LAUSR

Severe asthma remains a major unmet medical need and results in a significant demand on healthcare costs. One of the key characteristics of the severe phenotype is a neutrophilic inflammation that is resistant to steroid treatment usually effective in the mild/moderate disease. Steroid-resistant neutrophilic inflammation is also a key characteristic of Chronic Obstructive Pulmonary Disease (COPD) where it has been demonstrated to be due to reduced HDAC activity which can be reversed by the combination of low dose Theophylline and steroid. We established two house dust mite (HDM) models of allergic asthma and demonstrated one (Alum/HDM) to model the steroid-sensitive eosinophilic inflammation associated with mild/moderate asthma and the other (Complete Freund’s Adjuvant (CFA)/HDM) to model the steroid-resistant neutrophilic inflammation associated with severe asthma (Figures 1, 2, 3 and 4). We then investigated whether the steroid resistance of the severe asthma model could be reversed by using a combination of Theophylline and steroid previously shown to be effective in a mouse model of COPD (Fox JC et al, Proc. Am. Thorac. Soc., 2007). Introduction