GENETIC DISORDERS OF MUCOCILIARY CLEARANCE: RARE DISEASES: PCD, CF, & PHA

粘膜纤毛间隙遗传性疾病：罕见疾病：PCD、CF、

• 批准号: 7724741
• 负责人: Michael R Knowles
• 金额: $ 111.22万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7724741
• 关键词: Arts; Biological Markers; Caring; Chest; Classification; Clinical; Clinical Practice Guideline; Clinical Research; Colorado; Computer Retrieval of Information on Scientific Projects Database; Cystic Fibrosis; Diagnosis; Diagnostic; Diagnostic Procedure; Diagnostic tests; Disease; Evaluation; Funding; Genetic; Genetic screening method; Goals; Grant; Hereditary Disease; Impairment; Infant; Institution; Longitudinal Studies; Lung diseases; Measurement; Medical; Methodology; Morbidity - disease rate; Mucociliary Clearance; North Carolina; Other Genetics; Pathogenesis; Patients; Pilot Projects; Primary Ciliary Dyskinesias; Professional Education; Pseudohypoaldosteronism; Rare Diseases; Research; Research Design; Research Personnel; Resources; Screening procedure; Site; Source; Study Subject; Techniques; Testing; Therapeutic Agents; Training Programs; United States National Institutes of Health; Universities; Variant; Washington; Work; base; cohort; design; early onset; follow-up; improved; innovation; mortality; novel therapeutics; respiratory; tool

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. DESCRIPTION (provided by applicant): The overall goal of this application is to establish a Rare Disease Clinical Research Center (RDCRC) at the University of North Carolina (UNC), and an associated Network of geographically-dispersed Airways Research Centers (ARCs), to study rare diseases of the airways. These 4 sites (UNC; Washington Univ., St. Louis; Univ. of Colorado, Denver; and Univ. of Washington, Seattle) will collaborate in diagnostic, genetic, and other studies in patients with genetic impairments in mucociliary clearance, specifically primary ciliary dyskinesia (PCD), variant forms of cystic fibrosis (CF), and pseudohypoaldosteronism (PHA). Patients with these unusual disorders with increased morbidity and mortality often have delayed (or incorrect) diagnoses, because diagnostic tests are not readily available. The two central hypotheses of this application are that: 1) a broad-based, systematic approach to the diagnostic evaluation of these patients will yield more precise diagnostic criteria and better diagnostic techniques, including genetic testing; and 2) systematic evaluation of specific cohorts of these patients with state-of-the-art methodologies and rigorous cross-sectional and longitudinal study designs will provide better understanding of the clinical pathogenesis of these disorders. In a five-year longitudinal study of 300 patients with PCD, we will use innovative techniques, including measurement of PFTs and HRCTs of the chest in infants, to define early onset and progression of pulmonary disease in PCD. In addition, 10 geographically-dispersed sites will serve as PCD Clinical Centers, to assist in the follow-up care of PCD patients in the longitudinal study. This collaborative effort will improve care by defining clinical practice guidelines for PCD. Our Pilot projects in PCD are designed to develop better diagnostic tools and biomarkers, characterize the respiratory pathobiology, evaluate novel therapeutic agents, and develop screening tests for PCD. We will extend our training programs in rare airways diseases to established and young investigators at UNC, and to investigators at other sites. Finally, we will work with the DTCC to coordinate and expand current websites to provide information to the lay public, patients, and medical professionals for education, referral, and recruitment of study subject

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 描述（由申请人提供）：本申请的总体目标是在北卡罗来纳大学 (UNC) 建立一个罕见疾病临床研究中心 (RDCRC) 以及一个相关的地理分散的气道研究中心 (ARC) 网络，以研究罕见的气道疾病。这 4 个中心（北卡罗来纳大学、华盛顿大学圣路易斯分校、科罗拉多大学丹佛分校和华盛顿大学西雅图分校）将在粘膜纤毛清除方面存在遗传缺陷的患者中开展诊断、遗传学和其他研究合作，特别是原发性纤毛运动障碍 (PCD)、囊性纤维化 (CF) 变异型和假性醛固酮增多症 (PHA)。患有这些发病率和死亡率增加的罕见疾病的患者往往会延迟（或不正确）诊断，因为诊断测试不易获得。该应用的两个中心假设是：1）对这些患者进行基础广泛、系统的诊断评估方法将产生更精确的诊断标准和更好的诊断技术，包括基因检测； 2）采用最先进的方法和严格的横断面和纵向研究设计对这些患者的特定群体进行系统评估将有助于更好地了解这些疾病的临床发病机制。在一项对 300 名 PCD 患者进行的为期五年的纵向研究中，我们将使用创新技术，包括测量婴儿胸部 PFT 和 HRCT，来定义 PCD 肺部疾病的早期发作和进展。此外，10个地理位置分散的地点将作为PCD临床中心，协助纵向研究中PCD患者的后续护理。这项合作将通过制定 PCD 临床实践指南来改善护理。我们的 PCD 试点项目旨在开发更好的诊断工具和生物标志物、表征呼吸病理学、评估新型治疗药物以及开发 PCD 筛查测试。我们将把罕见气道疾病的培训计划扩展到北卡罗来纳大学的资深研究人员和年轻研究人员以及其他地点的研究人员。最后，我们将与 DTCC 合作，协调和扩展现有网站，为普通公众、患者和医疗专业人员提供教育、转诊和研究对象招募等信息