Comparison of central and intraesophageal factors between gastroesophageal reflux disease (GERD) patients and those with GERD‐related noncardiac chest pain

Gastroesophageal reflux disease (GERD) causes a wide range of symptoms. Some patients present with typical symptoms such as heartburn and regurgitation and others with atypical symptoms such as chest pain. The mechanism responsible for the varying clinical presentation of GERD is still not fully elucidated. The aim of this study was to prospectively evaluate differences in central and local intraesophageal factors between patients with typical GERD symptoms and those with noncardiac chest pain (NCCP). Patients presenting with typical and atypical symptoms suspicious of GERD underwent upper endoscopy and 24‐hour pH monitoring with four sensors, each positioned at a different esophageal level. All patients completed GERD symptom, Hospital Anxiety and Depression Scale, and Symptom Stress Rating questionnaires. From January 2006 to December 2009, 50 patients were recruited, 29 with typical symptoms, and 21 with NCCP. Patients with proven GERD and NCCP had higher proximal extension of acid during reflux episodes than patients with typical symptoms. They were found to be older, had a shorter history of symptom onset, worse anxiety scores, and more endoscopic findings compatible with gastritis. Proximal extension of acid during the reflux episodes in patients with GERD presenting with NCCP may play a role in symptom generation.     

Recent advances in noncardiac chest pain in Korea

Gastroesophageal reflux disease (GERD) is the most common cause of noncardiac chest pain (NCCP) and is present in up to 60% of patients with NCCP in Western countries. In Korea, after a reasonable cardiac evaluation, GERD is reported to underlie 41% of NCCP cases. Typical reflux symptoms are frequent in Korean patients suffering from NCCP. Therefore, a careful history of the predominant symptoms, including heartburn and acid regurgitation, is relatively indicative of the GERD diagnosis in Korea. In Korea, in contrast to Western countries, patients aged 40 years and over who have been diagnosed with NCCP but who are without alarming features should undergo endoscopy to exclude gastric cancer or peptic ulcers because of the higher prevalence of peptic ulcer disease and gastric cancers in the region. In a primary care setting, in the absence of any alarming symptoms, a symptomatic response to a trial of a proton pump inhibitor (PPI) is sufficient for the presumptive diagnosis of GERD. In addition, the optimal duration of a PPI test may be at least 2 weeks, as GERD symptoms tend to be less frequent or atypical in Korean patients than in patients from Western countries. In patients diagnosed with GERD-related NCCP, long-term therapy (more than 2 months) with double the standard dose of a PPI is required to alleviate symptoms. Esophageal dysmotility is relatively uncommon, and pain modulators seem to offer significant improvement of chest pain control in non-GERD-related NCCP. Most traditionally available tricyclics or heterocyclics have many undesirable effects. Therefore, newer drugs with fewer side effects (for example, the serotonin - norepinephrine reuptake inhibitors) may be needed.     

Short course of omeprazole: a better first diagnostic approach to noncardiac chest pain than endoscopy,manometry, or 24-hour esophageal pH monitoring

Noncardiac 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. GOALS: To test the efficacy of a potent acid-suppressing agent as a diagnostic test in the evaluation of NCCP and to compare it with three commonly used tests. STUDY: Eighteen men and 24 women, aged 22 to 77 years, who presented with recurrent chest pain complaints of a noncardiac etiology, as determined by rest/stress perfusion imaging with technetium Tc99m sestamibi (MIBI), were enrolled in a prospective, double-blinded, placebo-controlled, crossover trial using high-dose omeprazole. Thirty-seven patients completed both arms of the trial. Findings were compared with those of endoscopy, manometry, and ambulatory 24-hour two-channel esophageal pH monitoring. All patients underwent initial diagnostic upper endoscopy, esophageal manometry, and 24-hour pH monitoring. Patients were then randomly assigned to either placebo or omeprazole (40 mg/d orally twice daily) for 14 days, washed out for 21 days, and then crossed over. Patient's symptoms were determined using a Visual Analogue Scale to measure the severity of chest pain before and after each period. RESULTS: Seventy-one percent of patients in the omeprazole arm reported improved chest pain, whereas only 18% in the placebo arm did. Abnormal results on manometry (20%), 24-hour pH monitoring (42%), or endoscopy with visual evidence of esophagitis (26%) were found less frequently. Combination of the three tests did not significantly increase their usefulness. In NCCP patients with GERD, as defined by positive results on a 24-hour pH test or presence of esophagitis on endoscopy, omeprazole treatment led to a response in 95% of patients, whereas 90% of GERD-positive patients treated with placebo did not respond. Of NCCP patients determined to be GERD negative, 39% responded to omeprazole. CONCLUSIONS: Omeprazole as a first diagnostic tool in the evaluation of MIBI-negative NCCP is sensitive and specific for determining the cause of NCCP. Endoscopy, manometry, and 24-hour pH monitoring were not only less sensitive in diagnosing NCCP, but they were significantly more expensive.     

