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659 Pepsin in Saliva and Gastroesophageal Reflux Monitoring in 100 Healthy Asymptomatic Subjects
FH. Impaired BI levels are associated with abnormal acid exposure to the distal esophagus and low BI correlated with DIS which might reflect impaired mucosal integrity.
659
AGA Abstracts
Pepsin in Saliva and Gastroesophageal Reflux Monitoring in 100 Healthy Asymptomatic Subjects Jamal O. Hayat, Etsuro Yazaki, Jin-Yong Kang, Andrew Woodcock, Peter W. Dettmar, Jerry Mabary, Daniel Sifrim Background: Pepsin is a protease originating from pepsinogen secreted into gastric juice from chief cells, only found in the stomach. Its presence in the esophagus or more proximally (pharynx or airways) suggests gastro-esophageal reflux (GER). Several studies have measured pepsin in saliva to determine its value as marker of pathological GER. However, appropriate normal values and correlation with acid/non acid reflux are still limited. The aim of this study was to measure pepsin in expectorated saliva together with objective assessment of GER by pH-impedance in a large cohort of asymptomatic subjects. Methods: 100 healthy subjects, age 30.7 y (range 19-55), with no typical or atypical reflux symptoms underwent MII-pH monitoring "off" PPI. Esophageal pH was measured 5cm above the LES and impedance sensors were positioned at 3,7,9,12 and 15cm above LES. Subjects collected expectorated saliva on waking, one hour after lunch and one hour after dinner. Saliva was collected into tubes containing 0.5ml of 0.01M citric acid and analysed for the presence of pepsin using a lateral flow test comprising two unique human monoclonal antibodies to pepsin (Peptest™, RDBiomed Ltd). The cut off value to determine pepsin positivity was 25ng/ml. Results: Of 300 saliva samples tested, 19% were +ve for pepsin. 64% of subjects had all three saliva samples negative; 20% had 1 sample positive, 12% had 2 samples positive and 4% had 3 samples positive. A similar percentage of samples were positive after lunch (24%) and dinner (22%), but lower on waking (10%). Median acid exposure time was 0.3% (IQR - 0.1-0.8%, 95thcentile 3.5%). Median no. of reflux events was 32 (15-42, 77) being acid 11 (5-22,47) and non-acid 15 (8-25, 46). Saliva samples positive for pepsin were preceded by significantly more reflux events during the 60 min interval before sampling compared to negative samples both after lunch and dinner (+ve pepsin 6 reflux (4-9) vs. -ve pepsin 3 reflux (1-5) p ,0.0001). Supine acid exposure and no. of reflux episodes was not significantly different with +ve or -ve morning samples. Subjects with 3 saliva samples +ve for pepsin had a higher ratio of proximal reflux episodes than subjects with no +ve samples (37%(range 29-40%) vs. 19%(1233%), p,0.02). Only 6/300 samples contained more than 250 ng/ml pepsin. Conclusion: Pepsin was found in the expectorated saliva of a proportion of healthy individuals who did not experience reflux symptoms, particularly post-prandially. However, only 4% of healthy subjects had 3 positive samples. An increased number of reflux episodes were found prior to giving saliva samples with detectable levels of pepsin. Our results suggest that the presence of pepsin in saliva can be a potential screening tool for GERD when at least 3 samples throughout a day are positive or samples contain more than 250 ng/ml pepsin.
