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International audience; Background The effect of exposure to micro-organisms 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 (i.e., number of consumed types among 6 types: hard pressed, semi-pressed, soft, blue, fresh 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. non-consumption) 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). Conclusions 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.

Streszczenie • Odwrotna zaleznośc pomiedzy spozyciem nieprzetworzonego mleka krowiego a zakazeniami ukladu oddechowego u niemowląt wskazuje na obecnośc przeciwzakaźnych i immunomodulujących cząsteczek związanych z tego typu zakazeniami u ludzi. • Zapobieganie zakazeniom ukladu oddechowego we wczesnym okresie zycia moze nie tylko ogolnie poprawiac stan tego ukladu, ale moze takze korzystnie wplywac na poźniejszy rozwoj ciezkich chorob ukladu oddechowego, jak np. astmy. Bezpieczne mikrobiologicznie, choc minimalnie przetworzone mleko moze miec istotny wplyw na zdrowie spoleczne w odniesieniu do czestych zakazen ukladu oddechowego. Wprowadzenie Karmienie piersią zapobiega zakazeniom ukladu oddechowego w pierwszych miesiącach zycia. Biorąc pod uwage wspolne ewolucyjne procesy adaptacyjne ludzi i bydla, mozliwe, ze mleko krowie wywiera podobny efekt ochronny u niemowląt u ludzi. Cel pracy Analiza wplywu spozywania surowego i przetworzonego mleka krowiego na najczestsze zakazenia ukladu oddechowego u niemowląt. Metody W ramach kohorty urodzeniowej w badaniu PASTURE obserwowano 983 niemowleta z terenow wiejskich z Austrii, Finlandii, Francji, Niemiec i Szwajcarii przez pierwszy rok zycia, obejmując lącznie 37 306 osobo-tygodni. Na podstawie cotygodniowych wpisow w dzienniczku stanu zdrowia analizowano spozycie roznych rodzajow mleka krowiego oraz wystepowanie niezytu blony śluzowej nosa, zakazenia ukladu oddechowego, zapalenia ucha i gorączki. Po 12 miesiącach pobierano probki krwi i oznaczano stezenie bialka C-reaktywnego. Wyniki W porownaniu z mlekiem UHT ( ultra-heat treatment ) spozywanie surowego mleka wykazywalo odwrotną zaleznośc z wystepowaniem niezytu blony śluzowej nosa (skorygowany iloraz szans z modeli longitudinalnych [95% CI]: 0,71 [0,54–0,94]), zakazen ukladu oddechowego (0,77 [0,59–0,99]), zapalenia ucha (0,14 [0,05–0,42]) i gorączki (0,69 [0,47–1,01]). Gotowane mleko wiejskie wykazalo podobną, choc nieco slabszą zaleznośc. Fabrycznie przetworzone mleko pasteryzowane wykazalo odwrotną zaleznośc z wystepowaniem gorączki. Spozywanie surowego mleka wiejskiego wiązalo sie odwrotnie zaleznie ze stezeniami bialka C-reaktywnego po 12 miesiącach (stosunek średnich geometrycznych [95% CI]: 0,66 [0,45–0,98]). Wnioski Spozywanie surowego mleka krowiego we wczesnym okresie zycia zmniejsza ryzyko wystepowania zakazen ukladu oddechowego i gorączki o okolo 30%. Biorąc pod uwage bardzo czeste wystepowanie zakazen ukladu oddechowego w pierwszym roku zycia oraz związane z tym koszty pośrednie i bezpośrednie wydaje sie, ze eliminacja zagrozen zdrowotnych związanych ze spozywaniem surowego mleka moglaby umozliwic ogromny wplyw minimalnie przetworzonego, ale pozbawionego patogenow mleka na zdrowie publiczne.

