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Biomedical subjects

Stephan K Weiland

Publications and source records attributed to Stephan K Weiland.

At least 19 recordsLinked to original sources

Burden of overweight in Germany: prevalence differences between former East and West German children.

BACKGROUND: Given the increasing prevalence of childhood overweight, we aimed to quantify the population burden and evaluate potential regional differences in anthropometric characteristics and prevalence of overweight in fourth graders in two German cities. METHODS: Data were analysed from a cross-sectional school-based study conducted in 1995-96 in Dresden (former East Germany) and Munich (former West Germany) as part of the International Study of Asthma and Allergies in Childhood. Height and weight of the children were measured, and the parents completed a questionnaire. 2474 children age 9-10 years provided anthropometric data. Overweight was defined based on the age-specific and gender-specific international cut-off values for body mass index. RESULTS: Dresden children were on average 1.2 kg lighter and >1 cm taller than their Munich peers. The prevalence of overweight in Dresden was 15.2% in girls and 14.2% in boys compared with 24 and 22.2%, respectively, in Munich. Differences were observed between Dresden and Munich with respect to the proportion of children of non-German nationality, household smoking, breastfeeding practices, and individual dietary behaviours. Even in combination these factors were not able to explain entirely the between-city overweight differences. CONCLUSIONS: A substantial proportion of pre-adolescent children in Germany is now considered overweight with marked regional differences in prevalence. Comparison of population-level factors indicate that other unmeasured determinants of overweight may be responsible for the marked differences in the prevalence of overweight.

Body Mass Index↗

A cluster-randomized trial on smoking cessation in German student nurses.

OBJECTIVES: To evaluate the effect of a specific intervention on smoking cessation in health professionals. METHODS: Between 2003 and 2004, a cluster-randomized trial was performed in 32 schools of nursing with 956 student nurses in Southwest Germany. Students in the intervention group received three teaching units each lasting 1 day on how to give advice to people who want to stop smoking. The program addressed only nurses' professional role and not their individual smoking behavior. After a follow-up of 13 months, the change in smoking status was determined. Secondary endpoints included changes of smoking-related factors like stages of smoking or knowledge about health risks. RESULTS: Change of smoking status in the desired direction (stopping smoking or not starting smoking) occurred less often in the intervention than in the control group, but the difference did not reach statistical significance (odds ratio 0.69, 95% confidential interval: 0.43, 1.10). The program was successful in delivering medical knowledge (P=0.0056) and in enhancing competence in giving advice to smokers (P<0.0001). CONCLUSIONS: The applied approach is able to improve student nurses' medical knowledge and to augment their competence in giving advice to smokers, but it is not an effective strategy to reduce their own smoking behavior.

Adult↗

IL-4/IL-13 pathway genetics strongly influence serum IgE levels and childhood asthma.

BACKGROUND: IgE production, a hallmark of asthma and atopic disease, may be under genetic control. Genes of the IL-4 and IL-13 pathway, central for IgE regulation, have so far only been assessed in studies of single gene effects. OBJECTIVE: Here we analyzed combined extended haplotypes involving IL-4, IL-13, their shared receptor chain IL-4Ralpha, and the intracellular signal transducer and activator of transcription, STAT6, to assess the combined effect of single nucleotide polymorphisms in this important immunological signaling pathway. METHODS: We genotyped a large cross-sectional population of 1120 children age 9 to 11 years for 18 polymorphisms in the respective genes of the IL-4/IL-13 pathway. One polymorphism per gene was selected because of its putative functional role, and extended haplotypes were built in a stepwise procedure where gene-by-gene interactions were assessed by using a Cordell model. RESULTS: Combining polymorphisms in all 4 major pathway genes in a stepwise procedure, the risk for high serum IgE levels increased 10.8-fold (P = .02) and the risk for the development of asthma increased by a factor of 16.8-fold (P = .005) compared with the maximum effect of any single polymorphism. Significant interactions in a model with additive and dominant effects, for both pair and triplet combinations for asthma (lowest P = .005), and for pairs of polymorphisms in IgE regulation were observed (lowest P = .054). CONCLUSION: These data indicate that only the combined analyses of genetic alterations in the IL-4/IL-13 pathway reveal its actual significance to the development of atopy and childhood asthma.

Asthma↗

Social inequality in perceived environmental exposures in relation to housing conditions in Germany.

