Asthma in farm children is more determined by genetic polymorphisms and in non-farm children by environmental factors.

BACKGROUND: The asthma syndrome is influenced by hereditary and environmental factors. With the example of farm exposure, we study whether genetic and environmental factors interact for asthma. METHODS: Statistical learning approaches based on penalized regression and decision trees were used to predict asthma in the GABRIELA study with 850 cases (9% farm children) and 857 controls (14% farm children). Single-nucleotide polymorphisms (SNPs) were selected from a genome-wide dataset based on a literature search or by statistical selection techniques. Prediction was assessed by receiver operating characteristics (ROC) curves and validated in the PASTURE cohort. RESULTS: Prediction by family history of asthma and atopy yielded an area under the ROC curve (AUC) of 0.62 [0.57-0.66] in the random forest machine learning approach. By adding information on demographics (sex and age) and 26 environmental exposure variables, the quality of prediction significantly improved (AUC = 0.65 [0.61-0.70]). In farm children, however, environmental variables did not improve prediction quality. Rather SNPs related to IL33 and RAD50 contributed significantly to the prediction of asthma (AUC = 0.70 [0.62-0.78]). CONCLUSIONS: Asthma in farm children is more likely predicted by other factors as compared to non-farm children though in both forms, family history may integrate environmental exposure, genotype and degree of penetrance.

Correction to: Prevalence of wheezing and atopic diseases in Austrian schoolchildren in conjunction with urban, rural or farm residence.

Correction: Wien Klin Wochenschr 2014 https://doi.org/10.1007/s00508-014-0571-z The disclosure needs to additionally mention the following:Erika von Mutius is listed as inventor on the following patents: Publication number EP 1411977: Composition containing bacterial antigens used for the prophylaxis ….

High levels of butyrate and propionate in early life are associated with protection against atopy.

BACKGROUND: Dietary changes are suggested to play a role in the increasing prevalence of allergic diseases and asthma. Short-chain fatty acids (SCFAs) are metabolites present in certain foods and are produced by microbes in the gut following fermentation of fibers. SCFAs have been shown to have anti-inflammatory properties in animal models. Our objective was to investigate the potential role of SCFAs in the prevention of allergy and asthma. METHODS: We analyzed SCFA levels by high-performance liquid chromatography (HPLC) in fecal samples from 301 one-year-old children from a birth cohort and examined their association with early life exposures, especially diet, and allergy and asthma later in life. Data on exposures and allergic diseases were collected by questionnaires. In addition, we treated mice with SCFAs to examine their effect on allergic airway inflammation. RESULTS: Significant associations between the levels of SCFAs and the infant's diet were identified. Children with the highest levels of butyrate and propionate (≥95th percentile) in feces at the age of one year had significantly less atopic sensitization and were less likely to have asthma between 3 and 6 years. Children with the highest levels of butyrate were also less likely to have a reported diagnosis of food allergy or allergic rhinitis. Oral administration of SCFAs to mice significantly reduced the severity of allergic airway inflammation. CONCLUSION: Our results suggest that strategies to increase SCFA levels could be a new dietary preventive option for allergic diseases in children.

The protective effect of cheese consumption at 18 months on allergic diseases in the first 6 years.

BACKGROUND: The effect of exposure to microorganisms on allergic diseases has been well studied. The protective effect of early food diversity against allergic diseases was previously shown in the PASTURE cohort study. The consumption of cheese, a food potentially rich in microbial diversity, deserves further examination. We aimed to evaluate whether cheese consumption is associated with allergic diseases. METHODS: In the PASTURE study (birth cohort in 5 European countries), data on feeding practices, environmental factors, and allergic diseases were collected by questionnaires from birth to 6 years (N = 931). Cheese consumption at 18 months of age was quantified in terms of frequency and diversity (ie, number of consumed types among 6 types: hard pressed, semipressed, soft, blue, fresh cheese, and cheese from the farm). Multiple logistic regressions were performed to evaluate the effect of cheese consumption on atopic dermatitis (AD), food allergy (FA), allergic rhinitis, asthma, and atopic sensitization at 6 years after adjustment for confounders of atopy. RESULTS: Cheese consumption (vs. nonconsumption) had a significant protective effect on AD (OR = 0.51 [0.29-0.90], P = 0.02) and FA (OR = 0.32, [0.15-0.71], P = 0.004), but no effect on atopic sensitization, allergic rhinitis, and asthma at 6 years. This effect on AD and FA may be related to the diversity of consumed cheeses (OR = 0.64 [0.48-0.85] per cheese type, P = 0.002; OR = 0.55 [0.33-0.92], P = 0.02, respectively). CONCLUSION: Although reverse causality cannot totally be ruled out, cheese diversity at 18 months had a protective effect against AD and FA at 6 years in addition to the protective effect of diversity of other foods.

