Role of Genetic Factors in the Development of Lung Disease

Study Description

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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.

Condition or disease
Cystic Fibrosis; Sarcoidosis; Tuberous Sclerosis; Asthma

Detailed Description:

This study is designed to evaluate genetic mechanisms of lung disease by surveying polymorphic genes involved in respiratory function and examining gene expression in the lung cells of individuals with pulmonary disease (e.g., alpha 1-antitrypsin deficiency, asthma, chronic obstructive pulmonary disease, cystic fibrosis, sarcoidosis, history of infection, and genetic mutations consistent with lung pathology). Emphasis will be on defining the distribution of allelic variants of nitric oxide synthase, alpha 1-antitrypsin, and the cystic fibrosis transmembrane conductance regulator genes in patients and in age- and sex-matched healthy individuals in a control population.

Study Design

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Study Type :	Observational
Estimated Enrollment :	3600 participants
Official Title:	Role of Genetic Factors in the Pathogenesis of Lung Disease
Study Start Date :	June 6, 1996

Groups and Cohorts

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Outcome Measures

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Eligibility Criteria

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	8 Years to 90 Years (Child, Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

• INCLUSION CRITERIA:

Inclusion criteria for patients with AAT deficiency include: (1) Diagnosis of AAT with a confirmed phenotype considered in the high risk category; (2) Clinical phenotype consistent with potential genetic diseases and other genetic causes of lung diseases (3) symptoms consistent with pulmonary disease; (4) chest x-ray consistent with pulmonary disease; (5) pulmonary function tests consistent with pulmonary disease; (6) 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 quit smoking three or more years ago;

Inclusion criteria for individuals with chronic obstructive pulmonary diseases include:

1. symptoms consistent with pulmonary disease
2. chest x-ray consistent with pulmonary disease
3. pulmonary function tests consistent with pulmonary disease;
4. 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.

Inclusion criteria for patients with cystic fibrosis include a defined genetic mutation (i.e., any of the known variants of the CFTR gene, such as delta F508 allele) or a cystic fibrosis phenotype and clinical features consistent with this disease. Children with cystic fibrosis over eight years of age may be included.

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.

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.

Because radiation exposure is not required, pregnant women are not excluded from the study.

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.

EXCLUSION CRITERIA:

Exclusion criteria for all participants include:

1. 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;
2. 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.

An exclusion criteria for participating in the x-ray portion of the study is pregnancy.

Exclusion criteria for participating in the bronchoscopy portion of the study are:

1. presence of any contraindication for fiberoptic bronchoscopy, with lavage and/or bronchial brushing;
2. 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
3. allergy to topical anesthetic (e.g., lidocaine)
4. current or recent respiratory infection (within the last 4 weeks)
5. pregnancy or lactation
6. age less than 18 or greater than 65.

Contacts and Locations

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Contacts

Contact: Tania R Machado	(301) 496-3632	tania.machado@nih.gov
Contact: Joel Moss, M.D.	(301) 496-1597	mossj@nhlbi.nih.gov

Locations

United States, Maryland
Suburban Hospital	Recruiting
Bethesda, Maryland, United States, 20814
National Institutes of Health Clinical Center, 9000 Rockville Pike	Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 prpl@cc.nih.gov

Sponsors and Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Suburban Hospital

Investigators

Principal Investigator:	Joel Moss, M.D.	National Heart, Lung, and Blood Institute (NHLBI)

More Information

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

NIH Clinical Center Detailed Web Page 

Publications:

Rybicki BA, Beaty TH, Cohen BH. Major genetic mechanisms in pulmonary function. J Clin Epidemiol. 1990;43(7):667-75.

Welsh MJ, Fick RB. Cystic fibrosis. J Clin Invest. 1987 Dec;80(6):1523-6. Review.

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.

Responsible Party:	National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:	NCT00001532 History of Changes
Other Study ID Numbers:	960100; 96-H-0100
First Posted:	November 4, 1999
Last Update Posted:	April 4, 2018
Last Verified:	March 28, 2018

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) ):

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

Additional relevant MeSH terms:

Fibrosis; Cystic Fibrosis; Lung Diseases; Sarcoidosis; Tuberous Sclerosis; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Lymphoproliferative Disorders; Lymphatic Diseases	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