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Introduction: The concept of gut‐to‐brain communication via microbial or inflammatory pathways is gaining increased attention but genuine pathology directly linking gut perturbation to anxiety is lacking. We hypothesized that duodenal eosinophilia, as known to occur in functional dyspepsia (FD), may be an underlying cause of anxiety and may help explain the striking association between FD and anxiety. Methods: Randomly selected subjects from the national population register of Sweden completed the validated Abdominal Symptom Questionnaire; 1000 completed esophagogastroduodenoscopy and the Hospital Anxiety and Depression Scale questionnaire. Duodenal biopsies were obtained from 1st (D1) and 2nd portion (D2). Eligible subjects who underwent endoscopy (n = 887) were invited to participate in a 10‐year follow‐up study with the same questionnaires. Among endoscopy normal subjects, FD was identified by Rome criteria, and controls were symptom free. Duodenal eosinophilia was based on pre‐defined cut‐offs. Finding are reported as odds ratios (ORs) with 95% confidence interval and p‐value. Results: The study population comprised 89 cases with FD and 124 healthy controls (mean age 62 years, SD 12, 34% male). Clinical anxiety at follow‐up was elevated in those with D1 eosinophilia at baseline considering either new‐onset anxiety (OR = 4.5, 95% CI 0.8, 23.8; p = 0.08) or follow‐up anxiety adjusting for baseline anxiety (OR = 4.51 (95% CI 1.03, 19.81; p = 0.046). Conclusion: Duodenal eosinophilia may potentially be a mechanism linked to anxiety independent of FD. [ABSTRACT FROM AUTHOR]

Summary: Background: It is uncertain if functional dyspepsia (FD) or irritable bowel syndrome (IBS) are linked to smoking, and smoking cessation is not part of the routine advice provided to these patients. Aim: To assess if smoking is an independent risk factor for FD and IBS. Methods: Three population‐based endoscopy studies in Sweden with 2560 community individuals in total (mean age 51.5 years, 46% male). IBS (14.9%), FD (33.5%), and associated symptoms were assessed using the validated abdominal symptom questionnaire, and smoking (17.9%) was obtained from standardised questions during a clinic visit. The effect of smoking on symptom status was analysed in an individual person data meta‐analysis using mixed effect logistic regression, adjusted for snuffing, age and sex. Results: Individuals smoking cigarettes reported significantly higher odds of postprandial distress syndrome (FD‐PDS) (OR 10‐19 cig/day = 1.42, 95% CI 1.04‐1.98 P = 0.027, OR ≥20 cig/day = 2.16, 95% CI 1.38‐3.38, P = 0.001) but not epigastric pain. Individuals smoking 20 or more cigarettes per day reported significantly higher odds of IBS‐diarrhoea (OR = 2.40, 95% CI 1.12‐5.16, P = 0.025), diarrhoea (OR = 2.01, 95%CI 1.28‐3.16, P = 0.003), urgency (OR = 2.21, 95%CI 1.41‐3.47, P = 0.001) and flatus (OR = 1.77, 95%CI 1.14‐2.76, P = 0.012) than non‐smokers. Smoking was not associated with IBS‐constipation or IBS‐mixed. Conclusion: Smoking is an important environmental risk factor for postprandial distress syndrome, the most common FD subgroup, with over a twofold increased odds of PDS in heavy smokers. The role of smoking in IBS‐diarrhoea, but not constipation, is also likely important. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Symptomatic gastroesophageal reflux disease (GERD) is associated with a significantly increased risk of esophageal adenocarcinoma, but its natural history in the general population is poorly understood. Whether nonerosive reflux disease (NERD) is a risk factor for Barrett's esophagus (BE), the precursor of esophageal adenocarcinoma, is unknown. Furthermore, quantifying the risk of incident BE in those with untreated reflux esophagitis has not been possible. We aimed, in a prospective follow-up study with endoscopy, to evaluate the risk of BE in a cohort from the Swedish general population (the Kalixanda Study).METHODS:Those with endoscopic or histological findings suggestive of GERD and randomly half of those with NERD (n=481) were invited for follow-up investigation including endoscopy and a validated symptom questionnaire 5 years after the initial study. Multinomial logistic regression was used to estimate relative risk ratios (RRRs) and 95% confidence intervals (CIs) for change in presentation of GERD.RESULTS:Of the 405 subjects available for inclusion, endoscopy was performed in 284 (response rate 70.1%). The incidence of BE was 9.9/1,000 person-years. Of those with NERD at baseline (n=113), progression to erosive esophagitis was found in 11; 2 developed BE. Erosive esophagitis (n=90) progressed to a more severe grade in 12 and to BE in 8 cases. Erosive esophagitis at baseline was independently associated with BE at follow-up (RRR 5.2; 95% CI 1.2-22.9).CONCLUSIONS:Compared with being free of GERD at follow-up, erosive esophagitis is a major risk factor for BE (with a fivefold increased risk) after 5 years in the general population. [ABSTRACT FROM AUTHOR]

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 ≥11) was associated with uninvestigated dyspepsia (odds ratio [OR], 3.01; 95% CI, 1.39–6.54), as was obesity (body mass index ≥30 kg/m2) (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. [Copyright &y& Elsevier]

