As defined by the International Society for Heart and Lung Transplantation, the diagnosis of posttransplant obliterative bronchiolitis (OB) is based on histopathologic features and/or spirometric staging criteria, using FEV(1) to determine the extent of disease. However, this last parameter reflects an advanced bronchiolar process. The present study investigated whether physiologic parameters reflecting smaller airways dysfunction on one hand, and neutrophils in bronchoalveolar lavage fluid (BALF) on the other hand, could be useful for the earlier detection of bronchiolitis obliterans syndrome (BOS). We analyzed data obtained both from 765 pulmonary function test results and from 467 BALF specimens from 45 patients who survived at least 1 yr after surgery (n = 47, including two retransplantations). Of the transplant procedures, 22 were associated with BOS and 25 were not. The mean delay from transplantation to the diagnosis of BOS was 578 d (range: 122 to 2,619 d). The threshold values of the following parameters were studied: decline in the forced expiratory flow rate at 25% to 75% of FVC (FEF(25-75)) to </= 70% of the predicted value and of baseline values, increase in the slope of the nitrogen washout curve (DeltaN(2)) > 3%, and alveolar neutrophilia >/= 20% of the total BALF cell count. Agreement on the diagnosis of BOS (using the decline in FEV(1)) was equally good for each of the four markers (kappa coefficient > 0.65, p < 10(-)(5)). In the OB group, mean delays after the threshold was reached for each of these parameters were 110 d (p = 0.09), 173 d (p = 0.03), 150 d (p = 0.003), and 131 d (p = 0.1), respectively, before the FEV(1) criteria were fulfilled. At the chosen threshold values, the decline in FEF(25-75), increase in DeltaN(2), and development of a substantial alveolar neutrophilia all occurred significantly before a decline in FEV(1) in posttransplant OB.