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/R502121/1
• 负责人: Peter Openshaw
• 金额: $ 13.25万
• 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: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FR502121%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. Steroids have limited efficacy, and identification of druggable inflammatory pathways in severe RSV disease would be of great potential value. There are promising clinical assets ready for investigation, however, our ability to test novel therapeutics is limited by the currently available models of viral disease and clinical endpoints tied to disease processes. Observational studies of natural infection are constrained by sampling, timing and access. We therefore propose to extend the experimental human RSV infection studies established at Imperial College to investigate the pulmonary response to RSV infection in older adult non-smokers and smokers, with the development of novel clinical endpoints which can then be used to evaluate the possible impact of treatment with validated novel anti-inflammatory agents from GSK in human RSV disease and therefore in COPD.

基于广泛的临床前和临床研究，我们假设RSV疾病代表了一种对感染的调节失调和过度活跃的炎症反应。类固醇的疗效有限，在严重的呼吸道合胞病毒病中识别可药物的炎症途径将具有巨大的潜在价值。有希望的临床资产准备进行研究，然而，我们测试新疗法的能力受到目前可用的病毒疾病模型和与疾病过程相关的临床终点的限制。对自然感染的观察性研究受到采样、时间和获取途径的限制。因此，我们建议扩展帝国理工学院建立的实验性人类RSV感染研究，以调查老年非吸烟者和吸烟者对RSV感染的肺部反应，开发新的临床终点，然后可以用于评估GSK经过验证的新型抗炎药对人类RSV疾病和COPD治疗的可能影响。

项目成果

M1-like monocytes are a major immunological determinant of severity in previously healthy adults with life-threatening influenza.

• DOI: 10.1172/jci.insight.91868
• 发表时间: 2017-04-06
• 期刊: JCI insight
• 影响因子: 8
• 作者: Cole SL;Dunning J;Kok WL;Benam KH;Benlahrech A;Repapi E;Martinez FO;Drumright L;Powell TJ;Bennett M;Elderfield R;Thomas C;MOSAIC investigators;Dong T;McCauley J;Liew FY;Taylor S;Zambon M;Barclay W;Cerundolo V;Openshaw PJ;McMichael AJ;Ho LP
• 通讯作者: Ho LP

Progression of whole-blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in severe influenza.

• DOI: 10.1038/s41590-018-0111-5
• 发表时间: 2018-06
• 期刊: Nature immunology
• 影响因子: 30.5
• 作者: Dunning J;Blankley S;Hoang LT;Cox M;Graham CM;James PL;Bloom CI;Chaussabel D;Banchereau J;Brett SJ;Moffatt MF;O'Garra A;Openshaw PJM;MOSAIC Investigators
• 通讯作者: MOSAIC Investigators

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