Mechanisms of Familial Pulmonary Fibrosis

Purpose

This a prospective, longitudinal study of first-degree family members of patients diagnosed with familial interstitial pneumonia (FIP). FIP is the familial form of idiopathic pulmonary fibrosis (IPF), which is defined as 2 or more bloodline relatives which have a diagnosis of idiopathic interstitial pneumonia (IIP). The most common form of idiopathic interstitial pneumonia in FIP families is IPF (approximately 70%). The inheritance pattern in FIP is consistent with autosomal dominant inheritance with incomplete penetrance. Therefore, individuals in this study have approximately 50% risk of carrying a disease-associated allele. The causative gene is currently only known approximately 20% of families. The main goal of this longitudinal study is to better establish the natural history of FIP and to identify risk factors for later development of symptomatic disease. The investigators' plan is to follow these at-risk individuals with yearly questionnaires and planned in person 5 year follow-ups through age 70 or until they develop symptomatic FIP.

Conditions

  • Familial Pulmonary Fibrosis
  • Idiopathic Pulmonary Fibrosis
  • Familial Interstitial Pneumonia

Eligibility

Eligible Ages
Between 40 Years and 70 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Study Type
Observational
Observational Model
Family-Based
Time Perspective
Prospective

Arm Groups

ArmDescriptionAssigned Intervention
Familial Pulmonary Fibrosis Subjects asked to participate in this study will be unaffected family members of patients previously diagnosed with familial interstitial pneumonia (FIP) which is the familial form of idiopathic pulmonary fibrosis (IPF).

Recruiting Locations

Vanderbilt University Medical Center
Nashville, Tennessee 37232

More Details

NCT ID
NCT03437486
Status
Recruiting
Sponsor
Vanderbilt University Medical Center

Study Contact

Katrina N Douglas, BA
6153433941
Katrina.douglas@vumc.org

Detailed Description

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.