In Germany the impact of socioeconomic factors on environmental exposures and adverse housing conditions has been rarely studied up to now. The aim of our study was to assess whether and, if yes, how perceived exposure to noise and air pollution is influenced by socioeconomic status in Germany. We used data from a large-scale population-based survey. In this survey, data on perceived exposure to noise and air pollution and on socioeconomic status and housing conditions were collected on an individual basis. The study population consisted of 7,275 adults aged 17-98 years (40% women), each representing the head of one household. For the association between perceived environmental exposure and social factors confounder-adjusted odds ratios (OR) with 95% confidence intervals were calculated by binary or ordinal logistic regression. In bivariate analyses subjects with non-German nationality, East Germans, respondents with low income, those with lower educational and occupational status, and subjects living in adverse housing conditions were more likely to report being highly exposed. In multivariate analyses high perceived exposure to noise was associated with low household income (OR 1.52 [95% CI 1.13-2.05] lowest versus highest income group). Perceived air pollution exposure was also related to household income (1.67 [1.14-2.44] lower middle versus highest income group). Further associated variables were need for renovation of the house, type of house, and type of neighborhood. This study shows that in Germany, as in other industrial countries, environmental exposures are distributed unequally and that especially economic differences play important roles.

Adolescent↗

G-Protein-coupled receptor polymorphisms are associated with asthma in a large German population.

RATIONALE: Recently, a new asthma susceptibility gene, GPRA (G-protein-related receptor for asthma), has been identified by positional cloning. Initial association studies in a Finnish and Canadian population suggested an association with asthma and elevated serum IgE levels. OBJECTIVE: In a large, nested case-control study, associations between GPRA polymorphisms, asthma, and serum IgE levels were analyzed. METHODS: Using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) technology, 1,872 German children aged 9 to 11 years (including 624 children with asthma and/or bronchial hyperresponsiveness) were genotyped for seven polymorphisms in the GPRA gene. MEASUREMENTS: Hardy-Weinberg equilibrium was assessed, and association studies with single nucleotide polymorphisms (SNPs) and haplotypes were performed. MAIN RESULTS: SNP 546333 increased the risk for asthma (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.04-1.88; p = 0.025) and concomitant asthma and bronchial hyperresponsiveness (BHR; OR, 2.38; 95% CI, 1.22-4.66; p = 0.009). Also, SNP 585883 was associated with asthma (OR, 1.34; 95% CI, 1.04-1.72; p = 0.022) and asthma in combination with BHR (OR, 2.71; 95% CI, 1.45-5.09; p = 0.001). Furthermore, SNP 585883 was associated with elevated serum IgE levels (OR, 1.63; 95% CI, 1.10-2.42; p = 0.015). Haplotype combinations of risk alleles increased the OR for asthma to 1.83 (95% CI, 1.08-3.08; p = 0.024) and for asthma and concomitant BHR to OR 3.51 (95% CI, 1.08-11.37; p = 0.036). CONCLUSIONS: These results indicate that GPRA polymorphisms increase the susceptibility for asthma and BHR, and to a lesser degree for the elevation of serum IgE, in a German population, confirming initial observations in other white populations.

Analysis of Variance↗

NOD1 variation, immunoglobulin E and asthma.

Asthma is a familial inflammatory disease of the airways of the lung. Microbial exposures in childhood protect against asthma through unknown mechanisms. The innate immune system is able to identify microbial components through a variety of pattern-recognition receptors (PRRs). NOD1 is an intracellular PRR that initiates inflammation in response to bacterial diaminopimelic acid (iE-DAP). The NOD1 gene is on chromosome 7p14, in a region that has been genetically linked to asthma. We carried out a systematic search for polymorphism in the gene. We found an insertion-deletion polymorphism (ND(1)+32656) near the beginning of intron IX that accounted for approximately 7% of the variation in IgE in two panels of families (P<0.0005 in each). Allele*2 (the insertion) was associated with high IgE levels. The same allele was strongly associated with asthma in an independent study of 600 asthmatic children and 1194 super-normal controls [odds ratio (OR) 6.3; 95% confidence interval (CI) 1.4-28.3, dominant model]. Differential binding of the two ND(1)+32656 alleles was observed to a protein from nuclei of the Calu 3 epithelial cell line. In an accompanying study, the deletion allele (ND(1)+32656*1) was found to be associated with inflammatory bowel disease. The results indicate that intracellular recognition of specific bacterial products affects the presence of childhood asthma.

