Riccardo Franchi

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.

Proton pump inhibitor responders who are not confirmed as GERD patients with impedance and pH monitoring: who are they?

A short‐course of proton pump inhibitors (PPIs) is often used to confirm gastroesophageal reflux disease (GERD). However, some patients with PPI responsive heartburn do not seem to have evidence of GERD on impedance‐pH monitoring (MII‐pH). The aim of the study was to evaluate patients with reflux symptoms and a negative endoscopy, who well respond to PPIs with MII‐pH.

Esophageal testing: What we have so far

Gastroesophageal reflux disease (GERD) is a common disorder of the gastrointestinal tract. In the last few decades, new technologies have evolved and have been applied to the functional study of the esophagus, allowing for the improvement of our knowledge of the pathophysiology of GERD. High-resolution manometry (HRM) permits greater understanding of the function of the esophagogastric junction and the risks associated with hiatal hernia. Moreover, HRM has been found to be more reproducible and sensitive than conventional water-perfused manometry to detect the presence of transient lower esophageal sphincter relaxation. Esophageal 24-h pH-metry with or without combined impedance is usually performed in patients with negative endoscopy and reflux symptoms who have a poor response to anti-reflux medical therapy to assess esophageal acid exposure and symptom-reflux correlations. In particular, esophageal 24-h impedance and pH monitoring can detect acid and non-acid reflux events. EndoFLIP is a recent technique poorly applied in clinical practice, although it provides a large amount of information about the esophagogastric junction. In the coming years, laryngopharyngeal symptoms could be evaluated with up and coming non-invasive or minimally invasive techniques, such as pepsin detection in saliva or pharyngeal pH-metry. Future studies are required of these techniques to evaluate their diagnostic accuracy and usefulness, although the available data are promising.

Lower pH values of weakly acidic refluxes as determinants of heartburn perception in gastroesophageal reflux disease patients with normal esophageal acid exposure

Multichannel impedance pH monitoring has shown that weakly acidic refluxes are able to generate heartburn. However, data on the role of different pH values, ranging between 4 and 7, in the generation of them are lacking. The aim of this study was to evaluate whether different pH values of weakly acidic refluxes play a differential role in provoking reflux symptoms in endoscopy-negative patients with physiological esophageal acid exposure time and positive symptom index and symptom association probability for weakly acidic refluxes. One hundred and forty-three consecutive patients with gastroesophageal reflux disease, nonresponders to proton pump inhibitors (PPIs), were allowed a washout from PPIs before undergoing: upper endoscopy, esophageal manometry, and multichannel impedance pH monitoring. In patients with both symptom index and symptom association probability positive for weakly acidic reflux, each weakly acidic reflux was evaluated considering exact pH value, extension, physical characteristics, and correlation with heartburn. Forty-five patients with normal acid exposure time and positive symptom association probability for weakly acidic reflux were identified. The number of refluxes not heartburn related was higher than those heartburn related. In all distal and proximal liquid refluxes, as well as in distal mixed refluxes, the mean pH value of reflux events associated with heartburn was significantly lower than that not associated. This condition was not confirmed for proximal mixed refluxes. Overall, a low pH of weakly acidic reflux represents a determinant factor in provoking heartburn. This observation contributes to better understand the pathophysiology of symptoms generated by weakly acidic refluxes, paving the way toward the search for different therapeutic approaches to this peculiar condition of esophageal hypersensitivity.

657 Use of a Non-Invasive Pepsin Diagnostic Test to Detect GERD: Correlation With MII-pH Evaluation in a Series of Suspected NERD Patients. A Pilot Study

