闭塞性细支气管炎 课程课件讲义

PPT内容可自行编辑闭塞性细支气管炎主讲：XXXX凡大医治病，必当安神定志，无欲无求，先发大慈恻隐之心，誓愿普救含灵之苦。--孙思邈开始上课！PPT内容可自行编辑阻塞性肺疾病COPD哮喘其他阻塞性肺病上气道阻塞支气管扩张细支气管炎囊性肺纤维化大疱性肺疾病EplerGR.Constrictivebronchiolitisobliterans:thefibroticairwaydisorder.ExpertRevRespMed.2007;1(1):139–147.Thetermbronchiolitisobliteranshasbeenusedbycliniciansformorethanahundredyearsandalmostalwaysreflectsthefibrosing,constrictive,pathologicallesion.不同病理，不同结局闭塞性细支气管炎的病理分类Pathologistsmayseetwodistinctivelesions(Histologically,

proliferativebronchiolitisandconstrictivebronchiolitis)that,inturn,thetwolesionsarehaveadifferentclinicalcourseandresponsetotreatment增生性细支气管炎缩窄性细支气管炎虽均为BO，但两种不同的病理类型的临床过程与治疗反应明显不同增生性细支气管炎：病理学Proliferativebronchiolitis

isaninflammatorybronchiolitischaracterizedbyintraluminalpolypoidconnectivetissuemassesofmyxoidfibroblastictissuewhichresemblesgranulationtissuethatarisesfromwithinthebronchioles.1Centralclustersofmononuclearinflammatorycellsmaybefoundinthesepolypoidmasses.Thistypeofbronchiolitisincludesorganizedpolypoidgranulationinflammatorytissueinthedistalbronchioleairways,respiratorybronchioles,alveolarducts,andalveoliintheformofBOOP17AdditionaldistinctivehistologicalfindingswithproliferativebronchiolitisassociatedwithBOOPincludenodisruptioninthelungarchitecture,interstitialfibrosis,absenceoftractionbronchiectasis,orhistologicalhoneycombing(Fig.51-2).增生性细支气管炎细支气管腔内息肉样结缔组织和粘液样成纤维组织形成，类似于肉芽组织。息肉样组织中可见成簇的单个核炎性细胞浸润本型细支气管炎在远端细支气管、呼吸性细支气管和肺泡管内可见以BOOP形式表现的机化性息肉样肉芽组织病理学无肺结构破坏，间质纤维化，无牵拉支气管扩张和蜂窝肺范围：至远端小支气管并填充肺泡EplerGR.Bronchiolitisobliteransorganizingpneumonia(BOOP),25years.ExpertRevRespirMed.2011;5(3):353–361.缩窄性细支气管炎：病理学Constrictivebronchiolitis

isafibrotic,concentricbronchiolitislesionwithorwithoutcompleteobliteration(Fig.51-3).Thislesionisusuallyseeninthemidtodistalareaofbronchiolesanddoesnotextendintotherespiratorybronchiolesoralveoli.Thelesionischaracterizedbyaperibronchiolarfibroticprocessthatsurrounds,ratherthanfills,

thelumen,resultinginextrinsiccompressionandobliterationoftheairway.3Thereismuralthickeningbysubmucosalcollagenousfibrosiswithprogressiveconcentricnarrowingassociatedwithluminaldistortion,mucusstasis,andchronicinflammation.18Constrictivebronchiolitiswascalled“fibrosingbronchiolitis”intheGermanpathologyliterature.19缩窄性细支气管炎为细支气管炎同心园性周围纤维化病灶，导致细支气管中或远端区域部分或完全阻塞。不累及呼吸性细支气管或肺泡。病理特点：围绕细支气管周围的纤维化改变，并不填充管腔，而是由外周向心性压迫支气管甚至导致管腔闭塞细支气管粘膜下胶原纤维化导致管壁增厚、管腔变形、粘液淤积和慢性炎症，进而气道呈进行性同心性狭窄故德国病理学文献称之为“纤维化性细支气管炎”VisscherDWetal.Bronchiolitis.Thepathologist’sperspective.ProcAmThoracSoc.2006;3:41–47.闭塞性细支气管炎（吸入性）的影像组织学

