuel burning in the development of HIV-associated lung disease. Assessment, prevention and treatment strategies are largely extrapolated from data from HIV-uninfected people. Smoking cessation is essential. Data on the long-term consequences of HIV-associated lung disease are limited. Efforts to continue quantifying the effects of HIV infection on the lung, especially in low-income and middle-income countries, are essential to advance our knowledge and optimize respiratory care in people living with HIV.

Impact of Marijuana Smoking on COPD Progression in a Cohort of Middle-Aged and Older Persons.

Background: Limited data are available regarding marijuana smoking's impact on the development or progression of chronic obstructive pulmonary disease (COPD) in middle-aged or older adults with a variable history of tobacco cigarette smoking. Methods: We divided ever-tobacco smoking participants in the SubPopulations and InteRmediate Outcomes In COPD Study (SPIROMICS) into 3 groups based on self-reported marijuana use: current, former, or never marijuana smokers (CMSs, FMSs or NMSs, respectively). Longitudinal data were analyzed in participants with ≥2 visits over a period of ≥52 weeks. Measurements: We compared CMSs, FMSs, and NMSs, and those with varying amounts of lifetime marijuana use. Mixed effects linear regression models were used to analyze changes in spirometry, symptoms, health status, and radiographic metrics; zero-inflated negative binomial models were used for exacerbation rates. All models were adjusted for age, sex, race, baseline tobacco smoking amount, and forced expiratory volume in 1 second (FEV1) %predicted. Results: Most participants were followed for ≥4 years. Annual rates of change in FEV1, incident COPD, respiratory symptoms, health status, radiographic extent of emphysema or air trapping, and total or severe exacerbations were not different between CMSs or FMSs versus NMSs or between those with any lifetime amount of marijuana use versus NMSs. Conclusions: Among SPIROMICS participants with or without COPD, neither former nor current marijuana smoking of any lifetime amount was associated with evidence of COPD progression or its development. Because of our study's limitations, these findings underscore the need for further studies to better understand longer-term effects of marijuana smoking in COPD.

Association of Occupational Exposures and Chronic Obstructive Pulmonary Disease Morbidity.

OBJECTIVE: The aim of the study is to determine whether aggregate measures of occupational exposures are associated with chronic obstructive pulmonary disease (COPD) outcomes in the Subpopulations and Intermediate Outcome Measures in COPD study cohort. METHODS: Individuals were assigned to six predetermined exposure hazard categories based on self-reported employment history. Multivariable regression, adjusted for age, sex, race, current smoking status, and smoking pack-years determined the association of such exposures to odds of COPD and morbidity measures. We compared these with the results of a single summary question regarding occupational exposure. RESULTS: A total of 2772 individuals were included. Some exposure estimates, including "gases and vapors" and "dust and fumes" exposures resulted in associations with effect estimates over two times the estimated effect size when compared with a single summary question. CONCLUSIONS: Use of occupational hazard categories can identify important associations with COPD morbidity while use of single-point measures may underestimate important differences in health risks.

Lung Function in Women With and Without Human Immunodeficiency Virus.

BACKGROUND: Prior studies have found that human immunodeficiency virus (HIV) infection is associated with impaired lung function and increased risk of chronic lung disease, but few have included large numbers of women. In this study, we investigate whether HIV infection is associated with differences in lung function in women. METHODS: This was a cross-sectional analysis of participants in the Women's Interagency HIV Study, a racially and ethnically diverse multicenter cohort of women with and without HIV. In 2018-2019, participants at 9 clinical sites were invited to perform spirometry. Single-breath diffusing capacity for carbon monoxide (DLCO) was also measured at selected sites. The primary outcomes were the post-bronchodilator forced expiratory volume in 1 second (FEV1) and DLCO. Multivariable regression modeling was used to analyze the association of HIV infection and lung function outcomes after adjustment for confounding exposures. RESULTS: FEV1 measurements from 1489 women (1062 with HIV, 427 without HIV) and DLCO measurements from 671 women (463 with HIV, 208 without HIV) met standards for quality and reproducibility. There was no significant difference in FEV1 between women with and without HIV. Women with HIV had lower DLCO measurements (adjusted difference, -0.73 mL/min/mm Hg; 95% confidence interval, -1.33 to -.14). Among women with HIV, lower nadir CD4 + cell counts and hepatitis C virus infection were associated with lower DLCO measurements. CONCLUSIONS: HIV was associated with impaired respiratory gas exchange in women. Among women with HIV, lower nadir CD4 + cell counts and hepatitis C infection were associated with decreased respiratory gas exchange.

