Division of Pulmonary, Critical Care Medicine, Allergy, and Clinical Immunology, Department of Internal Medicine, The David Geffen School of Medicine at UCLA, Los Angeles, California.
Department of Pathology and Laboratory Medicine, The David Geffen School of Medicine at UCLA, Los Angeles, California.
Semin Respir Crit Care Med. 2018 Apr;39(2):155-171. doi: 10.1055/s-0037-1618567. Epub 2018 Mar 26.
Lung transplantation has become an established therapeutic option for a variety of end-stage lung diseases. Technical advances in graft procurement, implantation, perioperative care, immunosuppression, and posttransplant medical management have led to significant improvements in 1-year survival, but outcomes after the first year have improved minimally over the last two decades. The main limitation to better long-term survival after lung transplantation is chronic lung allograft dysfunction (CLAD). CLAD also impairs quality of life and increases the costs of medical care. Our understanding of CLAD manifestations, risk factors, and mechanisms is rapidly evolving. Recognition of different CLAD phenotypes (e.g., bronchiolitis obliterans syndrome and restrictive allograft syndrome) and the unique pathogenic mechanisms will be important for developing novel therapies. In addition to alloimmune-mediated rejection, we now recognize the importance of alloimmune-independent mechanisms of injury to the allograft. CLAD is the consequence of dysregulated repair of allograft injury. Unfortunately, currently available therapies for CLAD are usually not effective. However, the advances in knowledge, reviewed in this manuscript, should lead to novel strategies for CLAD prevention and treatment, as well as improvement in long-term outcomes after lung transplantation. We provide an overview of the evolving terminology related to CLAD, its varying clinical phenotypes and their diagnosis, natural history, pathogenesis, and potential treatments.
肺移植已成为多种终末期肺部疾病的一种既定治疗选择。在供体获取、移植、围手术期护理、免疫抑制和移植后医疗管理等方面的技术进步，使 1 年生存率显著提高，但在过去 20 年中，第 1 年后的结果仅略有改善。肺移植后长期生存的主要限制因素是慢性肺移植物功能障碍（CLAD）。CLAD 还会降低生活质量并增加医疗费用。我们对 CLAD 的表现、危险因素和机制的理解正在迅速发展。识别不同的 CLAD 表型（例如，闭塞性细支气管炎综合征和限制性移植物综合征）和独特的发病机制对于开发新疗法非常重要。除了同种异体免疫介导的排斥反应外，我们现在还认识到同种异体免疫非依赖性损伤同种异体移植物的重要性。CLAD 是同种异体移植物损伤调节不良修复的结果。不幸的是，目前用于 CLAD 的治疗方法通常效果不佳。然而，本文综述的知识进展，应该会为 CLAD 的预防和治疗以及肺移植后长期结果的改善提供新的策略。我们概述了与 CLAD 相关的不断发展的术语、其不同的临床表型及其诊断、自然史、发病机制和潜在的治疗方法。