---小叶中心结节及树芽征正常细支气管CT不能分辨细支气管损伤的主要影像：直接影像：

1小叶中央结节

2分枝状线样密度增高影（树芽征）

3细支气管扩张间接影像：马赛克征（airtrapping）马赛克征象：正常健康成年人空气潴留的发生率不一定马赛克征象或空气潴留都是病理性的，要结合临床表现为孤立性小叶性空气潴留（每层1~2个）约占正常健康人空气潴留的50%：通常在重力依赖部位；随年龄增长发生率而增加（所谓老年肺问题）表现为肺段或肺叶空气潴留约占8%BO的临床分类1特发性BO

（IdiopathicBronchiolitisObliterans）noobviousincitingagentorassociatedsystemicdisorderThisdisordercontinuestobeexceedinglyrare.Symptomsbeginwithanonproductivecough,andshortnessofbreathdevelopslater.Physicalexaminationshowsnowheezingbutmaydemonstrateanunusualfindingofearlyinspiratorycrackles.Thecracklesoccurearlybecauseofthescarringaroundthemidbronchioleairways,causingsnappingclosureoftheairwaysandresultantcracklingsoundPulmonaryfunctionstudiesshowirreversibledecreaseintheFEV1andFEV1/FVCwithnoimprovementafterbronchodilatorinhalation.Thediffusingcapacityishighlyvariable,fromincreased,tonormal,tomarkedlydecreased.患者无诱发因素和系统性病变本病属极其罕见开始症状：干咳、继之：气短体检：无哮鸣音，可闻及吸气爆裂音爆裂音：由于细支气管周围疤痕重构，顺应性低，吸气时关闭气道突然打开时不能适应性扩张而产生的声音。并非气流冲击气道分泌物所致FEV1和FEV1/FVC不可逆下降，吸入支气管扩张剂亦无改善肺弥散功能表现无特异性。可增加、正常、和显著降低特发性BO

（IdiopathicBronchiolitisObliterans）Thechestroentgenogramisoftennormalorshowshyperinflation.High-resolutionchestCTscansduringinspirationandexpirationcanbehelpfulforestablishingadiagnosis(Fig.51-1).Forexample,……hadanormalchestCTscanintheinspiratorystudy,buttheexpiratorystudyshowedextensivelobularairtrapping.21Theseexpiratoryimagesshowlow-attenuationareasinthesecondarypulmonarylobules,

