Making sense of oesophageal contents.

Everybody experiences gastro-oesophageal reflux on occasion. In health, reflux of air (‘‘belching’’) occurs most commonly during ‘‘transient lower oesophageal sphincter relaxations’’ (TLOSRs) triggered by gastric distension. Acid secretions and semidigested food may also pass into the oesophagus during such events. Gastrooesophageal reflux disease (GORD) is present when this reflux of gastric contents causes symptoms or mucosal damage. GORD patients do not necessarily have more TLOSRs than healthy controls. Rather, structural degradation and instability of the gastro-oesophageal junction increase the likelihood of reflux during TLOSRs and at other times (e.g. on straining). 4 It is likely that the same changes allow greater volumes of gastric contents to pass the reflux barrier and to extend further into the oesophagus. 6 Once reflux has occurred, ineffective motility and clearance are also important because prolonged exposure to acid and other noxious substances in refluxate (e.g. bile salts, pepsin) increase the risk of erosive reflux disease (ERD), Barrett’s columnar lined oesophagus (CLO) and other complications. 8 Whether reflux triggers patient symptoms depends on a dynamic interaction between several factors, including patient age and sex, dietary factors, the volume, composition and distribution of the refluxate, mucosal disease, visceral sensitivity, and central factors including stress and patient vigilance (see box). Oesophageal pH testing was popularised by Johnson and DeMeester in the belief that GORD was not a symptom driven condition, but should be diagnosed by measurement of objective pathology. On this basis, the condition was conceived as a continuous spectrum of disease because oesophageal acid exposure is associated with the severity of symptoms and oesophagitis. Nevertheless, the relationship between reflux events, acid exposure, endoscopic findings and symptoms is not straightforward. For example, patients with Barrett’s CLO often have high levels of acid exposure but few symptoms because the metaplastic, columnar lining of the oesophagus is relatively insensitive to acid. Conversely, severe symptoms and a relatively poor response to acid suppression are often reported by patients with normal or near-normal acid exposure and without mucosal injury on conventional endoscopy. 25 Ambulatory 24 h pH monitoring remains the standard investigation of GORD; however, it seems obvious that the value of pH studies is limited in patients in whom symptoms are not due to acid reflux. Multichannel intra-luminal impedance (MII) detects and follows the movement of oesophageal contents and can distinguish fluid and gas within the lumen. Combined pH and impedance monitoring has shown that proton pump inhibitors (PPIs) reduce acid reflux but have no effect on the number of reflux events per se. Moreover, clinical studies have found that weakly acid or non-acid reflux is a common cause of persistent symptoms in patients on PPI treatment, including those with atypical symptoms and chronic cough. 31 These findings led to rapid adoption of this technique in clinical practice; however, the analysis of MII data is time consuming and its place in the routine investigation of GORD is still being defined. In this edition of Gut, Emerenziani and colleagues (see page 443) compare the findings of combined pH and impedance monitoring in patients with ‘‘endoscopy negative reflux disease’’ (ENRD), to those with ERD and healthy controls. Overall, and consistent with previous studies, 32 about 80% of patient reports of heartburn and regurgitation were related to acid reflux. Moreover, the frequency of acid reflux as a proportion of all the reflux events was twice as high in patients than controls, adding to the evidence that increased gastric acid production, abnormal distribution of secretions or delayed gastric emptying play an important role in GORD. 33 Oesophageal acid exposure was lower in ENRD than ERD; in contrast, the percentage association of reflux events with symptoms (symptom index) was higher for both acid and weakly acid reflux. On detailed analysis it was found that only a small proportion of symptoms (12%) were triggered by weakly acid reflux in ERD patients; however, this was significantly higher in ENRD patients (22%), especially in the subgroup with physiological oesophageal acid exposure (32%). In addition, and independent of acid content, the presence of gas in the refluxate (i.e. mixed reflux) increased the likelihood that symptoms were reported in ENRD patients, almost certainly because of increased refluxate volume and oesophageal distension. The importance of these findings is not to suggest that the acquisition of more and more complex information about oesophageal contents improves the diagnostic yield of GORD. Rather it is to emphasise that patients with a sensitive oesophagus can experience typical reflux symptoms in response to chemical or mechanical stimulation in the clinical setting, and that a high symptom index is a surrogate marker for visceral hypersensitivity and/or abnormal central processing of visceral sensations. As explained below, this insight may be of value in interpreting reflux studies and predicting the outcome of treatment. Before recommending that combined pH and impedance replace conventional pH monitoring, technical factors that affect published comparison should be considered. Firstly, the use of antimony pH electrodes rather than ‘‘reference standard’’ glass electrodes in most studies (and most commercial catheters) could bias results. In clinical practice the diagnostic agreement between these systems is acceptable; 35 however, pH measurements acquired by antimony electrodes (with external reference) drift upwards over time due to oxidation in acid environs. As a consequence, antimony electrodes may register less ‘‘acid reflux’’ events than glass electrodes, especially when gastric pH is elevated in the post-prandial period and on PPI treatment. Secondly, the recording characteristics and signal processing of pH and MII systems are fundamentally different. The former provides a continuous assessment of oesophageal acid exposure. Each pH measurement represents the mean acid exposure over a period of time (typically 6 s), with reflux events recorded after two consecutive readings under pH 4 (i.e. 12 s). The latter detects discrete acid and non-acid reflux events, but does not provide an assessment of ‘‘refluxate exposure’’ because current MII techniques are insensitive to volume change. In addition, impedance measurements are acquired at 50 Hz and reflux events are identified by a characteristic distal to proximal impedance fall Clinic for Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland