Mechanistic insights into cardiovascular effects of ultrafine particle exposure: A longitudinal panel study.

BACKGROUND: Ultrafine particle (UFP) has been linked with higher risks of cardiovascular diseases; however, the biological mechanisms remain to be fully elucidated. OBJECTIVES: This study aims to investigate the cardiovascular responses to short-term UFP exposure and the biological pathways involved. METHODS: A longitudinal panel study was conducted among 32 healthy, non-smoking young adults in Shanghai, China, who were engaged in five rounds of follow-ups between December 2020 and November 2021. Individual exposures were calculated based on the indoor and outdoor real-time measurements. Blood pressure, arterial stiffness, targeted biomarkers, and untargeted proteomics and metabolomics were examined during each follow-up. Linear mixed-effect models were applied to analyze the exposure and health data. The differential proteins and metabolites were used for pathway enrichment analyses. RESULTS: Short-term UFP exposure was associated with significant increases in blood pressure and arterial stiffness. For example, systolic blood pressure increased by 2.10 % (95 % confidence interval: 0.63 %, 3.59 %) corresponding to each interquartile increase in UFP concentrations at lag 0-3 h, while pulse wave velocity increased by 2.26 % (95 % confidence interval: 0.52 %, 4.04 %) at lag 7-12 h. In addition, dozens of molecular biomarkers altered significantly. These effects were generally present within 24 h after UFP exposure, and were robust to the adjustment of co-pollutants. Molecular changes detected in proteomics and metabolomics analyses were mainly involved in systemic inflammation, oxidative stress, endothelial dysfunction, coagulation, and disturbance in lipid transport and metabolism. DISCUSSION: This study provides novel and compelling evidence on the detrimental subclinical cardiovascular effects in response to short-term UFP exposure. The multi-omics profiling further offers holistic insights into the underlying biological pathways.

Environmental exposure and child health in China.

Chinese children are exposed to broad environmental risks ranging from well-known hazards, such as pesticides and heavy metals, to emerging threats including many new man-made chemicals. Although anecdotal evidence suggests that the exposure levels in Chinese children are substantially higher than those of children in developed countries, a systematic assessment is lacking. Further, while these exposures have been linked to a variety of childhood diseases, such as respiratory, endocrine, neurological, behavioral, and malignant disorders, the magnitude of the associations is often unclear. This review provides a current epidemiologic overview of commonly reported environmental contaminants and their potential impact on children's health in China. We found that despite a large volume of studies on various topics, there is a need for more high-quality research and better-coordinated regional and national data collection. Moreover, prevention of such diseases will depend not only on training of environmental health professionals and enhanced research programs, but also on public education, legislation, and networking.

Particulate matter pollution, polygenic risk score and mosaic loss of chromosome Y in middle-aged and older men from the Dongfeng-Tongji cohort study.

Mosaic loss of chromosome Y (mLOY) is the most common somatic alteration as men aging and may reflect genome instability. PM exposure is a major health concern worldwide, but its effects with genetic factors on mLOY has never been investigated. Here we explored the associations of PM2.5 and PM10 exposure with mLOY of 10,158 males measured via signal intensity of 2186 probes in male-specific chromosome-Y region from Illumina array data. The interactive and joint effects of PM2.5 and PM10 with genetic factors and smoking on mLOY were further evaluated. Compared with the lowest tertiles of PM2.5 levels in each exposure window, the highest tertiles in the same day, 7-, 14-, 21-, and 28-day showed a 0.005, 0.006, 0.007, 0.007, and 0.006 decrease in mLRR-Y, respectively (all P < 0.05), with adjustment for age, BMI, smoking pack-years, alcohol drinking status, physical activity, education levels, season of blood draw, and experimental batch. Such adverse effects were also observed in PM10-mLOY associations. Moreover, the unweighted and weighted PRS presented significant negative associations with mLRR-Y (both P < 0.001). Participants with high PRS and high PM2.5 or PM10 exposure in the 28-day separately showed a 0.018 or 0.019 lower mLRR-Y level [ß (95 %CI) = -0.018 (-0.023, -0.012) and - 0.019 (-0.025, -0.014), respectively, both P < 0.001], when compared to those with low PRS and low PM2.5 or PM10 exposure. We also observed joint effects of PM with smoking on exacerbated mLOY. This large study is the first to elucidate the impacts of PM2.5 exposure on mLOY, and provides key evidence regarding the interactive and joint effects of PM with genetic factors on mLOY, which may promote understanding of mLOY development, further modifying and increasing healthy aging in males.

