期刊
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
卷 190, 期 2, 页码 145-154出版社
AMER THORACIC SOC
DOI: 10.1164/rccm.201312-2235OC
关键词
innate immunity; treatment; respiratory virus
资金
- Synairgen Research Limited
- University of Southampton spinout Company
- Asthma UK [MRC-AsthmaUKCentre] Funding Source: researchfish
- Medical Research Council [G1000758, G0501506, G0900453] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0510-10021] Funding Source: researchfish
- MRC [G0900453, G0501506] Funding Source: UKRI
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-beta. Exogenous IFN-beta restores antiviral activity. Objectives: To compare the efficacy and safety of inhaled IFN-beta 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-beta (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-beta 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-beta; n = 31 placebo), Asthma Control Questionnaire-6 increased significantly on placebo; this was prevented by IFN-beta (P = 0.004). Conclusions: Although the trial did not meet its primary endpoint, it suggests that inhaled IFN-beta 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.
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