Pulmonary Arterial Pruning and Longitudinal Change in Percent Emphysema and Lung Function: The Genetic Epidemiology of COPD Study

Abstract

Background: Pulmonary endothelial damage has been shown to precede 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 imaging or decline in lung function over 5 years?

Study design and methods: The Genetic Epidemiology of COPD Study enrolled ever smokers with and without COPD from 2008 through 2011. The percentage of emphysema-like lung, or "percent emphysema," was assessed at baseline and after 5 years on noncontrast CT imaging as the percentage of lung voxels < -950 Hounsfield units. An automated CT imaging-based tool assessed and classified intrapulmonary arteries and veins. Spirometry measures are postbronchodilator. Pulmonary arterial pruning was defined as a lower ratio of small artery volume (< 5 mm2 cross-sectional area) to total lung artery volume. Mixed linear models included demographics, anthropomorphics, smoking, and COPD, with emphysema models also adjusting for CT imaging scanner and lung function models adjusting for clinical center and baseline percent emphysema.

Results: At baseline, the 4,227 participants were 60 ± 9 years of age, 50% were women, 28% were Black, 47% were current smokers, and 41% had COPD. Median percent emphysema was 2.1 (interquartile range, 0.6-6.3) and progressed 0.24 percentage points/y (95% CI, 0.22-0.26 percentage points/y) over 5.6 years. Mean FEV1 to FVC ratio was 68.5 ± 14.2% and declined 0.26%/y (95% CI, -0.30 to -0.23%/y). Greater pulmonary arterial pruning was associated with more rapid progression of percent emphysema (0.11 percentage points/y per 1-SD increase in arterial pruning; 95% CI, 0.09-0.16 percentage points/y), including after adjusting for baseline percent emphysema and FEV1. Arterial pruning also was associated with a faster decline in FEV1 to FVC ratio (-0.04%/y per 1-SD increase in arterial pruning; 95% CI, -0.008 to -0.001%/y).

Interpretation: Pulmonary arterial pruning was associated with faster progression of percent emphysema and more rapid decline in FEV1 to FVC ratio over 5 years in ever smokers, suggesting that pulmonary vascular differences may be relevant in disease progression.

Trial registry: ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov.

Keywords: emphysema; imaging; longitudinal; lung function; pulmonary circulation.

Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Figures

Graphical abstract

Figure 1

A, B, Pulmonary arteries and veins defined by a deep learning technique in selected participants with Global Initiative for Chronic Obstructive Lung Disease 2 COPD without pruning of small arteries (volume of pulmonary arteries less than 5 mm2 in cross-sectional area [BV5a] per total arterial volume of interparenchymal vessels [TBVa] ratio > 50th percentile) (A) and pruning of small arteries (BV5a per TBVa < 50th percentile) (B). Vessels are a 3-dimensional reconstruction with 2-dimensional CT image for anatomic landmarks. Blue = artery; green overlay = emphysematous lung areas; red = vein.

Figure 2

Stratified analyses of the mean difference in yearly progression of percentage of lung volume with attenuation –950) for a 1-SD increase in arterial pruning (decrease in volume of pulmonary arteries less than 5 mm2 in cross-sectional area per total arterial volume of interparenchymal vessels). Model adjusts for baseline age, sex, race, education, and COPD status and time-varying height, weight, and smoking status, except when stratified by the variables. Three-way interaction P values for age, race, BMI category, smoking status, and spirometric category and baseline percent emphysema were < .001; P = .015 for sex; and P = .145 pulmonary artery diameter to aorta diameter ratio (P = 0.064 for CT imaging scanner manufacturer; not shown). GOLD = Global Initiative for Chronic Obstructive Lung Disease.

Figure 3

Sensitivity analyses of the mean difference in yearly progression of percentage of lung volume with attenuation 2 in cross-sectional area per total arterial volume of interparenchymal vessels). Model adjusts for baseline age, sex, race, education, and COPD status and time-varying height, weight, smoking status, and scanner terms. PA/A = pulmonary artery diameter to aorta diameter ratio.