Bronchiolitis obliterans syndrome in lung transplant recipients is associated with increased neutrophil activity and decreased antioxidant status in the lung

Abstract

Long-term survival of lung transplant recipients is limited by the advent of obliterative bronchiolitis and irreversible airways obstruction, e.g. bronchiolitis obliterans syndrome (BOS). This study investigated whether inflammatory cells and their activation markers were increased in bronchoalveolar lavage (BAL) and transbronchial biopsies (TBB) from patients with BOS. Levels of antioxidants in BAL fluid were also assessed. BAL fluid and TBB from six single-lung, two bilateral-lung, and five heart-lung transplanted patients with diagnosis of BOS were compared with 13 transplant recipients without BOS. BAL fluid levels of myeloperoxidase (MPO), eosinophil cationic protein (ECP) and interleukin (IL)-8 were used as markers for the activation and attraction of neutrophils and eosinophils, respectively. Immunohistochemical staining of TBB with monoclonal antibodies to MPO and ECP (EG2) was performed. Significantly increased BAL percentages of neutrophils and levels of MPO were found in patients with BOS. The findings correlated well with the degree of monoclonal staining for MPO in TBB. BAL levels of ECP and IL-8 were significantly increased in BOS patients. BAL concentrations of the water-soluble antioxidants ascorbate, urate and glutathione were generally lower in BOS patients. The results indicate that neutrophil infiltration and activation, as well as oxidative stress, may play a role in the development and/or progression of bronchiolitis obliterans syndrome. Markers for neutrophil activation could have a potential role in monitoring disease activity in patients with this syndrome.