รศ. นพ. ว ชรา บ ญสว สด M.D., Ph.D. ภาคว ชาอาย รศาสตร คณะแพทยศาสตร มหาว ทยาล ยขอนแก น

Transcription

1 รศ. นพ. ว ชรา บ ญสว สด M.D., Ph.D. ภาคว ชาอาย รศาสตร คณะแพทยศาสตร มหาว ทยาล ยขอนแก น

2 COPD Guideline Changing concept in COPD management Evidences that we can offer COPD patients better life

3 COPD Guidelines

4 Evidence-based Guidelines

5 Definition of COPD Chronic bronchitis Emphysema Irreversible FEV1 Δ <15% Reversible FEV1 Δ>15% 10 COPD Airflow obstruction Asthma

6 Definition of COPD COPD is a disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases.

7 FEV 1 Force Expiratory Volume in 1 second FVC Force Vital Capacity Post Bronchodilator FEV 1 /FVC < 70 % airflow limitation that is not fully reversible. การตรวจสมรรถภาพปอด (spirometry)

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10 COPD progression 100 FEV1 % of value at age 25 yr symptoms Disability Death COPD 60 ml/year Nonsmokers ml/year Age (year) Adapted from:fletcher C,et al.br Med J.1977;1:

11 Classification of COPD Severity by Spirometry Stage I: Mild FEV1 > 80% predicted Stage II: Moderate Stage III: Severe Stage IV: Very Severe 50% < FEV 1 < 80% predicted 30% < FEV 1 < 50% predicted FEV 1 < 30% predicted or FEV 1 < 50% predicted plus chronic respiratory failure

12 Systemic inflammation Weight loss Skeletal muscle dysfunction

13 COPD Airflow Obstruction Systemic inflammation Weight loss Muscle dysfunction Air trapping Exercise limitation Deconditioning Reduced activity Exacerbation Death

14 N Engl J Med 2004;350:

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16 Retard the progression of airflow obstruction Minimizing airflow obstruction Prevent complication Optimizing functional capacity

17 Retard the progression of airflow obstruction Minimizing airflow obstruction Prevent complication Optimizing functional capacity

18 100 FEV1 % of value at age 25 yr symptoms Disability Death COPD 60 ml/year Nonsmokers ml/year Age (year) Adapted from:fletcher C,et al.br Med J.1977;1:

19 No intervention SMK intervention +placebo SMK intervention + Ipratropium Follow-up, year Anthonisen NR, JAMA,1994;

20 Smoking cessation reduces the decline in FEV 1 Ipratropium bromide did not influence the longterm decline of FEV 1 Anthonisen NR, JAMA,1994;

21 n=1116 Lung Health Study. N Eng J Med 2000;343:1902-9

22 None of the existing medications for COPD have been shown to modify the long-term decline in lung function that is the hallmark of this disease (Evidence A). Therefore, pharmacotherapy for COPD is used to decrease symptoms and/or complications.

23 Retard the progression of airflow obstruction Minimizing airflow obstruction Prevent complication Optimizing functional capacity

24 Bronchodilators 1. Anticholinergics 2. B2 agonist 3. Theophylline Corticosteroids Oral Inhaled

25 Management of Stable COPD Pharmacotherapy: Glucocorticosteroids Pro Con

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27 Reduced risk of mortality and repeat hospitalization with ICSs COPD hospitalisation-free survival No inhaled Corticosteroids Inhaled corticosteroids Months after discharge ICSs are associated with a 26% lower relative risk for all-cause mortality and repeat hospitalisation Adapted from Sin & Tu, 2001

28 Exacerbations per year Placebo Fluticasone < >1.54 FEV1 ISOLDE. BMJ2000;320:

29 Retard the progression of airflow obstruction Minimizing airflow obstruction Prevent complication Optimizing functional capacity

30 Retard the progression of airflow obstruction Minimizing airflow obstruction Prevent complication Optimizing functional capacity

31 Management of Stable COPD Non-Pharmacologic Treatments Rehabilitation: All COPD patients benefit from exercise training programs, improving with respect to both exercise tolerance and symptoms of dyspnea and fatigue (Evidence A). Oxygen Therapy: The long-term administration of oxygen (> 15 hours per day) to patients with chronic respiratory failure has been shown to increase survival (Evidence A).

