1、2022-2-9Chronic Obstructive Pulmonary Disease (COPD)慢性阻塞性肺疾病慢性阻塞性肺疾病同济医院呼吸内科同济医院呼吸内科刘辉国刘辉国Character of COPDChronic bronchitis and emphysemaChronic Obstructive Pulmonary Disease(chronic, cough,sputum,dyspnea) Character of COPDChronic bronchitis慢支慢支 + emphysema肺气肿肺气肿1.not fully reversible airflow limi
2、tation不完全可逆气道阻塞不完全可逆气道阻塞2.an abnormal inflammatory response (Include respiratory and systemic)异常炎症反应异常炎症反应 Relationship of COPD and Chronic bronchitis, Asthma or EmphysemaNew DefinitionCOPD is a preventable and treatable disease state characterized by airflow limitation that is not fully reversible气
3、流受限不完全可逆气流受限不完全可逆. The airflow limitation is usually progressive进行进行性性 and is associated with an abnormal inflammatory response异常炎症反应异常炎症反应 of the lungs to noxious particles or gases, primarily caused by cigarette smoking.Although COPD affects the lungs, it also produces significant systemic consequ
4、ences全全身并发症身并发症.GOLD 2006慢性阻塞性肺疾病是一种可预防、可治疗的常见疾病特征为持续存在的气流受限气流受限呈进行性发展，伴有气道和肺对有害颗粒或气体所致慢性炎症反应的增加急性加重和合并症影响患者整体疾病的严重程度GOLD 2011 COPD的定义（GOLD2011)6 肺充气过度 肺泡附着丧失 气道弹性回缩能力丧失 支气管平滑肌收缩力增加气流受限气流受限COPD是一种以炎症为核心的多因素构成的疾病 杯状细胞增生/化生 粘液腺肥大 支气管平滑肌增多 气道纤维化 肺泡破坏结构改变结构改变 炎症细胞的数量/活性增加: - CD8+T 淋巴细胞 - 中性粒细胞 - 血液单核细胞
5、肺泡巨噬细胞 - 肥大细胞 炎症介质增多: - IL-8 - TNF- 蛋白酶/抗蛋白酶失衡气道炎症气道炎症 营养不良 体重减轻 骨骼肌受累 骨质疏松 因心血管疾病死亡全身效应全身效应粘液纤毛粘液纤毛功能障碍功能障碍 气道粘膜损伤 粘液产生过多 粘液清除减少肺部炎症肺部炎症全身炎症全身炎症靶器官靶器官肺部炎症通过全身炎症，肺部炎症通过全身炎症，引起全身效应引起全身效应Why COPD is Important ? COPD is the only chronic disease that is showing progressive upward trend in both mortality
6、 and morbidity It is expected to be the third leading cause of death by 2020 Approximately 8% Chinese above 15 are currently suffering form COPD*00.51.01.52.02.53.0Proportion of 1965 Rate 0.00.51.01.52.02.53.01965 - 19981965 - 19981965 - 19981965 - 19981965 - 199859%64%35%+163%7%CoronaryHeartDisease
7、StrokeOther CVDCOPDAll OtherCauses Definition: Inflammation of bronchi and the surrounding tissue. Feature: chronic mucus hypersecretion粘液分泌亢进 and cough咳嗽.Chronic Bronchitis慢性支气管炎慢性支气管炎Etiology 病因病因 Exposure外因外因Tobacco smoke吸烟吸烟Occupational dusts and chemicals职业职业Infections感染感染Socio-economic status经
8、济经济 Host Factors内因内因Genes 基因基因Hyper-responsiveness高反应性高反应性Lung growth and defense mechanism肺发育肺发育smokers lung Normal LungClinical manifestation symptoms Character特征特征: chronic onset, recurrent attack and long course of disease Main symptoms主要症状主要症状: cough咳咳: chronic, long term, repeated expectoratio
