单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,Click to edit Mastertitle style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Mastertitle style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Mastertitle style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Mastertitle style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Mastertitle style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Mastertitle style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Mastertitle style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Mastertitle style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Mastertitle style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Mastertitle style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Mastertitle style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Mastertitle style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Mastertitle style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,COPD,治疗,从指南到临床实践,气体陷闭是,COPD,疾病进展的核心,1,长效支气管扩张剂,-,指南推荐的,COPD,一线治疗,2,抗胆碱能药物,-COPD,长期治疗的基石,3,内 容,气体陷闭是,COPD,疾病进展的核心,1,长效支气管扩张剂,-,指南推荐的,COPD,一线治疗,2,抗胆碱能药物,-COPD,长期治疗的基石,3,内 容,COPD,概况,Global strategy for the diagnosis, management, and revention of chronic obstructive pulmonary disease.(updated 2021),一种进行性，不完全可逆的气流受限的慢性疾病,气流受限引起：呼吸困难，咳嗽，喘息，痰液增多等病症,正常,COPD,患者,COPD,的临床病程,生活质量下降,运动耐量下降,活动受限,健康状况下降,Adapted from Cooper CB.,Am J Med,2006; 119:S21-S31.,呼吸困难,COPD,呼气流速受限,气体陷闭,过度充气,疾病进展,急性加重,运动耐量下降,活动受限,健康状况,下降,生活质量下降,COPD,的气体陷闭和过度充气,气体陷闭对肺功能参数及病症的影响,运动性呼吸困难,运动耐受性,IRV,正常人,EILV,EELV,TLC,IC,IC,0,20,40,60,80,100,120,140,肺容积,(%,肺总量预计值,),COPD,Vt,FRC,COPD,患者肺容积,TLC =,肺总量,; Vt =,潮气量,; IC =,深吸气量,EILV =,吸气末肺容量；,EELV =,呼气末肺容量；,IRV =,补吸气量,FRC=,功能残气量,即使是轻度,COPD,患者,EELV,占,TLC,比例在运动后显著高于静息时,Batt et al. J Appl Physiol. 1991;70:223-230,小结,:,气体陷闭是,COPD,临床病程进展的核心,生活质量下降,运动耐量下降,活动受限,健康状况下降,Adapted from Cooper CB.,Am J Med,2006; 119:S21-S31.,呼吸困难,COPD,呼气流速受限,气体陷闭,过度充气,疾病进展,急性加重,运动耐量下降,活动受限,健康状况,下降,生活质量下降,气体陷闭是,COPD,疾病进展的核心,1,长效支气管扩张剂,-,指南推荐的,COPD,一线治疗,2,抗胆碱能药物,-COPD,长期治疗的基石,3,内 容,可逆因素,中央和外周气道平滑肌 的收缩,支气管内炎症细胞的聚集、,粘液的分泌和血浆渗出物,运动时肺动态充气过度,不可逆因素,气道纤维化性狭窄,肺泡破坏使弹性回缩力,减弱,肺泡支撑破坏使,小气道关闭,COPD,治疗主要针对可逆因素,姚婉贞，徐永健，主编。?慢性阻塞性肺疾病?，北京大学医学出版社，2007年，第一版,COPD,COPD的药物治疗原那么,以改善病症和提高生活质量为目标,根据疾病的严重程度逐步增加治疗,如果没有明显的副作用或病情的恶化,应该在同一水平维持长期规律治疗,药物治疗应该按照一定的顺序排列,以便根据疾病严重程度来选择适宜的治疗方案,Global strategy for the diagnosis, management, and revention of chronic obstructive pulmonary disease.