Prevalence of acid reflux in functional dyspepsia and its association with symptom profile

AIM: A subset of functional dyspepsia patients respond to acid suppressive therapy, but the prevalence of non-erosive reflux disease in functional dyspepsia and its relevance to symptoms have never been established. The aim of the present study was to study 24 hour pH monitoring in consecutive functional dyspepsia patients. METHODS: A total of 247 patients with dyspeptic symptoms (166 women, mean age 44 (SEM 1) year), with a negative upper gastrointestinal endoscopy and without dominant symptoms of heartburn participated in the study. In all patients, the severity of dyspeptic symptoms and the presence of heartburn was assessed by a questionnaire and a 24 hour oesophageal pH monitoring study was performed. All patients underwent a gastric emptying breath test and in 113 a gastric barostat study was performed. RESULTS: Abnormal pH monitoring (acid exposure >5% of time) was found in 58 patients (23%). Of 21 patients with a positive heartburn questionnaire, 76% had pathological pH monitoring, while this was the case in only 18.5% of patients with a negative heartburn questionnaire. Demographic characteristics and the prevalence of other pathophysiological mechanisms did not differ between heartburn negative patients with normal or abnormal acid exposure. Pathological acid exposure in heartburn negative patients was associated with the presence of epigastric pain (65 v 84%, p<0.005) and of moderate or severe pain (48 v 69%, p = 0.005). CONCLUSION: Pathological oesophageal acid exposure is only present in a subset of heartburn negative functional dyspepsia patients, which are characterised by a higher prevalence of epigastric pain.     

Importance of reflux symptoms in functional dyspepsia.

The relation between symptom severity in gastro-oesophageal reflux disease (GORD) and quantitated oesophageal acid reflux is variable. Furthermore, when oesophageal acid exposure lies within the conventional normal range, the cause of the symptoms is unknown. This prospective study evaluated 24 hour ambulatory oesophageal pH profiles in relation to objective symptom scores in 100 dyspeptic patients who were free from ulcer and gall stones. Twenty patients had raised oesophageal acid exposure and reflux symptoms consistent with GORD, and 80 had oesophageal pH profiles within the conventional normal range. Forty four of the 80 had severe or moderate reflux symptoms and were classified as having reflux like functional dyspepsia (RFD); 36 had minimal or absent reflux symptoms, and were categorised as having non-reflux dyspepsia (NFD). While oesophageal pH profiles lay within the conventional normal range in both functional dyspepsia subgroups, patients with RFD had consistently greater acid exposure values as follows: mean (SEM) total oesophageal acid exposure time, RFD 16.2 (2.56) min v NFD 9.05 (2.0) min (p < 0.03); percentage of time with pH < 4, RFD 1.4 (0.2) v NFD 0.8 (0.2) (p < 0.03); DeMeester scores, RFD 12.8 (0.5) v NFD 11.4 (0.4) (p < 0.03). The RFD group had a pain/reflux event correlation of 23.8 (5.3)% v 8.1 (3.7)% for the NFD group (p < 0.01). This study shows that patients with RFD have oesophageal acid exposure that lies below the diagnostic threshold for GORD, but exceeds that of patients with NFD. The high pain/reflux event correlation in RFD, suggests that subthreshold oesophageal acid exposure may be associated with troublesome reflux symptoms.     

