Outdoor air pollution and cancer: An overview of the current evidence and public health recommendations.

Outdoor air pollution is a major contributor to the burden of disease worldwide. Most of the global population resides in places where air pollution levels, because of emissions from industry, power generation, transportation, and domestic burning, considerably exceed the World Health Organization's health-based air-quality guidelines. Outdoor air pollution poses an urgent worldwide public health challenge because it is ubiquitous and has numerous serious adverse human health effects, including cancer. Currently, there is substantial evidence from studies of humans and experimental animals as well as mechanistic evidence to support a causal link between outdoor (ambient) air pollution, and especially particulate matter (PM) in outdoor air, with lung cancer incidence and mortality. It is estimated that hundreds of thousands of lung cancer deaths annually worldwide are attributable to PM air pollution. Epidemiological evidence on outdoor air pollution and the risk of other types of cancer, such as bladder cancer or breast cancer, is more limited. Outdoor air pollution may also be associated with poorer cancer survival, although further research is needed. This report presents an overview of outdoor air pollutants, sources, and global levels, as well as a description of epidemiological evidence linking outdoor air pollution with cancer incidence and mortality. Biological mechanisms of air pollution-derived carcinogenesis are also described. This report concludes by summarizing public health/policy recommendations, including multilevel interventions aimed at individual, community, and regional scales. Specific roles for medical and health care communities with regard to prevention and advocacy and recommendations for further research are also described.

Long-term exposure to wildland fire smoke PM2.5 and mortality in the contiguous United States.

Despite the substantial evidence on the health effects of short-term exposure to ambient fine particles (PM2.5), including increasing studies focusing on those from wildland fire smoke, the impacts of long-term wildland fire smoke PM2.5 exposure remain unclear. We investigated the association between long-term exposure to wildland fire smoke PM2.5 and nonaccidental mortality and mortality from a wide range of specific causes in all 3,108 counties in the contiguous United States, 2007 to 2020. Controlling for nonsmoke PM2.5, air temperature, and unmeasured spatial and temporal confounders, we found a nonlinear association between 12-mo moving average concentration of smoke PM2.5 and monthly nonaccidental mortality rate. Relative to a month with the long-term smoke PM2.5 exposure below 0.1 µg/m3, nonaccidental mortality increased by 0.16 to 0.63 and 2.11 deaths per 100,000 people per month when the 12-mo moving average of PM2.5 concentration was of 0.1 to 5 and 5+ µg/m3, respectively. Cardiovascular, ischemic heart disease, digestive, endocrine, diabetes, mental, and chronic kidney disease mortality were all found to be associated with long-term wildland fire smoke PM2.5 exposure. Smoke PM2.5 contributed to approximately 11,415 nonaccidental deaths/y (95% CI: 6,754, 16,075) in the contiguous United States. Higher smoke PM2.5-related increases in mortality rates were found for people aged 65 and above. Positive interaction effects with extreme heat were also observed. Our study identified the detrimental effects of long-term exposure to wildland fire smoke PM2.5 on a wide range of mortality outcomes, underscoring the need for public health actions and communications that span the health risks of both short- and long-term exposure.

Measuring long-term exposure to wildfire PM2.5 in California: Time-varying inequities in environmental burden.

