Abstract
RATIONALE: Despite the importance of bronchiolitis obliterans syndrome (BOS) in lung transplantation, little is known regarding the factors that influence survival after the onset of this condition, particularly among bilateral transplant recipients. OBJECTIVES: To identify factors that influence survival after the onset of BOS among bilateral lung transplant recipients. METHODS: The effect of demographic or clinical factors, occurring before BOS, upon survival after the onset of BOS was studied in 95 bilateral lung transplant recipient using Cox proportional hazards models. MEASUREMENTS AND MAIN RESULTS: Although many factors, including prior acute rejection or rejection treatments, were not associated with survival after BOS, BOS onset within 2 years of transplantation (early-onset BOS), or BOS onset grade of 2 or 3 (high-grade onset) were predictive of significantly worse survival (early onset P = 0.04; hazard ratio, 1.84; 95% confidence interval, 1.03-3.29; high-grade onset P = 0.003; hazard ratio, 2.40; 95% confidence interval, 1.34-4.32). The effects of both early onset and high-grade onset on survival persisted in multivariable analysis and after adjustment for concurrent treatments. Results suggested an interaction might exist between early onset and high-grade onset. In particular, high-grade onset of BOS, regardless of its timing after transplant, is associated with a very poor prognosis. CONCLUSIONS: The course of BOS after bilateral lung transplantation is variable. Distinct patterns of survival after BOS are evident and related to timing or severity of onset. Further characterization of these subgroups should provide a more rational basis from which to design, stratify, and assess response in future BOS treatment trials.