title: The effect of inhaled IFN-β on worsening of asthma symptoms caused by viral infections. A randomized trial.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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.affiliation: 1 NIHR Southampton Respiratory Biomedical Research Unit, Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton, United Kingdom.
authors.forename: Ratko
authors.initials: R
authors.lastname: Djukanović
authors.forename: Tim
authors.initials: T
authors.lastname: Harrison
authors.forename: Sebastian L
authors.initials: SL
authors.lastname: Johnston
authors.forename: Flic
authors.initials: F
authors.lastname: Gabbay
authors.forename: Peter
authors.initials: P
authors.lastname: Wark
authors.forename: Neil C
authors.initials: NC
authors.lastname: Thomson
authors.forename: Robert
authors.initials: R
authors.lastname: Niven
authors.forename: Dave
authors.initials: D
authors.lastname: Singh
authors.forename: Helen K
authors.initials: HK
authors.lastname: Reddel
authors.forename: Donna E
authors.initials: DE
authors.lastname: Davies
authors.forename: Richard
authors.initials: R
authors.lastname: Marsden
authors.forename: Christine
authors.initials: C
authors.lastname: Boxall
authors.forename: Sarah
authors.initials: S
authors.lastname: Dudley
authors.forename: Vincent
authors.initials: V
authors.lastname: Plagnol
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Holgate
authors.forename: Phillip
authors.initials: P
authors.lastname: Monk
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000821:virology; D018450:Disease Progression; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D016899:Interferon-beta / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012141:Respiratory Tract Infections / Q000150:complications / Q000188:drug therapy*; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D014777:Virus Diseases / Q000150:complications / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D000998:Antiviral Agents; D016899:Interferon-beta
keywords: innate immunity; respiratory virus; treatment