Persistent high BAL fluid granulocyte activation marker levels as early indicators of bronchiolitis obliterans after lung transplant.

The major cause of mortality in the long-term in lung transplant recipients is chronic rejection. This is a fibroproliferative process in the small airways leading to obliterative bronchiolitis and progressive loss of lung function, both constituting the clinical entity bronchiolitis obliterans syndrome (BOS). Granulocyte activation has been implicated as one factor behind BOS. Granulocyte markers in bronchoalveolar lavage (BAL) fluid were prospectively and longitudinally studied in order to identify possible association with BOS. BAL fluid from 266 bronchoscopy procedures performed in twelve single lung, eight bilateral lung and five heart/lung transplant recipients were analysed. The majority (19 of 25) were studied for a period of 2 yrs after surgery. Myeloperoxidase (MPO), eosinophil cationic protein (ECP) and interleukin-8 (IL-8) levels were used as indirect markers of activation and attraction of granulocytes. Five patients developed BOS. Ninety-eight episodes of acute rejection, nine of bacterial infection, 19 of cytomegalovirus pneumonitis, nine of Pneumocystis carinii infection, two of aspergillus infection and two of respiratory syncytial virus infection were diagnosed. BOS patients had significantly higher mean levels of MPO, ECP and IL-8 compared to patients without BOS, irrespective of acute rejection status. Over time, the five patients with BOS had significantly elevated BAL fluid levels of MPO and ECP as well as neutrophil percentages, and in four patients this increase preceded the clinical diagnosis of BOS by several months. Elevated bronchoalveolar lavage fluid neutrophil percentage as well as levels of the granulocyte activation markers myeloperoxidase and eosinophil cationic protein appear to be early signs of development of BOS in lung transplant recipients.