“Air That Once Was Breath” Part 2: Wildfire Smoke and Airway Disease – “Climate Change, Allergy and Immunology” Special IAAI Article Collection: Collegium Internationale Allergologicum Update 2023

The worldwide impact of wildfires involves more than the fire-related loss of life and property and can reach the everyday lives of millions of people far beyond the affected regions. For example, in North America in just the last 6 months, smoke from the hundreds of wildfires burning across Canada blanketed New York and Upper Midwest areas, pushing the air quality index (AQI) to its worst on record [1, 2]. A second extreme example is the death toll from the August 2023 wildfires in Maui, Hawaii, that stands at over 100 making it the deadliest US wildfire in over a century. Over the past 5 years, as the third example from California shows in Figures 1 and 2, not only the extent, but also the intensity and frequency became extreme, heavily affecting urban areas and producing destruction at an unprecedented scale. In 2020, more than 4% of California’s roughly 100 million acres of land was burned, making it the largest wildfire season recorded in California’s history [3, 4].

Figure 2 illustrates that over the last 3 years, the highest ever concurrent ozone and particulate matter (PM) concentrations were recorded, often for weeks at a time, coincident of wildfires in the Northern California region. Such intensity of the recent fire seasons is thought to be due at least in part (1) to the rapid growth of the wildland-urban interface raising wildfire risk globally [6, 7], (2) the warmer weather as a result of climate change [8, 9], (3) forest management practices [10, 11]. Wildfire-related morbidity and mortality are projected to be further impacted by climate change with higher temperatures and increasing frequency of heat waves [12].

The immediate consequences (fatalities, emergency room visits, and stress caused by the destruction of homes, livelihoods, and mass evacuations) are readily acknowledged, but little attention has been paid to the less obvious medium- and long-term health effects of wildfires. Of great additional concern is how vulnerable populations, firefighters, pregnant women, children, the elderly, and those from marginalized communities (due to ethnic or socioeconomic status), become at high risk of developing disease upon repeated wildfire exposures [13‒15]. This review is aimed at discussing these issues in light of currently available information. While our focus is primarily on asthma, it is examined in the context of cardiovascular and chronic obstructive pulmonary disease (COPD), frequent (an often overlapping) comorbidities.

For review purposes, we defined wildfires as wild and prescribed forest fires, tropical deforestation fires, peat fires, agricultural burning, and grass fires. We compared some findings on wildfire smoke, combustion of indoor household biomass fuels for cooking and heating, and ambient air pollution. We also used information from controlled in vivo and in vitro experimental exposure studies on the effects of PM, volatile organic compounds (VOCs), and ozone from varying sources. Our search covered the period between 1980 and 2023. We used “PubMed,” “Web of Science,” and “Google” search engines, and we referenced peer-reviewed original publications, reviews, government publications, and news articles (the latter only to highlight very recent wildfire occurrences).