Pulmonary Function Trajectories in People with HIV: Analysis of the Pittsburgh HIV Lung Cohort.

Rationale: Human immunodeficiency virus (HIV) infection is associated with chronic lung disease and impaired pulmonary function; however, longitudinal pulmonary function phenotypes in HIV are undefined. Objectives: To identify pulmonary function trajectories, their determinants, and outcomes. Methods: We used data from participants with HIV in the Pittsburgh HIV Lung Cohort with three or more pulmonary function tests between 2007 and 2020. We analyzed post-bronchodilator forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC, and diffusing capacity of the lung for carbon monoxide (DlCO) using group-based trajectory modeling to identify subgroups of individuals whose measurements followed a similar pattern over time. We examined the association between participant characteristics and trajectories using multivariable logistic regression. In exploratory adjusted analyses restricted to individuals with available plasma cytokine data, we investigated the association between 18 individual standardized cytokine concentrations and trajectories. We compared mortality, dyspnea prevalence, respiratory health status, and 6-minute-walk distance between phenotypes. Results: A total of 265 participants contributed 1,606 pulmonary function measurements over a median follow-up of 8.1 years. We identified two trajectories each for FEV1 and FVC: "low baseline, slow decline" and "high baseline, rapid decline." There were three trajectory groups for FEV1/FVC: "rapid decline," "moderate decline," and "slow decline." Finally, we identified two trajectories for DlCO: "baseline low" and "baseline high." The low baseline, slow decline FEV1 and FVC, rapid decline, and moderate decline FEV1/FVC, and baseline low DlCO phenotypes were associated with increased dyspnea prevalence, worse respiratory health status, and decreased 6-minute-walk distance. The baseline low DlCO phenotype was also associated with worse mortality. Current smoking and pack-years of smoking were associated with the adverse FEV1, FEV1/FVC, and DlCO phenotypes. Detectable viremia was the only HIV marker associated with the adverse DlCO phenotype. C-reactive protein and endothelin-1 were associated with the adverse FEV1 and FVC phenotypes, and endothelin-1 trended toward an association with the adverse DlCO phenotype. Conclusions: We identified novel, distinct longitudinal pulmonary function phenotypes with significant differences in characteristics and outcomes. These findings highlight the importance of lung dysfunction over time in people with HIV and should be validated in additional cohorts.

Optimal Lung Cancer Screening Criteria Among Persons Living With HIV.

BACKGROUND: The US Preventive Services Task Force (USPSTF) 2021 updated recommendations on lung cancer screening with chest computed tomography to apply to individuals 50-80 years of age (previously 55-80 years), with a ≥20 pack-year history (previously ≥30), whether currently smoking or quit ≤15 years ago. Despite being at higher risk for lung cancer, persons with HIV (PWH) were not well-represented in the National Lung Screening Trial, which informed the USPSTF 2013 recommendations. It is unknown or unclear how PWH are affected by the 2021 recommendations. SETTING: This study was a retrospective analysis of PWH with and without lung cancer in the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study. METHODS: We identified PWH, ages 40-80 years, who currently or previously smoked, with (cases) and without lung cancer (noncases). The sensitivity and specificity of the old, new, and alternative screening criteria were evaluated in each cohort. RESULTS: We identified 52 women and 19 men with lung cancer and 1950 women and 1599 men without lung cancer. Only 11 women (22%) and 6 men (32%) with lung cancer met 2013 screening criteria; however, more women (22; 44%) and men (12; 63%) met 2021 criteria. Decreased age and tobacco exposure thresholds in women further increased sensitivity of the 2021 criteria. CONCLUSIONS: The 2021 USPSTF lung cancer screening recommendations would have resulted in more PWH with lung cancer being eligible for screening at the time of their diagnosis. Further investigation is needed to determine optimal screening criteria for PWH, particularly in women.

