What are the best pulmonary function test parameters for early detection of post-lung transplant bronchiolitis obliterans syndrome in children?

Post-lung transplant bronchiolitis obliterans syndrome (BOS) is defined as an unexplained fall in forced expiratory volume in 1 s (FEV₁) ≥20% of baseline (B). There have been reports in adults that FEF_25-75% (> 30% decline from B) is more sensitive than FEV₁ for the early diagnosis of BOS. Yet, it is not known if other pulmonary function test (PFT) parameters - forced expiratory flow rates at 25-75% of vital capacity (FEF_25-75%) and maximal expiratory flow rate at 80% (V_max80%), 70% (V_max70%) and 60% (V_max60%) - are more sensitive indicators for early diagnosis of BOS than FEV₁ in post-lung transplant children. We reviewed serial PFTs of 18 patients (ages 14.1 ± 3.7 yr, 50% female) who had lung transplantation at our institution from 1993 to 1999, and who met the criteria for BOS diagnosis. There was no significant difference in post-transplant days when decline in FEV₁ ≥20% of B, FEF_25-75% > 30% of B, and V_max80%, V_max70% and V_max60% from normal occurred (635 ± 431, 551 ± 422 and 454 ± 287 days, respectively; p = 0.4). However, a decline in FEV₁ was the first abnormality in only 39% of the patients, while a decline in FEF_25-75% and V_max at specific lung volume were the first abnormality in 78% and 56% of the patients, respectively. The earliest signs of BOS would be missed in 61% of patients if FEV₁ was the primary parameter used for the diagnosis. In order to improve the sensitivity of the diagnosis of post-lung transplant BOS; we speculate that the diagnosis should be based on decreases in FEF_25-75% rather than on FEV₁.