Number Of Acid Reflux Episodes Research Articles

Efficacy and Safety of Once-Daily Esomeprazole for the Treatment of Gastroesophageal Reflux Disease in Neonatal Patients

To evaluate the efficacy and safety of proton pump inhibitors in infants aged <1 year with gastroesophageal reflux disease (GERD). In this randomized, double-blind, placebo-controlled multicenter study, neonates (premature to 1 month corrected age; n = 52) with signs and symptoms of GERD received esomeprazole 0.5 mg/kg or placebo once daily for up to 14 days. Change from baseline in the total number of GERD symptoms (from video monitoring) and GERD-related signs (from cardiorespiratory monitoring) was assessed with simultaneous esophageal pH, impedance, cardiorespiratory, and 8-hour video monitoring. There were no significant differences between the esomeprazole and placebo groups in the percentage change from baseline in the total number of GERD-related signs and symptoms (-14.7% vs -14.1%, respectively). Mean change from baseline in total number of reflux episodes was not significantly different between esomeprazole and placebo (-7.43 vs -0.2, respectively); however, the percentage of time pH was <4.0 and the number of acidic reflux episodes >5 minutes in duration was significantly decreased with esomeprazole vs placebo (-10.7 vs 2.2 and -5.5 vs 1.0, respectively; P ≤ .0017). The number of patients with adverse events was similar between treatment groups. Signs and symptoms of GERD traditionally attributed to acidic reflux in neonates were not significantly altered by esomeprazole treatment. Esomeprazole was well tolerated and reduced esophageal acid exposure and the number of acidic reflux events in neonates.

An Alginate-Antacid Formulation Localizes to the Acid Pocket to Reduce Acid Reflux in Patients With Gastroesophageal Reflux Disease

Alginate rafts (polysaccharide polymers that precipitate into a low-density viscous gel when they contact gastric acid) have been reported to form at the acid pocket, an unbuffered pool of acid that floats on top of ingested food and causes postprandial acid reflux. We studied the location of an alginate formulation in relation to the acid pocket and the corresponding effects on reflux parameters and acid pocket positioning in patients with gastroesophageal reflux disease (GERD). We randomly assigned patients with symptomatic GERD and large hiatal hernias to groups who were given either (111)In-labeled alginate-antacid (n = 8, Gaviscon Double Action Liquid) or antacid (n = 8, Antagel) after a standard meal. The relative positions of labeled alginate and acid pocket were analyzed for 2 hours by using scintigraphy; reflux episodes were detected by using high-resolution manometry and pH-impedance monitoring. The alginate-antacid label localized to the acid pocket. The number of acid reflux episodes was significantly reduced in patients receiving alginate-antacid (3.5; range, 0-6.5; P = .03) compared with those receiving antacid (15; range, 5-20), whereas time to acid reflux was significantly increased in patients receiving alginate-antacid (63 minutes; range, 23-92) vs those receiving antacid (14 minutes; range, 9-23; P = .01). The acid pocket was located below the diaphragm in 71% of patients given alginate-antacid vs 21% of those given antacid (P = .08). There was an inverse correlation between a subdiaphragm position of the acid pocket and acid reflux (r = -0.76, P < .001). In a study of 16 patients with GERD, we observed that the alginate-antacid raft localizes to the postprandial acid pocket and displaces it below the diaphragm to reduce postprandial acid reflux. These findings indicate the importance of the acid pocket in GERD pathogenesis and establish alginate-antacid as an appropriate therapy for postprandial acid reflux.

Therapeutic efficacy of baclofen in refractory gastroesophageal reflux-induced chronic cough

To evaluate the efficacy and safety of baclofen for treatment of refractory gastroesophageal reflux-induced chronic cough (GERC) unresponsive to standard anti-reflux therapy. Sixteen patients with refractory GERC were given an 8-wk course of baclofen 20 mg three times a day as an add-on therapy to omeprazole. Changes in the cough symptom score, cough threshold to capsaicin, reflux symptom score and possible adverse effects were determined after treatment. The variables of multi-channel intraluminal impedance combined with pH monitoring were compared between responders and non-responders to baclofen. Twelve of 16 patients completed treatment. Cough disappeared or improved in 56.3% (9/16) of patients, including 6 patients with acid reflux-induced cough (66.7%) and 3 patients with non-acid reflux-induced cough (33.3%). With baclofen treatment, the cough symptom score began to decrease at week 2, was clearly decreased at week 6 and reached a minimum at week 8. At the end of therapy, the lowest concentration of capsaicin required for induction of ≥ 2 and ≥ 5 coughs increased from 0.98 (1.46) to 1.95 (6.82) μmol/L (Z = -2.281, P = 0.024) and from 1.95 (7.31) to 7.8 (13.65) μmol/L (Z = -2.433, P = 0.014), respectively, and the reflux symptom score decreased from 8.0 ± 1.6 to 6.8 ± 0.8 (t = 2.454, P = 0.023). The number of acid reflux episodes was significantly lower in responders than in non-responders. The main adverse effects were somnolence, dizziness and fatigue. Baclofen is a useful, but suboptimal treatment option for refractory GERC.

