Original clinical science
Azithromycin is associated with increased survival in lung transplant recipients with bronchiolitis obliterans syndrome

https://doi.org/10.1016/j.healun.2009.12.003Get rights and content

Background

Previous studies have suggested that azithromycin improves lung function in lung transplant recipients with bronchiolitis obliterans syndrome (BOS). However, these studies did not include a non-treated BOS control cohort or perform survival analysis. This study was undertaken to estimate the effect of azithromycin treatment on survival in lung transplant recipients with BOS.

Methods

We conducted a retrospective cohort study of consecutive lung transplant recipients who developed BOS between 1999 and 2007. An association between azithromycin treatment and death was assessed using univariate and multivariate time-dependent Cox regression analysis.

Results

Of the 178 recipients who developed BOS in our study, 78 did so after 2003 and were treated with azithromycin. The azithromycin-treated and untreated cohorts had similar baseline characteristics. Univariate analysis demonstrated that azithromycin treatment was associated with a survival advantage and this beneficial treatment effect was more pronounced when treatment was initiated during BOS Stage 1. Multivariate analysis demonstrated azithromycin treatment during BOS Stage 1 (adjusted hazard ratio = 0.23, p = 0.01) and absolute forced expiratory volume in 1 second (FEV1) at the time of BOS Stage 1 (adjusted hazard ratio = 0.52, p = 0.003) were both associated with a decreased risk of death.

Conclusions

In lung transplant recipients with BOS Stage 1, azithromycin treatment initiated before BOS Stage 2 was independently associated with a significant reduction in the risk of death. This finding supports the need for a randomized, controlled trial to confirm the impact of azithromycin on survival in lung transplant recipients.

Section snippets

Study design

Institutional review board approval for this study was obtained prior to data acquisition. A retrospective review of medical records was conducted on consecutive adult patients (age ≥18 years) at WUSM/BJH who underwent lung transplantation between August 1, 1998 and June 30, 2004. Follow-up data were accrued on all eligible recipients until death or through January 1, 2008. Demographic and clinical characteristics were obtained from medical records and computerized databases. Recipients were

Cohort assembly and baseline comparison

Of the 297 patients who received a lung transplant at WUSM/BJH between August 1, 1998 and June 30, 2004, 106 were excluded because they did not develop BOS Stage 1 prior to January 1, 2008. During the follow-up period, 9 recipients were excluded due to death within 90 days of transplantation, and 3 were excluded because they did not have pulmonary function testing due to chronic tracheostomy. In our study population of 179 lung transplant recipients with BOS Stage ≥1, there were 95 patients who

Discussion

In this study, azithromycin treatment was associated with improved survival when analyzed as a time-dependent variable. This mortality benefit remained present even after adjusting for type of transplant, acute rejection scores, CARV infections, history of Pseudomonas in respiratory specimens, absolute FEV1 at BOS Stage 1, and anti-thymocyte globulin treatment of BOS Stage 1. In addition, our data suggest that initiation of azithromycin for BOS should begin prior to the progression to BOS Stage

Disclosure statement

We thank M. Gibson for help with data collection and J. Fassler, T. Francescon, C. Miller, W. Panus, L. Roldan, S. Rupp and M. Scavuzzo for assistance with chart reviews.

Supported by Grants T32 HL007317 and R01HL083894 from the National Institutes of Health/National Heart, Lung, and Blood Institute.

No authors involved in the preparation of this manuscript have any financial relationships with industry or other agencies related to azithromycin or other macrolide antibiotics.

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