Epigenome-wide association study on ambient PM2.5 exposure in Han Chinese, the NSPT study.

Ambient PM2.5 exposure has been recognized as a major health risk and related to aging, cardiovascular, respiratory and neurologic diseases, and cancer. However, underlying mechanism of epigenetic alteration and regulated pathways still remained unclear. The study on methylome effect of PM2.5 exposure was quite limited in Chinese population, and cohort-based study was absent. The study included blood-derived DNA methylation for 3365 Chinese participants from the NSPT cohort. We estimated individual PM2.5 exposure level of short-medium-, medium- and long-term, based on a validated prediction model. We preformed epigenome-wide association studies to estimate the links between PM2.5 exposure and DNA methylation change, as well as stratification and sensitive analysis to examined the robustness of the association models. A systematic review was conducted to obtain the previously published CpGs and examined for replication. We also conducted comparison on the DNA methylation variation corresponding to different time windows. We further conducted gene function analysis and pathway enrichment analysis to reveal related biological response. We identified a total of 177 CpGs and 107 DMRs associated with short-medium-term PM2.5 exposure, at a strict genome-wide significance (P < 5 × 10-8). The effect sizes on most CpGs tended to cease with the exposure of extended time scale. Associated markers and aligned genes were related to aging, immunity, inflammation and carcinogenesis. Enriched pathways were mostly involved in cell cycle and cell division, signal transduction, inflammatory pathway. Our study is the first EWAS on PM2.5 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.

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.

Ambient PM2.5 Exposure and Bone Homeostasis: Analysis of UK Biobank Data and Experimental Studies in Mice and in Vitro.

BACKGROUND: Previous evidence has identified exposure to fine ambient particulate matter (PM2.5) as a leading risk factor for adverse health outcomes. However, to date, only a few studies have examined the potential association between long-term exposure to PM2.5 and bone homeostasis. OBJECTIVE: We sought to examine the relationship between long-term PM2.5 exposure and bone health and explore its potential mechanism. METHODS: This research included both observational and experimental studies. First, based on human data from UK Biobank, linear regression was used to explore the associations between long-term exposure to PM2.5 (i.e., annual average PM2.5 concentration for 2010) and bone mineral density [BMD; i.e., heel BMD (n=37,440) and femur neck and lumbar spine BMD (n=29,766)], which were measured during 2014-2020. For the experimental animal study, C57BL/6 male mice were assigned to ambient PM2.5 or filtered air for 6 months via a whole-body exposure system. Micro-computed tomography analyses were applied to measure BMD and bone microstructures. Biomarkers for bone turnover and inflammation were examined with histological staining, immunohistochemistry staining, and enzyme-linked immunosorbent assay. We also performed tartrate-resistant acid phosphatase (TRAP) staining and bone resorption assay to determine the effect of PM2.5 exposure on osteoclast activity in vitro. In addition, the potential downstream regulators were assessed by real-time polymerase chain reaction and western blot. RESULTS: We observed that long-term exposure to PM2.5 was significantly associated with lower BMD at different anatomical sites, according to the analysis of UK Biobank data. In experimental study, mice exposed long-term to PM2.5 exhibited excessive osteoclastogenesis, dysregulated osteogenesis, higher tumor necrosis factor-alpha (TNF-α) expression, and shorter femur length than control mice, but they demonstrated no significant differences in femur structure or BMD. In vitro, cells stimulated with conditional medium of PM2.5-stimulated macrophages had aberrant osteoclastogenesis and differences in the protein/mRNA expression of members of the TNF-α/Traf6/c-Fos pathway, which could be partially rescued by TNF-α inhibition. DISCUSSION: Our prospective observational evidence suggested that long-term exposure to PM2.5 is associated with lower BMD and further experimental results demonstrated exposure to PM2.5 could disrupt bone homeostasis, which may be mediated by inflammation-induced osteoclastogenesis. https://doi.org/10.1289/EHP11646.

