Azithromycin is associated with increased survival in lung transplant recipients with bronchiolitis obliterans syndrome.
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 (FEV(1)) 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.
Department of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA. rjain@dom.wustl.edu
Raksha
R
Jain
Ramsey R
RR
Hachem
Matthew R
MR
Morrell
Elbert P
EP
Trulock
Murali M
MM
Chakinala
Roger D
RD
Yusen
Howard J
HJ
Huang
Thalachallour
T
Mohanakumar
G Alexander
GA
Patterson
Michael J
MJ
Walter
D000328:Adult; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017963:Azithromycin / Q000009:adverse effects / Q000627:therapeutic use*; D001989:Bronchiolitis Obliterans / Q000188:drug therapy* / Q000401:mortality*; D002423:Cause of Death; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D016040:Lung Transplantation / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections / Q000188:drug therapy* / Q000401:mortality*; D011183:Postoperative Complications / Q000188:drug therapy* / Q000401:mortality*; D016016:Proportional Hazards Models; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000401:mortality*; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis
D000900:Anti-Bacterial Agents; D017963:Azithromycin