Use of proton pump inhibitor as a diagnostic test in NCCP

Abstract:   Non-cardiac chest pain (NCCP) is the most common extra-esophageal manifestation of gastroesophageal reflux disease. The proton pump inhibitor empirical trial (PPI test) is a simple non-invasive, arcurate and cast-saving test for evaluating patients with GERD-related NCCP. The review will discuss the use of the PPI test as a diagnostic test for NCCP.     

Can symptoms predict esophageal motor function or acid exposure in gastroesophageal reflux disease? A comparison of esophageal manometric and twenty-four-hour pH parameters in typical and extraesophageal gastroesophageal reflux disease

It has been suggested that patterns of esophageal motor function and acid exposure may differ between those patients with gastroesophageal reflux disease (GERD) with classic symptoms and those with extraesophageal manifestations. Our objective was to compare various parameters of esophageal motility and acid exposure between groups of patients who had presented with extraesophageal manifestations of GERD alone, a combination of classic and extraesophageal manifestations, or classic GERD symptoms alone. A retrospective review of consecutive patients undergoing esophageal manometry and 24-hour dual-channel esophageal pH testing was performed. Information on patient demographics, symptoms, and results of various manometric and pH testing parameters was examined. We evaluated 84 patients: 32 with extraesophageal symptoms alone, 24 with both classic and extraesophageal symptoms, and 28 with classic symptoms alone. Apart from a trend toward less supine acid exposure in those with extraesophageal symptoms alone, no significant differences were evident among the three patient groups in any of the other parameters of proximal or distal esophageal acid reflux. With respect to motility parameters, lower esophageal sphincter pressure was lower in those with combined symptoms; otherwise, manometric findings were similar in the three patient groups. Our data do not support the hypothesis that the nature of the clinical presentation of GERD, whether in the form of classic or extraesophageal manifestations, is related to differing patterns of esophageal motor function or esophageal acid exposure.     

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.     

Role of clinical presentation in diagnosing reflux-related non-cardiac chest pain

INTRODUCTION: Non-cardiac chest pain (NCCP) presents as a frequent diagnostic challenge, with patients tending to use a disproportionate level of health-care resources. Gastroesophageal reflux disease (GERD) is the most frequent cause of NCCP. Thus the typical symptoms of reflux, such as heartburn and regurgitation, when present as predominant symptoms are quite specific for diagnosing GERD but in patients with NCCP the clinical diagnosis of reflux is difficult, and invasive methods or the omeprazole test are required for its detection. The aim of the present study was to evaluate the role of clinical presentation when diagnosing GERD among patients with NCCP. METHODS: Patients with NCCP underwent upper endoscopy, Bernstein and omeprazole tests. The patients were divided into two groups based on GER- or non-GER-related chest pain, and clinical presentation was compared between these two groups. Gastroesophageal reflux disease was considered positive when at least two methods were positive. RESULTS: From 78 NCCP patients (41 male; mean age 50.4 +/- 2.3 years), the chest pain was related to GERD in 35 patients (44.8%). The two groups were the same based on sex and age. The chest pain severity, site, radiation and relation to food, exercise, and sleep were equal in the two groups, except for two symptoms: pain that was relieved by antacid (P < 0.031) and presence of classical reflux symptoms (P < 0.009), seen in the GERD patients. With regard to recent patient history, heartburn and regurgitation symptoms were seen more frequently in GERD patients (P < 0.036 and P < 0.002, respectively). DISCUSSION: Clinical presentation is important in diagnosing GERD in NCCP. Although the chest pain is the same in reflux- and non-reflux-related NCCP, the symptoms of heartburn or regurgitation in the present or recent patient history are diagnostic for GERD-related chest pain.     

