Abdominal Compression by Waist Belt Aggravates Gastroesophageal Reflux, Primarily by Impairing Esophageal Clearance.

BACKGROUND & AIMS: Central obesity promotes gastroesophageal reflux, which may be related to increased intra-abdominal pressure. We investigated the effect of increasing abdominal pressure by waist belt on reflux in patients with reflux disease. METHODS: We performed a prospective study of patients with esophagitis (n = 8) or Barrett's esophagus (n = 6); median age was 56 years and median body mass index was 26.8. Proton pump inhibitors were stopped at least 7 days before the study and H2 receptor antagonists were stopped for at least 24 hours before. The severity of upper GI symptoms was assessed and measurements of height, weight, and waist and hip circumference taken. Combined high-resolution pH measurement and manometry were performed in fasted state for 20 minutes and for 90 minutes following a standardized meal. The squamocolumnar junction was marked by endoscopically placed radiopaque clips. The procedures were performed with and without a waist belt (a weight-lifter belt applied tightly and inflated to a constant cuff pressure of 50 mmHg). We compared variables between groups using the Wilcoxon Signed Rank test and tested for correlations using Spearman Rho bivariate analysis. RESULTS: Without the belt, intragastric pressure correlated with waist circumference (r = 0.682; P = .008), with the range in pressure between smallest and largest waist circumference being 15 mmHg. The belt increased intragastric pressure by a median of 6.9 mmHg during fasting (P = .002) and by 9.0 mmHg after the meal (P = .001). Gastroesophageal acid reflux at each of the pH sensors extending 5.5 cm proximal to the peak lower esophageal sphincter pressure point was increased by approximately 8-fold by the belt (all P < .05). Following the meal, the mean number of reflux events with the belt was 4, vs 2 without (P = .008). Transient lower esophageal sphincter relaxations were not increased by the belt, but those associated with reflux were increased (2 vs 3.5; P = .04). The most marked effect of the belt was impaired esophageal clearance of refluxed acid (median values of 23.0 seconds without belt vs 81.1 seconds with belt) (P = .008). The pattern of impaired clearance was that of rapid re-reflux after peristaltic clearance. CONCLUSIONS: In a prospective study of patients with esophagitis or Barrett's esophagus, we found belt compression increased acid reflux following a meal. The intragastric pressure rise inducing this effect is well within the range associated with differing waist circumference and likely to be relevant to the association between obesity and reflux disease.

The gastric acid pocket is attenuated in H. pylori infected subjects.

OBJECTIVE: Gastric acid secretory capacity in different anatomical regions, including the postprandial acid pocket, was assessed in Helicobacter pylori positive and negative volunteers in a Western population. DESIGN: We studied 31 H. pylori positive and 28 H. pylori negative volunteers, matched for age, gender and body mass index. Jumbo biopsies were taken at 11 predetermined locations from the gastro-oesophageal junction and stomach. Combined high-resolution pH metry (12 sensors) and manometry (36 sensors) was performed for 20 min fasted and 90 min postprandially. The squamocolumnar junction was marked with radio-opaque clips and visualised radiologically. Biopsies were scored for inflammation and density of parietal, chief and G cells immunohistochemically. RESULTS: Under fasting conditions, the H. pylori positives had less intragastric acidity compared with negatives at all sensors >1.1 cm distal to the peak lower oesophageal sphincter (LES) pressure (p<0.01). Postprandially, intragastric acidity was less in H. pylori positives at sensors 2.2, 3.3 and 4.4 cm distal to the peak LES pressure (p<0.05), but there were no significant differences in more distal sensors. The postprandial acid pocket was thus attenuated in H. pylori positives. The H. pylori positives had a lower density of parietal and chief cells compared with H. pylori negatives in 10 of the 11 gastric locations (p<0.05). 17/31 of the H. pylori positives were CagA-seropositive and showed a more marked reduction in intragastric acidity and increased mucosal inflammation. CONCLUSIONS: In population volunteers, H. pylori positives have reduced intragastric acidity which most markedly affects the postprandial acid pocket.

Hiatus hernia in healthy volunteers is associated with intrasphincteric reflux and cardiac mucosal lengthening without traditional reflux.

