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Biomedical subjects

Erika von Mutius

Publications and source records attributed to Erika von Mutius.

At least 37 records · Page 2Linked to original sources
PubMed2004

Factors associated with difference in prevalence of asthma in children from three cities in China: multicentre epidemiological survey.

OBJECTIVE: To determine the factors associated with difference in prevalence of asthma in children in different regions of China. DESIGN: Multicentre epidemiological survey. SETTING: Three cities in China. PARTICIPANTS: 10,902 schoolchildren aged 10 years. MAIN OUTCOME MEASURES: Asthma and atopic symptoms, atopic sensitisation, and early and current exposure to environmental factors. RESULTS: Children from Hong Kong had a significantly higher prevalence of wheeze in the past year than those from Guangzhou and Beijing (odds ratio 1.64, 95% confidence interval 1.35 to 1.99). Factors during the first year of life and currently that were significantly associated with wheeze were cooking with gas (odds ratio 2.04, 1.34 to 3.13), foam pillows (2.58, 1.66 to 3.99), and damp housing (1.89, 1.26 to 2.83). Factors protecting against wheeze were cotton quilts and the consumption of fruit and raw vegetables. CONCLUSION: Environmental factors and diet may explain the differences in prevalence of asthma between children living in different regions of China.

Asthma↗
PubMed2004

Influences in allergy: epidemiology and the environment.

Many decades after the first descriptions of hay fever in the 19th century, we still struggle with the formation of a cogent conception embracing all the many fragments of insight into the various aspects of allergic and asthmatic diseases. Although in daily practice we can grasp and allocate most of the clinical manifestations, in research the fundamental structures are only in part recognized. We therefore presume that the underlying mechanisms are complex and multifaceted. We have explored in countless directions while branching into ever more detailed analyses of phenomena, all of which are associated with the conditions of interest. But how can we rearrange these pieces to advance toward a broader understanding of asthma and allergies? Epidemiology as a scientific tool to study the occurrence, the natural course, and the determinants of a condition in various sociocultural environments might contribute to the edifice of such a scaffold. This review does not intend to present a comprehensive digest of the relevant literature: the reader can refer to other "state of the art" reviews. The intention is to discuss some conceptual cornerstones and to illustrate them with a few examples.

Adolescent↗
PubMed2004

Toll-like receptor 2 as a major gene for asthma in children of European farmers.

BACKGROUND: The finding that the prevalence of asthma and allergies is less frequent in children raised on animal farms has led to the conjecture that exposure to microbial products modifies immune responses. The toll-like receptors (TLRs) represent an evolutionarily conserved family of innate immunity receptors with microbial molecules as ligands. OBJECTIVES: We reasoned that polymorphisms in genes encoding TLRs might modulate the protective effects observed in farming populations. METHODS: Farmers' and nonfarmers' children living in rural areas in Austria and Germany and who were enrolled in the cross-sectional ALEX study were genotyped for single nucleotide polymorphisms in the TLR2 and TLR4 genes. The frequencies of asthma, allergic rhinitis, and atopic sensitization were compared between the genotypes in relation to exposure to farming and endotoxin. RESULTS: Among farmers' children, those carrying a T allele in TLR2/-16934 compared with children with genotype AA were significantly less likely to have a diagnosis of asthma (3% vs 13%, P = .012), current asthma symptoms (3% vs 16%, P = .004), atopic sensitization (14% vs 27%, P = .023), and current hay fever symptoms (3% vs 14%, P = .01). The association between TLR2/-16934 and asthma among children of farmers was independent of atopy. No such association was found among children from the same rural communities but not living on farms. CONCLUSION: Our results suggest that genetic variation in TLR2 is a major determinant of the susceptibility to asthma and allergies in children of farmers.

Adult↗
PubMed2004

The natural course of atopic dermatitis from birth to age 7 years and the association with asthma.

BACKGROUND: Atopic dermatitis (AD) is considered to be one of the first manifestations in the atopic march. However, few prospective studies on AD and its association with childhood asthma exist. OBJECTIVE: The aim of this study was to prospectively investigate the natural course of AD to determine factors influencing its prognosis and to analyze the relationship of AD with childhood asthma. METHODS: The Multicenter Allergy Study, a German birth cohort, followed 1314 children from birth to age 7 years. Physical examinations, parental interviews on atopic symptoms and diagnoses, and determination of specific IgE levels were performed regularly. RESULTS: The cumulative prevalence of AD in the first 2 years of life was 21.5%. Of these children with early AD, 43.2% were in complete remission by age 3 years, 38.3% had an intermittent pattern of disease, and 18.7% had symptoms of AD every year. Severity (adjusted cumulative odds ratio, 5.86; 95% CI, 3.04-11.29) and atopic sensitization (adjusted cumulative odds ratio, 2.76; 95% CI, 1.29-5.91) were major determinants of prognosis. Early wheeze and a specific sensitization pattern were significant predictors for wheezing at school age, irrespective of AD. Early AD without these cofactors constituted no increased risk of subsequent wheeze (adjusted odds ratio, 1.11; 95% CI, 0.56-2.20) or bronchial hyperreactivity. CONCLUSION: AD is a common condition in infancy but disappears around age 3 years in a significant proportion of children. The prognosis is mostly determined by the severity and the presence of atopic sensitization. Early AD is associated with asthma at school age, but in many of these asthmatic children, wheezing manifests before or with the onset of AD. Children with AD and wheeze have a marked loss in lung function, suggesting a distinct phenotype rather than a progressive development from AD to asthma.