Acute exposure to wildfire smoke can exacerbate pre-existing conditions, while prolonged exposures can lead to new onset of various diseases. Most investigations on the health effects during or immediately after wildfire smoke exposure focused on increased healthcare seeking and hospitalizations due to acute symptoms. These revealed that asthma exacerbations, bronchitis, bronchopneumonia, and COPD symptoms were the most common [6, 16‒21]. A positive association was found between acute healthcare utilization in asthma and COPD, with either levels of PM10 [22], PM2.5 [17, 20, 23], or both [13, 18, 24]. It is interesting to note that wildfire smoke PM2.5 levels are also associated with hospital admissions for congestive heart failure [25]. However, while there has been positive temporal association between cardiovascular mortality and burned area in general, the correlation between exposure to wildfire smoke has been less consistent with cardiovascular outcomes than with asthma. Stowell and colleagues [23] estimated the associations between cardiorespiratory acute events and exposure to smoke PM2.5 in Colorado using a novel exposure model to separate smoke PM2.5 from background ambient PM2.5 levels. They found statistically significant associations between wildfire smoke PM2.5 for asthma (odds ratio [OR] = 1.081 [1.058, 1.105]) and combined respiratory disease (OR = 1.021 [1.012, 1.031]) but not for cardiovascular disease [23]. Using the Weather Research and Forecasting Model with Chemistry, Alman et al. [17] also studied emergency department visits and acute hospitalizations for respiratory and cardiovascular outcomes during the 2012 Colorado wildfires. They observed positive correlations between lag 0 PM2.5 and asthma/wheeze (1-h max OR: 1.01, 95% confidence interval [CI]: 1.00, 1.01 per 10 μg/m³; 24-h mean OR: 1.04, 95% CI: 1.02, 1.06 per 5 μg/m³), and COPD (1-h max OR: 1.01, 95% CI: 1.00, 1.02 per 10 μg/m³; 24-h mean OR: 1.05, 95% CI: 1.02, 1.08 per 5 μg/m³). Cardiovascular results however showed no associations [17]. The “lag” number refers to the time between the two time series that are being correlated for the purpose of investigating how much the data sets at one point in time influence the data sets at a later point in time. For example, Alman et al. [17] used conditional logistic regression, where each spatial wildfire smoke-affected grid was matched to itself over the 32-day study period, to associate PM2.5 with emergency hospitalizations comparing the number of cases on each day with the number of cases on the other days within the same grid. This approach controls for time-invariant confounders that vary spatially but not those confounders that vary temporally (i.e., in this study, lag 0 means no delay in the wildfire smoke effect; lag 1 would be 1 day delay, etc.). In a more recent study, Chen and colleagues [20] examined wildfire smoke events (PM2.5 threshold = 13.5 μg/m³) and emergency department visits for respiratory, cardiovascular, diabetes, and mental health outcomes in California between 2016 and 2019. They showed that wildfire smoke events significantly associated with all respiratory diseases at lag 1 (14.4%, 95% CI: 6.8, 22.5), asthma at lag 0 (57.1% [44.5, 70.8]), chronic lower respiratory disease at lag 0 (12.7% [6.2, 19.6]), and all cardiovascular diseases at lag 10 with mixed results for mental health outcomes. The authors suggest that in comparison with airway disease, cardiovascular impacts may be delayed in response to wildfire smoke exposure [20]. The pathogenic reasons for this are unclear. These observations highlight our lack of understanding of the long-term effects of wildfires and warrant further clinical investigations focused on cardiovascular and airway disease outcomes and basic research to unravel the underlying mechanisms.

While other conditions are common, asthma exacerbations predominate the clinical picture of acute wildfire smoke exposures. Indeed, in a retrospective cohort study Moore et al. [26] using provincial claims identified 27,501 asthma exacerbations in 57,375 children with asthma between 2010 and 2021 in Calgary, Canada, and established that wildfire smoke events (based on daily average levels of PM2.5) demonstrated an increase in asthma exacerbations over the baseline (incidence rate ratio: 1.13; 95% CI: 1.02–1.24) that was not seen with air pollution in general.

It is important to note that asthma-like symptoms (airway obstruction, coughing, wheezing, breathing difficulties, and chest tightness) can arise without asthma and are often elicited by exposure to toxic/irritant material, such as wildfire smoke. Healthcare providers used to call asthma-like breathing symptoms without the actual asthma diagnosis as “reactive airway disease” (RAD). High-dose, single-event exposures causing new-onset asthma-like symptoms have been described both in response to disasters and in the workplace. RAD is not the same as reactive airway dysfunction syndrome (RADS). While these names and acronyms cover similar, overlapping features, it is important to understand the distinction between them as they drive different diagnostic and treatment approaches. RAD and RADS while are real clinical entities, they are both different from asthma in terms of pathophysiology, but can have a clinical presentation that mimic asthma. RADS is also distinguished from occupational asthma in that there is no preceding period of sensitization [27]. After the World Trade Center Disaster in 2001, an increased incidence of new-onset asthma was reported [28]. A spike in respiratory symptoms among first-responder fire department and clean-up personnel has been tracked for up to 15 years [29, 30]. In this group, the rate of new-onset asthma and/or bronchitis was estimated at 7%. Similarly, new-onset “asthma” after occupational inhalation of a high-dose irritant is well documented, though mostly as case series in certain workplaces, like hospitals, where spills of potent cleaning fluids can lead to respiratory symptoms [31‒34]. It is important, however, that asthma and occupational asthma both have a sensitization period and should be considered separately from RAD and RADS as these are not official clinical diagnoses, and do not have a precise definition [27]. Some providers use the terms RAD and asthma interchangeably, but they do not have the same meaning and should only be used as a placeholder term until an official diagnosis can be made. Interestingly, the effect of air quality on adverse respiratory events was significantly modified by RAD status (1.56 [1.02–2.40]) in a single-center retrospective double-cohort study on 625 pediatric surgery patients during two major wildfire events in Northern California [35]. Wildfire smoke exposure significantly increased the overall risk of a respiratory complication during general anesthesia in children with a history of RAD (1.50 [1.04–2.17]). These results indicate that individuals with a RAD history (even without an asthma diagnosis) should be considered vulnerable. The authors recommended postponing elective anesthetics in these patients during wildfire smoke events [35].

