C hronic O bstructive P ulmonary D isease

1. Chen xin M.D., Pulmonary Medicine zhujiang hospital, southern medical university Chronic Obstructive Pulmonary Disease

2. Introduction • Chronic Obstructive Pulmonary Disease (COPD) is a major cause of chronic morbidity and mortality throughout the world. Many people suffer from this disease for years and die prematurely from it or its complications. COPD is the fourth leading cause of death in the world, and further increases in its prevalence and mortality can be predicted in the coming decades.

3. Definition • 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 the chronic inflammatory response of the lung to noxious particles or gases. • acute exacerbations and It'scomplications influence the severity of the disease

4. Definition • Airflow limitation • Not completely reversible • Progressive • Inflammation • “Bronchitis” & “Emphysema” no longer in definition • The most common form of COPD is a combination of chronic bronchitis and emphysema.

5. Burden of COPD • COPD is a leading cause of morbidity and mortality worldwide and results in an economic and social burden that is both substantial and increasing. • COPD prevalence, morbidity, and mortality vary across countries and across different groups within countries. • The burden of COPD is projected to increase in the coming decades due to continued exposure to COPD risk factors and the changing age structure of the world’s population.

6. Percent Change in Age-Adjusted Death Rates, U.S., 1965-1998 Proportion of 1965 Rate 3.0 Coronary Heart Disease Stroke Other CVD COPD All Other Causes 2.5 2.0 1.5 1.0 0.5 –59% –64% –35% +163% –7% 0

7. Of the six leading causes of death in the United States, only COPD has been increasing steadily since 1970 Source:Jemal A. et al. JAMA 2005

8. Disease Trajectory of a Patients with COPD Symptoms Exacerbations Exacerbations Deterioration Exacerbations End of Life

9. Genes Exposure to particles Tobacco smoke Occupational dusts, organic and inorganic Indoor air pollution from heating and cooking with biomass in poorly ventilated dwellings Outdoor air pollution Lung growth and development Oxidative stress Gender Age Respiratory infections Socioeconomic status Nutrition Comorbidities Risk Factors

10. Risk Factors Nutrition Infections Socio-economic status Aging Populations

11. Pathology • Pathological changes characteristic of COPD are found in the proximal airways, peripheral airways, lung parenchyma, and pulmonary vasculature. These changes include chronic inflammation, and structural changes resulting from repeated injury and repair. • Inhaled cigarette smoke and other noxious particles cause lung inflammation, a normal response which appears to be amplified in patients who develop COPD.

12. Lung inflammation is further amplified by oxidative stress and an excess of proteases in the lung.

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

14. Inflammatory Cells Involved in COPD Cigarette smoke (and other irritants) Alveolar macrophage Epithelial cells Chemotactic factors CD8+ lymphocyte Fibroblast Neutrophil Monocyte Neutrophil elastase Cathepsins MMPs PROTEASES Mucus hypersecretion Fibrosis (Obstructive bronchiolitis) Alveolar wall destruction (Emphysema) Source: Peter J. Barnes, MD

15. Oxidative Stress in COPD Macrophage Neutrophil Anti-proteases NF-B SLPI 1-AT Proteolysis IL-8 TNF- ↓ HDAC2 ↑Inflammation Steroid resistance O2-, H202 OH., ONOO- Neutrophil recruitment Isoprostanes Bronchoconstriction Plasma leak  Mucus secretion Source: Peter J. Barnes, MD

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

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

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

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

20. COPD Cigarette smoke Y Y Y Alv macrophage Ep cells CD8+ cell (Tc1) Neutrophil Small airway narrowing Alveolar destruction ASTHMA Allergens Ep cells Mast cell CD4+ cell (Th2) Eosinophil Bronchoconstriction AHR Airflow Limitation Reversible Irreversible Source: Peter J. Barnes, MD

21. Pulmonary Hypertension in COPD Chronic hypoxia Pulmonary vasoconstriction Muscularization Intimal hyperplasia Fibrosis Obliteration Pulmonary hypertension Cor pulmonale Edema Death Source: Peter J. Barnes, MD

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

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

24. Chronic bronchitis • Chronic bronchitis is an inflammation and eventual scarring of the lining of the bronchial tubes. • Symptoms of chronic bronchitis include chronic cough, increased mucus, frequent clearing of the throat and shortness of breath.

25. Emphysema • Emphysema causes irreversible lung damage. The walls between the air sacs within the lungs lose their ability to stretch and recoil. They become weakened and break. Elasticity of the lung tissue is lost, causing air to be trapped in the air sacs and impairing the exchange of oxygen and carbon dioxide. Also, the support of the airways is lost, allowing for obstruction of airflow.