Predicting the efficacy of proton pump inhibitors in patients with non‐erosive reflux disease before therapy using dual‐channel 24‐h esophageal pH monitoring

We aimed to determine whether reflux- and symptom-related parameters can predict the efficacy of proton pump inhibitors (PPI) in non-erosive reflux disease (NERD). Twenty-seven NERD patients who had experienced heartburn more than once a week within the previous month were enrolled. Intraesophageal pH before therapy was measured simultaneously at 5 and 15 cm above the esophagogastric junction (EGJ) for 24 h. The PPI rabeprazole was administered at a dose of 10 mg once daily for 4 weeks. In the event that heartburn was not relieved, the dose was increased to 10 mg twice daily for an additional 2 weeks, and again to 20 mg twice daily for another 2 weeks. Univariate analysis demonstrated no significant associations between any reflux- or symptom-related parameters at either site and complete heartburn relief after 4 weeks, or cumulative complete heartburn relief after 8 weeks. However, post-hoc analysis demonstrated more satisfactory heartburn relief after 4 weeks in patients with a high symptom index compared with those with a low symptom index, at 5 cm above the EGJ (P = 0.009). Cumulative satisfactory heartburn relief after 8 weeks was also greater in patients with a high total number of acid reflux episodes compared with those with a low total number of episodes, at 15 cm above the EGJ (P = 0.037). Pre-therapeutic pH monitoring in the lower and mid-esophagus is useful for predicting the efficacy of PPI in NERD patients.

A Novel Partial 5HT3 Agonist Pumosetrag after a Standard Refluxogenic Meal Reduces Acid Reflux Events in GERD Patients: A Randomized, Double-Blind, Placebo-Controlled Pharmacodynamic Study

Purpose: Transient lower esophageal sphincter relaxations (TLESRs) are a major cause of gastro-esophageal reflux disease (GERD). Pumosetrag, a selective partial agonist at 5HT3 receptors, increases LES pressure and gastrointestinal motility in experimental animal models. In a previous study, it was shown to reduce the rate of reflux episodes after a refluxogenic meal in healthy subjects. Aims: To evaluate the effect of pumosetrag on esophageal related pharmacodynamic measurements, including changes in reflux episodes, lower esophageal sphincter pressure, and specific symptoms (heartburn, regurgitation, acid taste) in GERD patients receiving a refluxogenic meal, and to assess the safety and tolerability of pumosetrag. Methods: A randomized, double-blind, placebo-controlled study evaluated the pharmacodynamic effects of pumosetrag. Subjects were randomized to one of three dose levels of pumosetrag (0.2 mg, 0.5 mg, or 0.8 mg) or placebo. Before and after 7 days of treatment, GERD patients underwent manometry, and intraesophageal multichannel intraluminal impedance and pH (MII-pH) after a standard refluxogenic meal (a sausage-and-egg based meal [300 kCal, 60% fat] with eight ounces of Hershey's chocolate milk). Intent to treat analysis of covariance models were used to assess treatment effects. For evaluating the safety and tolerability of pumosetrag, each subject was monitored from the time of the first dose of study medication until the end of the study. Results: A total of 223 GERD patients (125[56%] females, mean [SD] age = 36[12] years) were enrolled. No overall treatment effects were detected for the total number of reflux episodes (p>0.5); however, significant treatment effects (p<0.05) on the number of acid reflux episodes were observed with lower values on pumosetrag 0.2 mg (10.8 ± 1.1), 0.5 mg (9.5 ± 1.1), and 0.8 mg (9.9 ± 1.1) compared to placebo (13.3 ± 1.1) (Table). Significant treatment effects (p<0.05) were also observed for the percentage of time pH was <4, with less time for pumosetrag at 0.5 mg (10%) and 0.8mg (10%) compared to placebo (16%). Differences in LESP (p>0.5), the number of nonacid reflux episodes after a refluxogenic meal (p>0.15), and specific symptom scores (p>0.4) were not detected (table). No serious adverse events on pumosetrag were reported.Table: Table. Reflux events, post-treatment mean LESP, and proportion time with pH < 4 (mean±SEM unless otherwise noted)Conclusion: In GERD patients, the partial 5HT3 agonist pumosetrag significantly reduced the rate of acid reflux events and proportion of time that pH <4 after a refluxogenic meal challenge, but did not affect the total number of reflux episodes or LES pressure. The results of the study suggest pumosetrag has effects on some pharmacodynamic endpoints associated with GERD and is worthy of additional study. Supported by Edusa Pharmaceuticals, Inc, Princeton, NJ. Disclosure: All authors - Grant research support from Edusa Pharmaceuticals, Inc.

