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Published ahead of print on May 6, 2004, doi:10.1164/rccm.200310-1359OC

Am. J. Respir. Crit. Care Med., Volume 170, Number 2, July 2004, 181-187

A more recent version of this article appeared on July 15, 2004
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Submitted on October 7, 2003
Accepted on April 29, 2004

Respiratory Viral Infections are a Distinct Risk for Bronchiolitis Obliterans Syndrome and Death

Anthony P Khalifah1, Ramsey R Hachem1, Murali M Chakinala1, Kenneth B Schechtman2, G. Alexander Patterson3, Daniel P Schuster1, Thalachallour Mohanakumar3, Elbert P Trulock1, and Michael J Walter1*

1 Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, MO, USA, 2 Biostatistics, Washington University School of Medicine, St. Louis, MO, USA, 3 Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, MO, USA

* To whom correspondence should be addressed. E-mail: mwalter{at}imwustl.edu.

Bronchiolitis obliterans syndrome (BOS) is the major obstacle to long-term survival following lung transplantation, in part because its pathogenesis is poorly understood and treatment options are limited. To identify unique risk factors for BOS and death, we performed a retrospective cohort study on 259 consecutive adult lung transplant recipients over a five-year period. The demographic and clinical characteristics of this population were analyzed for an association between BOS or death and potential risk factors including community-acquired respiratory viral (CARV) infections, acute rejection, and cytomegalovirus pneumonitis. Respiratory syncytial virus, parainfluenza, influenza, and adenovirus accounted for twenty-one CARV infections. Univariate and multivariate time-dependent Cox regression analysis demonstrated this CARV group was more likely to develop BOS, death, and death from BOS. Furthermore, these trends were more pronounced in patients with evidence of lower respiratory tract CARV (Lower-CARV) infections. Notably, the CARV and Lower-CARV infections were risk factors for BOS, death, and death from BOS distinct from the risk attributable to acute rejection. Identification of CARV and Lower-CARV infections as BOS and mortality risk factors has important clinical implications and may provide insight into disease pathogenesis and accelerate the development of novel treatment strategies to modify post-CARV BOS.
Key words: lung transplantation, viruses, bronchiolitis obliterans, risk factors, graft rejection




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