1. Chronic Obstructive Pulmonary Disease 연세대학교 의과대학 응급의학교실 강사 조준호

2. Definition of COPD ► Chronic bronchitis  Clinical criteria ► Emphysema  Anatomical definition ► “Airflow obstruction” ► “Progressive nature over time” ► “Not fully reversible”

3. Change in age adjust death rate in U.S. 0 0 0.5 1.0 1.5 2.0 2.5 3.0 Proportion of 1965 Rate 1965 - 1998 –59% –64% –35% +163% –7% Coronary Heart Disease Coronary Heart Disease Stroke Other CVD COPD All Other Causes All Other Causes Source: NHLBI/NIH/DHHS

4. Six leading cause of death in US

5. Risk factors for COPD Nutrition Infections Socio-economic status Aging Populations

7. Mucus gland hyperplasia Goblet cell hyperplasia Mucus hypersecretion Neutrophils in sputum Squamous metaplasia of epithelium ↑ Macrophages No basement membrane thickening Little increase in airway smooth muscle ↑ CD8 + lymphocytes Source: Peter J. Barnes, MD Changes in Large Airways of COPD Patients

8. Disrupted alveolar attachments Inflammatory exudate in lumen Peribronchial fibrosis Lymphoid follicle Thickened wall with inflammatory cells - macrophages, CD8 + cells, fibroblasts Source: Peter J. Barnes, MD Changes in Small Airways of COPD Patients

9. LUNG INFLAMMATION COPD PATHOLOGY Oxidativestress Proteinases Repairmechanisms Anti-proteinases Anti-oxidants Host factors Amplifying mechanisms Cigarette smoke Biomass particles Particulates Source: Peter J. Barnes, MD Pathogenesis of COPD

10. Cigarette smoke (and other irritants) PROTEASES PROTEASES Neutrophil elastase CathepsinsMMPs Alveolar wall destruction (Emphysema) Mucus hypersecretion CD8 + lymphocyte Alveolar macrophage Epithelialcells Fibrosis Fibrosis(Obstructivebronchiolitis) Fibroblast MonocyteNeutrophil Chemotactic factors Inflammatory Cells Involved in COPD Source: Peter J. Barnes, MD

11. Anti-proteases SLPI  1 -AT Proteolysis O 2 -, H 2 0 2 OH., ONOO -  Mucus secretion Plasma leak Bronchoconstriction NF-  B IL-8 Neutrophil recruitment TNF-  Isoprostanes ↓ HDAC2 ↑InflammationSteroidresistance MacrophageNeutrophil Oxidative Stress in COPD Source: Peter J. Barnes, MD

12. Macrophages TNF-  IL-8 IL-6 Bacteria Viruses Non-infective Pollutants Epithelial cells Oxidative stress Neutrophils Inflammation in COPD Exacerbations Source: Peter J. Barnes, MD

13. Alveolar wall destruction Loss of elasticity Destruction of pulmonary capillary bed ↑ Inflammatory cells macrophages, CD8 + lymphocytes Source: Peter J. Barnes, MD Changes in Lung Parenchyma in COPD

14. Endothelial dysfunction Intimal hyperplasia Smooth muscle hyperplasia ↑ Inflammatory cells (macrophages, CD8 + lymphocytes) Changes in Pulmonary Arteries in COPD Patients Source: Peter J. Barnes, MD

15. Inspiration Expiration loss of alveolar attachments Air Trapping in COPD Normal alveolar attachments Mild/moderate COPD loss of elasticity Severe COPD closure smallairway Dyspnea ↓ Exercise capacity Air trapping Hyperinflation ↓ Health status Source: Peter J. Barnes, MD

16. Pulmonary Hypertension in COPD Chronic hypoxia MuscularizationIntimalhyperplasiaFibrosisObliteration Pulmonary hypertension Cor pulmonale Death Edema Source: Peter J. Barnes, MD Chronic hypoxia Pulmonary vasoconstriction

17. Y Y Y Mast cell CD4+ cell (Th2)Eosinophil Allergens Ep cells ASTHMA BronchoconstrictionAHR Alv macrophage Ep cells CD8+ cell (Tc1) Neutrophil Cigarette smoke Small airway narrowing Alveolar destruction COPD ReversibleIrreversible Airflow Limitation

18. Guidelines

19. Four Components of COPD Management ► ► Assess and monitor disease ► ► Reduce risk factors ► ► Manage stable COPD   Education   Pharmacologic   Non-pharmacologic ► ► Manage exacerbations

20. SYMPTOMS cough sputum shortness of breath EXPOSURE TO RISK FACTORS tobacco occupation indoor/outdoor pollution SPIROMETRY Diagnosis of COPD è è è è è è

21. Spirometry: Normal and Patients with COPD

23. Management of Stable COPD

24. IV: Very Severe IV: Very Severe III: Severe III: Severe II: Moderate II: Moderate I: Mild I: Mild Therapy at Each Stage of COPD  FEV 1 /FVC < 70%  FEV 1 > 80% predicte d  FEV 1 /FVC < 70%  50% < FEV 1 < 80% predicted predicted  FEV 1 /FVC < 70%  30% < FEV 1 < 50% predicted  FEV 1 /FVC < 70%  FEV 1 < 30% predicte d or FEV 1 < 50% predict ed plus chronic respir atory failure Add regular treatment with one or more long-acting bronchodilators (when needed); Add rehabilitation Add inhaled glucocorticosteroids if repeated exacerbations Active reduction of risk factor(s); influenza vaccination Add short-acting bronchodilator (when needed) Add long term oxygen if chronic respiratory failure. Consider surgical treatments

25. 25 Management of Stable COPD  Antibiotics:  Only used to treat infectious exacerbations of COPD  Antioxidant agents  No effect of n-acetylcysteine on frequency of exacerbations, except in patients not treated with inhaled glucocorticosteroids  Mucolytic agents, Antitussives, Vasodilators  Not recommended in stable COPD

26. 26  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). Management of Stable COPD

28. 28 An exacerbation of COPD is defined as: “An event in the natural course of the disease characterized by a change in the patient’s baseline dyspnea, cough, and/or sputum that is beyond normal day-to-day variations, is acute in onset, and may warrant a change in regular medication in a patient with underlying COPD.” Management COPD exacerbation

29. Management COPD Exacerbation

30. 30  The most common causes of an exacerbation are infection of the tracheobronchial tree and air pollution, but the cause of about one-third of severe exacerbations cannot be identified (Evidence B).  Patients experiencing COPD exacerbations with clinical signs of airway infection (e.g., increased sputum purulence) may benefit from antibiotic treatment (Evidence B). Management COPD exacerbation

31. 31  Inhaled bronchodilators (particularly inhaled ß 2 - agonists with or without anticholinergics) and oral glucocortico-steroids are effective treatments for exacerbations of COPD (Evidence A). Management COPD exacerbation

32.  Noninvasive mechanical ventilation in exacerbations improves respiratory acidosis, increases pH, decreases the need for endotracheal intubation, and reduces PaCO 2, respiratory rate, severity of breathlessness, the length of hospital stay, and mortality (Evidence A).  Medications and education to help prevent future exacerbations should be considered as part of follow-up, as exacerbations affect the quality of life and prognosis of patients with COPD. Management COPD exacerbation