Mechanisms Of Gastroesophageal Reflux Disease Research Articles

Gastroesophageal Reflux Disease and Rhinosinusitis: A Bidirectional Mendelian Randomization Study

Introduction: Comorbidities, such as gastroesophageal reflux disease (GERD), are common in patients with rhinosinusitis (RS). However, the link between RS and GERD has not been fully understood. This study aimed to investigate the causal relationship between GERD and acute (ARS) or chronic RS (CRS), providing references for the pathogenesis and management of RS. Methods: The data were obtained from the Integrative Epidemiology Unit Open GWAS project and FinnGen. A total of 972,838 individuals were included. The inverse variance-weighted (IVW) method was applied to obtain the primary results of the study. Weighted median, MR-Egger, and mode-based methods were used to determine the robustness of the results. Cochran’s Q statistic and MR-Egger method were applied to detect heterogeneity and pleiotrophy in instrumental variables (IVs). Other sensitivity analyses included MR-PRESSO and leave-one-out analysis. Results: The MR study showed that GERD was associated with an increased risk of CRS (OR: 1.36, 95% CI: 1.18–1.57, p < 0.001). The results of other analysis methods were broadly consistent with the IVW estimate. No heterogeneity was detected by Cochran’s Q test (p = 0.061) and MR-PRESSO (p = 0.074). No horizontal pleiotropy was shown in IVs (p = 0.700). GERD was also associated with an increased risk of ARS (OR: 1.31, 95% CI: 1.17–1.48, p < 0.001). Some analytical results were inconsistent with the IVW estimate. No heterogeneity and pleiotropy were observed. There was no sufficient evidence for a reverse causal effect of RS on GERD. Conclusion: Our study supported that GERD promoted the risk of CRS and may be a potential risk factor for ARS. This provides additional support for further investigation into the mechanisms of GERD on RS.

The Role of a Plant-Only (Vegan) Diet in Gastroesophageal Reflux Disease: Online Survey of the Italian General Population.

The relationship between food and the pathophysiological mechanisms of gastroesophageal reflux disease (GERD) is unclear. There are few data on the impact of dietary habits on GERD symptoms and on the incidence of GERD in subjects undergoing plant-based diets. In this study, we investigated the association between diet and GERD, using data collected through an online survey of the Italian general population. In total, 1077 subjects participated in the study. GERD was defined according to the Montreal Consensus. For all subjects age, gender, body mass index (BMI), marital status, education, occupation, alcohol consumption, and smoking habits were recorded. All participants also completed the SF-36 questionnaire on Quality of Life. A total of 402 subjects (37.3%) were vegans and 675 (62.7%) non-vegans. The prevalence of GERD in the total population was 9%. Subjects with GERD-related symptoms recorded a worse quality of life according to SF-36 analysis (p < 0.05 for all dimensions). In multivariate analysis, after adjusting for confounders, participants undergoing a vegan diet had a significantly lower risk of GERD (OR = 0.47, 95% CI 0.28-0.81, p = 0.006). These findings should be taken into account to inform the lifestyle management of GERD.

Pressure dynamics of the esophagogastric junction at rest and during inspiratory maneuvers after Nissen fundoplication.

Low sphincter pressure and inability of the crural diaphragm to elevate it at the esophagogastric junction are important pathophysiological mechanisms of gastroesophageal reflux disease (GERD). The object of this study was to depict how Nissen fundoplication changed the resting and inspiratory pressures of the anti-reflux barrier. We selected 14 patients (eight males; mean age 42.7years; mean body mass index 27.8) for surgery. They answered symptoms questionnaires and underwent high-resolution manometry (HRM) before and 6months after Nissen fundoplication. We used a standard manometric protocol (resting and liquid swallows) and assessment of esophagogastric junction (EGJ) pressure metrics during standardized forced inspiratory maneuvers against increasing loads (Threshold Maneuvers). We used the Wilcoxon test for comparison of pre and postoperative data. After fundoplication, heartburn and regurgitation scores diminished remarkably (from 4.5 and 2, respectively, to zero; P = 0.002 and P = 0.0005, respective medians). Also, the median expiratory EGJ pressure had a significant increase from 8.1 to 18.1mmHg (P = 0.002), while mean respiratory pressure and EGJ contractility integral (EGJ-CI) increased without statistical significance (P = 0.064 and P = 0.06, respectively). Axial EGJ displacement was lower after fundoplication. The EGJ relaxation pressure (P = 0.001), the mean distal esophageal intrabolus pressure (P = 0.01) and the distal latency (P = 0.017) increased after fundoplication. There was a reduction in the contraction front velocity (P = 0.043). During evaluation with standardized inspiratory maneuvers, the inspiratory EGJ pressures (under loads of 12, 24, 36 and 48 cmH2O) were lower after surgery for all loads (median for load 12 cmH2O: 145.6 vs. 102.7mmHg; P = 0.004). Fundoplication and hiatal closure increased the expiratory EGJ pressure and promoted a great GERD symptom relief. The surgery seemed to overcompensate a reduced EGJ mobility and inspiratory pressure.

