Increased risk of preterm birth due to heat exposure during pregnancy: Exploring the mechanism of fetal physiology.

BACKGROUND: Heat exposure during pregnancy can increase the risk of preterm birth (PTB) through a range of potential mechanisms including pregnancy complications, hormone secretion and infections. However, current research mainly focuses on the effect of heat exposure on pathophysiological pathways of pregnant women, but ignore that that maternal heat exposure can also cause physiological changes to the fetus, which will affect the risk of PTB. OBJECTIVE: In this study, we aimed to explore the mediating role of fetal heart rate (FHR) in the relationship between maternal heat exposure and PTB incidence. METHODS: We assigned heat exposure to a multi-center birth cohort in China during 2015-2018, which included all 162,407 singleton live births with several times FHR measurements during the second and third trimesters. We examined the associations between heat exposure, FHR and PTB in the entire pregnancy, each trimester and the last gestational month. The inverse odds ratio-weighted approach applied to the Cox regression was used to identify the mediation effect of heat exposure on PTB and its clinical subtypes via FHR. FINDINGS: Exposure to heat significantly increased the risk of PTB during the third trimester and the entire pregnancy, hazard ratios and 95 % CIs were 1.266 (1.161, 1.379) and 1.328 (1.218, 1.447). Heat exposure during the third trimester and entire pregnancy increased FHR in the third trimester by 0.24 bpm and 0.14 bpm. The proportion of heat exposure mediated by FHR elevation on PTB and its subtype ranged from 3.68 % to 24.06 %, with the significant mediation effect found for both medically indicated PTB and spontaneous PTB. CONCLUSIONS: This study suggests that heat exposure during pregnancy has an important impact on fetal health, and FHR, as a surrogate marker of fetal physiology, may mediate the increased risk of PTB caused by extreme heat. Monitoring and managing physiological changes in the fetus would constitute a promising avenue to reduce adverse birth outcomes associated with maternal heat exposure.

Associations between long-term exposure to air pollution and kidney function utilizing electronic healthcare records: a cross-sectional study.

BACKGROUND: Chronic kidney disease (CKD) affects more than 38 million people in the United States, predominantly those over 65 years of age. While CKD etiology is complex, recent research suggests associations with environmental exposures. METHODS: Our primary objective is to examine creatinine-based estimated glomerular filtration rate (eGFRcr) and diagnosis of CKD and potential associations with fine particulate matter (PM2.5), ozone (O3), and nitrogen dioxide (NO2) using a random sample of North Carolina electronic healthcare records (EHRs) from 2004 to 2016. We estimated eGFRcr using the serum creatinine-based 2021 CKD-EPI equation. PM2.5 and NO2 data come from a hybrid model using 1 km2 grids and O3 data from 12 km2 CMAQ grids. Exposure concentrations were 1-year averages. We used linear mixed models to estimate eGFRcr per IQR increase of pollutants. We used multiple logistic regression to estimate associations between pollutants and first appearance of CKD. We adjusted for patient sex, race, age, comorbidities, temporality, and 2010 census block group variables. RESULTS: We found 44,872 serum creatinine measurements among 7,722 patients. An IQR increase in PM2.5 was associated with a 1.63 mL/min/1.73m2 (95% CI: -1.96, -1.31) reduction in eGFRcr, with O3 and NO2 showing positive associations. There were 1,015 patients identified with CKD through e-phenotyping and ICD codes. None of the environmental exposures were positively associated with a first-time measure of eGFRcr < 60 mL/min/1.73m2. NO2 was inversely associated with a first-time diagnosis of CKD with aOR of 0.77 (95% CI: 0.66, 0.90). CONCLUSIONS: One-year average PM2.5 was associated with reduced eGFRcr, while O3 and NO2 were inversely associated. Neither PM2.5 or O3 were associated with a first-time identification of CKD, NO2 was inversely associated. We recommend future research examining the relationship between air pollution and impaired renal function.

Effect of extreme high temperature on cognitive function at different time scales: A national difference-in-differences analysis.

