Role of Genetic Factors in the Development of Lung Disease

NCT00001532 | Recruiting

• 2 other identifiers: 96010096-H-0100
• Study Type: observational
• Target: 3,500
• Locations: 1 country
• Sites: 2

Brief Summary

This study is designed to evaluate the genetics involved in the development of lung disease by surveying genes involved in the process of breathing and examining the genes in lung cells of patients with lung disease. The study will focus on defining the distribution of abnormal genes responsible for processes directly involved in different diseases affecting the lungs of patients and healthy volunteers. Optional CT Sub-study The standard CT scan will be compared to the low dose radiation CT scan for the 150 subjects enrolled in the sub-study to assess the variation between the two techniques. Specifically, the quantitative computer aided detection of lung CT abnormalities from LAM can be compared to assess whether low radiation dose CT exams is an alternative to conventional CT to monitor disease status. This optional sub-study will be offered to up to 100 adult subjects with lung disease and up to 50 children age 9 and older with CF. Children will not be enrolled in the optional CT sub-study unless they have had a standard CT scan for medical purposes to use in comparison. One additional low dose radiation CT scan of the chest may be done as part of this sub-study when these subjects have their next annual CT scan.

Conditions

Cystic Fibrosis; Pulmonary Fibrosis; Tuberous Sclerosis; Asthma; Pulmonary Sarcoidosis

Keywords

Genetic Polymorphism; Nitric Oxide Synthesis; Alpha 1-Antitrypsin; Candidate Genes; Lung Pathology; Natural History; Lung Disease; Cystic Fibrosis; Asthma

Outcome Measures

Primary Outcomes (1)

• evaluating the role of hereditary factor

  distribution of genetic variants of nitric oxide synthases and other candidate genes involved in pulmonary function

  1 year

Secondary Outcomes (1)

• low dose radiation CT scan, and Zoom Scan

  on going

Study Arms (2)

1

Subjects with pulmonary disease or possible pulmonary disease and Relatives

2

Healthy

Eligibility Criteria

• Age: 2 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

individuals with pulmonary disease (e.g., alpha 1-antitrypsin deficiency, asthma, chronic obstructive pulmonary disease, cystic fibrosis, sarcoidosis,Wegener s Granulomatosis,Mycobacterium Avium, Tuberous Sclerosis Complex, other cystic lung diseases, lymphangioleiomyomatosis and diseases associated with lymphatic disorders, or history of pneumothorax, history of infection, and genetic mutations consistent with lung pathology)

You may qualify if:

• symptoms consistent with pulmonary disease
• chest x-ray consistent with pulmonary disease
• pulmonary function tests consistent with pulmonary disease;
• smokers, defined as individuals who are current smokers (1 pack per day for at least 2 years) and nonsmokers, defined as never-smokers or ex-smokers who have not smoked for three or more years.
• Patients with established diagnoses of sarcoidosis; mycobacterial infections; TSC (definite or possible); cystic lung diseases including genetic diseases; lymphangioleiomyomatosis or diseases associated with lymphatic disorders; history of pneumothorax; pulmonary fibrosis; asthma; histiocytosis X and diabetes mellitus will be included in this protocol. Relatives of patients may also be seen under this protocol. Children with lymphangiomatosis who are two years of age or older may be included. Participants with asthma may be enrolled at Suburban Hospital.
• Research volunteers in the pulmonary control group are defined as individuals with no pulmonary disease (e.g. rheumatoid arthritis without evidence of pulmonary disease). Research volunteers in the diabetes control group are defined as individuals with no history of diabetes, coronary artery disease, or pulmonary disease.
• Pregnant and or nursing women can be included in accordance with Federal Regulations at Subpart B of 45 CFR 46. Subjects who are pregnant and or nursing will be excluded from procedures during their pregnancy that are greater than minimal risk, until they are no longer pregnant and/or nursing. Procedures that will not be completed while the subject is pregnant and/or nursing including: PFTs, Six Minute Walk Test, thoracentesis, bronchoscopy, and measurements with imaging modalities requiring contrast or with radiation exposure such as Chest x-ray, CT scan, MRI. Allowing subjects to be included in the study may glean important information about individuals with uncommon pulmonary disease during and post pregnancy.
• Patients with abnormalities in ADP-ribosyltransferases, ADP-ribosyl-acceptor hydrolases, and their substrates. Children who are two years of age or older may be studied if they have a known defect in ADP-ribosylation, or if they have a family member with a defect in ADP-ribosylation and may be affected.

