Joint effects of per- and polyfluoroalkyl substance alternatives and heavy metals on renal health: A community-based population study in China.

BACKGROUND: Previous studies have indicated that chlorinated polyfluorinated ether sulfonic acids (Cl-PFESAs), when used as an alternative to per- and polyfluoroalkyl substances (PFASs), result in kidney toxicity. However, their co-exposure with heavy metals, has not yet been described. OBJECTIVES: To explore the joint effects of Cl-PFESAs and heavy metal exposure on renal health in Chinese adults, and identify specific pollutants driving the associations. METHODS: Our sample consists of 1312 adults from a cross-sectional survey of general communities in Guangzhou, China. We measured Cl-PFESAs, legacy PFASs (perfluorooctanoic acid [PFOA] and perfluorooctane sulfonated [PFOS]), and heavy metals (arsenic, cadmium, and lead). The relationship between single pollutant and glomerular filtration rate (eGFR) and the odds ratio (OR) of chronic kidney disease (CKD) was studied using Generalized additive models (GAMs). Bayesian Kernel Machine Regression (BKMR) models were applied to assess joint effects of Cl-PFESAs and heavy metals. Additionally, we conducted a sex-specific analysis to determine the modification effect of this variable. RESULTS: In single pollutant models, CI-PFESAs, PFOA, PFOS and arsenic were negatively associated with eGFR. Additionally, PFOA and heavy metals were positively correlated with the OR of CKD. For example, the estimated change with 95% confidence intervals (CI) of eGFR at from the highest quantile of 6:2 Cl-PFESA versus the lowest quantile was -5.65 ng/mL (95% CI: -8.21, -3.10). Sex played a role in modifying the association between 8:2 Cl-PFESA, PFOS and eGFR. In BKMR models, pollutant mixtures had a negative joint association with eGFR and a positive joint effect on CKD, especially in women. Arsenic appeared to be the primary contributing pollutant. CONCLUSION: We provide epidemiological evidence that Cl-PFESAs independently and jointly with heavy metals impaired kidney health. More population-based human and animal studies are needed to confirm our results.

Exploring the impacts of street-level greenspace on stroke and cardiovascular diseases in Chinese adults.

In recent years, cardiovascular diseases (CVDs) have become the primary cause of death in the world. Existing studies have found that greenspace is important for the prevention of CVDs and stroke. However, since they only focus on large green infrastructure (e.g., urban parks) or the general greenspace (usually being evaluated through normalized difference vegetation index), little information exists regarding the association between street-level greenspace and CVDs (stroke). In this study, the CVDs and stroke data of participants were retrieved from the 33 Chinese Community Health Study. We measured participants' exposure to street-level greenspace exposure using street view images and machine learning technique. Multilevel logistic regressions were applied. While controlling for confounders, we found that higher level of street-level greenspace exposure was associated with lower CVDs prevalence. However, street-level greenspace exposure was associated with stroke prevalence only for females. The associations were stronger among females, younger adults, participants with educational attainment above high school, physically active participants and participants who were not overweight. None of the mediators (air pollution, physical exercise, and BMI) can explain the associations between street-level greenspace exposure and CVDs (stroke) prevalence. Our findings suggest that street-level vegetation should be increased to cope with the rapid growth of the CVDs burdens. Also, the differences between the effect of street-level trees and grasses should be noted before formulating specific urban planning policies.

Exposure to ultrafine particles and childhood obesity: A cross-sectional analysis of the Seven Northeast Cities (SNEC) Study in China.