Residential greenspace counteracts PM2.5 on the risks of preterm birth subtypes: A multicenter study.

BACKGROUND: The association between residential greenspace and preterm birth (PTB) risk remained inconclusive. The PTB subtypes have been ignored and the effect of co-exposure of PM2.5 on PTB risk is still unclear. OBJECTIVE: To investigate the independent, interactive, and mixed effects of residential greenspace and PM2.5 on the risk of PTB subtypes. METHODS: A total of 19,900 singleton births from 20 hospitals in Shanghai, China, from 2015 to 2017 were included. The Normalized Difference Vegetation Index (NDVI) within 500 m and 1000 m buffers of the maternal residence and a combined geoscience-statistical model-derived PM2.5 and its six components were used as the exposure measures. PTB (<37 completed weeks of gestation) were divided into early PTB (24-33 weeks) vs. late PTB (34-36 weeks) and into spontaneous PTB (sPTB), preterm premature rupture of the fetal membranes (PPROM), and iatrogenic PTB. Multivariable logistic regression models were applied to assess the independent and interactive effects of NDVI and PM2.5 on PTB in each trimester. The quantile g-computation approach was employed to explore the mixture effect of PM2.5 components and greenspace across the pregnancy and to determine the main contributors. RESULTS: Levels of PM2.5 and greenspace were associated with increased [aOR (95%CI) ranging from 1.18 (1.07, 1.30) to 3.36 (2.45, 4.64)] and decreased risks [aORs (95%CI) ranging from 0.64 (0.53, 0.78) to 0.86 (0.73, 0.99)] of PTB subtypes, respectively. At the same PM2.5 level, higher residential greenspace was associated with lower risks, and vice versa. All these associations were more pronounced in late pregnancy. Early PTB and PPROM were the main affected subtypes, and the main drivers in PM2.5 were black carbon and ammonium. CONCLUSIONS: Residential greenspace may mitigate the PTB risks due to PM2.5 exposure during pregnancy.

Association of Fine Particulate Matter and Its Components with Macrosomia: A Nationwide Birth Cohort Study of 336 Chinese Cities.

To examine the associations between macrosomia risk and exposure to fine particulate matter (PM2.5) and its chemical components during pregnancy, we collected birth records between 2010 and 2015 in mainland China from the National Free Preconception Health Examination Project and used satellite-based models to estimate concentrations of PM2.5 mass and five main components, namely, black carbon (BC), organic carbon (OC), nitrate (NO3-), sulfate (SO42-), and ammonium (NH4+). Associations between macrosomia risk and prenatal exposure to PM2.5 were examined by logistic regression analysis, and the sensitive subgroups were explored by stratified analyses. Of the 3,248,263 singleton newborns from 336 cities, 165,119 (5.1%) had macrosomia. Each interquartile range increase in concentration of PM2.5 during the entire pregnancy was associated with increased risk of macrosomia (odds ratio (OR) = 1.18; 95% confidence interval (CI), 1.17-1.20). Among specific components, the largest effect estimates were found on NO3- (OR = 1.36; 95% CI, 1.35-1.38) followed by OC (OR = 1.23; 95% CI, 1.22-1.24), NH4+ (OR = 1.22; 95% CI, 1.21-1.23), and BC (OR = 1.21; 95% CI, 1.20-1.22). We also that found boys, women with a normal or lower prepregnancy body mass index, and women with irregular or no folic acid supplementation experienced higher risk of macrosomia associated with PM2.5 exposure.

Lead exposure suppresses the Wnt3a/ß-catenin signaling to increase the quiescence of hematopoietic stem cells via reducing the expression of CD70 on bone marrow-resident macrophages.