Background: Childhood asthma prevalence is significantly greater in urban areas compared with rural/farm environments. Murine studies have shown that TNF-alpha-induced protein 3 (TNFAIP3; A20), an anti-inflammatory regulator of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) signaling, mediates environmentally induced asthma protection. Objective: We aimed to determine the role of TNFAIP3 for asthma development in childhood and the immunomodulatory effects of environmental factors. Methods: In a representative selection of 250 of 2168 children from 2 prospective birth cohorts and 2 cross-sectional studies, we analyzed blood cells of healthy and asthmatic children from urban and rural/farm environments from Europe and China. PBMCs were stimulated ex vivo with dust from "asthma-protective'' farms or LPS. NF-kappa B signaling-related gene and protein expression was assessed in PBMCs and multiplex gene expression assays (NanoString Technologies) in isolated dendritic cells of schoolchildren and in cord blood mononuclear cells from newborns. Results: Anti-inflammatory TNFAIP3 gene and protein expression was consistently decreased, whereas proinflammatory Toll-like receptor 4 expression was increased in urban asthmatic patients (P

Background: Phenotypes of childhood-onset asthma are characterized by distinct trajectories and functional features. For atopy, definition of phenotypes during childhood is less clear. Objective: We sought to define phenotypes of atopic sensitization over the first 6 years of life using a latent class analysis (LCA) integrating 3 dimensions of atopy: allergen specificity, time course, and levels of specific IgE (sIgE). Methods: Phenotypes were defined by means of LCA in 680 children of the Multizentrische Allergiestudie (MAS) and 766 children of the Protection against allergy: Study in Rural Environments (PASTURE) birth cohorts and compared with classical nondisjunctive definitions of seasonal, perennial, and food sensitization with respect to atopic diseases and lung function. Cytokine levels were measured in the PASTURE cohort. Results: The LCA classified predominantly by type and multiplicity of sensitization (food vs inhalant), allergen combinations, and sIgE levels. Latent classes were related to atopic disease manifestations with higher sensitivity and specificity than the classical definitions. LCA detected consistently in both cohorts a distinct group of children with severe atopy characterized by high seasonal sIgE levels and a strong propensity for asthma; hay fever; eczema; and impaired lung function, also in children without an established asthma diagnosis. Severe atopy was associated with an increased IL-5/IFN-gamma ratio. A path analysis among sensitized children revealed that among all features of severe atopy, only excessive sIgE production early in life affected asthma risk. Conclusions: LCA revealed a set of benign, symptomatic, and severe atopy phenotypes. The severe phenotype emerged as a latent condition with signs of a dysbalanced immune response. It determined high asthma risk through excessive sIgE production and directly affected impaired lung function.

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., published version, peerReviewed

Background: Accurate diagnosis of allergic sensitization is essential in clinical practice and allergy research, and the choice of assessment method may have an important impact. The PASTURE study (Protection against Allergy: Study of Rural Environment) examines the influence of exposure to a dairy farm environment on the occurrence of allergy in a cohort of rural European children from birth to 10 years. The aim of our study was to analyze agreement between skin prick tests (SPTs), to aeroallergens and food allergens, and specific IgE and to evaluate the association of SPT with atopic dermatitis in the 204 French children of the PASTURE study. Methods: SPT, atopic dermatitis assessment, and specific IgE measurements were performed at 1, 4.5, and 6 years. Results: A total of 137 children attended all three visits. The agreement between SPTs and specific IgE was poor except for perennial aeroallergens at 6 years and for an IgE cutoff greater than 0.7 IU/ml (κ = 0.69, 0.5202 - 0.8621). The prevalence of positive SPTs increased with age. Positive SPTs were transient at 1 year, whereas they were persistent between 4.5 and 6 years. Positive SPTs at 1 year were predictive of the occurrence of atopic dermatitis during follow-up. Conclusion: SPTs did not have good agreement with serum-specific IgE in early childhood. Both tests (SPT and specific IgE) should be used. Skin allergenic reactivity increased with age and was transient at 1 year but associated with the occurrence of atopic dermatitis.