Age Factors↗
PubMed2004

Microbial exposure of rural school children, as assessed by levels of N-acetyl-muramic acid in mattress dust, and its association with respiratory health.

BACKGROUND: Endotoxin exposure has been shown to be associated with a decreased prevalence of atopic sensitization and symptoms. Yet endotoxin represents only a part of the indoor microbial exposure. Muramic acid, a constituent of peptidoglycan, is present in gram-negative and gram-positive bacteria in the environment and may therefore serve as an additional marker of microbial exposure. OBJECTIVE: To study the factors determining the level of indoor exposure to muramic acid/peptidoglycan, as well as its potential association with respiratory health. METHODS: In 553 farm and nonfarm school children from Austria, Switzerland, and Germany, mattress dust muramic acid concentrations were determined, and health was assessed by using IgE measurements and questionnaire information. RESULTS: The muramic acid concentration was found to be significantly higher in dust from farm children's mattresses than in dust from nonfarm children's mattresses (157 vs 131 ng/mg). Children with higher mattress dust muramic acid concentrations had a significantly lower prevalence of wheezing (odds ratio of highest vs lowest tertile of muramic acid concentration, 0.3; 95% CI, 0.1-0.9), regardless of farming status and endotoxin exposure. The association for asthma was similar, and no association was found with atopic sensitization. CONCLUSION: Next to endotoxin, muramic acid provides us with an independent marker of microbial exposure. Unlike endotoxin, muramic acid was inversely associated with wheezing rather than with atopic sensitization.

Asthma↗
PubMed2004

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↗
PubMed2004

Drug development strategies for asthma: in search of a new paradigm.

The spiraling costs of asthma treatment seem set to continue rising, given the equivocal performance of the latest generation of specific anti-inflammatory drugs in trials in adult asthmatics. We argue that the continuation of this trend is inevitable unless there is a substantial realignment of entrenched drug development policy in the pharmaceutical industry and a parallel shift in licensing policy by regulatory authorities to encourage the development of drugs capable of halting the progression from acute to chronic asthma when the disease first manifests in childhood. The theoretical framework for such an approach, including proof-of-principle data from studies in children with early-stage disease and a range of candidate drugs, already exists. What is needed is informed debate on the risks versus potential benefits of this approach.

Animals↗
PubMed2004

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↗
PubMed2004

Hygiene hypothesis and endotoxin: what is the evidence?

PURPOSE OF REVIEW: The hygiene hypothesis has gained strong support over the past few years. Exposure to microbial products in early life could be an underlying factor in this hypothesis, but the mechanisms that lead from a less clean and more crowded environment to a lower prevalence of asthma and allergies are not known. Among the variety of potential microbial molecules that may confer protection against the development of asthma and allergies, endotoxin, a component of Gram-negative bacteria, has incited lively as well as controversial discussions. This review focuses on recent studies on endotoxin and its role in the context of the hygiene hypothesis. RECENT FINDINGS: Results from cross-sectional surveys, prospective cohorts, and experimental studies in vitro and in rodents suggest that exposure to house dust endotoxin in early life protects from atopic sensitization and IgE-mediated diseases, but is a risk factor for wheezing in infancy. SUMMARY: Numerous studies have supported the hygiene hypothesis, but whether endotoxin by itself confers the protection or whether it acts as a marker for another environmental exposure is still unclear. The challenge for the future will be to identify those factors that confer the protection proposed by the hygiene hypothesis, and to find strategies to modify the environment without causing harm to susceptible individuals.

Allergens↗
PubMed2003

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↗
PubMed2003

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↗
PubMed2003

Longitudinal follow-up of the changing gender ratio in asthma from childhood to adulthood: role of delayed manifestation in girls.

