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.
This review describes the recent literature on microbial exposures and protective effects for asthma and atopy. Certain microorganism-associated molecular patterns have been identified as agents that ...might influence the development of the immune system, which in turn leads to protective effects for asthma and atopy. Endotoxins from gram-negative bacteria were the first agents associated with a reduced risk for asthma and atopy. In later studies, β(1→3)glucans, extracellular polysaccharides, and muramic acid from, respectively, molds and gram-positive bacteria were associated with a reduced risk of allergy and asthma separately in rural and urban populations. These results already suggested that not just one but several independent microbial signals from gram-negative and gram-positive bacteria, as well as molds, might play a role in explaining the protective effects. Recently, the diversity of microbial exposure has been associated with such a reduced risk in farmers’ children. Surprisingly, the diversity of both fungal and bacterial exposure seemed to have protective effects. These results open new areas of research and create complex challenges. Methodological issues, such as environmental exposure characterization and assessment and elucidation of potential underlying mechanisms, are discussed because these aspects have a major influence on how microbial diversity can be studied in future studies in relation to protective effects for asthma and atopy.
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 Certain dog breeds are described and marketed as being “hypoallergenic” on the basis of anecdotal reports that these dogs are better tolerated by patients allergic to dogs. Objective These ...observations were investigated by comparing Can f 1 (major dog Canis familiaris allergen) levels in hair and coat samples and in the home environment of various hypoallergenic (Labradoodle, Poodle, Spanish Waterdog, and Airedale terrier) and non-hypoallergenic dogs (Labrador retriever and a control group). Methods Hair and coat samples were obtained from dogs, and settled floor and airborne dust samples were taken from the dogs’ homes. Can f 1 concentrations were measured by using ELISA, and results were analyzed by using multiple linear regression analyses. Results Significantly higher Can f 1 concentrations were found in hair and coat samples of hypoallergenic dogs (n = 196, geometric mean GM, 2.26 μg/g, geometric standard deviation GSD, 0.73, and GM, 27.04 μg/g, GSD, 0.57, respectively) than of non-hypoallergenic dogs (n = 160, GM, 0.77 μg/g, GSD, 0.71, and GM, 12.98 μg/g, GSD, 0.76, respectively). Differences between breeds were small, relative to the variability within a breed. Can f 1 levels in settled floor dust samples were lower for Labradoodles, but no differences were found between the other groups. No differences in airborne levels were found between breeds. Conclusion So-called hypoallergenic dogs had higher Can f 1 levels in hair and coat samples than did control breeds. These differences did not lead to higher levels of environmental exposure to dog allergens. There is no evidence for the classification of certain dog breeds as being “hypoallergenic.”
Background Farm milk consumption has been identified as an exposure that might contribute to the protective effect of farm life on childhood asthma and allergies. The mechanism of action and the role ...of particular constituents of farm milk, however, are not yet clear. Objective We sought to investigate the farm milk effect and determine responsible milk constituents. Methods In rural regions of Germany, Austria, and Switzerland, a comprehensive questionnaire about farm milk consumption and other farm-related exposures was completed by parents of 8334 school-aged children, and 7606 of them provided serum samples to assess specific IgE levels. In 800 cow's milk samples collected at the participants' homes, viable bacterial counts, whey protein levels, and total fat content were analyzed. Asthma, atopy, and hay fever were associated to reported milk consumption and for the first time to objectively measured milk constituents by using multiple regression analyses. Results Reported raw milk consumption was inversely associated to asthma (adjusted odds ratio aOR, 0.59; 95% CI, 0.46-0.74), atopy (aOR, 0.74; 95% CI, 0.61-0.90), and hay fever (aOR, 0.51; 95% CI, 0.37-0.69) independent of other farm exposures. Boiled farm milk did not show a protective effect. Total viable bacterial counts and total fat content of milk were not significantly related to asthma or atopy. Increased levels of the whey proteins BSA (aOR for highest vs lowest levels and asthma, 0.53; 95% CI, 0.30-0.97), α-lactalbumin (aOR for interquartile range and asthma, 0.71; 95% CI, 0.52-0.97), and β-lactoglobulin (aOR for interquartile range and asthma, 0.62; 95% CI, 0.39-0.97), however, were inversely associated with asthma but not with atopy. Conclusions The findings suggest that the protective effect of raw milk consumption on asthma might be associated with the whey protein fraction of milk.
