Exposure to urban particulate matter alters responses of olfactory mucosal cells to SARS-CoV-2 infection.

Respiratory viruses have a significant impact on health, as highlighted by the COVID-19 pandemic. Exposure to air pollution can contribute to viral susceptibility and be associated with severe outcomes, as suggested by recent epidemiological studies. Furthermore, exposure to particulate matter (PM), an important constituent of air pollution, is linked to adverse effects on the brain, including cognitive decline and Alzheimer's disease (AD). The olfactory mucosa (OM), a tissue located at the rooftop of the nasal cavity, is directly exposed to inhaled air and in direct contact with the brain. Increasing evidence of OM dysfunction related to neuropathogenesis and viral infection demonstrates the importance of elucidating the interplay between viruses and air pollutants at the OM. This study examined the effects of subacute exposure to urban PM 0.2 and PM 10-2.5 on SARS-CoV-2 infection using primary human OM cells obtained from cognitively healthy individuals and individuals diagnosed with AD. OM cells were exposed to PM and subsequently infected with the SARS-CoV-2 virus in the presence of pollutants. SARS-CoV-2 entry receptors and replication, toxicological endpoints, cytokine release, oxidative stress markers, and amyloid beta levels were measured. Exposure to PM did not enhance the expression of viral entry receptors or cellular viral load in human OM cells. However, PM-exposed and SARS-CoV-2-infected cells showed alterations in cellular and immune responses when compared to cells infected only with the virus or pollutants. These changes are highly pronounced in AD OM cells. These results suggest that exposure of human OM cells to PM does not increase susceptibility to SARS-CoV-2 infection in vitro, but it can alter cellular immune responses to the virus, particularly in AD. Understanding the interplay of air pollutants and COVID-19 can provide important insight for the development of public health policies and interventions to reduce the negative influences of air pollution exposure.

Particulate matter from car exhaust alters function of human iPSC-derived microglia.

BACKGROUND: Air pollution is recognized as an emerging environmental risk factor for neurological diseases. Large-scale epidemiological studies associate traffic-related particulate matter (PM) with impaired cognitive functions and increased incidence of neurodegenerative diseases such as Alzheimer's disease. Inhaled components of PM may directly invade the brain via the olfactory route, or act through peripheral system responses resulting in inflammation and oxidative stress in the brain. Microglia are the immune cells of the brain implicated in the progression of neurodegenerative diseases. However, it remains unknown how PM affects live human microglia. RESULTS: Here we show that two different PMs derived from exhausts of cars running on EN590 diesel or compressed natural gas (CNG) alter the function of human microglia-like cells in vitro. We exposed human induced pluripotent stem cell (iPSC)-derived microglia-like cells (iMGLs) to traffic related PMs and explored their functional responses. Lower concentrations of PMs ranging between 10 and 100 µg ml-1 increased microglial survival whereas higher concentrations became toxic over time. Both tested pollutants impaired microglial phagocytosis and increased secretion of a few proinflammatory cytokines with distinct patterns, compared to lipopolysaccharide induced responses. iMGLs showed pollutant dependent responses to production of reactive oxygen species (ROS) with CNG inducing and EN590 reducing ROS production. CONCLUSIONS: Our study indicates that traffic-related air pollutants alter the function of human microglia and warrant further studies to determine whether these changes contribute to adverse effects in the brain and on cognition over time. This study demonstrates human iPSC-microglia as a valuable tool to study functional microglial responses to environmental agents.

Snapshots of wintertime urban aerosol characteristics: Local sources emphasized in ultrafine particle number and lung deposited surface area.

