Diagnostic Accuracy and Optimal Thresholds of Salivary Pepsin (Peptest) in Laryngopharyngeal Reflux: A Systematic Review and Meta-Analysis

Abstract

Objectives

Salivary pepsin has been proposed as a non-invasive biomarker for diagnosing laryngopharyngeal reflux (LPR); however, its diagnostic utility remains uncertain due to inconsistent findings across studies. This meta-analysis evaluated the diagnostic accuracy of a rapid lateral flow test (Peptest) compared to the reference standard of multichannel intraluminal impedance-pH (MII-pH) monitoring.

Design and Setting

Systematic review and meta-analysis of cohort studies.

Participants

Patients with LPR.

Main Outcome Measures

The primary outcomes were diagnostic odds ratio (DOR), summary receiver operating characteristic curve and area under the curve (AUC).

Results

In total, 11 studies comprising 928 samples were included. The diagnostic performance of salivary pepsin for LPR was analysed at cut-off values of 16, 45–50 and 100 ng/mL. The pooled DOR and AUC were 3.49 and 0.684 at 16 ng/mL, 6.08 and 0.772 at 45–50 ng/mL and 4.78 and 0.717 at 100 ng/mL, respectively. Multiple-time sampling significantly improved sensitivity compared to single-time sampling across all cut-off values (0.82 vs. 0.33–0.63 at 16 ng/mL; p < 0.0001), although specificity was slightly lower.

Conclusions

The Peptest demonstrates potential as a simple, non-invasive diagnostic alternative to 24-h-MII-pH monitoring for LPR. Among the evaluated thresholds, a cut-off of 45–50 ng/mL provided the highest diagnostic accuracy. Collecting multiple saliva samples may further enhance detection sensitivity. However, in patients with a high clinical suspicion of LPR but negative Peptest results, 24-h-MII-pH monitoring remains necessary to confirm the diagnosis due to the test's limited negative predictive value.