Pulmonary arterial enlargement and acute exacerbations of COPD

Abstract

Background: Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with accelerated loss of lung function and death. Identification of patients at risk for these events, particularly those requiring hospitalization, is of major importance. Severe pulmonary hypertension is an important complication of advanced COPD and predicts acute exacerbations, though pulmonary vascular abnormalities also occur early in the course of the disease. We hypothesized that a computed tomographic (CT) metric of pulmonary vascular disease (pulmonary artery enlargement, as determined by a ratio of the diameter of the pulmonary artery to the diameter of the aorta [PA:A ratio] of >1) would be associated with severe COPD exacerbations.

Methods: We conducted a multicenter, observational trial that enrolled current and former smokers with COPD. We determined the association between a PA:A ratio of more than 1 and a history at enrollment of severe exacerbations requiring hospitalization and then examined the usefulness of the ratio as a predictor of these events in a longitudinal follow-up of this cohort, as well as in an external validation cohort. We used logistic-regression and zero-inflated negative binomial regression analyses and adjusted for known risk factors for exacerbation.

Results: Multivariate logistic-regression analysis showed a significant association between a PA:A ratio of more than 1 and a history of severe exacerbations at the time of enrollment in the trial (odds ratio, 4.78; 95% confidence interval [CI], 3.43 to 6.65; P<0.001). A PA:A ratio of more than 1 was also independently associated with an increased risk of future severe exacerbations in both the trial cohort (odds ratio, 3.44; 95% CI, 2.78 to 4.25; P<0.001) and the external validation cohort (odds ratio, 2.80; 95% CI, 2.11 to 3.71; P<0.001). In both cohorts, among all the variables analyzed, a PA:A ratio of more than 1 had the strongest association with severe exacerbations.

Conclusions: Pulmonary artery enlargement (a PA:A ratio of >1), as detected by CT, was associated with severe exacerbations of COPD. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov numbers, NCT00608764 and NCT00292552.).

Figure 1. Measurement of the Diameters of the Pulmonary Artery and Aorta

Panel A shows an axial chest computed tomographic (CT) image at the level of the left and right main pulmonary arteries, obtained without the administration of contrast material. Measurements of the diameter of the main pulmonary artery (PA) and the diameter of the aorta (A) at the level of the bifurcation were used to calculate the PA:A ratio. In cases in which A was not uniform in diameter, two measurements were taken 90 degrees apart, and the larger diameter was used. Panel B is a digital three-dimensional reconstruction, in axial cross section, of the great vessels that shows the spatial relationship between PA and A. In Panel C, the three-dimensional reconstruction is overlaid on the axial CT image.

Figure 2. Relationship between the PA:A Ratio and Severe Exacerbations at Baseline and during Follow-up

A histogram shows the relationship between the PA:A ratio and the occurrence of severe exacerbations (those requiring hospitalization) at baseline and during follow-up in the COPDGene study. The rate of severe exacerbations of COPD is shown according to increments of 0.1-unit changes in the absolute PA:A ratio. The risk of severe exacerbation increased at a threshold PA:A ratio of 1. A similar pattern was observed in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) validation cohort.