National Jewish Health, Denver; University of Colorado, Anschutz Medical Campus, Aurora, CO.
National Jewish Health, Denver.
Chest. 2021 Jun;159(6):2244-2253. doi: 10.1016/j.chest.2021.01.004. Epub 2021 Jan 9.
COPD is a clinically heterogeneous syndrome characterized by injury to airways, airspaces, and lung vasculature and usually caused by tobacco smoke and/or air pollution exposure. COPD is also independently associated with nonpulmonary comorbidities (eg, cardiovascular disease) and malignancies (eg, GI, bladder), suggesting a role for systemic injury. Since not all those with exposure develop COPD, there has been a search for plasma and lung biomarkers that confer increased cross-sectional and longitudinal risk. This search typically focuses on clinically relevant COPD outcomes such as FEV, FEV decline, CT measurements of emphysema, or exacerbation frequency. The rapid advances in omics technology and the molecular phenotyping of COPD cohorts now permit large-scale evaluation of genetic, transcriptomic, proteomic, and metabolic biomarkers. This review focuses on protein biomarkers associated with clinically relevant COPD outcomes. The prototypic COPD protein biomarker is alpha-1 antitrypsin; however, this biomarker only accounts for 1% to 5% of COPD. This article reviews and summarizes the evidence for other validated biomarkers for each COPD outcome, and discusses their advantages, weaknesses, and required regulatory steps to move the biomarker from the bench into clinic. Although we highlight the emergence of many novel biomarkers (eg, fibrinogen, soluble receptor for advanced glycation, surfactant protein D, club cell secretory protein), there is increasing evidence that individual biomarkers only explain a fraction of the increased COPD risk and that multiple biomarker panels are needed to completely explain clinical variation and risk in individuals and populations.
COPD 是一种临床表现异质性的综合征，其特征为气道、肺泡和肺血管损伤，通常由吸烟和/或空气污染暴露引起。COPD 还与非肺部合并症（如心血管疾病）和恶性肿瘤（如胃肠道、膀胱）独立相关，提示存在全身性损伤。由于并非所有暴露者都会发展为 COPD，因此一直在寻找能够增加横断面和纵向风险的血浆和肺部生物标志物。这种寻找通常集中在与临床相关的 COPD 结局上，如 FEV、FEV 下降、肺气肿的 CT 测量或加重频率。组学技术的快速发展和 COPD 队列的分子表型分析现在允许对遗传、转录组、蛋白质组和代谢生物标志物进行大规模评估。这篇综述重点介绍了与临床相关的 COPD 结局相关的蛋白质生物标志物。典型的 COPD 蛋白质生物标志物是α-1 抗胰蛋白酶；然而，这种生物标志物仅占 COPD 的 1%至 5%。本文综述并总结了每种 COPD 结局的其他经过验证的生物标志物的证据，并讨论了它们的优点、缺点以及将生物标志物从实验室转移到临床所需的监管步骤。尽管我们强调了许多新型生物标志物（如纤维蛋白原、晚期糖基化终产物受体可溶性蛋白、表面活性蛋白 D、肺泡细胞分泌蛋白）的出现，但越来越多的证据表明，单个生物标志物仅能解释 COPD 风险增加的一部分，需要多个生物标志物组合才能完全解释个体和人群的临床变异和风险。