32 FEV1 <30% Regular bronchodilator treatment inhaled corticosteroids Oxygen therapy FEV % Regular bronchodilator treatment Consider inhaled corticosteroids FEV % Regular bronchodilator treatment FEV1>80% Short acting bronchodilator as needed

33 FEV1 <30% Regular bronchodilator LABA treatment inhaled corticosteroids ICS Oxygen therapy FEV % Regular bronchodilator LABA treatment Consider inhaled ICScorticosteroids FEV % Regular bronchodilator treatment FEV1>80% Short acting bronchodilator as needed

34 Seretide Diskus (Salmeterol +Fluticasone) 50/100 50/250 50/

35 TOwards a Revolution in COPD Health the TORCH trial TORCH FEB 07

36 TORCH: study design SFC 50/500 µg bd (N=1533) 2 week run-in FP 500 µg bd SAL 50 µg bd (N=1534) (N=1521) Placebo (N= 1524) 3-year study duration Vestbo et al. Eur Respir J 2004; Calverley et al. NEJM 2007 TORCH FEB 07

37 TORCH: main objectives Primary objective The effect of SFC 50/500 μg vs placebo on all-cause mortality over 3 years in patients with moderate-to-severe COPD Secondary objectives The effect of SFC 50/500 μg on the rate of moderate and severe exacerbations The effect of SFC 50/500 μg on health status (SGRQ) SGRQ = St. George s Respiratory Questionnaire Vestbo et al. Eur Respir J 2004 Calverley et al. NEJM 2007 TORCH FEB 07

38 Number1524 alive 1533 Probability of death (%) HR 0.825, p= % risk reduction 2.6% absolute reduction Placebo 15.2% SFC 12.6% Time to death (weeks) ertical bars are standard errors Calverley et al. NEJM 2007 TORCH FEB 07

39 Rate of moderate and severe exacerbations over three years Mean number of exacerbations/year % reduction * 0.93* 0.85* Placebo SALM FP SFC Treatment *p < vs placebo; p = vs SALM; p = vs FP Calverley et al. NEJM 2007 TORCH FEB 07

40 SGRQ total score Adjusted mean change SGRQ total score (units) Number of subjects Time (weeks) * Placebo SALM FP SFC *p = vs placebo; p < vs placebo; p < vs placebo, SALM and FP; vertical bars are standard errors Calverley et al. TORCH NEJM FEB

41 Post-bronchodilator FEV 1 Adjusted mean change FEV 1 (ml) * * * 150 Placebo SALM FP SFC Time (weeks) Number of subjects *p < vs placebo; p < vs SALM and FP Calverley et al. TORCH NEJM FEB

42 Summary of efficacy results SFC improved survival in COPD This was supported by Significantly fewer exacerbations compared with components or placebo Significantly fewer hospitalisations compared with placebo Significant improvements in health status superior to components and placebo Significant improvements in lung function superior to components and placebo 1. Calverley et al. NEJM Jones et al. Chest 2006 TORCH FEB 07

43 Management of Stable COPD Pharmacotherapy: Glucocorticosteroids The addition of regular treatment with inhaled glucocorticosteroids to bronchodilator treatment is appropriate for symptomatic COPD patients with an FEV1 < 50% predicted (Stage III: Severe COPD and Stage IV: Very Severe COPD) and repeated exacerbations (Evidence A). An inhaled glucocorticosteroid combined with a long-acting ß 2 -agonist is more effective than the individual components (Evidence A).

44 Investigating New Standards for Prophylaxis in Reducing Exacerbations INSPIRE Wedzicha JA, et al. AJRCCM 2008;177:19-26

45 Randomized, double-blind, double-dummy controlled trial with treatment optimisation Oral prednisolone 30mg/day + inhaled salmeterol 50μg b.d. 2 week run-in SFC 50/500μg b.d. via Accuhaler (n=658) 2-years treatment Discontinued all existing COPD maintenance medications Tiotropium bromide 18μg o.d. via Handihaler (n=665) Wedzicha JA, et al. AJRCCM 2008;177:19-26

46 Wedzicha JA, et al. AJRCCM 2008;177:19-26

47 Probability of withdrawal prior to wk 104 SFC 34.5% TIO 41.7% Wedzicha JA, et al. AJRCCM 2008;177:19-26

48 Wedzicha JA, et al. AJRCCM 2008;177:19-26

49 Wedzicha JA, et al. AJRCCM 2008;177:19-26

50 52% risk reduction p=0.012 Wedzicha JA, et al. AJRCCM 2008;177:19-26

51 Wedzicha JA, et al. AJRCCM 2008;177:19-26

52 Wedzicha JA, et al. AJRCCM 2008;177:19-26

53 Definition of COPD: GOLD2006 COPD is a preventable and treatable disease with some significant extrapulmonary effects that may contribute to the severity in individual patients. Its pulmonary component is characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lung to noxious particles or gases.

54 Changing concept in COPD management Irreversible vs incomplete reversible airway obstruction Inflammatory disease Systemic inflammation Preventable and treatable disease COPD Guideline is available ICS is effective in the treatment of COPD LABA / ICS is more effective than ICS We can offer COPD patients better life

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