Significance of FEV3/FEV6 in Recognition of Early Airway Disease in Smokers at Risk of Development of COPD: Analysis of the SPIROMICS Cohort.

BACKGROUND: Small airways are known to be affected early in the course of COPD; however, traditional spirometric indices may not accurately identify small airways disease. RESEARCH QUESTION: Can forced expiratory volume in 3 s/forced expiratory volume in 6 s (FEV3/FEV6) identify early airflow abnormalities and predict future clinically important respiratory-related outcomes, including development of COPD? STUDY DESIGN AND METHODS: The study included 832 current and former smokers with post-bronchodilator FEV1/FVC ≥ 0.7 from the Subpopulations and Intermediate Outcome Measures in COPD Study (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 less than the LLN at baseline, defined as reduced compared with FEV3/FEV6 at or above the LLN, was associated with lower FEV1, poorer health status (St. George's Respiratory Questionnaire score), more emphysema, and more functional small airways disease on quantitative imaging. FEV3 and FEV6 showed excellent agreement between repeat measurements. A reduced FEV3/FEV6 was associated with increased odds of a severe respiratory exacerbation within the first year of follow-up and decreased time to first exacerbation. A low FEV3/FEV6 was also associated with development of COPD according to spirometry results (post-bronchodilator FEV1/FVC < 0.7) during study follow-up. INTERPRETATION: FEV3/FEV6 is a routinely available and repeatable spirometric index that 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. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT01969344; URL: www. CLINICALTRIALS: gov: ClinicalTrials.gov.

Bronchoalveolar Lavage and Plasma Cathelicidin Response to 25-Hydroxy Vitamin D Supplementation: A Pilot Study.

INTRODUCTION: Cathelicidin is a vitamin D-regulated, antimicrobial peptide involved in the innate immune response of the airways. Reduced plasma cathelicidin concentrations are independently associated with worse pulmonary outcomes in current and former smokers. This study aimed to determine whether oral vitamin D supplementation in vitamin D-deficient current smokers increases plasma and bronchoalveolar lavage (BAL) cathelicidin levels. METHODS: Vitamin D-deficient (25-hydroxy vitamin D [25-OH vitamin D] <20 ng/ml) smokers (n=17) underwent collection of plasma and BAL for cathelicidin and 25-OH vitamin D measurements before and after 8 weeks of oral supplementation with 50,000 IU vitamin D3 weekly. Differences between baseline and 8-week levels of cathelicidin and 25-OH vitamin D in blood and BAL were assessed along with correlations between serum 25-OH vitamin D, plasma cathelicidin, and BAL cathelicidin. RESULTS: At baseline, there was no correlation between BAL and plasma cathelicidin. There was a significant increase in 25-OH vitamin D (median 17.0 to 43.3 ng/mL, p<0.001) after 8 weeks of vitamin D supplementation. There was no change in plasma cathelicidin (p=0.86), BAL cathelicidin (p=0.31), or BAL 25-OH vitamin D (p=0.89). There was no correlation between serum 25-OH vitamin D and either BAL or plasma cathelicidin post-supplementation. CONCLUSIONS: Oral vitamin D supplementation, while increasing serum 25-OH vitamin D levels, does not increase plasma or BAL cathelicidin levels in vitamin D-deficient, active smokers. The lack of increased BAL cathelicidin may be explained by multiple factors related to dosing, smoking effects, or putative mechanisms of engagement. Future studies are needed to determine the effects of vitamin D supplementation on lung and blood functional activity.

E-Cigarettes and Cardiopulmonary Health.

