Immunoprotective vs. immunopathogenic responses during fungal-associated allergic airway inflammation

Asthma is an increasing health concern affecting more than 25 million individuals in the United States and more than 300 million individuals worldwide. In some cases, sensitization or exposure to specific microbes can exacerbate asthma. In 2006, a new asthma phenotype termed “severe asthma with fungal sensitization” (SAFS) was described for individuals whose asthma was poorly-controlled and who were sensitized to fungi. We have previously reported that asthmatics sensitized to fungi demonstrate worse lung function, higher serum IgE, blood eosinophil and exhaled nitric oxide levels. A growing area of interest is the identification of factors that contribute to immunopathogenesis in allergic asthma, including those sensitized to fungi, and determining whether these could be viable therapeutic targets. Indeed, biologics targeting the type 2 cytokines IL-4, IL-5 and IL-13 have been successful in treating individuals with severe asthma. To this end, we have reported that human asthmatics sensitized to fungi have increased levels of multiple cytokines, chemokines and growth factors in bronchoalveolar lavage fluid and sputum, some of which correlate with lung function or atopic measurements. This presentation will provide an overview of these findings and how some of these mediators mechanistically contribute to disease severity using an experimental animal model of fungal-associated allergic airway inflammation.

Learning Objectives:

1. To understand the clinical significance of allergic asthma as it relates to fungal sensitization

2. To understand experimental animal models as it relates to determining immunoprotective vs. immunopathogenic responses during fungal asthma