UH3HL151865

Preclinical pulmonary fibrosis, an opportune rare disease cohort - Abstract FDR from FIP family. Our proposed rare disease cohort focuses on a critical unmet public health need in (N=1000) interstitial pneumonia, to understand the etiology, natural history, and phenotypic (N=650) subcohort (N=350) heterogeneity of preclinical pulmonary fibrosis (PREPF), before the lung is scarred irreversibly.

Our overall hypothesis is that common genetic variants and (100) PREPF (50) PREPF environmental risk factors predispose to the development, natural history, (300) unaffected and phenotypic heterogeneity of PREPF, and that defining these risk factors will allow us to uncover the common and unique subtypes of PREPF that differ case-cohort at baseline in disease onset and progression.

By leveraging our NHLBI-supported (150 cases; 300 unaffecteds) discoveries in PREPF, familial interstitial pneumonia (FIP), and idiopathic interstitial pneumonia (IIP), and our NHLBI-supported cohort of FIP families, our proposal subcohort and the original FIP cohort. Given the risk of PREPF FIP FDRs (15%), we anticipate result in the earliest stages of this highly morbid, phenotypically heterogeneous that 50 individuals in the disease.

We will focus on first-degree relatives (FDRs) previously phenotyped as subcohort will have PREPF at unaffected (N=2404) from our 1160 FIP families with two or more cases of baseline. Cases will be supplemented from the confirmed IIP. Within these 1160 FIP families, we will establish our rare disease remaining 650 subjects in the cohort of 1000 subjects by selecting up to two asymptomatic, previously phenotyped overall cohort so that our case- unaffected FDRs per family.

To combine the advantages of our cohort with the cohort population at baseline should include 150 cases of efficiency of a nested case-control study, we will establish a case-cohort study and PREPF and 300 unaffecteds. Compare 150 cases of PREPF to 300 unaffected controls (Figure 1). This approach will allow us to determine the individual and combined contributions of common genetic variants and environmental features that result in the development of PREPF.

By focusing on the natural history of IIP, our results can be used to identify high-risk populations, early forms of the disease, factors associated with disease progression, and biological targets for drug development. Moreover, a natural history study can also identify critical biomarkers that can be diagnostic of early or established forms of the disease, prognostic of the course of a disease, predictive of treatment response, or useful in guiding patient selection and dose selection in drug development programs.

Our proposal would establish a prospectively followed high-risk IIP cohort, will identify the genetic and environmental risk factors for PREPF, and will maximize the utility of this high-risk cohort for ancillary studies focused on primary and secondary prevention of IIP.

The Regents Of The Univ. Of Colorado

THE DIVISION OF LUNG DISEASES SUPPORTS RESEARCH AND RESEARCH TRAINING ON THE CAUSES, DIAGNOSIS, PREVENTION, AND TREATMENT OF LUNG DISEASES AND SLEEP DISORDERS. RESEARCH IS FUNDED THROUGH INVESTIGATOR-INITIATED AND INSTITUTE-INITIATED GRANT PROGRAMS AND THROUGH CONTRACT PROGRAMS IN AREAS INCLUDING ASTHMA, BRONCHOPULMONARY DYSPLASIA, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, CYSTIC FIBROSIS, RESPIRATORY NEUROBIOLOGY, SLEEP AND CIRCADIAN BIOLOGY, SLEEP-DISORDERED BREATHING, CRITICAL CARE AND ACUTE LUNG INJURY, DEVELOPMENTAL BIOLOGY AND PEDIATRIC PULMONARY DISEASES, IMMUNOLOGIC AND FIBROTIC PULMONARY DISEASE, RARE LUNG DISORDERS, PULMONARY VASCULAR DISEASE, AND PULMONARY COMPLICATIONS OF AIDS AND TUBERCULOSIS. THE DIVISION IS RESPONSIBLE FOR MONITORING THE LATEST RESEARCH DEVELOPMENTS IN THE EXTRAMURAL SCIENTIFIC COMMUNITY AS WELL AS IDENTIFYING RESEARCH GAPS AND NEEDS, OBTAINING ADVICE FROM EXPERTS IN THE FIELD, AND IMPLEMENTING PROGRAMS TO ADDRESS NEW OPPORTUNITIES. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, USE SMALL BUSINESS TO MEET FEDERAL RESEARCH AND DEVELOPMENT NEEDS, FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY SOCIALLY AND ECONOMICALLY DISADVANTAGED PERSONS, AND INCREASE PRIVATE-SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE R&D BETWEEN SMALL BUSINESSES AND RESEARCH INSTITUTIONS, AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL R&D.

93.837 - Cardiovascular Diseases Research

National Heart Lung and Blood Institute (NHLBI) [HHS - NIH]

Aurora, Colorado 800452560 United States

Single Zip Code

Rare Disease Cohorts in Heart, Lung, Blood and Sleep Disorders (UG3/UH3 Clinical Trial Not Allowed) (RFA-HL-20-014)

Amendment Since initial award the total obligations have increased 281% from $1,225,650 to $4,674,232.