Gastroesophageal reflux disease: Important considerations for the older patients

Gastroesophageal reflux disease (GERD) is the most common upper gastrointestinal disorder seen in the elderly. The worldwide incidence of GERD is increasing as the incidence of Helicobacter pylori is decreasing. Although elderly patients with GERD have fewer symptoms, their disease is more often severe. They have more esophageal and extraesophageal complications that may be potentially life threatening. Esophageal complications include erosive esophagitis, esophageal stricture, Barrett's esophagus and adenocarcinoma of the esophagus. Extraesophageal complications include atypical chest pain that can simulate angina pectoris; ear, nose, and throat manifestations such as globus sensation, laryngitis, and dental problems; pulmonary problems such as chronic cough, asthma, and pulmonary aspiration. A more aggressive approach may be warranted in the elderly patient, because of the higher incidence of severe complications. Although the evaluation and management of GERD are generally the same in elderly patients as for all adults, there are specific issues of causation, evaluation and treatment that must be considered when dealing with the elderly.     

Gastroesophageal reflux disease--state of the art

Gastroesophageal reflux disease (GERD) is defined as chronic symptoms or mucosal damage produced by the abnormal reflux of gastric contents into the esophagus; heartburn, its most common manifestation, occurs in 7% to 10% of the U.S. population on a daily basis. In addition, many so-called extraesophageal or atypical symptoms, including chronic cough, laryngitis and other otolaryngologic conditions, asthma, and unexplained chest pain, can be associated with GERD, but these patients appear to have a decreased frequency of heartburn, making the diagnosis of GERD difficult. All patients can be successfully managed with appropriate, titrated use of pharmacologic therapy. Antireflux surgery should thus be considered as an option only for patients who cannot afford or choose not to continue long-term medical therapy and for the rare patient with side effects or resistance to proton pump inhibitors. Endoscopic therapy for reflex should be considered as an experimental technology needing continuing evaluation.     

Recent advances in noncardiac chest pain in Korea

Gastroesophageal reflux disease (GERD) is the most common cause of noncardiac chest pain (NCCP) and is present in up to 60% of patients with NCCP in Western countries. In Korea, after a reasonable cardiac evaluation, GERD is reported to underlie 41% of NCCP cases. Typical reflux symptoms are frequent in Korean patients suffering from NCCP. Therefore, a careful history of the predominant symptoms, including heartburn and acid regurgitation, is relatively indicative of the GERD diagnosis in Korea. In Korea, in contrast to Western countries, patients aged 40 years and over who have been diagnosed with NCCP but who are without alarming features should undergo endoscopy to exclude gastric cancer or peptic ulcers because of the higher prevalence of peptic ulcer disease and gastric cancers in the region. In a primary care setting, in the absence of any alarming symptoms, a symptomatic response to a trial of a proton pump inhibitor (PPI) is sufficient for the presumptive diagnosis of GERD. In addition, the optimal duration of a PPI test may be at least 2 weeks, as GERD symptoms tend to be less frequent or atypical in Korean patients than in patients from Western countries. In patients diagnosed with GERD-related NCCP, long-term therapy (more than 2 months) with double the standard dose of a PPI is required to alleviate symptoms. Esophageal dysmotility is relatively uncommon, and pain modulators seem to offer significant improvement of chest pain control in non-GERD-related NCCP. Most traditionally available tricyclics or heterocyclics have many undesirable effects. Therefore, newer drugs with fewer side effects (for example, the serotonin - norepinephrine reuptake inhibitors) may be needed.     

Effect of Antisecretory Therapy on Atypical Symptoms in Gastroesophageal Reflux Disease

The effect of proton pump inhibitor (PPI) therapy on extraesophageal or atypical manifestations of gastroesophageal reflux disease (GERD) remains unclear. This study aimed to evaluate the prevalence of atypical manifestations in patients with acid reflux disease and the effect of PPI treatment. Patients with symptoms and signs suggestive of reflux were enrolled. Erosive esophagitis was stratified using the Los Angeles classification. Demographic data and symptoms were assessed using a questionnaire and included typical symptoms (heartburn, regurgitation, dysphagia, odynophagia), and atypical symptoms (e.g., chest pain, sialorrhea, hoarseness, globus sensation, chronic coughing, episodic bronchospasm, hiccup, eructations, laryngitis, and pharyngitis). Symptoms were reassessed after a 3-month course of b.i.d. PPI therapy. A total of 266 patients with a first diagnosis of GERD (erosive, 166; non-erosive, 100) were entered in the study. Presentation with atypical symptoms was approximately equal in those with erosive GERD and with non-erosive GERD, 72% vs 79% (P = 0.18). None of the study variables showed a significant association with the body mass index. PPI therapy resulted in complete symptom resolution in 69% (162/237) of the participants, 12% (28) had improved symptoms, and 20% (47) had minimal or no improvement. We conclude that atypical symptoms are frequent in patients with GERD. A trial of PPI therapy should be considered prior to referring these patients to specialists.     

