Nonerosive reflux disease

Nonerosive reflux disease (NERD) is the most common phenotype of gastroesophageal reflux disease. By definition, patients with NERD have typical reflux symptoms caused by the intraesophageal reflux of gastric contents but have no visible esophageal mucosal injury. This is in contrast to patients with erosive reflux disease (ERD) or Barrett's esophagus (BE) who have obvious esophageal mucosal injury on endosco-py. Only 50% of patients with NERD have pathologic esophageal acid exposure as detected on 24-h pH monitoring. NERD patients with physiologic esophageal acid exposure and good temporal correlation of symptoms with reflux events are considered to have esophageal hypersensitivity, while patients with no symptom-reflux correlation are considered to have functional heartburn. It is possible yet uncommon for NERD to progress to severe ERD (i.e. LA Grade C or D) or BE. Patients with NERD and pathologic esophageal acid exposure have motor dysfunction and acid reflux abnormalities that are similar to patients with ERD and BE, whereas NERD patients with physiologic esophageal acid exposure have minimal abnormalities and are not much different than healthy controls. The pathological feature most indicative of NERD is the presence of dilated intercellular spaces within squamous epithelium, an ultrastructural abnormality readily identified on transmission electron microscopy but also on light microscopy. A symptomatic response to an empiric trial of high-dose proton pump inhibitor (PPI) therapy is a simple and useful strategy to establish the diagnosis of NERD, although histology and pH monitoring may be useful in confirming the diagnosis. Patients with NERD suffer similar decrements in quality of life as do patients with erosive esophagitis. Therapy is aimed at eliminating or reducing symptoms and improving quality of life. PPIs are the most effective agents for the treatment of NERD although they are less effective in providing symptom relief than in patients with erosive esophagitis. Laparoscopic antireflux surgery is an effective therapy for selected patients with NERD and outcomes are better when performed in high volume centers.     

Nonerosive reflux disease: A pathophysiologic perspective

Nonerosive reflux disease (NERD) is the most common phenotype of gastroesophageal reflux disease. By definition, patients with NERD have typical reflux symptoms caused by the intraesophageal reflux of gastric contents but have no visible esophageal mucosal injury. This is in contrast to patients with reflux esophagitis, also known as erosive reflux disease, and Barrett’s esophagus, who have obvious esophageal mucosal injury on endoscopy. Only 50% of patients with NERD have pathologic esophageal acid contact time (ACT) as detected on 24-hour pH monitoring (ie, NERD-positive). NERD patients with physiologic esophageal ACT and good temporal correlation of symptoms with reflux events (symptom index > 50% or symptom-association probability > 95%) are considered to have esophageal hypersensitivity (ie, NERD-negative). Finally, patients with physiologic esophageal ACT but poor symptom-reflux correlation are now considered to have functional heartburn and not NERD. NERD-positive patients have motor dysfunction and acidic reflux abnormalities that are similar to patients with reflux esophagitis and Barrett’s esophagus, whereas NERD-negative patients have minimal abnormalities that are not much different than healthy controls. The histopathologic feature most indicative of NERD is the presence of dilated intercellular spaces within squamous epithelium, an ultrastructural abnormality readily identified on transmission electron microscopy and on light microscopy.     

Dilated intercellular spaces of esophageal epithelium in nonerosive reflux disease patients with physiological esophageal acid exposure