(updated 2021),长效支气管扩张剂指南推荐的COPD一线根本治疗药物,I:,轻度,FEV,1,80%,II:,中度,FEV,1,79-50%,III:,重度,FEV,1,49-30%,IV:,极重度,FEV,1,30%,防止风险因素;接种流感疫苗,必要时，,加用,短效支气管扩张剂,规律使用一种或多种长效支气管扩张剂,康复治疗,如果反复出现急性加重，,加用,吸入性糖皮质激素,如果出现慢性呼吸衰竭，,加用,长期氧疗,考虑,手术,Global strategy for the diagnosis, management, and revention of chronic obstructive pulmonary disease.(updated 2021),支气管扩张剂是COPD治疗的一线 ,根底用药,支气管扩张剂治疗,COPD,的地位,GOLD2021指南指出:,支气管舒张剂是控制COPD病症的最主要治疗措施A类证据,支气管扩张剂可以松弛支气管平滑肌，改善肺的排空，减少肺动态充气过度，缓解气流受限，提高生活质量。是控制COPD病症的主要治疗措施A类证据,常规使用长效支气管舒张剂比短效支气管舒张剂疗效更好,使用更方便A类证据,首选吸入治疗,Global strategy for the diagnosis, management, and revention of chronic obstructive pulmonary disease.(updated 2021),规律应用长效吸入抗胆碱能药物可以,减少,COPD,急性加重频率,改善肺康复训练的效果,噻托溴铵,PM,(n=35),时间,(,小时,),9,AM,3,PM,9,PM,3,AM,9,AM,噻托溴铵,AM,(n=37),抚慰剂,(n=33),FEV,1,(L),P0.01 ，噻托溴铵早晚给药与抚慰剂相比,Calverley PMA Thorax 2003;58:855860,思力华,: 24,小时持续扩张气道,小结,GOLD指南推荐支气管扩张剂是COPD治疗的一线治疗,思力华24小时扩张支气管,针对气体陷闭,改善COPD病症,是治疗COPD理想的长期支气管扩张剂,气体陷闭是,COPD,疾病进展的核心,1,长效支气管扩张剂,-,指南推荐的,COPD,一线治疗,2,抗胆碱能药物,-COPD,长期治疗的基石,3,内 容,COPD,治疗管理目标,缓解病症,改善运动耐量,预防和治疗急性加重,改善健康状况,短期,GOLD 2021,长期,预防和治疗并发症,预防疾病进展,降低死亡率,更好地生活延长寿命,帮助患者到达COPD治疗的短期目标,-1,轻度恶化,由于气促加剧而从事较轻工作和,/,或减少日常活动时间，包括任何比目前情况减退的表现,0,无变化,没有因气促所致的活动能力改变,+1,轻度改善,由于气促改善活动能力可以恢复至减退前水平或日常生活自理的能力比过去提高,TDI总评分到达1分或以上，具有临床意义的改善,TDI,总评分的临床意义,176,50,92,260,344,抚慰剂 (n=325),噻托溴铵,(n,=,507),思力华 显著提高TDI总评分改善呼吸困难病症,思力华组的TDI总评分显著高于抚慰剂组，且在第344天比抚慰剂组高出1.14分，具有临床意义的改善,*,P,0.0001,*,*,*,*,*,评价时间,TDI,总评分均值,T-P =1.14,Casaburi R et al. Eur Respir J (2002),-0.5,0.0,0.5,1.0,1.5,TDI,总评分,1,分的患者比例,(%),*,*P0.0001，与抚慰剂对照,P0.01，与异丙托溴铵对照P0.05，与抚慰剂对照,为期,1,年的,异丙托溴铵对照试验,异丙托溴铵,噻托溴铵,抚慰剂,沙美特罗,Casaburi R et al. Eur Respir J (2002)Vincken W et al. Eur Respir J (2002)Brusasco V et al. Thorax (2003),研究,思力华,增加,TDI,总评分,1,分的患者比例,0,10,20,30,40,50,为期1年的,抚慰剂对照试验,为期6个月的,沙美特罗/抚慰剂对照试验,思力华,显著提高,COPD,患者的运动耐受时间,ODonnell D et al, ERJ, June 2004 Trial 205.131,运动耐受时间,(,秒,),491.7,秒,+ 105.2,秒,+ 21.4 %,+ 66.8,秒,+ 13.6 %,*,p,0.01,*,p,0.05,*,*,噻托溴铵,(n=96),抚慰剂(n=91),基线,天数,运动时间,(,分钟,),p0.01,噻托溴铵: 运动,恢复,0,2,4,6,8,10,12,14,16,18,20,10,8,7,6,5,4,3,2,1,0,9,最大,很重,严重,有些重,中度,轻度,极轻,无,极重,安慰剂: 运动,恢复,第42天给药后2.25小时：在恒定运动速率的踏车运动试验中、在恢复期前5分钟的呼吸困难程度 (Borg 评分),思力华 提高COPD患者的运动耐受力第42天给药后2.25小时,Maltais et al. Chest 2005;128:1168-78 Trial 205.223,*,P,0.05,康复,研究药物,思力华,联合康复治疗改善运动耐受时间,*,*,16%,32%,42%,n=55 n=53,Casaburi R,et al. Chest,2005Trial 205.230,8,12,16,20,24,0,2,4,6,8,10,12,14,16,18,20,22,24,治疗时间周,耐受时间 (min),噻托溴铵,抚慰剂,思力华,治疗一年推迟,首次,COPD,急性加重时间,*Log Rank Test,Data on file (2001),噻托溴铵,(n,=,550),Placebo,(,n,=,371),至首次,COPD,急性加重发作的时间,P,=0.011*,安慰剂,治疗天数,无急性发作的可能性,0.4,0.5,0.6,0.7,0.8,0.9,1.0,0,50,100,150,200,250,300,350,月,HR=0.86 (0.81, 