Clinical utility of salivary pepsin measurement in patients with proton pump inhibitor-refractory gastroesophageal reflux disease symptoms: a prospective comparative study

Background Salivary pepsin measurement has been reported to be useful for diagnosing gastroesophageal reflux disease (GERD). This study aimed to clarify the usefulness of salivary pepsin measurement in patients with proton pump inhibitor (PPI)-refractory GERD symptoms without erosive esophagitis. Methods One hundred and two patients were included. Over seven days after terminating PPI treatment, all patients underwent a 24-h pH-impedance test and salivary pepsin measurement. In patients whose main symptoms included laryngopharyngeal symptoms, a hypopharyngeal multichannel intraluminal impedance (HMII) test was performed, whereas in other patients, a conventional combined multichannel intraluminal impedance-pH (MII-pH) test was performed. In the HMII tests, patients were divided into abnormal proximal exposure (APE) and non-APE groups. Salivary pepsin concentrations were compared according to acid exposure time (AET) values and were also compared between the APE and non-APE groups. Results The median salivary pepsin concentration in patients with AET > 6% was significantly higher than that in patients with AET ≤ 6% (345.0 [170.0–469.3] ng/mL vs. 120.0 [97.0–290.1] ng/mL, p < 0.01). The sensitivity, specificity, positive predictive value, and negative predictive value of a positive test (> 109 ng/mL) to diagnose patients with AET > 6% were 75.0%, 51.3%, 32.1%, and 86.9%, respectively. There was no significant difference between concentrations in the APE group and concentrations in the non-APE group. Conclusions In patients with PPI-refractory nonerosive reflux disease, salivary pepsin measurement may help diagnose patients who have conclusive evidence of reflux, whereas it is not adequate for identifying patients with APE.