BACKGROUND AND AIMS: Hiatus hernia (HH) is a key mediator of gastro-oesophageal reflux disease but little is known about its significance in the general population. We studied the structure and function of the gastro-oesophageal junction in healthy volunteers with and without HH. METHODS: We compared 15 volunteers with HH, detected by endoscopy or MRI scan, but without gastro-oesophageal reflux disease with 15 controls matched for age, gender and body weight. Jumbo biopsies were taken across the squamocolumnar junction (SCJ). High-resolution pH metry (12 sensors) and manometry (36 sensors) were performed upright and supine, before and after a meal. The SCJ was marked with an endoscopically placed clip and visualised fluoroscopically. RESULTS: Cardiac mucosa was longer in volunteers with HH (3.5 vs 2.5 mm, p=0.01). There was no excessive acid reflux 5 cm above the upper border of the lower oesophageal sphincter (LOS) in either group but those with HH had short segment reflux 11 mm above the pH transition point after the meal when supine (pH<4 for 5.5% vs 0.3% of time, p=0.01). The SCJ and pH transition point were proximally displaced within the gastro-oesophageal junction in those with HH versus controls (p<0.05). The pH transition point was proximal to the peak LOS pressure point in HH subjects but distal to it in controls after the meal (p<0.05). When supine, the postprandial pH transition point crossed the SCJ in those with HH (p=0.03). CONCLUSIONS: Healthy volunteers with HH have increased intrasphincteric reflux and lengthening of cardiac mucosa in the absence of traditional transsphincteric reflux.

In healthy volunteers, immunohistochemistry supports squamous to columnar metaplasia as mechanism of expansion of cardia, aggravated by central obesity.

INTRODUCTION: Recently, we showed that the length of cardiac mucosa in healthy volunteers correlated with age and obesity. We have now examined the immunohistological characteristics of this expanded cardia to determine whether it may be due to columnar metaplasia of the distal oesophagus. METHODS: We used the squamocolumnar junction (SCJ), antral and body biopsies from the 52 Helicobacter pylori-negative healthy volunteers who had participated in our earlier physiological study and did not have hiatus hernia, transsphincteric acid reflux, Barrett's oesophagus or intestinal metaplasia (IM) at cardia. The densities of inflammatory cells and reactive atypia were scored at squamous, cardiac and oxyntocardiac mucosa of SCJ, antrum and body. Slides were stained for caudal type homeobox 2 (CDX-2), villin, trefoil factor family 3 (TFF-3) and liver-intestine (LI)-cadherin, mucin MUC1, Muc-2 and Muc-5ac. In addition, biopsies from 15 Barrett's patients with/without IM were stained and scored as comparison. Immunohistological characteristics were correlated with parameters of obesity and high-resolution pH metry recording. RESULTS: Cardiac mucosa had a similar intensity of inflammatory infiltrate to non-IM Barrett's and greater than any of the other upper GI mucosae. The immunostaining pattern of cardiac mucosa most closely resembled non-IM Barrett's showing only slightly weaker CDX-2 immunostaining. In distal oesophageal squamous mucosa, expression of markers of columnar differentiation (TFF-3 and LI-cadherin) was apparent and these correlated with central obesity (correlation coefficient (CC)=0.604, p=0.001 and CC=0.462, p=0.002, respectively). In addition, expression of TFF-3 in distal oesophageal squamous mucosa correlated with proximal extension of gastric acidity within the region of the lower oesophageal sphincter (CC=-0.538, p=0.001). CONCLUSIONS: These findings are consistent with expansion of cardia in healthy volunteers occurring by squamo columnar metaplasia of distal oesophagus and aggravated by central obesity. This metaplastic origin of expanded cardia may be relevant to the substantial proportion of cardia adenocarcinomas unattributable to H. pylori or transsphincteric acid reflux.

Waist belt and central obesity cause partial hiatus hernia and short-segment acid reflux in asymptomatic volunteers.