BACKGROUND: Mounting evidence has demonstrated that high temperature was associated with adverse health outcomes, especially morbidity and mortality. Nonetheless, the impact of extreme high temperature on cognitive performance, which is the fundamental capacity for interpreting one's surroundings, decision-making, and acquiring new abilities, has not been thoroughly investigated. METHODS: We aimed to assess associations between extreme high temperature at different time scales and poor cognitive function. We used longitudinal survey data from the three waves of data from China Family Panel Study, providing an 8-year follow-up of 53,008 participants from China. We assessed temperature and extreme high temperature exposure for each participant based on the residential area and date of cognitive test. We defined the proportion of days/hours above 32 °C as the metric of the exposure to extreme high temperature. Then we used generalized additive model and difference-in-differences approach to explore the associations between extreme high temperature and cognitive function. RESULTS: Our results demonstrated that either acute exposure or long-term exposure to extreme high temperature was associated with cognitive decline. At hourly level, 0-1 hour acute exposure to extreme high temperature would induce -0.93 % (95 % CI: -1.46 %, -0.39 %) cognitive change. At annual level, 10 percentage point increase in the hours proportion exceeding 32 °C in the past two years induced -9.87 % (95 % CI: -13.99 %, -5.75 %) cognitive change. Furthermore, subgroup analyses indicated adaptation effect: for the same 10 percentage increase in hours proportion exceeding 32 °C, people in warmer areas had cognitive change of -6.41 % (-11.22 %, -1.61 %), compared with -15.30 % (-21.07 %, -9.53 %) for people in cool areas. CONCLUSION: Our results demonstrated that extreme high temperature was associated with reduced cognitive function at hourly, daily and annual levels, warning that people should take better measures to protect the cognitive function in the context of climate change.

Heat stroke-induced cerebral cortex nerve injury by mitochondrial dysfunction: A comprehensive multi-omics profiling analysis.

In recent years, global warming has led to frequent instances of extremely high temperatures during summer, arousing significant concern about the adverse effects of high temperature. Among these, heat stroke is the most serious, which has detrimental effects on the all organs of human body, especially on brain. However, the comprehensive pathogenesis leading to brain damage remains unclear. In this study, we constructed a mouse model of heat stroke and conducted multi-omics profiling to identify relevant pathogenesis induced by heat stroke. The mice were placed in a constant temperature chamber at 42 °C with a humidity of 50 %, and the criteria for success in modeling were that the rectal temperature reached 42 °C and that the mice were trembling. Then the mice were immediately taken out for further experiments. Firstly, we conducted cFos protein localization and identified the cerebral cortex, especially the anterior cingulate cortex as the region exhibiting the most pronounced damage. Secondly, we performed metabolomics, transcriptomics, and proteomics analysis on cerebral cortex. This multi-omics investigation unveiled noteworthy alterations in proteins and metabolites within pathways associated with neurotransmitter systems, heatstroke-induced mitochondrial dysfunction, encompassing histidine and pentose phosphate metabolic pathways, as well as oxidative stress. In addition, the cerebral cortex exhibited pronounced Reactive Oxygen Species (ROS) production, alongside significant downregulation of the mitochondrial outer membrane protein Tomm40 and mitochondrial permeability transition pore, implicating cerebral cortex mitochondrial dysfunction as the primary instigator of neural impairment. This study marks a significant milestone as the first to employ multi-omics analysis in exploring the molecular mechanisms underlying heat stroke-induced damage in cerebral cortex neurons. It comprehensively identifies all potentially impacted pathways by heat stroke, laying a solid foundation for ensuing research endeavors. Consequently, this study introduces a fresh angle to clinical approaches in heatstroke prevention and treatment, as well as establishes an innovative groundwork for shaping future-forward environmental policies.

Heat exposure intervention, anxiety level, and multi-omic profiles: A randomized crossover study.

BACKGROUND: Climate change has led to the frequent occurrence of high-temperature weather, which has various adverse effects on health, ranging from blood metabolism to systemic organ function. In particular, the sequelae of heat stress injury in most people are related to the nervous system. However, the mechanisms between heat stress and mental health conditions, especially heat stress and anxiety, remain unclear. OBJECTIVE: We attempted to elucidate the effect of heat exposure intervention on anxiety levels in the population and its mechanism. METHODS: We first carried out a randomized controlled trial in 20 college students in Beijing, China, to observe the results of the effects of heat exposure intervention on human anxiety. Then, we collected blood samples before and after heat exposure experiment and used metabolomic and transcriptomic approaches to quantify serum metabolites and ELISA measurements to explore the underlying mechanisms. RESULTS: We found that even 1.5-hour heat exposure intervention significantly increased anxiety levels. Heat stress-induced anxiety was mediated by the activation of the HPA axis, inflammation, oxidative stress, and subsequently unbalanced neurotransmitters. Metabolites such as BDNF, GABA, and glucocorticoids released by the adrenal glands are biomarkers of heat stress-induced anxiety. CONCLUSIONS: We have demonstrated a causal link between heat stress and anxiety, explored possible biological pathway between heat stress and anxiety. Heat stress can cause the activation of the HPA axis and lead to changes in the body's metabolism, resulting in a series of changes such as inflammation and oxidative stress, leading to anxiety. This study reveals hidden health cost of climate change that has been underexplored, and also reminds us the importance of immediate climate actions.

The joint effect and hemodynamic mechanism of PA and PM2.5 exposure on cognitive function: A randomized controlled trial study.

