Families-At-risk for Interstitial Lung Disease Study (FAR-ILD)

The Families-At-risk for Interstitial Lung Disease Study

The interstitial lung diseases (ILDs) are a family of closely related lung conditions characterized by alveolar inflammation, injury, and fibrosis not due to infection or neoplasia. While previously considered to be rare, a recent nationwide study found that idiopathic pulmonary fibrosis (IPF), a fibrotic ILD with a median survival of only 3.8 years, affects nearly 0.5% of older adults in the U.S. While pirfenidone and nintedanib slow the progression of IPF, neither reverses fibrosis nor prevents progression of the disease,and no studies to date have tested interventions that prevent the development of fibrotic ILDs.

Study Overview

• Status: Completed
• Conditions: Idiopathic Pulmonary Fibrosis; Interstitial Lung Disease

Detailed Description

The NHLBI has prioritized research focused on the primary prevention of chronic lung diseases, including ILD. The overall goal of this study is to conduct studies preparatory to and requisite for the testing of ILD preventative interventions.

In the current study, the investigators propose to examine the pulmonary histopathology and biology of early subclinical ILD in healthy adults with a first-degree relative with clinically diagnosed ILD. There are two currently accepted computed tomographic (CT)-based phenotypes of subclinical ILD: high attenuation areas (HAAs) and interstitial lung abnormalities (ILA). Investigators from Columbia University Medical Center have previously shown that HAA has strong construct validity as an imaging biomarker of early subclinical alveolar inflammation and fibrosis among community-dwelling adults using the Multi-Ethnic Study of Atherosclerosis (MESA), an ongoing NHLBI-funded prospective cohort study of 6,814 adults age 45 and older at enrollment in 2000-02. Investigators found that greater HAA at baseline was independently associated with reduced lung function and exercise capacity at 5-year follow-up, exertional dyspnea at 10-year follow-up, and elevated serum levels of matrix metalloproteinase-7 (MMP-7) and interleukin-6 (IL-6). ILA is a distinct qualitative and visually-identified early ILD phenotype on CT that has also shown strong construct validity for ILD. Neither HAA nor ILA has been validated histopathologically.

The lipoprotein substudy will examine the role of high density lipoproteins in patients with ILD. Patients with IPF have previously been shown to have low levels of high density lipoprotein (HDL) and high levels of low density lipoprotein (LDL). Investigators have previously shown that high levels of high-density cholesterol (HDL-C) are associated with a reduction in lung injury, inflammation and fibrosis (subclinical ILD) on CT in community-dwelling adults enrolled in the Multi-Ethnic Study of Atherosclerosis. These data are consistent with animal model data showing that treatment with apolipoprotein A-I (ApoA-I; the main component of HDL) attenuates lung fibrosis. Investigators at Columbia University Medical Center are therefore proposing to examine the associations of HDL and its main components (apolipoprotein A-I, apolipoprotein A-II, and paraoxonase-1) with clinical outcomes (FVC decline, death, lung transplantation and respiratory hospitalizations) and serum biomarkers of lung injury, inflammation and remodeling (SP-A, MMP-7, ICAM-1, IL-1, IL-18) in patients with ILD. Investigators will also explore the structure (using quantitative proteomics) and function (using a macrophage efflux assay and paraoxonase-1 activity assay) of HDL particles in adults with ILD and first-degree family members with subclinical ILD.

Obstructive sleep apnea (OSA) is highly prevalent among adults with interstitial lung disease (ILD) and maybe a risk factor based on our previous studies from MESA (https://www.mesa-nhlbi.org/) and other research studies completed at Columbia University Medical Center. Therefore, the investigators will examine the association between OSA and sub-clinical ILD in at-risk adults.

• Study Type: Observational
• Enrollment (Actual): 125

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Adult participants with and without a diagnosis of Interstitial Lung Disease. Adult participants with a diagnosis of interstitial lung disease as per American Thoracic Society (ATS) guidelines. Adult participants with a first-degree relative with a clinical diagnosis of interstitial lung disease. Adult participants who are at least 50 years of age with a smoking history of a minimum of 1 pack per day.

