Diffusing Capacity and Mortality in Chronic Obstructive Pulmonary Disease.

Rationale : Chronic Obstructive Pulmonary Disease (COPD) mortality risk is often estimated using the BODE index (including body mass index, forced expiratory volume in one second (FEV1), dyspnea score, and six-minute walk distance). Diffusing capacity (DLCO) is a potential predictor of mortality that reflects physiology distinct from that in the BODE index. Objectives : This study evaluated DLCO as a predictor of mortality using participants from the COPDGene study. Methods : We performed time-to-event analyses of individuals with COPD (former/current smokers with FEV1/FVC <0.7) and DLCO measurements from the COPDGene Phase 2 visit. Cox proportional hazard methods were used to model survival, adjusting for age, sex, pack-years, smoking status, BODE index, computed tomography (CT) percent emphysema (low attenuation areas <-950 Hounsfield units), CT airway wall thickness, and history of cardiovascular or kidney diseases. C-statistics for models with DLCO and BODE score were used to compare discriminative accuracy. Results : Of 2329 participants, 378(16.8%) died during the follow-up period (median 4.9 years). In adjusted analyses, for every 10% decrease in DLCO %predicted, mortality increased by 29% (Hazard ratio 1.29, 95% CI 1.17 - 1.41, p<0.001). When compared to other clinical predictors, DLCO %predicted performed similarly to BODE (C-statistic DLCO 0.68, BODE 0.70), and the addition of DLCO to BODE improved its discriminative accuracy (C-statistic 0.71). Conclusions : Diffusing capacity, a measure of gas transfer, strongly predicted all-cause mortality in individuals with COPD, independent of BODE index and CT evidence of emphysema and airway wall thickness. These findings support inclusion of DLCO in prognostic models for COPD.