Lead (Pb) is a heavy metal highly toxic to human health in the environment. The aim of this study was to investigate the mechanism of Pb impact on the quiescence of hematopoietic stem cells (HSC). WT C57BL/6 (B6) mice treated with 1250 ppm Pb via drinking water for 8 weeks had increased the quiescence of HSC in the bone marrow (BM), which was caused by the suppressed activation of the Wnt3a/ß-catenin signaling. Mechanically, a synergistic action of Pb and IFNγ on BM-resident macrophages (BM-Mφ) reduced their surface expression of CD70, which thereby dampened the Wnt3a/ß-catenin signaling to suppress the proliferation of HSC in mice. In addition, a joint action of Pb and IFNγ also suppressed the expression of CD70 on human Mφ to impair the Wnt3a/ß-catenin signaling and reduce the proliferation of human HSC purified from umbilical cord blood of healthy donors. Moreover, correlation analyses showed that the blood Pb concentration was or tended to be positively associated with the quiescence of HSC, and was or tended to be negatively associated with the activation of the Wnt3a/ß-catenin signaling in HSC in human subjects occupationally exposed to Pb. Collectively, these data indicate that an occupationally relevant level of Pb exposure suppresses the Wnt3a/ß-catenin signaling to increase the quiescence of HSC via reducing the expression of CD70 on BM-Mφ in both mice and humans.

Respiratory Effects of Traffic-Related Air Pollution: A Randomized, Crossover Analysis of Lung Function, Airway Metabolome, and Biomarkers of Airway Injury.

BACKGROUND: Exposure to traffic-related air pollution (TRAP) has been associated with increased risks of respiratory diseases, but the biological mechanisms are not yet fully elucidated. OBJECTIVES: Our aim was to evaluate the respiratory responses and explore potential biological mechanisms of TRAP exposure in a randomized crossover trial. METHODS: We conducted a randomized crossover trial in 56 healthy adults. Each participant was exposed to high- and low-TRAP exposure sessions by walking in a park and down a road with high traffic volume for 4 h in random order. Respiratory symptoms and lung function, including forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), the ratio of FEV1 to FVC, and maximal mid-expiratory flow (MMEF), were measured before and after each exposure session. Markers of 8-isoprostane, tumor necrosis factor-α (TNF-α), and ezrin in exhaled breath condensate (EBC), and surfactant proteins D (SP-D) in serum were also measured. We used linear mixed-effects models to estimate the associations, adjusted for age, sex, body mass index, meteorological condition, and batch (only for biomarkers). Liquid chromatography-mass spectrometry was used to profile the EBC metabolome. Untargeted metabolome-wide association study (MWAS) analysis and pathway enrichment analysis using mummichog were performed to identify critical metabolomic features and pathways associated with TRAP exposure. RESULTS: Participants had two to three times higher exposure to traffic-related air pollutants except for fine particulate matter while walking along the road compared with in the park. Compared with the low-TRAP exposure at the park, high-TRAP exposure at the road was associated with a higher score of respiratory symptoms [2.615 (95% CI: 0.605, 4.626), p=1.2×10-2] and relatively lower lung function indicators [-0.075L (95% CI: -0.138, -0.012), p=2.1×10-2] for FEV1 and -0.190L/s (95% CI: -0.351, -0.029; p=2.4×10-2) for MMEF]. Exposure to TRAP was significantly associated with changes in some, but not all, biomarkers, particularly with a 0.494-ng/mL (95% CI: 0.297, 0.691; p=9.5×10-6) increase for serum SP-D and a 0.123-ng/mL (95% CI: -0.208, -0.037; p=7.2×10-3) decrease for EBC ezrin. Untargeted MWAS analysis revealed that elevated TRAP exposure was significantly associated with perturbations in 23 and 32 metabolic pathways under positive- and negative-ion modes, respectively. These pathways were most related to inflammatory response, oxidative stress, and energy use metabolism. CONCLUSIONS: This study suggests that TRAP exposure might lead to lung function impairment and respiratory symptoms. Possible underlying mechanisms include lung epithelial injury, inflammation, oxidative stress, and energy metabolism disorders. https://doi.org/10.1289/EHP11139.

Long-Term Exposure to Fine Particulate Matter and Incidence of Esophageal Cancer: A Prospective Study of 0.5 Million Chinese Adults.