BACKGROUND: Studies on the obesogenic effect of air pollution on children have been mixed and sparse. Moreover, due to insufficient air monitoring, few studies have investigated the role of more tiny but unregulated particles (ambient particles with a diameter of 0.1 µm or less, ultrafine particles). OBJECTIVE: We sought to explore the associations between long-term exposure to ambient ultrafine particles (UFPs) and childhood obesity in Chinese children. METHODS: In this cross-sectional study, we randomly recruited 47,990 children, aged 6-18 years, from seven cities in Northeastern China between 2012 and 2013. Child age- and sex-specific z-scores for body mass index (BMI Z-score) and weight status were generated using the World Health Organization growth reference. Four-year average concentrations of UFPs and airborne particulates of diameter ≤ 1 µm (PM1), ≤2.5 µm (PM2.5), and ≤10 µm (PM10) were estimated at home, using neural network simulated WRF-Chem model and spatiotemporal model, respectively. Confounder-adjusted generalized linear mixed models examined the associations between air pollution and BMI Z-score and the prevalence of childhood obesity. RESULT: We found that UFPs exposure was associated with greater childhood BMI Z-score and a higher likelihood of obesity. Compared with the lowest quartile, higher quartiles of UFPs were associated with greater odds for obesity prevalence in children (i.e., the adjusted OR was 1.25; 95 % CI, 1.12-1.39; 1.43; 95 % CI, 1.27-1.61; and 1.41; 95 % CI, 1.25-1.58 for the second, third, and fourth quartile, respectively). Similar associations were observed for PM1, PM2.5, and PM10, and were greater in boys and children living close to roadways. CONCLUSIONS: Long-term UFPs exposure was associated with a greater likelihood of childhood obesity, and stronger associations on BMI Z-score were observed in boys and children living close to roadways. This study indicates that more attention should be paid to the health effects of UFPs, and routinely monitoring of UFPs should be considered.

Per- and perfluoroalkyl substances alternatives, mixtures and liver function in adults: A community-based population study in China.

Experimental evidence has shown that per- and polyfluoroalkyl substances (PFAS) alternatives and mixtures may exert hepatotoxic effects in animals. However, epidemiological evidence is limited. This research aimed to explore associations of PFAS and the alternatives with liver function in a general adult population. The study participants consisted of 1,303 adults from a community-based cross-sectional investigation in Guangzhou, China, from November 2018 to August 2019. We selected 13 PFAS with detection rates > 85% in serum samples and focused on perfluorooctane-sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and their alternatives [6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), 8:2 Cl-PFESA, and perfluorohexanoic acid (PFHxA)] as predictors of outcome. Six liver function biomarkers (ALB, ALT, AST, GGT, ALP, and DBIL) were chosen as outcomes. We applied regression models with restricted cubic spline function to explore correlations between single PFAS and liver function and inspected the combined effect of PFAS mixtures on liver by applying Bayesian kernel machine regression (BKMR). We discovered positive associations among PFAS and liver function biomarkers except for ALP. For example, compared with the 25th percentile of PFAS concentration, the level of ALT increased by 12.36% (95% CI: 7.91%, 16.98%) for ln-6:2 Cl-PFESA, 5.59% (95% CI: 2.35%, 8.92%) for ln-8:2 Cl-PFESA, 3.56% (95% CI: -0.39%, 7.68%) for ln-PFHxA, 13.91% (95% CI: 8.93%, 19.13%) for ln-PFOA, and 14.25% (95% CI: 9.91%, 18.77%) for ln-PFOS at their 75th percentile. In addition, higher exposed serum PFAS was found to be correlated with greater odds of abnormal liver function. Analysis from BKMR models also showed an adverse association between PFAS mixtures and liver function. The combined effect of the PFAS mixture appeared to be non-interactive, in which PFOS was the main contributor to the overall effect. Our findings provide evidence of associations between PFAS alternatives, PFAS mixtures, and liver function in the general adult population.

Associations between both legacy and alternative per- and polyfluoroalkyl substances and glucose-homeostasis: The Isomers of C8 health project in China.

