Meta-analysis identifies seven susceptibility loci involved in the atopic march.

Eczema often precedes the development of asthma in a disease course called the 'atopic march'. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P=2.1 × 10(-8)) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P=5.3 × 10(-9)). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema.

Differences in weight status and energy-balance related behaviors among schoolchildren in German-speaking Switzerland compared to seven countries in Europe.

BACKGROUND: Overweight in children and adolescents have increased significantly and are a major public health problem. To allow international comparisons, Switzerland joined the European study 'ENERGY' cross sectional survey consortium that investigated the prevalence of overweight and obesity as well as selected dietary, physical and sedentary behaviors of 10-12 years old pupils across seven other countries in Europe. The aims of the present study was to compare body composition and energy-balance related behaviors of Swiss schoolchildren to those of the seven European ENERGY-countries and to analyze overweight and energy-balance related behaviors of Swiss children according to socio-demographic factors. METHODS: A school-based cross-sectional study among 10-12 year old children was conducted in Switzerland and seven other European countries using a standardized protocol. Body height, weight and waist-circumference were measured by trained research assistants. Energy-balance related behaviors -i.e. selected dietary, physical activity and screen-viewing behaviors were assessed by questionnaires. Weight status and behaviors in Switzerland were compared to the seven European ENERGY countries. Within the Swiss sample, analyses stratified by gender, parental education and ethnicity were performed. RESULTS: Data of 546 Swiss children (mean age 11.6±0.8y, 48% girls) were obtained and compared to the ENERGY- results (N=7.148; mean age 11.5±0.8y, 48% girls). In Switzerland significantly less children were overweight (13.9%) or obese (2.3%) compared to the average across the ENERGY-countries (23.7% and 4.7%, respectively), and were even somewhat lower than the ENERGY countries with the lowest prevalence. Sugar sweetened beverage intakes and breakfast habits of Swiss children did not differ significantly from those of ENERGY. However, the mean time devoted by Swiss children to walking or cycling to school and attending sports activities was significantly higher and screen time significantly lower compared to the other ENERGY-countries. Within the Swiss, sample relatively large and consistent differences were observed between children from native and non-native ethnicity. CONCLUSIONS: The prevalence of overweight and obesity among Swiss children are substantial but significantly lower compared to all other European ENERGY-Partners, probably due to the fact that Swiss children were found to be more active and less sedentary comparing to the rest of the European sample.

Exposure to radiofrequency electromagnetic fields and sleep quality: a prospective cohort study.

BACKGROUND: There is persistent public concern about sleep disturbances due to radiofrequency electromagnetic field (RF-EMF) exposure. The aim of this prospective cohort study was to investigate whether sleep quality is affected by mobile phone use or by other RF-EMF sources in the everyday environment. METHODS: We conducted a prospective cohort study with 955 study participants aged between 30 and 60 years. Sleep quality and daytime sleepiness was assessed by means of standardized questionnaires in May 2008 (baseline) and May 2009 (follow-up). We also asked about mobile and cordless phone use and asked study participants for consent to obtain their mobile phone connection data from the mobile phone operators. Exposure to environmental RF-EMF was computed for each study participant using a previously developed and validated prediction model. In a nested sample of 119 study participants, RF-EMF exposure was measured in the bedroom and data on sleep behavior was collected by means of actigraphy during two weeks. Data were analyzed using multivariable regression models adjusted for relevant confounders. RESULTS: In the longitudinal analyses neither operator-recorded nor self-reported mobile phone use was associated with sleep disturbances or daytime sleepiness. Also, exposure to environmental RF-EMF did not affect self-reported sleep quality. The results from the longitudinal analyses were confirmed in the nested sleep study with objectively recorded exposure and measured sleep behavior data. CONCLUSIONS: We did not find evidence for adverse effects on sleep quality from RF-EMF exposure in our everyday environment.

Few associations between high-sensitivity C-reactive protein and environmental factors in 4.5-year-old children.

BACKGROUND: Low-grade inflammation in early childhood might protect from allergic diseases later in life. Our aim was to examine the effects of different environmental factors on low-grade inflammation measured with serum high-sensitivity C-reactive protein (hsCRP) at the age of 4.5 years. METHODS: The high-sensitivity CRP values (n = 653) and serum-specific IgE concentrations were measured from 4.5-year-old children in rural areas in five European countries (Austria, Finland, France, Germany, and Switzerland). Children belonged to the prospective multi-center PASTURE birth cohort. Data on early and current farming environment and domestic animal exposure were collected by questionnaires. RESULTS: Females as well as obese or very obese children at age of 4.5 years had higher hsCRP values than males (aOR 1.84 95% CI 1.27-2.66) and healthy weight children (aOR 4.47 95% CI 1.94-10.31), respectively. Levels were lowest in the summer. Few associations were detected between hsCRP values and farm environmental factors or atopic sensitization. However, there was evidence of children with low levels of hsCRP (below the detection limit) who had increased prevalence of sensitization to inhaled and seasonal allergens. Among non-sensitized children, spending time in stables was associated with reduced hsCRP (15 min-10 h aOR 0.40 95% CI 0.16-0.96 and ≥10 h aOR 0.25 95% CI 0.07-0.90), and among sensitized children, maternal smoking was associated with higher hsCRP values (aOR 2.51 95% CI 1.12-5.59). CONCLUSION: We found few associations between early environmental farming factors and hsCRP levels, and between hsCRP levels and atopic sensitization in 4.5-year-old children. However, our results suggest that the role played by the environmental factors in low-grade inflammation may differ between sensitized and non-sensitized children.