BACKGROUND: While PM2.5 has been shown to impair cognitive function, physical activity (PA) is known to enhance it. Nonetheless, considering the increased inhalation of PM2.5 during exercise, the potential of PA to counteract the detrimental effects of PM2.5, along with the underlying hemodynamic mechanisms, remains uncertain. METHODS: We conducted a double-blinded, randomized controlled trial among healthy young adults in Beijing, China. Ninety-three participants were randomly allocated to groups experiencing different intensities of PA interventions, and either subjected to purified or unpurified air conditions. Cognitive function was measured by the Color-Word Matching Stroop task, and the hemodynamic response was measured using functional near-infrared spectroscopy during participants performed the Stroop task both before and after the intervention. Linear mixed-effect models were used to estimate the impact of PA and PM2.5 on cognitive function and hemodynamic response. RESULTS: The reaction time for congruent and incongruent Stroop tasks improved by - 80.714 (95% CI: -136.733, -24.695) and - 105.843 (95% CI: -188.6, -23.085) milliseconds after high-intensity interval training (HIIT) intervention. PM2.5 and HIIT had interaction effects on cognition, such that every 1 µg/m3 increase in PM2.5 attenuated the benefits of HIIT on reaction time by 2.231 (95% CI: 0.523, 3.938) and 3.305 (95% CI: 0.791, 5.819) milliseconds for congruent and incongruent Stroop tasks. Moreover, we divided participants into high and low PM2.5 exposure groups based on average PM2.5 concentration (32.980 µg/m3), and found that HIIT intervention in high PM2.5 concentration led to 69.897 (95% CI: 9.317, 130.476) and 99.269 (95% CI: 10.054, 188.485) milliseconds increased in the reaction time of congruent and incongruent Stroop, compared with the control group among low PM2.5. Furthermore, we found a significant interaction effects of PM2.5 and moderate-intensity continuous training (MICT) on the middle frontal gyrus (MFG) and dorsolateral superior frontal gyrus (DLPFC). PM2.5 and HIIT had a significant interaction effect on the DLPFC. CONCLUSIONS: HIIT improved cognitive function, but the cognitive benefits of HIIT were attenuated or even reversed under high PM2.5 exposure. The activation of the DLPFC and MFG could serve as hemodynamic mechanisms to explain the joint effect of PA and PM2.5.

Leisure-time physical activity mitigated the cognitive effect of PM2.5 and PM2.5 components exposure: Evidence from a nationwide longitudinal study.

BACKGROUND: Exposure to fine particulate matter (PM2.5) impairs cognition, while physical activity (PA) improves cognitive function. However, whether taking PA with PM2.5 exposure is still beneficial to cognition remains unknown. METHODS: We utilized national representative longitudinal data from the China Family Panel Study (CFPS), comprising a total sample of 108,099 from 2010 to 2018 in three waves. Cognitive performance and leisure-time PA were measured using the standard cognitive module and Godin-Shephard Leisure-Time Physical Activity Questionnaire. Gridded overall PM2.5 and major chemical components of PM2.5 were estimated using a two-stage machine learning model and matched to each participant based on their residential location. Mixed-effect models and difference-in-difference models were employed to investigate the individual and joint effects of total PM2.5, PM2.5 components, and leisure-time PA on cognition. RESULTS: Every 1 µg/m3 increase in PM2.5 was associated with a -0.035 (95% confidence interval [CI] = -0.052, -0.018) point change in cognitive score. All PM2.5 components exhibited negative associations with cognitive change, with black carbon (BC) contributing the most significant cognitive decline (ß = -1.025, 95% CI = -1.367, -0.683). Every one-time (or one-hour) increase in leisure-time PA frequency (or PA time) per week was associated with an increase in cognitive score by 0.576 (0.270) points (PA frequency: 95% CI = 0.544, 0.608, PA time: 95% CI = 0.248, 0.293). PA frequency (ß = -0.005, 95% CI = -0.006, -0.003) and PA time (ß = -0.002, 95% CI = -0.003, -0.001) exhibited interactive effects with PM2.5. Increased PA frequency and time were more beneficial to cognitive function in the low PM2.5 exposure group compared to those exposed to high PM2.5 levels. Moreover, relative to lower PM2.5 exposure, the cognitive benefits of physically active individuals with higher PM2.5 exposure were attenuated but still improved cognition when compared to those with no PA. CONCLUSION: Engaging in leisure-time PA provides cognitive benefits even under PM2.5 exposure, although PM2.5 exposure attenuates these benefits. Among all PM2.5 components, BC demonstrated the most significant cognitive hazard and interaction with leisure-time PA. Promoting PA as a preventive measure may offer a cost-effective and convenient strategy to mitigate the negative impact of PM2.5 exposure on cognition. There is no excuse to avoid PA under PM2.5 exposure, as its cognitive benefits persist even in polluted environments.