BACKGROUND & AIMS: Evidence is sparse and inconclusive on the association between long-term fine (≤2.5 µm) particulate matter (PM2.5) exposure and esophageal cancer. We aimed to assess the association of PM2.5 with esophageal cancer risk and compared the esophageal cancer risk attributable to PM2.5 exposure and other established risk factors. METHODS: This study included 510,125 participants without esophageal cancer at baseline from China Kadoorie Biobank. A high-resolution (1 × 1 km) satellite-based model was used to estimate PM2.5 exposure during the study period. Hazard ratios (HR) and 95% CIs of PM2.5 with esophageal cancer incidence were estimated using Cox proportional hazard model. Population attributable fractions for PM2.5 and other established risk factors were estimated. RESULTS: There was a linear concentration-response relationship between long-term PM2.5 exposure and esophageal cancer. For each 10-µg/m3 increase in PM2.5, the HR was 1.16 (95% CI, 1.04-1.30) for esophageal cancer incidence. Compared with the first quarter of PM2.5 exposure, participants in the highest quarter had a 1.32-fold higher risk for esophageal cancer, with an HR of 1.32 (95% CI, 1.01-1.72). The population attributable risk because of annual average PM2.5 concentration ≥35 µg/m3 was 23.3% (95% CI, 6.6%-40.0%), higher than the risks attributable to lifestyle risk factors. CONCLUSIONS: This large prospective cohort study of Chinese adults found that long-term exposure to PM2.5 was associated with an elevated risk of esophageal cancer. With stringent air pollution mitigation measures in China, a large reduction in the esophageal cancer disease burden can be expected.

Fine particulate matter and cardiorespiratory health in China: A systematic review and meta-analysis of epidemiological studies.

This review aimed to systematically summarize the epidemiological literature on the cardiorespiratory effects of PM2.5 published during the 13th Five-Year Plan period (2016-2020) in China. Original articles published between January 1, 2016 and June 30, 2021 were searched in PubMed, Web of Science, the China National Knowledge Internet Database and Wanfang Database. Random- or fixed-effects models were used to pool effect estimates where appropriate. Of 8558 records identified, 145 met the full eligibility criteria. A 10 µg/m³ increase in short-term PM2.5 exposure was significantly associated with increases of 0.70%, 0.86%, 0.38% and 0.96% in cardiovascular mortality, respiratory mortality, cardiovascular morbidity, and respiratory morbidity, respectively. The specific diseases with significant associations included stroke, ischemic heart disease, heart failure, arrhythmia, chronic obstructive pulmonary disease, pneumonia and allergic rhinitis. The pooled estimates per 10 µg/m³ increase in long-term PM2.5 exposure were 15.1%, 11.9% and 21.0% increases in cardiovascular, stroke and lung cancer mortality, and 17.4%, 11.0% and 4.88% increases in cardiovascular, hypertension and lung cancer incidence respectively. Adverse changes in blood pressure, heart rate variability, systemic inflammation, blood lipids, lung function and airway inflammation were observed for either short-term or long-term PM2.5 exposure, or both. Collectively, we summarized representative exposure-response relationships between short- and long-term PM2.5 exposure and a wide range of cardiorespiratory outcomes applicable to China. The magnitudes of estimates were generally smaller in short-term associations and comparable in long-term associations compared with those in developed countries. Our findings are helpful for future standard revisions and policy formulation. There are still some notable gaps that merit further investigation in China.

Association of air pollution with dementia: a systematic review with meta-analysis including new cohort data from China.

