Post-transplant baseline FEV1 and the development of bronchiolitis obliterans syndrome: an important confounder?

BACKGROUND: Because bronchiolitis obliterans syndrome (BOS) is defined and graded according to the decline in forced expiratory volume in 1 second (FEV(1)) relative to a maximal baseline value obtained post-transplantation, the criteria discriminates against recipients with lower maximal baseline values (i.e., constitutes a statistical bias). This study describes the effect of transplant procedure on the development of BOS, adjusting for the absolute value of post-transplant baseline FEV(1).
METHODS: All patients receiving a cadaveric lung transplant from 1992 to 2004 were included in the study (n = 389). Exclusion criteria were patients surviving <3 months (n = 39) and missing spirometry measurements (n = 4).
RESULTS: Baseline FEV(1) was strongly associated with the freedom from BOS Grade 1, and longer-duration BOS-free survival in univariate and multivariate survival analyses. After adjusting for baseline FEV(1), and recipient-donor gender, bilateral lung transplantation (BLT) was associated with an increase in the cause-specific risk of BOS Grade 1 (hazard ratio [HR] 2.0, confidence interval [CI] 1.2 to 3.1, p = 0.004), and an increase in the cause-specific risk of death/re-transplantation or BOS Grade 1 as a combined end-point (HR 2.3, CI 1.5 to 3.4, p < 0.0001) compared with single-lung transplantation (SLT). In the competing risk regression model adjusting for recipient-donor gender and transplant procedure, only baseline FEV(1) remained independently associated with the cumulative incidence of BOS Grade 1 (p < 0.05); however, BLT recipients were more likely to have death/re-transplantation unrelated to BOS than SLT recipients.
CONCLUSIONS: The absolute value of baseline lung function appears to be an important confounder in the analyses of BOS, and should be considered in future risk factor analyses.