Risk Of Gastroesophageal Reflux Disease Research Articles

Association of educational attainment with esophageal cancer, Barrett's esophagus, and gastroesophageal reflux disease, and the mediating role of modifiable risk factors: A Mendelian randomization study.

Observational studies have reported that educational attainment has been related to the risk of esophageal cancer (EC) and its precancerous lesions. However, the causal relationship remains controversial. We aimed to apply the Mendelian randomization (MR) design to determine the causal associations between genetically predicted educational attainment and EC, Barrett's esophagus (BE), and gastroesophageal reflux disease (GERD), and to explore whether modifiable risk factors play a mediating role. Using summary statistics from genome-wide association studies (GWASs) based on European ancestry individuals of several years in education (EduYears, primary analysis, n = 293,723), college completion (College, secondary analysis, n = 95,427), EC (n = 420,531), BE (n = 361,194), and GERD (n = 420,531), genetic associations between two education phenotypes and EC, BE, and GERD were tested by two-sample MR analyses. Then, two-step MR mediation analyses were used to assess the proportion of the aforementioned association that might be mediated by body mass index (BMI), major depressive disorder (MDD), smoking, drinking, carbohydrates, fat, and protein intake. Genetically predicted EduYears was negatively associated with the risk of EC, BE, and GERD {odds ratio (OR), 0.64 [95% confidence interval (CI) 0.44-0.94], 0.86 (95% CI, 0.75-0.99), and 0.62 (95%CI, 0.58-0.67)}. EduYears was negatively associated with BMI, MDD, and smoking (range of OR: 0.76-0.84). There were positive associations between BMI, smoking with EC, BE, and GERD, as well as between MDD with GERD (range of OR: 1.08-1.50). For individual mediating effect, BMI and smoking mediated 15.75 and 14.15% of the EduYears-EC association and 15.46 and 16.85% of the EduYears-BE association. BMI, MDD, and smoking mediated 5.23, 4.98, and 4.49% of the EduYears-GERD association. For combined mediation, the aforementioned mediators explained 26.62, 28.38, and 11.48% of the effect of EduYears on EC, BE, and GERD. The mediating effects of drinking and dietary composition were not significant in the effect of education on EC, BE, and GERD. Our study supports that genetically predicted higher educational attainment has a protective effect on EC, BE, and GERD, and is partly mediated by reducing adiposity, smoking, and depression.

High Visceral-To-Subcutaneous Fat Ratio Is Associated with an Increased Risk of Gastroesophageal Reflux Disease in Nonobese Adults

Introduction: Abdominal obesity increases the risk of gastroesophageal reflux disease (GERD). This study aimed to determine the association between GERD and abdominal fat area quantified by computed tomography (CT). Methods: We analyzed the effect of abdominal fat area on gastroesophageal reflux symptoms and erosive esophagitis using logistic regression models in 5,338 participants who underwent abdominal fat measurement CT and screening esophagogastroduodenoscopy. Results: Participants with reflux symptoms and erosive esophagitis were diagnosed in 1,168 (21.9%) and 671 (12.5%), respectively. Multivariate analysis showed that subcutaneous and visceral fat areas were significantly associated with reflux symptoms and erosive esophagitis. The adjusted odds ratio (OR) in the fourth quartile of visceral fat area compared with that in the lowest quartile was 1.98 (95% confidence interval (CI) 1.63–2.39) for reflux symptoms and 2.33 (95% CI 1.80–3.01) for erosive esophagitis. Visceral fat area had a stronger effect in the younger age-group. In the group <50 years, the adjusted OR in fourth quartile of visceral fat area was 2.70 (95% CI 1.86–3.94) for reflux symptoms and 3.59 (95% CI 2.22–5.80) for erosive esophagitis. High visceral-to-subcutaneous fat ratio (VSR) increased the risk of reflux symptoms and erosive esophagitis in participants with body mass index <25 kg/m² and normal waist circumference. Conclusion: Subcutaneous and visceral fat areas were associated with an increased risk of reflux symptoms and erosive esophagitis. High VSR increased the risk of reflux symptoms and erosive esophagitis in participants with normal body weight and waist circumference.

The causal role of gastroesophageal reflux disease in anxiety disorders and depression: A bidirectional Mendelian randomization study.

