Abstract

A small elegant mixed-methods study examined the pathogenesis of asthma.1 Amish children were age and sex-matched with Hutterite children. Because they have similar genetic ancestries (Fig. 1a), this is a quasi-twin study. Both communities have large families, diets rich in fat, salt and raw milk and live in low-pollution, low-tobacco environments. However, Amish communities use traditional farming practices, whereas the Hutterites use modern technology. Investigators took immune and genetic blood samples, analysed house dust, and then used an ovalbumin mouse model of allergic asthma to compare immune responses and broncho-responsiveness. As expected, principal component analysis confirmed remarkable genetic similarities between the Amish and Hutterites. Dust analysis (Fig. 1b) revealed median endotoxin levels 6.8 times higher in Amish homes (P < 0.001). Amish children had more neutrophils, but lower eosinophils and median levels of 23 cytokines (P < 0.001). Gene expression profiles showed clustering around genes encoding inflammation (e.g. tumour necrosis factor and interferon regulatory factor 7). Mice exposed to Amish dust had less airway hyper-responsiveness and their bronchoalveolar lavage samples had less eosinophilia than mice exposed to Hutterite dust. The unique populations studied enable hypothesis generation from this small study. The risk of asthma may be reduced through environmental exposure to aeroallergens from microbe-rich dust which trigger activation of innate immunity, or through interventions targeting innate immunity triggering pathways.

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