Current Advancement on the Dynamic Mechanism of Gastroesophageal Reflux Disease

Gastroesophageal reflux disease (GERD) is a common clinical disease associated with upper gastrointestinal motility disorders. Recently, with improvements in living standards and changes in lifestyle and dietary habits, the incidence of GERD has been increasing yearly. However, the mechanism of GERD has not been fully elucidated due to its complex pathogenesis, and this had led to unsatisfactory therapeutic outcomes. Currently, the occurrence and development of GERD involve multiple factors. Its pathogenesis is mainly thought to be related to factors, such as lower esophageal sphincter pressure, transient lower esophageal sphincter relaxation, crural diaphragmatic dysfunction, hiatus hernia, and impaired esophageal clearance. Therefore, explaining the pathogenesis of GERD more clearly and systematically, exploring potential and effective therapeutic targets, and choosing the best treatment methods have gradually become the focus of scholars'' attention. Herein, we reviewed current advancements in the dynamic mechanism of GERD to better counsel patients on possible treatment options.     

胃食管反流病患者自我管理行为依从性及其影响因素调查

目的：调查分析胃食管反流病患者自我管理行为依从性情况及其影响因素。方法：选取2010年2月-2012年6月来我院就诊治疗的胃食管反流患者150例,利用自我行为管理量表、自我效能量表、焦虑自评量表（SAs）及抑郁自评量表（SDS）进行调查,并采用单因素分析及多因素分析法分析其影响因素。结果：所有150例患者的自我行为管理平均得分为37．12＋4．95分,处于中下游水平,其中治疗依从性较好而疾病知识认知方面较差;而从单因素及多因素分析中得知,胃食管反流病患者自我行为依从性的影响因素主要为自我效能、工作学习压力及文化程度（偏回顾系数=0．301、-2．264、1．403）。结论：胃食管返流病患者的自我管理行为依从性较差,这与其文化程度较低、工作学习压力较大有关,医务人员应指导患者减轻工作学习压力,改善生活方式以提高其自我管理行为依从性。     

胃食管反流病的治疗进展

胃食管反流病(gastroesophaeal reflux disease,GERD)是医疗实践中的最常见的疾病之一,其发病率在世界范围内呈逐年上升趋势,且随年龄增长而增加,40-60岁为高发年龄[1]。GERD是一种由胃、十二指肠内容物反流入食管引起不适症状和(或)并发症的疾病,GERD在临床上大致可分为:糜烂性食管炎(EE)(反流性食管炎(RE))和非糜烂性食管炎(NERD)。其中NERD最多见,约占60%。GERD远期危害较小,但其病情漫长且极易复发,严重影响了生活质量。主要表现为食管症状(包括典型的烧心和反流)和食管外症状(包括咽部异物感、咳嗽、声嘶、哮喘、咽喉炎等表现),还有增加发展为Barrett食管及食管癌的危险[2,3]。GERD的治疗目的是愈合食管炎,快速缓解症状、减少复发、提高生活质量,治疗方法主要包括以下4个方面:一般治疗,药物治疗,内镜下治疗和外科治疗。近年来已成为国内外研究的热点,本文就近年来对GERD的治疗进展做一综述。     

Decreased Prevalence of Helicobacter pylori Infection in Gastroesophageal Reflux Disease

Background.   An increased incidence of reflux esophagitis has been reported after eradication of H. pylori in patients with duodenal ulcer. To determine if H. pylori is associated with lower rates of esophagitis, we studied the prevalence of H. pylori infection in patients with and without reflux esophagitis and a subgroup of patients with concomitant peptic ulcer disease.
Methods.   Patients who underwent esophagogastroduodenoscopy and had diagnostic testing for H. pylori over a 30-month period were studied. H. pylori infection was determined by rapid urease testing, gastric histopathology, or serology. Reflux esophagitis was determined by endoscopic and/or histologic criteria.
Results.   Of 514 patients, 39.5% had H. pylori infection and 22.2% had reflux esophagitis. The prevalence of H. pylori infection in patients with reflux esophagitis was 30.7%, compared with 42.0% in patients without esophagitis ( p = 0.039). The odds ratio for esophagitis risk with H. pylori infection was 0.61 (95% CI, 0.39–0.95). Neither patient age nor gender affected H. pylori prevalence. In patients with duodenal ulcer, H. pylori was present in 36.4% of patients with esophagitis and in 69.2% of patients without esophagitis ( p = 0.018). The odds ratio for esophagitis with H. pylori infection in these patients was 0.25 (95% CI, 0.09–0.73).
Conclusions.   Our study demonstrates that H. pylori infection is significantly less prevalent in patients with reflux esophagitis and may protect against its development. In duodenal ulcer patients, this effect was more dramatic. Further study is required to confirm these findings and elucidate mechanisms underlying possible beneficial effects of H. pylori.     

