Low-level ambient ozone exposure associated with neutrophil extracellular traps and pro-atherothrombotic biomarkers in healthy adults.

BACKGROUND AND AIMS: Uncertainty of the causality determinations for ambient ozone (O3) on cardiovascular events is heightened by the limited understanding of the mechanisms involved in humans. We aimed to examine the pro-atherothrombotic impacts of O3 exposure and to explore the potential mediating roles of dysfunctional neutrophils, focusing on neutrophil extracellular traps (NETs). METHODS: A longitudinal panel study of 152 healthy adults was conducted in the cool to cold months with relatively low levels of O3 between September 2019 and January 2020 in Beijing, China. Four repeated measurements of indicators reflecting atherothrombotic balance and NETs were performed for each participant. RESULTS: Daily average exposure levels of ambient O3 were 16.6 µg/m3 throughout the study period. Per interquartile range increase in average concentrations of O3 exposure at prior up to 7 days, we observed elevations of 200.1-276.3% in D-dimer, 27.2-36.8% in thrombin-antithrombin complex, 10.8-60.3% in plasminogen activator inhibitor 1, 13.9-21.8% in soluble P-selectin, 16.5-45.1% in matrix metalloproteinase-8, and 2.4-12.4% in lipoprotein-associated phospholipase A2. These pro-atherothrombotic changes were accompanied by endothelial activation, lung injury, and immune inflammation. O3 exposure was also positively associated with circulating NETs indicators, including citrullinated histone H3, neutrophil elastase, myeloperoxidase, and double-stranded DNA. Mediation analyses indicated that NETs could mediate O3-associated pro-atherothrombotic responses. The observational associations remained significant and robust after controlling for other pollutants, and were generally greater in participants with low levels of physical activity. CONCLUSIONS: Ambient O3 exposure was associated with significant increases in NETs and pro-atherothrombotic potential, even at exposure levels well below current air quality guidelines of the World Health Organization.

Short-Term Effects of Primary and Secondary Particulate Matter on Ceramide Metabolism, Pro-Inflammatory Response, and Blood Coagulation.

Evidence of the precise biological pathway responsible for acute cardiovascular events triggered by particulate matter (PM) exposure from anthropogenic emissions is sparse. We investigated the associations of biomarkers relevant to the pathophysiology of atherothrombosis (ceramide metabolism, pro-inflammatory response, and blood coagulation) with primary and secondary components in particulate matter with aerodynamic diameters less than 2.5 µm (PM2.5). A total of 152 healthy participants were followed with four repeated clinical visits between September 2019 and January 2020 in Beijing. Exposure to ambient inorganic aerosols (sulfate, nitrate, ammonium, and chloride), as well as organic aerosols (OA) in PM2.5, was measured by a real-time aerosol chemical speciation monitor, and sources of OA were performed by positive matrix factorization. We found significant increases of 101.9-397.9% in ceramide indicators associated with interquartile-range increases in inorganic aerosols and OA prior to 72 h of exposure. Higher levels of organic and inorganic aerosols in PM2.5 were associated with increases of 3.1-6.0% in normal T cells regulated upon activation and expressed and secreted relevant to the pro-inflammatory response; increases of 276.9-541.5% were observed in D-dimers relevant to coagulation. Detrimental effects were further observed following OA exposure from fossil fuel combustion. Mediation analyses indicated that ceramide metabolism could mediate the associations of PM2.5 components with pro-inflammatory responses. Our findings expand upon the current understanding of potential pathophysiological pathways of cardiovascular events posed by ambient particulates and highlight the importance of reducing primary and secondary PM from anthropogenic combustions.

Association between short-term air pollution exposure and perturbation in thyrotropin levels in 1.38 million Chinese women: A national longitudinal analysis, 2014-2019.

