Functional gastroesophageal reflux disease (GERD)

Opinion statement  

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.     

Questionnaire based gastroesophageal reflux disease (GERD) assessment scales

Questionnaire based assessment scales for gastroesophageal reflux disease (GERD) have been utilized for assessment of the patient’s symptomatology, assessment of symptom severity and frequency, assessment of health-related quality of life and for assessment of response to treatment. A multitude of unidimensional and multidimensional questionnaires exist for making symptom assessment and monitoring quality of life in GERD. Many of the scales meet some of the parameters of an ideal evaluative GERD specific assessment instrument. Yet, there are certain shortcomings and challenges which are faced in development of GERD questionnaires. This review discusses the features of an ideal symptom assessment instrument, examines the strengths and weaknesses of currently available questionnaires.     

Review of gastroesophageal reflux disease (GERD) in the diabetic patient

This article reviews the known pathophysiological mechanisms of comorbid gastroesophageal reflux disease (GERD) in the diabetic patient, discusses therapeutic options in care, and provides an approach to its evaluation and management. We searched for review articles published in the past 10 years through a PubMed search using the filters diabetes mellitus, GERD, pathophysiology, and management. The search only yielded a handful of articles, so we independently included relevant studies from these review articles along with related citations as suggested by PubMed. We found diabetic patients are more prone to developing GERD and may present with atypical manifestations. A number of mechanisms have been proposed to elucidate the connection between these two diseases. Studies involving treatment options for comorbid disease suggest conflicting drug–drug interactions. Currently, there are no published guidelines specifically for the evaluation and management of GERD in the diabetic patient. Although there are several proposed mechanisms for the higher prevalence of GERD in the diabetic patient, this complex interrelationship requires further research. Understanding the pathophysiology will help direct diagnostic evaluation. In our review, we propose a management algorithm for GERD in the diabetic patient.     

Symptom assessment tools for gastroesophageal reflux disease (GERD) treatment

Relief of symptoms, both typical and atypical, is the mainstay of therapy for patients with gastroesophageal reflux disease (GERD); however, evaluation of GERD symptoms' response to treatment has been hampered by the lack of a questionnaire that meets all the criteria of an ideal evaluative GERD symptom assessment tool. These criteria are: sensitivity in GERD patients, covering all symptom dimensions (multidimensional construct), assessment of frequency and intensity of "typical" and "atypical" GERD symptoms, practical and economical, easy to understand, responsive over short time intervals, use as a patient self-assessment tool, amenable to daily use, psychometrically validated, and translation into many languages with cross-cultural adaptation. Thus far, 14 instruments have been developed to assess GERD symptoms and potentially can be used to evaluate treatment response during a therapeutic trial in GERD patients. However, comparison of the different evaluative tools is needed.     

Females without reflux symptoms or gastroesophageal reflux disease have less distal esophageal acid exposure than males without reflux symptoms or gastroesophageal reflux disease

Ambulatory 24‐hour esophageal pH monitoring is the gold standard examination to assess esophageal acid exposure. Gender‐related variation is a well‐recognized physiologic phenomenon in health and disease. To date, limited gender‐specific 24‐hour esophageal pH monitoring data are available. The aim of this study was to obtain values of esophageal pH monitoring in males and females without reflux symptoms or gastroesophageal reflux disease (GERD) to determine if gender variation exists in esophageal acid exposure among individuals without these factors. Twenty‐four‐hour dual esophageal pH monitoring was performed in male and female volunteers without reflux symptoms or GERD. Values for total number of reflux episodes, episodes longer than 5 minutes, total reflux time in minutes, % time with pH below 4, and longest reflux episode in the proximal/distal esophagus were obtained and recorded for both groups. The distal channel was placed 5 cm and proximal channel 15 cm above the manometrically determined lower esophageal sphincter. Means were compared using an independent sample t‐test. Sixty‐seven males and 69 females were enrolled. All subjects completed esophageal 24‐hour pH monitoring without difficulty. There was no age or body mass difference between groups. Females had significantly fewer reflux episodes at both esophageal measuring sites and, significantly less total reflux time and % time with pH below 4 in the distal esophagus than males. All other parameters were similar. Significant gender‐related differences exist in esophageal acid exposure, especially in the distal esophagus in individuals without reflux symptoms or GERD. These differences underscore the need for gender‐specific reference values for 24‐hour pH monitoring, allowing for an accurate evaluation of esophageal acid exposure in symptomatic patients.     

