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

2.1未满足的临床需求支气管扩张（BE）是一种进行性呼吸（肺）疾病，其特征是咳嗽、黏液和严重的复发性胸部细菌性感染，健康状况不佳、缺勤和与健康相关的生活质量明显下降。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。支气管扩张对患者和医生来说是一个巨大的挑战，因为没有有效的治疗方法。世界上第一个国家指南（由本提案的共同申请人撰写）和Cochrane关于支气管扩张的“最佳证据”综述都证实了这一情况，报告称，小规模的单中心研究和不明确的患者群体阻碍了研究临床干预/药物试验的少数尝试，使它们的使用未经证实。此前，MRC在20世纪50年代赞助了支气管扩张的英国试验：自那时以来，严重缺乏重大进展。这在一定程度上反映了一种感觉，即BE很少见。然而，最近的证据却与此相反：在英国和美国，由于BE和死亡率的医疗需求正在增加，2011年英国住院人数超过70,000人。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有多普遍，我们在英国的数据有限：然而，专家估计英国有30-6万名患者受到影响，但最近的研究表明，受影响的患者超过10万人。虽然迄今为止报告的小病例系列表明“不明原因”（特发性）和感染后支气管扩张是主要原因，但支气管扩张也可使常见肺部疾病（如哮喘和慢性阻塞性肺疾病（COPD））或免疫问题（如类风湿关节炎）复杂化。囊性纤维化是一种遗传性的支气管扩张，与COPD相关的支气管扩张有不同的结局、微生物学和治疗需求。囊性纤维化是罕见的（在英国有10,000例），但通过多中心合作和协调研究取得了重大进展。迄今为止，还没有对特发性支气管扩张的遗传原因进行过大型研究，因为这需要大量的患者，而不是一个中心可以提供的。目前在美国以外的任何地方都没有明确的支气管扩张患者登记。美国国家登记处最近启动，有1200名患者与英国患者不同。有一个迫切需要建立一个大队列的英国患者与支气管扩张可以进行足够大的研究；加入生物库是一个关键的额外优势。该队列将包括3500名有高分辨率CT扫描显示支气管扩张的有症状的成年患者。患者将根据临床病史，临床检查和详细调查进行特征描述，这些调查已经是常规临床护理的一部分，并进行年度审查。将收集DNA生物库（来自血液样本），并将形成世界上第一个支气管扩张的DNA生物库，为未来的基因研究提供独特的资源，以确定潜在的遗传原因和新的治疗靶点。该伙伴关系将9个招募中心与英国各地的成熟诊所和支气管扩张研究的记录联系起来，这些中心从未有过合作的资金。此外，具有相关领域专门知识的突破性科学伙伴将首次能够全面了解知识差距。未来的研究将能够利用集结队列的力量；我们可以开展临床试验项目，解决基本问题。因此，我们将解决三个主要未满足的需求：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——吸引熟练的科学家在该领域工作。

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.