Psychosocial stressors can compound the effects of wildfire smoke even in healthy individuals during wildfire events, by aggravating airway inflammation and inducing respiratory symptoms. Like other inherently unpredictable forces of nature that threaten person and property, wildfires can elicit potentially long-lasting emotional and psychosocial distress [36, 37]. In subjects with existing chronic airway disease, psychosocial stress increases the frequency and severity of acute exacerbations, particularly in patients with overlapping conditions between asthma, COPD, and cardiovascular disease, leading to increased severity of disease and a diminished (or more variable) treatment responsiveness [38, 39].

Exposures to wildfire smoke and stress in combination could have compounding and serious long-term consequences if delivered during an immunologically susceptible period such as pregnancy, early childhood, or in the elderly. Associations between traffic-related air pollution and lifetime asthma were stronger in children who reported other sources of stress, like violence exposure [40]. High stress levels in both children and parents predicted onset of wheeze and asthma morbidity (e.g., severity, subsequent attacks) in children [41‒45]. Chronic stress increased allergic airway inflammation and hyperresponsiveness in mouse models [46‒51] and in asthma patients [52, 53]. Stress may also increase immune dysregulation through direct effects on the endocrine system and autonomic neuronal control [54‒56]. Indeed, stress can affect neural efferent nerves that may directly interact with airway eosinophils and promote inflammation and airway hyperreactivity [57]. Both psychosocial stress [47‒50] and wildfire smoke exposure have been linked to the induction of glucocorticoid resistance [58, 59] with implications for asthma treatment [60]. In this complex interplay, the role of interleukin (IL)-17A is of particular significance. IL-17A is implicated in wildfire smoke-induced airway inflammation [61] and plays a central role in the immune response [62]. It directly activates signaling pathways like NF-κB, p38-MAPK, and PI3K, which antagonize glucocorticoid receptor function, further contributing to glucocorticoid resistance [58, 63]. Better understanding the potential central role of IL-17A in the interplay between wildfire smoke exposure, psychosocial stress, and glucocorticoid resistance is necessary to tailor treatment strategies for affected individuals.

Psychosocial stressors have been noted to be pronounced in vulnerable populations. In a comprehensive study spanning the wildfire seasons from 2016 to 2019 in California, Chen et al. [20] examined the associations between smoke events and emergency department visits for various health outcomes. They measured daily wildfire-specific PM2.5 concentrations and defined “smoke events” as air basin-days where PM2.5 levels exceeded the 98th percentile (threshold: 13.5 μg/m³). Their two-stage time series analysis, including stratified analyses by race/ethnicity, age, and sex, revealed significant associations between smoke events and increased emergency department visits for respiratory diseases (14.4% at lag 1), asthma (57.1% at lag 0), and chronic lower respiratory disease (12.7% at lag 0). Smoke events were also positively associated with emergency department visits for all cardiovascular diseases (with a lag of 10 days), while results for mental health outcomes were mixed. Notably however, stratified results revealed potential disparities by race/ethnicity and demonstrated that short-term exposure to smoke events was associated with not only increased respiratory but also schizophrenia emergency department visits [20]. Along with other studies, these results indicated that air pollution effects on asthma, asthma severity, and other respiratory conditions are more pronounced among individuals of lower socioeconomic status [64, 65], and this may result from psychological stress [66, 67].

Liu et al. [68] conducted a systematic review of 61 epidemiological studies linking wildfire and human health in communities. They found that the most commonly identified health problem was related to airway disease in children, the elderly, and those with underlying chronic diseases but there was also an increased susceptibility to asthma in response to wildfire smoke exposure among black people and women. Others showed increased wildfire susceptibility among members of lower socioeconomic groups [25]. Vargo and colleagues [69] used satellite-collected data on wildfire smoke with the locations of population centers in the USA and identified communities potentially exposed to light-, medium-, and heavy-density smoke plumes for each day from 2011 to 2021. They linked days of exposure to smoke in each category of smoke plume density with 2010 US Census data and community characteristics from the Centers for Disease Control and Prevention’s Social Vulnerability Index to describe the co-occurrence of smoke exposure and social disadvantage. During the 2011–2021 study period, the authors found increases in the number of days of heavy smoke in communities representing 87.3% of the US population, with notably large increases in communities characterized by racial or ethnic minority status, limited English proficiency, lower educational attainment, and crowded housing conditions [69].

