慢性肺曲霉病的診斷與管理

慢性肺曲霉病的診斷與管理第1頁，共29頁，2023年，2月20日，星期五目錄慢性肺曲霉病的定義慢性肺曲霉病的臨床表現(xiàn)類型慢性肺曲霉病的診斷慢性肺曲霉病的管理總結(jié)第2頁，共29頁，2023年，2月20日，星期五目錄慢性肺曲霉病的定義慢性肺曲霉病的臨床表現(xiàn)類型慢性肺曲霉病的診斷慢性肺曲霉病的管理總結(jié)第3頁，共29頁，2023年，2月20日，星期五DefinitionsofCPAThemostcommonformofCPAisCCPA.Untreateditmayprogresstochronicfibrosingpulmonaryaspergillosis(CFPA).LesscommonmanifestationsofCPAincludeAspergillusnoduleandsingleaspergilloma.Alltheseentitiesarefoundinnon-immunocompromisedpatientswithpriororcurrentlungdisease.Subacuteinvasivepulmonaryaspergillosis(formerlycalledchronicnecrotisingpulmonaryaspergillosis)isamorerapidlyprogressiveinfection(<3months)usuallyfoundinmoderatelyimmunocompromisedpatients.D.DENNINGETAL.ESCMID/ERSGUIDELINES.EurRespirJ2015.第4頁，共29頁，2023年，2月20日，星期五目錄慢性肺曲霉病的定義慢性肺曲霉病的臨床表現(xiàn)類型慢性肺曲霉病的診斷慢性肺曲霉病的管理總結(jié)第5頁，共29頁，2023年，2月20日，星期五PresentbyDavidDenningECCMID10thMay2015inBarcelona慢性曲霉菌病臨床表現(xiàn)分類ClinicalphenotypesofchronicAspergillussppdiseases單發(fā)曲霉球Single/simpleaspergilloma慢性壞死性/亞急性肺曲霉菌病Chronicnecrotizingpulmonaryaspergillosis(CNPA)orsubacuteInvasiveaspergillosis(SAI)慢性空腔性肺曲霉菌病Chroniccavitarypulmonaryaspergillosis(CCPA)慢性纖維化肺曲霉菌病Chronicfibrosingpulmonaryaspergillosis(CFPA)曲霉菌肉芽腫Aspergillusnodule(s)CCPA是最常見的CPA類型CCPA不治療可進(jìn)展為CFPA曲霉結(jié)節(jié)與單純性曲霉腫較少見免疫功能受損患者常見SAIA第6頁，共29頁，2023年，2月20日，星期五CPA的分類與定義CCPA-慢性空洞型肺曲霉病;CFPA-慢性纖維性肺曲霉病;SAIA-亞急性侵襲性曲霉病/慢性壞死性/半侵襲性曲霉病分類定義單純性曲霉腫非免疫功能受損的患者存在含有真菌球的單一肺部空洞，且血清學(xué)或微生物學(xué)證據(jù)提示曲霉屬(Aspergillusspp.)感染，無癥狀或僅有輕微癥狀，在至少3個月的觀察期內(nèi)未出現(xiàn)影像學(xué)進(jìn)展CCPA存在1個或多個含有≥1個曲霉球或不規(guī)則腔內(nèi)結(jié)構(gòu)的肺部空洞(薄壁或厚壁)，且血清學(xué)或微生物學(xué)證據(jù)提示曲霉屬感染，有明顯的肺部和/或系統(tǒng)癥狀，在至少3個月的觀察期內(nèi)出現(xiàn)明顯的影像學(xué)進(jìn)展(新空洞、空洞外周浸潤增加、或纖維化增加)CFPACCPA并發(fā)出現(xiàn)的至少2個肺葉出現(xiàn)嚴(yán)重的纖維化破壞并導(dǎo)致大部分肺功能喪失。單個存在空洞的肺葉出現(xiàn)嚴(yán)重纖維化破壞僅代表影響該肺葉的CCPA。通常纖維化表現(xiàn)為肺部實變，但也可表現(xiàn)為周圍出現(xiàn)纖維化的較大空洞曲霉結(jié)節(jié)一種少見的CPA類型，出現(xiàn)1個或多個形成或不形成空洞的結(jié)節(jié)?？膳c結(jié)核球、肺癌、球孢子菌病以及其他疾病相似，只有通過組織學(xué)檢查才能確診。盡管常出現(xiàn)壞死，但不會出現(xiàn)組織浸潤。SAIA/CNPA在1-3個月內(nèi)出現(xiàn)的侵襲性曲霉病，常發(fā)生在存在輕度免疫功能受損的患者之中，存在多種影像學(xué)特征，包括空洞形成、結(jié)節(jié)、“膿腫形成”的進(jìn)展性實變等。受累肺部組織活檢可見菌絲，微生物學(xué)檢查結(jié)果與侵襲性曲霉病一致，特別是血液(或呼吸道液體)曲霉半乳甘露聚糖抗原陽性D.DENNINGETAL.ESCMID/ERSGUIDELINES.EurRespirJ2015.