The financial burden of asthma in the United States is estimated to be over $10 billion. The disease is characterised by a complex of airway inflammation, remodelling and bronchial hyperresponsiveness, leading to recurring episodes of potentially reversible airflow limitation and in some patients fixed airflow obstruction. Currently AbMole 4-(Benzyloxy)phenol available therapies for the treatment of asthma are ineffective at relieving symptoms in approximately 10% of patients and offer no prospect of cure. These patients with apparently refractory disease have significant morbidity and mortality, and there is therefore an urgent need to identify better therapeutic approaches to treat asthma. Ion channels are emerging as interesting therapeutic targets for the management of asthma, particularly ion cannels that directly or indirectly facilitate the entry of calcium ions into cells. The KCa3.1 ion-channel is expressed by a wide variety of cells involved in asthma including mast cells, T cells, airway epithelial cells, fibroblasts, fibrocytes, and dedifferentiated, proliferative airway smooth muscle cells. The KCa3.1-channel is also expressed by both asthmatic and non-asthmatic ASM, and its inhibition attenuates human ASM proliferation in vitro. It is therefore possible that long term blockade of KCa3.1 is able to prevent increases in the amount of ASM in asthmatic airways. Previous studies using the sheep model have shown that 24-26 weeks of HDM challenge is sufficient to induce airway-remodelling changes typical of asthma including increases in airway collagen and ASM content. However, in the present study neither of these remodelling changes was observed, suggesting that 14 weeks of HDM challenges was not sufficient to induce structural airway changes. This raises the possibility that Senicapoc may have similar effects in this group of patients, and could offer an alternative therapeutic option for patients with relative steroid resistance. Interestingly, while there was a significant increase in neutrophils 48 hours post-HDM-challenge in both the vehicle and Senicapoc treated groups, the magnitude of the increase was tenfold higher in the Senicapoc treated group. Most of this change was due to the significant reduction in the number of neutrophils per mL in the Senicapoc group, compared to the vehicle treated group, immediately prior to HDM challenge. Endothelial cell proliferation and migration, which gives rise to the formation of new blood vessels, is induced by an elevation in angiogenic factors such as basic fibroblast growth factor and vascular endothelial growth factor and is initiated by a rise in intracellular Ca2+. Vascular remodeling is a feature of asthma, and is inversely associated with the post-bronchodilator FEV1 but not AHR. It 
is possible that this reduced vessel calibre contributes to a reduction in airway oedema in the airways following allergen exposure, and thus accounts for some of the observed improvements in lung function.