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

Am J Respir Crit Care Med. 2014 Jul 15;190(2):145-54. doi: 10.1164/rccm.201312-2235OC.

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).

Trial registration: ClinicalTrials.gov NCT01126177.

Keywords: innate immunity; respiratory virus; treatment.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Aged
  • Anti-Asthmatic Agents / therapeutic use
  • Antiviral Agents / therapeutic use*
  • Asthma / drug therapy*
  • Asthma / 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
  • Respiratory Tract Infections / drug therapy*
  • Severity of Illness Index
  • Surveys and Questionnaires
  • Treatment Outcome
  • Virus Diseases / complications
  • Virus Diseases / drug therapy*
  • Young Adult

Substances

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

Associated data

  • ClinicalTrials.gov/NCT01126177