NERD患者食道测压及应用埃索美拉唑治疗的临床研究

胃食管反流病（GERD）是一种消化道常见疾病,GERD主要包括反流性食管炎（RE）非糜烂性反流病（NERD）及Bar-rett食管（BE）。其中50%～70%的GERD表现为NERD,通常有典型的胃灼热、反酸及胸痛,其胸痛是最常见的非心源性胸痛原因之一,NERD内镜检查没有食管黏膜损伤的表现跚,因此,称为内镜下阴性的食管反流病或症状性胃食管反流病。本研究主要对NERD患者进行食管下括约肌（LES）压力及食管体部压力测定,并予以埃索美拉唑治疗,     

内科疾病处方用药解析（24）

三、消化系统疾病 3．1 胃食管反流病胃食管反流病（GERD）是指胃十二指肠内容物反流入食管引起烧心等症状,可引起反流性食管炎以及咽喉、气道等食管以外的组织损害。约半数GERD患者内镜下见食管黏膜糜烂、溃疡等炎性病变,称反流性食管炎（RE）;但相当部分患者内镜下可见无RE表现,这种GERD成为非糜烂性的胃食管反流病（NERD）。     

反流性疾病问卷对胃食管反流病的诊断价值

目的探讨反流性疾病问卷（RDQ）在诊断胃食管反流病中的价值。方法在接待消化内科门诊就诊病人中,对存在反流相关症状者进行问卷调查。记录烧心、反流、非心源性胸痛、反酸4个症状的频率及程度的积分,分析经内镜检查证实的反流性食管炎患者RDQ积分分布情况,计算诊断GERD的临界值。结果1655例门诊病人中379人有反流症状,男女比例1.11：1,平均年龄50.16±14.17岁。经内镜检查,诊断反流性食管炎122例,内镜正常者73例,二者RDQ评分差异有显著。以RDQ分值16为临界值,Youden指数最大,ROC曲线下面积为0.75,对GERD诊断阳性符合率81.48%,阴性符合率为60.92%,敏感度为72.13%,特异度为68.49%。RDQ分值与RE的洛杉矶分级无关。结论RDQ可作为初步诊断胃食管反流病易行有效的方法。     

胃食管反流病患者精神因素与临床症状的关系

胃食管反流病（GERD）是指胃、十二指肠内容物反流入食管引起的症状和并发症,近年来发病率呈上升趋势。Fass等110提出GERD由反流性食管炎（RE）、非糜烂性反流病（NERD）和Barrett食管3个独立亚型组成,3个亚型互相不转换,发病机制不同,精神因素的存在对不同亚型GERD患者的生活质量及疾病治疗有明显影响。NERD占GERD的60％～70％,目前发病率逐年升高,常规治疗效果差,患者常伴一定程度的抑郁、焦虑症状。本研究分析41例GERD患者胃食管反流精神因素与临床症状之间的关系,报告如下。     

埃索美拉唑治疗反流性食管炎的疗效评价

胃食管反流病（GERD）是胃肠动力障碍性疾病，同时也是酸相关性疾病。根据其内镜下表现可分为反流性食管炎（RE）、非糜烂性胃食管反流（NERD）。本研究是观察埃索美拉唑治疗反流性食管炎（RE）的疗效。     

不同亚型难治性胃食管反流病患者心理状态分析

目的 分析不同亚型难治性胃食管反流病（rGERD）患者的心理状态。方法 选择2017年1月至2019年10月在安徽医科大学附属省立医院消化内科门诊就诊的182例rGERD患者,均行24 h pH-阻抗监测,根据临床表现与病理学检查结果分为反流性食管炎组（RE组,n=54）、非糜烂性反流病组（NERD组,n=108）和Barrett食管组（BE组,n=20）,利用汉密尔顿焦虑量表（HAMA）与汉密尔顿抑郁量表（HAMD）评估患者的心理状态,应用GERD专用生活质量（GERD-HRQL）量表对3组患者的生活质量进行评价。结果 3组患者HAMA、HAMD评分的差异有统计学意义（P<0.05）,且NERD组患者HAMA和HAMD评分高于RE组,差异有统计学意义（P<0.05）。NERD组患者弱酸反流发生率高于RE组、BE组,差异均有统计学意义（P<0.0167）。结论 NERD患者比RE、BE患者更易发生弱酸反流,更易出现焦虑、抑郁症状,可能是rGERD的发病机制之一。     

