Impact of Wildfire Smoke on Acute Illness

Once inhaled, wildfire smoke PM directly stimulates airway and alveolar inflammation. Beyond these directly exposed tissues, wildfire smoke impacts organs through three primary mechanisms: autonomic dysregulation, a cascade of inflammation and oxidative stress (from the pulmonary vasculature), and direct translocation of PM into the bloodstream. Collectively, this exposure results in systemic inflammation, platelet activation, and endothelial dysfunction (fig. 1).

Inhalation of PM stimulates respiratory C-nerve fibers and rapidly adapting pulmonary receptors in the bronchial tree, resulting in vagal afferent signaling. This increase in parasympathetic tone is contrasted by a similarly associated reduction in carotid baroreceptors’ sensitivity.^17,18  The overall result appears to be sympathetic stimulation, with increased circulating concentrations of noradrenaline, renin, angiotensin II, and aldosterone.¹⁹  Adults exposed to either ambient wildfire or wood smoke in a laboratory setting experience significant and reproducible increases in blood pressure.²⁰  Even transient PM_2.5 exposure increases systolic, diastolic, and mean blood pressure for 12 h or more.^20,21  Long-term PM exposure is associated with a 41% increased risk of hypertension.²²  Additionally, heart rate variability is reduced among healthy middle-aged subjects in response to controlled exposure to both fine (PM_2.5) and ultrafine PM (0.1 μm, or PM_0.1).^23,24 

Wood smoke exposure causes inflammation of the pulmonary and systemic vascular endothelium, lipid peroxidation, and systemic oxidative stress. Wildfire smoke (especially through its metallic components) induces oxidative stress through redox cycling mechanisms²⁵  and triggers a vast inflammatory response in the pulmonary circulation, which initiates a systemic inflammatory response resulting in end-organ damage (table 1).

Fire-derived PM (especially ultrafine particulate matter, or PM_0.1) and gases cross the alveolar–capillary membrane to enter the bloodstream and reach the heart, peripheral vessels, and other organs, where they induce endothelial activation and platelet aggregation.³⁴  Metallic PM components stimulate platelet activation and aggregation.³⁵  Such effects are accompanied by a fibrinolytic response characterized by increased plasminogen activator inhibitor-1 and decreased tissue plasminogen activator. When combined with endothelial cell damage, a prothrombotic state is promoted. In a laboratory setting, NADPH oxidase inhibitors alleviated PM_2.5-induced endothelial dysfunction.²⁷  Merely 3 h of exposure to wood smoke increases circulating concentrations of endothelial adhesion molecules, intracellular adhesion molecule-1, and vascular cell adhesion molecule-1 in healthy adults,³⁰  while its gaseous components induce a pro-atherosclerotic vascular response.³⁶ 

The impact of PM on cardiovascular disease is well established³⁷  (table 2). The combination of endothelial injury, platelet activation, and coagulation increases the risk of acute coronary syndromes. Similarly, elevations in sympathetic tone and systemic inflammation increase the risk of myocardial infarction. This association between the incidence of myocardial infarction and PM concentration has been described across age ranges and geographies.^53–55  Similarly, PM concentrations greater than 8 μg/m³ resulting from forest fires increase cardiovascular mortality.⁵⁶ 

Driven by circulating inflammatory cytokines, oxidative stress, and increased sympathetic tone, short-term increases in PM concentrations raise the risk of new-onset atrial fibrillation.^56,57  Over a longer time, PM-induced inflammatory fibrosis, progressive atrial remodeling, and increased pulmonary artery pressures lead to right ventricular dysfunction and right atrial stretch, causing intra-atrial conduction abnormalities.⁵⁸ 

Through high sympathetic tone, systemic inflammation, and endothelial injury, wildfire smoke may drive myocardial injury, resulting in decompensation of existing heart failure. Both pulmonary artery pressures and right ventricular afterload are increased by exposure to ambient PM, while increased arterial vasoconstriction elevates left ventricular afterload. When combined with PM-induced blunting of urinary sodium excretion, wildfire smoke markedly increases the demand on a failing heart and can precipitate decompensation.^59–62 

Stroke is the second-leading cause of death and the third-leading cause of disability worldwide. PM-induced hypertension, atrial fibrillation, platelet aggregation, and oxidative stress increase stroke risk.⁶³  Ambient PM ranks fourth among 19 stroke risk factors summarized by the Global Burden of Diseases Study in 2019.⁶⁴ 

PM exposure is associated with insulin resistance and impaired pancreatic β-cell function, major risk factors for cardiac disease. With a 2-month lag, lower insulin sensitivity and higher fasting glucose concentrations were observed after high PM exposure in 1,000 Mexican-American patients.⁶⁵  In Eastern China, short-term PM exposure positively correlated with increased fasting blood glucose, especially in patients older than 65 yr.⁶⁶ 

