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

MICA：BRONCH-UK 是一项多中心、多学科合作伙伴关系赠款，旨在解决支气管扩张症方面未得到满足的需求

• 批准号: MR/L011263/1
• 负责人: Anthony De Soyza
• 金额: $ 90.65万
• 依托单位: Newcastle University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FL011263%2F1
• 关键词: MICA; BRONCH; UK; multicentre; multidisciplinary

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.

2.1支气管扩张症（BE）是一种进行性呼吸道（肺部）疾病，其特征为咳嗽、粘液和严重的复发性细菌性胸部感染，健康状况不佳、缺勤率高，与健康相关的生活质量显著降低。在几乎一半的病例中，支气管扩张的原因是未知的（特发性），这些患者的治疗仍然是“最佳猜测”或症状驱动。支气管扩张对患者和医生提出了巨大的挑战，因为没有有效的治疗方法。世界上第一个国家指导方针（由本提案的共同申请人撰写）和科克伦关于支气管扩张的“最佳证据”综述证实了这一情况，报告称，患者组定义不清的小型单中心研究阻碍了研究临床干预/药物试验的少数尝试，使其无法证明用途。自那时以来，重大的事态发展极为缺乏。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，由于BE和死亡率导致的医疗保健需求正在增加，2011年英国有70，000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。我们有有限的英国数据，这种支气管扩张症是多么常见：然而，专家们估计，在英国有30- 60，000名患者受到影响，但最近的研究表明，超过100，000人受到影响。（特发性）和感染后支气管扩张是主要原因，支气管扩张症还可使常见的肺部疾病（例如哮喘和慢性阻塞性肺病（COPD））或免疫问题（例如风湿性关节炎）复杂化。囊性纤维化是支气管扩张的一种遗传（遗传）形式，与COPD相关的支气管扩张一样，其具有与支气管扩张不同的结局、微生物学和管理需求。囊性纤维化是罕见的（10，000例在英国），但通过多中心的工作和协调研究取得了显着的成果。迄今为止，还没有进行大规模的研究，特发性支气管扩张症的遗传原因，因为这需要大量的患者超出了一个单一的中心可以提供。目前在美国以外的任何地方都没有充分表征的支气管扩张患者的登记研究。美国国家登记处最近启动，有1200名与英国患者不同的患者。迫切需要建立一个大型的英国支气管扩张症患者队列，其中可以进行足够大的研究;增加生物库是一个关键的额外力量。队列和合作伙伴关系的简要描述队列将包括3500例有症状的成人患者，高分辨率CT扫描显示支气管扩张。患者将根据临床病史、临床检查和详细检查进行特征描述，这些检查已经是常规临床护理的一部分，每年进行审查。将收集一个DNA生物库（来自血液样本），并将成为世界上第一个支气管扩张症的生物库，为未来的遗传研究提供独特的资源，以确定潜在的遗传原因和新的治疗目标。该合作伙伴关系将9个招募中心与遍布英国的支气管扩张症研究的既定诊所和跟踪记录联系起来，这些诊所和记录从未获得过合作资金。此外，在相关领域拥有专门知识的突破性科学伙伴将首次允许全面绘制知识差距。未来的研究将能够利用集合队列的优势;我们可以提供一个解决基本问题的临床试验计划。因此，我们将解决三个主要的未满足的需求：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。

项目成果

MOESM8 of A 2 × 2 factorial, randomised, open-label trial to determine the clinical and cost-effectiveness of hypertonic saline (HTS 6%) and carbocisteine for airway clearance versus usual care over 52 weeks in adults with bronchiectasis: a protocol...

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• DOI: 10.6084/m9.figshare.11415417
• 发表时间: 2019
• 作者: Bradley J

MOESM6 of A 2 × 2 factorial, randomised, open-label trial to determine the clinical and cost-effectiveness of hypertonic saline (HTS 6%) and carbocisteine for airway clearance versus usual care over 52 weeks in adults with bronchiectasis: a protocol...

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• DOI: 10.6084/m9.figshare.11415405
• 发表时间: 2019
• 作者: Bradley J

MOESM7 of A 2 × 2 factorial, randomised, open-label trial to determine the clinical and cost-effectiveness of hypertonic saline (HTS 6%) and carbocisteine for airway clearance versus usual care over 52 weeks in adults with bronchiectasis: a protocol...

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• DOI: 10.6084/m9.figshare.11415411
• 发表时间: 2019
• 作者: Bradley J

MOESM3 of A 2 × 2 factorial, randomised, open-label trial to determine the clinical and cost-effectiveness of hypertonic saline (HTS 6%) and carbocisteine for airway clearance versus usual care over 52 weeks in adults with bronchiectasis: a protocol...

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• DOI: 10.6084/m9.figshare.11415381
• 发表时间: 2019
• 作者: Bradley J

MOESM2 of A 2 × 2 factorial, randomised, open-label trial to determine the clinical and cost-effectiveness of hypertonic saline (HTS 6%) and carbocisteine for airway clearance versus usual care over 52 weeks in adults with bronchiectasis: a protocol...

MOESM2%20of%20A%202%20×%202%20因子、%20随机、%20开放标签%20试验%20至%20确定%20%20临床%20和%20成本效益%20of%20高渗%20盐水%20(HTS%206

• DOI: 10.6084/m9.figshare.11415372
• 发表时间: 2019
• 作者: Bradley J