Wildfires have become more frequent and intense due to climate change and outdoor wildfire fine particulate matter (PM2.5) concentrations differ from relatively smoothly varying total PM2.5. Thus, we introduced a conceptual model for computing long-term wildfire PM2.5 and assessed disproportionate exposures among marginalized communities. We used monitoring data and statistical techniques to characterize annual wildfire PM2.5 exposure based on intermittent and extreme daily wildfire PM2.5 concentrations in California census tracts (2006 to 2020). Metrics included: 1) weeks with wildfire PM2.5 < 5 µg/m3; 2) days with non-zero wildfire PM2.5; 3) mean wildfire PM2.5 during peak exposure week; 4) smoke waves (≥2 consecutive days with <15 µg/m3 wildfire PM2.5); and 5) mean annual wildfire PM2.5 concentration. We classified tracts by their racial/ethnic composition and CalEnviroScreen (CES) score, an environmental and social vulnerability composite measure. We examined associations of CES and racial/ethnic composition with the wildfire PM2.5 metrics using mixed-effects models. Averaged 2006 to 2020, we detected little difference in exposure by CES score or racial/ethnic composition, except for non-Hispanic American Indian and Alaska Native populations, where a 1-SD increase was associated with higher exposure for 4/5 metrics. CES or racial/ethnic × year interaction term models revealed exposure disparities in some years. Compared to their California-wide representation, the exposed populations of non-Hispanic American Indian and Alaska Native (1.68×, 95% CI: 1.01 to 2.81), white (1.13×, 95% CI: 0.99 to 1.32), and multiracial (1.06×, 95% CI: 0.97 to 1.23) people were over-represented from 2006 to 2020. In conclusion, during our study period in California, we detected disproportionate long-term wildfire PM2.5 exposure for several racial/ethnic groups.

Understanding the Cardiovascular and Metabolic Health Effects of Air Pollution in the Context of Cumulative Exposomic Impacts.

Poor air quality accounts for more than 9 million deaths a year globally according to recent estimates. A large portion of these deaths are attributable to cardiovascular causes, with evidence indicating that air pollution may also play an important role in the genesis of key cardiometabolic risk factors. Air pollution is not experienced in isolation but is part of a complex system, influenced by a host of other external environmental exposures, and interacting with intrinsic biologic factors and susceptibility to ultimately determine cardiovascular and metabolic outcomes. Given that the same fossil fuel emission sources that cause climate change also result in air pollution, there is a need for robust approaches that can not only limit climate change but also eliminate air pollution health effects, with an emphasis of protecting the most susceptible but also targeting interventions at the most vulnerable populations. In this review, we summarize the current state of epidemiologic and mechanistic evidence underpinning the association of air pollution with cardiometabolic disease and how complex interactions with other exposures and individual characteristics may modify these associations. We identify gaps in the current literature and suggest emerging approaches for policy makers to holistically approach cardiometabolic health risk and impact assessment.

Aquatic biomass is a major source to particulate organic matter export in large Arctic rivers.

Arctic rivers provide an integrated signature of the changing landscape and transmit signals of change to the ocean. Here, we use a decade of particulate organic matter (POM) compositional data to deconvolute multiple allochthonous and autochthonous pan-Arctic and watershed-specific sources. Constraints from carbon-to-nitrogen ratios (C:N), δ13C, and Δ14C signatures reveal a large, hitherto overlooked contribution from aquatic biomass. Separation in Δ14C age is enhanced by splitting soil sources into shallow and deep pools (mean ± SD: -228 ± 211 vs. -492 ± 173‰) rather than traditional active layer and permafrost pools (-300 ± 236 vs. -441 ± 215‰) that do not represent permafrost-free Arctic regions. We estimate that 39 to 60% (5 to 95% credible interval) of the annual pan-Arctic POM flux (averaging 4,391 Gg/y particulate organic carbon from 2012 to 2019) comes from aquatic biomass. The remainder is sourced from yedoma, deep soils, shallow soils, petrogenic inputs, and fresh terrestrial production. Climate change-induced warming and increasing CO2 concentrations may enhance both soil destabilization and Arctic river aquatic biomass production, increasing fluxes of POM to the ocean. Younger, autochthonous, and older soil-derived POM likely have different destinies (preferential microbial uptake and processing vs. significant sediment burial, respectively). A small (~7%) increase in aquatic biomass POM flux with warming would be equivalent to a ~30% increase in deep soil POM flux. There is a clear need to better quantify how the balance of endmember fluxes may shift with different ramifications for different endmembers and how this will impact the Arctic system.

Lessons learnt on the impact of an unprecedented soil decontamination program in Fukushima on contaminant fluxes.