How do we define non-cardiac chest pain?

Abstract:   Noncardiac chest pain (NCCP) is a heterogeneous disorder associated with substantial health-care costs and resource utilization. NCCP is defined by recurrent episodes of substernal chest pain in patients lacking a cardiac cause after a comprehensive evaluation. The magnitude of the problem is quite high because of fear of serious or life-threatening heart diseases. Patients with chest pain who present for the first time to ambulatory care or to the emergency room, only 11% to 39% are ultimately diagnosed with coronary artery disease. The likely causes of NCCP are numerous and often overlap. Diagnosing NCCP is difficult because NCCP remains a diagnosis of exclusion that encompasses heterogeneous patient populations. First, cardiac ischemic must be excluded and coronary angiography remains the gold standard. Once cardiac causes have been ruled out, a diagnosis of NCCP is made. Mostly, the source for NCCP originates in essence from the esophagus. Gastroesophageal reflux disease (GERD) is the most common esophageal diseases present in patients with NCCP. An initial empiric trail of high-dose acid suppression is the most cost-effective measure in the management of these patients. When a diagnostic workup is chosen, it centers on upper gastrointestinal endoscopy, 24-hr esophageal pH monitoring and esophageal manometry.     

Variation of health‐care resource utilization according to GERD‐associated complications

Complications associated with gastroesophageal reflux disease (GERD) can include esophageal stricture, Barrett's esophagus, gastrointestinal hemorrhage, and extraesophageal symptoms. The impact of GERD‐associated complications on health‐care utilization deserves further evaluation. We identified commercial enrollees 18–75 years old with claims for GERD (International Classification of Diseases, Ninth Revision, Clinical Modification Codes: 530.81 or 530.11) and subsequent usage of proton pump inhibitors from 01/01/05 to 06/30/09. The initial GERD diagnosis date was designated as the index date, and patients were studied for 6 months preindex and postindex. Eligible patients were subsequently stratified based on medical claims for GERD‐associated complications as follows: stage A (GERD diagnosis, no other symptoms), stage B (GERD + extraesophageal symptoms), stage C (GERD + Barrett's esophagus), stage D (GERD + esophageal stricture), and stage E (GERD + iron‐deficiency anemia or acute upper gastrointestinal hemorrhage). Patient characteristics, health‐care utilization, and costs were compared between stage A and each stage with complicated GERD (B–D). Of the 174,597 patients who were eligible for analysis, 74% were classified as stage A, 20% stage B, 1% stage C, 2% stage D, and 3% stage E. Relative to stage A, patients in stages C, D, and E were significantly more likely to visit a gastroenterologist (13% vs. 68%, 71%, and 38%, respectively) and had higher rates of esophageal ulcers (0.3% vs. 8%, 5%, and 3%, respectively) and Nissen fundoplication (0.05% vs. 0.6%, 0.3%, and 0.2%, respectively). Six‐month GERD‐related costs ranged from $615/patient (stage A) to $1714/patient (stage D); all‐cause costs ranged from $4195/patient (stage A) to $11,340/patient (stage E). Compared with stage A, all other cohorts had significantly higher all‐cause and GERD‐related costs (P < 0.0001 for all comparisons). While patients with more severe GERD represented a relatively small portion of the GERD cohort, they demonstrated significantly greater health‐care costs and overall utilization than patients with uncomplicated GERD.     