Introduction et but de l’étudeUne diversité alimentaire importante et précoce a été montrée protectrice contre des maladies allergiques (Roduit C. et al, JACI2012 Jul;130(1): 130-6). L’effet de la diversité de consommation de fromages, riches en microorganismes, n’a pas été étudié. Or l’exposition aux microorganismes est suspectée pour son rôle protecteur contre la survenue de maladies allergiques. Le but de notre étude était d’évaluer l’effet protecteur de la diversité de consommation de fromages contre des maladies allergiques (MA) : allergie alimentaire (AA), dermatite atopique (DA), asthme (AS), rhinite allergique (RA) et bronchite (BR).Matériel et méthodesL’étude a porté sur 941 enfants de la cohorte PATURE (Protection contre l’Allergie : étude du milieu Rural et de son Environnement) qui étudie l’influence de l’exposition à l’environnement fermier sur le développement des maladies allergiques dans 5 pays européens (France, Allemagne, Autriche, Suisse et Finlande). Les données concernant les habitudes alimentaires, l’atopie parentale et les facteurs environnementaux ont été colligées par questionnaire de la naissance à 6 ans. Les MA ont été définies par un diagnostic médical rapporté par les parents. Les fromages ont été classés en 6 catégories (à pâte dure pressée, semi-pressée, molle, bleu, frais, de la ferme). La diversité de consommation de fromages à 18 mois (DC18) a été définie par le nombre de différentes catégories de fromages consommées. L’effet de la diversité de consommation de fromages contre chaque MA à l’âge de 6 ans a été analysé par régressions logistiques linéaires multiples ajustées pour la diversité alimentaire à 6 mois, le pays, l’environnement fermier et les facteurs confondants d’atopie, comme l’atopie parentale.Résultats et Analyse statistiqueDC18 n’était pas corrélée à la diversité alimentaire à 6 ou 12 mois (P < 0,001). Une diversité élevée de fromages consommés avait un effet significativement protecteur contre la DA à 6 ans (P < 0,0007 ; OR = 0,60; IC[0,44;0,81]) et les AA à 6 ans (P < 0,041 ; OR = 0,57; IC[0,33;0,98]), mais pas contre les autres MA à 6 ans (AS, RA, BR).ConclusionLa consommation d’une diversité de fromages à 18 mois semble avoir un effet protecteur contre la DA et les A A à 6 ans, indépendamment de la diversité de consommation des autres groupes d’aliments.

Introduction et but de l’etude Une diversite alimentaire importante et precoce a ete montree protectrice contre des maladies allergiques (Roduit C. et al, JACI2012 Jul;130(1): 130-6). L’effet de la diversite de consommation de fromages, riches en microorganismes, n’a pas ete etudie. Or l’exposition aux microorganismes est suspectee pour son role protecteur contre la survenue de maladies allergiques. Le but de notre etude etait d’evaluer l’effet protecteur de la diversite de consommation de fromages contre des maladies allergiques (MA) : allergie alimentaire (AA), dermatite atopique (DA), asthme (AS), rhinite allergique (RA) et bronchite (BR). Materiel et methodes L’etude a porte sur 941 enfants de la cohorte PATURE (Protection contre l’Allergie : etude du milieu Rural et de son Environnement) qui etudie l’influence de l’exposition a l’environnement fermier sur le developpement des maladies allergiques dans 5 pays europeens (France, Allemagne, Autriche, Suisse et Finlande). Les donnees concernant les habitudes alimentaires, l’atopie parentale et les facteurs environnementaux ont ete colligees par questionnaire de la naissance a 6 ans. Les MA ont ete definies par un diagnostic medical rapporte par les parents. Les fromages ont ete classes en 6 categories (a pâte dure pressee, semi-pressee, molle, bleu, frais, de la ferme). La diversite de consommation de fromages a 18 mois (DC18) a ete definie par le nombre de differentes categories de fromages consommees. L’effet de la diversite de consommation de fromages contre chaque MA a l’âge de 6 ans a ete analyse par regressions logistiques lineaires multiples ajustees pour la diversite alimentaire a 6 mois, le pays, l’environnement fermier et les facteurs confondants d’atopie, comme l’atopie parentale. Resultats et Analyse statistique DC18 n’etait pas correlee a la diversite alimentaire a 6 ou 12 mois (P Conclusion La consommation d’une diversite de fromages a 18 mois semble avoir un effet protecteur contre la DA et les A A a 6 ans, independamment de la diversite de consommation des autres groupes d’aliments.

