Increased type 2 inflammation post rhinovirus infection in patients with moderate asthma

Abstract

Rhinovirus (RV) infections are a major cause of exacerbations in patients with asthma. Experimental RV challenges can provide insight into the pathophysiology of viral exacerbations. Previous reports, investigating mild or moderate asthma patients, have shown an upregulation in type 2 inflammation post RV infection, however, studies specifically involving asthma patients taking inhaled corticosteroids have concentrated on symptoms and lung function, rather than the inflammatory response.Eleven moderate asthma patients were inoculated with RV. Cold symptoms and asthma control were assessed at baseline and post infection. Nasal epithelial lining fluid and bronchial alveolar lavage (BAL) fluid were collected at baseline and 4 days post infection for assessment of inflammatory proteins.Patients suffered increased cold symptoms and decreased asthma control within 7 days of infection. Antiviral mechanisms were induced following inoculation, with increases in interferon -α, β, γ and λ, as well as CXCL10 and CXCL11. Type 2 inflammatory cytokines were also significantly elevated post RV infection in both nasal and bronchial samples. In BAL, epithelial derived IL-25 and IL-33 levels strongly correlated with Th2 cytokines, IL-4, IL-5 and IL-13.We show how experimental rhinovirus challenge regulates lung and nasal biomarkers in asthma patients taking inhaled corticosteroids. These biomarkers could be used to evaluate the effects of novel drugs for asthma.