Developmental Clinical Studies-validation of the utility of a novel smartprobe detecting neutrophil activation/elastase activity in acute lung injury

开发性临床研究 - 验证新型智能探针在急性肺损伤中检测中性粒细胞活化/弹性蛋白酶活性的实用性

• 批准号: MR/J010901/1
• 负责人: Christopher Haslett
• 金额: $ 251.7万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FJ010901%2F1
• 关键词: Developmental; Clinical; Studies; validation; utility

40% of all patients in the intensive care unit (ICU) need a ventilator to support their lungs, with many associated complications. Currently the main indication of clinical deterioration is the presence/spreading of shadowing on the chest x- ray. This has many different causes (all requiring different treatments). There is a pressing need for rapid bedside tests to provide definitive diagnostic information about what is happening in the lungs themselves. Many studies have used blood markers, but in patients with multi-system disease these are not specific for the lung and the results are too slow to be useful in the rapidly-changing ICU setting.We will employ cutting-edge technology to pass a tiny optical fibre deep into the lungs of ventilated patients and spray a 'microdose' of an imaging agent that will tell us the reasons for the lung deterioration. This approach has the potential to rapidly determine, at the bedside, if the lung shadowing is due to inflammation. Such an approach could revolutionise the way we deal with the critically ill patient and provide rapid, point of care diagnostics that would help tailor the patient's management.

重症监护病房（ICU） 40%的患者需要呼吸机来支持肺部，并伴有许多相关并发症。目前临床恶化的主要指征是胸部x线影的存在/扩散。这有许多不同的原因（都需要不同的治疗方法）。迫切需要快速的床边测试，以提供关于肺部本身发生的情况的明确诊断信息。许多研究使用了血液标记物，但在多系统疾病患者中，这些标记物并不针对肺部，而且结果太慢，无法在快速变化的ICU环境中使用。我们将采用尖端技术，将一根微小的光纤深入通气患者的肺部，并喷洒“微剂量”显像剂，这将告诉我们肺部恶化的原因。这种方法有可能在床边快速确定肺影是否是由炎症引起的。这种方法可以彻底改变我们处理危重病人的方式，并提供快速的护理点诊断，这将有助于量身定制病人的管理。

项目成果

Technical advance: autofluorescence-based sorting: rapid and nonperturbing isolation of ultrapure neutrophils to determine cytokine production.

• DOI: 10.1189/jlb.0113040
• 发表时间: 2013-07
• 期刊: Journal of leukocyte biology
• 影响因子: 5.5
• 作者: Dorward DA;Lucas CD;Alessandri AL;Marwick JA;Rossi F;Dransfield I;Haslett C;Dhaliwal K;Rossi AG
• 通讯作者: Rossi AG

Genetic and pharmacological inhibition of CDK9 drives neutrophil apoptosis to resolve inflammation in zebrafish in vivo.

• DOI: 10.1038/srep36980
• 发表时间: 2016-11-11
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Hoodless LJ;Lucas CD;Duffin R;Denvir MA;Haslett C;Tucker CS;Rossi AG
• 通讯作者: Rossi AG

In-situ imaging of neutrophil activation in the human alveolar space with neutrophil activation probe and pulmonary optical endomicroscopy

使用中性粒细胞激活探针和肺光学内窥镜对人肺泡腔中性粒细胞激活进行原位成像

• DOI: 10.1016/s0140-6736(16)00418-9
• 发表时间: 2016
• 期刊: The Lancet
• 作者: Craven T

Activated neutrophil fluorescent imaging technique for human lungs.

• DOI: 10.1038/s41598-020-80083-w
• 发表时间: 2021-01-13
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Craven TH;Walton T;Akram AR;Scholefield E;McDonald N;Marshall ADL;Humphries DC;Mills B;Campbell TA;Bruce A;Mair J;Dear JW;Newby DE;Hill AT;Walsh TS;Haslett C;Dhaliwal K
• 通讯作者: Dhaliwal K