Wildfire smoke causes lung inflammation, with alveolar macrophages and monocytes mounting a local immune response, resulting in direct tissue damage, impaired gas exchange, and airway irritation. Increases in both emergency department presentations and hospital admissions for asthma and chronic obstructive pulmonary disease result from exposure (table 2). Generally, finer particles are more toxic than coarser particles, and wildfire PM appears more toxic than urban PM.⁶⁷  Between 2013 and 2018 in Nevada, wildfire smoke resulted in a 6.1% higher incidence of asthma presentations compared to similar levels of PM originating from nonwildfire sources.⁶⁸  These effects are also modified by social factors. For example, North Carolina asthma emergency department visits stratified by socioeconomic status show that per 100 μg/m³ of peat smoke PM_2.5 exposure, emergency department visits increased by 85% in richer counties but by 124% in poor counties.⁶⁹ 

Black carbon, a component of PM_2.5, translocates into the systemic circulation and deposits in placental tissue. A two-photon microscopy study assessing black carbon load in placental villous tissue demonstrated that the placental barrier is permeable to air pollution components, which would allow pollution to reach the fetal circulation.⁷⁰  There is concern that the same processes of inflammation, oxidative stress, and endothelial dysfunction may also affect the maternal–fetal unit. Evidence suggests a dose-dependent placental inflammatory response to wildfire smoke exposure.⁷¹  Placental inflammation is strongly associated with preeclampsia and adverse birth outcomes, including preterm birth, low birth weight, and neonatal morbidity^72–74  (table 3). Likewise, oxidative stress–induced vascular and endothelial dysfunction are associated with preterm birth, hypertensive disorders of pregnancy, preeclampsia, and restricted fetal growth.⁸⁷  In rabbit models, exposure to PM from fossil fuel combustion decreased placental blood flow and increased umbilical artery resistance.⁸⁸ 

PM exposure may also impact endocrine signaling; in the second trimester, exposure among 222 mother–newborn pairs was associated with differences in the cord blood metabolites derived from the lipoxygenase pathways. These are key regulatory hormones for fetal metabolism and labor progression.⁸⁹  Premature birth negatively impacts health throughout a patient’s life,⁹⁰  and wildfire smoke exposure is consistently associated with increased rates of preterm birth. A dose-dependent decrease in birth weight is observed with respect to proximity to wildfires and the severity of smoke exposure. In vitro experimentation also shows that organogenesis, as well as migration and differentiation of neural crest cells, are sensitive to oxidative stress.⁹¹ 

Children are particularly vulnerable to PM pollution due to increased minute ventilation relative to body mass and reduced efficiency of nasopharyngeal particle deposition. This unique physiology results in a higher proportion of particles reaching lung tissue⁹²  (table 3). Since the mid-1990s, pediatric asthma presentations have been shown to increase during wildfire smoke exposure.⁹³  Furthermore, fire-derived ozone emissions account for more than 2,000 annual pediatric emergency department visits for asthma in the United States.⁹⁴ 

A host of negative cardiopulmonary, obstetric, and neonatal outcomes result from wildfire smoke exposure, driving a greater burden of comorbidities in the perioperative population. In addition, recent wildfire smoke exposure may directly increase perioperative risk: adverse respiratory events affected 37% of children with a past medical history of reactive airway disease during healthy air periods but affected 55% during periods with unhealthy air (1.50 [1.04 to 2.17]; P = 0.032).⁹⁵  This finding may well represent just the tip of the iceberg, with wildfire smoke exposure being responsible for a significant perioperative morbidity burden. Several key knowledge gaps are currently hampering our understanding of this perioperative risk factor.

Data pertaining to perioperative risk from wildfires are sparse. The Californian data from Marsh et al.⁹⁵  were the first of their kind to bring this risk to light with a specific focus on pediatric respiratory complications. Given the paucity of perioperative data, some insight may be gained from tobacco literature. While the harm from vitamin E acetate exposure associated with electronic cigarette use is mechanistically different from PM exposure, perioperative guidelines on electronic cigarette smoke exposure may form a useful starting point. Guidelines recommend that patients are screened preoperatively for electronic cigarette smoke exposure and recommend focused investigations for health impacts when the exposure is suspected.⁹⁶  Such an approach could be taken in relation to wildfire smoke, screening patients for risk of exposure based on their location. Passive cigarette smoke exposure has been associated with increased acute respiratory distress syndrome development in septic patients.⁹⁷  Similarly, pediatric patients with chronic cigarette smoke exposure demonstrate increased rates of coughing, laryngospasm, and hypoxia when undergoing procedural sedation.⁹⁸  Linking wildfire smoke exposure data to perioperative outcomes datasets will likely elucidate this relationship. Linking critical care outcome registries or intensive care unit admissions datasets to smoke exposure data will be helpful to identify the proportion of patients whose critical illness is exacerbated by PM exposure.

