What are the prevalence and potential risk factors for T2-low asthma?

Published online April 30, 2025

Asthma is a heterogenous syndrome comprising various phenotypes with distinct pathophysiological mechanisms or endotypes. T-helper 2 (T2)-high asthma has been thought to be the most common asthma subtype in children and adolescents. Recent evidence suggests that T2-low asthma is more common than previously assumed among school-aged youth. Relatively little is known about potential risk factors for T2-low asthma in this population.

In a study published in a recent issue of The Journal of Allergy and Clinical Immunology: In Practice, Han et al. examined the prevalence and factors associated with T2-low and T2-high asthma in 4,284 children and adolescents aged 6 to 17 years who participated in the 2007-2012 National Health and Nutrition Examination Survey. Using available biomarkers, T2-low asthma was defined by an absolute peripheral blood eosinophil count (AEC) <300 cells/uL and fractional exhaled nitric oxide (FeNO) < 25 ppb, and T2-high asthma was defined by AEC ≥ 300 cells/uL or FeNO ≥ 25 ppb. In a secondary analysis using more stringent criteria, T2-low asthma was defined by an AEC <428 cells/µL and a FeNO < 32.5 ppb (Yue, Gaietto et al, JAMA 2025). Multinomial logistic or linear regression was used for the multivariable analysis.

Among 505 participating children with asthma, T2-low asthma was identified in 231 (46%) children in the primary analysis and in 305 (60%) children in the secondary analysis. Compared with children without asthma (controls), those with T2-low asthma were 1.1 to 2.1 times significantly more likely to be older, female, and overweight or obese, and those with T2-high asthma were more likely to be male, non-Hispanic Black, and to have vitamin D insufficiency and bronchodilator responsiveness. Children with either asthma subtype were more likely to have a family history of asthma, hay fever episodes in the prior year, and lower %predicted FEV1 and FEV1/FVC than controls. In the secondary analysis, current second-hand smoke exposure was also significantly associated with T2-low asthma.  

In summary, results from this study further support T2-low asthma as a common asthma subtype among school-aged children in the U.S. and identify overweight or obesity and second-hand smoke exposure as factors associated with this asthma subtype. Longitudinal studies using more precise approaches to categorize asthma subtypes (e.g., airway epithelial omics) are needed to expand on these findings.

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.

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