Prevalence of subclinical hypothyroidism substantially increased during the last decade in China, which has been commonly/clinically diagnosed as elevation in thyrotropin (thyroid-stimulating hormone [TSH]). Tobacco smoke containing toxic substances has been linked to thyroid dysfunction; however, data on perturbation of TSH following air pollution exposure in human has not been assessed at nationwide population level. We investigated the longitudinal impact of daily ambient air pollution estimated at residential level on serum TSH in 1.38 million women from China's 29 mainland provinces between 2014 and 2019. We observed that particulate matter with aerodynamic diameter ≤ 10 and ≤ 2.5 µm (PM10, PM2.5) and nitrogen dioxide (NO2) at cumulative lag 0-7 days of exposure were associated with percent elevations in TSH (0.88% [95% CI: 0.71, 1.05] per [interquartile range, IQR: 54.8 µg/m3] of PM10; 0.89% [95% CI, 0.71, 1.07] per IQR [40.3 µg/m3] of PM2.5; 2.01% [95% CI: 1.81, 2.22] per IQR [27.4 µg/m3] of NO2). Greater associations were observed in participants living in areas with ≥adequate iodine intake and those with low BMI levels and high inflammation status. Our results suggest that increased concentrations of recent ambient air pollutants at exposure ranges commonly encountered in Asia were associated with increases in TSH, supporting disturbing role of short-term air pollution exposure on the regulation of thyroid hormone homeostasis.

Exposure to ambient oxidant pollution associated with ceramide changes and cardiometabolic responses.

Evidence of impact of ambient oxidant pollution on cardiometabolic responses remains limited. We aimed to examine associations of oxidant pollutants with cardiometabolic responses, and effect modification by ceramides. During 2019-2020, 152 healthy adults were visited 4 times in Beijing, China, and indicators of ceramides, glucose homeostasis, and vascular function were measured. We found significant increases in ceramides of 13.9% (p = 0.020) to 110.1% (p = 0.005) associated with an interquartile increase in oxidant pollutants at prior 1-7 days. Exposure to oxidant pollutants was also related to elevations in insulin and reductions in adiponectin, and elevations in systolic and diastolic blood pressure. Further, stratified analyses revealed larger changes in oxidant pollutant related cardiometabolic responses among participants with higher ceramide levels compared to those with lower levels. Our findings suggested cardiometabolic effects associated with exposure to oxidant pollutants, which may be modified by ceramide levels.

Adipocyte-Derived Exosomal NOX4-Mediated Oxidative Damage Induces Premature Placental Senescence in Obese Pregnancy.

Background: A recent study has reported that maternal obesity is linked to placental oxidative damage and premature senescence. NADPH oxidase 4 (NOX4) is massively expressed in adipose tissue, and its induced reactive oxygen species have been found to contribute to cellular senescence. While, whether, in obese pregnancy, adipose tissue-derived NOX4 is the considerable cause of placental senescence remained elusive. Methods: This study collected term placentas from obese and normal pregnancies and obese pregnant mouse model was constructed by a high fat diet to explore placental senescence. Furthermore, adipocyte-derived exosomes were isolated from primary adipocyte medium of obese and normal pregnancies to examine their effect on placenta functions in vivo and vitro. Results: The placenta from the obese group showed a significant increase in placental oxidative damage and senescence. Exosomes from obese adipocytes contained copies of NOX4, and when cocultured with HTR8/SVneo cells, they induced severe oxidative damage, cellular senescence, and suppressed proliferation and invasion functions when compared with the control group. In vivo, adipocyte-derived NOX4-containing exosomes could induce placental oxidative damage and senescence, ultimately leading to adverse pregnancy outcomes. Conclusion: In obesity, adipose tissue can secrete exosomes containing NOX4 which can be delivered to trophoblast resulting in severe DNA oxidative damage and premature placental senescence, ultimately leading to adverse pregnancy outcomes.

Pro-inflammation and pro-atherosclerotic responses to short-term air pollution exposure associated with alterations in sphingolipid ceramides and neutrophil extracellular traps.

