p38 MAPK activation as the basis for corticosteroid insensitivity in severe asthma

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Severe asthma affects only ~5% of all asthmatics, but these unfortunate patients are the most difficult group to treat because they do not get the same amount of benefit from corticosteroid medicines as other patients whose asthma remains well-controlled. These patients therefore desperately need newer treatments to control their asthma. Severe asthmatics suffer from persistent asthma symptoms and attacks and suffer from more side-effects of corticosteroid treatment because they need higher doses than usual. We have been studying how the steroids do not seem to provide more beneficial effects on patients with severe asthma and how cells from their lung (alveolar macrophages) and blood (blood mononuclear cells) are not responding to steroids in the test-tub, as those cells from a mild type of asthma. We have found that there is a protein that determines the release of a chemical from lung cells (called p38 MAPK for short, an enzyme that accelerates reactions in many cells) that is increased in severe asthma. We now wish to study how this protein gets to be active in severe asthma, and how it causes the steroids to be less effective in these cells in the test-tube. This work may provide more effective medicines that patients with severe asthma desperately need such as those medicines that block the effect of the p38 MAPK.