OBJECTIVES: It has been demonstrated that dilation of intercellular spaces of esophageal epithelium is a marker of tissue injury in GERD patients with a pathological esophageal acid exposure time. To evaluate the relationship among ultrastructural changes, acid esophageal exposure, and GERD symptoms, intercellular space diameters have been assessed in nonerosive reflux disease (NERD) patients with/without abnormal acid exposure time. METHODS: Following a pharmacological wash-out, 20 NERD patients underwent upper endoscopy, esophageal manometry, and 24-h pH monitoring. Biopsies were taken at 5 cm above the lower esophageal sphincter and intercellular space diameters were measured on transmission electron microscopy photomicrographs. Seven asymptomatic controls underwent the same protocol. RESULTS: Acid exposure time was in the normal range in all controls and in 11 patients (NERD pH-negative); it was abnormal in 9 patients (NERD pH-positive). Mean intercellular space diameter in NERD pH-negative and in NERD pH-positive patients was three times greater than in controls (1.45 and 1.49 microm vs 0.45, p < 0.001). Mean values of maximum intercellular spaces in all NERD patients were greater, two-fold or more, than those in controls (p < 0.001). No difference in mean and maximal space diameters was observed between NERD pH-positive and pH-negative patients. CONCLUSIONS: Dilation of intercellular spaces is a feature of NERD patients, irrespective of esophageal acid exposure, and can be considered an objective, structural marker of GERD symptoms. Impaired esophageal mucosal resistance, even to small amounts of acid refluxate, plays a key role in the pathophysiology of NERD.     

Esophageal epithelial surface in patients with gastroesophageal reflux disease： An electron microscopic study

A/M： To investigate the intercellular spaces between the most superficially located esophageal epithelial cells in patients with gastroesophageal reflux disease （GERD）.
METHODS： Eighteen patients with erosive esophagitis, 10 patients with non-erosive reflux disease （NERD）, and 18 normal asymptomatic volunteers were enrolled. Biopsy specimens were obtained from the lower esophageal mucosa without ulcer or erosion. Scanning electron microscopy was employed to investigate the tightness of the superficial cellular attachment.
RESULTS： The intercellular space between the most superficially located epithelial cells in patients with erosive esophagitis or NERD was not different from that in asymptomatic healthy individuals.
CONCLUSION： Widened luminal intercellular spaces of esophageal superficial epithelium are not responsible for the induction of reflux symptoms in patients with GERD.     

Comparison of esophageal acid exposure distribution along the esophagus among the different gastroesophageal reflux disease (GERD) groups

BACKGROUND: Patients with nonerosive reflux disease (NERD) have the lowest esophageal acid exposure profile compared with the other gastroesophageal reflux disease (GERD) groups. AIM: To compare lower esophageal acid exposure recordings 1 cm above the lower esophageal sphincter (LES) with those 6 cm above the LES as well as to determine the characteristics of esophageal acid exposure along the esophagus among the different GERD groups. METHODS: Patients with classic heartburn symptoms were enrolled into the study. Patients were evaluated by a demographics questionnaire and the validated GERD Symptom Checklist. Upper endoscopy was performed to evaluate the presence of esophageal erosions and Barrett's esophagus (BE). Ambulatory pH testing was performed using a commercially available 4-sensor pH probe with sensors located 5 cm apart. The distal sensor was placed 1 cm above the LES. RESULTS: Sixty-four patients completed the study. Of those, 21 patients had NERD, 20 had erosive esophagitis (EE), and 23 had BE. All patient groups demonstrated greater esophageal acid exposure 1 cm above the LES than 6 cm above the LES. In NERD and EE, this phenomenon was primarily a result of a higher mean percentage of upright time with pH <4. Unlike patients with EE and BE, those with NERD had very little variation in esophageal acid exposure throughout the esophagus (total and supine). CONCLUSIONS: ALL GERD groups demonstrated significant greater esophageal acid exposure at the very distal portion of the esophagus, primarily as a result of short upright reflux events. Unlike erosive esophagitis and BE, NERD patients demonstrate a more homogenous acid distribution along the esophagus.     