It remains unclear whether a total exposure to air pollution (AP) is associated with an increased risk of dementia. Little is known on the association in low- and middle-income countries. Two cohort studies in China (in Anhui cohort 1402 older adults aged ≥ 60 followed up for 10 years; in Zhejiang cohort 6115 older adults followed up for 5 years) were conducted to examine particulate matter - PM2.5 associated with all dementia and air quality index (AQI) with Alzheimer's disease, respectively. A systematic literature review and meta-analysis was performed following worldwide literature searched until May 20, 2020 to identify 15 population-based cohort studies examining the association of AP with dementia (or any specific type of dementia) through PubMed, MEDLINE, PsycINFO, SocINDEX, CINHAL, and CNKI. The cohort studies in China showed a significantly increased relative risk (RR) of dementia in relation to AP exposure; in Anhui cohort the adjusted RR was 2.14 (95% CI 1.00-4.56) in people with PM2.5 exposure at ≥ 64.5 µg/m3 versus <63.5 µg/m3 and in Zhejiang cohort the adjusted RR was 2.28 (1.07-4.87) in AQI>90 versus ≤ 80. The systematic review revealed that all 15 studies were undertaken in high income countries/regions, with inconsistent findings. While they had reasonably good overall quality of studies, seven studies did not adjust smoking in analysis and 13 did not account for depression. Pooling all eligible data demonstrated that dementia risk increased with the total AP exposure (1.13, 1.08-1.19). Data analysis of air pollutants showed that the RR significantly increased with PM2.5 (1.06, 1.03-1.10 in 2nd tertile exposure; 1.13, 1.07-1.19 in 3rd tertile versus 1st tertile), PM10 (1.05, 0.86-1.29; 1.62, 0.60-4.36), carbon monoxide (1.69, 0.72-3.93; 1.52, 1.35-1.71), nitrogen dioxide (1.06, 1.03-1.09; 1.18, 1.10-1.28) and nitrogen oxides (1.09, 1.04-1.15; 1.26, 1.13-1.41), but not ozone. Controlling air pollution and targeting on specific pollutants would reduce dementia globally.

Association of Long-term Exposure to Ambient Air Pollution With Cognitive Decline and Alzheimer's Disease-Related Amyloidosis.

BACKGROUND: Air pollution induces neurotoxic reactions and may exert adverse effects on cognitive health. We aimed to investigate whether air pollutants accelerate cognitive decline and affect neurobiological signatures of Alzheimer's disease (AD). METHODS: We used a population-based cohort from the Chinese Longitudinal Healthy Longevity Survey with 31,573 participants and a 10-year follow-up (5878 cognitively unimpaired individuals in Chinese Longitudinal Healthy Longevity Survey followed for 5.95 ± 2.87 years), and biomarker-based data from the Chinese Alzheimer's Biomarker and Lifestyle study including 1131 participants who underwent cerebrospinal fluid measurements of AD-related amyloid-ß (Aß) and tau proteins. Cognitive impairment was determined by education-corrected performance on the China-Modified Mini-Mental State Examination. Annual exposures to fine particulate matter (PM2.5), ground-level ozone (O3), and nitrogen dioxide (NO2) were estimated at areas of residence. Exposures were aggregated as 2-year averages preceding enrollments using Cox proportional hazards or linear models. RESULTS: Long-term exposure to PM2.5 (per 20 µg/m3) increased the risk of cognitive impairment (hazard ratio, 1.100; 95% CI: 1.026-1.180), and similar associations were observed from separate cross-sectional analyses. Exposures to O3 and NO2 yielded elevated risk but with nonsignificant estimates. Individuals exposed to high PM2.5 manifested increased amyloid burdens as reflected by cerebrospinal fluid-AD biomarkers. Moreover, PM2.5 exposure-associated decline in global cognition was partly explained by amyloid pathology as measured by cerebrospinal fluid-Aß42/Aß40, P-tau/Aß42, and T-tau/Aß42, with mediation proportions ranging from 16.95% to 21.64%. CONCLUSIONS: Long-term exposure to PM2.5 contributed to the development of cognitive decline, which may be partly explained by brain amyloid accumulation indicative of increased AD risk.

Lung cancer as adverse health effect by indoor radon exposure in China from 2000 to 2020: A systematic review and meta-analysis.

Indoor radon exposure is thought to be associated with adverse health effect as lung cancer. Lung cancer incidences in China have been the highest worldwide during the past two decades. It is important to quantitively address indoor radon exposure and its health effect, especially in countries like China. In this paper, we have conducted a meta-analysis based on indoor radon and its health effect studies from a systematic review between 2000 and 2020. A total of 8 studies were included for lung cancer. We found that the relative risk (RR) was 1.01 (95% CI: 1.01-1.02) per 10 Bq/m3 increase of indoor radon for lung cancer in China. The subgroup analysis found no significant difference between the conclusions from the studies from China and other regions. The health effect of indoor radon exposure is relatively consistent for the low-exposure and high-exposure groups in the subgroup analysis. With a better understanding of exposure level of indoor radon, the outcomes and conclusions of this study will provide supports for next phase of researches on estimation of environmental burden of disease by indoor radon exposures in countries like China.

