Manifestations Of Gastroesophageal Reflux Disease Research Articles

Nocturnal Gastroesophageal Reflux: Assessment and Clinical Implications

Nocturnal Gastroesophageal Reflux: Assessment and Clinical Implications

Dilated intercellular spaces and chronic cough as an extra-oesophageal manifestation of gastrooesophageal reflux disease

Dilated intercellular spaces and chronic cough as an extra-oesophageal manifestation of gastrooesophageal reflux disease

Randomised clinical trial: high-dose acid suppression for chronic cough - a double-blind, placebo-controlled study

Cough may be a manifestation of gastro-oesophageal reflux disease (GERD). The utility of acid suppression in GERD-related cough is uncertain. To assess the impact of high-dose acid suppression with proton pump inhibitors (PPI) on chronic cough in subjects with rare or no heartburn. Subjects were nonsmokers without history of asthma, with chronic cough for >8 weeks. All subjects underwent a baseline 24-h pH/impedance study, methacholine challenge test and laryngoscopy. Subjects were randomised to either 40 mg of esomeprazole twice daily or placebo for 12 weeks. The primary outcome measure was the Cough-Specific Quality of Life Questionnaire (CQLQ). Secondary outcomes were response on Fisman Cough Severity/Frequency scores and change in laryngeal findings. Forty subjects were randomised (22 PPI, 18 placebo) and completed the study. There was no difference between PPI and placebo in CQLQ (mean improvement 9.8 vs. 5.9 respectively, P = 0.3), or Fisman Cough Severity/Frequency scores. Proportion of patients who improved by >1 s.d. on the CQLQ was 27.8% (five of 18) and 31.8% (seven of 22) in the placebo and PPI groups respectively. In subjects with chronic cough and rare or no heartburn, high-dose proton pump inhibitor does not improve cough-related quality of life or symptoms.

Dilated intercellular spaces and chronic cough as an extra-oesophageal manifestation of gastrooesophageal reflux disease

Chronic cough is one of the extra-oesophageal manifestations of gastrooesophageal reflux disease (GORD). It is presumed to occur either directly by microaspiration of acidic gastric contents into the airway or indirectly by a reflex triggered by contact of acidic refluxates with the oesophageal epithelium in GORD. How contact of the oesophageal epithelium with acidic refluxates promotes sensitization for chronic cough is unknown, but like heartburn, which is a necessary accompaniment, it requires acid activation of nociceptors within the oesophageal mucosa. Dilated intercellular spaces within the oesophageal epithelium, a reflection of an increase in paracellular permeability, is a histopathologic feature of both erosive and non-erosive forms of GORD. Since it correlates with the symptom of heartburn, it is hypothesized herein that the increase in paracellular permeability to acid reflected by dilated intercellular spaces in oesophageal epithelium also serves as mediator of the signals that produce the reflex-induced sensitization for cough – a sensitization that can occur centrally within the medullary Nucleus Tractus Solitarius or peripherally within the tracheobronchial tree.

Patients with gastroesophageal reflux disease and respiratory manifestations do not present lung function disorders during cardiopulmonary exercise test

Gastroesophageal reflux disease (GERD) has been associated with a variety of pulmonary manifestations, but it is unclear if gastroesophageal reflux causes any abnormality in pulmonary function. Cardiopulmonary exercise test (CPET) is a specialized method that is used to evaluate respiratory function during exercise. The aim of this study was to reveal any abnormality of pulmonary function in patients with GERD and respiratory symptoms. We evaluated 34 patients with GERD (24 men and 10 women, aged 21-63) and extraesophageal respiratory symptoms (wheezing and/or cough) before therapy and after a 12-week treatment with double dose of omeprazole. No patient presented abnormal spirometry. CPET was performed in all the patients at baseline and after completion of the 12-week treatment. CPET parameters including VO(2) rest, VO(2) max, VCO(2) rest, VCO(2) max, O(2)-puls rest, O(2)-puls max, HR (heart rate) rest, HRmax, PETCO(2) rest, PETCO(2) max, and VE/VCO(2) slope were recorded pretreatment and posttreatment. Twenty-four patients (70.6%) had esophagitis (grade A-D), 16 patients had hiatal hernia (47.1%), and 13 patients (38.2%) tested positive for Helicobacter pylori. All of the patients completed the CPET. No one presented shortness of breath or respiratory symptoms. CPET parameters were within normal limits in all of the patients. Twenty-eight patients were reevaluated. No improvement in any CPET parameter posttreatment was observed despite remission of esophageal and extraesophageal respiratory symptoms in all patients. No statistically significant difference was observed pretreatment and posttreatment between the patients older and younger than 40 years, smokers and nonsmokers, Hp(+) and Hp(-) patients, and those with and without hiatal hernia and esophagitis. The patients with GERD and respiratory manifestations and normal spirometry present no pulmonary dysfunction during CPET. No alterations in CPET values posttreatment or differences in CPET values according to age, smoking, Hp status, presence of esophagitis, or hiatal hernia were observed.

