Twenty patients with bronchial asthma who also had gastro-oesophageal reflux were investigated. The severity of their reflux was graded using symptom score of heartburn and regurgitation and by the following investigations: barium swallow and meal, fibreoptic endoscopy and biopsy, manometry and pH monitoring of the distal oesophagus, and an acid infusion test. Full lung function studies were performed and patients were entered into a double-blind crossover study using cimetidine to control their reflux in order to assess beneficial effects with respect to their respiratory problems. Eighteen patients completed the study. Significant improvements were seen in reflux and night time asthmatic symptoms, both these indices being measured on a scoring system. Home monitoring of peak flow values showed a statistical improvement for th last peak flow reading of the day. Fourteen patients felt that their chest symptoms had significantly improved during the cimetidine period.
This study aimed to define the incidence and severity of gastro-oesophageal reflux (GOR), as measured using 24 hour oesophageal pH monitoring, in 38 infants with recurrent respiratory symptoms and to relate these findings to measures of respiratory function. Twenty one infants had a pH under 4 for more than 5% of the time (one definition of abnormal GOR) and nine had GOR exceeding age related normal values. Maximum expiratory flow at functional residual capacity was reduced in 37 infants, airways resistance was raised in 19 infants, and thoracic gas volume was abnormal in 11 infants. There was no association between indices of GOR and measures of lung function whether assessed by correlation or by chi 2 analysis for normal versus abnormal values. However, individual infants appeared to have respiratory symptoms produced by GOR. This suggests that host responsiveness to GOR may be of greater relevance than the amount of GOR.
Background—Associations have been shown between
irritable bowel syndrome (IBS) and gastro-oesophageal reflux, between
gastro-oesophageal reflux and asthma, and more recently between IBS and
bronchial hyper-responsiveness (BHR).
Aims—To explore the inter-relations between these conditions.
Subjects—A randomly selected community sample of
Methods—A validated postal symptom questionnaire
investigating the associations between IBS, gastro-oesophageal reflux
symptoms, and symptomatic BHR.
Results—3169 questionnaires (71.7%
response) returned by 1451 men and 1718 women were analysed. One year
prevalences, in men and women respectively, of IBS were 10.5% and
22.9%, of dyspepsia 26.3% and 25.25%, of gastro-oesophageal reflux
symptoms 29.4% and 28.2%, of BHR 13.2% and 14.6%, and of chronic
bronchitis 8.3% and 4.9%. Logistic regression showed independent
associations between IBS and BHR, gastro-oesophageal reflux symptoms,
and dyspepsia. There was no significant independent association between
IBS and chronic bronchitis. In men and women the odds ratio with 95%
confidence interval (CI) for IBS and gastro-oesophageal reflux symptoms
was 2.6 (2.1-3.1; p<0.001) and for IBS and BHR 2.1 (1.7-2.7;
p<0.001). These associations held on stratifying for sex and
consultation behaviour. IBS, gastro-oesophageal reflux symptoms, and
bronchial hyper-responsiveness occurred more frequently together than
expected, 2.5% (95% CI 2.41-2.57) of the sample having all three
conditions compared with an expected prevalence of 0.7% (95% CI
0.66-0.71). The conditions were independently associated with each other.
Conclusions—These observations may indicate the
presence of an underlying disorder producing symptoms in
gastrointestinal and respiratory systems.
irritable bowel syndrome; asthma; dyspepsia; gastro-oesophageal reflux; epidemiology
Background/Aim: The aetiology of gastro-oesophageal reflux is largely unknown. The authors’ aim was to examine the relation between lifestyle habits and gastro-oesophageal reflux symptoms.
Subjects: Participants of two consecutive public health surveys in Nord-Trondelag, Norway.
Methods: In a case control study within the two public health surveys, 3153 individuals who in the second survey reported severe heartburn or regurgitation during the last 12 months were defined as cases, while 40 210 people without reflux symptoms constituted the control group. The risk of reflux symptoms was estimated and multivariately calculated as odds ratios in relation to exposure to tobacco smoking, alcohol, coffee, tea, table salt, cereal fibres, and physical exercise.