Farmworkers face unique occupational exposures as they often cannot limit their exposures [70] and often also individuals that belong to the racial and ethnic minorities, with limited English proficiency, lower educational attainment, and living in crowded housing conditions that are all shown to affect the severity of response to wildfire smoke [69]. These disparities are amplified by psychosocial stress potentially leading to more frequent and severe health complications. Farmworkers may experience a disproportionate burden of respiratory distress and reduced treatment efficacy [71]. Understanding the compounding effects of psychosocial stress and wildfire smoke exposure is crucial for developing targeted interventions and support systems, especially for vulnerable populations like farmworkers. Addressing the psychological well-being of individuals during wildfire events is as essential as managing their physical health.

The heavily exposed firefighter populations are of particular interest for studies on onset of airway disease and allergic sensitization [72]. While most of the published investigations have focused on the acute effects of wildfire smoke exposure, in a study involving 218 Royal Canadian Mounted Police officers deployed during the Fort McMurray wildfires in 2016, researchers found that a marginal association between air pollution and increased residual volume (indicating potential peripheral airway effects) was significantly higher in participants who were screened within the first 3 months of deployment (2.80; 0.91–4.70) than those screened later indicating that short-term exposure to wildfire-related air pollutants may have subtle but clinically significant adverse effects on respiratory health, particularly in the peripheral airways [73]. In a different study using the Alberta Administrative Health Database, the authors identified five community-based controls for each firefighter in a cohort of 1,234 deployed to the 2016 Fort McMurray fire and estimated PM2.5 particle exposure. The study found that firefighters had an increased risk of asthma consultations post-fire, with a significant OR of 2.56 and a 95% CI of 1.75–3.74 for new-onset asthma. Spirometry results showed decreased forced expiratory volume in 1 s (FEV₁) and forced vital capacity (FVC) with increasing exposure levels. Clinical assessments revealed that 20% of firefighters had a positive methacholine challenge test, and 21% had a positive bronchial wall thickening. Notably, individuals with ongoing fire-related symptoms had a significantly higher concurrence of positive methacholine challenge test and bronchial wall thickening, with an OR of 4.35 and a 95% CI of 1.11–17.12. Higher exposure levels were associated with lower diffusion capacity. In conclusion, massive wildfire smoke exposures are linked to non-resolving airway damage in firefighters [74].

Symptoms reported among this young, generally healthy cohort of firefighters have been inconsistent, with some studies linking increased cough, sputum, and sinus symptoms with heavy wildfire smoke exposure [75, 76], while others reported persistent decrease in lung function [77]. Firefighters’ exposure to wildfire smoke transiently decreases lung function on spirometry as compared to baseline with one study showing lung function declines lasting as long as 1 month post-exposure [77], and there is evidence for increased reactivity to bronchoprovocation among exposed wildland firefighters [74]. Immunologic reactions to wildfire smoke exposure in firefighters include increased levels of eosinophilic cationic protein and myeloperoxidase [78], as well as elevated serum monocyte chemotactic protein-1 and IL-6 and IL-8 [76]. Self-contained breathing apparatuses are used to mitigate exposures to inhalable smoke. But firefighters frequently remove self-contained breathing apparatus during overhaul when the firegrounds appear clear of visible smoke. Using a mouse model of overhaul without airway protection, Gainey et al. [79] investigated the impact of fireground environment exposure on lung gene expression. Although gas metering showed that the fireground overhaul levels of carbon monoxide (CO), carbon dioxide, hydrogen cyanine, hydrogen sulfide, and oxygen (O₂) were within NIOSH ceiling recommendations, 3,852 lung genes were differentially expressed when mice exposed to overhaul were compared to mice on the fireground but outside the overhaul environment. Thus, without respiratory protection, exposure to the fireground overhaul environment is associated with transcriptional changes impacting proteins potentially related to inflammation-associated lung disease and cancer [79]. Hwang and colleagues pointed out that in addition to obstructive airway and cardiovascular disease, firefighters are also susceptible to developing cancer. In fact, recently, the International Agency for Research on Cancer has reclassified wildland firefighters’ occupational exposure as carcinogenic to humans (group 1) [72].