In the context of elevated concerns related to nuclear accidents and warfare, the lessons learnt from the Fukushima Daiichi Nuclear Power Plant accident in 2011 are important. In particular, Japanese authorities implemented an ambitious decontamination program to reduce the air dose rate in order to facilitate the return of the local inhabitants to previously evacuated areas. This approach contrasts the strategy adopted in Chernobyl, where the most contaminated areas remain off limits. Nonetheless, the effectiveness of the Japanese decontamination strategy on the dispersion of radioactive contaminant fluxes across mountainous landscapes exposed to typhoons has not been quantified. Based on the unique combination of river monitoring and modeling in a catchment representative of the most impacted area in Japan, we demonstrate that decontamination of 16% of the catchment area resulted in a decrease of 17% of sediment-bound radioactive fluxes in rivers. Decontamination operations were therefore relatively effective, although they could only be conducted in a small part of the area due to the dominance of steep forested slopes. In fact, 67% of the initial radiocesium contamination was calculated to remain stored in forested landscapes, which may contribute to future downstream radiocesium dispersion during erosive events. Given that only a limited proportion of the initial population had returned in 2019 (~30%), it raises the question as to whether decontaminating a small percentage of the contaminated area was worth the effort, the price, and the amount of waste generated?

Recent advances in the epithelial barrier theory.

The epithelial barrier theory links the recent rise in chronic non-communicable diseases, notably autoimmune and allergic disorders, to environmental agents disrupting the epithelial barrier. Global pollution and environmental toxic agent exposure have worsened over six decades because of uncontrolled growth, modernization, and industrialization, affecting human health. Introducing new chemicals without any reasonable control of their health effects through these years has led to documented adverse effects, especially on the skin and mucosal epithelial barriers. These substances, such as particulate matter, detergents, surfactants, food emulsifiers, micro- and nano-plastics, diesel exhaust, cigarette smoke, and ozone, have been shown to compromise the epithelial barrier integrity. This disruption is linked to the opening of the tight-junction barriers, inflammation, cell death, oxidative stress, and metabolic regulation. Consideration must be given to the interplay of toxic substances, underlying inflammatory diseases, and medications, especially in affected tissues. This review article discusses the detrimental effect of environmental barrier-damaging compounds on human health and involves cellular and molecular mechanisms.

Inhaled Fine Particles Induce Alveolar Macrophage Death and Interleukin-1α Release to Promote Inducible Bronchus-Associated Lymphoid Tissue Formation.

Particulate pollution is thought to function as an adjuvant that can induce allergic responses. However, the exact cell types and immunological factors that initiate the lung-specific immune responses are unclear. We found that upon intratracheal instillation, particulates such as aluminum salts and silica killed alveolar macrophages (AMs), which then released interleukin-1α (IL-1α) and caused inducible bronchus-associated lymphoid tissue (iBALT) formation in the lung. IL-1α release continued for up to 2 weeks after particulate exposure, and type-2 allergic immune responses were induced by the inhalation of antigen during IL-1α release and iBALT formation, even long after particulate instillation. Recombinant IL-1α was sufficient to induce iBALTs, which coincided with subsequent immunoglobulin E responses, and IL-1-receptor-deficient mice failed to induce iBALT formation. Therefore, the AM-IL-1α-iBALT axis might be a therapeutic target for particulate-induced allergic inflammation.

Air pollution aggravates renal ischaemia-reperfusion-induced acute kidney injury.