resultinginatypicalmosaicpatternwithscatteredareasoflowattenuation.Additionalthin-sectionCTfindingsincludeconstrictionofthepulmonaryvesselswithinthelowattenuationareas,expiratoryairtrapping,bronchialdilation,andsometimes,centrilobularnodulesorbranchinglineardensities.22胸片多正常或显示通气过度表现。吸气或呼气位HRCT有助于诊断。吸气位正常的患者，其呼气位CT可见广泛小叶气体陷闭（马赛克灌注）呼气位显像示次级肺小叶（SPL）的低衰减区域，从而形成典型的散在低衰减区域分布的马赛克征象薄层CT有时可见：低密度区肺血管收缩、呼气相气体陷闭、支气管扩张，小叶中心结节。特发性BO:治疗Treatmentconsistsofhigh-dosecorticosteroidssuchasprednisonewithaninitialdoseof60mgdaily,followedbylower-dosetherapyforusuallyoneyearinpatientswhorespond.Forthosewhodonotrespondbythreemonths,corticosteroidsarediscontinuedandemployedforlife-threateningexacerbations.Immune-suppressiontreatmentcanbeutilizedandlungtransplantationforindividualswithlife-threateningandseveredisease.Patientswhosurvivetheinitialepisodemaystabilizeforseveralyearsorprogresstoend-stageairflowdiseaseandcorpulmonale.23高剂量激素治疗：初始强的松剂量：对激素反应好者：60mg/d，逐步减量，低剂量维持一年激素反应差者：激素治疗3个月。对威胁生命的恶化重症患者仍应激素治疗免疫抑制剂治疗可考虑应用。重症者可考虑肺移植从最初重症发作存活下来的患者，病情可稳定或进展为肺心病特发性BO：病例报告a43-year-oldwomanhadidiopathicbronchiolitisobliteransfor24yearsandshowedrelentlessprogressionofairwayobstructionwith19admissionsforrespiratoryfailure.24Theautopsyinthispatientshowedcompleteobliterationofsmallerairways.TheFEV1decreasedfrom1.06Lto0.40Lterminally.Myongetal.25describedthreewomenaged41to54whodevelopedcoughandprogressiveshortnessofbreathduring6monthsto10years;lungtissueshowedconstrictivebronchiolitiswithbronchiolarairwayobliteration.Thethin-sectionCTscansshowedlow-attenuationchangesofthemosaicpattern.Nonerespondedtocorticosteroidtreatment.Onewomandied8monthsafterthediagnosisfromlymphomaandtheothertwowerestable.43岁女性。患特发性BO24年，因气道阻塞持续进展曾19次住院。尸检呈小气道完全阻塞。FEV1从1.06L最终降至0.40L一组3例女性BO报告：41～54岁；咳嗽/呼吸困难6个月至10年。组织病理学为缩窄性阻塞性支气管炎。HRCT示马赛克灌注的低衰减图像。均对激素治疗无反应。一例诊断后8个月死于淋巴瘤，余2例稳定。参考文献：NobleMI,FoxB,HorsfieldK,etal.Obliterativebronchiolitiswithatypicalfeatures:CTscanandnecropsyfindings.EurRespirJ.1993;6(8):1221–1225.MyongNH,ShinDH,LeeKY.Aclinicopathologicstudyonthreecasesofconstrictivebronchiolitis.JKoreanMedSci.2001;16(2):150–1542毒性烟雾吸入性BO

（ToxicFumeBronchiolitisObliterans）Toxicfumebronchiolitisobliteransisathree-phaseresponsedisease.Theexposureusuallyoccursfromanaccidentalexplosion，resultinginnose,throat,andeyeirritationwithnomajorrespiratory

symptoms.Phaseoneisanasymptomaticlatencyperiodof6

to12hoursafterexposure.Phasetwobeginssuddenlywithacute

onset

respiratoryfailureandacuterespiratorydistresssyndrome.

Successfultreatmentresultsinanotherasymptomaticlatencyperiod

of7to10days.Phasethreethenoccursasconstrictivebronchiolitis

withirreversibleairflowobstruction,progressiveshortnessof

breath,andchronicrespiratoryfailure.

毒性烟雾吸入性BO一般发生于意外暴露，而导致鼻、咽喉、眼睛的刺激毒性烟雾吸入性BO,分三个反应阶段阶段：第一阶段：暴露后6~12小时的无症状潜伏期第二阶段：发生急性呼吸衰竭和呼吸窘迫。若治疗及时成功可接着会有7~10天的无症状潜伏期第三阶段：然后可能出现不可逆气流阻塞的缩窄性细支气管炎，进行性呼吸困难，继之慢性呼吸衰竭毒性烟雾吸入性BO：毒性物质

（ToxicFumeBronchiolitisObliterans）Thisdisorderoccursafteraccidentalexposuresto:sulfurdioxidefumes,nitricacidfumes,andnitrogendioxideinfreshlyfilledcornsilos.thionylchlorideMustardgasattackasulfur-minefire（soldiersreturningfromIraqandAfghanistanandfoundacommonexposuretoasulfur-minefirein2003）Diacetylappearstobeacommonexposureamongartificialbutter

flavoringworkerswhodevelopedconstrictivebronchiolitis.A

reportofninemicrowavepopcornfactoryworkersshowedairflow

obstructionamongthemixers,andbiopsyofsomeindividuals

showedconstrictivebronchiolitis.33

二氧化硫硝酸新鲜充入锥形仓的二氧化氮氯化亚砜芥子气硫矿井大火（伊拉克和阿富汗战争）二乙酰基似乎是人造奶油调味工人发生缩窄性细支气管炎的常见致病暴露物质微波爆米花厂的搅拌过程可能导致气流阻塞，其中部分患者活检病理示缩窄性细支气管炎毒性烟雾吸入性BO：毒性物质的特例1

