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

The effect of inhaled IFN-? on worsening of asthma symptoms caused by viral infections. A randomized trial
The effect of inhaled IFN-? on worsening of asthma symptoms caused by viral infections. A randomized trial
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-?. Exogenous IFN-? restores antiviral activity. Objectives: To compare the efficacy and safety of inhaled IFN-? 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-? (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-? 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-?; n = 31 placebo), Asthma Control Questionnaire-6 increased significantly on placebo; this was prevented by IFN-? (P = 0.004). Conclusions: Although the trial did not meet its primary endpoint, it suggests that inhaled IFN-? 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).
1073-449X
145-154
Djukanovic, Ratko
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Harrison, Tim
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Johnston, Sebastian L.
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Gabbay, Flic
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Wark, Peter
ffada3aa-5413-41ff-ab27-6af7b684798c
Thomson, Neil C.
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Niven, Robert
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Singh, Dave
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Reddel, Helen K.
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Davies, Donna E.
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Marsden, Richard
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Boxall, Christine
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Dudley, Sarah
a7b1dfb4-4e02-4b96-8232-c9304136ae08
Plagnol, Vincent
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Holgate, Stephen T.
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Monk, Phillip
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Djukanovic, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
Harrison, Tim
e748a9cd-e54d-4dd8-91d8-afde1d6698f9
Johnston, Sebastian L.
90e0ef79-cfde-40e0-b301-90d3063ee036
Gabbay, Flic
1af1fe60-ceb9-4fa0-808d-72be266f06ce
Wark, Peter
ffada3aa-5413-41ff-ab27-6af7b684798c
Thomson, Neil C.
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Niven, Robert
0355e40e-e0e4-4e85-b4aa-7d2ac529f6df
Singh, Dave
5a8e5ba8-f961-4422-9a21-a6ef346041e5
Reddel, Helen K.
7b56a258-a1f5-40fc-a1a9-a03132a1a62f
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Marsden, Richard
27ccd3ff-cfe5-4edb-85d5-75d2e0050825
Boxall, Christine
122327f2-b62c-4b9f-abc3-920079c5d4a4
Dudley, Sarah
a7b1dfb4-4e02-4b96-8232-c9304136ae08
Plagnol, Vincent
2f197d12-c0f3-4306-94b9-d1d4352a7ba2
Holgate, Stephen T.
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Monk, Phillip
f0b35062-133d-4d96-8347-742d27a46fa6

Djukanovic, Ratko, Harrison, Tim, Johnston, Sebastian L., Gabbay, Flic, Wark, Peter, Thomson, Neil C., Niven, Robert, Singh, Dave, Reddel, Helen K., Davies, Donna E., Marsden, Richard, Boxall, Christine, Dudley, Sarah, Plagnol, Vincent, Holgate, Stephen T. and Monk, Phillip (2014) The effect of inhaled IFN-? on worsening of asthma symptoms caused by viral infections. A randomized trial. American Journal of Respiratory and Critical Care Medicine, 190 (2), 145-154. (doi:10.1164/rccm.201312-2235OC). (PMID:24937476)

Record type: Article

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-?. Exogenous IFN-? restores antiviral activity. Objectives: To compare the efficacy and safety of inhaled IFN-? 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-? (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-? 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-?; n = 31 placebo), Asthma Control Questionnaire-6 increased significantly on placebo; this was prevented by IFN-? (P = 0.004). Conclusions: Although the trial did not meet its primary endpoint, it suggests that inhaled IFN-? 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).

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Accepted/In Press date: 8 June 2014
e-pub ahead of print date: 15 July 2014
Published date: 15 July 2014
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 367152
URI: https://eprints.soton.ac.uk/id/eprint/367152
ISSN: 1073-449X
PURE UUID: c9a4fb53-ba66-40f1-9dd4-bafd986264a2
ORCID for Ratko Djukanovic: ORCID iD orcid.org/0000-0001-6039-5612
ORCID for Donna E. Davies: ORCID iD orcid.org/0000-0002-5117-2991

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Date deposited: 23 Jul 2014 14:15
Last modified: 03 Dec 2019 02:07

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Contributors

Author: Tim Harrison
Author: Sebastian L. Johnston
Author: Flic Gabbay
Author: Peter Wark
Author: Neil C. Thomson
Author: Robert Niven
Author: Dave Singh
Author: Helen K. Reddel
Author: Donna E. Davies ORCID iD
Author: Richard Marsden
Author: Christine Boxall
Author: Sarah Dudley
Author: Vincent Plagnol
Author: Stephen T. Holgate
Author: Phillip Monk

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