第7頁，共29頁，2023年，2月20日，星期五Single(simple)pulmonaryaspergillomaisasinglefungalballinasinglepulmonarycavity.Thereisnoprogressionovermonthsofobservationandveryfew,ifanypulmonaryorsystemicsymptomsandserologicalormicrobiologicalevidenceimplicatingAspergillusspp.Simpleaspergillomathatdevelopedwithinapost-tuberculouscicatricialatelectasisoftheleftupperlobewithsaccularbronchiectasis.Surgicalresectionbyvideo-assistedthoracicsurgerywasperformedbecauseofrecurrenthaemoptysisandarequirementforanticoagulanttherapy.D.DENNINGETAL.ESCMID/ERSGUIDELINES.EurRespirJ2015.第8頁，共29頁，2023年，2月20日，星期五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9頁，共29頁，2023年，2月20日，星期五Imagingshowingchroniccavitarypulmonaryaspergillosisshowinganaxialviewwitha)lungandb)mediastinalwindowsattheleveloftherightupperlobe.Multiplecavitiesarevisiblewithafungusballlyingwithinthelargestone.Thewallofthecavitiescannotbedistinguishedfromthethickenedpleuraortheneighbouringalveolarconsolidation.Theextrapleuralfatishyperattenuated(whitearrows).*:thedilatedoesophagusshouldnotbeconfusedwithacavity.a)b)**第10頁，共29頁，2023年，2月20日，星期五CFPAisoftenanendresultfromuntreatedCCPA.ExtensivefibrosiswithfibroticdestructionofatleasttwolobesoflungcomplicatingCCPA,leadingtoamajorlossoflungfunction.Usuallythefibrosisissolidinappearance,butlargeorsmallcavitieswithsurroundingfibrosismaybeseen.SerologicalormicrobiologicalevidenceimplicatingAspergillusspp.isrequiredfordiagnosis.Oneormoreaspergillomasmaybepresent.Imagingofchronicfibrosingpulmonaryaspergillosiscomplicatingchroniccavitarypulmonaryaspergillosis,whichfollowedtuberculosis,withmildchronicobstructivepulmonarydisease.Completeopacificationofthelefthemi-thoraxdevelopedbetweenFebruary1998,whenaleftupperlobecavitywithafluidlevelwaspresent,andMay1999.Multipleleftlungautopsypercutaneousbiopsiesshowedevidenceofchronicinflammation,butnogranulomasorfungalhyphae.第11頁，共29頁，2023年，2月20日，星期五Oneormorenodules(<3cm),whichdonotusuallycavitate,areanunusualformofCPA.Theymaymimiccarcinomaofthelung,metastases,cryptococcalnodule,coccidioidomycosisorotherrarepathogensandcanonlybedefinitivelydiagnosedonhistology.NodulesinpatientswithrheumatoidarthritismaybepurerheumatoidnodulesorcontainAspergillus.Tissueinvasionisnotdemonstrated,althoughnecrosisisfrequent.Sometimeslesionslargerthan3cmindiameterareseenandmayhaveanecroticcentre.Thesearenotwelldescribedintheliteratureandarebestdescribedas“masslesionscausedbyAspergillusspp.”.SuccessiveaxialviewswithinthelungwindowshowingAspergillusnodules,ofvariablesizeandborders,andafungusballfillingacavitywithawallofvariablethicknessinapatientwithpre-existingbronchiectasisandcicatricialatelectasisofthemiddlelobe.Aspergillusnodule(s)第12頁，共29頁，2023年，2月20日，星期五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13頁，共29頁，2023年，2月20日，星期五Thenewclinicaldiseaseentityofchronicprogressivepulmonaryaspergillosis.Newnomenclature,“chronic

