Observational Study
Copyright ©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
Research background

Eosinophilic esophagitis (EoE) is characterized by eosinophilic inflammation of esophageal mucosa and symptoms of esophageal dysfunction. To avoid the burden of multiple endoscopies and associated risks of procedures, search for a surrogate marker for esophageal inflammation has been ongoing and inconclusive till date. Previous low powered studies assessing Fractional exhaled nitric oxide (FeNO)’s utility in EoE were noted to have a trend for association. No previous studies investigated the effect of eosinophilia in stomach and duodenum on FeNO.

Research motivation

To identify a non-invasive marker of disease activity in EoE that could be a low-risk, low-cost alternative to endoscopic evaluation. FeNO measurements have been successfully utilized in management of eosinophilic airway inflammatory disorders such as asthma. Our study assessed FeNO as a potential biomarker to monitor esophageal eosinophilic inflammation in EoE.

Research objectives

Main objective of our study is to evaluate utility of FeNO in management of Pediatric EoE. Our study also analyzed if gastric and duodenal eosinophils (downstream eosinophilia) have any effect on FeNO scores.

Research methods

Pediatric patients with upper gastrointestinal symptoms and suspected EoE were enrolled in this cross-sectional study. Chemiluminescence nitric oxide analyzer (NIOX MINO, Aerocrine, Inc.; Stockholm, Sweden) machine was used to obtain FeNO measurements prior to endoscopy. Clinical characteristics data for all EoE and non-EoE patients was collected. Correlation of FeNO levels with esophageal eosinophils, EoE and abnormal downstream eosinophilia in the stomach and duodenum was analyzed. A comprehensive atopy questionnaire was utilized for presence of atopy, which was controlled for in a separate logistic regression analysis to assess its effect on FeNO in EoE patients.

Research results

Higher FeNO levels were found in patients with EoE compared to the non-EoE cohort, after adjusting for atopy. FeNO levels more than 30 ppb were noted to be more specific for active esophageal inflammation. Elevated FeNO levels were also noted in patients with high gastric and duodenal eosinophils, with a trend towards significance.

Research conclusions

Given the specificity of high FeNO levels (> 30 ppb) in prediction of histological diagnosis of EoE, a FeNO cutoff could be established for surveillance in EoE patients, particularly those with high initial FeNO levels. Cautious interpretation or perhaps a higher FeNO cut off may be needed in patients with high downstream eosinophils. FeNO may have a clinical role in management of EoE to suggest response to therapy in a subset of pediatric EoE patients. Future studies are needed to evaluate this further.

Research perspectives

Future studies should focus on including EoE patients from the time of diagnosis, and in remission while following an individual patient’s FeNO levels over time to allow monitoring of esophageal inflammation. This could provide a precise assessment for utilization of a FeNO cutoff in prediction of esophageal eosinophilic inflammation.