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.

Erratum: Structural and Functional Features on Quantitative Chest Computed Tomography in the Korean Asian versus the White American Healthy Non-Smokers.

This corrects the article on p. 20 in vol. 1236, PMID: 31270987.

The Effects of Rare Variants on Lung Function and Emphysema in SPIROMICS.

The role of PI (protease inhibitor) type Z heterozygotes and additional rare variant genotypes in the gene encoding alpha-1 antitrypsin, (serpin peptidase inhibitor, clade A, member 1), in determining chronic obstructive pulmonary disease risk and severity is controversial. To comprehensively evaluate the effects of rare variants on lung function and emphysema phenotypes in subjects with significant tobacco smoke exposure using deep gene resequencing and alpha-1 antitrypsin concentrations. DNA samples from 1,693 non-Hispanic white individuals, 385 African Americans, and 90 Hispanics with ≥20 pack-years smoking were resequenced for the identification of rare variants (allele frequency < 0.

Imaging-based clusters in former smokers of the COPD cohort associate with clinical characteristics: the SubPopulations and intermediate outcome measures in COPD study (SPIROMICS).

Background: Quantitative computed tomographic (QCT) imaging-based metrics enable to quantify smoking induced disease alterations and to identify imaging-based clusters for current smokers. We aimed to derive clinically meaningful sub-groups of former smokers using dimensional reduction and clustering methods to develop a new way of COPD phenotyping.

Methods: An imaging-based cluster analysis was performed for 406 former smokers with a comprehensive set of imaging metrics including 75 imaging-based metrics.

Structural and Functional Features on Quantitative Chest Computed Tomography in the Korean Asian versus the White American Healthy Non-Smokers.

Objective: Considering the different prevalence rates of diseases such as asthma and chronic obstructive pulmonary disease in Asians relative to other races, Koreans may have unique airway structure and lung function. This study aimed to investigate unique features of airway structure and lung function based on quantitative computed tomography (QCT)-imaging metrics in the Korean Asian population (Koreans) as compared with the White American population (Whites).

Materials And Methods: QCT data of healthy non-smokers (223 Koreans vs.

Gene Expression Alterations in the Bronchial Epithelium of e-Cigarette Users.

Background: Although e-cigarette (ECIG) use has increased in the United States, their potential health effects remain uncertain. Understanding the effects of tobacco cigarette (TCIG) smoke on bronchial airway epithelial gene expression have previously provided insights into tobacco-related disease pathogenesis. Identifying the impact of ECIGs on airway gene expression could provide insights into their potential long-term health effects.

Lung Function, Coronary Artery Disease, and Mortality in HIV.

Impaired lung function is a potent independent predictor of coronary artery disease (CAD) in individuals without human immunodeficiency virus (HIV) infection; however, the relationship between lung function and CAD in HIV remains undefined. To examine the relationship between lung function, CAD, mortality, and circulating biomarkers in HIV. Spirometry, diffusing capacity of the lung for carbon monoxide (Dl), emphysema, coronary artery calcium, mortality, cause of death, and biomarkers were examined in HIV-infected and uninfected individuals enrolled in a cohort study at the University of Pittsburgh.

Safety and Tolerability of Comprehensive Research Bronchoscopy in Chronic Obstructive Pulmonary Disease. Results from the SPIROMICS Bronchoscopy Substudy.

Rationale: There is an unmet need to investigate the lower airways in chronic obstructive pulmonary disease (COPD) to define pathogenesis and to identify potential markers to accelerate therapeutic development. Although bronchoscopy is well established to sample airways in various conditions, a comprehensive COPD research protocol has yet to be published.

Objectives: To evaluate the safety and tolerability of a comprehensive research bronchoscopy procedure suitable for multicenter trials and to identify factors associated with adverse events.

Heterogeneous burden of lung disease in smokers with borderline airflow obstruction.

Background: The identification of smoking-related lung disease in current and former smokers with normal FEV is complex, leading to debate regarding using a ratio of forced expiratory volume in 1 s to forced vital capacity (FEV/FVC) of less than 0.70 versus the predicted lower limit of normal (LLN) for diagnosis of airflow obstruction. We hypothesized that the discordant group of ever-smokers with FEV/FVC between the LLN and 0.

