慢性阻塞性肺疾病 課件

1、 慢性阻塞性肺疾病 Chronic Obstructive Pulmonary Disease (COPD) 山東大學(xué)齊魯醫(yī)院 曲 儀慶 慢性阻塞性肺疾?。–OPD）慢 性 支 氣 管 炎CHRONIC BRONCHITIS慢 性 阻 塞 性 肺 氣 腫CHRONIC OBSTRUCTIVE EMPHYSEMA慢 性 肺 源 性 心 臟 病CHRONIC COR PULMONALE 重要意義-診斷氣流受限吸入支氣管舒張劑后FEVl80預(yù)計值且FEVlFVC70者，可確定為氣流受限051423Liter165432FVCFVCFEV1FEV1正常COPDSeconds, 6543210Volum

2、e L t s RSVFRCERVRVIRVICVCTLC靜息COPD的診斷危險因素暴露吸煙油煙或燃料產(chǎn)生的煙塵職業(yè)性灰塵或化學(xué)物質(zhì)室內(nèi)/室外空氣污染癥狀慢性咳嗽咳痰呼吸困難考慮臨床診斷COPD肺功能測試確診Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease Revised 2011COPD的定義 COPD是一種具有氣流受限特征的可以預(yù)防和治 療的疾病 氣流受限不完全可逆、呈進行性發(fā)展（持續(xù)存在）與肺部對香煙煙霧等有害氣體或有害顆粒的異常 炎

3、癥反應(yīng)有關(guān) COPD主要累及肺臟，但也可引起全身(或稱肺外) 的不良效應(yīng)概述慢性阻塞性肺疾病（COPD）由于其患病人數(shù)多，死亡率高，社會經(jīng)濟負(fù)擔(dān)重，已成為一個重要的公共衛(wèi)生問題在世界，COPD居當(dāng)前死亡原因的第四位根據(jù)世界銀行、世界衛(wèi)生組織發(fā)表的研究，至2020年COPD將成為世界疾病經(jīng)濟負(fù)擔(dān)的第五位1965-1998年全美死亡率的變化00.51.01.52.02.53.01965 - 19981965 - 19981965 - 19981965 - 19981965 - 199859%64%35%+163%7%冠心病中風(fēng)其它腦血管病COPD其它COPD 患病率（1990年）India4.38

4、3.44China26.2023.70Other Asia 2.891.79Sub-Saharan Africa4.412.49Latin America and Caribbean3.362.72Middle Eastern Crescent2.692.83World9.347.33*From Murray & Lopez, 1996男/1000女/1000COPD在中國發(fā)病率高 1992年15歲以上人群COPD發(fā)病率為3% 2003年40歲以上發(fā)病率為8.2%死亡率高 COPD在我國死亡原因中：農(nóng)村中首位，城市中居第四位COPD發(fā)病率及死亡率逐年上升我國COPD經(jīng)濟負(fù)擔(dān)居所有疾病的首位每年

5、因COPD死亡的人數(shù)達100萬，致殘人數(shù)達100萬WHO和中國呼吸界關(guān)注COPD世界COPD日： 每年11月第三個星期三世界戒煙日：每年5月31日GOLD: Global Initiative for Chronic Obstructive Lung Disease(2002,2004，-2011)中國COPD診治規(guī)范（1997）中國慢性阻塞性肺疾病診治指南2002年, 2007年,2009年背景資料GOLD成立GOLD首次發(fā)布COPD診斷、處理和預(yù)防全球策略GOLD指南第一次重大修訂2011修訂版GOLD1998200120062011美國國立心肺和血液研究所、NIH和世界衛(wèi)生組織（WHO）

6、聯(lián)合發(fā)起成立“慢性阻塞性肺疾病全球倡議（GOLD）”。目的： 促進社會對COPD疾病負(fù)擔(dān)的認(rèn)識，增加對COPD的認(rèn)知，并讓衛(wèi)生機構(gòu)、醫(yī)保政策對COPD進一步了解。鼓勵社會對這一重大疾病的研究投入和改善臨床診治。1.柳濤 蔡柏薔Chin J Respir Crit Care Med, January 2012, Vol. 11, No. 1GOLD2011修改內(nèi)容要點GOLD2011舊版指南名稱定義診斷評估治療COPD全球策略文件COPD 是一種可以預(yù)防和可以治療的常見疾病, 其特征是持續(xù)存在的氣流受限。氣流受限呈進行性發(fā)展, 伴有氣道和肺對有害顆粒或氣體所致慢性炎癥反應(yīng)的增加。急性加重和合并癥

