Department of Pneumology and Phthisiology, University Hospital and Faculty of Medicine in Pilsen, Charles University Prague, Czech Republic.
Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands; Dept Microbiology Immunology & Transplantation, KU Leuven, Catholic University of Leuven, Belgium; Department of Respiratory Medicine, First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic.
Respir Med. 2024 Nov-Dec;234:107766. doi: 10.1016/j.rmed.2024.107766. Epub 2024 Aug 22.
Severe asthma represents a true challenge for clinicians from two basic perspectives, i.e.: a rational assessment of the underlying endo/phenotype and the subsequent selection of the best fitted (personalized) and effective treatment. Even though asthma is a heterogeneous disease, in the majority of therapy-compliant patients, it is possible to achieve (almost) complete disease control or even remission through conventional and quite uniform step-based pharmacotherapy, even without phenotyping. However, the absence of deeper assessment of individual patients revealed its handicap to its fullest extent during the first years of the new millennium upon the launch of biological therapeutics for patients with the most severe forms of asthma. The introduction of differentially targeted biologics into clinical practice became a challenge in terms of understanding and recognizing the etiopathogenetic heterogeneity of the asthmatic inflammation, pheno/endotyping, and, consequently, to choose the right biologic for the right patient. The answers to the following three questions should lead to correct identification of the dominant pheno/endotype: Is it really (severe) asthma? Is it eosinophilic asthma? If eosinophilic, is it (predominantly) allergen-driven? The identification of the best achievable and relevant alliance between endotypes and phenotypes ("euphenotypes") should be based not only on the assessment of the actual clinical characteristics and laboratory biomarkers, but more importantly, on the evaluation of their development and changes over time. In the current paper, we present a pragmatic three-step approach to severe asthma diagnosis and management.
从两个基本角度来看,严重哮喘对临床医生构成了真正的挑战,即:对内/表型进行合理评估,以及随后选择最佳(个体化)和有效的治疗方法。尽管哮喘是一种异质性疾病,但在大多数依从治疗的患者中,通过常规且相当统一的基于阶梯的药物治疗,即使没有表型分析,也有可能实现(几乎)完全控制疾病,甚至缓解。然而,在新千年初期生物疗法推出用于治疗最严重形式的哮喘患者时,由于对个体患者的深入评估不足,其最大程度地暴露出了这一方法的缺陷。针对哮喘炎症、表型/内型的病因发病机制异质性,针对不同靶点的生物制剂在临床实践中的引入,在理解和识别方面带来了挑战,因此需要为每位患者选择合适的生物制剂。正确识别主要的表型/内型需要回答以下三个问题:它真的(是严重的)哮喘吗?它是嗜酸性粒细胞性哮喘吗?如果是嗜酸性粒细胞性哮喘,它是否(主要)由过敏原驱动?在确定内型和表型(“优表型”)之间最佳可行和相关的联合治疗方案时,不仅要基于对实际临床特征和实验室生物标志物的评估,更重要的是要评估它们随时间的发展和变化。在本文中,我们提出了一种实用的三步方法来诊断和管理严重哮喘。