Wessex severe asthma cohort

Asthma is a common and disabling problem for many, particularly those with severe persistent disease that prevents them living a normal life. Standard asthma therapies are insufficient to control symptoms in these individuals and they live in fear of exacerbations that require emergency care and hospitalisation. There is thus an urgent need for the identification of novel therapeutic approaches that improve disease control and prevent disease exacerbation. To enable the more rapid conduct of trials with potential new treatments it is important to have well characterised patients, as it is recognised that severe asthma may arise from a range of causes and not all individuals are likely to benefit in the same way with specific interventions. With this in mind, this proposal will gather patients within the Wessex region with severe asthma, to form a Wessex severe asthma cohort, that can undergo detailed characterisation and be available to potentially take parts in trials of new therapies. This characterisation will involve documenting the impact of the disease on daily symptoms and quality of life, focusing on the presence and severity of nasal and sinus symptoms. Measures will be made of how well the lungs are working through a series of breathing tests. Biological samples, such as sputum, collected by inducing coughing, nasal washings, blood and urine will be collected and used to assess the nature, extent and severity of asthmatic inflammation within the airways and body. It is intended that the cohort would act as a focus for the evaluation of novel treatments that are being developed in the hope that they would lead to improvement in asthma in those with more severe disease. The characterisation would help determine which patients might best be selected for different interventions, dependent upon how these work, to give the best chance of identifying better treatments that can be developed to help improve the quality of life in those with severe asthma.

This cohort of patients with persistent and severe asthma specifically responds to a significant unmet clinical need and is not duplicated within National Service Framework strategies or any Topic Specific Clinical Research Networks, as none exist for asthma. This will provide well characterised subjects that facilitate the proof of principle investigation of novel therapies with a sound rationale in this group of patients. The collection and characterisation of these patients reflects a strong partnership between NHS and academic respiratory physicians in Wessex and the close geographic localisation makes possible the potential conduct of sophisticated, mechanistic, translational, pharmacological studies that would not be possible in a widely disseminated cohort and for which Southampton has a proven track record.
Three hundred patients with asthma who, despite regular maintenance therapy at level 4 or level 5 of the British Thoracic Society asthma management guidelines, remain symptomatic and have unstable disease, in that they have a history of severe exacerbation necessitating a course of oral steroids or an increased in maintenance oral steroid dose, will be recruited. Characterisation, in addition to a detailed history which will include details of smoking habit and medication use, will consist of 1) patient centered questionnaires and diary card recording of upper and lower airway symptoms, to evaluate the impact of the disease on the individual, 2) physiological measures of lung function at home and in the laboratory before and after bronchodilator therapy, to assess lung function in relationship to the norm (predicted values), the natural diurnal variation and the short term pharmacological reversibility of any impairment, 3) biological sample collection to evaluate airway inflammation within the upper and lower airways and to store samples from induced sputum, nasal lavage, peripheral blood (serum and plasma) and urine for subsequent biomarker evaluation, for which separate funding would need to be applied for. Additional assessments include documentation of atopic status, measurement of BMI and measurement of urinary cotinine to verify tobacco smoking history.
A range of potential mechanistic proof of principle studies on novel therapies that could be undertaken on this cohort of patients with severe asthma are detailed, along with possible industrial collaborators. These focus on modifying the effect or exposure to trigger factors (viruses and bacteria), the underlying abnormal airway inflammation (eosinophilic and neutrophilic) or specific disease processes through molecular targeting.