7、影響患者整體疾病的嚴(yán)重程度根據(jù)臨床癥狀和危險因素接觸史可考慮臨床診斷，肺功能檢查是確診的條件評估基于患者的癥狀，肺功能，急性加重史及合并癥個體化治療，根據(jù)患者癥狀嚴(yán)重程度、急性加重風(fēng)險、藥物可獲得性及患者對藥物療效反應(yīng)COPD治療指南COPD是一種可以預(yù)防和治療的疾病，常伴有一些明顯的肺外作用(即全身效應(yīng))，可對患病個體帶來嚴(yán)重后果，氣道不完全可逆性氣流受限為其特征，氣流受限通常進行性加重，并與氣道對有害微?；驓怏w的異常炎癥反應(yīng)有關(guān)結(jié)合癥狀和接觸危險因素，肺功能檢查是診斷的金標(biāo)準(zhǔn)評估嚴(yán)重程度分級基于肺功能升階梯治療，采用在基礎(chǔ)治療上添加不同種類藥物，或聯(lián)合使用不同治療方法7How TO Rea

8、lize COPD11慢性支氣管炎 慢性支氣管炎概念：是指氣管、支氣管及其周圍組織的慢性非特異性炎癥特征:咳嗽、咳痰或伴有喘息的反復(fù)發(fā)作的慢性過程患病率:人群患病率3.2%，50歲者高達15%危害:可進展為慢性阻塞性肺氣腫和肺心病【病因和發(fā)病機制】外因 吸煙 感染因素 理化因素 氣候因素內(nèi)因 過敏因素 全身或呼吸道局部防御及免疫功能減退 自主神經(jīng)功能失調(diào) 營養(yǎng)因素 遺傳因素Pathology of chronic bronchitis Shedding of cilia and epithelial cells, as well as metaplasia by squamous cells

9、Mucosal and submucosal inflammation infiltrated mainly by neutrophils and macrophages, as well as peribronchial fibrosis Hyperplasia of bronchial smooth muscles Hyperplasia and hypertrophy of Goblet cells and submucosal glands Shedding of cilia and epithelial cellssquamous epithelium replacement Hyp

10、erplasia and hypertrophy of Goblet cells and submucosal glandsMucosal and submucosal inflammationClinical manifestations of Chronic Bronchitis (Symptom)cough sputum production Wheezing Clinical manifestations of Chronic Bronchitis (Sign )normal in mild disease or in early stageAs the disease advance

11、s variable moist rales scattered wheezes 分型 單純型：僅有咳嗽、咳痰； 喘息型：除咳嗽、咳痰外，還有喘息 和哮鳴音分期 急性發(fā)作期：指一周內(nèi)出現(xiàn)膿性或粘液膿性痰，痰量明顯增加，或伴有發(fā)熱、白細胞計數(shù)增高等炎癥表現(xiàn) 或一周內(nèi)咳、痰、喘癥狀中任何一項明顯加劇; 輕、中、重度：氣短 痰量增加 膿性痰慢性遷延期：指咳、痰、喘癥狀遷延一 個月以上者;臨床緩解期：指癥狀基本消失或偶有輕微咳嗽，少量痰液，保持2個月以上者。 【laboratory findings】 血液檢查： 可有白細胞計數(shù)、 中性粒細胞增多， 喘息型嗜酸性粒細胞增加。痰液檢查：涂片或培養(yǎng)胸片檢查

12、 ：肺紋理增多、粗亂。肺功能檢查 ：早期無異常，隨病情發(fā)展?jié)u出現(xiàn)阻塞性通氣功能障礙。 【diagnosis】 咳嗽咳痰或伴喘息，每年發(fā)病持續(xù)3個月，連續(xù)2年以上，排除其他心肺疾患如癥狀每年持續(xù)不足3個月，而有明確客觀檢查為依據(jù)(如肺功能、X線胸片)亦可診斷【treatment】 急性發(fā)作期和遷延期 控制感染 解痙平喘 止咳祛痰 臨床緩解期 戒煙，加強鍛煉、增強體質(zhì)，提高機體抵抗力，預(yù)防上感。急性發(fā)作期和遷延期治療控制感染：抗生素治療 參照痰培養(yǎng)藥敏結(jié)果調(diào)整抗生素。 常用青霉素、紅霉素、頭孢菌素類及喹諾酮類。 支氣管擴張劑： 適用于喘息型患者腎上腺皮質(zhì)激素：喘息型合理使用支氣管擴張劑后，仍有明顯

