Prospective validation of reflux monitoring by impedance-pH in predicting PPI response in typical GERD

BackgroundThe Lyon Consensus proposed a hierarchical approach to GERD diagnosis based on conventional and new impedance-pH metrics, namely acid exposure time (AET), number of reflux episodes, post-reflux swallow-induced peristaltic wave (PSPW) index, and mean nocturnal baseline impedance (MNBI).AimsTo define the value of conventional and new impedance-pH parameters as predictors of response to label-dose PPI in typical GERD.MethodsConsecutive adult patients with typical esophageal symptoms were prospectively studied with impedance-pH monitoring and treated with 8-week label-dose PPI. At the end of the PPI course, symptoms response was assessed.ResultsAmong 255 patients who entered the study, 168 (65.9%) reported symptom remission. At ROC analysis, both MNBI and PSPW index were significantly associated to PPI responsiveness with AUC of 0.783 and 0.801, respectively. Cut-off values of 1747Ω for MNBI and 50% for PSPW index were identified as discriminators between response and non-response to label-dose PPI. At multivariate analysis, MNBI, PSPW index, and AET >6% were efficient predictors of PPI responses (OR 3, 5.4 and 2.3, respectively). Number of reflux episodes did not predict PPI response.ConclusionsThe novel MII-pH variables together with pathological are highly predictive of response of the typical GERD syndrome to label-dose PPI.     

Post-reflux swallow-induced peristaltic wave index and mean nocturnal baseline impedance predict PPI response in GERD patients with extra esophageal symptoms

BackgroundMean nocturnal baseline impedance (MNBI) and post-reflux swallow-induced peristaltic wave (PSPW) index are able to increase the diagnostic yield of impedance-pH and are associated to proton pump inhibitor (PPI) response. Few data concerning these variables in patients with extra-esophageal symptoms (EES) are available.AimsTo evaluate, in EES patients, the role of the conventional and new impedance-pH variables in diagnosing GERD and the predictive value of impedance-pH variables for PPI response.MethodsConsecutive patients presenting suspected GERD-related EES underwent impedance-pH. Patients treated in the last six months with double dose PPI therapy were enrolled. The presence of concomitant typical symptoms was assessed.Results239 EES patients were studied; 102 responders and 137 non-responders. Eighty-one (34%) were affected by non-erosive reflux disease (NERD), 61 (26%) presented reflux hypersensitivity (RH) and 97 (40%) were non-GERD. In NERD and RH groups, a significantly higher proportion of patients with pathological PSPW index or MNBI values compared to non-GERD group was observed. 24 (25%) non-GERD patients presented a pathological PSPW index and/or MNBI. Pathological PSPW index, MNBI and presence of typical symptoms were associated to PPI response.ConclusionsMNBI and PSPW index measurement increases the diagnostic yield of impedance-pH; abnormal values are associated with a satisfactory response to acid-suppressive therapy in EES patients.     

难治性胃食管反流病的诊疗策略

胃食管反流病（GERD）是临床常见疾病,约30%~50%的患者症状在质子泵抑制剂（PPI）治疗后不能得到完全缓 解,其中难治性GERD占较大比例。pH阻抗监测、高分辨率食管测压、内镜及活检等有助于分析导致难治性GERD 发生的原因。其中,pH阻抗对分析导致难治性GERD成因非常重要。反流后吞咽诱发蠕动波指数（PSPWI）和夜间平 均基线阻抗（MNBI）这两个新指标有助于提高诊断率。难治性GERD的治疗手段包括更换PPI种类、加用H2受体阻 滞剂、辅以促动力药物、外科手术、内镜下治疗等。个体化治疗策略的制定有赖于难治性GERD的具体成因。     

Esophageal chemical clearance and baseline impedance values in patients with chronic autoimmune atrophic gastritis and gastro-esophageal reflux disease

BackgroundThe factors influencing new markers of gastro-esophageal reflux disease detected by impedance-pH monitoring – mean nocturnal baseline impedance (MNBI) and post-reflux swallow-induced peristaltic wave (PSPW) index – need to be evaluated.AimTo compare endoscopy-negative heartburn with chronic autoimmune atrophic gastritis (CAAG).Materials and methods24 patients with CAAG, 25 with non-erosive reflux disease (NERD) and 25 with functional heartburn (FH) were included. In all patients the main impedance-pH monitoring parameters were calculated.ResultsCAAG and NERD patients had a number of reflux events (non-acid ones being more common among the former group) which was higher than that found in FH (p < 0.001). MNBI decreased progressively in FH (>3000 Ohm), CAAG (>2000 Ohm) and NERD (<1000 Ohm) patients (p = 0.0046). The PSPW index was similar between CAAG and NERD patients but significantly lower in comparison to FH (p < 0.0001).ConclusionPatients with CAAG have evidence of non-acid reflux based on the high number of reflux events and confirmed by low values of MNBI and PSPW index. MNBI is a strong marker of acid/non-acid reflux-induced mucosal damage, whereas the PSPW index can reliably discriminate patients with reflux from those with FH, independently of the acidity of refluxate.     

