Refractory Heartburn: A Challenging Problem in Clinical Practice

Gastroesophageal reflux disease (GERD) is a condition which develops when the reflux of stomach contents causes troublesome symptoms and/or complications. Heartburn and regurgitation are the typical symptoms of GERD. The treatment of GERD encompasses lifestyle modifications, pharmacological, endoscopic, and surgical therapy. The majority of the patients respond to 4–8 weeks of proton-pump inhibitors therapy, but 20–42% will demonstrate partial or complete lack of response to treatment. While these patients have been considered as having refractory heartburn, a subset of them does not have GERD or have not been adequately treated. The main causes of refractory heartburn include: poor compliance; inadequate proton-pump inhibitors dosage; incorrect diagnosis; comorbidities; genotypic differences; residual gastroesophageal reflux; eosinophilic esophagitis and others. Treatment is commonly directed toward the underlying cause of patients’ refractory heartburn.     

Role of clinical presentation in diagnosing reflux-related non-cardiac chest pain

INTRODUCTION: Non-cardiac chest pain (NCCP) presents as a frequent diagnostic challenge, with patients tending to use a disproportionate level of health-care resources. Gastroesophageal reflux disease (GERD) is the most frequent cause of NCCP. Thus the typical symptoms of reflux, such as heartburn and regurgitation, when present as predominant symptoms are quite specific for diagnosing GERD but in patients with NCCP the clinical diagnosis of reflux is difficult, and invasive methods or the omeprazole test are required for its detection. The aim of the present study was to evaluate the role of clinical presentation when diagnosing GERD among patients with NCCP. METHODS: Patients with NCCP underwent upper endoscopy, Bernstein and omeprazole tests. The patients were divided into two groups based on GER- or non-GER-related chest pain, and clinical presentation was compared between these two groups. Gastroesophageal reflux disease was considered positive when at least two methods were positive. RESULTS: From 78 NCCP patients (41 male; mean age 50.4 +/- 2.3 years), the chest pain was related to GERD in 35 patients (44.8%). The two groups were the same based on sex and age. The chest pain severity, site, radiation and relation to food, exercise, and sleep were equal in the two groups, except for two symptoms: pain that was relieved by antacid (P < 0.031) and presence of classical reflux symptoms (P < 0.009), seen in the GERD patients. With regard to recent patient history, heartburn and regurgitation symptoms were seen more frequently in GERD patients (P < 0.036 and P < 0.002, respectively). DISCUSSION: Clinical presentation is important in diagnosing GERD in NCCP. Although the chest pain is the same in reflux- and non-reflux-related NCCP, the symptoms of heartburn or regurgitation in the present or recent patient history are diagnostic for GERD-related chest pain.     

Gastroesophageal reflux disease

GERD is a common chronic gastrointestinal disorder, and its prevalence in Asia is increasing. Classical symptoms of heartburn and regurgitation are common presentations. There is no standard criterion for the diagnosis of GERD, and 24-h pH monitoring lacks sensitivity in NERD. Furthermore, diagnostic studies for gastroesophageal reflux disease have several limitations. A short course of PPI is often used in clinical practice as a diagnostic test for gastroesophageal reflux disease. Elderly patients with GERD usually present with atypical manifestations, and they tend to develop more severe disease. PPI remains the mainstay of treatment for GERD. In a subset of patients who wish to discontinue maintenance treatment, anti-reflux surgery is a therapeutic option.     

GERD evaluation: time for a new paradigm?

In the past there has been reliance on heartburn and acid regurgitation as the cardinal symptoms of gastro-esophageal reflux. Now it is recognized that diverse additional symptoms including extraesophageal manifestations are essential components of gastroesophageal reflux disease (GERD). Furthermore, previous reliance in mucosal damage at endoscopy as evidence of therapeutic success in the management of GERD has proven of only limited value in the diverse world of GERD symptoms. Indeed is now apparent that the relationship between symptoms and lesions is modest at best. Most patients with GERD have no overt erosions or ulceration at endoscopy and they frequently suffer from a wide array of complaints other than heartburn that contribute to their diminished perception of life's quality. To address these problems, multidimensional questionnaires designed to encompass the diverse symptomatology of GERD have been investigated, principally, to provide a reproducible metric of change in the subjective response to pharmacologic therapy during trials for patients with nonerosive reflux disease. The most promising of these instruments is The ReQuest questionnaire, because it has been extensively validated in multiple patient groups and cultures, appears highly promising in this regard and for erosive disease too and may ultimately prove to be of value for the initial evaluation of patients with GERD. We propose that accurate symptom delineation complemented with endoscopy performed in selected groups of patients will become the mainstay in diagnosis of GERD and the assessment of therapy efficacy.     

