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.     

The clinical characteristics of gastroesophageal reflux disease in patients with laryngeal symptoms who are referred to gastroenterology

The prevalence of gastroesophageal reflux disease (GERD) has increased recently in Asia‐Pacific countries. However, little is known about its prevalence and clinical characteristics in GERD patients with atypical symptoms in Asia. The aim of this study was to investigate the clinical characteristics of GERD in patients who had laryngeal symptoms in Korea. Data were gathered retrospectively from patients who presented with atypical symptoms, such as throat discomfort, globus pharyngeus, hoarseness, and chronic cough. They underwent a 24‐hour ambulatory intraesophageal pH monitoring and filled in a validated reflux questionnaire. Overall, 128 patients (36 men and 92 women) with laryngeal symptoms were included. Of these 128, 43 patients (34%) had erosive esophagitis or pathological reflux from 24‐hour ambulatory pH monitoring, and 24 (19%) had a positive Bernstein test or positive symptom index from 24‐hour pH monitoring. Sixty‐one patients (48%) had no evidence of reflux esophagitis on upper endoscopy and pathological acid reflux on 24‐hour pH monitoring. Fifty‐six patients (44%) had weekly heartburn or regurgitation. Typical symptoms and dyspepsia were significantly more common in patients with GERD who had laryngeal symptoms than non‐GERD. Fifty‐two percent of patients had laryngeal symptoms that were associated with GERD. The presence of typical reflux symptoms and dyspepsia are risk factors for GERD in patients who present with laryngeal symptoms.     

Gastroesophageal reflux disease: extraesophageal manifestations and therapy

Gastroesophageal reflux disease (GERD) can present with both typical symptoms such as heartburn and regurgitation as well as atypical symptoms. These symptoms may include chest pain, asthma, chronic cough, hoarseness, otitis media, atypical loss of dental enamel, idiopathic pulmonary fibrosis, recurrent pneumonia, chronic bronchitis and even sudden infant death. The diagnosis of GERD in these patients can often present a challenge and usually requires a combination of selected testing and therapeutic trials. Acid suppression by using proton pump inhibitors remains the treatment of choice in GERD, but some patients will also respond well to antireflux surgery. This article addresses the presentations, diagnostic challenges, and therapeutic opportunities in GERD patients with atypical presentations.     

Gastroösophageale Refluxerkrankung

Gastroesophageal reflux disease (GERD) is present when the passage of gastric contents into the esophagus causes symptoms or mucosal damage. Potent suppression of gastric acid secretion with proton pump inhibitors (PPIs) is an effective and safe treatment for many patients with this condition; however, acid suppression has not solved the problem of GERD. The relationship between reflux symptoms, endoscopic findings, and esophageal acid exposure is not straightforward. Some patients fail to respond to PPIs; at endoscopy, the esophagus is often normal, and pH studies may not reveal the cause of symptoms. It is clear that, although gastric acid secretion can be suppressed, we are far less successful at managing reflux itself. Apart from ?typical” reflux symptoms, other complaints, including dysphagia, noncardiac chest pain, and chronic cough, have been linked to GERD, but it can be difficult to identify those patients who will benefit from antireflux treatment. This is relevant because the risk of esophageal adenocarcinoma is elevated in patients with reflux symptoms, in particular those with Barrett’s esophagus.     

Diagnostic approach to gastro-oesophageal reflux disease

It is neither practical nor necessary to embark on a diagnostic evaluation of every patient with classic symptoms of gastroesophageal reflux disease (GERD). In most cases a well-taken history is usually sufficient to confirm the diagnosis of GERD and begin therapy. However, some patients may present with atypical symptoms; and many with classic symptoms are refractory to standard medical therapy. In these cases one must rely on diagnostic studies to confirm that abnormal acid reflux is present and potentially responsible for the symptoms in question. Modern technology has given us many different modalities to quantify esophageal acid exposure and determine whether symptoms are correlated to reflux events. Unfortunately, these studies are not perfect and the work-up of refractory patients typically requires more than one test. The goal of the following review will be to summarize the currently available techniques for diagnosis of GERD and also discuss the possible impact of new techniques, such as intraluminal impedance monitoring and wireless ambulatory pH monitoring.     