Laparoscopic fundoplication for gastroesophageal reflux disease

Gastroesophageal reflux disease(GERD) is a condition that develops when the reflux of gastric contents into the esophagus leads to troublesome symptoms and/or complications. Heartburn is the cardinal symptom, often associated with regurgitation. In patients with endoscopy-negative heartburn refractory to proton pump inhibitor(PPI) therapy and when the diagnosis of GERD is in question, direct reflux testing by impedance-pH monitoring is warranted. Laparoscopic fundoplication is the standard surgical treatment for GERD. It is highly effective in curing GERD with a 80% success rate at 20-year follow-up. The Nissen fundoplication, consisting of a total(360°) wrap, is the most commonly performed antireflux operation. To reduce postoperative dysphagia and gas bloating, partial fundoplications are also used, including the posterior(Toupet) fundoplication, and the anterior(Dor) fundoplication. Currently, there is consensus to advise laparoscopic fundoplication in PPI-responsive GERD only for those patients who develop untoward side-effects or complications from PPI therapy. PPI resistance is the real challenge in GERD. There is consensus that carefully selected GERD patients refractory to PPI therapy are eligible for laparoscopic fundoplication, provided that objective evidence of reflux as the cause of ongoing symptoms has been obtained. For this purpose, impedance-pH monitoring is regarded as the diagnostic gold standard.     

Diagnostic options for patients with refractory GERD

Patients with refractory gastroesophageal reflux disease (GERD) are those who have persistent symptoms while being treated with proton pump inhibitors (PPIs). One third of GERD patients requiring a daily PPI are estimated to eventually experience treatment failure. These patients are usually referred for further investigation to confirm the presence of GERD or to identify other entities as the cause of symptoms. Tools that can be used in this diagnostic process include upper gastrointestinal endoscopy with analysis of esophageal biopsies, esophageal pH monitoring, impedance-pH monitoring, and esophageal bilirubin monitoring. The conventional diagnostic approach includes upper gastrointestinal endoscopy and ambulatory pH monitoring while receiving PPI therapy. New diagnostic techniques that may be useful with refractory GERD include impedance-pH monitoring, which is very sensitive in detecting persistent weakly acidic reflux, and bilirubin monitoring, which detects increased esophageal exposure to bile. Gastric pH monitoring should be reserved for patients in whom PPI resistance is suspected.     

胃镜下胃食管阀瓣分级与基于里昂共识的胃食管反流病证据等级及反流新参数的相关性

目的探讨胃镜下胃食管阀瓣(gastroesophageal flap valve, GEFV)分级与基于里昂共识的胃食管反流病(gastroesophageal reflux disease, GERD)证据等级、平均夜间基线阻抗(mean nocturnal baseline impedance, MNBI)、反流后吞咽诱发的蠕动波指数(post-reflux swallow-induced peristaltic wave index, PSPWI)的相关性。方法收集就诊于首都医科大学附属北京同仁医院消化内科有典型胃食管反流症状且完成胃镜、24 h食管pH-阻抗监测及食管高分辨测压(high-resolution manometry, HRM)的421例患者。回顾性分析胃镜下GEFV分级与基于里昂共识的GERD证据等级、食管pH-阻抗监测常规指标,即总反流次数、pH<4时间百分比[AET4(%)]、DeMeester评分及新参数(MNBI及PSPWI)的关系。结果异常GEFV(GEFVⅢ+Ⅳ级)占所有患者的29.5%,在确定性GERD证据组比例最高(49.6%)。GEFV异常组的男性比例、糜烂性食管炎比例、AET4(%)、总反流次数显著高于GEFV正常组,而MNBI、PSPWI显著降低(P<0.05)。男性、BMI、AET4(%)、DeMeester评分、总反流次数与GEFV分级呈显著正相关,MNBI、PSPWI与GEFV分级呈显著负相关(P<0.05)。结论基于里昂共识的确定性GERD证据的患者中GEFV异常比例最高,GEFV异常提示糜烂性食管炎发生率升高、更重的反流负荷、MNBI及PSPWI降低。     

Wireless 24, 48, and 96 Hour or Impedance or Oropharyngeal Prolonged pH Monitoring: Which Test,When, and Why for GERD?

