Long-Term Macrolides in Chronic Respiratory Diseases: Dusk or a New Dawn? A Narrative Review

Macrolides—especially azithromycin—have been increasingly investigated in chronic respiratory diseases for their combined antimicrobial, anti-inflammatory, and immunomodulatory properties. Randomized controlled trials have demonstrated significant reductions in exacerbation frequency in selected patient populations with bronchiectasis, COPD, and asthma, although benefits on lung function and quality of life are variable. Beyond these advantages, concerns remain regarding antimicrobial resistance and uncertainties about long-term safety. Different guidelines across various diseases therefore recommend cautious and selective use of macrolides, with attention to phenotype selection, while alternative or emerging options such as biologics and novel anti-inflammatory agents are reshaping the therapeutic landscape. In this narrative review, we analyze the evidence for macrolide therapy across major chronic respiratory diseases, highlighting both the enduring clinical relevance and the limitations of long-term macrolide therapy, and discussing whether these drugs are approaching their therapeutic dusk or could still open a new dawn for selected patients. To this end we researched EMBASE and PubMed for articles published in English between 2000 and 2020 with restrictions to original articles, and freely between 2021 and 2025.