Non-erosive reflux disease (NERD)--acid reflux and symptom patterns

BACKGROUND: Recent reports suggest that patients with non-erosive reflux disease (NERD) treated with anti-reflux medications show lower symptom improvement rates than patients with erosive oesophagitis treated with the same medications. AIM: To determine the acid reflux and symptom patterns of patients with NERD in comparison with those with erosive oesophagitis and Barrett's oesophagus, and to identify different NERD subgroups. METHODS: One hundred and forty-nine consecutive patients seen for classic heartburn symptoms were evaluated for the study. Oesophageal mucosal injury was assessed by upper endoscopy and classified by Hetzel-Dent criteria. Patients with Hetzel-Dent grades 0-1 were considered to have NERD. The extent of oesophageal acid exposure was determined by ambulatory 24-h oesophageal pH monitoring. RESULTS: Seventy-one patients were found to have NERD, 36 erosive oesophagitis and 42 Barrett's oesophagus. Compared with patients with erosive oesophagitis (75%) and Barrett's oesophagus (93%), those with NERD (45%) were significantly less likely to have an abnormal pH test (P = 0.0001). Patients with Barrett's oesophagus had the highest mean number of acid reflux events (210 +/- 17.7), compared with those with erosive oesophagitis (139.7 +/- 15.2) and NERD (95.3 +/- 9.4) (P = 0.0001); however, the rate of perceived acid reflux events was similar and very low in all groups (NERD, 3.6%; erosive oesophagitis, 2.9%; Barrett's oesophagus, 2.17%). NERD-positive patients (abnormal pH test) had a similar extent of oesophageal acid exposure to those with erosive oesophagitis. NERD-positive patients were more likely to demonstrate a symptom index greater than 75% than NERD-negative patients (normal pH test) (61.9% vs. 10.5%; P = 0.0001). In the NERD-negative group, those with a negative symptom index reported having heartburn at pH < 4 only 12.7% of the time, compared with 70.7% of the time in those with a positive symptom index, despite a similar mean number of heartburn episodes. CONCLUSIONS: Patients with NERD commonly demonstrate a negative pH test. Acid reflux characteristics and symptom patterns suggest a heterogeneous group of patients.     

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

BACKGROUND: The reason why less than one-half of patients with gastro-oesophageal reflux disease develop complicated reflux disease (ulcerative oesophagitis, oesophageal strictures and Barrett's oesophagus) and erosive reflux oesophagitis is not fully understood. Supine nocturnal oesophageal acid reflux is considered to be critically involved in this phenomenon, but reliable data are lacking. AIM: To clarify whether high levels of supine nocturnal oesophageal acid exposure are associated with complicated reflux disease. METHODS: Ambulatory 24-h oesophageal pH monitoring was performed in 220 patients with gastro-oesophageal reflux disease (56 with complicated reflux disease, 76 with erosive reflux oesophagitis and 88 with non-erosive reflux disease). The total, supine nocturnal and upright diurnal percentage acid reflux times were calculated. RESULTS: The total percentage acid reflux time was significantly greater in complicated reflux disease than in either erosive reflux oesophagitis (P = 0.024) or non-erosive reflux disease (P = 0.000). These differences were entirely due to a greater supine nocturnal percentage acid reflux time (P = 0.038 and P = 0.000, respectively), whereas no difference was observed in the upright diurnal percentage acid reflux time. CONCLUSIONS: Complicated reflux disease is characterized by high levels of supine nocturnal percentage acid reflux time. Prospective studies would be appropriate to clarify whether the normalization of this parameter is relevant to the effective management of this subset of patients with gastro-oesophageal reflux disease.     

