Families-At-risk for Interstitial Lung Disease Study
Condition: Interstitial Lung Disease; Idiopathic Pulmonary Fibrosis
MeSH terms: Lung Diseases; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Lung Diseases, Interstitial; Fibrosis
Study type: Observational

Summary: 
      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.
    

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.
    

Observational model: Cohort
Time perspective: Prospective
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.
      
Biospecimen description: 
      -  Tissue samples

        -  Airway Brushings

        -  Urine

        -  Bronchoalveolar Lavage Fluid

        -  Buccal swab and or saliva; only if blood is unavailable.

        -  Blood
    
Keywords: Interstitial Lung Disease; Pulmonary Fibrosis