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Biomedical subjects

E von Mutius

Publications and source records attributed to E von Mutius.

At least 55 records · Page 3Linked to original sources

Early childhood infectious diseases and the development of asthma up to school age: a birth cohort study.

OBJECTIVE: To investigate the association between early childhood infections and subsequent development of asthma. DESIGN: Longitudinal birth cohort study. SETTING: Five children's hospitals in five German cities. PARTICIPANTS: 1314 children born in 1990 followed from birth to the age of 7 years. MAIN OUTCOME MEASURES: Asthma and asthmatic symptoms assessed longitudinally by parental questionnaires; atopic sensitisation assessed longitudinally by determination of IgE concentrations to various allergens; bronchial hyperreactivity assessed by bronchial histamine challenge at age 7 years. RESULTS: Compared with children with </=1 episode of runny nose before the age of 1 year, those with >/=2 episodes were less likely to have a doctor's diagnosis of asthma at 7 years old (odds ratio 0.52 (95% confidence interval 0.29 to 0.92)) or to have wheeze at 7 years old (0.60 (0.38 to 0.94)), and were less likely to be atopic before the age of 5 years. Similarly, having >/=1 viral infection of the herpes type in the first 3 years of life was inversely associated with asthma at age 7 (odds ratio 0.48 (0.26 to 0.89)). Repeated lower respiratory tract infections in the first 3 years of life showed a positive association with wheeze up to the age of 7 years (odds ratio 3.37 (1.92 to 5.92) for >/=4 infections v </=3 infections). CONCLUSION: Repeated viral infections other than lower respiratory tract infections early in life may reduce the risk of developing asthma up to school age.

Antibodies↗

Is obesity a risk factor for childhood asthma?

BACKGROUND: In adolescents and adults, an association between obesity and asthma was found in females. Does this sex-specific association already exist in young children? METHODS: Questionnaire data on 9357 5- and 6-year-old German children were collected in 1997 in two rural regions in Bavaria. The diagnosis of asthma, hay fever, and eczema was ascertained with the ISAAC core and other validated questions. Overweight was defined by a BMI of >90th and < or =97th percentile and obesity by a BMI of >97th percentile. RESULTS: The lifetime prevalence of doctor's diagnosed asthma in girls was 3.5% (95%, CI 2.9-4.1%) for normal weight, 5.8% (95% CI 3.2-8.4%) for overweight, and 10.3% (95% CI 5.3-15.2%) for obesity, whereas no relation to weight was found in boys. Hay fever and eczema were unrelated to weight in girls and boys. The adjusted odds ratio for asthma in girls was 2.12 (95% CI 1.22-3.68) for overweight and 2.33 (95% CI 1.13-4.82) for obesity. CONCLUSIONS: A sex-specific association with doctor's diagnosed asthma was also observed in girls at school entry. Since this association was confined to doctor's diagnosed asthma in the absence of other atopic conditions, and no association with other atopic manifestations was found, we hypothesize that this association is related to factors other than atopic sensitization.

Asthma↗

Inverse association of overweight and breast feeding in 9 to 10-y-old children in Germany.

OBJECTIVE: To evaluate whether breast feeding is associated with prevalent overweight in pre-adolescent children. METHODS: Cross-sectional studies of 9 to 10-y-old children attending fourth grade in 1995/1996 in Dresden (n=1046) and Munich (n=1062), Germany, according to the International Study of Asthma and Allergies in Childhood (ISAAC) Phase II protocol. A comprehensive questionnaire including detailed breast feeding history was filled out by the child's parent. Height and weight were measured in a random subsample of children undergoing spirometry. Overweight was defined as body mass index > or =90th age- and sex-specific percentile of the German reference. RESULTS: While the prevalence of overweight differed substantially between Dresden (girls 9.1%, boys 12.5%) and Munich (17% both), we observed a markedly lower overweight prevalence among breast fed than non-breast fed children in both cities. Controlling for age, sex and city, breast-fed children were substantially less likely to be overweight at 9-10 y (OR 0.55, 95% CI 0.41-0.74). Results were slightly attenuated after adjustment for nationality, socio-economic status, number of siblings, parental smoking (OR 0.66, 95% CI 0.52-0.87). A longer overall duration and duration of exclusive breast feeding was associated significantly with decreasing prevalence of overweight. CONCLUSION: The results highlight the importance and possible preventive potential of early nutrition in the development of overweight in children. Both feeding behaviors acquired by the nursing infant and metabolic effects may contribute to the observed inverse association of breast feeding and overweight in children.

