Plasma metabolomic signature of healthy lifestyle, structural brain reserve and risk of dementia.

Although the association between healthy lifestyle and dementia risk has been documented, the relationship between a metabolic signature indicative of healthy lifestyle and dementia risk and the mediating role of structural brain impairment remain unknown. We retrieved 136 628 dementia-free participants from UK Biobank. Elastic net regression was used to obtain a metabolic signature that represented lifestyle behaviours. Cox proportional hazard models were fitted to explore the associations of lifestyle-associated metabolic signature with incident dementia. Causal associations between identified metabolites and dementia were investigated using Mendelian randomization. Mediation analysis was also conducted to uncover the potential mechanisms involving 19 imaging-derived phenotypes (brain volume, grey matter volume, white matter volume and regional grey matter volumes). During a follow-up of 12.55 years, 1783 incident cases of all-cause dementia were identified, including 725 cases of Alzheimer's dementia and 418 cases of vascular dementia. We identified 83 metabolites that could represent healthy lifestyle behaviours using elastic net regression. The metabolic signature was associated with a lower dementia risk, and for each standard deviation increment in metabolic signature, the hazard ratio was 0.89 [95% confidence interval (CI): 0.85, 0.93] for all-cause dementia, 0.95 (95% CI: 0.88, 1.03) for Alzheimer's dementia and 0.84 (95% CI: 0.77, 0.91) for vascular dementia. Mendelian randomization revealed potential causal associations between the identified metabolites and risk of dementia. In addition, the specific structural brain reserve, including the hippocampus, grey matter in the hippocampus, parahippocampal gyrus and middle temporal gyrus, were detected to mediate the effects of metabolic signature on dementia risk (mediated proportion ranging from 6.21% to 11.98%). The metabolic signature associated with a healthy lifestyle is inversely associated with dementia risk, and greater structural brain reserve plays an important role in mediating this relationship. These findings have significant implications for understanding the intricate connections between lifestyle, metabolism and brain health.

Characterizing metabolomic signatures related to coffee and tea consumption and their association with incidence and dynamic progression of type 2 diabetes: A multi-state analysis.

Our study aimed to investigate the impact of tea and coffee consumption and related metabolomic signatures on dynamic transitions from diabetes-free status to incident type 2 diabetes (T2D), and subsequently to T2D-related complications and death. We included 438,970 participants in the UK Biobank who were free of diabetes and diabetes complications at baseline. Of these, 212,146 individuals had information on all metabolic biomarkers. We identified tea- and coffee-related metabolomic signatures using elastic net regression models. We examined associations of tea and coffee intake and related metabolomic signatures with the onset and progression of T2D using multi-state regression models. We observed that tea and coffee consumption and related metabolomic signatures were inversely associated with the risk of five T2D transitions. For example, HRs (95% CIs) per SD increase of the tea-related metabolomic signature were 0.87 (0.85, 0.89), 0.97 (0.95, 0.99), 0.91 (0.90, 0.92), 0.92 (0.91, 0.94), and 0.91 (0.90, 0.92) for transitions from diabetes-free state to incident T2D, from diabetes-free state to total death, from incident T2D to T2D complications, from incident T2D to death, and from T2D complications to death. These findings highlight the benefit of tea and coffee intake in reducing the risk of occurrence and progression of T2D.

Association of metabolic signatures of air pollution with MASLD: Observational and Mendelian randomization study.

