KEYSTONE, COLO. — Acute exacerbations of chronic obstructive pulmonary disease are a far more important driver of mortality than is generally appreciated.
Physicians often shrug off acute exacerbations of COPD as part of the natural course of the disease. Not so. There are several preventive therapies of proven efficacy, but to apply them most efficiently it's useful to turn to several large published studies that are instructive in identifying the high-risk subgroups, Dr. Barry Make said at a meeting on allergy and respiratory diseases.
“It's all about knowing how to prevent COPD exacerbations in the right COPD patient at the right time,” emphasized Dr. Make, director of pulmonary rehabilitation at National Jewish Health and professor of medicine at the University of Colorado, Denver.
He was senior author of a large Veterans Affairs study that brought to light the serious consequences of acute exacerbations. The retrospective study involved 51,353 COPD patients discharged after a severe exacerbation, defined as one entailing hospitalization (Chest 2007;132: 1748-55).
The key finding was that these patients had impressively high all-cause mortality: 21% over the subsequent year and 55% at 5 years. They also had COPD rehospitalization rates of 25% and 44% at 1 and 5 years, respectively. The greater the number of prior COPD hospitalizations, the higher the subsequent all-cause mortality.
Median survival after the index hospitalization was 4.2 years. The median length of stay during rehospitalization was 6.5 days. These hospitalizations are expensive; indeed, acute exacerbations account for the bulk of health care expenditures for COPD, which is arguably the costliest of all the respiratory diseases, Dr. Make said at the meeting, which was sponsored by the National Jewish Medical and Research Center.
Frequent COPD exacerbations also are an enormous burden on patients' health-related quality of life. This was underscored in a classic study in which patients with three or more exacerbations over the course of a year had a mean 14.8-point worse score on the St. George's Respiratory Questionnaire than those with 0–2 exacerbations (Am. J. Respir. Crit. Care Med. 1998;157:1418-22).
“There's nothing else that comes close to having that big an effect on quality of life,” said the pulmonologist, who noted that medications typically improve St. George's scores by only about 3.5 points.
The VA study showed that patients who have had a COPD exacerbation are at increased risk for another. In another study, British investigators showed that these recurrent exacerbations are not random events over time, but rather they cluster in such a way that the first 8 weeks after an initial exacerbation is a particularly high-risk period.
During 904 patient-years of follow-up in the British study, 27% of first exacerbations were followed by a discrete recurrent exacerbation within 8 weeks, despite what the investigators thought was full recovery from the first event (Am. J. Respir. Crit. Care Med. 2009;179:369-74).
The implication is that the first few weeks after an initial exacerbation are a particularly important time for monitoring, initiation of preventive therapy, and educating patients about early recognition of acutely worsening cough, dyspnea, and/or sputum in order to catch acute exacerbations early, Dr. Make said.
Another group at increased risk for acute exacerbations is patients with more severe COPD by the GOLD (Global Initiative for Chronic Obstructive Lung Disease) criteria.
Preliminary data from the National Heart, Lung, and Blood Institute's ongoing genetic epidemiology of COPD project show that roughly half of GOLD stage 3 patients have had an exacerbation within the past year, as have nearly 60% of those with stage 4 disease.
“If you want to target selected patients in your practice about information on what exacerbations are and how to prevent and treat them, the more severely diseased patients are the ones. But even among those with GOLD stage 1 COPD, 15% had an exacerbation within the previous year,” he said.
Diclosures: Dr. Make disclosed serving on advisory boards for Boehringer-Ingelheim, GlaxoSmithKline, AstraZeneca, Dey, Forest, Novartis, Nycomed, and Schering-Plough.