Farming exposure and asthma phenotypes:In mice and men

Abstract

Although several studies have shown that farmers and people with agricultural-related occupations have a higher risk of developing lung diseases such as nonallergic asthma, chronic bronchitis and chronic obstructive pulmonary disease (COPD), it has also been shown that exposure to the farm environment is associated with a protective effect on the development of atopy and allergic asthma.In this thesis, both effects of farm exposures on the immune system were studied: the protective effect against allergic asthma and the induction of non-allergic asthma. These studies were conducted among agricultural workers, and in mouse models of allergic and nonallergic lung disease. In addition, the presence of several macrophage phenotypes in animal models of allergic and non-allergic asthma was investigated, as well as the effects of exposure to farm dust extract on a macrophage cell line.This thesis demonstrated that occupational exposure to a farm environment and exposure to farm dust extracts in mice lead to a shift in the immune system towards non-allergic inflammation. This shift offers on the one hand protection against development of allergic diseases, such as allergic asthma, but is also associated with the risk of nonallergic asthma development. In addition, this thesis shows that, within the various phenotypes asthma, various inflammatory mediators and cells are important in the development and severity of airway hyperresponsiveness