BACKGROUND & AIMS: To identify metabolic signatures associated with exposure to ambient air pollution and to explore their associations with risk of metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: We utilized data from the UK Biobank Cohort. Annual mean concentrations of PM2.5, PM10, NO2 and NOx were assessed for each participant using bilinear interpolation. The Elastic Net regression model was used to identify metabolites associated with four air pollutants and to construct metabolic signatures, respectively. Associations between air pollutants, metabolic signatures and MASLD were analyzed using Cox models. Mendelian randomization (MR) analysis was used to examine potential causality. Mediation analysis was employed to examine the role of metabolic signatures in the association between air pollutants and MASLD. RESULTS: A total of 244,842 participants from the UK Biobank were included in this analysis. We identified 87, 65, 76, and 71 metabolites as metabolic signatures of PM2.5, PM10, NO2, and NOx, respectively. Metabolic signatures were associated with risk of MASLD, with hazard ratios (HRs) and 95% confidence intervals (95% CIs) were 1.10 (1.06, 1.14), 1.06 (1.02, 1.10), 1.24 (1.20, 1.29) and 1.14 (1.10, 1.19). The four pollutants were associated with increased risk of MASLD, with HRs (95% CIs) of 1.03 (1.01, 1.05), 1.02 (1.01, 1.04), 1.01 (1.01, 1.02) and 1.01 (1.00, 1.01). MR analysis indicated an association between PM2.5, NO2 and NOx-related metabolic signatures and MASLD. Metabolic signatures mediated the association of PM2.5, PM10, NO2 and NOx with MASLD. CONCLUSION: There may be association between PM2.5, PM10, NO2 and NOx-related metabolic signatures and MASLD, and metabolic signatures mediate the increase of PM2.5, PM10, NO2 and NOx in the risk of MASLD. IMPACT AND IMPLICATIONS: Air pollution is a significant public health issue and an important risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD), however, the mechanism by which air pollution affects MASLD remains unclear. Our study used integrated serological metabolic data of 251 metabolites from a large-scale cohort study to demonstrate that metabolic signatures play a crucial role in the elevated risk of MASLD caused by air pollution. These results are relevant to patients and policymakers because they suggest that air pollution-related metabolic signatures are not only potentially associated with MASLD but also involved in mediating the process by which PM2.5, PM10, NO2, and NOx increase the risk of MASLD. Focusing on changes in air pollution-related metabolic signatures may offer a new perspective for preventing air pollution-induced MASLD and serve as protective measures to address this emerging public health challenge.

Fresh fruit, dried fruit, raw vegetables, and cooked vegetables consumption associated with progression trajectory of type 2 diabetes: a multi-state analysis of a prospective cohort.

PURPOSE: To examine the effects of fresh fruit, dried fruit, raw vegetables, and cooked vegetables on type 2 diabetes (T2D) progression trajectory. METHODS: We included 429,886 participants in the UK Biobank who were free of diabetes and diabetes complications at baseline. Food groups were determined using a validated food frequency questionnaire. Outcomes were T2D incidence, complications, and mortality. Multi-state model was used to analyze the effects of food groups on T2D progression. RESULTS: During a follow-up of 12.6 years, 10,333 incident T2D cases were identified, of whom, 3961 (38.3%) developed T2D complications and 1169 (29.5%) died. We found that impacts of four food groups on T2D progression varied depending on disease stage. For example, compared to participants who ate less than one piece of dried fruit per day, the hazard ratios and 95% confidence intervals for those who ate ≥ 2 pieces of dried fruit per day were 0.82 (0.77, 0.87), 0.88 (0.85, 0.92), and 0.86 (0.78, 0.95) for transitions from diabetes-free state to incident T2D, from diabetes-free state to total death, and from incident T2D to T2D complications, respectively. Higher intake of fresh fruit was significantly associated with lower risk of disease progression from diabetes-free state to all-cause death. Higher intake of raw and cooked vegetables was significantly associated with lower risks of disease progression from diabetes-free state to incident T2D and to total death. CONCLUSIONS: These findings indicate that higher intake of fresh fruit, dried fruit, raw vegetables, and cooked vegetables could be beneficial for primary and secondary prevention of T2D.

Long-term exposure to ambient ozone and adult-onset asthma: A prospective cohort study.

BACKGROUND: The association between long-term exposure to ozone (O3) and adult-onset asthma (AOA) remains inconclusive, and analysis of causality is lacking. OBJECTIVES: To examine the causal association between long-term O3 exposure and AOA. METHODS: A prospective cohort study of 362,098 participants was conducted using the UK Biobank study. Incident cases of AOA were identified using health administrative data of the National Health Services. O3 exposure at participants' residential addresses was estimated by a spatio-temporal model. Instrumental variable (IV) modelling was used to analyze the causal association between O3 exposure and AOA, by incorporating wind speed and planetary boundary layer height as IVs into time-dependent Cox model. Negative control outcome (accidental injury) was also used to additionally evaluate unmeasured confounding. RESULTS: During a mean follow-up of 11.38 years, a total of 10,973 incident AOA cases were identified. A U-shaped concentration-response relationship was observed between O3 exposure and AOA in the traditional Cox models with HR of 0.916 (95% CI: 0.888, 0.945) for O3 at low levels (<38.17 ppb), and 1.204 (95% CI: 1.168, 1.242) for O3 at high levels (≥38.17 ppb). However, in the IV analysis we only found a statistically significant association between high-level O3 exposure and AOA risk, but not for low-level O3 exposure. No significant associations between O3 exposure and accidental injury were observed. CONCLUSION: Our findings suggest a potential causal relationship between long-term exposure to high-level ambient O3 and increased risks of AOA.

