COPD制大课版

What s the disease ?,A elderly patient,Long smoking history,Short breath,Dyspnea during exercise,Onset in mid-life ,Chronic cough and sputum production,Dyspnea is progressive ,worse during infections,Occupational dusts and chemicals, Cigarette smoker,What s the disease ?,Case Discussion,What s the disease ?What s incidence and mortality of the disease ?Whats causes and mechanism ?How to find earlier ?How to treat and prevention ?,Chronic Obstructive Pulmonary Disease COPD,呼吸内科 刘原,GOLD Definition COPD,它是以气流受限呈进行性发展，不完全可逆为特征的疾病状态。 气流受限具有进展性，伴有肺组织对有毒颗粒和气体的异常炎症反应。,A disease state characterised by progressive development of 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 and gases.,COPD概念,全球COPD控制指南（GOLD）,What is COPD （慢性阻塞肺病）?,(1) Chronic Obstructive Pulmonary Disease is a preventable and treatable disorder largely caused by smoking, and is characterized by the presence of airflow limitation that is not fully reversible .,COPD概念,What is COPD （慢性阻塞肺病）？,(2)Most patients with COPD have features of chronic bronchitis and emphysema which coexist irreversible airflow obstruction. (3)The chronic bronchitis or pulmonary emphysema without airflow limitation cannot be defined as COPD.,COPD概念,NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop Report. 2006 Update. Available at .,七版教材： COPD是一种具有气流受限特征的肺部疾病，气流受限不完全可逆，呈进行性发展，认为与肺部有害气体或有害颗粒的异常炎症反应有关，是可以预防和治疗的疾病。该病主要累及肺部，也可引起肺外各器官损坏。,What is COPD （慢性阻塞肺病） ?,COPD概念,What is chronic bronchitis(慢性支气管炎)?,Chronic bronchitis is a condition associated with the mucosal inflammation of tracheobronchi and with the mucus overproduction (支气管壁慢性、非特异性炎症)It is clinically characterized by cough,expectoration, and / or wheezing for 3 months or more in at least 2 consecutive years （咳、痰、气喘至少2年3个月）The absence of any other disease that might account for this symptom（排除其他病）,Chronic Bronchitis (慢性支气管炎),是气管、支气管黏膜及周围组织的慢性非特异性炎症,病因同COPD咳、痰、或伴气喘2年，每年3个月两型：单纯型，喘息型三期：急性发作期（1周内）； 慢性迁延期（1月）； 临床缓解期（2月）.肺功能检查：FEV1/FVC 和FEV1正常 （反映小气道流速指标可减低） 胸片:肺纹理粗,乱,多,What is Obstructive Pulmonary Emphysema阻塞性肺气肿（简称肺气肿）,由于吸咽、感染、大气污染等有害因素的刺激，引起呼吸细支气管、肺泡管、肺泡囊和肺泡的气道弹性减退，过度膨胀，充气和肺容量增大，并伴有气道壁破坏的病理状态，无明显纤维化，常与慢支同时存在。 Symptoms progressive dyspnea Signs Pulmonary Emphysema Signs Pulmonary function test TLC% 100% RV/TLC 40%,COPD概念及病种,红：慢支蓝：肺气肺绿：哮喘,COPD,气流阻塞,COPD概念,Chronic bronchitis （慢支）,Obstructive emphysema （阻塞性肺气肿）,Airflow Limitation 气流受限,COPD（慢阻肺）,不可逆,慢支-阻塞性肺气肿-慢阻肺三者的关系 疾病程度不同、肺功能可区别,为什么关注COPD？