Air pollution has been associated with the development of atherosclerosis; however, the pathophysiological mechanisms underlying pro-atherosclerotic effects of air pollution exposure remain unclear. We conducted a prospective panel study in Beijing and recruited 152 participants with four monthly visits from September 2019 to January 2020. Linear mixed-effect models were applied to estimate the associations linking short-term air pollution exposure to biomarkers relevant to ceramide metabolism, pro-inflammation (neutrophil extracellular traps formation and systemic inflammation) and pro-atherosclerotic responses (endothelial stimulation, plaque instability, coagulation activation, and elevated blood pressure). We further explored whether ceramides and inflammatory indicators could mediate the alterations in the profiles of pro-atherosclerotic responses. We found that significant increases in levels of circulating ceramides of 9.7% (95% CIs: 0.7, 19.5) to 96.9% (95% CIs: 23.1, 214.9) were associated with interquartile range increases in moving averages of ambient air pollutant metrics, including fine particulate matter (PM2.5), black carbon, particles in size fractions of 100-560 nm, nitrogen dioxide, carbon monoxide and sulfur dioxide at prior up to 7 days. Higher air pollution levels were also associated with activated neutrophils (increases in citrullinated histone H3, neutrophil elastase, double-stranded DNA, and myeloperoxidase) and exacerbation of pro-atherosclerotic responses (e.g., increases in vascular endothelial growth factor, lipoprotein-associated phospholipase A2, matrix metalloproteinase-8, P-selectin, and blood pressure). Mediation analyses further showed that dysregulated ceramide metabolism and potentiated inflammation could mediate PM2.5-associated pro-atherosclerotic responses. Our findings extend the understanding on potential mechanisms of air pollution-associated atherosclerosis, and suggest the significance of reducing air pollution as priority in urban environments.

Ambient Anthropogenic Carbons and Pediatric Respiratory Infections: A Case-Crossover Analysis in the Megacity Beijing.

Carbon loading in airway cells has shown to worsen function of antimicrobial peptides, permitting increased survival of pathogens in the respiratory tract; however, data on the impacts of carbon particles on childhood acute respiratory infection (ARI) is limited. We assembled daily health data on outpatient visits for ARI (bronchitis, pneumonia, and total upper respiratory infection [TURI]) in children aged 0-14 years between 2015 and 2019 in Beijing, China. Anthropogenic carbons, including black carbon (BC) and its emission sources, and wood smoke particles (delta carbon, ultra-violet absorbing particulate matter, and brown carbon) were continuously monitored. Using a time-stratified case-crossover approach, conditional logistic regression was performed to derive risk estimates for each outcome. A total of 856,899 children were included, and a wide range of daily carbon particle concentrations was observed, with large variations for BC (0.36-20.44) and delta carbon (0.48-57.66 µg/m3). Exposure to these particles were independently associated with ARI, with nearly linear exposure-response relationships. Interquartile range increases in concentrations of BC and delta carbon over prior 0-8 days, we observed elevation of the odd ratio of bronchitis by 1.201 (95% confidence interval, 1.180, 1.221) and 1.048 (95% CI, 1.039, 1.057), respectively. Stronger association was observed for BC from traffic sources, which increased the odd ratio of bronchitis by 1.298 (95% CI, 1.273, 1.324). Carbon particles were also associated with elevated risks of pneumonia and TURI, and subgroup analyses indicated greater risks among children older than 6 years. Our findings suggested that anthropogenic carbons in metropolitan areas may pose a significant threat to clinical manifestations of respiratory infections in vulnerable populations.

The prenatal diagnostic indicators of placenta accreta spectrum disorders.

Placenta accreta spectrum (PAS) disorders refers to a heterogeneous group of anomalies distinguished by abnormal adhesion or invasion of chorionic villi through the myometrium and uterine serosa. PAS frequently results in life-threatening complications, including postpartum hemorrhage and hysterotomy. The incidence of PAS has increased recently as a result of rising cesarean section rates. Consequently, prenatal screening for PAS is essential. Despite the need to increase specificity, ultrasound is still considered a primary adjunct. Given the dangers and adverse effects of PAS, it is necessary to identify pertinent markers and validate indicators to improve prenatal diagnosis. This article summarizes the predictors regarding biomarkers, ultrasound indicators, and magnetic resonance imaging (MRI) features. In addition, we discuss the effectiveness of joint diagnosis and the most recent research on PAS. In particular, we focus on (a) posterior placental implantation and (b) accreta after in vitro fertilization-embryo transfer, both of which have low diagnostic rates. At last, we graphically display the prenatal diagnostic indicators and each diagnostic performance.