A Multi-Center, Double-Blind, Parallel-Group Study to Evaluate Short-Term Safety and Efficacy and Long-Term Maintenance of Two Dose Levels of Rabeprazole Sodium Delayed-Release Pediatric Bead Formulation in 1- to 11-Year-Old Pediatric Subjects With Endoscopically Proven GERD

lasting >5 min showed a monotonic decline with increasing dose: placebo 3.8, naronapride 12 mg 2.9, naronapride 40 mg 2.1. The difference between placebo and naronapride 40 mg was significant (p=0.0007), as was the dose-response (p=0.0049). The mean duration of acid reflux episodes also showed some reduction with treatment: 0.67 min on placebo; 0.60 min on both naronapride 12 mg and 40 mg. The dose response was significant (p= 0.0057). Conclusions: Treatment with naronapride resulted in a consistent and dose-related decrease in several measures of esophageal acid exposure, including mean % of time with pH<4.0, total number of acid reflux episodes, the mean duration of acid reflux episodes and the number of acid reflux episodes over 5 min duration. Taken together, these findings suggest that naronapride may be effective in the treatment of acid reflux disorders, and further studies are warranted.

Influence of Food on the Pharmacokinetics of Rabeprazole After Oral Administration of 50-mg Rabeprazole Extended-Release Capsules to Healthy Volunteers

lasting >5 min showed a monotonic decline with increasing dose: placebo 3.8, naronapride 12 mg 2.9, naronapride 40 mg 2.1. The difference between placebo and naronapride 40 mg was significant (p=0.0007), as was the dose-response (p=0.0049). The mean duration of acid reflux episodes also showed some reduction with treatment: 0.67 min on placebo; 0.60 min on both naronapride 12 mg and 40 mg. The dose response was significant (p= 0.0057). Conclusions: Treatment with naronapride resulted in a consistent and dose-related decrease in several measures of esophageal acid exposure, including mean % of time with pH<4.0, total number of acid reflux episodes, the mean duration of acid reflux episodes and the number of acid reflux episodes over 5 min duration. Taken together, these findings suggest that naronapride may be effective in the treatment of acid reflux disorders, and further studies are warranted.

Azitromycin Reduces the Number of Acid Reflux Episodes by Changing the Position of the Gastric Acid Pocket

Azitromycin Reduces the Number of Acid Reflux Episodes by Changing the Position of the Gastric Acid Pocket

Acid-Suppressive Effect of Rabeprazole 5 mg and 10 mg Once Daily by 24-Hour Esophageal pH Monitoring in Patients with Non-erosive Reflux Disease in Japan: A Multicenter, Randomized, Parallel-Group, Double-Blind Pharmacodynamic Study

Acid suppression induced by rabeprazole 5 mg in patients with NERD has not been reported in the literature. The objective of this study was to investigate gastroesophageal acid suppression in NERD patients by rabeprazole 5 mg and 10 mg/day. Subjects were grade M (minimal changes) NERD patients. Twenty-two patients not responding to open label antacid therapy entered a double-blind treatment phase in which rabeprazole 5 mg or 10 mg/day for four weeks were compared. Twenty-four-hour esophageal pH monitoring was performed before and on treatment (at week 4) to assess the pharmacodynamic effect of these doses of rabeprazole. The frequency of heartburn episodes and the number of acid reflux episodes in the esophagus corresponded well in grade M NERD patients (r=0.44, P=0.042). Median percentage of time at pH<4 was 4.3% before treatment and 1.1% on treatment with rabeprazole 5 mg (change from baseline; -2.5%), whereas the median percentage of time at pH<4 in the rabeprazole 10 mg group was 7.4% before treatment and 0.5% on treatment (change from baseline; -6.6%). Likewise, treatment-related changes of median number of reflux episodes were -18.0 with rabeprazole 5 mg and -44.0 with rabeprazole 10 mg. For each esophageal pH data, no significant differences were observed between the two groups (P=0.377, P=0.077). Administration of 5 mg and 10 mg rabeprazole sufficiently inhibited pathological gastroesophageal acid reflux and relieved heartburn episodes in NERD patients who did not respond to an antacid. Further investigation would be necessary to determine proper usage of the two doses.

