Junfeng Zhang

<h4>Background</h4>It is important to identify risk and beneficial factors for children's lung function. This study aims to ascertain potential changes in children's lung function in relation to changes in socioeconomic, parental and household factors, based on a comparison between two periods spanning 25 years in Wuhan, the largest metropolis in central China.<h4>Methods</h4>In two cross-sectional studies, lung function measurements and questionnaire surveys were conducted on school-age children in 1993-1996 (Period I) and in 2018 (Period II). Children of 6-12 years old from elementary schools were selected by a multistage sampling method. Demographic information, socioeconomic status, feeding methods, parental illness and behavior patterns, as well as household characteristics, were collected through a questionnaire survey. Spirometric lung function was measured, including forced vital capacity (FVC), forced expiratory volume in the first second (FEV₁), forced expiratory flow at 25% and 75% of the pulmonary volume (FEF25-75), and peak expiratory flow (PEF). Wilcoxon analysis of variances was used to assess the differences in lung function indexes between Period I and Period II. Multiple linear regression models were used to estimate the association of lung function with regard to socioeconomic, parental and household factors, respectively.<h4>Results</h4>Significant prevalence reductions were observed for household coal use, paternal smoking and maternal asthma, while the prevalence increased significantly for children sleeping in their own rooms or own beds and breastfeeding, ventilation use during cooking, and parental education level from Period I to Period II. When adjusted for age, height, weight, sex and other factors assessed in the study, children had significant lower values of FVC, FEV₁, and PEF in Period II than in Period I. Enclosed kitchen was significantly associated with lower lung function in children in Period I. Urban living condition and higher maternal education level were each associated with a higher FVC, while father having no fixed income was associated with a lower FVC and a lower FEV₁, respectively, in Period II. In comparison with Period I, the beneficial impact of urban living and that of breastfeeding were enhanced and the detrimental effect of poor household condition was weakened in Period II.<h4>Conclusions</h4>Lung function was lower in 2018 than in 1993-1996 in school-age children living in Wuhan. Although improvements in urban living and household environmental conditions as well as increased breastfeeding in Period II could have contributed to increased lung function, other unmeasured risk factors may have played a more dominant role in leading to a net decrease in lung function from Period I to Period II. Future studies are needed to identify these risk factors.

<h4>Background</h4>The health impacts of ambient air pollution impose large costs on society. Although all people are exposed to air pollution, the older population (ie, those aged ≥60 years) tends to be disproportionally affected. As a result, there is growing concern about the health impacts of air pollution as many countries undergo rapid population ageing. We investigated the spatial and temporal variation in the economic cost of deaths attributable to ambient air pollution and its interaction with population ageing from 2000 to 2016 at global and regional levels.<h4>Methods</h4>In this global analysis, we developed an age-adjusted measure of the value of a statistical life-year (VSLY) to estimate the economic cost of deaths attributable to ambient PM_2·5 pollution using Global Burden of Diseases, Injuries, and Risk Factors Study 2017 data and country-level socioeconomic information. First, we estimated the global age-specific and cause-specific mortality and years of life lost (YLLs) attributable to PM_2·5 pollution using the global exposure mortality model and global estimates of exposure at 0·1° × 0·1° (about 11 km × 11 km at the equator) resolution. Second, for each year between 2000 and 2016, we translated the YLLs within each age group into a health-related cost using a country-specific, age-adjusted measure of VSLY. Third, we decomposed the major driving factors that contributed to the temporal change in health costs related to PM_2·5. Finally, we did a sensitivity test to analyse the variability of the estimated health costs to four alternative valuation measures. We identified the uncertainty intervals (UIs) from 1000 draws of the parameters and concentration-response functions by age, cause, country, and year. All economic values are reported in 2011 purchasing power parity-adjusted US dollars. All simulations were done with R, version 3.6.0.<h4>Findings</h4>Globally, in 2016, PM_2·5 was estimated to have caused 8·42 million (95% UI 6·50-10·52) attributable deaths, which was associated with 163·68 million (116·03-219·44) YLLs. In 2016, the global economic cost of deaths attributable to ambient PM_2·5 pollution for the older population was US$2·40 trillion (1·89-2·93) accounting for 59% (59-60) of the cost for the total population ($4·09 trillion [3·19-5·05]). The economic cost per capita for the older population was $2739 (2160-3345) in 2016, which was 10 times that of the younger population (ie, those aged <60 years). By assessing the factors that contributed to economic costs, we found that increases in these factors changed the total economic cost by 77% for gross domestic product (GDP) per capita, 21% for population ageing, 16% for population growth, -41% for age-specific mortality, and -0·4% for PM_2·5 exposure.<h4>Interpretation</h4>The economic cost of ambient PM_2·5 borne by the older population almost doubled between 2000 and 2016, driven primarily by GDP growth, population ageing, and population growth. Compared with younger people, air pollution leads to disproportionately higher health costs among older people, even after accounting for their relatively shorter life expectancy and increased disability. As the world's population is ageing, the disproportionate health cost attributable to ambient PM_2·5 pollution potentially widens the health inequities for older people. Countries with severe air pollution and rapid ageing rates need to take immediate actions to improve air quality. In addition, strategies aimed at enhancing health-care services, especially targeting the older population, could be beneficial for reducing the health costs of ambient air pollution.<h4>Funding</h4>National Natural Science Foundation of China, China Postdoctoral Science Foundation, and Qiushi Foundation.

