Effects of long-term macrolide therapy at low doses in stable COPD

Background: Chronic obstructive pulmonary disease (COPD) is currently the fourth largest fatal disease in the world, and is expected to rise to third place by 2020. Frequent acute exacerbations lead to increased mortality. Some suggestions for prophylactic use of macrolides in preventing COPD exacerbations have been raised, but there are still several issues that need to be addressed, such as target population, the course of treatment, therapeutic dose, and so on. Objective: To evaluate, via exploratory meta-analysis, the efficacy of long-term macrolide therapy at low doses in stable COPD. Methods: A systematic literature search was performed in PubMed, Embase, and Cochrane database from inception to March 28, 2019. Randomized controlled trials (RCT) which reported long-term use of macrolides in prevention of COPD were eligible. Results: A total of 10 articles were included in this study. It was found that there was a 23% relative risk reduction in COPD exacerbations among patients taking macrolides compared to placebo (P<0.01). The median time to first exacerbation was effectively prolonged among patients taking macrolides vs placebo (P<0.01). Sub-group analysis showed erythromycin was advantageous and older patients were less responsive to macrolides. Conclusions: Long-term low dose usage of macrolides could significantly reduce the frequency of the acute exacerbation of COPD. The treatment was well tolerated, with few adverse reactions, but it was not suitable for the elderly. It is recommended that this treatment regimen could be used in patients with GOLD grading C or D, because they have a higher risk of acute exacerbation and mortality. It needs to be further discussed whether this treatment should last for 12 months or longer.