Gastroparesis is Not Associated with Acid or Non-Acid Reflux

Purpose: Gastroparesis (GP) may often be misdiagnosed as gastroesophageal reflux disease (GERD) given the similarity in symptoms of regurgitation related to high volume reflux. Prior studies have suggested an association between delayed stomach emptying and refractory GERD. Unfortunately, unlike GERD, the symptoms of GP do not respond to acid suppression therapy. Whether non-acid reflux contributes to this lack of symptom improvement in patients with GP is unknown. Our study aims to determine whether an increased number and duration of acid and non-acid reflux episodes as measured using the Multichannel Intraluminal Impedance pH (MII-pH) is seen in patients with GP as compared to controls. Methods: The baseline characteristics, MII-pH data and gastric emptying scintigraphy (GES) results were reviewed on 40 consecutive patients undergoing clinical evaluation for continued heartburn and regurgitation despite acid suppression therapy. All enrolled subjects were continued on their PPI for the duration of the study. The 8 channel MII-pH probe recorded impedance data at 3, 5, 7, 9, 15 and 17 cm above the LES and pH data 5 cm above and 10 cm below the LES. The MII-pH parameters evaluated were as follows: total, supine and upright number of acid reflux episodes (pH <4); total, supine and upright number of non-acid reflux episodes as defined by pH >4; duration of acid and non-acid reflux in 24 hour period and the number of reflux episodes lasting over 5 minutes. GES results were reviewed with a normal study defined by gastric emptying half-time of 45-90 minutes. The control group (n=25, 6M, 19F, mean age 51) consisted of subjects with symptoms of regurgitation on PPI therapy and a normal GES, and the GP group (n=15, 4M, 11F, mean age 54) consisted of those subjects with an abnormal GES and/or history of GP. Results: Using SAS software, the impedance parameters listed above were compared between patients with GP and controls. The t-test for equality of the mean showed no statistical difference between the two groups with respect to the total number or duration of acid reflux events (p value=0.9), total number and duration of non-acid reflux events (p value=.6) or the duration of longest reflux episodes (p value=.5). The number of non-acid reflux events with pH >7 was slightly higher in the GP group than the controls (mean=5.47 ± 5.2 versus mean=4.84 ± .6.0, p value=0.7). Conclusion: Despite previous studies suggesting an association between refractory GERD and GP, we did not find increased reflux duration or increased number of reflux episodes in patients with GP. We conclude that delayed gastric emptying is not associated with either acid or nonacid reflux.

Effect of lesogaberan, a novel GABAB‐receptor agonist, on transient lower oesophageal sphincter relaxations in male subjects

Transient lower oesophageal sphincter relaxations (TLESRs) are a major mechanism behind gastro-oesophageal reflux disease (GERD). To assess the effect of lesogaberan (AZD3355) - a novel peripherally active GABA(B) receptor agonist - on TLESRs. Twenty-four healthy men were enrolled in this single-blind, placebo-controlled, randomized, single-centre, three-period crossover phase 1 study. Subjects were randomized to receive single oral doses of lesogaberan (0.8 mg/kg), baclofen (40 mg) and placebo, separated by washout periods of < or = 7 days. Subjects finished a meal 1 h after the dose. Oesophageal manometry and pH-metry measurements were taken during the 3 h after the meal. Twenty-one subjects completed the study. Compared with placebo, lesogaberan 0.8 mg/kg significantly reduced the number of TLESRs by 36% [geometric mean ratio (GMR): 0.64; 95% confidence interval (CI): 0.51-0.82] and significantly reduced the number of acid reflux episodes (mean reduction: 1.6; 95% CI: 0.34-2.9). Lesogaberan also significantly increased lower oesophageal sphincter (LES) pressure by 39% compared with placebo (GMR: 1.39; 95% CI: 1.18-1.64). Comparable results were observed with baclofen. Similar numbers of adverse events were reported by subjects taking lesogaberan and placebo. Compared with placebo, lesogaberan significantly reduced TLESRs and acid reflux episodes and increased LES pressure.

