Utility of eosinophil peroxidase as a biomarker of eosinophilic inflammation in asthma - 18/05/24

Doi : 10.1016/j.jaci.2024.03.023

Monica Tang, MD ^a, Annabelle R. Charbit, PhD ^a, Mats W. Johansson, PhD ^b, Nizar N. Jarjour, MD ^b, Loren C. Denlinger, MD, PhD ^b, Wilfred W. Raymond, BA ^a, Michael C. Peters, MD, MAS ^a, Eleanor M. Dunican, MD, PhD ^c, Mario Castro, MD, MPH ^d, Kaharu Sumino, MD, MPH ^e, Serpil C. Erzurum, MD ^f, Suzy A. Comhair, PhD ^f, Wendy C. Moore, MD ^g, Bruce D. Levy, MD ^h, Elliot Israel, MD ^h, Wanda Phipatanakul, MD, MS ⁱ, Brenda R. Phillips, MS ^j, David T. Mauger, PhD ^j, Eugene R. Bleecker, MD ^k, Sally E. Wenzel, MD ^l, Merritt L. Fajt, MD ^l, Prescott G. Woodruff, MD, MPH ^a, Annette T. Hastie, PhD ^g, John V. Fahy, MD, MSc ^a,^⁎
for the
National Heart Lung and Blood Institute Severe Asthma Research Program^a,^b,^c,^d,^e,^f,^g,^h,ⁱ
^a University of California San Francisco, San Francisco, Calif
^b University of Wisconsin-Madison, Madison, Wis
^c University College Dublin, Dublin, Ireland
^d University of Kansas, Kansas City, Kan
^e Washington University in St Louis, St Louis, Mo
^f Cleveland Clinic, Cleveland, Ohio
^g Wake Forest University, Winston-Salem, NC
^h Brigham and Women’s Hospital, Boston, Mass
ⁱ Boston Children’s Hospital, Boston, Mass
^j Pennsylvania State University College of Medicine, Hershey, Pa
^k University of Arizona, Tucson, Ariz
^l University of Pittsburgh, Pittsburgh, Pa

^∗Corresponding author: John V. Fahy. MD, MSc, University of California San Francisco, 513 Parnassus Ave, Health Sciences East, Rm 1307, San Francisco, CA 94143.University of California San Francisco513 Parnassus AveHealth Sciences EastRm 1307San FranciscoCA94143

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Saturday 18 May 2024

Graphical abstract

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Abstract

Background

The relative utility of eosinophil peroxidase (EPX) and blood and sputum eosinophil counts as disease biomarkers in asthma is uncertain.

Objective

We sought to determine the utility of EPX as a biomarker of systemic and airway eosinophilic inflammation in asthma.

Methods

EPX protein was measured by immunoassay in serum and sputum in 110 healthy controls to establish a normal reference range and in repeated samples of serum and sputum collected during 3 years of observation in 480 participants in the Severe Asthma Research Program 3.

Results

Over 3 years, EPX levels in patients with asthma were higher than normal in 27% to 31% of serum samples and 36% to 53% of sputum samples. Eosinophils and EPX correlated better in blood than in sputum (r_s values of 0.74 and 0.43, respectively), and high sputum EPX levels occurred in 27% of participants with blood eosinophil counts less than 150 cells/μL and 42% of participants with blood eosinophil counts between 150 and 299 cells/μL. Patients with persistently high sputum EPX values for 3 years were characterized by severe airflow obstruction, frequent exacerbations, and high mucus plug scores. In 59 patients with asthma who started mepolizumab during observation, serum EPX levels normalized in 96% but sputum EPX normalized in only 49%. Lung function remained abnormal even when sputum EPX normalized.

Conclusions

Serum EPX is a valid protein biomarker of systemic eosinophilic inflammation in asthma, and sputum EPX levels are a more sensitive biomarker of airway eosinophilic inflammation than sputum eosinophil counts. Eosinophil measures in blood frequently miss airway eosinophilic inflammation, and mepolizumab frequently fails to normalize airway eosinophilic inflammation even though it invariably normalizes systemic eosinophilic inflammation.

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Key words : Asthma, eosinophil, eosinophilic inflammation, sputum, mepolizumab, mucus plugs

Abbreviations used : EDN, EPX, SARP, UCSF