Observational studies have shown an association between gastroesophageal reflux disease (GERD) and anxiety disorders/depression. However, these evidences may be influenced by confounding factors. Therefore, our study aimed to determine the causal relationship between GERD and anxiety disorders/depression by conducting a bidirectional Mendelian randomization (MR) study. We performed a bidirectional MR analysis using summary statistics from genome-wide association studies (GWAS) in European individuals. The inverse-variance weighted (IVW) method was used as the primary analytical method to assess causality. In addition, five additional MR methods [maximum likelihood, MR-Egger, weighted median, robust adjusted profile score (MR-RAPS), and mode-based estimate (MR-MBE)] were performed to supplement the IVW results. Furthermore, several sensitivity analyses were performed to assess heterogeneity, horizontal pleiotropy, and stability. Finally, a multivariable MR (MVMR) analysis was performed to determine the causal relationship by adjusting for potential confounders. MR results of the IVW method indicated that GERD significantly increases the risk of anxiety disorders [odds ratio (OR) = 1.35, 95% confidence interval (CI) 1.15-1.59, P = 2.25 × 10-4] and depression (OR = 1.32, 95% CI: 1.15-1.52, P = 1.26 × 10-4). In addition, the MR results of maximum likelihood, MR-Egger, weighted median, MR-RAPS, and MR-MBE remained parallel to the IVW results. Furthermore, sensitivity analysis suggested that the results were robust, with no pleiotropy or heterogeneity detected. Nevertheless, reverse MR analysis showed that anxiety or depression did not increase GERD risk. Finally, MVMR analysis showed that the effect of GERD on increasing the risk of anxiety disorders/depression was independent of confounders. This MR study supports a causal association between GERD and an increased risk of anxiety disorders and depression. Therefore, complementing symptomatic treatment of GERD with psychological assessment and necessary psychological support therapy may help reduce the risk of future anxiety disorders and depression.

Stroke and the risk of gastrointestinal disorders: A Mendelian randomization study.

The issue of whether a stroke is causally related to gastrointestinal disorders was still not satisfactorily understood. Therefore, we investigated if there is a connection between stroke and the most prevalent gastrointestinal disorders, including peptic ulcer disease (PUD), gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD). We applied two-sample Mendelian randomization to investigate relationships with gastrointestinal disorders. We obtained genome-wide association study (GWAS) summary data of any stroke, ischemic stroke, and its subtypes from the MEGASTROKE consortium. From the International Stroke Genetics Consortium (ISGC) meta-analysis, we acquired GWAS summary information on intracerebral hemorrhage (ICH), including all ICH, deep ICH, and lobar ICH. Several sensitivity studies were performed to identify heterogeneity and pleiotropy, while inverse-variance weighted (IVW) was utilized as the most dominant estimate. No evidence for an effect of genetic predisposition to ischemic stroke and its subtypes on gastrointestinal disorders were found in IVW. The complications of deep ICH are a higher risk for PUD and GERD. Meanwhile, lobar ICH has a higher risk of complications for PUD. This study provides proof of the presence of a brain-gut axis. Among the complications of ICH, PUD and GERD were more common and associated with the site of hemorrhage.

Atopic dermatitis and risk of gastroesophageal reflux disease: A nationwide population-based study.

As atopic dermatitis (AD) has been found to be related to various comorbidities as well as substantial patient burden, questions of a possible relationship between AD and nonallergic diseases beyond allergic diseases have also been raised. The aim of this nationwide matched cohort study was to evaluate whether AD would increase the development of gastroesophageal reflux disease (GERD). Patients diagnosed with AD were identified from the National Health Insurance Service-National Sample Cohort (NHIS-NSC) 2.0 database in South Korea from 2002 to 2015. Finally, 9,164 adults with AD (≥20 years old) and age, sex, household income, region of residence, disability, and baseline year-matched 9,164 controls were included in the analysis. Hazard ratio (HR) with 95% confidence interval (CI) for the development of GERD was estimated using a Cox proportional hazard regression model. Overall, 12.3% of the patients in the AD group developed GERD, whereas 10.4% of the individuals in the control group developed GERD. The results of the adjusted model revealed that patients with AD had a significantly increased risk of developing GERD (adjusted HR, 1.15; 95% CI, 1.06-1.26) compared with the matched controls. Increased risk of developing GERD was consistent in subgroup analyses by sex or age groups under 60 years old as well as all the sensitivity analyses performed. This study suggested that appropriate management should be considered in adults with AD to prevent GERD, because AD was found to be associated with an increased risk of subsequent GERD.

