Non‐erosive reflux disease,functional heartburn and gastroesophageal reflux disease; insights into pathophysiology and clinical presentation

Non‐erosive reflux disease (NERD) has emerged as a real entity in the spectrum of gastroesophageal reflux disease (GERD) and may, indeed, represent the most common manifestation of reflux disease. Recent information indicates NERD can be further subclassified based on the results of pH studies and suggests that functional heartburn needs to be differentiated as that subgroup of patients in which there appears to be no relationship between symptoms, however ‘typical’ of GERD, and acid exposure. Other aspects of NERD need to be appreciated, including overlap with functional dyspepsia and the potential variations in response to such therapeutic interventions as acid‐suppressive therapy and fundoplication. It seems quite possible that our failure to separate functional heartburn from NERD, in general, has contributed, in large measure, to diagnostic difficulties and therapeutic disappointment in GERD. An appreciation of the range of entities, of different etiology and pathology, within NERD will foster the development of effective approaches to the assessment and therapy of this challenging disorder.     

胃食管反流病与心房颤动

心房颤动（房颤）是临床上最常见的持续性心律失常,可导致患者死亡率升高。胃食管反流是消化科的常见病症,是胃内容物反流入食管引起的不适症状和／或并发症。有研究报道胃食管反流可能会引起房颤。炎症、迷走神经刺激和慢性心房缺血可能是其中的重要机制,炎症反应和自主神经功能异常参与房颤和胃食管反流病的发生发展。本文结合国内外文献对房颤与胃食管反流间的关系及其可能机制进行综述。     

The relationship between gastroesophageal reflux disease and obstructive sleep apnea

There has been an accumulating body of research concerning the extraesophageal complications of gastroesophageal reflux disease over the past decade. Given the cardiological, pulmonological, laryngeal, and dental aspects of such complications, an interdisciplinary approach is required. The most recognized manifestations are noncardiac chest pain, bronchial asthma, chronic bronchitis, chronic cough, and posterior laryngitis, as well as the acidic damage of dental enamel. This article focuses on the potential relationship between reflux disease and obstructive sleep apnea, which has been raised only more recently. Because of the decrease of primary peristalsis and the reduced production of saliva, as well as the diminished acid and volume clearance of the esophagus, sleeping can be considered as a risk factor of the reflux event by itself. Moreover, it should also be taken into account that the transdiphragmatic pressure increases in parallel with the growing intrathoracic pressure generated during obstructive apnea episodes. This has a non-negligible effect on the phrenoesophageal ligament, which is connected to the lower esophageal sphincter. Repetition of the pressure changes results in insufficiency of the cardia. While this pressure change produces a considerable suction effect, further reducing the clearing mechanism of the gastric volume, lower esophageal sphincter insufficiency can directly lead to reflux disease. The challenge for gastroenterologists is to gain further insight into this relationship and to play a more active role in the complex therapy of the disease, as well as to develop a new diagnostic approach towards the severe forms of gastroesophageal reflux disease.     

特发性肺纤维化与胃食管反流的相关性研究

目的 探讨特发性肺纤维化(IPF)与胃食管反流的相关性,分析其临床特点.方法 选2011年1月至2013年10月中国医科大学附属第一医院住院或门诊IPF患者25例(IPF组),另选非IPF的间质性肺疾病患者23例作对照(非IPF组),两组患者行24 h食管pH值监测,分析胃食管反流特点及其临床特征.结果 胃食管反流阳性IPF组16例,非IPF组8例.IPF组DeMeester评分高于非IPF组,差异有统计学意义[(22.8±21.5)分比(15.7±14.0)分;P＜0.05].IPF组长反流(反流时间持续＞5 min)次数[(3.8±4.1)次]、反流指数(1.8±1.7)高于非IPF组[(2.1±2.1)次;1.3±1.2],但差异无统计学意义.IPF胃食管反流阳性者合计反流时间百分比(pH ＜4.0)[(9.2±5.1)％]、直立位反流时间百分比[(8.5±5.2)％]、仰卧位反流时间百分比[(10.8±10.7)％]、反流次数[(54.2±22.7)次]、长反流次数[(6.3±4.2)次]、最长反流时间[(14.5±15.3) nin]、反流指数(2.5±1.7)和DeMeester评分[(34.9±20.3)分]明显高于阴性者,差异有统计学意义(P值均＜0.05).DeMeester评分与胃食管反流病问卷(GerdQ)评分呈正相关(r=0.667,P＜0.01).IPF患者胃食管反流阳性者典型胃食管反流症状:烧心7例,反流6例,多于胃食管反流阴性者(烧心2例,反流1例).结论 IPF患者胃食管反流阳性率高,但往往缺少典型的胃食管反流症状.在不具备胃酸监测条件的医院,GerdQ可用于评价IPF患者是否存在胃食管反流.     

