Impact and management of biologic therapies on small airway dysfunction in severe asthma: a comprehensive review

Despite significant advances in precision medicine, managing severe asthma remains a major clinical challenge. Small airway dysfunction (SAD) is a crucial determinant of poor symptom control, airway remodeling, and frequent exacerbations. While conventional spirometry primarily assesses large airway mechanics, airway oscillometry (AO) provides a highly sensitive, effort-independent evaluation of peripheral resistance and reactance during normal breathing.

This review synthesizes current evidence from major biomedical databases (PubMed, Embase, Scopus, and Web of Science; 2000-2026) regarding the physiological role of SAD across severe asthma phenotypes (eosinophilic vs. non-eosinophilic). Furthermore, it systematically evaluates the specific impact of targeted biological therapies (anti-IgE, anti-IL-5/IL-5 R, anti-IL-4/13 Rα, and anti-TSLP) on distal respiratory mechanics.

SAD represents a vital treatable trait in severe asthma. Biologics exert distinct physiological effects on peripheral parameters, with upstream modulators such as dupilumab and tezepelumab demonstrating superior efficacy in reversing distal mucus plugging and frequency-dependent resistance abnormalities. Incorporating AO into routine clinical algorithms alongside T2 inflammatory biomarkers is essential to refine endophenotyping, improve overall risk stratification, guide personalized biologic selection, and accurately monitor functional therapeutic responses in patients with severe refractory asthma.