International audience; BACKGROUND: There is conflicting evidence on whether allergen-specific memory is primed prenatally, whether this priming affects persistent immunologic effects, and whether it is modulated by the first environmental exposures in infancy. OBJECTIVE: We sought to explore the course of atopic sensitization between birth and 12 months of age. METHODS: Specific IgE levels for 6 food and 13 common inhalant allergens were assessed in cord blood and 1-year blood samples in the Protection against Allergy-Study in Rural Environments (PASTURE) birth cohort including 793 children from rural regions of 5 European countries. Detailed information on children's health, nutrition, and farm-related exposures was gathered by using a pregnancy questionnaire, 2 questionnaires at 2 and 12 months of age, and a diary covering the time in between. RESULTS: Sensitization was more common at 12 months of age than at birth for almost all specificities. On an individual level, persistent sensitization to the same allergens was rare (1%), whereas transient (only at birth, 11%) and incident (only at 12 months, 34%) sensitization was seen in substantial proportions of children. Associations of transient sensitization with maternal sensitization differed with the allergen specificities, with the strongest associations for food allergens (odds ratio [OR], 10.6; 95% CI, 6.0-18.6) and the weakest associations for seasonal allergens (OR, 1.64; 95% CI, 0.94-2.86). Associations of maternal sensitization with incident sensitization were also seen. Incident sensitization was related to distinct prenatal and postnatal environmental exposures of mother and child, such as consumption of cereals for incident sensitization to seasonal allergens (OR, 0.66; 95% CI, 0.50-0.88). CONCLUSION: IgE sensitization patterns change between birth and 12 months and are related to maternal and environmental influences.

International audience; BACKGROUND: Early-life exposure to environmental microbial agents may be associated with development of wheezing and allergic diseases. OBJECTIVE: To assess the association of microbial exposure in rural homes with the risk of asthma, wheezing, atopic dermatitis and sensitization. METHODS: Birth cohorts of rural children (n = 1133), half from farmer families, were followed up from birth to 2 years of age by questionnaires in five European centres. Endotoxin and extracellular polysaccharides (EPS) of Penicillium and Aspergillus spp. were determined from living room floor and mother's mattress dust samples collected at 2 months of age. Specific IgE against 19 allergens was measured at 1 year of age. Discrete-time hazard models, generalized estimations equations (GEE) and logistic regression were used for statistical analyses. RESULTS: The incidence of asthma was inversely associated with the amount of dust (adjusted odds ratio (aOR) 0.73, 95% CI 0.58-0.93) and the loads (units/m(2)) of EPS (aOR 0.75, 95% CI 0.55-1.04) and endotoxin (aOR 0.79, 95% CI 0.60-1.05) in the mother's mattress. Similar associations were seen with wheezing and with living room floor dust. The microbial markers were highly correlated and their effects could not be clearly separated. The inverse associations were seen especially among non-farmers. The risk of sensitization to inhalant allergens increased with increasing endotoxin exposure from mattress dust. No associations were observed with concentrations (units/g) or with atopic dermatitis. CONCLUSION AND CLINICAL RELEVANCE: The amount and microbial content of house dust were inversely associated with asthma and wheezing, but due to high correlations between microbial agents and amount of dust, it was not possible to disentangle their individual effects. New ways to better measure and represent exposure to environmental microbes, including indexes of biodiversity, are needed especially among farmers.