Safety of Prolonged Exposure of Human Skin to Aqueous Ozone in a Test Hand Hygiene Model.

AIMS: This research assessed the safety of aqueous ozone (AO) on human skin after multiple exposures for up to 40 hours. METHODS AND RESULTS: Full thickness recombinant human skin (EpiDerm FT, EFT-400) was exposed to AO for 7 seconds per minute for the first 6 minutes of each hour, repeated hourly over four time periods (4, 10, 20 and 40 hours). An MTT assay assessed viability of skin cells after exposure, compared to incubator control, negative control and vehicle control (distilled water). No significant difference in tissue viability was found between the AO condition and any of the control conditions through 20 hours of exposures. At 40 hours of exposure, tissue viability was lower in the AO group when compared with negative control (p = 0.030) but not the other controls. CONCLUSIONS: The current study supports further consideration of repeated application of AO on human skin, such as for hand hygiene. IMPACT STATEMENT: The present research is the first well-controlled in vitro study assessing the cytotoxicity of repeated exposures of AO on a full-thickness human skin model. This information helps to inform the evaluation of AO as a potential alternative for hand and wound antisepsis.

Analysis of human health effects under ozone exposure in the oasis area of Hetao Plain.

This article, based on OMI data products, utilizes spatial distribution, ozone-sensitive control areas, Pearson correlation methods, and the Ben-MAP model to study the changes in ozone column concentration from 2018 to 2022, along with the influencing factors and the health of populations exposed to ozone. The findings suggest a spatial variation in the ozone column concentration within the study area, with an increasing trend observed from west to east and from south to north. Over time, the ozone column concentration exhibits an initial increase followed by a subsequent decrease, with the peak concentration observed in 2019 at 37.45 DU and the nadir recorded in 2022 at 33.10 DU. The monthly mean distribution exhibits an inverted V-shaped pattern during the warm season from April to September, with a peak in July (46.71 DU) and a trough in April (35.29 DU). The Hetao Plain Oasis area is primarily a NOx control area in sensitive control areas. The concentrations of O3 and precursor HCHO exhibited significant positive correlations with vegetation index and air temperature, while showing significant negative correlations with wind speed and air pressure. The precursor NO2, in contrast, exhibited a significant negative correlation with both the vegetation index and relative humidity. Based on the ground-based monitoring sites and analysis of human health benefits, the study area witnessed 1944.45 deaths attributed to warm season O3 exposure in 2018, with a subsequent reduction in premature deaths by 149.7, 588.2, and 231.75 for the years 2019 to 2021 respectively when compared to the baseline year. In 2021, the observed decrease in warm-season O3 concentration within that region compared to 2018 resulted in a significant reduction, leading to the prevention of 126 premature deaths.

A toxicological perspective on climate change and the exposome.

Climate change is accompanied by changes in the exposome, including increased heat, ground-level ozone, and other air pollutants, infectious agents, pollens, and psychosocial stress. These exposures alter the internal component of the exposome and account for some of the health effects of climate change. The adverse outcome pathways describe biological events leading to an unfavorable health outcome. In this perspective study, I propose to use this toxicological framework to better describe the biological steps linking a stressor associated with climate change to an adverse outcome. Such a framework also allows for better identification of possible interactions between stressors related to climate change and others, such as chemical pollution. More generally, I call for the incorporation of climate change as part of the exposome and for improved identification of the biological pathways involved in its health effects.

Altered metabolome and microbiome associated with compromised intestinal barrier induced hepatic lipid metabolic disorder in mice after subacute and subchronic ozone exposure.