E-cigarettes have surged in popularity over the last few years, particularly among youth and young adults. These battery-powered devices aerosolize e-liquids, comprised of propylene glycol and vegetable glycerin, typically with nicotine, flavors, and stabilizers/humectants. Although the use of combustible cigarettes is associated with several adverse health effects including multiple pulmonary and cardiovascular diseases, the effects of e-cigarettes on both short- and long-term health have only begun to be investigated. Given the recent increase in the popularity of e-cigarettes, there is an urgent need for studies to address their potential adverse health effects, particularly as many researchers have suggested that e-cigarettes may pose less of a health risk than traditional combustible cigarettes and should be used as nicotine replacements. This report is prepared for clinicians, researchers, and other health care providers to provide the current state of knowledge on how e-cigarette use might affect cardiopulmonary health, along with research gaps to be addressed in future studies.

Ratio of FEV1/Slow Vital Capacity of < 0.7 Is Associated With Clinical, Functional, and Radiologic Features of Obstructive Lung Disease in Smokers With Preserved Lung Function.

BACKGROUND: Mild expiratory flow limitation may not be recognized using traditional spirometric criteria based on the ratio of FEV1/FVC. RESEARCH QUESTION: Does slow vital capacity (SVC) instead of FVC increase the sensitivity of spirometry to identify patients with early or mild obstructive lung disease? STUDY DESIGN AND METHODS: We included 854 current and former smokers from the Subpopulations and Intermediate Outcome Measures in COPD Study cohort with a postbronchodilator FEV1/FVC ≥ 0.7 and FEV1 % predicted of ≥ 80% at enrollment. We compared baseline characteristics, chest CT scan features, exacerbations, and progression to COPD (postbronchodilator FEV1/FVC, < 0.7) during the follow-up period between 734 participants with postbronchodilator FEV1/SVC of ≥ 0.7 and 120 with postbronchodilator FEV1/SVC < 0.7 at the enrollment. We performed multivariate linear and logistic regression models and negative binomial and interval-censored proportion hazards regression models adjusted for demographics and smoking exposure to examine the association of FEV1/SVC < 0.7 with those characteristics and outcomes. RESULTS: Participants with FEV1/SVC < 0.7 were older and had lower FEV1 and more emphysema than those with FEV1/SVC ≥ 0.7. In adjusted analysis, individuals with postbronchodilator FEV1/SVC < 0.7 showed a greater percentage of emphysema by 0.45% (95% CI, 0.09%-0.82%), percentage of gas trapping by 2.52% (95% CI, 0.59%-4.44%), and percentage of functional small airways disease based on parametric response mapping by 2.78% (95% CI, 0.72%-4.83%) at baseline than those with FEV1/SVC ≥ 0.7. During a median follow-up time of 1,500 days, an FEV1/SVC < 0.7 was not associated with total exacerbations (incident rate ratio [IRR], 1.61; 95% CI, 0.97-2.64), but was associated with severe exacerbations (IRR, 2.60; 95% CI, 1.04-4.89). An FEV1/SVC < 0.7 was associated with progression to COPD during a 3-year follow-up even after adjustment for demographics and smoking exposure (hazard ratio, 3.93; 95% CI, 2.71-5.72). We found similar results when we examined the association of prebronchodilator FEV1/SVC < 0.7 or FEV1/SVC less than the lower limit of normal with chest CT scan features and progression to COPD. INTERPRETATION: Low FEV1 to SVC in current and former smokers with normal spirometry results can identify individuals with CT scan features of COPD who are at risk for severe exacerbations and is associated with progression to COPD in the future. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01969344T4; URL: www.clinicaltrials.gov.

Changes in lung function among treated HIV-positive and HIV-negative individuals: analysis of the prospective AGEhIV cohort study.