Diagnosis and treatment of gastroesophageal reflux disease

Gastroesophageal reflux disease(GERD) is a common disease with a prevalence as high as 10%-20% in the western world. The disease can manifest in various symptoms which can be grouped into typical,atypi-cal and extra-esophageal symptoms. Those with the highest specificity for GERD are acid regurgitation and heartburn. In the absence of alarm symptoms,these symptoms can allow one to make a presumptive diagnosis and initiate empiric therapy. In certain situations,further diagnostic testing is needed to confirm the diagnosis as well as to assess for complications or alternate causes for the symptoms. GERD complications include erosive esophagitis,peptic stricture,Barrett's esophagus,esophageal adenocarcinoma and pulmonary disease. Management of GERD may involve lifestyle modification,medical therapy and surgical therapy. Life-style modifications including weight loss and/or head of bed elevation have been shown to improve esophageal pH and/or GERD symptoms. Medical therapy involves acid suppression which can be achieved with antacids,histamine-receptor antagonists or proton-pump inhibitors. Whereas most patients can be effectively managed with medical therapy,others may go on to require anti-reflux surgery after undergoing a proper pre-operative evaluation. The purpose of this review is to discuss the current approach to the diagnosis and treatment of gas-troesophageal reflux disease.     

Extraesophageal gastroesophageal reflux disease (GERD) symptoms are not more frequently associated with proximal esophageal reflux than typical GERD symptoms

Extraesophageal (EE) symptoms such as cough and throat clearing are common in patients referred for reflux testing, but are less commonly associated with gastroesophageal reflux disease (GERD). Patients with reflux associated EE symptoms often lack typical GERD symptoms of heartburn and regurgitation. Our aim was to compare the frequency of proximal esophageal reflux between esophageal (typical) symptoms and EE (atypical) symptoms. Combined multichannel intraluminal impedance‐pH (MII‐pH) tracings were blinded by an investigator so that symptom markers were relabeled with a number without disclosure of symptom type. We selected 40 patients with at least five reflux‐related symptom events for one of four symptoms (heartburn, regurgitation, cough, or throat clearing). A blinded investigator analyzed all 200 reflux episodes, reporting the proximal esophageal extent of the reflux for all symptoms. The percentage of symptom‐related reflux extending proximally to 17 cm above the LES was similar among all four symptom types. At least 50% of all symptoms were associated with proximal esophageal reflux to 17 cm, with regurgitation having the highest frequency at 60%. Our data indicate that EE symptoms are not more frequently associated with proximal esophageal reflux than typical esophageal symptoms.     

Association of body mass index with heartburn, regurgitation and esophagitis: results of the Progression of Gastroesophageal Reflux Disease study

BACKGROUND: Overweight and obesity are believed to be risk factors for gastroesophageal reflux disease (GERD). The aim of the present study was to analyze the impact of body mass index (BMI) on the severity and frequency of reflux symptoms and esophagitis in a large cohort of reflux patients. METHODS: As part of the Progression of Gastroesophageal Reflux Disease (ProGERD) study, 6215 patients with clinically assessed GERD were included in the present investigation (53% male, 52 +/- 14 years; 47% female, 56 +/- 14 years). Heartburn and regurgitation symptoms were assessed using the validated Reflux Disease Questionnaire. Endoscopies were performed and patients were subsequently classified as having non-erosive or erosive disease. To examine the association between BMI, GERD symptoms, and esophagitis, odds ratios (OR) and 95% confidence intervals (95%CI) were calculated using logistic regression models. RESULTS: In patients with GERD, higher BMI was associated with more frequent and more severe heartburn and regurgitation, as well as with esophagitis. The effects were more pronounced for regurgitation than for heartburn. The strongest association was between obesity and severity of regurgitation symptoms (women: OR 2.11, 95%CI 1.60-2.77; men: OR 2.15, 95%CI 1.59-2.90). Obese women, but not men, had an increased risk of severe esophagitis compared to women with normal weight (OR 2.51, 95%CI 1.53-4.12). CONCLUSIONS: In patients with GERD, higher BMI was associated with more severe and more frequent reflux symptoms and esophagitis.     