Urban air fine particles are a major health-relating problem. However, it is not well understood how the health-relevant features of fine particles should be monitored. Limitations of PM2.5 (mass concentration of sub 2.5 µm particles), which is commonly used in the health effect estimations, have been recognized and, e.g., World Health Organization (WHO) has released good practice statements for particle number (PN) and black carbon (BC) concentrations (2021). In this study, a characterization of urban wintertime aerosol was done in three environments: a detached housing area with residential wood combustion, traffic-influenced streets in a city centre and near an airport. The particle characteristics varied significantly between the locations, resulting different average particle sizes causing lung deposited surface area (LDSA). Near the airport, departing planes had a major contribution on PN, and most particles were smaller than 10 nm, similarly as in the city centre. The high hourly mean PN (>20 000 1/cm3) stated in the WHO's good practices was clearly exceeded near the airport and in the city centre, even though traffic rates were reduced due to a SARS-CoV-2-related partial lockdown. In the residential area, wood combustion increased both BC and PM2.5, but also PN of sub 10 and 23 nm particles. The high concentrations of sub 10 nm particles in all the locations show the importance of the chosen lower size limit of PN measurement, e.g., WHO states that the lower limit should be 10 nm or smaller. Furthermore, due to ultrafine particle emissions, LDSA per unit PM2.5 was 1.4 and 2.4 times higher near the airport than in the city centre and the residential area, respectively, indicating that health effects of PM2.5 depend on urban environment as well as conditions, and emphasizing the importance of PN monitoring in terms of health effects related to local pollution sources.

Short-Term Effects of Particle Sizes and Constituents on Blood Biomarkers among Healthy Young Adults in Guangzhou, China.

Evidence of the effects of various particle sizes and constituents on blood biomarkers is limited. We performed a panel study with five repeated measurements in 88 healthy college students in Guangzhou, China between December 2017 and January 2018. Mass concentrations of particles with aerodynamic diameters ≤ 2.5 µm (PM2.5), PM1, and PM0.5 and number concentrations of particles with aerodynamic diameters ≤ 200 nm (PN0.2) and PN0.1 were measured. We used linear mixed-effect models to explore the associations of size-fractionated particulate matter and PM2.5 constituents with five blood biomarkers 0-5 days prior to blood collection. We found that an interquartile range (45.9 µg/m3) increase in PM2.5 concentration was significantly associated with increments of 16.6, 3.4, 12.3, and 8.8% in C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and endothelin-1(ET-1) at a 5-day lag, respectively. Similar estimates were observed for PM1, PM0.5, PN0.2, and PN0.1. For PM2.5 constituents, consistent positive associations were observed between F- and sVCAM-1 and CRP and between NH4+ and MCP-1, and negative associations were found between Na+ and MCP-1 and ET-1, between Cl- and MCP-1, and between Mg2+ and sVCAM-1. Our results suggested that both particle size and constituent exposure are significantly associated with circulating biomarkers among healthy Chinese adults. Particularly, PN0.1 at a 5-day lag and F- and NH4+ are the most associated with these blood biomarkers.

Urban air PM modifies differently immune defense responses against bacterial and viral infections in vitro.

Epidemiological evidence has shown the association between exposure to ambient fine particulate matter (PM) and increased susceptibility to bacterial and viral respiratory infections. However, to date, the underlying mechanisms of immunomodulatory effects of PM remain unclear. Our objective was to explore how exposure to relatively low doses of urban air PM alters innate responses to bacterial and viral stimuli in vitro. We used secondary alveolar epithelial cell line along with monocyte-derived macrophages to replicate innate lung barrier in vitro. Co-cultured cells were first exposed for 24 h to PM2.5-1 (particle aerodynamic diameter between 1 and 2.5 µm) and subsequently for an additional 24 h to lipopolysaccharide (TLR4), polyinosinic-polycytidylic acid (TLR3), and synthetic single-stranded RNA oligoribonucleotides (TLR7/8) to mimic bacterial or viral stimulation. Toxicological endpoints included pro-inflammatory cytokines (IL-8, IL-6, and TNF-α), cellular metabolic activity, and cell cycle phase distribution. We show that cells exposed to PM2.5-1 produced higher levels of pro-inflammatory cytokines following stimulation with bacterial TLR4 ligand than cells exposed to PM2.5-1 or bacterial ligand alone. On the contrary, PM2.5-1 exposure reduced pro-inflammatory responses to viral ligands TLR3 and TLR7/8. Cell cycle analysis indicated that viral ligands induced cell cycle arrest at the G2-M phase. In PM-primed co-cultures, however, they failed to induce the G2-M phase arrest. Contrarily, bacterial stimulation caused a slight increase in cells in the sub-G1 phase but in PM2.5-1 primed co-cultures the effect of bacterial stimulation was masked by PM2.5-1. These findings indicate that PM2.5-1 may alter responses of immune defense differently against bacterial and viral infections. Further studies are required to explain the mechanism of immune modulation caused by PM in altering the susceptibility to respiratory infections.

