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The Cornell and Stanford universities' statistical analysis of 22 trials with 15,276 participants found that common bronchodilators known as anticholinergics (generically named tiotropium and ipratropium) reduced severe respiratory events by 33 percent and respiratory-related deaths by 73 percent, compared with a placebo.

However, the same meta-analysis (which combines the results of the numerous studies) found that regularly inhaled beta-agonists (metaproterenol [Alupent], formoterol [Foradil], salmeterol [Serevent, Advair] and albuterol [Proventil, Ventolin, Volmax and others]) increased the risk of respiratory death more than twofold, compared with a placebo.

Yet only 5 percent of all prescriptions for COPD are anticholinergics, with beta-agonists dominating what doctors prescribe, the researchers report.

The study, now online, will be published in an upcoming issue of the Journal of General Internal Medicine.

COPD is a progressive lung disease characterized by difficulty breathing, wheezing and a chronic cough. Complications include bronchitis and pneumonia. It is often associated with smoking.

"When patients used the anticholinergics, they experienced fewer severe exacerbations requiring hospitalizations and fewer respiratory deaths than those taking only a placebo," said Edwin Salpeter, the J.G. White Distinguished Professor of Physical Sciences Emeritus at Cornell, who led the statistical analysis in the study. An eminent astrophysicist, Salpeter has more recently focused his attention on medical statistics. "With the beta-agonists, it's the other way around, where the number of respiratory deaths increased when compared with those who took only the placebo."

"These results suggest that anticholinergics should be the bronchodilator of choice in COPD," said Shelley Salpeter, M.D., Edwin Salpeter's daughter and the lead author. She is a clinical professor of medicine at Stanford's School of Medicine and a physician at Santa Clara Valley Medical Center in San Jose, Calif. "The long-term safety of beta-agonists in patients with COPD should be addressed."

A recent meta-analysis by the Salpeters also revealed that beta-agonist inhalers increased both hospitalizations and deaths in asthma sufferers of all ages.

Previous studies have shown that patients with COPD build up tolerance to beta-agonists' bronchodilator and bronchoprotective effects after regular treatment compared with the first dose.

While beta-agonists may reduce symptoms through bronchodilation, the researchers believe they also promote bronchial inflammation and sensitivity by reducing bronchial protection without any warning of increased symptoms, which can then lead to a life-threatening response.

In the trials that were analyzed, only two patients out of 4,036 who took anticholinergics died of respiratory causes, while 12 of 3,845 participants in the placebo group died of respiratory ailments. When patients inhaled beta-agonists, there were 21 respiratory deaths out of 1,320 patients and eight respiratory deaths out of 1,084 participants in the placebo group.

Contact: Krishna Ramanujan ksr32@cornell.edu 607-255-3290 Cornell University News Service

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