Race Adjusted for Social and Environmental Disparities Is the Principal Determinant of T2HIGH Inflammation in Children with Severe Asthma.

Abstract

Robust T-helper two (T2) inflammation drives a phenotype noted for difficult symptoms in children with asthma. Past studies show that Black children have greater T2 inflammation than White children. However, it is not clear how disparate social and environmental factors inform this difference. To examine the fundamental factors which differentiate T2^HIGH and ^LOW inflammation phenotypes in children with severe, treatment-refractory asthma. Children underwent bronchoscopy and measures of blood T2 markers. T2^HIGH children (n=202) had blood or lung lavage (BAL) eosinophilia and specific IgE to ≥ 1 allergens; T2^LOW (n=249) had neither. Factors associated with T2^HIGH inflammation were examined with multivariable logistic regression (MLR) and neural network (NN) models. The T2^HIGH phenotype was dominant by five years of age. Children with T2^HIGH inflammation, compared to T2^LOW, were older, had greater self-reported Black race, lower household income, greater hospital admissions, lower FEV₁, and greater BAL granulocytes. In regression models, Black race/ethnicity had the highest odds ratio (OR, 95% confidence interval) of T2^HIGH inflammation adjusted for social and environmental disparities (OR 2.88, 1.79-4.64, p < 0.001, E-estimate 5.2) and clinical outcomes (OR 3.84, 2.19-6.73, p < 0.001, E-estimate 7.14). These results were repeatable with NN models, although age performed better than Black race in the social/environmental analysis. In children with severe asthma, Black race confers the highest odds for T2^HIGH inflammation adjusted for demographic, social, environmental, and clinical factors. Both Race/ethnicity and the magnitude of T2 inflammation should guide the treatment of children with severe asthma.