554 Role of RNA Binding Protein CUGBP2 in Radiation-Mediated Autophagy

with increased GER which may allow reflux of small volumes to occur that can be detected by pH-metry but not by MII. Aim: To search for a mechanism that can explain the differences between MII and pH-metry in detecting acid reflux episodes in patients with HH. Methods: 19 patients with GERD symptoms (12 female, 7 male, median age 51yrs (19-65yrs)) were investigated with combined MII-pH. All of the patients were not taking acid suppressive medication for at least 10 days before investigation. Impedance and pH-metry data were analysed separately. The differences in the detection rate of acid reflux between pH-metry and MII were correlated with the presence of HH. Presence of HH was defined endoscopically and classified as present if larger than 1 cm. Additionally we used an In Vitro reflux model. Thereby the impedance probe was flushed with citric acid in plastic tubes (PT) of different size with capillary diameter and diameters of 2,5 mm and 4,5 mm. Citric acid was flushed through the PT repetitively while recording pH and Impedance. Results: HH was present in 6 patients and absent in 13 patients. The mean number of acid reflux episodes in all patients was 24 ± 20 using pH-metry and 18 ± 19 times using MII accounting for a difference of 27% detection rate. In patients with HH in comparison to patients with absent HH the difference of acid reflux detection between pH-metry and MII is significantly higher (26±11; 72% and 5±18; 14% respectively; p<0.01). In Vitro all simulated reflux lead to a fall in pH whereas a corresponding decrease in impedance was only recognizable in the 4.5 mm PT. Simulated reflux using capillaries and the 2.5 mm PT led to a decrease in pH without decrease in impedance. Conclusion: Acid reflux episodes in GERD patients with HH are more frequently detected by pH-metry than by MII. Small volume reflux that does not lead to a decrease in impedance is the likely explanation for this phenomenon.

W1061 Duodeno-Gastro-Esophageal Reflux and Bile Acids in Saliva in Adult Patients With Cystic Fibrosis

Introduction: It has been established that patients with cystic fibrosis (CF) have a high prevalence of gastroesophageal reflux (GER). Increased acid reflux is most common in CF, however a small subgroup of CF patients has increased weakly acidic reflux. The presence of bile acids (BA) in saliva in almost half of CF patients suggests pathological duodenogastro-esophageal reflux (DGER). The aim of this study was to quantify DGER and BA in saliva in adult CF patients. Methods: 14 adult CF patients [median age 29 (18-58), 5 male] were evaluated using combined 24 hrs impedance-pH and Bilitec monitoring. After an overnight fast, an impedance-pH catheter and Bilitec probe were inserted trans-nasally in the esophageal body with the pH and Bilitec sensors located 5 cm above the lower esophageal sphincter (LES). To avoid Bilitec artifacts patients consumed liquid meals. During the study day, lung function assessesment (FEV1 and FVC) and saliva samples were obtained for BA measurement. Results: 5/14 (35%) of the CF patients had increased DGER. 10 patients had isolated DGER events, mostly during daytime but 3 patients had predominantly nocturnal DGER. There was a significant correlation between DGER and total acid exposure (p<0.0001, r=0.85) and total bolus exposure (p=0.03, r=0.57). There was a significant correlation between DGER and the number of acid reflux episodes (p=0.01, r=0.62). Patients with increased DGER had a higher proximal extent of reflux (number of reflux events reaching up to 15 cm above the LES) compared to those with no DGER [17 (9-35) vs. 5 (3-12), p= 0.03]. There was a negative correlation between DGER and proportion of non-acid reflux events (p=0.03, r=-0.59). DGER was unaffected by age, BMI or history of sputum bacterial colonization. Bile acids were present in saliva of 8 CF patients. The concentration of BA in saliva was slightly higher in patients with increased DGER compared to patients without DGER but the difference did not reach statistical significance. There was no significant correlation between severity of DGER and lung function. Conclusion: Increased DGER is present in 1/3 of adult CF patients. DGER is clearly associated with increased acid reflux and high proximal extent of reflux. Presence of BA in saliva is common in adult patients with CF and its concentration tended to be higher in CF patients with increased DGER, however, a clear correlation between severity of DGER and BA concentration in saliva could not be established.

