Phenotypes and Trajectories of Tobacco-exposed Persons with Preserved Spirometry: Insights from Lung Volumes.

Among tobacco-exposed persons with preserved spirometry (TEPS), we previously demonstrated that different lung volume indices, specifically elevated total lung capacity (TLC) versus elevated ratio of functional residual capacity-to-TLC (FRC/TLC), identify different lung disease characteristics in the COPDGene cohort. Determine differential disease characteristics and trajectories associated with the lung volume indices among TEPS in the SPIROMICS cohort. We categorized TEPS (n=814) by tertiles (low, intermediate, high) of TLC or residual volume-to-TLC (RV/TLC) derived from baseline CT images, and then examined clinical and spirometric disease trajectories in mutually exclusive categories of participants with high TLC without high RV/TLC ([TLC]) versus high RV/TLC without high TLC ([RV/TLC]).

Vessel and Airway Characteristics in One-Year Computed Tomography-defined Rapid Emphysema Progression: SPIROMICS.

Rates of emphysema progression vary in chronic obstructive pulmonary disease (COPD), and the relationships with vascular and airway pathophysiology remain unclear. We sought to determine if indices of peripheral (segmental and beyond) pulmonary arterial dilation measured on computed tomography (CT) are associated with a 1-year index of emphysema (EI; percentage of voxels <-950 Hounsfield units) progression. Five hundred ninety-nine former and never-smokers (Global Initiative for Chronic Obstructive Lung Disease stages 0-3) were evaluated from the SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) cohort: rapid emphysema progressors (RPs;  = 188, 1-year ΔEI > 1%), nonprogressors ( = 301, 1-year ΔEI ± 0.

Lung Structure and Risk of Sleep Apnea in SPIROMICS.

Rationale: The SubPopulations and InteRmediate Outcome Measures in COPD Study (SPIROMICS) is a prospective cohort study that enrolled 2981 participants with the goal of identifying new chronic obstructive pulmonary disease (COPD) subgroups and intermediate markers of disease progression. Individuals with COPD and obstructive sleep apnea (OSA) experience impaired quality of life and more frequent exacerbations. COPD severity also associates with computed tomography scan-based emphysema and alterations in airway dimensions.

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).

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.

Impact of Bronchiectasis on COPD Severity and Alpha-1 Antitrypsin Deficiency as a Risk Factor in Individuals with a Heavy Smoking History.

Rationale: Bronchiectasis is common among those with heavy smoking histories, but risk factors for bronchiectasis, including alpha-1 antitrypsin deficiency, and its implications for COPD severity are uncharacterized in such individuals.

Objectives: To characterize the impact of bronchiectasis on COPD and explore alpha-1antitrypsin as a risk factor for bronchiectasis.

Methods: SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) participants (N=914; ages 40-80 years; ≥20-pack-year smoking) had high-resolution computed tomography (CT) scans interpreted visually for bronchiectasis, based on airway dilation without fibrosis or cicatrization.

Changes in Lung Volumes with Spirometric Disease Progression in COPD.

Background: Abnormal lung volumes representing air trapping identify the subset of smokers with preserved spirometry who develop spirometric chronic obstructive pulmonary disease (COPD) and adverse outcomes. However, how lung volumes evolve in early COPD as airflow obstruction develops remains unclear.

Methods: To establish how lung volumes change with the development of spirometric COPD, we examined lung volumes from the pulmonary function data (seated posture) available in the U.

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.

Bronchodilator Responsiveness in Tobacco-Exposed People With or Without COPD.

Background: Bronchodilator responsiveness (BDR) in obstructive lung disease varies over time and may be associated with distinct clinical features.

Research Question: 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?

Study Design And Methods: 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 FEV (FEV-BDR), change in FVC (FVC-BDR), and change in in FEV, FVC or both (ATS-BDR).

Black carbon content in airway macrophages is associated with increased severe exacerbations and worse COPD morbidity in SPIROMICS.

Background: Airway macrophages (AM), crucial for the immune response in chronic obstructive pulmonary disease (COPD), are exposed to environmental particulate matter (PM), which they retain in their cytoplasm as black carbon (BC). However, whether AM BC accurately reflects environmental PM exposure, and can serve as a biomarker of COPD outcomes, is unknown.

Methods: We analyzed induced sputum from participants at 7 of 12 sites SPIROMICS sites for AM BC content, which we related to exposures and to lung function and respiratory outcomes.

Bronchodilators in Tobacco-Exposed Persons with Symptoms and Preserved Lung Function.

Background: Many persons with a history of smoking tobacco have clinically significant respiratory symptoms despite an absence of airflow obstruction as assessed by spirometry. They are often treated with medications for chronic obstructive pulmonary disease (COPD), but supporting evidence for this treatment is lacking.