PM2.5 chemical components are associated with in-hospital case fatality among acute myocardial infarction patients in China.

Recent studies have linked the cardiovascular events with the exposure to ambient fine particulate matter (PM2.5); however, the impact of PM2.5 chemical components on acute myocardial infarction (AMI) case fatality remains poorly understood. To address this gap, we included 178,340 hospitalised patients with AMI utilising the inpatient discharge database from Sichuan, Shanxi, Guangxi, and Guangdong, China spanning 2014-2019. We evaluated exposure to PM2.5 and its components (black carbon (BC), organic matter (OM), sulphate (SO42-), nitrate (NO3-), and ammonium (NH4+)) using bilinear interpolation based on the patient's residential address. We used mixed-effects logistic regression models to investigate the associations of PM2.5 and its five components with in-hospital AMI case fatality. Per interquartile range (IQR) increment in short-term exposure (7-day average) to overall PM2.5 (odds ratio (OR): 1.086, 95 % confidence interval (CI): 1.045-1.128), SO42-(1.063, 1.024-1.104), BC (1.055, 1.023-1.089), OM (1.052, 1.019-1.086, and NO3- (1.045, 1.003-1.089) were significantly associated with high risk of in-hospital AMI case fatality. The ORs per IQR increment in long-term exposure (annual average) were 1.323 (95 % CI: 1.255-1.394) for PM2.5, followed by BC (1.271, 1.210-1.335), OM (1.243, 1.188-1.300), SO42- (1.212, 1.157-1.270), NO3- (1.116, 1.075-1.159), and NH4+ (1.068, 1.031-1.106). Our study suggests that PM2.5 chemical components might be important risk factors for in-hospital AMI case fatality, highlighting the importance of targeted reduction of PM2.5 emissions, particularly BC, OM, and SO42-.

Associations between maternal exposure to air pollution during pregnancy and trajectories of infant growth: A birth cohort study.

OBJECTIVE: We examined the relationships between infants' growth trajectories and prenatal exposure to air pollution, which is still under-investigated. METHODS: A birth cohort study was constructed using medical records of pregnant women and infants born between 2015 and 2019 in Foshan, China. Using satellite-based spatial-temporal models, prenatal exposure to air pollutants including particulate matter with an aerodynamic dimension of < 2.5 µm (PM2.5), sulfur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3) was assessed at each woman's residence. Latent class growth modeling was used to identify trajectories of physical (body length and weight) growth and neurodevelopment, which were repeatedly measured within 1 year after birth. Logistic regression models were used to investigate the associations between prenatal exposure to air pollution and the risks of growth disorders, adjusting for an array of potential confounders. RESULTS: We identified two growth trajectories for body length [normal: 3829 (93%); retardation: 288 (7%)], three for weight [normal: 2475 (59.6%); retardation: 390 (9.4%); overgrowth: 1287 (31%)], and two for neurodevelopment [normal: 956 (66.1%); retardation: 491 (33.9%)]. For exposure over whole pregnancy, SO2 was associated with an increased risk of body length retardation (OR for per 1 µg/m3 increment: 1.09, 95%CI: 1.01-1.17); PM2.5 (OR: 1.05, 95%CI: 1.03-1.07), SO2 (OR: 1.15, 95%CI: 1.08-1.22), and NO2 (OR: 1.05, 95%CI: 1.03-1.07) were positively associated with neurodevelopmental retardation. Such associations appeared stronger for exposures over the first and second trimesters. No significant associations were detected for weight growth. CONCLUSIONS: Maternal exposure to air pollution during pregnancy was associated with higher risks of impairments in both physical growth, particularly body length, and neurodevelopment.

Associations of Air Pollution and Genetic Risk With Incident Dementia: A Prospective Cohort Study.

Evidence on the association between air pollution and dementia is accumulating but still inconclusive, and the potential effect modification by genetics is unclear. We investigated the joint effects of air pollution exposure and genetic risk on incident dementia in a prospective cohort study, the UK Biobank study. Land use regression models were used to estimate exposure to ambient particulate matter (PM) in 3 fraction sizes (PM with diameter < 2.5 µm (PM2.5), coarse particles (PM with diameter 2.5-10 µm (PMc)), and PM with diameter < 10 µm (PM10)), PM2.5 absorbance, nitrogen dioxide levels, and nitrogen oxide levels at each individual's baseline residence. A polygenic risk score was calculated as a quantitative measure of genetic dementia risk. Incident cases of dementia were ascertained through linkage to health administrative data sets. Among the 227,840 participants included in the analysis, 3,774 incident dementia cases (including 1,238 cases of Alzheimer disease and 563 cases of vascular dementia) were identified. After adjustment for a variety of covariates, including genetic factors, positive associations were found between exposure to air pollution-particularly PM10, PM2.5 absorbance, and nitrogen dioxide-and incident all-cause dementia and Alzheimer disease but not vascular dementia. No significant interaction between air pollution and genetics was found, either on the multiplicative scale or on the additive scale. Exposure to air pollution was associated with a higher risk of developing dementia regardless of genetic risk.