Body Mass Index↗

Childhood risk factors for atopy and the importance of early intervention.

The increasing prevalence of atopic diseases, particularly atopy-associated asthma, has become a major challenge for allergists and public health authorities in many countries. The understanding of the natural history of the atopic march, including the determinants that are modifiable and might become candidates for preventive intervention, is still very limited. Information provided by cross-sectional studies can only generate hypotheses, which need to be supported by prospective, longitudinal, cohort studies. Ultimately, it will depend on the results of well-controlled intervention studies to identify which nutritional, environmental, or lifestyle-related factors should be considered for early intervention and might be useful to reverse the epidemiologic trend.

Biomarkers↗

The pattern of atopic sensitization is associated with the development of asthma in childhood.

BACKGROUND: Even though atopic sensitization has been shown to be strongly associated with childhood asthma, asthma eventually develops in only one third of atopic children. OBJECTIVE: The aim of this study was to prospectively investigate the pattern of atopic sensitization typically associated with the development of asthma in childhood. METHODS: The German Multicenter Allergy Study followed 1314 children from birth to the age of 7 years. Parental questionnaires on asthma and asthmatic symptoms were completed 6 times up to the age of 2 years and from then on yearly. Determination of specific IgE to 9 food and inhalant allergens was performed yearly, and at the age of 7 years, a bronchial histamine challenge was conducted. RESULTS: Onset of atopic sensitization in atopic children with current asthma at the age of 7 years was significantly earlier than in atopic children without current asthma (39.4% before age 1 year vs 21.0%, P =.015). Early atopic sensitization without any sensitization to inhalant allergens at the age of 7 years conferred no increased risk for asthma at this age. Only those children sensitized to any allergen early in life and sensitized to inhalant allergens by the age of 7 years were at a significantly increased risk of being asthmatic at this age (odds ratio, 10.12; 95% CI, 3.81-26.88). However, even in this group of persistently sensitized children, the risk of being asthmatic at the age of 7 years was only increased if a positive parental history of asthma or atopy was present (odds ratio, 15.56; 95% CI, 5.78-41.83), with the effect being strongest for maternal asthma. CONCLUSION: Our results indicate that an underlying factor pertaining to asthma and maternal transmission may determine both a certain pattern of sensitization and the expression of asthma.

Age Factors↗

Relation of body mass index to asthma and atopy in children: the National Health and Nutrition Examination Study III.

BACKGROUND: An increase in the prevalence of obesity and asthma over recent decades has been reported in affluent societies. Both overweight and obesity have been shown to be inversely related to having been breastfed, which is also a potential protective factor against childhood atopic diseases. The aim of this analysis was to explore the relation of body mass index (BMI) to asthma and atopy in a large representative sample of the United States population. METHODS: Children aged 4-17 years were included in the NHANES III survey. Prevalences of atopic diseases and potential confounding factors such as exposure to environmental tobacco smoke, birth weight, breast feeding, and household size were assessed using structured interviews with parents. Height and weight were measured, and BMI was calculated as kg/m(2) and transformed into Z scores. Children underwent skin prick tests for atopy to a battery of food and inhalant allergens. RESULTS: The prevalence of asthma (8.7% v 9.3% v 10.3% v 14.9%, p=0.0001) and atopy (48.6% v 50.5% v 53.0% v 53.2%, p=0.05) rose significantly with increasing quartiles of BMI. After adjustment for confounders, a significant positive association between BMI and asthma remained (adjusted OR 1.77, 95% confidence interval 1.44 to 2.19 between the highest and lowest quartiles of BMI), whereas no independent relation between BMI and atopy was evident. No effect modification by sex or ethnic group was seen. CONCLUSIONS: The effects of increased BMI on asthma may be mediated by mechanical properties of the respiratory system associated with obesity or by upregulation of inflammatory mechanisms rather than by allergic eosinophilic inflammation of the airway epithelium.

Adolescent↗

Infection: friend or foe in the development of atopy and asthma? The epidemiological evidence.

There is increasing evidence from epidemiological studies to support the "hygiene hypothesis" with regard to the development of allergic diseases. This review will discuss the epidemiological findings relating to atopy and asthma, separately. The strongest arguments in favour of the "hygiene hypothesis" are the findings relating early life day care attendance to a significantly reduced risk of atopy and asthma, and the strong link between sibship size and the occurrence of atopy as confirmed by numerous studies. Furthermore, data relating serological immune responses to certain infections such as hepatitis A and Toxoplasma gondii suggest a role for such infections, or alternatively the lack of hygiene, to be operative in the inhibition of the development of allergic immune responses. The effects described seem to be stronger for atopy than for asthma. Furthermore, biological plausibility for such a hypothesis can be found from findings of recent in vitro studies and from animal experiments. Epidemiological studies attempting to identify single infections as being harmful or beneficial could fail, because it may be the total burden of microbial stimuli rather than a certain infection that directs the maturing immune system into a Th1-type T-helper cell polarized response. The timing of the exposure seems to be essential for promoting beneficial or harmful effects, and may provide a "window of opportunity".

