內科學教學課件：支氣管哮喘

Bronchialasthma

支氣管哮喘ThosetoberememberedMorbidityofasthmaMortalityofasthma在中國有1500萬，全球3億哮喘患者，每100，000位哮喘患者中有36.7位哮喘患者會因哮喘死亡。DefinitionAsthmaisaheterogeneous

disease,characterizedbychronicairwayinflammation.Itisdefinedbyhistoryofrespiratorysymptomssuchaswheeze,shortnessofbreath,chesttightnessandcoughthatvaryintimeandintensity,togetherwithvariableexpiratoryflowlimitation.哮喘的定義Allergicinflammation氣道慢性變態(tài)反應性炎癥Inflammatorycells由多種炎癥細胞：如嗜酸粒細胞、肥大細胞、T淋巴細胞、嗜中性粒細胞、Structuralcells氣道結構細胞：平滑肌、氣道上皮細胞等）細胞組分(cellularelements)參與的氣道慢性炎癥性疾病慢性炎癥導致氣道高反應性（airwayhypersensitivity）引起反復發(fā)作性的喘息、氣急、胸悶或咳嗽等癥狀，常在夜間和（或）清晨發(fā)作、加劇通常出現廣泛多變的可逆性氣流受限，多數患者可自行緩解或經治療緩解

PathogenesisGeneticfactorsAllergicresponseNeuron-receptordisbalanceAirwayinflammationPathogenesisofasthma環(huán)境因素遺傳易感個體炎癥細胞、細胞因子及炎癥介質相互作用神經調節(jié)失衡、上皮細胞及氣道平滑肌結構功能異常氣道炎癥氣道高反應性癥狀性哮喘環(huán)境激發(fā)因子氣道高反應性氣道炎癥CardinalfeatureofasthmaVariablesymptomsofwheeze,shortnessofbreath,chesttightnessand/orcoughVariableairflowlimitationBothsymptomsandairflowlimitationvaryovertimeandinintensityTriggers:exercise,allergen,irritantexposure,changeinweather,viralrespiratoryinfectionResolutionspontaneouslyorwithmedicationAirwayhyperresponsivenessandinflammationpersists,evenwhensymptomsareabsent/normallungfunctionGenerallymorethan2typesofsymtomsSymptomsoccurvariablyovertimeandvaryinintensitySymptomsareworseatnightoronwakingSymptomsareoftentriggeredbyallergens,exercise,laughter,coldairSymptomsoftenappearorworsenwithviralinfectionCardinalmanifestations咳嗽喘息呼吸困難

誘發(fā)因素：活動后吸入冷空氣后夜間感冒后突然發(fā)作性體征呼氣時產生哮鳴音規(guī)律：節(jié)律性(夜間發(fā)作)季節(jié)性(春、秋)自然/用藥緩解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.反復發(fā)作性喘息、呼吸困難、胸悶或咳嗽，多與接觸變應原、冷空氣、物理化學剌激、病毒感染、運動等有關

2.可聞哮鳴音

3.上述癥狀可經治療或自行緩解

4.癥狀不典型者(如無明顯喘息和體征)至少應有下列三項中的一項陽性∶（1）支氣管激發(fā)試驗或運動試驗陽性；（2）支氣管舒張試驗陽性；（3）呼氣流量峰值（PEF）日內變異率或晝夜波動率≥20％

5.除外其他疾病所引起的喘息、胸悶和咳嗽符合1～4條或4、5條者，可診斷咳嗽變異性哮喘：DiagnosisSeverityandstagingSeverity:mild,moderate,severeStaging:Chronicpersistent:weeklyChronicremission:3monAcuteexacerbationSeverityof

asthma輕癥哮喘Mildasthma中度哮喘Moderateasthma重度哮喘severeasthmaGINAupdated2014表3哮喘急性發(fā)作時病情嚴重程度的分級

臨床特點輕度中度重度危重氣短

體位

講話方式

精神狀態(tài)