Prevalence of gastroesophageal reflux disease in a general population in Taiwan

Background and Aim: To evaluate the prevalence and risk factors of gastroesophageal reflux disease (GERD) in a general population in Taiwan. Methods: A validated symptom questionnaire, the Chinese GERD questionnaire, was utilized to determine the prevalence of GERD within a community in Taiwan. A cut‐off value for GERD diagnosis was a total score ≥12. Additionally, demographic data, including sex, age, body mass index, and consumption of tobacco and alcohol, were recorded, and a logistic regression analysis was conducted to search the independent risk factors for the development of GERD in a general population. Results: In total, 1238 residents were recruited for this study. The monthly frequencies of heartburn, epigastric acidic discomfort, and acid regurgitation were 4.4%, 3.7%, and 2.9%, respectively. The GERD prevalence was 25% in the community. The multivariate analysis showed that female sex and age of 40–49 years and 50–59 years were independent risk factors related to the development of GERD, with odd ratios of 1.71, 3.65, and 2.41, respectively (95% confidence intervals: 1.26–2.34, 1.62–8.21, and 1.11–2.54, respectively). Conclusions: GERD has become a common disorder in the general population in Taiwan. Female sex and age of 40–49 years and 50–59 years are risk factors for the development of GERD within a community.     

Epidemiological study of symptomatic gastroesophageal reflux disease in China: Beijing and Shanghai

OBJECTIVE : To explore the 1‐year point prevalences (July–September 1996) of symptomatic gastroesophageal reflux (GER), gastroesophageal reflux disease (GERD) and reflux esophagitis (RE) in the adult population of two Chinese city‐regions (Beijing and Shanghai) and to identify the conditions that predispose patients to GERD. METHODS : Phase I: 5000 residents of the two regions aged between 18 and 70 years were studied via a questionnaire. The study was carried out by cluster sampling from city, suburban and rural areas by using simple random sampling. Symptom scores (Sc) of the intensity and frequency of heartburn, acid reflux and regurgitation within 1 year of the time of study were taken as indices of acid reflux (highest score, Sc = 18) and Sc ≥ 6 indicated the presence of symptomatic GER. Phase II: a small number of patients who were identified as having symptomatic GER in the survey were enrolled in a case– control study using gastroscopy and 24‐h pH monitoring to obtain correct diagnostic rates of GERD and RE. Estimates of the prevalence of GERD and RE were then adjusted according to the rates of correct diagnosis. RESULTS : A total of 4992 subjects completed the survey, 2.5% had heartburn once daily, 8.97% had symptomatic GER (Sc ≥ 6) and the male to female ratio was 1:1.11. Point prevalences for the year for GERD and RE were 5.77 and 1.92%, respectively. Stratified analysis indicated that the prevalence of symptomatic GER in Beijing (10.19%) was higher than that in Shanghai (7.76%) and there was also a higher prevalence of GER in males, manual laborers, people from rural areas and people older than 40 years of age in Beijing as compared with Shanghai. Stepwise logistic analysis indicated that GER had a close relationship with dental, pharyngolaryngeal disorders and respiratory diseases. The conditions that predispose patients to GERD are (OR, odds ratio): age > 40 (OR = 1.01), eating greasy/oily food (OR = 6.56), overeating (OR = 1.99), tiredness (OR = 2.35), emotional stress (OR = 2.22), pregnancy (OR = 6.80) and constipation (OR = 1.65). CONCLUSIONS : Gastroesophageal reflux disease is a common disease in the adult Chinese population and it is more common in Beijing than in Shanghai.     

