Advances in the management of severe therapy-resistant pediatric asthma

Introduction: Severe therapy-resistant pediatric asthma (STRA) is an uncommon but high-impact form of childhood asthma, affecting 2–5% of patients yet causing disproportionate morbidity, healthcare use, and corticosteroid exposure. It is defined by uncontrolled disease despite optimized high-dose inhaled corticosteroids plus additional controllers, after exclusion and correction of modifiable factors. Accurate distinction from difficult-to-treat asthma is essential to avoid unnecessary treatment escalation and enable timely advanced interventions. Areas covered: This narrative review summarizes current knowledge on STRA pathophysiology, diagnosis, and management in children, with a focus on precision medicine. Mechanistic insights include epithelial barrier dysfunction, distinct inflammatory endotypes, early airway remodeling, and microbial–immune interactions. Biomarker-guided endotyping supports individualized care. The article evaluates the efficacy, safety, and positioning of approved biologics, while noting gaps in treating non-T2 phenotypes and in predicting biologic response. Expert opinion: STRA management is shifting from empirical escalation to endotype-driven strategies. Biologics benefit biomarker-selected patients by reducing exacerbations, improving lung function, and lowering steroid dependence, sometimes addressing comorbid allergies. Future priorities include expanding options for non-T2 and mixed phenotypes, validating predictive biomarkers, integrating digital monitoring, and reducing global inequities in access to advanced therapy.