Tropheryma whipplei colonization in HIV-infected individuals is not associated with lung function or inflammation.

Studies demonstrate that Tropheryma whipplei (T. whipplei) is present in the lungs of healthy individuals without acute respiratory symptoms or acute respiratory infection and is more common in the lungs of HIV-infected individuals and in smokers. The impact of T.

Imaging-based clusters in current smokers of the COPD cohort associate with clinical characteristics: the SubPopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS).

Background: Classification of COPD is usually based on the severity of airflow, which may not sensitively differentiate subpopulations. Using a multiscale imaging-based cluster analysis (MICA), we aim to identify subpopulations for current smokers with COPD.

Methods: Among the SPIROMICS subjects, we analyzed computed tomography images at total lung capacity (TLC) and residual volume (RV) of 284 current smokers.

Factors Associated With Progression of Lung Function Abnormalities in HIV-Infected Individuals.

Background: HIV is an independent risk factor for chronic obstructive pulmonary disease; however, baseline risk factors for lung function decline remain largely unknown in this population.

Methods: HIV-infected participants in the Pittsburgh Lung HIV Cohort with at least 3 pulmonary function measurements between 2007 and 2016 were included. Pulmonary function testing including postbronchodilator (BD) spirometry and diffusion capacity for carbon monoxide (DLco) was performed every 18 months.

Genome-wide association study of lung function and clinical implication in heavy smokers.

Background: The aim of this study is to identify genetic loci associated with post-bronchodilator FEV/FVC and FEV, and develop a multi-gene predictive model for lung function in COPD.

Methods: Genome-wide association study (GWAS) of post-bronchodilator FEV/FVC and FEV was performed in 1645 non-Hispanic White European descent smokers.

Results: A functional rare variant in SERPINA1 (rs28929474: Glu342Lys) was significantly associated with post-bronchodilator FEV/FVC (p = 1.

Measuring associations between the microbiota and repeated measures of continuous clinical variables using a lasso-penalized generalized linear mixed model.

Background: Human microbiome studies in clinical settings generally focus on distinguishing the microbiota in health from that in disease at a specific point in time. However, microbiome samples may be associated with disease severity or continuous clinical health indicators that are often assessed at multiple time points. While the temporal data from clinical and microbiome samples may be informative, analysis of this type of data can be problematic for standard statistical methods.

Sleep disruption as a predictor of quality of life among patients in the subpopulations and intermediate outcome measures in COPD study (SPIROMICS).

Study Objectives: Sleep quality is poor among patients with chronic obstructive pulmonary disease (COPD), and studies show that sleep disturbance is associated with low overall quality of life in this population. We evaluated the impact of patient-reported sleep quality and sleep apnea risk on disease-specific and overall quality of life within patients with COPD enrolled in the SPIROMICS study, after accounting for demographics and COPD disease severity.

Methods: Baseline data from 1341 participants [892 mild/moderate COPD (FEV1 ≥ 50% predicted); 449 severe COPD (FEV1 < 50%)] were used to perform three nested (blocks) regression models to predict quality of life (Short Form-12 mental and physical components and St.

Differentiation of quantitative CT imaging phenotypes in asthma versus COPD.

Introduction: Quantitative CT (QCT) imaging-based metrics have quantified disease alterations in asthma and chronic obstructive pulmonary disease (COPD), respectively. We seek to characterise the similarity and disparity between these groups using QCT-derived airway and parenchymal metrics.

Methods: Asthma and COPD subjects (former-smoker status) were selected with a criterion of post-bronchodilator FEV <80%.

Human airway branch variation and chronic obstructive pulmonary disease.

Susceptibility to chronic obstructive pulmonary disease (COPD) beyond cigarette smoking is incompletely understood, although several genetic variants associated with COPD are known to regulate airway branch development. We demonstrate that in vivo central airway branch variants are present in 26.5% of the general population, are unchanged over 10 y, and exhibit strong familial aggregation.

