Mechanisms of Familial Pulmonary Fibrosis

Potential research subjects will be sent a questionnaire (modified version of the ATS-DLD-78
questionnaire) and study consent form. Individuals with no prior history of lung disease and
a dyspnea score of 2 or less will be offered the opportunity to undergo further research
evaluation, which will include HRCT scanning, pulmonary function testing (PFTs) and blood
draw. Subjects with grade 3 or greater dyspnea or findings of extensive disease on HRCT scan
(see below), will be recommended to undergo clinical diagnostic evaluation outside the study.
For those subjects that participate in this study, demographic information will be collected
and stored in a database, including past medical history, smoking history, medications, and
occupational and environmental exposure history.

At 5 year intervals after initial enrollment, subjects without clinical disease will be
offered a repeat HRCT scan and PFTs.

Each year after enrollment, the investigators will perform follow-up to ascertain whether
subjects have: 1) developed respiratory symptoms consistent with FIP/IPF, 2) undergone
additional diagnostic evaluations for lung disease, or 3) begun any new treatments for lung
disease. Subjects who have developed respiratory symptoms will be encouraged to seek medical
evaluation. For those who have undergone any new diagnostic testing or have been diagnosed
with FIP, study coordinators will seek permission to obtain HRCTs, medical records, pulmonary
function test results, and lung blocks for evaluation by investigators in this study.

The investigators will use standard criteria established by the ATS/ERS to guide the
diagnostic classification of patients who develop FIP. Information will be reviewed by a
pathologist, a radiologist, and 3 clinicians. In all cases, the clinicians make the final
diagnosis and after reviewing the clinical material (clinical/demographic data and pulmonary
physiology), and the radiology and pathology data.

HRCT: A single prone HRCT scan without intravenous contrast will be performed and read by an
expert chest radiologist. He will assess the presence, extent, and distribution of areas of
ground-glass attenuation, interlobular reticular opacities, irregular thickening of
interlobular septa, traction bronchiectasis, and traction bronchiolectasis. The anatomic
distribution of each finding will be classified in each lung in one of 4 zones from apex to
base (upper, middle, lower, lowest). A score of 0 (absent), 1 (<5%), or 2 (>5% parenchymal
involvement) will be given for each descriptor in each lung zone based on visual estimation
(total score of 1-16). In addition, HRCT scans will be classified as: 1) normal, 2) abnormal,
consistent with early FIP, 3) abnormal, consistent with extensive disease, or 4) abnormal,
consistent with other diagnoses. Extensive disease is defined as >5% honeycombing in >2
zones. Other diagnoses could include suspicious lung nodules, extensive emphysema, or other
findings requiring clinical referral. Disease progression on HRCT is defined by an increase
in the total CT score.

Pulmonary function testing: PFTs will include spirometry, lung volumes, and DLCO.

Specimen collection, processing, and banking: Each subject will have 20 ml blood collected on
enrollment and on the day of repeat HRCT. Lymphocytes will be saved for generation of
lymphoblastoid cells, DNA isolation, and telomere length analysis. Both serum and plasma will
be saved for further studies.

Inclusion Criteria:

1. Bloodline members of an affected individual from a family in which two or more members
of a family bloodline are known to have had proven Idiopathic Interstitial Pneumonia
(IIP) and who have no known diagnosis of IIP or IPF

2. Age 40 to 70 or 5 years younger than the youngest case of FIP in the family.

Exclusion Criteria:

1. Inability to understand the requirements of the study or be unwilling to provide
written informed consent (as evidenced by signature on an informed consent document
approved by the IRB).

2. Inability to travel to Nashville for 1-2 outpatient visits and/or complete a written
or on line version of the Early Interstitial Lung Disease Questionnaire

3. Age < 40 or >75 years old not eligible for bronchoscopy and < 18 not eligible for CT

4. Underlying disease with signs and symptoms that could be confused with IIP or IPF
symptoms (i.e., rheumatoid arthritis or other connective tissue diseases, occupational
lung disease, chemotherapy, etc.)

5. Thought to be unsuitable for participation in the study in the opinion of the
investigator