Exposure to ozone has been associated with metabolic disorders in humans, but the underlying mechanism remains unclear. In this study, the role of the gut-liver axis and the potential mechanism behind the metabolic disorder were investigated by histological examination, microbiome and metabolome approaches in mice during the subacute (4-week) and subchronic (12-week) exposure to 0.5 ppm and 2.5 ppm ozone. Ozone exposure resulted in slowed weight gain and reduced hepatic lipid contents in a dose-dependent manner. After exposure to ozone, the number of intestinal goblet cells decreased, while the number of tuft cells increased. Tight junction protein zonula occludens-1 (ZO-1) was significantly downregulated, and the apoptosis of epithelial cells increased with compensatory proliferation, indicating a compromised chemical and physical layer of the intestinal barrier. The hepatic and cecal metabolic profiles were altered, primarily related to lipid metabolism and oxidative stress. The abundance of Muribaculaceae increased dose-dependently in both colon and cecum, and was associated with the decrease of metabolites such as bile acids, betaine, and L-carnitine, which subsequently disrupted the intestinal barrier and lipid metabolism. Overall, this study found that subacute and subchronic exposure to ozone induced metabolic disorder via disturbing the gut-liver axis, especially the intestinal barrier. These findings provide new mechanistic understanding of the health risks associated with environmental ozone exposure and other oxidative stressors.

Ultra-sensitive analysis of exhaled biomarkers in ozone-exposed mice via PAI-TOFMS assisted with machine learning algorithms.

Ground-level ozone ranks sixth among common air pollutants. It worsens lung diseases like asthma, emphysema, and chronic bronchitis. Despite recent attention from researchers, the link between exhaled breath and ozone-induced injury remains poorly understood. This study aimed to identify novel exhaled biomarkers in ozone-exposed mice using ultra-sensitive photoinduced associative ionization time-of-flight mass spectrometry and machine learning. Distinct ion peaks for acetonitrile (m/z 42, 60, and 78), butyronitrile (m/z 70, 88, and 106), and hydrogen sulfide (m/z 35) were detected. Integration of tissue characteristics, oxidative stress-related mRNA expression, and exhaled breath condensate free-radical analysis enabled a comprehensive exploration of the relationship between ozone-induced biological responses and potential biomarkers. Under similar exposure levels, C57BL/6 mice exhibited pulmonary injury characterized by significant inflammation, oxidative stress, and cardiac damage. Notably, C57BL/6 mice showed free radical signals, indicating a distinct susceptibility profile. Immunodeficient non-obese diabetic Prkdc-/-/Il2rg-/- (NPI) mice exhibited minimal biological responses to pulmonary injury, with little impact on the heart. These findings suggest a divergence in ozone-induced damage pathways in the two mouse types, leading to alterations in exhaled biomarkers. Integrating biomarker discovery with comprehensive biopathological analysis forms a robust foundation for targeted interventions to manage health risks posed by ozone exposure.

Growth, ultrastructural and physiological characteristics of Abelmoschus cytotypes under elevated ozone stress: a study on ploidy-specific responses.

Tropospheric ozone (O3 ) is a significant abiotic stressor whose rising concentration negatively influences plant growth. Studies related to the differential response of Abelmoschus cytotypes to elevated O3 treatment are scarce and need further exploration to recognise the role of polyploidisation in stress tolerance. In this study, we analysed the changes in growth pattern, ultrastructure, physiology and foliar protein profile occurring under O3 stress in Abelmoschus moschatus (monoploid), Abelmoschus esculentus (diploid) and Abelmoschus caillei (triploid). Our findings showed that higher stomatal conductance in A. moschatus triggered higher O3 intake, causing damage to stomatal cells and photosynthetic pigments. Additionally, it caused a reduction in photosynthetic rates, leading to reduced plant growth, total biomass and economic yield. This O3 -induced toxicity was less in diploid and triploid cytotypes of Abelmoschus . Protein profiling by sodium dodecyl sulpate-polyacrylamide gel electrophoresis showed a significant decrease in the commonly found RuBisCO larger and smaller subunits. The decrease was more prominent in monoploid compared to diploid and triploid. This study provides crucial data for research that aim to enhance plant ability to withstand O3 induced oxidative stress. Our findings may help in developing a tolerant variety through plant breeding techniques, which will be economically more advantageous in reaching the objective of sustainable production at the high O3 levels projected under a climate change scenario.

In Vitro Assessment of Ozone-Treated Deoxynivalenol by Measuring Cytotoxicity and Wheat Quality.

