慢性肺曲霉病诊断与管理

目录慢性肺曲霉病的定义慢性肺曲霉病的临床表现类型慢性肺曲霉病的诊断慢性肺曲霉病的管理总结第一页，共30页。目录慢性肺曲霉病的定义慢性肺曲霉病的临床表现类型慢性肺曲霉病的诊断慢性肺曲霉病的管理总结第二页，共30页。DefinitionsofCPAThemostcommonformofCPAisCCPA.Untreateditmayprogresstochronicfibrosingpulmonaryaspergillosis(CFPA).LesscommonmanifestationsofCPAincludeAspergillusnoduleandsingleaspergilloma.Alltheseentitiesarefoundinnon-immunocompromisedpatientswithpriororcurrentlungdisease.Subacuteinvasivepulmonaryaspergillosis(formerlycalledchronicnecrotisingpulmonaryaspergillosis)isamorerapidlyprogressiveinfection(<3months)usuallyfoundinmoderatelyimmunocompromisedpatients.D.DENNINGETAL.ESCMID/ERSGUIDELINES.EurRespirJ2015.第三页，共30页。目录慢性肺曲霉病的定义慢性肺曲霉病的临床表现类型慢性肺曲霉病的诊断慢性肺曲霉病的管理总结第四页，共30页。PresentbyDavidDenningECCMID10thMay2015inBarcelona慢性曲霉菌病临床表现分类ClinicalphenotypesofchronicAspergillussppdiseases单发曲霉球Single/simpleaspergilloma慢性坏死性/亚急性肺曲霉菌病Chronicnecrotizingpulmonaryaspergillosis(CNPA)orsubacuteInvasiveaspergillosis(SAI)慢性空腔性肺曲霉菌病Chroniccavitarypulmonaryaspergillosis(CCPA)慢性纤维化肺曲霉菌病Chronicfibrosingpulmonaryaspergillosis(CFPA)曲霉菌肉芽肿Aspergillusnodule(s)CCPA是最常见的CPA类型CCPA不治疗可进展为CFPA曲霉结节与单纯性曲霉肿较少见免疫功能受损患者常见SAIA第五页，共30页。CPA的分类与定义CCPA-慢性空洞型肺曲霉病;CFPA-慢性纤维性肺曲霉病;SAIA-亚急性侵袭性曲霉病/慢性坏死性/半侵袭性曲霉病分类定义单纯性曲霉肿非免疫功能受损的患者存在含有真菌球的单一肺部空洞，且血清学或微生物学证据提示曲霉属(Aspergillusspp.)感染，无症状或仅有轻微症状，在至少3个月的观察期内未出现影像学进展CCPA存在1个或多个含有≥1个曲霉球或不规则腔内结构的肺部空洞(薄壁或厚壁)，且血清学或微生物学证据提示曲霉属感染，有明显的肺部和/或系统症状，在至少3个月的观察期内出现明显的影像学进展(新空洞、空洞外周浸润增加、或纤维化增加)CFPACCPA并发出现的至少2个肺叶出现严重的纤维化破坏并导致大部分肺功能丧失。单个存在空洞的肺叶出现严重纤维化破坏仅代表影响该肺叶的CCPA。通常纤维化表现为肺部实变，但也可表现为周围出现纤维化的较大空洞曲霉结节一种少见的CPA类型，出现1个或多个形成或不形成空洞的结节。可与结核球、肺癌、球孢子菌病以及其他疾病相似，只有通过组织学检查才能确诊。尽管常出现坏死，但不会出现组织浸润。SAIA/CNPA在1-3个月内出现的侵袭性曲霉病，常发生在存在轻度免疫功能受损的患者之中，存在多种影像学特征，包括空洞形成、结节、“脓肿形成”的进展性实变等。受累肺部组织活检可见菌丝，微生物学检查结果与侵袭性曲霉病一致，特别是血液(或呼吸道液体)曲霉半乳甘露聚糖抗原阳性D.DENNINGETAL.ESCMID/ERSGUIDELINES.EurRespirJ2015.第六页，共30页。Single(simple)pulmonaryaspergillomaisasinglefungalballinasinglepulmonarycavity.Thereisnoprogressionovermonthsofobservationandveryfew,ifanypulmonaryorsystemicsymptomsandserologicalormicrobiologicalevidenceimplicatingAspergillusspp.Simpleaspergillomathatdevelopedwithinapost-tuberculouscicatricialatelectasisoftheleftupperlobewithsaccularbronchiectasis.Surgicalresectionbyvideo-assistedthoracicsurgerywasperformedbecauseofrecurrenthaemoptysisandarequirementforanticoagulanttherapy.D.DENNINGETAL.ESCMID/ERSGUIDELINES.EurRespirJ2015.第七页，共30页。CCPA,formerlycalledcomplexaspergilloma,usuallyshowsmultiplecavities,whichmayormaynotcontainanaspergilloma,inassociationwithpulmonaryandsystemicsymptomsandraisedinflammatorymarkers,overatleast3monthsofobservation.Untreated,overyears,thesecavitiesenlargeandcoalesce,developingpericavitaryinfiltratesorperforatingintothepleura,andanaspergillomamayappearordisappear.ThusserologicalormicrobiologicalevidenceimplicatingAspergillusspp.isrequiredfordiagnosis.Chroniccavitarypulmonaryaspergillosisshowingmarkedprogressionbetweena)2007andb)2012.Chestradiographspriorto2007(i.e.1990s)showed“upperlobefibrosis”,withoutafirmdiagnosis.Alargecavitywithpleuralthickeningisvisibleontheleftinbothimages,withadditionalsmallcavitiesinferiorlyin2012,andcontractionoftheleftupperlobe.Therightsideshowsintervaldevelopmentofalargecavity,withsomepleuralthickening.Neithercavitycontainsafungalball.a)b)第八页，共30页。