Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY.
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY; Division of Allergy and Immunology, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY.
J Allergy Clin Immunol. 2019 Jul;144(1):13-23. doi: 10.1016/j.jaci.2019.05.015.
Asthma is a highly heterogeneous disease, often manifesting with wheeze, dyspnea, chest tightness, and cough as prominent symptoms. The eliciting factors, natural history, underlying molecular biology, and clinical management of asthma vary highly among affected subjects. Because of this variation, many efforts have gone into subtyping asthma. Endotypes are subtypes of disease based on distinct pathophysiologic mechanisms. Endotypes can be clinically useful because they organize our mechanistic understanding of heterogeneous diseases and can direct treatment toward modalities that are likely to be the most effective. Asthma endotyping can be shaped by clinical features, laboratory parameters, and/or -omics approaches. We discuss the application of -omics approaches, including transcriptomics, epigenomics, microbiomics, metabolomics, and proteomics, to asthma endotyping. -Omics approaches have provided supporting evidence for many existing endotyping paradigms and also suggested novel ways to conceptualize asthma endotypes. Although endotypes based on single -omics approaches are relatively common, their integrated multi-omics application to asthma endotyping has been more limited thus far. We discuss paths forward to integrate multi-omics with clinical features and laboratory parameters to achieve the goal of precise asthma endotypes.
哮喘是一种高度异质性的疾病,常表现为喘息、呼吸困难、胸闷和咳嗽等突出症状。哮喘的诱发因素、自然病史、潜在分子生物学和临床管理在受影响的患者中差异很大。由于这种差异,人们已经做出了许多努力来对哮喘进行亚型划分。表型是基于不同病理生理机制的疾病亚型。表型可以在临床上发挥作用,因为它们可以帮助我们理解异质性疾病的机制,并指导我们针对最有可能有效的治疗方法。哮喘表型可以通过临床特征、实验室参数和/或组学方法来确定。我们讨论了组学方法(包括转录组学、表观基因组学、微生物组学、代谢组学和蛋白质组学)在哮喘表型中的应用。组学方法为许多现有的表型分类提供了支持证据,也为概念化哮喘表型提供了新的思路。尽管基于单一组学方法的表型相对常见,但迄今为止,它们在哮喘表型中的综合多组学应用还比较有限。我们讨论了将多组学与临床特征和实验室参数相结合以实现精准哮喘表型的目标的前进道路。