Biomarker–Phenotype Relationships in Clinically Suspected Laryngopharyngeal Reflux–Associated Dysphonia: A Multidomain Analysis of Salivary Pepsin, Salivary pH, Reflux Symptoms, Laryngeal Findings, and Voice Handicap

Abstract

Laryngopharyngeal reflux (LPR) can present with dysphonia, yet the extent to which salivary biomarkers correspond to symptom burden, laryngeal findings, and voice-related disability remains unclear. This analytical cross-sectional study examined relationships among salivary pepsin, salivary pH, Reflux Symptom Index (RSI), Reflux Finding Score (RFS), and Voice Handicap Index-30 (VHI-30) in 21 treatment-naïve adults with clinically suspected LPR-associated dysphonia, defined by RSI ≥13 and RFS ≥7. Salivary pepsin was quantified using sandwich ELISA, and salivary pH was measured with a digital pH meter. Ten pairwise associations were analyzed using Spearman correlations with 5,000-resample bias-corrected and accelerated bootstrap 95% confidence intervals. Benjamini–Hochberg false-discovery-rate correction was applied. Salivary pepsin and salivary pH showed weak correlations with RSI, RFS, and VHI-30, with all bootstrap confidence intervals crossing zero. Nominal positive associations were observed between RSI and RFS (ρ=0.556, p=0.009), RSI and VHI-30 (ρ=0.477, p=0.029), and RFS and VHI-30 (ρ=0.457, p=0.037), although none remained statistically significant after false-discovery-rate correction (all q≥0.090). Clinical phenotype measures therefore showed numerically stronger interrelationships than their associations with salivary biomarkers, although none remained statistically significant after multiplicity correction. Single-time salivary pepsin and pH measurements may therefore not reliably reflect clinical severity in suspected LPR-associated dysphonia.