Climate Penalty on Air Pollution Abated by Anthropogenic Emission Reductions in the United States.

Climate change poses direct and indirect threats to public health, including exacerbating air pollution. However, how a warmer temperature deteriorates air quality, known as the "climate penalty" effect, remains highly uncertain in the United States, particularly under rapid reduction in anthropogenic emissions. Here we examined the sensitivity of surface-level fine particulate matter (PM2.5) and ozone (O3) to summer temperature anomalies in the contiguous US and their decadal changes using high-resolution datasets generated by machine learning models. Our findings demonstrate that, in the eastern US, efficient emission control strategies have significantly reduced the climate penalty effects on PM2.5 and O3, lowering the associated population exposure. In contrast, summer and annual PM2.5 in the western US became more sensitive to temperature, highlighting the urgent need for the management and mitigation of worsening wildfires. Our results have important implications for air quality management and risk assessments of future climate change.

Associations between long-term fine particulate matter exposure and hospital procedures in heart failure patients.

BACKGROUND: Ambient fine particulate matter (PM2.5) contributes to global morbidity and mortality. One way to understand the health effects of PM2.5 is by examining its impact on performed hospital procedures, particularly among those with existing chronic disease. However, such studies are rare. Here, we investigated the associations between annual average PM2.5 and hospital procedures among individuals with heart failure. METHODS: Using electronic health records from the University of North Carolina Healthcare System, we created a retrospective cohort of 15,979 heart failure patients who had at least one of 53 common (frequency > 10%) procedures. We used daily modeled PM2.5 at 1x1 km resolution to estimate the annual average PM2.5 at the time of heart failure diagnosis. We used quasi-Poisson models to estimate associations between PM2.5 and the number of performed hospital procedures over the follow-up period (12/31/2016 or date of death) while adjusting for age at heart failure diagnosis, race, sex, year of visit, and socioeconomic status. RESULTS: A 1 µg/m3 increase in annual average PM2.5 was associated with increased glycosylated hemoglobin tests (10.8%; 95% confidence interval = 6.56%, 15.1%), prothrombin time tests (15.8%; 95% confidence interval = 9.07%, 22.9%), and stress tests (6.84%; 95% confidence interval = 3.65%, 10.1%). Results were stable under multiple sensitivity analyses. CONCLUSIONS: These results suggest that long-term PM2.5 exposure is associated with an increased need for diagnostic testing on heart failure patients. Overall, these associations give a unique lens into patient morbidity and potential drivers of healthcare costs linked to PM2.5 exposure.

The effect of exercise on cerebral blood flow and executive function among young adults: a double-blinded randomized controlled trial.

Studies have demonstrated that exercise benefits executive function. However, it remains unclear which type of exercise is optimal for preserving executive function among young adults and the cerebral blood flow (CBF) mechanisms that underlie exercise-induced cognitive benefits. Therefore, this study aims to compare the intervention effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on executive function and the CBF mechanism. This was a double-blinded, randomized, controlled trial study conducted between October 2020 and January 2021 (ClinicalTrials.gov identifier: NCT04830059). Ninety-three healthy young adults (25.23 ± 2.18 years old; 49.82% male) were randomized into the HIIT (N = 33), MICT (N = 32), and control (N = 28) groups. Participants in exercise groups were guided to perform 40 min of HIIT and MICT three times a week for 12 weeks, while the control group received health education for the same period. The primary outcomes, changes in executive function assessed by the trail-making test (TMT), and CBF measured by transcranial Doppler flow analyzer (EMS-9WA), were evaluated before and after the interventions. The time taken to complete the TMT task improved significantly in the MICT group compared to the control group [ß = -10.175, 95%, confidence interval (CI) = -20.320, -0.031]. Additionally, the MICT group showed significant improvements in the pulsatility index (PI) (ß = 0.120, 95% CI = 0.018, 0.222), resistance index (RI) (ß = 0.043, 95% CI = 0.005, 0.082), and peak-systolic/end-diastolic velocity (S/D) (ß = 0.277, 95% CI = 0.048, 0.507) of CBF compared to the control group. The time taken to complete the TMT was associated with the velocity of peak-systolic (F = 5.414, P = 0.022), PI (F = 4.973, P = 0.012), and RI (F = 5.845, P = 0.006). Furthermore, the accuracy of TMT was associated with PI (F = 4.797, P = 0.036), RI (F = 5.394, P = 0.024), and S/D (F = 4.312, P = 0.05) of CBF. A 12-week MICT intervention improved CBF and executive function more effectively than HIIT among young adults. Furthermore, the findings suggest that CBF was one of the potential mechanisms underlying the cognitive benefits of exercise in young people. These results provide practical evidence supporting the promotion of regular exercise to maintain executive function and improve brain health.