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 Nicola de Bortoli, Edoardo Savarino, Manuele Furnari, Irene Martinucci, Patrizia Zentilin, Lorenzo Bertani, Riccardo Franchi, Massimo Bellini, Vincenzo Savarino, Santino Marchi 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 AND METHODS: 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
660 Esophageal Mucosal Impedance Measurement: Time to Move Beyond pH Monitoring for GERD Diagnosis Elif Saritas Yuksel, James C. Slaughter, Tina Higginbotham, Jerry E. Mabary, Michael F. Vaezi INTRODUCTION: Current GERD diagnostics are suboptimal due to limited sensitivity and specificity, and they are constrained by measurement of esophageal reflux during a single time point at a specified location. They measure presence of reflux but do not measure the long-term mucosal consequences of GERD, a significant limitation of existing platforms. The feasibility of a novel, minimally invasive technology to assess esophageal mucosal conductivity changes due to GERD was recently established. The aims of this study were to test the accuracy and reliability of this device: 1) pre- and post-acid suppressive therapy and 2) relative to the standard pH monitoring in detecting GERD. METHODS: Six combinations of single channel Mucosal Impedance (MI) catheters with 360 degree rings were tested by varying ring length to 0.2 or 0.3 mm and ring separation to 0.2, 0.3 or 0.4 mm. Each catheter could be easily traversed through the working channel of an upper endoscope. 98 patients with GERD and controls were enrolled: Erosive Esophagitis (E+) (n=28); pH+/Nonerosive GERD (pH+) (n=30) and pH-/non-erosive controls (n=40). All patients underwent endoscopy and wireless 48-hour pH monitoring 10-days off PPI therapy. During index endoscopy, MI were measured from the esophagitis site as well as 2-, 5- and 10-cm above squamocolumnar junction (SCJ). The optimal MI sensor ring size and separation were determined based on ROC analysis. MI measurements were repeated in those with esophagitis after 2-4months of aggressive PPI therapy to determine test reliability pre- and post-therapy. Predictive value positive of MI measurements were then compared to pH monitoring in diagnosing GERD. RESULTS: Optimum sensitivity (0.9) and specificity (1.0) was achieved by 2mm sensor ring size with separation of 3mm. Median (IQ) mucosal measurements were significantly (p=0.001) lower at the site of erosive esophageal mucosa [1147 (530-1307)] than non-erosive regions at the same level [3654 (2315-6146)]. Among patients with erosive esophagitis, baseline MI [900 (520-1200)] significantly (p,0.001) increased post PPI therapy [4503 (4673-5100)]. The predicted probability of GERD for MI at 540 ohms was 90% and overall MI was superior to pH monitoring for predicting GERD (Figure). CONCLUSIONS: 1) Esophageal mucosal impedance is a reliable indicator of GERD. 2) MI is decreased with mucosal injury and the values increase with healing of mucosa post-acid suppressive therapy. 3) The positive predictive value for GERD is superior with MI than the traditionally employed pH monitoring. 4) The ability of MI device to diagnose GERD simply, efficiently and reliability by through the endoscope application during index endoscopy is an innovative step forward in reflux monitoring.
658 Surgical and Medical Treatment of GERD Lead to a Comparable Increase in Baseline Impedance Levels Nicolaas Fedde Rinsma, Nicole D. Bouvy, Ad Masclee, José M. Conchillo Recent data indicate that baseline esophageal intraluminal impedance levels reflect the electrical resistance of the esophageal wall and may serve as an instrument for the in vivo evaluation of impaired mucosal integrity in GERD patients. Reduction of acid reflux events by therapy may lead to recovery of mucosal integrity as reflected by increased baseline impedance levels. The aim of this study was to evaluate the effect of therapy by acid suppressive medication and through surgical treatment on baseline impedance levels in GERD patients. Methods: In 48 GERD patients (31 males; mean age 45 yrs, range 20-67 yrs) with abnormal acid exposure time (pH ,4 .4.0%) and hiatal hernia ≤2 cm, baseline impedance levels were studied after cessation of acid-suppressive medication for ≥7 days. Endoscopic fundoplication was performed in 33 patients and 24-h pH-impedance monitoring was repeated 6 months after the procedure. Fifteen patients were treated with a daily high dose of PPI and underwent 24-h pH-impedance monitoring on PPI after 6 months. Baseline impedance levels were assessed 3 cm above the lower esophageal sphincter every 2 hours during the 24-h measurement. Endoscopy was performed for assessment of esophagitis. Symptoms were evaluated by a disease-specific quality of life questionnaire (GERD-HRQL). Results: Distal baseline impedance levels at baseline of all patients correlated with acid exposure time and the number of acid and proximal reflux episodes (resp. r:-0.60; p ,0.001, r:-0.42, p,0.01 and r:-0.50; p,0.001), but not with symptom scores. Patients with esophagitis at baseline endoscopy (n=17) showed lower baseline impedance levels compared to patients without esophagitis (n=31) (1416±193 V vs. 1999±167 V, p=0.03). Acid exposure time was reduced by endoscopic fundoplication (from 9.7±0.8 % to 6.7±1.1 %, p ,0.05). Baseline impedance levels were higher after the procedure (from 1908±154 V to 2272±180 V, p,0.05) and correlated with acid exposure time (r:-0.63, p ,0.001). Baseline impedance levels of patients with normalized acid exposure time (pH ,4 ,4.0%) after fundoplication (n=18) were higher than in patients with abnormal acid exposure time (n=15) (2924±211 V vs. 1490±131 V, p,0.001). Acid exposure time was also reduced by PPI treatment (from 12.5±1.8 % to 5.9±1.9 %, p ,0.01) and baseline impedance levels were higher after 6 months (from 1415±221 V to 2487±311 V, p,0.01). Baseline impedance levels after surgical and medical treatment were comparable (2272±180 V vs. 2487±311 V, p=0.53). No correlation was found between baseline impedance levels and symptom scores after endoscopic fundoplication or PPI treatment. Conclusion: Reduction of acid exposure by either endoscopic fundoplication or PPI treatment leads to a comparable increase in baseline impedance levels in GERD patients which may indicate repair of mucosal integrity and therapy success.
