内科学教学课件：支气管哮喘

Bronchialasthma

支气管哮喘ThosetoberememberedMorbidityofasthmaMortalityofasthma在中国有1500万，全球3亿哮喘患者，每100，000位哮喘患者中有36.7位哮喘患者会因哮喘死亡。DefinitionAsthmaisaheterogeneous

disease,characterizedbychronicairwayinflammation.Itisdefinedbyhistoryofrespiratorysymptomssuchaswheeze,shortnessofbreath,chesttightnessandcoughthatvaryintimeandintensity,togetherwithvariableexpiratoryflowlimitation.哮喘的定义Allergicinflammation气道慢性变态反应性炎症Inflammatorycells由多种炎症细胞：如嗜酸粒细胞、肥大细胞、T淋巴细胞、嗜中性粒细胞、Structuralcells气道结构细胞：平滑肌、气道上皮细胞等）细胞组分(cellularelements)参与的气道慢性炎症性疾病慢性炎症导致气道高反应性（airwayhypersensitivity）引起反复发作性的喘息、气急、胸闷或咳嗽等症状，常在夜间和（或）清晨发作、加剧通常出现广泛多变的可逆性气流受限，多数患者可自行缓解或经治疗缓解

PathogenesisGeneticfactorsAllergicresponseNeuron-receptordisbalanceAirwayinflammationPathogenesisofasthma环境因素遗传易感个体炎症细胞、细胞因子及炎症介质相互作用神经调节失衡、上皮细胞及气道平滑肌结构功能异常气道炎症气道高反应性症状性哮喘环境激发因子气道高反应性气道炎症CardinalfeatureofasthmaVariablesymptomsofwheeze,shortnessofbreath,chesttightnessand/orcoughVariableairflowlimitationBothsymptomsandairflowlimitationvaryovertimeandinintensityTriggers:exercise,allergen,irritantexposure,changeinweather,viralrespiratoryinfectionResolutionspontaneouslyorwithmedicationAirwayhyperresponsivenessandinflammationpersists,evenwhensymptomsareabsent/normallungfunctionGenerallymorethan2typesofsymtomsSymptomsoccurvariablyovertimeandvaryinintensitySymptomsareworseatnightoronwakingSymptomsareoftentriggeredbyallergens,exercise,laughter,coldairSymptomsoftenappearorworsenwithviralinfectionCardinalmanifestations咳嗽喘息呼吸困难

诱发因素：活动后吸入冷空气后夜间感冒后突然发作性体征呼气时产生哮鸣音规律：节律性(夜间发作)季节性(春、秋)自然/用药缓解CardinalmanifestationsAsthmaTRIGGERS

ENVIRONMENTALFACTORSAllergens•Indoor:Domesticmites,furredanimals(dogs,cats,mice),cockroachallergen,fungi,molds,yeasts•Outdoor:Pollens,fungi,molds,yeastsInfections(predominantlyviral)ExerciseDrugs:aspirinDiet:fish,milk,egg,prawn,crabPsychiatricOccupationalsensitizersLabTesingLungfunctiontest

Bronchodilationtest:airwayreversibility

postFEV112%,∆FEV1>200ml

Bronchialprovocationtest:bronchialhyperreactivitypost-FEV120%

PEPvariationAllergentestFractionalExhalednitricoxide(FeNO)LabtestingBloodeosinophilsChestX-rayBloodgasanalysis1.反复发作性喘息、呼吸困难、胸闷或咳嗽，多与接触变应原、冷空气、物理化学剌激、病毒感染、运动等有关

2.可闻哮鸣音

3.上述症状可经治疗或自行缓解

4.症状不典型者(如无明显喘息和体征)至少应有下列三项中的一项阳性∶（1）支气管激发试验或运动试验阳性；（2）支气管舒张试验阳性；（3）呼气流量峰值（PEF）日内变异率或昼夜波动率≥20％

5.除外其他疾病所引起的喘息、胸闷和咳嗽符合1～4条或4、5条者，可诊断咳嗽变异性哮喘：DiagnosisSeverityandstagingSeverity:mild,moderate,severeStaging:Chronicpersistent:weeklyChronicremission:3monAcuteexacerbationSeverityof

asthma轻症哮喘Mildasthma中度哮喘Moderateasthma重度哮喘severeasthmaGINAupdated2014表3哮喘急性发作时病情严重程度的分级

