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 index hospitalization was 4.2 years. Median length of stay during rehospitalization was 6.5 days. These hospitalizations are expensive. Acute exacerbations account for the bulk of health care expenditures for COPD, 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).
The VA study demonstrated that patients who've 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 such that the first 8 weeks after an initial exacerbation is a particularly high-risk period (Am. J. Respir. Crit. Care Med. 2009;179:369–74).
Dr. Make disclosed serving on advisory boards for Boehringer-Ingelheim, GlaxoSmithKline, AstraZeneca, Dey, Forest, Novartis, Nycomed, and Schering-Plough.
How to Keep COPD Under Check
Preventing acute exacerbations is a top priority in patients with chronic obstructive pulmonary disease, and physicians can draw on three types of medication and one nonpharmacologic therapy of proven benefit for this purpose.
Each of the two drugs with Food and Drug Administration approval for the prevention of acute exacerbations is supported by a multiyear randomized trial of roughly 6,000 patients, which is unusually large for the field of COPD, Dr. Make noted.
Tiotropium (Spiriva, Boehringer-Ingelheim), a long-acting anticholinergic bronchodilator, received FDA approval for this indication last December.
In the massive 4-year Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) trial, use of tiotropium resulted in a 14% reduction in the annual rate of moderate to severe exacerbations, compared with usual care (N. Engl. J. Med. 2008; 359:1543–54).
The other approved medication, fluticasone/salmeterol (Advair Diskus, GlaxoSmithKline), reduced moderate to severe exacerbations by 25% over 3 years in the Towards a Revolution in COPD Health (TORCH) trial (N. Engl. J. Med. 2007;356:775–89).
Long-acting beta-agonists are also of proven efficacy in preventing acute exacerbations, as shown in a large meta-analysis that demonstrated a 21% reduction in relative risk (JAMA 2003;290:2301–12), but they are not FDA approved for this purpose, he said.
Pulmonary rehabilitation—a comprehensive program of education and physical exercise—is also of proven benefit in reducing acute exacerbations. A meta-analysis of six trials involving 230 patients demonstrated that pulmonary rehab reduced by 74% the relative risk of severe exacerbations entailing hospital admission (Respir. Res. 2005;6:54).
“For those patients who refuse to take medications, this is something else they can do.” Pulmonary rehab, he stressed, is of value across the broad spectrum of COPD severity.
“I don't wait for patients to reach GOLD [Global Initiative for Chronic Obstructive Lung Disease] stage 3 or 4 to turn to pulmonary rehabilitation. … I use this therapy in most of my patients,” he said.