# Project 2: Environmental exposures in pre-clinical FPF

> **NIH NIH P01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $399,950

## Abstract

PROJECT SUMMARY
Pulmonary fibrosis (PF) is a progressive lung disease that typically presents in older adults who have
moderately advanced disease and a limited life expectancy of 3-5 years after diagnosis. The current paradigm
of disease pathogenesis is one of recurrent, low-grade injury to the lung epithelium (e.g., by cigarette smoke)
with an abnormal repair process in a susceptible individual. The exposome is defined as the totality of
exposures experienced over a lifespan. Key stakeholders have called for integration across other ‘omics
platforms to understand how exposures impact health. A key gap in our current understanding of PF
pathobiology is a limited understanding of how environmental exposures contribute to disease development, as
few (if any) studies have integrated an assessment of environmental exposures with disease pathobiology. Our
group and others have demonstrated that clinical (symptomatic) PF develops after years when a more subtle
abnormality is present on lung imaging and/or tissue examination. Because family history is a major risk factor
for PF (up to 100-fold increased risk), we established the At-Risk for Familial PF Cohort to study the natural
history of pre-clinical PF among asymptomatic relatives of PF patients. This cohort of middle-aged adults is
enriched with individuals with pre-clinical PF; 22% had abnormal interstitial changes of the lung parenchyma,
termed interstitial lung abnormalities (ILA), on the enrollment screening chest CT scan, and 30% experienced
pre-symptomatic progression of ILA or developed symptomatic PF during a longitudinal observation period of
~5 years. At-Risk Cohort participants self-report environmental exposures at cohort enrollment, and several of
these exposures (e.g., coal dust, welding, mold) were associated with ILA and its progression. In addition, At-
Risk Cohort participants with ILA have alterations in peripheral blood gene expression in pathways also
associated with environmental exposures. The objectives of this Project are to identify specific environmental
exposures and potential biological intermediaries that are associated with pre-clinical PF. The central
hypothesis is that environmental exposures contribute to the development of PF by causing direct injury and/or
altering the repair response, with exposure-associated biological alterations detectible before the onset of
clinical disease. The Specific Aims are: 1) Determine the chemical, metal, and respirable environmental
exposures associated with pre-clinical PF; and 2) Identify putative metabolic or transcriptomic intermediaries
between environmental exposures and pre-clinical PF. In a sub-study nested in the At-Risk Cohort, exposures
are measured via complementary modalities, including wearable devices, and biological intermediaries via
serum metabolomics and single-cell RNA sequencing of peripheral blood mononuclear cells. Pre-clinical PF-
associated features will be identified among age- and sex-matched pairs with...

## Key facts

- **NIH application ID:** 10846189
- **Project number:** 1P01HL172729-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Margaret Louise Salisbury
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $399,950
- **Award type:** 1
- **Project period:** 2024-09-17 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10846189

## Citation

> US National Institutes of Health, RePORTER application 10846189, Project 2: Environmental exposures in pre-clinical FPF (1P01HL172729-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10846189. Licensed CC0.

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