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Original Research: Asthma |

Reduced Antiviral Interferon Production in Poorly Controlled Asthma Is Associated With Neutrophilic Inflammation and High-Dose Inhaled Corticosteroids

Jodie L. Simpson, PhD; Melanie Carroll, BS; Ian A. Yang, PhD; Paul N. Reynolds, PhD; Sandra Hodge, PhD; Alan L. James, MBBS, PhD; Peter G. Gibson, MBBS; John W. Upham, PhD
Author and Funding Information

FUNDING/SUPPORT: This study was funded by project grants from the National Health and Medical Research Council of Australia [Grants 569246 and 1046622].

CORRESPONDENCE TO: Jodie L. Simpson, PhD, Level 2, West Wing, Hunter Medical Research Institute, Lot 1 Kookaburra Circuit, New Lambton Heights, NSW, 2305, Australia


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;149(3):704-713. doi:10.1016/j.chest.2015.12.018
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Background  Asthma is a heterogeneous chronic inflammatory disease in which host defense 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 and others suggesting that type I IFN synthesis is relatively normal in asthma.

Objective  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. Peripheral blood mononuclear cells (PBMCs) were exposed to HRV serotype 1b, and IFN-α and IFN-β release was measured by enzyme-linked immunosorbent assay.

Results  Participants (mean age, 59 years; atopy, 76%) had suboptimal asthma control (mean asthma control questionnaire 6, 1.7). In those with neutrophilic asthma (n = 12), HRV1b-stimulated PBMCs produced significantly less IFN-α than PBMCs 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 after HRV1b exposure.

Conclusions  Antiviral type I IFN production is impaired in those with neutrophilic airway inflammation and in those prescribed high doses of inhaled corticosteroids. Our study is an important step toward identifying those with poorly controlled asthma who might respond best to inhaled IFN therapy during exacerbations.

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