Long-Term Azithromycin for Bronchiolitis Obliterans Syndrome After Lung Transplantation

• Published in: Transplantation Vol. 85; no. 1; pp. 36 - 41
• Main Authors: GOTTLIEB, Jens, SZANGOLIES, Jennifer, KOEHNLEIN, Thomas, GOLPON, Heiko, SIMON, André, WELTE, Tobias
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott 15-01-2008
• Subjects: Administration, Oral; Adult; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - therapeutic use; Azithromycin - administration & dosage; Azithromycin - therapeutic use; Biological and medical sciences; Bronchiolitis Obliterans - drug therapy; Bronchiolitis Obliterans - etiology; Bronchiolitis Obliterans - physiopathology; Chronic obstructive pulmonary disease, asthma; Cohort Studies; Disease Progression; Dose-Response Relationship, Drug; Female; Forced Expiratory Volume - physiology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Kaplan-Meier Estimate; Lung Transplantation - adverse effects; Male; Medical sciences; Middle Aged; Pneumology; Severity of Illness Index; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Tissue, organ and graft immunology; Treatment Outcome; Respiratory disease; Lung; Azithromycin; Transplantation; Homotransplantation; Respiratory system; Macrolide; Long term; Syndrome; Antibiotic; Treatment; Surgery; Bronchus disease; Graft; Bronchiolitis obliterans; Protein synthesis inhibitor; Antibacterial agent
• ISSN: 0041-1337; 1534-6080
• DOI: 10.1097/01.tp.0000295981.84633.bc

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.
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.
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).
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.