BACKGROUND: The AGEhIV cohort study is a prospective cohort study evaluating the occurrence of age-related comorbidities in people living with and without HIV. We previously reported a lower forced vital capacity (FVC) in HIV-positive compared with HIV-negative participants in those without heavy smoking exposure at time of enrolment in the AGEhIV cohort study. In this study we evaluate longitudinal changes in spirometry indices in the same AGEhIV cohort accounting for smoking behaviour and other risk factors. METHODS: We obtained pre-bronchodilator spirometry measurements in AGEhIV cohort participants during biennial visits over a median of 5·9 years (IQR 5·7-6·0). Adjusted declines in forced expiratory volume in 1 s (FEV1), FVC, and FEV1/FVC ratio were modelled using linear mixed-effects models and compared by HIV status and smoking status. To evaluate whether changes in spirometry measurements could be driven by increased levels of chronic inflammation, we assessed associations between rates of FEV1 and FVC decline and CD4 and CD8 T-cell counts, and plasma concentrations of C-reactive protein (CRP), interleukin 6, soluble CD14, soluble CD163, and intestinal fatty-acid-binding protein in separate models. The study is registered at ClinicalTrials.gov, NCT01466582. FINDINGS: 500 HIV-positive and 481 HIV-negative participants were included with spirometry data from Oct 29, 2010, to Aug 14, 2018. HIV-positive participants were virally suppressed (<40 copies per mL) during 1627 (95%) study visits, and 159 (32%) HIV-positive and 183 (38%) HIV-negative participants had never smoked. Adjusted declines in FEV1 were 10·0 mL per year faster in HIV-positive non-smokers (95% CI 4·2 to 15·7, p=0·00066) compared with HIV-negative non-smokers, and 11·1 mL per year faster in HIV-positive smokers (95% CI 0·7 to 21·4, p=0·036) compared with HIV-negative smokers. In comparison, smoking was associated with a 16·4 mL per year steeper decline in FEV1 among HIV-positive participants (95% CI 8·0 to 24·7, p=0·00012), and 15·3 mL per year steeper decline among HIV-negative participants (95% CI 6·7-24·0, p=0·00052) compared with not smoking. Adjusted yearly declines in FEV1 and FVC, but not FEV1/FVC, were significantly greater in HIV-positive than HIV-negative participants overall (additional decline in HIV-positive participants, FEV1 10·5 mL per year [95% CI 4·7 to 16·3], p=0·00040; FVC 11·5 mL per year [2·8 to 20·3], p=0·0096; FEV1/FVC 0·07% per year [-0·05 to 0·19], p=0·26), with a similar observation for never-smokers (FEV1 6·0 mL per year [-1·8 to 13·7], p=0·13; FVC 9·1 mL per year [-3·0 to 21·1], p=0·14; FEV1/FVC ratio 0·00% per year [-0·18 to -0·18], p=0·97). Higher CRP concentrations during follow-up were associated with accelerated declines in FEV1 and FVC among HIV-positive participants but not among HIV-negative participants. INTERPRETATION: Treated HIV infection was associated with faster declines in both FEV1 and FVC, but not in the FEV1/FVC ratio. These changes were independent of smoking and might have been driven by ongoing interstitial or small airway damage, potentially related to increased inflammation. FUNDING: ZonMW, Aidsfonds, Gilead Sciences, ViiV Healthcare, Janssen Pharmaceuticals, Merck.

Mucus Plugs and Emphysema in the Pathophysiology of Airflow Obstruction and Hypoxemia in Smokers.