Air pollution associated with incidence and progression trajectory of chronic lung diseases: a population-based cohort study.

BACKGROUND: No prior study has examined the effects of air pollution on the progression from healthy to chronic lung disease, subsequent chronic lung multimorbidity and further to death. METHODS: We used data from the UK Biobank of 265 506 adults free of chronic lung disease at recruitment. Chronic lung multimorbidity was defined as the coexistence of at least two chronic lung diseases, including asthma, chronic obstructive pulmonary disease and lung cancer. The concentrations of air pollutants were estimated using land-use regression models. Multistate models were applied to assess the effect of air pollution on the progression of chronic lung multimorbidity. RESULTS: During a median follow-up of 11.9 years, 13 863 participants developed at least one chronic lung disease, 1055 developed chronic lung multimorbidity and 12 772 died. We observed differential associations of air pollution with different trajectories of chronic lung multimorbidity. Fine particulate matter showed the strongest association with all five transitions, with HRs (95% CI) per 5 µg/m3 increase of 1.31 (1.22 to 1.42) and 1.27 (1.01 to 1.57) for transitions from healthy to incident chronic lung disease and from incident chronic lung disease to chronic lung multimorbidity, and 1.32 (1.21 to 1.45), 1.24 (1.01 to 1.53) and 1.91 (1.14 to 3.20) for mortality risk from healthy, incident chronic lung disease and chronic lung multimorbidity, respectively. CONCLUSION: Our study provides the first evidence that ambient air pollution could affect the progression from free of chronic lung disease to incident chronic lung disease, chronic lung multimorbidity and death.

Short-term air pollution exposure associated with death from kidney diseases: a nationwide time-stratified case-crossover study in China from 2015 to 2019.

BACKGROUND: Long-term exposure to air pollution has been associated with the onset and progression of kidney diseases, but the association between short-term exposure to air pollution and mortality of kidney diseases has not yet been reported. METHODS: A nationally representative sample of 101,919 deaths from kidney diseases was collected from the Chinese Center for Disease Control and Prevention from 2015 to 2019. A time-stratified case-crossover study was applied to determine the associations. Satellite-based estimates of air pollution were assigned to each case and control day using a bilinear interpolation approach and geo-coded residential addresses. Conditional logistic regression models were constructed to estimate the associations adjusting for nonlinear splines of temperature and relative humidity. RESULTS: Each 10 µg/m3 increment in lag 0-1 mean concentrations of air pollutants was associated with a percent increase in death from kidney disease: 1.33% (95% confidence interval [CI]: 0.57% to 2.1%) for PM1, 0.49% (95% CI: 0.10% to 0.88%) for PM2.5, 0.32% (95% CI: 0.08% to 0.57%) for PM10, 1.26% (95% CI: 0.29% to 2.24%) for NO2, and 2.9% (95% CI: 1.68% to 4.15%) for SO2.  CONCLUSIONS: Our study suggests that short-term exposure to ambient PM1, PM2.5, PM10, NO2, and SO2 might be important environmental risk factors for death due to kidney diseases in China.

Associations of risk factor burden and genetic predisposition with the 10-year risk of atrial fibrillation: observations from a large prospective study of 348,904 participants.

