Lars Agréus

High prevalence of gastroesophageal reflux symptoms and esophagitis with or without symptoms in the general adult Swedish population: A Kalixanda study report

Objective. Gastroesophageal reflux disease has been reported to be a common burden on health-care resources in the Western world, but its manifestations in the general population are as yet unclear. The aim of this study was to estimate the prevalence of, and to identify the risk factors for gastroesophageal reflux symptoms (GERS) and erosive esophagitis (EE) in the adult population of two Swedish municipalities. Material and methods. A random sample (n=3000) of the adult population (20–81 years of age) of two Swedish municipalities (n=21,610) was surveyed using a validated postal questionnaire assessing gastrointestinal symptoms. The response rate was 74%. A subsample (n=1000) of the responders was subsequently invited, in random order, for esophago-gastro-duodenoscopy with evaluation of GERS, risk factors and tests for Helicobacter pylori. Results. GERS were reported by 40.0% and EE was found in 15.5% of the population that had undergone endoscopy. Of those with GERS, 24.5% had EE while 36.8% of those with EE reported no GERS. Hiatus hernia and obesity remained significant risk factors for GERS and/or EE, with or without symptoms in a main effect model (OR up to 14 at EE). Those with active H. pylori infection had a higher risk of GERS without EE than those without H. pylori infection (OR=1.71 (1.23–2.38)). Conclusions. GERS and EE (of which one-third is asymptomatic) are highly prevalent in the Swedish adult population. H. pylori infection seems to play a role in the manifestations of gastroesophageal reflux.

Prevalence of oesophageal eosinophils and eosinophilic oesophagitis in adults: The population-based Kalixanda study

Background: Eosinophilic oesophagitis may be increasing but the prevalence in the general population remains unknown. Our aim was to assess this and the presence of eosinophils in the distal oesophageal epithelium in the community. Methods: Oesophagogastroduodenoscopy was performed in a random sample (n = 1000) of the adult Swedish population (mean age 54 years, 49% men). Oesophageal biopsy samples were obtained from 2 cm above, and at, the Z-line. Any eosinophil infiltration of the epithelium was defined as “eosinophils present”. Definite eosinophilic oesophagitis was defined as ⩾20, probable as 15–19, and possible as 5–14 eosinophils/high-power field (HPF, at magnification ×40) in oesophageal biopsy specimens. Results: Eosinophils were present in 48 subjects (4.8%, 95% CI 3.5 to 6.1%, mean age 54 years, 63% men), in 54% without troublesome reflux symptoms. Definite eosinophilic oesophagitis was present in four subjects (0.4%, 95% CI 0.01 to 0.8%, mean age 51 years, 75% men) and probable eosinophilic oesophagitis in seven subjects (0.7%, 95% CI 0.2 to 1.2%, mean age 58 years, 43% men). Erosive oesophagitis (OR = 2.99, 95% CI 1.58 to 5.66) and absence of dyspepsia (OR = 0.23, 95% CI 0.07 to 0.75) and Helicobacter pylori infection (OR = 0.41, 95% CI 0.19 to 0.92) were independent predictors for “eosinophils present”. Definite eosinophilic oesophagitis was associated with dysphagia (2/66 vs 2/926, p = 0.025), and probable eosinophilic oesophagitis with narrowing of the oesophageal lumen (2/15 vs 5/978, p = 0.005). Conclusions: Oesophageal eosinophils were present in nearly 5% of the general population; approximately 1% had definite or probable eosinophilic oesophagitis. Oesophageal eosinophils may be a manifestation of reflux disease in adults, but the condition is as likely to be asymptomatic and go unrecognised.