4 Is functional dyspepsia largely explained by gastro-oesophageal reflux disease?

Functional dyspepsia is a chronic disorder of unknown aetiology. The lack of endoscopic abnormalities in patients with this disorder has led many physicians to believe that gastrooesophageal reflux disease may be responsible for most symptoms. Our group has addressed this issue, by pathophysiological studies in a large cohort of Dundee patients with persistent dyspeptic symptoms. Peptic ulcer and gallstones were excluded in all patients by appropriate tests. Ambulatory pH monitoring showed oesophageal acid reflux that lay above the conventional diagnostic threshold in approximately 20% of patients. This subset was diagnosed as having gastro-oesophageal reflux disease.In the remainder, moderate or severe reflux-like symptoms were reported by approximately 44% patients, who were categorized as reflux-like functional dyspepsia. Reflux symptoms were mild or absent in 36% patients, who were categorized as non-reflux-like dyspepsia. While oesophageal pH profiles lay within the conventional normal range in both of these functional dyspepsia subgroups, patients with reflux-like functional dyspepsia had significantly greater acid exposure values, including total oesophageal acid exposure time, percentage time at a pH of less than 4.0, DeMeester scores and pain reflux event correlation. Hence patients with reflux-like functional dyspepsia have oesophageal acid exposure that lies below the diagnostic threshold for gastro-oesophageal reflux disease but exceeds that of patients with non-reflux dyspepsia. The high pain/reflux event correlation in reflux-like functional dyspepsia suggests that subthreshold oesophageal acid exposure may be associated with troublesome reflux symptoms.     

Helicobacter pylori infection, pattern of gastritis, and symptoms in erosive and nonerosive gastroesophageal reflux disease.

BACKGROUND: The aim of this study was to evaluate the prevalence of Helicobacter pylori infection and the characteristics of gastritis and symptoms of patients with erosive and nonerosive gastroesophageal reflux disease (GERD). METHODS: We studied 202 consecutive patients with a diagnosis of GERD (symptoms score and endoscopy): group A (n = 110), erosive GERD; group B (n = 92), nonerosive GERD; 200 patients with upper abdominal complaints without abnormalities at endoscopy (functional dyspepsia, group C); and 200 asymptomatic controls tested for H. pylori serum antibody (group D). Antral and body biopsy specimens were taken for histology and the rapid urease test in groups A, B, and C. RESULTS: The prevalence of H. pylori infection was higher in groups B and C (62% and 55%, respectively) than in A and D (36% and 40%) (P < 0.05). In positive patients H. pylori colonization and gastritis grade scores in the gastric body were higher in nonerosive than in erosive GERD and functional dyspepsia (P < 0.05). No differences in H. pylori colonization or gastritis grades were found in the antrum. Fifty-nine patients with nonerosive GERD (64%) and 42 with erosive GERD (38%) showed other dyspeptic symptoms associated with reflux symptoms (P < 0.05). CONCLUSIONS: H. pylori prevalence is higher in patients with nonerosive GERD than in normal subjects and in patients with erosive GERD and similar to that of patients with dyspepsia. Patients with nonerosive GERD often show dyspeptic symptoms and higher H. pylori colonization and inflammation grades in the proximal stomach. Our data support the hypothesis that in GERD H. pylori gastritis may, on the one hand, protect against the development of esophageal erosions and, on the other, contribute to the esophageal hypersensitivity to acid which is a feature of GERD.     

Reflux related symptoms in patients with normal oesophageal exposure to acid.

Several studies, using pH monitoring with event markers, have identified patients with normal oesophageal exposure to acid despite an apparent relation between symptoms and reflux episodes. In this series of 771 consecutive patients referred for 24 hour oesophageal pH monitoring, a probability calculation was used to evaluate the relation between symptoms and reflux episodes. Oesophageal exposure to acid was normal in 462 of 771 recordings (59.9%); despite this, 70.8% (327 of 462) of these patients used at least once the event marker. In 96 patients (12.5% of total patients) with normal oesophageal exposure to acid, there was a statistically significant association between symptoms and reflux episodes. The symptom cluster of such patients was similar to that usually seen in patients with gastro-oesophageal reflux disease, but symptoms like belching, bloating, and nausea were common thus overlapping with the symptom pattern of functional dyspepsia. In these patients both the duration and the minimum pH of reflux episodes (either symptom related or asymptomatic) were significantly shorter and higher, respectively, when compared with those of patients with gastro-oesophageal reflux disease. These results are consistent with the idea that oesophageal hypersensitivity to acid is the underlying pathophysiological feature of this syndrome.     