<h4>Background</h4>There are few oxidative biomarkers that can be used in resource-limited settings (e.g., rural Africa) where blood collection facilities are lacking. This study aims to evaluate the potential of malondialdehyde (MDA) in dried blood spots (DBS) as a useful biomarker to monitor cardiopulmonary health.<h4>Methods</h4>We first conducted a cross-validation comparison of matched capillary DBS, plasma, and whole venous blood collected from nine healthy volunteers for the measurement of total MDA (free + conjugated) and C-reactive protein (CRP), a well-established biomarker of systemic inflammation. Then a field study was conducted in a rural Senegal with a population of 441 women routinely exposed to severe household air pollution, examining associations of MDA and CRP levels in 882 DBS with self-reported cardiopulmonary symptoms.<h4>Results</h4>In the cross-validation study, CRP levels were strongly correlated across DBS, plasma, and whole blood. MDA levels were correlated between DBS and whole blood and were 1-2 orders of magnitude lower in plasma, suggesting that DBS MDA may reflect total oxidation levels in intracellular and extracellular compartments. In the field study, we observed significantly higher MDA levels in women with secondhand smoke exposure. An interquartile range increase in MDA concentration was associated with 27.0% (95% CI: 3.1-56.5%) and 21.1% (95% CI: -3.5% to 52.0%) increases in the incidence of chest tightness and breath difficulty, respectively. In contrast, CRP levels were not associated with worse outcomes or risk factors.<h4>Conclusions</h4>These results support the use of DBS as a convenient alternative to venous blood when MDA is measured as a biomarker for cardiopulmonary health risk.

BACKGROUND: Maternal smoking during pregnancy is related to altered DNA methylation in infant umbilical cord blood. The extent to which low levels of smoke exposure among nonsmoking pregnant women relates to offspring DNA methylation is unknown. OBJECTIVE: This study sought to evaluate relationships between maternal prenatal plasma cotinine levels and DNA methylation in umbilical cord blood in newborns using the Infinium HumanMethylation 450K BeadChip. METHODS: Participants from the Newborn Epigenetics Study cohort who reported not smoking during pregnancy had verified low levels of cotinine from maternal prenatal plasma (0 ng/mL to <4 ng/mL), and offspring epigenetic data from umbilical cord blood were included in this study (n=79). Multivariable linear regression models were fit to the data, controlling for cell proportions, age, race, education, and parity. Estimates represent changes in response to any 1-ng/mL unit increase in exposure. RESULTS: Multivariable linear regression models yielded 29,049 CpGs that were differentially methylated in relation to increases in cotinine at a 5% false discovery rate. Top CpGs were within or near genes involved in neuronal functioning (PRKG1, DLGAP2, BSG), carcinogenesis (FHIT, HSPC157) and inflammation (AGER). Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggest cotinine was related to methylation of gene pathways controlling neuronal signaling, metabolic regulation, cell signaling and regulation, and cancer. Further, enhancers associated with transcription start sites were enriched in altered CpGs. Using an independent sample from the same study population (n=115), bisulfite pyrosequencing was performed with infant cord blood DNA for two genes within our top 20 hits (AGER and PRKG1). Results from pyrosequencing replicated epigenome results for PRKG1 (cg17079497, estimate=-1.09, standard error (SE)=0.45, p=0.018) but not for AGER (cg09199225; estimate=-0.16, SE=0.21, p=0.44). DISCUSSION: Secondhand smoke exposure among nonsmoking women may alter DNA methylation in regions involved in development, carcinogenesis, and neuronal functioning. These novel findings suggest that even low levels of smoke exposure during pregnancy may be sufficient to alter DNA methylation in distinct sites of mixed umbilical cord blood leukocytes in pathways that are known to be altered in cord blood from pregnant active smokers. https://doi.org/10.1289/EHP8099.

The molecular mechanisms underlying the associations between air pollution exposure and adverse cardiopulmonary effects remain to be better understood. Altered amino acid metabolism may plays an important role in the development of cardiopulmonary diseases and may be perturbed by air pollution exposure. To test this hypothesized molecular mechanism, we conducted an association analysis from an existing intervention study to examine the relations of air pollution exposures with amino acids in 43 Chinese healthy adults. Plasma levels of amino acids were measured using a UPLC-QqQ-MS system. Time-weighted personal exposure to O₃, PM_2.5, NO₂, and SO₂ over four time windows, i.e., 12 h, 24 h, 1 week, and 2 weeks, were calculated using the measured indoor and outdoor concentrations coupled with the time-activity data for each participant. Linear mixed-effects models were used to estimate the associations between air pollutants at each exposure window and amino acids by controlling for potential confounders. We observed significant associations between exposures and plasma concentrations of amino acids, with the direction of associations varying by amino acid and air pollutant. While there is little evidence of associations for NO₂ and SO₂, the associations with amino acids were fairly pronounced for exposure to PM_2.5 and O₃. In particular, independent O₃ (12- and 24-hour) associations were observed with changes in the amino acids that were related to the urea cycle, including aspartate, asparagine, glutamate, arginine, citrulline, and ornithine. Our findings indicated that air pollution may cause acute perturbation of amino acid metabolism, and that O₃ and PM_2.5 may affect the metabolism of amino acids in different pathways. Main finding: Acute air pollution exposure might affect the perturbation of amino acid metabolism, and in particular, was associated with amino acids in relation to the urea cycle.