RATIONALE Atopic diseases are commonly present in childhood. We aimed to create a novel collaborative library of individual-level participant data for research on atopic diseases from birth through adolescence, and to demonstrate its prevalences and general high-risk groups. METHODS We harmonized and standardized individual-level data of 202,475 children from 14 European and Australian pregnancy and birth cohorts participating in the EU CHILD Cohort Network. Sex, geographic region, parental history of atopic diseases, physician-diagnosed current wheezing, asthma and eczema were primarily determined by parental-reported questionnaires, and physician-diagnosed inhalant allergy by parental-reported questionnaires and/or measurement of allergic sensitization by skin prick or allergen-specific Immunoglobulin E testing. Lung function measures were obtained by spirometry and converted into an age, sex, and ethnicity-adjusted obstructive lung function phenotype (FEV1/FVC < lower limited of normal). Statistical one-stage meta-analyses were performed through the shared federated R-based platform DataSHIELD. RESULTS Across cohorts, mean prevalences of eczema and wheezing were highest in infancy (<1y) or at preschool age (1-4y) after which they gradually declined into adolescence (≥12y)(21% to 5.2% and 23% to 16%, respectively), while those of inhalant allergy and asthma were reversely present (4.9% to 18% and 6.2% to 12%, respectively)(Figure 1). The prevalence of obstructive lung function remained consistent from school age (5-11y) through adolescence (5.5% to 5.9%). Compared to girls, boys had a higher prevalence of wheezing in infancy, at preschool age and at school age (27% vs. 19%; 26% vs. 21%; 19% vs. 16%, respectively), asthma in adolescence (13% vs. 10%), eczema at school age (14% vs. 13%), and inhalant allergy in adolescence (20% vs. 15%)(p-values <0.05 for meta-analyzed χ2 test for differences in prevalences). All atopic diseases from birth until adulthood were evenly present among children from Northern European/Western European/Australian and Southern European regions. Children with a family history of atopic diseases more often had wheezing in infancy and at preschool age, asthma in adolescence, eczema at school age and in adolescence, and inhalant allergy in adolescence than those without a family history of atopic diseases (p-values <0.05). CONCLUSION Prevalences of atopic diseases vary from birth through adolescence and are more commonly present among boys and children with a family history of atopic diseases. The novel developed collaborative library of individual-level participant data could be used as a resource for meta-analyses on the early origins of atopic diseases (https://data-catalogue.molgeniscloud.org/catalogue/ssr-catalogue/EUChildNetwork).

Abstract Background The pathogenesis of inflammatory bowel disease (IBD) has not been fully elucidated. The aim of this study was to analyze the pregnancy period, perinatal period, and infancy period risk factors for IBD in a well-characterized birth cohort from Northern Finland. Methods The Northern Finland Birth Cohort 1966 (NFBC1966) population comprises mothers living in the two northernmost provinces of Finland, Oulu, and Lapland, with dates of delivery between Jan 1st and Dec 31st, 1966 (12 055 mothers, 12 058 live-born children, 96.3% of all births during 1966). IBD patients were identified using hospital registries (from 1966 to 2020) and Social Insurance Institution (SII) registry reimbursement data for IBD drugs (from 1978 to 2016). The data were analyzed by Fisher’s exact test and logistic regression. Results In total, 6972 individuals provided informed consent for the use of combined SII and hospital registry data. Of those, 154 (2.1%) had IBD (113 [1.6%] had ulcerative colitis (UC), and 41 (0.6%) had Crohn’s disease (CD)). According to multivariate analysis, maternal smoking > 10 cigarettes/day during pregnancy was associated with a nearly 6-fold increased risk of CD in the offspring (OR 5.78, 95% CI 1.70–17.3). Breastfeeding (OR = 0.18, 95% CI 0.08–0.44) and iron supplementation during the first year of life (OR = 0.43, 95% CI 0.21–0.89) were negatively associated with CD. Conclusions Smoking during pregnancy was associated with the risk of CD while Breastfeeding and oral iron supplementation at infancy were negatively associated with the risk of CD later in life.

