May 24, 2011 (Denver, Colorado) — The addition of daily azithromycin to conventional treatment for chronic obstructive pulmonary disease (COPD) significantly helps reduce acute exacerbations associated with the disease, according to research presented here at the American Thoracic Society 2011 International Conference.
Macrolide antibiotics such as azithromycin are known to have antimicrobial and immunomodulary effects that can benefit patients with cystic fibrosis and various other inflammatory airways diseases.
Studies evaluating the effect of antibiotics on acute exacerbations of COPD have been inconclusive, however, according to lead author Richard Albert, MD, from Denver Health, and chief of the Department of Medicine and professor at the University of Colorado Health Sciences Center in Denver.
"There have been 2 negative studies and 5 positive studies; however, the largest of the studies is only 109 patients, and all have issues with their study design," he said.
To further evaluate the potential of macrolide antibiotics to control adverse events in COPD (AECOPD), Dr. Albert and his colleagues conducted a prospective double-blind, placebo-controlled trial in which 1142 patients with a clinical diagnosis of COPD were randomized to receive either azithromycin 250 mg (n = 558) or placebo (n = 559) daily for 1 year.
Subjects were 40 years of age or older and were required to have an increased risk for AECOPDs. All were using supplemental oxygen or received systemic corticosteroids for an AECOPD in the previous year.
Patients with asthma, bronchiectasis, hepatic or renal insufficiency, resting tachycardia, a prolonged QTc, or predefined audiometric abnormalities were excluded.
The results showed a statistically significant difference in the amount of time from baseline to the first AECOPD between the 2 groups; the median time to the first exacerbation was 266 days in the azithromycin group and just 174 days in the placebo group, Dr. Albert reported.
The frequency of acute exacerbations between the 2 groups was also significantly different, with the azithromycin group experiencing 741 acute exacerbations, translating into 1.47 episodes per patient year, and the placebo group experiencing 900 exacerbations, or 1.84 episodes per patient year (P = .004).
"This was a highly statistically significant difference," Dr. Albert noted.
The results showed a significantly lower frequency of visits to the doctor's office in the azithromycin group; there were no differences in adverse events such as pneumonia, QT prolongation, or fatal events.
One area of concern, however, was higher rate of hearing decrements in the azithromycin than in the placebo group (25% vs 19%; P = .022).
Although the difference was statistically significant, Dr. Albert noted that the mean change in hearing decibels was "extremely small" — 0.7 decibels in the azithromycin group compared with no change in the placebo group at 3 months. There was no significant difference at 0 to 12 months."
He added that the research team received data indicating that the audiometry used might have overestimated the degree of hearing decrement. Similar hearing decrements were observed in the placebo group.
"We believe that while there are differences in the degree of differences in which azithromycin causes hearing disorders, we think we have overestimated that frequency in both groups," he said.
Michael S. Schechter, MD, associate professor, division of pediatric pulmonary, allergy, cystic fibrosis, and sleep at Emory University in Atlanta, Georgia, noted that chronic macrolide therapy has, as Dr. Albert mentioned, been used for other indications, and hearing decrements have not been widely reported.
"The reason that we can be comfortable that this is probably not a big concern, but likely a statistical aberration, is that chronic macrolide therapy has been used in a number of diseases (including cystic fibrosis, which is my area of interest)," he said. "And hearing loss has not, to my knowledge, been found to be a problem."
The study and abstract were funded by National Institutes of Health–National Heart, Lung, and Blood Institute grants. Dr. Albert and Dr. Schechter have disclosed no relevant financial relationships.
American Thoracic Society (ATS) 2011 International Conference: Abstract 22714. Presented May 17, 2011.
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