,发病率高 发病率还在不断增加 致残和致死率高 社会经济负担重,COPD is a progressive and devastating disease worldwide,0,0.5,1.0,1.5,2.0,2.5,3.0,59%,64%,35%,+163%,7%,CoronaryHeartDisease,Stroke,Other CVD,COPD,All OtherCauses,Percent Change in Age-Adjusted Death Rates, U.S., 1965-1998-33年间,What is incidence of COPD ?,China 3% ( 15 yrs. 1992 ) 8.2%(40 yrs. 2003)Asia 6.3%( 30 yrs. )USA 4%6%( men ); 1%3%( women).,发病率,What is mortality of COPD ?,COPD causes 3 million deaths per year(in world) 1 million deaths per year(in China) 510 million disabilities per year(in China)全球第4位死亡原因 ( WHO report )USA 1st(country),目前全世界患COPD 6 亿，每年死亡300万！,死亡率,Whats Risk Factor and Mechanism for COPD ?,Exact cause and mechanism for COPD are uncertain, although there are popular current theories.,病因和发病机制,（1）吸烟 Cigarette smoking重要发病因素28倍 （2）空气污染 Air pollution（SO2，NO2，CL） （3）职业 Occupation exposure（职业粉尘和化学物质） （4）感染（炎症反应） Infection 发生发展重要因素 （流感病毒，鼻病毒、腺病毒、呼吸道合胞 病毒；肺炎球菌、 流感嗜血杆菌、甲型链菌、奈瑟球菌、卡他莫拉菌，葡萄球菌） （5）社会经济/贫穷、营养Nutrition 寒冷气候、氧化物增加（超氧阴离子） （6）生物燃料,COPD的高危因素 Risk Factors,Environmental factors环境因素,宿主因素 Host Factors,（1）a1抗胰蛋白酶缺乏 a rare hereditary deficiency of -1 antitrypsin蛋白酶与抗蛋白酶失衡 弹性蛋白酶、基质金属蛋白酶-破坏肺组织（2）气道高反应性 Airway hyperresponsiveness 副交感神经亢进 （3）遗传和家族史 Gestation & family history （4）肺生长不良 Defect of lung growth （5）老龄(防御功能减弱),氧化应激/蛋白酶与抗蛋白酶失衡/炎症反应,小气道疾病,肺实质破坏,COPD,有害气体、颗粒,肺、气道炎症细胞释放炎症介质,COPD发病机制,“Spillover” Theory,TNF-,IL-6,Liver-Lung Inflammation,Systemic inflammation,Pulmonary inflammation,Chronic Low-grade Systemic Inflammation,COPD,COPD Patients,Insomnia,Hypersomnia,失去胃口Loss of appetite,TNF-aIL-1IL-6NO,全身炎症骨骼肌功能不良,肌肉消瘦Muscle wasting,自主神经失調,Pathology of COPD（病理）-Anatomy （主要是慢支和肺气肿病理改变）,decreased elasticity,greyish white,volume expansion,大体解剖,Anatomy of emphysema,Bullae肺大疱,大体解剖,1、in Airways在气道-Chronic inflammation and narrow of airways 慢性炎症和气道狭窄,组织学,Pathology of COPD -Histology,the epithelium lining the airways loss of cilia（1） 气道上皮纤毛脱落,Increased number of epithelial goblet cells in COPD 杯状细胞增多,Squamous metaplasia 鳞状化生,smooth muscle breaking,increasing collagen content and scar tissue formation,Enlarged mucus-secreting glands and mucus hypersecretion,Bronchitis慢支平滑肌变性消失，周围肺组织纤维化,Asthma哮喘,粘膜内凹凸不平，平滑肌和基底膜明显增厚，大量嗜酸细胞淋巴细胞浸润,组织学,小结COPD在气道上改变,2、In Lung