Clinical Genetics and Screening for Pulmonary Fibrosis

 描述(申请人提供)：本提案的主要目标是证明基因检测在特发性肺纤维化(IPF)患者或高危患者的诊断和预后评估中的价值。特发性肺纤维化(IPF)是最常见和最严重的肺纤维化(PF)形式，其死亡率与许多终末期恶性肿瘤的死亡率相当。虽然IPF历史上对药物治疗无效，但最近的研究最终证明，药物治疗可以减少肺功能的下降，特别是在病程早期开始的时候。虽然这些发现为改进IPF的早期检测提供了动力，但最近的研究也表明，基因检测可能是帮助指导早期检测的关键因素。我们假设，特定的、已知的基因变异赋予PF患者不同的预后，靶向基因检测将有助于患者咨询、早期发现疾病，并最终更早地开始药物治疗。为了评估这些假说，我们建议解决以下具体目标：目的1)靶向基因检测是否有助于肺纤维化患者的诊断和预后评估？目的2)靶向基因检测是否有助于肺纤维化高危人群的早期发现和预测？目的3)我们将评估肺纤维化高危基因检测组的心理社会影响。这些研究的积极结果将为随后的试验奠定基础，这些试验可以前瞻性地评估靶向基因测试在确定是否需要进一步筛查以及在IPF高危人群中设计治疗试验的作用。

 DESCRIPTION (provided by applicant): The primary goal of this proposal is to demonstrate the value of genetic testing in the diagnostic and prognostic evaluation of patients with, or in those at-risk for, idiopathic pulmonary fibrosis (IPF). Idiopathic pulmonary fibrosis (IPF), the most common and severe form of pulmonary fibrosis (PF) has a mortality rate comparable to that of many end-stage malignancies Although IPF has historically been unresponsive to pharmacotherapy, recent studies have finally demonstrated that medical therapy can reduce the rate of decline in lung function, particularly when started early in the course of disease. While these findings provide motivation to improve early detection of IPF, recent studies also demonstrate that genetic testing may be a critical factor that can help guide early detection. We hypothesize that specific, known genetic variants confer variable prognosis in patients with PF, and that targeted genetic testing will aid in patient counseling, early disease detection, and ultimately, earlier initiation of medical therapy. To assess these hypotheses we propose to address the following specific aims: Aim 1) Does targeted genetic testing aid in the diagnostic and prognostic evaluation of patients with pulmonary fibrosis? Aim 2) Does targeted genetic testing aid in early detection, and prognostication of populations at-risk for pulmonary fibrosis? and Aim 3) We will assess the psychosocial impact of genetic testing groups at-risk for pulmonary fibrosis. Positive results from these studies will set the stage for subsequent trials that could prospectively evaluate the role of targeted genetic testing in determining the need for further screening, and in designing therapeutic trials in groups at-risk for IPF.