Chronic kidney disease (CKD) has emerged as a significant global public health concern. Recent epidemiological studies have highlighted the link between exposure to fine particulate matter (PM2.5) and a decline in renal function. PM2.5 exerts harmful effects on various organs through oxidative stress and inflammation. Acute kidney injury (AKI) resulting from ischaemia-reperfusion injury (IRI) involves biological processes similar to those involved in PM2.5 toxicity and is a known risk factor for CKD. The objective of this study was to investigate the impact of PM2.5 exposure on IRI-induced AKI. Through a unique environmentally controlled setup, mice were exposed to urban PM2.5 or filtered air for 12 weeks before IRI followed by euthanasia 48 h after surgery. Animals exposed to PM2.5 and IRI exhibited reduced glomerular filtration, impaired urine concentration ability, and significant tubular damage. Further, PM2.5 aggravated local innate immune responses and mitochondrial dysfunction, as well as enhancing cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway activation. This increased renal senescence and suppressed the anti-ageing protein klotho, leading to early fibrotic changes. In vitro studies using proximal tubular epithelial cells exposed to PM2.5 and hypoxia/reoxygenation revealed heightened activation of the STING pathway triggered by cytoplasmic mitochondrial DNA, resulting in increased tubular damage and a pro-inflammatory phenotype. In summary, our findings imply a role for PM2.5 in sensitising proximal tubular epithelial cells to IRI-induced damage, suggesting a plausible association between PM2.5 exposure and heightened susceptibility to CKD in individuals experiencing AKI. Strategies aimed at reducing PM2.5 concentrations and implementing preventive measures may improve outcomes for AKI patients and mitigate the progression from AKI to CKD. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Outdoor Ultrafine Particulate Matter and Risk of Lung Cancer in Southern California.

Rationale: Particulate matter ⩽2.5 µm in aerodynamic diameter (PM2.5) is an established cause of lung cancer, but the association with ultrafine particulate matter (UFP; aerodynamic diameter < 0.1 µm) is unclear. Objectives: To investigate the association between UFP and lung cancer overall and by histologic subtype. Methods: The Los Angeles Ultrafines Study includes 45,012 participants aged ⩾50 years in southern California at enrollment (1995-1996) followed through 2017 for incident lung cancer (n = 1,770). We estimated historical residential ambient UFP number concentrations via land use regression and back extrapolation using PM2.5. In Cox proportional hazards models adjusted for smoking and other confounders, we estimated associations between 10-year lagged UFP (per 10,000 particles/cm3 and quartiles) and lung cancer overall and by major histologic subtype (adenocarcinoma, squamous cell carcinoma, and small cell carcinoma). We also evaluated relationships by smoking status, birth cohort, and historical duration at the residence. Measurements and Main Results: UFP was modestly associated with lung cancer risk overall (hazard ratio [HR], 1.03 [95% confidence interval (CI), 0.99-1.08]). For adenocarcinoma, we observed a positive trend among men; risk was increased in the highest exposure quartile versus the lowest (HR, 1.39 [95% CI, 1.05-1.85]; P for trend = 0.01) and was also increased in continuous models (HR per 10,000 particles/cm3, 1.09 [95% CI, 1.00-1.18]), but no increased risk was apparent among women (P for interaction = 0.03). Adenocarcinoma risk was elevated among men born between 1925 and 1930 (HR, 1.13 [95% CI, 1.02-1.26] per 10,000) but not for other birth cohorts, and was suggestive for men with ⩾10 years of residential duration (HR, 1.11 [95% CI, 0.98-1.26]). We found no consistent associations for women or other histologic subtypes. Conclusions: UFP exposure was modestly associated with lung cancer overall, with stronger associations observed for adenocarcinoma of the lung.

High-Efficiency Particulate Air Filters for Preventing Wildfire-related Asthma Complications: A Cost-Effectiveness Study.