Long-term management of GERD in the elderly with pantoprazole

The prevalence of gastroesophageal reflux disease (GERD) increases with age and elderly are more likely to develop severe disease. Older patients often complain of less severe or frequent heartburn than younger patients and they may present with atypical symptoms such as dysphagia, weight loss, or extraesophageal symptoms. Proton pump inhibitors (PPIs) are central in the management of GERD and are unchallenged with regards to their efficacy. They are considered safe and more effective than histamine receptor antagonists for healing esophagitis and for preventing its recurrence using a long term maintenance treatment. PPI have minimal side effects and few slight drug interactions and are considered safe for long term treatment. Pantoprazole is significantly effective both for acute and long-term treatment with excellent control of relapse and symptoms. It is well tolerated even for long-term therapy and its tolerability is optimal. Pantoprazole shows to have minimal interactions with other drugs because of a lower affinity for cytocrome P450 than older PPIs. Although the majority of elderly has concomitant illnesses and receive other drugs, this does not adversely effect the efficacy of pantoprazole because of its pharmacokinetics, which are independent of patient age. Clinical practice suggests that a low dose maintenance of PPIs should be used in older patients with GERD.     

食管混合性酸反流和低动力在非心源性胸痛发作的作用研究

目的胃食管反流病（GERD）是引起非心源性胸痛（NCCP）的最常见因素,本研究探讨酸反流和食管动力障碍在NCCP患者中的作用。 方法按照纳入、排除标准选取2018年9月至2019年6月在新疆维吾尔自治区人民医院急救中心以及微创,疝和腹壁外科住院收治的40例NCCP患者和50例典型GERD症状患者,两组患者均行食管24 h pH监测以及高分辨率食管测压监测。 结果NCCP组食管远端收缩平均积分（DCI）明显低于GERD组,并具有统计学意义（P＜0.05）,提示食管运动功能受损。在NCCP组患者中,与胸痛有关的混合性酸反流明显高于GERD组（P＜0.05）。在NCCP组患者中,与NCCP相关的反流发作在食管5、9和15cm处的反流清除时间比GERD组患者期长（28.3±4.21)s vs(22.6±3.28)s;(13.7±1.32)s vs (18.3±1.47)s;(9.58±1.02)s vs(14.3±1.06)s（P＜0.05）。 结论酸反流性质,食管运动功能受损和延缓反流清除时间与NCCP患者症状发作可能存在密切的关系。     

Noncardiac chest pain

Noncardiac chest pain (NCCP) affects approximately 1 quarter of the adult population in the United States. The pathophysiology of the disorder remains to be fully elucidated. Identified underlying mechanisms for esophageal pain include gastroesophageal reflux disease (GERD), esophageal dysmotility, and visceral hypersensitivity. Aggressive antireflux treatment has been the main therapeutic strategy for GERD-related NCCP. NCCP patients with or without spastic esophageal motor disorders are responsive to pain modulators. The value of botulinum toxin injection, endoscopic treatment for GERD, and antireflux surgery in alleviating NCCP symptoms is limited.     

Comparison of central and intraesophageal factors between gastroesophageal reflux disease (GERD) patients and those with GERD‐related noncardiac chest pain

Gastroesophageal reflux disease (GERD) causes a wide range of symptoms. Some patients present with typical symptoms such as heartburn and regurgitation and others with atypical symptoms such as chest pain. The mechanism responsible for the varying clinical presentation of GERD is still not fully elucidated. The aim of this study was to prospectively evaluate differences in central and local intraesophageal factors between patients with typical GERD symptoms and those with noncardiac chest pain (NCCP). Patients presenting with typical and atypical symptoms suspicious of GERD underwent upper endoscopy and 24‐hour pH monitoring with four sensors, each positioned at a different esophageal level. All patients completed GERD symptom, Hospital Anxiety and Depression Scale, and Symptom Stress Rating questionnaires. From January 2006 to December 2009, 50 patients were recruited, 29 with typical symptoms, and 21 with NCCP. Patients with proven GERD and NCCP had higher proximal extension of acid during reflux episodes than patients with typical symptoms. They were found to be older, had a shorter history of symptom onset, worse anxiety scores, and more endoscopic findings compatible with gastritis. Proximal extension of acid during the reflux episodes in patients with GERD presenting with NCCP may play a role in symptom generation.     