6 Role of gastric acid in the aetiology of dyspeptic disease and dyspepsia

The main diseases associated with dyspepsia are peptic ulcer disease, gastro-oesophageal reflux disease and non-ulcer dyspepsia. Increased gastric acid secretion is a characteristic of most duodenal ulcer patients and of a small minority of non-ulcer dyspepsia and gastro-oesophageal reflux disease patients. Although acid secretion is normal in most gastro-oesophageal reflux disease patients, the condition is mainly the result of excess exposure of the distal oesophagus to acid refluxing from the stomach. Increased mucosal sensitivity to acid is involved in the aetiology of dyspeptic symptoms in the majority of patients with peptic ulcer disease and gastro-oesophageal reflux disease, and in a minority of non-ulcer dyspepsia subjects. Gastric acid, therefore, plays an important role in both the aetiology of dyspeptic diseases and in the aetiology of dyspeptic symptoms.     

Acid clearance and oesophageal sensitivity in patients with progressive systemic sclerosis.

This study examined the hypothesis that impaired oesophageal peristalsis was associated with delayed oesophageal clearance of acid in patients with progressive systemic sclerosis (PSS), some of whom are thought to have impaired oesophageal sensitivity to acid. Sixteen patients with PSS had: (a) oesophageal manometry and endoscopy; (b) acid perfusion of the oesophagus with simultaneous measurement of intraoesophageal pH during perfusion and for the next 10 minutes; (c) 22 hour monitoring of intraoesophageal pH; and (d) an evaluation of reflux symptoms during and after perfusion and during overnight pH monitoring. By oesophageal manometry, eight patients had normal peristalsis and eight patients had impaired peristalsis. Oesophageal endoscopy was unremarkable in patients with normal peristalsis, whereas all patients with impaired peristalsis had oesophagitis. The time needed to clear the oesophagus of perfused acid was shorter (p < 0.01) in patients with normal peristalsis and acid clearance time was significantly correlated (p < 0.01) with acid exposure time during overnight pH monitoring. During and after oesophageal perfusion, the nature, duration, and severity of symptoms did not differ between the groups, but overnight symptoms lasted longer (p < 0.05) in patients with impaired peristalsis. It is concluded that in PSS: (1) Impaired oesophageal motility delayed the clearance of acid and increased the exposure time to acid. (2) Acid clearance time is a useful parameter of impaired oesophageal motor function. The assessment of acid clearance time can be used as an alternative to overnight pH monitoring, to assess the impairment of oesophageal acid clearance. (3) Oesophageal sensitivity to acid was preserved in patients with impaired peristalsis and oesophagitis. (4) Reflux symptoms lasted longer in patients with prolonged oesophageal acid exposure but were still reported for a small fraction of the total acid exposure time. Thus, reflux symptoms reflect poorly prolonged exposure of the oesophagus to acid and are not a reliable guide to acid injury of the oesophagus in PSS.     

Helicobacter pylori Infection,Pattern of Gastritis,and Symptoms in Erosive and Nonerosive Gastroesophageal Reflux Disease

Background: The aim of this study was to evaluate the prevalence of Helicobacter pylori infection and the characteristics of gastritis and symptoms of patients with erosive and nonerosive gastroesophageal reflux disease (GERD). Methods: We studied 202 consecutive patients with a diagnosis of GERD (symptoms score and endoscopy): group A (n = 110), erosive GERD; group B (n = 92), nonerosive GERD; 200 patients with upper abdominal complaints without abnormalities at endoscopy (functional dyspepsia, group C); and 200 asymptomatic controls tested for H. pylori serum antibody (group D). Antral and body biopsy specimens were taken for histology and the rapid urease test in groups A, B, and C. Results: The prevalence of H. pylori infection was higher in groups B and C (62% and 55%, respectively) than in A and D (36% and 40%) (P &lt; 0.05). In positive patients H. pylori colonization and gastritis grade scores in the gastric body were higher in nonerosive than in erosive GERD and functional dyspepsia (P &lt; 0.05). No differences in H. pylori colonization or gastritis grades were found in the antrum. Fifty-nine patients with nonerosive GERD (64%) and 42 with erosive GERD (38%) showed other dyspeptic symptoms associated with reflux symptoms (P &lt; 0.05). Conclusions: H. pylori prevalence is higher in patients with nonerosive GERD than in normal subjects and in patients with erosive GERD and similar to that of patients with dyspepsia. Patients with nonerosive GERD often show dyspeptic symptoms and higher H. pylori colonization and inflammation grades in the proximal stomach. Our data support the hypothesis that in GERD H. pylori gastritis may, on the one hand, protect against the development of esophageal erosions and, on the other, contribute to the esophageal hypersensitivity to acid which is a feature of GERD.     

