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

To show that blood eosinophil counts in children and adolescents with exacerbation-prone asthma would predict 1 or more acute visits for asthma in the 6–12 months after measurement and that prediction of acute events could be improved with the addition of a second, noninvasive type 2 inflammatory marker.

589 children and adolescents with exacerbation-prone asthma (exacerbation requiring systemic steroid treatment in the previous year) who were participating in asthma research studies at Emory University between January 2007 and December 2016.

This was a secondary analysis. Data were collected concerning demographics, medical history and symptoms, neighborhood characteristics. All participants underwent spirometry before and after a bronchodilator, and those that did not have a significant response underwent methacholine challenge to confirm airway hyperresponsiveness. Exhaled nitric oxide, specific IgE to a variety of aeroallergens, blood eosinophil counts and total serum IgE were also measured. Phone call follow-up occurred at 6 and 12 months after the study visit. The primary outcome measure was 1 or more acute visits for asthma requiring systemic corticosteroids at 6 or 12 months. Secondary outcomes included time to first acute visit and hospitalization.

The majority of children were sensitized to aeroallergens. An acute visit for asthma occurred in 35.5% of children and 24.8% of adolescents. Hospitalizations occurred in 20.8% of children and 26.4% of adolescents. In children, blood eosinophils ≥150 cells/µl (adjusted OR 2.39, 95% CI 1.83–3.13) were most strongly associated with acute visit, but sensitization (adjusted OR 1.65, 95% CI 1.21–2.25) and frequency of daytime symptoms (adjusted OR 1.23, 95% CI 1.02–1.47) were also significant predictors. In adolescents, blood eosinophils ≥300 cells/µl (adjusted OR 2.04, 95% CI 1.60–2.60) were most strongly associated with an acute visit, additionally sensitization (adjusted OR 2.39, 95% CI 1.54–3.71), daytime symptoms (adjusted OR 1.85, 95% CI: 1.47–2.33), and serum IgE ≥100 kU/L (adjusted OR 1.43, 95% CI 1.06–1.92) were significant predictors, although specificity was poor for all measures in each age group. In children, the addition of a secondary T2 marker was not any more predictive than the blood eosinophil count alone, but in adolescents the association of serum eosinophils ≥300 cells/µl and sensitization increased the predictability of an acute visit.

In exacerbation-prone children and adolescents, elevated blood eosinophils are associated with increased odds and shorter time to the first acute visit for asthma. Sensitization to aeroallergens contributes to these odds in adolescents.

It is known that a history of an exacerbation in the last year is a predictor of additional exacerbations in the following year. This is evidenced by the 35% rate of acute visits and 20% rate of hospitalization in the study population. The presence of eosinophilia increases that risk, as does frequent symptoms and sensitization in adolescents. This study does not tell us whether treatment aimed at T2 inflammation (eg, higher doses of inhaled steroids or stronger avoidance of aeroallergens) will reduce the risk, but is something to be considered.