Intra-oesophageal distribution and perception of acid reflux in patients with non-erosive gastro-oesophageal reflux disease

BACKGROUND: The majority of patients with gastro-oesophageal reflux disease do not present with erosive oesophagitis and make up a heterogeneous group. Patients with non-erosive gastro-oesophageal reflux disease are less responsive than patients with oesophagitis to acid-suppressive therapy. AIM: To assess the role of acid reflux in gastro-oesophageal reflux disease symptoms. METHODS: The spatio-temporal characteristics of reflux events were analysed and related to reflux perception in 45 patients with non-erosive gastro-oesophageal reflux disease and 20 patients with erosive oesophagitis. RESULTS: Compared with healthy controls, all patients showed a higher intra-oesophageal proximal spread of acid, which was prominent in patients with non-erosive gastro-oesophageal reflux disease (> 50% of events lasting for 1-2 min). Irrespective of mucosal injury, the risk of reflux perception was very high when acid reached proximal sensors (odds ratio, 7.6; 95% confidence interval, 4.6-12.5), being maximal in patients with non-erosive gastro-oesophageal reflux disease with normal acid exposure time (odds ratio, 11; 95% confidence interval, 5.2-22.3). CONCLUSIONS: Patients with non-erosive gastro-oesophageal reflux disease are characterized by a significantly higher proportion of proximal acid refluxes and a higher sensitivity to short-lasting refluxes when compared with patients with oesophagitis. The highest proximal acid exposure and highest perception occurred in patients with non-erosive gastro-oesophageal reflux disease presenting with a normal pH-metric profile. The assessment of acid distribution and its perception in the oesophageal body can better identify reflux patients who should benefit from acid-suppressive treatment.     

Systematic review: does gastro‐oesophageal reflux disease progress?

BACKGROUND: Gastro-oesophageal reflux disease affects approximately 20% of western populations. Barrett's oesophagus, associated with severe gastro-oesophageal reflux disease, is premalignant and regular endoscopic surveillance is generally performed. In contrast, mild gastro-oesophageal reflux disease is thought not to progress and is not generally subjected to endoscopic follow-up. Aim To investigate whether gastro-oesophageal reflux disease progresses endoscopically. METHODS: Systematic review of the literature. RESULTS: Well-designed prospective studies are few, diagnostic criteria were not always standardized, management strategies varied and various sources of bias could not be excluded. Whilst most patients do not progress to more severe forms of gastro-oesophageal reflux disease, and some cases actually regress, progression is seen in a small proportion of patients. Annual progression rates for non-erosive gastro-oesophageal reflux disease developing erosive oesophagitis ranged from 0% to 30%. About 1-22% of patients with mild erosive oesophagitis developed more severe inflammation annually, while 1-13% of patients with erosive oesophagitis developed Barrett's oesophagus each year. CONCLUSION: Although most patients with gastro-oesophageal reflux disease do not progress, and some actually regress, progression does occur in a minority. Better data are required to determine whether patients with mild gastro-oesophageal reflux disease would benefit from increased surveillance with the aim of detecting more advanced disease.     

Comparisons of the distribution of oesophageal acid exposure throughout the sleep period among the different gastro-oesophageal reflux disease groups

BACKGROUND: Nocturnal gastro-oesophageal reflux diseases (GERD) can lead to oesophageal mucosal injury and extra-oesophageal complications. AIM: To compare distribution of oesophageal acid exposure during sleep time among patients with non-erosive reflux disease and abnormal pH test (NERD-positive), erosive oesophagitis (EO) and Barrett's oesophagus (BO). METHODS: Patients underwent endoscopy followed by 24-h oesophageal pH testing. Oesophageal acid exposure was assessed every 2 h of the sleep period (0-2, 2-4, 4-6 and 6-8 h). Each period of 2 h was evaluated for acid reflux parameters. All groups were matched by age, time from last meal and duration of sleep time. RESULTS: Thirty-eight patients were enrolled (NERD-positive, 16; EO, 1.4; and BO, 8). All GERD groups demonstrated higher oesophageal acid exposure in the first vs. second half of the sleep period as determined by percent time pH <4 (BO: 34.7 vs.11.6, EO: 13.5 vs. 6.9, NERD-positive: 8.8 vs. 2.5, all P < 0.01). In general, patients with BO had a significantly higher distribution of oesophageal acid exposure than those with NERD-positive and EO. CONCLUSIONS: Oesophageal acid exposure generally declines throughout the sleep period regardless of GERD group, but BO patients demonstrated the greatest decline during the sleep period.     

