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Think of COPD as a multisystem disease.

SALT LAKE CITY -- It's high time to recognize that chronic obstructive pulmonary disease is a multisystem disorder extending well beyond the lungs, Dr. Stanley B. Fiel said at a satellite symposium held in conjunction with the annual meeting of the American College of Chest Physicians.

Chronic obstructive pulmonary disease (COPD) is best viewed as a systemic inflammatory disorder, not merely an inflammatory disorder of the respiratory tract. The extrapulmonary systems where COPD takes its heaviest toll are the cardiovascular, muscular, and skeletal.

Even among patients with severe COPD, only about one-quarter of deaths are due to COPD. Among those with moderate COPD, it's closer to 5%. The predominant cause of mortality in COPD patients is atherosclerotic cardiovascular disease, added Dr. Fiel, chairman of medicine at Morristown (N.J.) Memorial Hospital. He has served as a consultant to Altana Pharma, which sponsored the satellite symposium.

Cardiovascular Risk

Major contributions to understanding the association between COPD and cardiovascular risk have been provided by Dr. Don D. Sin of the University of British Columbia, Vancouver, and his coinvestigators. They showed in an analysis of 1,861 participants in the first National Health and Nutrition Examination Survey Epidemiologic Followup Study that a reduced forced expiratory volume in 1 second ([FEV.sub.1]) is a risk factor for cardiovascular hospitalization or mortality independent of smoking history, Framingham risk score, and other potential confounders. Individuals in the lowest [FEV.sub.1] quintile had a 5.6-fold increased risk of fatal ischemic heart disease, compared with those in the top quintile. That was true even across a relatively narrow range of [FEV.sub.1] declines, from a mean of 109% to 88% of predicted (Chest 2005;127:1952-9).

As part of the same report, the Canadian investigators conducted a meta-analysis of 12 large published cohort studies that looked at cardiovascular mortality based on [FEV.sub.1] in nearly 84,000 subjects. Those in the worst [FEV.sub.1] quintile had an adjusted 75% increased risk of cardiovascular mortality, compared with those in the best quintile.

"So why don't primary care physicians do more routine measuring of [FEV.sub.1]? It's a good question, since we know that just as blood pressure is an independent risk factor for cardiovascular mortality, so is [FEV.sub.1] in patients regardless of whether they smoke or don't smoke," Dr. Fiel said.

One major difference between high blood pressure and low [FEV.sub.1] as cardiovascular risk factors, however, is that as yet there are no prospective data demonstrating how to intervene effectively in COPD patients to reduce their cardiovascular risk, he conceded. Investigative interest in potential targets for preventive therapy is focused on the elevated levels of fibrinogen, neutrophils, platelets, and C-reactive protein that Dr. Sin and his coworkers documented in patients with stage 3 and 4 COPD (Circulation 2003;107:1514-9).

Bone Abnormalities

British investigators have reported a dual-energy x-ray absorptiometry study showing that osteoporosis or osteopenia was present in fully 89% of a group of COPD patients with an [FEV.sub.1] less than 50% of predicted, corresponding to Gold stage 3 or 4 disease. Among patients with COPD and an [FEV.sub.1] greater than 50% of predicted, osteoporosis or osteopenia was present in 69% (Am. J. Respir. Crit. Care Med. 2004;170:1286-93).

Other data have shown that the bone density abnormalities in COPD can't be explained away as being a result of prolonged use of corticosteroids. Such abnormalities are present in most steroid-naive patients with advanced COPD.

Skeletal Muscle Atrophy

Loss of fat-free mass in COPD patients is associated with reduced endurance, poor quality of life, and decreased exercise ability. Dutch researchers have reported the prevalence of abnormal body composition (low body mass index and/or low fat-free mass index) was 43% in women and 21% in men in a cohort of 389 outpatients with moderate to severe COPD (Respir. Med. 2006;100:1349-55). The intermediary between systemic inflammation and cachexia in COPD is thought to be the nuclear transcription factor, kappa beta, Dr. Fiel said.


Denver Bureau
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Title Annotation:Pulmonary Medicine; chronic obstructive pulmonary disease
Author:Jancin, Bruce
Publication:Family Practice News
Geographic Code:1USA
Date:Feb 15, 2007
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