# Preclinical Pulmonary Fibrosis, an opportune rare disease cohort

> **NIH NIH UH3** · UNIVERSITY OF COLORADO DENVER · 2024 · $1,111,413

## Abstract

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 Figure 1. Relationship between
pneumonia (IIP), and our NHLBI-supported cohort of FIP families, our proposal Subcohort and the original FIP
seeks to explain how common genetic variants and the environment interact to 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.

## Key facts

- **NIH application ID:** 10898872
- **Project number:** 5UH3HL151865-05
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** David Albert Schwartz
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,111,413
- **Award type:** 5
- **Project period:** 2020-08-20 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10898872

## Citation

> US National Institutes of Health, RePORTER application 10898872, Preclinical Pulmonary Fibrosis, an opportune rare disease cohort (5UH3HL151865-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10898872. Licensed CC0.

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