Deoxynivalenol (DON), a trichothecene mycotoxin, could lead to cytotoxicity in both animal bodies and plant seed cells. Ozone degradation technology has been applied to DON control. However, the safety and quality of the contaminated grain after DON degradation are largely obscured. In this work, we evaluated the cytotoxicity of ozone-treated DON through seed germination experiments and cytotoxicity tests. Cell experiments showed that the inhibition rate of HepG2 viability gradually increased within the concentrations of 1-10 mg/L of DON, alongside which an IC50 (half maximal inhibitory concentration) of 9.1 mg/L was determined. In contrast, degrading DON had no significant inhibitory effect on cell growth. Moreover, a 1-10 mg/L concentration of DON increased production of a large amount of reactive oxygen radicals in HepG2, with obvious fluorescence color development. However, fluorescence intensity decreased after DON degradation. Further, DON at a concentration of >1 mg/L significantly inhibited the germination of mung bean seeds, whereas no significant inhibition of their germination or growth were observed if DON degraded. Changes in total protein content, fatty acid value, and starch content were insignificant in wheat samples suffering ozone degradation, compared to the untreated group. Lastly, the ozone-treated wheat samples exhibited higher tenacity and whiteness. Together, our study indicated that the toxicity of DON-contaminated wheat was significantly reduced after ozone degradation.

Untangling the role of leaf age specific osmoprotectant and antioxidant responses of two poplar clones under increasing ozone concentrations.

Plants possess different degrees of tolerance to abiotic stress, which can mitigate the detrimental effect of environmental inputs affecting carbon balance. Less is known about the functions of osmoprotectants in scavenging of reactive oxygen species (ROS), generated at different sites depending on leaf age. This study aimed to clarify the osmotic adjustments adopted by old and young leaves of Oxford and I-214 poplar clones [differing in ozone (O3) sensitivity] to cope with three levels of O3 [ambient (AA), and two elevated O3 levels]. In both clones, the impact of intermediate O3 concentrations (1.5 × AA) on ROS production appeared to be leaf age-specific, given the accumulation of hydrogen peroxide (H2O2) observed only in old leaves of the Oxford plants and in young leaves of the I-214 ones (2- fold higher than AA and +79%, respectively). The induction of an oxidative burst was associated with membrane injury, indicating an inadequate response of the antioxidative systems [decrease of lutein and ß-carotene (-37 and -85% in the old leaves of the Oxford plants), accumulation of proline and tocopherols (+60 and +12% in the young leaves of the I-214 ones)]. Intermediate O3 concentrations reacted with unsaturated lipids of the plasma membrane in old and young leaves of the Oxford plants, leading to an increase of malondialdehyde by-products (more than 2- fold higher than AA), while no effect was recorded for I-214. The impact of the highest O3 concentrations (2.0 × AA) on ROS production did not appear clone-specific, which may react with cell wall components by leading to oxidative pressure. Outcomes demonstrated the ability of young leaves of I-214 plants in contain O3 phytotoxic effects.

Associations between long-term ozone exposure and small airways function in Chinese young adults: a longitudinal cohort study.

BACKGROUND: Increasing evidence is appearing that ozone has adverse effects on health. However, the association between long-term ozone exposure and lung function is still inconclusive. OBJECTIVES: To investigate the associations between long-term exposure to ozone and lung function in Chinese young adults. METHODS: We conducted a prospective cohort study among 1594 college students with a mean age of 19.2 years at baseline in Shandong, China from September 2020 to September 2021. Lung function indicators were measured in September 2020 and September 2021, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), forced expiratory flow at the 25th, 50th, and 75th percentile of the FVC (FEF25, FEF50, and FEF75) and mean flow rate between 25% and 75% of the FVC (FEF25-75) were measured. Daily 10 km×10 km ozone concentrations come from a well-validated data-fusion approach. The time-weighted average concentrations in 12 months before the lung function test were defined as the long-term ozone exposure. The associations between long-term ozone exposure and lung function indicators in Chinese young adults were investigated using a linear mixed effects model, followed by stratified analyses regarding sex, BMI and history of respiratory diseases. RESULTS: Each interquartile range (IQR) (8.9 µg/m3) increase in long-term ozone exposure were associated with a -204.3 (95% confidence interval (CI): -361.6, -47.0) ml/s, -146.3 (95% CI: -264.1, -28.4) ml/s, and - 132.8 (95% CI: -239.2, -26.4) ml/s change in FEF25, FEF50, and FEF25-75, respectively. Stronger adverse associations were found in female participants or those with BMI ≥ 24 kg/m2 and history of respiratory diseases. CONCLUSION: Long-term exposure to ambient ozone is associated with impaired small airway indicators in Chinese young adults. Females, participants with BMI ≥ 24 kg/m2 and a history of respiratory disease have stronger associations.

