Esophageal Hypervigilance and Mucosal Integrity Predict Symptom Outcomes in Reflux Patients With Normal Acid Exposure

BACKGROUND: Managing esophageal symptoms with normal acid exposure is challenging, requiring focus on both physiological and psychological factors. However, no studies have explored how patients perceive symptom changes after using alginates or proton-pump inhibitors (PPIs) in this context. This study examines the interrelationships among changes in reflux symptom severity, esophageal hypervigilance, and psychological distress in patients with normal esophageal acid exposure treated with either alginate suspension or PPIs. METHODS: We conducted a 2-year prospective, randomized, open-label study with patients displaying typical reflux symptoms but normal acid exposure, confirmed via ambulatory pH-impedance monitoring. Participants completed validated questionnaires assessing esophageal hypervigilance and anxiety (EHAS), symptom severity, sleep quality, and depression at baseline and follow-up to evaluate symptom changes and predictors between treatments. RESULTS: Among 146 patients (mean age: 47.9, 63% female), 75 received alginate and 71 PPI therapy. Improvements in questionnaire scores were significant across both treatments (p < 0.001), with no differences between groups. However, only a few patients in both groups achieved a > 50% reduction in gastro-esophageal reflux disease questionnaire (GERDQ) and global symptom severity (GSS) after treatment. Multivariable regression revealed that the reduction in esophageal hypervigilance and lower mean nocturnal baseline impedance (MNBI) were significant predictors of symptom improvement. CONCLUSION: In reflux patients with normal acid exposure, neither PPIs nor alginates alone effectively improved symptoms, but reducing esophageal hypervigilance and anxiety led to better outcomes. Mucosal integrity and EHAS scores are independent predictors of treatment response. The EHAS is a useful tool for assessing treatment impact and guiding personalized care. A comprehensive approach addressing both psychological and physiological factors is essential, especially for those with normal acid levels.