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©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Endosc. May 16, 2023; 15(5): 407-419
Published online May 16, 2023. doi: 10.4253/wjge.v15.i5.407
Diagnostic role of fractional exhaled nitric oxide in pediatric eosinophilic esophagitis, relationship with gastric and duodenal eosinophils
Panamdeep Kaur, Rachel Chevalier, Craig Friesen, Jamie Ryan, Ashley Sherman, Stephanie Page
Panamdeep Kaur, Department of Pediatric Gastroenterology, Connecticut Children’s Medical Center, University of Connecticut School of Medicine, Hartford, Connecticut, CT 06106, United States
Rachel Chevalier, Craig Friesen, Jamie Ryan, Department of Pediatric Gastroenterology, Children's Mercy Kansas City, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, MO 64108, United States
Rachel Chevalier, Craig Friesen, Department of Pediatrics, University of Kansas School of Medicine, Kansas City, Kansas, KS 66160, United States
Ashley Sherman, Department of Biostatistics, Children's Mercy Kansas City, Kansas City, Missouri, MO 64108, United States
Stephanie Page, Department of Pediatric Gastroenterology, Midwest Pediatric Specialists, Overland Park, Kansas, KS 66215, United States
Author contributions: Kaur P modified the study design, collected, analyzed and interpreted the data, wrote and revised the manuscript; Chevalier R modified the study design, collected, analyzed and interpreted the data, wrote and revised the manuscript; Friesen C modified the study design, analyzed and interpreted the data, edited and revised the manuscript; Ryan J interpreted the data and edited the manuscript; Sherman A interpreted data, performed statistical analysis of the data and revised analysis and manuscript; Page S designed and performed the research study, interpreted the data and edited the manuscript; All authors have approved the manuscript.
Institutional review board statement: The study was reviewed and approved by the Children’s Mercy Institutional Review Board (Approval No. 11120665).
Informed consent statement: Informed consent was obtained from patients/caregivers prior to enrollment into the study.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Panamdeep Kaur, MD, Assistant Professor, Department of Pediatric Gastroenterology, Connecticut Children’s Medical Center, University of Connecticut School of Medicine, 282 Washington Street, Hartford, Connecticut, CT 06106, United States. dr.panam.chd@gmail.com
Received: October 2, 2022
Peer-review started: October 2, 2022
First decision: December 1, 2022
Revised: February 5, 2023
Accepted: April 4, 2023
Article in press: April 4, 2023
Published online: May 16, 2023
BACKGROUND
Eosinophilic esophagitis (EoE) is an eosinophilic-predominant inflammation of the esophagus diagnosed by upper endoscopy and biopsies. A non-invasive and cost-effective alternative for management of EoE is being researched. Previous studies assessing utility of fractional exhaled nitric oxide (FeNO) in EoE were low powered. None investigated the contribution of eosinophilic inflammation of the stomach and duodenum to FeNO.
AIM
To assess the utility of FeNO as a non-invasive biomarker of esophageal eosinophilic inflammation for monitoring disease activity.
METHODS
Patients aged 6-21 years undergoing scheduled upper endoscopy with biopsy for suspected EoE were recruited in our observational study. Patients on steroids and with persistent asthma requiring daily controller medication were excluded. FeNO measurements were obtained in duplicate using a chemiluminescence nitric oxide analyzer (NIOX MINO, Aerocrine, Inc.; Stockholm, Sweden) prior to endoscopy. Based on the esophageal peak eosinophil count (PEC)/high power field on biopsy, patients were classified as EoE (PEC ≥ 15) or control (PEC ≤ 14). Mean FeNO levels were correlated with presence or absence of EoE, eosinophil counts on esophageal biopsy, and abnormal downstream eosinophilia in the stomach (PEC ≥ 10) and duodenum (PEC ≥ 20). Wilcoxon rank-sum test, Spearman correlation, and logistic regression were used for analysis. P value < 0.05 was considered significant.
RESULTS
We recruited a total of 134 patients, of which 45 were diagnosed with EoE by histopathology. The median interquartile range FeNO level was 17 parts per billion (11-37, range: 7-81) in the EoE group and 12 parts per billion (8-19, range: 5-71) in the control group. After adjusting for atopic diseases, EoE patients had significantly higher FeNO levels as compared to patients without EoE (Z = 3.33, P < 0.001). A weak yet statistically significant positive association was found between the number of esophageal eosinophils and FeNO levels (r = 0.30, P < 0.005). On subgroup analysis within the EoE cohort, higher FeNO levels were noted in patients with abnormal gastric (n = 23, 18 vs 15) and duodenal eosinophilia (n = 28, 21 vs 14); however, the difference was not statistically significant.
CONCLUSION
After ruling out atopy as possible confounder, we found significantly higher FeNO levels in the EoE cohort than in the control group.
Core Tip: Multiple endoscopies are required as a part of diagnosis and surveillance in pediatric eosinophilic esophagitis (EoE). We assessed fractional exhaled nitric oxide (FeNO)’s role as a non-invasive marker to aid in management of EoE. FeNO may have a role in a subset of pediatric EoE patients to indicate response to therapy. This could potentially be used as an adjunct in pediatric EoE.
