Biologic Therapy for Severe Asthma: Biomarker-Guided Precision Treatment and Immunopathological Mechanisms

Severe asthma is a difficult-to-control airway disease with pronounced heterogeneity in both clinical manifestations and underlying inflammatory mechanisms. This review examines the mechanisms, biomarkers, and biologic therapies of severe asthma, with a focus on biomarker-guided treatment selection and emerging precision strategies for type 2-high (T2-high) and type 2-low (T2-low) disease. The development of biologic therapies has changed the treatment paradigm, particularly for patients with T2-high inflammation. By targeting immunoglobulin E (IgE), interleukin-5 (IL-5), interleukin-4 receptor alpha (IL-4Rα), and thymic stromal lymphopoietin (TSLP)-related pathways, these agents can decrease exacerbations, improve lung function and symptom control, and enhance quality of life. Biomarkers, including blood eosinophils, fractional exhaled nitric oxide (FeNO), total IgE, and sputum eosinophils, have been incorporated into clinical decision-making to support patient stratification. Emerging markers such as periostin, epithelial alarmins, gene-expression patterns, microRNAs, and multi-omics signatures are under investigation for more accurate phenotyping and response prediction. Despite these advances, current biomarkers do not always provide sufficient predictive accuracy, targeted options for T2-low asthma remain limited, biologics are costly, and long-term outcome data remain incomplete. Overall, integrating biomarker findings with clinical phenotype, comorbidities, and treatment history remains central to individualized biologic selection.