Natural history of gastroesophageal reflux disease and functional abdominal disorders: a population-based study

OBJECTIVE:Symptomatic gastroesophageal reflux disease (GERD), dyspepsia, and irritable bowel syndrome (IBS) are generally considered to be chronic conditions, but community-based studies are sparse, and long-term natural history data are unavailable. We aimed to determine the natural history of these conditions.METHODS:A representative Swedish sample (20–79 yr) completed a validated questionnaire over the preceding 3 months. The survey was repeated after 1 and 7 yr in the same target group (n = 1290, 1260, and 1065; response rates 90%, 87%, and 82%, respectively; 79% responded to all three mailings).RESULTS:The prevalence of GERD symptoms remained stable, whereas the prevalence of IBS increased over time, independent of aging. Dyspepsia decreased with advancing age. Although more than half of those with IBS reported the same symptom profile after 1 and 7 yr, there was a substantial symptom fluctuation and symptom profile flux between those reporting dyspepsia, IBS, or minor symptoms. Only a minority with GERD (<10%) changed to dyspepsia and/or IBS, or vice versa. The symptom-free patients remained symptom-free or reported only minor symptoms in ≥90% of cases.CONCLUSION:There seem to be two distinct populations of symptom reporters, those with dyspepsia or IBS, and those with GERD.

Detection of Celiac Disease and Lymphocytic Enteropathy by Parallel Serology and Histopathology in a Population-Based Study

BACKGROUND & AIMS Although serologic analysis is used in diagnosis of celiac disease, histopathology is considered most reliable. We performed a prospective study to determine the clinical, pathologic, and serologic spectrum of celiac disease in a general population (Kalixanda study). METHODS A random sample of an adult general population (n = 1000) was analyzed by upper endoscopy, duodenal biopsy, and serologic analysis of tissue transglutaminase (tTg) levels; endomysial antibody (EMA) levels were analyzed in samples that were tTg+. The cut off values for diagnosis of celiac disease were villous atrophy with 40 intraepithelial lymphocytes (IELs)/100 enterocytes (ECs). RESULTS Samples from 33 subjects were tTg+, and 16 were EMA+. Histologic analysis identified 7 of 1000 subjects (0.7%) with celiac disease; all were tTg+, and 6 of 7 were EMA+. Another 26 subjects were tTg+ (7/26 EMA+). This was addressed by a second quantitative pathology study (nested case control design) using a threshold of 25 IELS/100 ECs. In this analysis, all 13 samples that were tTg+ and EMA+ had > or =25 IELs/100 ECs. In total, 16 subjects (1.6%) had serologic and histologic evidence of gluten-sensitive enteropathy. IELs were quantified in duodenal biopsy samples from seronegative individuals (n = 500); 19 (3.8%) had >25 IELs and lymphocytic duodenosis. CONCLUSIONS Measurement of > or =25 IELs/100 ECs correlated with serologic indicators of celiac disease; a higher IEL threshold could miss 50% of cases. Quantification of tTg is a sensitive test for celiac disease; diagnosis can be confirmed by observation of > or =25 IELs/100ECs in duodenal biopsy specimens. Lymphocytic enteropathy (celiac disease and lymphocytic duodenosis) is common in the population (5.4%).

Duodenal mastocytosis, eosinophilia and intraepithelial lymphocytosis as possible disease markers in the irritable bowel syndrome and functional dyspepsia

Background  Irritable bowel syndrome (IBS) and functional dyspepsia (FD) are common functional disorders without defined pathology. Mast cells and eosinophils interact with T lymphocytes and may alter enteric nerve and smooth muscle function.

Anxiety Is Associated With Uninvestigated and Functional Dyspepsia (Rome III Criteria) in a Swedish Population-Based Study

