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 β-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.
Background Studies on the association of farm environments with asthma and atopy have repeatedly observed a protective effect of farming. However, no single specific farm-related exposure explaining ...this protective farm effect has consistently been identified. Objective We sought to determine distinct farm exposures that account for the protective effect of farming on asthma and atopy. Methods In rural regions of Austria, Germany, and Switzerland, 79,888 school-aged children answered a recruiting questionnaire (phase I). In phase II a stratified random subsample of 8,419 children answered a detailed questionnaire on farming environment. Blood samples and specific IgE levels were available for 7,682 of these children. A broad asthma definition was used, comprising symptoms, diagnosis, or treatment ever. Results Children living on a farm were at significantly reduced risk of asthma (adjusted odds ratio aOR, 0.68; 95% CI, 0.59-0.78; P < .001), hay fever (aOR, 0.43; 95% CI, 0.36-0.52; P < .001), atopic dermatitis (aOR, 0.80; 95% CI, 0.69-0.93; P = .004), and atopic sensitization (aOR, 0.54; 95% CI, 0.48-0.61; P < .001) compared with nonfarm children. Whereas this overall farm effect could be explained by specific exposures to cows, straw, and farm milk for asthma and exposure to fodder storage rooms and manure for atopic dermatitis, the farm effect on hay fever and atopic sensitization could not be completely explained by the questionnaire items themselves or their diversity. Conclusion A specific type of farm typical for traditional farming (ie, with cows and cultivation) was protective against asthma, hay fever, and atopy. However, whereas the farm effect on asthma could be explained by specific farm characteristics, there is a link still missing for hay fever and atopy.
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.
Because of the small number of children in the study, we were not able to determine specific differences in lifestyle, diet, exposures, or family history between those Amish children who were ...sensitized and those who were not sensitized. Previous studies in Switzerland and Crete show a protective effect of farm life or rural living, with a 50% reduction in the prevalence of allergic sensitization as compared with nonfarm or urban living. ...given the exceedingly low level of sensitization of 7.2% among Amish children, we feel that there may be additional protective factors in this population. n (%) Amish (n = 157) Swiss farmer (n = 3,006) Swiss nonfarmer (n = 10,912) Female sex 61 (39.9) 1,542 (51.3) 5,263 (48.3) Age (y), mean ± SD 10.1 ± 1.70 9.9 ± 1.89 9.9 ± 1.88 No. of children, mean ± SDlow * 5.9 ± 2.25 3.3 ± 1.27 2.4 ± 0.94 Maternal smokingdagger Never 64 (92.8) 1,567 (79.3) 5,171 (62.6) Ex-smoker 0 240 (12.1) 1685 (20.4) Current 5 (7.2) 170 (8.6) 1,398 (16.9) Parents or siblings affected by Asthma 8 (5.2) 451 (15.2) 2,064 (19.1) Hay fever 24 (15.4) 559 (18.8) 4,127 (38.3) Atopic dermatitis 10 (6.4) 482 (16.3) 2,078 (19.3) Family lives on a farmdagger 61 (84.7) 2,024 (100.0)
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.
Background Although it is known that atopic dermatitis (AD) can develop during adolescence, research on its course and predictors in this age group is thus far limited. Objective We aimed to describe ...the course of AD over puberty and prospectively determine risk factors for the incidence, recurrence, and persistence of AD until adolescence in a population-based cohort study. Methods German participants of the International Study of Asthma and Allergies in Childhood Phase II were followed prospectively. The final dataset comprised 2857 adolescents, of whom 2433 were unaffected by AD at baseline. Bivariate and multivariate prediction models for the incidence, recurrence, and persistence of AD using early-life factors, family history of atopic diseases, and job history as predictors were developed. Results The incidence of AD between ages 9 to 11 and 16 to 20 years was 1.7%, and recurrence was 2.4%. AD persisted in 47.6% of adolescents with AD symptoms at baseline (n = 424). High socioeconomic status, female sex, asthma symptoms and a positive skin prick test response at baseline, parental history of rhinitis/AD, and having worked in a high-risk job were significant predictors for the course of disease. With all the factors present, the probability of the incidence of AD was 21.4% (95% CI, 1.8% to 80.2%) and increased up to 81.7% (95% CI, 47.0% to 95.8%) for recurrence of AD and 87.6% (95% CI, 63.4% to 96.6%) for persistence of AD among those affected by AD. Early-life exposures did not predict the course of AD over puberty. Conclusion Genetic factors, early allergen sensitization, and having worked in a high-risk job seem to be more important for disease development in late adolescence than other early-life exposures.
Background Asthma is a disease in which both genetic and environmental factors play important roles. The farming environment has consistently been associated with protection from childhood asthma and ...atopy, and interactions have been reported with polymorphisms in innate immunity genes. Objective To detect gene-environment interactions for asthma and atopy in the farming environment. Methods We performed a genome-wide interaction analysis for asthma and atopy by using 500,000 genotyped single nucleotide polymorphisms (SNPs) and farm-related exposures in 1708 children from 4 rural regions of Central Europe. We also tested selectively for interactions between farm exposures and 7 SNPs that emerged as genome-wide significant in a large meta-analysis of childhood asthma and 5 SNPs that had been reported previously as interacting with farm exposures for asthma or atopy. Results Neither the asthma-associated SNPs nor the SNPs previously published for interactions with asthma showed significant interactions. The genome-wide interaction study did not reveal any significant interactions with SNPs within genes in the range of interacting allele frequencies from 30% to 70%, for which our study was well powered. Among rarer SNPs, we identified 15 genes with strong interactions for asthma or atopy in relation to farming, contact with cows and straw, or consumption of raw farm milk. Conclusion Common genetic polymorphisms are unlikely to moderate the protective influence of the farming environment on childhood asthma and atopy, but rarer variants, particularly of the glutamate receptor, metabotropic 1 gene, may do so. Given the limited statistical power of our study, these findings should be interpreted with caution before being replicated in independent farm populations.
