CHARACTERIZATION OF FAMILIAL IDIOPATHIC PULMONARY FIBROSIS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 特发性肺纤维化(IPF)是一种定义明确的临床实体，具有独特的临床、放射学和生理学特征。它的发生频率约为每100,000人中有13-20人。它是特发性肺炎中最致命的，没有已知的治愈方法，也几乎没有治疗方法。家族性更少见，占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。报告的这种疾病的最大家系表现为垂直传播、男性对男性传播和可变外显性。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，具有可变的外显性。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)家族的集合。这项建议寻求通过临床方法来描述受影响的和处于危险中的家庭成员的特征。我们建议利用GCRC的资源来促进对主题的定性。每个参与者都将接受体检，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，并接受支气管镜检查，以评估支气管肺泡灌洗液是否有炎症和纤维化的标志。肺功能测试将包括肺活量测定、身体体积描记、弥散能力测量和运动中的氧减饱和。将获得胸部的HRCT扫描，以评估IPF的特征性表现。这是一项利用我们独特的家族性IPF家庭资源进行的新型研究。如果遗传模式确实是常染色体显性遗传，外显性降低，那么这种类型的成人高危个体筛查可能会识别出一些具有疾病早期发现的人或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努力。

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 participant 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.