The relationship between acid and bile reflux and symptoms in gastro-oesophageal reflux disease.

BACKGROUND: The role of bile in the genesis of oesophageal symptoms and disease is incompletely understood. A new method of ambulatory bile monitoring may help to define this role. AIMS: To establish the relationship between symptom events and acid and bile reflux episodes. PATIENTS: 59 consecutive patients presenting for further investigation of gastro-oesophageal reflux disease. METHODS: All patients underwent combined ambulatory pH and bile monitoring. For each patient, a symptom index (SI) was calculated in relation to both acid reflux and bile reflux episodes. RESULTS: Patients were divided into those without (group 1, n = 21) and those with (group 2, n = 38) acid reflux. A total of 394 symptoms were identified in 59 patients. In group 1, there were fewer symptom events per patient (mean 4.1) than group 2 (mean 8.1). Twenty three per cent of symptom events were associated with acid reflux in group 1 and 41% in group 2. Only 6% of symptom events in both groups were related to bile reflux. In group 1 both the acid and bile related SI score were low. In group 2 the bile related SI score was low, but the acid related SI score was high. CONCLUSIONS: Symptoms are much more often related to acid reflux than bile reflux. Bile reflux does not seem to be a major factor in producing oesophageal symptoms.     

The association between gastro-oesophageal reflux disease and asthma: a systematic review

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.

Methods

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.

Results

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.

Conclusions

This systematic review indicates that there is a significant association between GORD and asthma, but a paucity of data on the direction of causality.Gastro‐oesophageal reflux disease (GORD) develops when the reflux of stomach contents into the oesophagus causes chronic troublesome symptoms or complications.¹ The most recognisable symptoms of GORD are heartburn and acid regurgitation, but the reflux of noxious material may have wider‐reaching effects. In addition to the well‐established oesophageal complications associated with the disease,² GORD is believed to lead to extra‐oesophageal symptoms and complications, primarily in the respiratory tract.³ An association between GORD and asthma has been accepted for many years, and has been the focus of numerous studies and reviews.^4,5 Asthma could arise as a result of acid reflux via two possible mechanisms: damage to the pulmonary tree after direct exposure to acid refluxate (reflux theory); or through bronchial constriction as a result of the stimulation of vagal nerve endings in the oesophagus (reflex theory).⁶ In addition, cough and increased respiratory effort may exacerbate GORD by bringing about an increased pressure gradient across the lower oesophageal sphincter.⁷ This could have particular relevance in patients with hiatus hernia, as gastro‐oesophageal junction competence is compromised by hiatus hernia during intra‐abdominal pressure increases.⁸The aim of this systematic review is to provide a realistic estimate of the strength and direction of the association between GORD and asthma in adults. Despite the large number of publications examining the clinical and epidemiological nature of this association, ambiguity remains. For example, estimates of the prevalence of GORD in individuals with asthma vary from 30% to 90%.⁹ A particular challenge is that the prevalence of GORD has been measured in a number of different ways in the literature. First, symptom frequency and/or severity have been used as a measure of disease. This is a patient‐focused method that can be used in large population‐based surveys, but a definitive symptom cutoff point for disease has not yet been established. At least weekly heartburn and/or acid regurgitation is known to impair quality of life,¹⁰ and this definition has been used in a recent systematic review,¹¹ which reported that 10–20% of the population in the western world have GORD. Oesophageal pH monitoring is a more objective way of measuring abnormal acid reflux, but its diagnostic accuracy is modest.^12,13 Endoscopy is an objective way of examining for the presence of oesophagitis, but it cannot distinguish microscopic changes in the oesophageal mucosa that may underlie symptoms in some individuals. Erosive oesophagitis is present in approximately 20–40% of individuals with GORD.^14,15,16We have therefore chosen to review all of these different methodologies to gain a realistic picture of the association between the two diseases. We examined studies that assess the prevalence or incidence of GORD in individuals with asthma, and the prevalence or incidence of asthma in individuals with GORD. We have employed an epidemiological framework for causality that assesses the strength of association, the consistency of association, the temporal association between GORD and asthma, and finally, the severity–response association between the two diseases.     

