Gastro-oesophageal reflux disease (GORD) is a very common disorder in which the reflux of gastric (or gastroduodenal) contents causes troublesome symptoms and/or lesions of the oesophageal mucosa. The harmful effects of acid injury on the oesophageal mucosa have been established for decades by experimental and clinical studies.¹ From a clinical and therapeutic viewpoint, the central role of acid in the pathogenesis of reflux symptoms and lesions of the oesophagitis was most convincingly confirmed by the introduction of acid suppressive therapy; the development of proton pump inhibitors (PPIs) achieved a level of efficacy not previously reached by antacids or H₂ blockers.²

Despite the progress made with PPIs, it has now however become clear that up to 40% of patients with GORD symptoms are either not completely satisfied with their acid suppressive therapy or may be resistant to PPIs.³ Several reasons may underlie an individual’s resistance to his or her PPI regimen. Firstly, it may be that symptoms are not related to acid reflux; this may be the case when atypical and non-specific symptoms are reported and endoscopy does not show mucosal breaks, for example. In addition, acid injury may not be completely eliminated by PPI treatment and acid exposure remains abnormal. The level of acidity necessary to cause symptoms is not precisely defined and is likely to vary from subject to subject or even in the same individual. Several studies have shown that “weakly acidic” or short lasting reflux episodes may cause symptoms similar to those reported in classical GORD despite an overall normal 24 hour oesophageal acid exposure time.^4,5 In these patients with an apparently hypersensitive …