Characterising airway epithelium and smooth muscle in severe asthma
Characterising the airway epithelium and airway smooth muscle in severe asthma: oxidative stress, innate immune dysfunction and epigenetic signatures
Kian Fan Chung
Asthma is a common chronic disorder characterised by symptoms of breathlessness and wheeze. About 10% of these patients have severe asthma and their symptoms are not controlled despite high doses of medications. There is an urgent need to find more effective treatments for these patients.
The mechanisms that underlie asthma are much better understood but we don't know whether the mechanisms are the same in severe asthma. Unlike in normal asthma the inflammation in severe asthma is resistant to the anti-inflammatory effects of medications like steroids. In addition, the airways of patients with severe asthma often remain constantly obstructed. Complex abnormalities of the immune system may lead to the development of severe asthma. In severe asthmatics, the cells lining the airways and layers of muscle underneath the lining become thickened and enlarged leading to the obstruction of the airways. These cells have been show to release chemicals which send signals to other cells that lead to alterations in the characteristics of the airway which results in the development of disease. Therefore treatments aimed at altering the function of these cells could be effective in severe asthma, which is why it would be useful to study these cells in a test tube.
Our hypothesis is that cells lining the airway of severe asthmatic patients produce an excess of compounds and that lead to worsening of inflammation in the airways and they respond in an abnormal way when stimulated by the immune system.There may also be differences in these cells at a genetic level.
We aim to stimulate the cells from airways of asthmatics and see if their response in terms of chemical signals and gene expression is different from that of normal patients. We will need to do obtain these cells by doing an invasive but safe procedure called bronchoscopy.
London - London Bridge Research Ethics Committee
Date of REC Opinion
22 Sep 2014
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