间质性肺疾病

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.间质性肺疾病

（InterstitialLungDisease,ILD)北京医院呼吸科与危重症医学科许小毛什么是肺间质肺泡间及终末气道上皮以外的支持组织，包括血管及淋巴管组织。肺实质指各级支气管及肺泡结构。概述以肺泡壁为主并包括肺泡周围组织及其相邻支持结构病变的一组疾病群,病因近200种。由于病变不仅局限于肺泡间质,还可累及肺泡上皮细胞、肺毛细血管内皮细胞和细支气管,并常伴有肺实质受累如肺泡炎、肺泡腔内蛋白渗出等改变,故也称为弥漫性肺实质疾病(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可以出现相同的病理表现，如RF和SLE可引起相同病理表现的ILD。同一种疾病可以表现为不同的病理表现，如干燥综合症可以表现为UIP，也可为NSIP。不同的ILD在病因、发病机制、病理改变、自然病程、治疗方法及预后方面都不完全相同。诊断的目的不仅限于ILD，而是要尽可能的明确病因和病理类型。临床表现呼吸困难咳嗽、咯血与结缔组织并相关的症状：发热、脱发、皮疹、关节痛、眼干、口干。体格检查肺部听诊爆裂音或Velcro罗音杵状指紫绀肺动脉高压征象实验室检查一般检查：免疫学指标、ANCA,SACE肺功能影像学支气管镜检查（BALF,TBLB,TBNA)肺组织活检（开胸肺活检，VATS)诊断思路病史、体格检查、胸部X线检查(特别是HRCT)和肺功能测定来进行综合分析。诊断步骤包括1、明确是否是ILD/DPLD2、明确属于哪一类ILD/DPLD3、如何对IIP进行鉴别诊断。是否为ILD

病史中最重要的症状是进行性气短、干咳和乏力。多数ILD患者体格检查可在双侧肺底闻及Velcro啰音。晚期病人缺氧严重者可见紫绀。

胸部X线对的诊断有重要作用。磨玻璃样改变,小结节影、线状(网状)影或二者混合的网状结节状阴影。肺泡充填性疾病表现为弥漫性边界不清的肺泡性小结节影,有时可见含气支气管征,晚期肺容积缩小可出现蜂窝样改变。

肺功能检查主要表现为限制性通气功能障碍和弥散功能(DLCO)下降。动脉血气分析可显示不同程度的低氧血症,而二氧化碳潴留罕见。属于哪一类ILD/DPLD

(1)详实的病史是基础:包括环境接触史、职业史、个人史、治疗史、用药史、家族史及基础疾病情况。

(2)胸部X线影像(特别是HRCT)特点可提供线索:根据影像学的特点、病变分布、有无淋巴结和胸膜的受累等,可对ILD/DPLD进行鉴别诊断。(3)BALF检查有确诊价值或者有助于诊断:①找到感染原,如卡氏肺孢子虫;②找到癌细胞;③肺泡蛋白沉积症:呈牛乳样,过碘酸-希夫染色阳性;④含铁血黄素沉着症:呈铁锈色并找到含铁血黄素细胞;⑤石棉小体计数超过1/ml:提示石棉接触。

(4)某些实验室检查包括:①抗中性粒细胞胞浆抗体:见于韦格纳肉芽肿;②抗肾小球基底膜抗体:见于肺出血肾炎综合征;③针对有机抗原测定血清沉淀抗体:见于外源性过敏性肺泡炎;④特异性自身抗体检测:提示相应的结缔组织疾病如何对IIP进行鉴别诊断

如经上述详实地检查及分析,仍不能确定为何种ILD/DPLD,就应归为IIP。其中IPF/UIP最常见,占所有IIP的60%以上,NSIP次之,而其余类型的特发性间质性肺炎相对少见。IIP的最后确诊,除了IPF可以根据病史、体征、支气管肺泡灌洗检查及胸部HRCT作出临床诊断外,其余确诊均需依靠病理诊断FinaldiagnosisCRPC-ClinicalR-RadiologistP-PathologistIdiopathicPulmonaryFibrosis

(IPF)

CLASSIFICATIONOFIIPCLASSIFICATIONOFIIPMajorIIPsIPFINSIPRB-ILDDIPAIP

RareIIPsILIPIdiopathicpleuroparenchymalfibroelastosisUnclassifiableIIPsATS/ERS2013特发性间质性肺炎(IdiopathicInterstitialPneumonia,IIP)属于ILD/DPLD中的一种。而特发性肺纤维化(IdiopathicPulmonaryFibrosis,IPF)属于IIP中的一种,病理学上称为寻常性间质性肺炎（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诊断标准排除其它已知原因导致的ILD(如：环境和职业导致的肺病，CTD-ILD，和药物性肺病等)。在没有外科肺活检资料条件下，胸部HRCT呈现典型的UIP表现。有外科肺活检资料条件下，胸部HRCT和病理均符合UIP表现。SubjectedtoexternalreviewHRCT诊断标准典型UIP

(allfourfeatures)可能UIP

(allthreefeatures)不符合UIP

(anyofthesevenfeatures)胸膜下,基底部为主网格状阴影蜂窝伴有或不伴有牵拉性支气管扩张缺少列表中不符合UIP的表现(第三列)胸膜下,基底部为主网格状阴影缺少列表中不符合UIP的表现(第三列)上,中肺野为主支气管血管周围病变明显广泛的磨玻璃影较多的小结节影散在的囊泡影弥漫性马赛克征/气体限闭支气管肺段或叶实变UIP的病理学标准明显纤维化/结构破坏,伴或不伴有胸膜下/间隔周围蜂窝样改变肺实质呈现斑片状纤维化出现成纤维母细胞灶缺乏不支持UIP诊断的特征病理诊断标准UIP满足所有4条ProbableUIP明显纤维化/结构破坏，伴或不伴蜂窝样改变；缺少斑片受累或成纤维母细胞灶，但不能二者均无；缺乏不支持UIP诊断的特征（非UIP）。或仅有蜂窝样改变（终末期）。PossibleUIP斑片或弥漫肺实质纤维化，伴或不伴肺间质炎症；缺乏典型UIP的其他标准；缺乏不支持UIP诊断的依据（非UIP）。NotUIP(anyofthesix)透明膜形成；机化性肺炎；肉芽肿；远离蜂窝区有明显炎性细胞浸润；显著的气道中心性病变；支持其他诊断的特征HRCT与肺活检结果联合诊断IPFHRCTPatternSurgicalLungBiopsyPattern(whenperformed)DiagnosisofIPFUIPUIPYESProbableUIPPossibleUIPNon-classifiablefibrosisNotUIPNoSubjectedtoexternalreview