Asthma is a disease of the respiratory system that affects approximately 300 million worldwide. In spite of extensive knowledge regarding disease pathogenesis, a cure is still out of reach. Allergic asthma is the most common subtype of asthma, and ubiquitous environmental agents such as pollen, animal dander, and fungi are common allergens. We generated a murine model system that faithfully recapitulates hallmarks of severe asthma with fungal sensitization using native conidia from Aspergillus fumigatus in an airborne inhalation delivery system to study disease pathogenesis. This model system can be used to interrogate pathways by which disease pathogenesis may occur.
Asthma exacerbations can be associated with respiratory infections, and some viruses are known inducers of asthma in predisposed individuals. Influenza is a disease caused by negative sense RNA viruses that can undergo rapid changes in antigens. These changes in the influenza virus genome can lead to the generation of a novel virus to which there is no herd immunity thereby increasing the likelihood of causing disease in pandemic proportions. During the last influenza pandemic in 2009, asthma was identified as a risk factor associated with hospitalization, although the reasons for this increased susceptibility were undetermined.
By combining our fungal asthma model with an established model of influenza, our laboratory created a model system of comorbidity to study the interplay between these two immunologically distinct diseases. Our studies were the first to show that the timing of influenza virus infection in hosts with allergic asthma had a direct impact on disease outcome. Our findings were corroborated by external epidemiologic studies wherein asthmatics were less likely to require intensive care or mechanical ventilation during the 2009 pandemic. Virus infection during an asthma exacerbation (heightened allergic inflammation) protected the host from influenza morbidity, while virus infection that occurs in an allergic lung that has undergone airway wall remodeling makes the host susceptible to severe influenza.
Our ongoing studies are aimed at delineating mechanisms by which this protection may occur. Our research is funded through the American Lung Association, the NIAID, and the Le Bonheur Foundation to investigate the following:
- The role of eosinophils in anti-viral and -bacterial immunity
- The role of antimicrobial peptides as immunomodulators during influenza
- Interdisease immune mechanisms that complicate disease severity