9、n痰痰: mucoid sputum, purulent sputum when infection wheezing喘喘: seen in some patientsClinical manifestation Sign体征体征: 1. no obvious sign in early stage2. sometimes moist rales湿罗音湿罗音 and rhonchi (sonorous)干罗音干罗音 be heard, or wheezing哮鸣哮鸣 Examination Chest x-ray imagingExamination Pulmonary function te
10、st肺功能肺功能: maybe normal in early stage. FEV75% decreased when small airway obstruction. Gradually obstructive airway function appeared.Blood routine血常规血常规: elevated neutrophil or eosinophil Sputum examination痰检痰检: bacterial culture guide antibiotic treatmentDiagnosis 诊断标准 Persistence of cough and exc
11、essive mucus secretion for most days out of 3 months in at least 2 successive years（3m/y2y）, excluding other chronic lung diseases (TB, Bronchiectasis ) Not enough course of disease but definite chest imaging or lung functionType分型 Typing :1、simple：cough, sputum2、wheezing：with wheezing (actually Chr
12、onic bronchitis plus asthma)Partially obstruction of bronchial lumenEasily inhaled due to enlargement of lumen when inspiredHard to exhale due to more narrowing of lumen when exspiredDilation of terminal airway due to higherPressure Chronic bronchitis emphysemaContributing factor协同因素协同因素Poorly nutri
13、tion of alveoli or respiratory bronchiole due to decreased blood supply because of oppression of high airway pressure血供减少血供减少Damaged bronchial cartilage and lead to the loss of supporting function软骨损伤软骨损伤Increased proteinase due to chronic airway inflammation or smoking炎症蛋白酶炎症蛋白酶Others: Alpha1-Antit
14、rypsin DeficiencyCigarette smokeAlveolar macrophageNeutrophil PROTEASES Alveolar wall destruction(Emphysema)Mucus hypersecretion(Chronic bronchitis)PROTEASEINHIBITORSNeutrophil chemotactic factors CELLULAR MECHANISMS OF COPD Neutrophil elastaseCathepsinsMatrix metalloproteinasesCytokines (IL-8)Media
15、tors (LTB4)4)?CD8+lymphocyte-MCP-1 Neutrophil elastase Cathepsins MMP-1, MMP-9, MMP12 Granzymes, perforins Others.PROTEASE-ANTIPROTEASE IMBALANCE IN COPD 1-Antitrypsin SLPI Elafin TIMPsPathology feature Alveolar wall became thinness肺泡壁薄肺泡壁薄 Alveolar sac enlargement肺泡肺泡扩大扩大 rupture of alveoli and for
16、mation of bleb肺泡破裂融合肺泡破裂融合Pathological Categorize病理类型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.Definition of COPD characterised by airflow
17、 limitation that is not fully reversible. The airflow limitation is usually progressive Some definite disease (cystic fibrosis or diffuse panbronchiolitis) have airflow limitation but is not COPD Chronic simple bronchitis or asthma even some emphysema without airflow limitation is not COPDCOPD Patho