Description

Inclusion Criteria: For "At Risk" participants without clinical ILD

• Age 35 years or older, however subjects who are 40 years old and above will undergo HRCT and subjects age 40-65 years old will be eligible to undergo bronchoscopy
• First-degree relative with one of the following clinical diagnoses:
• Idiopathic Pulmonary Fibrosis
• Idiopathic Non-Specific Interstitial Lung Disease (with fibrosis)
• Chronic Hypersensitivity Pneumonitis (with fibrosis)
• Unclassifiable Idiopathic Interstitial Pneumonia (with fibrosis)
• Patients with any ILD characterized by fibrosis on CT chest scan
• Ability to provide informed consent

Inclusion Criteria: For "At Risk Smoker" participants without clinical ILD

• At least 50 years of age
• Smoked at least 1 pack a day for 30 years

Exclusion Criteria: For "At-Risk" participants without clinical ILD

• Known history of interstitial lung disease
• History of illicit drug use within the past year.
• Lower respiratory tract infection in the past 90 days.
• History of chest CT scan in the past year.
• Known history of heart failure or chronic kidney or liver disease.
• Pregnancy or Lactation

Inclusion Criteria: For "Proband" participants with clinical ILD Age 18 years or older

• Has one of the following clinical diagnoses as per ATS guidelines:
• Idiopathic Pulmonary Fibrosis
• Idiopathic Non-Specific Interstitial Lung Disease (with fibrosis)
• Chronic Hypersensitivity Pneumonitis (with fibrosis)
• Unclassifiable Idiopathic Interstitial Pneumonia (with fibrosis)
• Patient with any ILD characterized by fibrosis on CT chest scan
• Ability to provide informed consent

Exclusion Criteria: For "Proband" participants with clinical ILD

• No Living 1st degree relatives.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
FAR-ILD Proband Participants; There will be no interventions administered to this group, only data collection.
FAR-ILD "At-Risk" Participants; There will be no interventions administered to this group, only data collection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With ILA (Interstitial Lung Abnormalities)	The visual identification of the presence of ILA (Interstitial Lung Abnormalities) on CT chest scan by a thoracic radiologist.	During imaging (up to 1 hour)

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); University of Iowa; Weill Medical College of Cornell University; University of Washington
• Investigators: Principal Investigator: Christine Garcia, MD, PhD, Columbia University

Publications and helpful links

General Publications

• Ost DE, Ernst A, Lei X, Kovitz KL, Benzaquen S, Diaz-Mendoza J, Greenhill S, Toth J, Feller-Kopman D, Puchalski J, Baram D, Karunakara R, Jimenez CA, Filner JJ, Morice RC, Eapen GA, Michaud GC, Estrada-Y-Martin RM, Rafeq S, Grosu HB, Ray C, Gilbert CR, Yarmus LB, Simoff M; AQuIRE Bronchoscopy Registry. Diagnostic Yield and Complications of Bronchoscopy for Peripheral Lung Lesions. Results of the AQuIRE Registry. Am J Respir Crit Care Med. 2016 Jan 1;193(1):68-77. doi: 10.1164/rccm.201507-1332OC.
• Pue CA, Pacht ER. Complications of fiberoptic bronchoscopy at a university hospital. Chest. 1995 Feb;107(2):430-2. doi: 10.1378/chest.107.2.430.
• Facciolongo N, Patelli M, Gasparini S, Lazzari Agli L, Salio M, Simonassi C, Del Prato B, Zanoni P. Incidence of complications in bronchoscopy. Multicentre prospective study of 20,986 bronchoscopies. Monaldi Arch Chest Dis. 2009 Mar;71(1):8-14. doi: 10.4081/monaldi.2009.370.
• Jin F, Mu D, Chu D, Fu E, Xie Y, Liu T. Severe complications of bronchoscopy. Respiration. 2008;76(4):429-33. doi: 10.1159/000151656. Epub 2008 Aug 21.
• Rosenthal E. New York seeks to tighten rules on medical research. N Y Times Web. 1996 Sep 27:B4. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2018
• Primary Completion (Actual): February 11, 2020
• Study Completion (Actual): July 1, 2023

Study Registration Dates

• First Submitted: August 20, 2018
• First Submitted That Met QC Criteria: August 21, 2018
• First Posted (Actual): August 22, 2018

Study Record Updates

• Last Update Posted (Estimated): November 17, 2023
• Last Update Submitted That Met QC Criteria: October 27, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Pulmonary Fibrosis; Interstitial Lung Disease
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Fibrosis; Lung Diseases; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Lung Diseases, Interstitial
• Other Study ID Numbers: AAAR1916; 2R01HL103676-05 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Researchers will be required to submit a written request to the PI describing the use of the data. The researcher must also document institutional review board (IRB) approval. No identifiable information will be released.
• IPD Sharing Access Criteria: De-identified data.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No