Kids with Asthma May Need a More Personalized Approach

Why do some kids with asthma continue to have exacerbations despite treatment with drugs aimed at controlling the underlying inflammation that causes the condition?

U.S. researchers from several leading academic centers set out to answer that question in a study published by JAMA Pediatrics. They specifically zeroed in on eosinophilic asthma, which is driven by type 2 (T2) inflammation, an immune response triggered by cytokines that promote the production and activation of eosinophils.

Targeted therapies exist to treat this type of inflammation, but children on these drugs still suffer from exacerbations. These investigators examined data from a previous trial involving low-income children who were treated with one such therapy, the biologic mepolizumab, yet still had exacerbations to see what else might be going on.

The 52-week trial compared kids on the drug with those taking a placebo.

In the new analysis, the researchers employed RNA sequencing to examine nasal samples collected during 176 of the acute asthma exacerbations experienced by the children in the initial study. Three distinct inflammatory drivers were identified:

1. Epithelial inflammatory pathways: These pathways were increased in children receiving mepolizumab, regardless of viral infection.
2. Macrophage-driven inflammation: This type of inflammation was specifically linked to viral respiratory illnesses.
3. Mucus hypersecretion and cellular stress responses: These were elevated in both treatment and placebo groups during flare-ups.

The investigators believe these findings suggest that tamping down eosinophilic and T2 inflammatory responses may increase other inflammatory pathways that contribute to acute exacerbations of asthma in children, highlighting the complexities of asthma and the need for personalized treatment.

“There are multiple different types of inflammatory responses that are involved in exacerbations, and they’re driving exacerbations differentially based on whether patients have a virus or are taking drugs to block different parts of the inflammatory response,” said study author Rajesh Kumar, MD, from Ann & Robert H. Lurie Children’s Hospital of Chicago. “This study gives us a better understanding of what results in persistent exacerbations and opens up the potential for new therapies or combinations of therapies based upon that.”

The study was supported by a grant from the National Institutes of Health.

Highlighted in RC Buzz April 13, 2026