（ToxicFumeBronchiolitisObliterans）Kingetal.30reportedconstrictivebronchiolitisamong38USsoldiersreturningfromIraqandAfghanistanandfoundacommonexposuretoasulfur-minefirein2003among28ofthem.A42-year-oldpoliceofficerexposedtothedustinthecloudfromtheNewYorkCityWorldTradeCenterdisasterofSeptember11,2001developeddecreasedFEV1andFEV1/FVCinApril2002.31Thelungbiopsyshowedregionsofconstrictivebronchiolitis.Hewastreatedwithoralcorticosteroidtherapyandazithromycin.ByApril2003,pulmonaryfunctionstudieshadreturnedtonormalvalues.King报告38例从伊拉克和阿富汗返回的美国士兵患BO，其中28例2003年暴露于硫化物大火环境的2001年9.11现场警察，42岁。2002年3月，FEV1下降，经肺活检确诊BO以激素和阿奇霉素治疗一年后肺功能恢复正常KingMS,EisenbergR,NewmanJH,etal.ConstrictivebronchiolitisinsoldiersreturningfromIraqandAfghanistan.NEnglJMed.2011;365(3):222–230.MannJM,ShaKK,KlineG,BreuerFU,MillerA.WorldTradeCenterDyspnea:bronchiolitisobliteranswithfunctionalimprovement.AmJIndMed.2005;48:225–229.毒性烟雾吸入性BO：毒性物质的特例2

（ToxicFumeBronchiolitisObliterans）Therehasbeenareportofbronchiolitisobliteransfrommustardgasoccurringfromachemicalwarfareattackina37-year-oldmanwhohadcough,sputumproduction,shortnessofbreath,andairflowobstructionfor14yearsaftertheexposure.28Later,investigators29usedhigh-resolutionchestCTscanfindingsforthediagnosisofbronchiolitisobliteransinagroupofindividualsexposedtothesamemustardgasattack.Theytreated18individualswithbronchodilatortreatmentand18withinterferongamma-1band7.5mgofprednisolone.PatientshadbaselineFEV1valuesof49.3%and48.7%predicted,respectively.Bothgroupsimprovedafter6monthsoftreatment;however,thegrouptreatedwithinterferongammahadasignificantlyhigherposttreatmentFEV1of66.3%comparedto57.3%forthegrouptreatedwithbronchodilators(p=0.001).一例37岁男性在化学战中暴露芥子气，14年后出现干咳、呼吸困难和气流阻塞研究者对有同样芥子气暴露史的患者进行HRCT扫描，发现符合BO诊断。分别以支气管扩张剂和r干扰素+7.5mg强的松两组治疗，患者的基础FEV1占预计值分别为的49.3%和48.7%半年后两组均改善，但干扰素组治疗后FEV1为66.3%，明显高于支气管扩张剂治疗组的57.3%ThomasonJW,RiceTW,MilstoneAP.Bronchiolitisobliteransinasurvivorofachemicalweaponsattack.JAMA.2003;290(5):598–599.3呼吸道感染后BO