Lung injuries induced by ozone exposure in female mice: Potential roles of the gut and lung microbes.

Ozone (O3) is one of the most harmful pollutants affecting health. However, the potential effects of O3 exposure on microbes in the gut-lung axis related to lung injuries remain elusive. In this study, female mice were exposed to 0-, 0.5- and 1-ppm O3 for 28 days, followed by routine blood tests, lung function tests and histopathological examination of the colon, nasal cavity and lung. Mouse faeces and lungs were collected for 16s rRNA sequencing to assess the overall microbiological profile and screen for key differential enriched microbes (DEMs). The key DEMs in faecal samples were Butyricimonas, Rikenellaceae RC9 and Escherichia-Shigella, whereas those in lung samples were DNF00809, Fluviicola, Bryobacter, Family XII AD3011 group, Sharpea, MND1 and unclassified Phycisphaeraceae. After a search in microbe-disease databases, these key DEMs were found to be associated with lung diseases such as lung neoplasms, cystic fibrosis, pneumonia, chronic obstructive pulmonary disease, respiratory distress syndrome and bronchiectasis. Subsequently, we used transcriptomic data from Gene Expression Omnibus (GEO) with exposure conditions similar to those in this study to cross-reference with Comparative Toxicogenomic Database (CTD). Il-6 and Ccl2 were identified as the key causative genes and were validated. The findings of this study suggest that exposure to O3 leads to significant changes in the microbial composition of the gut and lungs. These changes are associated with increased levels of inflammatory factors in the lungs and impaired lung function, resulting in an increased risk of lung disease. Altogether, this study provides novel insights into the role of microbes present in the gut-lung axis in O3 exposure-induced lung injury.

U-shaped relationship between ozone exposure and preterm birth risk associated with preconception telomere length.

There are conflicting findings regarding the association of ozone (O3) exposure with preterm birth (PTB) occurrence. In the present study, two cohorts were combined to explore the relationship between maternal O3 exposure during pregnancy and PTB risk, and analyze the underlying mechanisms of this relationship in terms of alterations in the preconception telomere length. Cohort 1 included mothers who participated in the National Free Preconception Health Examination Project in Henan Province from 2014 to 2018 along with their newborns (n = 1,066,696). Cohort 2 comprised mothers who conceived between 2016 and 2018 and their newborns (n = 1871) from six areas in Henan Province. The telomere length was assessed in the peripheral blood of mothers at the preconception stage. Data on air pollutant concentrations were collected from environmental monitoring stations and individual exposures were assessed using an inverse distance-weighted model. O3 concentrations (100.60 ± 14.13 µg/m3) were lower in Cohort 1 than in Cohort 2 (114.09 ± 15.17 µg/m3). Linear analyses showed that PTB risk decreased with increasing O3 exposure concentrations in Cohort 1 but increased with increasing O3 exposure concentrations in Cohort 2. Nonlinear analyses revealed that PTB risk tended to decrease and then increase with increasing O3 exposure concentrations in both cohorts. Besides, PTB risk was reduced by 88% for each-unit increase in telomere length in those exposed to moderate O3 concentrations (92.4-123.7 µg/m3, P < 0.05). While no significant association was observed between telomere length and PTB at extreme O3 concentration exposure during entire pregnancy (<92.4 or >123.7 µg/m3, P > 0.05) in Cohort 2. These findings reveal a nonlinear (U-shaped) relationship between O3 exposure and PTB risk. Furthermore, telomere with elevated length was associated with decreased risk of PTB only when exposed to moderate concentrations of O3, but not when exposed to extreme concentrations of O3 during pregnancy.