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.     

Pathophysiology, diagnosis and treatment of non-erosive reflux disease (NERD)

Up to 70% of patients with typical symptoms of gastroesophageal reflux disease (GERD) have neither definite endoscopic oesophageal breaks nor Barrett's oesophagus at upper endoscopy. These patients suffer from non-erosive reflux disease (NERD), also termed endoscopy-negative reflux disease or symptomatic GERD. NERD patients appear as a heterogeneous population with multiple and substantially different mechanisms implicated in the genesis of symptoms. In fact, patients with NERD may be divided into 3 groups on the basis of 24-hour pH monitoring: 1) patients with an abnormal acid exposure time (AET); 2) patients who demonstrate a normal AET, but in whom symptoms and reflux events are significantly correlated (hypersensitive oesophagus) and 3) patients with typical reflux symptoms but in whom all parameters of the pH study are normal. There is no gold standard for the diagnosis of NERD but a well-taken history can be, usually, sufficient to confirm the diagnosis and begin therapy. Thus, the more sensitive tool for the diagnosis of NERD is proton pump-inhibitor (PPI) test. The aims of NERD treatment are: symptoms relieve, restore quality of life and maintain clinical remission. Proton pump-inhibitors (PPIs) in full doses represent the treatment of choice of NERD patients, even if overall, clinical trials showed a lower efficacy in symptoms control when compared to patients with erosive oesophagitis. Patients with NERD often need long-term therapy for symptoms control. 'On demand' PPI therapy has been considered as the most cost-effective strategy for the long-term treatment of NERD. In conclusion, many data indicate that NERD is a disorder in its own right that shares symptoms with other GERD groups. However further studies are needed to better define the natural history and improve the treatment of this disorder.     

Gastroesophageal reflux disease

Opinion Statement Prior to the advent of proton pump inhibitors, internists recommended antireflux surgery primarily for patients whose gastroesophageal reflux disease (GERD) failed to respond to medical therapy. Although many physicians still cling to the notion that antireflux surgery is a procedure best reserved for “medical failures,” today this position is inappropriate. Modern medical treatments for GERD are extraordinarily effective in healing reflux esophagitis. It is uncommon to encounter patients with heartburn or esophagitis due to GERD who do not respond to aggressive antisecretory therapy. Indeed, the very diagnosis of GERD must be questioned for patients whose esophageal signs and symptoms are unaffected by the administration of proton pump inhibitors in high dosages. In the large majority of these so-called refractory patients, protracted esophageal pH monitoring reveals good control of acid reflux by the proton pump inhibitors. This finding indicates that the persistent symptoms usually are not due to acid reflux, but to other problems such as functional bowel disorders. Medical treatment fails in such patients because the diagnosis is mistaken, not because the drugs fail to control acid reflux. Modern antireflux surgery also is highly effective for controlling acid reflux, but fundoplication will not be effective for relieving symptoms in patients whose symptoms are not reflux-induced. Therefore, many patients deemed failures of modern medical therapy would be surgical failures as well. Antireflux surgery is an excellent treatment option for patients with documented GERD who respond well to medical therapy, but who wish to avoid the expense, inconvenience, and theoretical risks associated with lifelong medical treatment. Ironically, surgical therapy for GERD today is best reserved for patients who are medical successes.     

Supraesophageal manifestations of gastroesophageal reflux disease.

An increasing amount of evidence indicates that gastroesophageal reflux disease (GERD) is a contributing factor to hoarseness, throat clearing, throat discomfort, chronic cough, and shortness of breath. The association between GERD and these supraesophageal symptoms may be elusive. Heartburn and regurgitation are absent in more than 50% of patients. Acid reflux should be considered if signs of GERD are present, symptoms are unexplained, or symptoms are refractory to therapy. The diagnosis of GERD may be unclear, despite a careful history and initial evaluation. A high index of suspicion is required to make the diagnosis. An empiric trial of antireflux therapy is appropriate when GERD is suspected. Multiprobe ambulatory pH monitoring is currently the diagnostic test of choice, but the level of sensitivity and specificity for supraesophageal manifestations of GERD is uncertain. Response to antireflux therapy is less predictable than typical GERD. More intensive acid suppression and longer treatment duration are usually required.     

