Role of Genetic Factors in the Pathogenesis of Lung Disease

  • End date
    Sep 30, 2030
  • participants needed
  • sponsor
    National Heart, Lung, and Blood Institute (NHLBI)
Updated on 28 October 2022
ct scan
chest x-ray
pulmonary function test
chest ct
pulmonary disease
MRI Scan
pulmonary fibrosis
genetic disorder
obstructive lung disease
cftr gene
lung ct
lymphatic disorders
histiocytosis x
Accepts healthy volunteers


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


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....


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.

Condition Cystic Fibrosis, Pulmonary Fibrosis, Tuberous Sclerosis, Asthma, Pulmonary Sarcoidosis
Treatment Toshibia Aquilion One CT
Clinical Study IdentifierNCT00001532
SponsorNational Heart, Lung, and Blood Institute (NHLBI)
Last Modified on28 October 2022


Yes No Not Sure

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
symptoms consistent with pulmonary disease
smokers, defined as individuals who are current smokers (1 pack per day for at least 2
chest x-ray consistent with pulmonary disease
years) and nonsmokers, defined as never-smokers or ex-smokers who have not smoked for
pulmonary function tests consistent with pulmonary disease
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. 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
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

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
Exclusion criteria for all participants include
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
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
allergy to topical anesthetic (e.g., lidocaine)
Exclusion criteria for participating in the bronchoscopy portion of the study are
current or recent respiratory infection (within the last 4 weeks)
presence of any contraindication for fiberoptic bronchoscopy, with lavage and/or
pregnancy or lactation
bronchial brushing
age less than 18 or greater than 65
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
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact


Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider


Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 



Reply by • Private

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note