COPD: Guidelines Update and Newer Therapies • The Problem • Pathogenesis • Key Clinical Concepts – Life Prolonging vs. Symptomatic Therapy – Spirometry - The Sixth Vital Sign – Use of clinical practice guidelines • COPD Exacerbations • New Horizons Outline Percent Change in Age-Adjusted Death Rates, U.S., 1965-1998 0 0.5 1.0 1.5 2.0 2.5 3.0 Proportion of 1965 Rate 1965 - 98 –59% –64% –35% +163% –7% Coronary Heart Disease Stroke Other CVD COPD All Other Causes COPD in the United States Age-Adjusted Death Rates* for COPD by State: 1995-1997 Deaths/100,000 Pop Highest 46-61 (11) High 41-45 (13) Low 36-40 (13) Lowest 19-35 (13) *Morbidity and Mortality: 2000 Chart Book on Cardiovascular, Lung, and Blood Diseases. May 2000. x x x COPD - Pathogenesis Tobacco Smoke Chronic Inflammation* Emphysema Chronic Bronchitis *CD8+ T-lymphocytes Macrophages Neutrophils IL-8 and TNFα ProteinasesOxidative Stress Host factors Anti-oxidants Anti-proteinases Repair Mechanisms COPD Therapy Concepts • Life prolonging vs. symptomatic therapies • Spirometry - the 6th vital sign • Use of clinical practice guidelines COPD Therapy • Smoking Cessation • Oxygen • Reduce exacerbations • Pulmonary Rehabilitation • LVRS (selected patients) • Lung Transplantation • MDI Therapy – SA beta-2 agonists – LA beta-2 agonists – SA and LA Anticholinergics • Theophylline • Corticosteroids (inhaled or oral) • Combination Preparations – SABA and anticholinergic – LABA and corticosteroids Prolong Life Symptomatic Spirometry - The Sixth Vital Sign 0 5 1 4 2 3 Liter 1 654 32 FVC FVC FEV 1 FEV 1 Normal COPD 3.900 5.200 2.350 4.150 80 % 60 % Normal COPD FVC FEV 1 FVC FEV 1 / Seconds Indications: Symptoms or >10 pack year smoker COPD Practice Guidelines • European Thoracic Society - 1995 • American Thoracic Society - 1995 • British Thoracic Society - 1997 • Veterans Administration - 1998, 2001 • GOLD - 2003* (http:/www.goldcopd.com) • ACCP/ACP - 2001* (Ann Int Med 134:595, 2001) * Evidence-based Consensus and Evidence-based Guidelines For comparisons: Stoller JK. New Eng J Med 346:988, 2002 GOLD Workshop Report Four Components of COPD Management - www.goldcopd.com 1. Assess and monitor disease 2. Reduce risk factors 3. Manage stable COPD  Education  Pharmacologic  Non-pharmacologic 4. Manage exacerbations Management of COPD Stage 0: At Risk Characteristics Recommended Treatment • Risk factors • Chronic symptoms - cough - sputum • No spirometric abnormalities • Adjust risk factors • Immunizations [...]... http:/w w w goldcopd.com Therapy of COPD Exacerbation Guidelines Variable ACCP-ACP GOLD Steroids Yes, for up to two weeks Yes, oral or IV for 10-14 days Oxygen Yes Yes - target PaO2 60 torr or Sat of 90% with ABG check Chest PT No Maybe - for atelectasis or sputum control Mucokinetics No A nn Int Med 134:595, 2001 Not discussed http:/w w w goldcopd.com Therapy of COPD Exacerbation Guidelines Variable... Tiotropium Specific M1 and M3 Muscarinic Blockade • 470 patients - stable COPD • 3 month, randomized, double blind, once daily tiotropium vs placebo Conclusions: Increased FEV1 and FVC No tachyphylaxis Decreased rescue albuterol Decreased wheezing, SOB Dry mouth in 9.3% Casaburi et al CHEST 118:1294, 2000 Tiatroprium Specific M1 and M3 Muscarinic Blockade • 1207 patients, double blind, randomized trial,...Management of COPD Stage I: Mild COPD Characteristics Recommended Treatment • FEV1/FVC < 70 % • Short-acting • FEV1 > 80 % predicted bronchodilator as needed • With or without symptoms Management of COPD Stage II: Moderate COPD Characteristics •FEV1/FVC < 70% •50% < FEV1< 80% predicted •With or without symptoms Recommended... Mechanical Ventilation ACCP-ACP Yes - use NIPPV in severe exacerbation Other GOLD Yes if ≥2 of: Severe dyspnea, access muscle or paradox, pH 45, RR>25 LMWH, fluids, diet A nn Int Med 134:595, 2001 http:/w w w goldcopd.com COPD Therapy - New Horizons • Newer anti-inflammatory agents – Matrix metalloproteinase inhibitors – Specific phosphodiesterase (PDE4) inhibitors • Cilomilast • Rofumilast... bronchodilators •Rehabilitation Management of COPD Stage III: Severe COPD Characteristics •FEV1/FVC < 70% •30% < FEV1 < 50% predicted •With or without symptoms Recommended Treatment •Treatment with one or more long-acting bronchodilators •Rehabilitation •Inhaled glucocorticosteroids if repeated exacerbations (>3/year) Management of COPD Stage IV: Very Severe COPD Characteristics •FEV1/FVC < 70% •FEV1... A JRCCM 157:1418, 1998 COPD Exacerbation Effects on Lung Function Decline • • Infrequent Frequent 109 pts (mean FEV1 = 1.0 L over 4 years Frequent exacerbators: – faster decline in PEFR and FEV1 – more chronic symptoms (dyspnea, wheeze) – no differences in PaO2 or PaCO2 Conclusion: Frequent exacerbations accelerate decline in lung function Donaldson et al Thorax 57:847, 2002 COPD Exacerbation Pathophy... fatigue Depression Physical immobility Dyspnea COPD - Surgical Options • Giant Bullous Disease – Consider bullectomy if see normal lung compression • Lung Volume Reduction Surgery* – FEV1 ( . COPD: Guidelines Update and Newer Therapies • The Problem • Pathogenesis • Key Clinical Concepts – Life Prolonging. Sign 0 5 1 4 2 3 Liter 1 654 32 FVC FVC FEV 1 FEV 1 Normal COPD 3.900 5.200 2.350 4.150 80 % 60 % Normal COPD FVC FEV 1 FVC FEV 1 / Seconds Indications: Symptoms or >10 pack year smoker COPD Practice Guidelines • European Thoracic. 2002 GOLD Workshop Report Four Components of COPD Management - www.goldcopd.com 1. Assess and monitor disease 2. Reduce risk factors 3. Manage stable COPD  Education  Pharmacologic  Non-pharmacologic 4.