Targeting Chronic Obstructive Pulmonary Disease Phenotypes, Endotypes, and Biomarkers
Targeting Chronic Obstructive Pulmonary Disease Phenotypes, Endotypes, and Biomarkers
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DOI：
10.1513/annalsats.201808-533mg
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发表时间：
2018-12-01
影响因子：
8.3
通讯作者：
Woodruff, Prescott G.
中科院分区：
文献类型：
--
作者：
Garudadri, Suresh;Woodruff, Prescott G.
慢性阻塞性肺疾病（COPD）是一种表型异质性疾病，这种异质性是由生物学异质性支撑的。“内型”是由于共有的潜在生物学而共有相同的观察特征的一组患者，并且“内型”概念已经作为通过关注其生物学基础来使这种表型异质性有序化的一种方式而出现。原则上，生物标志物可以帮助识别内型，并将这些特定的患者群体标记为靶向生物治疗的合适候选人。在COPD的内型中，描述得更好的是α-1抗胰蛋白酶缺乏和嗜酸性粒细胞COPD。这两种内型都有生物标志物和至少一些证据表明靶向治疗的优先益处。可能定义COPD内型的其他生物学途径包括2型炎症、IL-17驱动的炎症（由于自身免疫或纳米颗粒炭黑沉积）、细菌定植、气道粘液凝胶的病理学改变等更一般的途径，以及超出本综述范围的其他途径。这些生物学途径最终是否被发现将患者分离成非常不同的内型或子集（如α-1抗胰蛋白酶缺乏症），或者相反，以各种组合形式作为“可治疗的特征”存在尚不确定。无论多么不完善，内型概念迫使人们关注生物学水平上的异质性，生物异质性生物标志物的开发应有助于推进COPD新疗法的开发目标。
Chronic obstructive pulmonary disease (COPD) is now well recognized to be a phenotypically heterogeneous disease, and this heterogeneity is underpinned by biological heterogeneity. An "endotype" is a group of patients who share the same observed characteristic(s) because of shared underlying biology, and the "endotype" concept has emerged as one way of bringing order to this phenotypic heterogeneity by focusing on its biological underpinnings. In principle, biomarkers can help identify endotypes and mark these specific groups of patients as suitable candidates for targeted biological therapies. Among the better-described endotypes of COPD are alpha-1 antitrypsin deficiency and eosinophilic COPD. Both of these endotypes have biomarkers and at least some evidence of preferential benefit from targeted therapy. Other biological pathways that may define endotypes of COPD include more general pathways of type 2 inflammation, IL-17-driven inflammation (due to autoimmunity or deposition of nanoparticulate carbon black), bacterial colonization, pathological alterations of the airway mucus gel, and others that are beyond the scope of this review. Whether these biological pathways ultimately are found to segregate patients into very distinct endotypes or subsets (like alpha-1 antitrypsin deficiency) or, instead, are present as "treatable traits" in various combinations is uncertain. However imperfect, the endotype concept forces a focus on heterogeneity at a biological level, and the development of biomarkers of biological heterogeneity should help advance the goal of developing new therapies for COPD.