Exposure to smoke in the wildland-urban interface is especially hazardous [79, 80] as different fire substrates produce disparate toxic effects that are difficult to predict. Such fires in addition to coarse and fine PM also emit large amounts of VOCs (e.g., aldehydes, n-alkanes), polycyclic aromatic hydrocarbons, gases (e.g., CO, SO₂, NO, NO₂), and metals [81, 82]. These are mostly released from materials used in building construction and interior furnishings including plastics, solvents, glues, metals, formaldehyde, and halogens during high-temperature combustion [82]. These components (also referred to as Hazardous Air Pollutants or Toxic Air Contaminants by the California Environmental Protection Agency [CalEPA]) [83, 84] may directly act in concert as respiratory irritants that exacerbate asthma. VOC is particularly hazardous for firefighters. These contaminants have a cumulative toxic effect and can be present in wildfire smoke in concentrations above the limit determined by the Office of Environmental Health Hazard Assessment (OEHHA) as toxic [84].

Firefighters may be specifically exposed to CO, which is also present in wildfire smoke, very close to the fire line. CO enters the bloodstream through the lungs and reduces O₂ delivery to the body’s organs and tissues. People with cardiovascular disease may experience chest pain or cardiac arrhythmias from lower levels of CO than healthy people. At high levels (such as those that occur in major structural fires), CO can cause headache, weakness, dizziness, confusion, nausea, disorientation, visual impairment, coma, and death, even in otherwise healthy individuals [83, 84]. Despite these risks, firefighters often lack adequate respiratory protection, emphasizing the need for further occupational epidemiological studies to better understand and address health risks [72].

While wildfire smoke exposure during pregnancy is primarily associated with respiratory and cardiovascular risks, it can indirectly impact hormonal regulation and maternal health in several ways. Exposure to stress and anxiety associated with wildfires and evacuation can lead to increased levels of stress hormones, such as cortisol, in pregnant women. Elevated stress hormones can have a range of effects on the body, including potential implications for fetal development [85, 86]. Endocrine disruption can occur in response to wildfire smoke containing a mixture of pollutants, including endocrine-disrupting chemicals that can interfere with the endocrine system’s normal functioning, potentially affecting hormone regulation during pregnancy [86]. Wildfire smoke exposure may alter metabolic changes and placental function, both critical in hormone production and regulation during pregnancy and necessary for fetal growth and development [86, 87]. Inhaling wildfire smoke pollutants, like PM2.5, heavy metals and endocrine-disrupting chemicals can hinder nutrient transfer from mother to fetus, lower maternal O₂ levels, reducing the placenta’s O₂ delivery to the fetus, and altering production of crucial pregnancy hormones like hCG, progesterone, and estrogen. Wildfire smoke-related placental disruptions can have long-term effects on the developing fetus. Inflammatory responses triggered by exposure to wildfire smoke constituents, such as polycyclic aromatic hydrocarbons, can directly disrupt thyroid hormone regulation, crucial for fetal brain development. It is important to note that while these mechanisms suggest potential hormonal effects, the extent and significance of these effects on pregnancy outcomes and maternal health require further research.

There is a significant gap in our understanding of the long-term consequences of wildfires and how those could impact pregnant people and pregnancy outcomes [86]. Hundreds of thousands of pregnant women are exposed during wildfire events, and the vast majority are unable to relocate to geographic areas with clean air. There are increased respiratory symptoms and infections, exacerbations of asthma, respiratory-related emergency room visits and hospitalizations, and deaths [16, 18, 19, 88]. During pregnancy, hormonal modulation of the immune system leads to differential responses depending on the specific triggers and stage of pregnancy [89]. These pregnancy-induced immune changes can impact local airway epithelial host responses to environmental triggers.

Animal in vivo studies have elucidated some mechanisms by which sex hormones appear to regulate airway inflammation, and demonstrated that ovarian hormones, including estrogen and progesterone, enhance the innate and adaptive immune responses driving airway inflammation in asthma, while androgens, including testosterone, suppressed them [90]. The impact of hormones on pulmonary immune mechanisms on airway hyperreactivity, inflammation, mucus production, wheezing, cough, and chest tightness has been described [91‒93]. Given that hormone concentrations fluctuate throughout pregnancy, the timing of respiratory exposure insults could also influence biological and clinical responses of the mother [94‒96].