Dietary approaches to stop hypertension (DASH)-style diet in association with gastroesophageal reflux disease in adolescents

BackgroundDietary patterns and food items have been associated with gastroesophageal reflux disease (GERD) risk and they have led to conflicting findings. The aim of this study was to determine the association between a dietary approach to stop hypertension (DASH)-style diet with the risk of GERD and its symptoms in adolescents.Study designCross-sectional.MethodsThis study was performed on 5,141 adolescents aged between 13 and 14 years. Dietary intake was evaluated using a food frequency method. The diagnosis of GERD was done by using a six-item GERD questionnaire that asked about GERD symptoms. A binary logistic regression was used to assess the association between the DASH-style diet score and GERD and its symptoms in crude and multivariable-adjusted models.ResultsOur findings revealed that after adjustment for all confounding variables, the adolescents with the highest adherence to the DASH-style diet had a lower chance of developing GERD [odds ratio (OR) = 0.50; 95%CI 0.33–0.75, Ptrend< 0.001)], reflux (OR = 0.42; 95%CI 0.25–0.71, Ptrend=0.001), nausea (OR = 0.59; 95% CI:0.32–1.08, Ptrend=0.05) and stomach pain (OR = 0.69; 95%CI 0.49–0.98, P trend=0.03) compared to those with the lowest adherence. Similar results were found for odds of GERD among boys, and the total population (OR = 0.37; 95%CI: 0.18–0.73, Ptrend=0.002, OR = 0.51; 95%CI: 0.34–0.77, P trend<0.0, respectively).ConclusionThe current study revealed that adherence to a DASH-style diet might protect against GERD and its symptoms including, reflux, nausea, and stomach pain in adolescents. Further prospective research is needed to confirm these findings.

Depression Promotes Gastroesophageal Reflux Disease: New Evidence Based on Mendelian Randomization.

Although observational studies have reported that depression is a risk factor for gastroesophageal reflux disease, it is difficult to determine the potential causal correlation. Thus, this study investigated the causal relevance of depression for gastroesophageal reflux disease using Mendelian randomization and provided new evidence for their association. Based on data from the UK Biobank, we assessed the causality of the 2 diseases by analyzing 135 458 severe depressive disorder cases and 41 024 gastroesophageal reflux disease cases. The causal inference was assessed using inverse-variance weighting, weighted median, Mendelian randomization-Egger, and weighted median methods. Simultaneously, pleiotropy and sensitivity analyses were used for quality control. Finally, we also explored whether depression affects gastroesophageal reflux disease through other risk factors. A positive causal relationship between depression and gastroesophageal reflux disease was found in the inverse-variance weighted and weighted median methods, both of which were statistically significant [odds ratio = 1.011, 95% CI: 1.004-1.017, P =.001; odds ratio = 1.011, 95% CI: 1.004-1.020, P =.002)]. Sensitivity analyses were consistent with a causal interpretation, and the main deviation of genetic pleiotropy was not found (Intercept β = 0.0005; SE = 0.005, P =.908). The genetic susceptibility to depression was also associated with smoking, insomnia, and sleep apnea (odds ratio = 1.166, 95% CI: 1.033-1.316, P =.013; odds ratio = 1.089, 95% CI: 1.045-1.134; and odds ratio = 1.004, 95% CI: 1.001-1.006, P =.001, respectively). Our results verified a causal correlation that depression could slightly increase the risk of gastroesophageal reflux disease.

The effect of combined oral contraceptives and Nexplanon on gastroesophageal reflux disease in premenopausal women: A nationwide database analysis.

