肺隱球菌病醫(yī)學(xué)知識(shí)專家講座

肺隱球菌病（PC，pulmonarycryptococcosis）

---從一種病例談起復(fù)旦大學(xué)附屬華山醫(yī)院北院呼吸科張有志病史簡(jiǎn)介患者，女性，47歲主述：因“反復(fù)咳嗽伴胸痛1月”入院（B院）現(xiàn)病史：患者于2023.9.5無(wú)明顯誘因出現(xiàn)咳嗽，少許白痰，伴右側(cè)胸痛，陣發(fā)性鈍痛，深吸氣時(shí)明顯，無(wú)放射痛，無(wú)發(fā)燒，無(wú)嘔吐、頭痛，某A院行胸部CT示“右下肺炎”，予以莫西沙星靜滴8天患者咳嗽、胸痛有所緩解，繼續(xù)口服莫西沙星6天，2023.9.27復(fù)查CT無(wú)吸收。于2023.10.12就診B院。既往：體健。否定性病冶游史。家中曾養(yǎng)寵物（鴿子、狗）。查體：T：37.9℃，淺表淋巴結(jié)不大，右下肺可及濕啰音。輔助檢驗(yàn)：血常規(guī)、肝腎功能、D-二聚體正常；ESR：65mm/h，CRP：48mg/L；血?dú)夥治稣＃籋IV（-）PPD試驗(yàn)陰性；LA試驗(yàn)、G試驗(yàn)陰性（送至C院檢測(cè)）2023.9.6A院CT2023.9.27A院CT病史簡(jiǎn)介A院氣管鏡檢驗(yàn)：鏡下：未見明顯異常；右下肺灌洗和刷檢：未見惡性細(xì)胞、TB陰性。

2023.10.12B院

CT引導(dǎo)下經(jīng)皮肺穿刺病理成果確診：肺隱球菌病上皮樣肉芽腫性病變；成堆隱球菌幾點(diǎn)疑問(wèn)真菌病一般都是免疫功能低下旳患者隱球菌怎樣侵襲到肺旳LA試驗(yàn)陰性肺隱球菌病CT體現(xiàn)和肺炎一樣有關(guān)隱球菌Ｃｒｙｐｔｏｃｏｃｃｕｓ帶厚莢膜旳酵母菌（乳膠凝集試驗(yàn)）腐生菌：土壤、鴿糞、霉?fàn)€蔬菜、水果等感染部位：中樞神經(jīng)系統(tǒng)、皮膚、肺

感染途徑：吸入呼吸道經(jīng)血行播散到其他部位分型：17個(gè)種、18個(gè)變種（新生隱球菌及變種具有致病性）EpidemiologyIAmulticentreretrospectivestudyofpulmonarymycosisclinicallyprovenfrom1998to2023Totally474casesofpulmonarymycosisfrom16centersin10cities.pulmonaryaspergillosis(180cases，37．9％)pulmonarycandidiasis(162cases，34．2％)pulmonarycryptococcosis(74cases，15．6％)pneumocystiscafiniipneumonia(23cases，4.8％)pulmonarymucormycosis(10cases，2．1％)中華結(jié)核和呼吸雜志，2023,34(2)EpidemiologyIIMeta-AnalysisofClinicalManifestationsofPulmonaryCryptococcosisinChinaMainland69.7%patientshadnounderlyingdiseases．Thecommonunderlyingdiseaseswereacquiredimmunedeficiencysyndrome(AIDS)diabetesmalignanttumor

中國(guó)臨床醫(yī)學(xué)，2023,20（3）：351-354EpidemiologyIIIRetrospectiveinvestigationof151pulmonarycryptococcosisnon-HIVcasesbetween1977and202344.4%patientshadnoUDs.ThecommonUDswerediabetes(32.1%)hematologicdisease(22.6%)collagendisease(22.6%)JapaneseSocietyofChemotherapyandTheJapaneseAssociationforInfectiousDiseases.JInfectChemother.2023Oct29

EpidemiologyIV219patientswithprovencryptococcosisat20hospitals

inTaiwan,1997-2023210isolateswereC.neoformans(95.9%);9isolateswereC.gattii(4.1%).

15.4%didnothaveanyunderlyingcondition.

HIVinfectionwasthemostcommonunderlyingcondition(54/219,24.6%).AmongHIV-negativepatients,liverdiseases(HBVcarrierorcirrhosis)werecommon(30.2%)TaiwanInfectiousDiseasesStudyNetworkforCryptococcosis.

PLoSOne.2023Apr17;8(4):e61921.EpidemiologyVClinicalanalysisof76patientspathologicallydiagnosedwithpulmonarycryptococcosis.Of76patients(54malesand22females),41(53.95%)wereimmunocompetentand35outofthe41wereasymptomatic.

