Djukanović 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, Monk Phillip
1 NIHR Southampton Respiratory Biomedical Research Unit, Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton, United Kingdom.
Am J Respir Crit Care Med. 2014 Jul 15;190(2):145-54. doi: 10.1164/rccm.201312-2235OC.
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.
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.
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.
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).
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).
在体外，哮喘患者的支气管上皮细胞因抗病毒蛋白IFN-β诱导不足而更易受到鼻病毒感染。外源性IFN-β可恢复抗病毒活性。
比较在出现感冒症状后给予哮喘患者吸入IFN-β与安慰剂预防或减轻呼吸道病毒引起的哮喘症状的疗效和安全性。
共有147例使用吸入性糖皮质激素（英国胸科学会2-5级）且有病毒相关加重病史的哮喘患者，在出现感冒症状的24小时内随机分为接受14天吸入IFN-β治疗组（n = 72）或安慰剂组（n = 75），并进行临床评估，收集相关样本以评估病毒感染和抗病毒反应。
共有91%的随机分组患者出现明确的感冒。在这个改良的意向性治疗人群中，哮喘症状在临床上没有显著恶化（六项哮喘控制问卷的平均变化<0.5），IFN-β治疗对这一主要终点没有显著影响，尽管它提高了早晨呼气峰值流速的恢复（P = 0.033），减少了额外治疗的需求，并通过血液和痰液生物标志物评估增强了先天免疫力。在对更难治疗的4-5级哮喘患者亚组（IFN-β组n = 27；安慰剂组n = 31）的探索性分析中，安慰剂组的哮喘控制问卷-6评分显著增加；IFN-β可预防这种情况（P = 0.004）。
尽管该试验未达到其主要终点，但提示吸入IFN-β对于难治疗的哮喘患者因病毒诱发的哮喘恶化是一种潜在的治疗方法，并支持在该人群中进行进一步的、有足够样本量的试验。临床试验已在www.clinicaltrials.gov注册（NCT 01126177）。