The majority of the world population carry the gastric pathogen Helicobacter pylori. Fortunately, most individuals experience only low-grade or no symptoms, but in many cases the chronic inflammatory infection develops into severe gastric disease, including duodenal ulcer disease and gastric cancer. Here we report on a protective mechanism where H. pylori attachment and accompanying chronic mucosal inflammation can be reduced by antibodies that are present in a vast majority of H. pylori carriers. These antibodies block binding of the H. pylori attachment protein BabA by mimicking BabA's binding to the ABO blood group glycans in the gastric mucosa. However, many individuals demonstrate low titers of BabA blocking antibodies, which is associated with an increased risk for duodenal ulceration, suggesting a role for these antibodies in preventing gastric disease.

Recombinant sequences of the SARS-CoV-2 Omicron variant were detected in surveillance samples collected in north-western Finland in January 2022. We detected 191 samples with an identical genome arrangement in weeks 3 to 11, indicating sustained community transmission. The recombinant lineage has a 5'-end of BA.1, a recombination breakpoint between orf1a and orf1b (nucleotide position 13,296-15,240) and a 3'-end of BA.2 including the S gene. We describe the available genomic and epidemiological data about this currently circulating recombinant XJ lineage.

Helicobacter pylori lives in the human stomach and has a population structure resembling that of its host. However, H. pylori from Europe and the Middle East trace substantially more ancestry from modern African populations than the humans that carry them. Here, we use a collection of Afro-Eurasian H. pylori genomes to show that this African ancestry is due to at least three distinct admixture events. H. pylori from East Asia, which have undergone little admixture, have accumulated many more non-synonymous mutations than African strains. European and Middle Eastern bacteria have elevated African ancestry at the sites of these mutations, implying selection to remove them during admixture. Simulations show that population fitness can be restored after bottlenecks by migration and subsequent admixture of small numbers of bacteria from non-bottlenecked populations. We conclude that recent spread of African DNA has been driven by deleterious mutations accumulated during the original out-of-Africa bottleneck.

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.

BACKGROUND/AIM:Prompted by the increasing demand of non-invasive diagnostic tools for screening of gastric cancer (GC) risk conditions, i.e., atrophic gastritis (AG) and Helicobacter pylori (Hp) infection, the GastroPanel® test (GP: biomarker panel of PGI, PGII, G-17, Hp IgG ELISA) that was developed in the early 2000's, was recently updated to a new-generation (unified GP) test version. This clinical validation study evaluated the diagnostic accuracy of the new-generation GP test in detection of AG and Hp among gastroscopy referral patients in a University Clinic.PATIENTS AND METHODS:Altogether, 522 patients were enrolled among the patients referred for gastroscopy at the Gastro Center, Oulu University Hospital (OUH). All patients underwent gastroscopy with biopsies classified using the Updated Sydney System (USS), and blood sampling for GP testing.RESULTS:Biopsy-confirmed AG was found in 10.2% (53/511) of the patients. The overall agreement between the GP and the USS classification was 92.4% (95%CI=90.0-94.6%), with the weighted kappa (κw) of 0.861 (95%CI=0.834-0.883). In ROC analysis using moderate/severe AG of the corpus (AGC2+) as the endpoint, AUC=0.952 (95%CI=0.891-1.000) and AUC=0.998 (95%CI=0.996-1.000) for PGI and PGI/PGII, respectively. Hp IgG antibody ELISA detected biopsy-confirmed Hp-infection with AUC=0.993 (95%CI=0.987-0.999).CONCLUSION:The new generation GastroPanel® is a precise test for non-invasive diagnosis of atrophic gastritis and Hp-infection in dyspeptic patients referred for diagnostic gastroscopy.

SummaryBackgroundIt 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.AimTo assess if smoking is an independent risk factor for FD and IBS.MethodsThree 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.ResultsIndividuals 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.ConclusionSmoking 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.