Intermediate and long-term exposure to air pollution and temperature and the extracellular microRNA profile of participants in the normative aging study (NAS).

BACKGROUND: The molecular effects of intermediate and long-term exposure to air pollution and temperature, such as those on extracellular microRNA (ex-miRNA) are not well understood but may have clinical consequences. OBJECTIVES: To assess the association between exposure to ambient air pollution and temperature and ex-miRNA profiles. METHODS: Our study population consisted of 734 participants in the Normative Aging Study (NAS) between 1999 and 2015. We used high-resolution models to estimate four-week, eight-week, twelve-week, six-month, and one-year moving averages of PM2.5, O3, NO2, and ambient temperature based on geo-coded residential addresses. The outcome of interest was the extracellular microRNA (ex-miRNA) profile of each participant over time. We used a longitudinal quantile regression approach to estimate the association between the exposures and each ex-miRNA. Results were corrected for multiple comparisons and ex-miRNAs that were still significantly associated with the exposures were further analyzed using KEGG pathway analysis and Ingenuity Pathway Analysis. RESULTS: We found 151 significant associations between levels of PM2.5, O3, NO2, and ambient temperature and 82 unique ex-miRNAs across multiple quantiles. Most of the significant results were associations with intermediate-term exposure to O3, long-term exposure to PM2.5, and both intermediate and long-term exposure to ambient temperature. The exposures were most often associated with the 75th and 90th percentile of the outcomes. Pathway analyses of significant ex-miRNAs revealed their involvement in biological pathways involving cell function and communication as well as clinical diseases such as cardiovascular disease, respiratory disease, and neurological disease. CONCLUSION: Our results show that intermediate and long-term exposure to all our exposures of interest were associated with changes in the ex-miRNA profile of study participants. Further studies on environmental risk factors and ex-miRNAs are warranted.

Associations between short-term exposure to PM2.5, NO2 and O3 pollution and kidney-related conditions and the role of temperature-adjustment specification: A case-crossover study in New York state.

Epidemiologic evidence on the relationship between air pollution and kidney disease remains inconclusive. We evaluated associations between short-term exposure to PM2.5, NO2 and O3 and unplanned hospital visits for seven kidney-related conditions (acute kidney failure [AKF], urolithiasis, glomerular diseases [GD], renal tubulo-interstitial diseases, chronic kidney disease, dysnatremia, and volume depletion; n = 1,209,934) in New York State (2007-2016). We applied a case-crossover design with conditional logistic regression, controlling for temperature, dew point temperature, wind speed, and solar radiation. We used a three-pollutant model at lag 0-5 days of exposure as our main model. We also assessed the influence of model adjustment using different specifications of temperature by comparing seven temperature metrics (e.g., dry-bulb temperature, heat index) and five intraday temperature measures (e.g., daily mean, daily minimum, nighttime mean), according to model performance and association magnitudes between air pollutants and kidney-related conditions. In our main models, we adjusted for daytime mean outdoor wet-bulb globe temperature, which showed good model performance across all kidney-related conditions. We observed the odds ratios (ORs) for 5 µg/m3 increase in daily mean PM2.5 to be 1.013 (95% confidence interval [CI]: 1.001, 1.025) for AKF, 1.107 (95% CI: 1.018, 1.203) for GD, and 1.027 (95% CI: 1.015, 1.038) for volume depletion; and the OR for 5 ppb increase in daily 1-hour maximum NO2 to be 1.014 (95% CI; 1.008, 1.021) for AKF. We observed no associations with daily 8-hour maximum O3 exposure. Association estimates varied by adjustment for different intraday temperature measures: estimates adjusted for measures with poorer model performance resulted in the greatest deviation from estimates adjusted for daytime mean, especially for AKF and volume depletion. Our findings indicate that short-term exposure to PM2.5 and NO2 is a risk factor for specific kidney-related conditions and underscore the need for careful adjustment of temperature in air pollution epidemiologic studies.

Long-term exposure to fine particulate matter and cardiovascular disease: The mitigation role of environmental concerns.