Results: There was a significant dose response association between tobacco smoking and reflux symptoms. Among people who had smoked daily for more than 20 years the odds ratio was 1.7 (95% confidence interval 1.5 to 1.9) compared with non-smokers. A similar positive association was found for table salt intake. The odds ratio for reflux was 1.7 (95% CI 1.4 to 2.0) among those who always used extra table salt compared with those who never did so. We found moderately strong negative associations between the risk of reflux and exposure to coffee, bread high in dietary fibre content, and frequent physical exercise. Intake of alcohol or tea did not affect the risk of reflux.
Conclusions: Tobacco smoking and table salt intake seem to be risk factors for gastro-oesophageal reflux symptoms. Dietary fibres and physical exercise may protect against reflux. Alcohol, coffee, and tea do not seem to be risk factors for reflux.
gastro-oesophageal reflux; risk factor; aetiology; lifestyle; population based
The Bernstein test has been used as a test of oesophageal acid sensitivity for over 30 years but its clinical value has been challenged by the advent of ambulatory pH monitoring. Furthermore, the relation between mucosal acid sensitivity, symptomatic reflux, and abnormal oesophageal acid exposure time is unclear. This study examined the relation between these three parameters in patients referred for pH monitoring with unexplained chest pain or heartburn. Fifty consecutive patients were studied - nine with non-cardiac chest pain and 41 with a history of heartburn. Symptomatic reflux was defined as a greater than or equal to 50% temporal association between pain episodes and reflux events (pH less than 4) during pH monitoring. A positive acid perfusion test (in which the patient's usual symptoms were evoked by acid, though not saline) had a 100% sensitivity, 73% specificity, and 81% accuracy for the detection of symptomatic reflux. All 10 patients with symptomatic reflux during pH monitoring had evidence of mucosal acid sensitivity. A negative acid perfusion test made symptomatic reflux unlikely. However, symptomatic reflux or a positive acid perfusion test, or both, were found in some patients with a normal oesophageal acid exposure time during pH monitoring. Mucosal acid sensitivity, abnormal oesophageal acid exposure time, and symptomatic reflux should be regarded as separate, though related aspects of reflux disease. The Bernstein test is simple, safe, and easily performed. A positive test helps to identify an oesophageal cause of symptoms, particularly in patients in whom other aspects of 'gastro-oesophageal reflux disease' are absent, or who do not have symptoms during pH monitoring.
Gastro-oesophageal reflux disease is a condition in which the reflux of gastric contents into the oesophagus provokes symptoms or complications and impairs quality of life. Typical symptoms of gastro-oesophageal reflux disease are heartburn and regurgitation but gastro-oesophageal reflux disease has also been related to extra-oesophageal manifestations, such as asthma, chronic cough and laryngitis. The pathogenesis of gastro-oesophageal reflux disease is multifactorial, involving transient lower oesophageal sphincter relaxations and other lower oesophageal sphincter pressure abnormalities. As a result, reflux of acid, bile, pepsin and pancreatic enzymes occurs, leading to oesophageal mucosal injury. Other factors contributing to the pathophysiology of gastro-oesophageal reflux disease include hiatal hernia, impaired oesophageal clearance, delayed gastric emptying and impaired mucosal defensive factors. Hiatal hernia contributes to gastro-oesophageal reflux disease by promoting lower oesophageal sphincter dysfunction. Impaired oesophageal clearance is responsible for prolonged acid exposure of the mucosa. Delayed gastric emptying, resulting in gastric distension, can significantly increase the rate of transient lower oesophageal sphincter relaxations, contributing to postprandial gastro-oesophageal reflux disease. The mucosal defensive factors play an important role against development of gastro-oesophageal reflux disease, by neutralizing the backdiffusion of hydrogen ion into the oesophageal tissue. While the pathogenesis of oesophageal symptoms is now well known, the mechanisms underlying extra-oesophageal airway manifestations are still poorly understood. Two hypotheses have been proposed: direct contact of gastric acid with the upper airway and a vago-vagal reflex elicited by acidification of the distal oesophagus, leading to bronchospasm. In conclusion, gastro-oesophageal reflux disease can be considered as the result of a complex interplay of factors, all promoting the contact of gastric acidic contents with the oesophageal mucosa, leading to different degrees of oesophageal damage.
