Growing up on a farm is associated with an asthma-protective effect, but the mechanisms underlying this effect are largely unknown. In the Protection against Allergy: Study in Rural Environments ...(PASTURE) birth cohort, we modeled maturation using 16S rRNA sequence data of the human gut microbiome in infants from 2 to 12 months of age. The estimated microbiome age (EMA) in 12-month-old infants was associated with previous farm exposure (β = 0.27 (0.12-0.43), P = 0.001, n = 618) and reduced risk of asthma at school age (odds ratio (OR) = 0.72 (0.56-0.93), P = 0.011). EMA mediated the protective farm effect by 19%. In a nested case-control sample (n = 138), we found inverse associations of asthma with the measured level of fecal butyrate (OR = 0.28 (0.09-0.91), P = 0.034), bacterial taxa that predict butyrate production (OR = 0.38 (0.17-0.84), P = 0.017) and the relative abundance of the gene encoding butyryl-coenzyme A (CoA):acetate-CoA-transferase, a major enzyme in butyrate metabolism (OR = 0.43 (0.19-0.97), P = 0.042). The gut microbiome may contribute to asthma protection through metabolites, supporting the concept of a gut-lung axis in humans.
Background Most infants developing atopic dermatitis have a low risk for atopy. Primary prevention of atopic dermatitis is difficult. Objective To assess the effect of supplementation of an infant ...and follow-on formula with prebiotic and immunoactive oligosaccharides on the occurrence of atopic dermatitis in the first year of life. Methods Healthy term infants from 5 European countries with low atopy risk were recruited before the age of 8 weeks, either having started with formula feeding or being on full breast-feeding (breast-feeding group). Formula-fed infants were randomized to feeding with a regular formula containing a specific mixture of neutral oligosaccharides and pectin-derived acidic oligosaccharides (prebiotic formula group) or regular formula without oligosaccharides (control formula group). Results A total of 414 infants were randomized to the prebiotic group and 416 infants to the control group. A total of 300 infants were followed in the breast-feeding group. Up to the first birthday, atopic dermatitis occurred in significantly fewer infants from the prebiotic group (5.7%) than from the control group (9.7%; P = .04). The cumulative incidence of atopic dermatitis in the prebiotic group was in the low range of the breast-feeding group (7.3%). In a Cox regression model, the rate of atopic dermatitis was significantly lower by 44% in the prebiotic group versus the control group ( P = .04). The number needed to prevent 1 case of atopic dermatitis by supplementation of prebiotics was 25 infants. Conclusion Formula supplementation with a specific mixture of oligosaccharides was effective as primary prevention of atopic dermatitis in low atopy risk infants.
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.
Background The role of dietary factors in the development of allergies is a topic of debate, especially the potential associations between infant feeding practices and allergic diseases. Previously, ...we reported that increased food diversity introduced during the first year of life reduced the risk of atopic dermatitis. Objective In this study we investigated the association between the introduction of food during the first year of life and the development of asthma, allergic rhinitis, food allergy, or atopic sensitization, taking precautions to address reverse causality. We further analyzed the association between food diversity and gene expression of T-cell markers and of Cε germline transcript, reflecting antibody isotype switching to IgE, measured at 6 years of age. Methods Eight hundred fifty-six children who participated in a birth cohort study, Protection Against Allergy Study in Rural Environments/EFRAIM, were included. Feeding practices were reported by parents in monthly diaries during the first year of life. Data on environmental factors and allergic diseases were collected from questionnaires administered from birth up to 6 years of age. Results An increased diversity of complementary food introduced in the first year of life was inversely associated with asthma with a dose-response effect (adjusted odds ratio with each additional food item introduced, 0.74 95% CI, 0.61-0.89). A similar effect was observed for food allergy and food sensitization. Furthermore, increased food diversity was significantly associated with an increased expression of forkhead box protein 3 and a decreased expression of Cε germline transcript. Conclusion An increased diversity of food within the first year of life might have a protective effect on asthma, food allergy, and food sensitization and is associated with increased expression of a marker for regulatory T cells.
Background Traditional farming represents a unique model situation to investigate the relationship of early-life farm-related exposure and allergy protection. Objectives To investigate associations ...between maternal farm exposures and cytokine production in cord blood (CB) mononuclear cells in a prospective multinational birth cohort of 299 farm and 326 nonfarm children and their families. Methods Supernatants from phorbol 12-myristate 13-acetate/ionomycin–stimulated CB mononuclear cells were assessed for the production of IFN-γ, TNF-α, IL-5, IL-10, and IL-12. Results Significantly higher levels of IFN-γ and TNF-α in farm compared with nonfarm children were found, whereas IL-5, IL-10, and IL-12 levels did not differ between study groups. Maternal contact with different farm animal species and barns and consumption of farm-produced butter during pregnancy enhanced the production of proinflammatory CB cytokines, whereas maternal consumption of farm-produced yogurt resulted in significant lower levels of IFN-γ and TNF-α in umbilical blood. Conclusion Maternal exposure to farming activities and farm dairy products during pregnancy modulated cytokine production patterns of offspring at birth.
