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COMBINATION THERAPY UTILIZING AZITHROMYCIN AND PHOTOPHERESIS FOR BRONCHIOLITIS OBLITERANS SYNDROME FOLLOWING LUNG TRANSPLANTATION

University of Alabama at Birmingham, Birmingham, AL

PURPOSE: Bronchiolitis obliterans syndrome (BOS) is an important cause of mortality following lung transplantation. At our institution, standard treatment of BOS includes photopheresis therapy (P) and modification of immunosuppression (IS). Recent studies suggest that macrolide antibiotics may improve lung function in patients with BOS, likely by immunomodulatory effects. We hypothesized that the addition of Azithromycin (A) to our standard BOS regimen may improve lung function and post-transplant survival, compared to the standard regimen alone.

METHODS: We retrospectively reviewed all lung transplant recipients at a tertiary center who underwent P for BOS from 1999-2006. Data collected include demographics, spirometry, post-transplant survival, and cause of death. The primary endpoints were survival from time of transplant and from BOS diagnosis. The secondary endpoint was change in FEV1 following BOS diagnosis. Survival was compared using Kaplan-Meier methods.

RESULTS: Of 51 BOS patients identified, 26 (51%) received P+IS therapy, while 25 (49%) received P+IS+A. Groups did not differ significantly in baseline characteristics, IS levels, time to BOS diagnosis, or FEV1 at BOS diagnosis. There was a survival advantage at 1 year after BOS diagnosis for the P+IS+A group (88% vs. 65%, with HR 0.28; [95% CI] 0.10-0.96; p=0.04); median survival from BOS diagnosis was 35.3 months for the P+IS group and 72.2 months for the P+IS+A group (HR 0.57; [95% CI] 0.26-1.23; p=0.16). Median post-transplant survival was 78.0 months for the P+IS group and 91.0 months for the P+IS+A group (HR 0.60; [95% CI] 0.28-1.30; p=0.20). Both groups had similar values for FEV1 and rates of decline of FEV1 at 6 and 12-months following treatment initiation.

CONCLUSION: We observe a survival advantage at 1 year following BOS diagnosis with P+IS+A, although FEV1 is not significantly altered.

CLINICAL IMPLICATIONS: Azithromycin may improve survival when administered for BOS; however, further studies are needed to determine the true impact of this treatment strategy.

DISCLOSURE: Amy Hajari, No Financial Disclosure Information; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. We will discuss the use of Azithromycin for bronchiolitis obliterans syndrome (BOS) after lung transplantation. Although this practice is widely accepted and employed at transplant programs, Azithromycin is not currently indicated for use in BOS.