Mepolizumab and IOS-Defined Small Airway Dysfunction in Children: AAAAI Secondary Analysis

Baseline impulse oscillometry (IOS) measures of airway resistance/reactance (eg, R5, R5-20, and AX) were reported to be associated with higher subsequent asthma exacerbation risk in children assigned to placebo, while IOS-assessed airway dysfunction was not associated with exacerbation risk in children assigned to mepolizumab.

The press release describes these findings as a secondary analysis presented at the 2026 AAAAI Annual Meeting, drawn from a randomized pediatric trial comparing mepolizumab with placebo. As summarized in the release, investigators examined whether baseline physiologic measures were linked to exacerbation frequency during follow-up and whether those associations differed by treatment assignment.

According to the release, the randomized trial included 271 participants aged 6-17 years with exacerbation-prone asthma and blood eosinophils who were assigned to placebo or mepolizumab injections added to guideline-based care for 52 weeks. Investigators collected spirometry using Global Lung Function Initiative (GLI) race-neutral values alongside impulse oscillometry (IOS) and examined baseline lung function in relation to the number of exacerbations during the trial. The release states that negative binomial regression models were used to evaluate associations between baseline measurements and exacerbation counts.

The analytic focus, as framed in the release, was whether baseline physiologic impairment (spirometry and IOS measures) aligned with exacerbation risk (ie, the number of exacerbations) over the randomized treatment period.

For IOS, the release describes an arm-specific pattern between baseline airway resistance and later exacerbation risk. Higher baseline resistance as captured by R5, R5-20, and the area under the curve of reactance (AX) was reported to be associated with increased exacerbation risk among children treated with placebo. In contrast, the release reports that airway dysfunction assessed by IOS was not associated with exacerbation risk in mepolizumab-treated children. The report also notes that, in a combined model, there was no significant interaction between treatment group and the IOS parameters in predicting exacerbation risk. In aggregate, the reported findings describe a placebo-linked association between higher IOS resistance measures and exacerbations that was not observed in the mepolizumab arm.

Spirometry was presented in the release as a distinct signal from IOS in this secondary analysis. Lower baseline FEV1/FVC was reported to be significantly associated with greater exacerbation frequency in both the placebo and mepolizumab groups. In the release's description, this spirometry-based association appeared across treatment assignments, whereas the IOS-based associations differed by arm. As reported, the secondary analysis links baseline measures of lung physiology to exacerbation patterns with differing arm-level alignment depending on the test modality.

Key Takeaways:

• Higher baseline IOS resistance measures (R5, R520, AX) were associated with increased exacerbation risk in children assigned to placebo.
• IOS-assessed airway dysfunction was not associated with exacerbation risk among children treated with mepolizumab.
• Lower baseline FEV1/FVC (spirometry) was reported to be significantly associated with greater exacerbation frequency in both groups in a pediatric randomized trial analyzed with negative binomial regression.