Salivary Pepsin Measurement in Laryngopharyngeal Reflux Disease: A Systematic Review of Diagnostic Accuracy and Performance.

Objective: To analyze the methods used for digestive enzyme measurements in saliva of patients with laryngopharyngeal reflux disease (LPRD) and to investigate their respective diagnostic performances.

Methods: Three independent investigators conducted a PubMED, Scopus, and Cochrane Library database search for studies investigating the digestive saliva enzyme measurements in LPRD patients according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements.

Results: Of the 183 screened studies, 38 studies met the inclusion criteria (1461 females (47.5%) and 1614 males (52.5%)). The mean age of patients was 43.5 years. Two studies assessed the accuracy of salivary pepsin in pediatric populations. Twelve studies included patients with an objective LPRD diagnosis at the 24-hour hypopharyngeal-esophageal multichannel intraluminal impedance-pH testing. The lateral flow immunohistochemistry (Peptest) and ELISA were the most common approaches for measuring pepsin. Sensitivity ranged widely (27.0-93.8%) across different methods and thresholds, with Peptest showing 27.0-87.1% sensitivity and 25.0-100% specificity at ≥16 ng/mL threshold. ELISA demonstrated 20.0-93.8% sensitivity and 45.5-84.3% specificity across various cutoff values. Higher thresholds generally improved specificity at the expense of sensitivity. Multiple saliva measurements throughout the 24-hour testing period improved the sensitivity and specificity of the pepsin test. Only three studies considered the measurement of other digestive enzymes, primarily bile salts, as biomarkers of LPRD.

Conclusion: The methods of salivary pepsin collection and measurement substantially influence its diagnostic performance. Future comparative studies are needed to determine the most accurate methodological approach and to establish consensus guidelines for salivary pepsin and other digestive enzyme measurements in LPRD diagnosis through standardized collection, storage, and measurement protocols.