Clinically distinct characteristics in patients younger than 40 years old with non-cardiac chest pain

Background and Aim: Little is known about non‐cardiac chest pain (NCCP) in young patients. We aimed to examine the proportion of gastroesophageal reflux disease (GERD) in young patients with NCCP compared to the average‐aged NCCP patients and to evaluate their symptomatic characteristics and the clinical efficacy of a 2‐week proton pump inhibitor (PPI) trial. Methods: Ninety‐six patients with NCCP ≥ 1/week were classified into the young‐aged (≤ 40 years, n = 38) and the average‐aged groups (> 40 years, n = 58). Typical reflux symptoms were assessed. The patients were defined into a GERD group and non‐GERD group according to reflux esophagitis on esophagogastroduodenoscopy and/or pathologic acid exposure on 24‐h esophageal pH monitoring. Then the patients were treated with 30 mg of lansoprazole bid for 14 days. Results: Nine patients (23%) in the young‐aged group and 22 patients (38%) in average‐aged group were diagnosed with GERD‐related NCCP (P = 0.144). The proportion of typical reflux symptoms was higher in the GERD group compared with the non‐GERD group in both age groups. A PPI test improved symptoms in the GERD group irrespective of age, but this improvement was not observed in non‐GERD group. Conclusions: In young NCCP patients, the prevalence of GERD was relatively low compared to average‐aged NCCP, but the difference was insignificant. The PPI test was very effective in diagnosing GERD in the NCCP patients in both age groups. Therefore, in young NCCP patients, if there is a negative response to a 2‐week PPI trial, the possibility of extra‐esophageal disease origin needs to be considered.     

食管混合性酸反流和低动力在非心源性胸痛发作的作用研究

目的胃食管反流病（GERD）是引起非心源性胸痛（NCCP）的最常见因素,本研究探讨酸反流和食管动力障碍在NCCP患者中的作用。 方法按照纳入、排除标准选取2018年9月至2019年6月在新疆维吾尔自治区人民医院急救中心以及微创,疝和腹壁外科住院收治的40例NCCP患者和50例典型GERD症状患者,两组患者均行食管24 h pH监测以及高分辨率食管测压监测。 结果NCCP组食管远端收缩平均积分（DCI）明显低于GERD组,并具有统计学意义（P＜0.05）,提示食管运动功能受损。在NCCP组患者中,与胸痛有关的混合性酸反流明显高于GERD组（P＜0.05）。在NCCP组患者中,与NCCP相关的反流发作在食管5、9和15cm处的反流清除时间比GERD组患者期长（28.3±4.21)s vs(22.6±3.28)s;(13.7±1.32)s vs (18.3±1.47)s;(9.58±1.02)s vs(14.3±1.06)s（P＜0.05）。 结论酸反流性质,食管运动功能受损和延缓反流清除时间与NCCP患者症状发作可能存在密切的关系。     

