間質(zhì)性肺疾病

CaseStudyChiefComplaint:

62-year-oldmanwithprogressiveshortnessofbreathoverthepast2yearsHistoryofPresentIllness:

Twoyearsbeforepatientbeganhavingshortnessofbreath(SOB).TheSOBhadbecomeprogressivelyworseinthepast12months.Amonthpriortopresentation,hedevelopedsevereSOBrequiringadmissiontoalocalhospital.Thepatientreportednoexposuresrelatedtohypersensitivitypneumonitisincludingbirds,mold.Hisonlychemicalexposurewastomalathionhesprayedinhisbackyardgarden.PastMedical&SurgicalHistory:unremarkableAllergies:PenicillinMedicines:Nifedipine,Furosemide,StatinFamilyHistory:NegativeforlungdiseaseorrheumatologicprocessesSocialHistory:30pack-yearscigaretteconsumptionandstopped15yearsearlierTravelHistory:NegativePhysicalExamination:

General:wellappearingVitalSigns:BP:110/70,Pulse:85RR,26breaths/minuteHEENT:NoskintightnessaroundhismouthNeck:NojugularveindistentionCardiovascularSystem:NofindingsofpulmonaryhypertensionRespiratorySystem:InspiratorycracklesoverlowerhalfofchestExtremities:clubbingMusculoskeletalSystem:noarthritisorsynovitisLaboratoryWorkup:

ANAnegative,speckledpatternwithanegativeSmantibody,negativeScl-70antibody;anechocardiogramrevealedanestimatedmeanpulmonaryarterypressureof55mmHg.InitialPFTData:FVC63%ofpredicted,FEV1/FVC85%DLCO30%ofpredictedTLC54%ofpredictedHRCTFINDINGSSlidecourtesyofGRaghu,MD.間質(zhì)性肺疾病

（InterstitialLungDisease,ILD)北京醫(yī)院呼吸科與危重癥醫(yī)學(xué)科許小毛什么是肺間質(zhì)肺泡間及終末氣道上皮以外的支持組織，包括血管及淋巴管組織。肺實(shí)質(zhì)指各級(jí)支氣管及肺泡結(jié)構(gòu)。概述以肺泡壁為主并包括肺泡周圍組織及其相鄰支持結(jié)構(gòu)病變的一組疾病群,病因近200種。由于病變不僅局限于肺泡間質(zhì),還可累及肺泡上皮細(xì)胞、肺毛細(xì)血管內(nèi)皮細(xì)胞和細(xì)支氣管,并常伴有肺實(shí)質(zhì)受累如肺泡炎、肺泡腔內(nèi)蛋白滲出等改變,故也稱為彌漫性肺實(shí)質(zhì)疾病(DiffuseParenchymalLungDisease,DPLD)ClassificationofDPLDDPLD感染全身性疾病家族史暴露史ILD不同的病因所致的ILD可以出現(xiàn)相同的病理表現(xiàn)，如RF和SLE可引起相同病理表現(xiàn)的ILD。同一種疾病可以表現(xiàn)為不同的病理表現(xiàn)，如干燥綜合癥可以表現(xiàn)為UIP，也可為NSIP。不同的ILD在病因、發(fā)病機(jī)制、病理改變、自然病程、治療方法及預(yù)后方面都不完全相同。診斷的目的不僅限于ILD，而是要盡可能的明確病因和病理類型。臨床表現(xiàn)呼吸困難咳嗽、咯血與結(jié)締組織并相關(guān)的癥狀：發(fā)熱、脫發(fā)、皮疹、關(guān)節(jié)痛、眼干、口干。體格檢查肺部聽(tīng)診爆裂音或Velcro羅音杵狀指紫紺肺動(dòng)脈高壓征象實(shí)驗(yàn)室檢查一般檢查：免疫學(xué)指標(biāo)、ANCA,SACE肺功能影像學(xué)支氣管鏡檢查（BALF,TBLB,TBNA)肺組織活檢（開(kāi)胸肺活檢，VATS)診斷思路病史、體格檢查、胸部X線檢查(特別是HRCT)和肺功能測(cè)定來(lái)進(jìn)行綜合分析。診斷步驟包括1、明確是否是ILD/DPLD2、明確屬于哪一類ILD/DPLD3、如何對(duì)IIP進(jìn)行鑒別診斷。是否為ILD