反流性疾病问卷表在军人胃食管反流病中的诊断价值

[目的]探讨反流性疾病问卷表(RDQ)在军人胃食管反流病(GERD)中的诊断价值。[方法]采用多阶段、分层、整群随机抽样的方法对驻闽某部军人进行反流性疾病问卷调查,记录被调查者过去4周内烧心、非心源性胸痛、反酸和反流4种症状出现的频率和程度积分,以RDQ评分≥12分作为GERD的诊断标准,计算军人中GERD的患病率,同时分析经电子胃镜检查证实为反流性食管炎(RE)患者的RDQ评分情况。[结果]研究得出军人GERD的患病率为6.77%,经胃镜检查420例中明确诊断为RE 60例(RE组)和内镜检查正常360例(非RE组)的RDQ评分差异有统计学意义(P0.01),说明评分与发生RE之间有较大关联。[结论]RDQ评分量表可以作为初步诊断军人GERD的一个良好的筛选试验。     

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.     

Multichannel intraluminal impedance and pH monitoring in gastroesophageal reflux disease

The role of acid is very well established in the pathogenesis of gastroesophageal reflux disease and acid suppression constitutes the main approach to its medical treatment. With the current frequent use of proton pump inhibitors, we are seeing increasing numbers of patients in whom symptoms persist despite pharmacological acid suppression. Reflux monitoring has been traditionally performed through esophageal pH measurement to detect acid reflux (i.e., drops in esophageal pH to below 4.0). Multichannel intraluminal impedance and pH measurement constitutes an important development in reflux monitoring because, in addition to detecting acid reflux, it enables measurement of nonacid reflux (i.e., with a pH > 4.0, also known as ‘weakly acidic’ for pH > 4 but < 7, or ‘weakly alkaline’ if pH > 7), which may be responsible for symptoms in some patients who are being treated with proton pump inhibitors. This review describes the approach to measuring nonacid reflux, the possible mechanisms responsible for symptoms due to this type of reflux, the clinical importance of this phenomenon and available treatment options; and the role of multichannel intraluminal impedance and pH monitoring in the evaluation of refractory gastroesophageal reflux disease.     

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.     

Association between gastroesophageal reflux disease and vocal fold polyps

The aim of this study is to explore the relationship between gastroesophageal reflux disease (GERD) and vocal fold polyps (VFPs).This is a Case-Control study and was performed with the help of The Second Affiliated Hospital of Chongqing Medical University.Twenty-seven patients with VFP and 20 controls without VFP were recruited between May and October 2018. All the subjects underwent a saliva pepsin test, completed the GerdQ questionnaire and 24-hour multichannel intraluminal impedance with pH (24-h MII-pH) monitoring. Twenty-five resected VFP specimens were examined with immunohistochemical (IHC) and double immunofluorescence (IF) staining.The incidence of GERD in the VFP group was significantly higher than that in the control group (P = .003). Patients with VFP had significantly higher GerdQ scores, pepsin concentrations, and pepsin-positive rates (P < .05). Moreover, the number of proximal and upright reflux events was significantly higher in the VFP group (P < .05). The pepsin concentration in saliva showed a significant positive correlation with the pepsin levels in tissues (r² = 0.50, P = .011). Pepsin and TGF-β1-positive cells were colocalized with CD45RO-positive cells. IHC staining showed that the majority of VFP patients had a positive expression of pepsin (20/25, 80%) and pepsin-positive cells were found in both the squamous epithelium and mesenchymal tissues. IHC staining of TGF-β1 in VFP revealed findings similar to those of pepsin staining.GERD is an important risk factor for VFP. Pepsin may promote the aggregation of immune cells, increase the local cytokines, and promote inflammatory reaction, suggesting a potential new pathogenesis for VFP. The saliva pepsin test is a reliable method for GERD diagnosis.     

Pharmacologic management and treatment of gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) is one of the most common diagnoses in daily practice. Diagnosis can be made on symptom evaluation, on pH-monitoring or on endoscopic findings. In contrast to commonly held opinion there is no strong evidence that lifestyle factors are a dominant factor in the pathophysiology of GERD. The various agents currently used for treatment of GERD include mucoprotective substances, antacids, H(2)-blockers and proton pump inhibitors. This article gives an overview of the pharmacological management of GERD and focuses on the differential therapy of endoscopy-negative GERD, GERD with esophagitis and maintenance therapy.     

