Innate Immunity and Asthma Exacerbations: Insights From Human Models

Asthma is a common chronic respiratory disease characterized by the presence of airway inflammation, airway hyperresponsiveness, and mucus hypersecretion. Repeated asthma exacerbations can lead to progressive airway remodeling and irreversible airflow obstruction. Thus, understanding and preventing asthma exacerbations are of paramount importance. Although multiple endotypes exist, asthma is most often driven by type 2 airway inflammation. New therapies that target specific type 2 mediators have been shown to reduce the frequency of asthma exacerbations but are incompletely effective in a significant number of asthmatics. Furthermore, it remains unknown whether current treatments lead to sustained changes in the airway or if targeting additional pathways may be necessary to achieve asthma remission. Activation of innate immunity is the initial event in the inflammatory sequence that occurs during an asthma exacerbation. However, there continue to be critical gaps in our understanding of the innate immune response to asthma exacerbating factors. In this review, we summarize the current understanding of the role of innate immunity in asthma exacerbations and the methods used to study them. We also identify potential novel therapeutic targets for asthma and future areas for investigation.