The effect of Inhaled IFN-β on worsening of asthma symptoms caused by viral infections. A randomized trial

Djukanović, R. et al. (2014) The effect of Inhaled IFN-β on worsening of asthma symptoms caused by viral infections. A randomized trial. American Journal of Respiratory and Critical Care Medicine, 190(2), pp. 145-154. (doi: 10.1164/rccm.201312-2235OC)

Abstract

Rationale: Ex vivo, bronchial epithelial cells from people with asthma are more susceptible to rhinovirus infection caused by deficient induction of the antiviral protein, IFN-β. Exogenous IFN-β restores antiviral activity.<p></p> Objectives: To compare the efficacy and safety of inhaled IFN-β with placebo administered to people with asthma after onset of cold symptoms to prevent or attenuate asthma symptoms caused by respiratory viruses.<p></p> Methods: A total of 147 people with asthma on inhaled corticosteroids (British Thoracic Society Steps 2–5), with a history of virus-associated exacerbations, were randomized to 14-day treatment with inhaled IFN-β (n = 72) or placebo (n = 75) within 24 hours of developing cold symptoms and were assessed clinically, with relevant samples collected to assess virus infection and antiviral responses.<p></p> Measurements and Main Results: A total of 91% of randomized patients developed a defined cold. In this modified intention-to-treat population, asthma symptoms did not get clinically significantly worse (mean change in six-item Asthma Control Questionnaire <0.5) and IFN-β treatment had no significant effect on this primary endpoint, although it enhanced morning peak expiratory flow recovery (P = 0.033), reduced the need for additional treatment, and boosted innate immunity as assessed by blood and sputum biomarkers. In an exploratory analysis of the subset of more difficult-to-treat, Step 4-5 people with asthma (n = 27 IFN-β; n = 31 placebo), Asthma Control Questionnaire-6 increased significantly on placebo; this was prevented by IFN-β (P = 0.004).<p></p> Conclusions: Although the trial did not meet its primary endpoint, it suggests that inhaled IFN-β is a potential treatment for virus-induced deteriorations of asthma in difficult-to-treat people with asthma and supports the need for further, adequately powered, trials in this population.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Thomson, Professor Neil
• Authors: Djukanović, R., Harrison, T., Johnston, S. L., Gabbay, F., Wark, P., Thomson, N. C., Niven, R., Singh, D., Reddel, H. K., Davies, D. E., Marsden, R., Boxall, C., Dudley, S., Plagnol, V., Holgate, S. T., and Monk, P.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: American Journal of Respiratory and Critical Care Medicine
• Publisher: American Thoracic Society
• ISSN: 1073-449X
• ISSN (Online): 1535-4970