Gastroesophageal Reflux Disease: diagnosis and treatment

Introduction and purpose of the work: The mechanism of gastroesophageal reflux disease depends on reflux of gastric contents into the esophagus as a result of reduced tone of the lower esophageal sphincter. It presents itself in the form of symptoms coming from the esophagus, e.g. heartburn, as well as from outside of it. The aim of this paper is to collect and present current knowledge on gastroesophageal reflux disease as well as diagnosis and treatment through a review of the available literature. Brief description of the state of the art: Gastroesophageal reflux disease affects 18.1 - 27.8% of the US population and 8.8 - 25.9% of the European population. It is defined as the presence of troublesome symptoms or complications of reflux of gastric contents into the esophagus. The etiology consists of many factors, such as improper diet, and low physical activity. The disease can manifest itself with symptoms from and outside the esophagus. Diagnosis is based primarily on the history, and in the presence of typical symptoms, therapy with proton pump inhibitors is initiated. Endoscopy and reflux measurement is used when there is no response to pharmacotherapy. The basic drugs are proton pump inhibitors, other drugs are complementary to the basic therapy. A lifestyle change is also recommended. Surgical treatment is an alternative, but it may not be a permanent solution. Other treatments include endoscopic incisionless fundoplication and radiofrequency treatment of the lower esophageal sphincter. Summary: Diagnosis of gastroesophageal reflux disease begins with an interview with the patient and empirical pharmacotherapy. If treatment is ineffective, endoscopy and pH measurement are performed. Proton pump inhibitors are the most effective drugs in the treatment of the disease, other drugs are used as a supplement. Surgical and endoscopic procedures are an alternative to chronic pharmacotherapy.

Analysis on the gastrointestinal motility disorder of gastroesophageal reflux disease and the mechanism of acupuncture-moxibustion from the perspective of autonomic nervous system

From the perspective of autonomic nervous system, this paper analyzes the mechanism, current western medicine treatment methods and acupuncture-moxibustion treatment mechanism of gastroesophageal reflux disease (GERD). It is believed that the main cause of GERD is that the gastric acid goes to the wrong place due to gastrointestinal motility disorder, which belongs to "acid dislocation". At present, western medical treatment cannot effectively target the pathogenesis of the disease, and its effect is limited. Acupuncture-moxibustion could regulate the neuroendocrine immune network to regulate the function of autonomic nerve, restore the power of digestive tract to treat GERD, which is worthy of further research.

Changes in serum somatostatin level and its association with calcium metabolism indicators in patients withgastroesophageal reflux disease and spinal injuries of degenerative-dystrophic andinflammatory genesis

