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Background and Aims

Improved diagnostics for airway disease managed in primary care. Important outcomes such as hospitalisation and deaths from airway diseases such as asthma and COPD have not improved over the last 10 years despite a three-fold increase in expenditure on our most effective treatment (inhaled corticosteroids) to £470 million/year and considerable investment in initiatives to encourage adherence to treatment and better self-management. In the absence of any fundamental advances in treatments there are only two ways to address this lack of progress: to continue to persuade more patients to take more inhaled corticosteroids; or to target treatment more effectively. We are investigating the second approach. We will investigate the use of two simple biomarkers to inform decisions about the use of inhaled corticosteroids to prevent attacks and oral corticosteroid to treat attacks. Our focus will be on primary and emergency care where most important treatment decisions are made in patients with airway disease. We have shown previously in secondary care based studies that exhaled nitric oxide (FeNO) and the peripheral blood eosinophil count show considerable promise. The former is ideal for use in a non-specialist setting as the test is easy to perform and accurate results are assured. The latter is readily available in an emergency setting and shows considerable promise as a means of directing therapy in patients with COPD. We hope to develop a new approach to applying existing treatments where therapy is initiated based on the likelihood of a response. This approach has already been shown to be important for the use of new treatments in severe airway disease (see below).

New treatments for severe airway disease. Progress has been made in the development of new treatments for severe airway disease. We have played a lead role in the development of three of the most promising: Mepolizumab, bronchial thermoplasty and CRTH2 antagonists. An important insight has been to recognise that these treatments only work in sub-groups of patients who have evidence of activity of the relevant pathway. We believe that the only rationale approach to new drug discovery is to identify sub-groups of patients who share common characteristics, understand the key mechanisms of their disease and identify opportunities to intervene. We will do this in patients with severe eosinophilic airway disease, patients with airway disease associated with allergy to aspergillus and patients with persistent airway infection with Haemophilus Influenzae. We have chosen these sub-groups as they are common patterns of severe airway disease, existing treatments have some efficacy and the mechanisms of disease look tractable.

Pavord Group Publications

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