The relationship between gastro-oesophageal reflux symptoms and achalasia

BACKGROUND AND AIMS: Patients with achalasia can experience heartburn, which may be misinterpreted as gastro-oesophageal reflux disease (GORD), leading to a delay in diagnosis and subsequent treatment. We investigated the relationship between gastro-oesophageal reflux (GOR) and reflux symptoms in a large cohort of patients with achalasia. METHODS: The symptoms of all patients with a manometric diagnosis of achalasia made over the past 15 years were studied. The types of treatment, onset and pattern of heartburn, lower oesophageal sphincter pressure (LOSP) and 24-h oesophageal pH studies were compared. RESULTS: A total of 110 out of 225 untreated (48.9%) and 57 out of 99 treated (57.6%) patients experienced heartburn. An oesophageal pH study was performed on 80 patients and GOR was found in only six out of 57 untreated (10.5%) and 10 out of 23 treated (43.5%) patients. A low LOSP (<10 mmHg) was associated with an increased risk of GOR [odds ratio (OR) 14.2; 95% confidence interval (CI) 1.6-128.7; P<0.02). Treated patients were also more likely to develop GOR (OR 7.9; 95% CI 2.0-32.1; P<0.005). Neither the LOSP nor previous treatment was, however, a predictor of heartburn. The timing of the onset of dysphagia and heartburn was categorized in 111 patients. There was no significant difference in mean (or median) LOSP between these three groups, indicating that the LOSP is unlikely to predict the occurrence of symptoms. CONCLUSIONS: Heartburn is common in patients with untreated and treated achalasia, but is a poor predictor of GORD. Such patients should always be investigated with a 24-h oesophageal pH study to clarify the presence of GORD.     

Smoking and gastro-oesophageal reflux disease

The role of smoking in the pathogenesis of gastrooesophageal reflux disease has been controversial since the early 1970s when Stanciu reported the two to be 92% epidemiologically associated (a study subsequently challenged by inconsistencies in the observational data). Mechanistically, reflux disease is caused by excessive oesophageal acid exposure, which is potentially attributable to excessive reflux events and/or prolonged acid clearance. Currently, the best available pH monitoring data confirm that smoking increases oesophageal acid exposure. Smoking reduces lower oesophageal sphincter (LOS) pressure and predisposes to strain-induced reflux. Consistent with this, smoking has been shown to cause an increased number of reflux events that are not attributable to increased transient LOS relaxations, but rather are associated with deep inspiration and coughing. Once reflux occurs, acid is cleared from the oesophagus by a two-step process consisting of oesophageal peristalsis followed by neutralization of the residual acid by swallowed saliva. Smoking prolongs acid clearance by decreasing salivation. The effects of smoking on LOS tone and acid clearance are most likely mainly due to nicotine but are incompletely understood. Transdermal nicotine has similar effects to smoking on LOS pressure and salivation. Thus, although perhaps not a dominant risk factor, smoking and nicotine impact on pathophysiological variables of gastro-oesophageal reflux disease. In itself, smoking cessation is unlikely to cure severe gastrooesophageal reflux disease, but, along with appropriate pharmacological therapy, it may be beneficial.     

Associations between different forms of gastro-oesophageal reflux disease

Abstract
Aims—To study the epidemiology and naturalhistory of gastro-oesophageal reflux disease (GORD).
Methods—Retrospective cohort study involving all172 hospitals of the Department of Veterans Affairs. A total of194 527 patients with GORD were followed between 1981 and 1994. Distribution of oesophagitis, oesophageal ulcer, oesophageal stricture,strictured hiatus hernia, hiatus hernia, and pyrosis by age, sex, andethnicity were determined. The comorbid occurrence of various forms ofGORD in identical patients was analysed by an age and race standardised morbidity ratio. The population of all hospitalised veterans was usedfor comparison.
Results—Severe forms of GORD associated withoesophageal erosions, ulcers, or strictures, affected elderly, white,male patients more often than their corresponding opposite demographicgroup. All forms of GORD clustered in the same patient population; on average, any form of GORD was 10 times more likely to occur in apatient with another form of GORD than without. The highest morbidityratio (22) was found in oesophageal ulcer and stricture. About onethird of all patients with oesophageal erosions, ulcers, or stricturesalso had hiatus hernia; 46% of patients with hiatus hernia werediagnosed as having other forms of GORD. While one third of alloesophageal strictures appeared in patients without other forms of GORDdiagnosed at any time, oesophageal ulcers were always associated withsome other form of GORD. No clear cut progression in different forms ofGORD was found.
Conclusions—Older age, male sex, and whiteethnicity are risk factors in the development of severe forms of GORD.The most severe grade of GORD is reached at the onset of the disease.

