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Air pollution is one of the leading causes of early deaths worldwide, with particulate matter (PM) as an emerging factor contributing to this trend. PM is classified based on its physical size, which ranges from PM 10 (diameter ≤10 μm) to PM 2.5 (≤2.5 μm) and PM 0.5 (≤0.5 μm). Smaller-sized PM can move freely through the air and readily infiltrate deep into the lungs, intensifying existing health issues and exacerbating complications. Lung complications are the most common issues arising from PM exposure due to the primary site of deposition in the respiratory system. Conditions such as asthma, COPD, idiopathic pulmonary fibrosis, lung cancer and various lung infections are all susceptible to worsening due to PM exposure. PM can epigenetically modify specific target sites, further complicating its impact on these conditions. Understanding these epigenetic mechanisms holds promise for addressing these complications in cases of PM exposure. This involves studying the effect of PM on different gene expressions and regulation through epigenetic modifications, including DNA methylation, histone modifications and microRNAs. Targeting and manipulating these epigenetic modifications and their mechanisms could be promising strategies for future treatments of lung complications. This review mainly focuses on different epigenetic modifications due to PM 2.5 exposure in the various lung complications mentioned above., Competing Interests: Conflict of interest: All the authors have nothing to disclose., (Copyright ©The authors 2024.)

Background: PM 2.5 is a complex mixture, with water-soluble inorganic ions (WSII), mainly NH 4 + , SO 4 2- , and NO 3 - , constituting major components. Early-life PM 2.5 exposure has been shown to induce adverse health consequence but it is difficult to determine whether such an effect occurs prenatally (preconception, gestational) or postnatally in human studies., Methods: Four groups of C57BL/6 J mice were assigned to four exposure conditions: PM 2.5 NO 3 - , PM 2.5 SO 4 2- , PM 2.5 NH 4 + and clean air, and exposure started at 4 weeks old. At 8 weeks old, mice bred within group. The exposure continued during gestation. After delivery, both the maternal and F 1 mice (offspring) were kept in clean air without exposure to PM 2.5 . Respiratory function and pulmonary pathology were assessed in offspring mice at 8 weeks of age. In parallel, placenta tissue was collected for transcriptome profiling and mechanistic investigation., Results: F 1 mice in PM 2.5 NH 4 + , SO 4 2- and NO 3 - groups had 32.2 % (p=6.0e-10), 30.3 % (p=3.8e-10) and 16.9 % (p=5.7e-8) lower peak expiratory flow (PEF) than the clean air group. Importantly, the exposure-induced lung function decline was greater in male than female offspring. Moreover, exposure to PM 2.5 WSII before conception and during gestation was linked to increased airway wall thickness and elevated pulmonary neutrophil and macrophage counts in the offspring mice. At the molecular level, the exposure significantly disrupted gene expression in the placenta, affecting crucial functional pathways related to sex hormone response and inflammation., Conclusions: PM 2.5 WSII exposure during preconception and gestational period alone without post-natal exposure substantially impacted offspring's respiratory function as measured at adolescent age. Our results support the paradigm of fetal origin of environmentally associated chronic lung disease and highlight sex differences in susceptibility to air pollution exposure., Competing Interests: Declaration of Competing Interest No conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Chronic exposure to air pollutants harms human health, and at a geographical level, concentrations of air pollutants are often associated with socioeconomic disadvantage., Objectives: The aim of this study was to investigate the effects of educational attainment and air pollution on lung function in older adults, and whether air pollution may mediate the effect of education., Methods: The study included 6381 individuals (mean age 58.24 ± 7.14 years) who participated in the Czech HAPPIE (Health, Alcohol, and Psychosocial Factors in Eastern Europe) study. Participants' residential addresses were linked to air pollution data, including mean exposures to PM 10 (particulate matter of aerodynamic diameter below 10 μm) and NO 2 (nitrogen dioxide). We used path analysis to link educational attainment and air pollutants to a standardized measure of the Forced Expiratory Volume in the first second (FEV1)., Results: Higher levels of participants' education were associated with lower exposures to PM 10 and NO 2 . Individuals with tertiary education had higher standardized FEV1 than individuals with primary education (88 % vs 95 %). Path analysis revealed a direct positive effect of education on FEV1, while about 12 % of the relationship between education and lung function was mediated by PM 10 and NO 2. CONCLUSIONS: Education (typically completed at young ages) appeared to have a protective effect on lung function later in life, and a small part of this effect was mediated by air pollution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The associations of ambient air pollution exposure and low-grade inflammation with lung function remain uncertain. In this study, 276,289 subjects were enrolled in the UK Biobank. Individual exposure to ambient air pollution (including nitrogen dioxide [NO 2 ], nitrogen oxides [NO x ]), and particulate matter [PM 2.5 , PM 10, PM coarse ]) were estimated by using the land-use regression model. Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV 1 ) were tested, and low-grade inflammation score (INFLA score) was calculated for each subject. In this cross-sectional study, the median concentrations of air pollution were 9.89 µg/m 3 for PM 2.5 , 15.98 µg/m 3 for PM 10 , 6.09 µg/m 3 for PM coarse , 25.60 µg/m 3 for NO 2 , and 41.46 µg/m 3 for NO x , respectively. We observed that PM 2.5 , PM 10 , PM coarse , NO 2 , NO x was negatively associated with lung function. Besides, significant positive associations between PM exposure and low-grade inflammation were noted. Per interquartile range (IQR) increase in PM 2.5 , PM 10 , and PM coarse was related to higher INFLA score, and the β (95 % CI) was 0.06 (0.03, 0.08), 0.03 (0.02, 0.05), and 0.03 (0.01, 0.04), respectively. Additionally, we found significant negative associations between INFLA scores and lung function. One-unit increase in INFLA score was linked with 12.41- and 11.31-ml decreases in FVC and FEV 1 , respectively. Compared with individuals with low air pollution exposure and low INFLA scores, participants with high air pollution and high INFLA scores had the lowest FVC and FEV 1 . Additionally, we observed that INFLA scores could modify the relationships of PM 2.5 , NO 2, and NO x with FVC and FEV 1 (P interaction <0.05). The negative impact of air pollutants on lung function was more pronounced in subjects with high INFLA scores in comparison to those with low INFLA scores. In conclusion, we demonstrated negative associations between ambient air pollution and lung function, and the observed associations were strengthened and modified by low-grade inflammation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Epidemiological evidence on the impact of airborne organic pollutants on lung function among the elderly is limited, and their underlying biological mechanisms remain largely unexplored. Herein, a longitudinal panel study was conducted in Jinan, Shandong Province, China, involving 76 healthy older adults monitored over a span of five months repetitively. We systematically evaluated personal exposure to a diverse range of airborne organic pollutants using a wearable passive sampler and their effects on lung function. Participants' pulmonary function indicators were assessed, complemented by comprehensive multi-omics analyses of blood and urine samples. Leveraging the power of interaction analysis, causal inference test (CIT), and integrative pathway analysis (IPA), we explored intricate relationships between specific organic pollutants, biomolecules, and lung function deterioration, elucidating the biological mechanisms underpinning the adverse impacts of these pollutants. We observed that bis (2-chloro-1-methylethyl) ether (BCIE) was significantly associated with negative changes in the forced vital capacity (FVC), with glycerolipids mitigating this adverse effect. Additionally, 31 canonical pathways [e.g., high mobility group box 1 (HMGB1) signaling, phosphatidylinositol 3-kinase (PI3K)/AKT pathway, epithelial mesenchymal transition, and heme and nicotinamide adenine dinucleotide (NAD) biosynthesis] were identified as potential mechanisms. These findings may hold significant implications for developing effective strategies to prevent and mitigate respiratory health risks arising from exposure to such airborne pollutants. However, due to certain limitations of the study, our results should be interpreted with caution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The evidence associating traffic-related air pollution (TRAP) with allergic asthma is growing, but the underlying mechanisms for this association remain unclear. The airway epithelium is the primary tissue exposed to TRAP, hence understanding its interactions with TRAP and allergen is important. Diesel exhaust (DE), a paradigm of TRAP, consists of particulate matter (PM) and gases. Modern diesel engines often have catalytic diesel particulate filters to reduce PM output, but these may increase gaseous concentrations, and their benefits on human health cannot be assumed. We conducted a randomized, double-blinded, crossover study using our unique in vivo human exposure system to investigate the effects of DE and allergen co-exposure, with or without particle depletion as a proxy for catalytic diesel particulate filters, on the airway epithelial transcriptome. Participants were exposed for 2 h before an allergen inhalation challenge, with each receiving filtered air and saline (FA-S), filtered air and allergen (FA-A), DE and allergen (DE-A), or particle-depleted DE and allergen (PDDE-A), over four different occasions, each separated by a 4-week washout period. Endobronchial brushings were collected 48 h after each exposure, and total RNA was sequenced. Differentially expressed genes (DEGs) were identified using DESeq2, followed by GO enrichment and pathway analysis. FA-A, DE-A, and PDDE-A exposures significantly modulated genes relative to FA-S, with 462 unique DEGs identified. FA-A uniquely modulated the highest number (↑178, ↓155), followed by DE-A (↑44, ↓23), and then PDDE-A exposure (↑15, ↓2); 6 DEGs (↑4, ↓2) were modulated by all three conditions. Exposure to PDDE-A resulted in modulation of 285 DEGs compared to DE-A exposure, further revealing 26 biological process GO terms, including "cellular response to chemokine" and "inflammatory response". The transcriptional epithelial response to diesel exhaust and allergen co-exposure is enriched in inflammatory mediators, the pattern of which is altered upon particle depletion., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: There are a few reports on the associations between fine particulate matter (PM 2.5 )-bound heavy metals and lung function., Objectives: To evaluate the associations of single and mixed PM 2.5 -bound heavy metals with lung function., Methods: This study included 316 observations of 224 Chinese adults from the Wuhan-Zhuhai cohort over two study periods, and measured participants' personal PM 2.5 -bound heavy metals and lung function. Three linear mixed models, including the single constituent model, the PM 2.5 -adjusted constituent model, and the constituent residual model were used to evaluate the association between single metal and lung function. Mixed exposure models including Bayesian kernel machine regression (BKMR) model, weighted quantile sum (WQS) model, and Explainable Machine Learning model were used to assess the relationship between PM 2.5 -bound heavy metal mixtures and lung function., Results: In the single exposure analyses, significant negative associations of PM 2.5 -bound lead, antimony, and cadmium with peak expiratory flow (PEF) were observed. In the mixed exposure analyses, significant decreases in forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC), maximal mid-expiratory flow (MMF), and forced expiratory flow at 75% of the pulmonary volume (FEF75) were associated with the increased PM 2.5 -bound heavy metal mixture. The BKMR models suggested negative associations of PM 2.5 -bound lead and antimony with lung function. In addition, PM 2.5 -bound copper was positively associated with FEV1/FVC, MMF, and FEF75. The Explainable Machine Learning models suggested that FEV1/FVC, MMF, and FEF75 decreased with the elevated PM 2.5 -bound lead, manganese, and vanadium, and increased with the elevated PM 2.5 -bound copper., Conclusions: The negative relationships were detected between PM 2.5 -bound heavy metal mixture and FEV1/FVC, MMF, as well as FEF75. Among the PM 2.5 -bound heavy metal mixture, PM 2.5 -bound lead, antimony, manganese, and vanadium were negatively associated with FEV1/FVC, MMF, and FEF75, while PM 2.5 -bound copper was positively associated with FEV1/FVC, MMF, and FEF75., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Evidence of the acute effects of high-level air pollution on small airway function and systemic inflammation in adults is scarce., Objective: To examined the associations of short-term (i.e., daily) exposure to multiple air pollutants with lung function and inflammatory markers., Methods: We assessed short-term (daily) effects of air pollutants, including particulate matter with aerodynamic diameter less than 2.5 μm (PM 2.5 ) and 10 μm (PM 10 ), nitrogen dioxide (NO 2 ), sulfur dioxide (SO 2 ) and carbon monoxide (CO), on lung function and peripheral immune cell counts over various lag times using generalized linear regression models., Results: A total of 4764 adults were included from the general community-dwelling population in Shanghai, China. Exposure to air pollutants and lung function were negatively correlated. Decline in FEF between 25% and 75% of vital capacity (FEF 25-75% ) were found associated with PM 2.5 , SO 2 , and CO, and decline in forced expiratory volume in 3 s (FEV 3 ) to forced vital capacity (FVC) ratio were associated with all examined pollutants, indicating obstruction in small airways. Obstructed airflow in large and middle airways as indicated by decline in FEV 1 /FVC were also associated with all pollutants. In subgroup analysis, significant negative associations between the five pollutants and SAD parameters were found only in males but not in females. The difference in the associations of SO 2 with FEF 75% between males and females achieved statistical significance. Additionally, all examined pollutants were significantly associated with lower peripheral neutrophil count., Impact Statement: Acute exposure to air pollutants were associated with airflow-limitation. Both small airways and proximal airways were affected. Acute exposure to air pollutants were accompanied with a lower neutrophil count., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objective: Air pollution is a leading public health issue. This study investigated the effect of air quality and pollutants on pulmonary function and inflammation in patients with asthma in Shanghai., Methods: The study monitored 27 asthma outpatients for a year, collecting data on weather, patient self-management [daily asthma diary, peak expiratory flow (PEF) monitoring, medication usage], spirometry and serum markers. To explore the potential mechanisms of any effects, asthmatic mice induced by ovalbumin (OVA) were exposed to PM 2.5 ., Results: Statistical and correlational analyses revealed that air pollutants have both acute and chronic effects on asthma. Acute exposure showed a correlation between PEF and levels of ozone (O 3 ) and nitrogen dioxide (NO 2 ). Chronic exposure indicated that interleukin-5 (IL-5) and interleukin-13 (IL-13) levels correlated with PM 2.5 and PM 10 concentrations. In asthmatic mouse models, exposure to PM 2.5 increased cytokine levels and worsened lung function. Additionally, PM 2.5 exposure inhibited cell proliferation by blocking the NF-κB and ERK phosphorylation pathways., Conclusion: Ambient air pollutants exacerbate asthma by worsening lung function and enhancing Th2-mediated inflammation. Specifically, PM 2.5 significantly contributes to these adverse effects. Further research is needed to elucidate the mechanisms by which PM 2.5 impacts asthma., (Copyright © 2024 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