OBJECTIVE: There is a high incidence of inflammation and metaplasia at the gastro-oesophageal junction (GOJ) in asymptomatic volunteers. Additionally, the majority of patients with GOJ adenocarcinomas have no history of reflux symptoms. We report the effects of waist belt and increased waist circumference (WC) on the physiology of the GOJ in asymptomatic volunteers. DESIGN: 12 subjects with normal and 12 with increased WC, matched for age and gender were examined fasted and following a meal and with waist belts on and off. A magnet was clipped to the squamo-columnar junction (SCJ). Combined assembly of magnet-locator probe, 12-channel pH catheter and 36-channel manometer was passed. RESULTS: The waist belt and increased WC were each associated with proximal displacement of SCJ within the diaphragmatic hiatus (relative to upper border of lower oesophageal sphincter (LOS), peak LOS pressure point and pressure inversion point, and PIP (all p<0.05). The magnitude of proximal migration of SCJ during transient LOS relaxations was reduced by 1.6-2.6 cm with belt on versus off (p=0.01) and in obese versus non-obese (p=0.04), consistent with its resting position being already proximally displaced. The waist belt, but not increased WC, was associated with increased LOS pressure (vs intragastric pressure) and movement of pH transition point closer to SCJ. At 5 cm above upper border LOS, the mean % time pH <4 was <4% in all studied groups. Acid exposure 0.5-1.5 cm above SCJ was increased, with versus without, belt (p=0.02) and was most marked in obese subjects with belt. CONCLUSIONS: Our findings indicate that in asymptomatic volunteers, waist belt and central obesity cause partial hiatus herniation and short-segment acid reflux. This provides a plausible explanation for the high incidence of inflammation and metaplasia and occurrence of neoplasia at the GOJ in subjects without a history of reflux symptoms.

Central obesity in asymptomatic volunteers is associated with increased intrasphincteric acid reflux and lengthening of the cardiac mucosa.

BACKGROUND & AIMS: In the West, a substantial proportion of subjects with adenocarcinoma of the gastric cardia and gastroesophageal junction have no history of reflux. We studied the gastroesophageal junction in asymptomatic volunteers with normal and large waist circumferences (WCs) to determine if central obesity is associated with abnormalities that might predispose individuals to adenocarcinoma. METHODS: We performed a study of 24 healthy, Helicobacter pylori-negative volunteers with a small WC and 27 with a large WC. Abdominal fat was quantified by magnetic resonance imaging. Jumbo biopsy specimens were taken across the squamocolumnar junction (SCJ). High-resolution pH-metry (12 sensors) and manometry (36 sensors) were performed in upright and supine subjects before and after a meal; the SCJ was visualized fluoroscopically. RESULTS: The cardiac mucosa was significantly longer in the large WC group (2.5 vs 1.75 mm; P = .008); its length correlated with intra-abdominal (R = 0.35; P = .045) and total abdominal (R = 0.37; P = .034) fat. The SCJ was closer to the upper border of the lower esophageal sphincter (LES) in subjects with a large WC (2.77 vs 3.54 cm; P = .02). There was no evidence of excessive reflux 5 cm above the LES in either group. Gastric acidity extended more proximally within the LES in the large WC group, compared with the upper border (2.65 vs 4.1 cm; P = .027) and peak LES pressure (0.1 cm proximal vs 2.1 cm distal; P = .007). The large WC group had shortening of the LES, attributable to loss of the distal component (total LES length, 3 vs 4.5 cm; P = .043). CONCLUSIONS: Central obesity is associated with intrasphincteric extension of gastric acid and cardiac mucosal lengthening. The latter might arise through metaplasia of the most distal esophageal squamous epithelium and this process might predispose individuals to adenocarcinoma.

Effect of nitrite delivered in saliva on postprandial gastro-esophageal function.

OBJECTIVE: Acid reflux produces troublesome symptoms (heartburn) and complications including esophagitis, Barrett's esophagus, and adenocarcinoma. Reflux occurs due to excessive and inappropriate relaxation of the lower esophageal sphincter. An important mediator of this is nitric oxide, high concentrations of which are generated within the lumen when swallowed saliva meets gastric acid. Saliva contains nitrite, derived from the enterosalivary recirculation of dietary nitrate, which is reduced to nitric oxide by gastric acid. The aim of this study was to investigate whether salivary nitrite contributes to dysfunction of the lower esophageal sphincter. MATERIALS AND METHODS: In 20 volunteers, studies of gastro-esophageal function were performed on four separate days, following consumption of a standardized meal, with saliva nitrite concentrations modified differently each day by intra-oral nitrite infusion. RESULTS: The infusions produced an appropriate range in saliva nitrite concentrations, from below to well above the physiological range. The standardized meal induced expected physiological changes in gastro-esophageal function confirming the recordings were sensitive and robust. Esophageal acid exposure (primary outcome) was similar on each study day. Secondary outcomes, including number and duration of reflux events, rate of transient lower esophageal sphincter relaxations, lower esophageal sphincter pressure and rate of gastric emptying were also unaffected by variations in saliva nitrite concentration. CONCLUSIONS: Nitrite in swallowed saliva does not modify gastro-esophageal junction function or predispose to gastro-esophageal reflux. The wide range in saliva nitrite concentrations, the sensitivity of the physiological recordings and the number of subjects studied make it very unlikely that an effect has been missed.