出汗

呼吸頻率

輔助呼吸肌活動及三凹征

哮鳴音

脈率

奇脈

使用β2激動劑后PEF預計值PaO2（吸空氣）

PaCO2

SaO2（吸空氣）

PH步行、上樓時

可平臥

連續(xù)成句

可有焦慮尚安靜

常無

輕度增加

常無

散在，呼吸末期

<100次／min

無，<10mmHg

>80％

正常

<45mmHg

>95％

稍事活動

喜坐位

單詞

時有焦慮或煩燥

有

增加

可有

響亮、彌漫

100～120次可有

60％～80％

≥60mmHg

≤45mmHg

91％一95％

休息時

端坐呼吸

單字

常有焦慮、煩躁

大汗淋漓

常>30次／min

常有

響亮、彌漫

>120次／min

常有，

<60％或<100％

<60mmHg

>45mmHg

≤90％

不能講話

嗜睡或意識模糊

胸腹矛盾運動

減弱、乃到無

脈率變慢不規(guī)則

無，提示呼吸肌疲勞

降低

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

Managementofasthma

一、治療目標

1．達到并維持哮喘控制

2．保持正?；顒?；包括運動能力

3．維持肺功能維持在接近正常水平

4．預防哮喘急性加重5．避免哮喘藥物的不良反應

6．預防哮喘死亡，降低哮喘死亡率

PharmacotherapyofasthmaRelieverInhaledshort-acting2agonistOralshort-acting2agonistAnticholinergicsMethylxanthinesSystemicsteroidControllerInhaledsteroidInhaledlong-acting2agonistOrallong-acting2agonistLeukotrienemodifierMethylxanthinesCromonesSystemicsteroidIgEAbImmunotherapyClassificationof?2agonists作用時間Inhaledsteroid布地奈德氟替卡松二丙酸倍氯米松環(huán)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哮喘的治療-達到哮喘控制為基礎LevelsofasthmacontrolDaytimesymptoms>2/wkNightawakingRelieverneeded>2/wkActivitylimitationNone1~2ofthose3~4ofthoseWellcontrolledPartlycontrolledUncontrolledGINAupdated2014Symptomspast4wksLevelofcontrol哮喘治療與評價多數哮喘從2級開始，癥狀頻繁者3級2-4wk復診，后1-3月復診哮喘評價：良好控制/部分控制/未控制達到控制后維持3月后減量激素減量50%低劑量改為qd聯(lián)合用藥者，減激素50%哮喘控制標準-癥狀控制控制級別日間哮喘癥狀>2次/周夜間哮喘癥狀控制癥狀藥物>2次/周哮喘引起活動受限無任何一項出現一到二項出現三到四項良好控制部分控制未控制GINAupdated2014過去4周癥狀哮喘升級治療持續(xù)升級（2-3月）：初始治療反應差短期升級（1-2周）：病毒感染、季節(jié)過敏原日間調整：含福莫特羅制劑，維持、緩解方案哮喘長期治療方案哮喘教育環(huán)境控制按需使用速效2-激動劑按需使用速效2-激動劑可選擇的控制藥物選用一種選用一種在第三級基礎上，選用一種或多種在第四級基礎上，加用一種低劑量ICS低劑量ICS加長效2-激動劑中/高劑量ICS加長效2-激動劑口服糖皮質激素(最小劑量)白三烯調節(jié)劑/茶堿中/高劑量ICS白三烯調節(jié)劑抗IgE治療低劑量ICS加白三烯調節(jié)劑緩釋茶堿低劑量ICS加緩釋茶堿第一級第二級第三級第四級第五級升級降級5.FromtheGlobalStrategyforAsthmaManagementandPrevention,GlobalInitiativeforAsthma(GINA)2011.Availablefrom:/.控制部分控制未控制急性加重控制水平維持治療并明確最低治療級別考慮升級治療，已達到控制升級治療直至達到控制按急性加重治療治療措施治療級別降級升級第1級第2級第3級第4級第5級降級升級OthertherapiesAvoidanceoftriggersImmunotherapyEducationOxygentherapySaO2>92%Bronchodilatortherapy:SABA+iprotropiumEpinephrineIHSteroidtherapy:methylprednisone40-160mg/dManagementofacid-baseandelectrolytedisturbanceFluidtherapy:2500ml/dAntibiotictherapyManagementofcomplicationManagementofsevereexacerbation-3ManagementofAsthmaExacerbationsinAcuteCareSettingOverallcontrolSymptomscontrolNormalactivityReducefuturerisks：AsthmaattackFixedairflowlimitationSideeffectsOverallcontrolofasthmaGINAupdated2014BatemanED,etal.JAllergyClinImmunol.2010;125(3):600-8.SummaryInflammatoryairwaydiseasewithBHRTriggersorenvironmentalexposureAsthmaticsymptomsAntiasthmaticdrugsManagementofasthma(includingexacerbation)INTERSTITIALLUNGDISEASE彌漫性間質性肺病肺間質肺間質包含肺泡上皮與肺血管內皮的空間，包含多種細胞如成纖維細胞、成纖維細胞母細胞、巨噬細胞，還有基質包括膠原、彈力蛋白和糖蛋白).Interstitium肺間質的概念

肺臟基本功能單位與肺間質肺容積縮小彌散量降低低氧血癥呼吸困難間質性肺病的概念間質性肺病（InterstitialLungDisease，ILD）為累及肺泡壁以及肺泡周圍組織和其周圍結構的非感染、非腫瘤性一組疾病。

ILD可累及細支氣管與肺實質，又被稱為彌漫性實質性肺病(DiffuseParenchymalLungDisease，DPLD)間質性肺病的共性肺容積縮小肺彌散功能減低呼吸困難，特別運動后運動后或疾病低氧血癥好影像學彌漫性改變病理學表現為肺實質/間質不同程度纖維化/炎癥已知原因的DPLD職業(yè)性肺病藥物性肺病結締組織疾病相關性ILD特發(fā)性間質性肺炎（IIP）肉芽腫所致DPLD結節(jié)病過敏性肺炎肉芽腫并血管炎少見DPLD肺泡蛋白沉積癥肺出血-腎炎綜合征淋巴管平滑肌肌瘤病朗格漢斯組織細胞增生癥特發(fā)性含鐵血黃素沉著癥慢性嗜酸細胞性肺炎彌漫性肺間質疾?。―PLD）間質性肺病的分類癥狀與體征