Does this patient have oesophageal motility abnormality or pathological acid reflux?

BACKGROUND AND AIMS: The diagnostic values of particular symptoms centred on oesophagus, among patients with suspected oesophageal motility abnormality or pathological acid exposure, are not yet fully understood. The aim of this study was to determine the predictive accuracy of these symptoms in diagnosis of oesophageal motility disorder or pathological acid exposure. PATIENTS AND METHODS.: A total of 462 patients who had undergone conventional oesophageal manometry and ambulatory 24-h pH monitoring to investigate a clinical suspicion of oesophageal motility disorder and pathological acid exposure were enrolled in this study. According to their principal complaints, the patients were divided into the dysphagia category, the non-cardiac chest pain category, the gastrooesophageal reflux disease-related symptom category and the extraoesophageal symptom category. RESULTS: Two hundred and two (44%) out of 462 patients yielded abnormal findings on manometry and/or pH monitoring. Dysphagia was associated with a likelihood ratio (LR) of 2.11 [95% confidence interval (CI), 1.02-4.00)] in patients exhibiting a combination of oesophageal motility abnormality and pathological acid exposure. During oesophageal manometry, the dysphagia substantially increased the likelihood of classic achalasia (LR, 6.24; 95% CI, 3.32-8.78) and diffuse oesophageal spasm (LR, 3.58; 95% CI, 1.03-7.12). When the patients with dysphagia were divided into two groups according to the severity of their symptoms, classic achalasia was significantly frequent in patients with severe dysphagia (P = 0.016). On the other hand, non-cardiac chest pain was the clinical factor that reduced the likelihood of classic achalasia (LR, 0.22; 95% CI, 0.04-0.93). The distribution of pathological acid exposure was significantly frequent between the groups of patients with and without gastrooesophageal reflux disease-related symptom (P = 0.011). CONCLUSION: A small number of oesophageal symptoms are helpful in predicting the likelihood of abnormal findings on oesophageal tests among patients with a clinical suspicion of oesophageal motility disorder and pathological acid exposure. The most useful finding is a severe dysphagia, which is likely to have classic achalasia.     

Studies of acid exposure immediately above the gastro-oesophageal squamocolumnar junction: evidence of short segment reflux

BACKGROUND AND AIMS: Oesophageal pH is conventionally recorded from a point 5 cm above the lower oesophageal sphincter. However, the mucosal changes of reflux oesophagitis and intestinal metaplasia tend to affect the segment of oesophagus distal to this and close to the squamocolumnar junction. This study set out to investigate oesophageal acid exposure of squamous mucosa close to the squamocolumnar junction. METHODS: Dual channel 24 hour pH monitoring was carried out in 11 patients with endoscopy negative dyspepsia and no evidence of gastro-oesophageal reflux by conventional oesophageal pH metry. Oesophageal pH was recorded from electrodes positioned 5 mm and 55 mm proximal to the squamocolumnar junction. A novel technique was developed using metal clips to secure the pH catheter to the oesophageal mucosa and maintain these electrode positions. Oesophageal manometry indicated that the distal electrode was within the high pressure zone of the lower oesophageal sphincter. RESULTS: We found that 24 hour oesophageal acid exposure (per cent time pH <4) was greater 5 mm above the squamocolumnar junction compared with the conventional position 5 cm more proximal (11.7% v 1.8%; p<0.001). The greater acid exposure at the distal versus the conventional site was apparent in both the upright (12.7% v 2.3%) and supine (10.5% v 1.3%) positions, as well as during preprandial (14.2% v 1.6%) and postprandial (21.8% v 2.8%) periods (p<0.001 for each). The number of reflux events recorded close to the squamocolumnar junction was also higher than at the conventional position (168 v 33; p<0.001). There was no correlation between acid exposure at the two sites. CONCLUSIONS: The squamous mucosa of the most distal oesophagus is exposed to substantial acidic reflux, even in patients without evidence of conventional reflux disease. This short segment reflux may explain the high incidence of metaplasia and neoplasia at the gastro-oesophageal junction.     

