Polymorphisms in the bradykinin B2 receptor gene and childhood asthma

Bradykinin has been suggested as one of the key mediators of bronchial asthma. Polymorphisms with a potential functional relevance have been described in the B2 bradykinin receptor gene. Study of these polymorphisms in 77 children with asthma and 73 controls revealed no association. However, when comparing the asthmatics according to their age at onset (before and after age 4), the exon 1 allele BE1-2G was significantly associated with late-onset asthma (p <0.05). Since BE1-2G has previously been shown to lead to a higher transcription rate of the B2 receptor, this result warrants further investigation of the role of bradykinin in conferring susceptibility to pediatric asthma

A comprehensive analysis of interleukin-4 receptor polymorphisms and their association with atopy and IgE regulation in childhood

Background: The interleukin (IL) 4/IL13 pathway is involved in the regulation of IgE production associated with atopic diseases. Numerous polymorphisms have been identified in the coding region of the IL4 receptor alpha chain (IL4Ra) and previous association studies have shown conflicting results. Based on their putative functional role, polymorphisms A148G, T1432C and A1652G, located in the coding region of IL4Ra, were selected for association and haplotype studies in a large German population sample (n = 1,120). Methods: Genotyping was performed using allele-specific PCR and restriction-enzyme-based assays. Haplotypes were estimated, and population-derived IgE percentiles (50% IgE >60 IU/ml, 66% IgE >115 IU/ml and 90% IgE >457 IU/ml) were calculated as outcome variables in a haplotype trend regression analysis. Results: In our population, only polymorphism T1432C showed a trend for a protective effect against atopic rhinitis ( odds ratio, OR: 0.52, 95% confidence interval, CI: 0.26 - 1.02, p = 0.05). When haplotypes were calculated, one haplotype was significantly associated with elevated serum IgE levels at the 50th percentile ( OR 1.60, 95% CI 1.08 - 2.37, p = 0.02). Conclusions: These data indicate that IL4Ra polymorphisms, although suggested to be functionally relevant by in vitro studies, have only a minor influence on IgE regulation in our large population sample. Copyright (C) 2004 S. Karger AG, Basel

NetCoMi: network construction and comparison for microbiome data in R

MOTIVATION Estimating microbial association networks from high-throughput sequencing data is a common exploratory data analysis approach aiming at understanding the complex interplay of microbial communities in their natural habitat. Statistical network estimation workflows comprise several analysis steps, including methods for zero handling, data normalization and computing microbial associations. Since microbial interactions are likely to change between conditions, e.g. between healthy individuals and patients, identifying network differences between groups is often an integral secondary analysis step. Thus far, however, no unifying computational tool is available that facilitates the whole analysis workflow of constructing, analysing and comparing microbial association networks from high-throughput sequencing data. RESULTS Here, we introduce NetCoMi (Network Construction and comparison for Microbiome data), an R package that integrates existing methods for each analysis step in a single reproducible computational workflow. The package offers functionality for constructing and analysing single microbial association networks as well as quantifying network differences. This enables insights into whether single taxa, groups of taxa or the overall network structure change between groups. NetCoMi also contains functionality for constructing differential networks, thus allowing to assess whether single pairs of taxa are differentially associated between two groups. Furthermore, NetCoMi facilitates the construction and analysis of dissimilarity networks of microbiome samples, enabling a high-level graphical summary of the heterogeneity of an entire microbiome sample collection. We illustrate NetCoMi's wide applicability using data sets from the GABRIELA study to compare microbial associations in settled dust from children's rooms between samples from two study centers (Ulm and Munich). AVAILABILITY R scripts used for producing the examples shown in this manuscript are provided as supplementary data. The NetCoMi package, together with a tutorial, is available at https://github.com/stefpeschel/NetCoMi. CONTACT Tel:+49 89 3187 43258; [email protected]. SUPPLEMENTARY INFORMATION Supplementary data are available at Briefings in Bioinformatics online

Diverging prevalences and different risk factors for childhood asthma and eczema: a cross-sectional study

Objective To compare the prevalences of and risk factors for asthma, wheeze, hay fever and eczema in primary schoolchildren in Aberdeen in 2014. Design Cross-sectional survey. Setting Primary schools in Aberdeen, North-East Scotland. Participants Children in Scottish school years primary 1–7 were handed a questionnaire by their class teacher to be completed by their parents and returned to the researchers by post or online. Main outcome measures Lifetime history of asthma, eczema and hay fever, and recent history of wheeze. Results 41 schools agreed to participate (87%). 11 249 questionnaires were distributed and 3935 returned (35%). A parent-reported lifetime history of asthma, eczema and hay fever was present in 14%, 30% and 24% of children, respectively. The odds of lifetime asthma increased with age (OR 1.1 per year, 95% CI 1.1 to 1.2), male sex (OR 1.89, 95% CI 1.4 to 2.3), parental smoking (OR 1.7, 95% CI 1.2 to 2.3) and eczema (OR 6.6, 95% CI 5.2 to 8.4). Prevalence of recent wheeze was also reported to be 14% and was positively associated with male sex, parental smoking and eczema. In contrast, parental eczema was the only identified predictor of childhood eczema risk. Conclusions The lifetime prevalence of asthma in primary schoolchildren was 14% in this survey, approximately half the prevalence of eczema. We report diverging prevalences in relation to previous studies in our locality, and different risk factors for asthma and eczema. These findings suggest that asthma and eczema are unlikely to have a common origin

