Performance Study of Noninvasive Salivary Biomarkers in Laryngopharyngeal Reflux

The diagnosis of laryngopharyngeal reflux disease (LPRD) mostly uses invasive techniques. Our aim was to carry out a performance study of noninvasive saliva biomarkers in LPRD patients and to investigate clinical utility.

The saliva of 201 patients with an LPRD diagnosis was prospectively collected using a Salivette® device. Findings were compared with 35 healthy controls using nonparametric statistics. Biomarker cut-offs were determined with receiver operating curves (ROCs).

The analytical performance study indicated satisfactory performance against biological acceptability goals for bias, imprecision, and total allowable error. The limit of detection (LOD) was evaluated for all biomarkers in the saliva matrix. Results fell within the analytical measurement range for salivary elastase, trypsin, and pH and close to the LOD for cholesterol. The clinical study reported significantly higher salivary pH and elastase and lower cholesterol in LPRD compared to controls (P < 0.05), while salivary trypsin did not differ significantly. Diagnostic cut-offs determined with ROC were salivary elastase >49 µg/mL, salivary pH >7.6, and salivary cholesterol <2.1 mg/dL (<0.054 mmol/L). The combination of salivary elastase with cholesterol gave a positive predictive value of 93% and a negative predictive value of 100% for the diagnosis of LPRD in this study. Salivary total bilirubin, lipase, and pepsin were mostly undetected.

Noninvasive diagnosis of LPRD is possible, based on a single saliva collection, although our cut-offs should be evaluated in further studies. A reproducible analytical protocol has been obtained. Salivary elastase, cholesterol, and pH show clinical utility for the presence of duodeno-gastric reflux in LPRD patients.