Complications of Gastroesophageal Reflux

An edited summary of an Interdepartmental Conference arranged by the Department of Medicine of the UCLA School of Medicine, Los Angeles. The Director of Conferences is William M. Pardridge, MD, Professor of Medicine.Several specialists have recently recognized that gastrointestinal reflux causes complications resulting in significant disease. It causes discomfort, indigestion, esophagitis, Barrett''s esophagus, and carcinoma of the esophagus. Pediatricians attribute many early pulmonary problems, and even some sudden deaths in infants, to the reflux of gastric contents. Otolaryngologists now recognize that many cases of nonbacterial, nonspecific pharyngitis and laryngitis are due to the reflux of gastrc acid secretions. Contact granuloma and cancer of the larynx may, in some instances, be secondary to nocturnal reflux. Thoracic surgeons and pulmonologists believe chronic tracheobronchitis and some cases of pulmonary disease are attributable to recurrent bathing of the respiratory epithelium by aspirated gastric contents. An awareness of the many complications of gastrointestinal reflux should lead to a multidisciplined attack on the factors responsible for these diseases.     

硝酸酯类药物及钙离子拮抗剂对胃食管反流的影响

目的:探讨硝酸酯类药物及钙离子拮抗剂对胃食管反流症状的影响.方法:选取2010年1月-2011年1月我院收治的心血管病患者99例,根据服用药物不同分为三组:单独使用硝酸酯类药物组35例;单独使用钙离子拮抗剂组31例;以及对照组(既无硝酸酯类药物也无钙离子拮抗剂)33例.比较三组患者胃食管反流症状积分.结果:单纯使用硝酸酯类药物组比其他药物组及钙离子拮抗剂组的病人在早饱、恶心和呕吐的症状积分上较高并存在明显差异(P＜0.05).钙离子拮抗剂组与硝酸酯类药物组比较烧心症状积分较高并有统计学上明显差异(P＜0.05).钙离子拮抗剂组与其他药物组比较烧心及返酸积分较高,但差异无统计学意义(P＞0.05).结论:硝酸酯类药物在早饱、恶心、呕吐几方面比使用其他类药物更多地引起症状.钙离子拮抗剂似乎更易引起反酸、烧心等胃食管反流症状,但未得到证实.     

Effects of Proton Pump Inhibitors on the Gastrointestinal Microbiota in Gastroesophageal Reflux Disease

Proton pump inhibitors(PPIs) are commonly used to lessen symptoms in patients with gastroesophageal reflux disease(GERD). However, the effects of PPI therapy on the gastrointestinal microbiota in GERD patients remain unclear. We examined the association between the PPI usage and the microbiota present in gastric mucosal and fecal samples from GERD patients and healthy controls(HCs) using 16 S rRNA gene sequencing. GERD patients taking PPIs were further divided into short-term and long-term PPI user groups. We showed that PPI administration lowered the relative bacterial diversity of the gastric microbiota in GERD patients. Compared to the non-PPIuser and HC groups, higher abundances of Planococcaceae, Oxalobacteraceae, and Sphingomonadaceae were found in the gastric microbiota from the PPI-user group. In addition, the Methylophilus genus was more highly abundant in the long-term PPI user group than in the short-term PPI-user group. Despite the absence of differences in alpha diversity, there were significant differences in the fecal bacterial composition of between GERD patients taking PPIs and those not taking PPIs. There was a higher abundance of Streptococcaceae, Veillonellaceae, Acidaminococcaceae,Micrococcaceae, and Flavobacteriaceae present in the fecal microbiota from the PPI-user group than those from the non-PPI-user and HC groups. Additionally, a significantly higher abundance of Ruminococcus was found in GERD patients on long-term PPI medication than that on shortterm PPI medication. Our study indicates that PPI administration in patients with GERD has a significant effect on the abundance and structure of the gastric mucosal microbiota but only on the composition of the fecal microbiota.     