Although it is widely acknowledged that environmental concerns can reduce PM2.5 pollution, few studies have empirically estimated whether environmental concerns could bring health benefits by mitigating PM2.5 pollution. Here, we quantified government and media environmental concerns with text-mining algorithm, matched with cohort data along with high-resolution gridded PM2.5 data. Accelerated failure time model and mediation model were used to explore the association between PM2.5 exposure and onset time to cardiovascular events, and the mitigation effect of environmental concerns. Every 1 µg/m3 increase in PM2.5 exposure was associated with shortened time to stroke and heart problem, with time ratios of 0.9900 and 0.9986, respectively. Each 1 unit increase in government and media environmental concerns, as well as their synergistic effect decreased PM2.5 pollution by 0.32 %, 0.25 % and 0.46 %, respectively; and decrease PM2.5 resulted in prolonged onset time to cardiovascular events. Mediation analysis revealed that reduced PM2.5 mediated up to 33.55 % of the association between environmental concerns and onset time to cardiovascular events, suggesting that other mediation pathways were also possible. Associations of PM2.5 exposure and environmental concerns with stroke and heart problem were similar in different subgroups. Overall, environmental concerns reduce risks of cardiovascular disease by mitigating PM2.5 pollution and other pathways in a real-world data set. This study provides insights for low-and-middle-income countries to address air pollution and improve health co-benefit.

Long-term air pollution exposure and diabetes risk in American older adults: A national secondary data-based cohort study.

Type 2 diabetes is a major public health concern. Several studies have found an increased diabetes risk associated with long-term air pollution exposure. However, most current studies are limited in their generalizability, exposure assessment, or the ability to differentiate incidence and prevalence cases. We assessed the association between air pollution and first documented diabetes occurrence in a national U.S. cohort of older adults to estimate diabetes risk. We included all Medicare enrollees 65 years and older in the fee-for-service program, part A and part B, in the contiguous United States (2000-2016). Participants were followed annually until the first recorded diabetes diagnosis, end of enrollment, or death (264, 869, 458 person-years). We obtained annual estimates of fine particulate matter (PM2.5), nitrogen dioxide (NO2), and warm-months ozone (O3) exposures from highly spatiotemporally resolved prediction models. We assessed the simultaneous effects of the pollutants on diabetes risk using survival analyses. We repeated the models in cohorts restricted to ZIP codes with air pollution levels not exceeding the national ambient air quality standards (NAAQS) during the study period. We identified 10, 024, 879 diabetes cases of 41, 780, 637 people (3.8% of person-years). The hazard ratio (HR) for first diabetes occurrence was 1.074 (95% CI 1.058; 1.089) for 5 µg/m3 increase in PM2.5, 1.055 (95% CI 1.050; 1.060) for 5 ppb increase in NO2, and 0.999 (95% CI 0.993; 1.004) for 5 ppb increase in O3. Both for NO2 and PM2.5 there was evidence of non-linear exposure-response curves with stronger associations at lower levels (NO2 ≤ 36 ppb, PM2.5 ≤ 8.2 µg/m3). Furthermore, associations remained in the restricted low-level cohorts. The O3-diabetes exposure-response relationship differed greatly between models and require further investigation. In conclusion, exposures to PM2.5 and NO2 are associated with increased diabetes risk, even when restricting the exposure to levels below the NAAQS set by the U.S. EPA.

Short-term air pollution and temperature exposure and changes in the extracellular microRNA profile of Normative Aging Study (NAS) participants.

BACKGROUND: While the health effects of air pollution and temperature are widely studied, the molecular effects are poorly understood. Extracellular microRNAs (ex-miRNAs) have the potential to serve as diagnostic or prognostic biomarkers and/or to act as intercellular signaling molecules that mediate the effects of environmental exposures on health outcomes. METHODS: We examined the relationship between short-term exposure to air pollution and ambient temperature and the ex-miRNA profiles of participants in the Normative Aging Study (NAS) from 1999 to 2015. Our exposures were defined as same-day, two-day, three-day, one-week, two-week, and three-week moving averages of PM2.5, NO2, O3, and temperature which were derived from high-resolution spatio-temporal models. The ex-miRNA profiles of the subjects were obtained during follow-up visits. We analyzed the data using a longitudinal quantile regression model adjusted for individual covariates, batch effects, and time trends. We adjusted for multiple comparisons using a false discovery rate (FDR) correction. Ex-miRNAs that were significantly associated with exposures were further investigated using pathway analyses. RESULTS: We found that all the examined exposures were associated with changes in ex-miRNA profiles in our study, particularly PM2.5 which was responsible for most of the statistically significant results. We found 110 statistically significant exposure-outcome relationships that revealed associations with the levels of 52 unique ex-miRNAs. Pathway analyses showed these ex-miRNAs have been linked to target mRNAs, genes, and biological mechanisms that could affect virtually every organ system, and as such may be linked to multiple clinical disease presentations such as cardiovascular disease, respiratory disease, and neurological disease. CONCLUSIONS: Air pollution and temperature exposures were significantly associated with alterations in the ex-miRNA profiles of NAS subjects with possible biological consequences.

Impact of ground-level ozone exposure on sleep quality and electroencephalogram patterns at different time scales.

