Families-At-risk for Interstitial Lung Disease Study
| Status: | Recruiting |
|---|---|
| Conditions: | Lung Cancer, Pulmonary, Pulmonary, Pulmonary |
| Therapuetic Areas: | Oncology, Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 35 - 100 |
| Updated: | 8/24/2018 |
| Start Date: | January 15, 2018 |
| End Date: | October 1, 2037 |
| Contact: | David J Lederer, MD |
| Email: | dl427@cumc.columbia.edu |
| Phone: | 212-305-8203 |
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.
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.
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.
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.
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.
We found this trial at
1
site
630 West 168th Street
Manhattan, New York 10032
Manhattan, New York 10032
Principal Investigator: David J Lederer, MD
Phone: 212-305-8203
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