RARE GENETIC DISORDERS OF THE AIRWAYS

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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. Patients with defects in clearance of mucus secretions from the airways (defective "mucociliary clearance"), including primary ciliary dyskinesia (PCD), variant cystic fibrosis (CF), and pseudohypoaldosteronism (PHA) reflect genetic defects in airway host defense, and typically result in chronic infection of the airways manifest as chronic otitis media, sinusitis, and bronchitis. Patients with these disorders of the conducting airways and sinuses have delayed (or incorrect) diagnoses, because diagnostic tests are not readily available. These patients may also have sub-optimal management of their clinical disease, because the cause of these disorders is not well-defined, and treatment regimens are usually not driven by evidence-based medicine. This current protocol is designed to employ a systematic approach to the diagnostic evaluation of these patients with chronic airways disease, which will yield more precise diagnoses in individual patients, and will be associated with development of better diagnostic techniques, including genetic testing. In addition, we will compare/contrast clinical features (phenotype) across these disorders. In this protocol, the systematic evaluation of these patients and a rigorous cross-sectional comparison of the clinical features will provide better understanding of the nature of the clinical disease of these disorders. In turn, this will lead not only to a better standard of clinical care, but will also assist in the identification of novel therapeutic approaches. We will be one of four Airway Research Center (ARC) sites to form a network of geographically-dispersed clinical research centers to study rare diseases of the airways. The 4 sites which include the University of North Carolina at Chapel Hill, Washington University in St. Louis, University of Washington in Seattle, and The Children's Hospital at the University of Colorado have formed the Genetic Disorders of Mucociliary Clearance Consortium under the umbrella of the Rare Diseases Clinical Research Network (RDCRN) which is funded by the NIH. The RDCRN website is http://www.rarediseasesnetwork.org/. We intend to become "Centers of Excellence" for the research and care of persons with PCD and other rare airway diseases.