Exposure to nonmicrobial N-glycolylneuraminic acid protects farmers' children against airway inflammation and colitis.

BACKGROUND: Childhood exposure to a farm environment has been shown to protect against the development of inflammatory diseases, such as allergy, asthma, and inflammatory bowel disease. OBJECTIVE: We sought to investigate whether both exposure to microbes and exposure to structures of nonmicrobial origin, such as the sialic acid N-glycolylneuraminic acid (Neu5Gc), might play a significant role. METHODS: Exposure to Neu5Gc was evaluated by quantifying anti-Neu5Gc antibody levels in sera of children enrolled in 2 farm studies: the Prevention of Allergy Risk factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle (PARSIFAL) study (n = 299) and the Protection Against Allergy Study in Rural Environments (PASTURE) birth cohort (cord blood [n = 836], 1 year [n = 734], 4.5 years [n = 700], and 6 years [n = 728]), and we associated them with asthma and wheeze. The effect of Neu5Gc was examined in murine airway inflammation and colitis models, and the role of Neu5Gc in regulating immune activation was assessed based on helper T-cell and regulatory T-cell activation in mice. RESULTS: In children anti-Neu5Gc IgG levels correlated positively with living on a farm and increased peripheral blood forkhead box protein 3 expression and correlated inversely with wheezing and asthma in nonatopic subjects. Exposure to Neu5Gc in mice resulted in reduced airway hyperresponsiveness and inflammatory cell recruitment to the lung. Furthermore, Neu5Gc administration to mice reduced the severity of a colitis model. Mechanistically, we found that Neu5Gc exposure reduced IL-17+ T-cell numbers and supported differentiation of regulatory T cells. CONCLUSIONS: In addition to microbial exposure, increased exposure to non-microbial-derived Neu5Gc might contribute to the protective effects associated with the farm environment.

Phenotypes of Atopic Dermatitis Depending on the Timing of Onset and Progression in Childhood.

Importance: Atopic dermatitis is an inflammatory, pruritic skin disease that often occurs in early infancy with a chronic course. However, a specific description of subtypes of atopic dermatitis depending on the timing of onset and progression of the disease in childhood is lacking. Objective: To identify different phenotypes of atopic dermatitis using a definition based on symptoms before age 6 years and to determine whether some subtypes are more at risk for developing other allergic diseases. Design, Setting, and Participants: The Protection Against Allergy Study in Rural Environments (PASTURE) is a European birth cohort where pregnant women were recruited between August 2002 and March 2005 and divided in 2 groups dependent on whether they lived on a farm. Children from this cohort with data on atopic dermatitis from birth to 6 years of age were included. Exposures: Atopic dermatitis, defined as an itchy rash on typical locations from birth to 6 years. Main Outcomes and Measures: The latent class analysis was used to identify subtypes of atopic dermatitis in childhood based on the course of symptoms. Multivariable logistic regressions were used to analyze the association between atopic dermatitis phenotypes and other allergic diseases. Results: We included 1038 children; of these, 506 were girls. The latent class analysis model with the best fit to PASTURE data separated 4 phenotypes of atopic dermatitis in childhood: 2 early phenotypes with onset before age 2 years (early transient [n = 96; 9.2%] and early persistent [n = 67; 6.5%]), the late phenotype with onset at age 2 years or older (n = 50; 4.8%), and the never/infrequent phenotype (n = 825; 79.5%), defined as children with no atopic dermatitis. Children with both parents with history of allergies were 5 times more at risk to develop atopic dermatitis with an early-persistent phenotype compared with children with parents with no history of allergies. Both early phenotypes were strongly associated with food allergy. The risk of developing asthma was significantly increased among the early-persistent phenotype (adjusted odds ratio, 2.87; 95% CI, 1.31-6.31). The late phenotype was only positively associated with allergic rhinitis. Conclusions and Relevance: Using latent class analysis, 4 phenotypes of atopic dermatitis were identified depending on the onset and course of the disease. The prevalence of asthma and food allergy by 6 years of age was strongly increased among children with early phenotypes (within age 2 years), especially with persistent symptoms. These findings are important for the development of strategies in allergy prevention.