BACKGROUND & AIMS The Rome III criteria for functional dyspepsia have been changed to include 2 distinct syndromes: postprandial distress syndrome and epigastric pain syndrome. We investigated risk factors for functional dyspepsia among the functional dyspepsia subgroups defined by the Rome III criteria. METHODS We performed a cross-sectional population-based study in a primary care setting (the Kalixanda study). A random sample (n = 2860) of the adult population from 2 northern Swedish municipalities (n = 21,610) was surveyed using a validated postal questionnaire to assess gastrointestinal symptoms (response rate, 74.2%; n = 2122). A randomly selected subgroup (n = 1001) of responders was invited to undergo an esophagogastroduodenoscopy (participation rate, 73.3%) including biopsy specimen collection, Helicobacter pylori culture and serology, and symptom assessments. RESULTS Of the 1001 subjects examined by endoscopy, 202 (20.2%; 95% confidence interval [CI], 17.7-22.7) were classified as having uninvestigated dyspepsia and 157 (15.7%; 95% CI, 13.4-18.0) as having functional dyspepsia. Major anxiety (Hospital Anxiety and Depression Scale score > or = 11) was associated with uninvestigated dyspepsia (odds ratio [OR], 3.01; 95% CI, 1.39-6.54), as was obesity (body mass index > or = 30 kg/m(2)) (OR, 1.86; 95% CI, 1.15-3.01). Major anxiety was associated with functional dyspepsia and postprandial distress syndrome (OR of 2.56 [95% CI, 1.06-6.19] and 4.35 [95% CI, 1.81-10.46], respectively), as was use of nonsteroidal anti-inflammatory drugs (OR, 2.49 [95% CI, 1.29-4.78] and 2.75 [95% CI, 1.38-5.50], respectively). Depression was not associated with any dyspepsia group. CONCLUSIONS Anxiety but not depression is linked to uninvestigated dyspepsia, functional dyspepsia, and postprandial distress syndrome but not to epigastric pain syndrome.

Gastro-oesophageal reflux symptoms and health-related quality of life in the adult general population--the Kalixanda study.

The impact of gastro‐oesophageal reflux symptoms on health‐related quality of life in the general population is poorly characterized.

Systematic review: probiotics in the management of lower gastrointestinal symptoms in clinical practice – an evidence-based international guide

Evidence suggests that the gut microbiota play an important role in gastrointestinal problems.

Association of TNFSF15 polymorphism with irritable bowel syndrome

Background Irritable bowel syndrome (IBS) is the most common gastrointestinal disorder, affecting more than 10% of the general population worldwide. Although a genetic component is suspected, unambiguous susceptibility genes have so far not been identified. This study tested the hypothesis that genes contributing to epithelial barrier integrity, control of mucosal immune responses and interactions with bacteria in the gut are associated with IBS. Methods Single nucleotide polymorphisms (SNPs) corresponding to top signals of association with Crohns disease at 30 known susceptibility loci were tested for their effect on IBS risk in 1992 individuals from two independent case–control cohorts from Sweden and the USA. Association tests included a conservative Bonferroni correction for multiple comparisons, and were also performed on specific subgroups of patients characterised by constipation (IBS-C), diarrhoea (IBS-D) or alternating constipation and diarrhoea (IBS-A). Results The Crohns disease risk allele rs4263839 G in the TNFSF15 gene was significantly associated with an increased risk of both IBS (p=2.2×10−5; OR 1.37) and more pronouncedly, IBS-C (p=8.7×10−7; OR 1.79) in the entire sample. Similar associations and risk effects of the same magnitude were observed in the two cohorts analysed separately. A correlation between rs4263839 genotype and TNFSF15 mRNA expression was detected both in peripheral blood and in rectal mucosal biopsies from healthy individuals (combined p=0.0033). Conclusions TNFSF15 is a susceptibility gene for IBS and IBS constipation. As TL1A, the protein encoded by TNFSF15, contributes to the modulation of inflammatory responses, the results support a role of immune activation in IBS.

The cost of gastro-oesophageal reflux disease, dyspepsia and peptic ulcer disease in Sweden

AbstractBackground and objective: Dyspepsia, peptic ulcer disease (PUD) and gastrooesophageal reflux disease (GORD) involve a substantial cost to Swedish society. There is a lack of up-to-date nationwide cost estimates after 1985. This study was conducted to present a comprehensive and updated cost analysis and study the change over time of the national cost of these disorders. Design and setting: Primarily, data from National Swedish databases and secondly, data from databases from the County of Uppsala for 1997 were used for the calculations and estimations. Perspective: Swedish societal perspective. Results: The total cost to Swedish society of dyspepsia, PUD and GORD in 1997 was