Integrative Omics of Eosinophils in Asthma and COPD: Deciphering Molecular Signatures for Targeted Therapy

Eosinophils are central effector and regulatory cells in asthma and eosinophilic respiratory disease, and a clinically relevant subset in a proportion of patients with chronic obstructive pulmonary disease (COPD) and asthma-COPD overlap. While eosinophil counts are established biomarkers to guide corticosteroid and biologic therapy, they do not capture the molecular heterogeneity of eosinophil activation across these conditions. Advances in integrative omics now permit comprehensive profiling of eosinophils at the transcriptomic, proteomic, and lipidomic levels. In this narrative review we summarize eosinophil-focused single-omics and multi-omics studies in asthma and COPD, with an emphasis on severe eosinophilic asthma and eosinophilic COPD. Multi-omics analysis of blood eosinophils in severe asthma has revealed IL-5-dominated pathways that coexist with IL-4 and microbe-responsive programs. In contrast, eosinophils in asthma-COPD overlap and eosinophilic COPD exhibit prominent interferon-γ, tumor necrosis factor-α, and IL-33 signatures. Mechanistic studies further demonstrate that IL-4/IL-13 enhances eosinophil responsiveness to IL-33 and that IL-33 induces extracellular trap formation (ETosis). We discuss how these disease- and context-specific molecular programs may refine biomarker interpretation and inform the rational selection of biologics targeting IL-5/IL-5R, IL-4Rα, TSLP, and IL-33/ST2 in asthma and COPD.