0.91),P,0.0001 (log-rank test),0,20,40,60,80,0,6,12,18,24,30,36,42,48,急性加重的可能性,(%),噻托溴铵,对照组,急性加重降低,14%,UPLIFT,研究思力华,治疗,4,年显著降低急性加重的风险,HR =,风险比,(95,%,可信区间,),Tashkin DP et al. UPLIFT Study Investigators. N Engl J Med 2021;359:1543-54,0,月,HR=0.86 (0.78, 0.95),P,=0.002 (log-rank test),10,20,30,40,0,6,12,18,24,30,36,42,48,急性加重住院的可能性,(%),噻托溴铵,抚慰剂,HR =,风险比,(95,%,可信区间,),Tashkin DP et al. UPLIFT Study Investigators. N Engl J Med 2021;359:1543-54,UPLIFT,研究思力华,显著降低急性加重住院的风险,UPLIFT,研究思力华降低中度,COPD,患者急性加重,延长,5.6,个月,P,0.0001,降低,20%,P,0.0001,Decramer M et al. Lancet 2021. Epub 28 August.,思力华,显著改善,SGRQ,总评分,*,P,0.05;,P,0.001,抚慰剂(n=324),噻托溴铵,(n,=,516),176,50,92,260,344,1,试验天数,*,*,基线,改善,改善,SGRQ,评分均值,第92天，抚慰剂组健康生活质量逐渐恶化，并在第260天超出基线范围,41,43,45,47,49,*,P,0.05;,P,0.001,Data on file (2001),Month,0,6,12,18,24,30,36,42,48,0,改善,*,*,*,*,*,*,*,*,Difference: 2.9 4.0 units (,P,0.001 at all time points),35,40,45,50,SGRQ,总分,(Units),Tiotropium,Control,思力华治疗,4,年提高,COPD,中度患者的生活质量,Decramer M et al. Lancet 2021. Epub 28 August.,对照组,:,继续原有治疗,;,其中,55%,使用,LABA;57%,使用,ICS;44%,使用,ICS/LABA,思力华组,:,添加在原有治疗上,;55%,使用,LABA;58%,使用,ICS;45%,使用,ICS/LABA,0,6,12,18,24,30,36,42,48,0,月,改善,*,*,*,*,*,*,*,*,思力华作为初始治疗,改善,SGRQ,达,4,分,*,P,0.05, 4.6,P,0.001,下降速率,= -1.05,P,=0.002,SGRQ总分单位,噻托溴铵,组,对照组,Troosters et al. Am J Respir Crit Care Med 2021;179:A2467,30,35,45,40,UPLIFT,研究中，入组前没有维持治疗的患者数据分析,思力华到达COPD管理的短期目标,缓解病症,改善运动耐量,预防和治疗急性加重,改善健康状况,短期,GOLD 2021,长期,预防和治疗并发症,预防疾病进展,降低死亡率,更好地生活延长寿命,帮助患者到达COPD治疗的长期目标-更好的生活,-60,-5,30,60,120,180,第,1,天,第,8,天,第,92,天,第,344,天,抚慰剂 (n=328),思力华,(,n,=518),FEV,1,(L),治疗第344天，思力华组FEV1均值和谷值仍显著优于抚慰剂组，且没有出现受体耐受现象,第,344,天,思力华,持续改善患者肺功能,Casaburi R et al. Eur Respir J (2002),*,P,0.0001 vs. control.,Post-bronch FEV,1,= 52 82 mL,Pre-bronch FEV,1,= 100 119 mL,1.80,*,Day 30,(steady state),*,*,*,*,*,*,*,*,0,6,12,18,24,30,36,42,48,0,1,Month,*,*,*,*,*,*,*,*,*,1.20,1.40,1.60,FEV,1,(L),Tiotropium,Control,Decramer M et al. Lancet 2021. Epub 28 August.,思力华持续,4,年改善,中度,COPD,患者肺功能,0,12,24,36,48,1.0,1.1,1.2,1.3,1.4,1.5,1.6,Time (Months),FEV,1,(L),支气管扩张剂前,FEV,1,134 ml(,P,0.0001),96 ml,P,0.0001,支气管扩张剂后,FEV,1,TiotropiumControl,TiotropiumControl,P,1% , 肺癌除外(不同的类型); P0.05,SAE =,严重不良事件,SOC =,系统器官水平,Tashkin DP et al. UPLIFT Study Investigators. N Engl J Med 2021;359:1543-54,思力华带给,COPD,患者更好的生活,缓解病症,改善运动耐量,预防和治疗急性加重,改善健康状况,短期,GOLD 2021,长期,预防和治疗并发症,预防疾病进展,降低死亡率,更好地生活延长寿命,?,思力华,-COPD,长期治疗的基石,病症及呼吸困难加重,初始治疗,第二步,第三步,思力华,+,短效支气管扩张剂,思力华,+,短效支气管扩张剂,加,LABA,思力华,+,短效支气管扩张剂,加,LABA,加,ICS,防止危险因素;接种疫苗,按需使用短效支气管扩张剂,GOLD II,级患者,Adapted from Cooper & Tashkin,谢 谢,