Prevalence of gastroesophageal reflux disease and gastroesophageal reflux disease symptoms in Japan

Background and Aim:  Epidemiological studies have shown that 10–48% of people in developed countries have gastroesophageal reflux disease (GERD) symptoms such as heartburn and acid regurgitation. The present study aimed to examine the prevalence of GERD symptoms and GERD in Japanese subjects.
Methods:  A cross-sectional study of Japanese subjects who visited a clinic for a routine health check up was carried out. Subjects were asked to fill out a self-report questionnaire. GERD was defined as the presence of heartburn and/or acid regurgitation at least twice per week.
Results:  Of the 6035 eligible subjects, 2662 (44.1%) reported having had heartburn and/or acid regurgitation during the past year: 124 (2.1%) daily, 275 (4.6%) twice per week, 773 (12.8%) twice per month and 1490 (24.7%) less than twice per month. Three hundred and ninety-nine (6.6%) subjects were diagnosed as having GERD and there was no relationship between the prevalence of GERD and either sex or age. The prevalence of bothersome GERD symptoms was significantly higher in subjects with GERD than in those without GERD.
Conclusion:  Approximately 6.6% of Japanese have GERD and most persons with GERD described heartburn or acid regurgitation as bothersome.     

Prevalence of gastroesophageal reflux disease and gastroesophageal reflux disease symptoms in Japan

BACKGROUND AND AIM: Epidemiological studies have shown that 10-48% of people in developed countries have gastroesophageal reflux disease (GERD) symptoms such as heartburn and acid regurgitation. The present study aimed to examine the prevalence of GERD symptoms and GERD in Japanese subjects. METHODS: A cross-sectional study of Japanese subjects who visited a clinic for a routine health check up was carried out. Subjects were asked to fill out a self-report questionnaire. GERD was defined as the presence of heartburn and/or acid regurgitation at least twice per week. RESULTS: Of the 6035 eligible subjects, 2662 (44.1%) reported having had heartburn and/or acid regurgitation during the past year: 124 (2.1%) daily, 275 (4.6%) twice per week, 773 (12.8%) twice per month and 1490 (24.7%) less than twice per month. Three hundred and ninety-nine (6.6%) subjects were diagnosed as having GERD and there was no relationship between the prevalence of GERD and either sex or age. The prevalence of bothersome GERD symptoms was significantly higher in subjects with GERD than in those without GERD. CONCLUSION: Approximately 6.6% of Japanese have GERD and most persons with GERD described heartburn or acid regurgitation as bothersome.     

老年胃食管反流病患者临床特征分析

目的 探讨老年胃食管反流病(GERD)患者的临床特征,为临床诊断、治疗提供帮助.方法 根据GERD蒙特利尔的标准、中国胃食管反流病共识意见等,将GERD患者分为老年组(年龄≥65岁)与中青年组(年龄＜65岁);通过问卷调查,分析2组GERD患者的食管裂孔疝(HH)、食管炎(洛杉矶标准)、临床症状(反流、烧心等)、生活质量.结果 两组性别比差异无统计学意义(P＞0.05).与中青年GERD患者比较:老年患者重度食管炎(LC级+LD级)比例高(P＜0.05);典型反酸、烧心症状轻(P＜0.05),食管外症状发生率高(P＜0.05);但HH发生率差异无统计学意义(P＞0.05).老年患者生理功能、总体健康、活力、社会功能、精神健康、躯体生理健康总评和精神心理健康总评积分与年轻组差异无统计学意义(P＞0.05),仅生理职能、躯体疼痛、情感职能积分较中青年组高(P＜0.05).结论 老年GERD患者典型反流症状(反食、烧心)较少见,易发生重度食管炎,但老年GERD患者生活质量无明显下降.     

Extra-esophageal gastroesophageal reflux disease and asthma: understanding this interplay

Gastroesophageal reflux disease (GERD) is a condition that develops when there is reflux of stomach contents, which typically manifests as heartburn and regurgitation. These esophageal symptoms are well recognized; however, there are extra-esophageal manifestations of GERD, which include asthma, chronic cough, laryngitis and sinusitis. With the rising incidence of asthma, there is increasing interest in identifying how GERD impacts asthma development and therapy. Due to the poor sensitivity of endoscopy and pH monitoring, empiric therapy with proton pump inhibitors (PPIs) is now considered the initial diagnostic step in patients suspected of having GERD-related symptoms. If unresponsive, diagnostic testing with pH monitoring off therapy and/or impedance/pH monitoring on therapy, may be reasonable in order to assess for baseline presence of reflux with the former and exclude continued acid or weakly acid reflux with the latter tests. PPI-unresponsive asthmatics, without overt regurgitation, usually have either no reflux or causes other than GERD. In this group, PPI therapy should be discontinued. In those with GERD as a contributing factor acid suppressive therapy should be continued as well as optimally treating other etiologies requiring concomitant treatment. Surgical fundoplication is rarely needed but in those with a large hiatal hernia, moderate-to-severe reflux by pH monitoring surgery might be helpful in eliminating the need for high-dose acid suppressive therapy.     