Purpose of Review

pH monitoring technologies are routinely utilized in practice to further evaluate symptoms of gastro-esophageal reflux disease and laryngopharyngeal reflux (LPR). This is a review of the recent literature of the available pH monitoring technology and creates an algorithm in the diagnostic work up of a patient with GERD or LPR.

Recent Findings

The catheter-free wireless pH monitor traditionally collects data for 48 h. Recent studies have found that extending to 96 h can be helpful in patients with conflicting results on the first 2 days of the study. In addition, 96 h can allow for testing both on and off of PPI therapy. The oropharyngeal monitoring device is a newer technology that is designed to aid in the diagnoses of LPR. There are limitations with this technology as there is no universal abnormal cutoff and some studies have suggested a poor correlation between multichannel intraluminal impedance-pH (MII-pH) and the oropharyngeal monitoring device. MII-pH has recently developed two additional parameters, the measurement of three 10-min nighttime periods and the post-reflux swallow-induced peristaltic wave (PSPW) index, both of which may increase accuracy of testing.

Summary

Each of these technologies can provide unique data regarding acid reflux exposure in the esophagus and oropharynx. The wireless pH monitor performed off of PPI therapy can help to establish or exclude the diagnosis of GERD. For those patients with refractory symptoms on PPI, MII-pH study can be performed while on therapy and provides data regarding the response to treatment. Oropharyngeal pH monitoring is being utilized in some practices to aid in diagnosis of LPR, but the scientific validity is controversial.

     

胃食管反流病诊断技术的进展

胃食管反流病（GERD）的患病率近年来在我国有上升趋势。目前诊断GERD的手段较多，如典型症状（烧心和反酸）、质子泵抑制剂（PPT）试验和上消化道内镜检查等，尤其是GERD的诊断技术，包括最初的X线钡餐以及食管放射性核素检查和24h食管pH监测，到新近出现的食管多通道腔内阻抗监测和无线pH监测等，为胃食管反流提供了客观的证据。     

Laboratory based investigations for diagnosing gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) still remains the most common out- GI-related condition in the out-patient setting. While primary care physicians often use empiric trials with proton pump inhibitors (PPI trial) to diagnose GERD, often specialised tests are required to confirm or exclude gastroesophageal reflux causing esophageal or extraesophageal symptoms. The most commonly used procedures to diagnose GERD include: conventional (catheter based) pH monitoring, wireless esophageal pH monitoring (Bravo), bilirubin monitoring (Bilitec), and combined multichannel intraluminal impedance-pH monitoring (MII-pH). Each technique has strengths and limitations of which clinicians and investigators should be aware when deciding which one to choose.     

Extra-Esophageal Manifestations of Gerd: Who Responds to GERD Therapy?

Gastroesophageal reflux disease (GERD) is a common disease that is defined as a condition that develops when the reflux of stomach contents causes troublesome symptoms. In addition to the esophageal manifestations of heartburn and regurgitation, the role of GERD in causing extra-esophageal symptoms, such as laryngitis, asthma, cough, chest pain, and dental erosions, is increasingly recognized with renewed interest. Due to the poor sensitivity of endoscopy and pH monitoring, and the poor specificity of laryngoscopy, empiric therapy with proton pump inhibitors (PPI) is now considered the initial diagnostic step in patients suspected of having GERD-related symptoms. In those who are unresponsive to such therapy, other diagnostic testing such as impedance/pH monitoring may be reasonable in order to exclude continued acid or weakly acid reflux. Recent data suggest that patients with extra-esophageal symptoms who have concomitant typical symptoms, moderate-sized hiatal hernia and moderate reflux on pH testing may respond better to acid suppressive therapy. This group only accounts for 20?30 % of patients commonly referred for suspected GERD. PPI-unresponsive patients usually have causes other than GERD for their extra-esophageal signs and symptoms and continued PPI therapy in this group is not recommended.     

Belching: dyspepsia or gastroesophageal reflux disease?

