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

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.