Chronic Obstructive Pulmonary Disease (COPD),Guohua Zhen Tongji Hospital,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 - 1998,1965 - 1998,1965 - 1998,1965 - 1998,1965 - 1998,59%,64%,35%,+163%,7%,Coronary Heart Disease,Stroke,Other CVD,COPD,All Other Causes,Why COPD is Important ?,COPD is the only chronic disease that is showing progressive upward trend in both mortality and morbidity It is expected to be the third leading cause of death by 2020 Approximately 3% Chinese above 15 are currently suffering from COPD,Definition,COPD is a preventable and treatable disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and is associated with an abnormal inflammatory response of the lungs to noxious particles or gases, primarily caused by cigarette smoking.,Relationship of COPD and Chronic bronchitis, Asthma or Emphysema,Chronic Bronchitis,Chronic Bronchitis,Definition: Chronic and unspecific inflammation of bronchi and the surrounding tissue. Feature: chronic mucus hypersecretion and cough. Morbidity: 3.2% in population over 15 y，up to 15% in elderly over 50 y.,Etiology and mechanism,Environment Factors Cigarette smoking Occupational dusts and chemicals Infections Host Factors Genes Lung growth and defense mechanism,Chronic Bronchitis,Clinical manifestation,Character: chronic onset, recurrent attack and long course of disease Main symptoms: cough: chronic, long term, repeatedly expectoration: mucoid sputum, purulent sputum when infection wheezing: seen in some patients,Clinical manifestation,Sign: 1. no obvious sign in early stage 2. sometimes moist rales and rhonchi,Examination,Chest x-ray imaging,Examination,Pulmonary function test: maybe normal in early stage. Gradually obstructive airway function appeared. Blood routine: elevated neutrophil or eosinophil Sputum examination: bacterial culture guide antibiotic treatment,Diagnosis,Chronic cough and sputum production for 3 consecutive months in at least 2 successive years（3m/y2y）, excluding other chronic lung diseases (TB, Bronchiectasis ) Definite chest imaging or lung function,Typing,Typing : 1、simple：cough, sputum 2、wheezing：with wheezing (actually Chronic bronchitis plus asthma),Emphysema,Definition,Emphysema is characterized by enlargement and destruction of respiratory bronchioles and /or alveoli in the lungs.,Etiology,Environment Factors Cigarette smoking Occupational dusts and chemicals Infections Host Factors Genes: Alpha1-antitrypsin deficiency,Contributing factor,Airway obstruction due to chronic inflammation Damaged bronchial cartilage and lead to the loss of supporting function Increased activity of proteinase due to chronic airway inflammation or smoking Alpha1-antitrypsin deficiency Others: Poor nutrition of alveoli or respiratory bronchiole due to decreased blood supply because of oppression of high airway pressure,Cigarette smoke,Alveolar macrophage,Neutrophil,PROTEASES,Alveolar wall destruction,(Emphysema),Mucus hypersecretion,(Chronic bronchitis),PROTEASE INHIBITORS,Neutrophil chemotactic factors,CELLULAR MECHANISMS OF COPD,Neutrophil elastase,Cathepsins,Matrix metalloproteinases,Cytokines (IL-8),Mediators (LTB4),?,CD8+,lymphocyte,-,MCP-1,1-Antitrypsin TIMPs SLPI Elafin,Neutrophil elastase Cathepsins MMP-1, MMP-9, MMP12 Granzymes, perforins Others,PROTEASE-ANTIPROTEASE IMBALANCE IN COPD,Pathology feature,Alveolar walls become thinner Alveolar sacs enlargement Rupture of alveoli and formation of bleb,Pathological Category,In panlobular emphysema, the enlargement and destruction of air space involve the acinus more or less uniformly.,In centrilobular emphysema, respiratory bronchioles are selectively and dominantly involved.,COPD - chronic bronchitis - emphysema,COPD Pathophysiology,Hypoventialtion- PaO2 , PaCO2 Airflow obstruction / airway narrowing mucus plugging airway inflammation, edema, fibrosis airway collapse due to alveolar wall destruction Hyperinflation: air trapping Gas exchange defects- PaO2 Destruction of alveolar wall/alveolar-capillary membrane V/Q mismatch (shunt),Clinical manifestation,Symptom 1. cough, sputum and/or wheezing 2. gradually progressive dyspnea, shortness of breath, chest tightness,Clinical manifestation,Sign: 1. not obvious in early stage 2. typical sign: barrel chest, decreased chest movement, diminished tactile fremitus, hyperresonance, decreased vesicular breath sound and prolong expiration or wheeze,Examination,Pulmonary function test Diagnosis Assessing severity Assessing prognosis Monitoring progression,Examination: pulmonary function test,Dynamic lung function airflow obstruction FEV1, FEV1/FVC Static lung function hyperinflation TLC, FRC air trapping RV,FEV1/FVC, FEV1 % predicted to estimate obstruction and severity。 Bronchodilator Reversibility Testing: to detect the reversibility, a