Adaptor Proteins, Signal Transducing↗

Socioeconomic factors in EU-funded studies of children's environmental health.

We performed a survey on socioeconomic factors in 27 studies of children's environmental health funded by EU FP4 and FP5. Parental education was the most common measure (74%). Socioeconomic factors were predominantly considered as confounder (74%) and less often as effect modifier (33%) or independent variable (37%). The awareness of the need to study the impact of socioeconomic factors further seems to have increased in recent years.

Child↗

Margarine consumption, asthma, and allergy in young adults: results of the German National Health Survey 1998.

PURPOSE: To examine whether frequent intake of margarine is associated with allergy prevalence in adults using data of a representative national health survey. METHODS: Data on 7124 subjects aged 18 to 79 years were obtained from the German National Health Survey 1998. Confounder-adjusted odds ratios (aOR) with 95% confidence intervals (CI) were calculated by multiple logistic regression, using the frequency of intake of low-fat butter, regular and low-fat margarine as explanatory variable in relation to frequent intake of regular butter as reference group. RESULTS: Frequent intake of margarine of any kind was positively associated with current asthma during the past 12 months in young adults aged 18 to 29 years (aOR, 2.33; 95% CI, 1.03-5.26). In subgroup analysis, the positive association was confined to frequent intake of low-fat margarine (4.51; 1.78-11.43) or the combination of low-fat margarine and low-fat butter (4.79; 1.84-12.44). Consumption of margarine of any kind was not related to hay fever, atopic dermatitis, and atopic sensitization to inhalant allergens. CONCLUSIONS: Frequent intake of margarine rich in n-6 PUFA is not consistently associated with allergic diseases in adults. Other constituents of low-fat margarine or certain dietary habits and lifestyle factors, characterized by use of low-fat margarine, may be related to current asthma.

Adolescent↗

The use of synthetic bedding in children. Do strategies of change influence associations with asthma?

BACKGROUND: Epidemiological data suggest in contrast to clinical recommendations a negative effect of synthetic bedding on asthma and respiratory symptoms. OBJECTIVE: To assess the effects of bedding filled with synthetic material on the risk of asthma and respiratory symptoms in 6- to 7-year-old children, taking into account allergy-related change of bedding material. METHODS: We analyzed data from the ISAAC Phase III cross-sectional survey (1999/2000) in Münster, Germany. Data were collected by parental report from representative school-based samples of 6- to 7-year old children (n = 3,529). We calculated prevalence ratios with 95% confidence intervals for the association between respiratory symptoms suggestive of asthma and synthetic pillows and blankets and adjusting for potential confounders. RESULTS: In the preliminary analyses, synthetic pillows and synthetic blankets were positively associated with the studied respiratory outcomes. For example, a high number of wheezing attacks was positively associated with synthetic pillows (PR = 4.44; 95% CI 2.84-6.94) and synthetic blankets (PR = 3.80; 95% CI 2.48-5.82). However, in the restricted analysis, excluding participants reporting allergy-related change of bedding (pillows n = 440; blankets n = 437), the positive associations disappeared for all studied outcomes. CONCLUSIONS: Our findings suggest that allergy-related choice of bedding is an important factor in the assessment of the relation between synthetic bedding and asthma symptoms. Ignoring those changes can lead to false-positive risk estimates. Prospective studies that allow to disentangle the temporal sequence of disease, exposure, and change of bedding should help to further clarify this issue.

Allergens↗

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.

Asthma↗

A signal transducer and activator of transcription 6 haplotype influences the regulation of serum IgE levels.

BACKGROUND: Because of its central role in the IL-4/IL-13 pathway, the intracellular signaling molecule signal transducer and activator of transcription 6 ( STAT6 ) may be crucial for IgE production in asthma and allergy. OBJECTIVE: We analyzed the association between polymorphisms in the STAT6 gene and the regulation of serum IgE levels. Methods In a population of 1120 German schoolchildren (age 9-11 years), we genotyped 6 previously identified polymorphisms spanning the STAT6 gene by using the matrix-assisted laser desorption ionization-time of flight mass spectrometry method. 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 modeled as outcome variables in haplotype-trend regression analysis. RESULTS: Polymorphisms located in intron 2 (C2892T) and the 3' untranslated region (T12888C) significantly and consistently contributed to elevated total serum IgE levels. One STAT6 haplotype showed increased odds ratios of 1.58 (95% CI, 1.08-2.32; P = .020), 1.82 (95% CI, 1.19-2.77; P = .006), and 3.92 (95% CI, 1.93-7.96; P = .0002) for elevated IgE levels at percentiles 50%, 66%, and 90%, respectively. Because C2892T is located within a nuclear factor kappaB transcription factor binding site, a functional role of this polymorphism is very likely. CONCLUSION: The data indicate that within the IL-4/IL-13 pathway, genetic variants in the STAT6 gene significantly contribute to the regulation of serum IgE levels.

