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. 2025 Sep 1;59(8):725-736.
doi: 10.1097/MCG.0000000000002068.

Noninvasive Disease Assessment in Eosinophilic Esophagitis With Fractionated Exhaled Nitric Oxide, Blood, and Fecal Biomarkers

Andreas Göldi  1 , Tanay Kaymak  1 , Luca Esposito  1 , Anouk Lehmann  1 , Simona Negoias  2 , Michael Tamm  3 , Jan Hendrik Niess  1 , Petr Hruz  1
Affiliations

Noninvasive Disease Assessment in Eosinophilic Esophagitis With Fractionated Exhaled Nitric Oxide, Blood, and Fecal Biomarkers

Andreas Göldi et al. J Clin Gastroenterol. .

Abstract

Background: Eosinophilic Esophagitis (EoE) is a chronic inflammatory condition of the esophagus triggered by food and aeroallergens. There is a need for noninvasive biomarkers that reliably detect EoE in patients with cardinal symptoms and predict treatment response to reduce endoscopic evaluations.

Study: Nonasthmatic patients 18 years or above with suspected or diagnosed EoE, gastroesophageal reflux disease (GERD), and control individuals with indication for endoscopy were enrolled prospectively between November 2020 and May 2022. Participants underwent body plethysmography with fractionated exhaled nitric oxide (FeNO) level measurement. Besides, serum and fecal biomarkers were measured by ELISA. A follow-up examination was scheduled after treatment initiation in patients with active EoE.

Results: The median FeNO level in active EoE (20 ppb) was higher compared with GERD (15 ppb, P =0.038) and control individuals (14 ppb, P =0.046). Median FeNO did not significantly differ in EoE patients who underwent follow-up assessment after treatment response (20 ppb vs. 18 ppb, P =0.771). Serum EDN, ECP, and the absolute eosinophil blood count (AEC) were elevated in active EoE compared with control individuals but not compared with GERD except for AEC. Serum EDN, ECP and AEC decreased in EoE in remission at follow-up assessment. None of the fecal biomarkers was elevated in active EoE or during treatment.

Conclusions: Assessment of FeNO may have diagnostic value in differentiating patients with active EoE from non-EoE patients but is not a suitable marker for monitoring disease activity. Serum EDN, ECP, TARC, and AEC levels are emerging as potential candidates for monitoring disease activity in EoE.

Keywords: ECP; EDN; FeNO; biomarker; eosinophilic esophagitis.

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Conflict of interest statement

The authors declare that they have nothing to disclose.

Figures

FIGURE 1
FIGURE 1
Flowchart of patient participation for body plethysmography and FeNO biomarker assessment. Among EoE patients, 29 patients presented with active EoE and 9 patients with EoE in remission. Of those with active EoE, 18 patients underwent follow-up assessment. GERD patients (n=14) and control individuals (n=17) scheduled for a routine gastroscopy served as control groups. FeNO indicates fractionated exhaled nitric oxide.
FIGURE 2
FIGURE 2
FeNO, AEC biomarker, and histologic activity assessment in EoE, GERD and control individuals in nonasthmatic subjects. Bars show median and IQR. Active EoE (n=29), EoE in remission (n=20) (including 11 patients from follow-up with successful treatment), GERD (n=14), controls (n=17). A, FeNO values in ppb. B, Absolute eosinophil blood count (AEC) in active EoE versus EoE in remission, GERD, and controls. C, Peak eosinophil count per high power field in esophageal biopsies of patients with active EoE compared with EoE in remission (Mann-Whitney test P<0.0001).
FIGURE 3
FIGURE 3
FeNO and AEC biomarker levels at baseline (BL) and after treatment initiation (EOT) in patients with EoE were shown for treatment responders and nonresponders. A, FeNO levels in responders and nonresponders (Wilcoxon test). B, AEC levels in responders and nonresponders (paired t test). C, Peak eos/hpf in responders and nonresponders (Wilcoxon test).
FIGURE 4
FIGURE 4
Serum biomarker levels in EoE, GERD, and controls. A, EDN at baseline; bars show median with IQR. B, EDN after treatment initiation in EoE patients (Wilcoxon test). C, ECP at baseline; bars show median with IQR. D, ECP after treatment initiation in EoE patients (paired t test). E, TARC at baseline Bars show mean and SD. ANOVA P=0.434. F, TARC after treatment initiation in EoE patients (calculated by paired t test).
FIGURE 5
FIGURE 5
Scatterplots of biomarker correlations in EoE. Calculation with the Spearman nonparametric correlation. Simple linear regression is shown in graphs. A, Correlation of FeNO versus AEC in active EoE. B, Correlation of FeNO versus eos/hpf in active EoE. C, Correlation of eos/hpf versus AEC in active EoE. D, Correlation of FeNO versus AEC in all EoE patients (active EoE and EoE in remission). E, Correlation of FeNO versus eos/hpf in all EoE patients. F, Correlation of eos/hpf versus AEC in all EoE patients.
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