Heterogeneity and Progression of Chronic Obstructive Pulmonary Disease: Emphysema-Predominant and Non–Emphysema-Predominant Disease
Year: 2023
Type: article
Abstract: While variation in emphysema severity between patients with chronic obstructive pulmonary disease (COPD) is well-recognized, clinically applicable definitions of the emphysema-predominant disease (EPD) and non-emphysema-predominant disease (NEPD) subtypes have not been established. To study the clinical relevance of the EPD and NEPD subtypes, we tested the association of these subtypes with prospective decline in forced expiratory volume in 1 second (FEV1) and mortality among 3,427 subjects with Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometric grade 2-4 COPD at baseline in the Genetic Epidemiology of COPD (COPDGene) Study, an ongoing national multicenter study that started in 2007. NEPD was defined as airflow obstruction with less than 5% computed tomography (CT) quantitative densitometric emphysema at -950 Hounsfield units, and EPD was defined as airflow obstruction with 10% or greater CT emphysema. Mixed-effects models for FEV1 demonstrated larger average annual FEV1 loss in EPD subjects than in NEPD subjects (-10.2 mL/year; P < 0.001), and subtype-specific associations with FEV1 decline were identified. Cox proportional hazards models showed higher risk of mortality among EPD patients versus NEPD patients (hazard ratio = 1.46, 95% confidence interval: 1.34, 1.60; P < 0.001). To determine whether the NEPD/EPD dichotomy is captured by previously described COPDGene subtypes, we used logistic regression and receiver operating characteristic (ROC) curve analysis to predict NEPD/EPD membership using these previous subtype definitions. The analysis generally showed excellent discrimination, with areas under the ROC curve greater than 0.9. The NEPD and EPD COPD subtypes capture important aspects of COPD heterogeneity and are associated with different rates of disease progression and mortality.
Source: American Journal of Epidemiology
DOI: 10.1093/aje/kwad114
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Pfizer, AstraZeneca, Bayer, GlaxoSmithKline, Novartis, Brigham and Women's Hospital, COPD Foundation, Sunovion, Vertex Pharmaceuticals, National Jewish Health, National Institutes of Health, Genentech, Anschutz Medical Campus, University of Colorado, National Heart, Lung, and Blood Institute
Awards: G2168838001, Identifying functional variants in COPD GWAS loci, Systems Biology of Airway Disease, Genetic and Functional Dissection of a Cluster of COPD GWAS Signals on Chromosome 4q, Prospective Health Outcomes and Inflammatory Biomarkers Associated with e-Cigarette Use, G3842720522, G5258357286, G5326023800, (2 of 2) Genetic Epidemiology of COPD, G5960470374, Using Integrative Genomics To Identify and Characterize Emphysema-Associated eQTL, Identifying Protein-Protein Network Interactions between COPD Susceptibility Genes, (1 of 2) Genetic Epidemiology of COPD, G8354759825, G8643874822, G8819318481, G9000091268, G9000228787, COPD Susceptibility, Heterogeneity, and Progression: Proteomics and Genetics, Distinct and Overlapping Pathways of Fibrosis and Emphysema in Cigarette Smokers
OpenAlex ID: W4376122064