Transplant-related bronchiolitis obliterans (BOS) demonstrates unique cytokine profiles compared to toxicant-induced BOS

Bronchiolitis obliterans (BOS - bronchiolitis obliterans syndrome - clinical diagnosis; CBO-histopathologic diagnosis), is a chronic disease process of fibrosis and cellular deposition in airways, complicating long term survival following lung transplantation. BOS is also the result of sporadic toxicant exposure, with airway signs, symptoms, and histology indistinguishable from allograft rejection. This study establishes a transplant BOS model in MHC-mismatched rats and compares their cytokine profiles and histopathology to that of our established toxicant-induced BOS model. Both models result in lung histopathology similar to human disease. Cytokines and inflammation markers that are elevated in human transplant BOS (TGFβ, iNOS, IFNγ) were also elevated significantly in both models. Anti-nuclear antibody was absent from all sera in transplant or toxicant models exhibiting advanced airway pathology. The cytokine osteopontin was highly elevated in BAL early in toxicant-induced BOS, but increased late in the transplant-induced BOS model. The data show that BOS is a disease of a pathologic endpoint that is induced by different triggers and processes. The highly elevated BAL osteopontin early in the toxicant-induced BOS model suggests a need for evaluation in the diagnostic setting.