Clinical and immunological evaluation of 12-month azithromycin therapy in chronic lung allograft rejection

Background: Bronchiolitis obliterans syndrome (BOS) is the leading cause of morbidity/mortality in lung-transplant recipients (LTRs). Recent studies demonstrated that azithromycin (AZI) can improve graft function in BOS. We here investigated whether a 12-month course of AZI could more efficiently impact the course of BOS if administered early in BOS development. Methods: Using a retrospective study, we examined AZI effects on graft function in 62 LTRs: 25 with potential BOS (BOS 0-p) and 37 with BOS grade 1-3. Response was defined as a≥10% FEV ₁ increase. Bronchoalveolar (BAL) neutrophilia and levels of IL-8, 8-isoprostane and other plasma cytokines were analyzed as parameters of lung or systemic inflammation. Results: After 12-month AZI, 13 patients were responders, 35 had graft function stabilization, and 14 further deteriorated. The frequency of responders was significantly higher in LTRs with BOS 0-p (44%) than in those with BOS grade 1-3 (6%). No association was found between BAL features and AZI response while a significant decrease in plasma levels of IL-8, MCP-1, I-309, MIP-1α, and TNF-α was detected. Conclusions: Long-term AZI can improve or stabilize lung graft function in LTRs with BOS, but the treatment impacts the course of the disease more efficiently if administered in BOS 0-p.