Wildfires are an escalating global issue, with their frequency and intensity rising significantly. This increase is largely attributed to climate change, which has altered temperature and precipitation patterns, resulting in prolonged fire seasons and larger areas affected. Each year, millions of individuals are exposed to smoke from wildfires, often multiple times during a single fire season. The expansion of urban development into fire-prone regions further amplifies the risk to human health and safety.
Wildfire smoke is becoming an increasing health threat, particularly for people with asthma and allergic airway conditions. It is known to trigger asthma flare-ups and increase sensitivity to allergens in the airways. However, research on the health effects, toxic properties, and biological mechanisms of wildfire smoke is very limited. This article highlights the possible underlying mechanisms that connect wildfire smoke exposure to the development of asthma and allergic airway diseases.
The primary components of wildfire smoke most studied for their role in triggering and worsening allergic and chronic airway diseases are particulate matter (PM), volatile organic compounds (VOCs), and ozone (O3).
Size and Impact of Particulate Matter (PM)
Wildfire smoke contains particles of varying sizes, with PM10 (coarse particles) being capable of reaching the lower airways and alveoli, while PM2.5 (fine particles) and PM0.1 (ultrafine particles) can penetrate even deeper into the respiratory system and potentially cause more severe damage. A global review of studies found that PM10 levels during wildfire events were 1.2–10 times higher compared to non-fire periods, significantly increasing the risk of respiratory issues, particularly asthma exacerbations. Studies have shown that exposure to both coarse PM10 and fine PM2.5 during wildfire events is strongly associated with the onset of asthma symptoms, increased use of oral steroids, and higher doses of reliever medication, suggesting that both types of particulate matter contribute to acute asthma flare-ups.
Wildfire smoke acts as a significant source of viable microbes, including both pathogenic and non-pathogenic fungal species. The smoke contains approximately four-fold higher microbial concentrations, with a viability of 78%, and exhibits five-fold higher taxon richness compared to non-smoke aerosols, highlighting its microbial diversity, altering the respiratory microbiome and immune environment, potentially triggering or worsening airway diseases. Under in vitro conditions, wildfire-derived PM2.5 was found to induce the expression of CYP1A1 and CYP1B1 genes more significantly than urban (non-combustion-derived) PM. Additionally, wildfire PM triggers cellular oxidative damage through a Fenton-like reaction involving transition metals (Fe++) and hydrogen peroxide (H2O2), resulting in the production of hydroxyl radicals.
VOCs, Toxic Gases, and Their Effects
Wildfire smoke contains diverse toxic gases such as SO2, NO, NO2, CO, and CO2, along with metals, polycyclic aromatic hydrocarbons (PAHs), and VOCs like aldehydes and n-alkanes. These pollutants originate from various fire substrates and construction materials, contributing to respiratory irritation and exacerbating asthma, especially in vulnerable groups like infants, pregnant women, and the elderly.
Even small amounts of SO2 can trigger bronchoconstriction and allergic asthma by interacting with sensory receptors in the lungs. VOC exposure, including substances like benzene, toluene, formaldehyde, and acrolein, is strongly associated with increased asthma risk in children and adults. Formaldehyde exposure, particularly at high levels, significantly raises the odds of asthma and respiratory issues.
VOCs and nitrogen oxides contribute to the formation of ground-level ozone (O3) through photochemical reactions, worsening air quality. NO2 exposure alone has been shown to enhance allergic airway inflammation and oxidative stress, increasing asthma susceptibility and airway remodelling.
CO exposure from biomass and fossil fuel combustion is linked to severe asthma exacerbations, respiratory diseases, and increased hospitalizations, especially among women. Elevated CO2 levels are associated with longer pollen seasons, increased allergen production, and heightened pollen allergenicity, further aggravating allergic airway conditions.
Health Risks of Ozone Exposure
Ozone (O3) exposure significantly increases the risk of airway disease, with over 30% higher mortality rates in cities with high O3 levels. Children engaged in outdoor sports in these areas have a threefold increased risk of developing asthma. O3 acts as a direct oxidative stressor, causing airway inflammation, reduced lung function, and respiratory symptoms like coughing, wheezing, and shortness of breath, particularly in individuals with pre-existing airway diseases.