Bacterial microbiota of the upper respiratory tract and childhood asthma.

BACKGROUND: Patients with asthma and healthy controls differ in bacterial colonization of the respiratory tract. The upper airways have been shown to reflect colonization of the lower airways, the actual site of inflammation in asthma, which is hardly accessible in population studies. OBJECTIVE: We sought to characterize the bacterial communities at 2 sites of the upper respiratory tract obtained from children from a rural area and to relate these to asthma. METHODS: The microbiota of 327 throat and 68 nasal samples from school-age farm and nonfarm children were analyzed by 454-pyrosequencing of the bacterial 16S ribosomal RNA gene. RESULTS: Alterations in nasal microbiota but not of throat microbiota were associated with asthma. Children with asthma had lower α- and ß-diversity of the nasal microbiota as compared with healthy control children. Furthermore, asthma presence was positively associated with a specific operational taxonomic unit from the genus Moraxella in children not exposed to farming, whereas in farm children Moraxella colonization was unrelated to asthma. In nonfarm children, Moraxella colonization explained the association between bacterial diversity and asthma to a large extent. CONCLUSIONS: Asthma was mainly associated with an altered nasal microbiota characterized by lower diversity and Moraxella abundance. Children living on farms might not be susceptible to the disadvantageous effect of Moraxella. Prospective studies may clarify whether Moraxella outgrowth is a cause or a consequence of loss in diversity.

IL-33 polymorphisms are associated with increased risk of hay fever and reduced regulatory T cells in a birth cohort.

BACKGROUND: IL-33 polymorphisms influence the susceptibility to asthma. IL-33 indirectly induces Th2-immune responses via dendritic cell activation, being important for development of atopic diseases. Furthermore, IL-33 upregulates regulatory T cells (Tregs), which are critical for healthy immune homeostasis. This study investigates associations between IL-33 polymorphisms during the development of childhood atopic diseases and underlying mechanisms including immune regulation of Tregs. METHODS: Genotyping of IL-33-polymorphisms (rs928413, rs1342326) was performed by MALDI-TOF-MS in 880 of 1133 PASTURE/EFRAIM children. In 4.5-year-old German PASTURE/EFRAIM children (n = 99), CD4+ CD25high FOXP3+ Tregs were assessed by flow cytometry following 24-h incubation of PBMCs with PMA/ionomycin, LPS or without stimuli (U). SOCS3, IL1RL1, TLR4 mRNA expression and sST2 protein levels ex vivo were measured in PASTURE/EFRAIM children by real-time PCR or ELISA, respectively. Health outcomes (hay fever, asthma) were assessed by questionnaires at the age of 6 years. RESULTS: rs928413 and rs1342326 were positively associated with hay fever (OR = 1.77, 95%CI = 1.02-3.08; OR = 1.79, 95%CI = 1.04-3.11) and CD4+ CD25high FOXP3+ Tregs (%) decreased in minor allele homozygotes/heterozygotes compared to major allele homozygotes (p(U) = 0.004; p(LPS) = 0.005; p(U) = 0.001; p(LPS) = 0.012). SOCS3 mRNA expression increased in minor allele homozygotes and heterozygotes compared with major allele homozygotes for both IL-33-polymorphisms (p(rs928413) = 0.032, p(rs1342326) = 0.019) and negatively correlated to Tregs. CONCLUSIONS: IL-33-polymorphisms rs928413 and rs1342326 may account for an increased risk of hay fever with the age of 6 years. Lower Tregs and increased SOCS3 in combined heterozygotes and minor allele homozygotes may be relevant for hay fever development, pointing towards dysbalanced immune regulation and insufficient control of allergic inflammation.

