41 The Mechanisms of Allergy to Fungal Bioaerosols in the Lung

Abstract Allergic airways disease (AAD) is a collective term for respiratory disorders that can be exacerbated upon exposure to airborne allergens. The contribution of fungal allergens to the pathogenesis of AAD has become well established over recent years and can be present in the air we breathe as bioaerosols. Understanding the mechanisms allergy to fungal bioaerosols can help to better manage symptoms and conditions, reducing the burden of disease. We conducted a comprehensive review to collate the current understanding of mechanisms involved in the allergic response to fungal bioaerosols in airway epithelia. To be included in the final analysis, studies were compared to defined inclusion/exclusion criteria, relevant data was extracted, and each paper was assessed using a quality scoring tool. The search string provided 440 initial results with 60 studies selected for final analysis. 120 potential target mechanisms were identified within the selected studies and 17 were identified in more than 5 studies. The major pathways identified in allergic response include 1) a role for proteases and the activation of the PAR2 receptor, 2) release of IL33, 3) EGFR pathway and mucin expression, and 4) a skewing towards a Th2 profile promoting eosinophil recruitment. However, there was conflicting evidence when comparing results from individual studies. Thus, further research is required to better understand which fungi/fungal components drive the allergic response. Funding: This work has been funded under the NIHR Health Protection Research Unit for Environmental Exposures and Health with Imperial College London