Introduction

Abstract

In the context of gastro-oesophageal reflux disease (GERD), the effects of bile and pepsin in clinical practice remains a controversial topic and one that is always in the background. Much of the data available are experimental rather than from clinical studies. Clinicians tend to fluctuate between regarding bile pepsin reflux as clinically unimportant, or conversely, as ascribing to them problems which do not resolve despite adequate acid suppression. The aim of this supplement, based on a series of presentations from eminent scientists and clinicians, was to revisit the role of these secretions and their importance in the clinical setting. There is indeed much uncertainty about the roles of pepsin, bile acids and other constituents of duodenal fluid in causing damage in GERD. Evidence supports the potential for them to cause tissue damage and there is no doubt about the occurrence of gastroduodenal reflux in GERD. However, many original investigations and reviews go no further than concluding that these agents ‘may’ be important contributors to oesophageal or airways injury. From a clinical perspective there is a need to clarify whether their potential to cause damage is a real factor towards actual tissue damage in patients with GERD. Two important questions arise in respect of each of these putative injurious agents: (i) Is exposure of the oesophagus to the agent in GERD comparable with the experimental exposure shown to cause tissue injury? (ii) Is the experimentally demonstrable tissue injury caused by the agent directly relevant to one or more clinically important tissue injuries encountered in GERD? Direct experimental studies addressing such questions are important. Although epidemiological observations on GERD may convincingly identify risk factors for oesophagitis, laryngitis or Barrett's oesophagus, and such observations are valuable, there is a problem establishing the magnitude of the causal contribution with epidemical data. The magnitude of the contribution is relevant for the potentially affected patient because it determines whether the clinician should use treatment to protect against a threat of significant injury. Part of the interest in revisiting the roles of pepsin, bile and duodenal gastro-oesophageal reflux incurred arises because incomplete resolution of reflux symptoms and incomplete healing of the oesophagitis are common despite proton-pump inhibitors (PPIs). This is the case even when gastric acid secretion is seemingly adequately suppressed. Could it be that gastro-oesophageal reflux or pepsin in ‘weak’ gastric acid (pH >4) or of duodenal fluid components is responsible for such problems? These issues are of importance for the practicing clinician because incomplete control of GERD is common, and neither the assessment nor the treatment of such patients is easy.