Gastroesophageal reflux disease: extraesophageal manifestations and therapy

Gastroesophageal reflux disease (GERD) can present with both typical symptoms such as heartburn and regurgitation as well as atypical symptoms. These symptoms may include chest pain, asthma, chronic cough, hoarseness, otitis media, atypical loss of dental enamel, idiopathic pulmonary fibrosis, recurrent pneumonia, chronic bronchitis and even sudden infant death. The diagnosis of GERD in these patients can often present a challenge and usually requires a combination of selected testing and therapeutic trials. Acid suppression by using proton pump inhibitors remains the treatment of choice in GERD, but some patients will also respond well to antireflux surgery. This article addresses the presentations, diagnostic challenges, and therapeutic opportunities in GERD patients with atypical presentations.     

Prevalence of gastroesophageal reflux disease in Moscow

Limited data exist to determine the prevalence and clinical spectrum of gastroesophageal reflux disease (GERD) in the Russian population, which might be different from those in Western countries. This study was performed in Moscow on randomized 1065 adults aged ≥15 years. A validated reflux questionnaire comprising 72 questions and an additional 29 sub‐questions were used. The questions assessed (heartburn and regurgitation) and related (dyspepsia, dysphagia, odynophagia and chest pain) symptoms, the triggering factors of these symptoms, family history and data on demographic and socioeconomic features. GERD was defined as heartburn and/or regurgitation once a week or common. Of the 1065 participants, 42.1% were male and 57.9% were female. The prevalences of frequent and occasional symptoms were 17.6 and 22.1% for heartburn and 17.5 and 21.8% for regurgitation, respectively, over the last 12 months. The prevalence of GERD was found to be 23.6%. The rate of GERD was significantly higher in females than in males (15.4 vs. 29.5%, P < 0.001) and significantly increased as the age of the participants increased (P = 0.011). GERD was present in 20.4% of smokers, 24.2% of coffee drinkers, 21.5% of alcohol consumers and 45.9% of stressed participants. Although the rate of alcohol consumers was lower in those with GERD compared with those without GERD, the rate of coffee drinkers and stressed participants was higher among those with GERD. The rate of additional symptoms was higher even in participants complaining of regurgitation/heartburn rarely, compared with those without complaints. Using the same questionnaire, which makes it possible to compare the present results with those from different countries, we found the prevalence of GERD in Moscow to be 23.6%, one of highest in the Western populations. The rates of heartburn and regurgitation were found to be similar, which constitutes a different result than has been found in similar studies. Additional symptoms should be assessed, in all GERD patients even in the presence of rare complaints of regurgitation/heartburn.     

State of the art: extraesophageal manifestations of gastroesophageal reflux disease

Although heartburn and regurgitation are the most common symptoms of gastroesophageal disease (GERD), several laryngeal, pharyngeal, and pulmonary symptoms, collectively known as laryngopharyngeal reflux, have also been associated with this disease. However, the case that GERD is the cause of these symptoms is difficult to make because neither endoscopy nor prolonged reflux monitoring has shown consistent evidence of either esophageal injury or abnormal reflux frequency. To date, there have been few controlled trials of antireflux therapy, and the data that are available are conflicting. Nevertheless, gastroenterologists are often confronted with difficult-to-manage patients with extraesophageal symptoms that are considered to be the result of GERD. This article reviews the current literature on this topic and discusses the author's approach to treating these patients.     

Barrett食管、反流性食管炎和非糜烂性胃食管反流病的反流物特点

目的应用食管24 h pH-阻抗(MII-pH)等检查方法,分析具有胃食管反流病(GERD)典型症状、并且食管MII-pH检查结果异常的GERD患者,比较分析其各亚型,即Barrett食管(BE)、反流性食管炎(RE)和非糜烂性胃食管反流病(NERD)患者的胃食管反流特点。 方法入选具有典型胃食管反流症状(烧心/反流),并且食管24 h MII-pH检查结果异常的GERD患者,根据内镜检查结果分为BE、RE、NERD三组,收集患者24 h的食管pH-阻抗信息,应用SPSS16.0统计软件进行组间Mann Whitney检验、多因素方差分析,P< 0.05认为具有统计学差异。 结果共入组103例具有典型反流症状且MII-pH监测阳性的GERD患者,其中有15例BE患者、32例RE患者、56例NERD患者。三组患者的平均年龄、性别构成、以及BMI无显著差异性。将三组患者的各项胃食管反流指标数值进行Mann-Whitney检验,显示RE、BE患者的DeMeester评分、pH<4反流时间百分比、长反流周期数显著高于NERD患者,具有显著性差异。BE患者的反流周期数显著多于RE和NERD患者,具有显著性差异。阻抗相关指标在三组患者之间均没有统计学差异。 结论与NERD相比,酸反流对于RE和BE具有更重要的致病意义。     

