Macrolide therapy for the prevention of acute exacerbations in chronic obstructive pulmonary disease

Acute exacerbations are a major contributor to health care costs and a leading cause of death in patients with chronic obstructive pulmonary disease (COPD). A reduction in acute exacerbations of COPD (AECOPD) would lead to significant improvements in patient well-being and survival. Bacterial and viral infections cause a majority of AECOPD episodes; however, with the exception of influenza and pneumococcal vaccines, preventative therapies for exacerbations do not directly address these infectious causes of AECOPD. Antibiotics were shown to have marginal benefit in preventing AECOPD several decades ago; however, since then, pathogens and antibiotics have changed substantially. Macrolides display immunomodulatory and anti-inflammatory effects in addition to their direct antibacterial effect. Several studies have examined macrolides in AECOPD prevention, with a recent landmark study by Albert et al. clearly demonstrating the efficacy of azithromycin in preventing AECOPD. Unfortunately, the rate of isolation of macrolide-resistant pathogens does increase with such treatment. Macrolides could also suppress bacterial colonization and thus decrease airway inflammation, thereby interrupting the vicious cycle of inflammation and infection in COPD. COPD patients with two or more exacerbations a year in spite of appropriate standard therapy are potential candidates for this therapeutic approach. However, optimal duration and dosing of macrolide prophylaxis for AECOPD remains uncertain.