COPD-like airway inflammation during RSV infection of older volunteers: INFLAMMAGE

老年志愿者 RSV 感染期间出现慢性阻塞性肺病 (COPD) 样气道炎症：INFLAMAGE

• 批准号: MR/T50256X/1
• 负责人: Peter Openshaw
• 金额: $ 151.6万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FT50256X%2F1
• 关键词: COPD; like; airway; inflammation; during

Based on extensive preclinical and clinical research we hypothesise that RSV disease represents a dysregulated and over-exuberant inflammatory response to infection. There is currently no specific treatment for RSV disease and identification of 'druggable' inflammatory pathways would be of great potential clinical value. Observational studies of natural infection are constrained by sampling, timing and access. The aim of INFLAMMAGE is to investigate the mechanisms of inflammation in adult volunteers using experimental human RSV infections at Imperial College London. This will enable us to investigate the RSV infection in older adult non-smokers and smokers up to 75 years of age; using in vivo and in vitro techniques, we will attempt to define novel clinical end-points and to discover pathways and biomarkers that predict outcome. This will allow us to select from a range of promising drugs in GSK's development pipeline that inhibit specific inflammatory pathways. This next phase of INFLAMMAGE will enable us to predict the possible impact of treatment with validated novel anti-inflammatory agents from GSK in human RSV disease and to discover new treatments for viral exacerbations of chronic respiratory disease, including COPD. The testing of potential drugs in disease will form the future final phase of INFLAMAGE.

基于广泛的临床前和临床研究，我们假设RSV疾病代表了对感染的炎症反应失调且过度过度的炎症反应。目前尚无针对RSV疾病的特定治疗方法，鉴定“可药”炎症途径将具有巨大的潜在临床价值。自然感染的观察性研究受到采样，时机和获取的限制。炎症的目的是使用伦敦帝国学院的实验性人RSV感染来调查成人志愿者的炎症机制。这将使我们能够调查年龄75岁的老年人非吸烟者和吸烟者的RSV感染；使用体内和体外技术，我们将尝试定义新的临床终点，并发现预测结果的途径和生物标志物。这将使我们能够从GSK的开发管道中从一系列有希望的药物中进行选择，这些药物抑制了特定的炎症途径。下一阶段的炎症将使我们能够预测gsk中验证的新型抗炎药对人类RSV疾病的治疗可能影响，并发现包括COPD在内的慢性呼吸道疾病的病毒病毒加剧的新治疗方法。疾病潜在药物的测试将形成未来的发病阶段。

项目成果

Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection.

• DOI: 10.1126/science.aba9301
• 发表时间: 2020-10-09
• 期刊: Science (New York, N.Y.)
• 作者: Habibi MS;Thwaites RS;Chang M;Jozwik A;Paras A;Kirsebom F;Varese A;Owen A;Cuthbertson L;James P;Tunstall T;Nickle D;Hansel TT;Moffatt MF;Johansson C;Chiu C;Openshaw PJM
• 通讯作者: Openshaw PJM