The Role of Type 2 Inflammation in the Pathogenesis of Asthma Exacerbations

Abstract

Asthma exacerbations are an important cause of asthma morbidity. Although viral infection of the upper airway is a common cause of asthma exacerbations, the reasons why some patients with asthma are exacerbation prone and others are exacerbation resistant are not fully understood. In this review, we examine whether Type 2 inflammation modifies airway function to make patients more susceptible to asthma exacerbations. The best data supporting a role for Type 2 inflammation in asthma exacerbations come from clinical trials of inhibitors of Type 2 inflammation in asthma. These trials include studies with omalizumab (an inhibitor of IgE) and others with inhibitors of Type 2 cytokines (IL-4, IL-5, and IL-13). All of these trials consistently show that inhibiting the Type 2 pathway causes a clinically significant reduction in asthma exacerbations. Thus, it is now clear that Type 2 inflammation is an important mechanism of susceptibility to asthma exacerbation.

Keywords: IL-13; IgE; Type 2 inflammation; asthma; exacerbation.

Figure 1.

Plasmacytoid dendritic cells (pDCs) secrete IFN-α to activate the innate immune response to virus in the airway. pDCs in healthy airways secrete large amounts of IFN-α in response to viruses. The presence of Type 2 inflammation in asthmatic airways is associated with increased expression of high-affinity IgE receptor FcεRI on the surface of pDCs, which causes a blunted IFN-α response to airway viral infection.