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Advances in the management of severe therapy-resistant pediatric asthma
Antonio Corsello1,2, Antonio Andrea Senatore2,3, Marta Bajeli2,3
1Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
Insights
Severe therapy-resistant pediatric asthma (STRA) requires precise diagnosis and endotype-driven management. Precision medicine, including biologics, offers improved outcomes for selected children, shifting care from empirical escalation to targeted interventions.
Area of Science:
- Pediatric pulmonology
- Asthma research
- Precision medicine
Background:
- Severe therapy-resistant pediatric asthma (STRA) affects 2-5% of children, causing significant morbidity and high healthcare costs.
- STRA is defined by uncontrolled symptoms despite optimized high-dose inhaled corticosteroids and controllers, after excluding modifiable factors.
- Distinguishing STRA from difficult-to-treat asthma is crucial for appropriate management and avoiding overtreatment.
Purpose of the Study:
- To review current knowledge on STRA pathophysiology, diagnosis, and management in children.
- To highlight the role of precision medicine and biomarker-guided endotyping in pediatric asthma care.
- To evaluate the efficacy and positioning of biologic therapies for STRA.
Main Methods:
- Narrative review of current literature on STRA.
- Analysis of mechanistic insights into STRA pathophysiology, including inflammation and immune interactions.
- Evaluation of approved biologic therapies and their application in biomarker-selected pediatric patients.
Main Results:
- STRA pathophysiology involves epithelial barrier dysfunction, diverse inflammatory endotypes, early airway remodeling, and microbial-immune interactions.
- Biomarker-guided endotyping facilitates individualized treatment strategies for pediatric asthma.
- Approved biologics demonstrate efficacy in reducing exacerbations, improving lung function, and decreasing steroid dependence in selected STRA patients.
Conclusions:
- STRA management is evolving towards endotype-driven strategies, moving beyond empirical treatment escalation.
- Biologics offer significant benefits for biomarker-selected pediatric patients with STRA, improving disease control and quality of life.
- Future research should focus on expanding treatment options for non-T2 and mixed phenotypes, validating predictive biomarkers, and addressing global access inequities.
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.
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