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 1 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.
Gottlieb
Jens
J
Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany. gottlieb.jens@mh-hannover.de
Szangolies
Jennifer
J
Koehnlein
Thomas
T
Golpon
Heiko
H
Simon
André
A
Welte
Tobias
T
D000284:Administration, Oral; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D017963:Azithromycin / Q000008:administration & dosage / Q000627:therapeutic use*; D001989:Bronchiolitis Obliterans / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D015331:Cohort Studies; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D053208:Kaplan-Meier Estimate; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D017963:Azithromycin