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

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, Lorcan McGarvey

Research output: Contribution to journalArticlepeer-review

167 Citations (Scopus)

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-b. Exogenous IFN-b restores antiviral activity.

Objectives: To compare the efficacy and safety of inhaled IFN-b 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-b (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-b 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 ofmore difficult-to-treat, Step 4-5 peoplewith asthma (n = 27 IFN-b; n = 31 placebo), Asthma Control Questionnaire-6 increased significantly on placebo; this was prevented by IFN-b (P = 0.004).

Conclusions: Although the trial did not meet its primary endpoint, it suggests that inhaled IFN-b is a potential treatment for virus-induced deteriorations of asthma in difficult-to-treat people with asthma and supports the needforfurther, adequately powered, trialsin this population. Clinical trial registered with www.clinicaltrials.gov (NCT 01126177).
Original languageEnglish
Pages (from-to)145-154
Number of pages10
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume190
Issue number2
DOIs
Publication statusPublished - 15 Jul 2014

Keywords

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

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