BACKGROUND: Presence of pepsin in bronchoalveolar lavage fluid, laryngeal biopsy and sputum may be a consequence of gastroesophageal reflux disease (GERD). A novel noninvasive test to detect it in saliva/sputum (PEP-Test) has been proposed to diagnose GERD. A correlation between PEP-Test and multichannel impedance pH monitoring (MII-pH) has never been performed. AIM: The aim was to evaluate the PEP-Test accuracy for the diagnosis of GERD in patients with reflux symptoms by means of MII-pH. PATIENTS ANDMETHODS: 35 patients with GER symptoms were studied. All patients with negative endoscopy underwent pathophysiological examinations, after wash-out from proton pump inhibitors. Samples of saliva/sputum were obtained by requesting the patient to cough up and spit into a tube containing 0.01 M citric acid within 15 minutes from experiencing reflux symptoms. Patients were grouped on the basis of MII-pH results as follows: True-NERD (increased acid exposure time, AET/reflux number); Hypersensitive Esophagus, HE (normal AET/reflux number, positive symptom association probability index, SAP); no-GERD patients (normal AET/reflux number, negative SAP). Roc curve was performed to obtain diagnostic accuracy of test. RESULTS: Male/Female was 18/17, mean age was 49.8 yrs, mean BMI was 24.9. The mean BMI was similar in three sub-groups. Nine patients were abitudinary smokers and five had a regular alimentary alcohol use. Eleven out of thirty-five patients presented hiatal hernia. No patients showed abnormal esophageal motility. MII-pH results showed: 16 True-NERD patients (median AET 9.5); 12 HE (median AET 3); 7 no-GERD (median AET 1.1). PEPTest was positive in 93.7% of True-NERD, in 58.3% of HE, and negative in 100% of noGERD patients. Accuracy of PEP-Test is reported in Table 1. CONCLUSIONS: PEP-Test is a simple, economic, reproducible, highly specific test to detect the presence of GERD. Accuracy PEP-Test

Obesity is a Risk Factor for Erosive Gastroesophageal Reflux Disease: Prospective Case-Control Study

Background and aim: An association between high body mass index (BMI) and gastroesophageal reflux disease (GERD) has been proposed but the relationship between the severity of obesity, the prevalence of symptoms and gravity of esophagitis is still unclear. Aim of this study was to evaluate the prevalence of symptomatic GERD and esophagitis in female obese subjects compared to a group of female with typical GERD symptoms. Material and methods: 193 obese women (Group A) scheduled for bariatric surgery and 193 normal weight female with typical GERD symptoms (Group B) were submitted to complete history (recording voluptuary habits) and validated questionnaire for symptomatic diagnosis of GERD (GIS: GERD Impact Scale). Each patient underwent upper GI endoscopy to evaluate the prevalence of erosive esophagitis. Erosive esophagitis was diagnosed according to Los Angeles Classification of esophagitis. Results: We enrolled 193 female patients in Group A and 193 patients in Group B. Mean age (± sd) was 48.6 ± 13.6 years in Group A and 51.4 ± 15.3 years in group B. Mean BMI was 43.6 ± 9.2 in group A and 23.6 ± 3.7 in Group B (P<0.001). The perception of GERD symptoms was higher in group B: the mean value of GIS was 1.72 when compared with 0.34 obtained in Group A (P<0.001). The mean value of score for typical GERD symptoms was 2.65 in group B and 0.85 in group A (P<0.001). All patients in Group B recorded at least one typical GERD symptom (heartburn and regurgitate) but only 26.9% of patients in Group A recorded these symptoms (P<0.001). Esophageal erosion were present in 97/193 (50.3%) in Group A and in 45/193 (23.3%) in Group B (P<0.001). Conclusions: We can conclude that the impact of erosive esophagitis in obese patients could be considered more severe than gravity and frequency of symptoms.

Sa1351 Voluntary and Controlled Weight Loss Can Reduce Symptoms and Allow a Lowering of Proton Pump Inhibitor Dosage in Patients With Gastroesophageal Reflux Disease. A Case-Control Study

Voluntary and Controlled Weight Loss Can Reduce Symptoms and Allow a Lowering of Proton Pump Inhibitor Dosage in Patients With Gastroesophageal Reflux Disease. A Case-Control Study Nicola de Bortoli, Giada Guidi, Edoardo Savarino, Lorenzo Bertani, Riccardo Franchi, Irene Martinucci, Lorenzo Macchia, Linda Ceccarelli, Salvatore Russo, Manuele Furnari, Massimo Bellini, Vincenzo Savarino, Santino Marchi

Tu1088 Distal and Proximal Esophageal Impedance Basal Values in Patients With Non-Erosive Reflux Disease and Functional Heartburn