Health Impacts of Active Transportation in Europe.

Policies that stimulate active transportation (walking and bicycling) have been related to heath benefits. This study aims to assess the potential health risks and benefits of promoting active transportation for commuting populations (age groups 16-64) in six European cities. We conducted a health impact assessment using two scenarios: increased cycling and increased walking. The primary outcome measure was all-cause mortality related to changes in physical activity level, exposure to fine particulate matter air pollution with a diameter <2.5 µm, as well as traffic fatalities in the cities of Barcelona, Basel, Copenhagen, Paris, Prague, and Warsaw. All scenarios produced health benefits in the six cities. An increase in bicycle trips to 35% of all trips (as in Copenhagen) produced the highest benefits among the different scenarios analysed in Warsaw 113 (76-163) annual deaths avoided, Prague 61 (29-104), Barcelona 37 (24-56), Paris 37 (18-64) and Basel 5 (3-9). An increase in walking trips to 50% of all trips (as in Paris) resulted in 19 (3-42) deaths avoided annually in Warsaw, 11(3-21) in Prague, 6 (4-9) in Basel, 3 (2-6) in Copenhagen and 3 (2-4) in Barcelona. The scenarios would also reduce carbon dioxide emissions in the six cities by 1,139 to 26,423 (metric tonnes per year). Policies to promote active transportation may produce health benefits, but these depend of the existing characteristics of the cities. Increased collaboration between health practitioners, transport specialists and urban planners will help to introduce the health perspective in transport policies and promote active transportation.

ω-3 fatty acids contribute to the asthma-protective effect of unprocessed cow's milk.

BACKGROUND: Living on a farm has repeatedly been shown to protect children from asthma and allergies. A major factor involved in this effect is consumption of unprocessed cow's milk obtained directly from a farm. However, this phenomenon has never been shown in a longitudinal design, and the responsible milk components are still unknown. OBJECTIVES: We sought to assess the asthma-protective effect of unprocessed cow's milk consumption in a birth cohort and to determine whether the differences in the fatty acid (FA) composition of unprocessed farm milk and industrially processed milk contributed to this effect. METHODS: The Protection Against Allergy-Study in Rural Environments (PASTURE) study followed 1133 children living in rural areas in 5 European countries from birth to age 6 years. In 934 children milk consumption was assessed by using yearly questionnaires, and samples of the "usually" consumed milk and serum samples of the children were collected at age 4 years. Doctor-diagnosed asthma was parent reported at age 6 years. In a nested case-control study of 35 asthmatic and 49 nonasthmatic children, 42 FAs were quantified in milk samples. RESULTS: The risk of asthma at 6 years of age was reduced by previous consumption of unprocessed farm milk compared with shop milk (adjusted odds ratio for consumption at 4 years, 0.26; 95% CI, 0.10-0.67). Part of the effect was explained by the higher fat content of farm milk, particularly the higher levels of ω-3 polyunsaturated FAs (adjusted odds ratio, 0.29; 95% CI, 0.11-0.81). CONCLUSION: Continuous farm milk consumption in childhood protects against asthma at school age partially by means of higher intake of ω-3 polyunsaturated FAs, which are precursors of anti-inflammatory mediators.

The Early Development of Wheeze. Environmental Determinants and Genetic Susceptibility at 17q21.