Ozone exposure is associated with various adverse health outcomes, but its impact on sleep quality is uncertain. Here we assessed the causal effect of long-term (yearly and monthly) exposure to ozone on nocturnal workday sleep time in a national representative sample from the China Family Panel Study, using a difference-in-differences approach. We further followed ninety healthy Chinese young adults four times in four seasons from September 2020 to June 2021, measured their daily sleep architecture using accelerometers, ascertained daily ozone exposure, recorded 5-min eye-closed resting-state electroencephalogram (EEG) signals at the last day of each one-week-long measurement session, and explored the effect of ozone exposure on objectively-measured sleep architecture. In the national sample, we found that every 1 interquartile range (IQR) µg/m3 increase in yearly and monthly ozone exposure was causally associated with 7.31 (p = 0.0039) and 4.19 (p = 0.040) minutes decline in nocturnal workday sleep time; the dose-response curve represented a quasi-linear pattern with no safety threshold, and plateaued at higher concentrations. In the small-scale study with objectively-measured sleep architecture, we found that every 1 IQR µg/m3 increase in the weekly ozone exposure was associated with 5.33 min decrease in night-time total sleep time (p = 0.031), 1.63 percentage points decrease in sleep efficiency (p < 0.001), 1.99 min increase in sleep latency (p = 0.0070), and 5.34 min increase in wake after sleep onset time (p = 0.0016) in a quasi-linear pattern. Notably, we found the accumulating trend of ozone exposure on sleep quality during both the short-term and long-term periods. We also found that short-term ozone exposure was associated with altered EEG patterns, mediated by sleep quality. This study indicates that long-term and short-term ozone exposures have negative and accumulating impacts on sleep quality and might impair brain functioning. More hidden health burdens of ozone are worth exploring.

Causal effects of prenatal and chronic PM2.5 exposures on cognitive function.

Growing evidence indicated an association between PM2.5 exposure and cognitive function, but the causal effect and the cognitive effect of prenatal PM2.5 exposure remain elusive. We obtained 15,099 subjects from a nationally representative sample of China and measured their cognitive performance. We ascertained subjects' prenatal PM2.5 exposure and chronic PM2.5 exposure of the recent two years. Using this national sample, we found that PM2.5 exposure during the mid- to late-pregnancy was significantly associated with declined cognition and income; chronic PM2.5 exposure was also independently associated with cognition and income measured at adulthood with greater magnitude. Negative effect modification was observed between prenatal and chronic PM2.5 exposure. Instrumental variable approach and difference-in-difference study verified causal effects: every 1 µg/m3 increase in prenatal and chronic PM2.5 exposures were causally associated with -0.22% (-0.38%, -0.06%) and -0.17% (-0.31%, -0.03%) changes in cognitive function, respectively. People with low cognition and low income were more vulnerable to PM2.5 exposure with greater cognitive and income decline. In the future, although China's improved air quality continues to benefit people and reduce cognitive decline induced by chronic PM2.5 exposure, high prenatal PM2.5 exposure will continue to hurt the overall cognition of Chinese population, since in total 360 million people were born during the 2000-2020 polluted era. Prenatal PM2.5-induced cognitive decline would remain largely unchanged before 2050 and gradually reduce after 2065, regardless of environmental policy scenarios. The long-lasting cognitive impact of PM2.5 is worth considering while enacting environmental policies.

Associations between long-term air pollution exposure and the incidence of cardiovascular diseases among American older adults.

BACKGROUND & AIM: Numerous studies have linked air pollution with cardiovascular diseases. Fewer studies examined the associations at low concentration levels or assessed potential modifiers. Some investigations only examined hospitalizations, which can miss incident cases. This study aims to address these gaps through a nationwide cohort study of Medicare enrollees. METHODS: Our study cohort comprise all Medicare enrollees (≥65 years old) continuously enrolled in the fee-for-service program and both Medicare part A and B across the contiguous U.S. from 2000 to 2016. We examined the associations of population-weighted ZIP code-level annual average PM2.5, NO2, and warm-season O3 (May-October), with the first diagnoses of atrial fibrillation (AF), congestive heart failure (CHF), and stroke. We fit multi-pollutant Cox proportional hazards models adjusted for individual demographic characteristics and area-level covariates. We further examined these associations at low pollutant concentration levels and the potential effect modifications by race/ethnicity and comorbidities (diabetes, hypertension, hyperlipidemia). RESULTS: Elevated PM2.5 and NO2 levels were associated with increased incidence of AF, CHF, and stroke. For each 1 µg/m3 increase in annual PM2.5, hazard ratios (HRs) were 1.0059 (95%CI: 1.0054-1.0064), 1.0260 (95%CI: 1.0256-1.0264), and 1.0279 (95%CI: 1.0274-1.0284), respectively. For each1 ppb increase in annual NO2, HRs are 1.0057 (95%CI: 1.0056-1.0059), 1.0112 (95%CI: 1.0110-1.0113), and 1.0095 (95%CI: 1.0093-1.0096), respectively. For warm-season O3, each 1 ppb increase was associated with increased incidence of CHF (HR=1.0035, 95%CI: 1.0033-1.0037) and stroke (HR=1.0026, 95%CI: 1.0023-1.0028). Larger magnitudes of HRs were observed when restricted to pollutants levels lower than NAAQS standards. Generally higher risks were observed for Black people and diabetics. CONCLUSIONS: Long-term exposure to PM2.5, NO2, and warm-season O3 were associated with increased incidence of cardiovascular diseases, even at low pollutant concentration levels. Black people and people with diabetes were found to be vulnerable populations.

