Genetic Disorders of Mucociliary Clearance

点击翻译按钮获取中文摘要

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.