Methods: We randomly assigned persons who had a tobacco-smoking history of at least 10 pack-years, respiratory symptoms as defined by a COPD Assessment Test score of at least 10 (scores range from 0 to 40, with higher scores indicating worse symptoms), and preserved lung function on spirometry (ratio of forced expiratory volume in 1 second [FEV] to forced vital capacity [FVC] ≥0.

Association Among Chronic Obstructive Pulmonary Disease Severity, Exacerbation Risk, and Anxiety and Depression Symptoms in the SPIROMICS Cohort.

Background: 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.

Objective: To determine the relationship among COPD symptom severity, exacerbation risk, and clinically significant anxiety and depression symptoms in ever smokers with COPD.

Ambient ozone effects on respiratory outcomes among smokers modified by neighborhood poverty: An analysis of SPIROMICS AIR.

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.

Forced Expiratory Flow at 25%-75% Links COPD Physiology to Emphysema and Disease Severity in the SPIROMICS Cohort.

Background: Forced expiratory volume in 1 second (FEV) is central to the diagnosis of chronic obstructive pulmonary disease (COPD) but is imprecise in classifying disease burden. We examined the potential of the maximal mid-expiratory flow rate (forced expiratory flow rate between 25% and 75% [FEF]) as an additional tool for characterizing pathophysiology in COPD.

Objective: To determine whether FEF helps predict clinical and radiographic abnormalities in COPD.

Comparative Impact of Depressive Symptoms and FEV% on Chronic Obstructive Pulmonary Disease.

Individuals with chronic obstructive pulmonary disease (COPD) have a high prevalence of depression, which is associated with increased COPD hospitalizations and readmissions. Examine the impact of depressive symptoms compared with FEV% on COPD morbidity. 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% respectively.

Polycythemia is Associated with Lower Incidence of Severe COPD Exacerbations in the SPIROMICS Study.

Secondary polycythemia has long been recognized as a consequence of chronic pulmonary disease and hypoxemia and is associated with lower mortality and fewer hospitalizations among individuals with chronic obstructive pulmonary disease (COPD)-prescribed long-term oxygen therapy. This study investigates the association of polycythemia with COPD severity, phenotypic features, and respiratory exacerbations in a contemporary and representative sample of individuals with COPD. Current and former smokers with COPD (forced expiratory volume in 1 second [FEV] to forced vital capacity [FVC] ratio <70%) without a history of hematologic/oncologic disorders were selected from the SubPopulations and InteRmediate Outcomes Measures In COPD Study (SPIROMICS), a multi-center observational cohort.

Longitudinal Imaging-Based Clusters in Former Smokers of the COPD Cohort Associate with Clinical Characteristics: The SubPopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS).

Purpose: Quantitative computed tomography (qCT) imaging-based cluster analysis identified clinically meaningful COPD former-smoker subgroups (clusters) based on cross-sectional data. We aimed to identify progression clusters for former smokers using longitudinal data.

Patients And Methods: We selected 472 former smokers from SPIROMICS with a baseline visit and a one-year follow-up visit.

Airway mucin MUC5AC and MUC5B concentrations and the initiation and progression of chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort.

Background: We previously described the contributions of increased total airway mucin concentrations to the pathogenesis and diagnosis of the chronic bronchitic component of chronic obstructive pulmonary disease (COPD). Here, we investigated the relative contribution of each of the major airway gel-forming mucins, MUC5AC and MUC5B, to the initiation, progression, and early diagnosis of airways disease in COPD.

Methods: SPIROMICS was a multicentre, observational study in patients aged 40-80 years recruited from six clinical sites and additional subsites in the USA.

Racial Segregation and Respiratory Outcomes among Urban Black Residents with and at Risk of Chronic Obstructive Pulmonary Disease.

Racial residential segregation has been associated with worse health outcomes, but the link with chronic obstructive pulmonary disease (COPD) morbidity has not been established. To investigate whether racial residential segregation is associated with COPD morbidity among urban Black adults with or at risk of COPD. 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.

The influence of social support on COPD outcomes mediated by depression.

Background: The purpose of this study was to explore the association between perceived social support and COPD outcomes and to determine whether the associations are mediated by depressive symptoms.

Methods: Subjects with COPD who were enrolled as part of SPIROMICS were included in this analysis. Questionnaires relating to quality of life, symptom burden, and functional status were administered at annual clinic visits for over a 3 year period.

Latent traits of lung tissue patterns in former smokers derived by dual channel deep learning in computed tomography images.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and the traditional variables extracted from computed tomography (CT) images may not be sufficient to describe all the topological features of lung tissues in COPD patients. We employed an unsupervised three-dimensional (3D) convolutional autoencoder (CAE)-feature constructor (FC) deep learning network to learn from CT data and derive tissue pattern-clusters jointly. We then applied exploratory factor analysis (EFA) to discover the unobserved latent traits (factors) among pattern-clusters.