BACKGROUND: Epidemiological studies on the associations of legacy per- and polyfluoroalkyl substances (PFASs) and glucose homeostasis remain discordant. Understanding of PFAS alternatives is limited, and few studies have reported joint associations of PFASs and PFAS alternatives. OBJECTIVES: To investigate associations of novel PFAS alternatives (chlorinated perfluoroalkyl ether sulfonic acids, Cl-PFESAs and perfluorobutanoic acid, PFBA) and two legacy PFASs (Perfluorooctanoic acid, PFOA and perfluorooctane sulfonate, PFOS) with glucose-homeostasis markers and explore joint associations of 13 legacy and alternative PFASs with the selected outcomes. METHODS: We used cross-sectional data of 1,038 adults from the Isomers of C8 Health Project in China. Associations of PFASs and PFAS alternatives with glucose-homeostasis were explored in single-pollutant models using generalized linear models with natural cubic splines for PFASs. Bayesian Kernel Machine Regression (BKMR) models were applied to assess joint associations of exposures and outcomes. Sex-specific analyses were also conducted to evaluate effect modification. RESULTS: After adjusting for confounders, both legacy (PFOA, PFOS) and alternative (Cl-PFESAs and PFBA) PFASs were positively associated with glucose-homeostasis markers in single-pollutant models. For example, in the total study population, estimated changes with 95% confidence intervals (CI) of fasting glucose at the 95th percentile of 6:2Cl-PFESA and PFOS against the thresholds were 0.90 (95% CI: 0.59, 1.21) and 0.44 (95% CI: 0.26, 0.62). Positive joint associations were found in BKMR models with 6:2Cl-PFESA contributing most. Sex-specific associations existed in both single- and multi-pollutant models. CONCLUSIONS: Legacy and alternative PFASs were positively associated with glucose-homeostasis markers. 6:2Cl-PFESA was the primary contributor. Sex-specific associations were also identified. These results indicate that joint associations and effect modification should be considered in risk assessment. However, further studies are recommended to strengthen our findings and to elucidate the mechanisms of action of legacy and alternative PFASs.

The effects of Cl-PFESAs exposure on blood lipids - A community-based large population study in Guangzhou.

Numerous epidemiological studies have investigated the lipid interference effects of legacy PFASs, however, no studies on PFAS alternatives and blood lipids have been published. In this study, we explored the association between Cl-PFESAs, a typical PFASs alternative in China, and blood lipid profiles in 1336 Guangzhou community residents using linear and non-linear regression models. The results showed a deleterious effect of Cl-PFESAs and blood lipids: adjusted estimates (ß) for TC, TG, LDL-C and HDL-C per natural log unit increase of 6:2 Cl-PFESA were 0.029 (95% CI: 0.020, 0.038), 0.075 (95% CI: 0.049, 0.101), 0.035 (95% CI: 0.021, 0.049) and -0.071 (95% CI: -0.084, -0.058), respectively. The association between Cl-PFESAs and dyslipidemia was also positively significant (P < 0.05). Furthermore, a non-linear relationship was observed in Cl-PFESAs and serum lipid levels using a restricted cubic splines (RCS) model. In summary, our research suggested a negative impact of Cl-PFESAs on blood lipid patterns and a possible non-linear association.

Exposure to second-hand smoke during early life and subsequent sleep problems in children: a population-based cross-sectional study.

BACKGROUND: Previous studies have revealed that current secondhand smoke exposure showed highly suggestive evidence for increased risk of simultaneous sleep problems in children. Data on the associations between early-life exposure to SHS with subsequent sleep problems in children were scarce. We aimed to evaluate the associations of early-life SHS exposure with sleep problems in children. METHODS: In this cross-sectional study, children were recruited from elementary and middle schools in Liaoning Province, China between April 2012 and January 2013. We assessed early-life SHS exposure (pregnancy and the first 2 years of life) via questionnaires. Sleep problems and different types of sleep-related symptoms were measured based on the validated tool of the Sleep Disturbance Scale for Children (SDSC). Generalized linear mixed models were applied to estimate the associations of early-life SHS exposure with sleep problems. RESULTS: We included a total of 45,562 children (22,657 [49.7%] males; mean [SD] age, 11.0 [2.6] years) and 6167 of them (13.5%) were exposed to early-life SHS during both pregnancy and the first 2 years of life. Compared with unexposed counterparts, children exposed to early-life SHS had higher total T-scores of SDSC (ß = 4.32; 95%CI: 4.06, 4.58) and higher odds of increased sleep problems (OR = 2.14; 95%CI: 1.89, 2.42). When considering different sleep-related symptoms, the associations between early-life SHS exposure and symptom of sleep-wake transition disorders (i.e., bruxism) were the strongest in all analyses. CONCLUSIONS: Early-life SHS exposure was associated with higher odds of global sleep problems and different sleep-related symptoms in children aged 6-18 years. Our findings highlight the importance to strengthen efforts to support the critical importance of maintaining a smoke-free environment especially in early life.