Post-RespiratoryInfectionBronchiolitisObliteransPost-respiratoryinfectionbronchiolitisobliteransmayoccurafteradenoviruspneumonia,influenzaorparainfluenzapneumonia,orafterMycoplasmapneumonia.Coughdevelopsseveraldaysaftertheinitialinfection.Chestradiographsmayshowdiffusereticulonodularopacitiesearlybutarenormalorshowhyperinflationlate.Expiratoryhigh-resolutionchestCTscansshowlow-attenuationmosaicpattern.Tissueshowsconstrictivebronchiolitiswithextensivescarringthatobliteratesmanyofthebronchioles,correspondingclinicallywithsevereairflowobstruction.Atthisstage,thelesionisnotresponsivetocorticosteroidmedication.Lungtransplantationhasbeenutilizedforseverepost-Mycoplasmapneumoniabronchiolitisobliterans腺病毒肺炎、流感或副流感病毒肺炎，甚至肺炎支原体肺炎后可发生感染后阻塞性支气管炎。临床表现：最初感染后数天内出现咳嗽。胸部平片早期可呈弥漫性网状结节影，后期可正常或膨胀过度（透亮度增强或空气潴留）。HRCT示低衰减马赛克征组织学显示广泛瘢痕形成的缩窄性细支气管炎，阻塞许多细支气管，临床表现为严重气流阻塞。此时，对激素治疗无反应。严重肺炎支衣原体肺炎后BO接受肺移植术的病例已有报道DaxbkFetal.AcaseoflungtransplantationfollowingMycoplasmapneumoniaeinfection.EurJClinMicrobiolInfectDis.2002;21(4):318–322.）Swyer-James综合征（SJS）：单侧透明肺病毒性肺炎后局限性透明肺1953年最早Swyer和James报道1例6岁儿童。1954年Macleod相续报道9例故又称Swyer-James-Macleod综合征或Macleod综合征。亦称单侧透明肺,单侧半透明肺或单侧获得性肺叶气肿最初认为与先天发育有关，但不久即被否定,因为其气管的分级和肺血管的分支数目并无异常。现认为SJS本质上是一种感染所致的闭塞性细支气管炎。婴幼儿期严重的肺部感染是本病的病因。腺病毒、麻疹、支原体、百日咳、结核、流感病毒等是其病原体。Swyer–Jamessyndromebronchiolitisobliteransisnotcongenitalinoriginbutissecondarytorespiratoryinfectionoccurringduringinfancy4结缔组织病相关性BO

ConnectiveTissueBronchiolitisObliteransConnectivetissuebronchiolitisobliteransoccursmostcommonlyinrheumatoidarthritisandhasbeenreportedinscleroderma,lupuserythematosus,andSjogren’ssyndrome.37,38Rheumatoidarthritis-relatedconstrictivebronchiolitisoftenhasapoorprognosis.Among25individualswithrheumatoidarthritisandbronchiolitisobliterans,mosthadsevereairflowobstruction,oftenwithanFEV1lessthan1L,andtheprocesswasnotresponsivetocorticosteroids.39Theoutcomewaspoor,aschronicrespiratoryfailureoccurredin40%ofthepatients;fourpatientsdied.结缔组织闭塞性细支气管炎最常见于类风湿性关节炎。此外，硬皮病、SLE和干燥综合征均有报告类风湿性关节炎所致的缩窄性细支气管炎预后常很差。有报告25例类风湿关节炎病BO中，多数患者严重气流阻塞，FEV1低于1L，且激素疗效很差。40%发生呼衰，4例死亡（DevouassouxG,CottinV,LiotéH,etal.Characterisationofsevereobliterativebronchiolitisinrheumatoidarthritis.EurRespirJ.2009;33:1053–1061）WhiteES,TazelaarHD,LynchJP.Bronchiolarcomplicationsofconnectivetissuediseases.SemRespCritCareMed.2003;24(5):547–565.ParambilJG,YiES,RyuJH.Obstructivebronchiolardiseaseidentifiedinthenon-transplantpopulation.Respirology.2009;14:443–448.5药物相关性BO

(Drug-relatedbronchiolitisobliterans)Drug-relatedbronchiolitisobliteranshasbeenreportedwithpenicillamineandgoldusedfortreatmentofrheumatoidarthritis.Thepenicillamine-relatedbronchiolitisobliteranshasapoorprognosis,sometimesrequiringlungtransplantationformanagement.40Fatalbronchiolitisobliteranshasbeenreportedina12-year-oldgirlwithjuvenilerheumatoidarthritisaftera6-monthcourseofintramusculargold.41Althoughcauseandeffectaredifficulttoconfirmforbothoftheseagents,patientsreceivingthesemedicationswhodevelopunexplainedcoughordyspneaneedtobeevaluatedforthepossibilityofbronchiolitisobliterans用于类风湿关节炎治疗的青霉胺和金制剂可导致BO。青霉胺诱导的BO预后极差，有时需要肺移植治疗一例12岁少年类风湿关节炎患者在应用金制剂半年后发生致命性细支气管炎。尽管上述两药引起BO的作用机理和原因不清，但如果接受该类药物治疗的患者出现无法解释的咳嗽和呼吸困难需要对是否发生BO进行评价6骨髓移植后BO