Lanzoptol efficacy at gastroesophageal reflux disease: results of multicenter study leader

Results of multicenter study "Efficacy of Lansoptol (lansoprazole, KRKA) and its influence on the Dynamics of GERD symptoms" (LIEDER) are presented. The impact of 56-days treatment with lansoprazole 30 mg once daily on symptoms relief, a quality of life of 121 patients with gastroesophageal reflux disease (GERD) and healing of esophageal lesions of 30 patients with reflux esophagitis were investigated. Rapid acid inhibition effect of first dose of lansoptol was shown by 48-hr pH-monitoring. At the first day of the treatment 43.1% of patients reported decreasing of intensity of heartburn and 36.5%--of regurgitation. It were shown that the treatment with lansoptol provided symptoms relief in 25% patients at day 3, in 50% of patients at day 5 and in 75% at day 8 for heartburn, and at days 2, 6 and 9--for regurgitation. It was conducted improvement of quality of life. Healing rate of esophagitis at 28 day was 83.3%.     

Diagnostic evaluation in gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) describes the clinical manifestations of reflux of gastric contents and the associated symptoms and patterns of tissue injury. Although its exact prevalence is difficult to determine, there is no doubt the GERD is the most common esophageal disease and probably among the most prevalent conditions seen in the primary care setting. GERD has a wide clinical spectrum, making the diagnostic evaluation challenging and complicated at times. Confirmatory test are rarely needed in patients with typical symptoms of heartburn or regurgitation who have a good clinical response to GERD therapy. This article describes the diagnostic tests necessary for some cases of GERD.     

胃食管反流病诊断技术的进展

胃食管反流病（GERD）的患病率近年来在我国有上升趋势。目前诊断GERD的手段较多，如典型症状（烧心和反酸）、质子泵抑制剂（PPT）试验和上消化道内镜检查等，尤其是GERD的诊断技术，包括最初的X线钡餐以及食管放射性核素检查和24h食管pH监测，到新近出现的食管多通道腔内阻抗监测和无线pH监测等，为胃食管反流提供了客观的证据。     

多中心临床观察雷贝拉唑联合多潘立酮治疗胃食管反流病的症状缓解情况

目的 观察雷贝拉唑联合多潘立酮治疗胃食管反流病(GERD)的临床疗效.方法 采用多中心、随机、开放、观察性研究方法,将收集的130例GERD门诊患者随机分为观察组(雷贝拉唑联合多潘立酮)64例和对照组(单用雷贝拉唑)66例,以胃食管反流病诊断问卷(GERD Q量表)和一般资料调查方式进行症状评分,症状评分根据烧心、反流、上腹痛等发生的频率和程度.随访4周,比较治疗后2周末和4周末两组患者症状的改善情况.结果 治疗前观察组和对照组GERD Q评分值基线一致,治疗2周末,两组GERD症状GERD Q评分值均有明显下降,分别为8.45±2.53和9.17±2.42;治疗4周末疗效更明显,分别为6.03±1.54和6.70±1.78;治疗前后差异有统计学意义(t=16.113,t=14.149;P值均＜0.01).观察组在治疗2周和4周末GERD Q分值较对照组下降更快,差异有统计学意义(t=-1.658,P=0.050;t=-2.292,P=0.012).观察组和对照组治疗2周后GERD症状分值均明显下降(t=2.006,P=0.047),4周后反流症状分值有明显下降,差异有统计学意义(t=2.287,P=o.022).治疗2周末观察组烧心和反流症状总有效率为79.0％和73.0％,对照组为67.7％和69.7％,观察组优于对照组;但治疗4周末观察组和对照组总有效率相似.结论雷贝拉唑联合多潘立酮能更快缓解GERD烧心和反流症状.     

酸敏感受体与心理因素在胃食管反流病内脏高敏感产生的作用研究

胃食管反流病（GERD）是一类常见的消化道良性疾病,通常以烧心和反酸为典型症状出现。临床上以质子泵抑制剂做为首选药物控制GERD患者的症状,但部分患者治疗效果并不理想。目前认为,食管内脏高敏感（VH）是GERD关键的发病机制之一,成为了近年来的研究热点。VH表现为低阈值刺激即可引起的相对强烈的反应或不适,本文从酸敏感受体和心理因素的角度对GERD内脏高敏感产生中的作用做一综述。