Development of a targeted method for DNA adductome and its application as sensitive biomarkers of ambient air pollution exposure.

DNA adducts are widely recognized as biomarkers of exposure to environmental carcinogens and associated health effects in toxicological and epidemiological studies. This study presents a targeted and sensitive method for comprehensive DNA adductome analysis using ultra-high-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry (UHPLC-QqQ-MS/MS). The method was developed using calf thymus DNA, with careful optimization of mass spectrometric parameters, chromatographic separation conditions, and pretreatment methods. Ultimately, a targeted method was established for 41 DNA adducts, which showed good linearity (R2 ≥0.992), recovery (80.1-119.4 %), accuracy (81.3-117.8 %), and precision (relative standard deviation <14.2 %). The established method was employed to analyze DNA adducts in peripheral blood cells from pregnant women in Shanxi and Beijing. Up to 23 DNA adducts were successfully detected in samples of varying sizes. From 2 µg of maternal DNA samples, seven specific adducts were identified: 5-methyl-2'-deoxycytidine (5-MedC), 5-hydroxymethyl-2'-deoxycytidine (5-HmdC), N6-methyl-2'-deoxyadenosine (N6-MedA), 8-hydroxy-2'-deoxyguanosine (8-OHdG), 5-hydroxy-2'-deoxycytidine (5-OHdC), 1,N6-etheno-2'-deoxyadenosine (1,N6-εdA), and N2-methyl-2'-deoxyguanosine (N2-MedG). This study reveals that exposure to higher concentrations of ambient air pollutants may elevate the levels of DNA methylation and oxidative damage at different base sites, highlighting the application potential of DNA adducts as sensitive biomarkers of air pollution exposure.

Development and validation of a simple and rapid HILIC-MS/MS method for the quantification of low-abundant lysoglycerophospholipids in human plasma.

Lysoglycerophospholipids (Lyso-GPLs) are an essential class of signaling lipids with potential roles in human diseases, such as cancer, central nervous system diseases, and atherosclerosis. Current methods for the quantification of Lyso-GPLs involve complex sample pretreatment, long analysis times, and insufficient validation, which hinder the research of Lyso-GPLs in human studies, especially for Lyso-GPLs with low abundance in human plasma such as lysophosphatidic acid (LPA), lysophosphatidylinositol (LPI), lysophosphatidylglycerol (LPG), lysophosphatidylserine (LysoPS), lyso-platelet-activating factor (LysoPAF), and cyclic phosphatidic acid (cPA). Herein, we report the development and validation of a simple and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of Lyso-GPLs with low abundance in plasma. Protein precipitation using MeOH for Lyso-GPL extraction, quick separation (within 18 min) based on hydrophilic interaction liquid chromatography (HILIC), and sensitive MS detection under dynamic multiple reaction monitoring (dMRM) mode enabled efficient quantification of 22 Lyso-GPLs including 2 cPA, 4 LPG, 11 LPA, 2 LysoPS, and 3 LysoPAF in 50 µL of human plasma. The present method showed good linearity (goodness of fit, 0.99823-0.99995), sensitivity (lower limit of quantification, 0.03-14.06 ng/mL), accuracy (73-117%), precision (coefficient of variation ≤ 28%), carryover (≤ 17%), recovery (80-110%), and stability (83-123%). We applied the method in an epidemiological study and report concentrations of 18 Lyso-GPLs in 567 human plasma samples comparable to those of previous studies. Significant negative associations of LysoPAF C18, LysoPAF C18:1, and LysoPAF C16 with homeostatic model assessment for insulin resistance (HOMA-IR) level were observed; this indicates possible roles of LysoPAF in glucose homeostasis. The application of the present method will improve understanding of the roles of circulating low-abundant Lyso-GPLs in health and diseases.

Pro-thrombotic changes associated with exposure to ambient ultrafine particles in patients with chronic obstructive pulmonary disease: roles of lipid peroxidation and systemic inflammation.