Associations of climate variability driven by El Niño-southern oscillation with excess mortality and related medical costs in Chinese elderly.

Climate variability driven by El Niño-Southern Oscillation (ENSO) is a significant public health concern in parallel with global population aging; however, its role in healthy aging is less studied. We examined the longitudinal impacts of ENSO exposure on excess mortality and related medical costs in the elderly from 23 provinces of China. A total of 27,533 non-accidental all-cause deaths were recorded in 30,763 participants during 1998-2018. We found that both low and high levels of ENSO metrics over lags of 0-12 months were associated with increased mortality risks. Specifically, comparing the 10th percentile (-1.8) and 90th percentile (2.0) multivariate El Niño index (MEI) levels to the reference level with the minimum effect of MEI exposure, the risk of mortality was 1.87 (95 % confidence interval [CI], 1.75, 2.00) and 4.89 (95 % CI, 4.36, 5.49), respectively. ENSO exposure was also positively related to medical costs. Further, the associations were stronger among drinkers, lower-income participants, and those with higher blood pressure and heart rate measured at the most recent follow-ups. Our results suggested that ENSO exposure was capable of heightening mortality risks and medical burden among older elderly adults, highlighting that climate variability driven by ENSO could be a crucial determinant of healthy aging.

Combustion-Derived Particulate PAHs Associated with Small Airway Dysfunction in Elderly Patients with COPD.

Evidence of the respiratory effects of ambient organic aerosols (e.g., polycyclic aromatic hydrocarbons, PAHs) among patients with chronic diseases is limited. We aimed to assess whether exposure to ambient particle-bound PAHs could worsen small airway functions in patients with chronic obstructive pulmonary disease (COPD) and elucidate the underlying mechanisms involved. Forty-five COPD patients were recruited with four repeated visits in 2014-2015 in Beijing, China. Parameters of pulmonary function and pulmonary/systemic inflammation and oxidative stress were measured at each visit. Linear mixed-effect models were performed to evaluate the associations between PAHs and measurements. In this study, participants experienced an average PAH level of 61.7 ng/m3. Interquartile range increases in exposure to particulate PAHs at prior up to 7 days were associated with reduced small airway functions, namely, decreases of 17.7-35.5% in forced maximal mid-expiratory flow. Higher levels of particulate PAHs were also associated with heightened lung injury and inflammation and oxidative stress. Stronger overall effects were found for PAHs from traffic emissions and coal burning. Exposure to ambient particulate PAHs was capable of impairing small airway functions in elderly patients with COPD, potentially via inflammation and oxidative stress. These findings highlight the importance of control efforts on organic particulate matter from fossil fuel combustion emissions.

Maternal exposure to traffic-related ambient particles and risk of gestational diabetes mellitus with isolated fasting hyperglycaemia: A retrospective cohort study in Beijing, China.

BACKGROUND: Ambient particles have been associated with gestational diabetes mellitus (GDM), however, no study has evaluated the effects of traffic-related ambient particles on the risks of GDM subgroups classified by oral glucose tolerance test (OGTT) values. METHODS: A retrospective analysis was conducted among 24,001 pregnant women who underwent regular prenatal care and received OGTT at Haidian Maternal and Child Health Hospital in Beijing, China, 2014-2017. A total of 3,168 (13.2%) pregnant women were diagnosed with GDM, including 1,206 with isolated fasting hyperglycaemia (GDM-IFH). At a fixed-location monitoring station, routinely monitored ambient particles included fine particulate matter (PM2.5), black carbon (BC) and particles in size ranges of 5-560 nm (PNC5-560). Contributions of PNC5-560 sources were apportioned by positive matrix factorization model. Logistic regression model was applied to estimate odds ratio (OR) of ambient particles on GDM risk. RESULTS: Among the 24,001 pregnancy women recruited in this study, 3,168 (13.2%) were diagnosed with GDM, including 1,206 with isolated fasting hyperglycaemia (GDM-IFH) and 1,295 with isolated post-load hyperglycaemia (GDM-IPH). We observed increased GDM-IFH risk with per interquartile range increase in first-trimester exposures to PM2.5 (OR = 1.94; 95% Confidence Intervals: 1.23-3.07), BC (OR = 2.14; 1.73-2.66) and PNC5-560 (OR = 2.46; 1.90-3.19). PNC5-560 originated from diesel and gasoline vehicle emissions were found in associations with increases in GDM-IFH risk, but not in GDM-IPH risk. CONCLUSION: Our findings suggest that exposure to traffic-related ambient particles may increase GDM risk by exerting adverse effects on fasting glucose levels during pregnancy, and support continuing efforts to reduce traffic emissions for protecting vulnerable population who are at greater risk of glucose metabolism disorder.

