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

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。

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.