Keywords:epidemiology of GORD; erosive oesophagitis; oesophageal stricture; oesophageal ulcer; hiatus hernia; naturalhistory; pyrosis; reflux oesophagitis

     

The extent of duodenogastric reflux in gastro-oesophageal reflux disease

BACKGROUND: It is known that duodenogastro-oesophageal reflux (DGOR) increases with worsening gastro-oesophageal reflux disease (GORD). It is unclear whether this is accompanied by increasing duodenogastric reflux (DGR). OBJECTIVE: To investigate the extent of DGR in a control group and 66 patients with GORD, using the technique of ambulatory gastric bilirubin monitoring. METHODS: Sixty-six patients with reflux symptoms (30 grade 0 or 1 oesophagitis (group 1), 16 grade 2 or 3 oesophagitis (group 2), 20 Barrett's oesophagus (group 3)) and 17 healthy controls were studied. All underwent oesophageal manometry followed by 24-h ambulatory oesophageal and gastric pH monitoring and gastric bilirubin monitoring. RESULTS: Median per cent total oesophageal acid exposure (pH < 4) was significantly less in the control group (0.6%) than in group 1 (2.8%, P< 0.05) and groups 2 and 3 (7.5% and 7.8% respectively, P< 0.001). There was no significant difference between any group in median per cent total time gastric pH was greater than 4. There was no significant difference in median per cent total gastric bilirubin exposure (absorbance > 0.14) between any group. However, in each group gastric bilirubin exposure was greater in the supine position than the upright position, being significantly greater in the control group (P< 0.05) and group 1 (P < 0.001). CONCLUSIONS: Gastric bilirubin exposure is similar across the spectrum of GORD severity. It is greater in the supine than in the upright position.     

Airway inflammation in subjects with gastro-oesophageal reflux and gastro-oesophageal reflux-related asthma

STUDY OBJECTIVES: Asthma and gastro-oesophageal reflux (GER) are both characterized by airway inflammation. DESIGN: The purposes of this work were (i) to study airway inflammation in patients troubled by gastro-oesophageal reflux (GER) and GER associated with asthma, (ii) to ascertain whether GER can aggravate asthma by exacerbating the pre-existing airway inflammation and oxidative stress and (iii) to establish the validity of analysing breath condensate and induced sputum when studying the airways of subjects affected by GER. PATIENT S AND METHODS: We enrolled 14 patients affected by mild asthma associated with GER (40 +/-12 years), nine with mild but persistent asthma (39 +/- 13 years), eight with GER (35 +/- 11 years) and 17 healthy subjects (37 +/- 9 years). Sputum cell counts and concentrations of interleukin-4 (IL-4), IL-6 and 8-isoprostane were measured in breath condensate and supernatant. MEASUREMENTS AND RESULTS: GER-related asthma is characterized by an eosinophilic inflammation, as determined by elevated concentrations of IL-4 in breath condensate and sputum supernatant, and by sputum cell analysis. GER alone presents a neutrophilic pattern of inflammation when determined by elevated concentrations of IL-6 in sputum cell analysis. A concomitant increase has been found in 8-isoprostane in GER associated (or not associated) with asthma. CONCLUSIONS: We conclude that GER is characterized by a neutrophilic airway inflammation and by increased oxidative stress. GER does not however aggravate pre-existing airway inflammation in asthma patients. Determinations of inflammatory and oxidant markers in the breath condensate of subjects with GER reflect these measured in the induced sputum.     