Background Chloroplatinate salts are well-known respiratory sensitizing agents leading to work-related sensitization and allergies in the work environment. No quantitative exposure-response relation ...has been described for chloroplatinate salts. Objective We sought to evaluate the quantitative exposure-response relation between occupational chloroplatinate exposure and sensitization. Methods A retrospective cohort study was conducted using routinely collected health surveillance data and chloroplatinate exposure data. Workers who newly entered work between January 1, 2000, and December 31, 2010, were included, and the relation between measured chloroplatinate exposure and sensitization (as determined by skin prick test responses) was analyzed in more than 1000 refinery workers from 5 refineries for whom a total of more than 1700 personal exposure measurements were available. Results A clear exposure-response relation was observed, most strongly for more recent platinum salt exposure. Average or cumulative exposure over the follow-up period was less strongly associated with sensitization risk. The exposure-response relation was modified by smoking and atopy. Conclusions Indications exist that recent exposure explains the risk of platinum salt sensitization most strongly. The precision of the estimate of the exposure-response relation derived from this data set appears superior to previous epidemiologic studies conducted on platinum salt sensitization and as a result, might have possible utility for the development of preventive strategies.
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.
Background Previous studies have demonstrated that children raised on farms are protected from asthma and allergies. It is unknown whether the farming effect is solely mediated by atopy or also ...affects nonatopic wheeze phenotypes. Objective We sought to study the farm effect on wheeze phenotypes and objective markers, such as lung function and exhaled nitric oxide, and their interrelation with atopy in children. Methods The GABRIEL Advanced Studies are cross-sectional, multiphase, population-based surveys of the farm effect on asthma and allergic disease in children aged 6 to 12 years. Detailed data on wheeze, farming exposure, and IgE levels were collected from a random sample of 8023 children stratified for farm exposure. Of those, another random subsample of 858 children was invited for spirometry, including bronchodilator tests and exhaled nitric oxide measurements. Results We found effects of exposure to farming environments on the prevalence and degree of atopy, on the prevalence of transient wheeze (adjusted odds ratio, 0.78; 95% CI, 0.64-0.96), and on the prevalence of current wheeze among nonatopic subjects (adjusted odds ratio, 0.45; 95% CI, 0.32-0.63). There was no farm effect on lung function and exhaled nitric oxide levels in the general study population. Conclusions Children living on farms are protected against wheeze independently of atopy. This farm effect is not attributable to improved airway size and lung mechanics. These findings imply as yet unknown protective mechanisms. They might include alterations of immune response and susceptibility to triggers of wheeze, such as viral infections.
Background Sensitization to occupational allergens is frequently found in laboratory animal workers (LAWs) and can cause serious health problems. Atopy is a major risk factor for sensitization, but ...it is considered insufficient to advise against working with animals. Objective We investigated whether immunologic measures, including serology and cytokine production profiles of blood cells, and parameters for airway inflammation are associated with the development of occupational sensitization. Methods In a prospective cohort study 110 starting LAWs were followed for 2 years. At inclusion, results of health questionnaires, skin test results, lung function measures, methacholine threshold levels, and nasal lavage fluid were obtained. Blood was taken for measuring total IgE and allergen-specific IgE antibodies. Cytokine production profiles were measured in whole blood. Results Twenty-two new cases of sensitization were identified during follow-up. In multivariate logistic regression analysis a model including atopy and total IgE level predicted sensitization best. This was corroborated in a separate validation cohort. Parameters for airway inflammation or cytokine production profiles did not further contribute to the prediction of sensitization. Based on these results, pre-employment counseling aimed at applicant LAWs with atopy and a total IgE level of greater than 100 IU/mL might be able to reduce occupational sensitization by up to 45% to 50% with less than 10% false-positive predictions. Conclusion The combination of atopy and total IgE level offered the best model to predict development of occupational sensitization. Other immunologic parameters and parameters of airway inflammation did not contribute significantly.
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