Barrett食管、糜烂性食管炎和非糜烂性反流病食管酸暴露及食管动力学分析

目的分析胃食管反流病(GERD)三种亚型Barrett食管(BE)、糜烂性食管炎(EE)和非糜烂性反流病(NERD)患者食管24 h pH监测与高分辨率食管测压结果,探讨不同亚型胃食管反流病食管酸暴露及动力学变化特点。 方法收集2015年12月至2017年12月,新疆维吾尔自治区人民医院接受住院治疗的90例GERD患者的临床资料,其中BE组28例、EE组35例、NERD组27例,通过食管24 h pH监测结果评价患食管酸暴露及反流特点,高分辨率食管测压检查评价食管动力学特点。 结果3组患者年龄及身体质量指数(BMI)等一般资料比较,差异无统计学意义(P>0.05);EE组患者24 h食管pH监测中pH≤4(酸反流)、40.05);3组Demeester评分比较,差异无统计学意义(P>0.05);LES长度3组无明显差异,BE组LES静息压及残余压较EE组和NERD组稍高,但差异无统计学意义(P均>0.05);3组在食管远端收缩积分比较,差异无统计学意义(P>0.05)。 结论食管测酸检查在GERD临床亚型的鉴别方面并无显著差别;Barrett食管、糜烂性食管炎、非糜烂性反流病均存在抗反流屏障功能减退,但不同程度的食管粘膜损伤对食管动力学的影响并无差异。     

Erosive esophagitis and nonerosive reflux disease (NERD): comparison of epidemiologic, physiologic, and therapeutic characteristics

Nonerosive reflux disease (NERD) and erosive esophagitis are the main presentations of gastroesophageal reflux disease. However, NERD is the most common presentation of gastroesophageal reflux disease in community-based patients. Patients with NERD differ in demographic characteristics from patients with erosive esophagitis, primarily in sex distribution, weight/body mass index, and prevalence of hiatal hernia. Physiologically, patients with NERD tend to have normal lower esophageal sphincter resting pressure, minimal esophageal body motility abnormalities, low esophageal acid exposure profile and minimal nighttime esophageal acid exposure. Patients with NERD have a lower symptom response rate to proton pump inhibitor once daily than patients with erosive esophagitis. Additionally, NERD patients demonstrate a longer lag-time for symptom resolution and lack of difference in symptom response rate between half to full dose proton pump inhibitor as compared with patients with erosive esophagitis.     

胃食管反流病患者雷贝拉唑52周维持治疗的多中心随访研究

背景：糜烂性食管炎（EE）和非糜烂性反流病（NERD）是胃食管反流病（GERD）两种常见的亚型,EE与NERD的关系仍存在争议。目的：探讨GERD患者雷贝拉唑52周维持治疗后2～3年随访时的反流症状、用药情况和内镜下表现变化。方法：2002年12月-2004年12月对67例EE患者和31例NERD患者行8周雷贝拉唑强化治疗和52周雷贝拉唑维持治疗,并于2～3年后随访上述患者。采用问卷调查了解患者的反流症状、用药情况,并复查内镜。结果：共随访到42例EE患者和21例NERD患者。EE患者和NERD患者所用的抑酸药类型和用药方式无明显差异。不同用药方式间患者的最严重反流症状总积分差异有统计学意义（P〈0．05）,但最近2周反流症状总积分无明显差异。与治疗前比较,EE和NERD组反流症状积分均显著改善（P〈0．01）。EE组中23例（55．0％）患者食管糜烂复发,6例（31．5％）NERD患者转变为EE;GERD患者黏膜糜烂发生率与用药方式无关。结论：52周雷贝拉唑维持治疗后2。3年随访时,GERD的反流症状仍得到控制。但质子泵抑制剂维持治疗不能预防EE复发。EE和NERD两种亚型之间可互相转化。     

Esophageal dilated intercellular spaces (DIS) and nonerosive reflux disease

Esophageal mucosal dilated intercellular spaces (DIS) are frequently observed in patients with nonerosive reflux disease (NERD) and patients with esophagitis. The specificity of DIS is questionable, as it is present in up to 30% of asymptomatic healthy subjects and in patients with other esophageal disorders. DIS occurs in parallel with a drop in potential difference, diminished transepithelial resistance, and increased esophageal mucosal permeability. These alterations arise with exposure to acid and pepsin during gastroesophageal reflux, but the exact pathway of damage to the intercellular junctions remains unclear and seems to be multifactorial. Other noxious contents of the refluxate, such as bile acids, are harmful and DIS can also be induced by acute psychological stress. DIS can be assessed quantitatively with electron microscopy (EM), but it is also recognizable with light microscopy (LM). DIS can disappear after treatment with proton pump inhibitors (PPI); however, this is not the case in all NERD patients. A recent study showed that patients with NERD who are refractory to PPI might still have DIS; and animal experiments showed that persistence of DIS might be due to esophageal mucosal exposure to bile acids and/or psychological stress. In conclusion, DIS is a frequent but nonspecific histological feature of NERD. It can be caused by acid reflux, but bile acids in the refluxate and/or psychological stress can modulate the development or persistence of DIS. Although a causal relationship between DIS and heartburn has been proposed, it still needs to be proven and the underlying mechanisms investigated before considering DIS as a target for treatment of NERD.     