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: To relate image-based measures of mucus plugs and emphysema to measures of airflow obstruction and oxygenation in patients with COPD.Methods: We analyzed computed tomographic (CT) lung images and lung function in participants in the Subpopulations and Intermediate Outcome Measures in COPD Study. Radiologists scored mucus plugs on CT lung images, and imaging software automatically quantified emphysema percentage. Unadjusted and adjusted relationships between mucus plug score, emphysema percentage, and lung function were determined using regression.Measurements and Main Results: Among 400 smokers, 229 (57%) had mucus plugs and 207 (52%) had emphysema, and subgroups could be identified with mucus-dominant and emphysema-dominant disease. Only 33% of smokers with high mucus plug scores had mucus symptoms. Mucus plug score and emphysema percentage were independently associated with lower values for FEV1 and peripheral oxygen saturation (P < 0.001). The relationships between mucus plug score and lung function outcomes were strongest in smokers with limited emphysema (P < 0.001). Compared with smokers with low mucus plug scores, those with high scores had worse COPD Assessment Test scores (17.4 ± 7.7 vs. 14.4 ± 13.3), more frequent annual exacerbations (0.75 ± 1.1 vs. 0.43 ± 0.85), and shorter 6-minute-walk distance (329 ± 115 vs. 392 ± 117 m) (P < 0.001).Conclusions: Symptomatically silent mucus plugs are highly prevalent in smokers and independently associate with lung function outcomes. These data provide rationale for targeting patients with mucus-high/emphysema-low COPD in clinical trials of mucoactive treatments.Clinical trial registered with www.clinicaltrials.gov (NCT01969344).

A population-based estimate of the health care burden of obstructive sleep apnea using a STOP-BAG questionnaire in South Carolina.

STUDY OBJECTIVES: Population based estimates of obstructive sleep apnea (OSA) frequency and health impact are incomplete. The aim of this study was to determine the prevalence of risk factors for physician and sleep study diagnosed OSA among individuals in a state-based surveillance program. METHODS: Using questions inserted into the 2016 (n = 5,564) and 2017 (n = 10,884) South Carolina Behavioral Risk Factor Surveillance System of the Centers for Disease Control and Prevention, we analyzed the prevalence of physician diagnosed OSA and associated comorbidities. The validated STOP-BANG questionnaire without neck circumference (STOP-BAG) defined populations at moderate risk (score 3-4) and high risk (score 5-7). Statistical analysis using weighted prevalence and means and their 95% confidence intervals (CI) thus reflect population estimates of disease burden. RESULTS: The population-based prevalence of physician diagnosed OSA in South Carolina was 9.7% (95% CI: 9.0-10.4). However, the populations with moderate risk (18.5%, 95% CI: 17.3-19.8) and high risk (25.5%, 95% CI: 23.9-27.1) for OSA, as determined by the STOP-BAG questionnaire, were much higher. Compared to those at low risk for OSA, those at high risk were more often diagnosed with coronary heart disease, stroke, asthma, skin cancer, other cancers, chronic obstructive pulmonary disease, arthritis, depression, kidney disease, and diabetes (all P < .001). CONCLUSIONS: OSA is common and strongly associated with major comorbidities. As such, this public health crisis warrants more diagnostic and therapeutic attention. The STOP-BAG questionnaire provides a public health platform to monitor this disease.

Defining Chronic Mucus Hypersecretion Using the CAT in the SPIROMICS Cohort.

Background: Chronic cough and phlegm are frequently reported chronic obstructive pulmonary disease (COPD) symptoms. Prior research classified chronic mucus hypersecretion (CMH) based on the presence of these symptoms for ≥3 months, called chronic bronchitis (CB) if respiratory infection symptoms were present for 1-2 years (Medical Research Council [MRC] definition). We explored whether the COPD Assessment Test (CAT), a simple measure developed for routine clinical use, captures CMH populations and outcomes similarly to MRC and St. George's Respiratory Questionnaire (SGRQ) definitions. Methods: We identified CMH in the SPIROMICS COPD cohort using (a) MRC definitions, (b) SGRQ questions for cough and phlegm (both as most/several days a week), and (c) CAT cough and phlegm questions. We determined optimal cut-points for CAT items and described exacerbation frequencies for different CMH definitions. Moderate exacerbations required a new prescription for antibiotics/oral corticosteroids or emergency department visit; severe exacerbations required hospitalization. Results were stratified by smoking status. Results: In a population of 1431 participants (57% male; mean FEV1% predicted 61%), 47% and 49% of evaluable participants had SGRQ- or CAT-defined CMH, respectively. A cut-point of ≥2 for cough and phlegm items defined CMH in CAT. Among SGRQ-CMH+ participants, 80% were also defined as CMH+ by the CAT. CMH+ participants were more likely to be current smokers. A higher exacerbation frequency was observed for presence of CMH+ versus CMH- in the year prior to baseline for all CMH definitions; this trend continued across 3 years of follow-up, regardless of smoking status. Conclusion: Items from the CAT identified SGRQ-defined CMH, a frequent COPD trait that correlated with exacerbation frequency. The CAT is a short, simple questionnaire and a potentially valuable tool for telemedicine or real-world trials. CAT-based CMH is a novel approach for identifying clinically important characteristics in COPD that can be ascertained in these settings.