Halimeter ppb Levels as the Predictor of Erosive Gastroesophageal Reflux Disease

In a previous issue published in Gut and Liver, we found that erosive changes in the esophagogastroduodenal mucosa were strongly correlated with increased levels of volatile sulfur-containing compounds (VSC), suggesting that halitosis could be a symptom reflecting the erosive status of the upper gut mucosa. Together with other studies showing a possible association between halitosis and gastroesophageal reflux disease (GERD), under the premise that halitosis could be one of extraesophageal manifestations of erosive GERD (ERD), we investigated the significance of Halimeter ppb levels on ERD compared to non-erosive gastroesophageal reflux disease (NERD). Subjects were assigned to the NERD group if there was no evidence of esophageal erosive changes on endoscopy, despite reflux symptoms, and to the ERD group if they had GERD A, B, C, or D (according to the Los Angeles classification). The VSC levels were measured in all patients with either a Halimeter (before endoscopy) or by gas chromatography of the gastric juices aspirated during endoscopy. The VSC level differed significantly between the NERD and ERD groups (p<0.0001), suggesting that this can be used to discriminate between NERD and ERD. However, the VSC level did not differ significantly with the severity of GERD. Even though hiatal hernia and a body mass index of >24 kg/m(2) was significantly associated with ERD, there was no correlation with Halimeter ppb levels. Minimal-change lesions exhibited the highest VSC levels, signifying that minimal change lesions can be classified as ERD based on our finding that halimeter ppb levels were descrimitive of erosive change. Erosive changes in the esophageal mucosa were strongly associated with VSC levels, supporting the hypothesis that halitosis can be a potential biomarker for the discrimination between ERD and NERD, reflecting the presence of erosive change in the lower esophagogastric junction.

Relationship between dental erosion and respiratory symptoms in patients with gastro-oesophageal reflux disease

Objectives Both dental erosion and respiratory symptoms are extra-oesophageal manifestations of gastro-oesophageal reflux disease (GERD). The aim of this study was to determine whether dental erosion was correlated with respiratory symptoms in GERD patients. Methods 88 GERD patients were recruited and assigned to three groups mainly according to the frequency of respiratory symptoms: Group I: never; Group II: occasional (1–2 days a week or less); Group III: frequent (3–5 days a week or more). All patients underwent medical evaluations, including medical history, questionnaire answering and alimentary tract examinations. Dental examinations were carried out on these patients and 36 healthy controls. Dental erosions were measured by modified method of Smith and Knight Tooth Wear Index (TWI). Location and severity of dental erosion were recorded. Results The prevalence of dental erosion in Group III (64.52%) was higher ( p < 0.05) than that in Groups I (36.67%) and II (44.44%). GERD patients were presented with dental erosion with TWI scores ranging from 1 to 4. Though proportion of dental erosion with Score 2 (7/20) in Group III was higher than that in Group I (2/11) and Group II (3/12), there was no statistical significance in the proportions of erosion scores among three patient groups. Correlation coefficient between airway symptoms and scores of dental erosion was 0.231 ( p < 0.05). Palatal erosion of upper incisor was seen in 8 persons (72.7%) in Group I, 9 persons (75%) in Group II and 16 persons (80%) in Group III ( p > 0.05). Labial erosion of upper incisors was found in 1 person in Groups I and II respectively and 4 persons in Group III. All patients with labial erosion on upper incisors had palatal erosion, except 1 patient in Group III. Conclusions In GERD patients, dental erosions are more prevalent in patients with frequent respiratory symptoms than those in patients with occasional and without respiratory symptoms. Palatal erosion of upper incisor is the main manifestation in patients. Acid reflux is the main causative factor of dental erosion in GERD patients with airway symptoms.