Gastro-oesophageal reflux; Aetiology; Physiopatology
Background and aim
Gastro‐oesophageal reflux disease (GORD) has been linked to a number of extra‐esophageal symptoms and disorders, primarily in the respiratory tract. This systematic review aimed to provide an estimate of the strength and direction of the association between GORD and asthma.
Studies that assessed the prevalence or incidence of GORD in individuals with asthma, or of asthma in individuals with GORD, were identified in Medline and EMBASE via a systematic search strategy.
Twenty‐eight studies met the selection criteria. The sample size weighted average prevalence of GORD symptoms in asthma patients was 59.2%, whereas in controls it was 38.1%. In patients with asthma, the average prevalence of abnormal oesophageal pH, oesophagitis and hiatal hernia was 50.9%, 37.3% and 51.2%, respectively. The average prevalence of asthma in individuals with GORD was 4.6%, whereas in controls it was 3.9%. Pooling the odds ratios gave an overall ratio of 5.5 (95% CI 1.9–15.8) for studies reporting the prevalence of GORD symptoms in individuals with asthma, and 2.3 (95% CI 1.8–2.8) for those studies measuring the prevalence of asthma in GORD. One longitudinal study showed a significant association between a diagnosis of asthma and a subsequent diagnosis of GORD (relative risk 1.5; 95% CI 1.2–1.8), whereas the two studies that assessed whether GORD precedes asthma gave inconsistent results. The severity–response relationship was examined in only nine studies, with inconsistent findings.
This systematic review indicates that there is a significant association between GORD and asthma, but a paucity of data on the direction of causality.
Nocturnal gastro-oesophageal reflux is known to be particularly damaging to the oesophageal mucosa, being associated with stricture formation and columnarisation. At present, this can only be detected by prolonged intra-oesophageal pH monitoring. A total of 50 patients with endoscopic oesophagitis were evaluated by ambulatory pH monitoring to detect the presence of nocturnal reflux. Whether certain symptoms in the presence of a hiatal hernia would identify those patients with reflux at night was investigated. Thirty-three patients had nocturnal reflux, two-thirds of whom had a hiatal hernia. Heartburn at night was of limited value (specificity = 65%) in detecting acid reflux whereas regurgitation and cough showed greater specificity (88% and 100% respectively) but lacked sensitivity (45% and 12% respectively). The combination of nocturnal symptoms and a hiatal hernia in patients with endoscopic oesophagitis correctly identified 58% of patients with nocturnal reflux and was highly specific (100%). This study has confirmed that symptoms and endoscopic findings can detect a significant proportion of 'at risk' patients, but the remainder will require pH monitoring to assess their pattern of acid exposure.
BACKGROUND--An association between asthma and gastro-oesophageal reflux is well recognised but the underlying mechanism is unclear. One suggestion is that gastric juice is aspirated into the tracheal and upper airways but detection of these events is difficult and involves radioisotopic studies. A new method of making direct measurements of tracheal and oesophageal pH over a 24 hour period is described, together with its application to patients with asthma. METHODS--The technique involves insertion of simultaneous tracheal and oesophageal pH probes under general anaesthesia. Continuous monitoring of pH over a 24 hour period is possible, permitting comparison with peak flow readings during wakefulness and at night should the patient be disturbed. Representative data from four patients with asthma (mean FEV1 62% predicted) and symptomatic gastro-oesophageal reflux, together with data from three non-asthmatics, is presented. RESULTS--Thirty seven episodes of gastro-oesophageal reflux lasting more than five minutes were recorded. Of these, five were closely followed by a fall in tracheal pH from a mean (SE) of 7.1 (0.2) to 4.1 (0.4) and a fall in peak expiratory flow (PEFR) of 84 (16) l/min. When gastro-oesophageal reflux occurred without tracheal aspiration the fall in PEFR was 8 (4) l/min. CONCLUSIONS--This new technique was well tolerated and allowed quantitation of the number, duration, and timing of episodes of tracheal micro-aspiration. Unlike acid reflux without aspiration, these events appear to be related to significant acute changes in lung function in asthmatic patients. Further studies with this new method may elucidate the role of gastro-oesophageal reflux in asthma.
