Genetic Disorders of Mucociliary Clearance

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航空研究中心网络(ARCS)，以研究罕见的呼吸道疾病。这4个地点(北卡罗来纳大学、华盛顿大学、圣路易斯大学、科罗拉多州、丹佛市和大学。西雅图华盛顿)将合作进行诊断、遗传学和其他研究，对黏膜纤毛清除方面存在遗传损害的患者进行研究，特别是原发性睫状体运动障碍(PCD)、各种形式的囊性纤维化(CF)和假性醛固酮减少症(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，因为诊断测试不容易获得。这一应用的两个中心假设是：1)对这些患者进行广泛、系统的诊断评估将产生更准确的诊断标准和更好的诊断技术，包括基因测试；以及2)使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队列进行系统评估将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，包括测量婴儿胸部的PFT和HRCT，以确定PCD肺部疾病的早期发病和进展。此外，10个地理上分散的地点将作为PCD临床中心，在纵向研究中协助PCD患者的后续护理。这一合作努力将通过定义PCD的临床实践指南来改善护理。我们在PCD的试点项目旨在开发更好的诊断工具和生物标记物，表征呼吸道病理生物学，评估新的治疗药物，并开发PCD的筛查测试。我们将把我们的罕见呼吸道疾病培训计划扩展到北卡罗来纳大学的老牌和年轻的调查人员，以及其他地点的调查人员。最后，我们将与DTCC合作，协调和扩展现有的网站，为非专业公众、患者和医疗专业人员提供有关教育、转介和招聘研究对象的信息。

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 subjects.