Several studies have demonstrated associations between prenatal exposure to wildfire smoke and adverse pregnancy outcomes, with replicated results for reduced [97‒99] and in some cases increased [100] birth weight as well as preterm birth [85, 101‒103]. Other studies have found that first and second-trimester exposure to wildfires was associated with higher risk of birth defects [87, 102]. Few studies have reported on the long-term impacts of gestational wildfire smoke exposure on children [102, 104]. A recent review pointed out that bushfire smoke exposure is commonly associated with young children’s emergency department visits and hospital admissions for respiratory problems, but there are no studies in children who were exposed to bushfire smoke in utero [85]. Changes to DNA methylation are potential epigenetic mechanisms linking both smoke particulate exposure and prenatal stress to poor childhood respiratory health outcomes. More research is needed in large pregnancy cohorts exposed to bushfire/wildfire events to explore this further and to design appropriate mitigation interventions, in this area of global public health importance [85].

Because of their developing respiratory and immune systems, children are especially vulnerable to the harmful effects of wildfire smoke [105]. In addition to worsen asthma symptoms, prolonged exposure to wildfire smoke during childhood can have lasting health consequences, potentially reducing lung function and increasing susceptibility to respiratory illnesses. Wildfires also disrupt children’s lives by causing school closures and limiting outdoor activities due to poor air quality. The emotional toll of evacuations, the loss of homes, or familiar environments can be significant on children and can lead to lasting psychological effects. The significance of children’s exposure to wildfire smoke is highlighted by a recent retrospective cohort study set in Calgary, Canada, in which provincial claims data identified 27,501 asthma exacerbations in 57,375 children with asthma between 2010 and 2021. Wildfire smoke days demonstrated an increase in asthma exacerbations over the baseline (incidence rate ratio: 1.13; 95% CI: 1.02–1.24) that was not seen with air pollution in general [26]. A comprehensive review of 5 pre-post and 11 cross-sectional studies of rural, urban, and mixed sites from the USA, Australia, Canada, and Spain found a significant increase in respiratory emergency department visits and asthma hospitalizations within the first 3 days of exposure to wildfire smoke, particularly in children <5 years old [106]. Obese asthmatic children are even more susceptible to wildfire smoke exposure [107].

Poorly controlled asthma is well recognized to lead to significant societal costs through morbidity, mortality, lost school and work time, and healthcare utilization. However, many of the effects of wildfire smoke exposure on respiratory development and later disease phenotypes remain unclear. In a recent study, Dhingra et al. [108] found that smoke exposure during postnatal periods was associated with earlier first use of upper respiratory medications and concluded that wildfire smoke exposure during early postnatal developmental periods impacts subsequent childhood respiratory health.

The effects of early-life wildfire exposure were also studied in animals. Infant macaques living outdoors during a nearby 2008 California wildfire were compared to those born a year later without exposure to wildfire smoke in infancy. Like the study of children exposed to urban particulates, macaques exposed to a large wildfire event as infants had significantly decreased lung function as adults when compared to controls [109]. An unpublished follow-up study on the same cohort showed that the offspring of exposed female macaques had abnormal proinflammatory cytokine levels in serum and in peripheral blood monocytes suggesting that early-life wildfire exposures may have generational effects. Whether the same occurs in exposed humans still is unknown and needs further investigation. Nasal epithelial samples collected in a cohort of adult macaques that were exposed to wildfire smoke during the 2008 wildfire season also demonstrated that long-term epigenetic changes in the methylome affected genes related to the nervous and immune systems [110].

Few studies have evaluated the complex effects of exposures to wildfire smoke, air pollution, and temperature that may act synergistically on health. Landguth et al. [111] studied exposure to air pollution and temperature on the risk of hospitalizations and found that short-term increases in PM2.5 were associated with elevated odds of hospitalizations for asthma at lag 7–13 days (1.87 [1.17–2.97]), for lower respiratory tract infections at lag 6–12 days (2.18 [1.20–3.97]), and for upper respiratory tract infections at a cumulative lag of 13 days (1.29 [1.07–1.57]). The strongest PM2.5 associations with hospital admissions for asthma and lower respiratory tract infections occurred during cold periods, in the winter [111]. These recent findings highlight the significance of proactive measures, including air quality monitoring and emergency plans. Further investigation into the complex interactions between wildfire smoke, air pollution, and temperature is essential for a comprehensive understanding of their impact on pediatric respiratory health.

