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哮喘表型和内型:对个体化治疗的启示。

Asthma Phenotypes and Endotypes: Implications for Personalised Therapy.

机构信息

University Hospital South Manchester, Manchester, UK.

Manchester Academic Health Science Centre, The University of Manchester and University Hospital South Manchester, Manchester, UK.

出版信息

BioDrugs. 2017 Oct;31(5):393-408. doi: 10.1007/s40259-017-0242-5.

Abstract

Asthma is increasingly recognised as a heterogeneous group of diseases with similar clinical presentations rather than a singular disease entity. Asthma was historically categorised by clinical symptoms; however, newer methods of subgrouping, describing and categorising the disease have sub-defined asthma. These sub-definitions are intermittently called phenotypes or endotypes, but the real meanings of these words are poorly understood. Novel treatments are currently and increasingly available, partly in the monoclonal antibody environment, and also some physical therapies (bronchial thermoplasty), but additionally small molecules are not far away from clinical practice. Understanding the disease pathogenesis and the mechanism of action more completely may enable identification of treatable traits, biomarkers, mediators and modifiable therapeutic targets. However, there remains a danger that clinicians become preoccupied with the concept of endotypes and biomarkers, ignoring therapies that are hugely effective but have no companion biomarker. This review discusses our understanding of the concept of phenotypes and endotypes in appreciating and managing the heterogeneous condition that is asthma. We consider the role of functional imaging, physiology, blood-, sputum- and breath-based biomarkers and clinical manifestations that could be used to produce a personalised asthma profile, with implications on prognosis, pathophysiology and most importantly specific therapeutic responses. With the advent of increasing numbers of biological therapies and other interventional options such as bronchial thermoplasty, the importance of targeting expensive therapies to patients with the best chance of clinical response has huge health economic importance.

摘要

哮喘越来越被认为是一组具有相似临床表现的异质性疾病,而不是单一的疾病实体。哮喘在历史上是根据临床症状分类的;然而,描述和分类疾病的新方法已经细分了哮喘。这些细分定义有时被称为表型或内型,但这些词的真正含义理解得很差。目前,新的治疗方法正在不断涌现,部分是在单克隆抗体环境中,还有一些物理疗法(支气管热成形术),但小分子治疗也即将进入临床实践。更全面地了解疾病的发病机制和作用机制可能有助于确定可治疗的特征、生物标志物、介质和可改变的治疗靶点。然而,临床医生仍然存在一种危险,即过于关注内型和生物标志物的概念,而忽略了那些非常有效但没有伴随生物标志物的治疗方法。这篇综述讨论了我们对表型和内型概念的理解,这些概念有助于理解和管理哮喘这种异质性疾病。我们考虑了功能成像、生理学、血液、痰液和呼气生物标志物以及临床表现的作用,这些可以用来生成个性化的哮喘特征,对预后、病理生理学以及最重要的特定治疗反应有影响。随着越来越多的生物治疗和其他干预选择(如支气管热成形术)的出现,将昂贵的治疗方法靶向具有最佳临床反应机会的患者具有巨大的健康经济重要性。

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