Respiratory Medicine, Department of Translational Medicine, University of Ferrara, Ferrara, Italy.
Department of Respiratory Diseases, University of Montpellier, CHU Montpellier, INSERM, Montpellier, France.
Adv Exp Med Biol. 2023;1426:239-252. doi: 10.1007/978-3-031-32259-4_11.
Asthma is defined as severe when it is uncontrolled despite the high intensity of treatment, or that loses control when a therapeutic step down is tried.These patients, for years, have been "uniformly" treated with massive doses of inhaled and oral corticosteroids regardless of their inflammatory state.Initially, asthma was considered of genesis "exclusively allergic." Subsequently, thanks to the development of noninvasive tools and of human monoclonal antibodies targeting interleukin 5, a pathogenetic role has been given to eosinophils. Management of steroids based on sputum eosinophil counts has been suggested according to clinical phenotypes identified through cluster analysis.The algorithms obtained from the cluster analysis have proved later to be poorly predictive of the inflammatory phenotype and difficult to apply in clinical practice.In the new era of precision medicine, the greatest challenge is finding clinical or biological elements predictive of response to therapies such as biologics. Cluster analyses performed on omics data or on cohorts of patients treated with biologics are more promising in this sense.In this article, starting from the current definition of severe asthma, we review the phenotypes proposed over time to date, showing the difficulty underlying the process of "phenotyping" due to the scarcity of available biomarkers.
哮喘被定义为尽管治疗强度很高但仍无法控制，或在尝试降低治疗强度时失去控制的严重情况。这些患者多年来一直“统一”接受大剂量吸入和口服皮质类固醇治疗，而不论其炎症状态如何。最初，哮喘被认为是“完全”由过敏引起的。随后，由于非侵入性工具和针对白细胞介素 5 的人单克隆抗体的发展，嗜酸粒细胞被赋予了发病作用。根据通过聚类分析确定的临床表型，已经提出了基于痰液嗜酸粒细胞计数的类固醇管理建议。从聚类分析中获得的算法后来被证明对炎症表型的预测能力较差，并且难以在临床实践中应用。在精准医学的新时代，最大的挑战是找到预测对生物制剂等治疗反应的临床或生物学因素。在这方面，基于组学数据或接受生物制剂治疗的患者队列进行的聚类分析更有希望。本文从目前严重哮喘的定义出发，回顾了迄今为止提出的表型，由于缺乏可用的生物标志物，显示了“表型”过程背后的困难。
