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.

A Case of Hypercapnic Respiratory Failurein a Patient with Eosinophilic Polymyositis / 대한류마티스학회지

Eosinophilic infiltration into skeletal muscles has been rarely reported in a variety of conditions such as parasite infection, sarcoidosis, rheumatoid arthritis, eosinophilia-myalgia syndrome, and idiopathic hypereosinophilic syndrome. Eosinophilic myositis (EM) is one of idiopathic inflammatory muscle diseases associated with muscle and/or blood eosiophilia. The case of EM complicated with hypercapnic respiratory failure has been extremely rarely reported. A 61-year-old woman was admitted with sudden-onset pain in both calves. She had elevated serum muscle enzymes and peripheral eosinophil count. Findings of electromyography were consistent with inflammatory myopathy. MRI showed diffuse hyperintensity of calf muscles on T2-weighted and enhanced T1 images. Muscle biopsy showed eosinophils' infiltration in the endomysium and perivascular area. During the diagnostic work-up, she presented with hypercapnic respiratory failure. She was successfully treated with mechanical ventilation and high doses of prednisolone. This case suggests EM can cause respiratory failure secondary to respiratory muscle involvement.