BY ESSEY AFEWERKI
57,000 acres of land in Los Angeles were razed in the span of 3 weeks from January 7th to 27th at the start of this year. The scorched earth across the Palisades and Eaton regions swallowed more land than exists in the whole of Manhattan or Washington DC 1. The immediate destruction wrought in the wake of these infernos is all too easy to visualize. Family homes charred to splinters, parks buried in ash, and scores of lives lost. Those that survive are often left with permanent scars from the ordeals, be it physical burns, respiratory injuries caused due to smoke inhalation, trauma, or a host of others. But while the fires wreak such visible havoc across TV screens and headlines nationwide, they’re simultaneously sowing the seeds for decades more damage that will be felt long after the last embers burn out, and that far too often goes unrecognized. A range of factors ravage the human body during and in the aftermath of a fire, and a great deal of them cause subtle but devastating damage to the human immune system. These impacts can lie in wait for years before being realized as the body begins to collapse under the incursion of an otherwise manageable illness. What are these effects, how can they arise, and can we prevent them?
Where there’s fire, there’s smoke, and that smoke is one of the leading causes of the
damage caused by fires to the immune system. Despite its gaseous nature and appearance, smoke is far from being that simplistic. It’s comprised of a destructive cocktail of agents that excel at causing inflammation – or harmful swelling – of the respiratory tract, including but not limited to fine particulate matter from vaporized -and potentially hazardous – material, resulting in soot and ash, as well as harmful chemicals like volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs). This inflammation is a form of immediate damage, causing pain and irritation, but it also opens the door to host of infections in the long term. In this weakened state the body is focused on trying to repair itself and, as a result, less capable of fighting off disease. To that point, in January 2020, when the Australian wildfires were raging in the midst of
the ongoing coronavirus pandemic, subsequent research on the topic found direct links between fire exposure and the impact of COVID-19 on populations that had experienced them both. Residents of New South Wales, an Australia state that was hit especially hard by the blaze, showed a greater risk of COVID-19 infections than the global average 2,3. This illustrated only a minutia of the myriad ways that fires can lay the foundation for long-term damage by attacking the immune system.
The mechanism that leads to the inflammation caused by smoke inhalation is intrinsically
linked to the molecular-level process of oxidative stress. Oxidative stress reaction is initiated by the introduction of VOC compounds composing smoke into the body via inhalation. These compounds proceed to disrupt the body’s internal processes by then inappropriately activating the NADPH oxidase protein that is found in immune cells. NADPH oxidase is an enzyme that works to produce a class of molecules known as Reactive Oxidative Species (ROS). At normal levels, ROS work to facilitate and maintain the proliferation and expansion of blood vessel networks, providing oxygen and blood-bound nutrients to damaged tissues to facilitate their repair. But with NADPH oxidase in overdrive, excess ROS are produced, leading to over development of blood vessels in a tissue. This commonly leads to redness, swelling, andtenderness; in other words, symptoms that are typically associated with the state of inflammation and immune system weakness leading to infection 2.
Beyond the indirect impacts of inciting inflammations, VOCs and PAHs found in smoke
also directly inhibit bodily immune responses through targeted attacks on key cellular machinery. VOCs specifically are known to directly alter immune cell function by decreasing their production rates of antibodies and lymphocytes. These are specialized structures that tag and hunt down invading particles respectively and are crucial to the body’s immune response. In a similar vein, PAHs are known to lead to a disease known as thymus atrophy. This is caused by the aryl hydrocarbon receptor being perpetually activated by PAHs, which disrupts biochemical reaction pathways and results in decreased thymus lymphocyte production. Thus, these compounds found in wildfire smoke are not only capable of leaving the body more vulnerable to infection via inflammation, but also actively degrading it’s ability to fight off said infections by
hijacking critical immune response systems 2.
Looking at this interaction from an order of magnitude above these chemical imbalances,
smoke inhalation also disrupts bodily function on the genetic level. It accomplishes this via the deactivation of specific genes critical to the production of immune cells that help the body fight off infection. This is achieved by the hijacking of an expression regulation system called methylation, that under normal conditions controls inhibition of select genes during development and the lifespan. In order to understand methylation, the higher order structure of DNA must be grasped. Thousands of unique segments on a single DNA strand will wrap around individual proteins called histones, ultimately forming what can be visualized as a chain of histones linked by one piece of DNA. Then, during methylation, methyl group compounds attach to the protruding tails of the histone proteins. When methyl groups attach to these tail groups, force the histones to pull their wrapped DNA tighter around themselves, compacting the overall strand. This closely compacted state directly inhibits the binding of transcription factors/machinery that
bind to free DNA segments and translate them into proteins that can do the work encoded by a given gene. Thus, methylation makes the DNA inexpressible. With that mechanism understood the relationship between smoke inhalation and gene repression becomes clearer.