18、physiology病生机制病生机制Airflow obstruction / airway narrowingmucus pluggingairway inflammation, edema, fibrosisairway collapsibility due to alveolar wall destructionbronchospasmHyperinflationGas exchange defectsMild-moderate disease PaO2Severe disease PaCO2COPD PathophysiologyDynamic lung functionairflow
19、 obstructionFEV1, FEV1/FVChyperreactivity15 - 20% prevalenceStatic lung functionhyperinflation TLC, FRCgas-trapping RVGas exchange and the ratio of ventilation-perfusionmild-mod COPDhypoxaemiasevere (FEV1 1L)hypercapniaemphysema DLcoClinical manifestationSymptom1. cough, sputum and/or wheezing咳,痰,喘2
20、. gradually progressive dyspnea or shortness of breath进行性加重的呼吸困难3. Chest pain or tightness胸痛或紧缩感Clinical manifestationSign:1. not obvious in early stage2. typical sign: barrel chest桶状胸桶状胸, decreased chest movement胸廓运动下降胸廓运动下降, diminished tactile fremitus触觉语音下降触觉语音下降, Hyperresonance过清音过清音, decreased
21、vesicular breath sound 肺泡呼吸音肺泡呼吸音下降下降and prolong expiration呼气延长呼气延长 or wheeze哮鸣音哮鸣音examination Spirometry肺量计肺量计 Diagnosis Assessing severity Assessing prognosis Monitoring progressionChest X-ray：ECG：Blood gas：to detect respiratory failure.Blood routine and sputum examination： Intercostal space widen
22、ingDepression and flattening of the diaphragmBlunting of the costophrenic angleIrregular radiolucency of the lung fieldShadow of the heart narrowingPlain chest radiograph胸部平片胸部平片low, flat diaphragms, retrosternal airspace, hyperlucencyDiagnosis evidence：1、smoking for long time2、chronic bronchitis+gr
23、adually progressive dyspnea3、sign：emphysema4、PFT: airway flow limitationCOPD classification based on spirometry肺功能分级肺功能分级 GOLDSPIROMETRY is not to substitute for clinical judgment in the evaluation of the severity of disease in individual patients.SeverityPostbronchodilator FEV1/FVCPostbronchodilato
24、r FEV1% predictedMild COPD80Moderate COPD0.750-80Severe COPD0.730-50Very severe COPD0.730Clinical Features of COPD Patients Mild COPD: no abnormal signs, smokers cough, little or no breathlessness Moderate COPD: breathlessness with/without wheezing, cough with/without sputum Severe COPD: breathlessn
25、ess on any exertion/at rest, wheeze and cough prominent, lung inflation usual, cyanosis, peripheral edema, and polycythemia in advanced disease评估方法的改变GOLD2006:COPD 严重程度是根据肺功能来分级 缺陷：肺功能级别不同的患者发生急性加重的频率、住院率及病死率是不一样的，但对于特定的个体，肺功能并不是衡量患者呼吸困难、运动耐力和健康状态的可靠指标。 GOLD 2011修订版：使用分期（grade） 保留COPD的肺功能分级系统，因为FEV1
