《COPD　素材》PPT课件.ppt

1、New advances in COPD between 2007 and 2008 (starting from 2006),Paul Jones MD, PhD Professor of Respiratory Medicine St Georges, University of London,COPD staging (FEV1/FVC 0.70),GOLD treatment guidelines 2007,GOLD 2006 treatment aims,Relieve symptoms Improve exercise tolerance Improve health status

2、 Prevent and treat exacerbations Prevent disease progression Reduce mortality Minimize side-effects,Inflammation in COPD,CD8+ T-Lymphocytes,* Adjusted for multiplicity (p = 0.004 unadjusted),Placebo (n = 68),Seretide (n = 55),0,40,80,120,160,200,240,280,320,Median cells/mm2,Baseline,Week 12,Baseline

3、,Week 12,Barnes et al AJRCCM 2006; 173: 736,SFC reduces a range of inflammatory cells and markers,Barnes et al AJRCCM 2006; 173: 736,Comparison of effect of 3 months treatment with SFC, FP or placebo on airway cellularity in COPD (total n=60),Difference in cell counts,Bourbeau et al Thorax 2007; 62:

4、 938,TORCH: Study Design,SFC 500/50 bd,FP 500 bd,Salmeterol 50 bd,Placebo,Duration = 3 years,1,533,1,534,1,524,1,521,6112 patients,2 week run-in,ITT population,(any PRN or regular short-acting bronchodliator and/or theophyline),Regions,* Australia, New Zealand, Argentina, Brazil, Chile, Mexico, Sout

5、h Africa 356: 775,GOLD 2006 COPD treatment aims,Relieve symptoms Improve exercise tolerance Improve health status Prevent and treat exacerbations Prevent disease progression Reduce mortality Minimize side-effects,Rate of decline of FEV1,-60,-50,-40,-30,-20,-10,0,Celli et al (ATS Abstract May 07),Cha

6、nge in FEV1 (ml/yr),Never smokers,0,0.5,1.0,1.5,2.0,2.5,3.0,Years,0,2,4,6,8,10,12,Change in SGRQ Score,(Worse),Weighted Regression Slope = 3.4 units/year,Spencer et al. Am J Respir Crit Care Med 2001;163:122-8.,3-year health status changes in patients receiving short-acting bronchodilators,Health st

7、atus and FEV1 worsen together over 3 years,-6,-4,-2,0,2,4,6,8,10,12,14,-0.3,-0.2,-0.1,0,0.1,SGRQ (units/yr),FEV1 slope (l/yr),r = 0.24,Spencer et al Eur Respir J 2004;23:1-5,Worse,Better,Exacerbations,GOLD treatment guidelines 2007,0,5,10,15,20,25,30,zero,0-1,1-2,2-3,3-4,4-6,6-8,8,% patients,Annuali

8、sed rate of exacerbations,ATS Moderate - Severe (FEV1 50% pred),Exacerbations of COPD (needing antibiotics steroids),Jones et al ERJ 2003;21:1-6,30,35,40,45,50,55,60,SGRQ score,4 wks,12 wks,26 wks,65,No further exacerbation,Baseline (at presentation with acute exacerbation),Spencer 58:589,COPD: time

9、 course of recovery from an exacerbation,Exacerbations and worsening in health status over 3 years,Exacerbation Category,0,0.5,1.0,1.5,2.0,2.5,3.0,None in 3 years,SGRQ slope (units/yr),Getting worse faster,Spencer et al. Eur Respir J 2004;23:1-5.,TORCH: Rate of moderate and severe exacerbations over

10、 three years,*p 0.001 vs placebo; p = 0.002 vs SAL p = 0.024 vs FP,1.13,0.97*,0.93*,0.85*,0,0.2,0.4,0.6,0.8,1.2,Placebo,SAL,FP,SFC,Mean number of exacerbations/year,Calverley et al NEJM 2007; 356: 775,1.0,Carbocisteine in COPD,Patients baseline demographic and characteristics,Repeat exacerbation-fre

11、e,P0.05,Carbocisteine reduces COPD exacerbations,Exacerbation-free,Risk Ratio 0.74 (95% CI 0.61, 0.89) p=0.002,Carbocisteine,Carbocisteine,Placebo,Placebo,Zheng J-P et al, Lancet 2008; 371: 2013,Carbocisteine improves health status,Zheng J-P et al, Lancet 2008; 371: 2013,GOLD 2006 COPD treatment aim

12、s,Relieve symptoms Improve exercise tolerance Improve health status Prevent exacerbations Prevent disease progression Reduce mortality Minimize side-effects,0,20,40,60,80,100,10,20,30,40,50,60,70,80,90,Upper limit of normal,COPD: Quality of life and FEV1,SGRQ score,Poor Health,Good Health,Jones Thor

13、ax 2001; 56: 880,FEV1 (% predicted),TORCH - SGRQ Total Score,-5,-4,-3,-2,-1,0,1,2,3,0,24,48,72,96,120,156,Adjusted mean Change SGRQTotal Score (Units),Weeks,Vertical bars represent standard errors,Calverley et al NEJM 2007; 356: 775,Getting worse,Change in SGRQ score in China (n=445),JP Zheng et al.