Base Sequence↗

Predictors of health care utilization of children with asthma in the community.

The aim of this study was to assess the pattern of use of health care services among children with asthma symptoms within the community, and assess groups at increased risk of emergency department (ED) visits or hospital admissions (HA). Using International Study of Asthma and Allergies in Childhood phase II protocol, information about asthma management and utilization of health care services was collected by parental questionnaire in a community-based random sample of 5-7- and 9-11-year-old children (n = 11,094) in Dresden and Munich. Only 11.2% of children with current wheeze did not utilize any health care facility or consultation for their asthma symptoms in the 12 months prior to survey, while 86.2%, 12.3%, and 3.6% had at least one asthma related physician's consultation, ED visits, or HA, respectively. Predictors of ED visits and HA among current wheezers were: younger age, male gender, speech-limiting wheeze, level of exposure to environmental tobacco smoke. In addition, children of low socioeconomic status were more likely to have ED visits because of their asthma. Childhood asthma is a major public health problem in Germany leading to substantial morbidity and utilization of health care services. Exposure to tobacco smoke comes out as the major modifiable risk factor related to asthma morbidity in children.

Asthma↗

Self-reported traffic density and atopic disease in children. Results of the ISAAC Phase III survey in Muenster, Germany.

Positive associations between traffic exposure and atopic respiratory disorders in children have been described in several studies. We analyzed data related to self-reported truck traffic density and several symptoms and diagnoses of asthma and hay fever (12-month wheezing and rhinitis symptoms, diagnoses of asthma and hay fever) from the ISAAC Phase III survey in Muenster, Germany, using core written and video questionnaires. Data were collected from representative school-based samples (n = 7345) of 6-7- and 13-14-yr-olds. In 13-14-yr-olds, according to exposure levels categorized into rare, frequent, and constant, with the 'never'-category used as reference, the sex-adjusted prevalence ratios were 1.29 (95% CI = 1.08-1.53), 1.58 (1.29-1.94), and 1.57 (1.18-2.10) for wheeze in the past 12 months, and 1.20 (1.06-1.34), 1.35 (1.17-1.55), and 1.69 (1.42-2.0) for rhinitis symptoms in the past 12 months. Prevalence ratios in 6-7-yr-olds and results for a diagnosis of asthma were less consistent while no positive association was detected between hay fever and truck traffic in both age groups. When analyses were based on a more general traffic indicator (self-reported traffic noise), no consistent associations were observed. Our data provide support for the hypothesis that residential exposure to truck traffic may adversely affect the health of children.

Adolescent↗

Positional cloning of a novel gene influencing asthma from chromosome 2q14.

Asthma is a common disease in children and young adults. Four separate reports have linked asthma and related phenotypes to an ill-defined interval between 2q14 and 2q32 (refs. 1-4), and two mouse genome screens have linked bronchial hyper-responsiveness to the region homologous to 2q14 (refs. 5,6). We found and replicated association between asthma and the D2S308 microsatellite, 800 kb distal to the IL1 cluster on 2q14. We sequenced the surrounding region and constructed a comprehensive, high-density, single-nucleotide polymorphism (SNP) linkage disequilibrium (LD) map. SNP association was limited to the initial exons of a solitary gene of 3.6 kb (DPP10), which extends over 1 Mb of genomic DNA. DPP10 encodes a homolog of dipeptidyl peptidases (DPPs) that cleave terminal dipeptides from cytokines and chemokines, and it presents a potential new target for asthma therapy.

Amino Acid Sequence↗

A complete screening of the IL4 gene: novel polymorphisms and their association with asthma and IgE in childhood.

