Patients with Chronic Obstructive Pulmonary Disease (COPD) and tracheostomy are at high risk for exacerbations and hospitalizations. Macrolide treatment has shown to reduce exacerbations in moderate-to-severe COPD. To evaluate the safety and the efficacy of long-term azithromycin use in outpatients with severe COPD and tracheostomy. A multicenter, randomized, uncontrolled, pilot trial evaluating the safety and the efficacy of azithromycin 500 mg three day-a-week for 6 months (AZI) vs. standard of care (SC) in severe COPD outpatients with tracheostomy. Patients were monitored for six months of treatment plus six months of follow up. The primary outcome was the reduction in the number of exacerbations and hospitalizations. A total of 22 patients was randomized (11 to SC and 11 to AZI). Patients in AZI had a significant lower cumulative number of exacerbations after the first 3 months of treatment when compared to patients in SC (p = 0.001), as well as hospitalizations (p = 0.02). Kaplan-Meier survival curves for time to first exacerbation showed a significant reduction in AZI of the rates of first exacerbation when compared to SC (log rank test = 12.14, p < 0.001), as well as to first hospitalization (log-rank = 4.09, p = 0.04). Azithromycin significantly improved the quality of life in comparison to SC. No serious adverse events in the AZI group were reported. Long-term azithromycin treatment seems to be safe and effective in severe COPD outpatients with tracheostomy in reducing exacerbations, hospitalizations, as well as in improving quality of life.
