Clinical Genetics and Screening for Pulmonary Fibrosis

肺纤维化的临床遗传学和筛查

• 批准号: 9197330
• 负责人: GARY MATTHEW HUNNINGHAKE
• 金额: $ 87.69万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9197330
• 关键词: Address; Age; Age of Onset; Attitude; Cessation of life; Characteristics; Cicatrix; Clinic; Clinical; Clinical Research; Complex; Counseling; Country; Detection; Diagnosis; Diagnostic; Disease; Early Diagnosis; Evaluation; Exhibits; Family member; First Degree Relative; Genes; Genetic; Genetic Counseling; Genetic Screening; Genetic screening method; Goals; Hamman-Rich syndrome; Human immunodeficiency virus test; Impairment; Length; Lung; Malignant Neoplasms; Medical; Medical Genetics; Motivation; Mucins; Mutation; Participant; Pathogenicity; Patients; Pattern; Pharmacotherapy; Phenotype; Physiological; Populations at Risk; Positioning Attribute; Prevalence; Pulmonary Fibrosis; Questionnaires; Radiology Specialty; Recruitment Activity; Registries; Relative Risks; Reporting; Research; Respiratory physiology; Risk; Role; Running; Severity of illness; Survival Rate; Telomerase; Testing; Therapeutic Trials; Time; Variant; X-Ray Computed Tomography; base; chest computed tomography; cohort; design; follow-up; genetic information; genetic variant; improved; individualized medicine; interstitial; mortality; mutation carrier; outcome forecast; precision medicine; prognostic; promoter; prospective; psychosocial; public health priorities; public health relevance; rare variant; risk variant; screening; telomere; treatment strategy

 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.

 描述（由申请人提供）：该提案的主要目标是证明基因检测在特发性肺纤维化（IPF）患者或有患特发性肺纤维化风险的患者的诊断和预后评估中的价值。特发性肺纤维化（IPF）是肺纤维化（PF）最常见和最严重的形式，其死亡率与许多终末期恶性肿瘤相当。尽管IPF历来对药物治疗无反应，但最近的研究最终证明药物治疗可以降低肺功能下降的速度，特别是在病程早期开始时。虽然这些发现为改善 IPF 的早期检测提供了动力，但最近的研究还表明，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、已知的基因变异会赋予 PF 患者不同的预后，而有针对性的基因检测将有助于患者咨询、早期疾病检测，并最终帮助更早开始药物治疗。为了评估这些假设，我们建议解决以下具体目标： 目标 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？目标 2) 靶向基因检测是否有助于肺纤维化高危人群的早期检测和预测？目标 3) 我们将评估基因检测对肺纤维化高危人群的社会心理影响。这些研究的积极结果将为后续试验奠定基础，这些试验可以前瞻性地评估靶向基因检测在确定是否需要进一步筛查以及为 IPF 高危人群设计治疗试验方面的作用。