REVIEW: Ambulatory Esophageal pH Monitoring: Technique, Interpretations, and Clinical Indications

Gastroesophageal reflux disease (GERD) is the most common esophageal disorder and perhaps among the most prevalent conditions seen in the primary care setting. The clinical manifestations of GERD, typical or atypical, such as noncardiac chest pain, respiratory or ear, nose, and throat symptoms, result from the reflux of gastric contents into the esophagus. Thus the clinical spectrum is wide and requires accurate diagnosis. Ambulatory 24-hr esophageal pH monitoring is not useful in all patients suspected to have GERD. This review describes the technique of ambulatory 24-hr esophageal pH monitoring, the interpretation of findings, and clinical applications of this test.     

Use of pH-impedance testing to evaluate patients with suspected extraesophageal manifestations of gastroesophageal reflux disease

GOALS: To report the use of pH-impedance testing in evaluating patients with suspected gastroesophageal reflux disease (GERD) with atypical symptoms. BACKGROUND: Although the role of acid reflux in causing atypical GERD symptoms is generally accepted, the role, if any, of nonacid reflux is controversial, largely because until recently it has not been possible to detect nonacid reflux. The advent of intraluminal combined pH impedance testing (MII-pH), to detect nonacid reflux has heightened interest in its possible contribution to atypical symptoms. STUDY: Fifty consecutive patients referred for MII-pH testing to evaluate the cause of atypical symptoms presumed due to GERD were evaluated. The symptoms were either refractory to acid inhibition therapy or so atypical that further work up was desired by the referring physician. Patients underwent MII-pH testing to determine whether reflux was present, and, if so, if it was due to acid, nonacid, or gas. RESULTS: Only 16%, 22%, and 2% patients were found to have symptoms due to acid reflux, nonacid reflux, or both, respectively. Ten percent of these patients had gas reflux. MII-pH testing was useful in redirecting the management of patients who did not have reflux as the cause of their symptoms. CONCLUSIONS: MII-pH testing is useful in determining whether gastroesophageal reflux is present in patients with atypical symptoms that have not responded to proton pump inhibitor therapy. It also distinguishes between reflux due to acid, nonacid, and gas, with consequences for management.     

Characteristics and clinical relevance of proximal esophageal pH monitoring

OBJECTIVE: It is well established that various ENT disorders and symptoms may be a manifestation of gastroesophageal reflux disease (GERD). Measuring proximal esophageal acid exposure might be useful in the evaluation of patients with suspected reflux-related ENT manifestations, but the limited available data are conflicting. The aim of the present study was to study the determinants of proximal esophageal acid exposure (PR) and to evaluate the clinical usefulness of ambulatory proximal pH monitoring. METHODS: Twenty healthy controls and 346 patients with suspected reflux disease underwent typical and atypical GERD symptom assessment, endoscopy, esophageal manometry and ambulatory combined dual esophageal pH, and Bilitec duodeno-gastro-esophageal reflux exposure (DGER) monitoring. The presence of pathological PR and its relation to symptom pattern and distal esophageal acid exposure (DR) and DGER exposure were analyzed. RESULTS: Fifty-seven patients (16%) had pathological PR. Demographic characteristics, symptom pattern, and manometric findings did not differ in patients with normal or pathological PR. Patients with pathological PR had significantly higher DR and DGER. The multivariate analysis identified only pathological DR as an independent risk factor for the presence of pathological PR (odds ratio 4.515, 95% CI 2.48-8.23, p < 0.0001). Only 20 patients (6%) had pathological proximal reflux without pathological distal acid reflux. CONCLUSION: The findings of the present article do not support routine proximal esophageal pH monitoring as a clinical tool: PR does not differentiate patients with typical or atypical GERD manifestations and depends mainly on DR.     