13、的氣道阻塞時促進痰液排出：保持氣道通暢，如深吸氣后有意識咳嗽，胸部叩擊和震顫及體位引流。充分飲水，避免分泌物粘稠。 祛痰藥 obstructive pulmonary emphysemadefinition： is characterized by abnormal permanent enlargement of the airspaces distal to the terminal bronchioles with destruction of their walls. 【 Pathogenesis 】機制不明，蛋白酶/抗蛋白酶失衡學(xué)說大部分由慢性支氣管炎發(fā)展形成慢性刺激因子造成氣道不完

14、全阻塞，吸氣時空氣較易進入肺泡，呼氣時氣道陷閉，空氣在肺內(nèi)滯留，肺泡過度膨脹壓迫肺泡間隔，加之局部炎癥的直接侵蝕，使肺泡壁的血液供應(yīng)減少，致肺泡壁破壞、彈性減退或融合成肺大泡，形成肺氣腫 慢性炎癥白細胞和巨嗜細胞釋放蛋白酶增加慢性炎癥破壞小支氣管壁軟骨Pathology of chronic obstructive emphysema distention and destruction of alveolar spaces loss of pulmonary capillary infiltration of inflammatory cells Pathology of chronic o

15、bstructive emphysema According to the pattern of involvement of the gas - exchanging unites of the lung distal to the terminal bronchiole, the emphysema can be classified as three subtypes Centrilobular emphysema Panacinar emphysema mixture CENTRILOBULAR EMPHYSEMAThe distal acinus or alveoli are unc

16、hanged. Occurs more commonly in the upper lobes. Most common type. Seen in cigarette smokers Involves primarily the respiratory bronchiole (proximal and central part of the acinus is expanded) Involves entire respiratory acinus, from respiratory bronchiole to alveoli is expanded. Occurs more commonl

17、y in the lower lobes, especially basal segments, and anterior margins of the lungs. It is 1/20 as common as centricular emphysema. It is the type seen in alpha 1 antitrypsin deficiencyPanacinar emphysema Clinical manifestations of emphysema (Symptom)The symptoms of bronchitisDyspnea Exertional dyspn

18、ea loss of physical capacity Recurrent respiratory infectionClinical manifestations of emphysema (Signs )Normal at early stageinspection : barrel chest, using accessory muscles of respiration, Cyanosis palpation :weakened respiratory movementpercussion :hyperresonance , low diaphragm Auscultation:di

19、minished breath sounds, rhonchi , cardiac dullness Complications respiratory failure Chronic cor pulmonalePneumothorax pneumothorax should be suspected in any patient whose pulmonary status suddenly worsensinfection 【laboratory findings】 影像檢查 胸廓前后徑增大，肋骨變平，肋間隙增寬，膈低平。 肺野透明度增加，肺血管紋理減少， 有些病例可見肺大泡。阻塞性肺氣腫

20、小葉中央性全小葉性間隔旁【laboratory findings】 肺功能檢查 殘氣量、功能殘氣量和RV/TLC均增高 呈阻塞型通氣功能障礙 并可伴有換氣功能障礙血氣分析 中、重癥病人有低氧血癥和高碳酸血癥。血常規(guī)：RBC、HB 心電圖：QRS 低電壓 【diagnosis】 在慢性咳嗽、咳痰基礎(chǔ)上出現(xiàn)呼吸困難 體檢有肺氣腫體征。 X線胸片有肺氣腫征象。 肺功能檢查： RV/TLC40% Chronic Obstructive Pulmonary Disease (COPD)GOLD(Global Initiative for Chronic Obstructive Lung Disease)

21、RISK FACTORS:Environmental factor Host factor RISK FACTORS Environmental factor Tobacco SmokeInfectionAir pollutionOccupational exposureFEV1(%of value of age 25)The effect of smoking on the FEV1 in men aged 25 years and olderRISK FACTORS( Environmental factor)Cigarette smoking impairs ciliary moveme