An observational study was conducted on a group of rhesus macaque monkey
populations (extremely genetically similar model organisms to humans) that were exposed to different levels of smoke compounds during their youth4. These consisted of ozone and particulate matter of less than 2.5 μm in diameter (PM2.5), which is especially dangerous for its ability to penetrate the mucous membranes protecting most respiratory system machinery. The genomes of these macaques were then sequenced, revealing their chemical makeup including the presence of methyl groups. This analysis revealed 3370 regions where methylation differed between the exposed and non-exposed populations, and 86% of these differently methylated sequences were then found to be instances of hypermethylation (excess methylation) in exposed individuals. Moreover, a significant fraction of these methylation instances were recorded on histones holding genes encoding immune response cells. It’s in this way that exposure to wildfires and their smoke can cause lasting damage on the genetic level that isn’t felt until
potentially years down the line when the immune system crumbles in the face of a manageable threat.
As has been shown, wildfires attack the human immune system in a multi-pronged
assault from which it takes considerable effort to properly protect oneself given the best of conditions to work with. That said, those without said means find themselves even more disproportionately at risk, and subject to major health inequities. For example, inhabitants of poorer urban areas more often live in significantly older homes, that were built during years past before understanding of the dangers of smoke inhalation was widespread. As such, these buildings often fail to meet the protective atmosphere insulation standards of modern homes and poorly if at all isolate the indoor air from that of the outdoors. This results in the effects of smoke inhalation being made considerably larger threats to specifically the Global South regions of the world. This demographic encompasses many other largely marginalized groups – be they based on race, ethnicity, or other factors – and only contributes to the stark inequity of global healthcare. Thankfully, some these impacts can be successfully staved off if they are faced while
well-prepared. N95 masks (while not providing perfect protection) are a good preventative measure at the first sign of poor air quality. They filter air before it enters one’s lungs, ideally removing much of the particulate matter and harmful compounds. If possible, sealing points of airflow within rooms and installing HEPA air filters is another significant step forward in purifying air and addressing concerns of smoke inhalation. Such practices are especially important in rooms housing infants or elderly persons, whose immune systems are already markedly weak and vulnerable. These efforts can help make tangible differences in the effort to prevent and bring attention to immune system damage that’s caused by wildfires5.
The damage caused by wildfires is great and extensive, reaching into our very bodies on a chemical and genetic level and sowing discord to haunt later years of our life. The immune system is a far too often undiscussed casualty of these blazes, and long after the last embers of the LA infernos fizzle out, their invisible scars will remain. Despite surviving the immediate blaze, the human body is left in a weakened and vulnerable state to infectious diseases, which can potentially remain true for the rest of one’s life. The fire doesn’t have to kill to be felt; the mere memory of one can leave a scar enough on the human body to bring one low years after the fact. As the climate clock ticks ever on, these fires and the dangers that they pose to subsequent decades of human health will only continue to worsen and remain ever-looming threats. Unless we want to live the next decades of our lives in the shadows of such preventable damage, we need to act now to fight climate change. For the sake of our world, our homes, and our health, the ever-changing climate demands our attention.
Essey Afewerki a first-year student in Yale College.
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References
- Guzman, C. D. (2025). Here’s the Size of the L.A. Fires So Far. Time, Time Magazines.
- Frumento, D. and Ș. Țãlu (2024). “Effects of Wildfire Exposure on the Human Immune System.” Fire 7(12).
- Christine Carson, L. K. (2025). Wildfires ignite infection risks, by weakening the body’s immune defences and spreading bugs in smoke. The Conversation.
- Brown, A. P., Cai, L., Laufer, B. I., Miller, L. A., LaSalle, J. M., Ji, Hi., (2022). “Long-term effects of wildfire smoke exposure during early life on the nasal epigenome in rhesus macaques.” Environ Int 158: 106993.
- Ryan, D. (2020). Health Impacts of Wildfire Smoke | Stanford Woods Institute for the
Environment, Stanford Woods Institute for the Environment.
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