Blood Eosinophils for Prediction of Exacerbation in Preschool Children With Recurrent Wheezing

Abstract

Although clinical features of type 2 inflammation have been associated with poorer longitudinal outcomes in preschool children with recurrent wheezing, it remains difficult to predict which children are at highest risk for poor outcomes during a routine clinical encounter. We tested the hypothesis that prespecified cut points of blood eosinophil counts would predict exacerbation and treatment response outcomes in preschool children with recurrent wheezing and that prediction could be improved with the addition of a second biomarker. Data from 3 clinical trials of 1,074 preschool children aged 12 to 71 months with recurrent wheezing were merged. The primary outcome was the occurrence of any exacerbation during follow-up. Secondary outcomes included the annualized rate of wheezing exacerbations and the occurrence of any exacerbation requiring hospitalization. Exploratory analyses focused on exacerbation outcomes, offline exhaled nitric oxide concentrations, and caregiver-reported asthma control scores after inhaled corticosteroid treatment initiation. Each blood eosinophil cut point was associated with increased odds of exacerbation, higher exacerbation rates, and greater hospitalization occurrence in preschool children with recurrent wheezing. However, outcome detection was improved in children with more elevated blood eosinophil counts. Addition of a second biomarker of type 2 inflammation improved outcome detection and was further associated with an improved response to initiation of daily inhaled corticosteroids in exploratory analyses. However, the specificity of blood eosinophils was poor. Although validation studies are warranted, blood eosinophil cut points may be useful for clinical assessment and future studies of exacerbation and treatment response in preschool children with recurrent wheezing.