胃食管反流病患者临床症状与精神因素关系研究

目的:研究胃食管反流病(GERD)患者临床症状与精神因素之间的关系.方法:34例经反流性疾病诊断问卷(RDQ)诊断为GERD的患者(经过内镜检查)和15例健康对照者,均填写Zung自评量表,Zung评分异常的GERD患者为GERD( )组;Zung评分正常患者为GERD(-)组.两组同时记录反流症状积分.结果:SAS平均分GERD组明显高于健康对照组(47.59±8.53,38.36±5.82,P＜0.05),SDS平均分GERD组亦显著高于健康对照组(48.42±10.68,40.79±6.25,P＜0.05).GERD( )组Zung评分与症状积分呈正相关,相关系数r为0.411、0.483 .结论:GERD患者反流症状、精神因素之间互相影响、互为因果,NERD发病机制中精神因素起一定作用, GERD患者需整体治疗.     

肠易激综合征患者血浆VIP与食管动力学关系的研究

目的 :探讨血浆VIP对肠易激综合征 (IBS)患者食管动力的影响。方法 :对40例肠易激综合征患者和20例健康人 (HS) ,采用放免法测定血浆VIP含量 ,采用核素法测定食管液体通过时间和胃食管反流。结果 :IBS组血浆VIP显著高于HS组 (P<0 05) ;IBS组胃食管反流率显著高于HS组 (P<0 05) ;IBS组中胃食管反流阳性组血浆VIP显著高于胃食管反流阴性组 (P<0 05) ;IBS组食管液体总通过时间与HS组相比结果差异无显著性 (P>0 05)。结论 :IBS患者血浆VIP含量的升高可使食管下括约肌 (LES)松弛而产生胃食管反流。     

胃食管反流病的临床分析

目的探讨胃食管反流病(GERD)的诊断及治疗。方法将病人按反流性食管炎(RE)和非糜烂性反流病(NERD)进行分组治疗,对两组资料进行比较。结果RE和NERD治疗效果不同,RENERD是否HP治疗效果亦不同。结论GERD治疗应区别对待。     

胃食管反流病诊治研究进展

胃食管反流病（gastroesophageal reflux disease．GERD）包括反流性食管炎（RE）、非糜烂性反流病（NERD）及Barrett食管（BE）。该病既有消化道症状，又有消化道外症状，同时增加了食管癌的危险。因此受到临床医生的普遍关注。     

The influence of co-morbid IBS and psychological distress on outcomes and quality of life following PPI therapy in patients with gastro-oesophageal reflux disease

Background  A subset of patients with gastro-oesophageal reflux disease (GERD) does not achieve complete symptom resolution with proton pump inhibitor (PPI) therapy. The factors which affect response to PPI therapy in GERD patients remain unclear.
Aims  To determine the prevalence and impact of irritable bowel syndrome (IBS) and psychological distress (PD) on GERD symptoms and disease-specific quality of life (QoL) before and after PPI therapy and to assess the same outcomes before and after PPI therapy in non-erosive reflux disease (NERD) and erosive oesophagitis (EO) GERD patients.
Methods  Patients undergoing oesophago-gastroduodenoscopy (OGD) for heartburn were recruited. Participants completed validated surveys: Digestive Health Symptom Index, Reflux Disease Questionnaire, Quality of Life in Reflux and Dyspepsia and Brief Symptom Inventory (BSI). IBS was defined as >3 Manning criteria and PD as BSI score >63. At OGD, patients were classified as NERD or EO. Patients were treated with rabeprazole 20 mg/day for 8 weeks before completing follow-up surveys.
Results  Of 132 GERD patients enrolled, 101 completed the study. The prevalence rates of IBS and PD were 36% and 41%, respectively. IBS independently predicted worse QoL before and after PPI therapy. PD independently predicted worse GERD symptoms and QoL before and after PPI therapy. There were no differences in symptoms or QoL between NERD and EO patients before or after PPI therapy.
Conclusions  IBS and PD impacted GERD symptoms and QoL before and after PPI therapy. Symptoms and QoL before and after PPI therapy were similar in NERD and EO patients.     