终末期肾病患者合并胃食管反流病的临床研究进展

胃食管反流病(GERD)是最常见的食管疾病之一。多项研究表明,终末期肾病(ERSD)患者GERD的患病率高于普通人群。目前对于ERSD患者特别是血液透析患者GERD的症状特点及严重程度的研究较少。ESRD患者常并发或伴发糖尿病、高血压等,而糖尿病神经病变可影响胃排空功能,钙拮抗剂和硝酸酯类药物可影响LES舒张功能。透析相关淀粉样变通过影响食管蠕动、食管下段括约肌张力和胃排空影响GERD的发生。ERSD患者中,相当比例的患者全身状况不佳,行胃镜风险较高,常常应用标准化量表或质子泵抑制剂诊断试验评估患者症状性GERD患病情况。ESRD及透析患者GERD的知晓率仍较低,部分患者自行服用碳酸氢钠等非一线药物控制症状。理论上对于ESRD及透析患者伴随的GERD进行早期诊断和治疗可能提高患者生活质量,并减少水钠摄入,改善血压及透析间期体重增加,降低心血管事件风险,具体的临床获益仍有待进一步研究证实。     

以胸痛为主要表现的胃食管反流病36例临床分析

目的：探讨以胸痛为主要表现的胃食管反流病的病因、临床特点及诊治方法。方法：选择本院近年来诊治的36例已排除心源性及食管器质性病变,诊断为胃食管反流病的胸痛患者,予以埃索美拉唑20mg,每日两次;吗叮林10mg,每日三次治疗8周,观察其疗效并分别于2周,4周,8周记录症状缓解情况。结果：经抗反流治疗8周后,30例（83.33%）胸痛完全消失,4例（11.11%）明显缓解,2例（5.56%）无效,总有效率达94.44%。胸痛症状在治疗2周后积分下降不明显,而治疗4周,8周后显著改善,与治疗前比较有显著性差异（P〈0.01）。结论：胃食管反流病病因复杂、临床表现多样易误诊漏诊,胃镜检查结合24小时食管动态ph监测,必要时给予质子泵抑制剂试验性治疗可提高本病的确诊率。     

Gastroesophageal Reflux Disease and Atrial Fibrillation: A Nationwide Population-Based Study

Objectives

Precise mechanisms of atrial fibrillation (AF) are uncertain, but their association with esophageal disorders has been recently proposed. The association between gastroesophageal reflux disease (GERD), the most common gastroesophageal disorder, and AF remains undetermined. We therefore aimed to investigate the association between GERD and later development of AF.

Methods and Results

Patients with GERD were identified from the 1,000,000-person cohort dataset sampled from the Taiwan National Health Insurance database. The study cohort comprised 29,688 newly diagnosed adult GERD patients; 29,597 randomly selected age-, gender-, comobidity-matched subjects comprised the comparison cohort. Cox proportional hazard regressions were performed as a means of comparing the AF-free survival rate for the two cohorts. During a maximum three years of follow-up, a total of 351 patients experienced AF, including 184 (0.62%) patients in the GERD cohort and 167 (0.56%) in the control group. The log-rank test showed that patients with GERD had significantly higher incidence of AF than those without GERD (p = 0.024). After Cox proportional hazard regression model analysis, GERD was independently associated with the increased risk of AF (hazard ratio, 1.31; 95% confidence interval, 1.06–1.61, p = 0.013).

Conclusion

GERD was independently associated with an increased risk of future AF in a nationwide population-based cohort.     