The respiratory effects of particulate matter (PM) in subway station platforms or tunnels have attracted considerable research attention. However, no studies have characterized the effects of subway PM on allergic immune responses. In this study, iron oxide (α-Fe 2 O 3 and Fe 3 O 4 ) particles-the main components of subway PM-were intratracheally administered to BALB/c mice where ovalbumin (OVA) induced allergic pulmonary inflammation. Iron oxide particles enhanced OVA-induced eosinophil recruitment around the bronchi and mucus production from airway epithelium. The concentrations of type 2 cytokines, namely, interleukin (IL)-5 and IL-13, in bronchial alveolar lavage fluids were increased by iron oxide particles. Iron oxide particles also increased the number of type 2 innate lymphoid cells and CD86 + cells in the lung. Moreover, phagocytosis of particles in lung cells was confirmed by Raman spectroscopy. In a subsequent in vitro study, bone marrow-derived antigen-presenting cells (APCs) isolated from NC/Nga mice were exposed to iron oxide particles and OVA. They were also exposed to outdoor ambient PM: Vehicle Exhaust Particulates (VEP) and Urban Aerosols (UA) as references. Iron oxide particles promoted the release of lactate dehydrogenase, C-X-C motif chemokine ligand 1 and IL-1α from APCs, which tended to be stronger than those of VEP. These results suggest that iron oxide particles enhance antigen presentation in the lungs, promoting allergic immune response in mice; iron oxide particles-induced death and inflammatory response of APCs can contribute to allergy exacerbation. Although iron oxide particles do not contain various compounds like VEP, iron oxide alone may have sufficient influence., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Allergic asthma is a chronic inflammatory airway disease with a high mortality rate and a rapidly increasing prevalence in recent decades that is closely linked to environmental change. Previous research found that high humidity (HH) and the traffic-related air pollutant NO 2 both aggregated allergic asthma. Their combined effect and mechanisms on asthma exacerbation, however, are unknown. Our study aims to toxicologically clarify the role of HH (90%) and NO 2 (5 ppm) on allergic asthma. Ninety male Balb/c mice were randomly assigned to one of six groups (n = 15 in each): saline control, ovalbumin (OVA)-sensitized, OVA + HH, OVA + NO 2 , OVA + HH + NO 2 , and OVA + HH + NO 2 +Capsazepine (CZP). After 38 days of treatment, the airway function, pathological changes in lung tissue, blood inflammatory cells, and oxidative stress and inflammatory biomarkers were comprehensively assessed. Co-exposure to HH and NO 2 exacerbated histopathological changes and airway hyperresponsiveness, increased IgE, oxidative stress markers malonaldehyde (MDA) and allergic asthma-related inflammation markers (IL-1β, TNF-α and IL-17), and upregulated the expressions of the transient receptor potential (TRP) ion channels (TRPA1, TRPV1 and TRPV4). Our findings show that co-exposure to HH and NO 2 disrupted the Th1/Th2 immune balance, promoting allergic airway inflammation and asthma susceptibility, and increasing TRPV1 expression, whereas CZP reduced TRPV1 expression and alleviated allergic asthma symptoms. Thus, therapeutic treatments that target the TRPV1 ion channel have the potential to effectively manage allergic asthma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Many environmental toxicants can cause systemic effects, such as fine particulate matter (PM 2.5 ), which can penetrate the respiratory barrier and induce effects in multiple tissues. Although metabolomics has been used to identify biomarkers for PM 2.5 , its multi-tissue toxicology has not yet been explored holistically. Our objective is to explore PM 2.5 induced metabolic alterations and unveil the intra-tissue responses along with inter-tissue communicational effects. In this study, following a single intratracheal instillation of multiple doses (0, 25, and 150 μg as the control, low, and high dose), non-targeted metabolomics was employed to evaluate the metabolic impact of PM 2.5 across multiple tissues. PM 2.5 induced tissue-specific and dose-dependent disturbances of metabolites and their pathways. The remarkable increase of both intra- and inter-tissue correlations was observed, with emphasis on the metabolism connectivity among lung, spleen, and heart; the tissues' functional specificity has marked their toxic modes. Beyond the inter-status comparison of the metabolite fold-changes, the current correlation network built on intra-status can offer additional insights into how the multiple tissues and their metabolites coordinately change in response to external stimuli such as PM 2.5 exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Atmospheric pollution can be defined as a set of changes that occur in the composition of the air, making it unsuitable and/or harmful and thereby generating adverse effects on human health. The regular practice of physical exercise (PE) is associated with the preservation and/or improvement of health; however, it can be influenced by neuroimmunoendocrine mechanisms and external factors such as air pollution, highlighting the need for studies involving the practice of PE in polluted environments. Herein, 24 male C57BL/6 mice were evaluated, distributed into four groups (exposed to a high concentration of pollutants/sedentary, exposed to a high concentration of pollutants/exercised, exposed to ambient air/sedentary, and exposed to ambient air/exercised). The exposure to pollutants occurred in the environmental particle concentrator (CPA) and the physical training was performed on a treadmill specially designed for use within the CPA. Pro- and anti-inflammatory markers in blood and bronchoalveolar lavage (BALF), BALF cellularity, and lung tissue were evaluated. Although the active group exposed to a high concentration of pollution showed a greater inflammatory response, both the correlation analysis and the ratio between pro- and anti-inflammatory cytokines demonstrated that the exercised group presented greater anti-inflammatory activity, suggesting a protective/adaptative effect of exercise when carried out in a polluted environment.