Reflux Esophagitis and the Risk of Stroke in Young Adults

Reflux esophagitis (RE) is the most common manifestation of gastro-esophageal reflux disease with esophageal injury. To the best of our knowledge, there has been no specific study to evaluate the risk of stroke after diagnosis of RE in young adults. This study aims to evaluate the risk of stroke among RE patients aged 18 to 50 years during a 1-year period after diagnosis of RE compared to a cohort of non-RE patients during the same period. This study used the Taiwan Longitudinal Health Insurance Database 2005. A total of 2340 RE patients were included as the study cohort and 11 700 non-RE patients were included as the comparison cohort. Each patient was individually tracked for 1 year from the index ambulatory visit to identify those in whom stroke developed. Out of the sample of 14 040 patients, 78 patients (0.56%) had strokes develop during the 1-year follow-up period: 22 from the study cohort (0.94% of the RE patients) and 56 from the comparison cohort (0.48% of patients without RE). Patients with RE were 1.68-times more likely to have strokes develop (95% confidence interval, 1.03-2.76) than patients in the comparison cohort during the follow-up period after adjusting for patients' medical comorbidities, such as hypertension, diabetes, coronary heart disease, renal disease, heart failure, and hyperlipidemia, as well as their demographic differences, such as the level of urbanization of their communities, monthly income, and geographical location. We conclude that RE is associated with an increased risk of subsequent stroke in young adults.

Extraesophageal manifestations of gastroesophageal reflux disease: real or imagined?

Extraesophageal reflux disease is a common clinical presentation to gastroenterology as well as ear, nose and throat, allergy, and asthma clinics. The diagnosis and management of this condition is challenging. We review the current dilemma in this area and discuss the latest studies which help guide our therapies for patients with suspected extraesophageal reflux. Diagnostic approach to patients with extraesophageal reflux disease involved the use of insensitive tools, which have hampered the ability to correctly identify patients at risk. Empiric trial using proton pump inhibitors is still the recommended initial approach to those suspected of having reflux as the cause for extraesophageal symptoms such as asthma, chronic cough, or laryngitis. Diagnostic testing should be reserved to those unresponsive to therapy. Most recent studies suggest that ambulatory impedance/pH monitoring performed on therapy may be most likely to help exclude reflux as the cause for persistent symptoms. Recent randomized placebo-controlled studies on chronic laryngitis, cough, and asthma have been disappointing in showing benefit of acid suppressive therapy. Gastroduodenal reflux may cause symptoms such as chronic cough, asthma, or laryngitis. However, we are currently limited in our diagnostic ability to identify the subgroup of patients who might respond to acid suppressive therapy. Impedance/pH monitoring may be a step in the right direction; however, outcome studies are needed to better understand the role of acid or nonacid reflux in patients with extraesophageal symptoms.

Persistent Reflux Symptoms in the Proton Pump Inhibitor Era: The Changing Face of Gastroesophageal Reflux Disease

Given the widespread use of potent acid suppressive therapies and primary caregivers’ increasing comfort with prescribing these medications at high doses, the patient population presenting to gastroenterologists for symptoms of gastroesophageal reflux disease (GERD) has changed. Whereas previous consultation often revolved around the control of erosive disease and other mucosal manifestations of GERD, and terminated with the prescription of proton pump inhibitor (PPI) therapy, gastroenterologists often now only enter the scene after failure of PPI therapy, for symptoms either resistant or only partially responsive to these medications. Because of the high proportion of subjects with esophagitis who are healed with PPI, 1,2 upper endoscopy of such individuals is low yield, 3 with only a small minority demonstrating erosive disease. The care of such patients is challenging. High-quality evidence supporting useful diagnostic testing or alternative effective therapies is largely lacking. However, the number of subjects with GERD symptoms incompletely or nonresponsive to PPI therapies is high, and their utilization of healthcare resources is substantial. The purpose of this mini-review is to examine the definition and epidemiology of esophageal GERD symptoms incompletely responsive to PPI therapy, the potential pathophysiologic mechanisms behind these symptoms, the differential diagnosis and evaluation of such patients, and current and developing therapeutic options.

