# Impact of Wildfire Smoke on Lung Injury

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2024 · $433,950

## Abstract

ABSTRACT
The US Environmental Protection Agency recognizes wildfire smoke as a significant source of particulate matter
under 2.5 microns diameter (PM2.5) emissions, which are expected to increase because of climate change. The
National Oceanic and Atmospheric Administration estimates that 200 million people in the United States live in
counties affected by wildfire smoke conditions. Exacerbation of pre-existing respiratory conditions, including
asthma and COPD, is associated with wildfire events. However, there is a paucity of data on whether wildfire
smoke exposure can promote the development of chronic disease. Understanding the human health risks of
wildfires is complicated by highly variable emissions from combined combustion of biomass and anthropogenic
materials at the wildland urban interface. Further, growing epidemiological evidence suggests that particulate
matter source and composition can be associated with more severe health outcomes. There is a compelling
need to understand the toxicology of wildfire smoke exposures for public health, particularly in vulnerable
populations such as young children. The goal of our revised R21 application is to address the significant
knowledge gap by which inhaled wildfire smoke can elicit cellular injury in the respiratory tract of pediatric
populations. We hypothesize that neonatal lung epithelium is more susceptible to inflammation and injury as a
result of wildfire smoke PM2.5 exposure. We further propose that wildfire smoke PM2.5 exposure can elicit
endoplasmic reticulum (ER) stress in lung epithelium, progressively leading to restrictive lung disease. Our
hypothesis is based upon preliminary data with evidence of immune dysregulation and restrictive lung disease
in adult rhesus monkeys exposed as infants to the 2008 Northern California Humboldt/Trinity County fires, as
well as altered expression of lung ER stress markers and surfactant protein C (SP-C) in juvenile rhesus monkeys
exposed to the 2018 Northern California Butte County “Camp” fire. We will test our hypothesis using wood smoke
particles as a surrogate for wildfire smoke PM2. in primary cell or organoid lung epithelial cell cultures, followed
by in vivo exposures using a neonatal mouse model. The Specific Aims of this revised R21 application will (1)
Define the contribution of chronologic age on impact of wood smoke particle toxicity in respiratory epithelium; (2)
Define the contribution of chronologic age on impact of wood smoke particle toxicity in alveolar epithelium; and
(3) Investigate the effect of early life wood smoke particle exposure on induction of immune dysregulation and
lung function decrements in the adult lung. To understand how the immune system and respiratory tract can be
functionally and persistently altered by air pollutants, an essential step is to determine the cellular mechanisms
of exposure in vulnerable populations such as young children. Our findings will inform on the unique toxicological
aspects of air pol...

## Key facts

- **NIH application ID:** 10993533
- **Project number:** 1R21ES036378-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Lisa A Miller
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $433,950
- **Award type:** 1
- **Project period:** 2024-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10993533

## Citation

> US National Institutes of Health, RePORTER application 10993533, Impact of Wildfire Smoke on Lung Injury (1R21ES036378-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10993533. Licensed CC0.

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