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

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).

• Authors: Ratko Djukanović, Tim Harrison, Sebastian L Johnston, Flic Gabbay, Peter Wark, Neil C Thomson, Robert Niven, Dave Singh, Helen K Reddel, Donna E Davies, Richard Marsden, Christine Boxall, Sarah Dudley, Vincent Plagnol, Stephen T Holgate, Phillip Monk, INTERCIA Study Group
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 190 Issue 2 Pg. 145-54 (Jul 15 2014) ISSN: 1535-4970 [Electronic] United States
• PMID: 24937476 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenal Cortex Hormones
• Anti-Asthmatic Agents
• Antiviral Agents
• Interferon-beta

Topics

• Administration, Inhalation
• Adolescent
• Adrenal Cortex Hormones (therapeutic use)
• Adult
• Aged
• Anti-Asthmatic Agents (therapeutic use)
• Antiviral Agents (therapeutic use)
• Asthma (drug therapy, virology)
• Disease Progression
• Double-Blind Method
• Drug Administration Schedule
• Drug Therapy, Combination
• Female
• Humans
• Intention to Treat Analysis
• Interferon-beta (therapeutic use)
• Male
• Middle Aged
• Respiratory Tract Infections (complications, drug therapy)
• Severity of Illness Index
• Surveys and Questionnaires
• Treatment Outcome
• Virus Diseases (complications, drug therapy)
• Young Adult