BACKGROUND: Understanding the effects of risk factor burden and genetic predisposition on the long-term risk of atrial fibrillation (AF) is important to improve public health initiatives. However, the 10-year risk of AF considering risk factor burden and genetic predisposition is unknown. METHODS: A total of 348,904 genetically unrelated participants without AF at baseline from the UK were categorized into three groups: index ages 45 years (n = 84,206), 55 years (n=117,520), and 65 years (n=147,178). Optimal, borderline, or elevated risk factor burden was determined by body mass index, blood pressure, diabetes mellitus, alcohol consumption, smoking status, and history of myocardial infarction or heart failure. Genetic predisposition was estimated using the polygenic risk score (PRS), constructed using 165 predefined genetic risk variants. The combined effects of risk factor burden and PRS on the risk of incident AF in 10 years were estimated for each index age. Fine and Gray models were developed to predict the 10-year risk of AF. RESULTS: The overall 10-year risk of AF was 0.67% (95% CI: 0.61-0.73%) for index age 45 years, 2.05% (95% CI: 1.96-2.13%) for index age 55 years, and 6.34% (95% CI: 6.21-6.46%) for index age 65 years, respectively. An optimal risk factor burden was associated with later AF onset regardless of genetic predisposition and sex (P < 0.001). Significant synergistic interactions were observed for risk factor burden with PRS at each index age (P < 0.05). Participants with an elevated risk factor burden and high PRS had the highest 10-year risk of AF in reference to those who had both an optimal risk factor burden and a low PRS. At younger ages, optimal risk burden and high PRS might also lead to later onset of AF, compared to the joint effect of elevated risk burden and low/intermediate PRS. CONCLUSIONS: Risk factor burden together with a genetic predisposition is associated with the 10-year risk of AF. Our results may be helpful in selecting high-risk individuals for primary prevention of AF and facilitating subsequent health interventions.

Sarcopenia and mild kidney dysfunction and risk of all-cause and cause-specific mortality in older adults.

BACKGROUND: Sarcopenia has been identified as a risk factor for increased mortality in individuals with CKD. However, when considering individuals with mild kidney dysfunction prior to CKD, the impact of sarcopenia on adverse outcomes, particularly mortality, remains uncertain. METHODS: This study included 323 801 participants from the UK Biobank. Mild kidney dysfunction was defined as eGFR between 60 and 89.9 mL/min/1.73 m2, and sarcopenia was defined according to the criteria of the 2019 European Working Group of Sarcopenia in Older People. Cox proportional hazard models with inverse probability weighting and competing risk models were used for analysis. RESULTS: During a median follow-up of 11.8 years, 20 146 participants died from all causes. Compared with participants with normal kidney function and without sarcopenia, those with mild kidney dysfunction or sarcopenia had significantly increased risks of all-cause mortality [hazard ratio (HR): 1.16, 95% confidence interval (CI): 1.12 to 1.19; HR: 1.29, 95% CI: 1.20 to 1.37]; those with both mild kidney dysfunction and sarcopenia had an even higher risk of all-cause mortality (HR: 1.61, 95% CI: 1.52 to 1.71), with a significant overall additive interaction (relative risk due to interaction 0.17, 95% CI: 0.05 to 0.29). Further subgroup analyses revealed that the associations of probable sarcopenia with all-cause and cause-specific mortality (non-accidental cause, non-communicable diseases, and cancer) were stronger among participants with mild kidney dysfunction than those with normal kidney function. CONCLUSIONS: The study indicates that sarcopenia and mild kidney dysfunction synergistically increase the risk of all-cause and cause-specific mortality. Early recognition and improvement of mild kidney function or sarcopenia in older people may reduce mortality risk but would require more prospective confirmation.

Air pollution and stroke hospitalization in the Beibu Gulf Region of China: A case-crossover analysis.

BACKGROUND: The relationship between air pollution and stroke has been extensively studied, however, the evidence regarding the association between air pollution and hospitalization due to stroke and its subtypes in coastal areas of China is limited. OBJECTIVE: To estimate the associations between air pollution and hospitalizations of stroke and its subtypes in the Beibu Gulf Region of China. METHODS: We conducted a time-stratified case-crossover study in 15 cities in Beibu Gulf Region in China from 2013 to 2016. Exposures to PM1, PM2.5, PM10, SO2, NO2, O3, and CO on the case and control days were assessed at residential addresses using bilinear interpolation. Conditional logistic regressions were constructed to estimate city-specific associations adjusting for meteorological factors and public holidays. Meta-analysis was further conducted to pool all city-level estimates. RESULTS: There were 271,394 case days and 922,305 control days. The odds ratios (ORs) for stroke hospitalizations associated with each interquartile range (IQR) increase in 2-day averages of SO2 (IQR: 10.8 µg/m3), NO2 (IQR: 11.2 µg/m3), and PM10 (IQR: 37 µg/m3) were 1.047 (95 % CI [confidence interval]: 1.015-1.080), 1.040 (95 % CI: 1.027-1.053), and 1.018 (95 % CI: 1.004-1.033), respectively. The associations with hospitalizations of ischemic stroke were significant for all seven pollutants, while the association with hemorrhagic stroke was significant only for CO. The associations of SO2, NO2, and O3 with stroke hospitalization were significantly stronger in the cool season. CONCLUSIONS: Short-term increase in SO2, NO2, and PM10 might be important triggers of stroke hospitalization. All seven air pollutants were associated with ischemic stroke hospitalization, while only CO was associated with hemorrhagic stroke hospitalization. These results should be considered in public health policy.