Some patients undergoing ambulatory oesophageal pH monitoring to investigate symptoms suggestive of gastro-oesophageal reflux disease (GORD) are found to have oesophageal acid exposure within the physiological range but show a close correlation between their symptoms and individual reflux episodes. It is suggested that these patients might exhibit enhanced oesophageal sensation, akin to the heightened perception of both physiological and provocative stimuli in the gut that has been described in patients with functional gastrointestinal disorders. This study tested the hypothesis by measuring the sensory thresholds for oesophageal balloon distension and discomfort in 20 patients with symptoms of GORD, in whom ambulatory pH monitoring had shown normal acid exposure times, but in whom the symptom index for reflux events was 50% or greater, and compared these with 15 healthy volunteer controls, and with control groups with confirmed excess reflux. The study group showed lower thresholds both for initial perception of oesophageal distension, and for discomfort, compared with healthy controls (median ml (range)); 7.5 (2-19) v 12 (6-30) (p = 0.002) and 10 (5-20) v 16 (8-30) (p < 0.0001), respectively. Sensory thresholds in the study group were also significantly lower than in patients with excess reflux, and than patients with Barrett's oesophagus, who also exhibited significantly higher sensory thresholds than healthy controls. No differences in sensory thresholds for somatic nerve stimulation were found between the study group and health controls. The results show a spectrum of visceral sensitivity in GORD, with enhanced oesophageal sensation in patients with symptomatic but not excess gastro-oesophageal reflux, suggesting that their symptoms result from a heightened perception of normal reflux events.
Background: Epidemiological studies have shown an association between gastro-oesophageal reflux disease (GORD) and asthma, and oesophageal acid perfusion may cause bronchial constriction. However, no causative relation has been proven.
Aim: To assess whether acid suppression would lead to reduced asthma symptoms in children with concomitant asthma and GORD.
Methods: Thirty eight children (mean age 10.8 years, range 7.2–16.8; 29 males) with asthma and a reflux index ⩾5.0 assessed by 24 hour oesophageal pH monitoring were randomised to 12 weeks of treatment with omeprazole 20 mg daily or placebo. The groups were similar in age, gender, mean reflux index, and asthma severity. Primary endpoints were asthma symptoms (daytime wheeze, symptoms at night, in the morning, and during exercise) and quality of life (PAQLQ). Secondary endpoints were changes in lung function and the use of short acting bronchodilators. At the end of the study a repeated pH study was performed to confirm the efficacy of acid suppression.
Results: The change in total symptom score did not differ significantly between the omeprazole and the placebo group, and decreased by 1.28 (95% CI –0.1 to 2.65) and 1.28 (95% CI –0.72 to 3.27) respectively. The PAQLQ score increased by 0.62 (95% CI 0.29 to 0.95) in the omeprazole group compared to 0.50 (95% CI 0.29 to 0.70) in the placebo group. Change in lung function and use of short acting bronchodilators were similar in the groups. The acid suppression was adequate (reflux index <5.0) under omeprazole treatment.
Conclusion: Omeprazole treatment did not improve asthma symptoms or lung function in children with asthma and GORD.