Inflammatory responses of urban air PM modulated by chemical composition and different air quality situations in Nanjing, China.

The health risks of air pollutants and ambient particulate matter (PM) are widely known. PM composition and toxicity have shown substantial spatiotemporal variability. Yet, the connections between PM composition and toxicological and health effects are vaguely understood. This is a crucial gap in knowledge that needs to be addressed in order to establish air quality guidelines and limit values that consider the chemical composition of PM instead of the current assumption of equal toxicity per inhaled dose. Here, we demonstrate further evidence for varying toxicological effects of urban PM at equal mass concentrations, and estimate how PM composition and emission source characteristics influenced this variation. We exposed a co-culture model mimicking alveolar epithelial cells and macrophages with size-segregated urban ambient PM collected before, during, and after the Nanjing Youth Olympic Games 2014. We measured the release of a set of cytokines, cell cycle alterations, and genotoxicity, and assessed the spatiotemporal variations in these responses by factorial multiple regression analysis. Additionally, we investigated how a previously identified set of emission sources and chemical components affected these variations by mixed model analysis. PM-exposure induced cytokine signaling, most notably by inducing dose-dependent increases of macrophage-regulating GM-CSF and proinflammatory TNFα, IL-6, and IL-1ß concentrations, modest dose-dependent increase for cytoprotective VEGF-A, but very low to no responses for anti-inflammatory IL-10 and immunoregulatory IFNγ, respectively. We observed substantial differences in proinflammatory cytokine production depending on PM sampling period, location, and time of day. The proinflammatory response correlated positively with cell cycle arrest in G1/G0 phase and loss of cellular metabolic activity. Furthermore, PM0.2 caused dose-dependent increases in sub-G1/G0 cells, suggesting increased DNA degradation and apoptosis. Variations in traffic and oil/fuel combustion emissions contributed substantially to the observed spatiotemporal variations of toxicological responses.

Air quality intervention during the Nanjing youth olympic games altered PM sources, chemical composition, and toxicological responses.

Ambient particulate matter (PM) is a leading global environmental health risk. Current air quality regulations are based on airborne mass concentration. However, PM from different sources have distinct chemical compositions and varied toxicity. Connections between emission control measures, air quality, PM composition, and toxicity remain insufficiently elucidated. The current study assessed the composition and toxicity of PM collected in Nanjing, China before, during, and after an air quality intervention for the 2014 Youth Olympic Games. A co-culture model that mimics the alveolar epithelium with the associated macrophages was created using A549 and THP-1 cells. These cells were exposed to size-segregated inhalable PM samples. The composition and toxicity of the PM samples were influenced by several factors including seasonal variation, emission sources, and the air quality intervention. For example, we observed a size-dependent shift in particle mass concentrations during the air quality intervention with an emphasized proportion of smaller particles (PM2.5) present in the air. The roles of industrial and fuel combustion and traffic emissions were magnified during the emission control period. Our analyses revealed that the PM samples demonstrated differential cytotoxic potencies at equal mass concentrations between sampling periods, locations, and time of day, influenced by variations in the predominant emission sources. Coal combustion and industrial emissions were the most important sources affecting the toxicological responses and displayed the least variation in emission contributions between the sampling periods. In conclusion, emission control mitigated cytotoxicity and oxidative stress for particles larger than 0.2 µm, but there was inadequate evidence to determine if it was the key factor reducing the harmful effects of PM0.2.

The role of influenza vaccination in mitigating the adverse impact of ambient air pollution on lung function in children: New insights from the Seven Northeastern Cities Study in China.