Acid and Non-Acid Reflux Patterns in Patients with Erosive Esophagitis and Non-Erosive Reflux Disease (NERD): A Study Using Intraluminal Impedance Monitoring

Background Non-erosive reflux disease (NERD) and erosive esophagitis (EE) are the most common phenotypic presentations of gastroesophageal reflux disease (GERD). Aim To assess acid and non-acid reflux patterns in patients with EE and NERD using combined esophageal pH-impedance monitoring. Methods A total of 26 GERD patients off acid-suppressive medication and ten healthy volunteers (HV) underwent upper endoscopy and 24-h pH-impedance monitoring. Analysis of the pH-impedance signals included total reflux time, number of reflux episodes according to gas–liquid composition, and pH (acid, non-acid). Results EE was identified in 13 patients and NERD in 13 patients. Pathologic acid reflux was found in 92.3 and 69.2% of patients with EE and NERD, respectively (P = 0.15). When compared to HV, EE patients and NERD patients showed a higher incidence of acid (P = 0.002 and P < 0.001, EE vs. HV and NERD vs. HV, respectively) and non-acid reflux episodes (P = 0.03 and P = 0.001, EE vs. HV and NERD vs. HV, respectively). Mean reflux times, as assessed by both pH-metry and impedance monitoring, and incidence of acid and non-acid reflux episodes were similar in EE and NERD patients. In the supine position, however, EE patients showed a higher incidence of acid (P = 0.048) and liquid reflux episodes (P = 0.07). Conclusion Whereas EE patients have more acid reflux episodes in the supine position than NERD patients, patients with EE and NERD have similar non-acid reflux patterns. This observation lends support to the notion that non-acid reflux is less damaging to the esophageal mucosa than acid reflux.     

反流性食管炎与非糜烂性反流病食管酸暴露的特点比较

目的　比较反流性食管炎 (RE)与非糜烂性反流病 (NERD)各亚组食管酸暴露特点。方法　具有典型反酸 烧心等症状的 12 8例患者 ,经胃镜等系统检查诊断为胃食管反流病 (GERD)。便携式 pH监测仪行胃食管 2 4hpH监测 ,DeMeester积分≥ 15分为存在病理性酸反流。 结果　 12 8例患者中 ,37例 (2 8 9% )存在RE ,91例 (71 1% )为NERD。pH监测阳性在RE组和NERD组中分别为 2 5例 (6 7 6 % )和 4 6例 (5 0 5 % ) ,差异无统计学意义 ;两组DeMeester积分均值差异亦无统计学意义 (5 3 4 5± 6 2 0 4比 4 0 0 4± 6 1 80 ,P >0 0 5 )。RE组长反流次数显著高于NERD组 (8 16±10 2 7比 3 96± 6 87,P =0 0 0 4 )。以症状指数 >5 0 %为阳性 ,NERD阳性组 (pH值监测异常 )症状指数阳性率显著高于NERD阴性组 (pH值监测正常 ) (43 5 %比 15 6 % ,P <0 0 0 1)。NERD阴性组中具有阳性症状指数的患者 7例 (15 6 % ) ,阴性症状指数者 38例。前者总反流次数及立位反流时间百分比显著高于后者。RE患者中 ,12例 pH监测阴性者食管及胃内pH的中位值显著高于 pH监测阳性者。结论　RE患者长反流发生率高于NERD患者 ;症状的发生与酸反流相关 ;NERD患者根据酸反流与症状关系可分为不同的亚组。RE阴性组可能存在混合反流或胆汁反流     

Structural abnormalities of endoscopy-negative reflux disease--real or perceived?