Development and validation of a probe allowing accurate and continuous monitoring of location of squamo-columnar junction.

INTRODUCTION: Most pathology of the upper gastrointestinal tract now occurs close to the gastro-oesophageal squamo-columnar junction (SCJ). Studying the pathophysiology of this region even using high resolution pH, impedance and manometry is unreliable due to constant movement with respiration, swallowing and transient lower oesophageal sphincter relaxations. AIMS AND METHODS: A technique is reported allowing continuous real-time monitoring of the position of the SCJ. It involves endoscopically clipping a magnet (2 mm × 1 mm) to the SCJ and monitoring its position relative to a probe in the oesophago-gastric lumen. The latter has 26 Hall-Effect sensors mounted at 5mm spacing on a circuit board within a silicone tube. RESULTS: Bench studies: The recorded position of the magnet along the length of the probe was compared with its actual position. Accuracy was related to the distance between magnet and probe, orientation of the magnet relative to the probe and whether the magnet was anterior, posterior or lateral to the probe. Including all possible orientations of the magnet at or nearer than 10mm from the probe, the median accuracy along the length of probe was 2.4 mm (IQR 2.1 mm). The proportion of all possible orientations within 10mm of the probe giving an accuracy of ±10 mm was 88.9%. In vivo studies: With simultaneous fluoroscopy, eight healthy subjects were asked to perform normal breathing, deep breathing, water swallows and finally advancement and retraction of probe over a 12 cm segment. The position recorded by fluoroscopy and probe at each second interval were compared. The correlation co-efficient for all 224 position readings was 0.96 (95% CI: 0.89-0.96). No significant interference was observed when the probe was tested alongside high resolution pH and manometry. CONCLUSION: Used in conjunction with high resolution pH, impedance and manometry, this technique will allow for the first time detailed studies at the squamo-columnar junction.

Mechanism of association between BMI and dysfunction of the gastro-oesophageal barrier in patients with normal endoscopy.

INTRODUCTION: The association between body mass index (BMI) and gastro-oesophageal pressure gradient (GOPG) is incompletely understood. We examined the association between BMI and gastro-oesophageal (GO) barrier function and the effect of mechanically increasing intra-abdominal pressure on GO physiology. METHODS: (A) 103 dyspeptic patients with normal endoscopy underwent 24 h pH-metry and upper gastrointestinal manometry. Relationships between BMI and acid reflux, intragastric pressure (IGP), GOPG and lower oesophageal sphincter (LOS) pressure were calculated using bivariate correlations. (B) In 18 healthy volunteers, the effects of increasing IGP by abdominal belt on GO manometry were studied. RESULTS: (A) There was a linear correlation between BMI and oesophageal acid exposure in erect (R=0.35, p<0.001) and supine (R=0.40, p<0.001) positions. BMI was strongly associated with IGP (inspiration: R=0.66, p<0.001; expiration: R=0.78, p<0.001) and inspiratory GOPG (R=0.50, p<0.001). There were a positive correlation between BMI and inspiratory LOS pressure relative to atmospheric pressure (R=0.29, p=0.016) and a negative correlation with LOS pressure relative to IGP on expiration (R=-0.25, p=0.018). Logistic regression models using all significant manometric variables and relevant interactions revealed marked decline in the magnitude and significance of relationship between BMI and oesophageal acid exposure in supine (from OR 1.12 (95% CI 1.03 to 1.22), p=0.009, to 1.00 (0.86 to 1.17), p=0.999) and upright positions (from 1.11 (1.02 to 1.20), p=0.020, to 1.03 (0.89 to 1.18), p=0.717). (B) Application of the constricting abdominal belt produced similar manometric changes to those associated with increased BMI. However, the belt did not reproduce the reduced LOS pressure relative to IGP. CONCLUSION: The association between reflux and BMI may be largely explained by effects of increased intra-abdominal pressure. However, the reduced LOS pressure associated with BMI may be mediated by another mechanism or effects of chronic rather than acute elevation of intra-abdominal pressure.

BMI is superior to symptoms in predicting response to proton pump inhibitor: randomised trial in patients with upper gastrointestinal symptoms and normal endoscopy.