You may not qualify if:

• age less than 18 or greater than 90 except for NIH patients with diseases /disorders as described in this protocol (except cystic fibrosis, lymphangiomatosis or defects in ADP-ribosylation) who are 16 years of age or older, patients with cystic fibrosis who are over eight years of age, patients who are two years of age or older with lymphangiomatosis or a known defect in ADP-ribosylation, or who have a family member with a defect in ADP-ribosylation, or unless patient-specific IRB approval is obtained and;
• inability to obtain reliable pulmonary function testing. As clarification, healthy volunteers, relatives of patients (except as noted for an ADP-ribosylation defect), and asthmatic patients from Suburban Hospital will be excluded if less than 18 or greater than 90 years of age.
• presence of any contraindication for fiberoptic bronchoscopy, with lavage and/or bronchial brushing;
• advanced stage of a pulmonary or a systemic illness such that the risk is judged to be significant even in the absence of a specific contraindication to the procedure
• allergy to topical anesthetic (e.g., lidocaine)
• current or recent respiratory infection (within the last 4 weeks)
• pregnancy or lactation
• age less than 18 or greater than 65.

Sponsors & Collaborators

• Suburban Hospital: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (2)

Suburban Hospital

Bethesda, Maryland, 20814, United States

COMPLETED

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (4)

• Rybicki BA, Beaty TH, Cohen BH. Major genetic mechanisms in pulmonary function. J Clin Epidemiol. 1990;43(7):667-75. doi: 10.1016/0895-4356(90)90037-p.

  PMID: 2370574 BACKGROUND

• Welsh MJ, Fick RB. Cystic fibrosis. J Clin Invest. 1987 Dec;80(6):1523-6. doi: 10.1172/JCI113237. No abstract available.

  PMID: 3316277 BACKGROUND

• Brantly ML, Paul LD, Miller BH, Falk RT, Wu M, Crystal RG. Clinical features and history of the destructive lung disease associated with alpha-1-antitrypsin deficiency of adults with pulmonary symptoms. Am Rev Respir Dis. 1988 Aug;138(2):327-36. doi: 10.1164/ajrccm/138.2.327.

  PMID: 3264124 BACKGROUND

• Hu-Wang E, Schuzer JL, Rollison S, Leifer ES, Steveson C, Gopalakrishnan V, Yao J, Machado T, Jones AM, Julien-Williams P, Moss J, Chen MY. Chest CT Scan at Radiation Dose of a Posteroanterior and Lateral Chest Radiograph Series: A Proof of Principle in Lymphangioleiomyomatosis. Chest. 2019 Mar;155(3):528-533. doi: 10.1016/j.chest.2018.09.007. Epub 2018 Oct 3.

  PMID: 30291925 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Cystic Fibrosis; Pulmonary Fibrosis; Tuberous Sclerosis; Asthma; Sarcoidosis, Pulmonary; alpha 1-Antitrypsin Deficiency; Lung Diseases

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Lung Diseases, Interstitial; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hamartoma; Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Nervous System Diseases; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Congenital Abnormalities; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Sarcoidosis; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Delayed; Liver Diseases; Subcutaneous Emphysema; Emphysema

Study Officials

• Joel Moss, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tatyana A Worthy, R.N.

CONTACT

(301) 827-1376; worthyt@mail.nih.gov

Joel Moss, M.D.

CONTACT

(301) 496-1597; mossj@nhlbi.nih.gov

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: September 13, 1996
• Last Updated: April 24, 2026

Record last verified: 2026-02-11

Locations

US (2)