Bronchiolitis obliterans syndrome: alloimmune-dependent and -independent injury with aberrant tissue remodeling

Semin Thorac Cardiovasc Surg. 2008 Summer;20(2):173-82. doi: 10.1053/j.semtcvs.2008.05.002.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Bronchiolitis Obliterans / etiology*
  • Bronchiolitis Obliterans / immunology
  • Bronchiolitis Obliterans / prevention & control
  • Bronchiolitis Obliterans / therapy
  • Graft Rejection / immunology
  • Humans
  • Lung / pathology
  • Lung / physiopathology
  • Lung Transplantation / adverse effects*