Whilst intraepithelial lymphocytes (IELs) are considered normal within the distal esophageal mucosa, they have an increasingly recognised role in the pathogenesis of reflux esophagitis, and IEL quantification establishes the diagnosis of lymphocytic esophagitis. Knowledge regarding the upper limit of a normal IEL count in health is lacking. We studied 117 non-healthcare seeking adult volunteers from a random community sample (the Kalixanda study) with esophageal biopsies 2 cm above the gastroesophageal junction. Subjects were divided into four groups based on the presence or absence of gastro-esophageal reflux symptoms and/or esophagitis on endoscopy. Asymptomatic subjects with no endoscopic esophagitis were selected as controls, and the cell counts in this group were used to define the upper limit of normal of IELs, eosinophils and neutrophils. The entire sample was used to identify independent predictors of increased cellular counts by logistic regression analysis. None of the healthy controls had an IEL count of more than three per five high power fields (HPF), and therefore this was considered as the upper limit of normal; no controls had eosinophils or neutrophils in esophageal biopsies. Independent predictors of an elevated IEL count were spongiosis on histology (OR 11.17, 95% CI 3.32-37.58, P < 0.01) and current smoking (OR 4.84, 95% CI 1.13-2.71, P = 0.03). A receiver operating characteristics analysis concluded that a threshold of 3 IELs/5HPFs performs best in predicting reflux symptoms when a normal esophageal mucosa is visualized on endoscopy (sensitivity = 100.0%, specificity = 35.2%). The healthy esophageal mucosa does not contain more than three IELs per five HPF in the distal esophagus.

BackgroundThere is a need for effective and cost-effective interprofessional care models that support older people to maintain their quality of life (QoL) and physical performance to live longer independently in their own homes.ObjectivesThe objectives were to evaluate effectiveness, QoL and physical performance, and cost-utility of a people-centred care model (PCCM), including the contribution of clinically trained pharmacists, compared with that of usual care in primary care.MethodsA randomised controlled trial (RCT) with a two-year follow-up was conducted. The participants were multimorbid community-living older people, aged ≥75 years. The intervention comprised an at-home patient interview, health review, pharmacist-led clinical medication review, an interprofessional team meeting, and nurse-led care coordination and health support. At the baseline and at the 1-year and 2-year follow-ups, QoL (SF-36, 36-Item Short-Form Health Survey) and physical performance (SPPB, Short Performance Physical Battery) were measured. Additionally, a physical dimension component summary in the SF-36 was calculated. The SF-36 data were transformed into SF-6D scores to calculate quality-adjusted life-years (QALYs). Healthcare resource use were collected and transformed into costs. A healthcare payer perspective was adopted. Incremental cost-effectiveness ratio (ICER) was calculated, and one-way sensitivity analysis was performed.ResultsNo statistically or clinically significant differences were observed between the usual care (n = 126) and intervention group (n = 151) patients in their QoL; at the 2-year follow-up the mean difference was −0.02, (95 % CI -0.07; 0.04,p = 0.56). While the mean difference between the groups in physical performance at the 2-year follow-up was −1.02, (−1.94;-0.10,p = 0.03), between the physical component summary scores it was −7.3, (−15.2; 0.6,p = 0.07). The ICER was −73 638€/QALY, hence, the developed PCCM dominated usual care, since it was more effective and less costly.ConclusionsThe cost-utility analysis showed that the PCCM including pharmacist-led medication review dominated usual care. However, it had no effect on QoL and the effect towards physical performance remained unclear.

Linked ContentThis article is linked to Ronkainen et al and Kanno and Moayyedi papers. To view these articles, visit https://doi.org/10.1111/apt.15308 and https://doi.org/10.1111/apt.15388.

Functional dyspepsia (FD) is a common condition in the population.It is associated with duodenal eosinophilia 1 and it has been shown that anxiety at baseline is associated with new-onset functional dyspepsia in long term. 2 Innate immunity response is linked with gutbrain/brain-gut regulation and psychological distress. 3Our aim was to investigate whether FD (Rome III) is associated with new-onset anxiety and/or depression and if this can be predicted by duodenal inflammation in a population based 10-year follow-up study.Methods: Participants of the study (n=3000) were randomly selected from the national Swedish population register and surveyed in 1998 by a validated abdominal symptom questionnaire (ASQ) and hospital anxiety and depression scale (HADS).1000 individuals were randomly selected to complete an esophagogastroduodenoscopy in 1999-2001.All eligible from the latter cohort (n=887, response rate 79%) were invited to a follow-up in 2010 with the ASQ and HADS.In a case-control study of 213 subjects (FD vs. healthy controls), histology from the duodenum was evaluated at baseline (the pre-specified cut off being the mean, 23 eosinophils in duodenal bulb (D1) and 24 eosinophils in second part of the duodenum (D2)) and the possible association of FD and duodenal eosinophilia to incident anxiety was analysed.Data were analyzed by Fisher's exact test and logistic regression.Results: FD was reported by 89 subjects (42%), duodenal eosinophilia in D1 was found in 78 subjects (37%) and in 84 subjects in D2 (39%) at baseline.Incident anxiety was found in 12 subjects (6%) and depression only in 2 subjects (1%).Incident anxiety was associated with baseline functional dyspepsia (10/83 vs. 2/116, p=0.004), especially postprandial distress syndrome (10/65 vs. 2/134, p<0.001) but not with epigastric pain syndrome (1/27 vs. 11/172, p= 1.0).Incident anxiety was also associated with duodenal eosinophilia in D1 at baseline (9/ 75 vs.3/124, p=0.011,OR=5.2, 95% CI 1.31-20.4,adjusting for age, gender and FD).Conclusions: Incident anxiety is significantly associated with baseline FD and duodenal eosinophilia is associated with a 5-fold increased risk of anxiety in a 10-year follow-up supporting the concept that mucosal immune system can regulate the bidirectional gutbrain communication. 1.

