Long-Term Exposure to Ambient PM2.5 and Age-Related Cataracts among Chinese Middle-Aged and Older Adults: Evidence from Two National Cohort Studies.

Cataract is one key cause of visual disability and blindness. Ambient particulate matter is more likely to increase cataract risk due to eye continuous exposure to the environment. However, less is known about whether long-term exposure to particulate matter 2.5 (PM2.5) is related to age-related cataracts. We conducted a population-based study among 22,298 adults from two multicenter cohort studies [China Family Panel Studies (CFPS) and Chinese Longitudinal Healthy Longevity Survey (CLHLS)]. The associations between PM2.5 and age-related cataracts were analyzed by Cox proportional hazard regression models, which were also stratified according to demographic characteristics. The restricted cubic spline (RCS) model was used to explore the dose-response relationships between PM2.5 and age-related cataracts. The population attributable fraction (PAF) was calculated to assess the burden of age-related cataracts that can be attributed to PM2.5. In the final analysis, 1897 participants reported age-related cataracts during follow-up. Long-term exposure to PM2.5 was associated with age-related cataracts, with HRs of 1.165 (1.130, 1.201), 1.138 (1.103, 1.173), and 1.091 (1.057, 1.126) for per 10 µg/m3 increase at one-, two-, and three-year before the end of follow-up, respectively. Furthermore, associations between PM2.5 and age-related cataracts were also demonstrated in RCS models. The PAF of age-related cataracts to PM2.5 in the total participants was 24.63%. Our research found that long-term exposure to PM2.5 may increase the risk of age-related cataracts, and age-related cataracts should be considered as an important public health issue due to air pollution.

Joint Effects of Long-Term Exposure to Ambient Fine Particulate Matter and Ozone on Asthmatic Symptoms: Prospective Cohort Study.

BACKGROUND: The associations of long-term exposure to air pollutants in the presence of asthmatic symptoms remain inconclusive and the joint effects of air pollutants as a mixture are unclear. OBJECTIVE: We aimed to investigate the individual and joint associations of long-term exposure to ambient fine particulate matter (PM2.5) and daily 8-hour maximum ozone concentrations (MDA8 O3) in the presence of asthmatic symptoms in Chinese adults. METHODS: Data were derived from the World Health Organization Study on Global Ageing and Adult Health (WHO SAGE) cohort study among adults aged 50 years or older, which was implemented in 1 municipality and 7 provinces across China during 2007-2018. Annual average MDA8 O3 and PM2.5 at individual residential addresses were estimated by an iterative random forest model and a satellite-based spatiotemporal model, respectively. Participants who were diagnosed with asthma by a doctor or taking asthma-related therapies or experiencing related conditions within the past 12 months were recorded as having asthmatic symptoms. The individual associations of PM2.5 and MDA8 O3 with asthmatic symptoms were estimated by a Cox proportional hazards regression model, and the joint association was estimated by a quantile g-computation model. A series of subgroup analyses was applied to examine the potential modifications of some characteristics. We also calculated the population-attributable fraction (PAF) of asthmatic symptoms attributed to PM2.5 and MDA8 O3. RESULTS: A total of 8490 adults older than 50 years were included, and the average follow-up duration was 6.9 years. During the follow-up periods, 586 (6.9%) participants reported asthmatic symptoms. Individual effect analyses showed that the risk of asthmatic symptoms was positively associated with MDA8 O3 (hazard ratio [HR] 1.12, 95% CI 1.01-1.24, for per quantile) and PM2.5 (HR 1.18, 95% CI 1.05-1.31, for per quantile). Joint effect analyses showed that per equal quantile increment of MDA8 O3 and PM2.5 was associated with an 18% (HR 1.18, 95% CI 1.05-1.33) increase in the risk of asthmatic symptoms, and PM2.5 contributed more (68%) in the joint effects. The individual PAFs of asthmatic symptoms attributable to PM2.5 and MDA8 O3 were 2.86% (95% CI 0.17%-5.50%) and 4.83% (95% CI 1.42%-7.25%), respectively, while the joint PAF of asthmatic symptoms attributable to exposure mixture was 4.32% (95% CI 1.10%-7.46%). The joint associations were greater in participants with obesity, in urban areas, with lower family income, and who used unclean household cooking fuel. CONCLUSIONS: Long-term exposure to PM2.5 and MDA8 O3 may individually and jointly increase the risk of asthmatic symptoms, and the joint effects were smaller than the sum of individual effects. These findings informed the importance of joint associations of long-term exposure to air pollutants with asthma.

