Salivary Pepsin Testing: A New Non-Invasive Tool for Screening Gastroesophageal Reflux Disease (GERD)

Gastroesophageal reflux disease (GERD), a common digestive disorder, is witnessing a rising prevalence worldwide. Traditional diagnostic methods such as endoscopy, while accurate, are invasive and may cause discomfort, making them less acceptable for certain patient groups. In recent years, salivary pepsin testing has emerged as a promising alternative for GERD screening and monitoring, thanks to its non-invasive and convenient nature.

Pepsinogen, the inactive precursor of pepsin, is activated in the acidic environment of the stomach (pH < 4). Under normal conditions, pepsin functions solely within the stomach to digest proteins. However, when dysfunction of the lower esophageal sphincter (LES) or transient LES relaxation occurs, gastric contents containing pepsin can reflux into the esophagus, and in some cases, pass through the upper esophageal sphincter (UES) into the throat and oral cavity.

Salivary pepsin testing detects the presence of pepsin in saliva — a key biomarker indicating reflux. A positive result suggests the occurrence of gastric reflux, providing an important clue for GERD diagnosis.

Advantages Over Traditional Methods

Compared to conventional diagnostic approaches, salivary pepsin testing offers significant benefits:

• Non-invasive and painless: Eliminates the discomfort and risks associated with endoscopy, such as throat irritation, nausea, vomiting, or esophageal mucosal injury.

• Simple sample collection: Requires only 2–3 mL of naturally secreted saliva. The test has minimal environmental and preparation requirements, and can be performed both in clinical settings and at home.

How the Test Works

One commonly used technique is immunochromatography, similar to rapid test strips. Saliva is applied to the strip, and if pepsin is present, it binds to specific antibodies, producing a visible colored band indicating a positive result.

Clinical Applications

Salivary pepsin testing is applicable in various clinical scenarios:

• Typical GERD symptoms: For patients with heartburn, regurgitation, chest pain, or upper abdominal discomfort, the test provides a fast screening option to assess reflux involvement.

• Atypical or extra-esophageal symptoms: For cases with chronic cough, laryngitis, asthma, hoarseness, or globus sensation where standard treatments fail, the test helps identify reflux as a potential underlying cause.

• Special populations: Offers a safe, effective alternative for patients who cannot tolerate invasive procedures — such as the elderly, children, or those with severe comorbidities like cardiopulmonary dysfunction or coagulation disorders.

Standardized Procedure

Saliva is collected through natural drooling or gentle parotid massage and placed in a dedicated collection tube. The sample is then sent to the hospital lab for testing. Results are reviewed by professionals:

• Negative results require verification of proper sample collection and equipment function.

• Positive results are rechecked to rule out false positives.

After verification, a formal report is issued, indicating the result and providing interpretation and clinical recommendations.

Clinical Guidelines and Recognition

Multiple authoritative Chinese clinical guidelines support salivary pepsin testing:

• The "Chinese GERD Expert Consensus (2020)" recommends the test as an effective first-line screening tool for suspected GERD patients, especially those with extra-esophageal symptoms or poor tolerance to endoscopy.

• The "Laryngopharyngeal Reflux Disease Diagnosis and Treatment Consensus (2022)" also highlights the test’s value in evaluating extra-esophageal reflux diseases like reflux laryngitis.

These guidelines reinforce the clinical credibility of salivary pepsin testing and encourage its standardized use in GERD diagnosis and management.

Clinical Integration and Future Prospects

Salivary pepsin testing is now widely used in clinical practice:

• As a cost-effective, convenient outpatient screening method.

• For monitoring treatment in refractory GERD patients.

• In ENT settings to support diagnosis of reflux-related laryngitis, subglottic stenosis, and more.

With advancing biotechnology, future developments may include:

1. Enhanced sensitivity and specificity through improved detection technology.

2. Combined biomarker panels to increase diagnostic accuracy.

3. Expanded interdisciplinary use for deeper insight into related disease mechanisms.

While salivary pepsin testing offers a non-invasive, convenient, and repeatable method for GERD management, it is not without limitations. Clinicians should integrate this tool appropriately based on individual patient conditions for personalized, precise diagnosis and treatment.

If you have questions about this test or GERD management, please consult a healthcare professional for personalized guidance.