Agriculture↗

Histamine challenges discriminate between symptomatic and asymptomatic children. MAS-Study Group. Multicentre Allergy Study.

The aims of this study were to investigate a threshold value for bronchial responsiveness in children aged 7 yrs, which discriminates between symptomatic and asymptomatic children, and to identify determinants of this responsiveness. Titrated bronchial histamine challenges using the reservoir method were performed in 645 children aged 7 yrs, from the birth cohort Multicentre Allergy Study (MAS). When defining a reference population of healthy children within the MAS cohort, the 95th percentile of the provocative concentration causing a 20% fall in forced expired volume in one second PC20 among these asymptomatic study subjects amounted to 0.60 mg x mL(-1). This resulted in a specificity of 93.0% and a sensitivity of 45.9%, for discriminating between "current wheezers" and "non-current wheezers". Determinants of airway responsiveness at this age were pulmonary function, sensitization to indoor allergens, total immunoglobulin E and current wheeze. The results indicate that a very low cut-off provocative concentration causing a 20% fall in forced expired volume in one second (<1.0 mg x mL(-1)) defines airway hyperresponsiveness in children aged 7 yrs using the reservoir method. Provocation protocols for histamine challenges in this age group should therefore start with concentrations markedly below 1.0 mg x mL(-1).

Allergens↗

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.

Adolescent↗

Early exposure to house-dust mite and cat allergens and development of childhood asthma: a cohort study. Multicentre Allergy Study Group.

BACKGROUND: In a prospective birth-cohort study, we assessed the relevance of mite and cat allergen exposure for the development of childhood asthma up to age 7 years. METHODS: Of 1314 newborn infants enrolled in five German cities in 1990, follow-up data at age 7 years were available for 939 children. Assessments included repeated measurement of specific IgE to food and inhalant allergens, measurement of indoor allergen exposure at 6 months, 18 months, and 3 years of age, and yearly interviews by a paediatrician. At age 7 years, pulmonary function was tested and bronchial hyper-responsiveness was measured in 645 children. FINDINGS: At age 7, the prevalence of wheezing in the past 12 months was 10.0% (94 of 938), and 6.1% (57 of 939) parents reported a doctor's diagnosis of asthma in their children. Sensitisation to indoor allergens was associated with asthma, wheeze, and increased bronchial responsiveness. However, no relation between early indoor allergen exposure and the prevalence of asthma, wheeze, and bronchial hyper-responsiveness was seen. INTERPRETATION: Our data do not support the hypothesis that exposure to environmental allergens causes asthma in childhood, but rather that the induction of specific IgE responses and the development of childhood asthma are determined by independent factors.

Air Pollution, Indoor↗

Does breast-feeding protect against childhood obesity?

The impact of breast-feeding on overweight and obesity in children at school entry was assessed in a cross sectional study in Bavaria in 1997. The school entry health examination enrolled 134,577 children. Data on early feeding were collected in two rural districts (eligible population n=13,345). The analyses were confined to 5 or 6 year old children with German nationality. The main outcome measures were overweight (BMI>90th percentile for all German children seen at the 1997 school entry health examination in Bavaria) and obesity (BMI>97th percentile). Information on breast-feeding was available for 9206 children of whom 56% had been breast-fed for any length of time. In non breast-fed children the upper tail of the BMI distribution was enlarged as compared to the breast-fed children whereas the median was almost identical. The prevalence of obesity in children who had never been breast-fed was 4.5% as compared to 2.8% in ever breast-fed children. A clear dose response effect for the duration of breast-feeding on the prevalence of obesity was found: 3.8%, 2.3%, 1.7% and 0.8% for exclusive breast-feeding for up to 2, 3 to 5, 6 to 12 and more than 12 months, respectively. The results for overweight were very similar. The protective effect of beast feeding on overweight and obesity could not be explained by differences in social class or lifestyle. The adjusted odds ratios of breast-feeding for any length of time was 0.71 (95% CI 0.56-0.90) for obesity and 0.77 (95%CI 0.66-0.88) for overweight. This data set did not allow to adjust for maternal weight, an important risk factor for obesity in children. Maternal overweight, however, could not explain the effect of breastfeeding on overweight and obesity in a similar study. The reduction in the risk for overweight and obesity is therefore more likely to be related to the properties of human milk than to factors associated with breast-feeding. The potential relevance of different components of human milk for the observed reduction in the risk for overweight and obesity is discussed. The preventive effect of breast-feeding on overweight and obesity is an important additional argument for the promotion of breast-feeding in industrialised countries.

