Systematic review on recent potential biomarkers of chronic obstructive pulmonary disease

<b>Introduction</b>: Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide and associated with decreased lung function and inflammation. The heterogeneity of COPD and its molecular and clinical features hinder efficient patient stratification and introduction of personalized therapeutic approaches. The available clinical tools do not efficiently predict the progression and exacerbations of the disease. <b>Areas covered</b>: An overview of the most recent studies on putative COPD protein biomarkers and the challenges for implementing their use in the clinical setting is presented. <b>Expert commentary</b>: Proteomics biomarker discovery in COPD has mostly focused on approaches evaluating specific proteins on a limited number of samples. The most promising protein candidates can be classified into five main biological categories: extracellular matrix (ECM) remodeling, inflammation/immune response, oxidative stress response, vascular tone regulation, and lipid metabolism. To efficiently stratify COPD patients and predict exacerbations, it will be necessary to implement biomarker panels to better represent the complex pathophysiology of this disease. The application of unbiased proteomics and bioinformatics followed by appropriate clinical validation studies will contribute to the achievement of this aim while increasing the number of validated biomarkers that can enter the qualification processes by the regulatory entities.

<b>引言</b>：慢性阻塞性肺疾病（COPD）是全球主要致死病因之一，与肺功能下降及炎症反应密切相关。COPD的异质性及其分子与临床特征，阻碍了高效的患者分层与个性化治疗方案的落地应用。现有临床工具无法有效预测疾病的进展与急性加重。
<b>涵盖领域</b>：本文综述了近年来有关慢性阻塞性肺疾病潜在蛋白质生物标志物的最新研究，以及将其应用于临床场景所面临的各项挑战。
<b>专家评述</b>：慢性阻塞性肺疾病的蛋白质组学生物标志物发现研究，大多聚焦于在有限样本中检测特定蛋白质的研究方案。最具潜力的候选蛋白质可分为五大主要生物学类别：细胞外基质（ECM）重塑、炎症/免疫应答、氧化应激应答、血管张力调节以及脂质代谢。若要实现慢性阻塞性肺疾病患者的高效分层与疾病急性加重的预测，有必要采用生物标志物组合，以更全面地反映该疾病复杂的病理生理机制。采用无偏倚蛋白质组学与生物信息学技术，并辅以规范的临床验证研究，将有助于实现这一目标，同时增加可进入监管机构资质认定流程的已验证生物标志物数量。