Wireless pH monitoring in patients with non-cardiac chest pain

OBJECTIVES: Gastroesophageal reflux disease (GERD) is an important cause of non-cardiac chest pain (NCCP), and its detection can require ambulatory pH monitoring. The purpose of this study was to determine the advantages of a wireless ambulatory pH monitoring system and 2 days of recording in diagnosing GERD in NCCP patients. METHODS: Results from ambulatory pH studies using the BRAVO capsule were reviewed from 62 subjects referred for evaluation of NCCP after non-diagnostic response to proton pump inhibitor therapy. Acid exposure time (AET) and symptom-reflux association tests were calculated after 1 day of recording and compared to the final outcome from the 2-day study. RESULTS: Extending the recording time increased the number of subjects having elevated AET from 16 after 1 day to 22 after 2 days of recording, a 9.7% gain in subjects (95% CI 4.6-19.6%). The number of chest pain episodes doubled from 1 to 2 days, and 4 subjects (7.3%) developed symptoms only on the second day of monitoring. Statistically significant reflux-symptom association probabilities surfaced in an additional 13 subjects (21.0%; 95% CI 12.7-32.7%) by the conclusion of the 2-day study. The effect primarily was to identify significant associations in patients with lower proportions of reflux-associated symptoms. Taken together, 19.4% (95% CI 11.5-30.9%) of the subject group gained meaningful information suggesting a reflux diagnosis by extending the pH monitoring time to 2 days. CONCLUSIONS: Extending monitoring to 2 days with a wireless pH monitoring system increases the detection of GERD in a clinically significant proportion of patients with NCCP.     

Prevalence of gastro-esophageal reflux disease in patients who attended the emergency room]

BACKGROUND AND AIMS: Gastroesophageal reflux disease (GERD) is a well-known important cause of non-cardiac chest pain (NCCP). It has been shown that in western countries this condition can be in 22-66% of the cases. However, this situation is unclear in Japanese hospitals. We performed this study to clarify the frequency of GERD in NCCP patients who attended the emergency room. METHODS: We investigated the final diagnosis of the patients with chest pain who attended the emergency room of our hospital in March, June, September and December of 2005. RESULTS: Forty patients with NCCP attended the emergency room in the study periods. In these patients, only one patient (2.5%) was diagnosed as GERD. Conclusions: The results of this study showed that the frequency of GERD in NCCP patients of emergency room of Japan is lower than that of western countries.     

Regression of gastroesophageal reflux disease symptoms using dietary supplementation with melatonin, vitamins and aminoacids: comparison with omeprazole

The prevalence of gastroesophageal reflux disease (GERD) is increasing. GERD is a chronic disease and its treatment is problematic. It may present with various symptoms including heartburn, regurgitation, dysphagia, coughing, hoarseness or chest pain. The aim of this study was to investigate if a dietary supplementation containing: melatonin, l-tryptophan, vitamin B6, folic acid, vitamin B12, methionine and betaine would help patients with GERD, and to compare the preparation with 20 mg omeprazole. Melatonin has known inhibitory activities on gastric acid secretion and nitric oxide biosynthesis. Nitric oxide has an important role in the transient lower esophageal sphincter relaxation (TLESR), which is a major mechanism of reflux in patients with GERD. Others biocompounds of the formula display anti-inflammatory and analgesic effects. A single blind randomized study was performed in which 176 patients underwent treatment using the supplement cited above (group A) and 175 received treatment of 20 mg omeprazole (group B). Symptoms were recorded in a diary and changes in severity of symptoms noted. All patients of the group A (100%) reported a complete regression of symptoms after 40 days of treatment. On the other hand, 115 subjects (65.7%) of the omeprazole reported regression of symptoms in the same period. There was statiscally significant difference between the groups (P < 0.05). This formulation promotes regression of GERD symptoms with no significant side effects.     

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.     

Extraesophageal and atypical manifestations of GERD

Abstract   Extraesophageal manifestations of gastroesophageal reflux disease (GERD) are essentially complications of GERD that primarily involve organs that are in proximity to the esophagus. Non-cardiac chest pain (NCCP) is an atypical manifestation of GERD, because symptoms originate in essence from the esophagus. In both atypical and extraesophageal manifestation of GERD frequent heartburn is uncommon and lack of GERD symptoms is not unusual. Esophageal mucosal injury is rarely present making upper endoscopy a low-yield procedure in both conditions. While association with GERD has been commonly reported, the extent of causality remains unknown. In NCCP, the usefulness of the proton pump inhibitor (PPI) test in diagnosing GERD-related NCCP has been established. Similar value in extraesophageal manifestations of GERD has been proposed, but rarely studied. While treatment of extraesophageal manifestations of GERD remains a challenge, PPIs in at least double the standard dose, should be considered for the initial therapy. Properly designed therapeutic studies are still lacking as well as the exact role of antireflux surgery in this patient population.     