OBJECTIVES: In most patients undergoing endoscopy for upper gastrointestinal (GI) symptoms in the Western world, no macroscopic abnormality or evidence of Helicobacter pylori infection is identified. Following this negative investigation, proton pump inhibitor (PPI) therapy is usually prescribed. The aim of this study was to assess the value of such treatment compared with placebo and to identify predictors of response. DESIGN: Prospective parallel randomised study. SETTING: Dyspepsia Research Clinic. PARTICIPANT: 105 patients (49 men, median age 44 years, IQR 22) with normal endoscopy and H pylori negative with ongoing upper GI symptoms following 2-week run-in period. Intervention Full demographic symptom severity and characteristics were assessed and 24 h oesophageal pH metry and oesophageal manometry were performed prior to randomisation to 2 weeks of treatment with lansoprazole 30 mg/day or placebo (2:1), with reassessment of symptom severity during the second week of treatment. PRIMARY OUTCOME: 50% reduction in Glasgow Dyspepsia Severity Score (GDSS). RESULTS: According to intention to treat analysis, the response was 35.7% for the active group and 5.7% for the placebo group (p < 0001). The only non-invasive independent predictor of response to PPI in multivariable analysis was the patient's body mass index (BMI) (p = 0.003). The association of BMI with response to PPI was apparent across the full range of quartiles (p values for trend=0.01). BMI had a similar predictive value to either 24 h oesophageal pH metry or manometry. Predominant symptom and symptom subgroups were unhelpful in predicting the response to PPI. Including all pretreatment assessments, only BMI (p < 0.05) and lower oesophageal sphincter pressure (p < 0.05) were independent predictors of response. CONCLUSION: The response to PPI therapy is likely to be related to underlying acid reflux. The strong predictive value of BMI is probably due to its association with underlying reflux disease and the fact that it is a more objective and reproducible measure than symptom characteristics. It is recommended that BMI should be measured in patients with upper GI symptoms. Trial Registration Number ISRCTN 32863375.

Nitrogenous chemicals generated from acidification of saliva influence transient lower oesophageal sphincter relaxations.

OBJECTIVE: Saliva contains high concentrations of nitrite derived from the enterosalivary recirculation of dietary nitrate and its reduction by buccal bacteria. Acidic gastric juice converts the swallowed nitrite to varying proportions ofnitrous acid and nitric oxide (NO) depending upon ascorbic acid availability. Neuronally generated NO is the key in the pathway of transient lower oesophageal sphincter relaxations in vivo. Furthermore, in vitro NO and nitrous acid relax the smooth muscle of the stomach, lower oesophageal sphincter (LOS) and oesophageal body. The objective of this article was to determine whether luminal administration of NO or nitrous acid affects the generation of transient LOS relaxations following a meal. MATERIAL AND METHODS: Fifteen healthy subjects were studied on three separate days. A manometry catheter was used to record oesophageal, LOS and gastric pressures, and two oesophageal pH probes were used to record reflux. One of three solutions was infused each day into the cardia after a standardized meal: 1) control solution ofhydrochloric acid pH 1.0, 2) nitrous acid and 3) nitrous acid plus ascorbic acid to generate NO. The solutions were randomized and double-blinded. RESULTS: The frequency of transient LOS relaxations was increased by the NO-generating solution at 5.2/h compared with both the control (3.5, p <0.01) and nitrous acid solution (3.1, p <0.0001). The NO-generating solution also increased oesophageal acid exposure to 62.2%, compared with both the control (37.5%, p <0.03) and nitrous acid solution (36.6%, p <0.002). CONCLUSIONS: Luminal NO at the gastro-oesophageal junction increases the generation of transient LOS relaxations following a meal. Chemicals generated by the acidification of salivary nitrite may contribute to gastro-oesophageal motility disorders.

N-nitrosamine generation from ingested nitrate via nitric oxide in subjects with and without gastroesophageal reflux.