Short-term exposure to traffic-related air pollution and STEMI events: Insights into STEMI onset and related cardiac impairment.

AIMS: Evidence on the impacts of traffic-related air pollution (TRAP) on ST-segment elevation myocardial infarction (STEMI) events is limited. We aimed to assess the acute effects of TRAP exposure on the clinical onset of STEMI and related cardiac impairments. METHODS AND RESULTS: We recruited patients who were admitted for STEMI and underwent primary percutaneous coronary intervention at Peking University Third Hospital between 2014 and 2020. Indicators relevant to cardiac impairments were measured. Concomitantly, hourly concentrations of traffic pollutants were monitored throughout the study period, including fine particulate matter, black carbon (BC), particles in size ranges of 5-560 nm, oxides of nitrogen (NOX), nitrogen dioxide, and carbon monoxide. The mean (SD) age of participants was 62.4 (12.5) years. Daily average (range) concentrations of ambient BC and NOX were 3.9 (0.1-25.0) µg/m3 and 90.8 (16.6-371.7) µg/m3. Significant increases in STEMI risks of 5.9% (95% CI: 0.1, 12.0) to 21.9% (95% CI: 6.0, 40.2) were associated with interquartile range increases in exposure to TRAP within a few hours. These changes were accompanied by significant elevations in cardiac troponin T levels of 6.9% (95% CI: 0.2, 14.1) to 41.7% (95% CI: 21.2, 65.6), as well as reductions in left ventricular ejection fraction of 1.5% (95% CI: 0.1, 2.9) to 3.7% (95% CI: 0.8, 6.4). Furthermore, the associations were attenuated in participants living in areas with higher residential greenness levels. CONCLUSIONS: Our findings extend current understanding that short-term exposure to higher levels of traffic pollution was associated with increased STEMI risks and exacerbated cardiac impairments, and provide evidence on traffic pollution control priority for protecting vulnerable populations who are at greater risks of cardiovascular events.

The effect of using personal-level indoor air cleaners and respirators on biomarkers of cardiorespiratory health: a systematic review.

BACKGROUND: Emerging studies have investigated potential cardiovascular and respiratory health impacts from the use of personal-level intervention equipment against air pollution exposure. The objective of this systematic review is to assess the efficacy of personal-level air pollution intervention on mitigating adverse health effects from air pollution exposure by using portable air cleaner or wearing respirator. METHODS: In this systematic review, we searched PubMed and Web of Science for published literatures up to May 31, 2020, focusing on personal-level air pollution intervention studies. Among these studies, we investigated the impacts on cardio-respiratory responses to the use of these interventions. The intervention of review interest was the use of personal-level equipment against air pollution, including using portable air cleaner indoors or wearing respirator outdoors. The outcome of review interest was impacts on cardio-respiratory health endpoints following interventions, including level changes in blood pressure, heart rate variability (HRV), lung function, and biomarkers of inflammation and oxidative stress. Weighted mean differences or percent changes were pooled in meta-analyses for these health endpoints. The heterogeneity across studies was assessed using the Cochran's Q-statistic test, and the individual study quality was assessed using the Cochrane risk of bias tool version 2 (RoB 2). We further applied the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method to evaluate the certainty of evidence. RESULTS: From systematic literature search and screening, we identified 29 related eligible intervention studies, including 21 studies on indoor portable air cleaner use and 8 studies on respirator use. For portable air cleaner intervention, we observed suggestive evidence of beneficial changes on cardio-respiratory health endpoints. Collectively in these studies, we found significantly beneficial changes of 2.01% decreases (95% CI: 0.50%, 3.52%) in systolic blood pressure, as well as non-significantly beneficial changes of 3.04% increases (95% CI: -2.65%, 8.74%) in reactive hyperemia index and 0.24% increases (95% CI: -0.82%, 1.31%) in forced expiratory volume in 1 s. We also observed non-significant reductions in levels of inflammation and oxidative stress biomarkers, including C-reactive protein, interleukin-6, fibrinogen, fractional exhaled nitric oxide and malondialdehyde. For respirator intervention, we observed some beneficial changes on cardiovascular health endpoints, such as significant increases in HRV parameters [SDNN (2.20%, 95% CI: 0.54%, 3.86%)], as well as non-significant decreases in blood pressure [SBP (0.63 mmHg, 95% CI: -0.39, 1.66)]; however, no sufficient data were available for meta-analyses on lung function and biomarkers. RoB 2 assessments suggested that most intervention studies were with a moderate to high overall risk of bias. The certainty of evidence for intervention outcome pairs was graded very low for either portable air cleaner or respirator intervention. The common reasons to downgrade study evidence included loss to follow-up, lack of blinding, lack of washout period, small sample size, and high heterogeneity across studies. CONCLUSIONS: The uses of indoor portable air cleaner and respirator could contribute to some beneficial changes on cardiovascular health, but with much limited evidence on respiratory health. Low certainty of the overall study evidence shed light on future research for larger sample size trials with more rigorous study design.