ShanghaiPulmonaryHospital.EurRespirJ.2023Nov;40(5):1191-200.summaryapproximatelyhalfofpatientshadnounderlyingdiseasesasignificantnumberofpatients

wereasymptomaticpathogenesisThecapsuleisthemostimportantvirulencefactorofthefungalpathogenCryptococcusneoformans.ThestructureProductionOfthecapsuleadhesionofCryptococcusneoformanstoepitheliallungcellsprotectiveimmuneresponsesagainstcryptococcosisThestructureofcapsuleThisstructureconsistsofhighlyhydratedpolysaccharides,includingglucuronoxylomannan(GXM)，葡萄糖醛酸木糖甘露聚糖galactoxylomannan(GalXM)，半乳糖木糖甘露聚糖mannoproteins(MPs)，甘露糖蛋白，lessthan1%ofthecapsularweightProductionOfthecapsuleICA/CO2-sensingpathways

.1Regulationofcapsulesynthesisbycarbondioxide．JClinInvest，1985，76(2):508-516．2ComparativetranscriptomeanalysisoftheCO2sensingpathwayviadifferentialexpressionofcarbonicanhydraseinCryptococcusneoformans.Genetics.2023Aug;185(4):1207-19.ProductionOfthecapsuleII

cryptococcalpolysaccharidesynthesisisincreasedbylimitationofferricironavailabilitytothecellandbydissolvedCO2,andthetwoeffectsareadditive.Regulationofcryptococcalcapsularpolysaccharidebyiron.JInfectDis.1993Jan;167(1):186-90.ProductionOfthecapsuleIIIcapsuleenlargementinlivingC.neoformanscellswasinfluencedbyCa(2+)intheculturemedium.

EukaryotCell.2023Aug;6(8):1400-10.

ProductionOfthecapsuleIVbasedontheaxiallengtheningofPSmolecules.CapsuleofCryptococcusneoformansgrowsbyenlargementofpolysaccharidemolecules.ProcNatlAcadSciUSA.2023Jan27;106(4):1228-33.PS，etccapsule?alveolarmicroenvironmentadhesiontoepitheliallungcells

anadhesion-likeinteractionbetweenMPonthefungalsurfaceandthecomplementaryreceptormoleculesontheepithelialcells.

FrontCellInfectMicrobiol.2023Aug19;4:106.PhagocytosisdefenceSizeofCryptococcusneoformans.DynamicchangesinthemorphologyofCryptococcusneoformansduringmurinepulmonaryinfection.

GXMagainstalveolarmacrophages(AM).Mechanismsofimmuneevasioninfungalpathogens.

1Microbiology.2023Aug;147(Pt8):2355-65.2CurrOpinMicrobiol.2023Dec;14(6):668-75.immuneresponseSP-DincreasessusceptibilitytoC.neoformansinfectionbypromotingC.neoformans-drivenpulmonaryIL-5andeosinophilinfiltration.Th1/Th2cytokineimbalance.BcellsprovideafirstlineofdefenseduringpulmonaryC.neoformansinfectioninmice

1GenetMolRes.2023Nov18;12(4):5733-422InfectImmun.2023Feb;82(2):683-933JImmunol.2023Dec15;189(12):5820-30MyopinioniChangealveolarmicroenvironmentAbrogationofIL-4receptor-α-dependentalternativelyactivatedmacrophagesissufficienttoconferresistanceagainstpulmonarycryptococcosisdespiteanongoingT(h)2response.

IntImmunol.2023Aug;25(8):459-70.RadiologyIPeripherallydistributedpulmonarynodules/massesweremostcommonlyseen.JapaneseSocietyofChemotherapyandTheJapaneseAssociationforInfectiousDiseases.JInfectChemother.2023Oct29Radiological(computedtomography)findingsshowedpredominantlyperipheralfindings(85.53%)includingnodularmasses(55.26%),pneumonicinfiltrates(23.68%)andmixedtype(21.05%).ShanghaiPulmonaryHospital.EurRespirJ.2023Nov;40(5):1191-200.71.8%patientswerecharacterizedbynodularlumpshadows;23.8%byflake-likeinfiltratedshadows，and7.4%haddiffusemixedlesions．ZhongshanHospital.ChineseJournalofClinicalMedicine，2023RadiologyII

CTscanfindingsof29immunocompetentand43immunocompromisedpatients

Pulmonarynodules/masses,eithersolitaryormultiple,werethemostcommonCTfinding,presentin65(90.3%)ofthe72patients

Cavitationswithinnodules/massesweremorecommonlyseeninimmunocompromisedpatients,especiallyAIDSpatientsairbronchogramsweremorecommonlyseeninimmunocompetentpatientsPulmonarycryptococcosis:comparisonofCTfindingsinimmunocompetentandimmunocompromisedpatients.

ActaRadiol.2023Apr22.MyopinioniiMolecular/functionalradiologycurrentsituationindiagnosis43.42%(33/76)wereinitiallymisdiagnosed,oftenascancerbyfalse-positive(18)FDG-PETFailureofthecryptococcalserumantigentesttodetectprimarypulmonarycryptococcosisinpatientsinfectedwithhumanimmunodeficiency

virus26.2%（17/65）wereconfirmedbysurge