Bronchiolitis obliterans syndrome: alloimmune-dependent and -independent injury with aberrant tissue remodeling.
Long-term success in lung transplantation continues to be challenged by chronic graft dysfunction, which is manifest as bronchiolitis obliterans syndrome (BOS). The mechanisms of BOS involve both immune-mediated pathways (rejection, autoimmune-like mechanisms), and alloimmune-independent pathways (infection, aspiration, ischemia, primary graft failure), which lead to a fibroproliferative responses. BOS correlates histologically with obliterative bronchiolitis in terminal bronchioles and evidence of aberrant remodeling in the airway epithelium, vasculature, stroma, and lymphoid system. A potentially important mechanism that supports the progressive and therapy-resistant nature of BOS is a continuous cycle of ongoing injury and aberrant remodeling. Namely, anatomical and functional abnormalities induce and exacerbate immune-mediated and alloimmune-independent pathways through various mechanisms (e.g., epithelial remodeling decreases mucociliary clearance that exacerbates aspiration-related injury). From this viewpoint, we review current therapeutic strategies and revisit the role of transplant surgeons in attenuating the initial transplant-related injuries to prevent the lung grafts from entering the remodeling-injury cycle.
Sato
Masaaki
M
Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Keshavjee
Shaf
S
D001989:Bronchiolitis Obliterans / Q000209:etiology* / Q000276:immunology / Q000517:prevention & control / Q000628:therapy; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D016040:Lung Transplantation / Q000009:adverse effects*