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 ai rways leading to obliterative bronchiolitis and progressive loss of lung fu nction, both constituting the clinical entity bronchiolitis obliterans synd rome (BOS), Granulocyte activation has been implicated as one factor behind BOS, Granulocyte markers in bronchoalveolar lavage (BAL) fluid were prospe ctively and longitudinally studied in order to identify possible associatio n with BOS. BAL fluid from 266 bronchoscopy procedures performed in twelve single lung, eight bilateral lung and five heart/lung transplant recipients were analys ed. The majority (19 of 25) were studied for a period of 2 yrs after surger y. 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 EOS. Ninety-eight episodes of acute rejection, nine of bacterial infection, 19 of cytomegalovirus pneumonitis, nine of Pneumoc ystis carinii infection, two of aspergillus infection and two of respirator y syncytial virus infection were diagnosed. BOS patients had significantly higher mean levels of MPO, ECP and IL-8 compared to patients without BOS, i rrespective of acute rejection status. Over time, the five patients with BO S had significantly elevated BAL fluid levels of MPO and ECP as well as neu trophil percentages, and in four patients this increase preceded the clinic al diagnosis of BOS by several months. Elevated bronchoalveolar lavage fluid neutrophil percentage as well as leve ls of the granulocyte activation markers myeloperoxidase and eosinophil cat ionic protein appear to be early signs of development of BOS in lung transp lant recipients.