26、仍是预测未来风险的重要因素。加入症状、风险等综合评估。42症状（mMRC or CAT 评分）如果 mMRC 0-1 or CAT 2 or CAT 10 较多症状 (B or D)STEP1：评估症状(C)(D) (A)(B)mMRC 0-1CAT 2CAT 10 GOLD 201143CAT（COPD评估测试）我从不咳嗽我从不咳嗽12345我一直咳嗽我一直咳嗽我一点痰也没有我一点痰也没有12345我有很多很多痰我有很多很多痰我一点也没有胸闷的感觉我一点也没有胸闷的感觉12345我有很重的胸闷的感觉我有很重的胸闷的感觉当我爬坡或爬一层楼时，我并不感到当我爬坡或爬一层楼时，我并不感到喘不过气来
27、喘不过气来12345当我爬坡或爬一层楼时，我感觉非常当我爬坡或爬一层楼时，我感觉非常喘不过气来喘不过气来我在家里的任何劳动都不受慢阻肺的我在家里的任何劳动都不受慢阻肺的影响影响12345我在家里的任何活动都很受慢阻肺的我在家里的任何活动都很受慢阻肺的影响影响每当我外出时就外出每当我外出时就外出12345因为我有慢阻肺，我所以从来没有外因为我有慢阻肺，我所以从来没有外出过出过我睡眠非常好我睡眠非常好12345因为我有慢阻肺，我的睡眠非常不好因为我有慢阻肺，我的睡眠非常不好我精力旺盛我精力旺盛12345我一点精力都没有我一点精力都没有评分3020评分30 10评分2010分疾病状态疾病状态非常严重
28、非常严重严重严重中等中等病情轻微病情轻微44呼吸困难指数（ mMRC）45Risk (GOLD Classification of Airflow Limitation)Risk (Exacerbation history) 2 1 0(C)(D) (A)(B)4321 Symptoms(mMRC ， CAT )低风险（A or B） 气流受限气流受限1 or 2 0或1次急性加重/年高风险(C or D) 气流受限气流受限 3 or 4 2 次急性加重/年只要出现一次由急性加重导致的住院即可被视为高风险STEP2 ：评估急性加重GOLD 201346Stage of disease分期分期A
29、cute Exacerbations急性加重期急性加重期Stable stage稳定期稳定期急性加重（AECOPD)GOLD2011 AECOPD是一次急性事件，特征是COPD患者呼吸系统症状的恶化，而且是超出每日正常的变化，导致用药方案的改变定义 降低患者的生活质量症状和肺功能的恢复延迟数周加剧了肺功能的下降速度与死亡增加有关，尤其是需要住院的患者加重社会经济负担重要性4880%感染因素所致感染因素所致 细菌感染细菌感染40- 60% 病毒感染病毒感染30% 非典型病原体非典型病原体5-10%20%非感染因素所致非感染因素所致 环境因素环境因素 服药依从性差服药依从性差80%20%Houss
30、et B et al. Inter J Antimicrobial Agents. 2007;29(suppl 1):s11-s16.AECOPD的病因49致病菌平均值(%)范围(%)流感嗜血杆菌352-69卡他莫拉菌162-33肺炎链球菌164-38铜绿假单胞菌92-35汇总结果来自汇总结果来自54项使用抗菌药物治疗项使用抗菌药物治疗AECOPD的研究的研究Martinez FJ et al.Expert Rev. Anti Infect. Ther. 2006;4:1011245051Complications of COPD并发症1. Cor Pulmonale 肺心病syncope,
31、hypoxia, pedal edema, passive hepatic congestion, and death. 2. Acute Exacerbations急性加重急性加重3. Chronic respiratory failure呼吸衰竭呼吸衰竭 4. Polycythemia hypoxia红细胞增多症5. Pneumothorax气胸气胸Differential diagnosis 鉴别诊断Bronchial asthma哮喘哮喘: reversibility of the airflowBronchiectasis支扩支扩:especially mild patients,
32、chronic cough and mucus sputumPulmonary TB肺结核：肺结核：positive anti-fast smearBronchogenic carcinoma肺癌：肺癌：Emphysema due to other cause其它肺气肿其它肺气肿: for compensation or elder Management of COPDPrevent decline in FEV1 延缓FEV1下降Reduce mortality降低死亡率Improve quality of life改善生存质量 symptoms exercise tolerance exa
33、cerbationsMinimal side-effects 缓解症状 提高运动耐力 改善健康状况 预防疾病进展 预防和治疗急性加重 降低死亡率GOLD 2013缓解症状缓解症状降低风险降低风险GOLD提出稳定期COPD的治疗目标 原则：原则： 根据患者症状严重程度、急性加重风险、药物可获得性及患者对药物疗效反应进行个体化治疗个体化治疗55Non-pharmacologic Therapies非药物治疗非药物治疗COPD Smoking cessation戒烟Physician intervention critical最关键干预措施Multidisciplinary approachWith
34、drawalanxiety, irritability, difficulty concentrating, sleep disruption, fatigue, drowsiness, depressionNicotine replacement withdrawal symptomsnicotine gum (2 mg = cigarette)transdermal nicotine patches x 8 wks20-40% / 6 mos vs 5-20% / 6 mos with placeboFEV1AgeFletcher C and Peto R, BMJ 1977; 1:164
