Long-term azithromycin for bronchiolitis obliterans syndrome after lung transplantation

Background. Bronchiolitis obliterans syndrome (BOS) is a major cause of morbidity and mortality after lung transplantation (LTx). Macrolides are a promising treatment option for BOS. The objective of this study was to determine long-term results of azithromycin treatment in patients with BOS. Variables to predict treatment response were evaluated. Methods. An observational study in a single center was performed. Eighty-one adult LTx-recipients (single, double, combined, and re-do) with at least BOS stage 0p (mean forced expired volume in I second [FEV1] 55 +/- 19%) were included. For treatment, 250 mg of oral azithromycin was administered three times per week. Results. Twenty-four of 81 (30%) patients showed improvement in FEV1 after 6 months, 22/24 already after 3 months of treatment. By univariate analysis, responders at 6 months had higher pretreatment bronchoalveolar lavage (BAL) neutrophils (51 +/- 29 vs. 21 +/- 24%). A cutoff value of < 20% in pretreatment BAL had a negative predictive value of 0.91 for treatment response. Thirty-three patients (40%) showed disease progression during follow-up (491 +/- 165 days). Cox regression analysis identified a rapid pretreatment decline in FEV1 and comedication of an mammalian target of rapamycin inhibitor as positive predictors and proton pump inhibitor comedication and a treatment response at 3 months as negative predictors for disease progression (FEV1 < 90% baseline). Conclusions. Azithromycin can improve airflow limitation in a significant proportion of patients with even long-standing BOS. The majority of responders were identified after 3 months of treatment. Results indicate the predictive value of BAL neutrophilia for treatment response and pretreatment course of FEV1 as a variable for disease progression. Beneficial effects on gastroesophageal reflux disease may be a mechanism of action.