MICA: Korea-UK PRISM consortium: Establishing Precision Medicine in severe asthma

在英国和韩国，重度哮喘被定义为对现有治疗（包括类固醇和支气管扩张剂）没有充分反应的哮喘。它影响高达5%的哮喘患者，并代表了重要的经济负担。在英国，重度哮喘的经济成本估计为每位患者每年3- 4，000英镑，这些成本取决于哮喘的严重程度以及患者是否使用口服皮质类固醇治疗。在英国和韩国，这些患者在英国由卫生部委托的专科严重哮喘中心接受管理。虽然严重哮喘被认为是一种具有不同类型（表型）的疾病，但直到最近才将这些患者分组。随着新治疗方法的引入，如阻断细胞因子如IL-5、IL-4和IL-13的抗体治疗，高血嗜酸性粒细胞计数用于选择对该治疗有反应的患者。然而，我们知道这种测量并不能准确预测反应。在患有严重哮喘的欧洲U-BIOPRED患者中已经做了大量工作，通过检查和分类受试者血液或痰细胞中表达的基因和蛋白质来定义不同类型的哮喘。应用这种分子分类尚未应用于重症哮喘临床。我们相信，当在临床上使用时，这将带来优势，因为这可以告诉我们每个患者可能参与引起哮喘的细胞过程或蛋白质的类型，以及最终，他或她可能需要控制哮喘的治疗类型。因此，英国（帝国理工学院的Chung教授）和韩国（首尔蔚山大学医学院的Kim教授）之间的这个合作项目称为PRISM的目的是将“精准医学”（也称为“个性化医学”）引入严重哮喘的治疗。精准医疗是为个体患者量身定制治疗，通常通过使用基于检查蛋白质或基因的诊断测试，该测试将指导针对该个体的最合适治疗，以便在正确的时间为正确的患者提供正确的治疗。我们建议对400例重度哮喘患者进行分子分类，这些患者将在英国和韩国专门治疗重度哮喘患者的几个中心接受为期一年的观察。我们希望了解什么类型的哮喘以及在血液或呼出气中测量的诊断生物标志物可以非常准确地告诉我们谁将对我们目前所拥有的抗体治疗（例如抗IL 5或抗IL 5 Ra或抗IL 4 Ra）的治疗反应良好。对于那些不能接受这种治疗的人，我们将使用基因和蛋白质来告诉我们哪种类型的治疗可能会改善他们的哮喘。因此，这种精准医学的方法将为严重哮喘的亚组带来更新更有效的治疗方法。我们预计，这项研究将告诉我们谁需要这些抗体治疗，这将使患者能够更好地控制他们的哮喘。这是一项开创性的研究，因为这是第一次将这种方法用于治疗哮喘或任何其他慢性疾病。如果我们成功实现了我们的目标，这可能会为不仅在严重哮喘中，而且在其他呼吸和非呼吸疾病中建立精准医学铺平道路，这将为患有严重哮喘等疾病的大量患者提供益处。

In both UK and Korea, severe asthma is defined as asthma that does not respond adequately to existing treatments including steroids and bronchodilators. It affects up to 5% of asthmatics and represents an important economic burden. In the UK, the economic costs for severe asthma are estimated to be £3-4,000 per patient per year, with these costs dependent on the severity of the asthma and as to whether the patient is using oral corticosteroid therapy. In both UK and Korea, these patients are managed in specialist severe asthma centres which in the UK are commissioned by the Department of Health. Although severe asthma is considered to be a disease with different types (phenotypes), only recently have these patients been divided into groups. With the introduction of new treatments such as antibody treatments to block cytokines such as IL-5, IL-4 and IL13, a high blood eosinophil count is used to choose patients who respond to this treatment. However, we know that this measurement is not an accurate predictor of the response. A lot of work has been done in the European U-BIOPRED patients with severe asthma to define the different types of asthma by examining and classifying the genes and proteins that are expressed in the subject's blood or sputum cells. Applying this molecular classification has not yet been applied in the severe asthma clinic. We believe that this will bring advantages when used in the clinic because this can tell us for each patient the type of cellular processes or proteins that may be involved in causing the asthma, and ultimately, what type of treatments he or she might need to control the asthma. Therefore, the aim of this collaborative project between the UK (Professor Chung at Imperial College) and Korea (Professor Kim at University of Ulsan College of Medicine, Seoul) called PRISM is to introduce 'Precision Medicine' (also termed 'personalised medicine') into the treatment of severe asthma. Precision Medicine is the tailoring of treatment to the individual patient usually by using a diagnostic test based on examining proteins or genes that will guide the most appropriate treatment for this individual person so that the right treatment can be provided to the right patient at the right time. We propose to do this molecular classification in 400 severe asthma patients who will be observed over a one-year period in several centres specialising in treating patients with severe asthma in both UK and Korea. We wish to see what type of asthma and what diagnostic biomarker measured in the blood or in the exhaled breath that can tell us with great accuracy who will respond well to treatment with the antibody treatments that we have at the moment such as the anti-IL5 or anti-IL5Ra or anti-IL4Ra. For those who cannot have this treatment, we will use the genes and proteins to tell us which type of treatments that might improve their asthma. Therefore, this approach of Precision Medicine will bring newer more effective treatments to subgroups of severe asthma. We foresee that this research will tell us exactly who needs treatment with these antibody treatments, and this will allow patients to take better control of their asthma. This is a pioneering piece of research because this is the first time that this approach has been taken in the treatment of asthma or any other chronic disease. If we are successful in our objectives, this might pave the way for the establishment of Precision Medicine not only in severe asthma but also in other respiratory and non-respiratory condition, that will provide benefits to a large range of patients suffering from diseases such as severe asthma.