Summary Background It is unexplained why functional dyspepsia and gastro‐oesophageal reflux disease (GERD) overlap more often than expected by chance. Post‐prandial distress syndrome has been linked to impaired gastric fundic accommodation which may induce increased transient lower oesophageal sphincter relaxations and consequent GERD. Duodenal eosinophilia has been linked to functional dyspepsia and post‐prandial distress syndrome. Aim To identify if there is an association between duodenal eosinophilia in functional dyspepsia and symptoms of GERD and whether post‐prandial distress syndrome or epigastric pain syndrome are associated with new onset GERD. Methods Participants (n = 1000) were randomly selected from the national Swedish population register and surveyed by questionnaires and oesophagogastroduodenoscopy in 1999‐2001. All eligible subjects (n = 887) were invited to a follow‐up study in 2010 (response rate 79%). In a case‐control study of 213 subjects (functional dyspepsia vs healthy controls), histology from the duodenum was evaluated at baseline and the possible association of eosinophilia to new onset GERD symptoms was analysed. Results Functional dyspepsia (OR 7.6; 95% CI 2.93‐19.4, P < 0.001) and post‐prandial distress syndrome at baseline (OR 9.0, 95% CI 3.36‐24.0, P < 0.001) were associated with an increased risk of GERD at follow‐up. Eosinophilia in the second part of duodenum only was independently associated with an increased risk of GERD amongst those with functional dyspepsia (OR 4.2; 95% CI 1.2‐4.77, P = 0.024) and post‐prandial distress syndrome at baseline (OR 6.0; 95% CI 1.50‐23.6, P = 0.011), respectively. Conclusions Duodenal eosinophilia is associated with increased risk of GERD at 10‐year follow‐up in those with functional dyspepsia and post‐prandial distress syndrome at baseline. Duodenal eosinophilia may explain the link between GERD and functional dyspepsia, suggesting subsets of functional dyspepsia and GERD may be part of the same disease spectrum.

BackgroundIrritable bowel syndrome (IBS) shows genetic predisposition, however, large-scale, powered gene mapping studies are lacking. We sought to exploit existing genetic (genotype) and epidemiological (questionnaire) data from a series of population-based cohorts for IBS genome-wide association studies (GWAS) and their meta-analysis. MethodsBased on questionnaire data compatible with Rome III Criteria, we identified a total of 1335 IBS cases and 9768 asymptomatic individuals from 5 independent European genotyped cohorts. Individual GWAS were carried out with sex-adjusted logistic regression under an additive model, followed by meta-analysis using the inverse variance method. Functional annotation of significant results was obtained via a computational pipeline exploiting ontology and interaction networks, and tissue-specific and gene set enrichment analyses. Key ResultsSuggestive GWAS signals (P5.0x10(-6)) were detected for 7 genomic regions, harboring 64 gene candidates to affect IBS risk via functional or expression changes. Functional annotation of this gene set convincingly (best FDR-corrected P=3.1x10(-10)) highlighted regulation of ion channel activity as the most plausible pathway affecting IBS risk. Conclusion & InferencesOur results confirm the feasibility of population-based studies for gene-discovery efforts in IBS, identify risk genes and loci to be prioritized in independent follow-ups, and pinpoint ion channels as important players and potential therapeutic targets warranting further investigation.