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1、Chronic Obstructive Pulmonary Disease (COPD)Guohua ZhenTongji HospitalPercent Change in Age-Adjusted Death Rates, U.S., 1965-199800.51.01.52.02.53.0Proportion of 1965 Rate 0.00.51.01.52.02.53.01965 - 19981965 - 19981965 - 19981965 - 19981965 - 199859%64%35%+163%7%CoronaryHeartDiseaseStrokeOther CVDC
2、OPDAll OtherCausesWhy COPD is Important ?COPD is the only chronic disease that is showing progressive upward trend in both mortality and morbidityIt is expected to be the third leading cause of death by 2020Approximately 3% Chinese above 15 are currently suffering from COPDDefinitionCOPD is a preven
3、table 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
4、 COPD and Chronic bronchitis, Asthma or EmphysemaChronic BronchitisChronic BronchitisDefinition: 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 a
5、nd mechanism Environment FactorsCigarette smokingOccupational dusts and chemicalsInfectionsHost FactorsGenes Lung growth and defense mechanismChronic BronchitisClinical manifestation Character: chronic onset, recurrent attack and long course of diseaseMain symptoms: cough: chronic, long term, repeat
6、edly expectoration: mucoid sputum, purulent sputum when infection wheezing: seen in some patientsClinical manifestation Sign: 1. no obvious sign in early stage2. sometimes moist rales and rhonchi Examination Chest x-ray imagingExamination Pulmonary function test: maybe normal in early stage. Gradual
7、ly obstructive airway function appeared.Blood routine: elevated neutrophil or eosinophil Sputum examination: bacterial culture guide antibiotic treatmentDiagnosis Chronic cough and sputum production for 3 consecutive months in at least 2 successive years(3m/y2y), excluding other chronic lung disease
8、s (TB, Bronchiectasis )Definite chest imaging or lung functionTyping Typing :1、simple:cough, sputum2、wheezing:with wheezing (actually Chronic bronchitis plus asthma)Emphysemacopd英文課英文課DefinitionEmphysema is characterized by enlargement and destruction of respiratory bronchioles and /or alveoli in th
9、e lungs.Etiology Environment FactorsCigarette smokingOccupational dusts and chemicalsInfectionsHost FactorsGenes: Alpha1-antitrypsin deficiencyContributing factorAirway obstruction due to chronic inflammationDamaged bronchial cartilage and lead to the loss of supporting functionIncreased activity of
10、 proteinase due to chronic airway inflammation or smokingAlpha1-antitrypsin deficiencyOthers: Poor nutrition of alveoli or respiratory bronchiole due to decreased blood supply because of oppression of high airway pressureCigarette smokeAlveolar macrophageNeutrophil PROTEASES Alveolar wall destructio
11、n(Emphysema)Mucus hypersecretion(Chronic bronchitis)PROTEASEINHIBITORSNeutrophil chemotactic factors CELLULAR MECHANISMS OF COPD Neutrophil elastaseCathepsinsMatrix metalloproteinasesCytokines (IL-8)Mediators (LTB4)?CD8+lymphocyte-MCP-1 1-Antitrypsin TIMPs SLPI Elafin Neutrophil elastase Cathepsins
12、MMP-1, MMP-9, MMP12 Granzymes, perforins Others.PROTEASE-ANTIPROTEASE IMBALANCE IN COPDPathology feature Alveolar walls become thinnerAlveolar sacs enlargementRupture of alveoli and formation of blebPathological CategoryIn panlobular emphysema, the enlargement and destruction of air space involve th
13、e acinus more or less uniformly.In centrilobular emphysema, respiratory bronchioles are selectively and dominantly involved.COPD- chronic bronchitis- emphysemaCOPD PathophysiologyHypoventialtion- PaO2 , PaCO2 Airflow obstruction / airway narrowing mucus plugging airway inflammation, edema, fibrosis
14、airway collapse due to alveolar wall destruction Hyperinflation: air trappingGas exchange defects- PaO2 Destruction of alveolar wall/alveolar-capillary membrane V/Q mismatch (shunt)Clinical manifestationSymptom1. cough, sputum and/or wheezing2. gradually progressive dyspnea, shortness of breath, che
15、st tightnessClinical manifestationSign:1. not obvious in early stage2. typical sign: barrel chest, decreased chest movement, diminished tactile fremitus, hyperresonance, decreased vesicular breath sound and prolong expiration or wheezeExaminationPulmonary function test Diagnosis Assessing severity A
