Nonsteroidal anti-inflammatory drug use as a risk factor for gastro-oesophageal reflux disease: an observational study

Background Although the associations between nonsteroidal anti‐inflammatory drugs (NSAIDs) and peptic ulcer disease or dyspepsia are well established, fewer data exist concerning the relationship between NSAIDs and gastro‐oesophageal reflux disease (GERD). Aim To examine the relationship between NSAIDs and GERD. Methods A self‐administered questionnaire covering NSAID use and GERD symptoms (heartburn and acid regurgitation) was sent to a representative national sample of 10 000 French adults (≥18 years) between 14 October and 21 November 2005. Risk factors associated with GERD were identified by logistic regression analysis in respondents who were not taking aspirin or proton pump inhibitors. Findings A total of 7259 completed questionnaires were returned of which 6823 were evaluable. Overall, 2262 respondents (33%) reported using NSAIDs during the previous 3 months. The lifetime and 3‐month prevalence rates of GERD symptoms were 37% and 21% respectively. GERD symptoms were significantly more common among NSAID users than among non‐users (27% vs. 19%, P ≤ 0.001) and a similar trend was seen for aspirin use. Proton pump inhibitors were received by 31% of respondents who reported experiencing GERD symptoms within the previous 3 months compared with 6% of those without symptoms (P < 0.01); however, only 20% of NSAID‐treated respondents were receiving proton pump inhibitors. NSAID use, age and female gender were independent predictors of GERD symptoms. Conclusion NSAID or aspirin use is a significant risk factor for GERD symptoms.     

Risk factors for gastro-oesophageal reflux disease symptoms: a community study

AIM: To examine the prevalence of gastro-oesophageal reflux disease symptoms and potential risk factors among community subjects. METHODS: A questionnaire was sent to 4000 subjects, stratified by age, gender and ethnicity to be representative of the local population. Gastro-oesophageal reflux disease symptoms were defined as at least weekly heartburn or acid regurgitation. RESULTS: 2231 responded (59%), 691 refused to participate and seven were incomplete. 1533 (41%) were evaluable (637 male, mean age 51 years, range: 20-80). The prevalence of gastro-oesophageal reflux disease symptoms was 21%. Smoking, excess alcohol, irritable bowel syndrome, increasing body mass index, a family history of upper gastrointestinal disease, increasing Townsend deprivation index, anticholinergic drugs (all P < 0.0001), weight gain, antidepressant drugs, inhaled bronchodilators, no educational attainment (all P < 0.01), south Asian origin (P = 0.02) and manual work (P < 0.05) were associated with gastro-oesophageal reflux disease symptoms. Multivariate logistic regression revealed increasing body mass index, a family history of upper gastrointestinal disease, irritable bowel syndrome, south Asian origin (all P < 0.0001), smoking, excess alcohol, no educational attainment and anticholinergic drugs (all P < 0.01) were independently associated with gastro-oesophageal reflux disease symptoms. CONCLUSIONS: Frequent gastro-oesophageal reflux disease symptoms affect 21% of the population. Increasing body mass index, a family history of upper gastrointestinal disease, irritable bowel syndrome, south Asian origin, smoking, excess alcohol, social deprivation and anticholinergic drugs are independently associated with gastro-oesophageal reflux disease symptoms.     

Management of gastro-oesophageal reflux disease in primary care: a European observational study

Abstract

Objective:

To describe the management of gastro-oesophageal reflux disease (GERD) in primary care, as part of the RANGE (Retrospective ANalysis of GERD) study.     

Pharmacological targets in gastro-oesophageal reflux disease

Although proton pump inhibitors have become the mainstay of treatment in gastro-oesophageal reflux disease (GORD), there are still unmet needs in the management of this very common disorder. For example, all current proton pump inhibitors have a relatively slow onset of action and their activity is limited mainly to the post-prandial period with far less effective inhibition of nocturnal acid secretion. In order to achieve more potent, rapid and sustained acid inhibition several compounds are currently under development, such as new proton pump inhibitors with a prolonged plasma half-life, potassium competitive ATPase blockers (PCABs), histamine H3 agonists, and gastrin antagonists. Acid suppression does not, however, cure the disease and relapses are frequently observed after discontinuation of proton pump inhibitor therapy. Among the different abnormalities involved in the pathophysiology of this multifactorial disease, transient lower oesophageal sphincter relaxations represent the major mechanism responsible for episodes of reflux. Baclofen, the prototype GABA(B) receptor agonist, is one of the most potent inhibitors of transient lower oesophageal sphincter relaxations identified. To date the transfer of these relaxation-controlling pharmacological agents into clinical practice has however been hampered by the occurrence of unacceptable side effects. Beside "anti-relaxation therapy", the potential of novel prokinetics such as motilin agonists has been explored, especially since the motilin receptor has been cloned. Thus far the broad therapeutic value of prokinetics in GORD does, however, seem very limited in terms of efficacy with respect to oesophageal motility and acid exposure. Lastly, further research is necessary to better understand the complex mechanisms involved in oesophageal sensitivity and mucosal defence.     