Pregnancy, combined oral contraceptives (COC), and hormone replacement therapy have been reported to increase the risk of gastroesophageal reflux disease (GERD). To date, no study has evaluated the effect of Nexplanon, a commonly used progesterone-based contraceptive, on GERD. We aimed to determine the effect of Nexplanon and COC on GERD. We performed a population-based analysis using the IBM Explorys national database (1999-2021). The study group included premenopausal women, defined as women less than 50 years of age while excluding the diagnosis of menopause. The effect of Nexplanon and COC on GERD (at least 30 days after Nexplanon/COC was initiated) was assessed by comparing it to premenopausal women who were not on contraceptives. Foregut surgery, esophageal dysmotility disorders, hiatal hernia, and delayed gastric emptying were excluded. Odds ratios (OR) with 95% confidence intervals (CI) were calculated. A multivariate logistic regression analysis was conducted. A total of 23,299,470 patients were identified as being premenopausal, of which 47,260 were on Nexplanon and 5480 on COCs. As compared to premenopausal women with GERD on no contraceptives (n=565,880), 690 patients developed GERD at least 30 days after being on Nexplanon (OR=0.55, 95% CI [0.51-0.59], p < 0.001) and 280 developed GERD after COC (1.93, [1.71-2.18], p < 0.001). A multivariate analysis accounting for Caucasian race, obesity, smoking, alcohol use, and NSAIDs revealed that COC is an independent risk factor for GERD (1.16, [1.12-1.20], p < 0.001), and Nexplanon was protective against GERD (0.90, [0.89-0.92], p < 0.001). Hydralazine was used as a control medication for data reliability. A total of 8420 patients developed GERD after initiating hydralazine, which was not statistically nor clinically significant (OR=1.02, 95% CI [0.99-1.04], p=0.08) when compared to those not on contraceptives. Combined oral contraceptives is an independent risk factor for GERD, while Nexplanon has a limited protective effect. Further studies are needed to confirm the different effects on GERD of these two contraceptives.

High Discovery Rate of Duodenal and Gastric Eosinophilia in Patients With Unexplained Moderate–Severe Abdominal Symptoms: A Prospective US Multisite Study

High Discovery Rate of Duodenal and Gastric Eosinophilia in Patients With Unexplained Moderate–Severe Abdominal Symptoms: A Prospective US Multisite Study

Clinical presentations of erosive esophagitis found at endoscopy in neurologically impaired children: a historical study

Data is lacking as to the clinical presentation of erosive esophagitis (EE) in neurologically impaired children compared to non-neurologically impaired children (non-NIC). To determinate the clinical presentation, associations, management, and outcomes of EE in neurologically impaired children compared to children without neurologic impairment. Retrospective chart review of all esophagogastroduodenoscopies performed in pediatric patients at the University of Mississippi Medical Center from 1998 to 2020 with the diagnosis of EE. Fisher's exact test was used to compare results from neurologically impaired children group and non-NIC. A probability <0.05 was considered statistically significant. Forty-seven patients were diagnosed with EE and met study criteria. Twenty-six patients were neurologically impaired children, and 21 were non-neurologically impaired children. No significant difference was seen between age at diagnosis, sex, or hematologic markers of anemia. The most common indication for esophagogastroduodenoscopies in neurologically impaired children was hematemesis (65.4%), whereas abdominal pain (33.3%) was the most common in non-NIC. Neurologically impaired children were more likely to be treated with acid-blockade. Nine neurologically impaired children had gastrostomy tubes prior to diagnosis as opposed to 0 non-neurologically impaired children. After diagnosis, 8 neurologically impaired children underwent gastrostomy tube placement compared to 0 non-neurologically impaired children, and fundoplication was performed in 11 neurologically impaired children as compared to 1 non-NIC. The sensitivity of fecal occult blood test for detecting EE was higher for neurologically impaired children (91.7%) than for non-NIC (33.3%). EE in neurologically impaired children presents differently than in non-neurologically impaired children with blood loss being the most common presentation in neurologically impaired children. Neurologically impaired children are more likely to be treated with acid-blockade prior to diagnosis, likely due to heightened risk for gastroesophageal reflux disease (GERD). Additionally, they are more likely to undergo surgical management of EE than non-neurologically impaired children.

