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1、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
2、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,COP
3、D 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.,R
4、elationship 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 o
5、ver 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
6、: 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
7、 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）, exc
8、luding 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 bro
9、nchioles 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 s
10、upporting 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,
11、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-A
12、ntitrypsin 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 e
13、mphysema, 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
14、/ 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, sputu
15、m 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 expir
16、ation 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 % pred
17、icted to estimate obstruction and severity。 Bronchodilator Reversibility Testing: to detect the reversibility, after bronchodilator, FEV1/FVC 40%,Examination: pulmonary function test,Chest X-ray： ECG： Blood gas：to detect respiratory failure. Blood routine and sputum examination：,Examination,Chest X-
18、ray,Intercostal space widening Diaphragm are low and flat Vascular marking deficiency Shadow of the heart narrowing,low, flat diaphragms, hyperlucency, vascular marking deficiency,Diagnosis,1、Smoking history 2、Symptom: cough, sputum production, gradually progressive dyspnea 3、Sign：emphysema 4、PFT: a
19、irway flow limitation,COPD classification based on pulmonary function test,Clinical Features of COPD Patients of different severity,Mild COPD: no abnormal signs, smokers cough, little or no breathlessness Moderate COPD: breathlessness with/without wheezing, cough with/without sputum Severe COPD: bre
20、athlessness on any exertion/at rest, wheeze and cough prominent, lung inflation usual, cyanosis, peripheral edema, and polycythemia in advanced disease,Stage of disease,Acute Exacerbations Stable,Acute exacerbation of COPD AE-COPD,“Exacerbation” of COPD Respiratory dyspnea / chest tightness cough /
21、sputum, purulent Systematic decreased activity, fatigue, headache, poor appetite, somnolence,Differential diagnosis,Bronchial asthma: reversibility of the airflow Bronchiectasis: especially mild patients, chronic cough and mucus sputum Pulmonary TB：positive anti-fast smear Bronchogenic carcinoma： Em
22、physema due to other cause: for compensation,Complications of COPD,Chronic respiratory failure Spontanous pneumothorax Cor pulmonale hypoxia, pedal edema, passive hepatic congestion.,Management of COPD,Prevent decline in FEV1 Reduce mortality Improve quality of life symptoms exercise tolerance exace
23、rbations Minimal side-effects,Goals,Non-pharmacologic Therapies,Adjustment Therapy & Education,Avoidance of Tobacco & Pollution,Vaccination,Nutrition,Lung Volume Reduction or Transplant,Exercise & Rehabilitation,COPD,Smoking cessation Physician intervention critical Multidisciplinary approach Withdr
24、awal anxiety, irritability, difficult concentrating, sleep disruption, fatigue, drowsiness, depression Nicotine replacement withdrawal symptoms nicotine gum (2 mg = cigarette) transdermal nicotine patches x 8 wks 20-40% / 6 mos vs 5-20% / 6 mos with placebo,Effects of Smoking and Smoking Cessation o
25、n FEV1,0,25,50,75,100,25,50,75,Age (years),FEV1 (%),COPD: Pharmacology,Bronchodilators Corticosteroids Long term oxygen therapy Management of COPD exacerbations,COPD: Pharmacology,2-agonist bronchodilators Rapid-acting 2-agonists (SABA) salbutamol, terbutaline symptomatic relief pre-exertional 2 puf
26、fs 4-6 x /d prn minimal risk Long acting 2-agonists (LABA) salmeterol, formoterol regular therapy 1-2 puffs bid benefit: activity / exertion, QOL,COPD: Pharmacology,Anticholinergic bronchodilators Benefits vs Risks Regular therapy Symptomatic benefit ? exacerbations Minimal s/e dry mouth, urinary re
27、tention Agents Ipratropium /Atrovent 4-6 puffs qid Tiotropium /Spiriva 1 puff qd,COPD: Pharmacology,Theophylline Multiple effects bronchodilation, respiratory stimulant, improved cardiovascular function, improved diaphragm function Limited role because of narrow therapeutic window s/e GI, CNS, cardi
28、ac qd - bid dosing with long-acting preparations,COPD: Pharmacology,Inhaled Steroids Symptomatic COPD patients with “asthmatic” tendency (20%) FEV1 50% predicted and repeated exacerbations requiring antibiotics and/or oral glucocorticosteroids,COPD: Management,Long term oxygen therapy Benefits with
29、18 hrs /d Improved survival, right heart failure Improved exercise tolerance, QOL Indications PaO2 55 mmHg (SaO2 88%) 56-59 cor pulmonale, impaired mental status, polycythemia Sleep-associated desaturation Exertional desaturation,Therapy at each stage of COPD,COPD: Exacerbations,Management Identify
30、cause Infection “Infectious” bronchitis common cause Most commonly viral Bacteria - S. pneumonia, H. influenzae, M. catarrhalis Antibiotics if 2 of 3: dyspnea, sputum volume, or purulence,COPD: Exacerbations,Management Bronchodilators Regular ipratropium, prn 2-agonists Systemic steroids x 3-10d, ho
