1. COPD Department of Internal Medicine Yonsei University College of Medicine Jae Ho Chung

2. Definition of COPD Chronic obstructive pulmonary disease (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. Chronic obstructive pulmonary disease (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.

3. n Diagnosis of COPD should be considered in cough, sputum production, or dyspnea, and/or exposure to risk factors for the disease n Dx is confirmatory by spirimetry n Post-bronchodilator FEV 1 <80 of predicted value and FEV 1 /FVC<70% n Diagnosis of COPD should be considered in cough, sputum production, or dyspnea, and/or exposure to risk factors for the disease n Dx is confirmatory by spirimetry n Post-bronchodilator FEV 1 <80 of predicted value and FEV 1 /FVC<70%

5. Definitions in COPD Condition Key features “Universe” of in Definition Definition Asthma ReversibilityPhysiology Chronic bronchitis Cough/sputumSymptoms Emphysema Alveolar destructionAnatomy

6. n Chronic bronchitis Clinical Dx Productive cough 3 months for 2 consecutive yrs n Emphysema Pathological Dx Permanent enlargement of the distal airspaces with destructions of their walls without fibrosis n Chronic bronchitis Clinical Dx Productive cough 3 months for 2 consecutive yrs n Emphysema Pathological Dx Permanent enlargement of the distal airspaces with destructions of their walls without fibrosis

8. Epidemiology

9. n COPD is the 4 th leading cause of death in the United States (behind heart disease, cancer, and cerebrovascular disease). n In 2000, the WHO estimated 2.74 million deaths worldwide from COPD. n In 1990, COPD was ranked 12 th as a burden of disease; by 2020 it is projected to rank 5 th. n COPD is the 4 th leading cause of death in the United States (behind heart disease, cancer, and cerebrovascular disease). n In 2000, the WHO estimated 2.74 million deaths worldwide from COPD. n In 1990, COPD was ranked 12 th as a burden of disease; by 2020 it is projected to rank 5 th.

10. Leading Causes of Deaths U.S. 1998 All other causes of death 469,314 10. Chronic liver disease24,936 9. Nephritis26,295 8. Suicide29,264 7. Diabetes 64,574 6. Pneumonia and influenza93,207 5. Accidents94,828 4. Respiratory Diseases (COPD) 114,381 3. Cerebrovascular disease (stroke)158,060 2. Cancer 538,947 1. Cause of Death Number Heart Disease 724,269

11. Percent Change in Age-Adjusted Death Rates, U.S., 1965-1998 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

12. n Between 1985 and 1995, the number of physician visits for COPD in the United States increased from 9.3 million to 16 million. n The number of hospitalizations for COPD in 1995 was estimated to be 500,000. Medical expenditures amounted to an estimated $14.7 billion. n Between 1985 and 1995, the number of physician visits for COPD in the United States increased from 9.3 million to 16 million. n The number of hospitalizations for COPD in 1995 was estimated to be 500,000. Medical expenditures amounted to an estimated $14.7 billion.

13. Physician Office Visits for Chronic and Unspecified Bronchitis, U.S. Source: National Ambulatory Medical Care Survey, NCHS 15 Number (Millions) Year 1980 10 5 5 0 0 1985 1990 1995 1998

14. Pathophysiology

15. Risk Factors for COPD Host FactorsGenes (e.g. alpha1-antitrypsin deficiency) Hyperresponsiveness Lung growth ExposureTobacco smoke Occupational dusts and chemicals Infections Socioeconomic status Host FactorsGenes (e.g. alpha1-antitrypsin deficiency) Hyperresponsiveness Lung growth ExposureTobacco smoke Occupational dusts and chemicals Infections Socioeconomic status

16. Smoking n Dose-response relationship n 90% of all COPD are smoker (1) cilia movement ↓ (2) alveolar macrophage function↓ (3) lead to hyperthrophy and hyperplasia of mucus- secretory gland (4) inhibit antiprotease (5) cause PMN leukocytosis → release proteolytic enzyme  Only 15-20% of smokers manifest COPD FEV 1 n Dose-response relationship n 90% of all COPD are smoker (1) cilia movement ↓ (2) alveolar macrophage function↓ (3) lead to hyperthrophy and hyperplasia of mucus- secretory gland (4) inhibit antiprotease (5) cause PMN leukocytosis → release proteolytic enzyme  Only 15-20% of smokers manifest COPD FEV 1

17. COPD Risk and Smoking Cessation The best guide to the progression of COPD is the change in FEV 1 over time 1 1.British Thoracic Society. Guidelines for the management of chronic obstructive pulmonary disease. Thorax 1997; 52(suppl 5).

