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

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

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

COPD Guidelines

Evidence-based Guidelines

Definition of COPD Chronic bronchitis 1 11 2 Emphysema Irreversible FEV1 Δ <15% Reversible 5 3 4 8 6 7 9 FEV1 Δ>15% 10 COPD Airflow obstruction Asthma

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.

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)

COPD progression 100 FEV1 % of value at age 25 yr 75 50 25 symptoms Disability Death COPD 60 ml/year Nonsmokers 20-30 ml/year 25 50 75 Age (year) Adapted from:fletcher C,et al.br Med J.1977;1:1645-1648

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

Systemic inflammation Weight loss Skeletal muscle dysfunction

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

N Engl J Med 2004;350:1005-12.

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

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

100 FEV1 % of value at age 25 yr 75 50 25 symptoms Disability Death COPD 60 ml/year Nonsmokers 20-30 ml/year 25 50 75 Age (year) Adapted from:fletcher C,et al.br Med J.1977;1:1645-1648

2.80 2.75 2.70 2.65 No intervention SMK intervention +placebo SMK intervention + Ipratropium 2.60 2.55 2.50 2.45 0 1 2 3 4 5 Follow-up, year Anthonisen NR, JAMA,1994;2721497-15

Smoking cessation reduces the decline in FEV 1 Ipratropium bromide did not influence the longterm decline of FEV 1 Anthonisen NR, JAMA,1994;2721497-1505

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

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.

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

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

Management of Stable COPD Pharmacotherapy: Glucocorticosteroids Pro Con

Reduced risk of mortality and repeat hospitalization with ICSs COPD hospitalisation-free survival 1.0 0.9 0.8 0.7 0.6 No inhaled Corticosteroids Inhaled corticosteroids 0.5 0 2 4 6 8 10 12 Months after discharge ICSs are associated with a 26% lower relative risk for all-cause mortality and repeat hospitalisation Adapted from Sin & Tu, 2001

Exacerbations per year 3 2.5 2 1.5 1 0.5 0 2.5 1.7 1.9 1.4 1.2 1.2 Placebo Fluticasone <1.25 1.25-1.54 >1.54 FEV1 ISOLDE. BMJ2000;320:1297-1303

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

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

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).

FEV1 <30% Regular bronchodilator treatment inhaled corticosteroids Oxygen therapy FEV1 30-50% Regular bronchodilator treatment Consider inhaled corticosteroids FEV1 50-80% Regular bronchodilator treatment FEV1>80% Short acting bronchodilator as needed

FEV1 <30% Regular bronchodilator LABA treatment inhaled corticosteroids ICS Oxygen therapy FEV1 30-50% Regular bronchodilator LABA treatment Consider inhaled ICScorticosteroids FEV1 50-80% Regular bronchodilator treatment FEV1>80% Short acting bronchodilator as needed

Seretide Diskus (Salmeterol +Fluticasone) 50/100 50/250 50/500 1999

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

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

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

8 6 4 2 0 Number1524 alive 1533 Probability of death (%) 18 16 14 12 10 1464 1487 1399 1426 HR 0.825, p=0.052 17.5% risk reduction 2.6% absolute reduction Placebo 15.2% SFC 12.6% 0 12 24 36 48 60 72 84 96 108 120 132 144 156 Time to death (weeks) 1293 1339 ertical bars are standard errors Calverley et al. NEJM 2007 TORCH FEB 07

Rate of moderate and severe exacerbations over three years Mean number of exacerbations/year 1.2 1.13 25% reduction 1 0.8 0.97* 0.93* 0.85* 0.6 0.4 0.2 0 Placebo SALM FP SFC Treatment *p < 0.001 vs placebo; p = 0.002 vs SALM; p = 0.024 vs FP Calverley et al. NEJM 2007 TORCH FEB 07

SGRQ total score Adjusted mean change SGRQ total score (units) 3 2 1 0 1 2 3 4 5 Number of subjects 0 24 48 72 96 120 156 Time (weeks) 1149 1148 1155 1133 854 906 942 941 781 844 848 873 726 807 807 814 675 723 751 773 635 701 686 731 * 569 634 629 681 Placebo SALM FP SFC *p = 0.057 vs placebo; p < 0.001 vs placebo; p < 0.001 vs placebo, SALM and FP; vertical bars are standard errors Calverley et al. TORCH NEJM FEB 2007 07

Post-bronchodilator FEV 1 Adjusted mean change FEV 1 (ml) 100 50 0 50 100 * * * 150 Placebo SALM FP SFC 0 24 48 72 96 120 156 Time (weeks) Number of subjects 1524 1521 1534 1533 1248 1317 1346 1375 1128 1218 1230 1281 1049 1127 1157 1180 979 1054 1078 1139 906 1012 1006 1073 819 934 908 975 *p < 0.001 vs placebo; p < 0.001 vs SALM and FP Calverley et al. TORCH NEJM FEB 2007 07

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 2007 2. Jones et al. Chest 2006 TORCH FEB 07

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).

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

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

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

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

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

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

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

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

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

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.

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