About two thirds of individuals affected by gastroesophageal reflux disease suffer from endoscopy-negative esophageal reflux disease. Often, these individuals do not receive adequate medication. In contrast, erosive reflux disease is much better defined and even subclassified as mucosal breaks of the esophageal epithelium. It is known from large trials that gastroesophageal reflux disease is probably not a categorical disease without further progression. On the other hand, the first structural changes of the esophageal epithelium indicating the beginning of reflux disease are unknown. Furthermore, it is not known when reflux esophagitis is structurally healed (besides symptom relief). Histological markers are based on observations made without clinical correlation. It has gradually become clear that there are no specific reflux-induced esophageal lesions. All described histological criteria can be also observed in other esophageal conditions. Structural abnormalities are believed to be found more often close to the lesser gastric curvature or the right esophageal wall. Furthermore, it could be shown with a standardized biopsy protocol that a good correlation with clinical findings is possible. Conventional histological criteria include thickness of basal cell layer, length of papillae and inflammatory infiltrates. New criteria include dilation of intercellular spaces and changes of protein distribution within intercellular spaces. All changes are reversible with PPI therapy. In conclusion, structural abnormalities are not specific for gastroesophageal reflux disease or NERD but are reversible with PPI, which underlines their relevance.     

Bowel symptoms in nonerosive gastroesophageal reflux disease: nature, prevalence, and relation to acid reflux

BACKGROUND: Nonerosive gastroesophageal reflux disease (NERD) patients frequently show features of the irritable bowel syndrome (IBS). AIMS: To investigate the prevalence and intensity of bowel symptoms and their relationship to esophageal acid exposure in NERD patients. METHODS: Bowel and reflux symptoms and IBS status were assessed in NERD patients (normal upper endoscopy; esophageal pH <4 for >or= 5% of the time on 24-h pH monitoring; n=326), in relation to nonpatient controls. Bowel symptoms were scored on the 3 scales: diarrhea, constipation, and pain/gas symptoms. RESULTS: NERD and age were independently associated with bowel symptoms. NERD patients scored significantly higher than controls on all bowel scales. In a multivariate analysis, the scores on the pain/gas scale were independently associated with NERD. In NERD patients, reflux symptoms independently predicted the bowel symptoms while acid exposure did not. Forty-nine percent of the NERD patients and 18% of the controls met the criteria for IBS [IBS(+)NERD]. IBS(+)NERD patients scored significantly higher than those not meeting IBS criteria [IBS(-)] on all bowel scales. Yet IBS(-) patients scored significantly higher than controls on the scales of constipation and pain/gas. IBS(+)NERD patients scored higher than IBS(-) also on the GERD symptoms scale. CONCLUSIONS: (1) NERD patients scored significantly higher than controls on all the bowel scales; (2) Bowel symptoms were associated with reflux symptom scores, but not with acid exposure. (3) The presence of IBS features in a large proportion of NERD patients reflects a high prevalence of visceral hypersensitivity that may aggravate acid reflux symptoms.     

非糜烂性反流病主要症状发生机制研究进展

非糜烂性反流病（NERD）是胃食管反流病（GERD）的一个亚型,其病理生理学机制复杂且目前对其认识存在争议．直接造成了临床上没有清晰的标准可指导医疗实践。本文重点对NERD主要临床症状的病理生理学机制,如胃十二指肠内容物反流、食管上皮细胞间隙增宽、内脏高敏感．炎症因素、心理因素等作一综述。     

非糜烂性反流病诊断进展

非糜烂性反流病（NERD）是最常见的胃食管反流表型，但其发病机制尚未完全明了。目前NERD尚无特异性诊断方法。细胞间隙增宽（DIS）是NERD一个常见但非特异性的组织学特征，可由酸反流引起。本文就NERD的诊断进展作一概述。     

