FeNO Levels Might Have Usefulness in EoE Monitoring

Significantly higher levels of fractional exhaled nitric oxide (FeNO) (>30 parts per billion) were found in a cohort of patients with eosinophilic esophagitis (EoE) who had inflammation than in any other group studied, according to World Journal of Gastrointestinal Endoscopy.

Because of this, FeNO might have a clinical role in evaluating treatment response in a subset of patients with EoE.

This study was conducted to evaluate the usefulness of FeNO as a noninvasive biomarker of esophageal eosinophilic inflammation for checking disease activity in EoE.

There have been previous studies evaluating utility of FeNO, but none examined the influence of eosinophilic inflammation of the stomach and duodenum to FeNo.

“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,” the authors wrote.

Active inflammation in EoE can lead to dysphagia and cause vomiting and abdominal pain in young patients. Chronic inflammation contributes to fibrosis and structuring, which require repeated, invasive dilations to manage sufficient swallowing.

Patients aged 6 to 21 years who were undergoing scheduled upper endoscopy with biopsy for presumed EoE were recruited in the observational study. A total of 134 patients were included, and 45 were diagnosed with EoE by histopathology.

FeNO measurements were acquired in duplicate using a chemiluminescence nitric oxide analyzer (NIOX MINO, Aerocrine, Inc; Stockholm, Sweden) before endoscopy.

The results showed that the median (IQR) FeNO level was 17 parts per billion (ppb) (11-37; range, 7-81) in the EoE group and 12 ppb (8-19; range, 5-71) in the control group. After atopic disease adjustment was complete, patients with EoE had significantly higher FeNO levels compared with patients without EoE (Z = 3.33; P < .001). A weak but still statistically significant positive association was seen between the number of esophageal eosinophils and FeNO levels (r = .30; P < .005). Upon subgroup analysis in the EoE cohort, higher FeNO levels were observed in patients with abnormal gastric (n = 23; 18 vs 15) and duodenal (n = 28; 21 vs 14) eosinophilia, but that difference wasn’t statistically significant.

Data from this study suggest that provided the specificity of high FeNO levels (over 30 ppb) in prediction of histological diagnosis of EoE, a similar FeNO limit could be created for surveillance in patients with EoE, especially those with initially high FeNO levels. Monitoring these levels over time could allow the observance of esophageal inflammation in this subgroup of patients with EoE who have high FeNO scores.

“The ATS [American Thoracic Society] guidelines further suggest that a reduction of at least 20% in FeNO for values > 50 ppb (or > 10 ppb for values lower than 50 ppb) be used as the cutoff point to indicate a significant response to anti-inflammatory therapy. New ATS guidelines suggest that FeNO should be combined with other clinical markers to assess disease control. Potentially, a similar reduction value in FeNO scores can be established for EoE patients that can be integrated with other clinical characteristics to demonstrate response to therapy,” the authors noted.

Because intestinal inflammation downstream might affect FeNO levels, overseeing esophageal inflammation by FeNO might not be reliable in patients with systemic inflammatory disease. More studies are needed to review if maybe a higher FeNO cutoff can be used for EoE surveillance in patients with high downstream eosinophils.

The present study is the first to judge any increases in FeNO levels that could be partly responsible for the eosinophils in the stomach and duodenum (downstream eosinophils). It also includes a substantial pediatric cohort and is the first to review downstream eosinophils as a possible confounder of FeNO levels.

“Overall, a greater percentage of our cohort had high FeNO levels than in previously published studies, indicating there might be a difference in FeNO product of pediatric EoE patients as compared to adults,” the authors added.

Some limitations of this study is that it was conducted at just 1 institution and did not include patients with asthma. The study authors also noted that future studies would find benefit in larger sample sizes.

“FeNO may have a clinical role in assessing treatment response in a subset of EoE patients,” the authors concluded.

Reference

Kaur P, Chevalier R, Friesen C, Ryan J, Sherman A, Page S. Diagnostic role of fractional exhaled nitric oxide in pediatric eosinophilic esophagitis, relationship with gastric and duodenal eosinophils. World J Gastrointest Endosc. 2023;15(5):407-419. doi:10.4253/wjge.v15.i5.407