Rationale: Air pollution caused by wildfire smoke is linked to adverse health outcomes, especially for people living with asthma. Objectives: To evaluate whether government rebates for high-efficiency particulate air (HEPA) filters, which reduce concentrations of smoke particles indoors, are cost effective in managing asthma and preventing exacerbations in British Columbia (BC), Canada. Methods: We used a Markov model to analyze health states for asthma control, exacerbation severity, and death over a retrospective time horizon of 5 years (2018-2022). Concentrations of wildfire smoke-derived particulate matter with an aerodynamic diameter ⩽2.5 µm (PM2.5) from the Canadian Optimized Statistical Smoke Exposure Model and relevant literature informed the model. The base-case analysis assumed continuous use of a HEPA filter. Costs and quality-adjusted life-years (QALYs) resulting from varying rebates were computed for each Health Service Delivery Area (HSDA). Measurements and Main Results: In the base-case analysis, HEPA filter use resulted in increased costs of $83.34 (SE, $1.03) and increased QALYs of 0.0011 (SE, 0.0001) per person. The average incremental cost-effectiveness ratio among BC HSDAs was $74,652/QALY (SE, $3,517), with incremental cost-effectiveness ratios ranging from $40,509 to $89,206 per QALY in HSDAs. Across the province, the intervention was projected to prevent 4,418 exacerbations requiring systemic corticosteroids, 643 emergency department visits, and 425 hospitalizations during the 5-year time horizon. A full rebate was cost effective in 1 of the 16 HSDAs across BC. The probability of cost-effectiveness ranged from 0.1% to 74.8% across HSDAs. A $100 rebate was cost effective in most HSDAs. Conclusions: The cost-effectiveness of HEPA filters in managing wildfire smoke-related asthma issues in BC varies by region. Government rebates up to two-thirds of the filter cost are generally cost effective, with a full rebate being cost effective only in Kootenay Boundary.

Childhood Air Pollution Exposure Associated with Self-reported Bronchitic Symptoms in Adulthood.

Rationale: Few studies have examined the effects of long-term childhood air pollution exposure on adult respiratory health, including whether childhood respiratory effects underlie this relation. Objectives: To evaluate associations between childhood air pollution exposure and self-reported adult bronchitic symptoms while considering child respiratory health in the Southern California Children's Health Study. Methods: Exposures to nitrogen dioxide (NO2), ozone, and particulate matter <2.5 µm and <10 µm in diameter (PM10) assessed using inverse-distance-squared spatial interpolation based on childhood (birth to age 17 yr) residential histories. Bronchitic symptoms (bronchitis, cough, or phlegm in the past 12 mo) were ascertained via a questionnaire in adulthood. Associations between mean air pollution exposure across childhood and self-reported adult bronchitic symptoms were estimated using logistic regression. We further adjusted for childhood bronchitic symptoms and asthma to understand whether associations operated beyond childhood respiratory health impacts. Effect modification was assessed for family history of asthma, childhood asthma, and adult allergies. Measurements and Main Results: A total of 1,308 participants were included (mostly non-Hispanic White [56%] or Hispanic [32%]). At adult assessment (mean age, 32.0 yr; standard deviation [SD], 4.7), 25% reported bronchitic symptoms. Adult bronchitic symptoms were associated with NO2 and PM10 childhood exposures. Odds ratios per 1-SD increase were 1.69 (95% confidence interval, 1.14-2.49) for NO2 (SD, 11.1 ppb) and 1.51 (95% confidence interval, 1.00-2.27) for PM10 (SD, 14.2 µg/m3). Adjusting for childhood bronchitic symptoms or asthma produced similar results. NO2 and PM10 associations were modified by childhood asthma, with greater associations among asthmatic individuals. Conclusions: Childhood NO2 and PM10 exposures were associated with adult bronchitic symptoms. Associations were not explained by childhood respiratory health impacts; however, participants with childhood asthma had stronger associations.

The Role of Neighborhood Air Pollution in Disparate Racial and Ethnic Asthma Acute Care Use.

