The true balance of risks and benefits with use of azithromycin to prevent COPD exacerbations is unknown, but physicians who choose to prescribe … Niewoehner reports receiving grants from the NIH during the conduct of the study, and personal fees from Boehringer Ingelheim, AstraZeneca and GlaxoSmithKline, outside the submitted work.Conflict of interest: R.K. Albert has nothing to disclose.Conflict of interest: P.D. No other potential conflict of interest relevant to this article was reported.This article (10.1056/NEJMoa1104623) was updated on April 5, 2012, at NEJM.org.We thank Dr. Peter Henson for first suggesting the hypothesis tested in this study; Angela Keniston, M.S.P.H., for assistance with the statistical analysis; and Marianne Dieterich and Kris Richardson for assistance with susceptibility testing.The affiliations of the authors are listed in the Appendix.Address reprint requests to Dr. Albert at Denver Health, 777 Bannock St., MC 4000, Denver, CO 80204-4507, or at The authors' affiliations are as follows: the Medicine Service, Denver Health and Department of Medicine (R.K.A., C.S.P. The COPD Clinical Research Network is supported by a Cooperative Agreement from the Division of Lung Diseases of the NHLBI. Two of the studies showed no effect, but one of these used a retrospective designSince approximately 80% of our participants were taking inhaled glucocorticoids with or without long-acting betaNone of the previous studies of the effect of macrolides on acute exacerbations of COPD either assessed or reported hearing problems as a complication.Participants receiving azithromycin were less likely to become colonized with respiratory pathogens but were more likely to become colonized with macrolide-resistant organisms (contrary to the findings of Seemungal and colleaguesWe chose a 250-mg dose of azithromycin because we thought that it was high enough to limit the possibility that a negative result might occur because of insufficient dosing.


The European COPD Audit found that 35% of patients admitted with acute exacerbation of COPD (AECOPD) were readmitted within 90 days [2].

All of the authors participated in interpreting the results.



The protocol was designed by the first author and was modified on the basis of input from the remaining authors. The frequency of exacerbations was 1.48 exacerbations per patient-year in the azithromycin group, as compared with 1.83 per patient-year in the placebo group (P=0.01), and the hazard ratio for having an acute exacerbation of COPD per patient-year in the azithromycin group was 0.73 (95% CI, 0.63 to 0.84; P<0.001). A total of 66 of the participants in the azithromycin group (12%) and 172 in the placebo group (31%) who had not had nasopharyngeal colonization at the time of enrollment became colonized during the course of the study (P<0.001).
The IWT, BVP-SBP, and TEVA were not involved in the study design; the collection, analysis, and interpretation of data; writing of the manuscript; or the decision to submit the manuscript for publication.Author Contributions: The protocol was initiated by W.J., designed in collaboration with G.G.B., and modified on the basis of input from the Consortium.

The study results, which appear in the New England Journal of Medicine, show azithromycin may reduce the burden of COPD and improve the quality of life for patients.