Mrs. Newton and Janice, her 2-year-old daughter, are seeing you for a child wellness check-up. Mrs. Newton asks you about asthma risks and reports that she’s read somewhere in a parenting magazine that letting children play in the dirt and be exposed to animals reduces risks of asthma and allergies. She asks what you know about this.
Both genetic risk factors and the environment play a critical role in the development of asthma and atopic diseases. Asthma has increased in recent decades especially in urban and modernized regions of the world. Epidemiologic studies show that children who grew up in rural areas have less asthma and atopy. It is thought that frequent exposure to farm animals and the associated endotoxins and microbiomes protect against the development of asthma.
Who are the Amish and the Hutterites and why does it matter?
The Amish populations in Indiana and the Hutterite populations in South Dakota are communities that originated from Europe who share a common ancestry. Both of these communities are farming communities that share similar faith and lead simple lives. However, the Amish live in single farms and practice traditional farming techniques using animals for fieldwork and transportation while the Hutterite live on large, highly-industrialized communal farms. The prevalence of childhood asthma is four-times higher in the Hutterite communities.
What explains the differences in rates of asthma?
What was this cross-sectional study about?
In a cross-sectional study, investigators studied sixty sex- and age-matched Amish and Hutterite children (thirty from each community) age 7 to 14 years in 2012 to determine the impact of environmental exposures on asthma immune responses. Investigators gathered questionnaire information on asthma symptoms, genetic and laboratory data, and sampled airborne house dust from the homes of the subjects. Dust was analyzed for endotoxin composition and allergen levels, and blood was analyzed for signs of activation of innate or adaptive immunity.
What were the results?
The analysis of genomic DNA markers and allele frequency of single-nucleotide polymorphism show the children from the two communities have remarkable genetic similarities. Yet, none of the Amish children and six (20%) of the Hutterite children had asthma. Hutterite children had 3-times the level of total serum median IgE levels (64 versus 21 kU/L) and a higher percentage of Hutterite children had high levels of specific IgE >3.5 kUA/L against common allergens. Although endotoxins were found in all homes, the median endotoxin level was nearly 7 times as high in Amish homes (4,3999 versus 648 EU/m2). Common allergens such as cat, dogs, house dust mite, and cockroaches were also detected more frequently in Amish homes.
Analysis of peripheral blood collected from the children showed differences between the two groups with increased proportions of neutrophils and decreased proportions of eosinophils in the Amish children. Dust extracts were tested in mouse models of experimental allergic asthma and showed significant inhibition of airway hyperresponsitivity and esosinophilia from the Amish dust extracts but not the Hutterites. Analysis of blood samples and mice experiments showed greater activation of the innate immune response in the Amish than in the Hutterites.
What are innate and adaptive immune responses?
In general, innate immune response refers to a “non-specific” defense mechanism. It involves cytokine production and the complement pathway, and clear foreign substances by activating macrophages. In contrast, adaptive immune systems are “specific” and are activated through pathways that involve presentation of specific antigens activating specific immune responses. These responses are longer-lasting.
So what is my take-away?
The authors postulated that frequent exposures to farming animals and its associated microbiomes and endotoxins as observed in the Amish community reduced the risk of asthma by engaging and shaping the innate immune responses.
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James was a 2015-2016 NEJM Editorial Fellow. He recently completed fellowship in General Internal Medicine at Brigham and Women’s Hospital. He is interested in evidence-based medicine, medical education, knowledge translation, and pharmacoepidemiology.