Study Reveals Why Some Children Still Have Asthma Attacks Even With Treatment

Study findings from a multicenter clinical trial published by investigators in JAMA Pediatrics identified inflammatory pathways that contribute to asthma flare-ups in children despite ongoing treatment. The results suggest that suppressing eosinophilic and non-type 2 (T2) inflammatory responses in children treated with mepolizumab (Nucala; GSK) can lead to an increase in other inflammatory pathways, which contribute to asthma exacerbations.^1,2

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“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,” Rajesh Kumar, MD, interim division head of allergy and immunology at Ann & Robert H. Lurie Children’s Hospital of Chicago, said in a news release.²

What is Eosinophilic Asthma?

According to the Asthma and Allergy Foundation of America, over 27 million individuals in the US have asthma, and about 10% of them have poorly controlled, severe asthma called eosinophilic asthma. This form of asthma is characterized by elevated levels of eosinophils, a type of white blood cell that typically fights infections and accumulates in the lungs and airways, leading to chronic inflammation, swelling, and respiratory system damage. As a type of severe asthma, eosinophilic asthma causes more frequent attacks and usually starts in adulthood, affecting more women than men. Additionally, eosinophilic asthma is caused by T2 inflammation, an immune response that uses cytokines to increase the production of eosinophils. This response determines why therapies targeting T2 inflammation are used to reduce eosinophil levels and prevent asthma attacks.^1-3

What Contributes to Persistent Asthma Flare-Ups?

Researchers conducted a secondary analysis of the phase 2, double-blind, placebo-controlled, parallel-group, randomized MUPPITS-2 clinical trial (NCT03292588) to identify distinct molecular mechanisms involved in asthma exacerbations in urban children with eosinophilic asthma. The study characterized respiratory illness in these children by comparing their treatment outcomes with either mepolizumab or a placebo.^1,2,4

“The previous trial raised questions about what happens when you take away some of the allergic inflammation using a biologic drug, and why is it that some children experience exacerbations and some don't?” Kumar said in the news release. “Different types of inflammation—allergic and different types of nonallergic inflammation—interact with exacerbations, both viral and non-viral. We wanted a more precise way of understanding what's driving some of the exacerbations in kids.”²

The MUPPITS-2 trial included a total of 108 participants who had at least 1 acute respiratory illness for which nasal lavage sampling was obtained. The participants were randomly assigned to receive either mepolizumab (ages 6-11 years: 40 mg; ages 12-17 years: 100 mg) or a matching placebo by subcutaneous injection once every 4 weeks for 52 weeks, according to the study authors.¹

Researchers identified 3 distinct inflammatory drivers of asthma exacerbations through RNA sequencing of 176 nasal samples from acute respiratory illnesses. First, epithelial inflammatory pathways increased in children on mepolizumab regardless of viral infection. Second, macrophage-driven inflammation was linked to viral illnesses, and lastly, mucus hypersecretion and cellular stress were elevated during flare-ups in both the mepolizumab and placebo groups.^1,2

“We found that children who still had exacerbation on the drug had less of this allergic type of inflammation, but they had other residual epithelial pathways, which were driving some of that inflammatory response that was involved in exacerbation,” Kumar said in the news release.²

The findings suggest that as asthma continues to impact children in urban communities, more personalized treatment strategies are needed for prevention and treatment.^1,2

“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,” Kumar concluded in the news release.²

REFERENCES

1. Altman MC, Janczyk T, Murphy RC, et al. Inflammatory Pathways in Residual Asthma Exacerbations Among Mepolizumab-Treated Urban Children: A Secondary Analysis of a Randomized Clinical Trial. JAMA Pediatr. Published online July 14, 2025. doi:10.1001/jamapediatrics.2025.2044

2. Study reveals hidden drivers of asthma flare-ups in children. EurekAlert! News release. August 1, 2025. Accessed August 21, 2025. https://www.eurekalert.org/news-releases/1093424

3. Asthma and Allergy Foundation of America. Understanding Eosinophilic Asthma | Asthma and Allergy Foundation of America. May 17, 2024. Accessed August 21, 2025. https://community.aafa.org/blog/understanding-eosinophilic-asthma

4. A Trial of Mepolizumab Adjunctive Therapy for the Prevention of Asthma Exacerbations in Urban Children (MUPPITS-2). Updated July 20, 2022. Accessed August 21, 2025. https://clinicaltrials.gov/study/NCT03292588