The Wessex Severe Asthma Cohort Study

  • Thomas Peter Rhys Newman Brown

Student thesis: Doctoral Thesis

Abstract

Aims
The Wessex Severe Asthma Cohort (WSAC) study aimed to create a well characterised ‘real-world’ severe asthma patient cohort both to facilitate recruitment into clinical trials of novel therapies and to enhance understanding of the physiological and biological characteristics underpinning proposed phenotypes and ‘targetable traits’ in severe asthma and to better identify patients at risk of adverse outcomes.

Methods
WSAC is an observational cross-sectional study providing a detailed characterisation of severe asthma patients recruited from specialist severe asthma clinics at Portsmouth and Southampton Hospitals between April 2009 and January 2014. Comparative healthy control and mild-moderate asthma groups were also recruited and underwent the same characterisation protocol with clinical, physiological and biological assessments, including sputum inflammatory cell counts and
over 40 sputum and serum cytokines, chemokines, and other inflammatory mediators with potential roles in severe asthma.

Results
WSAC is one of the largest published severe asthma cohorts globally, including 342 severe asthma patients and a comparator group of 69 mild-moderate asthmatics and 80 healthy controls. Importantly the severe asthma patients in this ‘real-world’ cohort were broadly comparable to those seen in previously published cohorts/registries suggesting findings from this study are generalisable to clinical practice. A significant disease burden was demonstrated in the severe asthma group with smoking, obesity, and depression highlighted as important ‘targetable traits’ identifying poorer asthma control. Different mechanisms likely underpin T2 eosinophilic airway inflammation, for example, in current smokers, whilst a non-T2 phenotype predominates in morbid obesity and significant depression with a probable bidirectional relationship. For patients with T2 asthma (including those on maintenance systemic corticosteroids), FeNO was the best predictive biomarker of treatable traits associated with an intermediate T2 biomarker signal. YKL40 shows promise as a biomarker for non-T2 disease, whilst a lack of reversibility predicts higher levels of airway inflammation in those with small airways dysfunction. Furthermore, clinical trials assessing biologic therapies in severe asthma have been shown to lack external validity.

Conclusions
There is evidence of a persistent unmet need for patients with severe asthma, particularly those with non-T2 disease. In addition, asthma phenotypes and ‘targetable traits’ can identify important differences in underlying pathobiology with potential implications for clinical practice.

Funding
MRC/NIHR Patient Research Cohorts Initiative

Date of AwardSept 2021
Original languageEnglish
SupervisorJan Shute (Supervisor) & Anoop Chauhan (Supervisor)

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