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Longitudinal Evaluation of Noninvasive Biomarkers for Eosinophilic Esophagitis

Min, Steve B. MD; Nylund, Cade M. MD; Baker, Thomas P. MD; Ally, Mazer MD; Reinhardt, Brian MS; Chen, Yen-Ju RN; Nazareno, Luz RN; Moawad, Fouad J. MD

Journal of Clinical Gastroenterology: February 2017 - Volume 51 - Issue 2 - p 127–135
doi: 10.1097/MCG.0000000000000621
ALIMENTARY TRACT: Original Articles

Background: The diagnosis and management of eosinophilic esophagitis (EoE) often requires multiple endoscopies. Serum biomarkers can be elevated in EoE patients, but their clinical utility in diagnosis and assessing response to treatment is not well established.

Goals: To evaluate serum biomarkers in EoE subjects compared with controls and assess longitudinally in response to treatment.

Study: We conducted a prospective cohort study of children and adults undergoing esophagogastroduodenoscopy for suspected EoE. After completing an 8-week course of proton-pump inhibitor therapy, esophageal mucosal biopsies were obtained, as well as, serum analysis of absolute eosinophil count (AEC), eotaxin-3, eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP) and interleukin-5. Subjects with normal endoscopic and histologic findings constituted controls. Those meeting criteria for EoE underwent repeat esophagogastroduodenoscopy and biomarker measurements following treatment with topical steroids for 8 weeks.

Results: Median levels of AEC (263.50 vs. 102 cu/mm, P<0.001), ECP (26.98 vs. 5.20 ng/mL, P<0.001) and EDN (31.70 vs. 14.18 ng/mL, P=0.004) were significantly elevated in EoE subjects compared with controls and correlated with esophageal eosinophilia. Levels of AEC (odds ratio, 1.79; 95% confidence interval, 1.28-2.64) and ECP (odds ratio, 1.61; 95% confidence interval, 1.23-2.36) were associated with a diagnosis of EoE. Among the 5 biomarkers evaluated, only AEC significantly predicted esophageal eosinophilia following topical steroid therapy in EoE subjects (P=0.006).

Conclusions: AEC, ECP, and EDN were higher in EoE subjects compared with controls and correlated with degree of esophageal eosinophilia. Furthermore, AEC predicted post-treatment eosinophilia, suggesting a potential role in monitoring EoE disease activity.

Departments of *Pediatrics

§Medicine, Gastroenterology Service

Research Programs, Walter Reed National Military Medical Center

Departments of Pediatrics

Medicine, Uniformed Services University of the Health Sciences, Bethesda

Joint Pathology Center, Defense Health Agency, Silver Spring, MD

S.B.M.: guarantor of the article.

S.B.M: original study concept and design; Institutional Review Board protocol submission and revision; recruited/consented subjects; acquisition, analysis and interpretation of data; draft of initial manuscript, editing manuscript, approval of final manuscript. C.M.N.: data analyzation and interpretation; editing manuscript, approval of final manuscript. T.P.B.: reviewed and analyzed all esophageal biopsy specimens for tissue eosinophil counts; approval of final manuscript. M.A.: assisted with patient recruitment, study supervision, material support; administrative and technical support; approval of final manuscript. B.R.: assisted with laboratory specimen analyzation, ordered laboratory supplies; approval of final manuscript. Y.-J.C.: assisted with patient recruitment, study supervision, material support; approval of final manuscript. L.N.: assisted with patient recruitment, study supervision, material support; approval of final manuscript. F.J.M.: study concept and design, assisted with Institutional Review Board submission and revisions, critical revision of manuscript, administrative and technical support, study supervision, approval of final manuscript.

The views expressed in this article are those of the authors and do not reflect the official policy or position of the United States Army, United States Air Force, United States Navy, the Department of Defense, or the US Government. Title 17 U.S.C. 105 provides that “copyright protection under this title is not available for any work of the United States Government.” Title 17 U.S.C. 101 defines a US government work as “a work prepared by a military service member or employee of the United States government as part of that person’s official duties.” This work was prepared as part of our official duties.

The authors declare that they have nothing to disclose.

Address correspondence to: Steve B. Min, MD, Department of Pediatric Gastroenterology and Nutrition, Walter Reed National Military Medical Center, 8901 Wisconsin Ave., Bethesda, MD 20889 (e-mail:

Received January 9, 2016

Accepted June 18, 2016

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