W1062 Gastric Emptying in Adult Patients With Cystic Fibrosis

Introduction: It has been established that patients with cystic fibrosis (CF) have a high prevalence of gastroesophageal reflux (GER). Increased acid reflux is most common in CF, however a small subgroup of CF patients has increased weakly acidic reflux. The presence of bile acids (BA) in saliva in almost half of CF patients suggests pathological duodenogastro-esophageal reflux (DGER). The aim of this study was to quantify DGER and BA in saliva in adult CF patients. Methods: 14 adult CF patients [median age 29 (18-58), 5 male] were evaluated using combined 24 hrs impedance-pH and Bilitec monitoring. After an overnight fast, an impedance-pH catheter and Bilitec probe were inserted trans-nasally in the esophageal body with the pH and Bilitec sensors located 5 cm above the lower esophageal sphincter (LES). To avoid Bilitec artifacts patients consumed liquid meals. During the study day, lung function assessesment (FEV1 and FVC) and saliva samples were obtained for BA measurement. Results: 5/14 (35%) of the CF patients had increased DGER. 10 patients had isolated DGER events, mostly during daytime but 3 patients had predominantly nocturnal DGER. There was a significant correlation between DGER and total acid exposure (p<0.0001, r=0.85) and total bolus exposure (p=0.03, r=0.57). There was a significant correlation between DGER and the number of acid reflux episodes (p=0.01, r=0.62). Patients with increased DGER had a higher proximal extent of reflux (number of reflux events reaching up to 15 cm above the LES) compared to those with no DGER [17 (9-35) vs. 5 (3-12), p= 0.03]. There was a negative correlation between DGER and proportion of non-acid reflux events (p=0.03, r=-0.59). DGER was unaffected by age, BMI or history of sputum bacterial colonization. Bile acids were present in saliva of 8 CF patients. The concentration of BA in saliva was slightly higher in patients with increased DGER compared to patients without DGER but the difference did not reach statistical significance. There was no significant correlation between severity of DGER and lung function. Conclusion: Increased DGER is present in 1/3 of adult CF patients. DGER is clearly associated with increased acid reflux and high proximal extent of reflux. Presence of BA in saliva is common in adult patients with CF and its concentration tended to be higher in CF patients with increased DGER, however, a clear correlation between severity of DGER and BA concentration in saliva could not be established.

Characteristics of Reflux Episodes and Symptom Association in Patients With Erosive Esophagitis and Nonerosive Reflux Disease: Study Using Combined Impedance–pH Off Therapy

We sought to compare reflux and symptom association patterns in patients with nonerosive reflux disease (NERD), erosive esophagitis (EE), and in healthy volunteers (HVs). Patients with EE and NERD underwent combined impedance-pH monitoring. Normal values were defined on the basis of previously collected data from 48 HVs. We evaluated distal esophageal acid exposure time (AET), number and type of reflux episodes (acid, nonacid), acid and bolus clearance times, proximal extension of reflux episodes, and symptom association probability (SAP). Distal AET (percentage time, pH<4) was higher (P<0.01) in 58 EE patients (median 7.4%, 25-75th percentile 4.2-9.9%) compared with 168 NERD patients (4.2% (1.2-6.4%)) and 48 HVs (0.7% (0.2-1.4%)). Patients with EE and NERD had a higher (P<0.01) number of acid reflux episodes compared with HVs (51 (37-66) vs. 34 (22-51) vs. 17 (8-31); P<0.05), but a similar number of nonacid reflux episodes (22 (15-39) vs. 23 (15-38) vs. 18 (14-26); P=NS). The percentage of reflux episodes reaching the proximal esophagus was higher (P<0.01) in EE patients (57% (45-73%)) than in NERD patients (45% (36-60%)) and HVs (33% (19-46%)). A positive SAP for heartburn or regurgitation was found in 161 of 168 (96%) NERD and 54 of 58 (93%) EE patients (P=NS). Acid reflux episodes, volume, and acid clearance are important factors in the pathogenesis of reflux-induced lesions. Nonacid reflux contributes less to esophageal mucosa damage, but is involved in the development of reflux symptoms in both NERD and EE patients.