食管远端鳞状上皮细胞间隙增宽对非糜烂性反流病诊断的价值

目的:研究非糜烂性反流病(NERD)食管远端鳞状上皮细胞间隙变化及与食管酸暴露、反流症状严重程度的关系,探讨细胞间隙增宽对NERD诊断的价值.方法:纳入NERD患者(66例)和正常对照者(38例).所有受试者行GerdQ调查、食管24hpH值监测、胃镜检查并在食管齿状线(Z线)和Z上2cm线位置取活检,透射电镜测量鳞状上皮细胞间隙;pH监测阴性NERD患者行质子泵抑制剂诊断试验确诊.结果:(1)NERD组Z线和Z线上2cm的平均细胞间隙分别为(0.90±0.11)μm、(0.92±0.16)μm,正常对照组分别为(0.65±0.08)μm、(0.67±0.08)μm,两组间差异有统计学意义(P<0.05),组内差异无统计学意义(P>0.05);(2)NERD患者Z线和Z线上2cm两部位pH(+)亚组与pH(-)亚组的细胞间隙比较,差异均无统计学意义(P>0.05);GerdQ(+)亚组与GerdQ(-)亚组的细胞间隙比较,差异也均无统计学意义(P>0.05);(3)Z线和Z线上2cm两部位的平均细胞间隙与DeMeester积分均呈正相关性,r分别为0.33(P=0.001)、0.35(P=0.001);与GerdQ评分也均呈正相关性,r分别为0.32(P=0.006)、0.45(P<0.001);(4)Z线平均细胞间隙的cut-off值为0.81μm时,约登指数最大(0.808),诊断的敏感度为80.8%,特异度为100.0%.Z线上2cm平均细胞间隙的cut-off值为0.81μm时,约登指数最大(0.731),诊断的敏感度为75.8%,特异度为97.4%.结论:NERD食管远端鳞状上皮细胞间隙明显增宽,细胞间隙与食管远端胃酸暴露和反流症状的严重程度呈正相关.细胞间隙增宽可作为NERD诊断的一种敏感客观结构指标.     

Capsaicin receptor (TRPV1) and non-erosive reflux disease

BACKGROUND/AIM: Non-erosive reflux disease (NERD) is a common and heterogeneous disorder. We hypothesized that changes in peripheral innervation may lead to hyperalgesia and contribute to the development of the disorder. METHODS: Patients referred for evaluation of reflux symptoms with wireless pH monitoring were asked to provide demographic and clinical data and complete a survey related to severity of reflux symptoms. Endoscopies were performed to rule out macroscopic abnormalities of the esophageal mucosa. Biopsies obtained 2 cm above the gastroesophageal junction were stained for protein gene product 9.5 (PGP 9.5; general neuronal marker) and TRPV1 (capsaicin receptor) immunoreactivity. The density of immunoreactive fibers in the esophageal mucosa was determined morphometrically. RESULTS: A total of 39 patients without evidence of Barrett's metaplasia, erosive or ulcerative esophagitis were enrolled. Most patients had daily symptoms. The total esophageal acid exposure time was 5.6+/-0.6%, with 16 patients (41%) having increased acid reflux. Immunoreactivity for PGP 9.5 or TRPV1 was detected in papillary structures as well as within the epithelium (free intra-epithelial endings). Total acid-exposure time, but not symptom score or duration correlated significantly with density of PGP 9.5 immunoreactivity and TRPV1 positive fibers. CONCLUSION: Even in the absence of macroscopic injury, esophageal acid exposure is associated with changes in mucosal innervation of the esophagus, thus potentially further enhancing symptoms in patients with gastroesophageal reflux.     