Background. The study of clinical features, factors and levels of various biologically active substances that may play an important role in the pathogenetic mechanism of gastroesophageal reflux disease (GERD) in combination with degenerative-dystrophic or inflammatory lesions of the spine, is an extremely important problem of the modern medical community. The purpose of the research is to determine the peculiarities of changes in the level of serum somatostatin (SST) and its relationship with calcium metabolism in patients with GERD and spine lesions of degenerative-dystrophic and inflammatory genesis. Materials and methods. 84 patients with spinal lesions of degenerative-dystrophic or inflammatory genesis in combination with GERD were examined. The examined patients with GERD were divided into two groups depending on the form of spine injury. GroupI included 44 patients with osteochondrosis (OS) of the cervical and thoracic spine (SpA). Group II consisted of 40patients with spinal arthritis. Results. There was a significant increase in the level of serum SST in both groups of the studied patients with GERD and spine injury of degenerative-dystrophic or inflammatory origin. At the same time, a more pronounced deviation from the norm was detected in group II of patients (increase up to (0.756±0.027)pg/ml, p&lt;0.01). Determination of level 25(OH)D in serum indicates vitamin D3 deficiency in patients with GERD and OS (decrease to (23.35±0.71) ng/ml, p&lt;0.05) and its deficiency in patients with SpA (decrease to (18.66±0.52)ng/ml, p&lt;0.01). Serum 25(OH)D levels also decreased more markedly in the atypical clinical course of GERD in the examined patients. Conclusions. In patients with GERD with degenerative-dystrophic and inflammatory lesions of the spine, an increase in the level of serum SST was found with the most pronounced deviation from the norm in atypical manifestation of GERD. A correlation between SST and a decrease in the level of 25(OH)D and Ca++, mainly in patients with atypical clinical course of GERD, was established.

Гастроезофагеальна рефлюксна хвороба і лужний рефлюкс: механізми розвитку і тактика лікування

Стаття присвячена гастроезофагеальній рефлюксній хворобі (ГЕРХ) — патології, що займає провідне місце серед усіх кислотозалежних захворювань. Основним механізмом розвитку ГЕРХ є порушення моторно-евакуаторної функції шлунка — уповільнення шлункової евакуації і дуоденогастральний рефлюкс. Уповільнене спорожнення шлунка сприяє почастішанню рефлюксу, а наявність дуоденального вмісту в рефлюктаті — лужний рефлюкс — є агресивним для слизової оболонки стравоходу (СОС). Це обумовлено наявністю в рефлюктаті, що закидається в стравохід, жовчних кислот, лізолецитину і панкреатичних ферментів. Тривало існуючий контакт агресивних чинників у шлунку і стравоході призводить до розвитку запально-деструктивних уражень слизової оболонки цих органів. За даними багатьох дослідників, саме жовчні кислоти відіграють провідну роль у патогенезі шкідливого впливу на СОС. Медикаментозна корекція ГЕРХ із лужним рефлюксом включає поряд із призначенням інгібіторів протонної помпи прокінетики (ітоприду гідрохлорид) і препарати урсодезоксихолієвої кислоти.

Narrative review of the role of inflammation in gastroesophageal reflux disease. Can food allergies play a part?

AbstractAcid suppression is the accepted treatment for gastroesophageal reflux disease, despite being ineffective in one third of patients. Certain conditions presenting as reflux may later be attributed to food allergy (infant cow's milk allergy; eosinophilic esophagitis), but the role of food allergy in adult reflux disease has rarely been investigated. The mechanisms of gastroesophageal reflux disease are examined to explore potential subgroups within the population, such as undisclosed food allergy, which may determine the responsiveness to treatment. The relevant literature was searched systematically using ProQuest Dialog, yielding 113 papers that were evaluated for quality. The extracted evidence was formed into a mechanistic diagram representing the processes of disease. As yet, insufficient research exists to evaluate the relationship between food allergies and reflux in adults. Of significance, however, is the potential for multiple variables to affect the integrity of the esophageal mucosa, thereby allowing symptoms to emerge which are independent of acid exposure. Where nonacidic drivers of inflammation exist, acid suppression is unlikely to offer adequate symptom resolution and may serve to explain the high proportion of nonresponders in this group. The review concludes that symptoms of gastroesophageal reflux may emerge in response to the coexistence of physiological reflux and esophageal mucosal inflammation. The latter may arise due to reflux‐induced acid erosion, or due to alternative endogenous sources of inflammation. When a patient presents with refractory reflux and a history of allergic disease, the role of antigen‐induced inflammation should be considered for further investigation. Nonallergic individuals presenting with refractory reflux symptoms may benefit from further analysis of relevant co‐morbidities that have the capacity to compromise mucosal integrity, including obesity or psychological stress. The identification of specific mediators of inflammation in refractory reflux disease may enable the development of personalized treatment regimes which improve outcomes and reduce the reliance on acid suppressants.