RATIONALE: Growing up on a farm protects from childhood asthma and early wheeze. Virus-triggered wheeze in infancy predicts asthma in individuals with a genetic asthma risk associated with chromosome 17q21. OBJECTIVES: To test environmental determinants of infections and wheeze in the first year of life, potential modifications of these associations by 17q21, and the implications for different trajectories of wheeze. METHODS: We followed 983 children in rural areas of Europe from birth until age 6 years. Symptoms of wheeze, rhinitis, fever, and environmental exposures were documented with weekly diaries during year 1. Asthma at age 6 was defined as ever having a reported doctor's diagnosis. Single-nucleotide polymorphisms related to ORMDL3 (rs8076131) and GSDMB (rs7216389, rs2290400) at 17q21 were genotyped. MEASUREMENTS AND MAIN RESULTS: Early wheeze was positively associated with presence of older siblings among carriers of known asthma risk alleles at 17q21 (e.g., rs8076131) (adjusted odds ratio [aOR], 1.53; 95% confidence interval [CI], 1.16-2.01). Exposure to farm animal sheds was inversely related to wheeze (aOR, 0.44; 95% CI, 0.33-0.60). Both effects were similarly observed in children with transient wheeze up to age 3 years without subsequent development of asthma (aOR, 1.71 [95% CI, 1.09-2.67]; and aOR, 0.48 [95% CI, 0.30-0.76], respectively). CONCLUSIONS: These findings suggest that the chromosome 17q21 locus relates to episodes of acute airway obstruction common to both transient wheeze and asthma. The previously identified asthma risk alleles are the ones susceptible to environmental influences. Thus, this gene-environment interaction reveals two faces of 17q21: The same genotype constitutes genetic risk and allows for environmental protection, thereby providing options for prospective prevention strategies.

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.

Bacterial Exposures and Associations with Atopy and Asthma in Children.

BACKGROUND: The increase in prevalence of asthma and atopic diseases in Western countries has been linked to aspects of microbial exposure patterns of people. It remains unclear which microbial aspects contribute to the protective farm effect. OBJECTIVE: The objective of this study was to identify bacterial groups associated with prevalence of asthma and atopy, and to quantify indoor exposure to some of these bacterial groups. METHODS: A DNA fingerprinting technique, denaturing gradient gel electrophoresis (DGGE), was applied to mattress dust samples of farm children and control children in the context of the GABRIEL Advanced study. Associations between signals in DGGE and atopy, asthma and other allergic health outcomes were analyzed. Quantitative DNA based assays (qPCR) for four bacterial groups were applied on the dust samples to seek quantitative confirmation of associations indicated in DNA fingerprinting. RESULTS: Several statistically significant associations between individual bacterial signals and also bacterial diversity in DGGE and health outcomes in children were observed. The majority of these associations showed inverse relationships with atopy, less so with asthma. Also, in a subsequent confirmation study using a quantitative method (qPCR), higher mattress levels of specifically targeted bacterial groups - Mycobacterium spp., Bifidobacteriaceae spp. and two different clusters of Clostridium spp. - were associated with a lower prevalence of atopy. CONCLUSION: DNA fingerprinting proved useful in identifying bacterial signals that were associated with atopy in particular. These findings were quantitatively confirmed for selected bacterial groups with a second method. High correlations between the different bacterial exposures impede a clear attribution of protective effects to one specific bacterial group. More diverse bacterial flora in mattress dust may link to microbial exposure patterns that protect against development of atopic diseases.

Regional differences of physical activity and sedentary behaviour in Swiss children are not explained by socio-demographics or the built environment.

OBJECTIVE: We evaluated whether regional differences in physical activity (PA) and sedentary behaviour (SB) existed along language boundaries within Switzerland and whether potential differences would be explained by socio-demographics or environmental characteristics. METHODS: We combined data of 611 children aged 4 to 7 years from four regional studies. PA and SB were assessed by accelerometers. Information about the socio-demographic background was obtained by questionnaires. Objective neighbourhood attributes could be linked to home addresses. Multivariate regression models were used to test associations between PA and SB and socio-demographic characteristics and neighbourhood attributes. RESULTS: Children from the German compared to the French-speaking region were more physically active and less sedentary (by 10-15 %, p < 0.01). Although German-speaking children lived in a more favourable environment and a higher socioeconomic neighbourhood (differences p < 0.001), these characteristics did not explain the differences in PA behaviour between French and German speaking. CONCLUSIONS: Factors related to the language region, which might be culturally rooted were among the strongest correlates of PA and SB among Swiss children, independent of individual, social and environmental factors.