Association of gastroesophageal reflux disease risk with exacerbations of chronic obstructive pulmonary disease

Gastroesophageal reflux disease (GERD) may be a potential risk factor for exacerbations of chronic obstructive pulmonary disease (COPD). The aim of the present study was to explore the association of GERD risk with exacerbations of COPD. Patients with COPD were consecutively recruited, and COPD Assessment Test (CAT) and Reflux Diagnostic Questionnaire (RDQ) were administered. If the CAT score was 5 points higher than that taken in the stable states, the patient was considered as having exacerbations of COPD. A RDQ score of ≥12 is defined high GERD risk. Univariate and multivariate logistic regression analyses were performed to evaluate the relationship between high GERD risk and exacerbations of COPD. Among 386 patients with COPD, the mean CAT score was 18.3 ± 6.6, and 76 (19.7%) patients had exacerbations during the 1‐year follow‐up. The mean RDQ score was 10.1 ± 4.7, and 132 (34.2%) patients were identified as having high GERD risk. Multivariate logistic regression analyses revealed that the high GERD risk (odds ratio, 2.31; 95% confidence interval, 1.29–3.87) was an independent risk factor of COPD exacerbations. In conclusion, high GERD risk appears to be associated with higher odds for COPD exacerbations.     

Definition and diagnosis of gastroesophageal reflux disease

Abstract   With widespread treatment of Helicobacter pylori infection, and that peptic ulcer diseases are no longer considered a chronic illness and are declining in most parts of the world, gastroesophageal reflux disease (GERD) predominates the upper gastrointestinal disease spectrum. GERD is a well-defined condition. More innovative research in GERD in recent years led us to new conceptual frameworks on pathogenesis and novel diagnostic tests. The proton pump inhibitor test has evolved to become the diagnostic test of choice for the investigation of patients with the disease spectrum of GERD. Multi-channel intraluminal impedance with pH sensor allows the detection of pH episodes irrespective of their pH values (acid and nonacid reflux). It is useful to measure gastroesophageal reflux in the postprandial period, and in patients with persistent symptoms while on therapy and those with atypical symptoms.     

Comparative analysis between psychological and endoscopic profiles in patients with gastroesophageal reflux disease: a prospective study based on screening endoscopy

BACKGROUND: Associations between psychological and endoscopic profiles are not clearly validated among the heterogeneous patients with gastroesophageal reflux disease (GERD). The purpose of the present paper was therefore to identify any associations by means of cross-sectional study. METHODS: Consecutive participants in a health screening program were enrolled. Definition and severity of erosive esophagitis were assessed with Los Angeles classification. Frequency and severity of psychological symptoms were measured with a 30-item Brief Symptom Rating Scale (BSRS) and personality traits with a short form of the Maudsley Personality Inventory (MPI). Statistic analyses were performed based on the presence of GERD symptoms or endoscopic esophagitis. RESULTS: A total of 4600 participants were recruited. There were 1331 subjects (29%) with manifestations suggesting GERD, including non-erosive reflux disease (NERD) in 488 (10.6%), symptomatic erosive esophagitis (SEE) in 164 (3.6%), and asymptomatic erosive esophagitis (AEE) in 679 (14.8%). The BSRS parameters were significantly higher in symptomatic subjects (i.e. NERD and SEE subjects; P < 0.001); neuroticism scores were also higher (P < 0.001), but extroversion scores (P < 0.001) were lower than those of asymptomatic subjects. Following logistic regression analysis, independent risk factors for GERD symptoms were female gender (odds ratio [OR]: 1.596; 95% confidence interval [CI]: 1.303-1.955) and higher neuroticism scores (OR: 1.046; 95%CI: 1.032-1.06). For erosive esophagitis, independent risk factors were male gender (OR: 2.943; 95%CI: 2.359-3.671) and higher body mass index scores (OR: 1.098; 95%CI: 1.069-1.127). CONCLUSIONS: Psychological characteristics predict likelihood of GERD symptoms but not structural state of esophagus. Male gender and obesity are risk factors for erosive esophagitis; whereas female gender and neuroticism are more likely to be associated with GERD symptoms.