Sato Masaaki, Keshavjee Shaf
Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada.
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.
肺移植的长期成功仍然受到慢性移植物功能障碍的挑战，这种功能障碍表现为闭塞性细支气管炎综合征（BOS）。BOS的机制涉及免疫介导途径（排斥反应、自身免疫样机制）和同种免疫非依赖途径（感染、误吸、缺血、原发性移植物功能衰竭），这些途径会导致纤维增生性反应。BOS在组织学上与终末细支气管的闭塞性细支气管炎以及气道上皮、血管、基质和淋巴系统异常重塑的证据相关。支持BOS进行性和治疗抵抗性的一个潜在重要机制是持续的损伤和异常重塑循环。也就是说，解剖和功能异常通过各种机制诱导并加剧免疫介导和同种免疫非依赖途径（例如，上皮重塑会降低黏液纤毛清除功能，从而加剧与误吸相关的损伤）。从这个角度出发，我们回顾了当前的治疗策略，并重新审视了移植外科医生在减轻初始移植相关损伤以防止肺移植物进入重塑-损伤循环中的作用。
