Severe Adult Asthmas: Integrating Clinical Features, Biology, and Therapeutics to Improve Outcomes.
Severe Adult Asthmas: Integrating Clinical Features, Biology, and Therapeutics to Improve Outcomes.
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DOI：
10.1164/rccm.202009-3631ci
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发表时间：
2021-04-01
影响因子：
24.7
通讯作者：
Wenzel SE
中科院分区：
文献类型：
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作者：
Wenzel SE
评估和有效管理哮喘，特别是严重哮喘，仍然是肺科实践的核心。在过去的20-30年里，人们越来越认识到“严重哮喘”包括多个不同的亚组或表型，每个亚组或表型具有不同的表现。使用临床表型，结合快速发展的分子工具和靶向单克隆抗体（人类基因敲除），对这些表型的理解以及我们治疗它们的能力已经大大提高。2型（T2）-高和低严重哮喘现在很容易识别。部分呼出的一氧化氮和血液嗜酸性粒细胞计数可以在临床环境中常规使用，以识别这些表型并预测对特定治疗的反应，满足精准医学的最初目标。分子信号、生物标志物和对靶向治疗的临床反应的整合使得能够鉴定关键分子途径，并且在某些表型中，将它们推进到近内源型状态。尽管取得了这些进展，但几乎没有指导来确定哪一类生物制剂适合特定患者，目前的“突破性”疗法仍然昂贵，甚至许多患者无法获得。许多最严重的哮喘，有或没有T2-生物标志物升高，仍然知之甚少和治疗。然而，对“严重哮喘”的概念性理解在短短25年内发生了巨大的变化，导致许多人的生活得到了显着改善。
Evaluation and effective management of asthma, and in particular severe asthma, remains at the core of pulmonary practice. Over the last 20–30 years, there has been increasing appreciation that “severe asthma” encompasses multiple different subgroups or phenotypes, each with differing presentations. Using clinical phenotyping, in combination with rapidly advancing molecular tools and targeted monoclonal antibodies (human knockouts), the understanding of these phenotypes, and our ability to treat them, have greatly advanced. Type-2 (T2)-high and -low severe asthmas are now easily identified. Fractional exhaled nitric oxide and blood eosinophil counts can be routinely employed in clinical settings to identify these phenotypes and predict responses to specific therapies, meeting the initial goals of precision medicine. Integration of molecular signals, biomarkers, and clinical responses to targeted therapies has enabled identification of critical molecular pathways and, in certain phenotypes, advanced them to near-endotype status. Despite these advances, little guidance is available to determine which class of biologic is appropriate for a given patient, and current “breakthrough” therapies remain expensive and even inaccessible to many patients. Many of the most severe asthmas, with and without T2-biomarker elevations, remain poorly understood and treated. Nevertheless, conceptual understanding of “the severe asthmas” has evolved dramatically in a mere 25 years, leading to dramatic improvements in the lives of many.