- Title
- The effect of inhaled IFN-β on worsening of asthma symptoms caused by viral infections: a randomized trial
- Creator
- Djukanovic, Ratko; Harrison, Tim; Marsden, Richard; Boxall, Christine; Dudley, Sarah; Plagnol, Vincent; Holgate, Stephen T.; Monk, Phillip; INTERCIA Study Group,; Johnston, Sebastian L.; Gabbay, Flic; Wark, Peter; Thomson, Neil C.; Niven, Robert; Singh, Dave; Reddel, Helen K.; Davies, Donna E.
- Relation
- American Journal of Respiratory and Critical Care Medicine Vol. 190, Issue 2, p. 145-154
- Publisher Link
- http://dx.doi.org/10.1164/rccm.201312-2235OC
- Publisher
- American Thoracic Society
- Resource Type
- journal article
- Date
- 2014
- Description
- 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).
- Subject
- innate immunity; treatment; respiratory virus
- Identifier
- http://hdl.handle.net/1959.13/1296281
- Identifier
- uon:19226
- Identifier
- ISSN:1073-449X
- Language
- eng
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