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. Aim To examine mast cell, eosinophil and intraepithelial lymphocyte populations in duodenal biopsies of subjects with IBS and FD. Methods A random sample of an adult Swedish population ( n = 1001; mean age 54 years; 51% female) underwent upper endoscopy and biopsy; 51 cases with FD and 41 cases with IBS were compared with 48 randomly selected controls. Eosinophils were identified by light microscopy; mast cells by immunocytochemistry (CD117). Intraepithelial lymphocytes were counted per 100 enterocytes. Cell counts were quantified by counting the number per high power field (HPF) in 5HPFs in the bulb (D1) and second part of duodenum (D2), summed over 5HPFs at each site. Results Cases and controls showed similar demographics. Compared to controls, IELs in IBS-constipation were significantly increased ( P = 0.005). Mast cells were significantly increased in IBS in D2 ( P < 0.001), while eosinophils were significantly increased in FD in D1 and D2 ( P < 0.001). Conclusion Duodenal mast cell hyperplasia is linked to IBS and eosinophilia to FD, and duodenal biopsy may identify subsets of these disorders. [ABSTRACT FROM AUTHOR]

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 (0R=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. [ABSTRACT FROM AUTHOR]

Background The impact of gastro-oesophageal reflux symptoms on health-related quality of life in the general population is poorly characterized. Aim To identify the frequency of troublesome reflux symptoms associated with impaired health-related quality of life in the general population. Methods A representative random sample of 3000 adult inhabitants of northern Sweden was surveyed using the validated Abdominal Symptom Questionnaire (response rate 74%). In total, 1001 random responders were endoscoped and assessed using the Short Form-36 Health Survey. Results Complete data were obtained for 999 subjects: 6% reported reflux symptoms (heartburn and/or regurgitation) daily, 14% weekly and 20% less than weekly during the previous 3 months. Compared with no reflux symptoms, a clinically relevant impairment of health-related quality of life (≥5 points and P < 0.05) was seen in all eight Short Form-36 dimensions for daily symptoms, in five dimensions for weekly symptoms and in one dimension for less than weekly symptoms. There were no meaningful differences in Short Form-36 scores between subjects with and without oesophagitis. Conclusions Most aspects of health-related quality of life were impaired in individuals with daily or weekly reflux symptoms. Troublesome reflux symptoms at least weekly may identify gastro-oesophageal reflux disease. [ABSTRACT FROM AUTHOR]

The authors' aim in this study was to explore the prevalence, symptomatology, and risk factors for peptic ulcer in a general adult population. Between December 1998 and June 2001, the authors surveyed a random sample (n = 3,000) of the adult population (n = 21,610) in two communities in northern Sweden using a validated questionnaire, the Abdominal Symptom Questionnaire (response rate = 74%). A subsample (n = 1,001) of the responders was randomly invited to undergo esophagogastroduodenoscopy and symptom assessment (response rate = 73%). The prevalence of peptic ulcer was 4.1% (20 gastric ulcers and 21 duodenal ulcers). Nausea and gastroesophageal reflux were significant predictors of peptic ulcer disease, but epigastric pain/discomfort was not. Six persons with gastric ulcer and two persons with duodenal ulcer were asymptomatic. Eight subjects with duodenal ulcer (38%) lacked evidence of current Helicobacter pylori infection. Five (25%) of the gastric ulcers and four (19%) of the duodenal ulcers were idiopathic (no use of aspirin or nonsteroidal antiinflammatory drugs, no H. pylori infection). Smoking, aspirin use, and obesity were risk factors for gastric ulcer; smoking, low-dose (≤160 mg) aspirin use, and H. pylori infection were risk factors for duodenal ulcer. Peptic ulcer disease often coexists with atypical symptoms or no symptoms at all, and idiopathic duodenal ulcer may be more common than anticipated. [ABSTRACT FROM AUTHOR]

Background: Upper oesophagogastroduodenoscopy is considered to be the gold standard for upper gastrointestinal disease assessment, but is currently seldom used in epidemiological studies. One concern is that the procedure may bias sampling among volunteers in a general adult population. The aim of this study was to explore whether the procedure affects symptom reporting. Methods: A random sample of 3000 adults aged 20-81 years (mean age 50.4), from two Swedish municipalities ( n = 21,610) was surveyed using a validated postal questionnaire (the Abdominal Symptom Questionnaire) assessing gastrointestinal symptoms. A subsample of the responders was invited, in random order, to undergo an upper endoscopy and repeated symptom reporting using the same questionnaire, as well as a serology test for Helicobacter pylori . Results: The response rate to the initial questionnaire was 74.2% and the participation rate for those eligible for the upper endoscopy was 73.3% ( n = 1001, mean age 54.0 years, 48.8% male). No major social or symptom sampling error was encountered from the selection process, with the exception of an excess of symptom reporters among the youngest subjects. The prevalence of reflux symptoms, dyspeptic symptoms and irritable bowel symptoms was 40%, 37.6% and 29.6%, respectively, which is relatively high, but in no way extreme. Conclusions: The upper endoscopy survey strategy was successful. The response rate was high and there was no major selection bias of clinical relevance. The cohort selected for this study appears to be representative of the general Swedish adult population. [ABSTRACT FROM AUTHOR]