Fine particulates in city air significantly impact human health, but the hazardous compositional mechanisms are still unclear. Besides the toxicity of environmental PM 2.5 to in vitro human lung epithelial cells (A549), the independent cytotoxicity of PM 2.5 -bound water-soluble (WS-PM 2.5 ) and water-insoluble (WIS-PM 2.5 ) fractions were also compared by cell viability, oxidative stress (reactive oxygen species, ROS), and inflammatory injury (IL-6 and TNF-α). The cytotoxicity of PM 2.5 varied significantly by sampling season and place, with degrees greater in winter and spring than in summer and autumn, related to corresponding trend of air PM 2.5 level, and also higher in industrial than urban site, although their PM 2.5 pollution levels were comparable. The PM 2.5 bound metals (Ni, Cr, Fe, and Mn) may contribute to cellular injury. Both WS-PM 2.5 and WIS-PM 2.5 posed significant cytotoxicity, that WS-PM 2.5 was more harmful than WIS-PM 2.5 in terms of decreasing cell viability and increasing inflammatory cytokines production. In particular, industrial samples were usually more toxic than urban samples, and those from summer were generally less toxic than other seasons. Hence, in order to mitigate the health risks of PM 2.5 pollution, the crucial targets might be components of heavy metals and soluble fractions, and sources in industrial areas, especially during the cold seasons., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Fine particulate matters-PM 2.5 in the air can have considerable negative effects on human health and the environment. Various human cell-based studies examined the effect of PM 2.5 on human health in different cities of the world using various chemical parameters. Unfortunately, limited information is available regarding the relationship between toxicity and chemical characteristics of PM 2.5 collected in Istanbul, Türkiye, located in one of the most populated cities in the world. To investigate the chemical characteristics and cytotoxicity of PM 2.5 in Istanbul, samples were collected for 12 months, then potentially toxic metals, oxidative potential, and particle indicators (e.g., functional groups and elements) were determined, and the cytotoxicity of PM 2.5 on human A549 lung alveolar epithelial cells was examined. The mean PM 2.5 mass concentration was 24.0 ± 17.4 µg m -3 and higher in cold months compared to other seasons. Moreover, the results of the metals, elemental, and functional groups indicated that seasonal and monthly characteristics were influenced by the regional anthropogenic sources and photochemistry input. The cytotoxicity results also showed that the viability of A549 cells was reduced with the exposure of PM 2.5 (30-53%) and higher cytotoxicity was obtained in summer compared to the other seasons due to the impact of the metals, elements, and oxidative characteristics of PM 2.5 .

Decreased lung function is an early hazard of respiratory damage from fine particulate matter (PM 2.5 ) exposure. Limited studies have explored the association between PM 2.5 -bound polycyclic aromatic hydrocarbons (PAHs) and lung function, but studies at the personal level in healthy young adults are scarce. Here, we assessed personal PM 2.5 and PM 2.5 -bound PAH levels in a panel of 45 healthy young adults by a time-weighted model. The aims were to investigate the relationship between personal exposure and lung function by a linear mixed effect model, and to explore the mediating effects of oxidative stress in this association. The results showed that personal exposure to PM 2.5 and PAHs had the greatest negative effect on forced expiratory volume in 1 s (FEV 1 ), peak expiratory flow rate (PEF) and forced expiratory flow between 25% and 75% vital capacity (FEF 25-75 ) at lag 3 days. An IQR increase in personal PM 2.5 exposure was associated with a change of 0.35% (95% CI: 0.27%, 0.42%) in FEV 1 , 0.39% (95% CI: 0.29%, 0.47%) in PEF and 0.36% (95% CI: 0.27%, 0.45%) in FEF 25-75 . An IQR increase in personal PAH exposure was associated with a decrease of 0.63% (95% CI: 0.55%, 0.69%) in FEV 1 , 0.69% (95% CI: 0.61%, 0.75%) in PEF and 0.66% (95% CI: 0.57%, 0.72%) in FEF 25-75 . Additionally, exposure to PM 2.5 and PAHs resulted in the strongest positive effects on urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-iso-prostaglandin-F 2α (8-iso-PGF 2α ). Of these, 8-OHdG mediated 10.33%, 8.87% and 9.45% of the associations of personal PM 2.5 exposure with FEV 1 , PEF and FEF 25-75 , respectively. Our results revealed that personal exposure to PM 2.5 and PAHs was associated with lung function decline in healthy young adults, and urinary 8-OHdG mediated the association between personal PM 2.5 and lung function., (Copyright © 2021. Published by Elsevier Ltd.)

Rationale: Infants born prematurely have impaired capacity to deal with oxidative stress shortly after birth. Objectives: We hypothesize that the relative impact of exposure to air pollution on lung function is higher in preterm than in term infants. Methods: In the prospective BILD (Basel-Bern Infant Lung Development) birth cohort of 254 preterm and 517 term infants, we investigated associations of particulate matter ⩽10 μm in aerodynamic diameter (PM 10 ) and nitrogen dioxide with lung function at 44 weeks' postconceptional age and exhaled markers of inflammation and oxidative stress response (fractional exhaled nitric oxide [Fe NO ]) in an explorative hypothesis-driven study design. Multilevel mixed-effects models were used and adjusted for known confounders. Measurements and Main Results: Significant associations of PM 10 during the second trimester of pregnancy with lung function and Fe NO were found in term and preterm infants. Importantly, we observed stronger positive associations in preterm infants (born 32-36 wk), with an increase of 184.9 (95% confidence interval [CI], 79.1-290.7) ml/min [Formula: see text]e per 10-μg/m 3 increase in PM 10 , than in term infants (75.3; 95% CI, 19.7-130.8 ml/min) ( p prematurity   ×   PM10 interaction  = 0.04, after multiple comparison adjustment p adj  = 0.09). Associations of PM 10 and Fe NO differed between moderate to late preterm (3.4; 95% CI, -0.1 to 6.8 ppb) and term (-0.3; 95% CI, -1.5 to 0.9 ppb) infants, and the interaction with prematurity was significant ( p prematurity   ×   PM10 interaction  = 0.006, p adj  = 0.036). Conclusions: Preterm infants showed significantly higher susceptibility even to low to moderate prenatal air pollution exposure than term infants, leading to increased impairment of postnatal lung function. Fe NO results further elucidate differences in inflammatory/oxidative stress response when comparing preterm infants with term infants.

Introduction: Air pollution is a risk factor for respiratory infections and asthma exacerbations. We previously reported impaired Type-I and Type-III interferons (IFN-β/λ) from airway epithelial cells of preschool children with asthma and/or atopy. In this study we analyzed the association between rhinovirus-induced IFN-β/λ epithelial expression and acute exposure to the principal outdoor air pollutants in the same cohort., Methods: We studied 34 children (17asthmatics/17non-asthmatics) undergoing fiberoptic bronchoscopy for clinical indications. Bronchial epithelial cells were harvested by brushing, cultured and experimentally infected with Rhinovirus Type 16 (RV16). RV16-induced IFN-β and λ expression was measured by quantitative real time PCR, as was RV16vRNA. The association between IFNs and the mean exposure to PM10, SO2 and NO 2 in the day preceding bronchoscopy was evaluated using a Generalized Linear Model (GLM) with Gamma distribution., Results: Acute exposure to PM10 and NO 2 was negatively associated to RV16-induced IFNβ mRNA. For each increase of 1ug/m 3 of NO 2 we found a significative decrease of 2.3x10 3 IFN-β mRNA copies and for each increase of 1ug/m 3 of PM10 a significative decrease of 1x10 3 IFN-β mRNA copies. No significant associations were detected between IFN-λ mRNA and NO 2 nor PM10. Increasing levels of NO 2 (but not PM10) were found to be associated to increased RV16 replication., Conclusions: Short-term exposure to high levels of NO 2 and PM10 is associated to a reduced IFN-β expression by the airway epithelium, which may lead to increased viral replication. These findings suggest a potential mechanism underlying the link between air pollution, viral infections and asthma exacerbations., Competing Interests: MS reports grants from Chiesi Farmaceutici, grants from Laboratori Guidotti, grants from Bottega Veneta, grants from University of Padova- Italy, outside the submitted work. AP reports grants, personal fees, non-financial support and other from GlaxoSmithKline, grants, personal fees and non-financial support from AstraZeneca, grants, personal fees, non-financial support and other from Boehringer Ingelheim, grants, personal fees, non-financial support and other from Chiesi Farmaceutici, grants, personal fees, non-financial support and other from TEVA, personal fees, non-financial support and other from Mundipharma, personal fees, non-financial support and other from Zambon, personal fees, non-financial support and other from Novartis, grants, personal fees and non-financial support from Menarini, personal fees, non-financial support and other from Sanofi/Regeneron, personal fees from Roche, grants from Fondazione Maugeri, grants from Fondazione Chiesi, personal fees from Edmondpharma, outside the submitted work. MC reports grants, personal fees and non-financial support from Chiesi, personal fees and non-financial support from AstraZeneca, personal fees and non-financial support from Boehringer Ingelheim, personal fees and non-financial support from Alk-Abello, grants, personal fees and non-financial support from GlaxoSmithKline, personal fees and non-financial support from Novartis, personal fees and non-financial support from Zambon, grants from University of Ferrara - Italy, outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bonato, Gallo, Turrin, Bazzan, Baraldi, Saetta, Gregori, Papi, Contoli and Baraldo.)

