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Study Description

We have established a consortium of 7 geographically-dispersed clinical research sites that are designed to study rare diseases of the airways, which involve defects in clearance of mucus secretions from the airways (defective "mucociliary clearance"). These sites will collaborate in diagnostic, genetic, and other studies in patients with impairments of mucociliary clearance, including primary ciliary dyskinesia (PCD), variant cystic fibrosis (CF), and pseudohypoaldosteronism (PHA). These disorders reflect genetic defects in airway host-defense, and typically result in chronic infection of the airways. 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 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. A rigorous cross-sectional comparison of the clinical features will provide better understanding 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.

The patient population for these studies includes individuals carrying a tentative diagnosis of the three disorders (PCD, variant CF or PHA), plus individuals suspected to have one of these disorders, but with inadequate or inconclusive diagnostic tests. Individuals in this latter category must have a preliminary clinical evaluation to evaluate for other more common disorders that may have similar manifestations including classical CF, immunodeficiency, asthma, and severe gastroesophageal reflux. We have an informal agreement with a network of pulmonologists across the United States to perform clinically-indicated (not research) preliminary clinical testing, if not directly available to patients who inquire about these studies.

Blood will be collected for DNA to test for genetic mutations. The blood samples will be processed to establish a cell line (lymphocyte transformation) for a source of DNA for future genetic studies, in participants with disease. For participants unable to provide a blood sample, a buccal sample will be obtained for DNA.

Authorized Access
Publicly Available Data (Public ftp)
Study Inclusion/Exclusion Criteria

Inclusion Criteria

The criteria for participants to enter the study mandates that each patient receiving a standard (current clinical practice) diagnostic evaluation, prior to enrolling in the Consortium study. To enter the study, individuals must meet one of 3 profiles:

  1. Have high suspicion for the diagnosis of PCD, based on ciliary ultrastructural changes on EM or clinical features (chronic sinopulmonary disease, chronic otitis media, history of neonatal respiratory distress or situs inversus), or PCD in a sibling and one of clinical features of PCD
  2. Have chronic sino pulmonary disease with clinical features that overlap with variant CF and PCD, but with diagnostic tests to rule out classical CF (sweat Cl- testing OR CF gene mutation screening)
  3. Known or suspected PHA (or variant PHA), which might include elevated (or borderline) sweat Cl- values.
Informed consent by participant or parent/legal guardian of minor participants (including HIPAA consent) will be required for all participants.

Exclusion Criteria

A participant should not be in the study if they have not had a standard clinical evaluation to rule out other disorders of chronic sino-pulmonary disease.

This study was activated on May 5, 2006, closed to accrual on October 2, 2012 and closed to accrual for data analysis on October 24, 2014

Study History

MCC is the primary defense mechanism for the lung. Inhaled particles (including microbial pathogens) are entrapped in mucus on the airway surface, then cleared by the coordinated action of cilia. The volume and composition of airway surface liquid (ASL) influence the efficiency of ciliary function and MCC (1-5). Genetic diseases of MCC include disorders in ciliary function (primary ciliary dyskinesia, PCD), and ion transport (cystic fibrosis, CF and pseudohypoaldosteronism, PHA). The clinical manifestations of these disorders overlap, and standardized diagnostic approaches, including the diagnosis and screening tests and genetic testing, will assist in defining the diagnosis and clinical pathogenesis of this group of disorders.

Selected Publications
Diseases/Traits Related to Study (MeSH terms)
Links to Related Resources
Authorized Data Access Requests
See research articles citing use of the data from this study
Study Attribution
  • Principal Investigator
    • Mike Knowles, MD. University of North Carolina, Chapel Hill, CA, USA.
  • Funding Source
    • HL096458. National Institutes of Health, Bethesda, MD, USA.