Value of the 24 hour intraoesophageal pH monitoring in children.

Twenty four hour oesophageal intraluminal pH probe studies were performed in 114 children (range age: one month-12 years) referred for symptoms or signs compatible with gastroesophageal reflux. Forty five patients had reflux disease alone, 69 had evidence of oesophagitis which was assessed endoscopically and histologically. Recordings were also performed in 63 control patients. The occurrence of reflux was analysed for the total study period and particularly while awake, asleep, fasting, and during postcibal periods. Oesophageal acid exposure time and the number of reflux episodes lasting greater than five minutes during the total study period provided the best discrimination between patients and controls; however, 20% and 30% of all reflux patients had both normal (with 2 SD of control) acid exposure time and number of long lasting reflux episodes, respectively. Patients with oesophagitis had significantly more acid reflux than those with simple uncomplicated disease during postcibal, fasting, awake periods, but not during sleep; however, increasing severity of oesophagitis was not associated with increasing acid exposure. The ability of the intraluminal oesophageal pH test to discriminate patients with various degrees of reflux disease decreased if only postprandial pH variables were taken into account. We conclude that: (1) the 24 hour intraoesophageal pH monitoring may present false negative results that limit overall sensitivity of the test; (2) the presence of oesophagitis does not seem to be associated with increased oesophageal acid exposure during sleep; (3) limiting the pH recording to postprandial periods reduces the discriminatory power of the test.     

Belching: dyspepsia or gastroesophageal reflux disease?

OBJECTIVES: Eructation (belching) is a common symptom seen in clinical practice. Because either belching or heartburn may result from transient lower esophageal sphincter relaxations, it has been proposed that belching may be a manifestation of gastroesophageal reflux disease (GERD). In this retrospective study we evaluated the prevalence of belching in dyspepsia and GERD and the relation of belching to acid reflux events documented by pH monitoring. METHODS: We examined the prevalence, frequency, and severity of belching and other GERD symptoms by use of standardized questionnaires in 180 GERD patients (group A) and 78 dyspeptic controls (group B) referred for evaluation at our institution. GERD was defined as either endoscopic esophagitis (or Barrett's esophagus) or positive DeMeester score (>14.2) on pH monitoring or both. Dyspeptic patients had normal endoscopy and pH studies. We also analyzed the relationship of belching to acid reflux events during the 24-h period of pH studies. RESULTS: Of 180 GERD patients, 132 (70%) reported belching during pH monitoring, versus 63 of 78 dyspeptic patients (80%) (p = ns). Similarly, 163 of 180 GERD patients (90%) reported heartburn versus 64 of 78 of dyspeptic patients (82%) (p = ns). Review of symptom questionnaires revealed no significant difference in belching severity between groups. However, heartburn and acid regurgitation were significantly more severe among GERD patients. There was a significantly higher correlation of both heartburn and belching with acid events in patients with GERD compared with patients with dyspepsia. In addition, although both belching and heartburn were significantly improved in patients with GERD, belching scores remained unchanged after proton pump inhibitor (PPI) therapy in patients with dyspepsia. CONCLUSIONS: Belching is as common and as severe in patients with dyspepsia as it is in patients with GERD. Belching and heartburn in GERD patients are more likely correlated with episodes of pathological acid reflux. Because belching cannot be clinically used as a discriminatory symptom, ambulatory pH monitoring should be considered to elucidate the relationship of belching to acid reflux in patients with dyspepsia or GERD.     

