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Protocol Details

Genetic Disorders of Mucociliary Clearance

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Heart, Lung and Blood Institute (NHLBI)

Recruitment Detail

Type: Completed Study; data analyses ongoing
Gender: Male & Female
Min Age: 2 Years
Max Age: 65 Years

Referral Letter Required


Population Exclusion(s)



Nontuberculous Mycobacterial Infection;
Primary Ciliary Dyskinesia;
Cystic Fibrosis;
Chronic Granulomatous Disease;
Natural History

Recruitment Keyword(s)

Mycobacterial Infection;
Nontuberculous Mycobacterial Infection;
Primary Ciliary Dyskinesia;
Cystic Fibrosis;
Healthy Volunteer;


Cystic Fibrosis;
Nontuberculous Mycobacterial Infection;
Chronic Granulomatous Disease;
Primary Ciliary Dyskinesia

Investigational Drug(s)


Investigational Device(s)




Supporting Site

National Heart, Lung, and Blood Institute

Healthy volunteers and patients with diseases that involve problems clearing mucus from the lungs will be examined and tested to better understand the reasons for recurring lung infections in these patients and to try to develop better ways to diagnose and treat them. The study will also try to identify the genes responsible for these diseases.

Healthy volunteers 18 years of age and older and patients 2 years of age or older with suspected primary ciliary dyskinesia (PCD), variant cystic fibrosis (CF) or pseudohypoaldosteronism (PHA) may be eligible for this study. Patients enrolled in the Natural History Study of Nontuberculous Mycobacteria at NIH or other NIH natural history protocols may also be enrolled. Participants undergo the following tests and procedures during a 1-day visit at the NIH Clinical Center, as follows:

All patients and normal volunteers have the following procedures:

-Physical examination and review of medical and genetic history and family genetic history.

-Lung function test and measurement of oxygen saturation level.

-Nitric oxide measurement to measure the amount of nitric oxide production in the nose: A small tube is placed in the nose while the subject breathes through the mouth into a cardboard tube.

All patients have the following additional procedures:

-Blood tests for liver and kidney function, blood count, immunoglobulins and pregnancy test (where appropriate).

-Blood test or buccal scrape (brushing the inside of the cheek) to obtain DNA to look for gene mutations that cause PCD, CF or PHA.

-Scrape biopsy of cell lining the inside of the nose: A small toothpick-sized plastic stick with a tiny cup on the end is used to get nasal lining cells to look at the cilia (hair-like structures that move mucus).

-Semen analysis (in some men) to test sperm tail function or structure.

Patients suspected of having a variant of CF or PHA, including nontuberculous mycobacterial lung disease, have the following additional procedures:

-Sweat chloride test: A medicine is placed on the arm to produce sweat; then, a very low level of electric current is applied for 5 to 12 minutes. Sweat is collected in a plastic tube and tested for salt content.

-Blood draw for CF genetic testing, if necessary, and to measure levels of the enzyme trypsin.

-Saliva collection to measure sodium and chloride content.

-Nasal potential difference to measure the electrical activity of the cells lining the inside of the nose: A soft plastic tube filled with a salt solution is passed into the nasal passage and a sterile needle is placed under the skin of the arm. This test provides information about how the lining of the nose is able to get used to changes in temperature and humidity. (Normal volunteers also have this test.)

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Overview: Inclusion criteria reflect the two-fold purpose of this protocol. It is primarily intended to evaluate the cohort of patients followed at the NIH Clinical Center under Protocol 01-I-0202, Natural History, Genetics, Phenotype, and Treatment of Mycobacterial Infections, and in this regard, the inclusion criteria mirror those of that protocol. Secondly it is part of the multicenter collaborative protocol as a participating site in the Genetic Disorders of Mucociliary Clearance Consortium, one of the Rare Disease Clinical Consortia sponsored by the Office of Rare Diseases. There is a clear-cut need for geographically dispersed centers to have expertise in the diagnostic evaluation and treatment of patients with rare diseases of the airways, including patients with suspected PCD, non-classical or variant CF, and PHA. The 5 sites will perform rigorous diagnostic evaluations utilizing innovative, but standardized methods (SOPs contained in Manual of Operations). As a participating site in the Consortium, we will cast a broad net to include as many participants as feasible. This will include a multi-center standardized diagnostic evaluation and clinical evaluation, giving us a better chance to define the clinical spectrum of disease.