胃食管反流病中安慰剂反应率的相关研究

目的：对胃食管反流病（GERD）随机对照试验中的安慰剂反应率进行Meta分析并研究影响该反应率的因素。方法：检索EMBASE,CochraneControlledTrialRegister和Medline数据库中公开发表的关于双盲、随机、安慰荆对照治疗GERD的英文文献,所有文献均包括质子泵抑制剂／H2受体阻滞剂,治疗时间至少为2周。对文献试验数据进行Meta分析,绘制森林图,同时绘制漏斗图检查发表偏倚。结果：纳入24个研究,共包括8917名患者。有效治疗的反应率与安慰剂反应率相比的OR为3．70（95％CI：2．77～4．95）。所有的安慰剂反应率为18．84％（2．93％-47．05％）。运用质子泵抑制剂治疗的患者与H：受体阻滞剂治疗者相比,安慰剂反应率明显降低（14．50％vs．24．68％,P=0．05）。糜烂性食管炎患者的安慰剂反应率与非糜烂性食管炎者相比略低,两者差异无显著性（P〉0．05）。结论：在GERD随机对照试验中,安慰剂反应率确实存在。该反应率降低与质子泵抑制剂的运用相关,而与腐蚀性食管炎的存在与否无关。     

Long-Term Benefits of Smoking Cessation on Gastroesophageal Reflux Disease and Health-Related Quality of Life

ObjectiveSmoking is associated with gastroesophageal reflux disease (GERD). Varenicline, a nicotinic receptor partial agonist, is used to aid smoking cessation. The purpose of this study was to prospectively examine the long-term benefits of smoking cessation on GERD and health-related quality of life (HR-QOL).MethodsPatients treated with varenicline were asked to fill out a self-report questionnaire about their smoking habits, gastrointestinal symptoms, and HR-QOL before and 1 year after smoking cessation. The prevalence of GERD, frequency of symptoms, and HR-QOL scores were compared. We also investigated associations between clinical factors and newly-developed GERD.ResultsA total of 141 patients achieved smoking cessation (success group) and 50 did not (failure group) at 1 year after the treatment. The GERD improvement in the success group (43.9%) was significantly higher than that in the failure group (18.2%). The frequency of reflux symptoms significantly decreased only in the success group. There were no significant associations between newly developed GERD and clinical factors including increased body mass index and successful smoking cessation. HR-QOL significantly improved only in the success group.ConclusionsSmoking cessation improved both GERD and HR-QOL. Smoking cessation should be recommended for GERD patients.     

Helicobacter pylori and Gastroesophageal Reflux Disease: A Case–Control Study

Background:  Gastric colonization with Helicobacter pylori is a proposed protective factor against gastroesophageal reflux disease (GERD), but little population-based data exist and other data conflict.
Methods:  We conducted a case–control study within the membership of a large integrated health-care system that compared GERD-free subjects with two groups: subjects with a physician-assigned GERD diagnosis and randomly selected members with self-described weekly GERD symptoms. Subjects completed interviews, GERD questionnaires, and antibody testing for H. pylori and its cagA protein.
Results:  Serologic data were available for 301 physician-assigned GERD patients, 81 general membership subjects with GERD symptoms, and 175 general membership subjects without GERD symptoms. Physician-assigned GERD patients were less likely to have H. pylori antibodies than GERD-free member controls (odds ratio (OR) = 0.27, 95% confidence interval (CI) 0.15–0.47); there was also an inverse association between H. pylori and GERD symptom severity (OR = 0.18, 95% CI 0.08–0.41; severe or very severe symptoms) and GERD frequency (OR = 0.18, 95% CI 0.09–0.38; for symptoms at least weekly). The association was stronger among persons with erosive GERD and was similar between H. pylori -positive subjects with and without cagA. There was no association among persons who were cagA positive, but H. pylori negative. Similar findings were found in analyses of the general membership with self-described GERD symptoms.
Conclusions:  H. pylori antibody status was inversely associated with a GERD diagnosis and GERD symptoms compared with a general membership population.     

