Non-Acidic Reflux Explains Lack of Response to H2 Blockers and PPIs

In vitro experimental studies show that exposure to pepsin depletes protective proteins. Dr. Johnston and colleagues have found that human pepsin is maximally active at pH 2.0 and inactive at pH 6.5. Pepsin is inactive at neutral pH, but it remains stable. Pepsin is not irreversibly inactivated until pH 8.0. Dr. Johnston explained that this is clinically important, because pepsin-detected in the laryngopharynx of patients with reflux-attributed injury or disease-could sit inactive or dormant in the laryngopharynx and have the potential to be reactivated following a decrease in pH. In vitro studies show that pepsin is taken up by the laryngeal epithelial cells by receptor-mediated endocytosis. Thus, pepsin may be reactivated intraceullarly, causing depletion of protective proteins and damage to the mitochondria.

These findings suggest that pepsin inhibitors and pepsin antagonists may have clinical utility in patients with reflux attributed to laryngeal injury, Dr. Johnston said. Research efforts to develop drugs for non-acidic reflux are ongoing.

Diagnosis

In diagnosing non-acidic reflux, a reflux finding score greater than 7 is considered significant, said Robert J. Toohill, MD, Professor in the Division of Laryngology and Professional Voice, Department of Otolaryngology and Communication Sciences at the Medical College of Wisconsin. The barium esophogram is a noninvasive test that is underutilized in diagnosing this disorder. The test is less invasive than other tests, takes up to 30 minutes to perform, and is less costly than other diagnostic techniques.

The barium esophogram will provide important information on duodenal gastroesophageal reflux [DGER] 60% to 70% of the time. It reveals the presence of motility and peristalsis problems, lower esophageal sphincter dysfunction, and spontaneous reflux, Dr. Toohill told listeners.

The 24-hour ambulatory pH study is considered the gold standard. The upper probe can be placed with an endoscope, which is preferable to a manometer, and this test can delineate upright or supine reflux. It provides useful information in 70% to 80% of cases. However, it is invasive, time-consuming, and expensive, he said.

Multichannel intraluminal impedance monitoring is another invasive, time-consuming, expensive test that is used to detect DGER. This test gives you reliable information, and if the probe reveals gastric contents in the upper esophagus, it is highly likely that the diagnosis is DGER, Dr. Toohill commented. Another advantage of multichannel intraluminal impedance monitoring is that it has built-in pH monitoring.

Transnasal esophagoscopy can be used to diagnose DGER in patients with GERD who have a poor response to acid suppression and for patients with cough and no diagnosis

Treatment

Although dietary measures and lifestyle changes are important for relieving symptoms of GERD, they are not as important for DGER, Dr. Toohill said. Events related to DGER occur mostly when patients are in an upright position. The most important lifestyle change [to relieve symptoms of DGER] is to stop smoking, he commented.