病史中最重要的癥狀是進(jìn)行性氣短、干咳和乏力。多數(shù)ILD患者體格檢查可在雙側(cè)肺底聞及Velcro啰音。晚期病人缺氧嚴(yán)重者可見(jiàn)紫紺。

胸部X線對(duì)的診斷有重要作用。磨玻璃樣改變,小結(jié)節(jié)影、線狀(網(wǎng)狀)影或二者混合的網(wǎng)狀結(jié)節(jié)狀陰影。肺泡充填性疾病表現(xiàn)為彌漫性邊界不清的肺泡性小結(jié)節(jié)影,有時(shí)可見(jiàn)含氣支氣管征,晚期肺容積縮小可出現(xiàn)蜂窩樣改變。

肺功能檢查主要表現(xiàn)為限制性通氣功能障礙和彌散功能(DLCO)下降。動(dòng)脈血?dú)夥治隹娠@示不同程度的低氧血癥,而二氧化碳潴留罕見(jiàn)。屬于哪一類ILD/DPLD

(1)詳實(shí)的病史是基礎(chǔ):包括環(huán)境接觸史、職業(yè)史、個(gè)人史、治療史、用藥史、家族史及基礎(chǔ)疾病情況。

(2)胸部X線影像(特別是HRCT)特點(diǎn)可提供線索:根據(jù)影像學(xué)的特點(diǎn)、病變分布、有無(wú)淋巴結(jié)和胸膜的受累等,可對(duì)ILD/DPLD進(jìn)行鑒別診斷。(3)BALF檢查有確診價(jià)值或者有助于診斷:①找到感染原,如卡氏肺孢子蟲(chóng);②找到癌細(xì)胞;③肺泡蛋白沉積癥:呈牛乳樣,過(guò)碘酸-希夫染色陽(yáng)性;④含鐵血黃素沉著癥:呈鐵銹色并找到含鐵血黃素細(xì)胞;⑤石棉小體計(jì)數(shù)超過(guò)1/ml:提示石棉接觸。

(4)某些實(shí)驗(yàn)室檢查包括:①抗中性粒細(xì)胞胞漿抗體:見(jiàn)于韋格納肉芽腫;②抗腎小球基底膜抗體:見(jiàn)于肺出血腎炎綜合征;③針對(duì)有機(jī)抗原測(cè)定血清沉淀抗體:見(jiàn)于外源性過(guò)敏性肺泡炎;④特異性自身抗體檢測(cè):提示相應(yīng)的結(jié)締組織疾病如何對(duì)IIP進(jìn)行鑒別診斷

如經(jīng)上述詳實(shí)地檢查及分析,仍不能確定為何種ILD/DPLD,就應(yīng)歸為IIP。其中IPF/UIP最常見(jiàn),占所有IIP的60%以上,NSIP次之,而其余類型的特發(fā)性間質(zhì)性肺炎相對(duì)少見(jiàn)。IIP的最后確診,除了IPF可以根據(jù)病史、體征、支氣管肺泡灌洗檢查及胸部HRCT作出臨床診斷外,其余確診均需依靠病理診斷FinaldiagnosisCRPC-ClinicalR-RadiologistP-PathologistIdiopathicPulmonaryFibrosis

(IPF)