Background: Cooking oil fumes (COF) is one of the primary sources of indoor air pollution in China, which is associated with respiratory diseases such as acute lung injury and lung cancer. However, evidence of COF toxic effect was few., Objectives: The research was aimed to investigate the toxic effect and the underlying mechanisms induced by COF., Methods: The female Wistar rats were randomly divided into several groups, including control group, COF exposure group and VE protection group, and instilled intratracheally with different COF suspensions (0.2, 2, 20 mg/kg) or saline once every 3 days for 30 days. After 24 h of final exposure, all rat were anesthetic euthanasia to draw materials. The alveolar lavage fluid (BALF) was for inflammatory cell count. The lung homogenate was to determine the biochemical indexes such as oxidative stress, apoptosis factors, carcinogenic toxicity and endoplasmic reticulum (ER) stress. The left lung was made for immunohistochemical and histopathological analysis., Results: The results showed that the levels of oxidative stress (ROS), apoptosis factors (NF-κB), carcinogenic toxicity (P53 and 8-OhdG), ER stress (IRE-1α and Caspase-12) in 2 mg/kg and 20 mg/kg COF exposure groups were significantly increased compared with the saline groups. The above pathological changes were improved after vitamin E (VE) supplementation. In addition, the immunohistochemical and histopathological analysis found the same trend., Conclusion: The COF had health risk of heredity and potential carcinogenicity. Besides, COFs can not only induce oxidative stress, but also induce ER stress in lung and airway epithelial cells of female rats through the unfolded protein reaction (UPR) pathway. It revealed that the oxidative stress and ER stress interacted in aggravating lung injury. VE could effectively alleviate the lung injury causing by COF exposure., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Decline in pulmonary function contributes to increasing cardiovascular disease (CVD) risk. Although adverse effects of short-term exposure to fine particulate matter (PM 2.5 ) on pulmonary function have been recognized in healthy people or patients with respiratory disease, these results were not well illustrated among people with elevated CVD risk., Materials and Methods: A panel study was conducted in three Chinese cities with three repeated visits among populations at intermediate to high-risk of CVD, defined as treated hypertension patients or those with blood pressure ≥ 130/80 mmHg, who met any of the three conditions including abdominal obesity, dyslipidemia, and diabetes mellitus. Individualized PM 2.5 exposure and pulmonary function were measured during each seasonal visit. Linear mixed-effect models were applied to analyze the associations of PM 2.5 concentrations with pulmonary function indicators, including forced expiratory volume in 1 s (FEV 1 ), FEV 1 /forced vital capacity (FVC), maximal mid-expiratory flow (MMF), and peak expiratory flow (PEF)., Results: Short-term PM 2.5 exposure was significantly associated with decreased pulmonary function and an increment of 10 μg/m 3 in PM 2.5 concentrations during lag 12-24 hour was associated with declines of 41.7 ml/s (95% confidence interval [CI]: 7.7-75.7), 0.35% (95% CI: 0.01, 0.69), and 20.9 ml/s (95% CI: 0.5-41.3) for PEF, FEV 1 /FVC, and MMF, respectively. Results from stratified and sensitivity analyses were generally similar with the overall findings, while the adverse effects of PM 2.5 on pulmonary functions were more pronounced in those who were physically inactive., Conclusions: This study first identified short-term exposure to PM 2.5 was associated with impaired pulmonary function and physical activity might attenuate the adverse effects of PM 2.5 among populations at intermediate to high-risk of CVD. These findings provide new robust evidence on health effects of air pollution and call for effective prevention measures among people at CVD risk., (Copyright © 2021. Published by Elsevier Inc.)

Inhalation exposure to ozone (O 3 ) causes adverse respiratory health effects that result from airway inflammation, a complex response mediated in part by changes to airway cellular transcriptional programs. These programs may be regulated by microRNAs transferred between cells (e.g., epithelial cells and macrophages) via extracellular vesicles (EV miRNA). To explore this, we exposed female C57BL/6J mice to filtered air (FA), 1, or 2 ppm O 3 by inhalation and collected bronchoalveolar lavage fluid (BALF) 21 h later for markers of airway inflammation, EVs, and EV miRNA. Both concentrations of O 3  significantly increased markers of inflammation (neutrophils), injury (total protein), and the number of EV-sized particles in the BALF. Imagestream analysis indicated a substantial portion of particles was positive for canonical EV markers (CD81, CD51), and Siglec-F, a marker of alveolar macrophages. Using high-throughput small RNA sequencing, we identified several differentially expressed (DE) BALF EV miRNAs after 1 ppm (16 DE miRNAs) and 2 ppm (99 DE miRNAs) O 3 versus FA exposure. O 3 concentration-response patterns in EV miRNA expression were apparent, particularly for miR-2137, miR-126-3p, and miR-351-5p. Integrative analysis of EV miRNA expression and airway cellular mRNA expression identified EV miR-22-3p as a candidate regulator of transcriptomic responses to O 3 in airway macrophages. In contrast, we did not identify candidate miRNA regulators of mRNA expression data from conducting airways (predominantly composed of epithelial cells). In summary, our data show that O 3 exposure alters EV release and EV miRNA expression, suggesting that further investigation of EVs may provide insight into their effects on airway macrophage function and other mechanisms of O 3 -induced respiratory inflammation., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Although considerable inter-individual variability exists in health effects associated with air pollutant exposure, underlying reasons remain unclear. We examined whether innate differences in stress axis function modify lung glucocorticoid and macrophage responses to ozone (O 3 ). Highly-stress responsive Fischer (F344) and less responsive Lewis (LEW) rats were exposed for 4 h by nose-only inhalation to air or O 3 (0.8 ppm). Ozone increased corticosterone recovered by bronchoalveolar lavage in both strains (F344 > LEW). Higher corticosterone in F344 was associated with a blunted response to O 3 of macrophage pro-inflammatory genes compared to LEW. Pharmacological inhibition of O 3 -dependent corticosterone production in F344 enhanced the inflammatory gene response to O 3, mimicking the LEW phenotype. Examination of potential impacts of glucocorticoids on macrophage function using a human monocyte-derived macrophage cell line (THP-1) showed that cortisol modified phagocytosis in a macrophage phenotype-dependent manner. Overall, our data implicate endogenous glucocorticoids in the regulation of pulmonary macrophage responses to O 3 ., (Crown Copyright © 2021. Published by Elsevier B.V. All rights reserved.)

Exposure to fine particulate matter with a diameter ≤2.5 μm (PM2.5) can cause a number of respiratory diseases. However, there is currently no safe treatment for PM2.5-induced lung damage. This study investigated the protective effect of IL-10 against lung injury and the possible involvement of AMPK/SIRT1/PGC-1α signaling. The mean diameter, particle size distribution, and zeta potential of PM2.5 samples were assessed using a Zetasizer Nano ZS90 analyzer. Thereafter, Wistar rats were exposed to PM2.5 (1.8, 5.4, or 16.2 mg/kg) alone or high-dose PM2.5 with recombinant rat IL-10 (rrIL-10; 5 μg/rat). Treatment with rrIL-10 ameliorated PM2.5-induced acute lung injury, reduced mitochondrial damage, and inhibited inflammation, oxidative stress, and apoptosis in the PM2.5-treated rats. Moreover, the mRNA and protein expression of AMPK, SIRT1, and PGC-1α were upregulated by rrIL-10 treatment. In conclusion, rrIL-10 protected lung tissues against PM2.5-induced inflammation by reducing oxidative stress and apoptosis via activating AMPK/SIRT1/PGC-1α signaling., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Exposure to ambient air-borne fine particulate matter (PM 2.5 ) increases respiratory morbidity and mortality. The mechanisms underlying PM 2.5 -induced adverse effects remain unclear. This study aimed to uncover the molecular mechanisms of PM 2.5 -induced lung toxicity using a mouse model., Methods: Scanning electron microscopy and inductively coupled plasma mass spectrometry were used to examine and analyze PM 2.5 morphology and element compositions, respectively. Twenty four male mice were randomly divided into three groups: control (PBS), PM 2.5 (4.0 mg/kg b.w.), and PM 2.5 + Z-YVAD-FMK. In the latter group, the pan-caspase inhibitor (Z-YVAD-FMK) was intraperitoneally injected into mice at a dose of 12.5 mg/kg body weight prior to intratracheal instillation of PM 2.5 (4.0 mg/kg b.w.) every other day for a total of 3 times (n = 8 in each group). Bronchoalveolar lavage fluids (BALFs) were collected 24 h after the last instillation of PM 2.5 . Levels of total proteins (TP), lactate dehydrogenase (LDH), IL-1β and IL-18 were analyzed for biomarkers of cell injury and inflammation. Additionally, histological alterations of lung tissues were assessed by hematoxylin-eosin staining. mRNA and protein expression of Caspase1, NLRP3 and GSDMD were examined by real-time fluorescent quantitative PCR and immunohistochemical staining., Results: Exposure to PM 2.5 increased levels of TP, LDH, IL-1β, IL-18 and inflammatory cell counts in lung. The mRNA and protein expression of Caspase1, NLRP3 and GSDMD were increased. Inhibition of the NALRP3/Caspase-1 signaling pathway ameliorated PM 2.5 -induced lung injury and inflammation, partially through suppressing pyroptosis in lung., Conclusion: PM 2.5 exposure induces lung injury and inflammation, which is mediated by the NALRP3/Caspase-1 signaling pathway., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The final results from this multi-dose, 90-day inhalation toxicology study in the rat with life-time post-exposure observation have shown a significant fundamental difference in pathological response and tumorgenicity between brake dust generated from brake pads manufactured with chrysotile or from chrysotile alone in comparison to the amphiboles, crocidolite and amosite asbestos. The groups exposed to brake dust showed no significant pathological or tumorigenic response in the respiratory track compared to the air control group at exposure concentrations and deposited doses well above those at which humans have been exposed. Slight alveolar/interstitial macrophage accumulation of particles was noted. Wagner grades were 1-2 (1 = control group), similar to the TiO 2 particle control group. Chrysotile was not biopersistent, exhibiting in the lung a deterioration of its matrix which results in breakage into particles and short fibers which can be cleared by alveolar macrophages and which can continue to dissolve. Particle-laden macrophage accumulation was observed, leading to a very-slight interstitial inflammatory response (Wagner grade 1-3). There was no peribronchiolar inflammation, occasional very-slight interstitial fibrosis (Wagner grade 4), and no exposure-related tumorigenic response. The pathological response of crocidolite and amosite compared to the brake dust and chrysotile was clearly differentiated by the histopathology and the confocal analysis. Crocidolite and amosite induced persistent inflammation, microgranulomas, persistent fibrosis (Wagner grades 4), and a dose-related lung tumor response. Confocal microscopy quantified extensive inflammatory response and collagen development in the lung, visceral and parietal pleura as well as pleural adhesions. These results provide a clear foundation for differentiating the innocuous effects of brake dust exposure from the adverse effects following amphibole asbestos exposure., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Air pollution (AP) is one of the leading causes of health risks because it causes widespread morbidity and mortality every year. Its impact on the environment includes acid rain and decreased visibility, but more importantly, it also has an impact on human health. The rise of COVID-19 demonstrates the cost of failing to manage AP. COVID-19 can be spread through the air, and atmospheric particulate matters (PMs) can create a good atmosphere for the long-distance spread of the virus. Moreover, these PMs can cause lung cell inflammation, thereby increasing sensitivity and the severity of symptoms in COVID-19 patients. In this study, we emphasized the potential role of PMs in the spread of COVID-19. The relationship among COVID-19, PMs, and angiotensin-converting enzyme 2 (ACE2) (receptor involved in virus entry into lung cells and inflammation) was also summarized., Competing Interests: The authors state no conflicts of interest., (Copyright © 2021 Zafran Khan et al.)

