MICA: BRONCH-UK a multicentre and multidisciplinary partnership grant tackling unmet needs in bronchiectasis

2.1未满足临床需要支气管扩张症(BE)是一种进行性呼吸道(肺部)疾病，以咳嗽、粘液和严重、反复发生的细菌性胸腔感染为特征，健康不良率高，休假时间长，与健康相关的生活质量显著下降。在几乎一半的病例中，支气管扩张的原因不明(特发性)，这些患者的治疗仍然是“最好的猜测”或症状驱动。由于没有有效的治疗方法，支气管扩张症给患者和医生带来了巨大的挑战。世界上第一份国家指南(由该提案的共同申请人撰写)和Cochrane对支扩的“最佳证据”审查都证实了这一情况，报告称，对定义不清的患者组进行的小型单中心研究阻碍了研究临床干预措施/药物试验的少数尝试，使它们的用途未经证实。以前，MRC在20世纪50年代赞助了英国对支扩的试验：自那以来，重大进展严重缺乏。这在一定程度上反映了一种感觉，即BE是罕见的。然而，最近的证据与此相反：在英国和美国，医疗保健需求和死亡率正在上升，2011年英国有7万多人入院。根据美国医疗保险索赔的预测，美国有10万名患者。关于这种支气管扩张症的常见程度，我们在英国的数据有限：然而，专家估计在英国有30-6万名患者受到影响，但最近的研究表明，超过10万人受到影响。虽然到目前为止报道的小病例系列表明，原因不明(特发性)和感染后支气管扩张症是主要原因，但支气管扩张症也会使常见的肺部疾病，如哮喘和慢性阻塞性肺疾病(COPD)或免疫问题，如类风湿性关节炎复杂化。囊性纤维化是一种遗传性(遗传性)支气管扩张症，与COPD相关的支气管扩张症一样，具有不同的预后、微生物学和治疗需求。囊性纤维化很少见(在英国有10,000例)，但通过多中心的工作和协调研究已经取得了显著的进展。到目前为止，还没有对特发性支气管扩张症的遗传原因进行大规模研究，因为这需要大量的患者，而不是单个中心所能提供的。目前在美国以外的任何地方都没有特征良好的支扩患者的登记。美国国家登记最近开始，有1200名患者与英国患者不同。迫切需要建立一个英国支气管扩张症患者的大队列，以便进行足够大的研究；增加生物库是一个关键的额外优势。该队列将包括3500名有症状的成人患者，他们的高分辨率CT扫描显示为支气管扩张症。患者的特征将基于临床病史、临床检查和详细调查，这些已经是常规临床护理的一部分，并每年进行审查。将收集一个DNA生物库(从血液样本中)，并将形成世界上第一个支气管扩张的生物库，提供一个独特的资源，使未来的基因研究能够确定潜在的遗传原因&治疗的新靶点。这一合作关系将9个招聘中心与现有的诊所联系起来，这些诊所是分布在英国各地的支气管扩张症研究的跟踪记录，这些诊所从未获得合作资金。此外，在相关领域拥有专门知识的开创性科学伙伴将首次能够全面绘制知识差距图。未来的研究将能够利用聚集的队列的力量；我们可以提供一项解决根本问题的临床试验计划。因此，我们将解决三个尚未得到满足的主要需求：1)缺乏该领域的专业知识；2)缺乏临床证据基础；3)基础科学--吸引有技能的科学家到该领域工作。

2.1 Unmet Clinical NeedBronchiectasis (BE) is a progressive respiratory (lung) disease characterised by cough, mucus and severe, recurrent bacterial chest infections with high rates of ill health, time off work and marked reductions in health-related quality-of-life. In almost half of cases, the cause of bronchiectasis is unknown (idiopathic) and treatment in these patients remains "best guess" or symptom driven. Bronchiectasis presents a huge challenge to patients and doctors because no effective treatment is available. Both the world's first national guidelines (authored by coapplicants of this proposal) and Cochrane "best evidence" review of Bronchiectasis confirms this situation, reporting that small single-centre studies with ill-defined patient groups have hampered the few attempts to study clinical interventions /drug trials, rendering them of unproven use.Previously the MRC sponsored UK trials in Bronchiectasis in the 1950s: Since then major developments have been sorely lacking. This partly reflects a feeling that BE is rare. However recent evidence is against this: In the UK and the US healthcare demands due to BE and mortality rates are increasing with 70,000+ hospital admissions in the UK 2011. Based on projections from US health insurance claims there are 100,000 US patients. We have limited UK data on how common this bronchiectasis is: Experts have however estimated 30-60,000 patients are affected in the UK but recent research suggests over 100,000 are affected.Whilst the small case series reported so far demonstrate that "unknown cause" (idiopathic) and post-infectious bronchiectasis are the leading causes, bronchiectasis can also complicate common lung diseases such as asthma and chronic obstructive pulmonary disease (COPD) or immune problems e.g. Rheumatoid arthritis. Cystic Fibrosis is an inherited (genetic) form of bronchiectasis which like COPD associated bronchiectasis has different outcomes, microbiology and management needs from Bronchiectasis. Cystic fibrosis is rare (10,000 cases in the UK) yet has made significant gains through multicentre working and coordinating research.To date no large studies of the genetic causes of idiopathic bronchiectasis have been conducted as this requires large numbers of patients beyond that a single centre can provide. There is currently no registry of well characterised patients with Bronchiectasis anywhere outside the US. The US national registry was commenced recently and has 1200 patients that differ to UK patients. There is an urgent need to build a large cohort of UK patients with Bronchiectasis in which large enough studies can be undertaken; adding in a biobank is a key additional strength. Brief description of the Cohort and Partnership The cohort will comprise 3500 symptomatic adult patients with a High Resolution CT scans demonstrating bronchiectasis. Patients will be characterised on the basis of clinical history, clinical examination and detailed investigations that are already part of routine clinical care with yearly reviews. A DNA biobank (from a blood sample) will be collected and will form a world's first in bronchiectasis providing a unique resource allowing future genetic studies to identify underlying genetic causes & new targets for treatment. The partnership links 9 recruiting centres with established clinics & track records in Bronchiectasis research spread across the UK that have never had funding to work together. Additionally ground-breaking scientific partners with expertise in relevant areas will for the first time allow comprehensive mapping of the knowledge gaps. Future research will be able to use the strength of the assembled cohort; we can deliver a programme of clinical trials that address fundamental issues. We will therefore tackle three major unmet needs 1) Lack of expertise in the area, 2) Lack of a clinical evidence base 3) Basic science- attracting skilled scientists to work in the area.