The relationship between gastroesophageal reflux and asthma: an update

Asthma and gastroesophageal reflux disease (GERD) are both common conditions and, hence, they often coexist. However, asthmatics have been found to have a much greater prevalence of GERD symptoms than the general population. There remains debate regarding the underlying physiologic mechanism(s) of this relationship and whether treatment of GERD actually translates into improved asthma outcomes. Based on smaller trials with somewhat conflicting results regarding improved asthma control with treatment of GERD, current guidelines recommend a trial of GERD treatment for symptomatic asthmatics even without symptoms of GERD. However, recently a large multicenter trial demonstrated that the treatment of asymptomatic GERD with proton-pump inhibitors did not improve asthma control in terms of pulmonary function, rate of asthma exacerbations, asthma-related quality of life, or asthma symptom frequency. These data suggest empiric treatment of asymptomatic GERD in asthmatics is not a useful practice. This review article provides an overview of the epidemiology and pathophysiologic relationships between asthma and GERD as well as a summary of current data regarding links between treatment of GERD with asthma outcomes.     

Complications of gastro-oesophageal reflux disease

Gastro-oesophageal reflux disease (GORD) is on the rise with more than 20% of the western population reporting symptoms and is the most common gastrointestinal disorder in the United States. This increase in GORD is not exactly clear but has been attributed to the increasing prevalence of obesity, changing diet, and perhaps the decreasing prevalence of H. pylori infection. Complications of GORD could be either benign or malignant. Benign complications include erosive oesophagitis, bleeding and peptic strictures. Premalignant and malignant lesions include Barrett's metaplasia, and oesophageal cancer. Management of both the benign and malignant complications can be challenging. With the use of proton-pump inhibitors, peptic strictures (i.e., strictures related to reflux) have significantly declined. Several aspects of Barrett's management remain controversial including the stage in the disease process which needs to be intervened, type of the intervention and surveillance of these lesions to prevent development of high grade dysplasia and oesophageal adenocarcinoma.     

The relation between body mass and gastro-oesophageal reflux

Obesity has, among physicians, since long been considered to cause gastro-oesophageal reflux. The evidence in support of this belief has been scarce, however. During the last few years some population-based studies have addressed this clinically important issue. These studies demonstrated a clear and dose-dependent association between increasing degrees of overweight and gastro-oesophageal reflux. The mechanisms by which obesity causes reflux are unknown, although there is some limited data suggesting that hiatal hernia may be the causal link between obesity and reflux. Moreover, some evidence has been presented showing that obesity is clearly a stronger risk factor among women than among men, and that the relation between overweight and reflux is substantially augmented by postmenopausal hormone therapy. The data so far available point in the direction of oestrogens, the activity of which is strengthened by increasing body mass, being responsible for this effect. If the results are repeated in future studies, postmenopausal therapy might be avoided among obese females suffering from severe reflux. Weight-reduction seems to reduce the risk of symptomatic gastro-oesophageal reflux disease, indicating that such strategy might be a useful tool in the treatment of reflux.     

The relationship between gastroesophageal reflux disease and sleep

Recent studies demonstrate a bidirectional relationship between gastroesophageal reflux disease (GERD) and sleep in which nighttime reflux leads to sleep deprivation and sleep deprivation can exacerbate GERD by enhancing perception of intraesophageal stimuli. Current treatment primarily focuses on reducing nighttime reflux, thus improving sleep quality. Future studies are needed to further explore the relationship between GERD and sleep and the potential of novel therapeutic options to interrupt the vicious cycle between them.     

Pathophysiology of gastro-oesophageal reflux disease

Gastro-oesophageal reflux disease (GERD), defined as symptoms or mucosal damage caused by reflux of gastric contents into the esophageal body, is a multifactorial disorder. Malfunctioning of the anti-reflux barrier at the esophagogastric junction, consisting of the right diaphragmatic crus and the lower esophageal sphincter (LES), is the pivotal abnormality. Other factors such as impaired esophageal clearance, decreased resistance of the esophageal mucosa and delayed gastric emptying, may contribute.     

