Exploring the Utility of Noninvasive Type 2 Inflammatory Markers for Prediction of Severe Asthma Exacerbations in Children and Adolescents

Abstract

Background: Noninvasive markers of type 2 inflammation are needed to identify children and adolescents who might benefit from personalized biologic therapy.

Objective: We hypothesized that blood eosinophil counts would predict 1 or more acute visits for asthma and that prediction could be improved with the addition of a second, noninvasive type 2 inflammatory biomarker.

Methods: Children and adolescents 5 to 21 years (N = 589) with an asthma exacerbation necessitating systemic corticosteroid treatment in the previous year completed a characterization visit and telephone calls at 6 and 12 months. The primary outcome was an acute visit for asthma with receipt of systemic corticosteroids. Acute visits were verified by medical record review. Exploratory outcomes included time to first acute visit and hospitalization.

Results: Acute visits occurred in 106 (35.5%) children and 72 (24.8%) adolescents. Elevated blood eosinophils were associated with increased odds and shorter time to first acute visit, but optimal cut-points differed by age (≥150 vs ≥300 cells/μL for children vs adolescents, respectively). The addition of a second marker of type 2 inflammation did not improve prediction in children, but increased the odds and hazard of an acute visit up to 16.2% and 11.9%, respectively, in adolescents. Similar trends were noted for hospitalizations.

Conclusions: Blood eosinophils and other noninvasive markers of type 2 inflammation may be useful in the clinical assessment of children and adolescents with asthma. However, features of type 2 inflammation vary by age. Whether children and adolescents also respond differently to management of type 2 inflammation is unclear and warrants further evaluation.

Keywords: Allergic sensitization; Asthma control; Asthma exacerbation; Biomarker; Eosinophil; Type 2 inflammation.

Figure 1.

Distribution of (A) blood eosinophils, (B) exhaled nitric oxide, (C) serum IgE, and (D) percentage of positive allergens and associations between blood eosinophils and (E) exhaled nitric oxide, (F) serum IgE, and (G) percentage of positive allergens in children 5–11 years (blue) and adolescents 12–21 years (green).

Figure 2.

Time to first acute visit in children age 5–11 years (left panels, blue) and adolescents (right panels, green) based on elevated blood eosinophils alone (panels A-B), elevated blood eosinophils plus any sensitization (panels C-D), and elevated blood eosinophils plus multiple sensitization (panels E-F). Models were adjusted for sex, ethnicity, race, household education level, tobacco smoke exposure, and inhaled corticosteroid use.