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Bile acids in refluxate contribute to esophageal and laryngeal symptoms and are quantifiable. The aim of this study was to compare salivary bile acid concentrations across healthy controls and symptomatic patients (esophageal or laryngeal) with or without objective gastroesophageal reflux disease (GERD). This prospective study enrolled adults into three groups: esophageal symptoms (heartburn, regurgitation, chest pain); laryngeal symptoms (cough, throat clearing, sore throat, dysphonia); and controls. Symptomatic patients primarily underwent prolonged wireless reflux monitoring off acid suppression and were categorized as symptomatic no GERD (acid exposure time <4%) or esophageal/laryngeal symptoms with GERD (acid exposure time ≥4%). Controls did not undergo reflux monitoring nor upper endoscopy. Saliva samples were provided for bile acid analysis via ultraperformance liquid chromatography tandem mass spectrometry. Thirty-five participants were enrolled (mean age 47.4 years [SD 18.9], 16 [46%] male), including 10 controls and 25 symptomatic: 9 no GERD, 5 esophageal symptoms + GERD, and 11 laryngeal symptoms + GERD. Total salivary bile acids were highest in the laryngeal symptoms + GERD group (24.2 nM [SD 24.7]) compared to other groups (controls: 5.8 [6.0], P  = 0.03; symptomatic no GERD: 3.1 [4.4]; P  < 0.01; esophageal symptoms + GERD: 7.1 [7.1], P  = 0.10). Bile acids were elevated in 45% (5/11) of the laryngeal symptoms + GERD group compared to 0% of the other three groups (P  < 0.01). Salivary bile acids were higher among patients with laryngeal symptoms and objective GERD versus other groups. Salivary bile acids are a quantifiable biomarker with diagnostic potential for laryngopharyngeal reflux. [ABSTRACT FROM AUTHOR]

Gastroesophageal reflux disease (GERD) is primarily diagnosed based on symptoms and response to a proton-pump inhibitor (PPI) trial. Gold standard testing requires an invasive endoscopic procedure, often with ambulatory pH monitoring. Salivary pepsin is a potential noninvasive modality for GERD diagnosis. This study aimed to assess diagnostic performance of salivary pepsin thresholds for GERD and determine optimal collection protocol of saliva in an external validation cohort. Over 10 months, adults with symptoms of GERD undergoing esophagogastroduodenoscopy with wireless pH-monitoring off PPI were enrolled. Saliva was self-collected by participants over 4 days across three different time points: fasting ante meridiem (AM), post-prandial, and bedtime (PM). Pepsin levels were calculated via Peptest. Pepsin variability and agreement were determined using linear mixed effects models and intraclass correlation. Validation of diagnostic threshold and performance characteristics were evaluated by receiver–operator curve analysis. Twenty participants enrolled in the study; 50% with physiologic acid exposure (acid exposure time < 4% no GERD) and 50% with elevated acid exposure (GERD). Mean pepsin concentrations were significantly lower in the AM (22.6 ± 25.2 ng/mL) compared to post-prandial (44.5 ± 36.7 ng/mL) and PM (55.4 ± 47.0 ng/mL). Agreement between pepsin concentrations across 3 days was substantial for AM samples (kappa 0.61), with lower agreement for post-prandial and PM samples. A single AM pepsin concentration of 25 ng/mL was 67% accurate for GERD with 56% sensitivity and 78% specificity. This validation study highlights fair accuracy and performance characteristics of a single fasting AM salivary pepsin concentration for the diagnosis of GERD. [ABSTRACT FROM AUTHOR]

Uncertain diagnostic performance has limited clinical adoption of salivary pepsin, a noninvasive diagnostic tool for gastroesophageal reflux disease (GERD). This study aimed to assess diagnostic performance of salivary pepsin, and test validity of thresholds in an external cohort of patients with or without GERD. This two-phase prospective study conducted at two centers enrolled adult asymptomatic volunteers, patients with symptoms of GERD undergoing reflux monitoring, and patients with Barrett's esophagus (BE). Fasting saliva samples were processed for pepsin concentration using Peptest. Phase 1 compared pepsin concentration between No GERD (volunteers/functional heartburn) and GERD (erosive reflux disease/nonerosive reflux disease (NERD)/BE). Phase 2 tested validity of the diagnostic thresholds identified from Phase 1 among external functional heartburn and NERD cohorts. Of 243 enrolled subjects, 156 met inclusion criteria. Phase 1 (n = 114): Pepsin concentrations were significantly higher in GERD (n = 84) versus No GERD (n = 30) (73.8 ng/mL vs. 21.1 ng/mL; P  < 0.001). Area under the curve for pepsin concentration was 0.74 (95% CI 0.65, 0.83). A salivary pepsin threshold of 24.9 ng/mL optimized the true negative rate and 100.0 ng/mL optimized the true positive rate. Phase 2 (n = 42): Pepsin concentrations were significantly higher in NERD (n = 22) versus Functional Heartburn (n = 20) (176.0 ng/mL vs. 53.3 ng/mL, P  < 0.001). Applying Phase 1 thresholds in this external cohort, salivary pepsin 24.9 ng/mL was 86% sensitive (64%, 97%) and 100.0 ng/mL was 72% specific for distinguishing NERD from functional heartburn. Given modest sensitivity and specificity for GERD, salivary pepsin may have clinical utility as a noninvasive office based diagnostic screening tool for GERD. [ABSTRACT FROM AUTHOR]