Mucosal integrity and acid sensitivity predict proton pump inhibitor response in patients with heartburn and normal acid exposure

Background: Patients with typical reflux symptoms and normal acid exposure time (AET) are classified as either reflux hypersensitivity (RH) or functional heartburn (FH), some of whom respond to proton pump inhibitors (PPIs). We determined if esophageal psychophysiological parameters predict PPI response in symptomatic RH and FH patients. Methods: We prospectively recruited adults with heartburn diagnosed with RH or FH on 24-h impedance-pH monitoring off PPI. Mucosal integrity was evaluated using mean nocturnal baseline impedance (MNBI). Symptom response required ≥50 % reduction in global symptom severity. Infusion of hydrochloric acid (0.1 N) into the mid-esophagus evaluated acid sensitivity, using time to initial typical symptom perception (lag time) and intensity rating. Factors influencing PPI response were identified using logistic regression. Results: Of 102 study participants (age 21–64 years, 69.6 % women, 54 RH, 48 FH), 37.3 % demonstrated PPI response (RH: 44.4 %, FH: 29.2 %, p = NS). On multivariable logistic regression, lower MNBI correlated with PPI response in both RH and FH, shorter lag time also correlated in RH. The optimal MNBI threshold for predicting PPI response was 2500 ohms. Conclusions: Lower MNBI indicating mucosal acid damage, and esophageal acid sensitivity prompting early symptom reporting are physiomarkers of PPIs response in RH and FH patients.