August 2024
Granule Gains: Eosinophils Release EPX to Expose Asthma Inflammation
Article: Utility of eosinophil peroxidase as a biomarker of eosinophilic inflammation in asthma
Tang M, Charbit AR, Johansson MW, et al
J Allergy Clin Immunol. 2024 April
Reviewed by Nicholas Genovese, Jefferson Einstein Philadelphia Hospital, Pennsylvania, United States
Eosinophil peroxidase (EPX), a key granule protein in eosinophils, is emerging as a significant biomarker in eosinophil-related inflammation. Traditional biomarkers like blood and sputum eosinophil counts have limitations, and this study investigates whether EPX measurements can address these gaps. Using data from 110 healthy controls and 480 asthma patients over three years, EPX levels were measured in serum and sputum samples from the Severe Asthma Research Program 3 (SARP-3). Read more
EPX levels were significantly higher in asthma patients compared to healthy controls. Blood eosinophil counts correlated well with serum EPX levels but less so with sputum EPX levels. Many patients exhibited high sputum EPX levels despite normal blood eosinophil counts, reinforcing the utility of sputum EPX as a more specific indicator of airway inflammation. The study also assessed the impact of mepolizumab, an anti-IL-5 therapy, finding it normalized serum EPX levels in 96% of patients but only sputum EPX levels in 49%.
Importantly, the observed discrepancy between serum and sputum EPX levels is the main advancement shown in this study. Strengths of this study include its large sample size and longitudinal design, providing extensive data over multiple years. The well-characterized SARP-3 cohort allowed for detailed analysis of asthma severity and treatment responses. The lack of correlation between sputum and blood EPX suggests that sputum EPX may serve as a more accurate biomarker for detecting airway inflammation, potentially capturing localized eosinophilic activity that might be overlooked with blood-based measurements. This distinction could explain why certain patients with elevated blood eosinophil counts do not respond to eosinophil-depleting therapies. Consequently, sputum EPX may be a superior predictive biomarker for identifying patients likely to benefit from specific biologic treatments, facilitating a more personalized approach to therapy and potentially improving clinical outcomes in patients with airway-specific eosinophilic inflammation.
This research provides robust support for the use of EPX as a biomarker to identify individuals with airway eosinophilia and for monitoring therapeutic responses to biologics.
Nicholas Paul Genovese is a dedicated pediatric resident at Jefferson Einstein Philadelphia Hospital, deeply committed to pursuing a fellowship in allergy and immunology upon completing his residency. His passion for allergy and immunology was ignited by his early research in evolutionary ecology, where he studied plant defense mechanisms and later their implications for allergenicity at Fordham University. This foundation was further solidified through his investigation of maternal and environmental factors contributing to severe atopic dermatitis within a NICU cohort. Nicholas has worked with Dr. Kathleen Sullivan on a congenital athymia case report, highlighting his dedication to complex case management. He is an active member of the International Eosinophil Society, mentored by Dr. Praveen Akuthota. Nicholas's commitment to advancing knowledge in this field is evidenced by his participation in the 2024 AAAAI Chrysalis Program and his active research on atopic dermatitis and primary immunodeficiencies. Prior to medical school, as a Jumpstart AmeriCorps member, he served as a preschool teacher in the South Bronx and is passionate about education in anaphylaxis among schools. His involvement in the "A Shot to Live" project, supported by a CATCH grant from the American Academy of Pediatrics, allows him to work with schools and community leaders, building strong relationships in the community and raising awareness.