Poto Remo, Portacci Andrea, Chan Rory, Lagnese Gianluca, Giovannini Mattia, Varricchi Gilda
Department of Translational Medical Sciences.
Center for Basic and Clinical Immunology Research (CISI) - University of Naples Federico II, Naples.
Curr Opin Allergy Clin Immunol. 2025 Aug 1;25(4):269-276. doi: 10.1097/ACI.0000000000001081. Epub 2025 Jun 13.
Asthma is a heterogeneous disease encompassing distinct phenotypes and endotypes. Advances in elucidating the pathogenic role of type 2 (T2) cytokines and epithelial-derived alarmins have profoundly reshaped our understanding of airway inflammation in asthma. This review provides an updated perspective on how these mediators contribute to asthma pathobiology and examines their integration into emerging precision medicine strategies.
Biologic agents targeting T2 cytokines (IL-4, IL-5, and IL-13) and alarmins (TSLP and IL-33) have demonstrated efficacy across a broad spectrum of severe asthma phenotypes. Recent evidence underscores the central role of alarmins in orchestrating both innate and adaptive immune responses within the airways. In parallel, the development of alarmin-associated molecular and clinical biomarkers is expanding patient stratification beyond traditional eosinophilic and allergic profiles.
Advancing our understanding of alarmins and T2 cytokines offers new opportunities to refine asthma endotyping, personalize therapeutic decisions, and pursue sustained disease remission. Future directions include the integration of multiomics, real-world evidence, and novel biomarker platforms to consolidate the next phase of precision medicine in asthma and optimize long-term disease modification strategies.
哮喘是一种异质性疾病，包含不同的表型和内型。在阐明2型（T2）细胞因子和上皮来源的警报素的致病作用方面取得的进展，深刻地重塑了我们对哮喘气道炎症的理解。本综述提供了关于这些介质如何促成哮喘病理生物学的最新观点，并探讨了它们如何融入新兴的精准医学策略。
靶向T2细胞因子（IL-4、IL-5和IL-13）和警报素（TSLP和IL-33）的生物制剂已在广泛的重度哮喘表型中显示出疗效。最近的证据强调了警报素在协调气道内固有免疫和适应性免疫反应中的核心作用。与此同时，与警报素相关的分子和临床生物标志物的发展正在将患者分层扩展到传统的嗜酸性粒细胞和过敏特征之外。
加深我们对警报素和T2细胞因子的理解为优化哮喘内型分类、个性化治疗决策以及实现疾病持续缓解提供了新机会。未来的方向包括整合多组学、真实世界证据和新型生物标志物平台，以巩固哮喘精准医学的下一阶段，并优化长期疾病改善策略。