BACKGROUND: Ambient air pollution exposure and influenza virus infection have been documented to be independently associated with reduced lung function previously. Influenza vaccination plays an important role in protecting against influenza-induced severe diseases. However, no study to date has focused on whether influenza vaccination may modify the associations between ambient air pollution exposure and lung function. METHODS: We undertook a cross-sectional study of 6740 children aged 7-14 years into Seven Northeast Cities (SNEC) Study in China during 2012-2013. We collected information from parents/guardians about sociodemographic factors and influenza vaccination status in the past three years. Lung function was measured using portable electronic spirometers. Machine learning methods were used to predict 4-year average ambient air pollutant exposures to nitrogen dioxide (NO2) and particulate matter with an aerodynamic diameter <1 µm (PM1), <2.5 µm (PM2.5) and <10 µm (PM10). Two-level linear and logistic regression models were used to assess interactions between influenza vaccination and long-term ambient air pollutants exposure on lung function reduction, controlling for potential confounding factors. RESULTS: Ambient air pollution were observed significantly associated with reductions in lung function among children. We found significant interactions between influenza vaccination and air pollutants on lung function, suggesting greater vulnerability to air pollution among unvaccinated children. For example, an interaction (pinteraction = 0.002) indicated a -283.44 mL (95% CI: -327.04, -239.83) reduction in forced vital capacity (FVC) per interquartile range (IQR) increase in PM1 concentrations among unvaccinated children, compared with the -108.24 mL (95%CI: -174.88, -41.60) reduction in FVC observed among vaccinated children. Results from logistic regression models also showed stronger associations between per IQR increase in PM1 and lung function reduction measured by FVC and peak expiratory flow (PEF) among unvaccinated children than the according ORs among vaccinated children [i.e., Odds Ratio (OR) for PM1 and impaired FVC: 2.33 (95%CI: 1.79, 3.03) vs 1.65 (95%CI: 1.20, 2.28); OR for PM2.5 and impaired PEF: 1.45 (95%CI: 1.12,1.87) vs 1.04 (95%CI: 0.76,1.43)]. The heterogeneity of the modification by influenza vaccination of the associations between air pollution exposure and lung function reduction appeared to be more substantial in girls than in boys. CONCLUSION: Our results suggest that influenza vaccination may moderate the detrimental effects of ambient air pollution on lung function among children. This study provides new insights into the possible co-benefits of strengthening and promoting global influenza vaccination programs among children.

Human airway construct model is suitable for studying transcriptome changes associated with indoor air particulate matter toxicity.

In vitro models mimicking the human respiratory system are essential when investigating the toxicological effects of inhaled indoor air particulate matter (PM). We present a pulmonary cell culture model for studying indoor air PM toxicity. We exposed normal human bronchial epithelial cells, grown on semi-permeable cell culture membranes, to four doses of indoor air PM in the air-liquid interface. We analyzed the chemokine interleukin-8 concentration from the cell culture medium, protein concentration from the apical wash, measured tissue electrical resistance, and imaged airway constructs using light and transmission electron microscopy. We sequenced RNA using a targeted RNA toxicology panel for 386 genes associated with toxicological responses. PM was collected from a non-complaint residential environment over 1 week. Sample collection was concomitant with monitoring size-segregated PM counts and determination of microbial levels and diversity. PM exposure was not acutely toxic for the cells, and we observed up-regulation of 34 genes and down-regulation of 17 genes when compared to blank sampler control exposure. The five most up-regulated genes were related to immunotoxicity. Despite indications of incomplete cell differentiation, this model enabled the comparison of a toxicological transcriptome associated with indoor air PM exposure.

Toxicological evaluation of exhaust emissions from light-duty vehicles using different fuel alternatives in sub-freezing conditions.

BACKGROUND: Emissions from road traffic are under constant discussion since they pose a major threat to human health despite the increasingly strict emission targets and regulations. Although the new passenger car regulations have been very effective in reducing the particulate matter (PM) emissions, the aged car fleet in some EU countries remains a substantial source of PM emissions. Moreover, toxicity of PM emissions from multiple new types of bio-based fuels remain uncertain and different driving conditions such as the sub-zero running temperature has been shown to affect the emissions. Overall, the current literature and experimental knowledge on the toxicology of these PM emissions and conditions is scarce. METHODS: In the present study, we show that exhaust gas PM from newly regulated passenger cars fueled by different fuels at sub-zero temperatures, induce toxicological responses in vitro. We used exhaust gas volume-based PM doses to give us better insight on the real-life exposure and included one older diesel car to estimate the effect of the new emissions regulations. RESULTS: In cars compliant with the new regulations, gasoline (E10) displayed the highest PM concentrations and toxicological responses, while the higher ethanol blend (E85) resulted in slightly lower exhaust gas PM concentrations and notably lower toxicological responses in comparison. Engines powered by modern diesel and compressed natural gas (CNG) yielded the lowest PM concentrations and toxicological responses. CONCLUSIONS: The present study shows that toxicity of the exhaust gas PM varies depending on the fuels used. Additionally, concentration and toxicity of PM from an older diesel car were vastly higher, compared to contemporary vehicles, indicating the beneficial effects of the new emissions regulations.

