定义哮喘表型:迈向个体化医疗的一步
2014/07/15
摘要
哮喘是一种发病机制复杂的常见疾病。它的临床表现各异,严重程度也不同。无偏差聚类分析已经阐明了一些哮喘表型,可代表各种严重程度的人群。重度哮喘包括那些需要大剂量皮质类固醇激素治疗(吸入/口服),并常伴有严重呼吸道阻塞的的患者。研究报道了一类患者表型,其临床表现与痰液嗜酸性粒细胞增加一致。其中包括以嗜酸性炎症反应为主的患者群体,这类患者几乎无临床症状和迟发型疾病,也是鼻窦炎、阿司匹林敏感和哮喘发作的高发人群。痰液嗜酸性粒细胞增多还可作为预测抗体基础治疗疗效的生物指标(抗体基础治疗:通过抗体阻断T辅助细胞(Th)-2细胞因子、IL-5的作用)。Th2细胞低表达可预测吸入类固醇激素治疗应答不佳。目前哮喘的治疗方案强调根据患者的临床严重程度采取相应的治疗措施。但是,由于重度哮喘是一种异质性特别明显的疾病,在某些更严重的患者中,需要通过表型和endotype(根据功能和病理生理机制分类)选择相应的治疗方案。我们对非嗜酸性粒细胞性哮喘的认知较少,对皮质类固醇激素反应低下及慢性气道阻塞的重度哮喘患者的表型特点也认知不足。随着转录组学及蛋白质组学技术的发展,系统生物学或药物治疗方法将逐渐应用于定义疾病表型及治疗效果相关生物指标,这将使表型驱动的哮喘治疗方案得到更好地发展,并为哮喘患者的个体化治疗及医疗护理铺平道路。
(刘国梁 审校)
Drugs. 2014 May 6. [Epub ahead of print]
Defining Phenotypes in Asthma: A Step Towards Personalized Medicine.
Chung KF.
ABSTRACT
Asthma is a common disease with a complex pathophysiology. It can present in various clinical forms and with different levels of severity. Unbiased cluster analytic methods have unravelled several phenotypes in cohorts representative of the whole spectrum of severity. Clusters of severe asthma include those on high-dose corticosteroid treatment, often with both inhaled and oral treatment, usually associated with severe airflow obstruction. Phenotypes with concordance between symptoms and sputum eosinophilia have been reported, including an eosinophilic inflammation-predominant group with few symptoms and late-onset disease who have a high prevalence of rhinosinusitis, aspirin sensitivity, and exacerbations. Sputum eosinophilia is also a biomarker that can predict therapeutic responses to antibody-based treatments to block the effects of the T-helper (Th)-2 cytokine, interleukin (IL)-5. Low Th2-expression has been predictive of poor therapeutic response to inhaled corticosteroid therapy. Current asthma schedules emphasise a step-up approach to treating asthma in relation to increasing severity, but, in more severe disease, phenotyping or endotyping of asthma will be necessary to determine new treatment strategies as severe asthma is recognized as being a particularly heterogeneous disease. Much less is known about 'non-eosinophilic' asthma. Phenotypic characterisation of corticosteroid insensitivity and chronic airflow obstruction of severe asthma is also needed. Phenotype-driven treatment of asthma will be further boosted by the advent of transcriptomic and proteomic technologies, with the application of systems biology or medicine approaches to defining phenotypes and biomarkers of disease and therapeutic response. This will pave the way towards personalized medicine and healthcare for asthma.
Drugs. 2014 May 6. [Epub ahead of print]