Imagingshowingchroniccavitarypulmonaryaspergillosisshowinganaxialviewwitha)lungandb)mediastinalwindowsattheleveloftherightupperlobe.Multiplecavitiesarevisiblewithafungusballlyingwithinthelargestone.Thewallofthecavitiescannotbedistinguishedfromthethickenedpleuraortheneighbouringalveolarconsolidation.Theextrapleuralfatishyperattenuated(whitearrows).*:thedilatedoesophagusshouldnotbeconfusedwithacavity.a)b)**第九页，共30页。CFPAisoftenanendresultfromuntreatedCCPA.ExtensivefibrosiswithfibroticdestructionofatleasttwolobesoflungcomplicatingCCPA,leadingtoamajorlossoflungfunction.Usuallythefibrosisissolidinappearance,butlargeorsmallcavitieswithsurroundingfibrosismaybeseen.SerologicalormicrobiologicalevidenceimplicatingAspergillusspp.isrequiredfordiagnosis.Oneormoreaspergillomasmaybepresent.Imagingofchronicfibrosingpulmonaryaspergillosiscomplicatingchroniccavitarypulmonaryaspergillosis,whichfollowedtuberculosis,withmildchronicobstructivepulmonarydisease.Completeopacificationofthelefthemi-thoraxdevelopedbetweenFebruary1998,whenaleftupperlobecavitywithafluidlevelwaspresent,andMay1999.Multipleleftlungautopsypercutaneousbiopsiesshowedevidenceofchronicinflammation,butnogranulomasorfungalhyphae.第十页，共30页。Oneormorenodules(<3cm),whichdonotusuallycavitate,areanunusualformofCPA.Theymaymimiccarcinomaofthelung,metastases,cryptococcalnodule,coccidioidomycosisorotherrarepathogensandcanonlybedefinitivelydiagnosedonhistology.NodulesinpatientswithrheumatoidarthritismaybepurerheumatoidnodulesorcontainAspergillus.Tissueinvasionisnotdemonstrated,althoughnecrosisisfrequent.Sometimeslesionslargerthan3cmindiameterareseenandmayhaveanecroticcentre.Thesearenotwelldescribedintheliteratureandarebestdescribedas“masslesionscausedbyAspergillusspp.”.SuccessiveaxialviewswithinthelungwindowshowingAspergillusnodules,ofvariablesizeandborders,andafungusballfillingacavitywithawallofvariablethicknessinapatientwithpre-existingbronchiectasisandcicatricialatelectasisofthemiddlelobe.Aspergillusnodule(s)第十一页，共30页。Subacuteinvasiveaspergillosis(SAIA)waspreviouslytermedchronicnecrotisingorsemi-invasivepulmonaryaspergillosis.SAIAoccursinmildlyimmunocompromisedorverydebilitatedpatientsandhassimilarclinicalandradiologicalfeaturestoCCPAbutismorerapidinprogression.SAIAtypicallyoccursinpatientswithdiabetesmellitus,malnutrition,alcoholism,advancedage,prolongedcorticosteroidadministrationorothermodestimmunocompromisingagents,chronicobstructivelungdisease,connectivetissuedisorders,radiationtherapy,non-tuberculousmycobacterial(NTM)infectionorHIVinfection.PatientsaremorelikelytohavedetectableAspergillusantigeninblood,andwillshowhyphaeinvadinglungparenchyma,ifabiopsyisdone.Thechestradiographshowsalargeirregularrightupper-lobecavitarylesionthatdevelopedwithmultiplesymptomsover6weeksduringtreatmentwithsorafenib.Thepatientpresentedwithunresectablehepatocellularcarcinoma.Thecomputedtomographyscanshowsadualcavitywithmoderatelythickwalls,anexternalirregularedgeandsomematerialwithinthecavityonanalmostnormallungbackground.apatientwithhepatocellularcarcinomabeingtreatedwiththesorafenib.