Urban air particulate matter induces mitochondrial dysfunction in human olfactory mucosal cells.

BACKGROUND: The adverse effects of air pollutants including particulate matter (PM) on the central nervous system is increasingly reported by epidemiological, animal and post-mortem studies in the last decade. Oxidative stress and inflammation are key consequences of exposure to PM although little is known of the exact mechanism. The association of PM exposure with deteriorating brain health is speculated to be driven by PM entry via the olfactory system. How air pollutants affect this key entry site remains elusive. In this study, we investigated effects of urban size-segregated PM on a novel cellular model: primary human olfactory mucosal (hOM) cells. RESULTS: Metabolic activity was reduced following 24-h exposure to PM without evident signs of toxicity. Results from cytometric bead array suggested a mild inflammatory response to PM exposure. We observed increased oxidative stress and caspase-3/7 activity as well as perturbed mitochondrial membrane potential in PM-exposed cells. Mitochondrial dysfunction was further verified by a decrease in mitochondria-dependent respiration. Transient suppression of the mitochondria-targeted gene, neuronal pentraxin 1 (NPTX1), was carried out, after being identified to be up-regulated in PM2.5-1 treated cells via RNA sequencing. Suppression of NPTX1 in cells exposed to PM did not restore mitochondrial defects resulting from PM exposure. In contrast, PM-induced adverse effects were magnified in the absence of NPTX1, indicating a critical role of this protein in protection against PM effects in hOM cells. CONCLUSION: Key mitochondrial functions were perturbed by urban PM exposure in a physiologically relevant cellular model via a mechanism involving NPTX1. In addition, inflammatory response and early signs of apoptosis accompanied mitochondrial dysfunction during exposure to PM. Findings from this study contribute to increased understanding of harmful PM effects on human health and may provide information to support mitigation strategies targeted at air pollution.

Influence of wood species on toxicity of log-wood stove combustion aerosols: a parallel animal and air-liquid interface cell exposure study on spruce and pine smoke.

BACKGROUND: Wood combustion emissions have been studied previously either by in vitro or in vivo models using collected particles, yet most studies have neglected gaseous compounds. Furthermore, a more accurate and holistic view of the toxicity of aerosols can be gained with parallel in vitro and in vivo studies using direct exposure methods. Moreover, modern exposure techniques such as air-liquid interface (ALI) exposures enable better assessment of the toxicity of the applied aerosols than, for example, the previous state-of-the-art submerged cell exposure techniques. METHODS: We used three different ALI exposure systems in parallel to study the toxicological effects of spruce and pine combustion emissions in human alveolar epithelial (A549) and murine macrophage (RAW264.7) cell lines. A whole-body mouse inhalation system was also used to expose C57BL/6 J mice to aerosol emissions. Moreover, gaseous and particulate fractions were studied separately in one of the cell exposure systems. After exposure, the cells and animals were measured for various parameters of cytotoxicity, inflammation, genotoxicity, transcriptome and proteome. RESULTS: We found that diluted (1:15) exposure pine combustion emissions (PM1 mass 7.7 ± 6.5 mg m- 3, 41 mg MJ- 1) contained, on average, more PM and polycyclic aromatic hydrocarbons (PAHs) than spruce (PM1 mass 4.3 ± 5.1 mg m- 3, 26 mg MJ- 1) emissions, which instead showed a higher concentration of inorganic metals in the emission aerosol. Both A549 cells and mice exposed to these emissions showed low levels of inflammation but significantly increased genotoxicity. Gaseous emission compounds produced similar genotoxicity and a higher inflammatory response than the corresponding complete combustion emission in A549 cells. Systems biology approaches supported the findings, but we detected differing responses between in vivo and in vitro experiments. CONCLUSIONS: Comprehensive in vitro and in vivo exposure studies with emission characterization and systems biology approaches revealed further information on the effects of combustion aerosol toxicity than could be achieved with either method alone. Interestingly, in vitro and in vivo exposures showed the opposite order of the highest DNA damage. In vitro measurements also indicated that the gaseous fraction of emission aerosols may be more important in causing adverse toxicological effects. Combustion aerosols of different wood species result in mild but aerosol specific in vitro and in vivo effects.