Exposure to isomers of per- and polyfluoroalkyl substances increases the risk of diabetes and impairs glucose-homeostasis in Chinese adults: Isomers of C8 health project.

Per- and polyfluoroalkyl substances (PFAS) exposure has been linked to diabetes, but evidence on the association of isomers of PFAS with type 2 diabetes (T2D) remains scant. This population based cross-sectional study aimed to investigate associations between serum PFAS isomers, glucose-homeostasis markers and T2D, adjusted for multiple potential confounders. We used data from "Isomers of C8 Health Project in China" from July 2015 to October 2016. A total of 10 PFAS including isomers of PFOS and PFOA were measured in serum of 1045 Chinese adults. Fasting blood glucose, fasting insulin, homeostasis model of insulin (HOMA-IR) and beta cell function (HOMA-ß) were considered as markers of glucose-homeostasis. We found significant positive associations between serum PFAS isomers and glucose-homeostasis markers, namely, fasting blood glucose, fasting insulin and HOMA-IR. Per log-unit increase in branched (br)-PFOS concentration was associated with increased fasting blood glucose (ß = 0.25, 95% CI: 0.18, 0.33), fasting insulin (ß = 2.19, 95% CI: 1.44, 2.93) and HOMA-IR (ß = 0.69, 95% CI: 0.50, 0.89). As compared to br-PFOS, linear (n)-PFOS and -PFOA showed lesser significant associations with glucose-homeostasis makers. Further, exposure to all PFAS including isomeric PFOS, PFOA and PFHxS increased the risk of T2D with br-PFOS exhibiting the highest risk (OR = 5.41, 95% CI: 3.68-7.96). The associations were stronger among women than men. In conclusion, chronic exposure to PFAS isomers was associated with impaired glucose-homeostasis and may increase the prevalence of T2D in Chinese adults. Given the ubiquity of PFAS in the environment and the public health burden of T2D, future studies are warranted to corroborate the findings.

Cost-consequence analysis of salvianolate injection for the treatment of coronary heart disease.

BACKGROUND: Complicated with the impact of aging population and urbanization, coronary heart disease (CHD) incurs more and more disease burdens in China. Salvianolate injection is a Chinese patent drug widely used for treating CHD in China. A series of studies have verified the efficacy of salvianolate injection , but the high drug cost has raised concerns. It is, therefore, important to conduct cost-consequence analysis to demonstrate whether salvianolate injection is associated with outcome improvement and cost containment. The aim of this study was to retrospectively evaluate the cost-consequence of salvianolate injection for the treatment of coronary heart disease by combining salvianolate injection with conventional treatment from a societal perspective. METHODS: We retrospectively studied hospitalized patients with CHD from August 2011 to December 2015 by using electronic medical record database. Patients who received salvianolate injection combined with conventional treatment were selected as exposed group, while those who received conventional treatment alone were selected as unexposed group. Propensity score matching (PSM) analysis was used to balance the characteristics of patients. After PSM, we evaluated hospital stay, total nitrates dosage, total medical costs, and subcategories costs. Patients with chronic ischemic heart disease were analyzed as a highly selected subcohort. RESULTS: For the overall group, hospital stay was significantly decreased by 2.9 days (P < 0.05) and total nitrates dosage was significantly decreased by 172.4 mg (P < 0.05) in exposed group; cost savings of pharmacy cost, examination cost, laboratory cost, operation cost and treatment was observed as significant (at P < 0.05); and the additional expenditure of Chinese patent drug (1174.9 CNY) was less than the saving of total medical costs (2636.4 CNY). For chronic ischemic heart disease subcohort, compared with unexposed group, significant decreases were also found in hospital stay and total nitrates dosage (P < 0.05); cost savings were significant (P < 0.05) for exposed group in terms of total medical costs (4339.5 CNY) and subcategories costs (including pharmacy cost, examination cost, operation cost and treatment cost); and the additional expenditure of Chinese patent drug (1189.3 CNY) was less than the saving of total medical costs. CONCLUSION: Compared with conventional treatment for the treatment of CHD, combination of salvianolate injection and conventional treatment was associated with a reduction in hospital stay and total nitrates dosage. The acquisition cost of Chinese patent drug (including salvianolate injection) was offset by a higher reduction in total medical costs, especially for chronic ischemic heart disease.