Mechanisms underlying excessive esophageal acid exposure in patients with gastroesophageal reflux disease

The cause of reflux esophagitis (RE) is excessive esophageal acid exposure. Acid reflux and acid clearance after acid reflux are important factors related to excessive esophageal acid exposure. The main mechanism responsible for acid reflux is transient lower esophageal sphincter relaxation (TLESR), which is LES relaxation not associated with swallowing, and acid reflux caused by low LES pressure is rare. The frequency of TLESR in the postprandial period does not significantly differ between healthy subjects and gastroesophageal reflux disease (GERD) patients; however, the proportion of acid reflux episodes during TLESR is significantly higher in GERD patients. The layer of acid that appears above the dietary layer immediately below the esophagogastric junction (acid pocket) is attracting increasing attention as a cause of the difference in the proportion of acid reflux episodes during TLESR. The proportion of acid reflux episodes during TLESR is significantly higher when the acid pocket is present in the hernia sac than when it is located below the diaphragm. The acid pocket also shows upward migration and reaches the esophageal side of the esophagogastric junction, and the acid pocket itself has been suggested to cause mucosal damage in the lower esophagus. The amplitude and success rate of primary peristalsis decreases with increases in the severity of RE, leading to excessive esophageal acid exposure. Furthermore, the success rate of secondary peristalsis is lower in GERD patients than in healthy subjects.     

胃食管反流病食管酸暴露和食管动力学变化特征

目的探讨无效食管动力(IEM)在胃食管反流病(GERD)中的作用,以及体质量对食管酸暴露及食管动力的影响。方法77例GERD典型症状患者全部行食管高分辨率压力测定(HRM)和24 h食管动态pH监测,分析IEM及正常食管动力患者酸暴露情况。结果 77例典型GERD症状患者中病理性酸暴露者38例(49%),在病理性酸暴露组中IEM 9例(24%),正常酸暴露组中IEM 5例(13%)。IEM组LES压力低于食管动力正常组(15.15±3.60 vs 22.15±6.73,P0.01);IEM组总pH4时间(百分比)较正常食管动力组高[(14.78±3.8)%vs(4.30±2.68)%,P0.01];IEM组患者BMI值较高。结论 IEM在GERD中较常见,其食管动力障碍中绝大多数为IEM,IEM与食管远端酸暴露密切相关。     

The role of excessive esophageal acid exposure in patients with gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD), especially reflux esophagitis (RE), is characterized by excessive esophageal acid exposure. Transient lower esophageal sphincter (LES) relaxation is the major mechanism of acid reflux episodes in both healthy subjects (HS) and patients with GERD. In the sitting position, where acid reflux episodes often occur, there is no difference in the frequency of transient LES relaxations between these two groups; however, in patients with GERD, at 5 cm above the LES, the proportion of acid reflux episodes during transient LES relaxations is significantly greater than in the HS group. This difference is considered to be one of the causes of excessive esophageal acid exposure in patients with GERD, but its cause is still unclear. A recent study, which investigated the proportion of acid reflux episodes during transient LES relaxations at 2 and 7 cm above the LES, showed that there was no difference at 2 cm above the LES between HS and patients with RE, but at 7 cm they were significantly greater in patients with RE than in HS. Evaluation of acid reflux at 2 cm above the LES is difficult to measure, but the proximal extent of refluxate could be one of the important factors of excessive acid esophageal exposure in patients with RE. Ineffective esophageal motility, found in patients with moderate to severe RE, impairs esophageal bolus clearance of acid, therefore both the proximal extent of refluxate and the delay of esophageal bolus clearance of acid could be major causes of excessive esophageal acid exposure. Hiatus hernia also causes acid reflux, due to its association with hypotensive LES, and also impairs esophageal bolus clearance of acid.     

胃食管反流病中医分型与酸反流的关系

目的研究胃食管反流病(gastroesophageal reflux disease,GERD)的中医的辨证分型与酸反流各项指标的关系,为本病辨证分型寻求特征性的客观指标.方法通过对97例经24 h食管pH值动态监测和内镜检查确诊为GERD的患者的临床观察,以临床四诊资料为基础,在中医理论指导下,对其进行病位、病性、病因、病机的辨证分析,从而筛选出本病的主要证型.在此基础上,选用24 h食管pH值动态监测的多项酸反流指标,运用多种统计学分析方法,研究各主要证型与食管酸反流多项指标之间的关系.结果 GERD 97例的辨证分型筛选出的主要证型有肝胃郁热、肝胃不和、脾胃虚弱、胃热气逆、痰气郁阻5型.总反流次数在肝胃郁热型中显著高于肝胃不和、脾胃虚弱、痰气郁阻型,在胃热气逆型中显著高于脾胃虚弱、痰气郁阻型(P＜0.05);总pH＜4时间百分率和反流总分在肝胃郁热、肝胃不和、胃热气逆型中显著高于脾胃虚弱型(P＜0.05).酸反流的症状指数≥50%病例数的百分率在肝胃不和、肝胃郁热、胃热气逆型中极显著高于其余各证型(P＜0.01).酸反流体位分型为混合型的病例数的百分率在脾胃不和、痰气郁阻型中显著高于其余各证型(P＜0.05).结论 GERD的中医辨证分型与某些食管酸暴露参数之间存在明显关系.     