Long-term trajectory of ozone impact on maize and soybean yields in the United States: A 40-year spatial-temporal analysis.

Understanding the long-term change trends of ozone-induced yield losses is crucial for formulating strategies to alleviate ozone damaging effects, aiming towards achieving the Zero Hunger Sustainable Development Goal. Despite a wealth of experimental research indicating that ozone's influence on agricultural production exhibits marked fluctuations and differs significantly across various geographical locations, previous studies using global statistical models often failed to capture this spatial-temporal variability, leading to uncertainties in ozone impact estimation. To address this issue, we conducted a comprehensive assessment of the spatial-temporal variability of ozone impacts on maize and soybean yields in the United States (1981-2021) using a geographically and temporally weighted regression (GTWR) model. Our results revealed that over the past four decades, ozone pollution has led to average yield losses of -3.5% for maize and -6.1% for soybean, translating into an annual economic loss of approximately $2.6 billion. Interestingly, despite an overall downward trend in ozone impacts on crop yields following the implementation of stringent ozone emission control measures in 1997, our study identified distinct peaks of abnormally high yield reduction rates in drought years. Significant spatial heterogeneity was detected in ozone impacts across the study area, with ozone damage hotspots located in the Southeast Region and the Mississippi River Basin for maize and soybean, respectively. Furthermore, we discovered that hydrothermal factors modulate crop responses to ozone, with maize showing an inverted U-shaped yield loss trend with temperature increases, while soybean demonstrated an upward trend. Both crops experienced amplified ozone-induced yield losses with rising precipitation. Overall, our study highlights the necessity of incorporating spatiotemporal variability into assessments of crop yield losses attributable to ozone pollution. The insights garnered from our findings can contribute to the formulation of region-specific pollutant emission policies, based on the distinct profiles of ozone-induced agricultural damage across different regions.

Drought mitigates the adverse effects of O3 on plant photosynthesis rather than growth: A global meta-analysis considering plant functional types.

Tropospheric ozone (O3 ) is a phytotoxic air pollutant adversely affecting plant growth. High O3 exposures are often concurrent with summer drought. The effects of both stresses on plants are complex, and their interactions are not yet well understood. Here, we investigate whether drought can mitigate the negative effects of O3 on plant physiology and growth based on a meta-analysis. We found that drought mitigated the negative effects of O3 on plant photosynthesis, but the modification of the O3 effect on the whole-plant biomass by drought was not significant. This is explained by a compensatory response of water-deficient plants that leads to increased metabolic costs. Relative to water control condition, reduced water treatment decreased the effects of O3 on photosynthetic traits, and leaf and root biomass in deciduous broadleaf species, while all traits in evergreen coniferous species showed no significant response. This suggested that the mitigating effects of drought on the negative impacts of O3 on the deciduous broadleaf species were more extensive than on the evergreen coniferous ones. Therefore, to avoid over- or underestimations when assessing the impact of O3 on vegetation growth, soil moisture should be considered. These results contribute to a better understanding of terrestrial ecosystem responses under global change.

Applicability of evaluation metrics/schemes for human health burden attributable to regional ozone pollution: A case study in the Guangdong-Hong Kong-Macao Greater Bay Area (GBA), South China.