W1072 A Pilot Study Evaluating the Role of Combined Impedance-pH Monitoring in the Evaluation of Asian Patients With Suspected Supra-Esophageal Manifestations of Gastro-Esophageal Reflux Disease (GERD): Establishing the Presence of Acid and Non-Acid Reflux (NAR)

W1072 A Pilot Study Evaluating the Role of Combined Impedance-pH Monitoring in the Evaluation of Asian Patients With Suspected Supra-Esophageal Manifestations of Gastro-Esophageal Reflux Disease (GERD): Establishing the Presence of Acid and Non-Acid Reflux (NAR)

T1127 A Comparison of Acid and Non-Acid Reflux in the Evaluation of Patients With Typical Versus Atypical Manifestations of Gastroesophageal Reflux Disease: Results From an Asian Cohort

T1127 A Comparison of Acid and Non-Acid Reflux in the Evaluation of Patients With Typical Versus Atypical Manifestations of Gastroesophageal Reflux Disease: Results From an Asian Cohort

The Overlap Between GERD and Functional Bowel Disorders - When East Meets Rome

The Overlap Between GERD and Functional Bowel Disorders - When East Meets Rome

Guidelines for the diagnosis and management of gastroesophageal reflux disease: an evidence-based consensus

Gastroesophageal reflux disease (GERD) is one of the most common disorders in medical practice. A number of guidelines and recommendations for the diagnosis and management of GERD have been published in different countries, but a Brazilian accepted directive by the standards of evidence-based medicine is still lacking. As such, the aim of the Brazilian GERD Consensus Group was to develop guidelines for the diagnosis and management of GERD, strictly using evidence-based medicine methodology that could be clinically used by primary care physicians and specialists and would encompass the needs of physicians, investigators, insurance and regulatory bodies. A total of 30 questions were proposed. Systematic literature reviews, which defined inclusion and/or exclusion criteria, were conducted to identify and grade the available evidence to support each statement. A total of 11,069 papers on GERD were selected, of which 6,474 addressed the diagnosis and 4,595, therapeutics. Regarding diagnosis, 51 met the requirements for the analysis of evidence-based medicine: 19 of them were classified as grade A and 32 as grade B. As for therapeutics, 158 met the evidence-based medicine criteria; 89 were classified as grade A and 69 as grade B. In the topic Diagnosis, answers supported by publications grade A and B were accepted. In the topic Treatment only publications grade A were accepted: answers supported by publications grade B were submitted to the voting by the Consensus Group. The present publication presents the most representative studies that responded to the proposed questions, followed by pertinent comments. Follow examples. In patients with atypical manifestations, the conventional esophageal pH-metry contributes little to the diagnosis of GERD. The sensitivity, however, increases with the use of double-channel pH-metry. In patients with atypical manifestations, the impedance-pH-metry substantially contributes to the diagnosis of GERD. The examination, however, is costly and scarcely available in our country. The evaluation of the histological signs of esophagitis increases the diagnostic probability of GERD; hence, the observation of the dimensions of the intercellular space of the esophageal mucosa increases the probability of diagnostic certainty and also allows the analysis of the therapeutic response. There is no difference in the clinical response to the treatment with PPI in two separate daily doses when compared to a single daily dose. In the long term (>1 year), the eradication of H. pylori in patients with GERD does not decrease the presence of symptoms or the high recurrence rates of the disease, although it decreases the histological signs of gastric inflammation. It seems very likely that there is no association between the eradication of the H. pylori and the manifestations of GERD. The presence of a hiatal hernia requires larger doses of proton-pump inhibitor for the clinical treatment. The presence of permanent migration from the esophagogastric junction and the hernia dimensions (>2 cm) are factors of worse prognosis in GERD. In this case, hiatal hernias associated to GERD, especially the fixed ones and larger than 2 cm, must be considered for surgical treatment. The outcomes of the laparoscopic fundoplication are adequate.

Pulmonary or otolaryngologic extraesophageal manifestations in patients with gastroesophageal reflux disease

The extraesophageal manifestations of gastroesophageal reflux disease that are similar to a heart attack or gastric diseases are well known, while those categorized as pulmonary or otolaryngological are less known and less studied. In this article, we introduce this less known aspect of gastroesophageal reflux.