a)b)第十二页，共30页。Thenewclinicaldiseaseentityofchronicprogressivepulmonaryaspergillosis.Newnomenclature,“chronic

progressivepulmonaryaspergillosis(CPPA)”fortheclinicalsyndromeincludingbothCNPAandCCPAisproposed.Itisdifficulttodistinguishbetweenthesetwoentitiesbasedontheclinicalcourseandcharacteristicsandradiologicalfindings.respiratoryinvestigation54(2016)85–91.第十三页，共30页。目录慢性肺曲霉病的定义慢性肺曲霉病的临床表现类型慢性肺曲霉病的诊断慢性肺曲霉病的管理总结第十四页，共30页。CPA:diagnosiscriteriaanddefinitions1Chronicpulmonaryorgeneralsymptomsincludingatleast1ofthefollowing(foraminimumof3monthsinduration):weightloss,productivecoughorhaemoptysis2Aprogressiveformationandexpansionofsingleormultiplepulmonarycavitationssurroundedbyawallandpossiblepleuralthickeningonradio-imaging3ApositiveresultforaserumAspergillusspp.precipitinstestoranisolationofAspergillusspp.fromthepulmonaryorpleuralcavity4Increasedbiologicalinflammatorysyndromemarkers(C-reactiveprotein,plasmaviscosityorerythrocytesedimentationrate)5Theexclusionofallothercausesthatcouldimitatethesymptoms(bronchialcarcinoma,TBandatypicalmycobacteria)6Noovertimmunocompromisingconditions(HIVinfection,leukaemiaandchronicgranulomatousdisease)ChronicPulmonaryAspergillosis:AnUpdateonDiagnosisandTreatment.Respiration2014;88:162–174第十五页，共30页。MethodsfordiagnosingCPAClinicalexaminationforriskfactors:Alcoholism,tobaccoabuse,diabetes,corticosteroiduse,COPDorundernourishment,ICUpatients,patientswithcirrhosisChestX-rayandCT:ImportantforapresumptivediagnosisRadiologicalappearancedescribedassimpleorcomplexaspergillomaSerologicaltestingSputum,bronchoscopyorbronchoscopywithBAL:DirectexaminationandcultureDetectionofGMinBAL1Biopsysample(perfibroscopicorpercutaneousTTNAbiopsy):WithhistologicalanalysisormicrobiologicalcultureVideo-assistedthoracoscopyDetectionofGMinserum2TTNA:Transthoracicneedleaspiration;1:Confirmatorystudiesareneeded;2:InformsofCNPAwithasemi-invasivenature,theantigencansometimesbepositiveforGM.Respiration2014;88:162–174第十六页，共30页。Frequencyofunderlyingcondition

inCPAChronicPulmonaryAspergillosis:AnUpdateonDiagnosisandTreatment.Respiration2014;88:162–174SAFS:Severeasthmawithfungalsensitisation.1:Community-acquiredpneumoniarequiringhospitalisation.第十七页，共30页。慢性肺曲霉菌病-抗体检测AspergillusantibodydiagnosisofCPAPresentbyDavidDenningECCMID10thMay2015inBarcelona患者人群Population目的Intention干预手段InterventionSoRQoE文献Reference备注Comment在非免疫抑制患者中伴有空腔/结节肺浸润CavitaryornodularpulmonaryinfiltrateinNon-immunocompromisedpatients诊断或排除慢性肺曲霉菌病DiagnosisOrexclusionofCPA曲霉抗体IgGAspergillusIgGantibodyAspergillusIgMantibodyAspergillusIgAantibodyAspergillusIgEantibodyAADDBIIIIIIIIIIIIGuitard,2012;Baxter,2012;VanToorenenbergen,2012BTS,1970;Uffredi,2003;Kitasato,2009;Ohba,2012;Baxter,2012Schonheyder1987;Nimomiya,1990;Denning,2003;Agarwal,