COPD Heterogeneity and Progression: Emphysema-Predominant and Non-Emphysema-Predominant Disease.

While variation in emphysema between COPD patients is well-recognized, clinically applicable definitions of emphysema-predominant (EPD) and non-emphysema-predominant (NEPD) subtypes have not been established. To study the clinical relevance of EPD and NEPD subtypes, we tested the association of these subtypes to prospective FEV1 decline and mortality in 3,427 subjects with GOLD spirometric grade 2-4 COPD at baseline in the COPDGene Study, an ongoing national multicenter study that started in 2007. NEPD was defined as airflow obstruction with <5% computed tomography (CT) quantitative densitometric emphysema at -950 Hounsfield units, and EPD was defined as airflow obstruction with >=10% CT emphysema. Mixed effects models for FEV1 demonstrated larger average annual FEV1 loss in EPD versus NEPD subjects (-10.2 ml/yr, p<0.001), and subtype-specific associations to FEV1 decline were identified. Cox proportional hazards models showed higher risk of mortality in EPD versus NEPD (HR 1.46, p<0.001). To determine whether the NEPD and EPD dichotomy is captured by previously described COPDGene subtypes, we used logistic regression and receiver-operator characteristic analysis to predict NEPD/EPD membership using these previous subtype definitions, which generally showed excellent discrimination with AUCs > 0.9. NEPD and EPD COPD subtypes capture important aspects of COPD heterogeneity and are associated with different rates of disease progression and mortality.