Stimulatory effect of gastroesophageal reflux disease (GERD) on pulmonary fibroblast differentiation

Epidemiological studies indicate that prolonged micro-aspiration of gastric fluid is associated in gastroesophageal reflux disease with the development of chronic respiratory diseases, possibly caused by inflammation-related immunomodulation. Therefore, we sought to ascertain the effect of gastric fluid exposure on pulmonary residential cells. The expression of α-smooth muscle actin as a fibrotic marker was increased in both normal human pulmonary fibroblast cells and mouse macrophages. Gastric fluid enhanced the proliferation and migration of HFL-1 cells and stimulated the expression of inflammatory cytokines in an antibody assay. Elevated expression of the Rho signaling pathway was noted in fibroblast cells stimulated with gastric fluid or conditioned media. These results indicate that gastric fluid alone, or the mixture of proinflammatory mediators induced by gastric fluid in the pulmonary context, can stimulate pulmonary fibroblast cell inflammation, migration, and differentiation, suggesting that a wound healing process is initiated. Subsequent aberrant repair in pulmonary residential cells may lead to pulmonary fibroblast differentiation and fibrotic progression. The results point to a stimulatory effect of chronic GERD on pulmonary fibroblast differentiation, and this may promote the development of chronic pulmonary diseases in the long term.     

Symptom- versus endoscopy-based diagnosis and treatment of gastroesophageal reflux disease (GERD)

The current guidelines of the German Society for Digestive Diseases (DGVS) endoscopy recommends for patients representing with reflux symptoms. In daily routine as well as in Guidelines from other countries and international guidelines, however, a symptom-based strategy for the management of patients with reflux disease is favoured. Since either strategies is dependent on specific clinical findings, neither can be recommended. The preference for one or the other strategy depends on the prevalence of so-called alarm symptoms, risk factors for a reflux carcinoma or Barrett's metaplasia, demographic factors, e. g., age and gender, patient's wish and initial response to empirical therapy with proton pump inhibitors (PPI). However, most patients with characteristic reflux symptoms without any alarm symptoms and/or other risk factors can be safely managed with a symptom-based strategy in acute and long-term care.     

胃食管反流病问卷评分对胃食管反流病患者食管酸暴露的预测意义

目的 确定胃食管反流病问卷(GerdQ)症状评分能否反映胃食管反流病(GERD)患者由24 h食管动态pH监测显示的酸暴露情况,进一步验证GerdQ的临床应用价值.方法 纳入2008年11月至2010年3月因烧心等上消化道症状就诊的门诊GERD病例134例,均完成胃镜检查、24 h食管动态pH监测和GerdQ量表.根据...     

Effectiveness of acid suppression in preventing gastroesophageal reflux disease (GERD) after successful treatment of Helicobacter pylori infection

There is evidence that Helicobacter pylori eradication might predispose to gastroesophageal reflux disease (GERD). The aim of this prospective study was to examine the effectiveness of antisecretory treatment, after successful H. pylori eradication, in preventing GERD, since no data exist so far. Eighty initially H. pylori(+) patients, without GERD at the time of H. pylori eradication [50 peptic ulcer (PU) and 30 nonulcer (NU), 55 men, 25 women, median age 38 years, range 19–57], after successful H. pylori eradication were randomized to recieve either omeprazole 20 mg daily (group A) or no treatment (group B) for one year. All patients underwent upper gastrointestinal endoscopy at 0, 6, and 12 months or when GERD symptoms occurred. There were 40 patients in each group, and there were no statistically significant differences between the two groups in terms of sex, age, body weight, ulcer/no ulcer ratio, and other demographic data. Seven patients from group A and five patients from group B were lost to follow-up, and therefore there were 33 and 35 patients in groups A and B, respectively, who completed the study. One of 33 patients in group A (3%) and 10/35 (28.5%) in group B developed GERD symptoms during follow-up (P = 0.0022). The respective values for esophagitis were 0/33(0%) and 6/35(17.1%) (P = 0.0083). In conclusion, antisecretory treatment in H. pylori(+) patients, after successful eradication, is effective in preventing GERD.     

老年胃食管反流病合并哮喘临床研究

目的探讨老年胃食管反流病(GERD)合并哮喘患者的临床特征,为临床诊断治疗提供帮助。方法收集江苏省老年医学研究所2007年1月至2011年12月就诊的83例老年GERD合并哮喘患者临床资料,在常规哮喘治疗基础上均给予口服埃索美拉唑(40mg,1次/d)联合枸橼酸莫沙必利(5mg,3次/d)抗反流治疗8周,之后埃索美拉唑(20mg,1次/d)联合枸橼酸莫沙必利(5mg,每日临睡前)维持治疗。结合2007年胃食管反流病治疗共识意见与2008年支气管哮喘防治指南哮喘控制水平分级标准来观察疗效。结果 83例患者经抗反流治疗8周后,胃食管反流症状控制有效率为97.6%(81/83),哮喘控制有效率为94.0%(78/83)。其中完全停用哮喘治疗药物56例、用量减半20例、继续原用药7例。随访5年,哮喘完全控制70例,仍偶有哮喘发作13例,但发作次数减少、程度减轻。无药物不良反应。结论抗反流治疗可以改善老年GERD合并哮喘患者的症状,提高生活质量。