BACKGROUND: IL-4, a cytokine with immunomodulatory functions, is involved in the upregulation of IgE production characteristic of asthma and allergy. Thus far, 2 single nucleotide polymorphisms (SNPs) in the promoter (C-589T) and 5' untranslated region (C-33T) of the IL4 gene have been identified. Polymorphism C-589T was reported to influence total serum IgE levels and bronchial hyperresponsiveness. However, no study has investigated the putative existence of further SNPs in exons, introns, and flanking regions of the IL4 gene. OBJECTIVE: A complete screening of the IL4 gene and its flanking regions for new polymorphisms was performed. Large-scale association studies in 1120 German schoolchildren were conducted to determine the effect of all polymorphisms present in the IL4 gene on the phenotypic expression of atopic diseases. METHODS: Denaturing HPLC and standard sequencing techniques were performed to detect novel polymorphisms in 33 unrelated subjects unselected for atopic diseases. Linkage disequilibrium was assessed for all polymorphisms in the IL4 gene, and association studies were performed. RESULTS: A total of 16 polymorphisms were identified in the IL4 gene, 14 of which were not reported previously. The pattern of linkage disequilibrium observed in IL4 could not be explained by physical distance. A significant association between a cluster of polymorphisms in strong linkage disequilibrium with each other and a physician's diagnosis of asthma and total serum IgE levels was found. CONCLUSION: These results indicate a possible involvement of SNPs in the IL4 gene in the development of asthma and the regulation of total serum IgE.

Asthma↗

Smoking among adolescents in Muenster, Germany: increase in prevalence (1995-2000) and relation to tobacco advertising.

BACKGROUND: Understanding patterns and trends of smoking among youths is of major importance for the assessment of the burden of smoking in the society and efforts to decrease it. OBJECTIVE: The aims were to determine the prevalence and trends of smoking among adolescents in Muenster, Germany, and to assess its relation to youths' awareness of tobacco advertisement. DESIGN: Information on smoking habits was collected during two school-based surveys (1994/1995 and 1999/2000) of 12- to 15-year-old adolescents (3934 students in 1994/5 and 4028 students in 1999/2000) in Muenster, Germany. In addition, in 1994/1995 information about youths' awareness and appreciation of tobacco advertisement was collected. RESULTS: During the 5-year period, the prevalence of current smoking increased from 21.3 to 28.3%, and daily smoking increased from 10.0 to 14.2%. Among girls, daily smoking increased by 62% during this period. Almost all participants (94%) in 1994/1995 knew a tobacco brand, and appreciation of tobacco advertisement was strongly associated with the frequency of smoking. CONCLUSION: Smoking is increasing among adolescents in Germany especially among girls. These data are a cause of concern and call for efforts to reverse these trends, which should include a ban on tobacco advertisement in Germany.

Adolescent↗

Association between polymorphisms in caspase recruitment domain containing protein 15 and allergy in two German populations.

BACKGROUND: Early exposure to microbial matter such as LPS may influence the development of asthma and allergies by activation of innate immunity pathways as indicated by studies in farming environments. Recently, polymorphisms in caspase recruitment domain containing protein 15 (CARD15), an intracellular LPS receptor protein, have been associated with Crohn's disease. Because these polymorphisms lead to changes in LPS recognition, they may affect the development of asthma and allergies. OBJECTIVE: We genotyped a large population of German schoolchildren (N = 1872) from East and West Germany for 3 functional relevant CARD15 polymorphisms for their role in the development of asthma and allergy. METHODS: By use of parental questionnaires, skin prick testing, pulmonary function tests, bronchial challenge tests, and measurements of serum IgE levels, children were phenotyped for the presence of atopic diseases. Genotyping was performed with PCR-based restriction enzyme assays. To assess associations between atopic phenotypes and genotypes standard statistical procedures were applied. RESULTS: Children with the polymorphic allele C2722 had a more than 3-fold risk to develop allergic rhinitis (P <.001) and an almost 2-fold risk for atopic dermatitis (P <.05). Furthermore, the T2104 allele was associated with an almost 2-fold risk for allergic rhinitis (P <.05). When a C insertion at position 3020 was present, the risk of atopy increased by 50% (P <.05) and serum IgE levels were elevated (P <.01). CONCLUSION: The shared genetic background between Crohn's disease and atopy may indicate that an impaired recognition of microbial exposures results in an insufficient downregulation of excessive immune responses, giving rise to either T(H)2 dominated allergies or T(H)1 related Crohn's disease.

Carrier Proteins↗