A pilot study on duodenal acid exposure and its relationship to symptoms in functional dyspepsia with prominent nausea

BACKGROUND: Duodenal hypersensitivity to acid and decreased duodenal clearance of exogenous acid have been reported in functional dyspepsia (FD). However, the relevance of these abnormalities to spontaneous duodenal acid exposure and dyspeptic symptoms in FD is unknown. AIMS: To determine spontaneous duodenal acid exposure and its relationship with symptoms, duodenal sensitivity to acid, and the effects of a 5-HT(3) receptor antagonist on duodenal responses to acid in FD. METHODS: Eleven FD patients with prominent nausea and 11 healthy controls underwent 24-h ambulatory duodenal pH monitoring with assessment of dyspeptic symptoms. On the next day, duodenal bolus infusions of 5 ml of acid and normal saline were given in a randomized double-blind manner and repeated after ondansetron or a placebo. RESULTS: Nighttime duodenal acid exposure was similar, but FD patients had lower duodenal pH and higher duodenal % time (pH < 4) than controls during the daytime and in the second postprandial 2 h (p < 0.05). Seven patients (64%) with duodenal acid exposure above the normal range had higher severity scores for several dyspeptic symptoms including nausea. However, the symptom severity was poorly or weakly correlated to duodenal pH, and brief duodenal acid infusion did not affect any symptoms. Duodenal responses to exogenous acid were unaffected by 5-HT(3) receptor antagonism. CONCLUSIONS: Spontaneous duodenal acid exposure is increased in a subset of FD patients with prominent nausea, and this is associated with more severe dyspeptic symptoms. However, a direct relationship between duodenal acid exposure and symptom severity is lacking.     

Patients with functional dyspepsia responding to omeprazole have a characteristic gastro-oesophageal reflux pattern.

BACKGROUND: The effect of acid secretion inhibitors in patients with functional dyspepsia (FD) is equivocal. One previous trial showed an effect in patients with a characteristic gastro-oesophageal reflux pattern. This double-blind trial compares the number of reflux episodes in responders and non-responders to omeprazole. METHODS: Twenty-four patients (men/women, 11:13; mean age, 49 years) with FD were included; those with reflux as the main symptom were excluded. An upper endoscopy and a 24-h oesophageal pH measurement were performed before randomization to treatment with 10-20 mg omeprazole or placebo for 4 weeks. Patients who at questioning considered themselves to have achieved sufficient relief of dyspeptic symptoms after 4 weeks were characterized as responders. RESULTS: The number of responders in the omeprazole and placebo groups was 8 of 14 (57%) and 2 of 10 (20%), respectively (P = 0.07). The mean number of reflux episodes at the 24-h oesophageal pH measurement in responders and non-responders to omeprazole was 57 and 25, respectively (P < 0.003). In the omeprazole group the number of responders was 0 of 5 (0%) in those with < 32 reflux episodes and 8 of 9 (89%) in those with > 32 reflux episodes (P < 0.003). CONCLUSION: Patients with FD responding to omeprazole were characterized by many reflux episodes.     

Dyspepsia in primary care: acid suppression as effective as prokinetic therapy. A randomized clinical trial

BACKGROUND: While dyspeptic patients in primary care often receive empirical treatment with antisecretory drugs, a substantial number suffer from motility disturbances which may be associated with their complaints. We aimed to compare the effectiveness of treatment with antisecretory treatment with a prokinetic agent in uninvestigated dyspepsia. METHODS: 563 patients presenting dyspeptic complaints to the general practitioner with a low likelihood of organic (ulcer, reflux or malignant) disease, i.e. absence of alarm symptoms or a history of peptic ulcer disease or gastro-oesophageal reflux disease were included. They entered a randomized, double-blind trial of 4 weeks of ranitidine 150 mg bid compared with 4 weeks of cisapride 10 mg bid, with 3 months follow-up. Treatment failure was defined as no response to treatment or a relapse of symptoms within the follow-up period. Also studied were the effect on dyspepsia severity, response to treatment after 4 weeks, and time to relapse. RESULTS: For all randomized patients, the incidence of overall treatment success after 3 months follow-up with antisecretory treatment was 107/271 (39.5%) and with a prokinetic agent 122/282 (43.3%); the risk difference was 3.8% (95% CI -4.4% to 12.0%); the difference in symptom severity score after 4 weeks of treatment was 0.3; 95% CI -0.4% to 1.0%. For patients responding to 4 weeks of treatment, relapse-free time was 86 days in the prokinetic group and 79 days in the acid suppression group (P = 0.005). CONCLUSIONS: Antisecretory and prokinetic therapies are equally effective in primary care patients with uninvestigated dyspeptic complaints, though relapse rates are lower in patients treated with prokinetic treatment.     

