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生物标志物能否帮助我们攻克治疗棘手的哮喘的难题?

Can biomarkers help us hit targets in difficult-to-treat asthma?

机构信息

Centre of Excellence in Severe Asthma, School of Medicine and Public Health, Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, Australia.

Centre for Experimental Medicine, Wellcome-Wolfson Institute for Experimental Medicine, Queens University Belfast, Belfast, UK.

出版信息

Respirology. 2017 Apr;22(3):430-442. doi: 10.1111/resp.13014. Epub 2017 Mar 1.

Abstract

Biomarkers may be a key foundation for the precision medicine of the future. In this article, we review current knowledge regarding biomarkers in difficult-to-treat asthma and their ability to guide the use of both conventional asthma therapies and novel (targeted) therapies. Biomarkers (as measured by tests including prednisolone and cortisol assays and the fractional exhaled nitric oxide (NO) suppression test) show promise in the assessment and management of non-adherence to inhaled and oral corticosteroids. Multiple markers of type 2 inflammation have been developed, including eosinophils in sputum and blood, exhaled NO, serum IgE and periostin. Although these show potential in guiding the selection of novel interventions for refractory type 2 inflammation in asthma, and in determining if the desired response is being achieved, it is becoming clear that different biomarkers reflect distinct components of the complex type 2 inflammatory pathways. Less progress has been made in identifying biomarkers for use in difficult-to-treat asthma that is not associated with type 2 inflammation. The future is likely to see further biomarker discovery, direct measurements of individual cytokines rather than surrogates of their activity and the increasing use of biomarkers in combination. If the promise of biomarkers is to be fulfilled, they will need to provide useful information that aids clinical decision-making, rather than being 'just another test' for clinicians to order.

摘要

生物标志物可能是未来精准医学的重要基础。在本文中,我们回顾了目前关于难治性哮喘中生物标志物的知识及其指导常规哮喘治疗和新型(靶向)治疗的应用的能力。生物标志物(通过包括泼尼松龙和皮质醇测定以及呼气一氧化氮(NO)抑制分数测定在内的测试进行测量)在评估和管理吸入和口服皮质类固醇的不依从性方面显示出一定的前景。已经开发出多种 2 型炎症标志物,包括痰和血液中的嗜酸性粒细胞、呼气一氧化氮、血清 IgE 和骨桥蛋白。尽管这些标志物在指导选择新型干预措施治疗难治性 2 型炎症以及确定是否达到预期反应方面显示出潜力,但很明显,不同的标志物反映了复杂的 2 型炎症途径的不同组成部分。在确定与 2 型炎症无关的难治性哮喘的生物标志物方面,进展较少。未来很可能会有更多的生物标志物被发现,包括直接测量单个细胞因子而不是它们活性的替代物,以及越来越多地将生物标志物联合使用。如果生物标志物的前景能够实现,它们将需要提供有助于临床决策的有用信息,而不仅仅是临床医生要开的“又一项测试”。

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