26. Emphysema • Symptoms of emphysema include cough, shortness of breath and a limited excercise tolerance. Diagnosis is made by pulmonary function tests, along with the patient’s history, examination and other tests.

28. COPD病理学特点 气道 结构 改变 气道 炎症 气道 阻塞 粘膜纤毛 功能障碍 增加炎症细胞数量/活性 - 中性粒细胞, - 巨噬细胞, - CD8+淋巴细胞 提高 IL-8, TNF, LTB4 蛋白酶/抗蛋白酶失衡 粘膜水肿 肺泡破坏 上皮增生 腺体过度增大 杯状细胞变形 气道纤维化 平滑肌收缩 增加胆碱能释放 支气管高反应性? 弹性收缩降低 粘液过度分泌 粘液粘性增加 减少纤毛转运 粘膜损伤

29. Pathophysiology • Increased mucus production and reduced mucociliary clearance - cough and sputum production • Loss of elastic recoil - airway collapse • Increase smooth muscle tone • Pulmonary hyperinflation • Gas exchange abnormalities - hypoxemia and/or hypercapnia

30. Chronic bronchitis Emphysema COPD asthma

32. GOALS of COPD MANAGEMENTUPDATED 2011 • Relieve symptoms • Prevent disease progression • Improve exercise tolerance • Improve health status • Prevent and treat complications • Prevent and treat exacerbations • Reduce mortality

33. Four Components of COPD Management • Assess and monitor disease • Reduce risk factors • Manage stable COPD • Education • Pharmacologic/Non-pharmacologic • Manage exacerbations • Diagnosis and Assessment of Severity • Home/Hospital Management

34. Assess and Monitor COPD: Key Points • A clinical diagnosis of COPD should be considered in any patient who has dyspnea, chronic cough orsputum production, and/or a history of exposureto risk factors for the disease. • The diagnosis should be confirmed by spirometry. A post-bronchodilator FEV1/FVC < 0.70 confirms the presence of airflow limitation that is not fully reversible. • Comorbidities are common in COPD and should be actively identified.

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

36. Key Indicators for COPD Diagnosis

37. Physical signs • Large barrel shaped chest (hyperinflation) • Prominent accessory respiratory muscles in neck and use of accessory muscle in respiration • Low, flat diaphragm • Diminished breath sound

38. Spirometry • Diagnosis • Assessing severity • Assessing prognosis • Monitoring progression

39. Spirometry • FEV1– Forced expired volume in the first second • FVC– Total volume of air that can be exhaled from maximal inhalation to maximal exhalation • FEV1/FVC% - The ratio of FEV1 to FVC, expressed as a percentage.

40. Flow-volume curve Flow Normal obstruction restrictions Mixed Volum RV TLC

41. Chest X-rays • Emphysema • Hyperinflation • Flattened diaphragms • Decreased vascular markings • Chronic Bronchitis • Usually normal

42. Chest X-rays Hyper- inflated Flat diaphragm Increased Retrosternal air

43. Assess and Monitor COPD: SpirometryGOLD 2006 • Spirometry should be performed after theadministration of an adequate dose of a short-acting inhaled bronchodilator to minimize variability. • A post-bronchodilator FEV1/FVC < 0.70 confirms the presence of airflow limitation that is notfullyreversible. • Where possible, values should be compared to age-related normal values to avoidoverdiagnosisof COPD in the elderly.

44. COPD classification based on spirometry GOLD 2006 SPIROMETRY is not to substitute for clinical judgment in the evaluation of the severity of disease in individual patients.

45. Assess and Monitor COPD: GOLD 2011 • Clinical symptoms • Spirometry • risk of acute exacerbations • complications Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease Revised 2011

46. Assess and Monitor COPD: Clinical symptoms • COPD assessment test (CAT) including eight common clinical problem, to evaluate the health damage of patients with COPD • modified british medical research council (mMRC) Having a good correlation with health condition and can predict the future risk of death

47. mMRC CAT

48. Assess and Monitor COPD: risk of acute exacerbations History of acute exacerbations : the number of acute exacerbations is more than 2 times in the last year Spirometry: FEV1 < 50 % Pred as a high risk index

49. Comprehensive Assessment Risk 4 Risk (GOLD) 3 ≥ 2 (AE) 2 1 1 0 mMRC 0-1 mMRC 2+ CAT< 10 CAT> 10+ symptoms（mMRC or CAT） A:Fewer symptoms, lower risk B: more symptoms, lower risk C: Fewer symptoms,higher risk D: more symptoms, higher risk

50. Arterial Blood Gas (ABGs) • An ABG is done from a sample drawn from one of your arteries. The blood is then analyzed by a special machine, which records the amount of carbon dioxide (waste gas) and oxygen in your blood. One of the uses of this test is to determine whether or not you need any extra oxygen.