Rationale: The share of Black or Latinx residents in a census tract remains associated with asthma-related emergency department (ED) visit rates after controlling for socioeconomic factors. The extent to which evident disparities relate to the within-city heterogeneity of long-term air pollution exposure remains unclear. Objectives: To investigate the role of intraurban spatial variability of air pollution in asthma acute care use disparity. Methods: An administrative database was used to define census tract population-based incidence rates of asthma-related ED visits. We estimate the associations between census tract incidence rates and 1) average fine and coarse particulate matter, nitrogen dioxide (NO2), and sulfur dioxide (SO2), and 2) racial and ethnic composition using generalized linear models controlling for socioeconomic and housing covariates. We also examine for the attenuation of incidence risk ratios (IRRs) associated with race/ethnicity when controlling for air pollution exposure. Measurements and Main Results: Fine and coarse particulate matter and SO2 are all associated with census tract-level incidence rates of asthma-related ED visits, and multipollutant models show evidence of independent risk associated with coarse particulate matter and SO2. The association between census tract incidence rate and Black resident share (IRR, 1.51 [credible interval (CI), 1.48-1.54]) is attenuated by 24% when accounting for air pollution (IRR, 1.39 [CI, 1.35-1.42]), and the association with Latinx resident share (IRR, 1.11 [CI, 1.09-1.13]) is attenuated by 32% (IRR, 1.08 [CI, 1.06-1.10]). Conclusions: Neighborhood-level rates of asthma acute care use are associated with local air pollution. Controlling for air pollution attenuates associations with census tract racial/ethnic composition, suggesting that intracity variability in air pollution could contribute to neighborhood-to-neighborhood asthma morbidity disparities.

Airborne Nanoparticle Concentrations Are Associated with Increased Mortality Risk in Canada's Two Largest Cities.

RATIONALE: Outdoor fine particulate air pollution (PM2.5) contributes to millions of deaths around the world each year, but much less is known about the long-term health impacts of other particulate air pollutants including ultrafine particles (a.k.a. nanoparticles) which are in the nanometer size range (<100 nm), widespread in urban environments, and not currently regulated. OBJECTIVES: Estimate the associations between long-term exposure to outdoor ultrafine particles and mortality. METHODS: Outdoor air pollution levels were linked to the residential addresses of a large, population-based cohort from 2001 - 2016. Associations between long-term exposure to outdoor ultrafine particles and nonaccidental and cause-specific mortality were estimated using Cox proportional hazards models. MEASUREMENTS: An increase in long-term exposure to outdoor ultrafine particles was associated with an increased risk of nonaccidental mortality (Hazard Ratio = 1. 073, 95% Confidence Interval = 1. 061, 1. 085) and cause-specific mortality, the strongest of which was respiratory mortality (Hazard Ratio = 1.174, 95% Confidence Interval = 1.130, 1.220). MAIN RESULTS: Long-term exposure to outdoor ultrafine particles was associated with increased risk of mortality. We estimated the mortality burden for outdoor ultrafine particles in Montreal and Toronto, Canada to be approximately 1100 additional nonaccidental deaths every year. Furthermore, we observed possible confounding by particle size which suggests that previous studies may have underestimated or missed important health risks associated with ultrafine particles. CONCLUSIONS: As outdoor ultrafine particles are not currently regulated, there is great potential for future regulatory interventions to improve population health by targeting these common outdoor air pollutants.

Impact of lowering fine particulate matter from major emission sources on mortality in Canada: A nationwide causal analysis.

Emissions of fine particulate matter (PM2.5) from human activities have been linked to substantial disease burdens, but evidence regarding how reducing PM2.5 at its sources would improve public health is sparse. We followed a population-based cohort of 2.7 million adults across Canada from 2007 through 2016. For each participant, we estimated annual mean concentrations of PM2.5 and the fractional contributions to PM2.5 from the five leading anthropogenic sources at their residential address using satellite observations in combination with a global atmospheric chemistry transport model. For each source, we estimated the causal effects of six hypothetical interventions on 10-y nonaccidental mortality risk using the parametric g-formula, a structural causal model. We conducted stratified analyses by age, sex, and income. This cohort would have experienced tangible health gains had contributions to PM2.5 from any of the five sources been reduced. Compared with no intervention, a 10% annual reduction in PM2.5 contributions from transportation and power generation, Canada's largest and fifth-largest anthropogenic sources, would have prevented approximately 175 (95%CI: 123-226) and 90 (95%CI: 63-117) deaths per million by 2016, respectively. A more intensive 50% reduction per year in PM2.5 contributions from the two sources would have averted 360 and 185 deaths per million, respectively, by 2016. The potential health benefits were greater among men, older adults, and low-income earners. In Canada, where PM2.5 levels are among the lowest worldwide, reducing PM2.5 contributions from anthropogenic sources by as little as 10% annually would yield meaningful health gains.