Current Advancement on the Dynamic Mechanism of Gastroesophageal Reflux Disease.

Gastroesophageal reflux disease (GERD) is a common clinical disease associated with upper gastrointestinal motility disorders. Recently, with improvements in living standards and changes in lifestyle and dietary habits, the incidence of GERD has been increasing yearly. However, the mechanism of GERD has not been fully elucidated due to its complex pathogenesis, and this had led to unsatisfactory therapeutic outcomes. Currently, the occurrence and development of GERD involve multiple factors. Its pathogenesis is mainly thought to be related to factors, such as lower esophageal sphincter pressure, transient lower esophageal sphincter relaxation, crural diaphragmatic dysfunction, hiatus hernia, and impaired esophageal clearance. Therefore, explaining the pathogenesis of GERD more clearly and systematically, exploring potential and effective therapeutic targets, and choosing the best treatment methods have gradually become the focus of scholars' attention. Herein, we reviewed current advancements in the dynamic mechanism of GERD to better counsel patients on possible treatment options.

A perspective on risk factors for esophageal adenocarcinoma: emphasis on Helicobacter pylori infection.

Gastroesophageal reflux disease (GERD) and the increasing rate of its associated complications, including esophageal adenocarcinoma (EAC), has stimulated a plethora of studies attempting to evaluate provocative and protective factors. Helicobacter pylori (Hp) infection (Hp-I) was initially considered as a beneficial condition in GERD management based on rather limited data. Large-scale regional studies revealed an alternative approach, by suggesting a positive relationship between Hp-I and EAC development. Regarding pathophysiology, Hp-I induces gastric microbiota disturbances through hypochlorhydria and chronic inflammation, with a subsequent possible effect on the GERD-Barrett's esophagus (BE)-EAC cascade. Additionally, both direct effects on esophageal mucosa and indirect effects on known mechanisms of GERD, such as acid pocket and transient lower esophageal sphincter relaxation, remain to be elucidated. Hp contribution to carcinogenesis is related to oncogenic gastrin, cyclooxygenase-2, and prostaglandins; Ki-67 is also expressed and represents an index of BE-related malignancy. Moreover, Hp-I is vigorously suggested as a risk factor for metabolic syndrome, which may be the link between Hp-I and EAC. Although further studies are necessary to establish a pathophysiologic risk between Hp-I and the GERD-BE-EAC sequence, the theory of Hp protection against GERD seems outdated.

Esophageal motility and reflux characteristics in gastroesophageal reflux disease patients with or without extra-esophageal symptoms

Objective: To investigate esophageal motility and reflux characteristics in gastroesophageal reflux disease (GERD) with and without extra-esophageal symptoms by high-resolution manometry and 24 h esophageal multichannel intraluminal impedance combined pH (MII-pH) monitoring. Methods: From February 2016 to June 2017, GERD patients with and without extra-esophageal symptoms were enrolled in this prospective controlled study. Esophageal HRM and 24 h MII-pH monitoring were performed. The differences in esophageal motility and reflux parameters were further analyzed between 30 GERD patients with extra-esophageal symptoms and 30 simple GERD patients. Results: The GERD symptom scores didn't show statistical difference between two groups. The GERD symptom scores didn't show statistical difference between two groups. The relaxation pressure of lower esophageal sphincter(LES), the integrated relaxation pressure, and the recovery time of upper esophageal sphincter(UES) of GERD patients with extra-esophageal symptoms were all lower than those of patients without extra-esophageal symptoms [(15±7) vs (21±11)mmHg, (8±3) vs (10±5)mmHg, (388±168) vs (492±170)ms, 1 mmHg=0.133 kPa], and the differences were statistically significant(all P<0.05). The main classification of esophageal motility type of GERD patients with extra-esophageal symptoms was mild esophageal motility disorders (27%, 8/30), and the occurrence of ineffective esophageal motivation was 20% (6/30), which were similar with simple GERD patients. The proximal reflux percentages of weak acid reflux and nonacid reflux, abnormal nonacid reflux in GERD patients with extra-esophageal symptoms were significantly higher than those in simple GERD patients [84.6% (73.2%, 100.0%) vs 75.0% (60.0%, 87.65%), P=0.048; 90.0% (45.8%, 100.0%) vs 0(0, 100.0%), P=0.017; 46.7% vs 3.3%, P=0.03]. Conclusions: The pathogenesis of GERD with extra-esophageal symptoms may be different from typical GERD. Increase of proximal esophageal reflux and abnormal nonacid reflux may all participate in the mechanisms of GERD with extra-esophageal symptoms.