Functional heartburn vs. non-erosive reflux disease: similarities and differences

Background  Bowel symptoms have been associated with non-erosive reflux disease (NERD). However, their role in functional heartburn (FH) has not been established.
Aims  To characterize bowel symptoms in FH and NERD patients, and investigate their role as predictors of severity of reflux symptoms.
Methods  A prospective study of patients with normal upper endoscopy undergoing a 24-h oesophageal pH monitoring for the evaluation of reflux symptoms. Patients with oesophageal acid exposure <3.1% and a symptom index <50% were classified as FH ( n  = 60), while those with oesophageal acid exposure >4% were defined as NERD ( n  = 160). Symptom severity was scored on validated scales.
Results  In FH, a female predominance was noted ( P  < 0.001). Reflux symptoms were scored higher in NERD patients ( P  < 0.001) while bowel symptoms were similarly scored in the two groups. In both groups, severity of reflux symptoms was independently associated with a composite score on the bowel scales ( P  < 0.001) and was not predicted by oesophageal acid exposure. In FH, reflux symptom severity was inversely related to age ( P  = 0.03), while in NERD, the opposite was true ( P  = 0.01).
Conclusions  In both FH and NERD, bowel symptoms were the strongest predictors of reflux symptoms severity. A female preponderance, and an opposite relationship between reflux symptom severity and age, indicate that FH and NERD may be distinct entities.     

Nondigestive symptoms in non-erosive reflux disease: nature, prevalence and relation to acid reflux

Background Nondigestive symptoms are frequent in the irritable bowel syndrome (IBS). Aim To characterize nondigestive symptoms in non‐erosive gastro‐oesophageal reflux disease (NERD) patients, as features of IBS are common in patients with NERD. Methods A prospective, case–control study. NERD was defined in patients with reflux symptoms, a normal oesophageal mucosa and oesophageal pH <4 for ≥5% of the time during 24‐h pH monitoring. Nondigestive symptoms were scored on validated scales of somatic pain, urinary, sleep and neurasthenia. IBS was defined by the Rome I criteria. Results pH‐positive NERD patients (n = 326) scored significantly higher than controls (nonpatient hospital visitors; n = 174) on all scales. The scores of pain, sleep and neurasthenia were highly specific in the discrimination of NERD patients from controls. In patients, nondigestive symptoms were independently associated with age, reflux symptoms severity and IBS status, but not with oesophageal acid exposure. NERD patients who met diagnostic criteria for IBS (49%) scored significantly higher on all the nondigestive symptoms scales than those had not met [IBS(?)]. Yet, IBS(?) patients scored significantly higher than controls on all scales. Conclusions Nondigestive symptoms were highly prevalent in NERD patients and were specific in their discrimination from controls. Nondigestive symptoms correlated with reflux symptoms and were predicted by IBS status.     

The impact of pre-endoscopy proton pump inhibitor use on the classification of non-erosive reflux disease and erosive oesophagitis

Aliment Pharmacol Ther 2010; 32: 1266–1274

Summary

Background Factors associated with non‐erosive reflux disease (NERD) and erosive oesophagitis (EO) are incompletely understood and the overlap between the two entities is debated. Aim To compare clinical, demographic, and endoscopic findings in a large cohort of NERD and EO patients. Methods After they completed a validated GERD questionnaire, patients who presented for index endoscopy were enrolled and categorized as NERD or EO. Analysis was performed using Chi‐square, Mann–Whitney U‐test and multivariate logistic regression. Results A total of 696 GERD patients [455 (65.4%) NERD; 241 (34.6%) EO]; mean age 57 years; 92% men and 82% Caucasian were prospectively enrolled. Using logistic regression, patients on PPI were more likely to be classified as NERD (OR: 3.2; P < 0.001). NERD patients were older (OR: 1.50; P = 0.05), less likely to have nocturnal symptoms (OR: 0.63; P = 0.04) and hiatal hernia (OR: 0.32; P < 0.001). Compared with PPI‐naïve NERD patients, those on PPI were more likely to have nocturnal symptoms (69% vs. 29%, P = 0.048) and less likely to have mild‐moderate symptoms (63% vs. 79%, P < 0.001) – similar to the EO group. Conclusions Pre‐endoscopy PPI usage contributes significantly to the classification of GERD patients into the NERD‐phenotype. NERD patients on PPI therapy demonstrate some features that are significantly different from PPI‐naïve patients, but similar to EO patients. This observation supports the notion that some PPI NERD patients are actually healed EO patients, and that an overlap does exist between the GERD phenotypes.     