Short-term PM2.5 exposure and cognitive function: Association and neurophysiological mechanisms.

BACKGROUND: Although converging evidence has demonstrated that exposure to fine particulate matter (PM2.5) caused adverse effects on brain structure and cognitive function, the association between the short-term exposure to PM2.5 and cognition dysfunction remained underexplored, especially possible neurophysiological mechanisms. METHODS: We conducted a longitudinal observational study with four repeated measurement sessions among 90 young adults from September 2020 to June 2021. During each measurement session, we measured participants' personal-level air pollution exposure for one week with portable monitors, followed by executive function assessment and electrophysiological signal recording at an assessment center. Standard Stroop color-word test was used accompanied with electroencephalogram (EEG) recording to assess performance on executive function. We used linear mixed-effect model with lagged values of PM2.5 levels to analyze the association between PM2.5 exposure and changes in executive function, and mediation analysis to investigate mediation effect by EEG signal. RESULTS: Adjusted mixed-effect models demonstrated that elevated PM2.5 exposure three days prior to cognitive assessment (lag-3) was associated with (1) declined performance in both congruent and incongruent tasks in Stroop test, (2) reduced lower and upper alpha event-related desynchronization (ERD) during 500-1000 ms after stimuli, both indicating impaired executive control. Lower and upper alpha ERD also mediated observed associations between short-term PM2.5 exposure and executive function. No significant associations were found between short-term PM2.5 exposure or aperiodic exponents in tonic and phasic states, or periodic alpha oscillations in tonic state. CONCLUSION: Our results provided evidence that short-term PM2.5 exposure was associated with executive dysfunction. Reduced alpha ERD was likely to be the underlying pathway through which PM2.5 induced adverse effects on neuron activities during cognitive tasks.

Associations between long-term exposures to airborne PM2.5 components and mortality in Massachusetts: mixture analysis exploration.

BACKGROUND: Numerous studies have documented PM2.5's links with adverse health outcomes. Comparatively fewer studies have evaluated specific PM2.5 components. The lack of exposure measurements and high correlation among different PM2.5 components are two limitations. METHODS: We applied a novel exposure prediction model to obtain annual Census tract-level concentrations of 15 PM2.5 components (Zn, V, Si, Pb, Ni, K, Fe, Cu, Ca, Br, SO42-, NO3-, NH4+, OC, EC) in Massachusetts from 2000 to 2015, to which we matched geocoded deaths. All non-accidental mortality, cardiovascular mortality, and respiratory mortality were examined for the population aged 18 or over. Weighted quantile sum (WQS) regression models were used to examine the cumulative associations between PM2.5 components mixture and outcomes and each component's contributions to the cumulative associations. We have fit WQS models on 15 PM2.5 components and a priori identified source groups (heavy fuel oil combustion, biomass burning, crustal matter, non-tailpipe traffic source, tailpipe traffic source, secondary particles from power plants, secondary particles from agriculture, unclear source) for the 15 PM2.5 components. Total PM2.5 mass analysis and single component associations were also conducted through quasi-Poisson regression models. RESULTS: Positive cumulative associations between the components mixture and all three outcomes were observed from the WQS models. Components with large contribution to the cumulative associations included K, OC, and Fe. Biomass burning, traffic emissions, and secondary particles from power plants were identified as important source contributing to the cumulative associations. Mortality rate ratios for cardiovascular mortality were of greater magnitude than all non-accidental mortality and respiratory mortality, which is also observed in cumulative associations estimated from WQS, total PM2.5 mass analysis, and single component associations. CONCLUSION: We have found positive associations between the mixture of 15 PM2.5 components and all non-accidental mortality, cardiovascular mortality, and respiratory mortality. Among these components, Fe, K, and OC have been identified as having important contribution to the cumulative associations. The WQS results also suggests potential source effects from biomass burning, traffic emissions, and secondary particles from power plants.