Body Mass Index↗

The environmental predictors of allergic disease.

The prevalence of allergic diseases has been on the rise for the last 200 years, when hay fever, an easy and obvious-to-recognize illness, was virtually unknown in Europe and North America. Genetic factors are unlikely to explain these rapid increases. Among the potential environmental factors, exposure to ambient air pollution has been intensely debated. Besides passive smoking, which has convincingly been shown to increase the risk for asthma and bronchial hyperresponsiveness among exposed children, the evidence to suggest that outdoor pollution to sulfur dioxide, particulate matter, diesel exhaust, and ozone is causally related with the inception of allergic diseases is poor. Rather, factors associated with the lifestyle of populations or families, such as socioeconomic status, allergen exposure, sibship size, early childhood infections, dietary habits, and growing up in anthroposophic families or a farming environment, may prove to be of greater relevance. The future challenge is to tackle the complex interplay between environmental factors and genetic determinants that will eventually contribute to a better understanding and to better prevention strategies for such multifactorial conditions as asthma and allergies.

Air Pollution↗

Exposure to endotoxin or other bacterial components might protect against the development of atopy.

BACKGROUND: Several recent studies have shown that growing up on a farm confers significant protection against the development of atopy. These findings point particularly towards the importance of exposure to stable dust and farm animals. It has furthermore been reported that endotoxin, an intrinsic part of the outer membrane of gram negative bacteria, is abundant in environments where livestock and poultry is kept. The aim of this study was therefore to measure the level of environmental endotoxin exposure in homes of farmers' children, children with regular contact to livestock and control children with no contact to farm animals. METHODS: Eighty-four farming and nonfarming families were identified in rural areas in Southern Germany and Switzerland. Samples of settled and airborne dust were collected in stables, and of settled dust indoors from kitchen floors and the children's mattresses. Endotoxin concentrations were determined by a kinetic Limulus assay. RESULTS: Endotoxin concentrations were highest in stables of farming families, but were also significantly higher indoors in dust from kitchen floors (143 EU/mg vs 39 EU/mg, P < 0.001) and children's mattresses (49479 EU/m2 vs 9383 EU/m2, P < 0.001) as compared to control children from nonfarming families. In addition, endotoxin levels were also significantly higher in mattresses and dust from kitchen floors in households where children had regular contact to farm animals (38.6 EU/mg and 23340 EU/m2, respectively) as compared to control subjects. CONCLUSION: We propose that the level of environmental exposure to endotoxin and other bacterial wall components is an important protective determinant for the development of atopic diseases in childhood.

Adolescent↗

A cluster of seven tightly linked polymorphisms in the IL-13 gene is associated with total serum IgE levels in three populations of white children.

BACKGROUND: Increased levels of total serum IgE are a strong risk factor for the development of asthma. IgE is also involved in host defenses against parasites and fungi. Linkage of total serum IgE with markers located close to the 3 Mb cluster of cytokine genes in chromosome 5q31 has been reported. IL-4 or IL-13 are regarded as essential for IgE synthesis. OBJECTIVE: We tested whether polymorphisms in the IL-13 gene might explain the linkage between chromosome 5q31 and total serum IgE levels. METHODS: We used denaturing HPLC to detect polymorphisms in overlapping PCR fragments of the IL-13 gene including promoter and 3' untranslated regions. After sequencing was performed to identify the locations of the polymorphisms, PCR and primer-induced restriction site assays were used to genotype subjects in 3 unselected populations. RESULTS: We report here 7 polymorphisms (6 novel) in IL-13. Four of these polymorphisms are tightly linked to a variant in the terminal portion of the coding region of the gene that results in a predicted amino acid change in residue 130 (Arg130Gln). The Gln form is strongly associated (P =.000002) with increased serum IgE levels in 3 different populations comprising a total of 1399 children. Two additional polymorphisms in the promoter region of IL-13 are more loosely linked to Arg130Gln and are also less significantly associated with total serum IgE levels. CONCLUSION: These data suggest that the Arg130Gln polymorphism in IL-13, or others in close linkage with it, is associated with the development of the elevated serum IgE phenotype.

Asthma↗