Azithromycin is associated with increased survival in lung transplant recipients with bronchiolitis obliterans syndrome

Abstract

Background Previous studies have suggested that azithromycin improves lung function in lung transplant recipients with bronchiolitis obliterans syndrome (BOS). However, these studies did not include a non-treated BOS control cohort or perform survival analysis. This study was undertaken to estimate the effect of azithromycin treatment on survival in lung transplant recipients with BOS. Methods We conducted a retrospective cohort study of consecutive lung transplant recipients who developed BOS between 1999 and 2007. An association between azithromycin treatment and death was assessed using univariate and multivariable time-dependent Cox regression analysis. Results Of the 178 recipients that developed BOS in our study, 78 developed BOS after 2003 and were treated with azithromycin. The azithromycin treated and untreated cohorts had similar baseline characteristics. Univariate analysis demonstrated that azithromycin treatment was associated with a survival advantage and this beneficial treatment effect was more pronounced when treatment was initiated during BOS stage 1. Multivariable analysis demonstrated azithromycin treatment during BOS stage 1 (adjusted hazard ratio=0.23, p=0.01) and absolute FEV1 value at the time of BOS stage 1 (adjusted hazard ratio=0.52, p=0.003) were both associated with a decreased risk for death. Conclusion In lung transplant recipients with BOS stage 1, azithromycin treatment initiated before BOS stage 2 was independently associated with a significant reduction in the risk of death. This finding supports the need for a randomized controlled trial to confirm the impact of azithromycin on survival in lung transplant recipients.

Long-term macrolide treatment for chronic respiratory disease

“…Azithromycin treatment has also been associated with increased survival. In a large retrospective cohort study of lung transplant recipients (n5178), this beneficial effect was more pronounced when treatment was initiated during BOS stage 1 [87].…”

Lung Transplantation: Advances and Roadblocks in Treatment

“…(Davis et al 2003) Additionally, a retrospective study of transplant recipients with BOS identified a possible advantage of treatment with Azithromycin (Az), though the mechanism of action remains unclear. (Jain et al 2010) Patients with a higher initial neutrophil burden responded better to the treatment and had better outcomes. What is most interesting is the fact that azithromycin is a macrolide antibiotic, a class known to be inhibitors of matrix metalloproteinases.…”

International practical guidelines on diagnosis, prevention and treatment of bronchiolitis obliterans syndrome

“…Азитромицин. Положительный эффект азитромици на описан у ≈ 35-40 % больных СОБ, перенесших трансплантацию легких [25,26,[110][111][112][113][114][115][116], у некото рых возможна полная стабилизация ОФВ1. У боль ных с нейтрофилией БАС высока вероятность поло жительного эффекта от терапии азитромицином [25,26,114].…”

“…У больных с СОБ II ста дии летальность не снижалась [116]. В другом иссле довании при приеме азитромицина улучшилось со стояние у 40 % больных, среди которых летальность также снизилась (HR -0,96; 95% ный ДИ -0,95-0,98).…”