Sex-specific relationships between prenatal exposure to metal mixtures and birth weight in a Chinese birth cohort.

Birth weight is an indicator linking intrauterine environmental exposures to later-life diseases, and intrauterine metal exposure may affect birth weight in a sex-specific manner. We investigated sex-specific associations between prenatal exposure to metal mixtures and birth weight in a Chinese birth cohort. The birth weight of 1296 boys and 1098 girls were recorded, and 10 metals in maternal urine samples collected during pregnancy were measured using inductively coupled plasma mass spectrometry. Bayesian Kernel Machine Regression was used to estimate the association of individual metals or metal mixtures and birth weight for gestational age (BW for GA). The model showed a sex-specific relationship between prenatal exposure to metal mixtures and BW for GA with a significant negative association in girls and a non-significant positive association in boys. Cadmium (Cd) and nickel (Ni) were positively and negatively associated with BW for GA in girls, respectively. Moreover, increasing thallium (Tl) concentration lowered the positive association between Cd and BW for GA and enhanced the negative association between Ni and BW for GA in girls. When exposure to other metals increased, the positive association with Cd diminished, whereas the negative association with Ni or Tl increased. Our findings provide evidence supporting the complex effects of intrauterine exposure to metal mixtures on the birth weight of girls and further highlight the sex heterogeneity in fetal development influenced by intrauterine environmental factors.

Mortality burden based on the associations of ambient PM2.5 with cause-specific mortality in China: Evidence from a death-spectrum wide association study (DWAS).

Although studies have estimated the associations of PM2.5 with total mortality or cardiopulmonary mortality, few have comprehensively examined cause-specific mortality risk and burden caused by ambient PM2.5. Thus, this study investigated the association of short-term exposure to PM2.5 with cause-specific mortality using a death-spectrum wide association study (DWAS). Individual information of 5,450,764 deaths during 2013-2018 were collected from six provinces in China. Daily PM2.5 concentration in the case and control days were estimated by a random forest model. A time-stratified case-crossover study design was applied to estimate the associations (access risk, ER) of PM2.5 with cause-specific mortality, which was then used to calculate the population-attributable fraction (PAF) of mortality and the corresponding mortality burden caused by PM2.5. Each 10 µg/m3 increase in PM2.5 concentration (lag03) was associated with a 0.80 % [95 % confidence interval (CI): 0.73 %, 0.86 %] rise in total mortality. We found greater mortality effect at PM2.5 concentrations < 50 µg/m3. Stratified analyses showed greater ERs in females (1.01 %, 95 %CI: 0.91 %, 1.11 %), children ≤ 5 years (2.17 %, 95 %CI: 0.85 %, 3.51 %), and old people ≥ 70 years. We identified 33 specific causes (level 2) of death which had significant associations with PM2.5, including 16 circulatory diseases, 9 respiratory diseases, and 8 other causes. The PAF estimated based on the overall association between PM2.5 and total mortality was 3.16 % (95 %CI: 2.89 %, 3.40 %). However, the PAF was reduced to 2.88 % (95 %CI: 1.88 %, 3.81 %) using the associations of PM2.5 with 33 level 2 causes of death, based on which 250.15 (95 %CI: 163.29, 330.93) thousand deaths were attributable to short-term PM2.5 exposure across China in 2019. Overall, this study provided a comprehensive picture on the death-spectrum wide association between PM2.5 and morality in China. We observed robust positive cause-specific associations of PM2.5 with mortality risk, which may provide more precise basis in assessing the mortality burden of air pollution.

Effect of long-term exposure to PM2.5 on the risk of type 2 diabetes and arthritis in type 2 diabetes patients: Evidence from a national cohort in China.

