Wildfire season isn’t waiting for summer anymore. By mid-March 2025—just days before the 2025 Hot Topic Session “Impacts and Implications of Wildfire Smoke on the Lung-Brain Axis”—9,988 wildfires had already burned more than 300,000 acres across the US. From Los Angeles in January to the Carolinas and Oklahoma in February and March, the data is changing week to week, but the trend is clear: more fires, more smoke, more exposure.
During this session, researchers dove into the emerging science behind how wildfire smoke affects not only our lungs and hearts but also our brains and reproductive systems. The session was chaired by Bruce Buchholz and Dorothy You of Lawrence Livermore National Laboratory, with presentations from Dr. Buchholz, Brenna Baird, and Luke Montrose.
Wildfire Smoke: A Complex, Moving Target
Kicking off the session, Dr. Buchholz emphasized the immense variability in wildfire smoke composition, depending on what’s burning, the temperature, and environmental factors. The result is a complex chemical cocktail of particulate matter (PM), volatile organic compounds (VOCs), and other combustion products. A stunning chart of hundreds of identified and unknown compounds drove home just how much is still being uncovered.
Using 14C-labeled wood smoke and accelerator mass spectrometry (a technique originally developed for radiocarbon dating), Dr. Buchholz’s team tracked where combustion products go after inhalation. Catechol, benzo(a)pyrene, and palmitic acid all appeared in the bloodstream and organs—including the brain—within hours. While most cleared quickly, palmitic acid lingered in the brain two weeks post-exposure.
Their findings suggest that these compounds reach the brain both via systemic circulation and through nasal pathways like the olfactory bulb—and that they may be disrupting the blood-brain barrier (BBB). In vitro exposure of brain endothelial cells to wood smoke extract led to decreased expression of tight junction markers and a dose-dependent increase in IL-8, a pro-inflammatory cytokine.
Smoke in the Brain: Inflammation and Immune Infiltration
Ms. Baird’s presentation dug deeper into the downstream effects of wildfire smoke on the brain. Preclinical mouse studies showed that even short-term exposure to wildfire smoke activated glial cells and immune pathways in the brain—and those changes persisted for weeks.
In one study, mice exposed to smoke while fed a saturated fat–enriched diet showed even greater inflammation and immune cell infiltration. Molecular markers like ICAM and VCAM remained elevated for up to 28 days. Promisingly, treatment with Fasudil (a Rho kinase inhibitor) reduced BBB disruption and immune trafficking, though it didn’t affect circulating peptides, suggesting a localized effect at the BBB.
Impacts Beyond the Brain: Reproductive Toxicology and Epigenetic Risk
Dr. Montrose wrapped up the session with research on how wildfire smoke impacts reproductive systems. His lab takes a “cell to society” approach, studying not just mice but also cattle, firefighters, and human cohort data.
Findings revealed differential gene expression in the prefrontal cortex of smoke-exposed male mice, changes in DNA methylation in sperm, and dose-dependent cytotoxicity in glial cells. Smoke also appeared to disrupt signaling in the hypothalamus-pituitary-gonadal (HPG) axis, suppressing spermatogenesis through inflammatory pathways.
Dr. Montrose’s team is also collecting data from wildland firefighters, and preliminary results are sobering: 19% of participants have self-reported fertility issues. The combination of occupational exposure, inflammation, and epigenetic shifts raises long-term questions about fertility and potential intergenerational effects.
Takeaways and What’s Next
Across all three talks, the message was clear: wildfire smoke doesn’t stop at the lungs. It’s capable of triggering persistent neuroinflammation, hormonal disruption, and even changes in reproductive cell integrity.
As wildfire seasons grow longer and more intense, understanding the full-body effects of wildfire smoke becomes a critical public health issue. The data is growing—and so is the need for action.
This blog reports on the Hot Topic Session titled “Impacts and Implications of Wildfire Smoke on the Lung-Brain Axis” that was held during the 2025 SOT Annual Meeting and ToxExpo. An on-demand recording of this session is available for meeting registrants on the SOT Online Planner and SOT Event App.
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