Background and aim: Several studies have shown that proximal extent of reflux episodes plays an important role in gastro-esophageal reflux symptom perception. The relative hypersensitivity of the proximal esophagus is most evident in patients with non-erosive reflux disease (NERD). Recent studies demonstrated that low distal basal impedance values may reflect impaired mucosal integrity and increased acid sensitivity. The aim was to compare distal and proximal basal impedance values in patients with NERD and functional heartburn (FH). Methods: According to impedance and pH (MII-pH) monitoring off-therapy, we selected patients with NERD (i.e. pathological acid exposure time, AET) and FH (i.e. normal AET and reflux number; negative symptom association). FH patients did not show any symptom relief after acid suppression therapy. For each patient, we evaluated basal impedance values at the distal (3 cm) and proximal (17 cm) channel, during the overnight rest, at three different times: 1, 2, 3 am. Results: Male/female ratio was 23/23 in NERD and 13/33 in FH patients. Mean age was 52.3±13.2 in NERD and 49.2±11.3 in FH. Mean AET was higher in NERD (6.1%±3.8%) than in FH (0.6%±0.7%) (p<0.05). NERD group recorded higher total reflux number (67.8±18.2) than FH group (23.7±9.4) (p<0.05). Basal impedance values were significantly (p<0.05) lower in NERD than in FH, both at the distal (1294.3±529.9 Ohm vs 3502.1±809.2 Ohm) and proximal (3480.7 ±1322.6 Ohm vs 4344.9±976.2 Ohm) channels. Distal basal values were significantly lower than proximal basal values, both in NERD and FH group (p<0.05). Moreover, in NERD group, 24/46 patients (52.2%) had an abnormal number of proximal refluxes. These NERD patients with pathological proximal refluxes did not show lower basal impedance values than NERD patients with normal number of proximal refluxes even if distal (1226.7±453 vs 1243.1±497.1; P=0.5239) or proximal channels (2670.8±1163.4 vs 2849.2±1434.2; p=0.5046) were compared. Summary and conclusion: Patients with NERD showed lower basal impedance values both at the distal and proximal esophagus. Consistently with the concept that low basal impedance may reflect impaired mucosal integrity, our results might be helpful to better investigate the pathophysiological role of proximal refluxes.

Tu1089 Evaluation of Sleep Disruptions by Means of Impedance-pH Monitoring in Patients With NERD

Background and aim: Several studies have shown that proximal extent of reflux episodes plays an important role in gastro-esophageal reflux symptom perception. The relative hypersensitivity of the proximal esophagus is most evident in patients with non-erosive reflux disease (NERD). Recent studies demonstrated that low distal basal impedance values may reflect impaired mucosal integrity and increased acid sensitivity. The aim was to compare distal and proximal basal impedance values in patients with NERD and functional heartburn (FH). Methods: According to impedance and pH (MII-pH) monitoring off-therapy, we selected patients with NERD (i.e. pathological acid exposure time, AET) and FH (i.e. normal AET and reflux number; negative symptom association). FH patients did not show any symptom relief after acid suppression therapy. For each patient, we evaluated basal impedance values at the distal (3 cm) and proximal (17 cm) channel, during the overnight rest, at three different times: 1, 2, 3 am. Results: Male/female ratio was 23/23 in NERD and 13/33 in FH patients. Mean age was 52.3±13.2 in NERD and 49.2±11.3 in FH. Mean AET was higher in NERD (6.1%±3.8%) than in FH (0.6%±0.7%) (p<0.05). NERD group recorded higher total reflux number (67.8±18.2) than FH group (23.7±9.4) (p<0.05). Basal impedance values were significantly (p<0.05) lower in NERD than in FH, both at the distal (1294.3±529.9 Ohm vs 3502.1±809.2 Ohm) and proximal (3480.7 ±1322.6 Ohm vs 4344.9±976.2 Ohm) channels. Distal basal values were significantly lower than proximal basal values, both in NERD and FH group (p<0.05). Moreover, in NERD group, 24/46 patients (52.2%) had an abnormal number of proximal refluxes. These NERD patients with pathological proximal refluxes did not show lower basal impedance values than NERD patients with normal number of proximal refluxes even if distal (1226.7±453 vs 1243.1±497.1; P=0.5239) or proximal channels (2670.8±1163.4 vs 2849.2±1434.2; p=0.5046) were compared. Summary and conclusion: Patients with NERD showed lower basal impedance values both at the distal and proximal esophagus. Consistently with the concept that low basal impedance may reflect impaired mucosal integrity, our results might be helpful to better investigate the pathophysiological role of proximal refluxes.