Integrating farm and air pollution studies in search for immunoregulatory mechanisms operating in protective and high-risk environments.

BACKGROUND: Studies conducted in farm environments suggest that diverse microbial exposure promotes children's lung health. The underlying mechanisms are unclear, and the development of asthma-preventive strategies has been delayed. More comprehensive investigation of the environment-induced immunoregulation is required for better understanding of asthma pathogenesis and prevention. Exposure to air pollution, including particulate matter (PM), is a risk factor for asthma, thus providing an excellent counterpoint for the farm-effect research. Lack of comparable data, however, complicates interpretation of the existing information. We aimed to explore the immunoregulatory effects of cattle farm dust (protective, Finland) and urban air PM (high-risk, China) for the first time using identical research methods. METHODS: We stimulated PBMCs of 4-year-old children (N = 18) with farm dust and size-segregated PM and assessed the expression of immune receptors CD80 and ILT4 on dendritic cells and monocytes as well as cytokine production of PBMCs. Environmental samples were analysed for their composition. RESULTS: Farm dust increased the percentage of cells expressing CD80 and the cytokine production of children's immune cells, whereas PM inhibited the expression of important receptors and the production of soluble mediators. Although PM samples induced parallel immune reactions, the size-fraction determined the strength of the effects. CONCLUSIONS: Our study demonstrates the significance of using the same research framework when disentangling shared and distinctive immune pathways operating in different environments. Observed stimulatory effects of farm dust and inhibitory effects of PM could shape responses towards respiratory pathogens and allergens, and partly explain differences in asthma prevalence between studied environments.

Particulate emissions from the combustion of birch, beech, and spruce logs cause different cytotoxic responses in A549 cells.

According to the World Health Organization particulate emissions from the combustion of solid fuels caused more than 110,000 premature deaths worldwide in 2010. Log wood combustion is the most prevalent form of residential biomass heating in developed countries, but it is unknown how the type of wood logs used in furnaces influences the chemical composition of the particulate emissions and their toxicological potential. We burned logs of birch, beech and spruce, which are used commonly as firewood in Central and Northern Europe in a modern masonry heater, and compared them to the particulate emissions from an automated pellet boiler fired with softwood pellets. We determined the chemical composition (elements, ions, and carbonaceous compounds) of the particulate emissions with a diameter of less than 1 µm and tested their cytotoxicity, genotoxicity, inflammatory potential, and ability to induce oxidative stress in a human lung epithelial cell line. The chemical composition of the samples differed significantly, especially with regard to the carbonaceous and metal contents. Also the toxic effects in our tested endpoints varied considerably between each of the three log wood combustion samples, as well as between the log wood combustion samples and the pellet combustion sample. The difference in the toxicological potential of the samples in the various endpoints indicates the involvement of different pathways of toxicity depending on the chemical composition. All three emission samples from the log wood combustions were considerably more toxic in all endpoints than the emissions from the pellet combustion. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1487-1499, 2017.

Acute exposure to wood smoke from incomplete combustion--indications of cytotoxicity.

