Measurement of fibroblast proliferative activity in bronchoalveolar lavagefluid in the analysis of obliterative bronchiolitis among lung transplant recipients

Background: Bronchiolitis obliterans occurs in 30% to 80% of lung-transplan t recipients and is a direct cause of death in more than 40% of patients wi th this complication. This study assessed the potential utility of measurin g fibroblast-proliferative activity in bronchoalveolar lavage fluid from lu ng-transplant recipients to better understand the pathogenesis of this proc ess. Methods: The capacity of bronchoalveolar lavage fluid obtained from transpl ant recipients, during routine surveillance bronchoscopy, to stimulate the proliferation of human lung fibroblasts in vitro was assessed retrospective ly and compared to that of control subjects. For each recipient, a correlat ion was made between the fibroblast-proliferative activity in serial lavage samples over time and the other modalities employed for detecting post-tra nsplant complications including spirometry, transbronchial lung biopsy, and high-resolution computed tomography. Results: There was a significant difference in fibroblast-proliferative act ivity between volunteer and transplant recipient groups (p = 0.002). Furthe r, for each transplant recipient, the decline in the forced expired flow ra te between 25% and 75% of expired volume (FEF25%-75%) was correlated with t he mean fibroblast-proliferative activity during the period of this study ( r = 0.83; p = 0.04). Conclusions: A sustained increase in fibroblast-proliferative activity in l avage supernatant precedes both histologic and physiologic evidence of bron chiolitis obliterans. Relative to an increase in fibroblast-proliferative a ctivity or abnormalities in FEF25%-75%, a decrease in forced expiratory vol ume in 1 second is a late finding.