Fine particulate matter (PM 2.5 ) air pollution exposure increases the risk of developing cardiovascular disease (CVD). Although the precise mechanisms by which air pollution exposure increases CVD risk remain uncertain, research indicates that PM 2.5 -induced endothelial dysfunction contributes to CVD risk. Previous studies demonstrate that concentrated ambient PM 2.5 (CAP) exposure induces vascular inflammation and impairs insulin and vascular endothelial growth factor (VEGF) signaling dependent on pulmonary oxidative stress. To assess whether CAP exposure induces these vascular effects via plasmatic factors, we incubated aortas from naïve mice with plasma isolated from mice exposed to HEPA-filtered air or CAP (9 days) and examined vascular inflammation and insulin and VEGF signaling. We found that treatment of naïve aortas with plasma from CAP-exposed mice activates NF-κBα and induces insulin and VEGF resistance, indicating transmission by plasmatic factor(s). To identify putative factors, we exposed lung-specific ecSOD-transgenic (ecSOD-Tg) mice and wild-type (WT) littermates to CAP at concentrations of either ∼60 µg/m 3 (CAP60) or ∼100 µg/m 3 (CAP100) and measured the abundance of plasma metabolites by mass spectrometry. In WT mice, both CAP concentrations increased levels of fatty acids such as palmitate, myristate, and palmitoleate and decreased numerous phospholipid species; however, these CAP-induced changes in the plasma lipidome were prevented in ecSOD-Tg mice. Consistent with the literature, we found that fatty acids such as palmitate are sufficient to promote endothelial inflammation. Collectively, our findings suggest that PM 2.5 exposure, by inducing pulmonary oxidative stress, promotes unique lipidomic changes characterized by high levels of circulating fatty acids, which are sufficient to trigger vascular pathology. NEW & NOTEWORTHY We found that circulating plasma constituents are responsible for air pollution-induced vascular pathologies. Inhalation of fine particulate matter (≤PM 2.5 ) promotes a unique form of dyslipidemia that manifests in a manner dependent upon pulmonary oxidative stress. The air pollution-engendered dyslipidemic phenotype is characterized by elevated free fatty acid species and diminished phospholipid species, which could contribute to vascular inflammation and loss of insulin sensitivity.

Background: High serum bilirubin levels have been shown to be associated with an improved pulmonary function test results. Their potential ability to similarly benefit pulmonary function in an environment of polluted air has not been tested. We retrospectively analyzed data of 15,605 apparently healthy individuals in order to evaluate the effect of serum bilirubin levels on forced expiratory volume in 1 s (FEV1)., Methods: Individuals attended the Tel-Aviv Medical Center Inflammatory Survey for a routine annual health check between February, 2002 and June, 2009 and were divided into low, medium and high serum bilirubin levels. Their FEV1 results were compared under various levels of air pollution. Air pollution and weather data were obtained from air pollution monitoring stations of the Israeli Ministry of Environmental Protection., Results: The elevated serum bilirubin concentrations on FEV1 were evaluated under moderate and high pollution levels FEV1 and were significantly higher in participants with high blood bilirubin levels compared to medium or low levels (p < 0.001 and p = 0.018, respectively). Participants with high levels of bilirubin had preserved FEV1 under exposure to high and medium pollution levels of both Nitrogen Oxide (NOx) and Carbon Monoxide (CO) pollutants (p = 0.003 and p = 0.022, respectively). The multivariate regression analysis revealed that the influence of bilirubin under conditions of air pollution remained significant even after adjustment for FEV1 confounders, but the interaction was not significant., Conclusions: Elevated serum bilirubin concentrations are associated with preserved lung function in healthy individuals in Israel exposed to high levels of air pollution.

Air pollution has association with chronic obstructive pulmonary disease (COPD) and reduced life expectancy. This study investigated the deleterious effects caused by tobacco smoke and diesel exhaust particles (DEP) from vehicles operating under EURO 3 and EURO 5 standards. Experiments were carried out on C57BL/6 mice divided into six groups: control group, group exposed to cigarette smoke (CS), two groups exposed to DEP (AAE3 and AAE5), and two groups exposed to tobacco smoke and vehicle DEP (CSE3 and CSE5). Results showed that, when compared to AA, groups AAE3 and AAE5 showed changes in respiratory mechanics, and that DEP originating from EURO 5 diesel vehicles was less harmful when compared to DEP originating from EURO 3 diesel vehicles. Analyses of groups CSE3 and CSE5 revealed increased inspiratory capacity and decreased tissue elastance, when compared to their respective controls, suggesting an exacerbation of changes in respiratory system mechanics compatible with COPD development., (Copyright © 2021 Elsevier B.V. All rights reserved.)

PM 2.5 exposure is associated with a glomerular filtration rate (GFR) reduction, and renal tissue damage. The goal of this study was demonstrate the acute effect of PM 2.5 on the kidney. Male rats were acutely exposed to PM 2.5 or filtered air. Blood pressure was mesure and early kidney biomarkers were evaluated in serum and urine samples, and also IL-1β, IL-6 and TNFα were determined. Oxidative biomarkers, angiotensin/bradykinin-related proteins, KIM-1, IL-6 and histology were determined. Blood pressure, GFR, and early kidney damage biomarkers increase together with oxidative biomarkers and angiotensin/bradykinin endocrine-related proteins increased after exposure to PM 2.5 . Urinary IL-6 increased after exposure to PM 2.5 , whereas in kidney cortex decreased. Histological changes were observed and accompanied by the induction of KIM-1. Acute exposure to PM 2.5 not decline kidney function. However, it can induce early kidney damage biomarkers, oxidative stress, inflammation and angiotensin mediators, which perhabs culminates in a lose of renal function., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Airway pollution can affect the central nervous system, but whether this causes glial activation and inflammation in the nucleus of solitary tract (NTS) remains unclear. We used a rat model with exposure to diesel exhaust particulate matter (DEP) at 200 μg/m 3 (low exposure) and 1000 μg/m 3 (high exposure) for 14 days. Activation of microglia and astrocytes in the NTS was assessed using Iba-1 and glial fibrillary acidic protein (GFAP) staining. The expression of neurotrophic factors including brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), and nerve growth factor (NGF) in the NTS were evaluated by immunofluorescence. Changes in the intracellular structure of NTS neurons were observed via electron microscopy. Inflammatory cytokines and oxidant stress levels in the medulla were also measured. Exposure to DEP can cause NTS inflammation as well as airway inflammation, especially in the H-exposure group. We showed that the numbers of microglia and astrocytes in the NTS, as well as NGF expression in the NTS, were significantly higher in both exposure groups than in controls, but BDNF or GDNF expression was not detected. Exposure to DEP induced ultrastructural changes in NTS neurons as reflected by endoplasmic reticulum dilation, ribosomal loss, mitochondrial vacuolization, and a sparse myelin sheath. Medulla inflammation and an imbalance of oxidants and antioxidants also resulted from exposure to DEP. The H-exposure group showed an imbalance of oxidants and antioxidants with decreased levels of SOD and GSH and increased levels of MDA and ROS compared to the control group (both p < 0.01) in the medulla. Inflammatory cytokines (IL-1β, IL-6, and TNF-α) were also significantly increased in the H-exposure group. Fourteen days of exposure to DEP can affect the NTS neurons in rat. Glial activation and inflammation may play important roles in the response of the NTS to DEP., (Copyright © 2021. Published by Elsevier B.V.)