Fungi stabilize connectivity in the lung and skin microbial ecosystems.

Background: No microbe exists in isolation, and few live in environments with only members of their own kingdom or domain. As microbiome studies become increasingly more interested in the interactions between microbes than in cataloging which microbes are present, the variety of microbes in the community should be considered. However, the majority of ecological interaction networks for microbiomes built to date have included only bacteria.

Decreased Lung Function and All-Cause Mortality in HIV-infected Individuals.

Rationale: Human immunodeficiency virus (HIV) infection is associated with pulmonary disease and worse lung function, but the relationship of lung function with survival in HIV is unknown.

Objectives: To determine whether lung function is associated with all-cause mortality in HIV-infected individuals.

Methods: HIV-infected participants from cohorts in three locations underwent pre- and post-bronchodilator spirometry and determination of single-breath diffusing capacity of the lung for carbon monoxide (Dl) in 2008-2009, computed tomographic (CT) scanning of the chest for quantitative emphysema and airway measures, and echocardiography for estimated left ventricular systolic and diastolic function and tricuspid regurgitant velocity.

Association of sputum and blood eosinophil concentrations with clinical measures of COPD severity: an analysis of the SPIROMICS cohort.

Background: Increased concentrations of eosinophils in blood and sputum in chronic obstructive pulmonary disease (COPD) have been associated with increased frequency of exacerbations, reduced lung function, and corticosteroid responsiveness. We aimed to assess whether high eosinophil concentrations in either sputum or blood are associated with a severe COPD phenotype, including greater exacerbation frequency, and whether blood eosinophils are predictive of sputum eosinophils.

Methods: We did a multicentre observational study analysing comprehensive baseline data from SPIROMICS in patients with COPD aged 40-80 years who had a smoking history of at least 20 pack-years, recruited from six clinical sites and additional subsites in the USA between Nov 12, 2010, and April 21, 2015.

Variability in objective and subjective measures affects baseline values in studies of patients with COPD.

Rationale: Understanding the reliability and repeatability of clinical measurements used in the diagnosis, treatment and monitoring of disease progression is of critical importance across all disciplines of clinical practice and in clinical trials to assess therapeutic efficacy and safety.

Objectives: Our goal is to understand normal variability for assessing true changes in health status and to more accurately utilize this data to differentiate disease characteristics and outcomes.

Methods: Our study is the first study designed entirely to establish the repeatability of a large number of instruments utilized for the clinical assessment of COPD in the same subjects over the same period.

Respiratory Symptoms Items from the COPD Assessment Test Identify Ever-Smokers with Preserved Lung Function at Higher Risk for Poor Respiratory Outcomes. An Analysis of the Subpopulations and Intermediate Outcome Measures in COPD Study Cohort.

Rationale: Ever-smokers without airflow obstruction scores greater than or equal to 10 on the COPD Assessment Test (CAT) still have frequent acute respiratory disease events (exacerbation-like), impaired exercise capacity, and imaging abnormalities. Identification of these subjects could provide new opportunities for targeted interventions.

Objectives: We hypothesized that the four respiratory-related items of the CAT might be useful for identifying such individuals, with discriminative ability similar to CAT, which is an eight-item questionnaire used to assess chronic obstructive pulmonary disease impact, including nonrespiratory questions, with scores ranging from 0 to 40.

Assessment of coronary artery calcium by chest CT compared with EKG-gated cardiac CT in the multicenter AIDS cohort study.

Rationale: Individuals with HIV are at increased risk for coronary artery disease (CAD). Early detection of subclinical CAD by assessment of coronary artery calcium (CAC) may help risk stratify and prevent CAD events in these individuals. However, the current standard to quantify CAC i.

Use of rosuvastatin in HIV-associated chronic obstructive pulmonary disease.

Objectives: Chronic obstructive pulmonary disease (COPD) is more prevalent in HIV-infected individuals and is associated with persistent inflammation. Therapies unique to HIV are lacking. We performed a pilot study of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor rosuvastatin to determine effects on lung function.