CLASSIFICATIONOFIIPCLASSIFICATIONOFIIPMajorIIPsIPFINSIPRB-ILDDIPAIP

RareIIPsILIPIdiopathicpleuroparenchymalfibroelastosisUnclassifiableIIPsATS/ERS2013特發(fā)性間質(zhì)性肺炎(IdiopathicInterstitialPneumonia,IIP)屬于ILD/DPLD中的一種。而特發(fā)性肺纖維化(IdiopathicPulmonaryFibrosis,IPF)屬于IIP中的一種,病理學(xué)上稱為尋常性間質(zhì)性肺炎（usualinterstitialpneumonia,UIP)。OVERVIEWPrevalence:13–20/100,000inUS(approximately35,000-55,000cases)Onset:Usuallybetween50and70yrClinicalpresentationProgressivedyspneaonexertionParoxysmalcough,usuallynonproductiveAbnormalbreathsoundsonchestauscultationAbnormalchestx-rayorHRCTRestrictivepulmonaryphysiologywithreducedlungvolumesandDLCOandwidenedAaPO2themeanlengthofsurvivalfromthetimeofdiagnosisvariedbetween3.2and5yrInanotherstudy,themediansurvivalwas28.2mofromtheonsetofrespiratorysymptomsPOTENTIALRISKFACTORSCigaretteSmokingExposuretoCommonlyPrescribedDrugsChronicAspirationEnvironmentalFactorsInfectiousAgentsGeneticPredispositiontoIPFWhatisthecauseofIPF?Oldidea-inflammationcausesfibrosisNewidea-epithelialinjurywithabnormalhealingcausefibrosisLimitation-patientspresentlateincourseofdiseaseOldideaInflammationcausesfibrosis-BALoflungsshowedinflammatorycellsinthelungTreatmentwithantiinflammatorymedications-prednisone-imuran-cytoxanEffectivein15-30%ofpatientNewideaIPFisaconsequenceofongoingalveolarepithelialinjuryandcelldeath.EpithelialcellinjuryprobablyleadstoactivationofTGF-β,activationorinductionthroughepithelialtomesenchymaltransformation(EMT).SymptomsIPFusuallypresentsinsidiously,withthegradualonsetofanonproductivecoughanddyspnea.Dyspneaisusuallythemostprominentanddisablingsymptom.Itisusuallyprogressiveandinmostpatientsitisreportedtohavebeenpresentfor>6mobeforepresentation.paroxysmaldrycoughthatisrefractorytoantitussiveagents.Physicalexaminationcracklesaredetectedonchestauscultationinmorethan80%ofpatients.Thesearetypically“dry,”end-inspiratory,and“Velcro”inquality,andaremostprevalentinthelungbases.Clubbingisnotedin25to50%ofpatients.Cyanosis,corpulmonale,anaccentuatedpulmonicsecondsound,rightventricularheave,andperipheraledemamaybeobservedinthelatephasesofthediseaseLaboratoryandSerologicalTestsTheroutinelaboratoryevaluationofapatientsuspectedofhavingIPFisoftennothelpfulexceptto“ruleout”othercausesofILD.Positivecirculatinganti-nuclearantibodies(ANAs)orrheumatoidfactoroccurin10to20%ofpatientswithIPF,butrarelyaretitershigh.Thepresenceofhightiters(>1:160)wouldsuggestthepresenceofaconnectivetissuediseaseHighResolutionCTScanningpatchy,predominantlyperipheral,subpleural,bibasalreticularabnormalities.Theremayalsobeavariableamountofgroundglassopacitythatisusuallylimitedinextent.Inareasofmoresevereinvolvementthereisoftentractionbronchiectasisandbronchiolectasisand/orsubpleuralhoneycombing.HRCTFINDINGSPulmonaryFunctionTestingThetypicalfindingsofpulmonaryfunctiontestsareconsistentwithrestrictiveimpairment(reducedvitalcapacity[VC]andtotallungcapacity[TLC])TheDLCisreducedandmayactuallyprecedethereductionoflungvolume.LungBiopsyUsualinterstitialpneumonia(UIP)isthehistopathologicalpatternthatidentifiespatientswithIPF.SurgicallungbiopsyrecommendedinpatientswithsuspectedIPF,especiallythosewithatypicalclinicalorradiographicfeaturesMajorpurposeofhistologicexaminationistodistinguishUIPfromotherhistologicsubsetsofIIPThepotentialrisksandcostassociatedwithsurgicallungbiopsyneedtobebalancedagainsttheaccuracyofaclinicaldiagnosis,thelikelihoodofidentifyingamoretreatableformofILD,andtheefficacyofthetreatment.lungbiopsymaybeoutweighedbyincreasedriskforsurgicalcomplications(e.g.,age>70yr,extremeobesity,concomitantcardiacdisease,extremeimpairmentinpulmonaryfunction).Histopathologicalassessment.Thehistologichallmarkandchiefdiagnosticcriterionisaheterogeneousappearanceatlowmagnificationwithalternatingareasofnormallung,interstitialinflammation,fibrosis,andhoneycombchange.SlidecourtesyofKOLeslie,MD.HISTOPATHOLOGICELEMENTS

