An eosinophil peroxidase activity assay accurately predicts eosinophilic chronic rhinosinusitis

Kristine A Smith; Amarbir S Gill; Chelsea E Pollard; Jorgen S Sumsion; Hedieh Saffari; Shaelene Ashby; Benjamin L Witt; Paige A Shipman; David A Gabrielsen; Michael T Yim; Joshua M Levy; Gretchen M Oakley; Richard R Orlandi; Gerald J Gleich; Jeremiah A Alt; Abigail Pulsipher

doi:10.1016/j.jaci.2023.04.012

An eosinophil peroxidase activity assay accurately predicts eosinophilic chronic rhinosinusitis

J Allergy Clin Immunol. 2023 Aug;152(2):400-407. doi: 10.1016/j.jaci.2023.04.012. Epub 2023 May 4.

Authors

Kristine A Smith¹, Amarbir S Gill¹, Chelsea E Pollard¹, Jorgen S Sumsion¹, Hedieh Saffari², Shaelene Ashby¹, Benjamin L Witt³, Paige A Shipman¹, David A Gabrielsen¹, Michael T Yim⁴, Joshua M Levy⁵, Gretchen M Oakley¹, Richard R Orlandi¹, Gerald J Gleich⁶, Jeremiah A Alt⁷, Abigail Pulsipher⁸

Affiliations

¹ Department of Otolaryngology-Head and Neck Surgery, Division of Rhinology, University of Utah School of Medicine, Salt Lake City, Utah.
² Department of Dermatology, University of Utah School of Medicine, Salt Lake City, Utah.
³ Cytopathology Section, University of Utah School of Medicine, Salt Lake City, Utah.
⁴ Department of Otolaryngology-Head and Neck Surgery, Division of Rhinology, University of Utah School of Medicine, Salt Lake City, Utah; Department of Otolaryngology-Head and Neck Surgery, Louisiana State University Shreveport, Shreveport, La.
⁵ Department of Otolaryngology-Head and Neck Surgery, Emory University School of Medicine, Atlanta, Ga.
⁶ Department of Dermatology, University of Utah School of Medicine, Salt Lake City, Utah; Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah.
⁷ Department of Otolaryngology-Head and Neck Surgery, Division of Rhinology, University of Utah School of Medicine, Salt Lake City, Utah; Department of Molecular Pharmaceutics, University of Utah College of Pharmacy, Salt Lake City, Utah; Utah Center for Nanomedicine, University of Utah, Salt Lake City, Utah. Electronic address: abigail.pulsipher@utah.edu.
⁸ Department of Otolaryngology-Head and Neck Surgery, Division of Rhinology, University of Utah School of Medicine, Salt Lake City, Utah; Department of Molecular Pharmaceutics, University of Utah College of Pharmacy, Salt Lake City, Utah; Utah Center for Nanomedicine, University of Utah, Salt Lake City, Utah. Electronic address: jeremiah.alt@hsc.utah.edu.

Abstract

Background: A definitive diagnosis of eosinophilic chronic rhinosinusitis (eCRS) requires invasive surgical tissue sampling and histologic enumeration of intact eosinophils. Eosinophil peroxidase (EPX) is an accurate biomarker of sinonasal tissue eosinophilia in CRS regardless of polyp status. A less invasive and rapid method that accurately identifies tissue eosinophilia would be of great benefit to patients.

Objective: We sought to evaluate a new clinical tool that uses a nasal swab and colorimetric EPX activity assay to predict a diagnosis of eCRS.

Methods: A prospective, observational cohort study was conducted using nasal swabs and sinonasal tissue biopsies obtained from patients with CRS electing endoscopic sinus surgery. Patients were classified as non-eCRS (n = 19) and eCRS (n = 35) on the basis of pathologically determined eosinophil counts of less than 10 or greater than or equal to 10 eosinophils/HPF, respectively. Swab-deposited EPX activity was measured and compared with tissue eosinophil counts, EPX levels, and CRS-specific disease metrics.

Results: EPX activity was significantly increased in patients with eCRS than in patients without eCRS (P < .0001). With a relative absorbance unit cutoff value of greater than or equal to 0.80, the assay demonstrated high sensitivity (85.7%) and moderate specificity (79.0%) for confirming eCRS. Spearman correlations between EPX activity and tissue eosinophil counts (r_s = 0.424), EPX levels (r_s = 0.503), and Lund-Kennedy endoscopy scores (r_s = 0.440) in eCRS were significant (P < .05).

Conclusions: This investigation evaluates a nasal swab sampling method and EPX activity assay that accurately confirms eCRS. This method could potentially address the unmet need to identify sinonasal tissue eosinophilia at the point-of-care, as well as to longitudinally monitor eosinophil activity and treatment response.

Keywords: Eosinophilic chronic rhinosinusitis; eosinophil peroxidase activity; ethmoid biopsy; nasal polyps; tissue eosinophilia.

Publication types

Observational Study
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Chronic Disease
Eosinophil Peroxidase
Eosinophilia* / drug therapy
Eosinophils / pathology
Humans
Nasal Polyps* / diagnosis
Nasal Polyps* / pathology
Prospective Studies
Rhinitis* / drug therapy
Sinusitis* / drug therapy

Substances

Eosinophil Peroxidase

Grants and funding

R44 AI126987/AI/NIAID NIH HHS/United States