BACKGROUND: Exposure to particulate matter air pollution is associated with an increased risk of cardiovascular mortality in patients with chronic obstructive pulmonary disease (COPD), but the underlying mechanisms are not yet understood. Enhanced platelet and pro-thrombotic activity in COPD patients may explain their increased cardiovascular risk. We aim to explore whether short-term exposure to ambient particulate matter is associated with pro-thrombotic changes in adults with and without COPD, and investigate the underlying biological mechanisms in a longitudinal panel study. Serum concentration of thromboxane (Tx)B2 was measured to reflect platelet and pro-thrombotic activity. Lipoxygenase-mediated lipid peroxidation products (hydroxyeicosatetraenoic acids [HETEs]) and inflammatory biomarkers (interleukins [ILs], monocyte chemoattractant protein-1 [MCP-1], tumour necrosis factor alpha [TNF-α], and macrophage inflammatory proteins [MIPs]) were measured as potential mediating determinants of particle-associated pro-thrombotic changes. RESULTS: 53 COPD and 82 non-COPD individuals were followed-up on a maximum of four visits conducted from August 2016 to September 2017 in Beijing, China. Compared to non-COPD individuals, the association between exposure to ambient ultrafine particles (UFPs) during the 3-8 days preceding clinical visits and the TxB2 serum concentration was significantly stronger in COPD patients. For example, a 103/cm3 increase in the 6-day average UFP level was associated with a 25.4% increase in the TxB2 level in the COPD group but only an 11.2% increase in the non-COPD group. The association in the COPD group remained robust after adjustment for the levels of fine particulate matter and gaseous pollutants. Compared to the non-COPD group, the COPD group also showed greater increases in the serum concentrations of 12-HETE (16.6% vs. 6.5%) and 15-HETE (9.3% vs. 4.5%) per 103/cm3 increase in the 6-day UFP average. The two lipid peroxidation products mediated 35% and 33% of the UFP-associated increase in the TxB2 level of COPD patients. UFP exposure was also associated with the increased levels of IL-8, MCP-1, MIP-1α, MIP-1ß, TNF-α, and IL-1ß in COPD patients, but these inflammatory biomarkers did not mediate the TxB2 increase. CONCLUSIONS: Short-term exposure to ambient UFPs was associated with a greater pro-thrombotic change among patients with COPD, at least partially driven by lipoxygenase-mediated pathways following exposure. Trial registration ChiCTR1900023692 . Date of registration June 7, 2019, i.e. retrospectively registered.

Ceramide metabolism mediates the impaired glucose homeostasis following short-term black carbon exposure: A targeted lipidomic analysis.

BACKGROUND: Ambient particulate matter (PM), especially its carbonaceous composition black carbon (BC) increases cardiometabolic risks, yet the underlying mechanisms are incompletely understood. Ceramides (Cer; a class of sphingolipids) are biological intermediates in glucose metabolism. OBJECTIVES: To explore whether Cer metabolism mediates impaired glucose homeostasis following short-term PM exposure. METHODS: In a panel study in Beijing, China, 112 participants were followed-up between 2016 and 2017. Targeted lipidomic analyses quantified 26 sphingolipids in 387 plasma samples. Ambient BC and PM with aerodynamic diameter ≤ 2.5 µm (PM2.5) were continuously monitored in a station. We examined the associations of sphingolipid levels with average BC and PM2.5 concentrations 1-14 days before clinical visits using linear mixed-effects models, and explored the mediation effects of sphingolipids on PM-associated fasting blood glucose (FBG) difference using mediation analyses. RESULTS: Increased levels of FBG and multiple sphingolipids in Cer metabolic pathways were associated with BC exposure in 1-14-day time window, but not with PM2.5 exposure. For each 10 µg/m3 increase in the average BC concentration 1-14 days before the clinical visits, species in the Cer C24:1 pathway (Cer, dihydroceramide, hexosylceramide, lactosylceramide, and sphingomyelin C24:1) increased in levels ranging from 11.8% (95% confidence interval [CI]: -6.2-33.2) to 48.7% (95% CI: 8.8-103.4), as did the Cer C16:0, C18:0, and C20:0 metabolic pathway species, ranging from 3.2% (95% CI: -5.6-12.9) to 32.4% (95% CI: 7.0-63.8), respectively. The Cer C24:1 metabolic pathway species mediated 6.5-25.5% of the FBG increase associated with BC exposure in 9-day time window. The Cer C16:0, C18:0, and C20:0 metabolic pathway species mediated 5.4-26.2% of the BC-associated FBG difference. CONCLUSIONS: In conclusion, Cer metabolism may mediate impaired glucose homeostasis following short-term BC exposure. The current findings are preliminary, which need to be corroborated by further studies.