56 Gastroesophageal reflux disease in children with neurological impairment: a population-based retrospective cohort study

Abstract Background Children with neurological impairment (NI) are at increased risk of gastroesophageal reflux disease (GERD) and may be more susceptible to complications such as esophagitis and aspiration. Diagnosis is challenging due to communication impairments and frequent comorbidities, such as dysphagia, that present similarly to GERD. There is a risk of both under and over diagnosis with detrimental effects. Prior research has suggested the prevalence of GERD is as high as 75%. However, these studies examined subpopulations such as children presenting with symptoms or living in institutions, often many decades ago. Objectives Our aim was to determine the incidence and prevalence of GERD diagnosis and treatment in children with NI at a population level. Design/Methods This is a retrospective cohort study using provincial administrative data. Children with NI were identified by International Classification of Diseases (ICD-10) codes in the Discharge Abstract Database (DAD) between 2006 and 2018. GERD was defined as: (1) 1+ codes in DAD or National Ambulatory Care Reporting System; (2) 2+ specialist claims; (3) 1+ ASM prescription. Age, gender, complex chronic conditions (CCC) and technology assistance (TA) were covariates. ASM prescriptions and anti-reflux procedures were collected. Descriptive statistics included means with standard deviations and counts with proportions. Univariable and multivariable Poisson regressions calculated incidence rates and rate ratios for the presence of GERD and prescription of ASM. Results Among 10,309 children with NI, 2,772 (26.9%) met the GERD definition. The unadjusted incidence rate was 52.1 per 1000 person-years. Increasing numbers of CCCs were associated with a higher risk of GERD. Children with four or more CCCs had an incidence almost three times that of children with no CCCs. A gastrostomy tube incurred a five times higher rate of GERD. Overall, 2486 (23.7%) of the children were treated with ASMs of which 1535 (61.7%) met no other GERD criteria. The incidence rate was 16.9 prescriptions per year. Neonatal, respiratory and congenital CCCs were associated with higher rates of ASM prescribing. The prevalence of gastrojejunostomy tubes was 1.1% (n=121), surgical jejunostomy tubes was 0.7% (n=79) and fundoplication was 3.3% (n=351). Conclusion The incidence of GERD in children with NI is dramatically higher than in the general pediatric population, as is the use of ASM. Both disparities are heightened in children with gastrostomy tubes, perhaps due to increased severity of NI or relevant comorbidities. Regardless, GERD is clearly a significant clinical issue in this population that warrants additional study to determine optimal diagnosis and treatment practices.

Mendelian Randomization Analysis Reveals a Complex Genetic Interplay among Atopic Dermatitis, Asthma, and Gastroesophageal Reflux Disease.

Rationale: Gastroesophageal reflux disease (GERD) is commonly associated with atopic disorders, but cause-effect relationships remain unclear. Objectives: We applied Mendelian randomization analysis to explore whether GERD is causally related to atopic disorders of the lung (asthma) and/or skin (atopic dermatitis [AD]). Methods: We conducted two-sample bidirectional Mendelian randomization to infer the magnitude and direction of causality between asthma and GERD, using summary statistics from the largest genome-wide association studies conducted on asthma (Ncases = 56,167) and GERD (Ncases = 71,522). In addition, we generated instrumental variables for AD from the latest population-level genome-wide association study meta-analysis (Ncases = 22,474) and assessed their fidelity and confidence of predicting the likely causal pathway(s) leading to asthma and/or GERD. Measurements and Main Results: Applying three different methods, each method revealed similar magnitude of causal estimates that were directionally consistent across the sensitivity analyses. Using an inverse variance-weighted method, the largest effect size was detected for asthma predisposition to AD (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.34-1.59), followed by AD to asthma (OR, 1.34; 95% CI, 1.24-1.45). A significant association was detected for genetically determined asthma on risk of GERD (OR, 1.06; 95% CI, 1.03-1.09) but not genetically determined AD on GERD. In contrast, GERD equally increased risks of asthma (OR, 1.21; 95% CI, 1.09-1.35) and AD (OR, 1.21; 95% CI, 1.07-1.37). Conclusions: This study uncovers previously unrecognized causal pathways that have clinical implications in European-ancestry populations: 1) asthma is a causal risk for AD, and 2) the predisposition to AD, including asthma, can arise from specific pathogenic mechanisms manifested by GERD.

Aging Combined with High Waist-to-Hip Ratio Is Associated with a Higher Risk of Gastro-Esophageal Reflux Disease.