Effect of pantoprazole in patients with chronic laryngitis and pharyngitis related to gastroesophageal reflux disease: clinical, proximal, and distal pH monitoring results

Few studies had evaluated the results of proton pump inhibitors on distal and proximal pH recording using a dual-channel probe. The aim of this study was to determine the clinical and pH-metric effect of treatment with pantoprazole 80 mg for 8 weeks in patients with ear, nose, and throat (ENT) manifestations of gastroesophageal reflux disease associated with pathological proximal acid exposure. We conducted a prospective open study. Patients included had to have chronic pharyngitis or laryngitis, and a pathological gastroesophagopharyngeal reflux. All patients received treatment with pantoprazole 80 mg daily for 8 weeks. One week after the end treatment, patients had a second ENT examination and a 24-hour pH monitoring using dual-channel probe. We included 33 patients (11 men, 22 women). A pathological distal acid reflux was found in 30 patients (91%). After treatment, the improvement of ENT symptoms was found in 51.5% of patients. Normalization of 24-hour proximal esophageal pH monitoring was observed in 22 patients (66%). After treatment, the overall distal acid exposure, the number of distal reflux events, and the number of reflux during more than 5 minutes were significantly decreased (respectively: 19.4% vs 7.2% [P < 0.0001], 62.7 vs 28.4 [P < 0.0001], and 10.4 vs 3.9 [P < 0.0001] ). Similarly, in proximal level, the same parameters were significantly decreased after treatment (respectively: 6.8% vs 1.6% [P < 0.0001], 32.6 vs 8.1 [P < 0.0001], and 3.4 vs 0.6 [P= 0.005] ). Treatment with pantoprazole reduced the frequency and severity of gastroesophagopharyngeal acid reflux in patients with chronic pharyngitis and laryngitis.

Systematic review: the effects of conservative and surgical treatment for obesity on gastro‐oesophageal reflux disease

Incidence rates of both obesity and gastro-oesophageal reflux disease (GERD) are increasing, particularly in the Western world. It has been suggested that GERD symptoms may be improved by weight reduction. To review the literature on the effect of various weight reducing modalities on manifestations of GERD in obese patients. A literature search was performed using PubMed, EMBASE and the Cochrane Library, combining the words obesity and gastro-oesophageal reflux with bariatric surgery, diet, lifestyle intervention and weight loss. With regard to diet/lifestyle intervention (conservative), four of seven studies reported an improvement of GERD. For Roux-en-Y gastric bypass, a positive effect on GERD was found in all studies, although this was mainly evaluated by questionnaires. In contrast, for vertical banded gastroplasty, no change or even an increase of GERD was noted, whereas the results for laparoscopic adjustable gastric banding were conflicting. Dietary and lifestyle intervention may improve GERD in obese patients; however, the most favourable effect is likely to be found after bariatric surgery, especially after Roux-en-Y gastric bypass. Future studies need to elucidate for which GERD patients laparoscopic adjustable gastric banding might have a beneficial effect and how they can be identified preoperatively.

Chronic Cough – About a Clinical Case …

Gastro-oesophageal reflux is the third most frequent cause of chronic cough. The diagnosis is not easy, especially when gastro-oesophageal reflux disease (GORD) has extra-oesophageal manifestations. The treatment is based on behavioural, pharmacological or surgical measures. The patient, aged 20 years, was a chronic smoker and since 2004 had a chronic cough. Therefore she had repeatedly been treated by several physicians with different antibiotics for respiratory infections. The family doctor in 2008 decided to investigate this cough. After investigation of the cardiorespiratory tract revealed no changes, the family doctor investigated the upper digestive tract. An endoscopy diagnosed gastro-oesophageal reflux. The patient was treated with pantoprazole 40 mg, with symptomatic relief. One important issue is that the patient went to see her family doctor instead of resorting to complementary consultations. It is also necessary to emphasize the need to think of the extra-oesophageal manifestations of GORD.

A Soon To Be Common Endoscopic Finding?