Epidemiology and mechanisms of gastroesophageal reflux disease in the elderly: a perspective.

Gastroesophageal reflux disease (GERD) seems to be more common in older individuals. Disturbed esophageal motility; anatomical disorders, such as hiatal hernia, increased obesity, defective mucosal integrity, and alteration in salivary secretion; and concomitant medications all attribute to the higher rate of GERD in the elderly. In this review, we discuss the underlying mechanisms that could explain this higher rate of GERD in the elderly.

Specific Movement of Esophagus During Transient Lower Esophageal Sphincter Relaxation in Gastroesophageal Reflux Disease

Background/AimsTransient lower esophageal sphincter relaxation (TLESR) is the main mechanism of gastroesophageal reflux disease (GERD). The aim of this study was to investigate the characteristics of transient lower esophageal sphincter movement in patients with or without gastroesophageal reflux by high-resolution manometry (HRM).MethodsFrom June 2010 to July 2010, we enrolled 9 patients with GERD (GERD group) and 9 subjects without GERD (control group), prospectively. The manometry test was performed in a semi-recumbent position for 120 minutes following ingestion of a standardized, mixed liquid and solid meal. HRM was used to identify the frequency and duration of TLESR, esophageal shortening length from incomplete TLESR, upper esophageal sphincter (UES) response, and the related esophageal motor responses during TLESR.ResultsTLESR occurred in 33 in the GERD group and 34 in the control group after 120 minutes following food ingestion. Duration of TLESR and length of esophageal shortening did not differ between 2 groups. UES pressure increase during TLESR was mostly detected in patients with GERD, and UES relaxation was observed frequently in the control group during TLESR. TLESR-related motor responses terminating in TLESR were predominantly observed in the control group.ConclusionsIncreased UES pressure was noted frequently in the GERD group, suggesting a mechanism for preventing harmful reflux, which may be composed mainly of fluid on the larynx or pharynx. However, patients with GERD lacked the related motor responses terminating in TLESR to promote esophageal emptying of refluxate.

Improved Reflux Monitoring in the Acute Gastroesophageal Reflux Porcine Model Using Esophageal Multichannel Intraluminal Impedance Measurement

BackgroundAcute animal models are needed to obtain further insights into the mechanism of gastroesophageal reflux disease. Existing acute models use imprecise methods to detect reflux. The aim of the present study was to evaluate the potential of esophageal multichannel intraluminal impedance measurement (MII) to improve the quality of results of acute reflux porcine models. Materials and MethodsMII was used in ten pigs to monitor gastroesophageal reflux. Measurements were obtained (A) before and (B) after mobilization of the esophagus and (C) after myotomy. The results were compared to those obtained when reflux was monitored by esophageal drainage of intragastrically infused blue solution (DBS). ResultsThe times to first appearance of reflux were 67% (A), 86% (B), and 57% (C) of those by DBS when detected by MII; p < 0.05. The respective values for intragastric pressures needed to provoke reflux were 46%, 76%, and 66%; p < 0.05. Although the lower esophageal sphincter pressure decreased by 69% after (B) the intragastric pressure needed to provoke reflux increased by 140%; p < 0.05. ConclusionsMII improves the detection of reflux in the acute reflux porcine model. The finding that after sole mobilization of the esophagus the intragastric pressure needed to provoke reflux was increased although the finding that the pressure of the lower esophageal sphincter was decreased needs further investigation.