BACKGROUND: It remains unclear whether type 2 diabetes and the complication of arthritis are causally related to the PM2.5 pollutant. Therefore, we aimed to investigate the associations of long-term PM2.5 exposure with type 2 diabetes and with arthritis in type 2 diabetes patients. MATERIALS AND METHODS: This study used data from the China Health and Retirement Longitudinal Survey (CHARLS) implemented during 2011-2018. The associations were analyzed by Cox proportional hazards regression models, and the population-attributable fraction (PAF) was calculated to assess the burden of type 2 diabetes and arthritis-attributable to PM2.5. RESULTS: A total of 21,075 participants were finally included, with 19,121 analyzed for PM2.5 and type 2 diabetes risk and 12,427 analyzed for PM2.5 and arthritis risk, of which 1,382 with newly-diagnosed type 2 diabetes and 1,328 with arthritis during the follow-up. Overall, each 10 µg/m3 increment in PM2.5 concentration was significantly associated with an increase in the risk of type 2 diabetes (HR = 1.26, 95 %CI1.22 to 1.31), and the PAF of type 2 diabetes attributable to PM2.5 was 13.54 %. In type 2 diabetes patients, each 10 µg/m3 increment in PM2.5 exposure was associated with an increase in arthritis (HR = 1.42, 95 %CI: 1.28 to 1.57), and the association was significantly greater than that (H = 1.23, 95 %CI: 1.19 to 1.28) in adults without type 2 diabetes. The PAFs of arthritis-attributable to PM2.5 in participants with and without type 2 diabetes were 18.54 % and 10.69 %, respectively. CONCLUSION: Long-term exposure to PM2.5 may increase the risk of type 2 diabetes and make type 2 diabetes patients susceptible to arthritis.

Effect of early-life exposure to PM2.5 on childhood asthma/wheezing: a birth cohort study.

BACKGROUND: Although studies have investigated the association between early-life exposure to fine particulate matter (PM2.5 ) and childhood asthma/wheezing, results are inconsistent and the susceptible exposure window remains largely unknown. METHODS: A prospective birth cohort study was conducted to recruit pregnant women during their early pregnancy, and to follow up them and their children up to 3-4 years old. Diagnosis of asthma/wheezing was extracted from children's medical records. A spatiotemporal land-use regression (ST-LUR) model was used to assess maternal exposure to PM2.5 during pregnancy and their children's exposure after birth. The Cox proportional hazards model and accelerated failure time model (for violation of proportional hazards assumption) were applied to estimate the effects of prenatal and postnatal exposures to PM2.5 on the risk of childhood asthma/wheezing. RESULTS: A total of 3725 children were included, and 392 children (10.52%) were diagnosed with asthma/wheezing. Both prenatal and postnatal exposures to PM2.5 were positively associated with the risk of asthma/wheezing. Each interquartile range (IQR) increment in PM2.5 exposure during the entire pregnancy (4.8 µg/m3 ) and the period from birth to the end of follow-up (1.5 µg/m3 ) was associated with adjusted hazard ratios (HRs) of 1.44 [95% confidence interval (CI): 1.13, 1.85] and 2.74 (95% CI: 2.59, 2.91), respectively. Subgroup analyses showed greater HRs for PM2.5 exposures during the pseudoglandular stage (6-16 gestational weeks [GWs]: IQR = 4.8 µg/m3 , HR = 1.10, 95% CI: 1.02, 1.18) and canalicular stage (16-24 GWs: IQR = 4.8 µg/m3 , HR = 1.13, 95% CI:1.03, 1.23) than other stages, and also showed significant effects in the first three-year period after birth (IQR = 1.5 µg/m3 , HR = 2.37, 95% CI: =2.24, 2.51). CONCLUSION: Higher prenatal and postnatal PM2.5 exposures may increase the risk of childhood asthma/wheezing. The pseudoglandular stage, canalicular stage, and the first three years after birth may be key susceptible to exposure windows.

Effect of maternal ozone exposure before and during pregnancy on wheezing risk in offspring: A birth cohort study in Guangzhou, China.

Ozone (O3) exposure may lead to the development and exacerbation of asthma or wheezing in postnatal children; however, it has rarely been studied before and during pregnancy. Wheezing is one of the most common symptoms when diagnosing of asthma; thus, we investigated the associations of O3 exposure before and during pregnancy with wheezing in preschool children and the potential susceptible exposure windows from a heavily polluted city in China. This population-based birth cohort study, which included 3725 mother-child pairs from Guangzhou, began in 2016, and the follow-up period ended on July 31, 2020. We used a spatiotemporal land-use-regression model combined with activity patterns to estimate the daily O3 exposure levels during the pre-pregnancy period and each trimester, and wheezing was recorded by reviewing medical records. We used the Cox proportional hazard model to quantify the effects of O3 exposure on childhood wheezing adjusted for potential confounders. No significant association was detected between pre-pregnancy exposure to O3 and childhood wheezing. However, increased ambient O3 exposures throughout pregnancy and in the second trimester were positively associated with the risk of childhood wheezing, with hazard ratios (HRs) and 95% confident intervals (CIs) per interquartile range (IQR) increment of 1.22 (95% CI: 1.04-1.44) and 1.31 (95% CI: 1.09-1.58), respectively. The effects of maternal O3 exposure on childhood wheezing risk was stronger when the exposure occurred in the warm conception season (P < 0.05). Significant childhood wheezing risk could be attributable to maternal O3 exposure, especially during the second trimester and with warm-season conception in Guangzhou. Further cohorts of children, particularly school age children who have more robust asthma diagnoses, should be investigated in the future.

