Early Detection of Airway Involvement in Obliterative Bronchiolitis after Lung Transplantation

Abstract

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.

Post-transplant bronchiolitis obliterans

“…With BOS development, BAL neutrophilia (and eosinophilia) increase [99][100][101][102] above levels seen in stable patients [26,101,103,104]. However, whether this is a specific feature of BOS or whether it reflects concomitant airway infection is still debated.…”

“…This concern recently led to formulation of a revised classification system for BOS [17], which includes a new "potential BOS" stage (BOS 0-p) defined as a decrease in forced mid-expiratory flow rates (FEF25-75%) and/or FEV1 (table 3). The rationale for including FEF25-75% comes from studies that showed that this variable deteriorates before FEV1 at the onset of BOS [100,125,126]. The new BOS 0-p stage is meant to alert the physician and to indicate the need for close functional monitoring and for in-depth assessment using surrogate markers for BOS (see below).…”

“…Alterations in the distribution of ventilation in peripheral airways may also contribute to the early detection of BOS. Two recent prospective studies in heart-lung and bilaterallung recipients have shown that the slope of the alveolar plateau for nitrogen or helium obtained during single-breath washouts (that reflects the heterogeneity of ventilation distribution) may increase up to several months before the criteria for BOS 0-p are met [100,125]. Finally, the presence of nonspecific bronchial hyperreactivity may also precede BOS.…”

Outcome and treatment of late-onset noninfectious pulmonary complications after allogeneic haematopoietic SCT

“…9,12 However, we used this criterion because it is recommended to be one of the diagnostic criteria for BO 25 in the disease category derived from obliterative bronchiolitis after lung transplantation as BO syndrome (BOS). 31,32 The criteria of BOS are based on the idea that recognition of small air way obstruction is more sensitive than that of decline of FEV1/FVC. 31 Otherwise, reduction of FVC would mask obstructive change, thus we considered that these criteria are reasonable.…”

“…31,32 The criteria of BOS are based on the idea that recognition of small air way obstruction is more sensitive than that of decline of FEV1/FVC. 31 Otherwise, reduction of FVC would mask obstructive change, thus we considered that these criteria are reasonable. Four patients were actually diagnosed according to these criteria.…”