Dilated intercellular spaces and acid reflux at the distal and proximal oesophagus in patients with non-erosive gastro-oesophageal reflux disease

BACKGROUND: Acid exposure of proximal oesophagus and dilated intercellular space diameters of oesophageal epithelium are relevant in the perception of gastro-oesophageal reflux. AIM: To explain the relationship between gastro-oesophageal reflux disease symptoms, acid exposure and intercellular space diameter along the oesophageal epithelium and to assess time-related variability of intercellular space diameter. METHODS: Thirty-three non-erosive reflux disease (NERD), six erosive oesophagitis patients and 12 asymptomatic controls underwent oesophageal manometry and 24-h dual-channel oesophageal pH-monitoring following endoscopy. Biopsies were taken 5 cm above the LES and 10 cm below the UES, at comparable levels, as pH sensors. A total of 100 intercellular space diameters per patient/control were measured blindly at transmission electron microscopy. In 15 patients, the investigation was repeated after 1 year. RESULTS: In all NERD patients, acid exposure was higher at mid-proximal oesophagus (P < 0.01) and mean intercellular space diameters, at distal and mid-proximal oesophagus, was three- and twofold higher (1.5 and 0.82 micro m, respectively) compared with controls. Intra-patient intercellular space diameter values were stable over time, not overlapping with those of controls. CONCLUSIONS: Dilation of intercellular space diameter occurs along the distal and proximal oesophageal epithelium in NERD patients and could be responsible for the enhanced perception of proximal acid reflux. This finding appears to be time-reproducible and to represent a sensitive, histopathological marker of NERD.     

Dilated intercellular spaces as a marker of oesophageal damage: comparative results in gastro-oesophageal reflux disease with or without bile reflux

BACKGROUND: The dilation of oesophageal intercellular spaces, clearly apparent in transmission electron microscopy images, is a marker of cellular damage induced by acid. AIM: To analyse the presence of dilated intercellular spaces and to quantify the scores in controls and in patients with gastro-oesophageal reflux disease or duodenal gastro-oesophageal reflux accompanied by erosive or non-erosive reflux disease. METHODS: Thirty-eight symptomatic patients with gastro-oesophageal reflux disease or duodenal gastro-oesophageal reflux and 12 asymptomatic controls, classified on the basis of pH-metry and bilimetry, underwent endoscopy. Six tissue biopsies were taken from the normal mucosa for light microscopy and transmission electron microscopy evaluation. Dilated intercellular spaces were measured on photomicrographs of the specimens (at least 100 transects were measured for each patient). RESULTS: Twenty-two patients with gastro-oesophageal reflux disease had normal macroscopic mucosa but, at histology, five patients with erosive gastro-oesophageal reflux disease had mild oesophagitis and one had moderate oesophagitis. Seven patients with duodenal gastro-oesophageal reflux had normal mucosa, whilst three with erosive duodenal gastro-oesophageal reflux had mild oesophagitis at histology. At transmission electron microscopy, all controls had dilated intercellular spaces of less than 1.69 microm. Each symptomatic patient had a mean dilated intercellular space value and a mean value of the maximum dilated intercellular space at least three or more times greater than that in controls (P < 0.001). No statistical differences were observed between erosive and non-erosive oesophagitis. CONCLUSIONS: The dilated intercellular space is an extremely sensitive marker of damage in gastro-oesophageal reflux disease, duodenal gastro-oesophageal reflux and non-erosive reflux disease, and serves as the most appropriate marker of damage evaluation in non-erosive reflux disease reported to date. A mean dilated intercellular space of 0.74 micro m provides a cut-off score for damage. No quantitative or qualitative differences in dilated intercellular space scores were found between pure and mixed acid reflux.     

Comparison of the main oesophageal pathophysiological characteristics between short- and long-segment Barrett's oesophagus

