苗丽君胆碱能机制与COPD分析.ppt

* Chaudhary NI,Park JE Acetylcholine indrced proliferation of fibroblast and myofibroblasts in vitro is inhibited by tiotropium bromide Life Sci 2007;80 Holz O et al .MAPK pathway mediates muscarinic receptor-induced human lung fibroblast proliferation Life Sci 2007;80 Inhibition of allergen-induced airaway remodeling by tiotropium and budesonide:a comparison Eur Respir J 2007;30 Muscarinic receptors mediate stimulation of humanlung fibroblast proliferation Arn J Respir Cell Mol Biol 2006;35 Muscarinic receptors mediate stimulation of collagen synthesis in human lung fibroblasts Eur Respir J 2008;31 Protective effects of tiotropium bromide in the progression of airway smooth muscle remodeling Am J Respir Crit Care Med 2005 LTB4：强力吸引中性粒细胞、嗜酸性细胞、单核细胞至炎症部位； 增强血管通透性及炎症成分渗出； 激活环加氧酶途径产生PG；促使钙离子内流、引起气道高分泌和平滑肌收缩。 * * 思力华? (噻托溴铵)改善FEV1，减少了气体陷闭IC，改善了肺功能。影响了COPD的临床进程的核心因素 * The prolonged duration of pharmacologic effect translates into a prolonged clinical duration of action.11 In a 6-week, double-blind study, 121 patients were randomized to either 9 AM dosing with tiotropium 18 μg, 9 PM dosing with tiotropium 18 μg, or matching placebo. FEV1 responses were measured every 3 hours for 24 hours before taking the first dose of study drug (after a 1-week run-in) and after 6 weeks of treatment. Tiotropium, whether given in the morning or evening, improved FEV1 significantly compared with placebo throughout the 24-hour period. The graph also illustrates that tiotropium attenuates the early morning decline in FEV1 seen at around 3 to 6 AM in the placebo group. Calverley PMA, Lee A, Towse LJ. Effect of tiotropium bromide on circadian variation in airflow limitation in chronic obstructive pulmonary disease. Thorax. 2003; in press. * 思力华? (噻托溴铵)改善了FEV1，减少急性加重,影响了COPD的临床进程的其它相关因素。 * 同时，与对照组相比, 噻托溴铵组使每年的急性加重次数降低14%。 * 每一次的急性加重对COPD病人来说不仅仅是疾病的快速进展和不好的预后，同时也带来巨大的经济损失。在中国，因COPD急性加重发作而住院一次的平均费用约为RMB 8,000 – 10,000，而思力华?一年的治疗费用仅为RMB 6,372。思力华?的长期治疗可以延缓患者因COPD而导致的首次住院时间达4.1个月。