31、spital stay Supplemental O2,COPD: Exacerbations,Management Oxygenation Tissue and cellular hypoxia are life-threatening Controlled O2 therapy Baseline blood gas Titrate O2 slowly: 20-30 min steady state Goal: PaO2 60-65 mmHg (SaO2 88%),COPD: Exacerbations,Oxygenation: low concentration oxygen therap
32、y Risks of excessive O2 (PaO2 100 mmHg) hypercapnia ( PaCO2 ) acidemia ( pH 7.20) Mechanisms V/Q mismatch due to release of hypoxic vasoconstriction respiratory drive,COPD: Exacerbations,Respiratory Failure Pathogenesis Worse obstruction and/or gas-exchange PaO2 or PaCO2 Respiratory muscle fatigue M
33、echanical ventilation Goals: support of oxygenation, ventilation Indications Refractory hypoxaemia despite O2 Worsening PaCO2, pH Altered mental status,COPD: Surgery,Lung resection surgery Risk based on FEV1 post-resection (0.8 L) Lung volume reduction surgery (LVRS),prognosis,Relate to the value of
34、 FEV1 FEV11.2L survive for 10y， FEV11.0 L survive for 5y ，FEV1700ml survive for 2y,Cor Pulmonale,Cor pulmonale,An alteration in the structure and/or function of the right ventricle resulting from disorder of airway, pulmonary parenchyma and blood vessels, chest wall.,Chronic pulmonary heart disease,
35、Disorders of airway, parenchyma or blood vessels, chest wall Hypoxic vasoconstriction Pressure of PA rise hypertrophy of RV failure of RV,Etiology,Disease affecting airway or lung parenchyma：COPD, asthma, TB, pulmonary fibrosis Disease affecting the thoracic cage：kyphoscoliosis, thoracoplasty, neuro
36、muscular disease causing muscle weakness Disease affecting pulmonary vasculature：primary pulmonary hypertension, polyarteritis, SLE Hypoventilatory disorders：sleep apnea syndrome,Mechanism and pathophysiological features,1、vasospasm：functional，mainly due to hypoxia, hypercapnia and acidosis, is part
37、ially reversible. 2、blood wall thickening and lumen decreased: remodeling of vessel due to chronic arteritis. 3、high alveolar pressure causing compression of Pulmonary capillary：by emphysema。 4、destruction of pulmonary capillary bed：by emphysema or bleb. 5、increased blood volume and viscosity.,Decre
38、ased capillary bed and remodeling of blood vessel,Vasospasm due to hypoxia and hypercapnia,Resistance of blood flow increase due to high blood volume and viscosity,Increased Resistance of PA and pulmonary hypertension,Increased RV cardiac load and thickening of RV,Failure of RV,Clinical stage,Compen
39、sation of lung and cardiac function mainly presentation of underlying disease and PAH and hypertrophy of RV。 Decompensation of lung and cardiac function mainly exhibit the manifestation of respiratory failure and failure of RV。,Clinical presentation,Sign and symptom of the underlying disease： dyspne
40、a is a frequent symptom and is associated with hypoxia and hypercapnia.,Clinical presentation,Manifestation of PAH： 1、P2 accentuation: a loud pulmonic component of the S2. 2、Assistant examination：chest X-ray.,Clinical presentation,Hypertrophy of RV： Symptom palpitation on exertion chest pain: in som
41、e severe PHD, not usually response to nitrate Sign - a loud heart beat sound under xiphoid Assistant examination: X-ray, ECG and UCG,Clinical presentation,Presentation of respiratory failure: Pulmonary encephalopathy,Clinical presentation,Enlargement and failure of RV： 1、systolic murmur along the le
42、ft sternal border: relative tricuspid insufficiency or regurgitation； 2、obstruction of superior venous return ：distension of jugular vein（？）； 3、obstruction of inferior venous return: enlargement of liver（？）, edema of lower extremity, ascites,Examination,X-ray, ECG and echocardiographyassisting diagn
43、osis（helpful for finding PAH, hypertrophy of RV） Other examination：blood gas analysis（for respiratory failure）、blood routine（infection）、lung function、sputum culture（guide the use of antibiotics）。,Distension of right descending PA, and its diameter 15mm； Ratio of diameter of right descending PA to br
44、onchi 1.07； Protrusion of left hilar PA ； Enlargement of RV,Right axis deviation clockwise rotation of the electric axis (R/S amplitude in V11, in V51) Rv1+Sv5 1.05mV P-pulmonale pattern (an increase in P wave amplitude in II, III, AVF),Examination,Echocardiography 1、inner diameter of RV outflow (30
45、mm)， 2、RV internal dimension(20mm)， 3、RV anterior wall thickening 4、enlargement of right atrium,Differential diagnosis,Coronary artery disease：can exist together. Rheumatic heart disease: systolic murmur. Primary cardiomyopathy：accompanied with distension of whole heart.,Complication,Pulmonary encep
46、halopathy： Acid-base imbalance and electrolyte disturbance： arrhythmia： shock： Digestive tract hemorrhage： Disseminated intravascular coagulation（DIC）：,Treatment,Treatment of the underlying disease: for example, treatment of infection and bronchodilation in COPD. Treatment of respiratory failure: mo
47、st important therapeutic measure. Treatment of cardiac failure: especially when above measure no response or serious condition.,Treatment of RV failure,Diuretics: excessive diuresis can lead to metabolic alkalosis, and also induce the difficulty in coughing sputum. So always be used in low dosage an
48、d short course of therapy. Cardiac glycosides: Poor tolerance due to hypoxemia, so low dosage(1/2 1/3 routine dose). Vasodilating agent: be tried for intractable heart failure.,Treatment,Treatment of complication：always related to respiratory failure. Pulmonary encephalopathy, Acid-base imbalance and electrolyte disturbance, arrhythmia, shock, GI bleeding, DIC. Nutritional support,Prognosis,Unfavorable prognosis, mortality 10-15.,