Bone-MarrowTransplantationBronchiolitisObliteransBone-marrowtransplantationbronchiolitisobliteransoccursmuchlessfrequentlyasallogeneicstem-celltransplantationhasbecomesocommon;however,bronchiolitisobliteransmayoccurinupto9%ofallogeneicbone-marrowrecipients.42Bronchiolitisobliteransoccursonlyaftergraft-versus-hostreaction,andtherefore,israrelyseenafterautologousbone-marrowtransplantation.Ascomplicationsofchronicgraft-versus-hostdevelopafter100days,bronchiolitisobliteransisusuallyseen6to12monthsaftertransplantation.Donortype-2T-helperlymphocytesappeartobetheprimarymediators.Thepathologicallesionisconcentricbronchiolarfibrosistypicalofconstrictivebronchiolitis.Thereisgenerallyapoorresponsetocorticosteroidtherapy;mortalityrangesfrom40%to100%.42Livingdonorlobarlungtransplantationhasbeenusedsuccessfullyforbone-marrowtransplant-relatedbronchiolitisobliterans.43由于同种异体造血干细胞移植增加，因此骨髓移植相关性BO发生明显减少但约9%同种异体骨髓移植的受体可发生BOBO仅见于移植物抗宿主反应后，因此罕见于自体骨髓移植者。骨髓移植100天后发生慢性移植物抗宿主反应，BO通常发生于移植后6~12个月。供体2型T辅助细胞似乎起主要作用。病理呈中心细支气管纤维化，典型的缩窄性细支气管炎表现激素疗效差，病死率40%~100%。供体肺叶肺移植已成功用于骨髓移植相关性BO患者SanoY,DateH,NagahiroI,AoeM,ShimizuN.Living-donorlobarlungtransplantationforbronchiolitisobliteransafterbonemarrowtransplantation.AnnThoracSurg.2005;79:1051–1052.ChienJW,DuncanS,WilliamsKM,PavleticSZ.Bronchiolitisobliteranssyndromeafterallogeneichematopoieticstemcelltransplantation–anincreasinglyrecognizedmanifestationofchronicgraft-versus-hostdisease.BiolBloodMarrowTransplant.2010;16(1Suppl):S106-S114.7干细胞移植后BO

Stem-CellTransplantBronchiolitisObliteransInastudyof2087allogeneicstem-celltransplantationrecipientsfrom1994to2005,therewere57(2.8%)whodevelopedbronchiolitisobliterans.45Theprevalenceofbronchiolitisobliteransrangesfrom2%to3%amongallallogeneicrecipientsto6%amongthosewhodevelopchronicgraft-versus-hostdisease(cGVHD)theincidenceofbronchiolitis

obliteranswhenusinganannualizedrateofdeclineinFEV1

of5%.ThosewithcGVHDhadarateof30%,butmoreimportantly,theyhadamortalityrateof40%at10years.cGVHDisthemajorriskfactorforbronchiolitisobliterans,ashighas80%ofpatientswithbronchiolitisobliteransareprecededwithcGVHD一组2087同种异体干细胞移植的受体（1994~2005，57例（2.8%）发生闭塞性细支气管炎文献报告的在所有同种异体干细胞移植患者，BO的总体患病率于2%~3%。在cGVHD患者可高达6%左右，明显被低估发病率：若以年FEV1下降5%为标准，10年BO的发病率为30%，而病死率达40%。

cGVHD是BO主要的高危因素。约80%的BO患者之前患有cGVHDChienJW,.Bronchiolitisobliteranssyndromeafterallogeneichematopoieticstemcelltransplantation–anincreasinglyrecognizedmanifestationofchronicgraft-versus-hostdisease.BiolBloodMarrowTransplant.2010;16(1Suppl):S106-S114.干细胞移植后BO

