Review article: physiologic and clinical effects of proton pump inhibitors on non-acidic and acidic gastro-oesophageal reflux.

The control of oesophageal acid exposure through gastric acid inhibition, as the basis for gastro-oesophageal reflux disease (GERD) treatment, arose from the apparent pH dependency of erosive oesophagitis and relationship to GERD symptoms. The current perception is that reflux disease is an entirely acid-mediated condition, and antisecretory therapies, particularly proton pump inhibitors, are the treatment of choice for patients with erosive and non-erosive reflux disease. A positive patient response to an empiric trial of proton pump inhibitor (PPI) therapy, or the 'PPI test', is commonly suggested as a method of GERD diagnosis. Recent studies have modified our understanding of the relationship between oesophageal acid exposure and GERD pathology, manifestations and symptoms. Whereas the use of PPIs to reduce oesophageal acid exposure in patients with erosions is associated with increased healing rates, non-erosive reflux disease patients are less likely to have an abnormal oesophageal pH profile. Patterns of oesophageal acid exposure, particularly nocturnal oesophageal acid exposure, have been linked to increased disease severity. Non-acidic reflux and the effect of PPIs on this parameter, including bile reflux and the toxicity of bile acids, may also be an important factor in GERD. This article explores some of these assumptions, practices and relationships, including: the association between oesophageal acid exposure and erosive and non-erosive gastro-oesophageal reflux disease; the effect of PPIs on oesophageal acid exposure in erosive oesophagitis patients; the influence of nocturnal acid secretion in GERD and the use of PPIs to control this parameter; the relevance of the PPI test for reflux disease diagnosis; and PPI influence on non-acidic reflux.