P4929 - Hydrogen Sulfide Levels on Breath Testing Are Associated With GERD and Esophageal Symptoms, Independent of PPI Use

Gabriela Leite, PhD¹, Amrit K. Kamboj, MD², Ali Rezaie, MD, MSc², Ruchi Mathur, MD¹, Mohamad Rashid, MD², Ava Hosseini, MPH¹, Daniel Brimberry, PhD², Matthew Mitcho, ³, Fabrice Wilfong, ³, David Richardson, MSc⁴, Mark Pimentel, MD, FACG²
1Cedars-Sinai Medical Center, West Hollywood, CA; 2Cedars-Sinai Medical Center, Los Angeles, CA; 3Gemelli Biotech, Raleigh, NC; 4Gemelli Biotech, Mesa, AZ

Introduction: Breath testing (BT) is used in the workup of patients with chronic gastrointestinal symptoms and measures hydrogen (H₂), methane (CH₄) and now, hydrogen sulfide (H₂S). The relationship between breath test results and GERD is underexplored. Recently, we showed that GERD subjects have an increased levels of the H₂S producer, Bilophila sp in the foregut. H₂S can have detrimental effects on lower esophageal sphincter (LES) tone. In this study, we examine the relashionship between breath H₂S among GERD and non-GERD in a nationwide study.

Methods: Consecutive subjects undergoing an in-home three gas BT were asked to complete a symptom questionnaire, medication intake (e.g., Proton Pump Inhibitors [PPI]), and if they ever were diagnosed with reflux. Subjects prepared for BT per the North American Consensus. After fasting, subjects provided an end-expiratory breath sample and then ingested lactulose (10g) or glucose (75g) at the discretion of the physician. Breath samples were collected in consecutive bags every 15 minutes for 2 hours. Bags were then compiled and processed using a specialized gas chromatography instrument that measured H₂S at baseline and at each time point. H₂S >2.0ppm was considered positive.

Results: Of 6000 subjects, 3029 (50.4%) completed a breath test and questionnaire (F=74.5%, age=50.3±18.1yrs). Of these, a total of 1064 subjects had GERD (Table 1) with an average age higher than subjects without reflux (54.6±17.5 yrs vs. 49.0±46.8 yrs, respectively) (P< 0.0001). As expected, more subjects with reflux were on PPI (P< 0.0001), and had more severe "burning esophagus" sensation than those without reflux (P< 0.0001). Subjects with reflux had significantly higher H₂S AUC when compared to those without reflux (P=0.039), and this signal was still observed when reflux subjects not taking PPI were compared to subjects without reflux also not taking PPI (P=0.042). In addition, the symptom severity of the "burning esophagus" sensation correlated positively with H₂S AUC (P=0.002). Subjects without reflux but taking PPI had higher H₂S AUC when compared to subjects without reflux and not taking PPI (129.2±31.6 vs. 122.7±29.7, respectively) (P=0.001). As previously described, H₂S correlated with diarrhea severity as well (P=0.003).

Discussion: This study demonstrates that elevated H₂S levels on breath testing are associated with GERD with or without PPI use. In addition, H₂S levels correlate with the severity of GERD symptoms as well as diarrhea.


Figure: Table 1. Subject’s demographics, H2S and GERD symptom severity profiles.

Disclosures:
Gabriela Leite indicated no relevant financial relationships.
Amrit Kamboj: Sanofi – Speakers Bureau.
Ali Rezaie: Ardelyx, Blueprint Medicine and Salix Pharmaceuticals – Consultant. Gemelli Biotech, and Good LFE – Equity stake.
Ruchi Mathur: Gemelli Biotech – Royalties, Stock-privately held company. goodLFE – Stock-privately held company.
Mohamad Rashid indicated no relevant financial relationships.
Ava Hosseini indicated no relevant financial relationships.
Daniel Brimberry indicated no relevant financial relationships.
Matthew Mitcho: Gemelli Biotech – Employee.
Fabrice Wilfong: Gemelli Biotech – Employee.
David Richardson indicated no relevant financial relationships.
Mark Pimentel: Ardelyx – Consultant. Gemelli Biotech – Advisory Committee/Board Member, Royalties, Stock-privately held company. GoodLFE – Stock-privately held company. Salvo Health, Cylinder Health – Stock Options.

Gabriela Leite, PhD¹, Amrit K. Kamboj, MD², Ali Rezaie, MD, MSc², Ruchi Mathur, MD¹, Mohamad Rashid, MD², Ava Hosseini, MPH¹, Daniel Brimberry, PhD², Matthew Mitcho, ³, Fabrice Wilfong, ³, David Richardson, MSc⁴, Mark Pimentel, MD, FACG². P4929 - Hydrogen Sulfide Levels on Breath Testing Are Associated With GERD and Esophageal Symptoms, Independent of PPI Use, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.