兰索拉唑治疗胃食管反流病的临床疗效及食管功能变化观察

目的:探讨兰索拉唑治疗胃食管反流病的临床疗效,并观察食管功能变化.方法:回顾性分析我院2009年10月-2012年5月收治的GERD患者500人,根据治疗方法不同分为分为兰索拉唑组和法莫替丁组,比较两组的治疗效果;并采用超声内镜测定食管运动功能的在服药前后的变化.结果:兰索拉唑组有效率为89.2％,法莫替丁组有效率为78.4％,二者进行比较,X2=16.850,P＜0.05,差异有统计学意义.兰索拉唑组与法莫替丁组治疗Ⅰ级、Ⅱ级、Ⅲ级和Ⅳ级胃食管反流病效果比较,P均＜0.05,差异有统计学意义(X2=3.943,X2=5.223,X2=4.028,X2=3.988).兰索拉唑组顶端收缩指数、收缩周期、顶端被动扩张管腔的最大截面积与法莫替丁组比较,P均＜0.05,差异有统计学意义(t=4.271,t=3.982,t=4.028).兰索拉唑组的不良反应发生率为4.8％,法莫替丁组不良反应发生率为13.6％,两组不良反应发生率比较,X2=11.588,P＜0.05,差异有统计学意义.结论:兰索拉唑治疗胃食管反流病效果良好,不良反应发生率低,安全性高,适应临床应用.     

Surgical Models of Gastroesophageal Reflux with Mice

Multiple surgical procedures have been reported to induce gastroesophageal reflux in animals. Herein, we report three surgical models with mice aiming to induce reflux of gastric contents, duodenal contents or mixed contents. Surgical procedures and general principles have been described in detail. A researcher with surgical experience should be able to grasp the technique after a short period of practice. After surgery, most mice can survive and develop reflux esophagitis similar to that in humans. However, it should be noted that histological differences between mouse and human esophagus are the inherent limitations of these surgical models. If used for research on Barrett’s esophagus and adenocarcinoma, these procedures may need to be combined with genetic modifications.     

Associations of Circulating Gut Hormone and Adipocytokine Levels with the Spectrum of Gastroesophageal Reflux Disease

Objective

The pathogenesis of gastroesophageal reflux disease (GERD) is complex and poorly understood. We aim to investigate the association of various circulating peptide hormones with heterogenous manifestations of GERD.

Methods

One hundred and four patients that had experienced typical GERD symptoms (heartburn and/or acid regurgitation) for at least 3 episodes per week in the past 3 months were enrolled. All patients received a baseline assessment of symptom severity and frequency with the Reflux Disease Questionnaire and an upper endoscopy to classify GERD into erosive esophagitis (EE, n = 67), non-erosive esophagitis (NE, n = 37), and Barrett’s esophagus (BE, n = 8). Fifty asymptomatic subjects with an endoscopically normal esophagus were recruited as the control group. Complete anthropometric measures and blood biochemistry were obtained and fasting serum levels of adipocytokines (adiponectin and leptin) and gut hormones (ghrelin and peptide YY (PYY)) were determined by enzyme-linked immunosorbent assay in all subjects.

Results

All circulating peptide hormone levels were not statistically different between the GERD and control groups. However, GERD patients appeared to have lower PYY levels [median (25^th-75^th percentile), 80.1 (49.8–108.3) vs. 99.4 (65.8–131.9) pg/ml, p = 0.057] compared with control subjects. Among the GERD patients, ghrelin levels were inversely associated with the frequency and severity of acid regurgitation. In male GERD patients, EE was associated with significantly higher PYY levels [107.0 (55.0–120.8) vs. 32.8 (28.7–84.5) pg/ml, p = 0.026] but lower adiponectin levels [6.7 (5.6–9.3) vs. 9.9 (9.6–10.6) μg/ml, p = 0.034] than NE. Patients with BE had significantly lower adiponectin levels [6.0 (5.1–9.2) vs. 9.2 (7.1–11.2) μg/ml, p = 0.026] than those without BE.

Conclusions

Humoral derangement of circulating peptide hormones might participate in inflammation and symptom perception in patients suffering from GERD. Further studies to clarify the exact role of these hormones in the pathogenesis of GERD are warranted.     