AGA Abstracts
S-118
659
AGA Abstracts
Pepsin in Saliva and Gastroesophageal Reflux Monitoring in 100 Healthy Asymptomatic Subjects Jamal O. Hayat, Etsuro Yazaki, Jin-Yong Kang, Andrew Woodcock, Peter W. Dettmar, Jerry Mabary, Daniel Sifrim Background: Pepsin is a protease originating from pepsinogen secreted into gastric juice from chief cells, only found in the stomach. Its presence in the esophagus or more proximally (pharynx or airways) suggests gastro-esophageal reflux (GER). Several studies have measured pepsin in saliva to determine its value as marker of pathological GER. However, appropriate normal values and correlation with acid/non acid reflux are still limited. The aim of this study was to measure pepsin in expectorated saliva together with objective assessment of GER by pH-impedance in a large cohort of asymptomatic subjects. Methods: 100 healthy subjects, age 30.7 y (range 19-55), with no typical or atypical reflux symptoms underwent MII-pH monitoring "off" PPI. Esophageal pH was measured 5cm above the LES and impedance sensors were positioned at 3,7,9,12 and 15cm above LES. Subjects collected expectorated saliva on waking, one hour after lunch and one hour after dinner. Saliva was collected into tubes containing 0.5ml of 0.01M citric acid and analysed for the presence of pepsin using a lateral flow test comprising two unique human monoclonal antibodies to pepsin (Peptest™, RDBiomed Ltd). The cut off value to determine pepsin positivity was 25ng/ml. Results: Of 300 saliva samples tested, 19% were +ve for pepsin. 64% of subjects had all three saliva samples negative; 20% had 1 sample positive, 12% had 2 samples positive and 4% had 3 samples positive. A similar percentage of samples were positive after lunch (24%) and dinner (22%), but lower on waking (10%). Median acid exposure time was 0.3% (IQR - 0.1-0.8%, 95thcentile 3.5%). Median no. of reflux events was 32 (15-42, 77) being acid 11 (5-22,47) and non-acid 15 (8-25, 46). Saliva samples positive for pepsin were preceded by significantly more reflux events during the 60 min interval before sampling compared to negative samples both after lunch and dinner (+ve pepsin 6 reflux (4-9) vs. -ve pepsin 3 reflux (1-5) p ,0.0001). Supine acid exposure and no. of reflux episodes was not significantly different with +ve or -ve morning samples. Subjects with 3 saliva samples +ve for pepsin had a higher ratio of proximal reflux episodes than subjects with no +ve samples (37%(range 29-40%) vs. 19%(1233%), p,0.02). Only 6/300 samples contained more than 250 ng/ml pepsin. Conclusion: Pepsin was found in the expectorated saliva of a proportion of healthy individuals who did not experience reflux symptoms, particularly post-prandially. However, only 4% of healthy subjects had 3 positive samples. An increased number of reflux episodes were found prior to giving saliva samples with detectable levels of pepsin. Our results suggest that the presence of pepsin in saliva can be a potential screening tool for GERD when at least 3 samples throughout a day are positive or samples contain more than 250 ng/ml pepsin.
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 Nicola de Bortoli, Edoardo Savarino, Manuele Furnari, Irene Martinucci, Patrizia Zentilin, Lorenzo Bertani, Riccardo Franchi, Massimo Bellini, Vincenzo Savarino, Santino Marchi 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 AND METHODS: 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
660 Esophageal Mucosal Impedance Measurement: Time to Move Beyond pH Monitoring for GERD Diagnosis Elif Saritas Yuksel, James C. Slaughter, Tina Higginbotham, Jerry E. Mabary, Michael F. Vaezi INTRODUCTION: Current GERD diagnostics are suboptimal due to limited sensitivity and specificity, and they are constrained by measurement of esophageal reflux during a single time point at a specified location. They measure presence of reflux but do not measure the long-term mucosal consequences of GERD, a significant limitation of existing platforms. The feasibility of a novel, minimally invasive technology to assess esophageal mucosal conductivity changes due to GERD was recently established. The aims of this study were to test the accuracy and reliability of this device: 1) pre- and post-acid suppressive therapy and 2) relative to the standard pH monitoring in detecting GERD. METHODS: Six combinations of single channel Mucosal Impedance (MI) catheters with 360 degree rings were tested by varying ring length to 0.2 or 0.3 mm and ring separation to 0.2, 0.3 or 0.4 mm. Each catheter could be easily traversed through the working channel of an upper endoscope. 