This is a study to identify the applicable/preferable short- and long-term metrics/schemes to evaluate the premature mortality attributable to the ozone pollution in the Guangdong-Hong Kong-Macao Greater Bay Area (GBA), one of the most representative populous ozone pollution regions in China, by comprehensively accounting the uncertainty sources. The discrepancy between the observation and the CAQRA reanalysis datasets (2013-2019) was investigated in terms of the concentration variation pattern, which determines the exposure metric change. A set of domestic short-term C-R coefficients for the all-age population were integrated using the meta-analysis respectively corresponding to the metrics of MDA1, MDA8, and Daily average. The dataset-based deviations of the short-term attributable factors (AFs) and their corresponding premature mortalities were respectively about 16.9 ± 13.3 % and <5 % based on MDA8, much smaller than other two metrics; and the MDA8-based evaluation results were the most sensitive to the deteriorative ozone pollution, with the maximum upward trends of 0.095-0.129 %/year. Accordingly, MDA8 was recognized as the most applicable short-term metric. For the long-term exposure, the domestic summer metric SMDA8 could not exactly represent the peak-season ozone maximum level in the GBA, with the deviation from 6MMDA8 as much as 30 %. By considering the ability of metric to represent the peak-season ozone, the relatively smaller dataset-based discrepancies of AFs (6MMDA8-WHO2021: 23.3 ± 16.9 %, AMDA8-T2016: 20.7 ± 15.8 %) and the attributable premature mortalities (6MMDA8-WHO2021: 5 %, AMDA8-T2016: 8 %), and the higher sensitivity of the evaluation results to the deteriorative ozone pollution (6MMDA8-WHO2021: 0.13 %;year, p = 0.01; AMDA8-T2016: 0.15 %/year, p = 0.03), the schemes of 6MMDA8-WHO2021 and AMDA8-T2016 were recognized relatively more preferable for the adult (≥25-year) long-term evaluation. Based on the recognized metric/schemes, the central and the eastern PRE areas of higher NO2 level in the GBA were experiencing the highest health burdens from 2013 to 2019.

Long-term ozone exposure and lung function in middle childhood.

BACKGROUND: Ozone (O3) exposure interrupts normal lung development in animal models. Epidemiologic evidence further suggests impairment with higher long-term O3 exposure across early and middle childhood, although study findings to date are mixed and few have investigated vulnerable subgroups. METHODS: Participants from the CANDLE study, a pregnancy cohort in Shelby County, TN, in the ECHO-PATHWAYS Consortium, were included if children were born at gestational age >32 weeks, completed a spirometry exam at age 8-9, and had a valid residential history from birth to age 8. We estimated lifetime average ambient O3 exposure based on each child's residential history from birth to age 8, using a validated fine-resolution spatiotemporal model. Spirometry was performed at the age 8-9 year study visit to assess Forced Expiratory Volume in the first second (FEV1) and Forced Vital Capacity (FVC) as primary outcomes; z-scores were calculated using sex-and-age-specific reference equations. Linear regression with robust variance estimators was used to examine associations between O3 exposure and continuous lung function z-scores, adjusted for child, sociodemographic, and home environmental factors. Potential susceptible subgroups were explored using a product term in the regression model to assess effect modification by child sex, history of bronchiolitis in infancy, and allergic sensitization. RESULTS: In our sample (n = 648), O3 exposure averaged from birth to age 8 was modest (mean 26.6 [SD 1.1] ppb). No adverse associations between long-term postnatal O3 exposure were observed with either FEV1 (ß = 0.12, 95% CI: -0.04, 0.29) or FVC (ß = 0.03, 95% CI: -0.13, 0.19). No effect modification by child sex, history of bronchiolitis in infancy, or allergic sensitization was detected for associations with 8-year average O3. CONCLUSIONS: In this sample with low O3 concentrations, we did not observe adverse associations between O3 exposures averaged from birth to age 8 and lung function in middle childhood.

The impact of short-term exposures to ambient NO2, O3, and their combined oxidative potential on daily mortality.

It is widely recognized that air pollution exerts substantial detrimental effects in human health and the economy. The potential for harm is closely linked to the concentrations of pollutants like nitrogen dioxide (NO2) and ozone (O3), as well as their collective oxidative potential (OX). Yet, due to the challenges of directly monitoring OX as an independent factor and the influences of different substances' varying ability to contain or convey OX, uncertainties persist regarding its actual impact. To provide further evidence to the association between short-term exposures to NO2, O3, and OX and mortality, this study conducted multi-county time-series analyses with over-dispersed generalized additive models and random-effects meta-analyses to estimate the mortality data from 2014 to 2020 in Jiangsu, China. The findings reveal that short-term exposures to these pollutants are linked to increased risks of all-cause, cardiovascular, and respiratory mortality, where NO2 demonstrates 2.11% (95% confidence interval: 1.79%, 2.42%), 2.28% (1.91%, 2.66%), and 2.91% (2.13%, 3.69%) respectively per every 10 ppb increase in concentration, and the effect of O3 is 1.11% (0.98%, 1.24%), 1.39% (1.19%, 1.59%), and 1.82% (1.39%, 2.26%), and OX is 1.77% (1.58%, 1.97%), 2.19% (1.90%, 2.48%), and 2.90% (2.29%, 3.52%). Notably, women and individuals aged over 75 years exhibit higher susceptibility to these pollutants, with NO2 showing a greater impact, especially during the warm seasons. The elevated mortality rates associated with NO2, O3, and OX underscore the significance of addressing air pollution as a pressing public health issue, especially in controlling NO2 and O3 together. Further research is needed to explore the underlying mechanisms and possible influential factors of these effects.