The criteria for participants to enter this study mandates that each patient either be enrolled in the 01-I-0202, Natural History, Genetics, Phenotype, and Treatment of Mycobacterial Infections or related NIH Natural History Protocol, or if referred as part of the Consortium, have received a standard (current clinical practice) diagnostic evaluation that includes testing for asthma, severe gastroesophageal reflux and/or classic CF, prior to enrolling in the Consortium study. Healthy adult control participants will be enrolled for comparison assessment of noninvasive nasal nitric oxide and nasal potential difference measurements only. The health status of these control participants will be assessed with the standardized clinical history, family history, physical exam including height and weight, vital signs, oximetry, and spirometry measurements.

To enter the study, individuals with a suspected mucociliary clearance defect (n=100) must be age 2 years or older and meet one of the 4 following profiles:

1. Have known or suspected nontuberculous mycobacterial lung disease and enrolled in Protocol 01-I-0202, Natural History, Genetics, Phenotype, and Treatment of Mycobacterial Infections.

2. Have high suspicion for the diagnosis of PCD, based on ciliary ultrastructural changes on EM (if performed elsewhere prior to referral) 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 the clinical features of PCD.

3. 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 and CF gene mutation screening). This may include patients with other known immune deficiencies such as chronic granulomatous disease followed on NIH natural history protocols.

4. Known or suspected PHA (or variant PHA), which might include elevated (or borderline) sweat Cl- values.

To enter the study as a healthy control (n=25), individuals must be age 18 or older and free of any known disease, chronic medical conditions, family history of cystic fibrosis or primary ciliary dyskinesia, or any cognitive impairment or significant disability that might preclude voluntary consent or the ability to safely comply with the instructions or sit through the testing.


Persons who cannot be evaluated at the Clinical Center or who have severe cognitive impairment or other severe disability that precludes the ability to understand instructions or sit/lie still for the evaluation will be excluded. Certain conditions may preclude specific procedures included in the protocol, but may still allow pertinent parts of this diagnostic evaluation. These conditions/procedures may include: pregnancy/Chest PA/Lat x-ray; allergy to pilocarpine /sweat testing. For reversible conditions such as acute upper airway infection, significant epistaxis within the prior week (not related to #2 below), or lower airway infection with uncontrollable coughing, the participant may need to be rescheduled upon resolution.

For nasal nitric oxide and nasal potential difference measurements or nasal mucosal scrape biopsies:

1. Anatomic abnormality of the nose or sinuses (e.g. complete sinus blockage or turbinatectomy) that precludes either the measurement of nasal nitric oxide or nasal potential difference.

2. A severe bleeding diathesis or condition such as hereditary hemorrhagic telangiectasia syndrome that may predispose to significant nasal bleeding or result in severely excoriated nasal mucosa.

3. Inability to sit still for up to 15 minutes while the nasal catheters are held on the mucosal surface for transepithelial potential difference measurements. This would include the presence of acute or chronic lower respiratory tract infection that results in uncontrollable coughing.

4. Diffuse skin condition that would preclude placement of the subcutaneous reference electrode (butterfly needle) for nasal PD measurement.

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Not Provided

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Principal Investigator

Referral Contact

For more information:

Andrew J. Lipton, M.D.
National Heart, Lung and Blood Institute (NHLBI)
NIHBC 10 - CRC BG RM 5-1409
(301) 451-4950

Chevalia Robinson, R.N.
National Heart, Lung and Blood Institute (NHLBI)
National Institutes of Health
Building 10
Room 4-5350
10 Center Drive
Bethesda, Maryland 20892
(301) 496-3973

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: TTY Users Dial 7-1-1

Clinical Trials Number:


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