Forty eight patients with moderate to severe asthma were enrolled in a double blind crossover study designed to evaluate the effects of ranitidine treatment, 150 mg twice daily for four weeks, on gastro-oesophageal reflux, asthma control, and bronchial reactivity. All 48 had a history of reflux symptoms and 27 had in addition reflux associated respiratory symptoms. Thirty two patients had objective evidence of acid reflux on 24 hour pH monitoring (pH of less than 4 for more than 1% of the 24 hours) and 27 patients had a positive result in the acid perfusion test. Reflux symptoms were significantly improved after ranitidine treatment. Ranitidine treatment was associated with modest improvements in nocturnal asthma and daily use of inhaled bronchodilator drugs but there was no significant change in bronchial reactivity, lung function, peak flow, or the number of eosinophils in the blood. Comparisons between the effect of ranitidine treatment on asthma control were performed between patients with and without a history of reflux associated respiratory symptoms, with and without a positive result in the acid perfusion test, and with and without objective evidence of gastro-oesophageal reflux. A history of reflux associated respiratory symptoms was the only factor that predicted an improvement in asthma control after ranitidine treatment. These results indicate that antireflux treatment will produce only small improvements in asthma control in asthmatic patients with a history of gastro-oesophageal reflux.
Symptomatic assessment and oesophageal investigations were done in 25 consecutive patients with the irritable bowel syndrome attending a gastroenterological clinic. Symptoms of gastro-oesophageal reflux, dysphagia, and a globus sensation were significantly commoner than in a control group of fracture clinic patients. Ambulatory oesophageal pH monitoring showed clearly abnormal reflux in 11 of 22 patients (50%). Nine patients had macroscopic endoscopic changes and a further 11 biopsy changes alone, of oesophagitis which was thus present in 80% overall. Lower oesophageal sphincter pressure was significantly less in irritable bowel patients than in age and sex matched controls, but upper oesophageal sphincter pressure was comparable in the two groups and disordered peristalsis was not found. Oesophageal symptoms in the irritable bowel syndrome are mainly caused by gastro-oesophageal reflux predisposed to by a subnormal lower oesophageal sphincter pressure, rather than by oesophageal spasm.
Gastro-oesophageal reflux disease (GORD) symptoms are common in asthma and have been extensively studied, but less so in the Asian continent. Reflux-associated respiratory symptoms (RARS) have, in contrast, been little-studied globally. We report the prevalence of GORD symptoms and RARS in adult asthmatics, and their association with asthma severity and medication use.
A cross-sectional analytical study. A validated interviewer-administered GORD scale was used to assess frequency and severity of seven GORD symptoms. Subjects were consecutive asthmatics attending medical clinics. Controls were matched subjects without respiratory symptoms.
The mean (SD) composite GORD symptom score of asthmatics was significantly higher than controls (21.8 (17.2) versus 12.0 (7.6); P < 0.001) as was frequency of each symptom and RARS. Prevalence of GORD symptoms in asthmatics was 59.4% (95% CI, 59.1%-59.6%) versus 28.5% in controls (95% CI, 29.0% - 29.4%). 36% of asthmatics experienced respiratory symptoms in association with both typical and atypical GORD symptoms, compared to 10% of controls (P < 0.001). An asthmatic had a 3.5 times higher risk of experiencing a GORD symptom after adjusting for confounders (OR 3.5; 95% CI 2.5-5.3). Severity of asthma had a strong dose-response relationship with GORD symptoms. Asthma medication use did not significantly influence the presence of GORD symptoms.
GORD symptoms and RARS were more prevalent in a cohort of Sri Lankan adult asthmatics compared to non-asthmatics. Increased prevalence of RARS is associated with both typical and atypical symptoms of GORD. Asthma disease and its severity, but not asthma medication, appear to influence presence of GORD symptoms.
To evaluate the associations between abdominal obesity and gastro‐oesophageal reflux disease (GORD), and their interactions with ethnicity and gender.
A cross‐sectional study. Participants completed detailed symptom questionnaires and underwent a standardised examination, including anthropometric measurements.
A large integrated healthcare system.
80 110 members of the Kaiser Permanente multiphasic health check‐up cohort.
Main outcome measures
Gastro‐oesophageal reflux‐type symptoms.