Many existing studies have determined exposure using total measured PM concentration, with some combining satellite images of smoke clouds or seasonal smoke patterns to attribute this measured PM to wildfire sources. Modern chemical transport models allow the impacts of wildfire PM to be studied in isolation.

Many of these existing data originate from relatively high-income countries. A substantial portion of global wildfire smoke exposure occurs in Sub-Saharan Africa and South Asia, where access to healthcare and healthcare data is limited. Data collected in low-resource settings would be highly valuable in producing better estimates of the true global burden of wildfire smoke impact.

Studies typically have included linear models reporting the odds ratio or relative risk of developing a clinical endpoint for a given change in PM concentration, typically 1 or 10 μg/m³. PM concentrations can exceed 500 μg/m³ in regions close to fires, and it is not known whether the exposure–response function is linear at these concentrations. Studies that explore the nonlinear effects of smoke exposure would allow for more complete estimates of current and future health impacts. Developing such an exposure response function will allow health systems to prepare for future impacts while providing vital data to guide policy decisions. Likewise, impacts of dynamic responses need to be studied (i.e., might a sudden but small rise be more acutely harmful than a sustained higher concentration of toxicants?)

Although a broad array of pathophysiologic mechanisms of smoke exposure has been described, it is challenging to identify a targeted intervention for exposed individuals, and thus there are no established treatments or practice guidelines. No randomized controlled trials have investigated treatment of PM or wildfire smoke exposure. Instead, care is typically supportive and defined by the presenting pathology. Emergency medicine guidelines do exist regarding smoke inhalation but are not specific to wildfires. These guidelines focus on supportive respiratory care with high-flow oxygen and bronchodilators as needed, testing for carbon monoxide toxicity, and administration of thromboprophylaxis. Perioperative wildfire smoke exposure protocols should consider the need for additional thromboprophylaxis, the need for antihypertensives in the acute setting, the role of additional hemodynamic monitoring among those with heart failure, the role of bronchodilators or other airway clearance interventions, and risk stratification for obstetric patients.

Modern weather forecasting allows for accurate smoke plume spread prediction, which facilitates targeted air pollution warning systems. If research reveals increased perioperative complications after smoke exposure, then changes could be made in the scheduling of surgical cases in high-risk patients at times of high smoke exposure. Reactive airway disease or obstructive lung diseases typically present on lag days 0 to 2.⁴⁷  Hypertension develops within hours and can resolve after 12 h.⁶³  Downstream cardiac effects are variable in timing and peak between days 0 and 6 across different studies.³⁸  These risk peaks typically span 1 day, and in the few studies that employ longer time series, the effects were not significant during a 7-day window. While some patients present at lag day 0, within hours of smoke exposure, others will present several days into the exposure. As a period of PM exposure persists, the risk of health impacts increases. Beyond day 15, the exposure response curves for cardiovascular and respiratory admissions become nonlinear and appear to plateau.⁹⁹  During periods of heavy smoke, high hourly maximum PM concentration is highly predictive of elevated 24-h mean values.¹⁰⁰  As such, any evidence of high PM exposure should be treated with high suspicion for the presence of adverse effects suspected. Work is being undertaken by this research group to develop a nonlinear, time-dependent exposure–response function. It is envisaged that this work will better characterize the response at high PM levels. Detailed data on the time variance of the exposure–response function can form the basis for surgical scheduling around periods of wildfire smoke.

The health impact of wildfire smoke is just one symptom of a far broader systemic problem in the human ecosystem. Through changes in surface temperatures, rainfall patterns, wind speed, and relative humidity, the adverse effects of wildfires will increase as we continue warming the planet through the combustion of fossil fuels (e.g., gasoline, natural gas, oil, coal, and diesel). As leaders in the perioperative space (the most carbon-intensive area of healthcare), anesthesiologists can lead the charge in rapidly reducing healthcare-related greenhouse gas emissions and those across society. Moreover, the healthcare industry has a global market more than three times the value of the fossil fuel industry. If leveraged effectively through coordinated action, the economic might of the healthcare community and academic institutions could reduce future damage to human health caused by the continued use of fossil fuels. As the window to limit global warming to 1.5° or 2°C closes, clinicians should act urgently and decisively to safeguard human health.

Dr. Montgomery is partly funded through the United Kingdom National Institute for Health Research’s Comprehensive Biomedical Research Center at University College London Hospitals (London, United Kingdom). This work was funded by a grant from Duke University (Durham, North Carolina).

Dr. Montgomery is cochair of the Lancet Countdown on Health and Climate Change and is a member of other organizations that address this issue. Dr. Montgomery is cofounder of a nonprofit company to help decarbonize healthcare. Dr. Shindell is a consultant for the Institute for Governance and Sustainable Development. Dr. Levy has received funding from Merck, Octapharma, and Werfen unrelated to this work. The other authors declare no competing interests.