CAJ | 학술논문

目的通过观察家族性特发性肺间质纤维化(FIPF)的临床特点并检测相关基因,明确特发性肺间质纤维化(IPF)表现形式,了解相关发病机制,寻找可能的治疗方法.方法收集1970-2014年确诊的1个中国北方汉族FIPF家系连续3代共7例患者,其中男4例,女3例,发病年龄30～57岁.先证者为Ⅱ-4,最先发病者为Ⅰ-1,Ⅱ代6名成员中5例发病,其中男2例,女3例,Ⅲ代11名成员中目前l例成年男性发病,遗传特点符合常染色体显性遗传.通过影像学及肺功能等检查确诊IPF.搜集家族成员基本信息、影像学及病理学检查等临床资料,分析病情特点并比较临床表现,并进行肺组织病理学检查以及基因检测.结果该家系发病后平均生存期3年,糖皮质激素(激素)治疗效果欠佳.3例临床资料完整的患者间质性肺疾病相关免疫学检查结果均为阴性.3例肺功能可见明显限制性通气功能障碍,DLCO分别为50％、23％和46％,弥散功能严重减低.3例影像学资料完整的患者,1例表现为UIP,2例表现为NSIP.3例影像学表现虽然不同,但应用激素治疗均效果不佳,其中2例死亡.对该家系中Ⅱ-4患者进行了外周血基因检测和尸检.结论家族性肺间质纤维化家族患病成员平均死亡年龄为50.2岁,患者影像学特征和病理表现可表现为UIP或NSIP,即使肺活检病理诊断为NSIP,激素治疗也可能无效.该家系中Ⅱ-4患者基因检测未检出TERT、TERC和SFPTC基因突变.
목적 통과관찰가족성특발성폐간질섬유화(FIPF)적림상특점병검측상관기인,명학특발성폐간질섬유화(IPF)표현형식,료해상관발병궤제,심조가능적치료방법.방법 수집1970-2014년학진적1개중국북방한족FIPF가계련속3대공7례환자,기중남4례,녀3례,발병년령30～57세.선증자위Ⅱ-4,최선발병자위Ⅰ-1,Ⅱ대6명성원중5례발병,기중남2례,녀3례,Ⅲ대11명성원중목전l례성년남성발병,유전특점부합상염색체현성유전.통과영상학급폐공능등검사학진IPF.수집가족성원기본신식、영상학급병이학검사등림상자료,분석병정특점병비교림상표현,병진행폐조직병이학검사이급기인검측.결과 해가계발병후평균생존기3년,당피질격소(격소)치료효과흠가.3례림상자료완정적환자간질성폐질병상관면역학검사결과균위음성.3례폐공능가견명현한제성통기공능장애,DLCO분별위50％、23％화46％,미산공능엄중감저.3례영상학자료완정적환자,1례표현위UIP,2례표현위NSIP.3례영상학표현수연불동,단응용격소치료균효과불가,기중2례사망.대해가계중Ⅱ-4환자진행료외주혈기인검측화시검.결론 가족성폐간질섬유화가족환병성원평균사망년령위50.2세,환자영상학특정화병리표현가표현위UIP혹NSIP,즉사폐활검병리진단위NSIP,격소치료야가능무효.해가계중Ⅱ-4환자기인검측미검출TERT、TERC화SFPTC기인돌변.
Objective To identify the manifestations and pathogenesis of idiopathic pulmonary fibrosis (IPF) after studying the clinical features of familial idiopathic pulmonary fibrosis (FIPF) and detecting relevant genes.Methods Seven persons with FIPF from one family of Han nationality in northern China,which had FIPF patients in three consecutive generations,were included in this study.The incidence age of the 7 subjects (4 males and 3 females) ranged from 30 to 57 years.The propositus was Ⅱ-4,while the first person attacked by FIPF was Ⅰ-1.Five patients (2 males,3 females) in the second generation and one case in the third generation were found at the time of this study.The genetic characteristics of FIPF in this study were complied with the pattern of autosomal dominant inheritance.Imaging examinations and pulmonary function tests were conducted to confirm the diagnosis of pulmonary fibrosis.Meanwhile,personal information and clinical data such as imaging examinations and pathological tests were acquired;clinical features and manifestations were analyzed and compared;and pathological tests and gene detection were performed.Results The average survival time was 3 years,and poor response to glucocorticoid treatment was observed.Three patients had detailed clinical information,whose interstitial pneumonia related immunologic tests were negative.Concerning pulmonary function,three patients had significant decrease of diffusion function and obvious restrictive ventilatory disorder,with DLCO value as 50％,23％ and 46％,respectively.Among the 3 patients with complete imaging data,1 was considered as UIP,while 2 as NSIP.The 3 subjects who had different imaging findings all responded poorly to glucocorticoid treatment,and two of them died.Genetic test for TERT,TERC and SFTPC in peripheral blood and autopsy were performed for Ⅱ-4 but all were negative.Conclusions The average death age of family members with FIPF was 50.2 years.The patients presented various imaging features and pathological findings.Glucocorticoid treatment may be ineffective,even for persons diagnosed as NSIP by lung biopsy.