Traffic-related air pollution associated pulmonary pathophysiologic changes and cardiac injury in elderly patients with COPD.

Traffic-related air pollution (TRAP) has shown enormous environmental toxicity, but its cardiorespiratory health impact on chronic obstructive pulmonary disease (COPD) has been less studied. We followed a panel of 45 COPD patients with 4 repeated clinical visits across 14 months in a traffic-predominated urban area of Beijing, China, with concurrent measurements of TRAP metrics (fine particulate matter, black carbon, oxides of nitrogen and carbon monoxide). Linear mixed-effect models were performed to evaluate the associations and potential pathways linking traffic pollution to indicators of spirometry, cardiac injury, inflammation and oxidative stress. We observed that interquartile range increases in moving averages of TRAP exposures at prior up to 7 days were associated with significant reductions in large and small airway functions, namely decreases in forced vital capacity of 3.1-9.3% and forced expiratory flow 25-75% of 5.9-16.4%. Higher TRAP levels were also associated with worsening of biomarkers relevant to lung injury (hepatocyte growth factor and surfactant protein D) and cardiac injury (high-sensitivity cardiac troponin I, B-type natriuretic peptide and soluble ST2), as well as enhanced airway/systemic inflammation and oxidative stress. Mediation analyses showed that TRAP exposures may prompt cardiac injury, possibly via worsening pulmonary pathophysiology. These findings highlight the importance of traffic pollution control priority in urban areas.

Maternal exposures to fine and ultrafine particles and the risk of preterm birth from a retrospective study in Beijing, China.

Maternal exposure to fine particulate matter (PM2.5) has been associated with increased risk of preterm birth (PTB), but evidence on particles in smaller sizes and PTB risk remains limited. In this retrospective analysis, we included birth records of 24,001 singleton live births from Haidian Maternal and Child Health Hospital in Beijing, China, 2014-2017. Concurrently, number concentrations of size-fractioned particles in size ranges of 5-560 nm (PNC5-560) and mass concentrations of PM2.5, black carbon (BC) and gaseous pollutants were measured from a fixed-location monitoring station in central Haidian District. Logistic regression models were used to estimate the odds ratio (OR) of air pollutants on PTB risk after controlling for temperature, relative humidity, and individual covariates (e.g., maternal age, ethnicity, gravidity, parity, gestational weight gain, fetal gender, the year and season of conception). Positive matrix factorization models were then used to apportion the sources of PNC5-560. Among the 1062 (4.4%) PTBs, increased PTB risk was observed during the third trimester of pregnancy per 10 µg/m3 increase in PM2.5 [OR = 1.92; 95% Confidence Interval (95% CI): 1.76, 2.09], per 1000 particles/cm3 increase in PNC25-100 (OR = 1.09; 95% CI: 1.03, 1.15) and PNC100-560 (OR = 1.22; 95% CI: 1.05, 1.42). Among the identified sources of PNC5-560, emissions from gasoline and diesel vehicles were significantly associated with increased PTB risk, with ORs of 1.14 (95% CI: 1.01, 1.29) and 1.11 (95% CI: 1.04, 1.18), respectively. Exposures to other traffic-related air pollutants, such as BC and nitrogen dioxide (NO2) were also significantly associated with increased PTB risk. Our findings highlight the importance of traffic emission reduction in urban areas.

