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慢性肺曲霉病的诊断与管理 1 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 2 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 3 DefinitionsofCPA ThemostcommonformofCPAisCCPA Untreateditmayprogresstochronicfibrosingpulmonaryaspergillosis CFPA LesscommonmanifestationsofCPAincludeAspergillusnoduleandsingleaspergilloma Alltheseentitiesarefoundinnon immunocompromisedpatientswithpriororcurrentlungdisease Subacuteinvasivepulmonaryaspergillosis formerlycalledchronicnecrotisingpulmonaryaspergillosis isamorerapidlyprogressiveinfection 3months usuallyfoundinmoderatelyimmunocompromisedpatients D DENNINGETAL ESCMID ERSGUIDELINES EurRespirJ2015 4 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 5 PresentbyDavidDenning ECCMID10thMay2015inBarcelona 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 6 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 D DENNINGETAL ESCMID ERSGUIDELINES EurRespirJ2015 7 Single simple pulmonaryaspergillomaisasinglefungalballinasinglepulmonarycavity Thereisnoprogressionovermonthsofobservationandveryfew ifanypulmonaryorsystemicsymptomsandserologicalormicrobiologicalevidenceimplicatingAspergillusspp Simpleaspergillomathatdevelopedwithinapost tuberculouscicatricialatelectasisoftheleftupperlobewithsaccularbronchiectasis Surgicalresectionbyvideo assistedthoracicsurgerywasperformedbecauseofrecurrenthaemoptysisandarequirementforanticoagulanttherapy D DENNINGETAL ESCMID ERSGUIDELINES EurRespirJ2015 8 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 9 Imagingshowingchroniccavitarypulmonaryaspergillosisshowinganaxialviewwitha lungandb mediastinalwindowsattheleveloftherightupperlobe Multiplecavitiesarevisiblewithafungusballlyingwithinthelargestone Thewallofthecavitiescannotbedistinguishedfromthethickenedpleuraortheneighbouringalveolarconsolidation Theextrapleuralfatishyperattenuated whitearrows thedilatedoesophagusshouldnotbeconfusedwithacavity a b 10 CFPAisoftenanendresultfromuntreatedCCPA ExtensivefibrosiswithfibroticdestructionofatleasttwolobesoflungcomplicatingCCPA leadingtoamajorlossoflungfunction Usuallythefibrosisissolidinappearance butlargeorsmallcavitieswithsurroundingfibrosismaybeseen SerologicalormicrobiologicalevidenceimplicatingAspergillusspp isrequiredfordiagnosis Oneormoreaspergillomasmaybepresent Imagingofchronicfibrosingpulmonaryaspergillosiscomplicatingchroniccavitarypulmonaryaspergillosis whichfollowedtuberculosis withmildchronicobstructivepulmonarydisease Completeopacificationofthelefthemi thoraxdevelopedbetweenFebruary1998 whenaleftupperlobecavitywithafluidlevelwaspresent andMay1999 Multipleleftlungautopsypercutaneousbiopsiesshowedevidenceofchronicinflammation butnogranulomasorfungalhyphae 11 Oneormorenodules 3cm whichdonotusuallycavitate areanunusualformofCPA Theymaymimiccarcinomaofthelung metastases cryptococcalnodule coccidioidomycosisorotherrarepathogensandcanonlybedefinitivelydiagnosedonhistology NodulesinpatientswithrheumatoidarthritismaybepurerheumatoidnodulesorcontainAspergillus Tissueinvasionisnotdemonstrated althoughnecrosisisfrequent Sometimeslesionslargerthan3cmindiameterareseenandmayhaveanecroticcentre Thesearenotwelldescribedintheliteratureandarebestdescribedas masslesionscausedbyAspergillusspp SuccessiveaxialviewswithinthelungwindowshowingAspergillusnodules ofvariablesizeandborders andafungusballfillingacavitywithawallofvariablethicknessinapatientwithpre existingbronchiectasisandcicatricialatelectasisofthemiddlelobe Aspergillusnodule s 12 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 13 Thenewclinicaldiseaseentityofchronicprogressivepulmonaryaspergillosis Newnomenclature chronicprogressivepulmonaryaspergillosis CPPA fortheclinicalsyndromeincludingbothCNPAandCCPAisproposed Itisdifficulttodistinguishbetweenthesetwoentitiesbasedontheclinicalcourseandcharacteristicsandradiologicalfindings respiratoryinvestigation54 2016 85 91 14 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 15 CPA diagnosiscriteriaanddefinitions ChronicPulmonaryAspergillosis AnUpdateonDiagnosisandTreatment Respiration2014 88 162 174 16 MethodsfordiagnosingCPA TTNA Transthoracicneedleaspiration 1 Confirmatorystudiesareneeded 2 InformsofCNPAwithasemi invasivenature theantigencansometimesbepositiveforGM Respiration2014 88 162 174 17 FrequencyofunderlyingconditioninCPA ChronicPulmonaryAspergillosis AnUpdateonDiagnosisandTreatment Respiration2014 88 162 174 SAFS Severeasthmawithfungalsensitisation 1 Community acquiredpneumoniarequiringhospitalisation 18 慢性肺曲霉菌病 抗体检测AspergillusantibodydiagnosisofCPA PresentbyDavidDenning ECCMID10thMay2015inBarcelona 患者人群Population 目的Intention 干预手段Intervention SoR QoE 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IgG AspergillusIgGantibody AspergillusIgMantibody AspergillusIgAantibody AspergillusIgEantibody A A D D B II II III III II Guitard 2012 Baxter 2012 VanToorenenbergen 2012 BTS 1970 Uffredi 2003 Kitasato 2009 Ohba 2012 Baxter 2012 Schonheyder1987 Nimomiya 1990 Denning 2003 Agarwal 2012 IgG和曲霉沉淀素的标准建立尚未完成 哮喘 变态反应性肺曲霉菌病 ABPA 囊性纤维化 CF Asthma ABPA CF Aspergillusprecipitins 曲霉沉淀素 曲霉抗体IgM 曲霉抗体IgA 曲霉抗体IgE Brouwer 1988 多数室内测试尚未应
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