Associations of maternal ambient temperature exposures during pregnancy with the risk of preterm birth and the effect modification of birth order during the new baby boom: A birth cohort study in Guangzhou, China.

Maternal exposures to ambient temperatures during pregnancy may increase the preterm birth (PTB) risk; however, which periods have stronger effects remain controversial. The effects of temperature exposure on PTB in first- and second-born neonate groups may be different during the new baby boom that has followed the Two-child Policy in China. We examined a birth cohort of 4928 pregnant women beginning in 2016 in Guangzhou, China. An inverse distance weighted method was used to estimate the temperature exposure at each individual residential address. A distribution lag non-linear model incorporating a Cox proportional hazard model was employed to estimate the effects of temperature exposure on PTB and test the effects modification of birth order related to the new baby boom. A total of 4101 pregnant women were included, of which 234 (5.7%) experienced PTB. Compared with the mean temperature (23.0 °C), we found a significantly higher risks of PTB associated with high temperatures (i.e, 30 °C [95th centile]) from the 4th to 8th, and 22nd to 27th gestational weeks. A peak effect was found during the 6th week (HR = 1.79, 95% CI: 1.26, 2.54) and 24th week (HR = 1.83, 95% CI: 1.27, 2.62). The risks of PTB were reduced for low temperatures (i.e. 14 °C [5th centile] versus 23.0 °C) from the 2nd to 10th and 20th to 26th gestational weeks, and the negative peak effect was found during the 4th week (HR = 0.43, 95% CI: 0.26, 0.72) and 23rd week (HR = 0.59, 95% CI: 0.43, 0.83). Stratification analyses showed that significant effects of 30 °C versus 23 °C on PTB were observed during the 4th to 8th weeks in the second-born neonate, and the peak effect was found in the 6th week (HR = 2.13, 95% CI: 1.31, 3.47). However, we did not find significant effects of 30 °C during the same weeks in the first-born neonate group. Maternal exposures to higher temperatures during pregnancy may increase the risk of PTB, and lower temperatures may decrease the risk of PTB. Stronger effects of temperature exposures during the first trimester on PTB risk were found among the second-born neonates than among the first-born neonates.

Associations of ambient temperature exposure during pregnancy with the risk of miscarriage and the modification effects of greenness in Guangdong, China.

Miscarriage is one of the commonest complications of pregnancy. Although previous studies suggested that environmental factors were important causes of miscarriage, evidence is still inadequate. Here, we examined the association of maternal exposure to temperature with the risk of miscarriage and further assessed the modifying effects of surrounding residential greenness. A case-control study was conducted at a large hospital in Guangzhou, China. All participants' information was extracted from hospital records. An inverse distance weighted method was used to estimate the temperature exposure at each residential address, where the greenness was measured by Normalized Difference Vegetation Index (NDVI). A logistic regression model was applied to estimate the association of temperature exposure with the risk of miscarriage. A total of 2044 cases of miscarriage and 2285 controls were included in the present study. We observed a generally non-linear positive relationship between temperature exposure and the risk of miscarriage. More pronounced effects of high temperatures vs. low temperatures were found during the two months prior to hospitalization than in other periods. The odds ratio (OR) of 29.4 °C (95th centile) compared with 15 °C during the first month prior to hospitalization was 1.480 (95% CI: 1.021-2.145). Smaller effects of temperatures were seen on the risk of miscarriage among participants with moderately great surrounding greenness compared with those with less greenness. We concluded that maternal exposure to moderately high temperature during pregnancy may increase the risk of miscarriage, but the modifying effects of greenness on these associations need to be further tested in future studies.

Effects of prenatal exposure to air particulate matter on the risk of preterm birth and roles of maternal and cord blood LINE-1 methylation: A birth cohort study in Guangzhou, China.