Stem-CellTransplantBronchiolitisObliteransPreventivetreatmentofstem-celltransplantationbronchiolitisobliteransconsistsofearlyandaggressivetreatmentofrespiratoryinfectionsandcGVHDTreatmentincludeshigh-dosesystemiccorticosteroidsandimmunosuppressionwithcalcineurininhibitors,sirolimus,azathioprine,andanti-thymocyteglobulin.Prognosiscontinuestobepoordespitetreatmentandsupportivecare,withanoverallsurvivalrateof44%at2yearsand13%at5years.44干细胞移植BO的预防治疗由呼吸道感染和慢性GVHD的早期和积极治疗组成。包括：大剂量糖皮质激素；钙调神经磷酸酶抑制剂西罗莫斯硫唑嘌呤；抗胸腺细胞球蛋白。尽管治疗，预后亦较差。总存活率：2年44%，5年13%ChienJW,DuncanS,WilliamsKM,PavleticSZ.Bronchiolitisobliteranssyndromeafterallogeneichematopoieticstemcelltransplantation–anincreasinglyrecognizedmanifestationofchronicgraft-versus-hostdisease.BiolBloodMarrowTransplant.2010;16(1Suppl):S106-S114.干细胞移植后BO

Stem-CellTransplantBronchiolitisObliteransThetimeintervalbetweentransplantationandbronchiolitisobliteransrangedfrom83daysto907dayswithamediantimeof335days.Acutegraft-versus-hostdiseasewasnotfoundtobeariskfactor,whereascGVHDwasasignificantriskfactor.Thedevelopmentofbronchiolitisobliteranswasrelatedtothestem-cellsource,withrelatedperipheralbloodstem-celltransplantation(3.83%)thehighest.Unrelatedbone-marrowtransplantation(2.91%)andcord-bloodtransplantation(2.65%)werelower,withrelatedbone-marrowtransplantation(1.62%)thelowest.Theoutcomeamongthese57patientsshowedthat8(16.7%)improved,10(21.7%)showednochange,and28(60.9%)died;thecauseofdeathwasrespiratoryfailurein17(60.7%).干细胞移植与发生BO的时间间隔83~907天，中位时间是335天。急性GVHD不是BO危险因素，cGVHD是BO的高危因素。BO与干细胞的来源相关联：相关外周血干细胞移植BO，3.83%:最高不相关（unrelated）骨髓移植：2.91%相关（Related）骨髓移植，最低：1.62%脐带血移植：2.65%一组57例移植后BO患者：8例缓解（16.7%）；10例无变化（21.7%）；28例死亡（60.9%）。17例死亡原因系呼吸衰竭（60.7%）DAH:弥漫性肺泡出血PERDS（peri-engraftmentrespiratorydistresssyndrome）：围植入期呼吸窘迫综合征IPS（Idiopathicpneumoniasyndrome）：特异性肺炎综合征.移植后肺部非感染并发症NoninfectiousPulmonary

ComplicationsintheHSCT

Recipient干细胞移植分三期：I期：植入前期（pre-engraftmentphase）0~30天II期：植入早期（earlypost-engraftmentphase）30~100天III期：植入后期（lateposttransplantphase）＞100天干细胞移植后BO

Stem-CellTransplantBronchiolitisObliteransExtracorporealphotodynamictherapy

Mesenchymalstem-celltreatmentwas.Thismaybeaneffectivetreatmentonacase-by-casebasis,butatthistime,therearetoomanyunknownvariablesinvolvedtoadvocateitsuse(e.g.,absenceoflargescalestudies,availabilityofastandardizedsourceofmesenchymalcells,andanunderstandingofpotentialcarcinogeniceffects).体外光动力治疗间充质干细胞移植因缺乏大规模研究、间充质细胞标准化来源的可变性和是否有潜在致癌作用等均有待进一步研究。8肺移植BO