Wildfire smoke’s adverse effects on respiratory health are established, especially in those patients with pre-existing disease. However, the long-term effects of wildfire smoke on human health remain largely unexplored, especially the long-term effects on lung function during childhood exposure. Many studies have demonstrated wildfire smoke toxicity in animal models or human cells in vitro, while showing similar and often greater toxicity when compared with urban particulates or cigarette smoke. Relatively few studies, however, have studied the risks of cumulative exposure compared to known harmful aerosols like cigarette smoke, and whether this produces diseases akin to tobacco-associated lung diseases, lung disease related to heavy pollution, or lung disease due to use of indoor biomass stoves – the so-called hut lung [112, 113]. Additional research is needed to assess these effects, especially for the young who may be at increased risk for the long-term sequelae of early-life wildfire smoke exposure. Future studies should focus on whether wildfire smoke predisposes individuals to developing specific disease phenotypes such as Th2-high or Th2-low asthma, fixed airway obstruction, or restrictive lung diseases, and whether these disease phenotypes differ with respect to their prognosis and their response to current treatment strategies. Novel treatment approaches may need to be developed for this unique wildfire smoke exposure population.

Older adults (65 years and above) are more vulnerable to the adverse effects of wildfire smoke. In the 1997 Indonesian haze disaster, using multivariate analysis, the authors found that while more than 90% of the respondents had respiratory symptoms, elderly individuals suffered serious deterioration of overall health [114]. The elderly often have pre-existing respiratory and cardiovascular conditions, such as COPD, asthma, or heart disease that are exacerbated by wildfire smoke, in addition to little known conditions such as accelerated aging and brain/mental impacts leading to more severe symptoms and complications [115, 116]. A population-based epidemiologic analysis conducted for daily respiratory, cardiovascular, and cerebrovascular emergency department visits and wildfire smoke exposure in 2015 among adults in 8 California air basins showed that rates of all-cause cardiovascular emergency department visits were elevated across all lags, with the greatest increase on dense smoke days and among those aged >/ = 65 years at lag 0 (relative risk 1.15, 95% CI: 1.09, 1.22). But all-cause cerebrovascular and respiratory visits were also associated with smoke, especially among those 65 years and older [115].

With age, lung function naturally declines and exposure to wildfire smoke can further reduce lung function and increase the risk of respiratory distress. A study on 38,595 elderly persons included in India’s second National Family Health Survey conducted in 1998–1999 demonstrated that elderly men and women above 60 years of age living in households using biomass fuels have a significantly higher prevalence of asthma than those in households using cleaner fuels (OR = 1.59; 95% CI: 1.30–1.94), even after controlling for the effects of several potentially confounding factors [117]. Some authors argue that exposure to biomass fuel smoke is a bigger risk factor for developing COPD than tobacco smoking [118]. In a study by Orr et al. [116], the investigators recruited a cohort of 95 (average age: 63 years) subjects, for a rapid response screening after a wildfire event, and then two follow-up visits in 2018 and 2019. Analysis of spirometry data showed a significant decrease in lung function (FEV₁/FVC ratio) and a more than doubling of participants that fell below the lower limit of normal (10.2% in 2017–45.9% in 2018) 1 year after the wildfire event, and remained decreased 2 years (33.9%) post-exposure. In addition, the observed FEV₁ was significantly lower than predicted values suggesting that wildfire smoke has long-lasting effects [116]. In an Indonesian retrospective cohort study, the authors evaluated the long-term effects of wildfire smoke exposure and found that after 10 years, greater wildfire smoke exposure was associated with decreased overall health status and expiratory peak flow measurements. Interestingly, an effect was only seen in older adults and not in children [119].