Evaluating outcomes of endoscopic full-thickness plication for gastroesophageal reflux disease (GERD) with impedance monitoring

Endoscopic full-thickness plication allows transmural suturing at the gastroesophageal junction to recreate the antireflux barrier. Multichannel intraluminal impedance monitoring (MII) can be used to detect nonacid or weakly acidic reflux, acidic swallows, and esophageal clearance time. This study used MII to evaluate the outcome of endoscopic full-thickness plication. In this study, 12 subsequent patients requiring maintenance proton pump inhibitor therapy underwent endoscopic full-thickness plication for treatment of gastroesophageal reflux disease. With patients off medication, MII was performed before and 6-months after endoscopic full-thickness plication. The total median number of reflux episodes was significantly reduced from 105 to 64 (p = 0.016). The median number of acid reflux episodes decreased from 73 to 43 (p = 0.016). Nonacid reflux episodes decreased from 23 to 21 (p = 0.306). The median bolus clearance time was 12 s before treatment and 11 s at 6 months (p = 0.798). The median acid exposure time was reduced from 6.8% to 3.4% (p = 0.008), and the DeMeester scores were reduced from 19 to 12 (p = 0.008). Endoscopic full-thickness plication significantly reduced total reflux episodes, acid reflux episodes, and total reflux exposure time. The DeMeester scores and total acid exposure time for the distal esophagus were significantly improved. No significant changes in nonacid reflux episodes and median bolus clearance time were encountered.

Does the Presence of a Hiatal Hernia Affect the Efficacy of the Reflux Inhibitor Baclofen During Add-On Therapy?

Reflux inhibitors, like the gamma-aminobutyric acid type B (GABA(B)) receptor agonist, baclofen, block transient lower esophageal sphincter relaxations (TLESRs) and are proposed as an add-on therapy in patients with proton pump inhibitor (PPI)-resistant gastroesophageal reflux. However, as other mechanisms of reflux become more important in the presence of a hiatal hernia (HH), the efficacy of reflux inhibitors to reduce acid and non-acid exposure may be hampered. Therefore, we compared the effect of baclofen in patients with no HH (-HH) and those with a large HH during PPI treatment. A total of 27 gastroesophageal reflux disease (GERD) patients on PPI were included; 16 had -HH and 11 had a large (> or =3 cm) HH (+HH). During PPI treatment, the effect of baclofen (3 x 20 mg) on acid and non-acid reflux was evaluated in a randomized, double-blind, placebo-controlled cross-over study. Reflux was measured during 24 h using combined esophageal impedance and pH-metry. The majority of reflux events consisted of both gaseous and liquid reflux with a significant increase in non-acid, mixed reflux episodes in +HH patients compared with those in -HH patients. Acid exposure time was in the normal range in both patient groups during both placebo and baclofen. In this study, baclofen significantly reduced the total number of reflux episodes with 36% in -HH patients and 43% in +HH patients, but did not change the number of acid reflux episodes or total acid exposure time. This study shows that baclofen is also effective in patients with GERD with +HH, further underscoring the potential of reflux inhibitors as treatment of GERD.

M1882 Response to Air Insufflation in Patients with Non-Erosive Gastroesophageal Reflux Disease (NERD) - Including Assessment Under a Rabeprazole Load

Gastro-esophageal reflux disease (GERD) is a multifactorial condition whose main pathogenetic factor is represented by Transient Lower Esophageal Sphincter Relaxations (TLESRs). Many hypotheses have been proposed to identify the mechanisms underlying the onset of TLESRs. One evidence suggested that colonic fermentation of indigestible carbohydrates (fructooligosaccharides, FOS) increases the rate of TLESRs and the number of acid reflux episodes. Alpha-galactosidase is an enzyme allowing better digestion of food rich in FOS that is commonly used to control symptoms of patients affected by Irritable Bowel Sindrome. Aim of our study was therefore to test the possible effect of the assumption of alphagalactosidase on esophageal pH profile in GERD patients. Patients and methods: 9 patients with low-grade esophagitis and typical GI symptoms underwent a basal 24-hour esophageal pH-metric recording. Once confirmed the GERD diagnosis, patients were instructed to assume 1 tablet of alpha-galactosidase 300 GalU (n=5) or placebo (n=4) before meals for the following four weeks. At the end of treatment a second 24-h esophageal pH-metry was performed. Heartburn and regurgitation were also scored (score: intensity x duration) at baseline and after 4 weeks. Results: Patients receiving alpha-galactosidase showed a reduced number of acid reflux episodes/24 hours as compared to baseline (60±25 vs 118±40, p<0.01); percentage of time with pH<4 was also reduced in such patients as compared to baseline values (4.2±1.7 vs 6.7±2.7, p<0.05); no difference was detected in the group receiving placebo. Heartburn was reduced in patients assuming alpha-galactosidase as compared to baseline (1.2±0.4 vs 2±0.6, p<0.05) with no differences in the placebo group. Regurgitation showed a trend toward a decrease after alpha-galactosidase which did not reach statistical significance (1.2±0.4 vs 1.5±0.3, n.s.). Summary and Conclusions: chronic assumption of alpha-galactosidase is associated to a decreased amount of gastro-esophageal reflux episodes in GERD patients. Such patients also experienced an initial improvement in clinical features of the disease. It seems likely that this change in esophageal pH pattern could depend on the modulation of TLESRs due to the reduced fermentation of FOS in the colon.

