Plasma Biomarkers and Fractional Exhaled Nitric Oxide in the Diagnosis of Eosinophilic Esophagitis

To identify noninvasive biomarkers that could help diagnose eosinophilic esophagitis (EoE) and differentiate those with active disease from those in remission and controls.

The study included 128 children aged 5 to 18 years scheduled to undergo an upper endoscopy at Children’s Memorial Hermann Hospital between January 2019 and December 2021. Exclusion criteria included patients with active respiratory infection, active symptoms of asthma, active allergic rhinitis, history of active or passive smoke exposure, known parasitic infection, or a medical history of inflammatory bowel disease.

In this prospective cohort study, participants were categorized into 3 groups by blinded pathologists based on published guidelines for EoE into those with active EoE (n = 21), EoE in remission (n = 16), and controls (n = 91). Before endoscopy, fractionated exhaled nitric oxide (FeNo) was measured using a breath analyzer and blood was collected for peripheral absolute eosinophil count, plasma amino acids, and plasma polyamine analysis. Amino acid levels, polyamine concentrations, absolute eosinophil count, and FeNo were compared across the 3 groups using the Kruskal-Wallis test with a posthoc Dunn’s test; the Mann-Whitney test was used to compare FeNo levels across dichotomous categorical variables.

Specific plasma amino acids (citrulline, β-alanine and cysteine) were higher in the active EoE group versus controls (P < .05), and the polyamine spermine was found to be lower in the active EoE group versus controls (P < .05). FeNo levels were significantly higher in the active EoE group compared with EoE in remission and controls. (P = .011) Receiver operator characteristic curve to assess the predictive capability of a combined score comprising FeNo, β- alanine, cysteine, and spermine had an area under curve of 0.90 (95% confidence interval: 0.80–0.96) in differentiating active EoE from controls and 0.87 (95% confidence interval: 0.74–1.00) when differentiating active EoE from EoE in remission.

FeNo, β-alanine, cysteine, and spermine are noninvasive markers that can aid in the diagnosis of EoE, as well as differentiate patients with active disease from patients in remission and controls.

Given the invasive nature of endoscopy, issues surrounding its accessibility and its role in serial monitoring of disease activity and response to therapy in patients with EoE, novel noninvasive methodologies for diagnosis, and monitoring of EoE have become an attractive focus of study. One consideration is to analyze a composite score comprising only the plasma markers in this study, which may be more feasible clinically than a combined plasma and breath scoring system. Although this study’s results may indicate potential, further studies are warranted in larger patient populations with longitudinal follow up before considering the application of noninvasive biomarkers as an alternative to endoscopy in patients with EoE in clinical practice.