AIM: To assess the oesophageal manometric characteristics and 24-h pH profiles of patients with both short-segment and long-segment Barrett's oesophagus and compare them with those of patients with reflux oesophagitis and controls. METHODS: Seventy-nine patients who had undergone upper digestive endoscopy were recruited: 16 had short-segment Barrett's oesophagus, 13 had long-segment Barrett's oesophagus, 25 had grade III oesophagitis according to the Savary-Miller classification and 25 were used as controls. The diagnosis of Barrett's oesophagus was based on the histological detection of specialized intestinal metaplasia, which extended < 3 cm into the oesophagus in patients with short-segment disease and > 3 cm in patients with long-segment disease. All subjects underwent oesophageal manometry and basal 24-h oesophageal pH monitoring. RESULTS: The lower oesophageal sphincter pressure was significantly lower in patients with reflux oesophagitis and short-segment and long-segment Barrett's oesophagus than in controls (P=0.0004-0.0001), but there was no difference among the three reflux groups. The peristaltic wave amplitude of patients with long-segment Barrett's oesophagus was significantly lower than that of controls (P=0.002) and patients with short-segment Barrett's oesophagus (P=0.02), but was no different from that of patients with reflux oesophagitis. The percentage of non-propagated wet swallows was significantly higher in patients with reflux oesophagitis and short-segment and long-segment Barrett's oesophagus when compared with that of controls (P=0.0004-0.0001). The total percentage of time the oesophagus was exposed to pH < 4.0 was significantly higher in patients with reflux oesophagitis and short-segment and long-segment Barrett's oesophagus (P=0.0001) than in controls, and was higher in patients with long-segment disease than in those with short-segment disease (P=0.01). CONCLUSIONS: Long-segment Barrett's oesophagus is characterized by a greater impairment of peristaltic wave amplitude and a higher oesophageal acid exposure than is short-segment Barrett's oesophagus. However, both forms are linked to increased acid reflux.     

Lansoprazole heals erosive reflux oesophagitis in patients with Barrett's oesophagus

Background : Barrett's oesophagus is thought to be a complication of severe gastro-oesophageal reflux.
Aim : To determine whether the proton pump inhibitor, lansoprazole, is effective in healing erosive reflux oesophagitis in patients with Barrett's oesophagus.
Methods : An 8-week, randomized, double-blind study was conducted using patients with both erosive reflux oesophagitis and Barrett's oesophagus. Erosive reflux oesophagitis was defined as grades 2–4 oesophagitis; Barrett's oesophagus, as specialized columnar epithelium obtained by biopsy from the tubular oesophagus; and healing, as a return to grade 0 or 1 oesophageal mucosa (complete re-epithelialization). One-hundred and five (105) patients from one centre were randomized to receive either lansoprazole 30 mg daily or ranitidine 150 mg twice daily. Unhealed or symptomatic lansoprazole patients at week 4 were randomized to receive the same 30 mg dose daily or an increased dose of 60 mg daily. Endoscopy was performed at baseline and at weeks 2, 4, 6 and 8.
Results : The treatment groups were similar in regards to baseline characteristics, erosive reflux oesophagitis grades and length of Barrett's oesophagus. At each 2-week interval, lansoprazole patients had significantly greater healing rates and less day and night heartburn and regurgitation than ranitidine patients. There were no significant differences between treatment groups in antacid use, quality of life parameters, or rate of reported adverse events. Median values for fasting serum gastrin levels remained within the normal range for both groups.
Conclusion : In patients with both Barrett's oesophagus and erosive reflux oesophagitis, lansoprazole is significantly more effective than ranitidine in relieving reflux symptoms and healing erosive reflux oesophagitis.     

Does Barrett's oesophagus develop over time in patients with chronic gastro‐oesophageal reflux disease?

BACKGROUND: Barrett's oesophagus is present in 8-10% of patients with gastro-oesophageal reflux disease (GERD). AIM: We performed a cohort study to determine the incidence of Barrett's oesophagus in patients with chronic heartburn symptoms. METHODS: We identified patients, with GERD and/or Barrett's oesophagus between 1998 and 2004 by primary or secondary International Classification of Diseases (ICD-9) codes of 530.81 and/or 530.2, who had two or more oesophagogastroduodenoscopies performed at least 6 months apart. RESULTS: We screened 11 040 patients (41 390 random data entries by ICD-9 code) and enrolled 515 (4.6%) GERD patients and 169 (1.5%) Barrett's oesophagus patients. The mean (+/-s.d.) number of oesophagogastroduodenoscopies in the GERD cohort was 3.2 +/- 1.8 (range: 2-15) over 3.4 +/- 2.2 (range: 0.5-11) years. None of the 412 (80%) GERD patients with non-erosive disease developed Barrett's oesophagus over a mean follow-up time of 3.4 +/- 2.2 years (95% CI: 0-0.9%). Five (1%) of the 103 GERD patients with erosive oesophagitis developed subsequent Barrett's oesophagus. Fifty-seven per cent of the GERD patients were on PPI therapy at the time of index endoscopy. None of the 169 Barrett's oesophagus patients had normal index oesophagogastroduodenoscopies within a mean retrospective time period of 4.5 +/- 2.8 years (95% CI: 0-2%). Using the ICD-9 code of 530.2 as a predictor of the presence of Barrett's oesophagus, the sensitivity was 79% with a specificity of 88%. CONCLUSION: The majority of patients with GERD do not appear to develop Barrett's oesophagus when it is not present on the index endoscopy.     

