Evaluating the efficacy and safety of macrolide therapy in primary ciliary dyskinesia

Vollständiger Abstract

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Background: Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by impaired ciliary function, defective mucociliary clearance, recurrent respiratory infections, and progressive respiratory morbidity. Macrolides, particularly azithromycin, have antibacterial, anti-inflammatory, and immunomodulatory properties and may therefore provide therapeutic benefit in PCD. This systematic review evaluated the efficacy and safety of macrolide therapy in patients with PCD. Methods: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines and was prospectively registered in International Prospective Register of Systematic Reviews (CRD42024553793). PubMed, Scopus, Web of Science, Embase, Cochrane, and Google Scholar were searched for studies published from January 1, 1990, to June 18, 2024. Eligibility criteria were defined using the population, intervention, comparator, outcomes, and study design framework. Study selection, data extraction, and risk of bias assessment were performed independently by 3 reviewers. A meta-analysis was not performed because of substantial methodological heterogeneity across the included studies. Results: Of 765 records identified, 9 studies met the inclusion criteria. These included 2 in vitro studies and 7 clinical studies, comprising case reports, case series, retrospective observational studies, and 1 randomized, placebo-controlled phase 3 trial. Across the clinical studies, sample sizes ranged from 1 to 90 participants. Overall, the available evidence suggested that macrolide therapy, particularly azithromycin, may reduce respiratory exacerbations and improve selected clinical symptoms in patients with PCD. Mechanistic in vitro evidence further indicated that azithromycin may reduce pro-inflammatory cytokine production and promote epithelial barrier repair. However, the included studies varied considerably in design, population characteristics, treatment protocols, and outcome definitions. Conclusion: Macrolides, especially azithromycin, may have a beneficial role in the management of PCD by reducing respiratory exacerbations, improving selected symptoms, and modulating airway inflammation. Nevertheless, the certainty of evidence remains limited by methodological heterogeneity, small sample sizes, and the scarcity of randomized controlled trials. Further large-scale, well-designed, PCD-specific clinical studies are required to confirm these preliminary findings and establish standardized treatment protocols.