临床特点轻度中度重度危重气短

体位

讲话方式

精神状态

出汗

呼吸频率

辅助呼吸肌活动及三凹征

哮鸣音

脉率

奇脉

使用β2激动剂后PEF预计值PaO2（吸空气）

PaCO2

SaO2（吸空气）

PH步行、上楼时

可平卧

连续成句

可有焦虑尚安静

常无

轻度增加

常无

散在，呼吸末期

<100次／min

无，<10mmHg

>80％

正常

<45mmHg

>95％

稍事活动

喜坐位

单词

时有焦虑或烦燥

有

增加

可有

响亮、弥漫

100～120次可有

60％～80％

≥60mmHg

≤45mmHg

91％一95％

休息时

端坐呼吸

单字

常有焦虑、烦躁

大汗淋漓

常>30次／min

常有

响亮、弥漫

>120次／min

常有，

<60％或<100％

<60mmHg

>45mmHg

≤90％

不能讲话

嗜睡或意识模糊

胸腹矛盾运动

减弱、乃到无

脉率变慢不规则

无，提示呼吸肌疲劳

降低

AsthmainspecialpopulationExercise-inducedasthmaDrug-inducedasthmaObesityasthmaOccupationalasthma>>>>>>>>>>>>>>>>>>>>DifferentialdiagnosisLungcancerChroniceosinophiliclunginfiltration(cardiacasthma)ComplicationsPneumothoraxPneumomediastinumLungatelectasisbronchiectasis

Managementofasthma

一、治疗目标

1．达到并维持哮喘控制

2．保持正常活动；包括运动能力

3．维持肺功能维持在接近正常水平

4．预防哮喘急性加重5．避免哮喘药物的不良反应

6．预防哮喘死亡，降低哮喘死亡率

PharmacotherapyofasthmaRelieverInhaledshort-acting2agonistOralshort-acting2agonistAnticholinergicsMethylxanthinesSystemicsteroidControllerInhaledsteroidInhaledlong-acting2agonistOrallong-acting2agonistLeukotrienemodifierMethylxanthinesCromonesSystemicsteroidIgEAbImmunotherapyClassificationofß2agonists作用时间Inhaledsteroid布地奈德氟替卡松二丙酸倍氯米松环索奈德CombinationtherapyInhaledcorticosteroid(ICS)+long-actingbetaagonist(LABA)fluticasone+salmeterol(Advair.Seretide舒利迭)Budesonide+formoterol(Symbicort信必可)MDIDiskhalerNebulizerStep1:Asneededrelieverinhaler,orICS(riskexacerbation.Step2:lowdosereliever+SABAprn(ICS/LTA/theo)Step3:1or2controller+asneededreliever(lowICS+LABA/LTA/theo)Step4:2ormorecontroller+asneededreliever(moderateICS+LABA/LTA/theo)Step5:added-ontherapy:anti-IgE,thermoplasty,OCSStepwisecontrolforasthmaStepwisecontrolofasthmaandreducerisks哮喘的治疗-达到哮喘控制为基础LevelsofasthmacontrolDaytimesymptoms>2/wkNightawakingRelieverneeded>2/wkActivitylimitationNone1~2ofthose3~4ofthoseWellcontrolledPartlycontrolledUncontrolledGINAupdated2014Symptomspast4wksLevelofcontrol哮喘治疗与评价多数哮喘从2级开始，症状频繁者3级2-4wk复诊，后1-3月复诊哮喘评价：良好控制/部分控制/未控制达到控制后维持3月后减量激素减量50%低剂量改为qd联合用药者，减激素50%哮喘控制标准-症状控制控制级别日间哮喘症状>2次/周夜间哮喘症状控制症状药物>2次/周哮喘引起活动受限无任何一项出现一到二项出现三到四项良好控制部分控制未控制GINAupdated2014过去4周症状哮喘升级治疗持续升级（2-3月）：初始治疗反应差短期升级（1-2周）：病毒感染、季节过敏原日间调整：含福莫特罗制剂，维持、缓解方案哮喘长期治疗方案哮喘教育环境控制按需使用速效2-激动剂按需使用速效2-激动剂可选择的控制药物选用一种选用一种在第三级基础上，选用一种或多种在第四级基础上，加用一种低剂量ICS低剂量ICS加长效2-激动剂中/高剂量ICS加长效2-激动剂口服糖皮质激素(最小剂量)白三烯调节剂/茶碱中/高剂量ICS白三烯调节剂抗IgE治疗低剂量ICS加白三烯调节剂缓释茶碱低剂量ICS加缓释茶碱第一级第二级第三级第四级第五级升级降级5.FromtheGlobalStrategyforAsthmaManagementandPrevention,GlobalInitiativeforAsthma(GINA)2011.Availablefrom:/.控制部分控制未控制急性加重控制水平维持治疗并明确最低治疗级别考虑升级治疗，已达到控制升级治疗直至达到控制按急性加重治疗治疗措施治疗级别降级升级第1级第2级第3级第4级第5级降级升级OthertherapiesAvoidanceoftriggersImmunotherapyEducationOxygentherapySaO2>92%Bronchodilatortherapy:SABA+iprotropiumEpinephrineIHSteroidtherapy:methylprednisone40-160mg/dManagementofacid-baseandelectrolytedisturbanceFluidtherapy:2500ml/dAntibiotictherapyManagementofcomplicationManagementofsevereexacerbation-3ManagementofAsthmaExacerbationsinAcuteCareSettingOverallcontrolSymptomscontrolNormalactivityReducefuturerisks：AsthmaattackFixedairflowlimitationSideeffectsOverallcontrolofasthmaGINAupdated2014BatemanED,etal.JAllergyClinImmunol.2010;125(3):600-8.SummaryInflammatoryairwaydiseasewithBHRTriggersorenvironmentalexposureAsthmaticsymptomsAntiasthmaticdrugsManagementofasthma(includingexacerbation)INTERSTITIALLUNGDISEASE弥漫性间质性肺病肺间质肺间质包含肺泡上皮与肺血管内皮的空间，包含多种细胞如成纤维细胞、成纤维细胞母细胞、巨噬细胞，还有基质包括胶原、弹力蛋白和糖蛋白).Interstitium肺间质的概念