Maintenance therapy in gastro-oesophageal reflux disease

Gastro-oesophageal reflux disease (GORD) is a chronic condition. Symptom control and the maintenance of healing of erosive oesophagitis, if present, are important topics. In patients responding to a proton pump inhibitor (PPI) and showing no treatment symptoms it is appropriate to consider long-term treatment strategies, whether continuous, intermittent or on demand. Maintenance PPI therapy is well tolerated for up to 10 years of continuous use. Furthermore, tachyphylaxis does not occur during long-term maintenance PPI therapy. Previous concerns about risks of long-term PPI therapy in Heliobacter pylori-negative or H. pylori-positive patients have not materialized, while no cases of intestinal metaplasia with dysplasia or adenocarcinoma were found. The choice between medical and surgical therapy should depend upon informed patient preference. The optimal candidate for antireflux surgery is a young patient, with typical GORD symptoms, with erosive oesophagitis, with previous complete symptom resolution on acid-suppression therapy and unable to undergo continuous therapy, or alternatively in patients with regurgitation predominating over heartburn as long as the surgical procedures are conducted by an expert surgical team. Endoscopic therapy for erosive GORD should currently be regarded as experimental. The endoscopic procedures are safe, although they remain untested in patients with severe erosive oesophagitis and/or significant hiatal hernia.     

Non-erosive reflux disease and atypical gastro-oesophageal reflux disease manifestations: treatment results

Gastro-oesophageal reflux disease (GERD) is a widespread complex disorder that may be responsible for a variety of different symptoms and clinical features. Despite the presence of symptoms, the majority of patients do not have endoscopic lesions of oesophagitis. Non-erosive reflux disease (NERD) is a chronic, relapsing condition that can adversely affect the quality of life despite the absence of mucosal breaks at endoscopy. In many patients GERD is associated with extra-oesophageal or atypical manifestations, including cough, asthma, laryngitis or non-cardiac chest pain. Acid suppression with proton pump inhibitors (PPI) remains the mainstay of GERD therapy. However, patients with NERD and extra-oesophageal manifestations are often poorly responsive to PPI therapy. Accurate diagnosis followed by adequate PPI dosage and compliance with therapy are essential for the successful control of NERD and extra-oesophageal manifestations. The better detection and characterization of acid and non-acid reflux episodes using developing technologies, such as combined pH-impedance monitoring, is extending our understanding of the pathophysiology of NERD and the extra-oesophageal manifestations of GERD, and will lead to the improved management of these often poorly responsive conditions. This article reviews the treatment results and outlines approaches to the evaluation, diagnosis and therapy of NERD and atypical GERD manifestations.     

Review article: the role of non-acid reflux in gastro-oesophageal reflux disease

The role of acid in the pathogenesis of gastro‐oesophageal reflux disease (GERD) has been extensively studied and is well accepted. The role, if any, of non‐acid reflux, in particular duodenogastro‐oesophageal reflux, is much debated. The availability of new technology to detect non‐acid reflux has heightened interest in this question. This article reviews the following: How do we define non‐acid reflux? Does duodenogastro‐oesophageal reflux (alone or in combination) cause oesophageal injury, symptoms or both? What is its role in complicated GERD? What methods are available to assess non‐acid reflux? Does non‐acid reflux need treatment and if so what modalities are available?     

Supra-oesophageal manifestations of gastro-oesophageal reflux disease

The extra-oesophageal signs that are most commonly related to gastro-oesophageal reflux include chest pain, asthma, chronic cough, posterior laryngitis and dental erosions. It is characteristic to find in such patients a poor presence of symptoms and endoscopic and pH-metric findings that are common in typical reflux. The therapeutic response to antisecretory drugs has become the most cost-effective tool for the diagnosis and treatment of this condition. Both the evidence available and expert agreement in consensus conferences support the use of proton pump inhibitors with doubled standard doses for at least 12 weeks in most cases. While an acceptable response is achieved with this significant acid inhibition, there are still questions to be answered in these and other aspects, such as the true prevalence, path physiology and diagnosis of this condition. It is therefore necessary and increasingly useful to create multidisciplinary teams with the aim to improve and promote understanding and the care of patients suffering from these supra-oesophageal symptoms caused by gastro-oesophageal reflux.     