Background and Objective: To assess whether the combination of high waist-to-hip ratio (WHR) and elderly age is associated with higher risk of GERD. Material and Methods: A total of 16,996 subjects aged ≥20 years who received esophagogastroduodenoscopy (EGD) between January 2010 and December 2019. We evaluated the risk of GERD in different age groups and WHR groups in unadjusted analysis and multivariate logistic regression models for predictors of GERD. Results: There was a trend towards more participants with both age ≥65 years and WHR ≥ 1 (n = 129) (n = 66, 51%) than participants with age < 65 and WHR < 0.9 (n = 10,422) (n = 2814, 27%) presenting with GERD. Participants who had both age ≥ 65 years and high WHR ≥ 1 had the highest risk of any type of GERD (adjusted OR, 2.07; 95% CI, 1.44–2.96, p value < 0.05) based on multivariate logistic regression analysis. Conclusions: The combination of having a high WHR and being elderly was associated with a higher risk of GERD, and preventing central obesity in the elderly population reduced the risk of GERD and the requirement for medical resources.

Role of Non-pharmacological Interventions and Weight Loss in the Management of Gastroesophageal Reflux Disease in Obese Individuals: A Systematic Review.

With the increasing prevalence of obesity, the worldwide risk of gastroesophageal reflux disease (GERD) has also increased. Abdominal obesity increases intragastric pressure, disturbing the integrity of the gastroesophageal junction, thus facilitating reflux. Other than obesity, some lifestyle factors also cause GERD, including smoking, consumption of alcohol and caffeine, late-night meals, and high fat intake. This review study aimed to assess the impact of weight loss and lifestyle modifications on GERD. In this systematic review, the databases used were PubMed, PubMed Central (PMC), Science Direct, and Google Scholar. Boolean system and Medical Subject Headings (MeSH) strategy were used to form suitable keywords. Patients from the pediatric and geriatric populations were excluded from the study and quality assessment was done using different assessment tools. A positive association between obesity and GERD was found. It was also found that the long-term use of proton pump inhibitors (PPIs) causes complications, so lifestyle interventions should be used more than PPIs for treating GERD, especially in obese patients. We concluded that weight loss could lead to the resolution of gastroesophageal reflux disease, and therefore, conservative measures, including dietary modifications such as reducing the consumption of alcohol, caffeine, and chocolate, behavioral changes such as smoking cessation and elevation of the head of the bed, and weight loss, should be used as first-line management for GERD. Although awareness has increased regarding the adverse effects of proton pump inhibitors, future studies are required to assess these negative effects.

Associated factors of primary snoring and obstructive sleep apnoea in patients with sleep bruxism: A questionnaire study.

BackgroundBy being aware of the associated factors of primary snoring (PS) and obstructive sleep apnoea (OSA) in sleep bruxism (SB) patients, dentists may contribute to the screening and early recognition of SB patients with PS or OSA.ObjectiveTo identify the associated factors of PS and OSA from questionnaire‐based data in SB patients.MethodsA total of 968 self‐reported SB patients (31.6% men; median age 44.5 years) were retrospectively enrolled. Self‐reported sleep‐related breathing status (viz., no sleep‐related breathing condition, PS and OSA) was the dependent variable. Independent variables were questionnaire‐based data on demographics, lifestyle, psychological status, pain and sleep.ResultsFor PS, no statistically significant associated factor was identified in analyses. For OSA, increased age (OR = 1.04 [1.03–1.06]), male gender (OR = 3.33 [2.17–5.00]), daily alcohol consumption (OR = 1.96 [1.18–3.33]), depression (OR = 1.10 [1.06–1.14]), daytime sleepiness (OR = 2.94 [1.85–4.76]) and high risk of gastroesophageal reflux disease (GERD; OR = 2.63 [1.52–4.76]) were found to be significant risk factors, while high risk of temporomandibular disorder (TMD) pain (OR = 0.51 [0.30–0.86]) and chronic pain (OR = 0.73 [0.59–0.90]) were significant protective factors. These results were confirmed in the subsequent network analysis.ConclusionWithin the limitations of this study, no associated factor is identified for PS. For OSA, dentists should keep in mind that increased age, male gender, daily alcohol consumption, depression, daytime sleepiness and high GERD risk are associated with increased OSA risk in SB patients, while high TMD‐pain risk and chronic pain are associated with decreased OSA risk in this population.

Atrophic gastritis is inversely associated with gastroesophageal reflux disease in a twin register based study.