Recent reflux‐type symptoms were present in 11% of the population. The multivariate OR for symptoms with an abdominal diameter (adjusted for body mass index (BMI)) of ⩾26 vs <16.3 cm was 1.85 (95% CI 1.55 to 2.21) for the white population, 0.95 (95% CI 0.61 to 1.48) for the black population and 0.64 (95% CI 0.18 to 2.30) for Asians. The mean abdominal diameter was greater in men (22.0 cm, 95% CI 21.9 to 22.0) than in women (20.1 cm, 95% CI 20.0 to 20.1, p<0.01), but the risk of symptoms for any given diameter did not differ markedly by gender. The association between increasing BMI and symptoms was also much stronger among the white population than among the black population. The association between BMI and reflux‐type symptoms was partially mediated through abdominal diameter.
There was a consistent association between abdominal diameter (independent of BMI) and reflux‐type symptoms in the white population, but no consistent associations in the black population or Asians. The BMI association was also strongest among the white population. These findings, combined with the increased prevalence of abdominal obesity in male subjects, suggest that an increased obesity may disproportionately increase GORD‐type symptoms in the white population and in male subjects.
BACKGROUND—There is a widespread notion that obesity leads to gastro-oesophageal reflux but scientific evidence of an association is limited and inconsistent.
AIMS—To estimate the strength of the association between body mass and reflux symptoms, we performed a population based cross sectional interview study.
SUBJECTS—Population based, randomly selected, middle aged or elderly persons in Sweden in 1995-1997.
METHODS—At face-to-face interviews we asked a stratified sample of Swedes about body measures and occurrence of reflux symptoms. Odds ratios (OR) with 95% confidence intervals (CI), calculated by logistic regression with multivariate adjustments for covariates, were the measures of association.
RESULTS—Reflux symptoms occurring at least once a week more than five years before the interview were reported by 135 (16%) of the 820 interviewees. Among those who had ever been overweight during adulthood (body mass index (BMI) ⩾25 kg/m2), the OR of having recurrent reflux symptoms was 0.99 (95% CI 0.66-1.47) compared with those who were never overweight. There was no association between BMI at age 20, BMI 20 years before the interview, or maximum adult BMI and occurrence of reflux symptoms: ORs per unit increase in BMI were 1.00 (95% CI 0.93-1.09), 1.03 (95% CI 0.96-1.10), and 1.01 (95% CI=0.95 1.07), respectively. There was no association between BMI and severity or duration of reflux symptoms.
CONCLUSIONS—Gastro-oesophageal reflux symptoms occur independently of body mass index. Weight reduction may not be justifiable as an antireflux therapy.
Keywords: gastro-oesophageal reflux; body mass index; obesity; population based study
Background: A number of families have been described which include multiple members with symptomatic, endoscopic, or complicated gastro-oesophageal reflux disease (GORD). First degree relatives of patients with GORD are more likely to suffer with GORD symptoms. These observations raise the possibility of a genetic contribution to the aetiology of GORD.
Aims: To determine the relative contribution of genetic factors to GORD by evaluating GORD symptoms in monozygotic (MZ) and dizygotic (DZ) twins.
Methods: A total of 4480 unselected twin pairs, identified from a national volunteer twin register, were asked to complete a validated symptom questionnaire. GORD was defined as symptoms of heartburn or acid regurgitation at least weekly during the past year.
Results: Replies were obtained from 5032 subjects (56% response rate). A total of 1960 twin pairs were evaluable: 928 MZ pairs (86 male pairs, mean (SD) age 52 (13) (range 19–81) years) and 1032 DZ pairs (71 male pairs, mean age 52 (13) (20–82) years). The prevalence of GORD among both groups of twins was 18%. Casewise concordance rates were significantly higher for MZ than DZ twins (42% v 26%; p<0.001). Multifactorial liability threshold modelling suggests that additive genetic effects combined with unique environmental factors provide the best model for GORD. Heritability estimates suggest that 43% (95% confidence interval 32–55%) of the variance in liability to GORD is due to additive genetic factors.
