Eosinophils Play Distinct Roles Across Asthma Phenotypes
Twenty-five years after the first clinical trial of the anti–IL-5 antibody mepolizumab in allergic asthma, accumulated evidence shows that eosinophils contribute very differently across asthma phenotypes, according to a new review examining the evolving understanding of asthma immunopathology.
The review highlights that most children and adolescents with asthma have allergen-driven, early-onset disease. In this phenotype, blood eosinophil counts fluctuate based on allergen exposure and are not central drivers of symptoms. The authors describe eosinophils in this setting as playing “only a minor role (as a so-called sidekick) in allergen-induced asthma symptoms,” emphasizing that eosinophilia alone does not define disease mechanism.
In contrast, the intrinsic eosinophilic form of asthma, which typically begins in adulthood, is characterized by persistently elevated eosinophil levels that actively drive airway inflammation and disease severity. In these patients, eosinophils are not incidental but pathogenic. This distinction helps explain why anti–IL-5 therapies show clear benefit in some patients while offering limited value in others.
Based on these observations, the authors caution against oversimplified biomarker-driven treatment decisions. They conclude that “eosinophilia should not be considered a treatable trait in people with chronic airway diseases, but only a complement to an accurate clinical diagnosis.” Rather than serving as a standalone target, eosinophil counts should be interpreted within the broader clinical context, including age of onset, triggers, and disease course.
For immunologists, the key takeaway is that asthma should be approached as a collection of biologically distinct diseases rather than a single entity defined by biomarkers alone. Accurate phenotyping—particularly distinguishing early-onset allergic asthma from adult-onset eosinophilic asthma—is essential for selecting the “right biologic” and avoiding ineffective therapy. The review underscores the need to align immunologic mechanisms with clinical presentation to optimize outcomes as targeted asthma therapies continue to expand.
Reference
Marek Lommatzsch, Buhl R, Bergmann KC, et al. Eosinophils in asthma phenotypes: perpetrators or guilty by association? The Lancet Respiratory Medicine. Published online July 1, 2025. Doi: 10.1016/S2213-2600(25)00174-2
