Decline in 25% to 75% forced expiratory flow as an early predictor of chronic airway rejection in pediatric lung transplant recipients.

Background: Bronchiolitis obliterans (BO) is the major obstacle to long-term lung allograft viability. Its clinical correlate, BO syndrome (BOS), is defined as a decline of at least 20% in forced expiratory volume in 1 second (FEV(1)) from baseline. BOS is often diagnosed after significant organ dysfunction has occurred. Because BO is a small-airways disease, we hypothesized that a 20% decline in the 25% to 75% forced expiratory flow (FEF(25-75)) from baseline should occur before a decline in FEV(1) and should predict progression to BOS with high sensitivity and specificity.

Methods: Pulmonary function tests and records of pediatric lung transplantation patients at Texas Children's Hospital from 2002 to 2007 were reviewed. Declines in FEV(1) and FEF(25-75) from the best post-transplant baseline values were recorded and analyzed. Sensitivity, specificity, and positive and negative predictive values were calculated.

Results: Thirty-one patients were eligible for the study. In 11 BOS patients, the mean±standard deviation number of days from transplant until a 20% decline in FEV(1) was 896.5±400 compared with 728.0±475 (p = 0.022) until a 20% decline in FEF(25-75) was reached. The sensitivity, specificity, and positive predictive and negative predictive values of a 20% reduction in FEF(25-75) in determining BOS were 100%, 90.0%, 84.6%, and 100%, respectively.

Conclusions: All patients who developed BOS had a decline in FEF(25-75) at or before the decline in FEV(1). The reduction in FEF(25-75) occurred statistically significantly earlier than the decline in FEV(1), by an average of 168.5 days. This decline in FEF(25-75) was also highly sensitive and specific for the diagnosis of BOS.