Journal Article

The Effect of Inhaled IFN-β on Worsening of Asthma Symptoms Caused by Viral Infections. A Randomized Trial

Dudley, Sarah, Marsden, Richard, Djukanović, Ratko, Thomson, Neil C., Reddel, Helen K., Davies, Donna E., Holgate, Stephen T., Plagnol, Vincent, Harrison, Tim, Monk, Phillip, Johnston, Sebastian L., Gabbay, Flic, Wark, Peter, Niven, Robert, Boxall, Christine, Singh, Dave

2014

Overview

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. 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. 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. 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). 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. Clinical trial registered with www.clinicaltrials.gov (NCT 01126177).

• Publisher: Oxford University Press,American Thoracic Society
• Subject: Administration, Inhalation / Adolescent / Adrenal Cortex Hormones - therapeutic use / Adult / Aged / Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy / Anti-Asthmatic Agents - therapeutic use / Antiviral Agents - therapeutic use / Asthma / Asthma - drug therapy / Asthma - virology / Biological and medical sciences / Chronic obstructive pulmonary disease, asthma / Disease Progression / Double-Blind Method / Drug Administration Schedule / Drug Therapy, Combination / Female / Humans / Infectious diseases / Intensive care medicine / Intention to Treat Analysis / Interferon-beta - therapeutic use / Male / Medical sciences / Middle Aged / Original / Pneumology / Questionnaires / Respiratory Tract Infections - complications / Respiratory Tract Infections - drug therapy / Severity of Illness Index / Surveys and Questionnaires / Treatment Outcome / Viral diseases / Viral infections / Virus Diseases - complications / Virus Diseases - drug therapy / Viruses / Young Adult