LungTransplantBronchiolitisObliteransTheterminologyhasbecomethebronchiolitisobliteranssyndrome(BOS),whichisaclinicalclassificationbasedonFEV1.TheclassificationwasdevelopedbecauseBOSisacommonproblemamonglungtransplantationrecipients.Theapproacheliminatestheneedforlow-yieldtransbronchialbiopsyorotherinvasiveproceduretoestablishadefinitivediagnosisofbronchiolitisobliterans.Aclinicalseverityclassificationhasbeenused.49ANationalInstitutesofHealth(NIH)diagnosticclassificationofBOSincGVHD50hasalsobeendeveloped(Table51-4).闭塞性细支气管炎综合征（BOS）:BOS通常仅指移植后闭塞性细支气管炎系肺移植受体的常见合并症根据FEV1分类:FilipovichAH,WeisdorfD,PavleticS,etal.NationalInstitutesofHealthconsensusdevelopmentprojectoncriteriaforclinicaltrialsinchronicgraft-versus-hostdisease:I.Diagnosisandstagingworkinggroupreport.BiolBloodMarrowTransplant.2005;11(12):945–956.肺移植BO

LungTransplantBronchiolitisObliteransBOSremainsacommonprocesswithdevastatingconsequences.51Atleastone-halfoflungtransplantationrecipientssurviving5yearswilldevelopairflowobstruction.BOShasnotdeclinedsignificantlyinincidence,andnototallyeffectivetreatmentisavailable.Lungtransplantrecipientswhohadmorethanthreeepisodesofacuterejectioninany12-monthperiodeventuallyhada100%incidenceofbronchiolitisobliterans.52Bothtypesofacuterejectionareinvolved,includingacutevascularrejectionandlymphocyticbronchiolitis.Gradualonsetofprogressiveshortnessofbreathisthemostcommonsymptom.Earlyinspiratorycracklesmaybeheard.ThedecreasesinFEV1maybemildtosevereandlife-threatening.Thechestx-rayisoftennormal;however,thecombinationofnewlydecreasedFEV1andtheexpiratoryhigh-resolutionchestCTscanshowingmosaicpatternhavevirtuallybecomediagnostic.6BOS目前依然是肺移植的一个常见并发症，预后极差。存活5年的肺移植治疗受者，至少有一半将发生气流阻塞。BOS尚无有效治疗方法。一年时间内有3次以上急性排斥反应发作的肺移植患者100%会发生BO。急性排斥反应包括急性血管排斥和淋巴细胞细支气管炎两种类型。进行性呼吸困难是主要临床症状。早期即可闻及吸气爆裂因音FEV1轻至重度降低，甚或危及生命胸部X线：常常正常。如果新出现FEV1降低加之呼气相HRCT显示马赛克征则几乎可作出诊断。肺移植BO

LungTransplantBronchiolitisObliteransPrimarygraftdysfunction(PGD)isatermusedforaprocessthatoccursduringtheinitialpostoperativephasecharacterizedbypulmonaryedemaandacuterespiratoryfailure.Thisprocesshasbeenassociatedwithhighperioperativemortalityandisariskfactorforthesubsequentseverityofbronchiolitisobliterans.53AclassificationsystemforPGD(Table51-5)hasbeenestablishedbasedonoxygenationandthepresenceofpulmonaryedema.54原发性移植物功能障碍（PGD）是肺移植术后发生急性肺水肿和呼吸衰竭的一种情况，为严重BO的高危因素。PGD分类系统如下（根据氧合和肺水肿而评价）：肺移植BO:治疗

LungTransplantBronchiolitisObliteransManagementoflungtransplantationbronchiolitisobliteransbeginswithearlyandaggressivetreatmentofacuteorganrejection,includingboththeacutevascularrejectionandlymphocyticbronchiolitis.Treatmentofbronchiolitisobliteransgenerallyincludesacalcineurininhibitor,apurinesynthesisinhibitor,andacorticosteroid.Themacrolides,suchaserythromycin,appeartobeaneffectivetreatmentinasubsetofpatientswithBOS.Thefindingofbronchoalveolarlavageneutrophilsmaydistinguishrespondersfromnonresponders.67Theprocessintherespondersisreferredtoasneutrophilicreversibleallograftairwaydysfunction(NRAD).68Extracorporealphotopheresis(ECP)appearstobeeffectiveforearlytreatm