Sub-Theme Leaders: Ian Pavord, Mona Bafadhel, Luzheng Xue
Key Researchers: Timothy Hinks, Richard Russell, Jennifer Cane, Jian Luo, Sophie Morgan, Sanjay Ramakrishnan
Over the last 20 years treatment guidelines for common respiratory conditions including COPD and asthma have encouraged generic one-size-fits-all treatment. We believe that this leads to poor targeting of treatment, underestimation of potential treatment effects, and unnecessary treatment associated cost and toxicity. Our overall vision is to develop a new, mechanism-based classification of common respiratory diseases to allow more accurate assessment and more focussed and effective treatments.
In the video, our Respiratory Theme Lead, Professor Ian Pavord, explains why we need a sea-change in the way that asthma is diagnosed, categorised and treated. Prof Pavord is co-chair of a special Lancet Commission on asthma, which says that progress in treating the condition has stagnated over the past 10 years, despite recent breakthroughs, such as the use of biomarkers, which can deliver more precise and targeted treatment.
In previous research we have shown that eosinophilic airway inflammation is a readily identifiable and important treatable feature in patients with severe asthma and COPD, and that specific inhibition of this process with mepolizumab is associated with important clinical benefits in patients with this type of airway inflammation. Subsequent studies led by the theme leader have shown that, in patients with a highly eosinophilic profile, mepolizumab given in addition to standard care is associated with an 80% reduction in the frequency of asthma attacks and large improvements in lung function, symptoms and quality of life. Mepolizumab was approved for use in severe eosinophilic asthma in 2015 and is the first new class of treatment for asthma for 20 years. This work has been the catalyst for the successful clinical development of six other medicines targeting eosinophilic inflammation in airways disease.
Following the approach used in this successful case study this subtheme aims to further investigate established mechanistic pathways of airway disease by:
- Investigating the key driving factors responsible for dysregulated IL-5 production in the airways of a subgroup of patients with severe eosinophilic airway disease and to determine novel ways to inhibit this process.
- Investigating the use of the blood eosinophil count as a means of stratifying patients with acute wheezing illness for targeted treatment with oral corticosteroids and biological agents.
- Developing novel and specific methods to identify and treat persistent airway infection with the bacterium Haemophilus influenza, which we have shown to be the most important potentially treatable aspect in patients with non-eosinophilic airway disease.
- Testing the hypothesis that deficiency of a recently discovered airway epithelial damping mechanism is a key driving factor in the development of asthma.