OBJECTIVES: Eructation (belching) is a common symptom seen in clinical practice. Because either belching or heartburn may result from transient lower esophageal sphincter relaxations, it has been proposed that belching may be a manifestation of gastroesophageal reflux disease (GERD). In this retrospective study we evaluated the prevalence of belching in dyspepsia and GERD and the relation of belching to acid reflux events documented by pH monitoring. METHODS: We examined the prevalence, frequency, and severity of belching and other GERD symptoms by use of standardized questionnaires in 180 GERD patients (group A) and 78 dyspeptic controls (group B) referred for evaluation at our institution. GERD was defined as either endoscopic esophagitis (or Barrett's esophagus) or positive DeMeester score (>14.2) on pH monitoring or both. Dyspeptic patients had normal endoscopy and pH studies. We also analyzed the relationship of belching to acid reflux events during the 24-h period of pH studies. RESULTS: Of 180 GERD patients, 132 (70%) reported belching during pH monitoring, versus 63 of 78 dyspeptic patients (80%) (p = ns). Similarly, 163 of 180 GERD patients (90%) reported heartburn versus 64 of 78 of dyspeptic patients (82%) (p = ns). Review of symptom questionnaires revealed no significant difference in belching severity between groups. However, heartburn and acid regurgitation were significantly more severe among GERD patients. There was a significantly higher correlation of both heartburn and belching with acid events in patients with GERD compared with patients with dyspepsia. In addition, although both belching and heartburn were significantly improved in patients with GERD, belching scores remained unchanged after proton pump inhibitor (PPI) therapy in patients with dyspepsia. CONCLUSIONS: Belching is as common and as severe in patients with dyspepsia as it is in patients with GERD. Belching and heartburn in GERD patients are more likely correlated with episodes of pathological acid reflux. Because belching cannot be clinically used as a discriminatory symptom, ambulatory pH monitoring should be considered to elucidate the relationship of belching to acid reflux in patients with dyspepsia or GERD.     

Extra-esophageal gastroesophageal reflux disease and asthma: understanding this interplay

Gastroesophageal reflux disease (GERD) is a condition that develops when there is reflux of stomach contents, which typically manifests as heartburn and regurgitation. These esophageal symptoms are well recognized; however, there are extra-esophageal manifestations of GERD, which include asthma, chronic cough, laryngitis and sinusitis. With the rising incidence of asthma, there is increasing interest in identifying how GERD impacts asthma development and therapy. Due to the poor sensitivity of endoscopy and pH monitoring, empiric therapy with proton pump inhibitors (PPIs) is now considered the initial diagnostic step in patients suspected of having GERD-related symptoms. If unresponsive, diagnostic testing with pH monitoring off therapy and/or impedance/pH monitoring on therapy, may be reasonable in order to assess for baseline presence of reflux with the former and exclude continued acid or weakly acid reflux with the latter tests. PPI-unresponsive asthmatics, without overt regurgitation, usually have either no reflux or causes other than GERD. In this group, PPI therapy should be discontinued. In those with GERD as a contributing factor acid suppressive therapy should be continued as well as optimally treating other etiologies requiring concomitant treatment. Surgical fundoplication is rarely needed but in those with a large hiatal hernia, moderate-to-severe reflux by pH monitoring surgery might be helpful in eliminating the need for high-dose acid suppressive therapy.     

联合食管多通道腔内阻抗-pH监测在诊断胃食管反流病中的价值

目的 了解联合食管多通道腔内阻抗pH(MII-pH)监测诊断胃食管反流病(GERD)的价值.方法 纳入具有烧心症状且食管黏膜无损伤患者44例,首先行MII-pH监测,然后行14 d的雷贝拉唑试验(试验结束时烧心症状完全消失定义为雷贝拉唑试验阳性).70名健康志愿者行MII-pH监测的结果作为正常值进行参照.结果 根据食管pH监测存在异常食管酸暴露或酸反流症状指数(SI)阳性者20例(45.4%).MII-pH监测提示弱酸反流SI阳性者2例,据此检查诊断烧心患者GERD的比例增至50%(22/44).雷贝拉唑试验阳性4例,据此则将烧心患者诊断为GERD的比例增至54.5%(24/44).结论 联合食管MII-pH监测可增加GERD检出率.     