Health effects of exposure to sulfur dioxide, nitrogen dioxide, ozone, and carbon monoxide between 1980 and 2019: A systematic review and meta-analysis.

The burden of disease attributed to the indoor exposure to sulfur dioxide (SO2 ), nitrogen dioxide (NO2 ), ozone (O3 ), and carbon monoxide (CO) is not clear, and the quantitative concentration-response relationship is a prerequisite. This is a systematic review to summarize the quantitative concentration-response relationships by screening and analyzing the polled effects of population-based epidemiological studies. After collecting literature published between 1980 and 2019, a total of 19 health outcomes in 101 studies with 182 health risk estimates were recruited. By meta-analysis, the leave-one-out sensitivity analysis and Egger's test for publication bias, the robust and reliable effects were found for SO2 (per 10 µg/m3 ) with chronic obstructive pulmonary diseases (COPD) (pooled relative risks [RRs] 1.016, 95% CI: 1.012-1.021) and cardiovascular diseases (CVD) (RR 1.012, 95%CI: 007-1.018), respectively. NO2 (per 10 µg/m3 ) had the pooled RRs for childhood asthma, preterm birth, lung cancer, diabetes, and COPD by 1.134 (1.084-1.186), 1.079 (1.007-1.157), 1.055 (1.010-1.101), 1.019 (1.009-1.029), and 1.016 (1.012-1.120), respectively. CO (per 1 mg/m3 ) was significantly associated with Parkinson's disease (RR 1.574, 95% CI: 1.069-2.317) and CVD (RR 1.024, 95% CI: 1.011-1.038). No robust effects were observed for O3 . This study provided evidence and basis for further estimation of the health burden attributable to the four gaseous pollutants.

Deficiency of interleukin-6 receptor ameliorates PM2.5 exposure-induced pulmonary dysfunction and inflammation but not abnormalities in glucose homeostasis.

BACKGROUND: Ambient fine particulate matter (PM2.5) exposure increases local and systemic interleukin-6 (IL-6). However, the pathogenic role of IL-6 signalling following PM2.5 exposure, particularly in the development of pulmonary dysfunction and abnormal glucose homeostasis, has hardly been investigated. RESULTS: In the study, IL-6 receptor (IL-6R)-deficient (IL-6R-/-) and wildtype littermate (IL-6R+/+) mice were exposed to concentrated ambient PM2.5 (CAP) or filtered air (FA), and their pulmonary and metabolic responses to these exposures were analyzed. Our results demonstrated that IL-6R deficiency markedly alleviated PM2.5 exposure-induced increases in lung inflammatory markers including the inflammation score of histological analysis, the number of macrophages in bronchoalveolar lavage fluid (BALF), and mRNA expressions of TNFα, IL-1ß and IL-6 and abnormalities in lung function test. However, IL-6R deficiency did not reduce the hepatic insulin resistance nor systemic glucose intolerance and insulin resistance induced by PM2.5 exposure. CONCLUSION: Our findings support the crucial role of IL-6 signalling in the development of pulmonary inflammation and dysfunction due to PM2.5 exposure but question the putative central role of pulmonary inflammation for the extra-pulmonary dysfunctions following PM2.5 exposure, providing a deep mechanistic insight into the pathogenesis caused by PM2.5 exposure.

Indoor formaldehyde levels in residences, schools, and offices in China in the past 30 years: A systematic review.

