Enlarged Pulmonary Artery Signals Risk for COPD Exacerbation

September 28, 2012 (Vienna, Austria) — The ratio of the diameter of the pulmonary artery to the diameter of the aorta is a metric that not only indicates arterial enlargement and possible pulmonary disease, it also identifies patients with chronic obstructive pulmonary disease (COPD) who are at risk of experiencing an exacerbation, a new study suggests.

A pulmonary artery:aorta (PA:A) ratio greater than 1 is significantly associated with a risk for future severe exacerbation; the association becomes stronger in patients with a high ratio plus a history of exacerbations, according to results presented here at the European Respiratory Society 2012 Annual Congress.

They findings were also published in the September 6 issue of the New England Journal of Medicine.

COPD exacerbations accelerate disease progression and the loss of lung capacity. Nearly half the patients with COPD who experience a severe exacerbation will die within 5 years of the exacerbation, making the identification of at-risk patients crucial.

J. Michael Wells MD, from the University of Alabama at Birmingham, and colleagues reasoned that because cardiovascular disease is a component of advanced COPD, cardiovascular factors such as the PA:A ratio might be an indicator of exacerbations. The PA:A ratio can be determined with computed tomography (CT), which is already used to screen for and detect lung cancer in smokers.

Current or past smokers with 10 pack-years or more of smoking and GOLD stages II to IV COPD were eligible for the trial. Data from 3464 patients participating in the COPDGene trial with complete CT scan data were analyzed using multivariate logistic regression. Patients were 45 to 80 years of age.

A PA:A ratio greater than 1 was significantly associated with a patient's history of severe exacerbations, with an odds ratio (OR) of 4.78 (95% confidence interval [CI], 3.43 to 6.65; P < .0001), and had the strongest association to exacerbation of all variables examined.

This ratio was also independently associated with increased risk for future exacerbations in both the trial cohort (OR, 3.44; 95% CI, 2.78 to 4.25; P < .0001) and an external validation cohort (OR, 2.80; 95% CI, 2.11 to 3.71; P < .0001).

"We do not know the exact mechanism of the increase in PA:A ratio," Dr. Wells told Medscape Medical News. "Pulmonary hypertension likely represents the majority of the cases of an elevated PA:A ratio, but other factors could also be responsible, such as heart failure, sleep apnea, thromboembolic disease, and obesity," he added.

"We are currently investigating the exact mechanism for developing a PA:A ratio greater than 1 and examining what changes exacerbations have in the PA:A ratio over time. I think the idea of addressing interventions to decrease BMI is great, and should improve other factors in overall patient health," he explained.

In an accompanying editorial, Matthew B. Stanbrook, MD, PhD, from the Asthma and Airway Centre of the University Health Network at the University of Toronto in Ontario, Canada, notes that there are existing medications that are expected to reduce the risk for exacerbations in patients with COPD, but there is no evidence that they will work in patients with increased artery size.

"It is unclear how COPD medications such as inhaled glucocorticoids, phospodiesterase-4 inhibitors, or macrolides, which reduce the risk of exacerbations primarily on the basis of their antiinflammatory properties, would be effective against exacerbations driven by heart disease, thromboembolic disease, or impaired pulmonary reserve," he writes.

"The editorial raises some important questions about the utility of the PA:A ratio," Dr. Wells told Medscape Medical News. "We know that subjects with an elevated PA:A ratio have the highest risk of hospitalization from exacerbation, regardless of the mechanism of developing the elevated PA:A ratio. We believe that an increased PA:A ratio reflects a unique phenotype of the COPD population, possibly serving as a composite of subjects with underlying cardiovascular trouble, sleep apnea, thromboembolic disease, obesity, etc," he said.

"While these subjects would not necessarily have more bronchitic symptoms, they may not be able to compensate for the increased cardiovascular demands in the event of an acute exacerbation — leading to hospitalization," he added. "Therefore, using medications such as azithromycin or roflumilast in an effort to reduce exacerbation risk would be reasonable in the group we know is at highest risk for exacerbation and hospitalization."

He pointed out that there is some suggestion that statin medications might reduce pulmonary arterial pressure in COPD and that the PA:A ratio might be a useful way to identify patients who derive the most benefit from this medication, although the trial to evaluate the actual response to statin therapy is ongoing and the true effect on exacerbations is unknown.

The study authors suggest that future studies test antiinflammatory agents as targeted therapy in COPD patients with a high PA:A ratio to determine the effect on exacerbations or the time to next exacerbation.

Dr. Stanbrook notes that CT scans are "costly and involve radiation exposure."

"We agree that performing CT scans solely in an effort to perform this measurement is not recommended, and it would be premature to suggest that providers start ordering CT scans for this purpose," Dr. Well explained. "However, as CT scans are now being increasingly used in smokers for lung cancer surveillance, we suggest that this metric could be performed without any additional cost to patients, at minimal effort of the CT interpreter, and would provide valuable information about future risk of exacerbation and hospitalization for these patients."

The COPDGene project is supported by grants from the National Heart, Lung, and Blood Institute (U01HL089897 and U01HL089856). The project is also supported by the COPD Foundation through contributions made to an industry advisory board comprised of AstraZeneca, Boehringer Ingelheim, Novartis, and Sepracor. Dr. Wells and Dr. Stanbrook have disclosed no relevant financial relationships.

N Engl J Med. 2012;367:913-921, 946-948. Abstract, Editorial

European Respiratory Society (ERS) 2012 Annual Congress Presented September 3, 2012.