In COPD, larger pulmonary artery assoc. with severe exacerbations (NEJM)

Exacerbations of chronic obstructive pulmonary disease (COPD exacerbations) occur with wide variability in people with COPD, and no one really knows why. Respiratory infections, interactions with coexistent cardiovascular disease, and pulmonary embolism have all been implicated as causes of exacerbations. But some people with COPD experience exacerbations that are mild and infrequent, while others have repeated severe attacks requiring hospitalization. Factors like a history of past exacerbations, low lung function and GERD predict future attacks somewhat, but not very well.

After a detailed parsing of two large observational registries, J. Michael Wells, George Washko, Mark Dransfield et al found that the size of the main pulmonary artery — namely, if it is larger in diameter than the aorta — is highly predictive of future COPD exacerbations severe enough to require hospitalization. The finding, reported in the September 3, 2012 New England Journal of Medicine, could help identify people with COPD at high risk who might benefit from better coordinated care or disease management programs, and contribute to the understanding of COPD’s complex interactions with other medical conditions.

What They Did

Investigators used data from more than 3,500 patients enrolled in the COPDGene and ECLIPSE studies, with moderate to severe COPD who had baseline CT scans. Authors looked both backward and forward through time, collecting a past history of exacerbations prior to trial entry, and longitudinally/prospectively observing patients for ~2-3 years for COPD exacerbations.

The pulmonary artery was defined as either larger (at its point of bifurcation) than the aorta, or not, based on CT images. That binary outcome was regressed against the number of COPD exacerbations and various other variables. COPD exacerbations were identified by symptom diaries, but had to require prednisone or antibiotics (“mild-moderate”) or hospitalization (“severe COPD exacerbation”).

What They Found

Having an enlarged main pulmonary artery was highly associated with severe COPD exacerbations: it predicted a history of severe exacerbations prior to study entry (odds ratio of 7), and subsequent severe COPD exacerbations during longitudinal follow-up (odds ratio 4.56).

An enlarged main pulmonary artery was a better predictor of future severe COPD exacerbations than any other identifiable factor, including FEV1 and history of previous exacerbations.

The association between an enlarged main PA and milder COPD exacerbations (not requiring hospitalization) was much weaker, not reaching statistical significance.

An enlarged main pulmonary artery was also associated with worse COPD and with medical comorbidities including obesity, asthma, congestive heart failure, pulmonary embolism history, chronic hypoxemia, GERD, and obstructive sleep apnea.

What It Means

An enlarged pulmonary artery may predict severe COPD exacerbations in at least two ways. It may be evidence of more severe COPD itself, with pulmonary hypertension and cor pulmonale. In patients without end-stage COPD, an enlarged pulmonary artery is probably a marker of underlying cardiovascular disease, a major cause of hospitalization for dyspnea in its own right.

When a patient living with both cardiovascular disease and COPD (one or both of which are severe enough to cause remodeling of the pulmonary artery) is hospitalized for dyspnea, who among us is a skilled enough doctor to say precisely what is due to COPD vs. congestive heart failure? When they occur together, these two pathologies might interact in ways so complex that they could almost be thought of as a distinct medical condition.

Given the great diversity among people living with COPD, and the frequent disconnect between objective lung function and more important outcomes like exacerbations, daily dyspnea and exercise ability, having a measure that can better predict severe disease is helpful. It’s possible that identifying patients at high risk could result in more effective disease management programs (although the benefits of these are still under debate).

Some may read these findings and feel tempted to try vasodilators for presumed pulmonary hypertension on their patients with COPD and enlarged pulmonary arteries. But remember that vas0dilators have been studied in clinical trials of patients with COPD and pulmonary hypertension, that they can be very harmful, and are not recommended.

Wells JM et al. Pulmonary Arterial Enlargement and Acute Exacerbations of COPD. NEJM 2012; ePub September 3, 2012.