Ambient particulate matter and in-hospital case fatality of acute myocardial infarction: A multi-province cross-sectional study in China.

The acute myocardial infarction (AMI) outcomes have been extensively linked with ambient particulate matter (PM). However, whether a smaller particle has greater impact and the consequent attributable burden associated with PM of different sizes remain unclear. We conducted a multi-province cross-sectional study among AMI patients using the inpatient discharge datasets from four Chinese provinces (Shanxi, Sichuan, Guangxi, and Guangdong) from 2014 to 2019. Ambient PM exposure for each patient was assessed using the ChinaHighAirPollutants dataset. We employed the mixed-effects logistic regression models to evaluate the association of PM of different sizes (PM1, PM2.5, PM10) on in-hospital case fatality. The potential reducible fractions in in-hospital case fatality were estimated through counterfactual analyses. Of 177,749 participants, 125,501 (70.6 %) were male and the in-hospital case fatality rate was 4.9%. For short-term (7-day average) exposure, the odds ratios (ORs) for PM1, PM2.5, and PM10 (per 10 µg/m3) were 1.052 (95 % confidence interval [CI], 1.032-1.071), 1.026 (95 % CI, 1.014-1.037), and 1.016 (95% CI, 1.008-1.024), respectively. The estimated ORs for long-term exposure (annual average) were 1.303 (95 % CI, 1.252-1.356) for PM1, 1.209 (95 % CI, 1.178-1.241) for PM2.5, 1.157 (95 % CI, 1.134-1.181) for PM10. Short-term exposure to PM1 showed the highest potential reducible fraction (8.5 %, 95 % CI, 5.0-11.7 %), followed by PM2.5 and PM10, while the greatest potential reducible fraction of long-term exposure was observed in PM10 (30.9 %, 95 % CI, 27.2-34.4%), followed by PM2.5 and PM1. In summary, PM with smaller size had a more pronounced impact on in-hospital AMI case fatality, with PM1 exhibiting greater effects than PM2.5 and PM10. Substantial health benefits for AMI patients could be achieved by mitigating ambient PM exposure.

Dynamic association of ambient air pollution with incidence and mortality of pulmonary hypertension: A multistate trajectory analysis.

BACKGROUND: There is little evidence regarding the association between ambient air pollution and incidence and the mortality of pulmonary hypertension (PH). METHODS: We included 494,750 participants at baseline in the UK Biobank study. Exposures to PM2.5, PM10, NO2, and NOx were estimated at geocoded participants' residential addresses, utilizing pollution data provided by UK Department for Environment, Food and Rural Affairs (DEFRA). The outcomes were the incidence and mortality of PH. We used multivariate multistate models to investigate the impacts of various ambient air pollutants on both incidence and mortality of PH. RESULTS: During a median follow-up of 11.75 years, 2517 participants developed incident PH, and 696 died. We observed that all ambient air pollutants were associated with increased incidence of PH with different magnitudes, with adjusted hazard ratios (HRs) [95% confidence intervals (95% CIs)] for each interquartile range (IQR) increase of 1.73 (1.65, 1.81) for PM2.5, 1.70 (1.63, 1.78) for PM10, 1.42 (1.37, 1.48) for NO2, and 1.35 (1.31, 1.40) for NOx. Furthermore, PM2.5, PM10, NO2 and NO2 influenced the transition from PH to death, and the corresponding HRs (95% CIs) were 1.35 (1.25, 1.45), 1.31 (1.21, 1.41), 1.28 (1.20, 1.37) and 1.24 (1.17, 1.32), respectively. CONCLUSION: The results of our study indicate that exposure to various ambient air pollutants might play key but differential roles in both the incidence and mortality of PH.

Association between ambient sulfur dioxide pollution and asthma mortality: Evidence from a nationwide analysis in China.