Emerging drugs for gastro-oesophageal reflux disease

Gastro-oesophageal reflux disease is a common medical problem caused by the exposure of the distal oesophagus to gastric contents. Existing medical therapy is very effective, but symptomatic relief with acid suppressants is often delayed. Treatment focuses on the suppression of gastric acid rather than on the underlying pathophysiological abnormalities, such as transient non-swallow-related lower oesophageal sphincter relaxation. Current pharmacological developments concentrate on drugs with lasting acid suppression and a faster onset of action. Compounds interacting with the complex neuromuscular regulation of the gastro-oesophageal junction are also being developed and offer exciting prospects.     

Emerging drugs for gastro-oesophageal reflux disease

Gastro-oesophageal reflux disease is a common medical problem caused by the exposure of the distal oesophagus to gastric contents. Existing medical therapy is very effective, but symptomatic relief with acid suppressants is often delayed. Treatment focuses on the suppression of gastric acid rather than on the underlying pathophysiological abnormalities, such as transient non-swallow-related lower oesophageal sphincter relaxation. Current pharmacological developments concentrate on drugs with lasting acid suppression and a faster onset of action. Compounds interacting with the complex neuromuscular regulation of the gastro-oesophageal junction are also being developed and offer exciting prospects.     

Management strategies for gastro-oesophageal reflux disease

New trials allow management strategies to be proposed with greater confidence than in the past for the entire spectrum of gastro-oesophageal reflux disease. Symptom evaluation is of key importance, as it is the most cost-effective and sensitive method for diagnosis of gastro-oesophageal reflux disease, and for tailoring of long-term therapy to individual patients. Endoscopy is an important adjunct to symptom assessment, but needs to be used sparingly and critically to be cost-effective. Empirical therapy, with evaluation of symptom response, is a central management strategy that can minimize overall costs. In cases of diagnostic uncertainty, a 1–2-week diagnostic/therapeutic test with high dose acid pump inhibitor is an emerging attractive alternative to oesophageal pH monitoring. Choice of therapy, and its subsequent adjustment to individual patients, should be made in the light of a now well-defined hierarchy of efficacy, which is essentially the same for endoscopy-negative and oesophagitis patients. Management strategies must acknowledge that gastro-oesophageal reflux disease is a chronic disorder in the majority of oesophagitis and endoscopy-negative patients. Management steps should identify the most cost-effective long-term treatment that gives adequate relief of symptoms and so corrects any symptom-related impairment of quality of life. The strategies that are recommended are largely based on clinical trial outcomes. There is a need for formal clinical trials of management strategies as distinct from evaluations of specific therapies.     

Heartburn in patients with gastro-oesophageal reflux disease in Germany and Sweden: a study on patients' burden of disease

BACKGROUND: Gastro-oesophageal reflux disease (GORD) is widespread in the general population and presents in most cases with heartburn as the main symptom. The severity of symptoms is not necessarily related to erosive damage to the oesophagus due to acid reflux, but the frequency and severity of symptoms have an impact on the health-related QOL (HR-QOL) of the patient. OBJECTIVE: To characterise patients with GORD who consult a physician because of heartburn with respect to medical background and burden of disease in Germany and Sweden. METHODS: A total of 1011 patients who had been experiencing symptoms of GORD, including heartburn, for at least 1 year were recruited by physicians, who collected data on the patients' previous diagnosis and treatment. The patients themselves were interviewed by telephone about their heartburn. The EuroQOL 5-dimensional HR-QOL questionnaire (EQ-5D) and the Gastrointestinal Symptom Rating Scale (GSRS) were used to measure patient-reported outcomes. RESULTS: About half of the patients had been experiencing symptoms of GORD for >5 years. The majority (54%) perceived the severity of their heartburn as moderate. Thirty-eight percent of the patients had been examined by endoscopy during the last 12 months and 79% of these had macroscopic oesophagitis. Medical treatment for heartburn had been prescribed to 88% of the patients. The mean annual number of days with heartburn was assessed as 170 days per patient, with the majority of patients (64%) experiencing heartburn every week. HR-QOL was reduced in these patients as expressed by EQ-5D scores compared to scores for a general population. Patients with GORD had problems related to gastrointestinal symptoms as rated by GSRS scores. More severe heartburn was associated with a greater number of symptom days and reduced HR-QOL scores, whereas a relationship between the findings at endoscopy and the severity of symptoms or HR-QOL could not be found. CONCLUSION: This study demonstrates that heartburn confers a significant burden on patients with GORD, related to the frequency and severity of symptoms and reflected in the reduction in HR-QOL as perceived by the patients.