Cohort study on the effects of everyday life radio frequency electromagnetic field exposure on non-specific symptoms and tinnitus.

BACKGROUND: There is public concern regarding potential health effects of radio frequency electromagnetic fields (RF-EMF) exposure, as produced by mobile phones or broadcast transmitters. The objective of this study was to investigate the association between RF-EMF exposure and non-specific symptoms and tinnitus in a prospective cohort study. METHODS: In 2008, 1375 randomly selected participants from Basel, Switzerland, were enrolled in a questionnaire survey with follow-up after one year (participation rate 82%). A score for somatic complaints (von Zerssen list) and headache (HIT-6) was assessed. Far-field environmental RF-EMF exposure was predicted using a validated prediction model. Regarding near-field exposure, self-reported mobile and cordless phone use as well as mobile phone operator data were collected. In multivariate regression models, we investigated whether exposure at baseline (cohort analysis) or changes in exposure between baseline and follow-up (change analysis) were related to changes in health scores. RESULTS: For participants in the top decile of environmental far-field RF-EMF exposure at baseline, in comparison to participants exposed below the median value, the change in the von Zerssen- and HIT-6-scores between baseline and follow-up was -0.12 (95%-CI: -1.79 to 1.56) and -0.37 (95%-CI: -1.80 to 1.07) units, respectively. Exposure to near-field sources and a change in exposure between baseline and follow-up were not related to non-specific symptoms. Similarly, no association between RF-EMF exposure and tinnitus was observed. CONCLUSIONS: In this first cohort study using objective and well-validated RF-EMF exposure measures, we did not observe an association between RF-EMF exposure and non-specific symptoms or tinnitus.

Classification of personal exposure to radio frequency electromagnetic fields (RF-EMF) for epidemiological research: Evaluation of different exposure assessment methods.

The use of personal exposure meters (exposimeters) has been recommended for measuring personal exposure to radio frequency electromagnetic fields (RF-EMF) from environmental far-field sources in everyday life. However, it is unclear to what extent exposimeter readings are affected by measurements taken when personal mobile and cordless phones are used. In addition, the use of exposimeters in large epidemiological studies is limited due to high costs and large effort for study participants. In the current analysis we aimed to investigate the impact of personal phone use on exposimeter readings and to evaluate different exposure assessment methods potentially useful in epidemiological studies. We collected personal exposimeter measurements during one week and diary data from 166 study participants. Moreover, we collected spot measurements in the participants' bedrooms and data on self-estimated exposure, assessed residential exposure to fixed site transmitters by calculating the geo-coded distance and mean RF-EMF from a geospatial propagation model, and developed an exposure prediction model based on the propagation model and exposure relevant behavior. The mean personal exposure was 0.13 mW/m(2), when measurements during personal phone calls were excluded and 0.15 mW/m(2), when such measurements were included. The Spearman correlation with personal exposure (without personal phone calls) was 0.42 (95%-CI: 0.29 to 0.55) for the spot measurements, -0.03 (95%-CI: -0.18 to 0.12) for the geo-coded distance, 0.28 (95%-CI: 0.14 to 0.42) for the geospatial propagation model, 0.50 (95%-CI: 0.37 to 0.61) for the full exposure prediction model and 0.06 (95%-CI: -0.10 to 0.21) for self-estimated exposure. In conclusion, personal exposure measured with exposimeters correlated best with the full exposure prediction model and spot measurements. Self-estimated exposure and geo-coded distance turned out to be poor surrogates for personal exposure.

A prediction model for personal radio frequency electromagnetic field exposure.