Helicobacter pylori infection is not involved in the pathogenesis of either erosive or non-erosive gastro-oesophageal reflux disease

BACKGROUND: The majority of reflux patients have non-erosive reflux disease. AIM: To evaluate the influence of Helicobacter pylori on oesophageal acid exposure in patients with both non-erosive and erosive reflux disease and in a group of controls. The pattern and distribution of chronic gastritis were also assessed. METHODS: One hundred and twelve consecutive patients with symptoms of gastro-oesophageal reflux disease agreed to undergo both upper gastrointestinal endoscopy and 24-h oesophageal pH-metry. Patients were grouped as H. pylori-positive or H. pylori-negative on the basis of both CLO-test and histology, and as cases with or without oesophagitis on the basis of endoscopy. The controls consisted of 19 subjects without reflux symptoms and with normal endoscopy and oesophageal pH-metry. RESULTS: H. pylori was positive in 35 patients (31%) and in six controls (31%); oesophagitis was found in 44 patients (39%) and non-erosive reflux disease in 68 (61%). The prevalence of chronic gastritis in the antrum and corpus was higher in H. pylori-positive than in H. pylori-negative patients (P < 0.001), but was more frequently mild (P < 0.001) than moderate or severe. The percentage total time the oesophageal pH < 4.0 was higher in patients than in controls (P < 0.008-0.001), but there was no difference between H. pylori-positive and H. pylori-negative patients (12.3% vs. 12%, P = 0.43) or H. pylori-positive and H. pylori-negative controls (1.07% vs. 1.47%, P = 0.19). CONCLUSIONS: H. pylori infection had the same prevalence in reflux patients and in controls. It did not affect oesophageal acid exposure, as there was no difference between H. pylori-positive and H. pylori-negative individuals. The high prevalence of mild body gastritis in H. pylori-positive patients suggests that H. pylori eradication is unlikely to lead to gastric functional recovery, which might precipitate or worsen symptoms and lesions in patients with gastro-oesophageal reflux disease.     

Acid-related oesophageal sensitivity, not dysmotility, differentiates subgroups of patients with non-erosive reflux disease

Background  Patients with non-erosive reflux disease can experience reflux symptoms with similar frequency and severity as those with erosive reflux disease. Oesophageal motility and acid sensitivity are thought to influence symptom occurrence.
Aim  To compare the effect of infused hydrochloric acid on oesophageal physiology in patients with non-erosive reflux disease and erosive reflux disease.
Methods  Twelve healthy controls and 39 patients with reflux disease [14 erosive reflux disease, 11 non-erosive reflux disease with normal (functional heartburn) and 14 non-erosive reflux disease with excess acid exposure] had hydrochloric acid and saline infused into distal and then proximal oesophagus. Oesophageal contraction amplitude, lower oesophageal sphincter pressure and pain intensity were documented at baseline and during each infusion.
Results  Patients with non-erosive reflux disease had higher pain sensitivity to acid than those with erosive reflux disease and controls. Proximal acid infusion caused greater pain than distal in patients with non-erosive reflux disease. Acid and saline sensitivity were more pronounced in patients with functional heartburn. Lower oesophageal sphincter pressure and oesophageal contraction amplitudes were lower in the erosive reflux disease and non-erosive reflux disease groups, but did not change during infusions.
Conclusions  Patients with non-erosive reflux disease and, to a lesser extent, patients with erosive reflux disease, are sensitive to acid in the oesophagus, being more sensitive to proximal acid. Hypersensitivity is most marked in functional heartburn patients. This acid sensitivity is not associated with motility change.     

