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. During the years 2024-2029, these visits will also contain an additional questionnaire, a urine specimen, and the use of wearable devices to further investigate the environmental factors that may contribute to pulmonary fibrosis. 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.

Approximately every 3 years, we may contact you to return to Vanderbilt for another round of blood draw, high resolution CT scan of your lungs, and Pulmonary Function Tests (PFTs). These tests are repeated to help us understand whether changes in blood, CT scan, or lung function can predict the development of pulmonary fibrosis in relatives of patients with pulmonary fibrosis. We expect the follow-up period to last approximately 10 years (from the first study visit). Subjects will be asked to complete no more than 6 total blood/HRCT/PFT collections.

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.