Consumption of unprocessed cow's milk protects infants from common respiratory infections.

BACKGROUND: Breast-feeding is protective against respiratory infections in early life. Given the co-evolutionary adaptations of humans and cattle, bovine milk might exert similar anti-infective effects in human infants. OBJECTIVE: To study effects of consumption of raw and processed cow's milk on common infections in infants. METHODS: The PASTURE birth cohort followed 983 infants from rural areas in Austria, Finland, France, Germany, and Switzerland, for the first year of life, covering 37,306 person-weeks. Consumption of different types of cow's milk and occurrence of rhinitis, respiratory tract infections, otitis, and fever were assessed by weekly health diaries. C-reactive protein levels were assessed using blood samples taken at 12 months. RESULTS: When contrasted with ultra-heat treated milk, raw milk consumption was inversely associated with occurrence of rhinitis (adjusted odds ratio from longitudinal models [95% CI]: 0.71 [0.54-0.94]), respiratory tract infections (0.77 [0.59-0.99]), otitis (0.14 [0.05-0.42]), and fever (0.69 [0.47-1.01]). Boiled farm milk showed similar but weaker associations. Industrially processed pasteurized milk was inversely associated with fever. Raw farm milk consumption was inversely associated with C-reactive protein levels at 12 months (geometric means ratio [95% CI]: 0.66 [0.45-0.98]). CONCLUSIONS: Early life consumption of raw cow's milk reduced the risk of manifest respiratory infections and fever by about 30%. If the health hazards of raw milk could be overcome, the public health impact of minimally processed but pathogen-free milk might be enormous, given the high prevalence of respiratory infections in the first year of life and the associated direct and indirect costs.

The relevance of commuter and work/school exposure in an epidemiological study on traffic-related air pollution.

Exposure during transport and at non-residential locations is ignored in most epidemiological studies of traffic-related air pollution. We investigated the impact of separately estimating NO2 long-term outdoor exposures at home, work/school, and while commuting on the association between this marker of exposure and potential health outcomes. We used spatially and temporally resolved commuter route data and model-based NO2 estimates of a population sample in Basel, Switzerland, to assign individual NO2-exposure estimates of increasing complexity, namely (1) home outdoor concentration; (2) time-weighted home and work/school concentrations; and (3) time-weighted concentration incorporating home, work/school and commute. On the basis of their covariance structure, we estimated the expectable relative differences in the regression slopes between a quantitative health outcome and our measures of individual NO2 exposure using a standard measurement error model. The traditional use of home outdoor NO2 alone indicated a 12% (95% CI: 11-14%) underestimation of related health effects as compared with integrating both home and work/school outdoor concentrations. Mean contribution of commuting to total weekly exposure was small (3.2%; range 0.1-13.5%). Thus, ignoring commute in the total population may not significantly underestimate health effects as compared with the model combining home and work/school. For individuals commuting between Basel-City and Basel-Country, ignoring commute may produce, however, a significant attenuation bias of 4% (95% CI: 4-5%). Our results illustrate the importance of including work/school locations in assessments of long-term exposures to traffic-related air pollutants such as NO2. Information on individuals' commuting behavior may further improve exposure estimates, especially for subjects having lengthy commutes along major transportation routes.

Prevalence of wheezing and atopic diseases in Austrian schoolchildren in conjunction with urban, rural or farm residence.

