Silent reflux and Peptest

We are often approached by patients with distressing upper airway or other laryngeal symptoms that can have a devastating effect on quality of life, are difficult to diagnose and consequently difficult for the patient, and doctor, to find an effective treatment.

Many of these patients have used Peptest and gained reassurance and a new course of action from a positive diagnosis for the presence of pepsin in their samples. However, some patients are also consistently negative for pepsin which points to a potential other cause for their symptoms.

A negative Peptest in such cases is often a more important discovery in the eyes of the physician and may indicate that an alternative diagnosis needs to be sought.

So why do we sometimes get a negative result for pepsin in suspected silent reflux patients?

The answer is complex and the first thing to note is that no diagnostic is 100% accurate, so for any single test there is a small chance that a false negative result is received. However, particularly if multiple diagnostic procedures or multiple Peptest results point away from reflux, it is important to realise that other causes for these symptoms do exist.

I recently came across the reflux guidelines issued by the University of Michigan and I thought they might help to answer some of these questions. The excerpt reproduced below is specifically aimed at what they refer to as atypical signs of GERD or LPR. (The full text can be found here )

Extract from GERD practice guidelines:

Reflux may manifest atypically as pulmonary (asthma, chronic cough), ENT (laryngitis, hoarseness, sore throat, globus, throat clearing) or cardiac
(chest pain) symptoms, often without symptoms of heartburn and regurgitation. Mechanisms for this include direct contact and microaspiration of small amounts of noxious gastric contents into the larynx and upper bronchial tree (triggering local irritation, and cough), and acid stimulation of vagal afferent neurons in the distal esophagus (causing non-cardiac chest pain and vagally-mediated bronchospasm/asthma). Laryngeal neuropathy has been implicated recently as a cause for laryngitis symptoms and cough.


Asthma and GERD are common conditions that often coexist with 50-80% of asthmatics having GERD and up to 75% having abnormal pH testing. However, only 30% of patients who have both GERD and asthma will have GERD as the cause for their asthma. The causal relationship between asthma and GERD is difficult to establish because either condition can induce the other (GERD causing asthma as above, and asthma causing increased reflux by creating negative intrathoracic pressure and overcoming LES barrier). Furthermore, medications used for asthma, such as bronchodilators, are associated with increased reflux symptomatology. Historical clues to GERD-related asthma may include asthma symptoms that worsen with big meals, alcohol, and supine position, or adult-onset and medically refractory asthma. Diagnostic testing with pH probe and EGD have limited utility in establishing causality in this population.

Ear, nose, and throat.

In patients presenting with ENT symptoms, 10% of hoarseness, up to 60% of chronic laryngitis and refractory sore throat, and 25-50% of globus sensation may be due to reflux. EGD and pH testing are frequently normal in this population. Reflux laryngitis is usually diagnosed based on the laryngoscopic findings of laryngeal erythema and edema, posterior pharyngeal coblestoning, contact ulcers, granulomas, and interarytenoid changes. However, a recent study found these signs to be nonspecific for GERD, noting at least 1 sign in 91 of 105 (87%) healthy people without reflux or laryngeal complaints. Many of these signs may be due to other laryngeal irritants such as alcohol, smoking, postnasal drip, viral illness, voice overuse, or environmental allergens, suggesting their use may contribute to over-diagnosis of GERD. This also may explain why many patients (up to 40-50%) with laryngeal signs don’t respond to aggressive acid therapy. Posterior laryngitis, medial erythema of false/true vocal cords and contact changes (ulcers and granulomas) are more common in GERD patients and predict a better response to acid reduction.

Although we may not agree entirely with the breakdown of cause of symptoms presented here the key message is that getting an accurate diagnosis for the cause of symptoms is vital for the management and treatment of the condition. Peptest is a highly accurate predictor of reflux in all types of patients and a positive Peptest tells a patient and their doctor that they need to manage their reflux in order to help with their symptoms. A negative Peptest on the other hand is a key indicator that other factors could be involved in causing the symptoms and is equally as important to the physician in the ongoing treatment of the patient.

The key factors to getting an accurate diagnosis using Peptest are:

  1. Always collect samples when you are symptomatic.
  2. Always clear the throat with a cough to ensure that saliva from the throat and mouth are mixed prior to collection
  3. Always collect samples before undertaking a lifestyle changes or new medication etc. so that you can be sure reflux is the cause. (It is possible that symptoms will persist for a period of time after the actual reflux has improved or stopped due to the treatment).
  4. Always follow the instructions provided carefully and note anything that might affect your reflux.

For further information please contact us or visit our website

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