BACKGROUND: Smoke from combustion of biomass fuels is a major risk factor for respiratory disease, but the underlying mechanisms are poorly understood. The aim of this study was to determine whether exposure to wood smoke from incomplete combustion would elicit airway inflammation in humans. METHODS: Fourteen healthy subjects underwent controlled exposures on two separate occasions to filtered air and wood smoke from incomplete combustion with PM1 concentration at 314 µg/m(3) for 3 h in a chamber. Bronchoscopy with bronchial wash (BW), bronchoalveolar lavage (BAL) and endobronchial mucosal biopsies was performed after 24 h. Differential cell counts and soluble components were analyzed, with biopsies stained for inflammatory markers using immunohistochemistry. In parallel experiments, the toxicity of the particulate matter (PM) generated during the chamber exposures was investigated in vitro using the RAW264.7 macrophage cell line. RESULTS: Significant reductions in macrophage, neutrophil and lymphocyte numbers were observed in BW (p < 0.01, <0.05, <0.05, respectively) following the wood smoke exposure, with a reduction in lymphocytes numbers in BAL fluid (<0.01. This unexpected cellular response was accompanied by decreased levels of sICAM-1, MPO and MMP-9 (p < 0.05, <0.05 and <0.01). In contrast, significant increases in submucosal and epithelial CD3+ cells, epithelial CD8+ cells and submucosal mast cells (p < 0.01, <0.05, <0.05 and <0.05, respectively), were observed after wood smoke exposure. The in vitro data demonstrated that wood smoke particles generated under these incomplete combustion conditions induced cell death and DNA damage, with only minor inflammatory responses. CONCLUSIONS: Short-term exposure to sooty PAH rich wood smoke did not induce an acute neutrophilic inflammation, a classic hallmark of air pollution exposure in humans. While minor proinflammatory lymphocytic and mast cells effects were observed in the bronchial biopsies, significant reductions in BW and BAL cells and soluble components were noted. This unexpected observation, combined with the in vitro data, suggests that wood smoke particles from incomplete combustion could be potentially cytotoxic. Additional research is required to establish the mechanism of this dramatic reduction in airway leukocytes and to clarify how this acute response contributes to the adverse health effects attributed to wood smoke exposure. TRIAL REGISTRATION: NCT01488500.

Reference particles for toxicological studies of wood combustion: formation, characteristics, and toxicity compared to those of real wood combustion particulate mass.

Multiple studies show that particulate mass (PM) generated from incomplete wood combustion may induce adverse health issues in humans. Previous findings have shown that also the PM from efficient wood combustion may induce enhanced production of reactive oxygen species (ROS), inflammation, and cytotoxicity in vitro and in vivo. Underlying factors of these effects may be traced back to volatile inorganic transition metals, especially zinc, which can be enriched in the ultrafine fraction of biomass combustion particulate emission. In this study, nanoparticles composed of potassium, sulfur, and zinc, which are the major components forming inorganic fine PM, were synthesized and tested in vitro. In addition, in vitro toxicity of PM from efficient combustion of wood chips was compared with that of the synthesized particles. Cytotoxicity, cell cycle arrest, ROS generation, and tumor necrosis factor alpha release were related to zinc concentration in PM. Potassium sulfate and potassium carbonate did not induce toxic responses. In light of the provided data, it can be concluded that zinc, enriched in wood combustion emissions, caused the toxicity in all of the measured end points.

Role of microbial and chemical composition in toxicological properties of indoor and outdoor air particulate matter.

BACKGROUND: Ambient air particulate matter (PM) is increasingly considered to be a causal factor evoking severe adverse health effects. People spend the majority of their time indoors, which should be taken into account especially in future risk assessments, when the role of outdoor air particles transported into indoor air is considered. Therefore, there is an urgent need for characterization of possible sources seasonally for harmful health outcomes both indoors and outdoors. METHODS: In this study, we collected size-segregated (PM(10-2.5), PM(2.5-0.2)) particulate samples with a high volume cascade impactor (HVCI) simultaneously both indoors and outdoors of a new single family detached house at four different seasons. The chemical composition of the samples was analyzed as was the presence of microbes. Mouse macrophages were exposed to PM samples for 24 hours. Thereafter, the levels of the proinflammatory cytokines, NO-production, cytotoxicity and changes in the cell cycle were investigated. The putative sources of the most toxic groups of constituents were resolved by using the principal component analysis (PCA) and pairwise dependencies of the variables were detected with Spearman correlation. RESULTS: Source-related toxicological responses clearly varied according to season. The role of outdoor sources in indoor air quality was significant only in the warm seasons and the significance of outdoor microbes was also larger in the indoor air. During wintertime, the role of indoor sources of the particles was more significant, as was also the case for microbes. With respect to the outdoor sources, soil-derived particles during a road dust episode and local wood combustion in wintertime were the most important factors inducing toxicological responses. CONCLUSIONS: Even though there were clear seasonal differences in the abilities of indoor and outdoor air to induce inflammatory and cytotoxic responses, there were relatively small differences in the chemical composition of the particles responsible of those effects. Outdoor sources have only a limited effect on indoor air quality in a newly built house with a modern ventilation system at least in a low air pollution environment. The most important sources for adverse health related toxicological effects were related to soil-derived constituents, local combustion emissions and microbes.