Accumulating evidence is indicating that hormonal factors play a role in new-onset allergic rhinitis and asthma after puberty.
To determine whether age at menarche and use of hormonal contraceptives ...predict new-onset allergic rhinitis and asthma after puberty in young German women.
A prospective community-based cohort study followed 1,191 girls 9 to 11 years old to early adulthood (19-24 years old). Self-administrated questionnaires concerning age at menarche, use of hormonal contraceptives, and status and age at onset of physician-diagnosed allergic rhinitis and asthma were collected at 16 to 18 and 19 to 24 years of age. Logistic regression models were used to analyze the incidence of asthma and allergic rhinitis after puberty and pooled estimates were obtained from the final model.
Eleven percent of girls developed allergic rhinitis after menarche and 3% reported new-onset asthma. Late menarche (>13 years of age) was statistically significantly inversely related to allergic rhinitis (adjusted odds ratio OR 0.32, 95% confidence interval CI 0.14-0.74) but did not reach the level of statistical significance for asthma (OR 0.32, 95% CI 0.07-1.42). Use of hormonal contraceptives was inversely associated with new-onset allergic rhinitis (OR 0.14, 95% CI 0.08-0.23) and asthma (OR 0.27, 95% CI 0.12-0.58) after puberty.
This study shows that girls with late onset of menarche are less likely to develop allergic rhinitis after puberty compared with those who have menarche at an average age. These findings also suggest that, in addition to endogenous hormones, hormonal contraceptives play a role and might protect young women from allergies and asthma.
In most children with asthma and atopy, onset of disease occurs early in life, indicating a crucial role of in utero and early childhood environment. However, only a small part of this burden of ...disease established early in life has been explained.
To examine the effects of early environmental exposures on the development of asthma and atopy within the setting of an affluent urban population.
The authors followed 526 German children from birth to 5 years of age. Parental interviews in pregnancy and then yearly assessed the health of the child and environmental characteristics. Endotoxin and allergens in house dust were measured at 3 months. Atopic sensitization was assessed at 1 and 5 years.
In atopic mothers, acute atopic symptoms during pregnancy were associated with increased risk of early atopic dermatitis (adjusted odds ratio aOR 1.74, 95% confidence interval CI 1.00-3.02) and allergic rhinitis at 5 years (aOR 2.11, 95% CI 1.01-4.41). Further, maternal illnesses during pregnancy (ie, repeated common colds) increased the risk of asthma at 5 years (aOR 2.31, 95% CI 1.12-4.78). Endotoxin in the child's mattress was inversely associated with atopic sensitization (aOR 0.79, 95% CI 0.64-0.97) and asthma (aOR 0.71, 95% CI 0.55-0.93). A contrasting effect of early endotoxin and mite exposure was observed for mite sensitization: mite exposure increased the risk of mite sensitization at 5 years (aOR 1.30, 95% CI 1.11-1.53), whereas endotoxin exposure was inversely associated with mite sensitization (aOR 0.73, 95% CI 0.57-0.95).
Factors affecting the in utero environment, such as maternal atopy and infections, and bacterial exposure in pregnancy or early life may act as immunomodulators enhancing or inhibiting the development of asthma and atopy in childhood.
Background There is evidence that gene expression of innate immunity receptors is upregulated by farming-related exposures. Objective We sought to determine environmental and nutritional exposures ...associated with the gene expression of innate immunity receptors during pregnancy and the first year of a child's life. Methods For the Protection Against Allergy: Study in Rural Environments (PASTURE) birth cohort study, 1133 pregnant women were recruited in rural areas of Austria, Finland, France, Germany, and Switzerland. mRNA expression of the Toll-like receptor (TLR) 1 through TLR9 and CD14 was assessed in blood samples at birth (n = 938) and year 1 (n = 752). Environmental exposures, as assessed by using questionnaires and a diary kept during year 1, and polymorphisms in innate receptor genes were related to gene expression of innate immunity receptors by using ANOVA and multivariate regression analysis. Results Gene expression of innate immunity receptors in cord blood was overall higher in neonates of farmers ( P for multifactorial multivariate ANOVA = .041), significantly so for TLR7 (adjusted geometric means ratio aGMR, 1.15; 95% CI, 1.02-1.30) and TLR8 (aGMR, 1.15; 95% CI, 1.04-1.26). Unboiled farm milk consumption during the first year of life showed the strongest association with mRNA expression at year 1, taking the diversity of other foods introduced during that period into account: TLR4 (aGMR, 1.22; 95% CI, 1.03-1.45), TLR5 (aGMR, 1.19; 95% CI, 1.01-1.41), and TLR6 (aGMR, 1.20; 95% CI, 1.04-1.38). A previously described modification of the association between farm milk consumption and CD14 gene expression by the single nucleotide polymorphism CD14/C-1721T was not found. Conclusion Farming-related exposures, such as raw farm milk consumption, that were previously reported to decrease the risk for allergic outcomes were associated with a change in gene expression of innate immunity receptors in early life.
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