Summary Background : Acid plays a significant role in the development of gastro‐oesophageal reflux symptoms and tissue damage. It is generally assumed that acid suppressive therapy with proton pump inhibitors improves or eliminates symptoms of gastro‐oesophageal reflux disease by normalizing intra‐oesophageal pH. However, the degree of acid suppression induced by proton pump inhibitor therapy in patients with gastro‐oesophageal reflux disease and/or Barrett's oesophagus has not been adequately studied. Aim : To assess the efficacy of proton pump inhibitors in normalizing intra‐oesophageal and intra‐gastric pH in patients with gastro‐oesophageal reflux disease with and without Barrett's oesophagus who have been rendered symptom‐free by acid‐suppressive therapy. Methods : Patients with gastro‐oesophageal reflux disease and Barrett's oesophagus were prospectively evaluated by dual sensor 24‐h pH monitoring while receiving proton pump inhibitor therapy for complete control of gastro‐oesophageal reflux disease symptoms. Analyses and comparisons of intra‐oesophageal and intra‐gastric pH profiles on therapy were then made. Results : One hundred and ten patients, 98 men and 12 women, with gastro‐oesophageal reflux disease (n = 62) and/or Barrett's oesophagus (n = 48), were studied. All tolerated proton pump inhibitors well and were asymptomatic at the time of the study. Thirty‐six (58%) patients with gastro‐oesophageal reflux disease and 24 (50%) patients with Barrett's oesophagus (P = 0.4) normalized their intra‐oesophageal pH profiles on proton pump inhibitors. Compared with patients with gastro‐oesophageal reflux disease, patients with Barrett's oesophagus were more likely to have higher degree of pathologic acid reflux despite proton pump inhibitor therapy (DeMeester score 50.5 ± 8.2 vs. 31.4 ± 4.6, P = 0.03) and exhibited less intra‐gastric acid suppression (% total pH<4.0: 53.9 ± 2.7 vs. 39.9 ± 2.6, P =0.0004), particularly supine (% pH<4.0: 62.1 ± 3.4 vs. 44.8 ± 3.4, P =0.0006). Conclusions : Gastro‐oesophageal reflux disease patients with or without Barrett's oesophagus continue to exhibit pathologic gastro‐oesophageal reflux disease and low intra‐gastric pH despite proton pump inhibitor therapy that accomplishes complete reflux symptom control. Further, intra‐oesophageal and intra‐gastric pH control is significantly more difficult to achieve in patients with Barrett's oesophagus. These findings may have significant therapeutic implications.

Proton Pump Inhibitors (PPIs) are widely used in the treatment of acid-peptic diseases. Their mechanism of action involves inhibition of the H-K-adenosine triphosphatase enzyme present in the parietal cells of the gastric mucosa. Because PPIs are the most potent inhibitors of gastric acid secretion available, they effectively alleviate acid-peptic symptoms and facilitate healing of inflamed or ulcerated mucosa. Although the use of PPIs is nowadays short term in patients with Helicobacter pylori-related peptic ulcer disease, these drugs are increasingly used long term, frequently for a lifetime, in patients with typical or atypical symptoms of gastro-oesophageal reflux disease, and in NSAID or aspirin users at risk for gastrotoxicity and related complications, such as bleeding, perforation and gastric outlet obstruction. This review outlines the essentials of PPI pharmacology, the safety and adverse profiles of the various available agents, and balances them against their clinical short- and long-term benefits. PPI use, prophylactically or with a therapeutic intent may also be combined with other strategies, such as endoscopic therapy, surgery or antibacterial use. Various clinical endpoints, such as symptom relief, mucosal healing, prevention of disease recurrence or complications, and cancer chemoprevention, are discussed and unmet needs are highlighted.