Extra-esophageal disorders in gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) is a common condition that effects about 10% of the adult population comprising a broad spectrum of symptoms and varying degrees of severity and frequency. Extra-esophageal manifestations are increasingly being recognized. Up to 50% of patients with an endoscopically proven or negative esophagitis suffer from symptoms other than heartburn or acid regurgitation such as laryngitis, hoarseness, chronic cough, asthma, or non-cardiac chest pain. The therapy of choice is proton pump inhibitors.     

Bronchopulmonale Manifestationen der gastroösophagealen Refluxerkrankung

Gastroesophageal reflux disease (GERD) is a common disease in the western world. Usually it occurs with typical symptoms like heartburn and regurgitation, but almost every third GERD-patient presents with extraesophageal symptoms and diseases in which a causal relation with GERD is discussed. The extraesophageal symptoms possibly associated with GERD are chronic cough, bronchial asthma, sleep disturbances including obstructive sleep apnea, hoarseness, dental erosions, non-cardiac chest pain and idiopathic pulmonary fibrosis. This article gives an overview of the reflux-associated diseases of the airways as well as the proposed pathomechanisms and therapeutic options.     

胃食管反流病患者的行为干预治疗

背景:胃食管反流病(GERD)为临床常见病,部分患者药物治疗效果不佳。不良生活方式和饮食习惯可影响GERD的发病,目前关于药物联合行为干预治疗GERD的研究报道尚少。目的:评估行为干预辅助治疗GERD患者胃食管反流症状的临床疗效。方法:120例GERD患者随机分为2组,研究组予埃索美拉唑20mg bid联合行为干预治疗,对照组仅予埃索美拉唑,疗程均为8周。治疗期间记录烧心、反酸、胸痛症状并分级,根据症状总体改善情况评估临床疗效。结果:研究组59例、对照组58例患者完成治疗方案。治疗8周末,研究组显效率和总有效率分别为76.3%和91.5%,对照组分别为58.6%和77.6%,组间差异有统计学意义(P0.05)。结论:埃索美拉唑联合行为干预对GERD患者的胃食管反流症状有明显疗效。     

泮托拉唑合旋覆代赭汤治疗反流性食管炎

目的：观察伴托拉唑合旋覆代赭汤治疗反流性食管炎(RE)的疗效。方法：60例经内镜证实的RE患者，随机分为两组，治疗组30例，予以伴托拉唑40mg，1次／d口服，同时服用中药旋覆代赭汤100m1，3次／d口服；对照组30例，予以奥美拉唑20mg，1次／d口服，同时服用旋覆代赭汤100m1，3次／d，疗程均为4周。两组分别记录治疗前后反酸、烧心、胸痛、胃胀等症状积分，于4周后复查内镜。结果：两组治疗后1周，烧心、反酸、胸痛、胃胀等症状积分较治疗前均明显下降(均P＜0．01)，4周后达到缓解。治疗组内镜下食管炎治愈率为80．0％，有效率为93．3％，与对照组(76．7％及90．0％)比较，差异无显著性意义(P＞0.05)。结论：国产伴托拉唑治疗RE与奥美拉唑的疗效相同。     

Efficacy of omeprazole for the treatment of symptomatic acid reflux disease without esophagitis

BACKGROUND: Up to three quarters of patients with gastroesophageal reflux disease (GERD) have symptoms, such as heartburn, but no macroscopic evidence of erosive esophagitis, making symptomatic GERD a common clinical problem in the primary care setting. OBJECTIVE: To compare the efficacy and safety of omeprazole, 20 mg once daily; omeprazole, 10 mg once daily; and placebo in the treatment of symptomatic GERD without erosive esophagitis. METHODS: Patients with a history of heartburn (> or =12 months) and episodes of moderate to severe heartburn on 4 or more of the 7 days before endoscopy were eligible to participate in this 4-week, randomized, double-blind, placebo-controlled trial. The absence of erosive esophagitis was established through endoscopy. Eligible patients were randomized to 1 of 3 treatment groups: omeprazole, 20 mg once daily; omeprazole, 10 mg once daily; or placebo. Patients were assessed at weeks 2 and 4. The efficacy of omeprazole for the treatment of heartburn was determined mainly through the following diary card data: daily resolution of heartburn and complete resolution of heartburn every day during 1 week of treatment. The efficacy of omeprazole for the treatment of acid regurgitation, dysphagia, epigastric pain, and nausea was also assessed. RESULTS: Of 359 randomized patients, 355 were included in the statistical analysis (intention-to-treat population). Daily proportions of patients with no heartburn were consistently greater in the 20-mg omeprazole group (62%, day 7; 74%, day 27) than in the 10-mg omeprazole group (41%, day 7; 49%, day 27) or the placebo group (14%, day 7; 23%; day 27). Complete resolution of heartburn every day during the last treatment week was significantly (P< or =.002) higher in the 20-mg omeprazole group (48%) than in the 10-mg omeprazole (27%) or placebo (5%) group. Omeprazole was significantly (P< or =.003) more effective than placebo for the treatment of acid regurgitation, dysphagia, epigastric pain, and nausea. CONCLUSIONS: Patients with symptomatic GERD require profound acid suppression to achieve symptomatic relief. Omeprazole, 20 mg once daily, was superior to omeprazole, 10 mg once daily, and to placebo in providing early and sustained resolution of heartburn, as well as treatment of other troublesome GERD symptoms.     