Cost-of-disease analysis in patients with gastro-oesophageal reflux disease and Barrett's mucosa

BACKGROUND: Gastro-oesophageal reflux disease (GERD) is a common and frequently chronic condition that causes considerable costs. AIM: To estimate the economic burden caused by patients with erosive and non-erosive reflux disease, and Barrett's oesophagus. METHODS: The Progression of Gastro-oesophageal Reflux Disease study includes a total of 6,215 patients. At baseline, patients were categorized as non-erosive reflux disease, erosive reflux disease, or Barrett's oesophagus according to endoscopic findings alone or as confirmed by histology. Direct and indirect disease-related costs were calculated based on 5,273 patients with complete information in the second year of the study. RESULTS: A total of 73% of the Progression of Gastro-oesophageal Reflux Disease patients had taken GERD medication, 61% had visited a doctor, and 2% had been hospitalized because of GERD during the previous 12 months. Of all employed persons, 6% reported days off work because of GERD. This health resource utilization caused direct costs of 342+/-864 (mean+/-s.d.) and indirect costs of 40+/-473 per patient and year. Total costs for patients with Barrett's oesophagus or erosive reflux disease were higher than those for patients with non-erosive reflux disease. CONCLUSION: Patients with GERD frequently need long-term medication and doctor care. The disorder is associated with a considerable health economic burden to society.     

There are no reliable symptoms for erosive oesophagitis and Barrett's oesophagus: endoscopic diagnosis is still essential

AIMS: To evaluate the sensitivity and specificity of different symptoms in erosive reflux oesophagitis and Barrett's oesophagus. METHODS: The presence of reflux symptoms was compared between a case population of 306 patients with endoscopically determined erosive reflux oesophagitis, 235 patients with biopsy-proven Barrett's oesophagus and a control population of 198 subjects without reflux disease. RESULTS: Heartburn at any time and heartburn at night represented the only two symptoms to be simultaneously sensitive and specific. Symptoms that were induced by various foods, such as fat, tomato, chocolate, citrus or spices, tended to cluster in the same sub-group of patients. Similarly, heartburn induced by exercise, lying down or bending over tended to occur in the same sub-groups. The frequency of symptoms was influenced more by the presence of mucosal erosions than by the presence of Barrett's oesophagus. Reflux symptoms occurred more frequently in the presence rather than the absence of Barrett's oesophagus, and in long segment rather than short segment of Barrett's mucosa. CONCLUSIONS: Endoscopic inspection of the oesophageal mucosa remains the only certain method by which to reliably diagnose erosive reflux oesophagitis and Barrett's oesophagus.     

The role of proton pump inhibitors in gastro-oesophageal reflux disease

The proton pump inhibitors (PPIs) are the most successful class of drugs that have been introduced for the treatment of gastro-oesophageal reflux disease (GORD) because of their profound and consistent effect on gastric acid secretion. The PPIs have demonstrated an excellent adverse effect profile after approximately 18 years of clinical use. Healing rates in erosive oesophagitis surpass 90%. Complete symptom resolution is achievable in close to 80% of patients with Barrett's oesophagus. Complications of these conditions, such as oesophageal stricture, ulceration and others, are becoming less frequent because of PPI treatment. In non-erosive reflux disease, PPIs provide 50-65% symptom response rate, which is the highest amongst all currently available anti-reflux interventions. PPIs have also helped to improve success rates in treating patients with atypical/extra-oesophageal manifestations of GORD. The use of PPI treatment as a diagnostic tool for GORD is well accepted. However, PPIs have changed the face of GORD in the new millennium as the focus in gastroenterology practice has shifted to primarily treating patients who fail PPI therapy.     

Irritable bowel, smoking and oesophageal acid exposure: an insight into the nature of symptoms of gastro-oesophageal reflux