There is a lack of research on the effects of acute exposure to ambient sulfur dioxide (SO2) on mortality caused by asthma, especially nationwide research in China. To explore the acute effect of exposure to ambient SO2 on asthma mortality using nationwide dataset in China from 2015 to 2020 and further evaluate the associations in subgroups with different geographical and demographic characteristics. We used data from China's Disease Surveillance Points system with 29,553 asthma deaths in China during 2015-2020. The exposure variable was the daily mean concentrations of SO2 from the ChinaHighSO2 10 km × 10 km daily grid dataset. Bilinear interpolation was used to estimate each individual's exposure to air pollutants and meteorological variables. We used a time-stratified case crossover design at the individual level to analyze the exposure response relationship between short-term exposure to SO2 and asthma mortality. Stratified analyses were carried out by sex, age group, marital status, warm season and cold season, urbanicity and region. Significant associations between short-term exposure to ambient SO2 and increased asthma mortality were found in this nationwide study. The excess risk (ER) for each 10 µg/m3 increase in SO2 concentrations at lag07 was 7.78 % (95 % CI, 4.16-11.52 %). Season appeared to significantly modify the association. The associations were stronger in cold season (ER 9.78 %, 95 % CI:5.82 -13.89 %). The association remained consistent using different lag periods, adjusting for other pollutants, and in the analysis during pre-Corona Virus Disease 2019 (COVID-19) period. Our study indicates increased risk of asthma mortality with acute exposures to SO2 in Chinese population. The current study lends support for greater awareness of the harmful effect of SO2 in China and other countries with high SO2 pollution.

Long-term exposure to ambient PM2.5 constituents is associated with dyslipidemia in Chinese adults.

BACKGROUND: Ambient particulate matter with aerodynamic diameter ≤ 2.5 µm (PM2.5) consists of various toxic constituents. However, the health effect of PM2.5 may differ depending on its constituents, but the joint effect of PM2.5 constituents remains incompletely understood. OBJECTIVE: Our goal was to evaluate the joint effect of long-term PM2.5 constituent exposures on dyslipidemia and identify the most hazardous chemical constituent. METHODS: This study included 67,015 participants from the China Multi-Ethnic Cohort study. The average yearly levels of PM2.5 constituents for all individuals at their residences were assessed through satellite remote sensing and chemical transport modeling. Dyslipidemia was defined as one or more following abnormal blood lipid concentrations: total cholesterol (TC) ≥ 6.22 mmol/L, triglycerides (TG) ≥ 2.26 mmol/L, high-density lipoprotein cholesterol (HDL-C) < 1.04 mmol/L, and low-density lipoprotein cholesterol (LDL-C) ≥ 4.14 mmol/L. The logistic regression model was utilized to examine the single effect of PM2.5 constituents on dyslipidemia, while the weighted quantile sum regression model for the joint effect. RESULTS: The odds ratio with a 95 % confidence interval for dyslipidemia positively related to per-SD increase in the three-year average was 1.29 (1.20-1.38) for PM2.5 mass, 1.25 (1.17-1.34) for black carbon, 1.24 (1.16-1.33) for ammonium, 1.33 (1.24-1.43) for nitrate, 1.34 (1.25-1.44) for organic matter, 1.15 (1.08-1.23) for sulfate, 1.30 (1.22-1.38) for soil particles, and 1.12 (1.05-1.92) for sea salt. Stronger associations were observed in individuals < 65 years of age, males, and those with low physical activity. Joint exposure to PM2.5 constituents was positively related to dyslipidemia (OR: 1.09, 95 %CI: 1.05-1.14). Nitrate was identified as the constituent with the largest weight (weighted at 0.387). CONCLUSIONS: Long-term exposure to PM2.5 constituents poses a significant risk to dyslipidemia and nitrate might be the most responsible for the risk. These findings indicate that reducing PM2.5 constituent exposures, especially nitrate, could be beneficial to alleviate the burden of disease attributed to PM2.5-related dyslipidemia.

Ambient PM2.5 and its components associated with 10-year atherosclerotic cardiovascular disease risk in Chinese adults.