Noctural Asthma: Role of Nocturnal Gastroesophageal Reflux

Gastroesophageal reflux (GER) is common in those with asthma, with 77% of asthmatics complaining of heartburn, with 41% experiencing reflux-associated respiratory symptoms. Likewise, 24% of those with asthma that is difficult to control have “clinically silent” GER. There are no studies examining nocturnal reflux symptoms in asthmatics. Esophageal dysmotility is also common, and abnormal esophageal acid contact times on 24h esophageal pH tests were found in 82% of asthmatics examined consecutively. Most asthmatics with GER also have abnormal esophageal acid contact times while in the supine position, reflecting sleep time. Endoscopic evidence of esophagitis was found in 43% of asthmatics. Two mechanisms of bronchoconstriction induced by esophageal acid have been proposed: a vagally mediated reflex, by which esophageal acid in the distal esophagus causes reflex bronchoconstriction, and microaspiration. Although there is conflicting evidence, distal esophageal acid causes a decrease in peak expiratory flow rates, an increase in respiratory resistance, and an increase in minute ventilation. If microaspiration is present, there is further augmentation of this airway response. Although only a few studies have been performed in those with nocturnal asthma with GER, one study in a pediatric population showed that esophageal acid infusions caused more airway responses at 04:00 than at 24:00. Also, asthmatic children with nocturnal asthma symptoms have a higher re-flux score, with a positive correlation between reflux score and nighttime-associated wheezing. Despite these findings in children, a study performed in sleeping adults with nocturnal asthma noted no alterations in airflow resistance with esophageal acid, concluding that GER contributed little to the nocturnal worsening of asthma. There are also gastroesophageal circadian issues that may influence GER in asthmatics. Gastric acid secretion peaks at approximately 21:00, and gastric emptying is delayed when a meal is given at 20:00 versus 08:00. Esophageal acid clearance is delayed significantly during sleep, and acid clearance occurs during arousals. Upper esophageal sphincter (UES) pressure also decreases with sleep onset, which may predispose to microaspiration. Further research is needed to clarify what role nocturnal reflux has on nocturnal asthma and airway inflammation and whether circadian rhythm factors alter airway responses to esophageal acid.     

Inhibitory Effect of Nasal Intermittent Positive Pressure Ventilation on Gastroesophageal Reflux

Non-invasive intermittent positive pressure ventilation can lead to esophageal insufflations and in turn to gastric distension. The fact that the latter induces transient relaxation of the lower esophageal sphincter implies that it may increase gastroesophageal refluxes. We previously reported that nasal Pressure Support Ventilation (nPSV), contrary to nasal Neurally-Adjusted Ventilatory Assist (nNAVA), triggers active inspiratory laryngeal closure. This suggests that esophageal insufflations are more frequent in nPSV than in nNAVA. The objectives of the present study were to test the hypotheses that: i) gastroesophageal refluxes are increased during nPSV compared to both control condition and nNAVA; ii) esophageal insufflations occur more frequently during nPSV than nNAVA. Polysomnographic recordings and esophageal multichannel intraluminal impedance pHmetry were performed in nine chronically instrumented newborn lambs to study gastroesophageal refluxes, esophageal insufflations, states of alertness, laryngeal closure and respiration. Recordings were repeated without sedation in control condition, nPSV (15/4 cmH₂O) and nNAVA (~ 15/4 cmH₂O). The number of gastroesophageal refluxes recorded over six hours, expressed as median (interquartile range), decreased during both nPSV (1 (0, 3)) and nNAVA [1 (0, 3)] compared to control condition (5 (3, 10)), (p < 0.05). Meanwhile, the esophageal insufflation index did not differ between nPSV (40 (11, 61) h^-1) and nNAVA (10 (9, 56) h^-1) (p = 0.8). In conclusion, nPSV and nNAVA similarly inhibit gastroesophageal refluxes in healthy newborn lambs at pressures that do not lead to gastric distension. In addition, the occurrence of esophageal insufflations is not significantly different between nPSV and nNAVA. The strong inhibitory effect of nIPPV on gastroesophageal refluxes appears identical to that reported with nasal continuous positive airway pressure.