Pulmonary Arterial Pruning and Longitudinal Change in Percent Emphysema and Lung Function: the COPDGene Study.

BACKGROUND Pulmonary endothelial damage has been shown to preceed the development of emphysema in animals, and vascular changes in humans have been observed in COPD and emphysema. RESEARCH QUESTION Is intraparenchymal vascular pruning associated with longitudinal progression of emphysema on CT or decline in lung function over 5 years? STUDY DESIGN AND METHODS The COPDGene Study enrolled ever-smokers with and without COPD in 2008-2011. The percent of emphysema-like lung was assessed at baseline and after 5 years on non-contrast CT as the percentage of lung voxels <-950 Hounsfield units. An automated CT-based tool assessed and classified intrapulmonary arteries and veins. Spirometry measures are post-bronchodilator. Pulmonary arterial pruning was defined as a lower ratio of small artery volume (<5mm2 cross sectional area) to total lung artery volume. Mixed linear models included demographics, anthropomorphics, smoking and COPD; with emphysema models also adjusting for CT scanner and lung function models adjusting for clinical center and baseline percent emphysema. RESULTS At baseline the 4,227 participants were 60±9 years old, 50% female, 28% black, 47% current smokers and 41% had COPD. Median percent emphysema was 2.1 (IQR: 0.6, 6.3) and progressed 0.24 percentage points/year (95% CI: 0.22, 0.26) over 5.6 years. Mean FEV1/FVC was 68.5±14.2% and declined 0.26%/year (95% CI: -0.30, -0.23). Greater pulmonary arterial pruning was associated with more rapid progression of percent emphysema (0.11 percentage points/year per SD arterial pruning, 95% CI: 0.09, 0.16), including after adjusting for baseline percent emphysema and FEV1. Arterial pruning was also associated with a faster decline in FEV1/FVC (-0.04%/year per SD arterial pruning, 95% CI: -0.008, -0.001). INTERPRETATION Pulmonary arterial pruning was associated with faster progression of percent emphysema and more rapid decline in FEV1/FVC over 5 years in ever-smokers, suggesting pulmonary vascular differences may be relevant in disease progression.