BackgroundThe association between atrophic gastritis (AG) and symptomatic gastroesophageal reflux disease (GERD) needs to be better assessed.ObjectiveWe aimed to study this association in a twin setting, controlling for genetic and familial factors, in addition to a range of known covariates.MethodsWe performed a co‐twin control study based on the Swedish Twin Registry, including confirmed monozygotic (MZ) and dizygotic (DZ) twins. AG was determined by the measurement of serum pepsinogen I (PGI) and pepsinogen II (PGII), with different cut‐off values. GERD was defined using a structured questionnaire, by questions on symptoms of heartburn, acid regurgitation, pain behind the breastbone, and drug history. Patients were grouped into total GERD, less frequent (<1/week), and frequent GERD (≥1/week).ResultsA total of 12,533 twins were included in the study, among whom 37.7% showed less frequent GERD, and 18.7% had frequent GERD. There was an inverse association between AG and GERD, especially for frequent GERD. When PGI<30 was used as cut‐off value for AG, the odds ratio (OR) and corresponding 95% confidence interval (CI) was 0.52 (0.44, 0.62). When PGI<70 and PGI/PGII<3 was used as cut‐off value for AG, the OR (95% CI) was 0.53 (0.46, 0.63). A risk reduction for GERD was also observed in AG patients when the analysis was restricted in MZ or DZ twins.ConclusionIn this co‐twin control study from the Swedish Twin Register, AG is persistently associated with a reduced risk for GERD, after controlling for genetic and shared familial factors.

Mechanisms for the Sex-Specific Effect of H. Pylori on Risk of Gastroesophageal Reflux Disease and Barrett's Esophagus.

Mechanisms for how Helicobacter pylori infection affects risk of gastroesophageal reflux disease (GERD) and Barrett's esophagus are incompletely understood and might differ by sex. In a case-control study nested in the Melbourne Collaborative Cohort Study with 425 GERD cases and 169 Barrett's esophagus cases (identified at 2007-2010 follow-up), we estimated sex-specific odds ratios for participants who were H. pylori seronegative versus seropositive at baseline (1990-1994). To explore possible mechanisms, we (i) compared patterns of H. pylori-induced gastritis by sex using serum pepsinogen-I and gastrin-17 data and (ii) quantified the effect of H. pylori seronegativity on Barrett's esophagus mediated by GERD using causal mediation analysis. For men, H. pylori seronegativity was associated with 1.69-fold [95% confidence interval (CI), 1.03-2.75] and 2.28-fold (95% CI, 1.27-4.12) higher odds of GERD and Barrett's esophagus, respectively. No association was observed for women. H. pylori-induced atrophic antral gastritis was more common in men (68%) than in women (56%; P = 0.015). For men, 5 of the 15 per 1,000 excess Barrett's esophagus risk from being seronegative were mediated by GERD. Men, but not women, who were H. pylori seronegative had increased risks of GERD and Barrett's esophagus. A possible explanation might be sex differences in patterns of H. pylori-induced atrophic antral gastritis, which could lead to less erosive reflux for men. Evidence of GERD mediating the effect of H. pylori on Barrett's esophagus risk among men supports this proposed mechanism. The findings highlight the importance of investigating sex differences in the effect of H. pylori on risk of GERD and Barrett's esophagus in future studies.

Gastroesophageal reflux disease: risk factors, current possibilities of diagnosis and treatment optimisation

Gastroesophageal reflux disease (GERD) is one of the most common causes of health care seeking at the primary care level in many countries. At an epidemiological level, GERD has been shown to be associated with a number of risk factors: obesity, tobacco smoking, alcohol abuse, certain patterns of eating behaviour, and the use of several medications. GERD is now regarded as a heterogeneous disease and includes different phenotypes (erosive reflux disease, non-erosive reflux disease, hypersensitive oesophagus, functional heartburn), the proper diagnosis of which improves the effectiveness of therapy in patients with heartburn symptoms. Daily impedance–pH monitoring is known to be an integral part of the diagnostic algorithm for GERD and is a functional diagnostic method to record all types of refluxes entering the oesophagus regardless of pH, to assess their association with symptoms, and to determine whether patients with heartburn symptoms belong to a particular phenotype. Esophageal manometry plays a key role in the evaluation of patients with heartburn symptoms, as it helps to rule out other conditions that may mimic GERD: achalasia cardia and scleroderma esophagus. This technique is used to assess thoracic esophageal motility and sphincter function and in the assessment of patients prior to antireflux surgery or in the refractory course of GERD. The article describes in detail GERD risk factors (triggers of heartburn), as well as diagnostic aspects, taking into account a differentiated approach to patients with heartburn based on daily impedance–pH monitoring data in accordance with the current guidelines and recommendations.

