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5902: Rare Genetic Disorders of the Airways: Cross-sectional Comparison of Clinical Features, and Development of Novel Screening and Genetic Tests

For Impairments of Mucociliary Clearance, including:

  • primary ciliary dyskinesia (PCD)
  • variant cystic fibrosis (CF)
  • pseudohypoaldosteronism (PHA)


In this study, a consortium of clinical research sites are working together to study rare diseases of the airways. These disorders involve defects in mucociliary clearance (clearing mucus from the airways). Researchers will conduct diagnostic, genetic, and other studies in patients with impairments in mucociliary clearance, including:

  • primary ciliary dyskinesia (PCD) - a rare inherited disease affecting the cilia (tiny, hair-like structures that line the airways and sinuses) leading to recurrent or persistent respiratory infections and sinusitis. Cilia carry mucus to be removed from the body, by coughing. When cilia are not working well, bacteria are trapped in the airways causing breathing problems and infections in the lungs. Defective cilia also lead to recurrent sinus and ear infections as well as male infertility.
  • variant cystic fibrosis (CF) - an inherited disease of the mucus and sweat glands that affects mostly the lungs, pancreas, liver, intestines, sinuses and fertility . In CF, mucus is thick and sticky, clogging the lungs, causing breathing problems and making it easy for bacteria to grow. In variant CF, patients can have lung disease but normal or borderline elevated sweat tests or no identifiable mutant CF genes.
  • pseudohypoaldosteronism (PHA) - a rare disease that causes increased lung fluids, and recurrent episodes of chest congestion and persistent cough.

These disorders involve problems in genes that regulate controlling airway host defense (protecting the airways from the effects of bacteria). When the airway host defense is not working properly, the result is 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. Patients may not have good control over symptoms, since the cause of these disorders is not well-defined, and treatment plans may vary.


About this Study

This study is designed to study the way in which patients with chronic airway disease are evaluated and diagnosed. The goal of these studies is to improving diagnostic techniques, including genetic testing.

In addition, clinical features (phenotype) across these disorders will be studied to better understand the disorders. This will lead not only to a better standard of clinical care, but will assist in identifying of new treatment options.

Targeted Enrollment

These studies will target patients with:

  • A tentative diagnosis of one or more of the three disorders (PCD, variant CF or PHA),
  • A suspected diagnosis of one of these disorders, but with inadequate or inconclusive diagnostic test results. Individuals in this category must have already had a clinical evaluation to rule out other more common disorders with similar symptoms (including classical CF, immunodeficiency, asthma, or severe gastroesophageal reflux).

To be eligible to participate, you must:

Meet one of 3 profiles:

  1. Have high suspicion for the diagnosis of PCD, based on changes in the structure of cilia as seen through a microscope or clinical features [chronic disease of the sinuses and the airways of the lungs, chronic middle ear infections, history of respiratory distress at birth or situs inversus (internal organs reversed)], or a sibling with PCD and one of the clinical features of PCD
  2. Have chronic disease of the sinuses or airways with clinical features that overlap with variant CF and PCD, and with diagnostic tests ruling out classical CF (sweat chloride testing or screening for the CF gene mutation)
  3. Known or suspected PHA (or variant PHA), which might include elevated (or borderline) sweat chloride values.

Informed consent by participant or parent/legal guardian of minor participants (including HIPAA consent) will be required for all participants

You are not eligible to participate if:
You have not had a standard clinical evaluation to rule out other disorders of chronic disease of the sinuses or airways of the lungs.