Uncovering eco-friendly design in the ancient bronze goose-and-fish lamp: an unnoticeable gap boosts ventilation.

The bronze goose-and-fish lamp exhibited in the national museum of China is a 2,000-y-old artifact once used for indoor lighting by nobility in the Western Han dynasty (206 BCE TO 25 CE). The beauty of this national treasure arises from its elegant shape vividly showing a goose catching fish with beautiful colors painted over the whole body. Beyond the artistic and historical value, what enchants people most is the eco-design concept of this oil-burning lamp. It is widely believed that the smoke generated by burning animal oil can flow into the goose belly through its long neck, then be absorbed by prefilled water in the belly, hence mitigating indoor air pollution. Although different mechanistic hypotheses such as natural convection and even the siphon effect have been proposed to qualitatively rationalize the above-claimed pollution mitigation function, due to the absence of a true scientific analysis, the definitive mechanism remains a mystery. By rigorous modeling of the nonisothermal fluid flow coupled with convection-diffusion of pollutant within and out of the lamp, we discover that it is the unnoticeable gap between goose body and lamp tray (i.e., an intrinsic feature of the multicompartmental design) that can offer definitive ventilation in the lamp. The ventilation is facilitated by natural convection due to oil burning. Adequate ventilation plays a key role in enabling pollution mitigation, as it allows pollutant to reach the goose belly, travel over and be absorbed by the water.

Passage of exogeneous fine particles from the lung into the brain in humans and animals.

There are still significant knowledge gaps in understanding the intrusion and retention of exogeneous particles into the central nervous system (CNS). Here, we uncovered various exogeneous fine particles in human cerebrospinal fluids (CSFs) and identified the ambient environmental or occupational exposure sources of these particles, including commonly found particles (e.g., Fe- and Ca-containing ones) and other compositions that have not been reported previously (such as malayaite and anatase TiO2), by mapping their chemical and structural fingerprints. Furthermore, using mouse and in vitro models, we unveiled a possible translocation pathway of various inhaled fine particles from the lung to the brain through blood circulation (via dedicated biodistribution and mechanistic studies). Importantly, with the aid of isotope labeling, we obtained the retention kinetics of inhaled fine particles in mice, indicating a much slower clearance rate of localized exogenous particles from the brain than from other main metabolic organs. Collectively, our results provide a piece of evidence on the intrusion of exogeneous particles into the CNS and support the association between the inhalation of exogenous particles and their transport into the brain tissues. This work thus provides additional insights for the continued investigation of the adverse effects of air pollution on the brain.

Location-specific strategies for eliminating US national racial-ethnic [Formula: see text] exposure inequality.

Air pollution levels in the United States have decreased dramatically over the past decades, yet national racial-ethnic exposure disparities persist. For ambient fine particulate matter ([Formula: see text]), we investigate three emission-reduction approaches and compare their optimal ability to address two goals: 1) reduce the overall population average exposure ("overall average") and 2) reduce the difference in the average exposure for the most exposed racial-ethnic group versus for the overall population ("national inequalities"). We show that national inequalities in exposure can be eliminated with minor emission reductions (optimal: ~1% of total emissions) if they target specific locations. In contrast, achieving that outcome using existing regulatory strategies would require eliminating essentially all emissions (if targeting specific economic sectors) or is not possible (if requiring urban regions to meet concentration standards). Lastly, we do not find a trade-off between the two goals (i.e., reducing overall average and reducing national inequalities); rather, the approach that does the best for reducing national inequalities (i.e., location-specific strategies) also does as well as or better than the other two approaches (i.e., sector-specific and meeting concentration standards) for reducing overall averages. Overall, our findings suggest that incorporating location-specific emissions reductions into the US air quality regulatory framework 1) is crucial for eliminating long-standing national average exposure disparities by race-ethnicity and 2) can benefit overall average exposures as much as or more than the sector-specific and concentration-standards approaches.

