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

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).

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).

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.

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.