The critical role of environmental exposures in asthma development is illustrated by asthma protection among European children raised on traditional farms, but specific protective exposures and the underlying mechanisms are unknown. Differences in asthma prevalence are recapitulated in two farming populations in the United States, the Indiana Amish and the South Dakota Hutterites, who share multiple lifestyles associated with asthma risk or protection. However, asthma prevalence is 2–3% among the Amish, who practice traditional farming, and 15% or higher among the Hutterites, who embrace modern farming.
To begin dissecting the mechanisms underlying asthma protection and risk among the Amish and Hutterites, aqueous extracts of dust collected from Amish or Hutterite homes were administered in an ovalbumin (OVA) model of experimental asthma. Amish dust extracts (DE) were sufficient to protect OVA-treated Balb/c mice from airway hyperresponsiveness and bronchoalveolar lavage (BAL) eosinophilia. BAL IL-13 and IL-5 were abrogated, whereas IL-17 and IFN-γ were unaffected. In contrast, Hutterite DE exacerbated OVA-induced airway hyperresponsiveness and did not affect BAL eosinophilia and cytokine production. Lung gene expression profiling revealed multipronged suppression of OVA-dependent pathways related to airway remodeling and epithelial, dendritic, alternative macrophage and Th2 cell activation in mice treated with Amish but not Hutterite DE.
Because treatment with Amish and Hutterite house DE recapitulates the asthma protection and risk profiles found in the two populations, we conclude that the different asthma prevalence among the Amish and Hutterites depends on distinct environmental exposures.
Footnotes
Author Contributions: J.G. performed experiments. M.H. and C.O. collected dust samples. N.M. and P.S.T. prepared dust extracts. D.V., C.O., E.v.M., and F.D.M. designed the study and wrote the abstract. All authors edited the abstract.
Author disclosures are available with the text of this article at www.atsjournals.org.