Parenchyma在肺实质-呼吸性支气管和肺泡扩张和破坏，毛细血管网毁损,Dilatation and destruction of the respiratory bronchioles & alveolar walls and pulmonary capillary bed.,组织学,normal alveolar sacs,Emphysema alveoli hyperinflation loss of elastic recoil,destruction of alveolar spaces,normal alveolar sacs,destruction of alveolar spaces,Enlargement of terminal air spaces due to destruction of alveolar walls,pulmonary capillary,destruction of alveolar walls,Destruction of the Alveolar Walls and Pulmonary Capillary Bed.,Remodeling of pulmonary arteries,which thickens the vessel walls and reduces the lumen.,3、In Pulmonary Vasculature在肺血管-以血管壁增厚、管腔缩小为特征,组织学,terminal bronchiole（T） alveolar ducts () tiny bronchiole(B) small artery（ A） small bronchiole(),1、小叶中央型 Centrilobular form （COPD典型改变）,Normal Alveoli,特点 终末细支气管或一级呼吸性细支气管狭窄，导致二级呼吸性细支气管囊状扩张（肺上部常见）,组织学分型,dilatation & destruction of alveolar ducts and sacs,2、全小叶型Panacianr form,特点呼吸性细支气管狭窄，导致肺泡管、肺泡囊及肺泡扩张（肺下部常见）,3、混合型Mixed form,in Airways 在气道- 慢性炎症和气道狭窄（气道重建，管壁僵硬）In Lung Parenchyma 在肺实质- 呼吸性支气管和肺泡扩张和破坏（肺气肿）， 毛细血管网毁损In Pulmonary Vasculature 在肺血管- 以血管壁增厚、管腔缩小为特征,总结组织病理学 Pathology of COPD,可逆因素中央和外周气道平滑肌 的收缩支气管内炎症细胞的聚集、 粘液的分泌和血浆渗出物,不可逆因素 气道纤维化性狭窄 肺泡破坏使弹性回缩力减弱 肺泡支撑破坏使小气道关闭,COPD气流受限的不完全可逆因素,pathological changes in COPD lead to corresponding physiological abnormalities.,Pathophysilogy（病理生理）,病理生理,Pathophysiology,COPD,气道狭窄,肺泡壁破坏,通气障碍,肺毛细血管减少,缺O2和CO2潴留,肺A高压,呼吸衰竭,右心肥大、右心衰,FEV1.0MVVMMEF,RVRV/TLC,病理生理,Clinical Manifestations-Symptoms症状,Cough 咳 present intermittently or every day. Often present throughout the day;seldom only nocturnal (可无咳嗽)Sputum 痰any pattern of chronic sputum production may indicate COPD（可无咳痰）.Dyspnea气短 that is progressive ,persistent increased effort to breath 标志性症状晚期常有体重下降、食欲减退、精神抑郁和/或焦虑,临床表现,生活质量下降，甚至丧失劳动能力,Clinical Manifestations-Signs体征,Physical signs of airflow limitation are usually not present until significant impairment of lung function has occurred;Their detection has a relatively low sensitivity and specificity 体征敏感性和特异性低;Absence of physical sign does not exclude the diagnosis 早期可无体征,临床表现,anteroposterior transverse,Inspection cyanosis; shallow and fast breathing;pursed-lip breathing(which may serve to slow expiratory flow and permit more efficient lung emptying); barrel chest 桶状胸,临床表现,Palpation tactile fremitus语颤 动度 Percussion hyperresonant 过清音 decreased excursion of diaphragmAuscultation vesicular