Digestive Biomarkers of Laryngopharyngeal Reflux: A Preliminary Prospective Controlled Study

Introduction: To investigate the digestive enzymes and biomarkers in the saliva of patients with laryngopharyngeal reflux (LPR) and asymptomatic individuals.

Methods: The design was a prospective controlled study. The setting was a multicenter study. Patients with LPR at the hypopharyngeal-esophageal impedance-pH monitoring (HEMII-pH) and asymptomatic individuals were consecutively recruited from January 2020 to April 2023 from two university hospitals. The saliva of patients (off PPIs) and asymptomatic individuals was collected to measure pH, elastase, bile salts, cholesterol, gastric and pancreatic lipases. Anxiety, symptoms and findings were studied through perceived stress scale (PSS), reflux symptom score (RSS) and reflux sign assessment (RSA).

Results: In total, 67 LPR patients and 57 asymptomatic individuals completed the evaluations. LPR patients reported higher PSS, RSS, and RSA than asymptomatic individuals. The mean saliva pH was more alkaline in LPR patients (7.23: 95%CI: 7.08,7.38) compared to controls (6.13; 95%CI: 5.95,6.31; p=0.001). The mean concentration of elastase was higher in patients (51.65µg/ml; 95%CI: 44.47,58.83µg/ml) versus asymptomatic individuals (25.18µg/ml; 95%CI: 21.64,28.72µg/ml; p=0.001). The saliva cholesterol reported higher concentration in healthy individuals (3.43mg/dL; 95%CI: 3.21,3.65mg/dL) compared to patients (1.16mg/dL; 95%CI: 1.05,1.27mg/dL; p=0.001). The saliva pH and elastase concentration were significantly associated with the baseline RSS, while saliva cholesterol was negatively associated with the severity of RSS and RSA.

Conclusions: Cholesterol, bile salts, and elastase are biomarkers of LPR and should be considered to develop future non-invasive saliva device for the detection of LPR.