Marzio Frazzoni

The added value of impedance-pH monitoring to Rome III criteria in distinguishing functional heartburn from non-erosive reflux disease

INTRODUCTION Functional heartburn is defined by Rome III criteria as an endoscopy-negative condition with normal oesophageal acid exposure time, negative symptom association to acid reflux and unsatisfactory response to proton pump inhibitors. These criteria underestimated the role of non-acid reflux. AIM To assess the contribution of impedance-pH with symptom association probability (SAP) analysis in identifying endoscopy-negative patients with reflux disease and separating them from functional heartburn. METHODS Consecutive endoscopy-negative patients treated with proton pump inhibitors (n=219) undergoing impedance-pH monitoring off-therapy were analysed. Distal acid exposure time, reflux episodes, SAP and symptomatic response to proton pump inhibitors were measured. RESULTS Based on impedance-pH/SAP, 67 (31%) patients were pH+/SAP+, 6 (2%) pH+/SAP-, 83 (38%) hypersensitive oesophagus and 63 (29%) functional heartburn. According to pH-metry alone/response to proton pump inhibitors, 62 (28%) were pH+/SAP+, 11 (5%) pH+/SAP-, 61 (28%) hypersensitive oesophagus and 85 (39%) functional heartburn. In the normal-acid exposure population the contribution of impedance-pH/SAP compared to pH-metry alone/response to proton pump inhibitors in identifying patients with reflux disease and functional heartburn resulted to be 10%. In patients with abnormal-acid exposure, the contribution of impedance-pH/SAP increased by 3%. CONCLUSION Comparing impedance-pH testing with pH-metry alone plus the response to proton pump inhibitor therapy demonstrated that the latter ones cause underestimation of reflux disease patients and overestimation of functional heartburn patients.

Different patterns of oesophageal acid exposure distinguish complicated reflux disease from either erosive reflux oesophagitis or non‐erosive reflux disease

Background : The reason why less than one‐half of patients with gastro‐oesophageal reflux disease develop complicated reflux disease (ulcerative oesophagitis, oesophageal strictures and Barretts oesophagus) and erosive reflux oesophagitis is not fully understood. Supine nocturnal oesophageal acid reflux is considered to be critically involved in this phenomenon, but reliable data are lacking.

Esophageal baseline impedance levels in patients with pathophysiological characteristics of functional heartburn.

Recently, it has been suggested that low esophageal basal impedance may reflect impaired mucosal integrity and increased acid sensitivity. We aimed to compare baseline impedance levels in patients with heartburn and pathophysiological characteristics related to functional heartburn (FH) divided into two groups on the basis of symptom relief after proton pump inhibitors (PPIs).

Pathophysiological characteristics of patients with non‐erosive reflux disease differ from those of patients with functional heartburn

Background : Patients with endoscopy‐negative heartburn can be subdivided into non‐erosive reflux disease and functional heartburn on the basis of abnormal and normal, respectively, oesophageal acid exposure. Different pathophysiological characteristics could explain the reportedly low efficacy of proton pump inhibitors in functional heartburn.

Characteristics of gastro-esophageal reflux episodes in Barrett's esophagus, erosive esophagitis and healthy volunteers

Background  Gastro‐esophageal reflux is considered a major culprit in the pathogenesis of Barrett’s esophagus (BE). Still, there is controversy on the role of weakly acidic and weakly alkaline reflux in BE. To compare characteristics of reflux episodes patients with BE, erosive esophagitis (EE), and healthy volunteers (HV).

Esophageal chemical clearance is impaired in gastro-esophageal reflux disease--a 24-h impedance-pH monitoring assessment.

Impedance‐pH monitoring allows assessment of retrograde and antegrade intra‐esophageal movement of fluids and gas. Reflux is followed by volume clearance and chemical clearance, elicited by secondary and swallow‐induced peristalsis, respectively. We aimed to assess whether chemical clearance is impaired in gastro‐esophageal reflux disease (GERD).

Reflux patterns in patients with short-segment Barrett's oesophagus: a study using impedance-pH monitoring off and on proton pump inhibitor therapy.

Background  In short‐segment Barrett’s oesophagus (SSBO) heartburn may be absent and oesophageal acid exposure time (OAET) assessed with pH‐only monitoring may be normal. By detecting reflux episodes independently of their acidity, multichannel intraluminal impedance‐pH (MII‐pH) monitoring allows a comprehensive characterization of reflux events, either off or on proton pump inhibitor (PPI) therapy.

Quantitative assessment of the mucosal architecture of jejunal biopsy specimens: a comparison between linear measurement, stereology, and computer aided microscopy.

Fifty jejunal biopsy specimens obtained from normal subjects and from untreated and treated patients with coeliac disease were assessed blindly by three independent observers, each of them using different morphometric techniques-namely, linear measurement, stereology, and computer aided microscopy. In two of 26 control biopsy specimens linear measurement was not possible because of distortion of villi. Highly significant (p less than 0.001) correlation coefficients were found between the different techniques. With all methods significant differences between controls and patients with coeliac disease and between treated and untreated coeliac patients were found. Only by stereology, however, was there no overlap between results for patients and those for controls. In view of the limitations of linear measurement and the high cost and complexity of computer aided microscopy, we propose that a simple stereological technique using an eyepiece graticule is the method of choice in the quantitative assessment of mucosal architecture in jejunal biopsy specimens.

Association Between Baseline Impedance Values and Response Proton Pump Inhibitors in Patients With Heartburn

BACKGROUND & AIMS Esophageal impedance measurements have been proposed to indicate the status of the esophageal mucosa, and might be used to study the roles of the impaired mucosal integrity and increased acid sensitivity in patients with heartburn. We compared baseline impedance levels among patients with heartburn who did and did not respond to proton pump inhibitor (PPI) therapy, along with the pathophysiological characteristics of functional heartburn (FH). METHODS In a case-control study, we collected data from January to December 2013 on patients with heartburn and normal findings from endoscopy who were not receiving PPI therapy and underwent impedance pH testing at hospitals in Italy. Patients with negative test results were placed on an 8-week course of PPI therapy (84 patients received esomeprazole and 36 patients received pantoprazole). Patients with more than 50% symptom improvement were classified as FH/PPI responders and patients with less than 50% symptom improvement were classified as FH/PPI nonresponders. Patients with hypersensitive esophagus and healthy volunteers served as controls. In all patients and controls, we measured acid exposure time, number of reflux events, baseline impedance, and swallow-induced peristaltic wave indices. RESULTS FH/PPI responders had higher acid exposure times, numbers of reflux events, and acid refluxes compared with FH/PPI nonresponders (P < .05). Patients with hypersensitive esophagus had mean acid exposure times and numbers of reflux events similar to those of FH/PPI responders. Baseline impedance levels were lower in FH/PPI responders and patients with hypersensitive esophagus, compared with FH/PPI nonresponders and healthy volunteers (P < .001). Swallow-induced peristaltic wave indices were similar between FH/PPI responders and patients with hypersensitive esophagus. CONCLUSIONS Patients with FH who respond to PPI therapy have impedance pH features similar to those of patients with hypersensitive esophagus. Baseline impedance measurements might allow for identification of patients who respond to PPIs but would be classified as having FH based on conventional impedance-pH measurements.

Reflux parameters as modified by EsophyX or laparoscopic fundoplication in refractory GERD

Aliment Pharmacol Ther 2011; 34: 67–75