Conclusions: There is a substantial genetic contribution to the aetiology of GORD.
gastro-oesophageal reflux disease; twin study; heritability; genetics
Mechanisms of gastro-oesophageal reflux were studied by oesophageal manometry and pH monitoring in 33 children: nine controls, 15 with gastro-oesophageal reflux alone, and nine with reflux oesophagitis. A total of 122 episodes of reflux were analysed in detail: 82 (67%) were synchronous with swallowing and 40 (33%) asynchronous. Infants with trivial symptoms had gastro-oesophageal reflux synchronous with swallowing, whereas those with serious symptoms had slower acid clearance and asynchronous reflux. There were significant differences in lower oesophageal sphincter pressure and amplitude of oesophageal contractions between controls and patients with both gastro-oesophageal reflux and reflux oesophagitis. In reflux oesophagitis there was a decrease in lower oesophageal sphincter pressure and the contractions had a bizarre waveform suggesting a neuropathic process.
The relationship between the different symptoms of gastro-oesophageal reflux disease remain markedly obscure due to the high underlying non-linearity and the lack of studies focusing on the problem. Aim of this study was to evaluate the hidden relationships between the triad of symptoms related to gastro-oesophageal reflux disease using advanced mathematical techniques, borrowed from the artificial intelligence field, in a cohort of patients with oesophagitis. A total of 388 patients (from 60 centres) with endoscopic evidence of oesophagitis were recruited. The severity of oesophagitis was scored by means of the Savary-Miller classification. PST algorithm was employed. This study shows that laryngo-pharyngeal symptoms related to gastro-oesophageal reflux disease are correlated even if in a non-linear way.
GERD; Laryngo-pharyngeal symptoms; Non-linear association; Artificial intelligence
A causal relation between gastro-oesophageal reflux and nocturnal asthma has been postulated. Forty four adult asthmatics underwent ambulatory monitoring of their oesophageal pH over 24 hours to find out if there was such a relation. Of these 21 showed significant "morning dipping" in which the peak expiratory flow falls during the night. Asthmatics with morning dipping had a history of nocturnal wheeze and a higher incidence of reflux symptoms, but measurement of oesophageal pH showed no significant difference in the amount or pattern of reflux when compared with "non-dippers." Overall, 15 asthmatics had gastro-oesophageal reflux, and these participated in a randomised, double blind crossover trial of ranitidine versus placebo. No significant difference was found in the peak expiratory flow rates or subjective evaluation of well being of the patients.
In order to establish whether alcohol in amounts in amounts customarily imbibed during social drinking causes gastro-oesophageal reflux, 12 healthy young individuals, without symptoms of gastro-oesophageal reflux, were studied twice. Each time, distal oesophageal pH was monitored continuously for three hours after a standard meal which included either 180 ml 100 proof vodka or 180 ml water. The order of studies with and without alcohol was random. Peak blood alcohol concentrations ranged between 0.63 and 1.29 g/l. Eleven of the 12 subjects refluxed more after alcohol; and the difference in mean reflux scores for studies with and without alcohol was highly significant. We conclude that relatively modest quanttities of alcohol induce gastro-oesophageal reflux in healthy people.
Gastro-oesophageal reflux (GOR) occurs frequently in children with cystic fibrosis (CF) but has not been studied in adult CF. We surveyed such symptoms by structured questionnaire in 50 adult CF patients (mean age 26 years, range 16-50; 24 male) and performed oesophageal manometry and 24-hour pH recording in 10 who had reflux symptoms (mean age 28 years, range 21-35; 8 men). 47 patients (94%) had upper gastrointestinal symptoms: 40 (80%) heartburn (27 worse when supine); 26 (52%) regurgitation; and 28 (56%) dyspepsia. At oesophageal manometry, lower oesophageal sphincter barrier pressure (LOSBP) was subnormal in 6 of the 10 patients and 3 had uncoordinated peristalsis in the mid oesophagus. 8 patients had raised DeMeester scores, indicating significant GOR. Those patients with a LOSBP < 5mm Hg had a higher DeMeester score (mean 81.0, range 47.9-128.8) than the patients with a normal LOSBP (26.9, 8.7-56.5; p < 0.002). These results show that adult CF patients have high rates of GOR symptoms, diminished LOSBP, and acid reflux.