肺脏基本功能单位与肺间质肺容积缩小弥散量降低低氧血症呼吸困难间质性肺病的概念间质性肺病（InterstitialLungDisease，ILD）为累及肺泡壁以及肺泡周围组织和其周围结构的非感染、非肿瘤性一组疾病。

ILD可累及细支气管与肺实质，又被称为弥漫性实质性肺病(DiffuseParenchymalLungDisease，DPLD)间质性肺病的共性肺容积缩小肺弥散功能减低呼吸困难，特别运动后运动后或疾病低氧血症好影像学弥漫性改变病理学表现为肺实质/间质不同程度纤维化/炎症已知原因的DPLD职业性肺病药物性肺病结缔组织疾病相关性ILD特发性间质性肺炎（IIP）肉芽肿所致DPLD结节病过敏性肺炎肉芽肿并血管炎少见DPLD肺泡蛋白沉积症肺出血-肾炎综合征淋巴管平滑肌肌瘤病朗格汉斯组织细胞增生症特发性含铁血黄素沉着症慢性嗜酸细胞性肺炎弥漫性肺间质疾病（DPLD）间质性肺病的分类症状与体征

RespiratorySymptomsandSignsDyspnea:Progressivedyspnea,exertional/resting--themostcommoncomplaint.10%ILDmaypresentwithdyspneawithanormalchestradiograph.SuspectionafterexclusionofCOPD,Pulmonarythromboembolism.Cough:IPF,sarcoidosis,HP,COPChestPain:CTD-ILD,pneomothoraxwithLMWheezing:sarcoidosis,HypersensitivitypneumoniaBibasilarinspiratorycrackles(爆裂音):characteristicphysicalsigninILD.Mechanism.DryralesDigitalclubbing,(杵状指)amarkerofadvancedfibroticdisease,ofteninIPF;症状与体征RespiratorySymptomsandSigns实验室检查

LaboratoryInvestigationAutoantibodies(rheumatoidfactor,antinuclearfactors)CVD,IPF,WG,MPA,NSIPSerumangiotensinconvertingenzyme:SarcoidosisEosinophilia:EosinophilicpneumoniaAntibasementmembraneantibody:Antineutrophiliccytoplasmicantibody:WG,MPAIncreasedserumLDH:IPF影像学检查