Extraösophageale Manifestationen der Refluxerkrankung an den Atmungsorganen

Gastroesophageal reflux disease (GERD) is a common medical condition with a prevalence of 10–20% in the western world and almost every third GERD-patient presents with extraesophageal symptoms. The extraesophageal symptoms and disorders associated with GERD are chronic cough, bronchial asthma, sleep disturbances or aggravation of sleep disordered breathing, hoarseness, dental erosions and non-cardiac chest pain. The severity of the symptoms is variable. Typical GERD symptoms like heartburn and regurgitation can occur only faintly or not at all, and extraesophageal symptoms may be predominant. Causality and pathogenesis are not clarified conclusively, however recurrent microaspirations and nerval mechanisms are suggested. Recurrent aspirations, especially in patients with structural oesophageal disorders predispose to pulmonary infections. One hypothesis postulates a causal relationship between microaspirations and idopathic pulmonary fibrosis. This article gives an overview of reflux associated bronchopulmonary diseases and summarizes treatment options.     

Extraesophageal manifestations in gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) is a common condition that affects about 20-30% of the adult population, presenting with a broad spectrum of symptoms and varying degrees of severity and frequency. Other manifestations are being increasingly recognized: the so-called 'extraesophageal' manifestations, such as laryngitis, hoarseness, chronic cough, asthma, or non-cardiac chest pain. Epidemiological studies consistently demonstrate significant associations between pulmonary manifestations and GERD. Up to 50% of patients with an endoscopically proven esophagitis suffer from symptoms other than heartburn or acid regurgitation. However, the published estimates of extraesophageal disorders in patients with GERD vary widely, which may be a result of referral bias. The most effective initial approach in suspected reflux-related extraesophageal symptoms is empiric proton pump inhibitor (PPI) therapy. However, studies demonstrated that the advantage of long-term PPI treatment over placebo could have been overestimated.     

Effects of Omeprazole Versus Placebo in Treatment of Noncardiac Chest Pain and Gastroesophageal Reflux

Gastroesophageal reflux (GER) occurs in 22-66%of patients with noncardiac chest pain (NCCP). Althoughopen-label investigations have shown beneficial effectsof antireflux therapy in NCCP, no double-blind, prospective, placebo-controlled studies havebeen conducted. The purpose of this study was toevaluate the effects of omeprazole compared to placeboin a prospective, double-blind, randomized trial ofpatients with NCCP and GER. Thirty-six consecutivepatients with NCCP and GER documented by 24-hrambulatory pH testing entered this study. The subjectswere randomized to omeprazole, 20 mg by mouth twice aday (17 patients), or placebo (19 patients) foreight weeks. Patients on omeprazole obtainedsignificantly more improvement in the fraction of chestpain days (P = 0.006) and severity (P = 0.032) whencompared to placebo. More patients in the omeprazolegroup reported improvement in individual daily painscores (81% vs 44%, P = 0.03) and individual severityscores (81% vs 50%, P = 0.057). Thirteen (81%) of the subjects in the treatment arm reported overallsymptomatic improvement versus one (6%) in the placebogroup (P = 0.001). The results of this study indicatethat acid suppression with omeprazole effectively improves chest pain in patients with NCCP andGER.     

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.     

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.