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

Jain, Raksha; Hachem, Ramsey R.; Morrell, Matthew R.; Trulock, Elbert P.; Chakinala, Murali M.; Yusen, Roger D.; Huang, Howard J.; Mohanakumar, Thalachallour; Patterson, G. Alexander; Walter, Michael J.

doi:10.1016/j.healun.2009.12.003

« Previous Next »The Journal of Heart and Lung Transplantation
Volume 29, Issue 5 , Pages 531-537, May 2010

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

Raksha Jain, MD
- Department of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, Missouri
- Reprint requests: Raksha Jain, MD, Division of Pulmonary and Critical Care Medicine, Campus Box 8052, 660 South Euclid Avenue, St. Louis, MO 63110. Telephone: 314-362-8920. Fax: 314-362-8987
Ramsey R. Hachem, MD
- Department of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, Missouri
Matthew R. Morrell, MD
- Department of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, Missouri
Elbert P. Trulock, MD
- Department of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, Missouri
Murali M. Chakinala, MD
- Department of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, Missouri
Roger D. Yusen, MD, MPH
- Department of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, Missouri
Howard J. Huang, MD
- Department of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, Missouri
Thalachallour Mohanakumar, BVSc, PhD
- Department of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, Missouri
G. Alexander Patterson, MD
- Department of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, Missouri
Michael J. Walter, MD
- Department of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, Missouri

published online 04 February 2010.

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.

Keywords: lung transplant, survival, chronic rejection, bronchiolitis, macrolides, azithromycin