progressivepulmonaryaspergillosis(CPPA)”fortheclinicalsyndromeincludingbothCNPAandCCPAisproposed.Itisdifficulttodistinguishbetweenthesetwoentitiesbasedontheclinicalcourseandcharacteristicsandradiologicalfindings.respiratoryinvestigation54(2016)85–91.第14頁，共29頁，2023年，2月20日，星期五目錄慢性肺曲霉病的定義慢性肺曲霉病的臨床表現(xiàn)類型慢性肺曲霉病的診斷慢性肺曲霉病的管理總結(jié)第15頁，共29頁，2023年，2月20日，星期五CPA:diagnosiscriteriaanddefinitions1Chronicpulmonaryorgeneralsymptomsincludingatleast1ofthefollowing(foraminimumof3monthsinduration):weightloss,productivecoughorhaemoptysis2Aprogressiveformationandexpansionofsingleormultiplepulmonarycavitationssurroundedbyawallandpossiblepleuralthickeningonradio-imaging3ApositiveresultforaserumAspergillusspp.precipitinstestoranisolationofAspergillusspp.fromthepulmonaryorpleuralcavity4Increasedbiologicalinflammatorysyndromemarkers(C-reactiveprotein,plasmaviscosityorerythrocytesedimentationrate)5Theexclusionofallothercausesthatcouldimitatethesymptoms(bronchialcarcinoma,TBandatypicalmycobacteria)6Noovertimmunocompromisingconditions(HIVinfection,leukaemiaandchronicgranulomatousdisease)ChronicPulmonaryAspergillosis:AnUpdateonDiagnosisandTreatment.Respiration2014;88:162–174第16頁，共29頁，2023年，2月20日，星期五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17頁，共29頁，2023年，2月20日，星期五Frequencyofunderlyingcondition

inCPAChronicPulmonaryAspergillosis:AnUpdateonDiagnosisandTreatment.Respiration2014;88:162–174SAFS:Severeasthmawithfungalsensitisation.1:Community-acquiredpneumoniarequiringhospitalisation.第18頁，共29頁，2023年，2月20日，星期五慢性肺曲霉菌病-抗體檢測AspergillusantibodydiagnosisofCPAPresentbyDavidDenningECCMID10thMay2015inBarcelona患者人群Population目的Intention干預(yù)手段InterventionSoRQoE文獻(xiàn)Reference備注Comment在非免疫抑制患者中伴有空腔/結(jié)節(jié)肺浸潤CavitaryornodularpulmonaryinfiltrateinNon-immunocompromisedpatients診斷或排除慢性肺曲霉菌病DiagnosisOrexclusionofCPA曲霉抗體IgGAspergillusIgGantibodyAspergillusIgMantibodyAspergillusIgAantibodyAspergillusIgEantibodyAADDBIIIIIIIIIIIIGuitard,2012;Baxter,2012;VanToorenenbergen,2012BTS,1970;Uffredi,2003;Kitasato,2009;Ohba,2012;Baxter,2012Schonheyder1987;Nimomiya,1990;Denning,2003;Agarwal,2012IgG和曲霉沉淀素的標(biāo)準(zhǔn)建立尚未完成哮喘/