Different anti-remodeling effect of nilotinib and fluticasone in a chronic asthma model

BACKGROUND/AIMS: Inhaled corticosteroids are the most effective treatment currently available for asthma, but their beneficial effect against airway remodeling is limited. The tyrosine kinase inhibitor nilotinib has inhibitory activity against c-kit and the platelet-derived growth factor receptor. We compared the effects of fluticasone and nilotinib on airway remodeling in a chronic asthma model. We also examined whether co-treatment with nilotinib and fluticasone had any synergistic effect in preventing airway remodeling. METHODS: We developed a mouse model of airway remodeling, including smooth muscle thickening, in which ovalbumin (OVA)-sensitized female BALB/c-mice were repeatedly exposed to intranasal OVA administration twice per week for 3 months. Mice were treated with fluticasone and/or nilotinib intranasally during the OVA challenge. RESULTS: Mice chronically exposed to OVA developed eosinophilic airway inflammation and showed features of airway remodeling, including thickening of the peribronchial smooth muscle layer. Both fluticasone and nilotinib attenuated airway smooth muscle thickening. However, only nilotinib suppressed fibrotic changes, demonstrating inhibition of collagen deposition. Fluticasone reduced pro-inflammatory cells, such as eosinophils, and several cytokines, such as interleukin 4 (IL-4), IL-5, and IL-13, induced by repeated OVA challenges. On the other hand, nilotinib reduced transforming growth factor β1 levels in bronchoalveolar lavage fluid and inhibited fibroblast proliferation significantly. CONCLUSIONS: These results suggest that fluticasone and nilotinib suppressed airway remodeling in this chronic asthma model through anti-inflammatory and anti-fibrotic pathways, respectively.

Paediatric use of IV magnesium sulphate in severe asthma exacerbation: Report of a case and review of literature

Nebulization with B-agonist and administration of systemic corticosteroids are standard treatments for severe asthma exacerbations, but corticosteroids take several hours to become effective. IV magnesium sulphate (MgSO 4 ) acts faster and has both anti- inflammatory and bronchodilating properties. It appears to have played a pivotal role in the successful management of a child with severe asthma exacerbation and atelectasis unresponsive to conventional therapy. A literature review reveals that the results of IV MgSO 4 are much greater in children than in adults, and can avoid the need to hospitalize 25% of children presenting with severe asthma. Magnesium sulphate appears safe to use.