Summary
This statement was written by a group of pulmonologists and pediatric pulmonologists belonging to the corresponding professional associations ÖGP (Austrian Society for Pulmonology) and ÖGKJ ...(Austrian Society for pediatric and adolescent medicine) to provide a concise overview of the latest updates in the 2015 GINA Guidelines and to include aspects that are specific to Austria.
Background European cross-sectional studies have suggested that prenatal and postnatal farm exposure decreases the risk of allergic diseases in childhood. Underlying immunologic mechanisms are still ...not understood but might be modulated by immune-regulatory cells early in life, such as regulatory T (Treg) cells. Objective We sought to assess whether Treg cells from 4.5-year-old children from the Protection against Allergy: Study in Rural Environments birth cohort study are critical in the atopy and asthma-protective effect of farm exposure and which specific exposures might be relevant. Methods From 1133 children, 298 children were included in this study (149 farm and 149 reference children). Detailed questionnaires until 4 years of age assessed farming exposures over time. Treg cells were characterized as upper 20% CD4+ CD25+ forkhead box protein 3 (FOXP3)+ (intracellular) in PBMCs before and after stimulation (with phorbol 12-myristate 13-acetate/ionomycin or LPS), and FOXP3 demethylation was assessed. Atopic sensitization was defined by specific IgE measurements; asthma was defined by a doctor's diagnosis. Results Treg cells were significantly increased in farm-exposed children after phorbol 12-myristate 13-acetate/ionomycin and LPS stimulation. Exposure to farm milk was defined as a relevant independent farm-related exposure supported by higher FOXP3 demethylation. Treg cell (upper 20% CD4+ CD25+ , FOXP3+ T cells) numbers were significantly negatively associated with doctor-diagnosed asthma (LPS stimulated: adjusted odds ratio, 0.26; 95% CI, 0.08-0.88) and perennial IgE (unstimulated: adjusted odds ratio, 0.21; 95% CI, 0.08-0.59). Protection against asthma by farm milk exposure was partially mediated by Treg cells. Conclusions Farm milk exposure was associated with increased Treg cell numbers on stimulation in 4.5-year-old children and might induce a regulatory phenotype early in life, potentially contributing to a protective effect for the development of childhood allergic diseases.
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 finding that the prevalence of asthma and allergies is less frequent in children raised on animal farms has led to the conjecture that exposure to microbial products modifies immune responses. ...The toll-like receptors (TLRs) represent an evolutionarily conserved family of innate immunity receptors with microbial molecules as ligands.
We reasoned that polymorphisms in genes encoding TLRs might modulate the protective effects observed in farming populations.
Farmers' and nonfarmers' children living in rural areas in Austria and Germany and who were enrolled in the cross-sectional ALEX study were genotyped for single nucleotide polymorphisms in the
TLR2 and
TLR4 genes. The frequencies of asthma, allergic rhinitis, and atopic sensitization were compared between the genotypes in relation to exposure to farming and endotoxin.
Among farmers' children, those carrying a T allele in
TLR2/−16934 compared with children with genotype AA were significantly less likely to have a diagnosis of asthma (3% vs 13%,
P = .012), current asthma symptoms (3% vs 16%,
P = .004), atopic sensitization (14% vs 27%,
P = .023), and current hay fever symptoms (3% vs 14%,
P = .01). The association between
TLR2/−16934 and asthma among children of farmers was independent of atopy. No such association was found among children from the same rural communities but not living on farms.
Our results suggest that genetic variation in
TLR2 is a major determinant of the susceptibility to asthma and allergies in children of farmers.
A farming environment protects against development of asthma, hay fever, and atopic sensitisation in children. We aimed to establish whether increased exposure to microbial compounds has to occur ...early in life to affect maturation of the immune system and thereby reduces risk for development of allergic diseases.
We did a cross-sectional survey in rural areas of Austria, Germany, and Switzerland. 2618 (75%) of 3504 parents of 6-13-year-old children completed a standardised questionnaire on asthma, hay fever, and atopic eczema. Children from farming families, and a random sample of non-farmers' children, who gave consent for blood samples to be obtained for measurements of specific serum IgE antibodies to common allergens were invited to participate (n=901).
Exposure of children younger than 1 year, compared with those aged 1-5 years, to stables and consumption of farm milk was associated with lower frequencies of asthma (1% 3/218 vs 11% 15/138), hay fever (3% 7 vs 13% 18), and atopic sensitisation (12% 27 vs 29% 40). Protection against development of asthma was independent from effect on atopic sensitisation. Continual long-term exposure to stables until age 5 years was associated with the lowest frequencies of asthma (0.8% 1/122), hay fever (0.8% 1), and atopic sensitisation (8.2% 10).
Long-term and early-life exposure to stables and farm milk induces a strong protective effect against development of asthma, hay fever, and atopic sensitisation.
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