Review article: symptomatic non-acid reflux - the new frontier in gastro-oesophageal reflux disease

Over the past 20 years as effective acid suppression has been achievable through the use of proton pump inhibitors (PPIs), a new type of clinical presentation has evolved. Patients with persistent symptoms suspected to be due to gastro-oesophageal reflux disease (GERD) are being identified as PPI failures. These symptoms include typical GERD symptoms such as heartburn and regurgitation and atypical or extra-oesophageal symptoms such as cough and throat clearing. As PPIs have little effect on changing the mechanism by which reflux occurs, particularly the postprandial transient lower oesophageal sphincter relaxation, one could argue that PPI therapy has unmasked the phenomenon of symptomatic non-acid reflux. The diagnosis begins with the history, based on the continuing symptom considered likely due to GERD despite adequate acid suppression. At that point in the patient's clinical course old fashioned pH monitoring has a limited role. Some argue that documentation of abnormal acid reflux and a positive reflux/symptom association while off therapy is appropriate and adequate. Our belief is that such a finding fails to resolve the question of the mechanism underlying persistent symptoms while taking PPI therapy. Fortunately, the development of the technology that allows measurement of all types of reflux based on changes in electrical impedance within the oesophageal lumen has provided the means to identify a symptom/reflux relationship where the pH of the refluxant is >4. Numerous studies have shown that such non-acid, or 'weakly acidic', reflux may be related to persisting reflux type symptoms in approximately 30-35% of patients studied with the impedance technique.