Extraesophageal manifestations in gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) is a common condition that affects about 20-30% of the adult population, presenting with a broad spectrum of symptoms and varying degrees of severity and frequency. Other manifestations are being increasingly recognized: the so-called 'extraesophageal' manifestations, such as laryngitis, hoarseness, chronic cough, asthma, or non-cardiac chest pain. Epidemiological studies consistently demonstrate significant associations between pulmonary manifestations and GERD. Up to 50% of patients with an endoscopically proven esophagitis suffer from symptoms other than heartburn or acid regurgitation. However, the published estimates of extraesophageal disorders in patients with GERD vary widely, which may be a result of referral bias. The most effective initial approach in suspected reflux-related extraesophageal symptoms is empiric proton pump inhibitor (PPI) therapy. However, studies demonstrated that the advantage of long-term PPI treatment over placebo could have been overestimated.     

Utilization of wireless pH monitoring technologies: a summary of the proceedings from the Esophageal Diagnostic Working Group

Gastroesophageal reflux disease (GERD) can be difficult to diagnose – symptoms alone are often not enough, and thus, objective testing is often required. GERD is a manifestation of pathologic levels of reflux into the esophagus of acidic, nonacidic, and/or bilious gastric content. However, in our current evidence‐based knowledge approach, we only have reasonable outcome data in regards to acid reflux, as this particular type of refluxate predictably causes symptoms and mucosal damage, which improves with medical or surgical therapy. While there are data suggesting that nonacid reflux may be responsible for ongoing symptoms despite acid suppression in some patients, outcome data about this issue are limited. Therefore, this working group believes that it is essential to confirm the presence of acid reflux in patients with ‘refractory’ GERD symptoms or extraesophageal symptoms thought to be caused by gastroesophageal reflux before an escalation of antireflux therapy is considered. If patients do not have pathologic acid reflux off antisecretory therapy, they are unlikely to have clinically significant nonacid or bile reflux. Patients who do not have pathologic acid gastroesophageal reflux parameters on ambulatory pH monitoring then: (i) could attempt to discontinue antisecretory medications like proton pump inhibitors and H2‐receptor antagonists (which are expensive and which carry risks – i.e. C. diff, etc.); (ii) may undergo further evaluation for other causes of their esophageal symptoms (e.g. functional heartburn or chest pain, eosinophilic esophagitis, gastroparesis, achalasia, other esophageal motor disorders); and (iii) can be referred to an ear, nose, and throat/pulmonary/allergy physician for assessment of non‐GERD causes of their extraesophageal symptoms.     

The proton pump inhibitor (PPI) test in GERD: does it still have a role?

The proton pump inhibitor (PPI) test is a short course of high-dose PPI, used to diagnose gastroesophageal reflux disease (GERD). This diagnostic strategy is commonly used globally, primarily because of its availability, simplicity, and high sensitivity. The PPI test has been proven to be a sensitive tool for diagnosing GERD in noncardiac chest pain patients and in preliminary trials in extraesophageal manifestations of GERD. Several recent meta-analyses reevaluated the value of the PPI test in patients with classic GERD-related symptoms and noncardiac chest pain. Although the results were conflicting, the PPI test remains a popular tool for determining the presence of GERD. Attempts to challenge the PPI test without offering attractive alternatives are unlikely to alter clinical practice.     

小肠细菌过度生长和胃食管反流病

胃食管反流病（GERD）患者多伴有其它功能性胃肠病症状。特别是与肠易激综合征（IBS）和小肠细菌过度生长（SIBO）的症状存在高度的重叠性。胃食管反流病患者中小肠细菌过度生长的发病率明显高于对照组,反之,小肠细菌过度生长患者中胃食管反流病的发病率也明显高于对照组。小肠细菌过度生长的一个明显特点是在小肠过度增生的细菌酵解碳水化合物产生氢气和二氧化碳,在有产甲烷菌存在的情况下还会产生甲烷。过量的气体会通过三种机制导致胃食管反流：1.导致腹胀和腹内压增加,压迫胃内容物逆行进入食管;2.部分气体在压力作用下上行,通过胃和食管溢出;3.引起反射性下食管括约肌松弛。了解胃食管反流病和小肠细菌过度生长的关系有助于为寻找胃食管反流病的致病原因,制定合理的治疗胃食管反流病提供新的方向。     

