肺移植后闭塞性细支气管炎综合征的危险因素与发病机制

Pathogenetic factors and mechanisms of bronchiolitis obliterans syndrome after lung transplantation

闭塞性细支气管炎综合征(bronchiolitis obliterans syndrome,BOS)是影响肺移植术后长期存活的最主要并发症,且加强免疫抑制和抗炎治疗效果不佳。肺移植后导致闭塞性细支气管炎综合征的机制涉及免疫和非免疫因素启动气道上皮、细胞外基质、新生血管及淋巴管系统的进行性损伤与异常增生重塑,形成恶性循环。其中内源性免疫是导致细支气管闭塞和发展为BOS的主要致病因素,但各种感染或化学损伤可能导致激活树突状细胞的危险信号释放,从而激发排斥反应。因此,降低非依赖同种异体免疫因素的风险与治疗免疫排斥同样重要。

Bronchiolitis obliterans syndrome （BOS） is the single most important complication that limits the long-term survival following lung transplantation. Current treatment of BOS is disappointing despite advances in immunosuppressive and anti-inflammatory therapies. 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 continuous cycle of ongoing injury and aberrant remodeling in the airway epithelium, stroma, vasculature and lymphoid system. Although most studies suggest that immune injury is the main pathogenic event in small airway obliteration and the development of BOS. The triggering of innate immunity by various infections or chemical injuries may lead to the release of danger signals that are able to activate dendritic cells, a crucial link with adaptive immunity. Inflammation can also increase the expression and display of major histocompatibility alloantigens and thus favor the initiatiorl of rejection episodes. Therefore, reducing the risk of alloimmuneindependent factors may be as important as treating acute episodes of lung rejection.