雷贝拉唑对不同类型胃食管反流病疗效和食管黏膜环氧化酶2的影响

目的：观察雷贝拉唑对不同类型胃食管反流病(CERD)的疗效和对食管黏膜环氧化酶2(COX-2)的影响。方法：GERD病人89例,其中反流性食管炎(RE)组51例和内镜检查阴性的胃食管反流病(NERD)组38例,2组均予雷贝拉唑10 mg,po,qd,共8 wk。正常对照组30例。症状和胃镜表现采用分级和记分法记录；抑郁和焦虑采用Hamilton抑郁量表和焦虑量表评价；COX-2应用链霉菌抗生物蛋白-过氧化物酶(SP)免疫组化法检测。结果：治疗前RE组和NERD组的症状评分无显著差异(P＞0.05)。治疗后RE组与NERD组的烧心样胸痛和反酸的评分明显减低,并可明显改善黏膜的损害,使内镜表现积分明显减低。RE组治愈率和总有效率明显高于NERD组(P＜0.01,P＜0.05)；有效率与进步率NERD组明显高于RE组(P＜0.01,P＜0.05)。RE组复发率和伴随抑郁或焦虑均明显低于NERD。治疗后,RE组的COX-2的阳性率明显减低(P＜0.01)。结论：雷贝拉唑对RE治疗的总有效率明显高于NERD组,并可明显地下调RE的COX-2的表达。     

Efficacy of rabeprazole on heartburn symptom resolution in patients with non-erosive and erosive gastro-oesophageal reflux disease: a multicenter study from Japan

BACKGROUND: Few studies have compared the efficacy of proton pump inhibitors in resolving the symptoms of non-erosive reflux disease (NERD) and of erosive gastro-oesophageal reflux disease (GERD) in Japan. AIM: To investigate and compare the efficacy of 4-week course of rabeprazole 10 mg/day on symptom resolution in NERD and erosive GERD in Japan. METHODS: The modified Los Angeles classification was used to grade endoscopically GERD in patients with heartburn (Grades N and M: NERD, Grades A and B: mild reflux oesophagitis (RO), and Grades C and D: severe RO). Rabeprazole 10 mg/day was administered for 4 weeks to 180 patients who kept symptom diaries. RESULTS: Complete relief of the symptoms was achieved in 35.8% of the NERD group and 55.4% of the erosive GERD group (mild RO: 51.1% and severe RO: 77.8%). Rabeprazole was significantly more effective in erosive GERD than in NERD patients. Among the NERD subgroups (Grades N and M), no difference in symptom improvement was observed. CONCLUSIONS: Four-week, rabeprazole 10 mg/day acid suppression therapy was effective in resolving symptoms in Japanese GERD patients. This therapy was more effective in erosive GERD than in NERD patients, and in those with severe RO than in those with mild RO.     

Oesophageal motility and bolus transit abnormalities increase in parallel with the severity of gastro-oesophageal reflux disease

Aliment Pharmacol Ther 2011; 34: 476–486

Summary

Background Limited data are available regarding the frequency of oesophageal motility and bolus transit abnormalities in subgroups of patients with gastro‐oesophageal reflux disease (GERD). Aim To assess oesophageal motility and bolus transit in endoscopically defined GERD subgroups. Methods Patients (N = 755) with typical reflux symptoms underwent upper endoscopy, conventional or impedance oesophageal manometry and/or impedance‐pH testing. They were divided into: erosive oesophagitis (EO; N = 340), Barrett Oesophagus (BO; N = 106), non‐erosive reflux disease (NERD; endoscopy?, abnormal pH and/or SAP/SI+; N = 239) and functional heartburn (FH; endoscopy?, normal pH and SAP/SI?; N = 70). Manometric patterns and bolus transit were defined according to previously published criteria. Results Increasing GERD severity was associated with decreased lower oesophageal sphincter resting pressure (P < 0.05) and distal oesophageal amplitude (P < 0.01), higher prevalence of hiatal hernia (P < 0.01) and increased prevalence of ineffective oesophageal motility (P < 0.01). Patients with EO and BO had a significantly lower percentage of complete bolus transit compared with NERD and FH (P < 0.01). Overall, abnormal bolus transit (ABT) for liquid swallows was found in 12% of FH, 20% of NERD, 54% of EO and 56% of BO (P < 0.01). Combined impedance‐manometry showed abnormal oesophageal function in 4% of FH, 4% of NERD, 22% of EO and 21% of BO patients with normal oesophageal manometry. Conclusions Oesophageal motility abnormalities increase in parallel with the severity of GERD from NERD to EO and BO. Bolus transit abnormalities in severe reflux disease underscore the importance of impaired oesophageal function in the development of mucosal injury.