547 A Study On the Intercellular Space of Squamous Epithelium in Lower-Esophagus with Light Microscopy in the Diagnosis of GERD

(between 53.0 and 66.4%) or alkaline (between 0.5 and 1.3%) was similar in all groups. However, the median nadir pH of reflux episodes decreased with increasing severity of mucosal damage and was highest in the controls (pH 3.8) and lowest in the patients with Barrett (pH 2.5). Besides an increased number of reflux episodes, the acid clearance time of the acid reflux episodes was significantly longer in the patients with severe esophagitis (134±20 s) and Barrett's esophagus (104±21 s) compared to the controls (58±30 s), patients with NERD (73±14 s), LA A (84±49 s) and LA B (70±35 s). Comparison with normal values revealed that none of the controls, 40% of the patients with NERD, 50% of the patients with LA A, 80% of the patients with LA B and all patients with LA C/D or Barrett's esophagus had an abnormally high total number of reflux episodes. In the patients with severe esophagitis a significantly higher percentage of reflux episodes reached the proximal esophagus (43.8%) compared to the patients with Barrett's esophagus (19.2%). Conclusions: Not only the number of acid reflux episodes but also the number of weakly acidic reflux episodes is increased in patients with increasing severity esophagitis and Barrett's esophagus. However, a large overlap between the groups exists which implies that comparison to normal values is of limited relevance. In patients with Barrett's esophagus fewer reflux episodes reach the (more sensitive) proximal esophagus which might explain their low sensitivity to reflux.

Pharmacokinetics and Acid‐suppressive Effects of Esomeprazole in Infants 1–24 Months Old With Symptoms of Gastroesophageal Reflux Disease

To evaluate the pharmacokinetics and acid-suppressive effects of esomeprazole in infants with gastroesophageal reflux disease (GERD). In this single-blind, randomized, parallel-group study, 50 infants 1 to 24 months old with symptoms of GERD, and >or=5% of time with intraesophageal pH <4 during 24-hour dual pH monitoring, received oral esomeprazole 0.25 mg/kg (n = 26) or 1 mg/kg (n = 24) once daily for 1 week. Intraesophageal and intragastric pH were recorded at 1 week, and blood samples were taken for pharmacokinetic analysis. At baseline, mean percentages of time with intragastric pH >4 and intraesophageal pH <4 were 30.5% and 11.6%, respectively, in the esomeprazole 0.25 mg/kg group and 28.6% and 12.5% in the esomeprazole 1 mg/kg group. After 1 week of treatment, times with intragastric pH >4 were 47.9% and 69.3% in the esomeprazole 0.25 mg/kg and 1 mg/kg groups, respectively (P < 0.001 vs baseline), and times with intraesophageal pH <4 were 8.4% (P < 0.05 vs baseline) and 5.5% (P < 0.001 vs. baseline), respectively. The mean number of acid reflux episodes of >5 minutes duration decreased from 6 at baseline to 3 and 2 with esomeprazole 0.25 mg/kg and 1 mg/kg, respectively. The geometric mean AUC0-t of esomeprazole were 0.24 and 1.79 micromol x h/L for the 0.25 mg/kg and 1 mg/kg dosages of esomeprazole, respectively. Both esomeprazole dosages were well tolerated. Oral treatment with esomeprazole 0.25 mg/kg and 1 mg/kg was well tolerated and provided dose-related acid suppression, dose-related exposure to esomeprazole, and decreased esophageal acid exposure in infants 1-24 months old with GERD.