Healing of severe reflux esophagitis with Ppi does not improve esophageal dysmotility

Esophageal dysmotility is frequently associated with gastroesophageal reflux disease (GERD). The aim of this study was to investigate the relationship between the severity of reflux esophagitis and esophageal dysmotility and evaluate the effect of prolonged treatment with proton pump inhibitor (lansoprazole 30 mg/day) on esophageal motility in patients with severe reflux esophagitis associated with esophageal motility disorder. Twelve healthy subjects (HS) and 100 patients with reflux disease were involved in the study consisting of two parts: (i) comparison of esophageal motility in HS and patients with non-eroseive reflux disease (NERD), mild esophagitis and severe esophagitis; (ii) effect of 3-6 months lansoprazole therapy on esophageal motility in 23 patients with severe esophagitis, pathologic acid reflux and esophageal peristaltic dysfunction. Results included the following. (i) Esophageal dysmotility was noted in both patients with NERD and erosive GERD. (ii) Severe esophagitis was associated with severe esophageal dysmotility. (iii) Healing of severe esophagitis did not improve esophageal dysmotility. The resting lower esophageal sphincter pressure was 3.9 mmHg (range 1.7-20) before treatment and 4.8 mmHg (range 1.2-18.3) after esophagitis healing (P = 0.23, vs. before treatment), the amplitude of distal esophageal contraction was 28.8 mmHg (range 10.9-80.6) before treatment and 33.3 mmHg (range 10.0-72.5) after esophagitis healing (P = 0.59, vs. before treatment) and the frequency of failed peristalsis was 70% (range 0-100%) before treatment and 70% (range 0-100%) after esophagitis healing (P = 0.78, vs. before treatment). Both esophageal motility disorders and acid reflux play important roles in the mechanism of GERD, especially in severe esophagitis. Esophageal dysmotility is not secondary to acid reflux and esophagitis; it should be a primary motility disorder.

Recent developments in the pathophysiology and therapy of gastroesophageal reflux disease and nonerosive reflux disease

Purpose of review Gastroesophageal reflux disease is a very common disorder. Proton pump inhibitors are the highly successful mainstay of medical gastroesophageal reflux disease treatment. However, some limitations of proton pump inhibitor therapy continue to drive studies that aim at better understanding and managing manifestations of gastroesophageal reflux disease. This review summarizes recent progress in our understanding of the pathophysiology and treatment of gastroesophageal reflux disease. Recent findings Recent studies have demonstrated a potential role of increased gastric acid secretion in gastroesophageal reflux disease, a factor largely neglected during the last decade. Failure to respond adequately to proton pump inhibitor therapy has been attributed to diagnostic inaccuracy, to nocturnal acid breakthrough, to ongoing non-acid reflux and to esophageal hypersensitivity. The relevance of nocturnal acid breakthrough has been recently challenged. Transient lower esophageal sphincter relaxations are a major mechanism of gastroesophageal reflux disease; inhibition of transient lower esophageal sphincter relaxations is a potentially important therapeutic target. Recent studies have focused on GABA receptor stimulation using baclofen or sodium valproate. The role of esophageal body peristalsis in the clearance of reflux events has been questioned. Endoscopic antireflux therapies aim at perendoscopic reinforcement of the antireflux barrier as a novel therapeutic approach to gastroesophageal reflux disease. At present, long-term and controlled data are scarce. Recent observations have challenged the long-term efficacy of surgical antireflux therapy. Summary Increased understanding of the pathophysiology of gastroesophageal reflux disease may lead to new or improved treatments. Major advances have been made in the role of gastric acid secretion, the control of transient lower esophageal sphincter relaxations and mechanisms underlying esophageal hypersensitivity. Recent studies have highlighted some shortcomings of proton pump inhibitor therapy and of antireflux surgery. Novel approaches are treatments aimed at decreasing transient lower esophageal sphincter relaxations and endoscopic antireflux procedures. Large-scale controlled studies are lacking for both treatments.

Pathophysiological mechanisms of gastroesophageal reflux disease in children.

Gastroesophageal reflux (GER) is an extremely common pediatric problem, but only in the past few years have we developed a better understanding of its pathophysiology. This is related to the wider use of investigative tools such as flexible endoscopy, 24-hour pH monitoring, and more recently, micromanometric methods and noninvasive breath tests, which have been particularly useful in infants. This paper reviews our current understanding of the esophageal and gastric mechanisms contributing to the pathophysiology of GER. In this context, we also highlight areas where new therapeutic approaches may be beneficial.