22、nt leads to hyperplasia and hypertrophy of mucus - secreting glands causes PMN (polymorphonuclear leukocytes) to release protease increases vagally mediated smooth muscles constriction RISK FACTORS( Environmental factor)Passive smokingEasily to ignoreRoom pollution More toxic substancesDifficult to

23、judgeRISK FACTORS( Environmental factor)InfectionStill not clearenhance inflammation in the lung predispose to bronchial hyperreactivity aggravate airflow obstruction Latent infectionRISK FACTORS( Environmental factor)Air pollution and occupational exposure Inhaled anxious substances comprised of pa

24、rticulates and gases with some background radioactivity relationship between levels of atmospheric pollution and respiratory problemsMore sever in smokerRISK FACTORS Host factorHypersensitivitySusceptibilityOld age 1 - antitrypsin deficiency Family historyDelayed lung development Pathogenesis of COP

25、DChronic airway inflammationProteinase-antiproteinase imbalanceOxidants antioxidants imbalanceClinical manifestations Chronic Long termRecurrentProgressiveLaboratory Tests and Accessory Findings Blood testSputum examRadiographic exam Respiratory function testing Blood testNormal at stable stageExace

26、rbation : WBC count neutrophil differentiationSputum examSmear simple wayCulture with sensitivity test select appropriate antibioticsRadiographic examNormal at early stageProminent lung markingCOBSever emphysema :clearLung function testFEV1/FVC：sensitive value to mild COPDFEV1 of the predicted norma

27、l value ：to assess the severity FEV180% predicted ，and FEV1/FVC70%， not fully reversible Examples of Spirometric Tracings and Calculation of FEV1, FVC, and FEV1/FVC RatioCOPD的診斷危險因素暴露吸煙油煙或燃料產(chǎn)生的煙塵職業(yè)性灰塵或化學(xué)物質(zhì)室內(nèi)/室外空氣污染癥狀慢性咳嗽咳痰呼吸困難考慮臨床診斷COPD肺功能測試確診11Global strategy for the diagnosis, management, and prev

28、ention of chronic obstructive pulmonary disease Revised 2011Classification of Severity of COPD stagecharacteristics 0: At Risk normal spirometrychronic symptoms (cough, sputum production) I: Mild COPD FEV 1 /FVC 70% FEV 1 80% predictedWith or without chronic symptoms(cough, sputum production) II: Mo

29、derate COPD FEV 1 /FVC 70% 50% FEV 1 80% predicted with or without chronic symptoms III: Severe COPD FEV 1 /FVC 70% 30% FEV 1 50% predicted With or without chronic symptoms IV: Very Severe COPD FEV 1 /FVC 70% FEV 1 30% predicted or FEV 1 50% predicted plus chronic respiratory failure GOLD風(fēng)險（氣流受限分級）4

30、321風(fēng)險（急性加重史）CAmMRC 0-1CAT 210癥狀（mMRC 或 CAT 評分）23Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease Revised 2011Differential diagnosis Bronchiectasis Asthma Pulmonary TB Interstitial lung disease Congestive Heart FailureLung cancer COPDOnset in mid-

31、lifeSymptoms slowly progressiveLong smoking historyDyspnea during exerciseLargely irreversible airflow limitationDifferential diagnosis withBronchiectasis Recurrent cough and expectoration a large amount of purulent sputum may occur accompanied acute infection Hemoptysis is commonRadiographic examin

32、ation shows bronchial dilation, bronchial wall thickening. CT scan ,HRCT Bronchogram Dilated bronchiDifferential diagnosis withasthmaOnset early in life (often childhood).Allergy, rhinitis, and/or eczema also present.family history specifican episodic attack without chronic productive cough A sympto

33、m - free interval in asthma is specific.Largely reversible airflow limitation. Differential diagnosis withasthma FEV1(after inhaled b2-Agonists) FEV1 Improved rate of FEV1(%)=- FEV112% and value of FEV1(after inhaled b2-Agonists) FEV1 200mlDifferential diagnosis withPulmonary TB Onset all agesFever,

34、Fatigue,weight loss,Hemoptysisanti - acid stain is positive Chest X-ray shows lung infiltrate.High local prevalence of tuberculosis.Reactivation TBDifferential diagnosis with interstitial lung diseaseVelcro ralesLung function:limited ventilation disturbanceradiographic findingsInterstitial lung dise