Epithelial barrier dysfunction is involved in allergic inflammation and asthma, due to increased exposure of sub-epithelial tissues to inhaled allergens and air pollutants. The tight junction proteins claudins (CLDNs) are important regulators of paracellular permeability. CLDN7 is expressed in the alveolar epithelium; however, its contribution to airway barrier function remains unclear. The aim of this study was to assess the effects of TiO 2 on epithelial barrier function in asthma. Mice were sensitized and challenged with OVA or exposed to TiO 2 on days 21-23. The effect of TiO 2 on CLDN7 was assessed by ELISA, immunoblotting, and immunohistochemical analysis. The levels of CLDN7 in the plasma of patients with asthma and healthy individuals were also examined. CLDN7 levels were lower in plasma from patients with asthma compared with healthy individuals. CLDN7 levels were associated with FEV 1 /FVC and the blood eosinophils (%) in patients with asthma. Although CLDN7 expression was elevated in the lungs of mice with asthma and in NHBE cells treated with HDM extracts, its expression was suppressed by exposure to TiO 2 . p-AKT and p-ERK was increased in asthmatic mice and decreased in mice with TiO 2 treatment. p-AKT and p-ERK was decreased in NHBE cells treated with TiO 2 and HDM extracts. Trans-epithelial electrical resistance (TEER) was higher in NHBE cells treated with TiO 2 or HDM extracts; however, this was decreased by concurrent TiO 2 and HDM extracts treatment. Our data suggest that particulate matter contributes to airway epithelial barrier dysfunction and results in airway inflammation and responsiveness., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Despite numerous reports that ambient particulate matter is a key determinant for human health, toxicity data produced based on physicochemical properties of particulate matters is very lack, suggesting lack of scientific evidence for regulation. In this study, we sampled inhalable particulate matters (PM10) in northern Seoul, Korea. PM10 showed atypical- and fiber-type particles with the average size and the surface charge of 1,598.1 ± 128.7 nm and -27.5 ± 2.8, respectively, and various toxic elements were detected in the water extract. On day 90 after the first pulmonary exposure, total cell number dose-dependently increased in the lungs of both sexes of mice. PM10 induced Th1-dominant immune response with pathological changes in both sexes of mice. Meanwhile, composition of total cells and expression of proteins which functions in cell-to-cell communication showed different trends between sexes. Following, male and female mice were mated to identify effects of PM10 to the next generation. PM10 remained in the lung of dams until day 21 after birth, and the levels of IgA and IgE increased in the blood of dams exposed to the maximum dose compared to control. In addition, the interval between births of fetuses, the number of offspring, the neonatal survival rate (day 4 after birth) and the sex ratio seemed to be affected at the maximum dose, and particularly, all offspring from one dam were stillborn. In addition, expression of HIF-1α protein increased in the lung tissue of dams exposed to PM10, and level of hypoxia-related proteins was notably enhanced in PM10-exposed bronchial epithelial cells compared to control. Taken together, we suggest that inhaled PM10 may induce Th1-shifting immune response in the lung, and that it may affect reproduction (fetus development) by causing lung hypoxia. Additionally, we propose that further study is needed to identify particle-size-dependent effects on development of the next generation., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Air pollutants may increase risk for cardiopulmonary disease, particularly in susceptible populations with metabolic stressors such as diabetes and unhealthy diet. We investigated effects of inhaled ozone exposure and high-cholesterol diet (HCD) in healthy Wistar and Wistar-derived Goto-Kakizaki (GK) rats, a non-obese model of type 2 diabetes. Male rats (4-week old) were fed normal diet (ND) or HCD for 12 weeks and then exposed to filtered air or 1.0 ppm ozone (6 h/day) for 1 or 2 days. We examined pulmonary, vascular, hematology, and inflammatory responses after each exposure plus an 18-h recovery period. In both strains, ozone induced acute bronchiolar epithelial necrosis and inflammation on histopathology and pulmonary protein leakage and neutrophilia; the protein leakage was more rapid and persistent in GK compared to Wistar rats. Ozone also decreased lymphocytes after day 1 in both strains consuming ND (~50%), while HCD increased circulating leukocytes. Ozone increased plasma thrombin/antithrombin complexes and platelet disaggregation in Wistar rats on HCD and exacerbated diet effects on serum IFN-γ, IL-6, KC-GRO, IL-13, and TNF-α, which were higher with HCD (Wistar>GK). Ex vivo aortic contractility to phenylephrine was lower in GK versus Wistar rats at baseline(~30%); ozone enhanced this effect in Wistar rats on ND. GK rats on HCD had higher aortic e-NOS and tPA expression compared to Wistar rats. Ozone increased e-NOS in GK rats on ND (~3-fold) and Wistar rats on HCD (~2-fold). These findings demonstrate ways in which underlying diabetes and HCD may exacerbate pulmonary, systemic, and vascular effects of inhaled pollutants., (Published by Elsevier Inc.)

Aim: Ambient fine particulate matter (PM 2.5 ) consists of various components, and their respective contributions to the toxicity of PM 2.5 remains to be determined. To provide specific recommendations for preventing adverse effects due to PM 2.5 pollution, we determined whether the induction of pulmonary inflammation, the putative pathogenesis for the morbidity and mortality due to PM 2.5 exposure, was fractioned through solubility-dependent fractioning., Methods: In the present study, the water and heptane solubilities-dependent serial fractioning of diesel exhaust particulate matter (DEP), a prominent source of urban PM 2.5 pollution, was performed. The pro-inflammatory actions of these resultant fractions were then determined using both an intratracheal instillation mouse model and cultured BEAS-2B cells, a human bronchial epithelial cell line., Results: Instillation of the water-insoluble, but not -soluble fraction elicited significant pulmonary inflammatory and acute phase responses, comparable to those induced by instillation of DEP. The water-insoluble fraction was further fractioned using heptane, a polar organic solvent, and instillation of heptane-insoluble, but not -soluble fraction elicited significant pulmonary inflammation and acute phase responses. Furthermore, we showed that DEP and water-insoluble DEP, but not water-soluble DEP, activated pro-inflammatory signaling in cultured BEAS-2B cells, ruling out the possibility that the solubility impacts the in vivo distribution and thus the pulmonary inflammatory response., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Particulate matter 2.5 (PM2.5)-induced pulmonary inflammation has become a public concern in recent years. In which, the activation of the NLRP3/caspase-1 pathway was closely related to the inflammatory response of various diseases. However, the promotion effect of the NLRP3/caspase-1 pathway on PM2.5-induced pulmonary inflammation remains largely unclear. Here, our data showed that PM2.5 exposure caused lung injury in the mice by which inflammatory cell infiltration occurred in lung and alveolar structure disorder. Meanwhile, the exposure of human bronchial epithelial cells (16HBE) to PM2.5 resulted in suppressed cell viability, as well as elevated cell apoptosis. Moreover, a higher level of inflammatory cytokine and activation of the NLRP3/caspase-1 pathway in PM2.5-induced inflammation mice models and 16HBE cells. Mechanistically, pretreatment with MCC950, a NLRP3/caspase-1 pathway inhibitor, prevented PM2.5-induced lung injury, inflammatory response, and the number of inflammatory cells in BALFs, as well as promoted cell viability and decreased inflammatory cytokine secretion. Collectively, our findings indicated that the NLRP3/caspase-1 pathway serves a vital role in the pathological changes of pulmonary inflammation caused by PM2.5 exposure. MCC950 was expected to be the therapeutic target of PM2.5 inhalation mediated inflammatory diseases., (© 2020 The Authors. Environmental Toxicology published by Wiley Periodicals LLC.)

This paper presents a review of the nature, range, and incidences of background pathology findings in the respiratory tract of cynomolgus monkeys and rats. Data were collected from 81 inhalation studies and 133 non-inhalation studies evaluated at 3 geographically distinct contract research organization facilities. The inhalation studies were comprised of 44 different small molecule pharmaceuticals or chemicals which were also analyzed in order to understand the patterns of induced changes within the respiratory tract. The lung was the most frequently affected organ in both species, with increased alveolar macrophages being the most common background and test article-related finding. In the upper respiratory tract (URT), inflammatory cell infiltrates were the most common background findings in the nasal cavity in monkeys. Induced URT findings were more frequent in rats than monkeys, with squamous metaplasia in the larynx, and goblet cell hyperplasia in the nasal cavity being the most common. Overall, the data revealed a limited pattern of response to inhaled molecules in the respiratory tract, with background and test article-related findings often occurring in the same regions. It is hoped that these data will assist in the interpretation of findings in the respiratory tract induced by novel inhaled small molecule entities.

Particulate matter (PM2.5) exposure is reported to have deleterious effects on health. Maternal PM2.5 exposure has been confirmed to damage the growth of somatic cells and enhance the incidence of chronic respiratory diseases in children. Here we aim to investigate the impact of in utero PM2.5 exposure on early birth weight and postnatal lung development. Pregnant Sprague-Dawley rats were administered PM2.5 (0.1, 0.5, 2.5, or 7.5 mg/kg) intraperitoneally every 3 days until birth. Maternal and birth outcomes and somatic growth were monitored. Lungs were collected on PND1 (where PND = postnatal day) and PND28; the lung wet-to-dry weight ratio (W/D) was analyzed, and reactive oxygen species (ROS) levels were measured. Expression of Toll-like receptor 4 (TLR4) and NF-κB were evaluated by Western blotting and quantitative RT-PCR. There were no significant intergroup differences for maternal outcomes; however, offspring exposed in utero to 2.5 and 7.5 mg/kg PM2.5 were significantly smaller in litter weight than the controls. In utero exposure to 2.5 and 7.5 mg/kg PM2.5 led to lower body weight after birth and disrupted lung development during infancy. ROS levels were significantly increased in the 7.5 mg/kg PM2.5 group. PM2.5-treated rats showed upregulated pulmonary expression of TLR4 and NF-κB. Maternal PM2.5 exposure enhances the risk of low birth weight and affects lung alveolar development. The underlying molecular mechanisms may involve TLR4/NF-κB signaling.