BACKGROUND: In gastro-oesophageal reflux disease, oesophageal acid exposure correlates with symptoms but explains only a small fraction of their variance. AIMS: To elucidate the effects of irritable bowel syndrome and smoking on gastro-oesophageal reflux disease symptoms and to clarify whether they modulate the relationship between oesophageal acid exposure and symptoms. METHODS: The relationship between oesophageal acid exposure, irritable bowel syndrome (Rome I criteria), smoking status and symptoms was investigated in patients with a normal gastroscopy who underwent a 24-h oesophageal pH monitoring. RESULTS: Of 256 patients with gastro-oesophageal reflux disease, 16% were smokers and 50% met the criteria for irritable bowel syndrome (irritable bowel syndrome+). The extent of oesophageal acid exposure was unrelated to smoking or irritable bowel syndrome status. Oesophageal acid exposure, irritable bowel syndrome status and current smoking independently predicted symptoms. Irritable bowel syndrome and smoking modulated the effect of oesophageal acid exposure on symptoms: oesophageal acid exposure was predictive of symptoms only in non-smokers. However, irritable bowel syndrome was a significant predictor of symptoms both in smokers and in non-smokers. Smoking was associated with symptoms only in irritable bowel syndrome+, while oesophageal acid exposure was associated with symptoms irrespective of irritable bowel syndrome status. CONCLUSIONS: In patients with non-erosive gastro-oesophageal reflux disease, smoking and irritable bowel syndrome independently predicted symptoms, without affecting the extent of oesophageal acid exposure. The relationship between oesophageal acid exposure and symptoms was affected significantly, and in opposite directions, by smoking and irritable bowel syndrome.     

Dysfunction of oesophageal motility in Helicobacter pylori-infected patients with reflux oesophagitis

BACKGROUND: Helicobacter pylori infection has been suggested to be protective against gastro-oesophageal reflux disease. However, a significant proportion of patients with gastro-oesophageal reflux disease are infected by H. pylori. AIM: To study oesophageal motor function in H. pylori-infected patients with reflux oesophagitis. METHODS: Patients with erosive reflux oesophagitis were recruited prospectively for stationary oesophageal manometry and 24-h ambulatory oesophageal pH monitoring. H. pylori status was determined by biopsy urease test. Non-reflux volunteers were recruited as controls. RESULTS: Seventy-four patients with erosive oesophagitis (34 H. pylori-positive, 40 H. pylori-negative) and 48 non-reflux patient controls (22 H. pylori-positive, 26 H. pylori-negative) were recruited. There was no difference in severity of oesophagitis (median grade, 1; P=0.53) or oesophageal acid exposure (total percentage time oesophageal pH < 4, 7.6% vs. 6.8%; P=0.57) between H. pylori-positive and H. pylori-negative groups. Compared to H. pylori-negative patients, H. pylori-positive patients had significantly lower basal lower oesophageal sphincter pressure (12.2 mmHg vs. 15.3 mmHg; P=0.03) and amplitude of distal peristalsis (56.9 mmHg vs. 68.4 mmHg; P=0.03). Ineffective oesophageal motility (14% vs. 7%; P=0.02) and failed oesophageal peristalsis were also significantly more prevalent in H. pylori-positive patients. CONCLUSIONS: Among patients with a similar degree of reflux oesophagitis, H. pylori-infected patients have more severe oesophageal dysmotility and lower oesophageal sphincter dysfunction. Oesophageal motor dysfunction probably plays a dominant role in the development of gastro-oesophageal reflux disease in patients with H. pylori infection.     

Oesophageal and gastric pH profiles in patients with gastro-oesophageal reflux disease and Barrett's oesophagus treated with proton pump inhibitors