18. Risk Factors n hereditary in 10% (alpha-1-antitrypsin) n environmental exposure (SO 2, NO 2 ) n socioeconomic factors (poverty) n hereditary in 10% (alpha-1-antitrypsin) n environmental exposure (SO 2, NO 2 ) n socioeconomic factors (poverty)

19. Pathogenesis of COPD NOXIOUS AGENT (tobacco smoke, pollutants, occupational agent) COPD Genetic factors Respiratory infection Other

23. Causes of Airflow Limitation n Reversible Ô Accumulation of inflammatory cells, mucus, and plasma exudate in bronchi Ô Smooth muscle contraction in peripheral and central airways Ô Dynamic hyperinflation during exercise n Reversible Ô Accumulation of inflammatory cells, mucus, and plasma exudate in bronchi Ô Smooth muscle contraction in peripheral and central airways Ô Dynamic hyperinflation during exercise

24. Causes of Airflow Limitation n Irreversible Ô Fibrosis and narrowing of the airways Ô Loss of elastic recoil due to alveolar destruction Ô Destruction of alveolar support that maintains patency of small airways n Irreversible Ô Fibrosis and narrowing of the airways Ô Loss of elastic recoil due to alveolar destruction Ô Destruction of alveolar support that maintains patency of small airways

26. Pathophysiology n 1. Airway limitation n 2. Hyperinflation n 3. Impaired gas exchange n 4. Pulmonary circulation n 5. Renal and Hormonal dysfunction n 6. Cachexia: TNF-alpha n 7. Peripheral muscle dysfunction n 8. Osteoporosis n 1. Airway limitation n 2. Hyperinflation n 3. Impaired gas exchange n 4. Pulmonary circulation n 5. Renal and Hormonal dysfunction n 6. Cachexia: TNF-alpha n 7. Peripheral muscle dysfunction n 8. Osteoporosis

27. Factors affecting dynamic compression n Reduced Lung recoil n e.g. low lung volumes or emphysema / loss of parenchyma n Airway structural stiffness. n  peripheral resistance Ô  pressure loss Ô EPP more peripheral location n  peripheral resistance Ô  pressure loss Ô EPP more peripheral location

28. Flow -Volume Curves in Health & Disease n Note changes in lung volume and  in flow in COPD and  relative flow in restrictive disease

29. Flow -Volume Curve:COPD

30. Natural History n FEV1 decline: 35ml/year after 25 yrs n COPD decline: 50~100ml/year n Exertional dyspnea: FEV1 <40% n Resting dyspnea: FEV1 <25% n Exacerbation: dyspnea, wheeze, cough, sputum (volume, viscosity, purulence), worsening hypoxemia n Usually infection n LV failure, arrhythmia, pneumothorax, pneumonia, pulmonary thromboembolism n FEV1 decline: 35ml/year after 25 yrs n COPD decline: 50~100ml/year n Exertional dyspnea: FEV1 <40% n Resting dyspnea: FEV1 <25% n Exacerbation: dyspnea, wheeze, cough, sputum (volume, viscosity, purulence), worsening hypoxemia n Usually infection n LV failure, arrhythmia, pneumothorax, pneumonia, pulmonary thromboembolism

31. Diagnosis

32. Symptom n Chronic cough : Present intermittently or every day Often present throughout the day; seldom only nocturnal n Chronic sputum production : Any pattern of chronic sputum production may indicate COPD n Chronic cough : Present intermittently or every day Often present throughout the day; seldom only nocturnal n Chronic sputum production : Any pattern of chronic sputum production may indicate COPD

33. n Dyspnea: Progressive (worsens over time) Persistent (present every day) Described by the patient as: "increased effort to breathe," "heaviness,""air hunger," or "gasping" Worse on exercise Worse on respiratory infection n Dyspnea: Progressive (worsens over time) Persistent (present every day) Described by the patient as: "increased effort to breathe," "heaviness,""air hunger," or "gasping" Worse on exercise Worse on respiratory infection

36. Bronchodilator reversibility test n Useful to help rule out asthma, pt`s prognosis, pt`s treatment decision n Who do not show FEV1 response may benefically symptomatically from longterm Tx n FEV1 or FVC 12% and 200ml n Useful to help rule out asthma, pt`s prognosis, pt`s treatment decision n Who do not show FEV1 response may benefically symptomatically from longterm Tx n FEV1 or FVC 12% and 200ml