Ambient ozone pollution impairs glucose homeostasis and contributes to renal function decline: Population-based evidence.

Particulate matter pollution could increase the risk of kidney disease, while evidence for ozone exposure is less well-established. Here, we aimed to evaluate the effect of ozone pollution on renal function and explore mechanisms. We first conducted a cross-sectional study based on Wuhan Chronic Disease Cohort Study baseline information. We recruited 2699 eligible participants, estimated their residential ozone concentrations, collected fasting peripheral blood samples for biochemical analysis and calculated the estimated glomerular filtration rate (eGFR). The linear regression model was applied to evaluate the long-term association between ozone pollution and eGFR. Then, we recruited another 70 volunteers as a panel with 8 rounds follow-up visits. We calculated the eGFR and measured fasting blood glucose and lipid levels. The linear mixed-effect model along with mediation analysis were performed to confirm the short-term association and explore potential mechanisms, respectively. For the long-term association, a 10.95 µg/m3 increment of 3-year ozone exposure was associated with 2.96 mL/min/1.73 m2 decrease in eGFR (95%CI: -4.85, -1.06). Furthermore, the drinkers exhibited a pronounced declination of eGFR (-7.46 mL/min/1.73 m2, 95%CI: -11.84, -3.08) compared to non-drinkers in relation to ozone exposure. Additionally, a 19.02 µg/m3 increase in 3-day ozone concentrations was related to 2.51 mL/min/1.73 m2 decrease in eGFR (95%CI: -3.78, -1.26). Hyperglycemia and insulin resistance mediated 12.2% and 16.5% of the aforementioned association, respectively. Our findings indicated that higher ozone pollution could affect renal function, and the hyperglycemia and insulin resistance linked to ozone might be the underlying mechanisms.

Long-term ambient ozone, omega-3 fatty acid, genetic susceptibility, and risk of mental disorders among middle-aged and older adults in UK biobank.

BACKGROUND: Evidence linking ozone to depression and anxiety disorders remains sparse and results are heterogeneous. It remains unknown whether omega-3 fatty acid, or genetic susceptibility of mental disorders modify the impacts of ozone. The aim is to assess the associations of ambient ozone with depression and anxiety, and further explore the potential modification effects of omega-3 fatty acid and genetic susceptibility. METHODS: In total of 257,534 participants were enrolled from 2006 to 2010 and followed up to 2016. Depression and anxiety were assessed using mental health questionnaires, primary care records and hospital admission records. The annual average concentrations of ozone were calculated and linked to individuals by home address. Dietary intake and plasma concentration were selected to reflect levels of omega-3 fatty acid. Polygenetic risk scores were selected to reflect genetic susceptibility. We examined the associations of ozone and incident mental disorders, and potential modification of omega-3 fatty acid and genetic susceptibility. RESULTS: Incidences of depression (N = 6957) and anxiety (N = 6944) was associated with increase of ozone. Higher levels of omega-3 fatty acid might attenuate the ozone related depression risk. However, the modification effects of genetic susceptibility were not found. CONCLUSIONS: Long-term exposure to ambient ozone increase the risk of mental disorders among the middle aged and older adults, and omega-3 fatty acid could reduce the adverse effects of ozone on mental health. Higher intake of omega-3 fatty acid is a potential strategy to prevent the risks caused by ozone on public mental health.

