Introduction
The evaluation of volatile organic compounds (VOCs) in exhaled breath shows promise as an entirely non-invasive strategy to evaluate for inflammation with high patient acceptance. Our prior work has suggested that exhaled VOCs can be used to discriminate patients with ulcerative colitis (UC) from healthy controls. Using selective-ion flow tube mass spectrometry (SIFT-MS), we aimed to evaluate the VOC breathprint and its link with luminal inflammation and other disease states in UC patients.

Methods
We performed a prospective longitudinal study of UC patients scheduled for endoscopic evaluation between 3/2021 and 10/2023. Exclusion criteria included patients with a history of Crohn’s disease, colectomy, ileostomy, recent or current use of antibiotics, pregnancy, active malignancy, co-morbid medical conditions that could affect VOC analysis, or positive C.dfficile testing. Exhaled breath evaluations was obtained at a clinic visit prior to receipt of bowel preparation. UC endoscopic disease activity assessment was measured using the UC Mayo Endoscopic Score (MES). Principle component analysis and a receiver operative characteristic (ROC) analysis were used to determine the ability of exhaled breath analysis to discriminate patients with normal/mild endoscopic disease (MES 0-1) compared to patients with moderate/severe endoscopic activity (MES 2-3).

Results
A total of 38 patients [55.3% female, average age at consent: 36.5 (28.8-56.8)] with a confirmed diagnosis of ulcerative colitis, were included in the analysis, 25 patients with an MES 0-1 and 13 patients with an MES 2-3. Patient characteristics are described in TABLE 1. The average fecal calprotectin of patients with an MES 0-1 was 121 ug/g (100-353 ug/g) and the average fecal calprotectin for patients with an MES 2-3 was 1532 ug/g (923-2667 ug/g). VOCs which were upregulated in MES 2-3 compared to MES 0-1 were 2-hepatonone, 2-nonene, cyclohexanone, methyl cyclohexane, and propylcyclohexane. Hydrogen cyanide were downregulated in MES 2-3. ROC analysis to discriminate MES 0-1 vs. MES 2-3 was 0.8 (95% confidence interval: 0.64-0.96).

Conclusion
VOC exhaled breath analysis shows a robust ability to discriminate patients with severe endoscopic disease from patients with minimal to no endoscopic inflammation. The differences in reported VOC point toward metabolic differences in bacterial fermentation, lipid and carbohydrate metabolism, and an increase in reactive oxygen species in patients with active disease.

Stephen Laroux

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