BACKGROUND & AIMS: Nitrate ingestion leads to high luminal concentrations of nitric oxide being generated where saliva meets gastric acid. Nitric oxide generates N-nitrosative stress on reacting with oxygen at neutral pH. We aimed to ascertain if luminal nitric oxide exerts nitrosative stress in the human upper gastrointestinal tract, and to assess the influence of acid reflux on this phenomenon. METHODS: A silicone tube, segmented every 15 mm and containing phosphate buffer pH 7.4 and the secondary amine morpholine, was inserted into the upper gastrointestinal tract of 16 healthy volunteers and 16 Barrett's esophagus patients. The tube wall has the same permeability properties as an epithelial lipid membrane, allowing passage of gases such as nitric oxide, but not hydrogen ions. After 2 hours, the tube was removed and the concentrations of nitrite and N-nitrosomorpholine in each segment were measured. Healthy volunteers were studied with and without ingestion of (15)N-enriched nitrate and Barrett's esophagus patients were studied with and without stimulation of acid reflux. RESULTS: In healthy volunteers, N-nitrosomorpholine was generated in the tube sections exposed to gastric acid and increased 2-fold after nitrate. The N-nitrosomorpholine was 77% enriched with (15)N, confirming its source was the ingested nitrate. In the Barrett's patients, generation of N-nitrosomorpholine was shifted proximally with 80% of nitrosative stress occurring within the esophagus during periods of acid reflux. CONCLUSIONS: This study demonstrates the in situ formation of N-nitrosamine from dietary nitrate via nitric oxide. During acid reflux, nitrosative stress occurs almost entirely within the esophagus and may contribute toward carcinogenesis at this site.

Helicobacter pylori eradication releases prolonged increased acid secretion following omeprazole treatment.

BACKGROUND & AIMS: Rebound increased acid secretion has been observed at 2 weeks after discontinuing omeprazole treatment in Helicobacter pylori -negative, but not H. pylori -positive, subjects. It is unknown whether this is a prolonged phenomenon or whether a similar phenomenon appears later in H. pylori positives or is released by eradication therapy. The aims of this study were to answer these 3 questions. METHODS: Twelve H. pylori -negative and 20 H. pylori -positive subjects were studied. Each had a basal, submaximal, and maximal pentagastrin-stimulated acid secretion study before, during, and at 7, 14, 28, 42, and 56 days after a 56-day course of omeprazole 40 mg/day. Ten of the H. pylori -positive subjects had their infection eradicated during the last week of treatment. RESULTS: In the H. pylori -negative subjects, there was rebound secretion of submaximal (P < 0.003) and maximal (P < 0.003) acid output, which persisted until at least 56 days after discontinuing omeprazole. The H. pylori -uneradicated subjects had no rebound increased secretion other than in maximal acid output at 28 (P < 0.01) and at 42 days after treatment (P < 0.02). In those eradicated of H. pylori close to the end of omeprazole, there was rebound increased secretion of submaximal acid output (P < 0.04) lasting until 56 days and of maximal acid output (P < 0.01) lasting until 28 days after treatment. CONCLUSIONS: Rebound increased acid secretion following omeprazole is a prolonged phenomenon in H. pylori -negative subjects. There is little evidence of it in H. pylori -infected subjects, but eradicating the infection releases the phenomenon. The accentuated H. pylori -related oxyntic gastritis induced by omeprazole is likely to protect against the rebound phenomenon.

Barrett's esophagus evokes a quantitatively and qualitatively altered response to both acid and hypertonic solutions.

OBJECTIVE: The stomach contents become hypertonic after a meal and provide esophageal refluxate that is both acidic and hypertonic. This study examined the symptomatic response to esophageal exposure to hypertonic and acidic solutions in patients with gastroesophageal reflux disease (GERD) and Barrett's esophagus. METHODS: Symptom intensity and character were measured in double-blind fashion during esophageal instillation of water, hypertonic saline (osmolality 1030 mOsm/kg), hydrochloric acid (pH 1 and 2.5), and acidified hypertonic saline (pH 1 and 2.5). The studies were performed in healthy controls and GERD patients with and without Barrett's esophagus. RESULTS: The GERD patients with Barrett's differed from the non-Barrett's GERD patients in being less sensitive to acid (mean intensity score, 2.3 vs 4.8, p < 0.05), more sensitive to hypertonic saline (1.3 vs 0.4, p < 0.05) and by showing an additive effect when the acid and hypertonic solutions were combined, resulting in similar scores in the two patient groups to the combination (4.4 vs 4.3). The frequency of nausea was higher in the Barrett's group compared to the other GERD patients after hypertonic saline (21% vs 0%, p < 0.05), acid (50% vs 21%, p < 0.05) and the acid hypertonic combination (71% vs 29%, p < 0.05). CONCLUSIONS: Barrett's mucosa is associated with reduced symptomatic response to acid, increased response to hypertonic solutions, and a higher incidence of nausea in response to either stimulus.