Abstract: Introduction: Azithromycin (AZI) may be an effective immune modulator in lung transplant (LT) recipients, and can decrease chronic lung allograft dysfunction (CLAD) rates, the leading cause of mortality after the first year post-LT. The aim of the study is to assess the effect of AZI initiation and its timing on the incidence and severity of CLAD in LT recipients. Methods: Single-center retrospective study, including LT recipients from 01/01/2011 to 30/06/2020. Four groups were established: those who started AZI at the 3rd week post-LT (group A), those who received AZI later than the 3rd week post-LT and had preserved FEV1 (B), those who did not receive AZI (C) and those who started AZI due to a decline in FEV1 (D). The dosage of AZI prescribed was 250 mg three times per week. CLAD was defined and graduated according to the 2019 ISHLT criteria. Results: We included 358 LT recipients: 139 (38.83%) were in group A, 94 (26.25%) in group B, 91 (25.42%) in group C, and 34 (9.50%) in group D. Group A experienced the lowest CLAD incidence and severity at 1 (p = 0.01), 3 (p < 0.001), and 5 years post-LT, followed by Group B. Groups C and D experienced a higher incidence and severity of CLAD (p = 0.015). Initiation of AZI prior to FEV1 decline (groups A and B) proved to be protective against CLAD after adjusting for differences between the treatment groups. Conclusions: Early initiation of AZI in LT recipients could have a role in decreasing the incidence and severity of CLAD. In addition, as long as FEV1 is preserved, initiating AZI at any time could also be useful to prevent the incidence of CLAD and reduce its severity. This article is protected by copyright. All rights reserved.

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