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,(杵狀指)amarkerofadvancedfibroticdisease,ofteninIPF;癥狀與體征RespiratorySymptomsandSigns實驗室檢查

LaboratoryInvestigationAutoantibodies(rheumatoidfactor,antinuclearfactors)CVD,IPF,WG,MPA,NSIPSerumangiotensinconvertingenzyme:SarcoidosisEosinophilia:EosinophilicpneumoniaAntibasementmembraneantibody:Antineutrophiliccytoplasmicantibody:WG,MPAIncreasedserumLDH:IPF影像學檢查

RadiographicFeaturesGround-glassopacification毛玻璃影Reticularornodular網格/結節(jié)影Honey-combing蜂窩影Reticularpattern網格影Nodule-結節(jié)影Honey-combing蜂窩肺IPFGroundglassopacity(GGO)pulmonaryalveolarproteinosisBronchoalveolarLavage肺泡灌洗Normal：細胞總數5~10x106，巨噬細胞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經氣管鏡肺活檢Percutaneouslungbiopsy經皮肺活檢Video-assitedthoracosopiclungbiopsy胸腔鏡活檢Openlungbiopsy開胸肺活檢DiagnosisThyerapyAvoidanceofexposureSteroidtherapyAntifibrotictherapySymptomatictherapyOthersIDIOPATHICPULMONARYFIBROSIS(IPF)特發(fā)性肺纖維化IDIOPATHICINTERSTITIALPNEUMONIA(IIP)

特發(fā)性間質性肺炎IIPsareagroupofdiffuseparenchymallungdiseases(DPLDs),agroupalsodescribedasinterstitiallungdiseasesTheIIPsareaheterogeneousgroupofnonneoplasticdisordersresultingfromdamagetothelungparenchymabyvaryingpatternsofinflammationandfibrosis.Idiopathicindicatesunknowncauseandinterstitialpneumoniareferstoinvolvementofthelungparenchymabyvaryingcombinationsoffibrosisandinflammation,incontrasttoairspacediseasetypicallyseeninbacterialpneumonia.特發(fā)性間質性肺炎（IIP）特發(fā)性肺纖維化（IPF/UIP）呼吸性細支氣管炎伴間質性肺?。≧BILD）隱原性機化性肺炎（COP）脫屑型間質性肺炎（DIP）急性間質性肺炎（AIP）非特異性間質性肺炎(NSIP)淋巴細胞間質性肺炎(LIP)間質性肺病的分類主要IIP少見

IIP未能分類的IIP特發(fā)性胸膜肺實質的彈力纖維增生癥AmJRespirCritCareMedVol188,Iss.6,pp733–748,Sep15,2013ClassificationsofIIPs特發(fā)性間質性肺炎的病理學特征Idiopathicpulmonaryfibrosis(IPF)isdefinedasaspecificformofchronic,progressivefibrosinginterstitialpneumoniaofunknowncause,occurringprimarilyinolderadults,andlimitedtothelungs.Itischaracterizedbyprogressiveworseningofdyspneaandlungfunctionandisassociatedwithapoorprognosis.IPFasadistinctclinicalentityassociatedwiththehistologicappearanceofusualinterstitialpneumonia(UIP).IPF-DefinitionPotentialRiskFactorsCigarettesmokingEnvironmentalfactorMicrobialagentsGastroesophagealrefluxClinicalFeaturesSymptoms&SignsExertionaldyspneaCoughBasilarcrackle（Velcro啰音）HRCT診斷UIP征象UIP征象(所有4項)可能UIP征象(所有3項)不符合UIP征象(任何1項)胸膜下、基地分布網格樣改變蜂窩肺+伴支氣管擴張無不符合UIP征象胸膜下、基地分布網格樣改變無不符合UIP征象上或中肺野分布支氣管周圍分布廣泛磨玻璃陰影為主廣泛微結節(jié)分散囊樣病變彌漫馬賽克征肺支氣管葉、段實變SubjectedtoexternalreviewDEFINITIONOFUIPPATTERNInconsistentwithUIPpatternDiagnosisofIPFIPF診斷標準

DiagnosticCriteria1.除外其它已知原因ILD(如室內或職業(yè)性環(huán)境暴露，結締組織病、藥物毒性等).2.HRCT具備典型UIP特征無需性外科肺活檢。3.不典型需要結合HRCT及外科活檢病理特征。肺功能、癥狀、體征---輔助作用AcuteExacerbationofIPF（AEIPF）CriteriaforAEIPF:unexplainedworseningofdyspneawithin1month,Hypoxemianewradiographicalveolarinfiltratesabsenceofanalternativeexplanationinfectionpulmonaryembolismpneumothoraxheartfailure.TherapyforIPFIPF–Evidence-BasedTreatment:Strongrecommendationagainsttheuse:Corticosteroidmonotherapy(verylow)Colchicine(verylow)秋水仙堿CyclosporineA(verylow)環(huán)孢霉素Combinedcorticosteroidandimmune-modulatort