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生物标志物在2型细胞因子介导的哮喘管理中的当前及未来作用。

The current and future role of biomarkers in type 2 cytokine-mediated asthma management.

作者信息

Pavord I D, Afzalnia S, Menzies-Gow A, Heaney L G

机构信息

Respiratory Medicine Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

Roche Products Ltd, Welwyn Garden City, Hertfordshire, UK.

出版信息

Clin Exp Allergy. 2017 Feb;47(2):148-160. doi: 10.1111/cea.12881.

Abstract

Assessment and management of asthma is complicated by the heterogeneous pathophysiological mechanisms that underlie its clinical presentation, which are not necessarily reflected in standardized management paradigms and which necessitate an individualized approach to treatment. This is particularly important with the emerging availability of a variety of targeted forms of therapy that may only be appropriate for use in particular patient subgroups. The identification of biomarkers can potentially aid diagnosis and inform prognosis, help guide treatment decisions and allow clinicians to predict and monitor response to treatment. Biomarkers for asthma have been identified from a variety of sources, including airway, exhaled breath and blood. Biomarkers from exhaled breath include fractional exhaled nitric oxide, measurement of which can help identify patients most likely to benefit from inhaled corticosteroids and targeted anti-immunoglobulin E therapy. Biomarkers measured in blood are relatively non-invasive and technically more straightforward than those measured from exhaled breath or directly from the airway. The most well established of these are the blood eosinophil count and serum periostin, both of which have demonstrated utility in identifying patients most likely to benefit from targeted anti-interleukin and anti-immunoglobulin E therapies, and in monitoring subsequent treatment response. For example, serum periostin appears to be a biomarker for responsiveness to inhaled corticosteroid therapy and may help identify patients as suitable candidates for anti-IL-13 treatment. The use of biomarkers can therefore potentially help avoid unnecessary morbidity from high-dose corticosteroid therapy and allow the most appropriate and cost-effective use of targeted therapies. Ongoing clinical trials are helping to further elucidate the role of established biomarkers in routine clinical practice, and a range of other circulating novel potential biomarkers are currently being investigated in the research setting.

摘要

哮喘的评估和管理因构成其临床表现基础的异质性病理生理机制而变得复杂,这些机制不一定反映在标准化管理模式中,因此需要个体化的治疗方法。随着各种靶向治疗形式的出现,这一点尤为重要,因为这些治疗可能仅适用于特定的患者亚组。生物标志物的识别有可能辅助诊断并提供预后信息,帮助指导治疗决策,并使临床医生能够预测和监测治疗反应。哮喘的生物标志物已从多种来源被识别出来,包括气道、呼出气体和血液。呼出气体中的生物标志物包括呼出一氧化氮分数,对其进行测量有助于识别最有可能从吸入性糖皮质激素和靶向抗免疫球蛋白E治疗中获益的患者。血液中测量的生物标志物相对非侵入性,在技术上比从呼出气体或直接从气道测量的生物标志物更简单。其中最成熟的是血液嗜酸性粒细胞计数和血清骨膜蛋白,两者在识别最有可能从靶向抗白细胞介素和抗免疫球蛋白E治疗中获益的患者以及监测后续治疗反应方面都已证明具有实用性。例如,血清骨膜蛋白似乎是对吸入性糖皮质激素治疗反应性的生物标志物,可能有助于识别适合抗IL - 13治疗的患者。因此,生物标志物的使用有可能帮助避免高剂量糖皮质激素治疗带来的不必要的发病率,并使靶向治疗得到最恰当且具有成本效益的使用。正在进行的临床试验有助于进一步阐明既定生物标志物在常规临床实践中的作用,并且目前正在研究环境中对一系列其他循环中的新型潜在生物标志物进行调查。

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