CHARACTERIZATION OF FAMILIAL IDIOPATHIC PULMONARY FIBROSIS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。特发性肺纤维化（IPF）是一种定义明确的临床实体，具有特征性的临床、影像学和生理学特征。它发生的频率大约是每10万人中有13-20人。它是最致命的特发性肺炎，目前尚无治愈方法，治疗方法也很少。这种疾病的家族性形式更为罕见，占所有IPF病例的0.5-3.7%。这种疾病家族性形式的分子基础尚不清楚。据报道，该疾病最大的家族表现为垂直传播、男性间传播和不同的外显率。我们假设家族性特发性肺纤维化是一种罕见的疾病，表现为常染色体显性遗传模式，具有可变外显率。为了验证这一假设，我们通过患者接触和转诊建立了家族性特发性肺纤维化（IPF）家庭的集合。本建议旨在通过临床方法确定受影响和有风险的家庭成员的特征。我们建议使用GCRC资源来促进受试者的表征。每位参与者将接受体检，提交血液进行常规分析，进行肺功能测试，高分辨率CT （HRCT）扫描，并进行支气管镜检查以评估支气管肺泡灌洗液的炎症和纤维化标志物。肺功能测试将包括肺活量测定、体体积脉搏图、扩散能力测量和运动时的氧饱和度。将获得胸部HRCT扫描以评估IPF的特征性表现。这是一种新型的研究，利用我们独特的家族性IPF家庭资源。如果遗传模式确实是常染色体显性的，外显率降低，那么这种对成年高危个体的筛查可能会发现一些早期发现的疾病或那些具有疾病中间表型的人。这些研究将直接补充我们通过经典连锁技术确定这种疾病的遗传基础的尝试。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Idiopathic pulmonary fibrosis (IPF) is a well defined clinical entity that has characteristic clinical, radiographic, and physiologic characteristics. It occurs at a frequency of approximately 13-20 per 100,000. It is the most deadly of the idiopathic pneumonias with no known cure and few treatments. The familial form of the disease is even more rare, accounting for 0.5-3.7% of all the cases of IPF. The molecular basis of the familial form of the disease is unknown. The largest reported families with this disease exhibit vertical transmission, male to male transmission, and variable penetrance. We hypothesize that familial idiopathic pulmonary fibrosis is a rare disease displaying an autosomal dominant pattern of inheritance with variable penetrance. To test this hypothesis we have established a collection of families with familial idiopathic pulmonary fibrosis (IPF) through patient contact and referrals. This proposal seeks to characterize affected and at-risk family members by clinical methods. We propose using the GCRC resources to facilitate characterization of subjects. Each partcipant will undergo a physical exam, submit blood for routine analyses, have pulmonary function testing, a high-resolution CT (HRCT) scan, and undergo bronchoscopy to evaluate bronchoalveolar lavage fluid for markers of inflammation and fibrosis. The pulmonary function testing will include spirometry, body plethysmography, diffusion capacity measurement, and oxygen desaturation with exercise. HRCT scans of the chest will be obtained to evaluate for the characteristic findings of IPF. This is a novel type of study using our unique resources of families with familial IPF. If the pattern of inheritance is indeed autosomal dominant with reduced penetrance, then this type of screening of adult at-risk individuals may identify some with early findings of the disease or those with an intermediate phenotype of the disease. These studies will directly complement our attempts to identify the genetic basis of this disease by classical linkage techniques.