OFUIPIPF診斷標(biāo)準(zhǔn)排除其它已知原因?qū)е碌腎LD(如：環(huán)境和職業(yè)導(dǎo)致的肺病，CTD-ILD，和藥物性肺病等)。在沒(méi)有外科肺活檢資料條件下，胸部HRCT呈現(xiàn)典型的UIP表現(xiàn)。有外科肺活檢資料條件下，胸部HRCT和病理均符合UIP表現(xiàn)。SubjectedtoexternalreviewHRCT診斷標(biāo)準(zhǔn)典型UIP

(allfourfeatures)可能UIP

(allthreefeatures)不符合UIP

(anyofthesevenfeatures)胸膜下,基底部為主網(wǎng)格狀陰影蜂窩伴有或不伴有牽拉性支氣管擴(kuò)張缺少列表中不符合UIP的表現(xiàn)(第三列)胸膜下,基底部為主網(wǎng)格狀陰影缺少列表中不符合UIP的表現(xiàn)(第三列)上,中肺野為主支氣管血管周圍病變明顯廣泛的磨玻璃影較多的小結(jié)節(jié)影散在的囊泡影彌漫性馬賽克征/氣體限閉支氣管肺段或葉實(shí)變UIP的病理學(xué)標(biāo)準(zhǔn)明顯纖維化/結(jié)構(gòu)破壞,伴或不伴有胸膜下/間隔周圍蜂窩樣改變肺實(shí)質(zhì)呈現(xiàn)斑片狀纖維化出現(xiàn)成纖維母細(xì)胞灶缺乏不支持UIP診斷的特征病理診斷標(biāo)準(zhǔn)UIP滿足所有4條ProbableUIP明顯纖維化/結(jié)構(gòu)破壞，伴或不伴蜂窩樣改變；缺少斑片受累或成纖維母細(xì)胞灶，但不能二者均無(wú)；缺乏不支持UIP診斷的特征（非UIP）?；騼H有蜂窩樣改變（終末期）。PossibleUIP斑片或彌漫肺實(shí)質(zhì)纖維化，伴或不伴肺間質(zhì)炎癥；缺乏典型UIP的其他標(biāo)準(zhǔn)；缺乏不支持UIP診斷的依據(jù)（非UIP）。NotUIP(anyofthesix)透明膜形成；機(jī)化性肺炎；肉芽腫；遠(yuǎn)離蜂窩區(qū)有明顯炎性細(xì)胞浸潤(rùn)；顯著的氣道中心性病變；支持其他診斷的特征HRCT與肺活檢結(jié)果聯(lián)合診斷IPFHRCTPatternSurgicalLungBiopsyPattern(whenperformed)DiagnosisofIPFUIPUIPYESProbableUIPPossibleUIPNon-classifiablefibrosisNotUIPNoSubjectedtoexternalreview