Role of Genetic Factors in the Pathogenesis of Lung Disease

Inclusion 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, probable, 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.