Boys suffer more often from asthma than girls, while in adults the gender ratio is reversed. It is not clear when exactly this change occurs and by what mechanism. From a cohort of all 5030 German 4th grade pupils (age 10 years) in Munich, 274 children with current asthma were identified (164 males, 110 females) through a questionnaire, and skin prick tests were performed. These subjects were re-evaluated at ages 14 and 20 years with a questionnaire. A random sample (n = 1000) of all 3538 German children without current asthma at age 10 was also re-evaluated at age 20 (controls). At age 20, only 24.5% (21 males, eight females) of the initial asthma group still had symptoms, and their gender ratio remained male dominated. In the controls, 4.8% (48/1000) had current asthma at age 20 and these were predominantly female: 6.4% (31/485) of control girls vs. 3.3% (17/515) of boys (p = 0.022). Half of the new asthma cases had had no symptoms or diagnoses until age 10, and atopy at age 10 was not associated with subsequent asthma in these. Asthma at age 10 has no better prognosis in boys than in girls, and the mechanism of the changing gender ratio appears to be late incidence of asthma among girls. Because the latter constitute a considerable part of adult asthma cases, it appears important to further explore this asthma phenotype and the risk factors associated with it.

Adolescent↗
PubMed2003

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↗
PubMed2002

Environmental exposure to endotoxin and its relation to asthma in school-age children.

BACKGROUND: In early life, the innate immune system can recognize both viable and nonviable parts of microorganisms. Immune activation may direct the immune response, thus conferring tolerance to allergens such as animal dander or tree and grass pollen. METHODS: Parents of children who were 6 to 13 years of age and were living in rural areas of Germany, Austria, or Switzerland where there were both farming and nonfarming households completed a standardized questionnaire on asthma and hay fever. Blood samples were obtained from the children and tested for atopic sensitization; peripheral-blood leukocytes were also harvested from the samples for testing. The levels of endotoxin in the bedding used by these children were examined in relation to clinical findings and to the cytokine-production profiles of peripheral-blood leukocytes that had been stimulated with lipopolysaccharide and staphylococcal enterotoxin B. Complete data were available for 812 children. RESULTS: Endotoxin levels in samples of dust from the child's mattress were inversely related to the occurrence of hay fever, atopic asthma, and atopic sensitization. Nonatopic wheeze was not significantly associated with the endotoxin level. Cytokine production by leukocytes (production of tumor necrosis factor alpha, interferon-gamma, interleukin-10, and interleukin-12) was inversely related to the endotoxin level in the bedding, indicating a marked down-regulation of immune responses in exposed children. CONCLUSIONS: A subject's environmental exposure to endotoxin may have a crucial role in the development of tolerance to ubiquitous allergens found in natural environments.

Adolescent↗
PubMed2002

Expression of CD14 and Toll-like receptor 2 in farmers' and non-farmers' children.

Children of farmers are at decreased risk of developing allergies. Results of epidemiological studies suggest increased exposure to microbial compounds might be responsible for this reduced risk. Alterations in adaptive immune response are thought to be the underlying mechanism. We measured expression of receptors for microbial compounds known to trigger the innate immune response. We showed that blood cells from farmers' children express significantly higher amounts of CD14 (0.96 vs 0.43, p=0.0013), and Toll-like receptor 2 (0.11 vs 0.04, p<0.0001) than those from non-farmers' children. We propose that the innate immune system responds to the microbial burden in the environment and modulates the development of allergic disease.

Agriculture↗
PubMed2002

Modeling annual benzene, toluene, NO2, and soot concentrations on the basis of road traffic characteristics.

The investigation of potential adverse health effects of urban traffic-related air pollution is hampered by difficulties encountered with exposure assessment. Usually public measuring sites are few and thereby do not adequately describe spatial variation of pollutant levels over an urban area. In turn, individual monitoring of pollution exposure among study subjects is laborious and expensive. We therefore investigated whether traffic characteristics can be used to adequately predict benzene, NO2, and soot concentrations at individual addresses of study subjects in the city area of Munich, Germany. For all road segments with expected traffic volumes of at least 4000 vehicles a day (n = 1840), all vehicles were counted manually for a single weekday in 1995. The proportion of vehicles in "stop-go" mode, an estimate of traffic jam, was determined. Furthermore, annual concentrations of benzene, NO2, and soot from 18 high-concentration sites (means: 8.7, 65.8, and 12.9 micrograms/m3, respectively) and from 16 school sites with moderate concentrations (means: 2.6, 32.2, and 5.7 micrograms/m3, respectively) were measured from 1996 to 1998. Statistical analysis of the data was performed using components of two different statistical models recently used to predict air pollution levels in comparable settings. Two traffic characteristics, traffic volume and traffic jam percentage, adequately described air pollutant concentrations (R2: 0.76-0.80, P < 0.0001). This study shows that air pollutant concentrations can be accurately predicted by two traffic characteristics and that these models compare favorably with other more complex models in the literature.

Air Pollutants↗