Landscape fire smoke airway exposure impairs respiratory and cardiac function and worsens experimental asthma.

BACKGROUND: Millions of people are exposed to landscape fire smoke (LFS) globally, and inhalation of LFS particulate matter (PM) is associated with poor respiratory and cardiovascular outcomes. However, how LFS affects respiratory and cardiovascular function is less well understood. OBJECTIVE: We aimed to characterize the pathophysiologic effects of representative LFS airway exposure on respiratory and cardiac function and on asthma outcomes. METHODS: LFS was generated using a customized combustion chamber. In 8-week-old female BALB/c mice, low (25 µg/m3, 24-hour equivalent) or moderate (100 µg/m3, 24-hour equivalent) concentrations of LFS PM (10 µm and below [PM10]) were administered daily for 3 (short-term) and 14 (long-term) days in the presence and absence of experimental asthma. Lung inflammation, gene expression, structural changes, and lung function were assessed. In 8-week-old male C57BL/6 mice, low concentrations of LFS PM10 were administered for 3 days. Cardiac function and gene expression were assessed. RESULTS: Short- and long-term LFS PM10 airway exposure increased airway hyperresponsiveness and induced steroid insensitivity in experimental asthma, independent of significant changes in airway inflammation. Long-term LFS PM10 airway exposure also decreased gas diffusion. Short-term LFS PM10 airway exposure decreased cardiac function and expression of gene changes relating to oxidative stress and cardiovascular pathologies. CONCLUSIONS: We characterized significant detrimental effects of physiologically relevant concentrations and durations of LFS PM10 airway exposure on lung and heart function. Our study provides a platform for assessment of mechanisms that underpin LFS PM10 airway exposure on respiratory and cardiovascular disease outcomes.

Exposure to urban particulate matter (UPM) impairs mitochondrial dynamics in BV2 cells, triggering a mitochondrial biogenesis response.

World Health Organisation data suggest that up to 99% of the global population are exposed to air pollutants above recommended levels. Impacts to health range from increased risk of stroke and cardiovascular disease to chronic respiratory conditions, and air pollution may contribute to over 7 million premature deaths a year. Additionally, mounting evidence suggests that in utero or early life exposure to particulate matter (PM) in ambient air pollution increases the risk of neurodevelopmental impairment with obvious lifelong consequences. Identifying brain-specific cellular targets of PM is vital for determining its long-term consequences. We previously established that microglial-like BV2 cells were particularly sensitive to urban (U)PM-induced damage including reactive oxygen species production, which was abrogated by a mitochondrially targeted antioxidant. Here we extend those studies to find that UPM treatment causes a rapid impairment of mitochondrial function and increased mitochondrial fragmentation. However, there is a subsequent restoration of mitochondrial and therefore cell health occurring concomitantly with upregulated measures of mitochondrial biogenesis and mitochondrial load. Our data highlight that protecting mitochondrial function may represent a valuable mechanism to offset the effects of UPM exposure in the neonatal brain. KEY POINTS: Air pollution represents a growing risk to long-term health especially in early life, and the CNS is emerging a target for airborne particulate matter (PM). We previously showed that microglial-like BV2 cells were vulnerable to urban (U)PM exposure, which impaired cell survival and promoted reactive oxygen species production. Here we find that, following UPM exposure, BV2 mitochondrial membrane potential is rapidly reduced, concomitant with decreased cellular bioenergetics and increased mitochondrial fission. However, markers of mitochondrial biogenesis and mitochondrial mass are subsequently induced, which may represent a cellular mitigation strategy. As mitochondria are more vulnerable in the developing brain, exposure to air pollution may represent a greater risk to lifelong health in this cohort; conversely, promoting mitochondrial integrity may offset these risks.