Develoment and clinical evaluation of a POC theranostic assay to inform therapy choice in Acute Respiratory Distress Syndrome

急性呼吸窘迫综合征(ARDS)是由感染或受伤引起的危重病人的一种危及生命的疾病。感染和损伤导致肺部发炎，导致肺部充满液体，从而阻止氧气从肺到血液的正常运动，从而分配到身体的其他部分。ARDS通常会进展到对身体其他器官的进一步损伤，并与高死亡率或幸存者的长期残疾有关。据估计，ARDS的发病率在英国每年为4万人，在美国为20万人，在全球为300万人。死亡率在30%至45%之间，这取决于确诊时的最初严重程度。尽管有许多临床试验来评估可能的候选者，但目前还没有有效的药物治疗这种疾病。然而，新的证据表明，以前尝试过的和打折的药物可能会使某些患者亚群受益。我们项目联盟内的医学专家发现，某些炎症标志物水平非常高的ARDS患者更有可能对几种治疗产生反应。已经确定了几种生物标志物(我们可以在血液中测量的物质)来识别这些高度炎症的患者。这就是分层医学的本质，在分层医学中，诊断测试可以为个人的治疗决定提供信息，也被称为治疗分析。为了能够快速识别患有ARDS的高炎症患者，从而在重症监护病房入院时指导最有效的治疗，需要进行近距离的鼻腔测试。Randox与我们的临床和学术合作伙伴合作，开发了一种用于识别高炎症ARDS患者的测试，并通过测试120多个血液样本证实了这一方法的有效性。该项目提案将进一步开发这一生物标记物测试，以便使用我们新的护理点(POC)诊断分析仪进行快速近距离患者分析。一旦准备就绪，我们在贝尔法斯特女王大学的临床/学术合作伙伴将在英国的重症监护病房协调一项多中心临床评估，以表明该测试可在护理点用于准确地将患者分成高度炎症和轻度炎症表型(亚组)。这将为治疗决策提供信息。因此，该项目旨在开发一种鼻腔ARDS测试，并证明它在识别更有可能对定制治疗有反应的危重患者方面是有效的。“

"Acute Respiratory Distress Syndrome (ARDS) is a life threatening condition in critically ill patients, caused by infection or injury. Infection and injury induce inflammation in the lungs, causing the lungs to fill up with fluid thus preventing the normal movement of oxygen from the lungs to the blood, for distribution to the rest of the body. ARDS often progresses to further injury to other organs in the body, and is associated with high rates of mortality or long term disability in survivors.The incidence of ARDS is estimated to be 40,000 patients annually in the UK, 200,000 in the US and 3 million globally. Mortality rates range between 30-45%, depending on initial severity at diagnosis. There is no effective drug treatment for the condition despite numerous clinical trials to evaluate possible candidates. However, new evidence suggests that previously tried and discounted drugs may benefit certain patient sub-groups. Medical experts within our project consortium have found that ARDS patients with very high levels of certain markers of inflammation are more likely to respond to several therapies. Several biomarkers (substances we can measure in blood) have been identified to allow identification of these hyper-inflamed patients. This is the essence of stratified medicine, where a diagnostic test can inform individual therapy decisions, also known as theranostics. To allow rapid identification of the hyper-inflamed patient with ARDS, and hence guide the most effective therapy at the point of admission to Intensive Care Units, a near-patient theranostic test is required.Working with our clinical and academic partners, Randox have developed a test to identify hyper-inflamed ARDS patients and confirmed this works by testing over 120 blood samples. This project proposal will further develop this biomarker test to allow rapid near-patient analysis, using our new point of care (POC) diagnostic analyser. Once ready, our clinical / academic partners at Queen's University Belfast will co-ordinate a multi-centre clinical evaluation across Intensive Care Units in the UK to show that the test can be used at point of care to accurately stratify patients into hyper-inflamed and hypo-inflamed phenotypes (sub-groups). This will inform therapy decisions.The project thus aims to develop a theranostic ARDS test and prove that it is effective in identifying those critically ill patients that are more likely to respond to a tailored therapy."