BACKGROUND: Epidemiological studies have found that increased risk of preterm birth (PTB) is associated with higher prenatal exposure to PM10 and PM2.5, but few studies have been conducted to assess the impacts of extremely fine particulate matter (PM1) which may have more toxic effects than other types of ambient particulate air pollution (PM). Several studies have separately investigated the associations between DNA methylation and PTB risk and PM. Maternal LINE-1 methylation level negatively correlated with prenatal exposure to PM and risk of PTB. A comprehensive picture is lacking regarding the associations between prenatal exposure to PM, LINE-1 methylation, and risk of PTB. OBJECTIVES: This study aimed to estimate the effects of exposure to ambient PM (PM10, PM2.5, and PM1) of different sizes during pregnancy on risk of PTB, identify susceptible exposure windows, and illustrate the roles of LINE-1 methylation in the associations between PM and PTB risk. METHODS: The Birth Cohort Study on Prenatal Environments and Offspring Health (PEOH) has been ongoing since 2016 in Guangzhou, China. A total of 4928 pregnant women were recruited during early pregnancy, and 4278 (86.8%) were successfully followed-up. Each individual weekly exposure to PM10 and PM2.5 from 3 months before pregnancy to childbirth was assessed using a spatiotemporal land use regression model, and the weekly PM1 exposure was estimated by employing a generalized additive model. Maternal and cord blood LINE-1 methylation levels (%5mC) were tested using bisulfite-PCR pyrosequencing. A distributed lag nonlinear model incorporated with a Cox proportional hazard model was applied to assess the effect of weekly-specific maternal PM exposure on PTB risk, and a multiple-linear regression model was employed to investigate the associations between PM exposure and LINE-1 methylation levels of maternal and cord bloods. We also assessed the associations between LINE-1 methylation levels and PTB risk by using a logistic regression model. RESULTS: The risk of PTB was positively associated with PM2.5 and PM1 concentrations during the 12th to 20th gestational weeks, and the strongest association was in the fourth quartile (Q4) versus the first quartile (Q1) and observed during the 16th gestational week (PM2.5: harzard ratio [HR] = 1.18, 95%CI: 1.04-1.35, IQR = 11.94 µg/m3. PM1: HR = 1.20, 95%CI: 1.03-1.39, IQR = 11.36 µg/m3). We observed significantly negative associations of PM10(ß = -0.51%5mC per 10 µg/m3, P = 0.014), PM2.5 (ß = -0.66%5mC per 10 µg/m3, P = 0.032) and PM1 (ß = -0.67%5mC per 10 µg/m3, P = 0.032) concentrations with cord blood LINE-1 methylation levels, and a negative association between PM1 concentration and maternal LINE-1 methylation level (ß = -0.86%5mC per 10 µg/m3, P = 0.034). CONCLUSION: Higher prenatal exposure to PM1 and PM2.5 during the 12th to 20th gestational weeks was associated with increased risk of PTB. Maternal and fetal LINE-1 methylation alternation might be an underlying mechanism of PM that increasing the risk of PTB.

The associations of air pollution exposure during pregnancy with fetal growth and anthropometric measurements at birth: a systematic review and meta-analysis.

Fetal growth has been demonstrated to be an important predictor of perinatal and postnatal health. Although the effects of maternal exposure to air pollution during pregnancy on fetal growth have been investigated using ultrasound in many previous studies, the results were inconsistent and disputable. We aimed to qualitatively and quantitatively investigate the associations of air pollution exposure during different periods of pregnancy with fetal growth and anthropometric measurements at birth. We searched for all studies investigating the associations of air pollution exposure during pregnancy with fetal growth and birth anthropometric measurements in English and Chinese databases published before July 31, 2017. A random-effects model was employed in the meta-analysis to estimate the pooled effects of each 10 µg/m3 increment in air pollutant exposure. The ACROBAT-NRSI tool was applied to assess the quality of each included study, and the GRADE tool was employed to assess the overall quality of the meta-analysis. Maternal PM2.5 exposure (10 µg/m3) during the entire pregnancy was negatively associated with head circumference at birth (ß = - 0.30 cm, 95% CI - 0.49, - 0.10), and NO2 exposure during the entire pregnancy was significantly linked to shorter length at birth (ß = - 0.03 cm, 95% CI - 0.05, - 0.02). Maternal exposure to higher NO2 and PM2.5 during pregnancy may impair neonatal head circumference and length development, respectively. More studies are needed to confirm the effects of NO2 and PM2.5 and to identify the sources and major toxic components of PMs.