Decreased Lymphocytic Bronchitis Severity in the Era of Azithromycin Prophylaxis

BACKGROUND. Large-airway lymphocytic inflammation (LB), assessed on endobronchial biopsies, has been associated with acute cellular rejection and chronic lung allograft dysfunction (CLAD). Azithromycin (AZI) prophylaxis has been used to prevent airway inflammation and subsequent CLAD, with inconsistent results. We hypothesized that AZI prophylaxis would be associated with reduced LB, changes in bronchoalveolar lavage (BAL) immune cell populations, and improved CLAD-free survival. METHODS. We compared frequencies of LB from endobronchial biopsies before (N = 1856) and after (N = 975) protocolized initiation of AZI prophylaxis at our center. LB was classified as none, minimal, mild, or moderate by histopathologic analysis. LB grades were compared using ordinal mixed-model regression. Corresponding automated BAL leukocyte frequencies were compared using mixed-effects modeling. The effect of AZI prophylaxis on CLAD-free survival was assessed by a Cox proportional hazards model adjusted for age, sex, ethnicity, transplant indication, and cytomegalovirus serostatus. RESULTS. Biopsies in the pre-AZI era had 2-fold increased odds (95% confidence interval, 1.5-2.7; P < 0.001) of higher LB grades. LB was associated with BAL neutrophilia in both eras. However, there was no difference in risk for CLAD or death between AZI eras (hazard ratio 1.3; 95% confidence interval, 0.7-2.0; P = 0.45). CONCLUSIONS. Decreased airway inflammation in the era of AZI prophylaxis may represent a direct effect of AZI therapy or reflect other practices or environmental changes. In this cohort, AZI prophylaxis was not associated with improved CLAD-free survival.