RadiographicFeaturesGround-glassopacification毛玻璃影Reticularornodular网格/结节影Honey-combing蜂窝影Reticularpattern网格影Nodule-结节影Honey-combing蜂窝肺IPFGroundglassopacity(GGO)pulmonaryalveolarproteinosisBronchoalveolarLavage肺泡灌洗Normal：细胞总数5~10x106，巨噬细胞85~90%，L10~15%，N+E1%Diagnosis:E>25%eosinophilicpneumoniaperiodicacid–Schiff(PAS)+:alveolarproteinosisBALlymphocytes(>35%)sarcoidosis,HP,LIP,drug-inducedILDResponsetotherapy:lymphocytosisBAL-AlveolarproteinosisPhysiologicTestingRestrictionDiffusiondefectPreservationofairflowIncreaseinP(A-a)O2Exercise-inducedhypoxaemiaHyperventilationPFTLungBiopsy-definitivediagnosisThefinalstepinthediagnosticevaluationofapatientwithILDistodecidewhetheritisnecessarytoobtainlungtissue.TranbronchialLungBiopsy经气管镜肺活检Percutaneouslungbiopsy经皮肺活检Video-assitedthoracosopiclungbiopsy胸腔镜活检Openlungbiopsy开胸肺活检DiagnosisThyerapyAvoidanceofexposureSteroidtherapyAntifibrotictherapySymptomatictherapyOthersIDIOPATHICPULMONARYFIBROSIS(IPF)特发性肺纤维化IDIOPATHICINTERSTITIALPNEUMONIA(IIP)

特发性间质性肺炎IIPsareagroupofdiffuseparenchymallungdiseases(DPLDs),agroupalsodescribedasinterstitiallungdiseasesTheIIPsareaheterogeneousgroupofnonneoplasticdisordersresultingfromdamagetothelungparenchymabyvaryingpatternsofinflammationandfibrosis.Idiopathicindicatesunknowncauseandinterstitialpneumoniareferstoinvolvementofthelungparenchymabyvaryingcombinationsoffibrosisandinflammation,incontrasttoairspacediseasetypicallyseeninbacterialpneumonia.特发性间质性肺炎（IIP）特发性肺纤维化（IPF/UIP）呼吸性细支气管炎伴间质性肺病（RBILD）隐原性机化性肺炎（COP）脱屑型间质性肺炎（DIP）急性间质性肺炎（AIP）非特异性间质性肺炎(NSIP)淋巴细胞间质性肺炎(LIP)间质性肺病的分类主要IIP少见

IIP未能分类的IIP特发性胸膜肺实质的弹力纤维增生症AmJRespirCritCareMedVol188,Iss.6,pp733–748,Sep15,2013ClassificationsofIIPs特发性间质性肺炎的病理学特征Idiopathicpulmonaryfibrosis(IPF)isdefinedasaspecificformofchronic,progressivefibrosinginterstitialpneumoniaofunknowncause,occurringprimarilyinolderadults,andlimitedtothelungs.Itischaracterizedbyprogressiveworseningofdyspneaandlungfunctionandisassociatedwithapoorprognosis.IPFasadistinctclinicalentityassociatedwiththehistologicappearanceofusualinterstitialpneumonia(UIP).IPF-DefinitionPotentialRiskFactorsCigarettesmokingEnvironmentalfactorMicrobialagentsGastroesophagealrefluxClinicalFeaturesSymptoms&SignsExertionaldyspneaCoughBasilarcrackle（Velcro啰音）HRCT诊断UIP征象UIP征象(所有4项)可能UIP征象(所有3项)不符合UIP征象(任何1项)胸膜下、基地分布网格样改变蜂窝肺+伴支气管扩张无不符合UIP征象胸膜下、基地分布网格样改变无不符合UIP征象上或中肺野分布支气管周围分布广泛磨玻璃阴影为主广泛微结节分散囊样病变弥漫马赛克征肺支气管叶、段实变SubjectedtoexternalreviewDEFINITIONOFUIPPATTERNInconsistentwithUIPpatternDiagnosisofIPFIPF诊断标准

DiagnosticCriteria1.除外其它已知原因ILD(如室内或职业性环境暴露，结缔组织病、药物毒性等).2.HRCT具备典型UIP特征无需性外科肺活检。3.不典型需要结合HRCT及外科活检病理特征。肺功能、症状、体征---辅助作用AcuteExacerbationofIPF（AEIPF）CriteriaforAEIPF:unexplainedworseningofdyspneawithin1month,Hypoxemianewradiographicalveolarinfiltratesabsenceofanalternativeexplanationinfectionpulmonaryembolismpneumothoraxheartfailure.TherapyforIPFIPF–Evidence-BasedTreatment:Strongrecommendationagainsttheuse:Corticosteroidmonotherapy(verylow)Colchicine(verylow)秋水仙碱CyclosporineA(verylow)环孢霉素Combinedcorticosteroidandimmune-modulatort