Beyond the Usual Suspects: Unmasking Low-T2 Asthma in Children

Background: T2 low asthma in children is an emerging yet underexplored endotype that challenges traditional views of type 2 inflammation. Recent data suggest that it is more prevalent than previously thought and is defined by low type 2 biomarkers, non-allergic clinical profiles, and strong associations with modifiable comorbidities such as obesity, passive smoke exposure, and recurrent respiratory infections. This phenotype often shows a poor response to standard inhaled corticosteroid therapy and T2-targeted biologics, underscoring the urgent need for improved diagnostic and therapeutic approaches. Methods: This narrative review conducted a literature search from PubMed and WoS databases (2020–2025), focusing on T2-low asthma defined by low blood eosinophils (<150–300/µL), FeNO (<20–25 ppb), and absent atopy in children under 18. Results: This review highlights the heterogeneity of T2-low asthma, including subtypes from neutrophilic/Th 17-high to paucigranulocytic airway remodeling and metabolic driven forms, as well as diagnostic challenges from biomarker supresssion by high-dose therapies. Pragmatic phenotyping algorithms using routine tests enable identification, directing comorbidity management over ineffective biologics. Conclusions: Systematic T2-low phenotyping in pediatric practice, alongside prospective studies and non-T2 therapy trials, promises precision medicine to enhance outcomes for these children, moving beyond eosinophil-centric care.