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

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

Third Follow-Up of the Study on Occupational Allergy Risks (SOLAR III) in Germany: Design, Methods, and Initial Data Analysis

Introduction: Asthma and allergies are complex diseases affected by genetic and environmental factors, such as occupational and psychosocial factors, as well as interactions between them. Although childhood is a critical phase in the development of asthma and allergies, few cohort studies on occupational outcomes followed up participants from childhood onwards. We present design, methods, and initial data analysis for the third follow-up of SOLAR (Study on Occupational Allergy Risks), a prospective and population-based German asthma and allergy cohort. Methods: The SOLAR cohort was initially recruited in 1995–1996 for Phase II of the German branch of the International Study of Asthma and Allergies in Childhood (ISAAC II) and followed up three times since, in 2002–2003, 2007–2009, and 2017–2018. During the third follow-up (SOLAR III), participants were between 29 and 34 years old. Since SOLAR focuses on occupational exposures, follow-ups were conducted at important points in time of the development of participants' career. To evaluate the potential of selection bias, responders and non-responders were compared based on variables from earlier study phases. In responders, frequency and pattern of missing values were examined and compared within the subsets of paper and online versions of the used questionnaires. Results: In total, 1,359 participants completed the questionnaire of the third follow-up (47.3% of eligible participants). Initially, the cohort started with 6,399 participants from the ISAAC II questionnaire study. A selection process led to a study population that is more female, higher educated, smokes less and has a higher proportion of certain asthma and allergy symptoms (also in their parents) than the initial cohort. Pattern and frequency of missing values were different for paper and online questionnaires. Discussion: The third follow-up of the SOLAR cohort offers the opportunity to analyze the course of asthma and allergies and their associations to environmental, occupational and psychosocial risk factors over more than 20 years from childhood to adulthood. Selection processes within the cohort might lead to bias that needs to be considered in future analyses

Health-related quality of life in rural children living in four European countries: the GABRIEL study

Objective: Measuring children's health-related quality of life (HRQOL) is of growing importance given increasing chronic diseases. By integrating HRQOL questions into the European GABRIEL study, we assessed differences in HRQOL between rural farm and non-farm children from Germany, Austria, Switzerland and Poland to relate it to common childhood health problems and to compare it to a representative, mostly urban German population sample (KIGGS). Methods: The parents of 10,400 school-aged children answered comprehensive questionnaires including health-related questions and the KINDL-R questions assessing HRQOL. Results: Austrian children reported highest KINDL-R scores (mean: 80.9; 95% CI [80.4, 81.4]) and Polish children the lowest (74.5; [73.9, 75.0]). Farm children reported higher KINDL-R scores than non-farm children (p=0.002). Significantly lower scores were observed in children with allergic diseases (p<0.001), with sleeping difficulties (p<0.001) and in overweight children (p=0.04). The German GABRIEL sample reported higher mean scores (age 7-10years: 80.1, [79.9, 80.4]; age 11-13years: 77.1, [74.9, 79.2]) compared to the urban KIGGS study (age 7-10years: 79.0, [78.7-79.3]; age 11-13years: 75.1 [74.6-75.6]). Socio-demographic or health-related factors could not explain differences in HRQOL between countries. Conclusions: Future increases in chronic diseases may negatively impact children's HRQO

Effect of Processing Intensity on Immunologically Active Bovine Milk Serum Proteins

Consumption of raw cow's milk instead of industrially processed milk has been reported to protect children from developing asthma, allergies, and respiratory infections. Several heat-sensitive milk serum proteins have been implied in this effect though unbiased assessment of milk proteins in general is missing. The aim of this study was to compare the native milk serum proteome between raw cow's milk and various industrially applied processing methods, i.e., homogenization, fat separation, pasteurization, ultra-heat treatment (UHT), treatment for extended shelf-life (ESL), and conventional boiling. Each processing method was applied to the same three pools of raw milk. Levels of detectable proteins were quantified by liquid chromatography/tandem mass spectrometry following filter aided sample preparation. In total, 364 milk serum proteins were identified. The 140 proteins detectable in 66% of all samples were entered in a hierarchical cluster analysis. The resulting proteomics pattern separated mainly as high (boiling, UHT, ESL) versus no/low heat treatment (raw, skimmed, pasteurized). Comparing these two groups revealed 23 individual proteins significantly reduced by heating, e.g., lactoferrin (log2-fold change = -0.37, p = 0.004), lactoperoxidase (log2-fold change = -0.33, p = 0.001), and lactadherin (log2-fold change = -0.22, p = 0.020). The abundance of these heat sensitive proteins found in higher quantity in native cow's milk compared to heat treated milk, renders them potential candidates for protection from asthma, allergies, and respiratory infections

Acetaminophen use and risk of asthma, rhinoconjunctivitis and eczema in adolescents : ISAAC Phase Three

Rationale: There is epidemiological evidence that the use of acetaminophen may increase the risk of developing asthma. Objectives: To investigate the risk of asthma and other allergic disorders associated with the current use of acetaminophen in 13- to 14-year-old children in different populations worldwide. Methods: As part of the International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three, 13- to 14-year-old children completed written and video questionnaires obtaining data on current symptoms of asthma, rhinoconjunctivitis, and eczema, and a written environmental questionnaire obtaining data on putative risk factors, including acetaminophen use in the past 12 months. Measurements and Main Results: The primary outcome measure was the odds ratio (OR) of current asthma symptoms associated with acetaminophen use calculated by logistic regression. A total of 322,959 adolescent children from 113 centers in 50 countries participated. In the multivariate analyses the recent use of acetaminophen was associated with an exposure-dependent increased risk of current asthma symptoms (OR, 1.43 [95% confidence interval, 1.33–1.53] and 2.51 [95% confidence interval, 2.33–2.70] for medium and high versus no use, respectively). Acetaminophen use was also associated with an exposure-dependent increased risk of current symptoms of rhinoconjunctivitis and eczema. Conclusions: Acetaminophen use may represent an important risk factor for the development and/or maintenance of asthma, rhinoconjunctivitis, and eczema in adolescent children.peer-reviewe