Radio frequency electromagnetic fields (RF-EMF) in our daily life are caused by numerous sources such as fixed site transmitters (e.g. mobile phone base stations) or indoor devices (e.g. cordless phones). The objective of this study was to develop a prediction model which can be used to predict mean RF-EMF exposure from different sources for a large study population in epidemiological research. We collected personal RF-EMF exposure measurements of 166 volunteers from Basel, Switzerland, by means of portable exposure meters, which were carried during one week. For a validation study we repeated exposure measurements of 31 study participants 21 weeks after the measurements of the first week on average. These second measurements were not used for the model development. We used two data sources as exposure predictors: 1) a questionnaire on potentially exposure relevant characteristics and behaviors and 2) modeled RF-EMF from fixed site transmitters (mobile phone base stations, broadcast transmitters) at the participants' place of residence using a geospatial propagation model. Relevant exposure predictors, which were identified by means of multiple regression analysis, were the modeled RF-EMF at the participants' home from the propagation model, housing characteristics, ownership of communication devices (wireless LAN, mobile and cordless phones) and behavioral aspects such as amount of time spent in public transports. The proportion of variance explained (R2) by the final model was 0.52. The analysis of the agreement between calculated and measured RF-EMF showed a sensitivity of 0.56 and a specificity of 0.95 (cut-off: 90th percentile). In the validation study, the sensitivity and specificity of the model were 0.67 and 0.96, respectively. We could demonstrate that it is feasible to model personal RF-EMF exposure. Most importantly, our validation study suggests that the model can be used to assess average exposure over several months.

Temporal and spatial variability of personal exposure to radio frequency electromagnetic fields.

BACKGROUND: Little is known about the population's exposure to radio frequency electromagnetic fields (RF-EMF) in industrialized countries. OBJECTIVES: To examine levels of exposure and the importance of different RF-EMF sources and settings in a sample of volunteers living in a Swiss city. METHODS: RF-EMF exposure of 166 volunteers from Basel, Switzerland, was measured with personal exposure meters (exposimeters). Participants carried an exposimeter for 1 week (two separate weeks in 32 participants) and completed an activity diary. Mean values were calculated using the robust regression on order statistics (ROS) method. RESULTS: Mean weekly exposure to all RF-EMF sources was 0.13 mW/m(2) (0.22 V/m) (range of individual means 0.014-0.881 mW/m(2)). Exposure was mainly due to mobile phone base stations (32.0%), mobile phone handsets (29.1%) and digital enhanced cordless telecommunications (DECT) phones (22.7%). Persons owning a DECT phone (total mean 0.15 mW/m(2)) or mobile phone (0.14 mW/m(2)) were exposed more than those not owning a DECT or mobile phone (0.10 mW/m(2)). Mean values were highest in trains (1.16 mW/m(2)), airports (0.74 mW/m(2)) and tramways or buses (0.36 mW/m(2)), and higher during daytime (0.16 mW/m(2)) than nighttime (0.08 mW/m(2)). The Spearman correlation coefficient between mean exposure in the first and second week was 0.61. CONCLUSIONS: Exposure to RF-EMF varied considerably between persons and locations but was fairly consistent within persons. Mobile phone handsets, mobile phone base stations and cordless phones were important sources of exposure in urban Switzerland.

Molecular fingerprinting of the fecal microbiota of children raised according to different lifestyles.

In this population-based study, 90 children from three European countries were examined to determine the impact of lifestyle on the fecal microbiota. The study was designed to assess the impact of two extreme lifestyles that we hypothesized could impact the microbial composition in the gut: i.e., an anthroposophic lifestyle (restricted use of antibiotics, greater consumption of fermented vegetables, etc.) versus living on a farm (greater consumption of farm milk, contact with animals, etc.). In previous studies, these lifestyles correlated with lower prevalence of allergies. Terminal restriction fragment length polymorphism (T-RFLP) was used to assess the bacterial composition in fecal samples since recent studies have shown that the majority of this community cannot be cultivated. The T-RFLP data were used to calculate richness and evenness of the fecal microbiota. Children that were attending Steiner schools (anthroposophic children) had a significantly higher diversity of microbes in their feces than farm children, who in turn also had lower diversity than the control groups. Specific primers were also used to focus on the Lactobacillus-like community (lactic acid bacteria [LAB]). Large differences were found in the LAB subpopulations in the sampled groups. In some children, the LAB subpopulation was dominated by a species that has not yet been cultivated.

A school-based physical activity program to improve health and fitness in children aged 6-13 years ("Kinder-Sportstudie KISS"): study design of a randomized controlled trial [ISRCTN15360785].

