Impact of Wildfire Smoke on Lung Injury

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 pollution exposures resulting from wildfires and lead to development of biomarkers and preventative measures to limit the adverse health effects of restrictive lung diseases.