Ineffective esophageal motility: the most common motility abnormality in patients with GERD-associated respiratory symptoms

OBJECTIVE: The association of gastroesophageal reflux disease (GERD) and respiratory symptoms is well known. The coexistence of ineffective esophageal motility (IEM, low-amplitude [< 30 mm Hg] or nontransmitted contractions in > or = 30% of 10 wet swallows in the distal esophagus) in patients with GERD has recently been demonstrated. Our aim was to determine the prevalence of IEM in patients with GERD-associated respiratory symptoms. METHODS: Manometry and pH studies of 98 consecutive patients with respiratory symptoms and abnormal reflux shown by pH-metry were reviewed. Symptoms were chronic cough (n = 43), asthma (n = 13), and laryngitis (n = 42). Sixty-six patients with heartburn with no extraesophageal manifestations were used as a control group. Total esophageal acid clearance (EAC) time was calculated for each patient. RESULTS: IEM was the most common motility abnormality seen in all groups of GERD patients. It was seen significantly more often in patients with chronic cough (41%) (p = 0.003) or asthma (53%) (p = 0.01), and numerically more often in patients with laryngitis (31%) than in patients with heartburn (19%). Diffuse esophageal spasm and nutcracker esophagus were rarely seen. Incidence of hypertensive or hypotensive lower esophageal sphincter was similar across all groups. The total EAC time was longer (median: 1.51 min/episode) (p = 0.01) in patients with GERD-associated respiratory symptoms than in patients with heartburn (median: 0.72 min/episode). CONCLUSIONS: IEM is the most prevalent motility abnormality in patients with GERD-associated respiratory symptoms. Coexistence of IEM with GER may place patients at high risk for respiratory symptoms due to the associated delayed esophageal acid clearance seen with this motility abnormality.     

Functional heartburn, nonerosive reflux disease, and reflux esophagitis are all distinct conditions—A debate: Con

Opinion statement Gastroesophageal reflux disease (GERD) is currently defined as a condition that develops when the reflux of stomach contents causes recurrent symptoms and/or complications. The clinical presentation of GERD has been recognized to be much broader than before, when the typical symptoms of heartburn and acid regurgitation were considered as the main clinical presentation. However, now it is recognized that GERD can present with various other mainly extraesophageal symptoms, abdominal pain, and even sleep disturbance. Moreover, there is an important overlap with functional gastrointestinal disorders such as functional dyspepsia and irritable bowel syndrome. The morphologic spectrum of esophageal involvement in GERD encompasses erosive (erosive reflux disease [ERD]), Barrett’s esophagus (BE), and nonerosive reflux disease (NERD). However, there is still no consensus on whether GERD represents one disease that can progress from NERD to ERD and BE, or whether it is a spectrum of different conditions with its own clinical, pathophysiologic, and endoscopic characteristics. Recently published data suggest that mild erosive esophagitis behaves in a way similar to NERD and that there is considerable movement between these categories. But follow-up data also show that after 2 years, some patients with NERD or GERD Los Angeles A or B went on to develop severe GERD or even BE. A practical approach is to categorize patients with reflux symptoms into “functional heartburn” (ie, reflux symptoms and negative endoscopy and absent objective evidence of acid reflux into the esophagus), NERD (negative endoscopy but positive documentation of acid reflux into the esophagus), and ERD (erosions documented endoscopically). In conclusion, it appears that GERD is a disease with a spectrum of clinical and endoscopic manifestations, with characteristics that make it a continuum and not a categorical condition with separate entities. It is difficult to clearly delineate the spectrum of GERD based on the clinical, endoscopic, and pathophysiologic characteristics, but therapeutic trials and follow-up studies suggest that GERD is not composed of different conditions.