Stronger Associations of Centrilobular Than Paraseptal Emphysema With Longitudinal Changes in Diffusing Capacity and Mortality in COPD

BACKGROUND: The factors associated with longitudinal changes in diffusing capacity remain unclear among patients with COPD. Centrilobular emphysema (CLE) and paraseptal emphysema (PSE) are major emphysema subtypes that may have distinct clinical-physiological impacts in these patients. RESEARCH QUESTION: Are CLE and PSE differently associated with longitudinal changes in diffusing capacity and mortality in patients with COPD? STUDY DESIGN AND METHODS: This pooled analysis included 399 patients with COPD from two prospective observational COPD cohorts. CLE and PSE were visually assessed on CT scan according to the Fleischner Society statement. The diffusing capacity and transfer co-efficient of the lung for carbon monoxide (DLCO and KCO) and FEV1 were evaluated at least annually over a 5-year period. Mortality was recorded over 10 years. Longitudinal changes in FEV1, DLCO, and KCO and mortality were compared between mild or less severe and mod-erate or more severe CLE and between present and absent PSE in each Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage. RESULTS: The DLCO and KCO decline was weakly associated with FEV1 and greater in GOLD stage 3 or higher than in GOLD stages 1 and 2. Furthermore, moderate or more severe CLE, but not present PSE, was associated with steeper declines in DLCO for GOLD stages 1 and 3 or higher and KCO for all GOLD stages independent of age, sex, height, and smoking history. The moderate or more severe CLE, but not present PSE, was associated with additional FEV1 decline and higher 10-year mortality among patients with GOLD stage 3 or higher. INTERPRETATION: A CT scan finding of moderate or more severe CLE, but not PSE, was associated with a subsequent accelerated impairment in diffusing capacity and higher long-term mortality in severe GOLD stage among patients with COPD.