Bronchiolitis obliterans syndrome after (heart-)lung transplantation - Impaired antiprotease defense and increased oxidant activity

Increased numbers of neutrophils are a common finding in bronchoalveolar la vage fluid (BALF) samples obtained from patients after (heart-)Iung transpl antation [(H)LTX]. Since proteases and reactive oxygen species secreted by neutrophils are capable of causing substantial damage to the lung tissue if not counterbalanced by the antiprotease and antioxidant screen, we hypothe sized that neutrophil products may play a role in the development of oblite rative bronchiolitis (OB). A total of 72 BALF samples obtained from 33 pati ents after (H)LTX were evaluated. Sixteen of these patients were suffering from bronchiolitis obliterans syndrome (BOS) at the time of bronchoaveolar lavage (BAL). As a control, BALF samples from 17 healthy volunteers were an alyzed. Anti-neutrophil elastase (NE) activity was quantified by a titratio n assay. Concentrations of al-protease inhibitor (API), secretory leukocyte protease inhibitor (SLPI), NE-API complex, and myeloperoxidase (MPO) were measured by ELISA. Oxidized methionine [Met(O)] was quantified by high-perf ormance liquid chromatography (HPLC). Epithelial lining fluid (ELF) from pa tients suffering from BOS showed significantly increased neutrophil counts, significantly elevated concentrations of NE-API complex and Met(O), and a significant decrease in the concentration of SLPI. Furthermore, a trend tow ard an increased NE activity and MPO concentration was observed. These find ings suggest that neutrophils may be involved in the development of BOS.