Exposure to formaldehyde causes a variety of adverse health outcomes, while the distributions of indoor formaldehyde in different building types are still not clear in China. In this study, based on the systematic review of previously published data and Monte Carlo simulation, we assessed geographical and temporal distributions of indoor formaldehyde concentrations in residences, schools, and offices across China. A total of 397 studies covered 34 provincial-level regions since 1986 were collected. The results showed that indoor formaldehyde concentrations in residences, schools, and offices in nationwide were decreasing over years due to the publishment of indoor air quality standards since 2002. During 2011 to 2015, the median concentrations of indoor formaldehyde in newly renovated residences, schools, and offices were 153 µg/m3 , 163 µg/m3 , and 94 µg/m3 , with an exceeding rate of 82%, 46%, and 91% considering a standard threshold of 100 µg/m3 at that time, while the exceeding rate was less than 5% for buildings that were renovated beyond one year. Our findings release the temporal trends and geographic distributions of indoor formaldehyde concentrations in residences, schools, and offices in China in the past 30 years, and provide basic data for the comprehensive evaluation of disease burden attributable to indoor formaldehyde exposure.

Mechanistic insights into the health benefits of fish-oil supplementation against fine particulate matter air pollution: a randomized controlled trial.

BACKGROUND: Dietary fish-oil supplementation might attenuate the associations between fine particulate matter (PM2.5) and subclinical biomarkers. However, the molecular mechanisms remain to be elucidated. This study aimed to explore the molecular mechanisms of fish-oil supplementation against the PM2.5-induced health effects. METHODS: We conducted a randomized, double-blinded, and placebo-controlled trial among healthy college students in Shanghai, China, from September 2017 to January 2018. A total of 70 participants from the Fenglin campus of Fudan University were included. We randomly assigned participants to either supplementation of 2.5-gram fish oil (n = 35) or sunflower-seed oil (placebo) (n = 35) per day and conducted four rounds of health measurements in the last two months of the trial. As a post hoc exploratory study, the present untargeted metabolomics analysis used remaining blood samples collected in the previous trial and applied a Metabolome-Wide Association Study framework to compare the effects of PM2.5 on the metabolic profile between the sunflower-seed oil and fish oil groups. RESULTS: A total of 65 participants completed the trial (34 of the fish oil group and 31 of the sunflower-seed oil group). On average, ambient PM2.5 concentration on the day of health measurements was 34.9 µg/m3 in the sunflower-seed oil group and 34.5 µg/m3 in the fish oil group, respectively. A total of 3833 metabolites were significantly associated with PM2.5 in the sunflower-seed oil group and 1757 in the fish oil group. Of these, 1752 metabolites showed significant between-group differences. The identified differential metabolites included arachidonic acid derivatives, omega-3 fatty acids, omega-6 fatty acids, and omega-9 fatty acids that were related to unsaturated fatty acid metabolism, which plays a role in the inflammatory responses. CONCLUSION: This trial suggests fish-oil supplementation could mitigate the PM2.5-induced inflammatory responses via modulating fatty acid metabolism, providing biological plausibility for the health benefits of fish-oil supplementation against PM2.5 exposure. TRIAL REGISTRATION: This study is registered at ClinicalTrails.gov (NCT03255187).

Indoor exposure levels and risk assessment of volatile organic compounds in residences, schools, and offices in China from 2000 to 2021: A systematic review.

The last two decades have witnessed rapid urbanization and economic growth accompanied by severe indoor air pollution of volatile organic compounds (VOCs) in China. However, indoor VOC pollution across China has not been well characterized and documented. This study is a systematic review of field measurements of eight target VOCs (benzene, toluene, xylenes, acetaldehyde, p-dichlorobenzene, butadiene, trichloroethylene, and tetrachloroethylene) in residences, offices, and schools in China from 2000 to 2021. The results show that indoor pollution of benzene, toluene, and xylenes has been more serious in China than in other countries. Spatiotemporal distribution shows lower indoor VOC levels in east and south-east regions and a declining trend from 2000 to 2021. Moving into a dwelling more than 1 year after decoration and improving ventilation could significantly reduce exposure to indoor VOCs. Reducing benzene exposure is urgently needed because it is associated with greater health risks (4.5 × 10-4 for lifetime cancer risk and 8.3 for hazard quotient) than any other VOCs. The present study enriches the database of indoor VOC levels and provides scientific evidence for improving national indoor air quality standards as well as estimating the attributable disease burden caused by VOCs in China.