Ulceration of the oesophageal squamous mucosa (ulcerative oesophagitis) is a pathological manifestation of gastro-oesophageal reflux disease, and is a major risk factor for the development of Barrett’s oesophagus. Barrett’s oesophagus is characterised by replacement of reflux-damaged oesophageal squamous epithelium with a columnar intestinal-like epithelium. We previously reported discovery of microRNAs that are differentially expressed between oesophageal squamous mucosa and Barrett’s oesophagus mucosa. Now, to better understand early steps in the initiation of Barrett’s oesophagus, we assessed the expression, location and function of these microRNAs in oesophageal squamous mucosa from individuals with ulcerative oesophagitis.
Quantitative real-time PCR was used to compare miR-21, 143, 145, 194, 203, 205 and 215 expression levels in oesophageal mucosa from individuals without pathological gastro-oesophageal reflux to individuals with ulcerative oesophagitis. Correlations between microRNA expression and messenger RNA differentiation markers BMP-4, CK8 and CK14 were analyzed. The cellular localisation of microRNAs within the oesophageal mucosa was determined using in-situ hybridisation. microRNA involvement in proliferation and apoptosis was assessed following transfection of a human squamous oesophageal mucosal cell line (Het-1A).
miR-143, miR-145 and miR-205 levels were significantly higher in gastro-oesophageal reflux compared with controls. Elevated miR-143 expression correlated with BMP-4 and CK8 expression, and elevated miR-205 expression correlated negatively with CK14 expression. Endogenous miR-143, miR-145 and miR-205 expression was localised to the basal layer of the oesophageal epithelium. Transfection of miR-143, 145 and 205 mimics into Het-1A cells resulted in increased apoptosis and decreased proliferation.
Elevated miR-143, miR-145 and miR-205 expression was observed in oesophageal squamous mucosa of individuals with ulcerative oesophagitis. These miRNAs localised to the basal layer of the oesophageal epithelium. They reduced proliferation and increased apoptosis, and may play roles in regulating epithelial restoration in response to injury caused by gastro-oesophageal reflux.
microRNA; Gastro-oesophageal reflux disease; Ulcerative oesophagitis; Apoptosis; Proliferation; Barrett’s oesophagus
Oestrogen and progestogen have the potential to influence gastro-intestinal motility; both are key components of hormone replacement therapy (HRT). Results of observational studies in women taking HRT rely on self-reporting of gastro-oesophageal symptoms and the aetiology of gastro-oesophageal reflux disease (GORD) remains unclear. This study investigated the association between HRT and GORD in menopausal women using validated general practice records.
51,182 menopausal women were identified using the UK General Practice Research Database between 1995–2004. Of these, 8,831 were matched with and without hormone use. Odds ratios (ORs) were calculated for GORD and proton-pump inhibitor (PPI) use in hormone and non-hormone users, adjusting for age, co-morbidities, and co-pharmacy.
In unadjusted analysis, all forms of hormone use (oestrogen-only, tibolone, combined HRT and progestogen) were statistically significantly associated with GORD. In adjusted models, this association remained statistically significant for oestrogen-only treatment (OR 1.49; 1.18–1.89). Unadjusted analysis showed a statistically significant association between PPI use and oestrogen-only and combined HRT treatment. When adjusted for covariates, oestrogen-only treatment was significant (OR 1.34; 95% CI 1.03–1.74). Findings from the adjusted model demonstrated the greater use of PPI by progestogen users (OR 1.50; 1.01–2.22).
This first large cohort study of the association between GORD and HRT found a statistically significant association between oestrogen-only hormone and GORD and PPI use. This should be further investigated using prospective follow-up to validate the strength of association and describe its clinical significance.
Gastro-oesophageal reflux disease; Hormone replacement therapy; Menopause
Recurrent attacks of life-threatening dyspnoea and choking occurred in a patient with tetraplegia. Conventional investigations for gastro-oesophageal reflux were normal, but 24-hour oesophageal pH recording revealed gross reflux in association with an attack of dyspnoea. Surgical correction of the reflux abolished the attacks. The possibility of autonomic dysreflexia as the mechanism linking reflux and respiratory symptoms in this patient is discussed.