Symptom severity and oesophageal chemosensitivity to acid in older and young patients with gastro-oesophageal reflux

INTRODUCTION: elderly patients appear to have a more aggressive form of gastro-oesophageal reflux disease than younger patients. Reduced pain perception with age is a possible underlying mechanism. AIMS: to compare the extent of oesophageal mucosal injury, acid exposure, symptom severity and perception thresholds for acid infusion in older (aged 60 or older) and younger patients with gastro-oesophageal reflux. METHODS: twenty-five younger and 23 older patients completed the study. We determined acid exposure and oesophageal mucosal injury by ambulatory 24-h oesophageal pH monitoring and upper endoscopy, respectively. We determined chemosensitivity by infusing 0.1 N hydrochloric acid into the mid-oesophagus for 10 min at 10 ml/min after a 2-min infusion of normal saline at a similar rate. We quantified acid perception thresholds by the lag time to initial typical symptom perception, intensity rating at the end of acid infusion and an acid perfusion sensitivity score, calculated from the fractional duration of symptom perception and intensity rating. RESULTS: mean percentage of total time with pH <4 was higher in the older (15.8+/-2.4) than in the younger patients (11.9+/-1.8; P = 0.18). Of the older group, 74% had erosive oesophagitis versus 64% in the younger group. Frequency of symptoms (heartburn, acid regurgitation and dysphagia) was lower in the elderly group. Older patients perceived heartburn and acid regurgitation as much less severe than younger patients (P < 0.05).Younger patients had a significantly shorter lag time to initial symptom perception (P < 0.05) and a higher sensory intensity rating (P < 0.08). The acid perfusion sensitivity score was significantly lower in the older group (P < 0.05). CONCLUSIONS: older patients with gastro-oesophageal reflux disease have reduced symptom severity for heartburn despite a tendency towards increased severity of oesophageal mucosal injury and acid exposure. Age-related reduction in chemosensitivity to acid is a possible underlying mechanism.     

Diagnostic value of histology in non-erosive gastro-oesophageal reflux disease.

BACKGROUND: In the absence of oesophageal erosions longterm pH monitoring is the present gold standard for diagnosing gastro-oesophageal reflux disease (GORD). This method, however, is invasive, time consuming, expensive, and not generally available. AIMS: As histological changes have been described in GORD, this study looked at the possibility of whether the diagnosis of non-erosive reflux disease could be made by histological examination routinely during endoscopy. SUBJECTS: A total of 24 prospectively selected patients with symptoms suggestive of GORD and seven healthy volunteers. METHODS: Oesophageal erosions and other peptic lesions were excluded by oesophago-gastroduodenoscopy. Oesophageal pinch biopsy specimens were taken 2 cm and 5 cm above the oesophagogastric junction and evaluated blindly for the histological parameters cellular infiltration, basal zone hyperplasia, and papillary length. Twenty four hour pH monitoring was used as gold standard for the definition of reflux disease. It was abnormal in 13 patients (reflux patients) and normal in 11 patients (symptomatic controls) and in seven healthy volunteers. RESULTS: Sparse infiltration of the epithelium with lymphocytes in at least one biopsy specimen was found in all patients and volunteers, with neutrophils in three reflux patients, and with eosinophils in two reflux patients and in two healthy volunteers. The basal zone thickness was increased in three reflux patients, in one symptomatic control, and in one healthy volunteer. The papillary length was greater than two thirds of total epithelium in six of 13 reflux patients in contrast with none in 11 symptomatic controls (p < 0.05) and to one healthy volunteer. The sensitivity of the parameter papillary length hence was only 46%. CONCLUSIONS: Although gastro-oesophageal reflux produces slight histological changes apart from oesophageal erosions in a few subjects, none of the established histological parameters can fulfil the for the diagnosis of GORD in patients without visible oesophageal erosions.     

