Wessex Asthma Cohort of Difficult Asthma
Wessex Asthma Cohort of Difficult Asthma
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.
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.
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).