Purpose: Introduction: The long term complications of eosinophilic esophagitis(EoE) are still unknown. There have been reports of EoE with Barrett's esophagus (BE) but whether or not EoE is a pre-malignant condition is still unknown. Esophageal stricture formation can occur in both patients with GERD and EoE, but when stricture formation occurs in both settings it is difficult to discern which disease process caused the stricture. Case Presentation: A 62 year old Caucasian male with a past medical history of ankylosing spondylitis and hypertension presented to the emergency room with abrupt onset of midsternal pain and inability to control secretions after eating. An emergent esophagogastroduodenoscopy (EGD) was performed in which retained food debris was removed. Mucosal changes of concentric rings throughout the entire length of the visualized esophagus were noted, suspicious for EoE. Additionally, a significant stricture was found at endoscopic length 20-24 cm and a medium sized hiatal hernia. The gastroesophageal junction was difficult to visualize due to retained food debris. Pathology specimens of the mid-esophagus did confirm EoE. The patient was begun on fluticasone 220 mcg swallowed inhaler, 2 puffs bid. A repeat endoscopy was performed 4 weeks later in which the esophageal stricture underwent balloon dilatation. On repeat endoscopy, the patient was noted to have an irregular Z-line and the endoscopic appearance of BE near the gastroesophageal junction in addition to the mucosal changes of EoE. Biopsies of the distal esophagus did confirm BE. Discussion: This case illustrates two distinct disease processes occurring concomitantly. There are reports of both disease states occurring, but none with a stricture according to our literature search. Long term manifestations of gastroesophageal reflux disease (GERD) include esophageal stricture formation but it can not be said for certain if the stricture in the patient was from EoE or GERD. There have been no reports of an association with EoE and rheumatologic diseases such as ankylosing spondylitis. Conclusion: It is still unclear if aggressive surveillance in patients with EoE should be performed. Further insight is needed to discern if a patient's endoscopic findings such as a hiatal hernia or even esophageal strictures are risk factors for complications or malignancy from EoE. In light of the increased awareness for EoE, there will likely more cases reported of EoE and BE. There have been no reported cases of a patient with EoE, esophageal stricture and BE from our extensive literature search.

Quantification of Dental Erosions in Patients With GERD Using Optical Coherence Tomography Before and After Double-Blind, Randomized Treatment With Esomeprazole or Placebo

Dental erosion, the chemical dissolution of enamel without bacterial involvement, is a rarely reported manifestation of gastroesophageal reflux disease (GERD), as well as of recurrent vomiting and dietary habits. It leads to loss of tooth substance, hypersensitivity, functional impairment, and even tooth fracture. To date, dental erosions have been assessed using only very basic visual methods, and no evidence-based guidelines or studies exist regarding the prevention or treatment of GERD-related dental erosions. In this randomized, double-blind study, we used optical coherence tomography (OCT) to quantify dental tissue demineralization and enamel loss before and after 3 weeks of acid-suppressive treatment with esomeprazole 20 mg b.i.d. or placebo in 30 patients presenting to the Berne University Dental Clinic with advanced dental erosions and abnormal acid exposure by 24-h esophageal pH manometry (defined as >4% of the 24-h period with pH<4). Enamel thickness, reflectivity, and absorbance as measures of demineralization were quantified by OCT before and after therapy at identical localizations on teeth with most severe visible erosions as well as several other predefined changes in teeth. The mean+/-s.e.m. decrease of enamel thickness of all teeth before and after treatment at the site of maximum exposure was 7.2+/-0.16 black trianglem with esomeprazole and 15.25+/-0.17black trianglem with placebo (P=0.013), representing a loss of 0.3% and 0.8% of the total enamel thickness, respectively. The change in optical reflectivity to a depth of 25 black trianglem after treatment was-1.122 +/-0.769 dB with esomeprazole and +2.059+/-0.534 dB with placebo (P 0.012), with increased reflectivity signifying demineralization. OCT non-invasively detected and quantified significantly diminished progression of dental tissue demineralization and enamel loss after only 3 weeks of treatment with esomeprazole 20 mg b.i.d. vs. placebo. This suggests that esomeprazole may be useful in counteracting progression of GERD-related dental erosions. Further validation of preventative treatment regimens using this sensitive detection method is required, including longer follow-up and correlation with quantitative reflux measures.