Long-term survival after lung transplantation depends on development and severity of bronchiolitis obliterans syndrome

Background: The objectives of this study were to describe the natural history of bronchiolitis obliterans syndrome (BOS) in a large consecutive series of patients from a national center in accordance with the most recent grading criteria, and to examine the prognosis with respect to onset and severity of BOS. Methods: All patients receiving a cadaveric lung transplant between 1992 and 2004 were included in the study (n = 389). Exclusion criteria were patients not surviving at least 3 months after transplantation (n = 39) and lack of available lung function measurements (n = 4). Results: The 1-, 3-, 5- and 10-year actuarial survival rates for the entire series were 81%, 67%, 60% and 36%, respectively. The 1-, 3-, 5- and 10-year actuarial freedom from BOS Grade >= 1 was 81%, 53%, 38% and 15%, respectively. A Cox regression model with BOS grade as a time-dependent covariate was performed in a sub-group of patients surviving at least 3 years (n = 237). Both progression from BOS Grade I to 2 and from BOS Grade 2 to 3 were associated with a significant increase in mortality: hazard ratio (HR) = 3.1 (confidence interval [CI] 1.2 to 7.9) and HR = 2.9 (CI 1.6 to 5-3), respectively. The addition of a non-time-dependent covariate to signify early (within 18 months of transplantation) or late (after 18 months) development of BOS was not significant (P = 0-5). Conclusions: The development and progression of chronic allograft rejection after lung transplantation (BOS Grades 2 and 3) is associated with a 3-fold increase in the risk of death at each stage, irrespective. of whether BOS developed early or late.