35、aseDifferential diagnosis with lung cancerStimulating coughBloody sputumradiographic findingsSputum cellsbronchoscopyCOPD并發(fā)癥慢性呼吸衰竭慢性肺源性心臟病自發(fā)性氣胸Treatment Therapy of stable COPDManagement of acute exacerbations 緩解癥狀 提高運動耐力 改善健康狀況 預(yù)防疾病進展 預(yù)防和治療急性加重 降低死亡率GOLD 2013減少當(dāng)前癥狀降低未來風(fēng)險GOLD指南提出穩(wěn)定期COPD的治療目標(biāo)81緩解期慢性阻塞

36、性肺疾病的推薦治療方案 戒煙康復(fù)治療藥物治療 短效支氣管舒張劑 長效支氣管舒張劑 吸入糖皮質(zhì)激素長期氧療外科治療GOLD指南：COPD穩(wěn)定期藥物治療方案GOLD 2013.患 者首 選次選備選ASAMA 必要時或SABA 必要時LAMA或LABA或SABA+SAMA茶堿BLAMA或LABALAMA+LABASABA 和/或 SAMA茶堿CICS + LABA或LAMALAMA和LABA或LAMA+PDE4抑制劑或LABA+PDE4抑制劑SABA和/或SAMA茶堿DICS + LABA和/或LAMAICS+LABA+LAMA或ICS+LABA+PDE4抑制劑或LAMA+LABA或LAMA+PDE

37、4抑制劑羧甲司坦SABA和/或SAMA茶堿83FEV1(%of value of age 25)The effect of smoking on the FEV1 in men aged 25 years and older25-30ml/year150ml/yearLTOTGoal: PaO2 more than 60mmHg,SaO2 more than 90%Method: 12L/mTIME: more than 15h指征：PaO255mmHg或SaO288%，有或沒有高碳酸血癥。PaO2 55-60mmHg，或SaO289%，并有肺動脈高壓、心力衰竭水腫或紅細胞增多癥（血細胞比容0

38、55）。 Management of acute exacerbationsControlled oxygen therapyAntibioticsBronchodilator CorticosteroidsTreatment of complicationControlled oxygen therapyCalculation Oxygen Concentration Oxygen Concentration(%)=21+4* Oxygen flow(L/min)Goal To reach PaO2 greater than 60mmHg PaCO2 increased a little o

39、r not Method hypoxemia with 30% without hypercapnia moreAECOPD 的病因Sethi et al. Chest 2000;117:380s-385s80% 由感染誘發(fā)20%是 非感染因素細菌病原體 40 - 50%病毒感染30 - 40% 非典型致病菌 5 - 10%環(huán)境因素服藥的依從性差A(yù)ECOPD患者需要抗生素使用 Anthonisen標(biāo)準(zhǔn)類患者同時具有氣促加重，咳嗽痰量增加，膿性痰，推薦使用抗生素類患者具有2項表現(xiàn)如有膿性痰，推薦應(yīng)用抗生素如無膿性痰，不推薦應(yīng)用抗生素類患者僅具有1項表現(xiàn)不推薦應(yīng)用抗生素90細菌閾值理論與COPD急

40、性發(fā)作Miravitlles M, et al. Eur Respir J. 2002; 20 (Suppl 36) : 9s19s.Olaf Burkhardt,et al. Anti Infect Ther. 2009；7(6), 645668 .細菌負(fù)荷量 (CFU/ml)時間(天)臨床閾值急性加重期抗菌藥物治愈停用抗菌藥物COPD患者無論在穩(wěn)定期和加重期氣道都可分離出細菌，急性加重患者呼吸道分泌物中致病菌的數(shù)量比穩(wěn)定期增加。而且，宿主局部炎癥反應(yīng)與細菌負(fù)荷量增加成正比Miravitlles推測，在COPD穩(wěn)定期，氣道內(nèi)存在一定的負(fù)荷量的細菌定植，氣道內(nèi)細菌負(fù)荷量增加到一定水平時會引起急性加重，即有一個引起急性加重的細菌負(fù)荷量閾值A(chǔ)ntibioticsEmpiric therapySputum Culture plus drug sensitive test community acquired infection positive