Prophylactic azithromycin for chronic lung allograft dysfunction following lung transplantation: a systematic review and meta-analysis.

Background: Azithromycin (AZI) has proven effective in improving pulmonary function and survival in certain patients with established chronic lung allograft dysfunction (CLAD) following lung transplantation (LTx), but its prophylactic effects on CLAD remain controversial. This study aimed to assess the outcomes of prophylactic AZI for CLAD following LTx.

Methods: A systematic review was conducted based on PubMed, Embase and Cochrane Library. All included studies reported the primary or secondary outcomes in the prophylactic azithromycin (pAZI) and control groups. The CLAD onset, disease-free survival and overall survival (OS) data were pooled using fixed-effect or random-effect models. Sensitivity analysis was employed to evaluate the robustness of the pooled results, while a funnel plot was utilized to assess the publication bias.

Results: Six eligible studies involving 1,251 LTx recipients were included. The pooled analysis revealed a lower risk of CLAD onset in the pAZI group compared to the control group [relative risk (RR) 0.64, 95% confidence interval (CI): 0.51-0.81, P<0.001]. Moreover, the pAZI group exhibited superiority in the 3-year [hazard ratio (HR) 0.57, 95% CI: 0.39-0.83, P=0.003] and 5-year CLAD-free survival (HR 0.61, 95% CI: 0.43-0.86, P=0.005); but this superiority was not observed in the 3-year (HR 0.69, 95% CI: 0.31-1.54, P=0.36) and 5-year OS (HR 0.59, 95% CI: 0.30-1.14, P=0.12).

Conclusions: Prophylactic AZI may reduce the risk of CLAD onset and improve 3- and 5-year CLAD-free survival, providing supporting evidence for its application in LTx community. More high-quality and well-designed studies are warranted to determine the prophylactic effects of AZI on CLAD and its phenotypes following LTx.