35、5-1648. Imagery courtesy ODonnell D非药物治疗非药物治疗康复治疗：改善活动耐力，乏力和呼吸困难康复治疗：改善活动耐力，乏力和呼吸困难症状。症状。长期家庭氧疗：流量长期家庭氧疗：流量1-2L/min,151-2L/min,15小时小时/ /天天，适用于极重度伴有慢性呼衰的患者，能够，适用于极重度伴有慢性呼衰的患者，能够改善生存率。改善生存率。GOLD 201359COPD: Pharmacology药物治疗药物治疗Bronchodilators支气管扩张剂: 2-agonist bronchodilators 激动剂Theophylline茶碱Corticost
36、eroids激素Long term oxygen therapy长期氧疗Management of COPD exacerbations急性发作期处理COPD: Pharmacology 2-agonist bronchodilators 激动剂Rapid-acting 2-agonists速效salbutamol, terbutalinesymptomatic reliefpre-exertional2 puffs 4-6 x /d prnminimal riskLong acting 2-agonists长效salmeterol, formoterolregular therapy1-2
37、puffs bidbenefit: activity / exertion, QOLCOPD: Pharmacology Anticholinergic bronchodilators抗胆碱类Benefits vs RisksRegular therapySymptomatic benefit? exacerbationsMinimal s/e dry mouth, urinary retentionAgentsIpratropium /Atrovent4-6 puffs qidTiotropium /Spiriva 1 puff QDCOPD: Pharmacology Theophylli
38、ne茶碱Multiple effectsbronchodilation, respiratory stimulant, improved cardiovascular function, improved diaphragm functionLimited role because of narrow therapeutic windows/eGI, CNS, cardiacOD - bid dosing with long-acting preparationsCOPD: Pharmacology Inhaled Steroids吸入糖皮质激素Symptomatic COPD patient
39、s with “asthmatic” tendency (20%)FEV1 50% predicted and repeated exacerbations requiring antibiotics and/or oral glucocorticosteroids (Evidence B)? Oral steroid respondersExacerbations per year 0CAT 10 mMRC 2GOLD 3 GOLD 2 GOLD 1 SAMA prnor SABA prnLABA or LAMAICS + LABAor LAMACOPD稳定期药物治疗-首选ABDCICS +
40、 LABAand/or LAMA 2014 Global Initiative for Chronic Obstructive Lung Disease2 or more or 1 leading to hospital admission1 (not leading to hospital admission)65COPD: Exacerbations Management急性加重处理Identify cause明确诱因Infection-最常见但不是唯一的诱因“Infectious” bronchitis common causeMost commonly viralBacteria -
41、S. pneumonia, H. influenzae, M. catarrhalisAntibiotics if 2 of 3: dyspnea, sputum volume, or purulenceAgentsClavulan, cefuroxime, macrolides, FQsAECOPD治疗-氧疗 氧疗是氧疗是AECOPD 住院患者的住院患者的基础治疗基础治疗 吸入氧浓度不宜过高吸入氧浓度不宜过高,需注意可能发生潜在的需注意可能发生潜在的CO2 潴留潴留及呼吸性酸中毒。及呼吸性酸中毒。 氧疗氧疗30min后应复查动脉血气，以确认氧合满意，且未后应复查动脉血气，以确认氧合满意，且未
42、引起引起CO2 潴留和潴留和(或或)呼吸性酸中毒呼吸性酸中毒 在有给氧设施情况下在有给氧设施情况下,吸入雾化液最好在氧流量吸入雾化液最好在氧流量68L/min的条件下给予雾化吸入的条件下给予雾化吸入AECOPD诊治中国专家共识（2014年修订版）. 国际呼吸杂志, 2014, 34(1): 1-11.GOLD201467AECOPD治疗-支气管扩张剂 首选短效支气管扩张剂为首选短效支气管扩张剂为2 受体激动剂受体激动剂,若效果不显著若效果不显著,建议加用抗胆碱能药物建议加用抗胆碱能药物 长效支气管扩张剂合并长效支气管扩张剂合并/不合并吸入糖皮质激素在急性不合并吸入糖皮质激素在急性加重时的治疗效