BACKGROUND: Exposure to particulate matter with aerodynamic diameters less than 2.5 µm (PM2.5) may increase the risk of 10-year atherosclerotic cardiovascular disease (ASCVD) risk. While PM2.5 is comprised of various components, the evidence on the correlation of its components with 10-year ASCVD risk and which component contributes most remains limited. METHODS: Data were derived from the baseline assessments of China Multi-Ethnic Cohort (CMEC). In total, 69,722 individuals aged 35-74 years were included into this study. The annual average concentration of PM2.5 and its components (black carbon, ammonium, nitrate, sulfate, organic matter, soil particles, and sea salt) were estimated by satellite remote sensing and chemical transport models. The ASCVD risk of individuals was calculated by the equations from the China-PAR Project (prediction for ASCVD risk in China). The relationship between single exposure to PM2.5 and its components and predicted 10-year ASCVD risk was assessed using the logistic regression model. The effect of joint exposure was estimated, and the most significant contributor was identified using the weighted quantile sum approach. RESULTS: Totally 69,722 participants were included, of which 95.8 % and 4.2 % had low and high 10-year ASCVD risk, respectively. Per standard deviation increases in the 3-year average concentration of PM2.5 mass (odds ratio [OR] 1.23, 95 % confidence interval [CI]: 1.12-1.35), black carbon (1.21, 1.11-1.33), ammonium (1.21, 1.10-1.32), nitrate (1.25, 1.14-1.38), organic matter (1.29, 1.18-1.42), sulfate (1.17, 1.07-1.28), and soil particles (1.15, 1.04-1.26) were related to high 10-year ASCVD risk. The overall effect (1.19, 1.11-1.28) of the PM2.5 components was positively associated with 10-year ASCVD risk, and organic matter had the most contribution to this relationship. Female participants were more significantly impacted by PM2.5, black carbon, ammonium, nitrate, organic matter, sulfate, and soil particles compared to others. CONCLUSION: Long-term exposure to PM2.5 mass, black carbon, ammonium, nitrate, organic matter, sulfate, and soil particles were positively associated with high 10-year ASCVD risk, while sea salt exhibited a protective effect. Moreover, the organic matter might take primary responsibility for the relationship between PM2.5 and 10-year ASCVD risk. Females were more susceptible to the adverse effect.

Constituents of fine particulate matter and asthma in 6 low- and middle-income countries.

BACKGROUND: Evidence concerning the effects of different chemical components of particulate matter with an aerodynamic diameter of 2.5 µm or less (PM2.5) on asthma is limited, and the methodology to compare the relative importance of different PM2.5 components is lacking. OBJECTIVE: Our aim was to examine the associations between PM2.5 components and asthma and investigate which constituent of PM2.5 possessed the most harmful effect on asthma. METHODS: A total of 45,690 subjects in 6 countries were surveyed from 2007 to 2010. We geocoded the residential community addresses of the participants and used satellite remote sensing and chemical transport modeling to estimate their annual average concentrations of PM2.5 constituents. Mixed-effects generalized additive models were utilized to examine the associations between PM2.5 constituents and prevalence of asthma. We further used counterfactual analyses to determine the potential number of asthma cases. RESULTS: We identified 6178 patients with asthma among the participants, producing an asthma prevalence of 13.5%. The odds ratio for asthma associated with per-SD increment was 1.12 for PM2.5 mass, 1.12 for organic carbon, 1.18 for black carbon, 1.19 for sulfate, 1.28 for ammonium, and 1.21 for nitrate after controlling for potential confounders. Our counterfactual analyses suggested that ammonium was responsible for a substantial decline in asthma cases (by 1382 cases, corresponding to 22.37% of overall cases) if the concentration was reduced to the 5th percentile of the current level. CONCLUSIONS: Our study suggests that some chemical components of PM2.5 (including black carbon, organic carbon, sulfate, ammonium, and nitrate) might be hazardous constituents contributing to the prevalence of asthma; among them, ammonium might be responsible for a substantial proportion of asthma cases if reduced to a certain level.

Risk/benefit tradeoff of habitual physical activity and air pollution on chronic pulmonary obstructive disease: findings from a large prospective cohort study.

BACKGROUND: The combined health impact of physical activity (PA) and air pollution on chronic obstructive pulmonary disease (COPD) remains unclear. We investigated the joint effects of habitual PA and long-term fine particulate matter (PM2.5) exposure on COPD incidence in a prospective population-based cohort. METHODS: A prospective cohort study was conducted using data from the UK Biobank. Incidence of COPD was ascertained through linkage to the UK National Health Services register. Annual mean PM2.5 concentration was obtained using land use regression model. PA was measured by questionnaire and wrist-worn accelerometer. Cox proportional hazard models were applied to examine the associations between PM2.5, PA, and COPD. Additive and multiplicative interactions were examined. RESULTS: A total of 266,280 participants free of COPD at baseline were included in data analysis with an average follow-up of 10.64 years, contributing to around 2.8 million person-years. Compared with participants with low level of PA, those with higher PA levels had lower risks of COPD incidence [hazard ratio (HR): 0.769, 95% CI: 0.720, 0.820 for moderate level; HR: 0.726, 95% CI: 0.679, 0.776 for high level]. By contrast, PM2.5 was associated with increased risk of COPD (HR per interquartile range increment: 1.065, 95% CI: 1.032, 1.099). Limited evidence of interaction between habitual PA and PM2.5 exposure was found. Similar results were found for accelerometer-measured PA. CONCLUSIONS: Our study suggests that habitual PA could reduce risk of COPD incidence, and such protective effects were not affected by ambient PM2.5 pollution exposure.