Comparison of a pediatric practice-based therapy and an interdisciplinary ambulatory treatment in social pediatric centers for migraine in children: a nation-wide randomized-controlled trial in Germany: \textquotedblmoma - modules on migraine activity\textquotedbl

BACKGROUND Migraine is common in childhood, peaks in adolescents and persists into adulthood in at least 40% of patients. There is need for early interventions to improve the burden of disease and, if possible, reduce chronification. The aim of the project is to compare two types of ambulatory treatment strategies regarding their effect on headache days and quality of life in 6 to 11 year old children with migraine: 1) the routine care in pediatricians' practices (intervention group A) and 2) a structured interdisciplinary multimodal intervention administered at social pediatric centers (intervention group B). METHODS The study is a nation-wide cluster-randomized study. Based on the postal codes the regions are randomly assigned to the two intervention-strategies. Children with migraine are recruited in the pediatric practices, as common outpatient-care in the German health-care system. Parents rate headache frequency, intensity and acute medication intake at a daily basis via a digital smartphone application specifically designed for the study. Migraine-related disability and quality of life are assessed every 3 months. Study duration is 9 months for every participant: 3 months of baseline at the pediatric practice (both groups); 3 months of intervention at the pediatric practice (intervention group A) or at the social pediatric center (intervention group B), respectively; 3 months of follow-up at the pediatric practice (both groups). DISCUSSION Results of the planned comparison of routine care in pediatric practices and interdisciplinary social pediatric centers will be relevant for treatment of children with migraine, both for the individual and for the health care system. TRIAL REGISTRATION The study was approved by the ethics committee at the Ludwig-Maximilians-University Munich (number 18-804) and was retrospectively registered on 27 April 2021 in the WHO approved German Clinical Trials Register (number DRKS00016698 )

Unifying candidate gene and GWAS Approaches in Asthma.

The first genome wide association study (GWAS) for childhood asthma identified a novel major susceptibility locus on chromosome 17q21 harboring the ORMDL3 gene, but the role of previous asthma candidate genes was not specifically analyzed in this GWAS. We systematically identified 89 SNPs in 14 candidate genes previously associated with asthma in >3 independent study populations. We re-genotyped 39 SNPs in these genes not covered by GWAS performed in 703 asthmatics and 658 reference children. Genotyping data were compared to imputation data derived from Illumina HumanHap300 chip genotyping. Results were combined to analyze 566 SNPs covering all 14 candidate gene loci. Genotyped polymorphisms in ADAM33, GSTP1 and VDR showed effects with p-values <0.0035 (corrected for multiple testing). Combining genotyping and imputation, polymorphisms in DPP10, EDN1, IL12B, IL13, IL4, IL4R and TNF showed associations at a significance level between p = 0.05 and p = 0.0035. These data indicate that (a) GWAS coverage is insufficient for many asthma candidate genes, (b) imputation based on these data is reliable but incomplete, and (c) SNPs in three previously identified asthma candidate genes replicate in our GWAS population with significance after correction for multiple testing in 14 genes

Early life exposure to farm animals and symptoms of asthma, rhinoconjunctivitis and eczema : an ISAAC Phase Three study

We are grateful to the children and parents who willingly cooperated and participated in ISAAC Phase Three and the coordination and assistance by the school staff is sincerely appreciated. The authors also acknowledge and thank the many funding bodies throughout the world that supported the individual ISAAC centres and collaborators and their meetings. The funders of the study had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.Background: Associations between early life exposure to farm animals and respiratory symptoms and allergy in children have been reported in developed countries, but little is known about such associations in developing countries. Objective: To study the association between early life exposure to farm animals and symptoms of asthma, rhinoconjunctivitis and eczema in a worldwide study. Methods: Phase Three of the International Study of Asthma and Allergies in Childhood (ISAAC) was carried out in 6- to 7-year-old children in urban populations across the world. Questions about early life exposure to farm animals (at least once/week) were included in an additional questionnaire. The association between such exposures and symptoms of asthma, rhinoconjunctivitis and eczema was investigated with logistic regression. Adjustments were made for gender, region of the world, language, gross national income and 10 other subject-specific covariates. Results: A positive association was found between early exposure to farm animals and the prevalence of symptoms of asthma, rhinoconjunctivitis and eczema, especially in non-affluent countries. In these countries, odds ratios (ORs) for 'current wheeze', 'farm animal exposure in the first year of life' and 'farm animal exposure in pregnancy' were 1.27 [95% confidence interval (CI) 1.12-1.44] and 1.38 (95% CI 1.21-1.58), respectively. The corresponding ORs for affluent countries were 0.96 (95% CI 0.86-1.08) and 0.95 (95% CI 0.84-1.08), respectively. Conclusion: Exposure to farm animals during pregnancy and in the first year of life was associated with increased symptoms of asthma, rhinoconjunctivitis and eczema in 6- to 7-year-old children living in non-affluent but not in affluent countries.peer-reviewe