16、ssessing prognosis Monitoring progressionExamination: pulmonary function test Dynamic lung function airflow obstructionFEV1, FEV1/FVC Static lung function hyperinflation TLC, FRC air trapping RVExamination: pulmonary function testChest X-ray:ECG:Blood gas:to detect respiratory failure.Blood routine
17、and sputum examination: ExaminationChest X-rayIntercostal space wideningDiaphragm are low and flatVascular marking deficiencyShadow of the heart narrowinglow, flat diaphragms, hyperlucency, vascular marking deficiencyDiagnosis 1、Smoking history2、Symptom: cough, sputum production, gradually progressi
18、ve dyspnea3、Sign:emphysema4、PFT: airway flow limitationCOPD classification based on pulmonary function testSeverityPostbronchodilator FEV1/FVCPostbronchodilator FEV1% predicted0: At risk0.780I: Mild COPD80II: Moderate COPD0.750-80III: Severe COPD0.730-50IV: Very severe COPD0.730Clinical Features of
19、COPD Patients of different severityMild COPD: no abnormal signs, smokers cough, little or no breathlessnessModerate COPD: breathlessness with/without wheezing, cough with/without sputumSevere COPD: breathlessness on any exertion/at rest, wheeze and cough prominent, lung inflation usual, cyanosis, pe
20、ripheral edema, and polycythemia in advanced diseaseStage of diseaseAcute ExacerbationsStableAcute exacerbation of COPDAE-COPD“Exacerbation” of COPD Respiratory dyspnea / chest tightness cough / sputum, purulent Systematic decreased activity, fatigue, headache, poor appetite, somnolenceDifferential
21、diagnosis Bronchial asthma: reversibility of the airflowBronchiectasis: especially mild patients, chronic cough and mucus sputumPulmonary TB:positive anti-fast smearBronchogenic carcinoma:Emphysema due to other cause: for compensationComplications of COPDChronic respiratory failure Spontanous pneumo
22、thorax Cor pulmonale hypoxia, pedal edema, passive hepatic congestion. Management of COPDPrevent decline in FEV1 Reduce mortalityImprove quality of life symptoms exercise tolerance exacerbationsMinimal side-effectsNon-pharmacologic TherapiesCOPDSmoking cessation Physician intervention critical Multi
23、disciplinary approach Withdrawalanxiety, 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 placeboEffects of Smoki
24、ng and Smoking Cessation on FEV10255075100255075Age (years)FEV1(%)Nonsmoker or Non-susceptibleStopped at 45Stopped at 65Susceptible Smoker COPD: Pharmacology Bronchodilators Corticosteroids Long term oxygen therapy Management of COPD exacerbationsCOPD: Pharmacology2-agonist bronchodilators Rapid-act
25、ing 2-agonists (SABA) salbutamol, terbutaline symptomatic relief pre-exertional 2 puffs 4-6 x /d prn minimal risk Long acting 2-agonists (LABA) salmeterol, formoterol regular therapy 1-2 puffs bid benefit: activity / exertion, QOLCOPD: PharmacologyAnticholinergic bronchodilators Benefits vs Risks Re
26、gular therapy Symptomatic benefit ? exacerbations Minimal s/edry mouth, urinary retention Agents Ipratropium /Atrovent4-6 puffs qid Tiotropium /Spiriva1 puff qdCOPD: PharmacologyTheophylline Multiple effects bronchodilation, respiratory stimulant, improved cardiovascular function, improved diaphragm
27、 function Limited role because of narrow therapeutic window s/e GI, CNS, cardiac qd - bid dosing with long-acting preparationsCOPD: PharmacologyInhaled Steroids Symptomatic COPD patients with “asthmatic” tendency (20%) FEV1 18 hrs /d Improved survival, right heart failure Improved exercise tolerance
28、, QOL Indications PaO2 55 mmHg (SaO2 88%)COPD: ExacerbationsOxygenation: low concentration oxygen therapy Risks of excessive O2 (PaO2 100 mmHg) hypercapnia ( PaCO2 ) acidemia ( pH 0.8 L) Lung volume reduction surgery (LVRS)prognosisRelate to the value of FEV1 FEV11.2L survive for 10y, FEV11.0 L surv
29、ive for 5y ,F(xiàn)EV11, in V51)Rv1+Sv5 1.05mVP-pulmonale pattern(an increase in P wave amplitude in II, III, AVF)ExaminationEchocardiography 1、inner diameter of RV outflow (30mm),2、RV internal dimension(20mm),3、RV anterior wall thickening4、enlargement of right atriumDifferential diagnosisCoronary artery disease:can exist together.Rheumatic heart disease: systolic murmur.Primary cardiomyopathy:accompanied with distension of whole heart.ComplicationPulmonary encephalopathy:Acid-base imbalance and
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