Background: As cooking is an essential part of people's daily life, cooking oil fumes (COF) has been recognized as one of the major indoor air pollutant. Mounting epidemiological evidence has indicated that COF exposure is significantly associated with an increased risk of various health effects including lung cancer, but toxicological studies are very limited., Objectives: We conduct a systematic study to provide toxicological evidence of COF exposure on the lungs, to examine the underlying toxicological mechanism, and to suggest intervention measures to mitigate this toxicity., Methods: A total 96 female rats were randomly divided into control groups, COF exposure groups (0.2, 2, 20 mg/kg) and vitamin E protection groups, receiving appropriate treatment for 30 days. First we measured airway hyperresponsiveness (AHR) followed by a lung histological analysis to investigate the toxicological effects of COF. We next analyzed the biomarkers of oxidative stress, inflammation, and apoptosis to examine the underlying toxicological mechanism, and finally we investigated the protective effects of vitamin E against the toxicity of COF., Results: AHR measurement indicated that the airway resistance increased with the COF dose and the lung histological assay showed narrowing of the airway lumen, which provided evidence of the toxicological effects of COF. The biomarkers of oxidative stress (ROS and MDA), pro-inflammation (TNF-α and IL-1β), and apoptosis (NF-κB and Caspase-3) were all significantly increased with COF dose. We observed that above toxicological effects and biomarker levels induced by COF were significantly ameliorated after administration of VE., Conclusion: The toxicity of cooking oil fumes on the lungs is clear from the evidence and mechanism, and can be ameliorated by vitamin E. We suggested that oxidative stress may be primarily responsible for the observed cooking oil fumes-induced toxicity., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Rationale: Physical activity while being exposed to high concentrations of air pollution may lead to greater inhalation of pollutant particles and gases. Thus, owing to features of the built city environment, specific locations where physical activity take place may put individuals at increased risk for harmful inhaled exposures leading to decrements in lung function. Objectives: The objectives were to determine locations throughout an urban landscape where children engage in moderate to vigorous activity (MVA). We hypothesized that outdoor activity would be associated with increased exposure to air pollution and reduced lung function. Methods: Children aged 9-14 years living in New York City (NYC) ( n  = 151) wore global positioning system devices and wrist accelerometers for two 24-hour periods. Time-stamped global positioning system points and accelerometer data were aggregated and mapped using ArcGIS to determine locations where children engaged in MVA. Location-specific particulate matter <2.5 microns and nitrogen dioxide (NO 2 ) was determined based on land use regression models of street-level pollution. Temporal air pollution exposure was determined based on daily concentrations collected at one central site in NYC. Forced expiratory volume in 1 second (FEV 1 ), forced vital capacity (FVC), and forced expiratory flow, midexpiratory phase (FEF 25-75 ) were collected following each 24-hour period. Data were analyzed using multivariable linear regression models to examine associations between MVA time and both lung function and air pollution in separate models. Additionally, a multiplicative interaction term (MVA time × season) was included to test whether the association between MVA time and lung function outcomes varied by warmer versus colder months. Results: On average, children spent less MVA time outdoors (38.2 ± 39.6 min/d) compared with indoors (71.9 ± 74.7 min/d, P  < 0.01), regardless of season. The majority of outdoor MVA occurred along sidewalks and roadbeds (30.2 ± 33.3 min/d, 76.9% of outdoor) where annual average concentrations of NO 2 were relatively high. Interquartile range (IQR) increase in outdoor MVA time (44 min) was associated with higher levels of annual average NO 2 ( P  < 0.01) but not particulate matter <2.5 microns. In warmer months, for IQR increase in outdoor MVA time, children had 1.41% lower FEV 1 /FVC (95% confidence interval [95% CI], -2.46 to -0.36) and 4.40% lower percent predicted FEF 25-75 (95% CI, -8.02 to -0.78). These results persisted even after adjustment for location-specific annual average concentrations of NO 2 . No association was observed between MVA time and lung function in colder months ( P  > 0.05), and a formal test for interaction (MVA time × season) was significant ( P value for interaction = 0.01 and 0.03 for FEV 1 /FVC and FEF 25-75 , respectively). Conclusions: Children in NYC spent less time active outdoors compared with indoors. Outdoor activity was greatest near traffic sources and associated with higher annual average concentrations of NO 2 . In warmer months, outdoor activity was associated with lower lung function, but this association did not appear to be mediated by higher exposure to outdoor pollution during exercise.

Environmental air pollutants pose significant threats to public health, especially the toxicity and diseases caused by the atmospheric fine particulate matters (PM 2.5 ). Since the health risks vary with both the concentrations and compositions of PM 2.5 which are determined by aerosol sources, how are their toxic effects relevant to the pollution level becomes an important issue, such as the haze episodes covering clean and polluted days. With the transition from non-pollution to pollution stage, daily PM 2.5 samples were collected from both the urban and industrial areas of Nanjing city, eastern China, covering a typical haze event in autumn-winter. Their unpropitious effects on human lung epithelial cells (A549) were compared by in vitro toxicity assays and chemical component analysis. Both air levels and cytotoxic effects of PM 2.5 varied with the transition of haze event. Although the concentration of PM 2.5 in air is of course the highest in pollution stage driven by local stable meteorological condition, unit mass of them posed higher toxicity (lower cell viability and higher IL-6) but induced lower cell oxidative (evidences of ROS and NQO1 mRNA expression) and inflammatory cytokine TNF-α responses than those particles during non-pollution stage. These patterns were explained by the metals and water-soluble components decreased with the haze development. Non-soluble particulate carbonaceous aerosol compositions might play a significant role in inducing cytotoxicity. Moreover, the regional pattern of episode pollution weakened the spatial variation within a city scale. Since the haze development intensified both the quantity and toxicity of PM 2.5 in air, the health risks of overall aerosol exposure were synthetically amplified during haze weather, so the increased air particles with higher toxic components from fuel combustion sources should be key targets of pollution control., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Fine particulate matter (PM2.5) airborne pollution increases the risk of chronic respiratory diseases, such as idiopathic pulmonary fibrosis (IPF), which is characterized by non-specific inflammation of the interstitial lung and extensive deposition of collagen fibers. Type 2 alveolar epithelial cells (AEC2s) are alveolar stem cells in the adult lung that contribute to the lung repair process through complex signaling. Our previous studies demonstrated that OGG1, a kind of DNA repair enzyme, have a critical role in protecting cells from oxidative damage and apoptosis induced by PM2.5, but the contribution of OGG1 in proliferation and self-renewal of AEC2s is not known. Here, we constructed OGG1 -/- mice to test the effect and mechanism of OGG1 on PM2.5-induced pulmonary fibrosis and injury in vivo. We detected proliferation and self-renewal of OGG1 overexpression or OGG1 knockout AEC2s after PM2.5 injury by flow cytometry and clone formation. We observed that knockout of OGG1 aggravated pulmonary fibrosis, oxidative stress, and AEC2 cell death in PM2.5-injured mice. In addition, OGG1 is required for the proliferation and renewal of AEC2s after PM2.5 injury. Overexpression of OGG1 promotes the proliferation and self-renewal of AEC2s by inhibiting PM2.5-mediated oxidative stress and NF-κB signaling hyperactivation in vitro. Furthermore, NF-κB inhibitors promoted proliferation and self-renewal of OGG1-deficient AEC2s cells after PM2.5 injury, and attenuated PM2.5-induced pulmonary fibrosis and injury in mice. These data establish OGG1 as a regulator of NF-κB signal that serves to regulate AEC2 cell proliferation and self-renewal, and suggest a mechanism that inhibition of the NF-κB signaling pathway may represent a potential therapeutic strategy for IPF patients with low-expression of OGG1., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Inhalation of multi-walled carbon nanotubes (MWCNTs) poses a potential risk to human health. In order to safeguard workers and consumers, the toxic properties of MWCNTs need to be identified. Functionalization has been shown to either decrease or increase MWCNT-related pulmonary injury, depending on the type of modification. We, therefore, investigated both acute and chronic pulmonary toxicity of a library of MWCNTs derived from a common pristine parent compound (NC7000)., Methods: MWCNTs were thermally or chemically purified and subsequently surface functionalized by carboxylation or amination. To evaluate pulmonary toxicity, male C57BL6 mice were dosed via oropharyngeal aspiration with either 1.6 or 4 mg/kg of each MWCNT type. Mitsui-7 MWCNT was used as a positive control. Necropsy was performed at days 3 and 60 post-exposure to collect bronchoalveolar lavage fluid (BALF) and lungs., Results: At day 3 all MWCNTs increased the number of neutrophils in BALF. Chemical purification had a greater effect on pro-inflammatory cytokines (IL-1β, IL-6, CXCL1) in BALF, while thermal purification had a greater effect on pro-fibrotic cytokines (CCL2, OPN, TGF-β1). At day 60, thermally purified, carboxylated MWCNTs had the strongest effect on lymphocyte numbers in BALF. Thermally purified MWCNTs caused the greatest increase in LDH and total protein in BALF. Furthermore, the thermally purified and carboxyl- or amine-functionalized MWCNTs caused the greatest number of granulomatous lesions in the lungs. The physicochemical characteristics mainly associated with increased toxicity of the thermally purified derivatives were decreased surface defects and decreased amorphous content as indicated by Raman spectroscopy., Conclusions: These data demonstrate that the purification method is an important determinant of lung toxicity induced by carboxyl- and amine-functionalized MWCNTs.

The inhalation of metal (including lead) nanoparticles poses a real health issue to people and animals living in polluted and/or industrial areas. In this study, we exposed mice to lead(II) nitrate nanoparticles [Pb(NO 3 ) 2 NPs], which represent a highly soluble form of lead, by inhalation. We aimed to uncover the effects of their exposure on individual target organs and to reveal potential variability in the lead clearance. We examined (i) lead biodistribution in target organs using laser ablation and inductively coupled plasma mass spectrometry (LA-ICP-MS) and atomic absorption spectrometry (AAS), (ii) lead effect on histopathological changes and immune cells response in secondary target organs and (iii) the clearance ability of target organs. In the lungs and liver, Pb(NO 3 ) 2 NP inhalation induced serious structural changes and their damage was present even after a 5-week clearance period despite the lead having been almost completely eliminated from the tissues. The numbers of macrophages significantly decreased after 11-week Pb(NO 3 ) 2 NP inhalation; conversely, abundance of alpha-smooth muscle actin (α-SMA)-positive cells, which are responsible for augmented collagen production, increased in both tissues. Moreover, the expression of nuclear factor κB ( NF-κB ) and selected cytokines, such as tumor necrosis factor alpha ( TNFα ), transforming growth factor beta 1 ( TGFβ1 ), interleukin 6( IL-6 ), IL-1α and IL-1β , displayed a tissue-specific response to lead exposure. In summary, diminished inflammatory response in tissues after Pb(NO 3 ) 2 NPs inhalation was associated with prolonged negative effect of lead on tissues, as demonstrated by sustained pathological changes in target organs, even after long clearance period.