BACKGROUND: Childhood obesity is the result of a long lasting imbalance between energy intake and energy expenditure. A major contributing factor is physical inactivity which is closely linked to bone health, cardiovascular disease risk, fitness and psychological factors. The school seems to provide an excellent setting to enhance levels of physical activity (PA). However, there is insufficient data from previous school-based intervention trials on how to enhance overall PA. It is also unknown whether an intervention aimed at increasing PA is effective in improving the children's health. The purpose of this paper is to outline the design of a school-based randomized, controlled trial (RCT) aiming to increase overall PA and to improve fitness and health in 6- to 13-year-old children. METHODS/DESIGN: 15 schools were randomized to the intervention (n = 9) or the control (n = 6) group, stratified by geographic region (urban vs. rural) and by age (1st and 5th grade). Participation was given for all children in the intervention group since in this group the intervention was part of the normal school curriculum. The intervention during one academic year consisted of: 1. two additional physical education classes per week given by trained physical education teachers adding up to a total of five PA classes per week, 2. short PA breaks (2-5 min each) during academic lessons, 3. PA home work, and 4. adaptation of recreational areas around the school. All children underwent anthropometric measurements, blood pressure assessment, fitness testing, measurement of PA and they filled out questionnaires. At least 70% of all children agreed to blood sampling and measurements of body composition and bone mineral measurements by dual energy x-ray absorptiometry. The primary endpoints of the study after one year were an increase in total PA by accelerometry, an increase in aerobic fitness measured by the 20 m shuttle run, a decrease in percent body fat derived from skinfold measurements and an increase in quality of life as assessed by the child health questionnaire in the intervention group compared to the control group. Secondary outcomes were overall fitness, differences in body composition including body fat distribution, cardiovascular risk factors, psychosocial health, bone mineral content and density of femur, lumbar spine and total body and food intake. DISCUSSION: Our preliminary data suggest that the children were representative of Swiss children with respect to sex, socio-demographic status, and body mass index. Short-term results can be expected by the beginning of 2007. We hypothesized that our intervention will lead to an increase in PA, fitness and overall health. Based on our data, we aim to provide important information regarding the influence of such an intervention on these outcome measures in school-aged children and to provide nationwide guidelines to improve PA in children.

Single pollutant versus surrogate measure approaches: do single pollutant risk assessments underestimate the impact of air pollution on lung cancer risk?

Cancer risk as a result of air pollution may be quantified by different approaches. We compared the sum of unit risk based effects of single pollutants with an epidemiology-based method by using PM(10) as a surrogate of the total air pollution. The excess rate for lung cancer cases attributable to an increase of 10 microg/m3 in average PM(10) exposure was estimated from available cohort studies. Applying the epidemiology-based risk method to the air pollution situation in the Basel area (Switzerland) resulted in 13.3 (95% CI = 6.9-19.8) excess lung cancer cases per 100,000 person years. This estimate was considerably higher than the unit risk-based estimate yielding 1.1 (range, 0.45-2.8) cancer cases per 100,000 person years. We discuss these discrepancies in light of inherent differences between approaches in toxicology and epidemiology.

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.

Ultraviolet emission spectra of sunbeds.

It is well known that UV radiation contributes to the development of skin cancer. Exposure to solar radiation is predominantly responsible for the high incidence rate of skin cancer, but there are also indications that sunbeds are involved. The aim of the present investigation was to determine the UV emission spectra of sunbeds. It included the most common sunbed models, which cover more than 50% of the Swiss market. The UV emission spectra of sunbeds have special characteristics and are different from the sun spectrum, which can be seen in high-resolution spectral measurements. Sunbed emission spectra are similar to the sun spectrum in the UVB (280-320 nm) range but reach values 10 to 15 times higher in the UVA (320-400 nm) range. An average erythema-effective irradiance of 0.33 W/m2 was determined for sunbeds. This corresponds to a UV index of 13, which is significantly higher than the UV index of 8.5 of the high summer sun at noon at intermediate latitudes. The measurements were spread over the whole effective area of the sunbeds, and an inhomogeneous distribution of the irradiances with variations of up to 30% from the average value was found.

[Behavior of sunbed users in Switzerland]. / Benützungsverhalten von Solarienbesucherinnen und -besuchern in der Schweiz.

OBJECTIVES: A constant rise in the number of skin cancer cases has been observed during the last few years. An important reason for this trend is that exposure of the population to UV radiation is higher. Although natural UV radiation is the major source, exposure due to use of sunbeds must be considered from the point of view of prevention. METHODS: 151 sunbed users in Bern and Basel were questioned on their reasons for visiting a solarium, their behaviour when using a sunbed and their awareness of risks resulting from UV radiation. RESULTS: It was shown that young women are the most frequent sunbed users. Also, sunbeds are often used regularly, not only for cosmetic reasons but also from a desire for relaxing and well-being in the warmth and light. Although most of the persons questioned were aware of certain health risks resulting from UV radiation, this knowledge hardly influenced their behaviour. Thus, more than half the people questioned use sunbeds longer and more often than advised by international recommendations. CONCLUSIONS: In view of a continuing increase in the number of skin cancer cases the improvement of preventive strategies for sunbed users is of major importance. Another urgent requirement is informing the public and increasing the general awareness of possible adverse health effects caused by UV radiation.