37. ABG n Perform FEV1<40% or clinical sign of respiratory failure or right heart failure (central cyanosis, ankle swelling, jugular venous Pr increase) n Respiratory failure: PaO 2 <60mmHg with or without PaCO 2 <50mmHg n Perform FEV1<40% or clinical sign of respiratory failure or right heart failure (central cyanosis, ankle swelling, jugular venous Pr increase) n Respiratory failure: PaO 2 <60mmHg with or without PaCO 2 <50mmHg

38. n Symptoms free intervals in asthma n Long history of smoking in most patients with COPD n Progression of airflow obstruction in COPD n Aggravation of underlying symptoms in COPD n Right heart failure signs in COPD n Purulent sputum is a prominent feature in AECB n Symptoms free intervals in asthma n Long history of smoking in most patients with COPD n Progression of airflow obstruction in COPD n Aggravation of underlying symptoms in COPD n Right heart failure signs in COPD n Purulent sputum is a prominent feature in AECB Medical History in Asthma and COPD

39. Emphysema Bronchial asthma FEF 50 /FIF 50 = 0.16 FEF 50 /FIF 50 = 0.26 Difference in mechanisms of airway obstruction

40. CXR Spirometry Not compatible with COPD; make other diagnosis Compatible with COPD Clinical diagnosis / grading 1)Forced expiratory time 2)PEFR Not suggestiveSuggestive Review clinical diagnosis Suspected COPD Other diagnosis Management of COPD according to GOLD guideline Yes No

41. Early and prompt diagnosis of COPD Suspected walk-in patient a)Age > 40 years b)Smoking > 20 pack-years c)Progressive dyspnea d)Daily sputum production e)Cough/cold in winter Health care personnel pick up by screening questionnaire Physical Examination a)Barrel chest / prolonged expiration time b)Hyperresonance c)Subxyphoid apical pulse d)Wheezing with unforced expiration e)Diminished breath sounds CXR

42. Clinical Manifestation

43. Clinical Manifestations n All three disorders are present to some degree in clients with COPD n eventually chronic hypoxemia & hypercapnia result n All three disorders are present to some degree in clients with COPD n eventually chronic hypoxemia & hypercapnia result

44. Emphysema ( “ pink puffer ” ) n Characterized by enlargement of the air spaces distal to the terminal bronchioles and eventual destruction of alveolar walls where gas exchange takes place n due to loss of elastic recoil n Characterized by enlargement of the air spaces distal to the terminal bronchioles and eventual destruction of alveolar walls where gas exchange takes place n due to loss of elastic recoil

45. Chronic Bronchitis ( “ blue bloater ” ) n Characterized by excessive mucus production, reduced mucus clearance, and chronic cough (>3 months/year X two years) n associated with enlargement of bronchial mucous glands,  number of goblet cells, and impaired cilia function n Characterized by excessive mucus production, reduced mucus clearance, and chronic cough (>3 months/year X two years) n associated with enlargement of bronchial mucous glands,  number of goblet cells, and impaired cilia function

47. Responses to hypoxia n Emphysema: n proportionate loss of V & P (no V/Q mismatch) n struggle and often over ventilate in an attempt to maintain normal blood gas levels hence, known as “ pink puffers ” n Emphysema: n proportionate loss of V & P (no V/Q mismatch) n struggle and often over ventilate in an attempt to maintain normal blood gas levels hence, known as “ pink puffers ”

48. n Chronic bronchitis: n excessive bronchial secretions and a/w obstruction lead to V/Q mismatch (  V) n hypoxemia, cyanosis, and eventually cor pulmonale with peripheral edema) hence, known as “ blue bloaters ” n Chronic bronchitis: n excessive bronchial secretions and a/w obstruction lead to V/Q mismatch (  V) n hypoxemia, cyanosis, and eventually cor pulmonale with peripheral edema) hence, known as “ blue bloaters ”

49. AP diameter ↑ Hoover`s sign

50. Kussmaul`s sign: 흡기시에 neck vein 이 collapse 되지 않고 distention

54. Complications n respiratory infections n rupture of blebs leading to spontaneous pneumothorax n polycythemia vera n cor pulmonale n respiratory failure n respiratory infections n rupture of blebs leading to spontaneous pneumothorax n polycythemia vera n cor pulmonale n respiratory failure