Reduced anti-viral interferon production in poorly-controlled asthma is associated with neutrophilic inflammation and high dose inhaled corticosteroids

Background

Asthma is a heterogeneous chronic inflammatory disease where host defence against respiratory viruses such as human rhinovirus (HRV) may be abnormal. This is a matter of some controversy, with some investigators reporting reduced type I interferon (IFN) synthesis while others suggest that type I IFN synthesis is relatively normal in asthma.The objective of this study was to examine the responsiveness of circulating mononuclear cells to HRV in a large cohort of participants with poorly controlled asthma and determine whether IFN-α and IFN-β synthesis varies across different inflammatory phenotypes.

Methods

Eligible adults with asthma (n=86) underwent clinical assessment, sputum induction and blood sampling. Asthma inflammatory subtypes were defined by sputum cell count, and supernatant assessed for IL-1β. PBMC (peripheral blood mononuclear cells) were exposed to HRV serotype 1b and IFN-α and IFN-β release was measured by ELISA.

Results

Participants (mean age of 59 years, atopy 76%) had sub-optimal asthma control (mean ACQ6 1.7). In those with neutrophilic asthma (n=12), HRV1b stimulated PBMC produced significantly less IFN-α than PBMC from participants with eosinophilic (n=35) and paucigranulocytic asthma (n=35). Sputum neutrophil proportion and the dose of inhaled corticosteroids were independent predictors of reduced IFN-α production following HRV1b exposure.

Conclusion

Anti-viral type I IFN production is impaired in those with neutrophilic airway inflammation and in those prescribed high doses of ICS. Our study is therefore an important step towards identifying those with poorly controlled asthma that might respond best to inhaled IFN therapy during exacerbations.

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