Lab of Respiratory Diseases, BREATH, Department of CHROMETA, KU Leuven, Leuven, Belgium.
Institute of Pathology, Hannover Medical School (MHH), Hanover, Germany.
Am J Transplant. 2020 Oct;20(10):2644-2651. doi: 10.1111/ajt.15864. Epub 2020 Apr 15.
Although chronic lung allograft dysfunction (CLAD) remains the major life-limiting factor following lung transplantation, much of its pathophysiology remains unknown. The discovery that CLAD can manifest both clinically and morphologically in vastly different ways led to the definition of distinct subtypes of CLAD. In this review, recent advances in our understanding of the pathophysiological mechanisms of the different phenotypes of CLAD will be discussed with a particular focus on tissue-based and molecular studies. An overview of the current knowledge on the mechanisms of the airway-centered bronchiolitis obliterans syndrome, as well as the airway and alveolar injuries in the restrictive allograft syndrome and also the vascular compartment in chronic antibody-mediated rejection is provided. Specific attention is also given to morphological and molecular markers for early CLAD diagnosis or histological changes associated with subsequent CLAD development. Evidence for a possible overlap between different forms of CLAD is presented and discussed. In the end, "tissue remains the (main) issue," as we are still limited in our knowledge about the actual triggers and specific mechanisms of all late forms of posttransplant graft failure, a shortcoming that needs to be addressed in order to further improve the outcome of lung transplant recipients.
尽管慢性肺移植物功能障碍（CLAD）仍然是肺移植后限制患者生命的主要因素，但它的大部分病理生理学仍然未知。CLAD 可以在临床上和形态上以截然不同的方式表现出来，这一发现导致了 CLAD 的不同亚型的定义。在这篇综述中，我们将讨论对不同 CLAD 表型的病理生理机制的理解的最新进展，特别关注基于组织和分子的研究。本文概述了目前对气道中心性细支气管炎闭塞综合征、限制性移植物综合征中的气道和肺泡损伤以及慢性抗体介导排斥反应中血管隔室的机制的认识。还特别关注 CLAD 早期诊断的形态学和分子标志物或与随后 CLAD 发展相关的组织学变化。提出并讨论了不同形式的 CLAD 之间可能存在重叠的证据。最后，正如我们对所有移植后移植物晚期失功的实际触发因素和特定机制的了解仍然有限一样，“组织仍然是（主要的）问题”，为了进一步改善肺移植受者的预后，这一缺点需要得到解决。