breath sounds 呼吸音 delayed expiratory sounds 呼气延长 rhonchi or moist rales 干湿性罗音,膈肌下移,Laboratory Findings & Imaging, FEV1/FVC 一秒率是评价气流受限较敏感的指标 FEV1（一秒量）是评估COPD程度的良好指标 吸入支气管剂后FEV1/FVC 40%提示肺气肿 ） Dlco（弥散量）VA（肺泡）均下降 支气管扩张试验阴性 （ 15% 阳性 ） 糖皮质激素试验（FEV1200ml， 15%）用激素6W-3M,Pulmonary function test 最重要的检查,辅助检查,肺功能: 正常和 COPD,Chest X-ray,Early stage - normal；Late- Prominent lung marking or / emphysema,Normal thorax,Emphysema,Chronic bronchitis,CT scanning,HRCT can identify areas of bullous disease and various pathological types of emphysema,辅助检查,Arterial Blood Gas Measurement,型呼衰 PaO2 60 mmHg 型呼衰 PaO2 60 mmHg PaCO250mmHg 呼吸性酸中毒（失代偿） PH7.35 ， PaCO2 45mmHg,辅助检查,Blood Test,Sputum Examination,辅助检查,Diagnosis诊断,History of exposure to risk factors高危因素；Symptoms：chronic cough慢性咳嗽 chronic sputum production长期咳痰 progressive & persistent dyspnea气短Signs： emphysemasigns 肺气肿体征， expiratory phase becomes longer呼气相PFT（肺功能确诊是必备检查） 吸入支气管舒张剂后FEV1/FVC 70% 确诊COPD的金标准,有气流受限 但无临床症状亦可诊断COPD！,诊断,COPD分期急性加重期 短期内咳嗽、咳痰、呼吸困难 加重；痰量增多、或脓痰； 可伴发热。稳定期 临床症状稳定或轻微,2007GOLD分级标准,进展 COPD病情严重程度评估,FEV1/FVC 70% 和 FEV1 80%体重指数呼吸困难程度（MRC评分）活动耐力（6分钟步行距离）生活质量评估（圣乔治呼吸问卷）,Differential Diagnosis鉴别诊断,1、Asthma支气管哮喘 2、Bronchiectasis支气管扩张 3、Pulmonary tuberculosis肺结核 4、lung cancer肺癌 5、others emphysema其他肺气肿,COPD,Bronchiectasis,正常支气管造影,右侧正位,左侧正位,囊状支气管扩张,右侧正位,右侧位,Complications并发症,Spontaneous pneumothorax气胸Chronic pulmonary heart disease肺心病Respiratory failure呼吸衰竭,高危因素多样性：吸烟、环境污染、感染、 过敏、植物神经、1-AT 等主要症状： 咳嗽、咳痰、气短等病程： 慢性进行性加重，肺功能和 生活质量逐渐下降，反复急 性发作，随疾病进展发作频 率增高肺功能： 气流受阻, 经支气管舒张剂治疗 不能完全逆转(与哮喘不同),小结COPD的临床特点,急性加重期治疗,治疗原则：去除诱因，改善呼吸功能，治疗并发症,1、抗感染 最多见诱因；2、改善呼吸功能 支气管舒张剂：沙丁胺醇、异丙托溴铵、茶碱类； 新进展：吸入糖皮质激素长效2受体激动剂及 噻托溴氨控制性氧疗：低浓度、低流量、持续性；糖皮质激素：强的松3040mg/d 1014天 或静滴甲强龙40mg/d 35天祛痰；机械通气。3、治疗合并症如肺心病、呼衰、气胸等；4、一般性治疗、营养支持等。,治疗,COPD急性加重：无创通气的参考指征,中重度气促伴有辅助呼吸肌肉动用 或反常呼吸 中重度酸中毒（pH7.30-7.35)和 高碳酸血症（ PaCO2 45-60mmHg) RR 25 BPM,治疗,COPD急性加重：插管通气的参考指征,严重气促伴有辅助呼吸肌肉动用或反常呼吸 RR 35 BPM危及生命的低氧（ PaO2 60mmHg)呼吸停止昏睡，神志丧失心血管并发症（低血压，休克，心衰）其他并发症（代谢紊乱，败血症，肺炎，肺栓塞，胸积液等）无创通气治疗后无效,治疗,COPD稳定期的治疗,1.戒烟、避免或防止粉尘、烟雾及有害气体的吸入。2.支气管扩张剂：抗胆碱能药物或/和2激动剂吸入治疗或/和茶碱的缓释剂。3.恢复人体局部和全身的防御功能：有痰者宜使用祛痰药、体位引流等。,4.呼吸困难明显或支气管舒张剂吸入试验阳性者，激素试验治疗（7-14天）。有效者渐减量并使用吸入激素，无效则及时停用。5. 可考虑应用肺炎球菌疫苗、流感病毒疫苗或应用免疫增强剂预防感染。6.康复治疗；有低氧血症者宜长期家庭氧疗。,治疗,稳定期治疗-长期家庭氧疗（LTOT）,LTOT指征,1、 PaO255mmHg 或 SaO288% 2 、PaO2 55-60mmHg 或 SaO289% 并有肺动脉高压、心衰水肿或红细胞增多。,LTOT方法,低流量（1-2升/分），吸氧时间1