联合食管多通道腔内阻抗-pH监测在诊断胃食管反流病中的价值

目的 了解联合食管多通道腔内阻抗pH(MII-pH)监测诊断胃食管反流病(GERD)的价值.方法 纳入具有烧心症状且食管黏膜无损伤患者44例,首先行MII-pH监测,然后行14 d的雷贝拉唑试验(试验结束时烧心症状完全消失定义为雷贝拉唑试验阳性).70名健康志愿者行MII-pH监测的结果作为正常值进行参照.结果 根据食管pH监测存在异常食管酸暴露或酸反流症状指数(SI)阳性者20例(45.4%).MII-pH监测提示弱酸反流SI阳性者2例,据此检查诊断烧心患者GERD的比例增至50%(22/44).雷贝拉唑试验阳性4例,据此则将烧心患者诊断为GERD的比例增至54.5%(24/44).结论 联合食管MII-pH监测可增加GERD检出率.     

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.     

Complete elimination of reflux symptoms does not guarantee normalization of intraesophageal and intragastric pH in patients with gastroesophageal reflux disease (GERD)

BACKGROUND: Acid plays a significant role in the development of gastroesophageal reflux symptoms, such as heartburn and regurgitation. It is generally assumed that acid suppressive therapy improves or eliminates symptoms by normalizing intraesophageal pH. AIMS: The aim of this article was to assess the efficacy of proton-pump inhibitors (PPIs) in normalizing intraesophageal and intragastric pH in patients with GERD without Barrett's esophagus (BE) rendered symptom free by therapy. METHODS: Patients were evaluated by dual-sensor 24-h pH monitoring while receiving PPI therapy for complete control of GERD symptoms. Analyses of intraesophageal and intragastric pH profiles were then made. RESULTS: Fifty patients, 39 men and 11 women, with GERD, without BE, were studied. All tolerated PPIs well and were asymptomatic at the time of the study. Fifty percent of patients had abnormal intraesophageal pH profiles despite adequate symptom control on PPIs, which was associated with significant breakthrough of intraesophageal acid control in both the upright and supine positions. Low intragastric pH correlated highly with intraesophageal acid reflux only in patients with persistent abnormal esophageal acid exposure (p= 0.001). CONCLUSIONS: Fifty percent of patients with GERD without BE continue to exhibit pathologic GERD and low intragastric pH despite PPI therapy that achieves complete reflux symptom control.     

Gastroesophageal reflux disease

GERD is a common chronic gastrointestinal disorder, and its prevalence in Asia is increasing. Classical symptoms of heartburn and regurgitation are common presentations. There is no standard criterion for the diagnosis of GERD, and 24-h pH monitoring lacks sensitivity in NERD. Furthermore, diagnostic studies for gastroesophageal reflux disease have several limitations. A short course of PPI is often used in clinical practice as a diagnostic test for gastroesophageal reflux disease. Elderly patients with GERD usually present with atypical manifestations, and they tend to develop more severe disease. PPI remains the mainstay of treatment for GERD. In a subset of patients who wish to discontinue maintenance treatment, anti-reflux surgery is a therapeutic option.     

食管阻抗-pH监测在胃食管反流病诊断中的作用

阻抗-pH监测是目前监测胃食管反流病(GERD)的新技术,可通过对胃反流物的pH值和阻抗值进行检测,从而了解反流物为酸反流、弱酸反流或非腹反流,并可区分反流物的性状。阻抗-pH监测可应用于GERID的诊断,尤其适用于对弱酸反流或非酸反流的诊断、对难治性GERD的诊断以及非典型症状GERD的诊断。本文主要就阻抗-pH监测的机制和临床应用作一论述。     

Heartburn refractory to proton-pump inhibitors

Opinion statement The most appropriate diagnostic and therapeutic approach to patients with heart-burn that persists despite the use of proton-pump inhibitor (PPI) therapy currently is not known. In general, patients with heartburn refractory to PPIs may have more than one explanation for their persistent symptoms. These include uncontrolled esophageal acid exposure (“PPI failure”) in a small subset of patients, as well as other potential etiologies in the majority of patients who have controlled esophageal acid exposure on PPI therapy (“PPI success”). Some potential explanations for persistent heartburn in this latter group include hypersensitivity to acid reflux, nonacidic or duodenogastric esophageal reflux, as well as functional heartburn. Patients who present with heartburn refractory to PPIs should be investigated further to determine the potential cause. We believe the diagnostic modality with the most clinical usefulness is 24-hour pH and multichannel intraluminal impedance monitoring with symptom index performed while the patient is on high-dose PPI therapy. This approach allows the patient to be properly categorized and also identifies a substantial proportion of patients who will have functional heartburn, a condition that should discourage the use of endoscopic or surgical therapies. Therapeutic options for patients with heartburn refractory to PPIs are limited and have not been thoroughly studied. As a result of the paucity of information, we favor a therapeutic approach based on the outcome of diagnostic testing.