Supplementary Material for: Macrolide Therapy Decreases Chronic Obstructive Pulmonary Disease Exacerbation: A Meta-Analysis

Background: Macrolide antibiotics have anti-inflammatory effects, and long-term administration may reduce chronic obstructive pulmonary disease (COPD) exacerbations. Objective: To investigate the effects of long-term treatment of macrolide therapy for COPD. Methods: We searched the PubMed and Embase databases to identify randomized controlled trials that evaluated the effect of macrolide therapy (of at least 2 weeks) for COPD. The primary outcome assessed was the frequency of acute exacerbations during follow-up. Results: Six trials involving 1,485 COPD patients were included in the analysis. Analysis of the pooled data of all 6 trials showed that macrolide administration reduced the frequency of acute exacerbations of COPD [risk ratio (RR) = 0.62; 95% CI 0.43-0.89, p = 0.01]. Subgroup analysis showed that only erythromycin might be associated with decreased COPD exacerbations (erythromycin: p = 0.04, azithromycin: p = 0.22, clarithromycin: p = 0.18). Moreover, macrolide therapy for 3 months did not significantly reduce the number of exacerbations (p = 0.18), whereas a beneficial effect was conclusive in the 6-month (p = 0.009) and 12-month (p = 0.03) treatment subgroups. In addition, nonfatal adverse events were more frequent in the macrolide treatment groups than in the controls (RR = 1.32; 95% CI 1.06-1.64, p = 0.01). However, related clinical factors had no influence on the overall result (p = 0.19). There was no publication bias among the included trials. Conclusions: Macrolide therapy was effective and safe in decreasing the frequency of exacerbations in patients with COPD. Treatment might provide a significant benefit but only when therapy lasts more than 6 months.