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Concurrent blood eosinophil counts and FeNO Predict Response to T2-Biologics in severe asthma

Published online March 18, 2025

Type 2 inflammation is a common phenotype of severe asthma (SA), driven by the excessive release of inflammatory cytokines like IL-4, IL-5, and IL-13. These substances increase blood eosinophil counts (BEC), which can damage the airways and increase the risk of asthma exacerbation. Monoclonal antibody (mAbs) treatments, such as anti-IL-5/IL-5Rα or IL-4Rα, effectively block these inflammatory pathways and improve asthma control. High levels of BEC or FeNO before treatment have been linked to improved treatment outcomes with these biologics. However, BEC and FeNO levels do not always correlate. It remains unclear whether differences between these markers (e.g., high BEC but low FeNO) affect treatment outcomes.

A recent article in The Journal of Allergy and Clinical Immunology: In Practice by Pham et al. examined how different combinations of BEC and FeNO levels before treatment affect treatment response in patients with SA receiving mAb therapy. In this multicenter cohort study, 278 adult patients were classified into four groups based on pre-treatment BEC and FeNO levels, using thresholds of 300 cells/μL for BEC and 25 ppb for FeNO. Patients were followed for 6–12 months. Annual exacerbation rates, changes in BEC and FeNO levels, lung function, asthma control status, and remission rates were compared across the groups.

Approximately 75% of patients receiving anti-IL-5/IL-5Rα and 63% of those receiving anti-IL-4Rα had both elevated BEC and FeNO before treatment. In the anti-IL-5/IL-5Rα group, no significant differences in exacerbation rates or remission were observed across BEC–FeNO subgroups. However, patients with both high BEC and high FeNO showed greater improvements in lung function, asthma control status, and more substantial reductions in inflammatory markers compared to those with high FeNO but low BEC. In the anti-IL-4Rα group, patients with both low BEC and FeNO—or with high BEC but low FeNO—had significantly lower remission rates and slower lung function recovery compared to those with both markers elevated. In summary, having both high BEC and FeNO levels before treatment is associated with better response to T2-biologics in patients with SA.

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.

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