Animal models that accurately mimic clinical disease are invaluable research tools. The characterization of allergic asthma associated with airborne, fungal sensitization provides the opportunity to explore, in detail, the localization of fungal aeroallergens in the normal spatial environment and the immune response mounted against them. One of the challenges of asthma research is the ability to relate experimental observations with those occurring clinically. Fungal asthma research has been limited by animal models that do not accurately reflect the native means of sensitization that is seen in clinical settings. We will explore airway responses in a new airborne Aspergillus fumigatus model and compare these data against the well-established model that uses a liquid phase to deliver the challenge allergen. Airborne delivery allows the conidia to contact the distal airways in a manner consistent with the evolution of clinical asthma, thus incorporating the contribution of the small airways in the experimental model. We propose the following specific aims for this work: 1. To determine the efficacy of allergic sensitization through airborne delivery of Aspergillus conidia. Our working hypothesis is that allergic sensitization will be possible with low-, multi-dose inhalations of mature Aspergillus conidia, as assessed by significant elevation of IgE. 2. To characterize the acute allergic response to airborne delivery of Aspergillus conidia in a sensitized animal. Our working hypothesis is that airborne delivery (AD) of conidia will result in acute allergic airway hyperresponsiveness that will be more pronounced using this method than using liquid delivery (LD) due to the increased mucosal surface that may be contacted in this way. 3. To characterize the chronic allergic response to airborne delivery of Aspergillus conidia in a sensitized animal. Our working hypothesis is that animals receiving airborne conidia at allergen challenge will develop airway remodeling features consistent with chronic asthma and that these responses will be more robust in the AD animals than in those treated traditionally. We will use physiological, histological, and protein analysis to compare the AD to the LD treatment method. We anticipate that the development of an airborne delivery method that more closely reflects the natural progression of allergic sensitization and challenge will be an important step in our understanding of the airway remodeling process that occurs in chronic asthma. ? ? ?
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