Studies using animal models (mice and rhesus macaques) and human subjects, including those with asthma and COPD, have shown that O3 exposure induces airway inflammation and hyperreactivity. These effects lead to increased medication use, hospital visits, and school absences, underscoring its significant burden on respiratory health.
Epithelial Barrier Hypothesis and Wildfire Smoke
Wildfire smoke exposure can disrupt epithelial barrier integrity by altering zonulin levels, leading to tolerance breakdown and increased susceptibility to allergic sensitization, asthma, and COPD.
Oxidative Stress and Lung Function
Oxidative stress caused by wildfire smoke disrupts the balance between pro- and antioxidant mechanisms, leading to lipid peroxidation, protein oxidation, depletion of antioxidants, and DNA damage. These changes impair pulmonary surfactant function, cell membrane integrity, and airway health.
Oxidative stress is driven by free radicals like oxyl, peroxyl, and hydroxyl radicals, as well as non-radical species like singlet oxygen, ozone (O3), and peroxynitrite (ONOO−). These reactive species are either directly inhaled or produced endogenously by inflammatory cells through enzymatic activity.
Wildfire smoke-induced oxidative stress activates immune cells, including macrophages, mast cells, neutrophils, eosinophils, and basophils. These cells produce reactive oxygen species and enzymes like myeloperoxidase and eosinophil peroxidase, contributing to airway inflammation and asthma exacerbation.
High levels of exhaled nitric oxide (NO) and urine bromotyrosine serve as biomarkers for oxidative stress and eosinophil activation in asthma. These markers indicate airway inflammation and are used in diagnosing and monitoring eosinophilic, type 2 asthma.
Inflammatory Mechanisms
Oxidative stress leads to the release of alarmins (IL-1β, IL-6, IL-25, IL-33, TNF-α, TSLP, etc.), arachidonic acid derivatives, and damage-associated molecular patterns (DAMPs). Neutrophils are the first inflammatory cells to respond to oxidative injury, followed by eosinophils in allergen-sensitized or asthmatic individuals.
Severe Asthma Exacerbations: Amplified by mediators such as IL-25, IL-33, and TSLP.
Exposure to pollutants like O₃ and particulate matter (PM) can diminish the effectiveness of glucocorticoids in asthma management due to neutrophil-driven inflammation.
IL-17A Role drives steroid-resistant neutrophilia, worsens oxidative stress, and disrupts glucocorticoid receptor (GR) function via pathways like NF-κB and p38-MAPK.
Aryl Hydrocarbon Receptor (AhR) Activates cytokines (IL-17A, IL-22) via the RORγt signaling pathway, promoting mixed eosinophilic and neutrophilic inflammation.
Airborne PM induces DNA methylation, histone modifications, and microRNA changes, affecting inflammation and oxidative stress pathways.
Long-Term Effects:
Early-life exposure to pollutants may lead to persistent epigenetic changes affecting immune and nervous systems.
Tet Proteins: Play a central role in regulating gene expression, including asthma-related genes, by mediating DNA demethylation.
Clinical Implications
- Glucocorticoid Resistance: Highlighted as a significant clinical challenge, especially in managing severe, pollutant-induced asthma exacerbations.
- Biomarkers: SP-D and IL-17A are identified as potential indicators of oxidative lung injury and treatment resistance.
- Epigenetic Targets: Future therapies could focus on modulating Tet protein activity or reversing pollutant-induced epigenetic changes to mitigate long-term health effects.
The underlying mechanisms strongly indicate the pivotal role of epigenetic regulation, such as DNA methylation and histone modifications, in the physiological responses to wildfire exposure. Gaining deeper insights into these processes is essential for devising targeted prevention and treatment strategies during wildfire events. This underscores the critical importance of fundamental mechanistic research in mitigating the health impacts of such environmental challenges.
Bowman WS, Schmidt RJ, Sanghar GK, et al. Air That Once Was Breath: Wildfire-Smoke-Induced Mechanisms of Airway Inflammation. Int Arch Allergy Immunol. 2024;185(6):600-616. doi:10.1159/000536578