14、 Chest 2007; 132: 1756,Placebo,SFC,-5,-4,-3,-2,-1,0,1,2,3,0,24,48,72,96,120,156,Adjusted mean Change SGRQTotal Score (Units),Weeks,TORCH - SGRQ Total Score,Placebo,SFC,“The treatment is no longer working”,Without treatment would be here,GOLD 2006 COPD treatment aims,Relieve symptoms Improve exercise

15、 tolerance Improve health status Prevent exacerbations Prevent disease progression Reduce mortality Minimize side-effects,TORCH: All cause mortality at 3 years,0,2,4,6,8,10,12,14,16,18,3-year mortality (%),Log rank test p=0.052 Coxs Proportional Hazard p=0.03,15.2,12.6,Calverley et al NEJM 2007; 356

16、: 775,Placebo,SFC,Cause of Death(Adjudicated by CEC),0,1,2,3,4,5,6,7,Cardio-vascular,Pulmonary,Cancer,Other,Unknown,Deaths (% of ITT Pop),All-cause mortality by GOLD Stage,*Kaplan-Meier estimate,All-cause mortality by GOLD Stage,*Kaplan-Meier estimate,All-cause mortality by GOLD Stage,*Kaplan-Meier

17、estimate,All-cause mortality by GOLD Stage,*Kaplan-Meier estimate,Other trials,2 week Run-in,2-years treatment,Prednisolone 30mg/day + salmeterol 50mg b.d.,Tiotropium bromide 18mg o.d. via Handihaler (n=665),SFC 50/500mg b.d. via DISKUS (n=658),INSPIRE: Study design,Seemungal et al. J COPD 2007,(FEV

18、1 39% pred, n=1323),Inspire: Exacerbation rate and FEV1,Wedzicha et al AJRCCM 2008; 177: 19,Inspire: Difference in response of SGRQ (SFC vs tiotropum),MCID = minimal clinically important difference,-5,-4,-3,-2,-1,0,1,Mean Change in SGRQ Total Score SFC vs tiotropium,Week,MCID,SFC more effective,34,-

19、2,10,22,46,58,70,82,94,106,Wedzicha et al AJRCCM 2008; 177: 19,No difference,Mean 95% CI,Inspire: Mortality,On-treatment Comparison from Coxs Proportional Hazards Model,013263952657891104,0,1,2,3,4,5,6,7,Probability of Event (%),Time to Event (Weeks),Tiotropium,Wedzicha et al AJRCCM 2008; 177: 19,8,

20、250 COPD patients with history of exacerbations Weaned off previous therapy and put on tiotropium Randomised to either: Placebo Salmeterol SFC,Aaron et al. Ann Int Med. 2007; 146:545,Optimal: trial design,Optimal Study - exacerbations,Tio + SFC,Tio + Salmeterol,Tio + Placebo,p0.1,Aaron et al. Ann In

21、t Med. 2007; 146:545,Change in FEV1 (ml),4,36,20,52,Time (weeks),0,180,120,90,60,30,0,150,p=0.049,Optimal Study FEV1,Aaron et al. Ann Int Med. 2007; 146:545,0,-2,-4,-6,-10,-8,4,36,20,52,Change in SGRQ Total score,Time (weeks),Tiotropium + Placebo,Aaron et al. Ann Int Med. 2007; 146:545,0,Optimal Stu

22、dy health status,p=0.02,p=0.01,GOLD 2006 treatment aims,Relieve symptoms Improve exercise tolerance Improve health status Prevent and treat exacerbations Prevent disease progression Reduce mortality Minimize side-effects,TORCH: Expected Adverse Events starting during treatment - rate per 1000 treatm

23、ent years,SFC N=1546,FP N=1552,SAL N=1542,Plc N=1544,Change in total hip BMD (sub-study),Vertical bars represent standard errors,0,48,108,158,Plc,SAL,FP,SFC,-5,-4,-3,-2,-1,0,1,Adj. Mean Percent Change BMD Hip,161 162 158 162,87 105 112 118,Numberof Subjects,72 82 80 95,52 78 65 82,Time (Weeks),Summary,All aspects of COPD respond to SFC treatment SFC slows disease progression FEV1 maintained longer and rate of declined slowed