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.     

The proton pump inhibitor test and the diagnosis of gastroesophageal reflux disease

There continues to be significant controversy related to diagnostic testing for gastroesophageal reflux disease (GERD). Symptoms of GERD may be associated with physiologic esophageal acid exposure measured by intraesophageal pH monitoring or pH-impedance monitoring, and a significant percentage of patients with abnormal esophageal acid (or weak acid) exposure have no or minimal clinical symptoms of reflux. On the other hand, endoscopic lesions are only present in a minority of GERD patients. In clinical practice, presumptive diagnosis of GERD is reasonably assumed by the substantial reduction or elimination of suspected reflux symptoms during the therapeutic trial of acid reduction therapy, the so-called proton pump inhibitor (PPI) test. We aimed to assess the optimal cutoff value and duration of this test in GERD patients with and without esophagitis. We conducted a prospective study of 544 patients, endoscopically investigated and treated for 2 weeks with PPIs at double dose, and for an additional 3 months at standard dose. The status of the patient at the end of the study was used as an independent diagnostic standard. We found esophagitis present in 55.8% and absent in 44.2% of patients (corresponding to a diagnosis of nonerosive reflux disease [NERD]). The test was positive in 89.7–97.8% of the patients according to the cutoff or duration of the test used. The sensitivity of the PPI test was excellent, ranging from 95.5 to 98.8%, whereas the specificity was poor, not exceeding 36.3%. Erosive esophagitis patients responded more favorably to the PPI test and subsequent PPI therapy compared with NERD patients. In conclusion, the PPI test is a sensitive but less specific test. Its optimal duration is 1 week, and the optimal cutoff value is a decrease of heartburn score of more than 75%. NERD patients respond less satisfactorily to PPIs, even when functional heartburn patients are excluded and only ‘true’ NERD patients are considered.     

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.     

Reflux-induced laryngitis (laryngopharyngeal reflux)

Opinion statement Gastroesophageal reflux disease (GERD) has been increasingly associated with ear, nose, and throat (ENT) signs and symptoms. This condition, often referred to as laryngopharyngeal reflux (LPR) has become increasingly prevalent. However, the cause and effect relationship between GERD and laryngeal signs or symptoms is far from established. Many patients diagnosed initially with GERD as the cause of laryngeal signs do not symptomatically or laryngoscopically respond to aggressive acid suppression and do not have abnormal esophageal acid exposure by pH monitoring. This has resulted in frustration on the part of both gastroenterologists and ENT physicians and confusion on the part of patients. The current recommendations for the management of LPR patients call for initial empiric therapy with twice daily proton-pump inhibitors (PPIs) for 2 to 4 months. In those unresponsive to such therapy, diagnostic testing with prolonged pH monitoring may be indicated. However, in the majority of such patients, the reason for lack of response to PPI therapy may be irritation of the larynx by causes other than GERD. Surgical fundoplication in this group of patients has lower efficacy than in those with typical symptoms of GERD and is reserved for those with improvement on acid-suppressive therapy.     

Strategies for the diagnosis of gastro-esophageal reflux disease

With patients referring symptoms of gastro-esophageal reflux disease (GERD), 2 initial approaches should be considered: an empiric therapy (treat and test strategy) or a strategy based on instrumental investigations (test and treat). In most cases a well-taken history is usually sufficient to confirm the diagnosis of GERD and initiate treatment. However, some patients may present with 'atypical' symptoms, classic symptoms refractory to standard medical therapy or 'alarm' symptoms. In these cases, one must rely on diagnostic studies to document the presence of mucosal damage related or not to GERD and/or quantify the degree of gastro-esophageal reflux. The most relevant test to diagnose esophageal injury and complications of GERD is represented by upper gastrointestinal endoscopy, while the most diffuse procedure to quantify the degree of acid reflux is pH monitoring. Further studies are required to delineate the appropriate use and the possible impact of new techniques, such as intraluminal impedance monitoring, Bilitec and, wireless ambulatory pH monitoring in the management of GERD.     