Patients with Functional Dyspepsia Responding to Omeprazole Have a Characteristic Gastro-oesophageal Reflux Pattern

Background: The effect of acid secretion inhibitors in patients with functional dyspepsia (FD) is equivocal. One previous trial showed an effect in patients with a characteristic gastro-oesophageal reflux pattern. This double-blind trial compares the number of reflux episodes in responders and non-responders to omeprazole. Methods: Twenty-four patients (men/women, 11:13; mean age, 49 years) with FD were included; those with reflux as the main symptom were excluded. An upper endoscopy and a 24-h oesophageal pH measurement were performed before randomization to treatment with 10-20 mg omeprazole or placebo for 4 weeks. Patients who at questioning considered themselves to have achieved sufficient relief of dyspeptic symptoms after 4 weeks were characterized as responders. Results: The number of responders in the omeprazole and placebo groups was 8 of 14 (57%) and 2 of 10 (20%), respectively (P = 0.07). The mean number of reflux episodes at the 24-h oesophageal pH measurement in responders and non-responders to omeprazole was 57 and 25, respectively (P     

Can symptoms discriminate among those with delayed or normal gastric emptying in dysmotility-like dyspepsia?

OBJECTIVE: Different subgroups can be identified in functional dyspepsia based on symptom type or severity, and may correlate with pathophysiological disturbances. In particular, female sex and severe fullness and vomiting have been reported to be strong independent predictors of slow solid gastric emptying. We aimed to determine if symptom patterns or severity could identify those with abnormal gastric emptying among patients with dysmotility-like functional dyspepsia and, for comparison, type I diabetes mellitus. METHODS: Patients with postprandial symptoms and documented functional dyspepsia by endoscopy (n = 551) and patients with type I diabetes who had postprandial dyspepsia (n = 247) enrolling in two separate randomized controlled trials were evaluated at baseline. Patients were assigned to either the delayed or normal gastric emptying strata, based on a validated C13 octanoic acid breath test with sampling over 4 h. A self-report questionnaire measured the presence and severity of eight symptoms on visual analog scales. The validated Nepean Dyspepsia Index measured the frequency, severity, and bothersomeness of 15 upper GI symptoms on Likert scales. RESULTS: Gastric emptying was definitely delayed (t1/2 > 192 min) in 24% of patients with functional dyspepsia and 28% with diabetes. Delayed gastric emptying was associated with female gender but not age or Helicobacter pylori status. The age- and sex-adjusted risk (odds ratio) of delayed gastric emptying for the upper GI symptoms ranged from 0.99 to 1.0 (all p values > or =0.2). The results were very similar in functional dyspepsia and diabetes. There was also no correlation between t1/2 and number of symptoms or symptom severity scores. CONCLUSIONS: Symptom prevalence and severity were similar in dyspeptic patients with and without delayed gastric emptying. Specific symptoms do not seem to be of predictive value in dysmotility-like dyspepsia for identifying alterations of gastric emptying.     

A randomized,double-blind,placebo-controlled clinical study of the histamine H<Subscript>2</Subscript>-receptor antagonist famotidine in Japanese patients with nonerosive reflux disease

BACKGROUND: To investigate whether histamine H2-receptor antagonists are sufficient to treat heartburn in nonerosive reflux disease in Japanese, who produce less gastric acid than Westerners, the efficacy of famotidine in Japanese nonerosive reflux disease patients was studied in a double-blind, placebo-controlled, parallel group-comparative, multicenter study. METHODS: The Los Angeles classification system with Japanese modifications was used to assess the severity of nonerosive reflux disease. Famotidine (10-or 20-mg doses) or placebo was administered to patients twice daily for 8 weeks. Heartburn symptoms were recorded daily by patients. RESULTS: A total of 528 patients participated in the study. The percentage of days without heartburn, the primary end point of the efficacy evaluation, was 62% for 40 mg and 59% for 20 mg of famotidine, and 55% for placebo, with a statistically significant difference between the 40-mg dose and placebo (P = 0.001; significance level, 0.025 one-sided). Famotidine at both doses provided immediate relief from heartburn, and relief persisted throughout the 8-week study with the 40-mg dose. CONCLUSIONS: The results indicate that famotidine relieves heartburn symptoms in Japanese nonerosive reflux disease patients.