Reflux profile of Chinese gastroesophageal reflux disease patients with combined multichannel intraluminal impedance-pH monitoring

Background and Aims:  To investigate the reflux profile of Chinese gastroesophageal reflux disease (GERD) patients with the aid of combined multichannel intraluminal impedance-pH (MII-pH) monitoring technique.
Methods:  Consecutive patients presented with GERD symptoms were enrolled to erosive esophagitis (EE) group, non-erosive reflux disease (NERD) group and functional heartburn (FH) group after upper endoscopy, combined MII-pH monitoring and rabeprazole test. Another 20 healthy controls (HC) were recruited.
Results:  Sixty-four GERD patients (EE:20, NERD:22, FH:22, HC:20) were enrolled. There were more episodes of liquid reflux and proximal reflux in EE and NERD groups than that in FH and HC groups ( P  < 0.05). Patients in FH and HC groups had higher proportion of mixed reflux ( P  = 0.000). The percentage of acid reflux in EE and NERD was much higher, while there was a higher percentage of weakly acidic reflux in FH and HC ( P  = 0.000). No significant difference was found in MII-pH parameters between groups with and without response to rabeprazole test except recumbent percentage time of esophageal pH value below 4 and episodes of proximal reflux.
Conclusion:  Erosive esophagitis and NERD patients had more liquid and proximal reflux episodes than FH patients and healthy controls. Acid and liquid reflux was predominant in the former two groups, while weakly acidic and mixed reflux was predominant in the latter two groups.     

不同亚型胃食管反流病食管黏膜下层炎症因子变化特点研究

目的分析3种亚型胃食管反流病患者与对照组食管黏膜的组织变化和局部IL-4、IL- 6表达,探讨Th2型炎症因子在胃食管反流病发生发展中的作用。 方法选取2016年12月至2017年12月新疆维吾尔自治区人民医院69例患者临床资料,根据Gerd Q评分和内镜结果将所有入选研究者分为Barrett食管（BE）、糜烂性食管炎（EE）、非糜烂性反流病（NERD）和对照4组,利用食管24 h pH监测法评价胃食管反流病（GERD）患者食管酸暴露及反流特点;通过食管组织HE染色进行组织病理学评分,使用免疫组化法和酶联免疫吸附剂测定法检测食管局部及血清中IL-4、IL-6表达情况。 结果食管24 h pH监测结果中,3亚组间DeMeester指数、弱酸反流次数、反流总事件数比较,差异均无统计学意义（P均>0.05）,NERD组酸反流次数较其余2组低,差异有统计学意义（P均<0.05）;4组样本食管黏膜组织病理学评分中发现,BE组、EE组与其余2组相比均明显升高,差异有统计学意义（P均<0.05）,BE组与EE组评分之间亦有显著差异（P<0.05）,NERD组与对照组间差异不明显;IL-4在4组食管标本中均有不同程度表达,但4组间IL-4阳性率的比较并无显著差异（P均>0.05）;IL-6在NERD组和对照组表达量较低甚至不表达,EE组IL-6阳性率明显高于对照组（P<0.05 ）,但与NERD组间无显著差异,BE组阳性率与对照组和NERD组之间均有明显差异（P均<0.05 ）。 结论GERD食管黏膜上皮组织学炎症等级随食管炎的恶化而升高,其中NERD的食管组织学已出现炎性化趋势,但尚不足以与正常食管区别;IL-4在不同亚型GERD食管黏膜组织中的表达差异不及IL-6显著。     

六味安消对非糜烂性反流病患者食道动力及酸反流的影响

[目的]观察六味安消对非糜烂性反流病（NERD）患者食道动力及胃食管反流的影响,并与莫沙必利比较疗效.[方法]选取具有典型胃食管反流症状的NERD患者52例,行胃食管反流症状评估、食管测压及24 h pH监测,随机分成试验组26例和对照组26例.给予药物治疗（试验组六味安消,对照组莫沙必利）4周后,对比治疗前后临床症状、食管动力学及胃食管反流的改变情况.[结果]试验组与对照组症状总积分、食管蠕动功能、pH＜4反流次数、反流＞5 min次数、总计pH＜4的百分比、DeMeester评分自身治疗前后相比较,差异均有显著统计学意义（P＜0.05）,而2组组间比较差异均无统计学意义.[结论]六味安消能有效缓解NERD患者的胃食管反流症状,改善食管蠕动功能及减少酸反流.