The effect of inhaled IFN-β on worsening of asthma symptoms caused by viral infections. A randomized trial.
Ratko Djukanovic,Tim Harrison,Sebastian L. Johnston,Flic Gabbay,Peter A. B. Wark,Neil C. Thomson,Robert Niven,Dave Singh,Helen K. Reddel,Donna E. Davies,Richard J Marsden,Christine B. Boxall,Sarah Dudley,Vincent Plagnol,Stephen T. Holgate,Phillip Monk +15 more
TLDR
It is suggested 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.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).read more
Citations
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The immunology of asthma
Bart N. Lambrecht,Hamida Hammad +1 more
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After asthma: redefining airways diseases
Ian D. Pavord,Richard Beasley,Alvar Agusti,Gary P. Anderson,Elisabeth H. Bel,Guy Brusselle,Guy Brusselle,Paul Cullinan,Adnan Custovic,Francine M. Ducharme,John V. Fahy,Urs Frey,Peter G. Gibson,Peter G. Gibson,Liam G Heaney,Patrick G. Holt,Marc Humbert,Marc Humbert,Clare M. Lloyd,Guy B. Marks,Fernando D. Martinez,Peter D. Sly,Erika von Mutius,Sally E. Wenzel,Heather J. Zar,Andrew Bush +25 more
TL;DR: The only way to make progress in the future is to be much more clear about the meaning of the labels used for asthma and to acknowledge the assumptions associated with them, which are believed to be the most important causes of the stagnation in key clinical outcomes observed in the past 10 years.
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Mepolizumab for Severe Eosinophilic Asthma (DREAM): A Multicentre, Double-Blind, Placebo-Controlled Trial
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Role of viral infections in the development and exacerbation of asthma in children
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Safety and efficacy of inhaled nebulised interferon beta-1a (SNG001) for treatment of SARS-CoV-2 infection: a randomised, double-blind, placebo-controlled, phase 2 trial.
Phillip Monk,Richard J Marsden,Victoria Tear,Jody Brookes,Toby N Batten,Marcin Mankowski,Felicity J Gabbay,Donna E. Davies,Stephen T. Holgate,Stephen T. Holgate,Ling-Pei Ho,Tristan W Clark,Ratko Djukanovic,Tom Wilkinson,Michael G. Crooks,Davinder Dosanjh,Salman Siddiqui,Najib M. Rahman,Jacklyn A Smith,Alex Horsley,Tim Harrison,Dinesh Saralaya,Lorcan McGarvey,Alastair Watson,Edmund Foster,Adam Fleet,Dave Singh,Sophie Hemmings,Sandra Aitken,Sarah Dudley,Rona Beegan,Angela Thompson,Pedro Mb Rodrigues +32 more
TL;DR: Patients who received SNG001 had greater odds of improvement and recovered more rapidly from SARS-CoV-2 infection than patients who received placebo, providing a strong rationale for further trials.
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