Exposure to source-specific air pollution in residential areas and its association with dementia incidence: a cohort study in Northern Sweden.

The aim of this study was to investigate the relationship between source-specific ambient particulate air pollution concentrations and the incidence of dementia. The study encompassed 70,057 participants from the Västerbotten intervention program cohort in Northern Sweden with a median age of 40 years at baseline. High-resolution dispersion models were employed to estimate source-specific particulate matter (PM) concentrations, such as PM10 and PM2.5 from traffic, exhaust, and biomass (mainly wood) burning, at the residential addresses of each participant. Cox regression models, adjusted for potential confounding factors, were used for the assessment. Over 884,847 person-years of follow-up, 409 incident dementia cases, identified through national registers, were observed. The study population's average exposure to annual mean total PM10 and PM2.5 lag 1-5 years was 9.50 µg/m3 and 5.61 µg/m3, respectively. Increased risks were identified for PM10-Traffic (35% [95% CI 0-82%]) and PM2.5-Exhaust (33% [95% CI - 2 to 79%]) in the second exposure tertile for lag 1-5 years, although no such risks were observed in the third tertile. Interestingly, a negative association was observed between PM2.5-Wood burning and the risk of dementia. In summary, this register-based study did not conclusively establish a strong association between air pollution exposure and the incidence of dementia. While some evidence indicated elevated risks for PM10-Traffic and PM2.5-Exhaust, and conversely, a negative association for PM2.5-Wood burning, no clear exposure-response relationships were evident.

Traffic-related ultrafine particles impair mitochondrial functions in human olfactory mucosa cells - Implications for Alzheimer's disease.

Constituents of air pollution, the ultrafine particles (UFP) with a diameter of ≤0.1 µm, are considerably related to traffic emissions. Several studies link air pollution to Alzheimer's disease (AD), yet the exact relationship between the two remains poorly understood. Mitochondria are known targets of environmental toxicants, and their dysfunction is associated with neurodegenerative diseases. The olfactory mucosa (OM), located at the rooftop of the nasal cavity, is directly exposed to the environment and in contact with the brain. Mounting evidence suggests that the UFPs can impact the brain directly through the olfactory tract. By using primary human OM cultures established from nasal biopsies of cognitively healthy controls and individuals diagnosed with AD, we aimed to decipher the effects of traffic-related UFPs on mitochondria. The UFP samples were collected from the exhausts of a modern heavy-duty diesel engine (HDE) without aftertreatment systems, run with renewable diesel (A0) and petroleum diesel (A20), and from an engine of a 2019 model diesel passenger car (DI-E6d) equipped with state-of-the-art aftertreatment devices and run with renewable diesel (Euro6). OM cells were exposed to three different UFPs for 24-h and 72-h, after which cellular processes were assessed on the functional and transcriptomic levels. Our results show that UFPs impair mitochondrial functions in primary human OM cells by hampering oxidative phosphorylation (OXPHOS) and redox balance, and the responses of AD cells differ from cognitively healthy controls. RNA-Seq and IPA® revealed inhibition of OXPHOS and mitochondrial dysfunction in response to UFPs A0 and A20. Functional validation confirmed that A0 and A20 impair cellular respiration, decrease ATP levels, and disturb redox balance by altering NAD and glutathione metabolism, leading to increased ROS and oxidative stress. RNA-Seq and functional assessment revealed the presence of AD-related alterations in human OM cells and that different fuels and engine technologies elicit differential effects.