Associations of ultrafine and fine particles with childhood emergency room visits for respiratory diseases in a megacity.

BACKGROUND: Ambient fine particulate matter with aerodynamic diameter less than 2.5 µm (PM2.5) has been associated with deteriorated respiratory health, but evidence on particles in smaller sizes and childhood respiratory health has been limited. METHODS: We collected time-series data on daily respiratory emergency room visits (ERVs) among children under 14 years old in Beijing, China, during 2015-2017. Concurrently, size-fractioned number concentrations of particles in size ranges of 5-560 nm (PNC5-560) and mass concentrations of PM2.5, black carbon (BC) and nitrogen dioxide (NO2) were measured from a fixed-location monitoring station in the urban area of Beijing. Confounder-adjusted Poisson regression models were used to estimate excessive risks (ERs) of particle size fractions on childhood respiratory ERVs, and positive matrix factorisation models were applied to apportion the sources of PNC5-560. RESULTS: Among the 136 925 cases of all-respiratory ERVs, increased risks were associated with IQR increases in PNC25-100 (ER=5.4%, 95% CI 2.4% to 8.6%), PNC100-560 (4.9%, 95% CI 2.5% to 7.3%) and PM2.5 (1.3%, 95% CI 0.1% to 2.5%) at current and 1 prior days (lag0-1). Major sources of PNC5-560 were identified, including nucleation (36.5%), gasoline vehicle emissions (27.9%), diesel vehicle emissions (18.9%) and secondary aerosols (10.6%). Emissions from gasoline and diesel vehicles were found of significant associations with all-respiratory ERVs, with increased ERs of 6.0% (95% CI 2.5% to 9.7%) and 4.4% (95% CI 1.7% to 7.1%) at lag0-1 days, respectively. Exposures to other traffic-related pollutants (BC and NO2) were also associated with increased respiratory ERVs. CONCLUSION: Our findings suggest that exposures to higher levels of PNC5-560 from traffic emissions could be attributed to increased childhood respiratory morbidity, which supports traffic emission control priority in urban areas.

The mediating role of vascular inflammation in traffic-related air pollution associated changes in insulin resistance in healthy adults.

AIM: The precise pathophysiologic pathway linking traffic-related air pollution (TRAP) to diabetes mellitus is not well elucidated. We aimed to investigate whether activation of vascular inflammation can be a mechanistic linkage between ambient TRAP and insulin resistance. METHODS: Study outcomes were determined by assessing a series of circulating biomarkers indicative of insulin resistance and vascular inflammation among 73 healthy adults who underwent repeated clinical visits in Beijing, China, 2014-2016. Concomitantly, concentrations of ambient TRAP indices, including particulate matter in diameter <2.5 µm (PM2.5), particles in size fractions of 5-560 nm, black carbon, carbon monoxide, nitrogen dioxide, and oxides of nitrogen, were continuously monitored. RESULTS: Participants experienced extremely high levels of TRAP exposures, with mean (standard deviation) PM2.5 concentrations of 91.8 (48.3) µg/m3, throughout the study. We found that interquartile range increases in exposure to moving average concentrations of various TRAP indices at prior up to 7 days were associated with significant elevations of 8.9-49.6% in insulin levels. Higher pollutant levels were also related to worsening metrics of insulin resistance (soluble insulin receptor ectodomain, adipokines, and homeostasis model assessment of insulin resistance) and heightened vascular inflammatory responses, particularly disruptions of the receptor activator of nuclear factor κB ligand/osteoprotegerin system balance and elevations of monocyte/macrophage and T cell activation markers. Mediation analyses showed that activation of vascular inflammation could explain up to 66% of the alterations in metrics of insulin resistance attributable to air pollution. CONCLUSION: Our results suggest that ambient traffic pollution exposure was capable of promoting insulin resistance possibly via generating vascular inflammation.