43、果不确定。加重时的治疗效果不确定。 患者接受机械通气治疗时患者接受机械通气治疗时,可通过特殊接合器进行吸入可通过特殊接合器进行吸入治疗。由于药物颗粒可沉淀在呼吸机管道内治疗。由于药物颗粒可沉淀在呼吸机管道内,因此因此所需所需药量为正常的药量为正常的24倍倍。 静脉使用甲基黄嘌呤类药物静脉使用甲基黄嘌呤类药物(茶碱或氨茶碱茶碱或氨茶碱) 为为二线用药二线用药,适用于对短效支气管扩张剂疗效不佳以及某些较为严适用于对短效支气管扩张剂疗效不佳以及某些较为严重的重的AECOPD患者。患者。AECOPD诊治中国专家共识（2014年修订版）. 国际呼吸杂志, 2014, 34(1): 1-11.GOLD20
44、14682014GOLD加重期管理中关于糖皮质激素的更新n 推荐使用泼尼松3040mg/d，1014天改为推荐使用泼尼松40mg/d连续5天（B类证据），尽管没有充足的数据得出确切的结论关于最佳的激素治疗AECOPD持续时间。n 单独雾化布地奈德可替代口服激素。n 雾化镁剂（硫酸镁等）作为沙丁胺醇的辅助来治疗AECOPD对于FEV1改善是无效的。69n 目前不推荐应用抗病毒药物治疗AECOPD 除扎那米韦和金刚烷胺能够有效地治疗流感之外,其他所有抗病毒药物均未证实有临床治疗效应 。 目前没有任何抗病毒药物批准用于治疗鼻病毒属感染,尤其是鼻病毒属感染诱发的AECOPD。n 抗病毒治疗仅适用于出现
45、流感症状(发热、肌肉酸痛、全身乏力和呼吸道感染)时间小于2d、并且正处于流感爆发时期的高危患者。n 目前AECOPD患者发生呼吸衰竭时不推荐使用呼吸兴奋剂。只有在无条件使用或不建议使用无创通气时,可使用呼吸兴奋剂AECOPD治疗-抗病毒、呼吸兴奋剂AECOPD诊治中国专家共识（2014年修订版）. 国际呼吸杂志, 2014, 34(1): 1-11.70序贯通气的优势序贯通气显著降低：住院病死率VAP发生率住ICU时间总住院时间有创通气时间中机械通气时间712014GOLD对AECOPD并发症管理的更新n 住院的COPD 急性加重患者会增加深静脉血栓和肺栓塞的风险，应加强预防血栓发生的措施。A
46、ECOPD 患者并发肺栓塞的发病率高达24.7%。 未经治疗的肺栓塞,病死率几乎为30%。低血压和低血压和/或高流量吸氧后或高流量吸氧后PaO2 不能升至不能升至60mmHg以上常提示以上常提示肺栓塞可能肺栓塞可能AECOPD 并发肺栓塞的原因:(1)低氧血症导致继发性红细胞增多使血液黏稠度增加、血小板功能异常;(2)AECOPD 患者并发肺源性心脏病时常伴有右室壁栓子形成(3)AECOPD 患者的心肺储备功能差,体力活动受限,长期卧床,深静脉血栓发病率增加。72AECOPD并发肺栓塞AECOPDAECOPD并发肺栓塞的预防并发肺栓塞的预防: : 对卧床、红细胞增多症或脱水的AECOPD患者,
47、无论是否有血栓栓塞性疾病史,均需考虑使用肝素或低分子肝素抗凝治疗。AECOPDAECOPD并发肺栓塞的治疗并发肺栓塞的治疗: : 参见肺血栓栓塞症诊断与治疗指南和急性肺血栓栓塞症诊断治疗中国专家共识。73Prognosis预后预后 Relate to the value of FEV1 FEV11.2L survive for 10y， FEV11.0 L survive for 5y ，FEV130mmHg latent PAH。Clinical presentation表现表现Sign and symptom of the underlying disease基础疾病表现：基础疾病表现：D
48、yspnea呼吸困难呼吸困难 is a frequent symptom and is associated with hypoxia 低氧症低氧症and hypercapnia高二氧化碳症高二氧化碳症. But in many patients, especialy those with fibrotic lung disease or vascula obstruction, dyspnea is not necessary accompanied by resting hypoxemia.Clinical presentationManifestation of PAH肺动脉高压表现：肺
49、动脉高压表现： 1、P2 accentuationP2亢进亢进: a loud pulmonic component of the S2. 2、auxiliary examination辅助检查如辅助检查如肺动脉段突出：肺动脉段突出：seen in chest roentgenogram.Clinical presentationHypertrophy of RV右室肥厚表现：右室肥厚表现： 1、palpitation on exertion活动后心悸活动后心悸 2、anginal chest pain胸痛胸痛: in some severe PHD, not usually response
50、 to nitrate 3、a loud heart beat sound under xiphoid剑突下心音增强剑突下心音增强 4 、auxiliary examination: X-ray, ECG and UCG辅助检查辅助检查Clinical presentationEnlargement and failure of RV右室扩大衰竭：右室扩大衰竭： 1、systolic murmur along the left sternal border胸骨左侧杂音胸骨左侧杂音: relative tricuspid insufficiency or regurgitation； 2、obs