Castleman flare or COPD exacerbation- can biomarkers override availability bias?

Effective treatments for human herpes virus 8 (HHV-8) associated multicentric Castleman disease (MCD) have led to prolonged survival for this complex systemic lymphoproliferative inflammatory disease. Nonetheless, significant challenges remain for the recognition of disease exacerbations, particularly when overlapping with common comorbid conditions. We present a case of a 60-year-old man with a 22-year history of MCD, current advanced COPD, and medication-controlled HIV. His recurrent presentations with flares of fatigue, worsening dyspnea, and productive cough were confusing to clinicians who were attempting to distinguish between exacerbations of MCD or COPD. Published biomarkers of MCD flare include HHV-8 and CRP, which were proposed by the patient to his clinicians as useful in guiding treatment. This case illustrates the value of patient insight as an antidote to the problem of availability bias.

Clinical Phenotypes of Atopy and Asthma in COPD: A Meta-analysis of SPIROMICS and COPDGene.

BACKGROUND: Little is known about the concordance of atopy with asthma COPD overlap. Among individuals with COPD, a better understanding of the phenotypes characterized by asthma overlap and atopy is needed to better target therapies. RESEARCH QUESTION: What is the overlap between atopy and asthma status among individuals with COPD, and how are categories defined by the presence of atopy and asthma status associated with clinical and radiologic phenotypes and outcomes in the Genetic Epidemiology of COPD Study (COPDGene) and Subpopulation and Intermediate Outcome Measures in COPD Study (SPIROMICS)? STUDY DESIGN AND METHODS: Four hundred three individuals with COPD from SPIROMICS and 696 individuals from COPDGene with data about specific IgEs to 10 common allergens and mixes (simultaneous assessment of combination of allergens in similar category) were included. Comparison groups were defined by atopic and asthma status (neither, atopy alone, atopic asthma, nonatopic asthma, with atopy defined as any positive specific IgE (≥0.35 KU/L) to any of the 10 allergens or mixes and asthma defined as self-report of doctor-diagnosed current asthma). Multivariable regression analyses (linear, logistic, and zero inflated negative binomial where appropriate) adjusted for age, sex, race, lung function, smoking status, pack-years smoked, and use of inhaled corticosteroids were used to determine characteristics of groups and relationship with outcomes (exacerbations, clinical outcomes, CT metrics) separately in COPDGene and SPIROMICS, and then adjusted results were combined using meta-analysis. RESULTS: The prevalence of atopy was 35% and 36% in COPD subjects from SPIROMICS and COPDGene, respectively, and less than 50% overlap was seen between atopic status with asthma in both cohorts. In meta-analysis, individuals with nonatopic asthma had the most impaired symptom scores (effect size for St. George's Respiratory Questionnaire total score, 4.2; 95% CI, 0.4-7.9; effect size for COPD Assessment Test score, 2.8; 95% CI, 0.089-5.4), highest risk for exacerbations (incidence rate ratio, 1.41; 95% CI, 1.05-1.88) compared with the group without atopy or asthma. Those with atopy and atopic asthma were not at increased risk for adverse outcomes. INTERPRETATION: Asthma and atopy had incomplete overlap among former and current smokers with COPD in COPDGene and SPIROMICS. Nonatopic asthma was associated with adverse outcomes and exacerbation risk in COPD, whereas groups having atopy alone and atopic asthma had less risk.