Gastric emptying and duodeno-gastro-oesophageal reflux in gastro-oesophageal reflux disease

BACKGROUND: Previous studies present conflicting results regarding relationship between gastric emptying and gastro-oesophageal reflux disease. Reflux of duodenal content to oesophagus is generally considered to be associated with more severe disease. AIM: To assess presence of a gastric emptying disorder in persons with reflux of duodenal contents to oesophagus and to identify any correlation with gastric emptying and oesophageal motility. METHODOLOGY: A total of 15 subjects with (B+) and 15 subjects without (B-) bile reflux to oesophagus determined by 24-hour bilirubin monitoring were studied with scintigraphic solid gastric emptying and 24-hour oesophageal manometry. RESULTS: There was no difference in lag phase [median 23.7 (range 10.8-44.0) vs 24.6 (8.1-40.1) min], half emptying time [74.6 (48.0-93.6) vs 82.8 (54.4-153.9) min] or emptying rate [0.89 (0.59-1.34) vs 0.83 (0.36-1. 15)%/min] for B- and B+ subjects, respectively. In addition, there was no difference in emptying rate of gastric fundus between B- and B+ subjects. Subjects with bile reflux had less effective oesophageal contractions of oesophageal body [9.4(3.3-37)%] compared to subjects without bile reflux [32(19-47)%, p = 0.002]. However, there was no correlation between oesophageal motility and gastric emptying. CONCLUSION: Results suggest that a gastric emptying disorder is a less likely contributing cause of bile reflux to the oesophagus, but bile reflux is associated with less effective oesophageal motility.     

The interplay between Helicobacter pylori, gastro-oesophageal reflux disease, and intestinal metaplasia

Helicobacter pylori infection and gastro-oesophageal reflux disease (GERD) account for most upper gastrointestinal pathologies with a wide spectrum of clinical manifestations. The interplay of both conditions is complex, in part intriguing, and has become a matter of debate because of conflicting results. The cardia is an area where both H pylori and abnormal GERD exert their damaging potential, inducing inflammation and its consequences, such as intestinal metaplasia. While the role of intestinal metaplasia within columnar lined epithelium (Barrett's oesophagus) in the context of GERD is well established as a risk for neoplasia development, the role of intestinal metaplasia at the cardia in the context of H pylori infection is unclear. A particular challenge is the distinction of intestinal metaplasia as a consequence of GERD or H pylori if both conditions are concomitant. Available data on this issue, including follow up of a small patient series, are presented, but more studies are required to shed light on this issue because they will help to identify those patients that need surveillance.     

Relationship between asthma and gastro-oesophageal reflux: Significance of endoscopic grade of reflux oesophagitis in adult asthmatics

BACKGROUND: The association between asthma and gastro-oesophageal reflux disease (GERD) is well known. The aim of this study was to elucidate the causal relationship between reflux oesophagitis (RE) and asthma. METHODS: Seventy-two adult asthmatics were examined regarding their GERD symptoms, and each underwent an endoscopic examination. According to the Los Angeles classification, we divided the patients into three groups: group 1 (n= 52), no mucosal break; group 2 (n= 15), RE corresponding to grades A or B; group 3 (n = 5), RE corresponding to grades C or D. The asthmatics in groups 2 and 3 received anti-reflux treatment for their GERD for 8 weeks. Their morning and evening peak expiratory flow rates (PEFR), daily variability of the PEFR and daily use of an inhalation bronchodilator were compared before and after this treatment. RESULTS: The percentage of severe asthma and postprandial exacerbation of asthma in group 3 were significantly higher than those in the other two groups. In contrast, the number of eosinophiles and the serum level of immunoglobulin E in group 3 were significantly lower than those in the other two groups. After the antireflux treatment, significant improvements of both PEFR and daily use of the inhalation bronchodilator were observed only in group 3. CONCLUSIONS: The endoscopic severity of RE is associated with the characteristics of adult asthmatics and the treatment of severe RE improved the asthmatics' condition.