A review on reducing indoor particulate matter concentrations from personal-level air filtration intervention under real-world exposure situations.

Improving air quality in indoor environments where people live is of importance to protect human health. In this systematic review, we assessed the effectiveness of personal-level use of air filtration units in reducing indoor particulate matters (PM) concentrations under real-world situations following systematic review guidelines. A total of 54 articles were included in the review, in which 20 randomized controlled/crossover trials that reported the changes in indoor fine PM (PM2.5 ) concentrations were quantitatively assessed in meta-analysis. Standardized mean differences (SMDs) were calculated for changes in indoor PM concentrations following air filtration interventions. Moderate-to-large reductions of 11%-82% in indoor PM2.5  concentrations were observed with SMD of -1.19 (95% CI: -1.50, -0.88). The reductions in indoor PM concentrations varied by geographical locations, filtration technology employed, indoor environmental characteristics, and air pollution sources. Most studies were graded with low-to-moderate risk of bias; however, the overall certainty of evidence for indoor PM concentration reductions was graded at very low level. Considering the effectiveness of indoor air filtration under practical uses, socio-economic disparities across study populations, and costs of air filter replacement over time, our results highlight the importance of reducing air pollution exposure at the sources.

Combustion-derived particulate organic matter associated with hemodynamic abnormality and metabolic dysfunction in healthy adults.

Epidemiological evidence on cardiometabolic health of particulate organic matter (POM) and its sources is sparse. In a panel of 73 healthy adults in Beijing, China, daily concentrations of ambient fine particulate matter-bound polycyclic aromatic hydrocarbons (PAHs) and n-alkanes were measured throughout the study period, and Positive Matrix Factorization approach was used to identity PAHs sources. Linear mixed-effect models and mediation analyses were applied to examine the associations and potential interlink pathways between POM and biomarkers indicative of hemodynamics, insulin resistance, vascular calcification and immune inflammation. We found that significant alterations in cardiometabolic measures were associated with POM exposures. In specific, interquartile range increases in PAHs concentrations at prior up to 9 days were observed in association with significant elevations of 2.6-2.9% in diastolic blood pressure, 6.6-8.1% in soluble ST2, 10.5-14.5% in insulin, 40.9-45.7% in osteoprotegerin, and 36.3-48.7% in interleukin-17A. Greater associations were generally observed for PAHs originating from traffic emissions and coal burning. Mediation analyses revealed that POM exposures may prompt the genesis of hemodynamic abnormalities, possibly via worsening insulin resistance and calcification potential. These findings suggested that cardiometabolic health benefits would be achieved by reducing PM from combustion emissions.

Perturbation of amino acid metabolism mediates air pollution associated vascular dysfunction in healthy adults.

The molecular mechanisms of air pollution-associated adverse cardiovascular effects remain largely unknown. In the present study, we investigated the impacts of ambient air pollution on vascular function and the potential mediation effects of amino acids in a longitudinal follow-up of 73 healthy adults living in Beijing, China, between 2014 and 2016. We estimated associations between air pollutants and serum soluble intercellular adhesion molecule 1 (sICAM-1) and plasma levels of amino acids using linear mixed-effects models, and elucidated the biological pathways involved using mediation analyses. Higher air pollutant levels were significantly associated with increases in sICAM-1 levels. Metabolomics analysis showed that altered metabolites following short-term air pollution exposure were mainly involved in amino acid metabolism. Significant reductions in levels of plasma alanine, threonine and glutamic acid of 2.1 µM [95% confidence interval (CI): -3.8, -0.3] to 62.0 µM (95% CI: -76.1, -47.9) were associated with interquartile range increases in moving averages of PM2.5, BC, CO and SO2 in 1-7 days prior to clinical visits. Mediation analysis also showed that amino acids can mediate up to 48% of the changes in sICAM-1 associated with increased air pollution exposure. Our results indicated that air pollution may prompt vascular dysfunction through perturbing amino acid metabolism.