     

Prevalence of extra-oesophageal manifestations in gastro-oesophageal reflux disease: an analysis based on the ProGERD Study

BACKGROUND AND AIMS: Gastro-oesophageal reflux disease (GERD) can be associated with a variety of extra-oesophageal disorders (EED) such as chronic cough, asthma, laryngeal disorder or chest pain. The aim of the study was to estimate and compare the prevalence of EED in a population with symptomatic GERD presenting as either erosive reflux disease (ERD) or non-erosive reflux disease (NERD). METHODS: Baseline data were collected from a prospective, multicentre, open cohort study (ProGERD) in which patients will be followed for 5 years after initial treatment with esomeprazole. Within the framework of this trial, all patients underwent gastroscopy and filled out a questionnaire designed to assess EED. The influence of potential prognostic factors on the prevalence of EED was analysed by multivariate (stepwise logistic regression) analysis. RESULTS: 6215 patients (3303 male, 2912 female; mean age 54 years) presenting with heartburn were included. EED was detected in 32.8% of all patients. The proportion was significantly higher (P = 0.0002) in ERD patients (34.9%) than in NERD patients (30.5%). As judged from the multivariate analysis, female gender, age, oesophagitis of LA grade C/D, duration of GERD disease greater than 1 years and smoking were significantly associated with EED. ERD patients with oesophagitis of LA grade A or B did not have a significantly higher risk of EED than patients with NERD. CONCLUSIONS: Patients with GERD have a high probability of experiencing EED, which may be associated with a number of prognostic factors such as duration and severity of GERD. Extra-oesophageal disorders are slightly, but statistically, more prevalent in ERD than in NERD patients.     

Dilated intercellular spaces and lymphocytes on biopsy relate to symptoms in erosive GERD but not NERD

Aliment Pharmacol Ther 2011; 33: 1202–1208

Summary

Background Mechanisms of symptom perception among patients with gastro‐oesophageal reflux disease (GERD) remain to be fully elucidated. Aim To correlate quantitative reflux symptom scores with microscopic oesophageal histopathology. Methods Prior to endoscopy, patients with reflux symptoms completed a validated reflux disease questionnaire (score 0–36). Erosive oesophagitis (EO) was graded using the LA classification. Oesophageal biopsies were graded 0–2 for basal cell hyperplasia, papillary elongation, dilated intercellular spaces (DIS), necrosis or erosion, eosinophils and neutrophils by a blinded gastrointestinal pathologist as previously described. Additionally, lymphocyte density was also evaluated. Pearson’s correlation coefficients were computed. Results Thirty‐two EO and 21 non‐erosive reflux disease (NERD) patients were prospectively enrolled. For EO vs. NERD, mean reflux symptom scores (10.7 vs. 8.8, P = 0.35) and histology scores were similar (4.29 vs. 4.25; P = 0.9). However, when symptom scores were compared with histology scores, a correlation was found in the EO group, but not in the NERD group (r = 0.34, P = 0.05 vs. r = 0.22, P = 0.36). On further analysis, DIS was associated with symptom scores in the EO group (P ≤ 0.001), but not in the NERD group (P = N.S.). Similarly, lymphocyte density was associated with symptom scores in the EO group (r = 0.56, P = 0.0009), but not in the NERD group (r = 0.002, P = 0.9). Conclusions Although mean symptom and histology scores were similar in the EO and NERD groups, a significant correlation of symptom scores with histology scores, DIS and lymphocytes was found in the former, but not in the latter. EO and NERD patients may have different symptom perception mechanisms and thus, dissimilar symptom resolution rates with acid suppression.     

雷贝拉唑对非糜烂性反流病症状和心理的影响

目的:探讨雷贝拉唑对非糜烂性反流病(NERD)症状及心理因素的影响。方法:对符合入选标准的169例NERD患者进行胃食管反流病诊断问卷(GerdQ)调查,仔细询问患者近1周的胃食管反流相关症状并进行症状记分。结果:159例患者完成治疗,治疗前非糜烂性反流病的GerdQ评分为(10.44±1.62)分,Zung自评焦虑量表(SAS)评分为(47.11±10.92)分,自评抑郁量表(SDS)评分为(44.59±11.2)分。治疗1周后,反流相关症状明显缓解,SAS、SDS评分均明显低于治疗前,4周后降低更明显,差异有统计学(P<0.05)。结论:非糜烂性反流病存在焦虑抑郁状态,使用雷贝拉唑治疗非糜烂性反流病可改善患者的症状和心理因素。