The diagnostic value of GerdQ in subjects with atypical symptoms of gastro-esophageal reflux disease

Background: Symptoms are essential in the clinical diagnosis of gastro-esophageal reflux disease (GERD). Questionnaires such as GerdQ have been developed as diagnostic aids. GerdQ has been thoroughly validated in well-characterized GERD patients, but has not yet been fully evaluated in a population that includes subjects with atypical symptoms.

Aim: To evaluate GerdQ in a population with typical and/or atypical symptoms of GERD, defined by 24-h pH monitoring. The secondary aim was to investigate the outcome of GerdQ depending on the response to proton pump inhibitor (PPI) treatment.

Methods: The study included 646 subjects referred for 24-h pH monitoring due to a clinical suspicion of GERD. All subjects completed GerdQ before performing a 24-h pH monitoring.

Results: In total, 377 (58%) subjects were diagnosed with GERD based on symptoms and 24-h pH monitoring (GERD_pH). Of these, 46% had atypical main symptoms. Overall, GerdQ (at cut-off 8) predicted GERD_pH with a sensitivity and specificity of 62% and 74%, respectively. A high specificity but poor sensitivity for diagnosis of GERD_pH was found for atypical main symptoms such as cough, dysphagia and globus. GerdQ had a relatively high sensitivity and specificity in predicting PPI response and a PPV of 99% at cut-off 8.

Conclusions: GerdQ has a diagnostic value in an unselected population presenting with typical and/or atypical symptoms of GERD, but a low sensitivity for diagnosis of GERD_pH was found in subjects with predominant symptoms such as cough, dysphagia and globus.     

Esophageal impedance–pH monitoring

Classical techniques like endoscopy and esophageal pH-metry are routinely used to study patients with symptoms related to gastroesophageal reflux disease (GERD). Although these techniques have been useful over the years both for diagnosis and therapeutic guidance, there are still many patients with typical or atypical GERD symptoms with normal endoscopy and pH-metry that do not respond adequately to antisecretory therapy. Ambulatory esophageal impedance-pH monitoring is a new technique that can be used to evaluate all types of gastroesophageal reflux, achieving higher rates of sensitivity and specificity than standard techniques. This review describes esophageal impedance-pH monitoring, summarizing the current literature on validation studies and clinical application.     

Extraesophageal manifestations of GERD

The association between gastroesophageal reflux disease (GERD) and extraesophageal disease is often referred to as extraesophageal reflux (EER). This article reviews EER, discussing epidemiology, pathogenesis, diagnosis, and treatment with a focus on the most studied and convincing EER disorders-asthma, cough, and laryngitis. Although EER comprises a heterogeneous group of disorders, some general characterizations can be made, as follows. First, although GERD's association with extraesophageal diseases is well-established, definitive evidence of causation has been more elusive, rendering epidemiological data scarce. Secondly, regarding the pathogenesis of EER, 2 basic models have been proposed: direct injury to extraesophageal tissue by acid and pepsin exposure or injury mediated through an esophageal reflex mechanism. Third, because heartburn and regurgitation are often absent in patients with EER, GERD may not be suspected. Even when GERD is suspected, the diagnosis may be difficult to confirm. Although endoscopy and barium esophagram remain important tools for detecting esophageal complications, they may fail to establish the presence of GERD. Even when GERD is diagnosed by endoscopy or barium esophagram, causation between GERD and extraesophageal symptoms cannot be determined. Esophageal pH is the most sensitive tool for detecting GERD, and it plays an important role in EER. However, even pH testing cannot establish GERD's causative relationship to extraesophageal symptoms. In this regard, effective treatment of GERD resulting in significant improvement or remission of the extraesophageal symptoms provides the best evidence for GERD's pathogenic role. Finally, EER generally requires more prolonged and aggressive antisecretory therapy than typical GERD requires.