BACKGROUND: A large number of studies have consistently shown that children growing up on a farm have a reduced prevalence of allergic disorders. The GABRIEL Advanced Study was conducted in five rural areas of southern Germany, Switzerland, Austria and Poland to shed light on the protective 'farm effect' on asthma and atopic disease. Whereas, the GABRIEL Advanced Study focussed on rural children only, the present study incorporates data from Innsbruck town children also. METHODS: A screening questionnaire was developed to identify children with and without atopic disease within their living environment. Children were stratified into farm children, rural children and Innsbruck-town children. Within the farming environment, regular exposure to the following key factors of interest was predefined: the animal shed, the hay loft and farm milk. Wheezing in the past 12 months (W12), doctor-diagnosed (dd)-asthma, dd-allergic rhinitis and dd-atopic dermatitis were evaluated by using standardized questions from the International Study of Asthma and Allergies in Childhood (ISAAC) RESULTS: Farm children with regular exposure showed a lower risk for W12 (odds ratios (OR) = 0.3; 95%; confidence interval (CI) 0.2-0.5), dd-asthma (OR = 0.4; 95% CI 0.2-0.9) and dd-hay fever (OR 0.2; 95% CI 0.1-0.4). The protective effect of regular exposure extended to rural children but included W12 and dd-hay fever only. Multivariate logistic regression analysis for children being regularly exposed revealed protective attributes for the animal shed, the hay loft and farm milk. CONCLUSION: These data show that regular exposure to a farming environment protects against wheezing, asthma and hay fever. Regarding wheezing and hay fever, this effect was not restricted to children living on a farm but also notable in rural children with regular farm contact.

Immunoglobulin A and immunoglobulin G antibodies against ß-lactoglobulin and gliadin at age 1 associate with immunoglobulin E sensitization at age 6.

BACKGROUND: Serum immunoglobulin A (IgA) and immunoglobulin G (IgG) antibodies against wheat gliadin and cow's milk ß-lactoglobulin (BLG) are considered markers of gut permeability and inflammation which modulate the development of mucosal tolerance. Living on a farm has been shown to decrease allergies in children. Our aim was to study whether farm environment affected mucosal tolerance, immunoglobulin E (IgE) sensitization, or allergic diseases. METHODS: The PASTURE birth cohort study was conducted in Finland, France, Germany, Austria, and Switzerland. At age 1, we measured serum IgA and IgG against wheat gliadin (N = 636) and cow's milk BLG (N = 639) using ELISA. Serum-specific IgE was measured at ages 1 and 6 (N = 459). Data on environmental factors and allergic diseases were collected by questionnaires. Discrete time hazard and multivariate logistic regression models were used for analyses. RESULTS: Increased IgA or IgG antibodies against BLG at age 1 increased the risk of sensitization to at least one of the measured allergens or food allergens at age 6. Increased IgG against gliadin at age 1 increased the risk of sensitization to any, at least one inhalant, or at least one food allergen at age 6. Early exposure to cow's milk formula associated with increased IgA or IgG against BLG. No association with farming or clinical allergy was found. CONCLUSIONS: Increased IgA or IgG against BLG or gliadin at age 1 was associated with IgE sensitization at age 6. We suggest that an enhanced antibody response to food antigens reflects mucosal tolerance aberrancies, e.g., altered microbiota and/or increased gut permeability, which is later seen as sensitization to allergens.

Simulation of population-based commuter exposure to NO2 using different air pollution models.

We simulated commuter routes and long-term exposure to traffic-related air pollution during commute in a representative population sample in Basel (Switzerland), and evaluated three air pollution models with different spatial resolution for estimating commute exposures to nitrogen dioxide (NO2) as a marker of long-term exposure to traffic-related air pollution. Our approach includes spatially and temporally resolved data on actual commuter routes, travel modes and three air pollution models. Annual mean NO2 commuter exposures were similar between models. However, we found more within-city and within-subject variability in annual mean (±SD) NO2 commuter exposure with a high resolution dispersion model (40 ± 7 µg m(-3), range: 21-61) than with a dispersion model with a lower resolution (39 ± 5 µg m(-3); range: 24-51), and a land use regression model (41 ± 5 µg m(-3); range: 24-54). Highest median cumulative exposures were calculated along motorized transport and bicycle routes, and the lowest for walking. For estimating commuter exposure within a city and being interested also in small-scale variability between roads, a model with a high resolution is recommended. For larger scale epidemiological health assessment studies, models with a coarser spatial resolution are likely sufficient, especially when study areas include suburban and rural areas.