Long-term ozone exposure and all-cause mortality: Cohort evidence in China and global heterogeneity by region.

BACKGROUND: Cohort evidence linking long-term ozone (O3) exposure to mortality remained largely mixed worldwide and was extensively deficient in densely-populated Asia. This study aimed to assess the long-term effects of O3 exposure on all-cause mortality among Chinese adults, as well as to examine potential regional heterogeneity across the globe. METHODS: A national dynamic cohort of 42153 adults aged 16+ years were recruited from 25 provinces across Chinese mainland and followed up during 2010-2018. Annual warm-season (April-September) O3 and year-round co-pollutants (i.e., nitrogen dioxide [NO2] and fine particulate matter [PM2.5]) were simulated through validated spatial-temporal prediction models and were assigned to each enrollee in each calendar year. Cox proportional hazards models with time-varying exposures were employed to assess the O3-mortality association. Concentration-response (C-R) curves were fitted by natural cubic spline function to investigate the potential nonlinear association. Both single-pollutant model and co-pollutant models additionally adjusting for PM2.5 and/or NO2 were employed to examine the robustness of the estimated association. The random-effect meta-analysis was adopted to pool effect estimates from the current and prior population-based cohorts (n = 29), and pooled C-R curves were fitted through the meta-smoothing approach by regions. RESULTS: The study population comprised of 42153 participants who contributed 258921.5 person-years at risk (median 6.4 years), of whom 2382 death events occurred during study period. Participants were exposed to an annual average of 51.4 ppb (range: 22.7-74.4 ppb) of warm-season O3 concentration. In the single-pollutant model, a significantly increased hazard ratio (HR) of 1.098 (95% confidence interval [CI]: 1.023-1.179) was associated with a 10-ppb rise in O3 exposure. Associations remained robust to additional adjustments of co-pollutants, with HRs of 1.099 (95% CI: 1.023-1.180) in bi-pollutant model (+PM2.5) and 1.093 (95% CI: 1.018-1.174) in tri-pollutant model (+PM2.5+NO2), respectively. A J-shaped C-R relationship was identified among Chinese general population, suggesting significant excess mortality risk at high ozone exposure only. The combined C-R curves from Asia (n = 4) and North America (n = 17) demonstrated an overall increased risk of all-cause mortality with O3 exposure, with pooled HRs of 1.124 (95% CI: 0.966-1.307) and 1.023 (95% CI: 1.007-1.039) per 10-ppb rise, respectively. Conversely, an opposite association was observed in Europe (n = 8, HR: 0.914 [95% CI: 0.860-0.972]), suggesting significant heterogeneity across regions (P < 0.01). CONCLUSIONS: This study provided national evidence that high O3 exposure may curtail long-term survival of Chinese general population. Great between-region heterogeneity of pooled O3-mortality was identified across North America, Europe, and Asia.

Epigenome-wide association study on short-, intermediate- and long-term ozone exposure in Han Chinese, the NSPT study.

Epidemiological and epigenetic studies have acknowledged ambient ozone exposure associated with inflammatory and cardiovascular disease. However, the molecular mechanisms still remained unclear, and epigenome-wide analysis in cohort were lacking, especially in Chinese. We included blood-derived DNA methylation for 3365 Chinese participants from the NSPT cohort and estimated individual ozone exposure level of short-, intermediate- and long-term, based on a validated prediction model. We performed epigenome-wide association studies which identified 59 CpGs and 30 DMRs at a strict genome-wide significance (P < 5 ×10-8). We also conducted comparison on the DNA methylation alteration corresponding to different time windows, and observed an enhanced differentiated methylation trend for intermediate- and long-term exposure, while the short-term exposure associated methylation changes did not retain. The targeted genes of methylation alteration were involved in mechanism related to aging, inflammation disease, metabolic syndrome, neurodevelopmental disorders, and oncogenesis. Underlying pathways were enriched in biological activities including telomere maintenance process, DNA damage response and megakaryocyte differentiation. In conclusion, our study is the first EWAS on ozone exposure conducted in large-scale Han Chinese cohort and identified associated DNA methylation change on CpGs and regions, as well as related gene functions and pathways.