98 patients with GERD and controls were enrolled: Erosive Esophagitis (E+) (n=28); pH+/Nonerosive GERD (pH+) (n=30) and pH-/non-erosive controls (n=40). All patients underwent endoscopy and wireless 48-hour pH monitoring 10-days off PPI therapy. During index endoscopy, MI were measured from the esophagitis site as well as 2-, 5- and 10-cm above squamocolumnar junction (SCJ). The optimal MI sensor ring size and separation were determined based on ROC analysis. MI measurements were repeated in those with esophagitis after 2-4months of aggressive PPI therapy to determine test reliability pre- and post-therapy. Predictive value positive of MI measurements were then compared to pH monitoring in diagnosing GERD. RESULTS: Optimum sensitivity (0.9) and specificity (1.0) was achieved by 2mm sensor ring size with separation of 3mm. Median (IQ) mucosal measurements were significantly (p=0.001) lower at the site of erosive esophageal mucosa [1147 (530-1307)] than non-erosive regions at the same level [3654 (2315-6146)]. Among patients with erosive esophagitis, baseline MI [900 (520-1200)] significantly (p,0.001) increased post PPI therapy [4503 (4673-5100)]. The predicted probability of GERD for MI at 540 ohms was 90% and overall MI was superior to pH monitoring for predicting GERD (Figure). CONCLUSIONS: 1) Esophageal mucosal impedance is a reliable indicator of GERD. 2) MI is decreased with mucosal injury and the values increase with healing of mucosa post-acid suppressive therapy. 3) The positive predictive value for GERD is superior with MI than the traditionally employed pH monitoring. 4) The ability of MI device to diagnose GERD simply, efficiently and reliability by through the endoscope application during index endoscopy is an innovative step forward in reflux monitoring.
658 Surgical and Medical Treatment of GERD Lead to a Comparable Increase in Baseline Impedance Levels Nicolaas Fedde Rinsma, Nicole D. Bouvy, Ad Masclee, José M. Conchillo Recent data indicate that baseline esophageal intraluminal impedance levels reflect the electrical resistance of the esophageal wall and may serve as an instrument for the in vivo evaluation of impaired mucosal integrity in GERD patients. Reduction of acid reflux events by therapy may lead to recovery of mucosal integrity as reflected by increased baseline impedance levels. The aim of this study was to evaluate the effect of therapy by acid suppressive medication and through surgical treatment on baseline impedance levels in GERD patients. Methods: In 48 GERD patients (31 males; mean age 45 yrs, range 20-67 yrs) with abnormal acid exposure time (pH ,4 .4.0%) and hiatal hernia ≤2 cm, baseline impedance levels were studied after cessation of acid-suppressive medication for ≥7 days. Endoscopic fundoplication was performed in 33 patients and 24-h pH-impedance monitoring was repeated 6 months after the procedure. Fifteen patients were treated with a daily high dose of PPI and underwent 24-h pH-impedance monitoring on PPI after 6 months. Baseline impedance levels were assessed 3 cm above the lower esophageal sphincter every 2 hours during the 24-h measurement. Endoscopy was performed for assessment of esophagitis. Symptoms were evaluated by a disease-specific quality of life questionnaire (GERD-HRQL). Results: Distal baseline impedance levels at baseline of all patients correlated with acid exposure time and the number of acid and proximal reflux episodes (resp. r:-0.60; p ,0.001, r:-0.42, p,0.01 and r:-0.50; p,0.001), but not with symptom scores. Patients with esophagitis at baseline endoscopy (n=17) showed lower baseline impedance levels compared to patients without esophagitis (n=31) (1416±193 V vs. 1999±167 V, p=0.03). Acid exposure time was reduced by endoscopic fundoplication (from 9.7±0.8 % to 6.7±1.1 %, p ,0.05). Baseline impedance levels were higher after the procedure (from 1908±154 V to 2272±180 V, p,0.05) and correlated with acid exposure time (r:-0.63, p ,0.001). Baseline impedance levels of patients with normalized acid exposure time (pH ,4 ,4.0%) after fundoplication (n=18) were higher than in patients with abnormal acid exposure time (n=15) (2924±211 V vs. 1490±131 V, p,0.001). Acid exposure time was also reduced by PPI treatment (from 12.5±1.8 % to 5.9±1.9 %, p ,0.01) and baseline impedance levels were higher after 6 months (from 1415±221 V to 2487±311 V, p,0.01). Baseline impedance levels after surgical and medical treatment were comparable (2272±180 V vs. 2487±311 V, p=0.53). No correlation was found between baseline impedance levels and symptom scores after endoscopic fundoplication or PPI treatment. Conclusion: Reduction of acid exposure by either endoscopic fundoplication or PPI treatment leads to a comparable increase in baseline impedance levels in GERD patients which may indicate repair of mucosal integrity and therapy success.
AGA Abstracts
S-118