Children receiving mepolizumab have increased expression of gene modules linked to epithelial and macrophage inflammatory pathways
By Elana Gotkine HealthDay Reporter
TUESDAY, Aug. 12, 2025 (HealthDay News) — Inflammatory pathways that contribute to asthma exacerbations have been identified in children with eosinophilic asthma receiving mepolizumab, according to a study published online July 14 in JAMA Pediatrics.
Matthew C. Altman, M.D., from the University of Washington in Seattle, and colleagues characterized respiratory illnesses among 290 urban children with eosinophilic asthma enrolled in the Mechanisms Underlying Asthma Exacerbations Prevented and Persistent With Immune-Based Therapy: A Systems Approach Phase 2 trial, comparing treatment with mepolizumab versus placebo to identify distinct molecular mechanisms implicated in asthma exacerbations.
Overall, 108 participants were sampled during 176 acute respiratory illness events. The researchers found that children receiving mepolizumab had reduced expression of an eosinophil-associated module associated with T2 inflammation during illness events resulting in asthma exacerbations but had increased expression of gene modules associated with epithelial and macrophage inflammatory pathways relative to children receiving placebo. Relative to nonexacerbation illnesses, during exacerbations, both groups showed higher expression of mucus secretion and cellular stress response pathways. Upregulation of epithelial inflammatory pathways was seen in the mepolizumab group in exacerbations, regardless of a respiratory virus, while there was a specific contribution for macrophage pathways to viral exacerbations. The majority of the heterogeneity among exacerbations in the two groups was seen for three distinct, semiorthogonal inflammatory axes.
“There are multiple different types of inflammatory responses that are involved in exacerbations, and they’re driving exacerbations differentially,” coauthor Rajesh Kumar, M.D., from the Ann and Robert H. Lurie Children’s Hospital of Chicago, said in a statement.
Several authors disclosed ties to biopharmaceutical companies.
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