BACKGROUND: Acid plays a significant role in the development of gastro-oesophageal reflux symptoms and tissue damage. It is generally assumed that acid suppressive therapy with proton pump inhibitors improves or eliminates symptoms of gastro-oesophageal reflux disease by normalizing intra-oesophageal pH. However, the degree of acid suppression induced by proton pump inhibitor therapy in patients with gastro-oesophageal reflux disease and/or Barrett's oesophagus has not been adequately studied. AIM: To assess the efficacy of proton pump inhibitors in normalizing intra-oesophageal and intra-gastric pH in patients with gastro-oesophageal reflux disease with and without Barrett's oesophagus who have been rendered symptom-free by acid-suppressive therapy. METHODS: Patients with gastro-oesophageal reflux disease and Barrett's oesophagus were prospectively evaluated by dual sensor 24-h pH monitoring while receiving proton pump inhibitor therapy for complete control of gastro-oesophageal reflux disease symptoms. Analyses and comparisons of intra-oesophageal and intra-gastric pH profiles on therapy were then made. RESULTS: One hundred and ten patients, 98 men and 12 women, with gastro-oesophageal reflux disease (n = 62) and/or Barrett's oesophagus (n = 48), were studied. All tolerated proton pump inhibitors well and were asymptomatic at the time of the study. Thirty-six (58%) patients with gastro-oesophageal reflux disease and 24 (50%) patients with Barrett's oesophagus (P = 0.4) normalized their intra-oesophageal pH profiles on proton pump inhibitors. Compared with patients with gastro-oesophageal reflux disease, patients with Barrett's oesophagus were more likely to have higher degree of pathologic acid reflux despite proton pump inhibitor therapy (DeMeester score 50.5 +/- 8.2 vs. 31.4 +/- 4.6, P = 0.03) and exhibited less intra-gastric acid suppression (% total pH < 4.0: 53.9 +/- 2.7 vs. 39.9 +/- 2.6, P = 0.0004), particularly supine (% pH < 4.0: 62.1 +/- 3.4 vs. 44.8 +/- 3.4, P = 0.0006). CONCLUSIONS: Gastro-oesophageal reflux disease patients with or without Barrett's oesophagus continue to exhibit pathologic gastro-oesophageal reflux disease and low intra-gastric pH despite proton pump inhibitor therapy that accomplishes complete reflux symptom control. Further, intra-oesophageal and intra-gastric pH control is significantly more difficult to achieve in patients with Barrett's oesophagus. These findings may have significant therapeutic implications.     

Circadian pattern of intragastric acidity in patients with non-erosive reflux disease (NERD)

BACKGROUND: Most patients with gastro-oesophageal reflux disease have non-erosive reflux disease. Proton pump inhibitors are less effective than expected in these patients, but no previous study has measured their 24-h gastric pH values. AIMS: To evaluate whether there are differences in 24-h intragastric acidity between reflux patients with and without oesophagitis and controls. The influence of Helicobacter pylori on the gastric pH of reflux patients was also assessed. METHODS: Sixty-three consecutive patients with gastro-oesophageal reflux disease symptoms who agreed to undergo endoscopy and 24-h pH-metry were recruited. Twenty-five (39%) had erosive oesophagitis and 38 (61%) did not. H. pylori was diagnosed by CLO test, histology and 13C-urea breath test. Gastric pH was also measured in 30 controls without digestive symptoms. RESULTS: H. pylori was found in seven of the 25 (28%) patients with oesophagitis and 14 of the 38 (37%) patients with non-erosive reflux disease. Oesophageal pH-metry was abnormal in 21 of the 25 (84%) patients with oesophagitis and in 32 of the 38 (84%) patients with non-erosive reflux disease. The median gastric pH did not differ between patients with and without oesophagitis or between them and controls during the 24 h (P = 0.8) and other time intervals (P = 0.2-0.4). The gastric pH did not differ between infected and non-infected patients with oesophagitis (P = 0.2-0.4) or non-erosive reflux disease (P = 0.3-0.8). CONCLUSIONS: The circadian pattern of intragastric acidity does not differ between patients with non-erosive reflux disease and oesophagitis. Moreover, the study confirms that H. pylori infection does not affect the gastric pH in either group of reflux patients.     

The role of the hiatus hernia in gastro-oesophageal reflux disease

A sliding hiatus hernia disrupts both the anatomy and physiology of the normal antireflux mechanism. It reduces lower oesophageal sphincter length and pressure, and impairs the augmenting effects of the diaphragmatic crus. It is associated with decreased oesophageal peristalsis, increases the cross-sectional area of the oesophago-gastric junction, and acts as a reservoir allowing reflux from the hernia sac into the oesophagus during swallowing. The overall effect is that of increased oesophageal acid exposure. The presence of a hiatus hernia is associated with symptoms of gastro-oesophageal reflux, increased prevalence and severity of reflux oesophagitis, as well as Barrett's oesophagus and oesophageal adenocarcinoma. The efficacy of treatment with proton pump inhibitors is reduced. Our view on the significance of the sliding hiatus hernia in gastro-oesophageal reflux disease has changed enormously in recent decades. It was initially thought that a hiatus hernia had to be present for reflux oesophagitis to occur. Subsequently, the hiatus hernia was considered an incidental finding of little consequence. We now appreciate that the hiatus hernia has major patho-physiological effects favouring gastro-oesophageal reflux and hence contributing to oesophageal mucosal injury, particularly in patients with severe gastro-oesophageal reflux disease.