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失调和过度旺盛的炎症反应。目前还没有针对RSV疾病的特异性治疗方法，并且鉴定“可药物化的”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、时间和访问的限制。INFLAMMAGE的目的是在伦敦帝国理工学院使用实验性人RSV感染研究成年志愿者的炎症机制。这将使我们能够研究老年非吸烟者和75岁以下吸烟者的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开发管道中的一系列有前途的药物中选择抑制特定炎症通路的药物。INFLAMMAGE的下一阶段将使我们能够预测GSK经验证的新型抗炎药治疗人类RSV疾病的可能影响，并发现慢性呼吸道疾病（包括COPD）病毒性加重的新治疗方法。对疾病中潜在药物的测试将构成INFLAMAGE未来的最后阶段。

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