Division of Pulmonary, Allergy & Critical Care, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Pulmonary institute, Rabin Medical Center, Petach Tikva, Israel; Sackler School of Medicine, Tel Aviv, Israel.
Expert Rev Mol Diagn. 2020 May;20(5):467-475. doi: 10.1080/14737159.2020.1738929. Epub 2020 Mar 12.
: Lung transplantation remains an important treatment for patients with end stage lung disease. Chronic lung allograft dysfunction (CLAD) remains the greatest limiting factor for long term survival. As the diagnosis of CLAD is based on pulmonary function tests, significant lung injury is required before a diagnosis is feasible, likely when irreversible damage has already occurred. Therefore, research is ongoing for early CLAD recognition, with biomarkers making up a substantial amount of this research.: The purpose of this review is to describe available biomarkers, focusing on those which aid in predicting CLAD and distinguishing between different CLAD phenotypes. We describe biomarkers presenting in bronchial alveolar lavage (BAL) as well as circulating in peripheral blood, both of which offer an appealing alternative to lung biopsy.: Development of CLAD involves complex, multiple immune and nonimmune mechanisms. Therefore, evaluation of potential CLAD biomarkers serves a dual purpose: clinically, the goal remains early detection and identification of patients at increased risk. Simultaneously, biomarkers offer insight into the different mechanisms involved in the pathophysiology of CLAD, leading to the development of possible interventions. The ultimate goal is the development of both preventive and early intervention strategies for CLAD to improve the overall survival of our lung transplant recipients.
肺移植仍然是治疗终末期肺病患者的重要手段。慢性肺移植物功能障碍(CLAD)仍然是长期生存的最大限制因素。由于 CLAD 的诊断基于肺功能测试,因此在可行的诊断之前需要有明显的肺损伤,这可能已经发生了不可逆转的损伤。因此,目前正在进行早期 CLAD 识别的研究,生物标志物是该研究的重要组成部分。
本综述的目的是描述现有的生物标志物,重点介绍那些有助于预测 CLAD 并区分不同 CLAD 表型的生物标志物。我们描述了支气管肺泡灌洗液(BAL)中存在的生物标志物以及外周血中循环的生物标志物,这两者都为肺活检提供了有吸引力的替代方法。
CLAD 的发展涉及复杂的、多种免疫和非免疫机制。因此,评估潜在的 CLAD 生物标志物有双重目的:临床上,目标仍然是早期发现和识别风险增加的患者。同时,生物标志物提供了对 CLAD 病理生理学中涉及的不同机制的深入了解,从而为可能的干预措施的发展提供了依据。最终目标是为 CLAD 开发预防和早期干预策略,以提高我们肺移植受者的总体生存率。