Association Between Psychosocial Disorders and Gastroesophageal Reflux Disease: A Systematic Review and Meta-analysis.

Background/AimsThe incidence of gastroesophageal reflux disease (GERD) is increasing annually. Studies have suggested that psychosocial disorders may be linked to the development of GERD. However, studies evaluating the association between psychosocial disorders and GERD have been inconsistent. Thus, we conducted a systematic review and meta-analysis of observational studies that evaluated the association between psychosocial disorders and GERD.MethodsWe systematically searched the PubMed, Embase, Cochrane, and Web of Science databases until October 17, 2020. Pooled OR with 95% CI and subgroup analyses were calculated using a random-effects model. Subgroup analyses were performed to identify the sources of heterogeneity. Sensitivity analysis by one-study removal was used to test the robustness of our results.ResultsThis meta-analysis included 1 485 268 participants from 9 studies. Studies using psychosocial disorders as the outcome showed that patients with GERD had a higher incidence of psychosocial disorders compared to that in patients without GERD (OR, 2.57; 95% CI, 1.87-3.54; I2 = 93.8%; P < 0.001). Studies using GERD as an outcome showed an association between psychosocial disorders and an increased risk of GERD (OR, 2.23; 95% CI, 1.42-3.51; I2 = 97.1%; P < 0.001). The results of the subgroup analysis showed that the non-erosive reflux disease group had a higher increased risk of anxiety than erosive reflux disease group (OR, 9.45; 95% CI, 5.54-16.13; I2 = 12.6%; P = 0.285).ConclusionResults of our meta-analysis showed that psychosocial disorders are associated with GERD; there is an interaction between the two.

Inverse correlation between gastroesophageal reflux disease and atrophic gastritis assessed by endoscopy and serology.

BACKGROUND Helicobacter pylori (H. pylori) infection is known to prevent the occurrence of gastroesophageal reflux disease (GERD) by inducing gastric mucosal atrophy. However, little is known about the relationship between atrophic gastritis (AG) and GERD. AIMTo confirm the inverse correlation between AG and the occurrence and severity of GERD.METHODSIndividuals receiving health checkups who underwent upper gastrointestinal endoscopy at Seoul National University Healthcare System Gangnam Center were included. The grade of reflux esophagitis was evaluated according to the Los Angeles classification. Endoscopic AG (EAG) was categorized into six grades. Serologic AG (SAG) was defined as pepsinogen I ≤ 70 ng/mL and pepsinogen I/II ratio ≤ 3.0. The association between the extent of EAG and SAG and the occurrence and severity of GERD was evaluated using multivariate logistic regression analysis.RESULTSIn total, 4684 individuals with GERD were compared with 21901 healthy controls. In multivariate logistic regression analysis, advanced age, male sex, body mass index > 23 kg/m2, presence of metabolic syndrome, current smoking, and alcohol consumption were associated with an increased risk of GERD. Seropositivity for H. pylori immunoglobulin G antibodies was associated with a decreased risk of GERD. There was an inverse correlation between the extent of EAG and occurrence of GERD: Odds ratio (OR), 1.01 [95% confidence interval (CI): 0.90-1.14] in C1, 0.87 (0.78-0.97) in C2, 0.71 (0.62-0.80) in C3, 0.52 (0.44-0.61) in O1, 0.37 (0.29-0.48) in O2, and 0.28 (0.18-0.43) in O3. Additionally, the extent of EAG showed an inverse correlation with the severity of GERD. The presence of SAG was correlated with a reduced risk of GERD (OR = 0.49, 95%CI: 0.28-0.87, P = 0.014).CONCLUSIONThe extent of EAG and SAG exhibited strong inverse relationships with the occurrence and severity of GERD. AG followed by H. pylori infection may be independently protect against GERD.