Background: Fine particulate matter (PM 2.5 ) related mild inflammation, altered autonomic control of cardiovascular function, and changes to cell function have been observed in controlled human exposure studies., Methods: To measure the systemic and cardiopulmonary impacts of low-level PM exposure, we exposed 20 healthy, young volunteers to PM 2.5 , in the form of concentrated ambient particles (mean: 37.8 μg/m 3 , SD 6.5), and filtered air (mean: 2.1 μg/m 3 , SD 2.6). In this double-blind, crossover study the exposure order was randomized. During the 4 h exposure, volunteers (7 females and 13 males) underwent light intensity exercise to regulate ventilation rate. We measured pulmonary, cardiac, and hematologic end points before exposure, 1 h after exposure, and again 20 h after exposure., Results: Low-level PM 2.5 resulted in both pulmonary and extra-pulmonary changes characterized by alterations in systematic inflammation markers, cardiac repolarization, and decreased pulmonary function. A mean increase in PM 2.5 concentration (37.8 μg/m 3 ) significantly increased serum amyloid A (SAA), C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1), 1 h after exposure by 8.7, 9.1, 10.7, and 6.6%, respectively, relative to the filtered air control. SAA remained significantly elevated (34.6%) 20 h after PM 2.5 exposure which was accompanied by a 5.7% decrease in percent neutrophils. Decreased pulmonary function was observed 1 h after exposure through a 0.8 and 1.2% decrease in forced expiratory volume in 1 s (FEV 1 ) and FEV 1 / forced vital capacity (FEV 1 /FVC) respectively. Additionally, sex specific changes were observed in repolarization outcomes following PM 2.5 exposure. In males, P-wave and QRS complex were increased by 15.4 and 5.4% 1 h after exposure., Conclusions: This study is the first controlled human exposure study to demonstrate biological effects in response to exposure to concentrated ambient air PM 2.5 particles at levels near the PM 2.5 US NAAQS standard., Clinical Trial Registration Information: clinicaltrials.gov ; Identifier: NCT03232086 . The study was registered retrospectively on July 25, 2017, prior to final data collection on October 25, 2017 and data analysis.

Epidemiological studies have found strong associations between air pollution and respiratory effects including development and/or exacerbation of asthma and chronic obstructive pulmonary disease (COPD) as well as increased occurrence of respiratory infections and lung cancer. It has become increasingly clear that also polycyclic aromatic hydrocarbons (PAHs) may affect processes linked to non-malignant diseases in the airways. The aim of the present paper was to review epidemiological studies on associations between gas phase and particle-bound PAHs in ambient air and non-malignant respiratory diseases or closely related physiological processes, to assess whether PAH-exposure may explain some of the effects associated with air pollution. Based on experimental in vivo and in vitro studies, we also explore possible mechanisms for how different PAHs may contribute to such events. Epidemiological studies show strongest evidence for an association between PAHs and asthma development and respiratory function in children. This is supported by studies on prenatal and postnatal exposure. Exposure to PAHs in adults seems to be linked to respiratory functions, exacerbation of asthma and increased morbidity/mortality of obstructive lung diseases. However, available studies are few and weak. Notably, the PAHs measured in plasma/urine also represent other exposure routes than inhalation. Furthermore, the role of PAHs measured in air is difficult to disentangle from that of other air pollution components originating from combustion processes. Experimental studies show that PAHs may trigger various processes linked to non-malignant respiratory diseases. Physiological- and pathological responses include redox imbalance, oxidative stress, inflammation both from the innate and adaptive immune systems, smooth muscle constriction, epithelial- and endothelial dysfunction and dysregulated lung development. Such biological responses may at the molecular level be initiated by PAH-binding to the aryl hydrocarbon receptor (AhR), but possibly also through interactions with beta-adrenergic receptors. In addition, reactive PAH metabolites or reactive oxygen species (ROS) may interfere directly with ion transporters and enzymes involved in signal transduction. Overall, the reviewed literature shows that respiratory effects of PAH-exposure in ambient air may extend beyond lung cancer. The relative importance of the specific PAHs ability to induce disease may differ between the biological endpoint in question.

Objective To observe the effect of acute severe air pollution exposure on cytokines and chemokines in lung tissues of rats and explore its significance. Methods During the period of severe air pollution in Beijing from December 17 to 22, 2016, rats were exposed to air pollution for 6 days, and then sacrificed on the 7th day. Lung tissues were taken and their histological changes were observed by HE staining. The levels of 22 cytokines/chemokines in the lung tissue homogenate supernatant were detected by liquid chip method. Results Compared with the control group, the lung tissues of the rats in the air pollution exposure group were characterized by widened alveolar septum, inflammatory cell infiltration and vascular bleeding. Chemokines eotaxin, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-2 (MIP-2), regulated on activation, normal T cell expressed and secreted factor (RANTES), and proinflammatory cytokines interleukin 1β (IL-1β), IL-17, IL-18, tumor necrosis factor α (TNF-α) in the supernatant of lung homogenate of rats in the air pollution exposure group significantly increased. But anti-inflammatory IL-10 significantly decreased. Th1 cytokines IL-2 and interferon-γ (IFN-γ) did not change, and Th2 cytokines IL-5 increased by 1.65 times and IL-10 decreased by 0.82 times. Conclusion Acute severe air pollution exposure can lead to inflammatory response in lung tissues of rats. The secretion of chemokines eotaxin, MCP-1, MIP-2, RANTES and proinflammatory cytokines IL-1β, IL-17, IL-18, TNF-α are promoted in this process. The infiltrated T cells in lung tissues are dominated by Th2 cells.

The presence of bronchus-associated lymphoid tissue (BALT) and its size in humans largely depends upon age. It is detected in 35% of children less than 2 years of age, but absent in the healthy adult lung. Environmental gases or allergens may have an effect on the number of BALT. Lungs of rhesus macaque monkeys were screened by histology for the presence, size, and location of BALT after exposure to filtered air for 2, 6, 12, or 36 months or 12 and 36 months to ozone or 2, 12, or 36 months of house dust mite or a combination of ozone and house dust mite for 12 months. In the lungs of monkeys housed in filtered air for 2 months, no BALT was identified. After 6, 12, or 36 months, the number of BALT showed a significantly increased correlation with age in monkeys housed in filtered air. After 2 months of episodic house dust mite (HDM) exposure, no BALT was found. Monkeys exposed to HDM or HDM + ozone did not show a significant increase in BALT compared to monkeys housed in filtered air. However, monkeys exposed to ozone alone did show significant increases in BALT compared to all other groups. In particular, there were frequent accumulations of lymphocytes in the periarterial space of ozone exposed animals. In conclusion, BALT in rhesus monkeys housed under filtered air conditions is age-dependent. BALT significantly increased in monkeys exposed to ozone in comparison with monkeys exposed to HDM., (© 2020 American Association for Anatomy.)

Epidemiological studies have shown that particulate matter with an aerodynamic diameter less than 2.5 μm (PM 2.5 ) is closely associated with human health issues, especially pulmonary diseases such as chronic obstructive pulmonary disease (COPD), asthma and lung cancer. In this study, particles were characterized by scanning electron microscopy (SEM), microbeam energy-dispersive X-ray spectroscopy (EDS), inductively coupled plasma mass spectrometry (ICP-MS) and high-performance liquid chromatography (HPLC). A rat model of PM 2.5 exposure was established by nonsurgical intratracheal instillation, and the effects of biochanin A (BCA) treatment were examined. BCA showed a protective effect; it reduced PM 2.5 -induced apoptosis and the production of proinflammatory factors, such as tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), interleukin-6 (IL-6), and the chemokine interleukin-8 (IL-8), as measured using ELISA. These effects were accompanied by increases in the levels of antioxidant enzymes and decreases in the levels of malondialdehyde (MDA), lactate dehydrogenase (LDH) and alkaline phosphatase (AKP). Furthermore, isobaric tag for relative and absolute quantitation (iTRAQ)-based analytical techniques and bioinformatics tools were used to identify putative biomarkers, including XRCC1, MP2K5, IGJ, and F1LQ12, and the results were verified by Western blot analysis. In conclusion, our findings have scientific significance for the application of flavonoids in preventive and therapeutic strategies for PM 2.5 -associated pulmonary diseases and for the promotion of human health., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Black carbon (BC) is a product of incomplete combustion of fossil fuels and vegetation. The compelling evidence has demonstrated that it has a close relationship with several respiratory and cardiovascular diseases. BC provides the reactive sites and surfaces to absorb various chemicals, such as polycyclic aromatic hydrocarbons (PAH). Naphthoquinone is a typical PAHs which was found in particulate matter (PM) and 1,4NQ-BC owned high oxidative potential and cytotoxicity. IL-33 is an alarmin which increases innate immunity through Th2 responses. It was reported that IL-33 was a potent inducer of pro-inflammatory cytokines, like IL-6. In our previous study, it was revealed that 1,4NQ-BC instilled intratracheally to mice could trigger the lung inflammation and stimulate the secretion of IL-33 in lung tissue. We found that IL-33 could induce inflammation in lung itself. When the macrophages were eliminated, the secretion of IL-33 was reduced and the pathological damage in the lung was relieved after exposure to 1,4NQ-BC. Both MAPK and PI3K/AKT signal pathways were involved in the process of IL-33 secretion and the lung inflammation induced by 1,4NQ-BC. The findings herein support the notion that after exposure to 1,4NQ-BC, the increased secretion of IL-33 was mainly derived from macrophages through both MAPK and PI3K/AKT signal pathways., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)