In older populations, asthma and COPD are complicated by the cumulative effects of lifestyle, environmental exposures, obesity, allergies, as well as risk factors like tobacco and biomass smoke. An aged immune system can also make older adults more susceptible to respiratory infections, endotoxin-induced inflammation, and allergen sensitization caused by exposure to pollutants in wildfire smoke [120‒122]. It is important to note that diagnosing chronic airflow limitation in the elderly using traditional criteria (i.e., asthma by the presence of eosinophilic airway inflammation driven by Th2 and reversible airway hyperresponsiveness; and COPD by small airway neutrophilic inflammation, CD8 T cells, and emphysema) is challenging and often leads to COPD overdiagnosis. The presence of asthma COPD overlap increases with age [123]. In a Japanese study on 1892 subjects aged 40–89 years, 323 patients had an FEV₁/FVC <0.7, of whom 280 did not have asthma and 34% were non-smokers [124]. Airflow obstruction in older non-smoking elderly patients needs careful prognostic and management considerations. Due to overlapping clinical and laboratory features, distinguishing between asthma and COPD requires multidimensional assessment based on age of onset, symptom variability, airflow reversibility, and atopy across various airway aspects [123, 125].

During wildfire events, elderly individuals face unique challenges due to mobility limitations, medication management complexities, and potential social isolation (Table 1). To safeguard their well-being, it is essential to keep them informed about wildfire alerts, develop emergency plans that encompass evacuation routes and medication lists, and monitor indoor air quality while encouraging them to stay indoors during poor conditions. Access to medical care, including telehealth options, should be ensured, and connections with local community resources must be encouraged. Clinicians should focus on respiratory and cardiovascular health, medication management, heat-related illness prevention, and mental well-being while also assisting in the creation of evacuation plans and providing access to follow-up care. Proactive measures are vital for protecting and supporting the elderly population during wildfire events [126].

In both the adult and pediatric populations, wildfire smoke causes significant respiratory health compromise, including in pregnant adult females. A clinical approach that includes a proper history with the attendant physical exam, lung function testing, and laboratory testing is essential to determining the underlying etiology of the presenting respiratory ailment. For example, the temporal relationship to the exposure, whether it was a single or repeated exposure, the geographic location and type of wildfire (which can be linked to other allergen and PM data), and underlying cardiopulmonary health of the patient plus comorbid conditions all play a role in helping the clinician in refining the diagnosis. In addition, the interactions with tobacco smoke, inhaled marijuana, electronic cigarettes, and other acute or chronic inhaled toxic exposures are important considerations.

As urban wildfires are now becoming commonplace in the western USA and elsewhere around the globe, clinical confirmation of new-onset asthma after such events would be a sentinel contribution, especially in those who are likely to be at higher risk. As mentioned above, RAD is not the same as “asthma” or “occupational asthma,” and COPD or bronchiectasis does not develop over brief time spans and instead requires years and decades of exposure to manifest in the susceptible host. In addition, an assessment for subclinical or occult infection may be warranted in patients with persistent cough, wheezing, and typical “bronchitis” symptoms even in the absence of fever or leukocytosis. The pregnant patient may be particularly challenging given the management of two lives, the mother and fetus, and the challenges inherent to interpretation of lung function data and related pitfalls [127]. In short, it takes a careful assessment by experienced pulmonary subspecialists to rule out other conditions and to make the proper pulmonary diagnosis in the setting of wildfire smoke exposure and related lung disease. In addition, further studies are needed to investigate the longitudinal effects of wildfire smoke on symptoms, lung health, and overall mortality.

As the human population expands and climate change evolves, the “fire season” has changed from being seasonal to becoming near year-round. If recent history is any indication of the coming future, then we can expect more wildfires and increased human exposure at all levels and among the entire age span. Given the economic burden and emerging public health implications of wildfire smoke exposures, we stand to benefit from additional and more structured research efforts in this emerging area of lung health.

The authors are very grateful to Julie Postma, PhD, RN, Professor and Associate Dean for Research, WSU College of Nursing, and Leda Kobziar, PhD, Indiana University, for their constructive comments. Members of the Wildfire Exposure – Cardiovascular and Airway Inflammation Research (WE-CAIR) Program discussed and commented different aspects of the science.

A.H.: TERP advisory board and associate editor in Karger. The other authors have no conflict of interest to declare.

Grant funding: R42AI132012; TRDRP 27IR-0053C (A.H.). The funder had no role in the design, data collection, data analysis, and reporting of this study.

W.S.B. drafted the first draft of the manuscript; R.J.S., G.K.S., G.R.T. III, H.J. A.A.Z., and A.H. wrote various sections and contributed to others. A.H. arranged the final version and finalized the paper. All authors participated in editing and approved the final draft.

Edited by: H.-U. Simon, Bern.“Air that once was breath” [Caelica 83 by Baron Brooke Fulke Greville].