Wessex Asthma Cohort of Difficult Asthma

Study Overview
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Brief Summary
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Asthma is now widely recognised to be a heterogeneous disease. The last two decades have seen the identification of a number of biological targets and development of various novel therapies. Despite this, asthma still represents a significant health and economic burden worldwide. Why some individuals should continue to suffer remains unclear. The Wessex Asthma Cohort of Difficult Asthma (WATCH) is an ongoing 'real-life', prospective study of patients in the University Hospital Southampton Foundation Trust (UHSFT) Difficult Asthma service. Research data capture is aligned with the extensive clinical characterisation required of a commissioned National Health Service (NHS) Specialist Centre for Severe Asthma. Data acquisition includes detailed clinical, health and disease-related questionnaires, anthropometry, allergy and lung function testing, radiological imaging (in a small subset) and collection of biological samples (blood, urine and sputum). Prospective data are captured in parallel to clinical follow up appointments, with data entered into a bespoke database. The pragmatic ongoing nature of the WATCH study allows comprehensive assessment of the real world clinical spectrum seen in a Specialist Asthma Centre and allows a longitudinal perspective of deeply phenotyped patients. It is anticipated that the WATCH cohort would act as a vehicle for potential collaborative asthma studies and will build upon our understanding of mechanisms underlying difficult asthma.

Detailed Description
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Asthma is estimated to affect 5.2 million people in the United Kingdom (UK), half of whom experience severe symptoms at some point in their lives, and 500,000 of whom may be unresponsive to currently available therapies (Asthma UK; living on a knife edge 2004). Severe Asthma probably accounts for 80% of asthma-related health expenditure (Chung KF, Eur Res Mon 2003, 23: 313). In this regard it is estimated to directly cost the NHS (National Health Service) £1 billion per year but also poses considerable hidden societal costs through disability, missed schooling and lost work days. While Severe Asthma is a significant health-economic problem, the availability of effective treatments in clinical practice remains limited. However there is a growing realisation of the heterogeneity of asthma, which is not a single condition, but composed of numerous potential phenotypes (Wenzel S Nat Med 2012 18(5):716-25) some of which may show association to more severe disease status. In this regard recent adoption of unbiased statistical techniques such as cluster analysis has consistently demonstrated presence of severe asthma clusters in both adult and paediatric populations. These clinical phenotypes may show specific pathophysiological associations leading to classification of endotypes. Accompanying this growing understanding of the diverse nature of asthma is the realisation that there are also a diverse range of treatment responses dependent on the underlying nature of an individual's disease. This naturally leads to the concept of personalised therapy regimes for patients with Severe Asthma that better target their individual disease. Omalizumab is the first biological asthma treatment to meet that need in patients with severe allergic asthma. Numerous potential biological agents are in development that show promise in targeting patients with particular disease phenotypes/ endotypes such as mepolizumab, lebrikizumab and dupilimumab. The organisation of Clinical Services for Severe Asthma is undergoing major change with the initiation of Specialised Commissioning of such Services by NHS England in 2014. A core requirement for Specialist Centres being Commissioned under this process will be the maintenance of accurate clinical disease registers which link to the BTS Difficult Asthma Registry and support collaborative research studies in the future. The Difficult Asthma Clinics at Southampton and Portsmouth currently care for 1000 and 400 patients with problematic disease respectively. The two asthma services already collaborate as the Wessex Asthma Network to provide education across the Wessex region. Both services in their roles as Commissioned Specialist Clinical Centre for Severe Asthma receive regional referrals from a wide geographical area. We intend to initiate a comprehensively assessed Difficult Asthma Cohort by inviting all patients in our clinics to participate and contribute data gained through their clinical assessment. This would support ongoing contribution to research via the BTS Difficult Asthma Registry. In addition, a real-life clinical characterisation of Difficult Asthma would provide the basis for a better understanding of the nature of that disease relevant to clinical practice. It would also provide opportunity to develop a better endotype defined understanding of Difficult Asthma that facilitates stratified development of more effective treatment strategies. The Cohort will become a resource for future therapeutic studies in Difficult Asthma with Cohort participants being invited to consent separately into those studies based upon their characterisation through the Cohort.

Official Title
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WATCH (Wessex AsThma CoHort of Difficult Asthma): A Longitudinal Cohort Study to Facilitate Better Understanding and Management of Difficult Asthma Encountered in Clinical Practice

Conditions
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Asthma

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients referred to the Adult or Transitional Regional Asthma Clinics at participating hospitals. On high-dose therapies, with or without the addition of continuous or frequent use of oral steroids (or steroid sparing therapies), as defined by the BTS (British Thoracic Society) Adult Asthma Management Guidelines (2016). Exclusion Criteria: Asthma patients who are not referred to the Adult or Transitional Regional Asthma Clinics at participating hospitals. Any patients who are not on high-dose therapies, with or without the addition of continuous or frequent use of oral steroids (or steroid sparing therapies), as per the BTS (British Thoracic Society) Adult Asthma Management Guidelines (2016).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort Characterisation | To develop a phenotypic characterisation of the heterogeneous nature of severe asthma seen in clinical practice that reflects disease natural history and treatment intervention responsiveness | 35 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Endotyping | To relate well characterised clinical disease phenotypes to pathophysiological endotypes of severe asthma. | 35 years | 
| Patient Stratification | To enable accurate stratification of patients for trials of novel pharmacological and non-pharmacological treatment strategies that facilitates an era of individualised patient management. | 35 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Difficult Asthma, Severe Asthma