The associations of nitrated polycyclic aromatic hydrocarbon exposures with plasma glucose and amino acids.

Nitrated polycyclic aromatic hydrocarbons (nitro-PAHs) have been widely studied for their mutagenic and carcinogenic effects. This study aims to investigate whether exposure to nitro-PAHs is associated with biomarkers of carbohydrate metabolism, an underlying risk factor for metabolic disorder. Early morning urine and blood samples were longitudinally collected two times with a four-week interval from 43 healthy adults. Five urinary amino-PAHs (1-aminonaphthalene, 2-aminonaphthalene, 9-aminophenanthrene, 2-aminofluorene, and 1-aminopyrene) were measured as biomarkers of nitro-PAH exposures. We measured plasma concentrations of glucose and six amino acids that can regulate insulin secretion, including aspartate (Asp), glutamate (Glu), glutamine (Gln), alanine (Ala), Arginine (Arg), and ornithine (Orn). We found that increasing concentrations of 9-aminophenanthrene were significantly associated with increasing glucose levels and with decreasing Asp, Glu, Ala, and Orn levels. We estimated that 26.4 %-43.8 % of the 9-aminophenanthrene-associated increase in glucose level was mediated by Asp, Glu, and Orn. These results suggest that exposure to certain nitro-PAHs affects glucose homeostasis, partly resulting from the depletion of insulin-stimulating amino acids (Asp, Glu, and Orn).

The effects of indoor and outdoor air pollution on the prevalence of adults' respiratory diseases in four Chinese cities: a comparison between 2017-2018 and 1993-1996.

BACKGROUND: Over the past decades, both ambient and household air pollution have changed in several aspects, including the emission sources and the concentrations of pollutants, in many Chinese cities. It is unknown whether these changes are associated with changes in health conditions, especially given changes in other factors due to rapid economic growth. METHODS: Two cross-sectional surveys were conducted in two periods spanning more than twenty years (1993-1996 vs. 2017-2018) in four Chinese cities of Chongqing, Wuhan, Lanzhou, and Guangzhou. Data were collected regarding adults' respiratory disease, smoking status, education, occupation, and household characteristics. Ambient air pollution data were obtained for each study. We first used logistic regression models to construct the district-specific adjusted disease prevalences. In the second stage, first-difference regression models were employed to examine whether the change in respiratory diseases prevalences was associated with the change in outdoor air pollution and indoor air pollution surrogates. RESULTS: A total of 7,557 and 9,974 households were participating in Period 1 (1993-1996) and Period 2 (2017-2018), respectively. Compared to Period 1, we found substantial reductions in the ambient air pollution concentrations, and a suggestive improvement in cooking-related indoor air pollution in Period 2. We observed decreases in the district-specific covariate-adjusted prevalences of both asthma and chronic bronchitis among participants, with an average reduction of 3.6% (range: 0.0% to 24.3%). From Period 1 to Period 2, one percent decrease in the proportion of cooking with coal was associated with a 19.0% (95% CI, 0.96-37.04%) decrease in the prevalence of males' chronic bronchitis and a 1.86% (0.69-3.04%) increase in the prevalence of females' asthma. Little evidence was observed regarding the potential health benefits associated with the decreases in ambient air pollution levels. CONCLUSIONS: The substantial reduction in household use of coal for cooking might be an important contributor to the decrease in adults' respiratory disease prevalence from 1993-1996 to 2017-2019 in four Chinese cities. Changes in this indoor air pollution source, along with other risk factors for respiratory diseases, may have masked respiratory health benefits associated with reductions in outdoor air pollution levels.

Household environmental factors and children's respiratory health: comparison of two cross-sectional studies over 25 years in Wuhan, China.

BACKGROUND: Over the recent decades, residential lifestyle and household environment have changed substantially with rapid development of industrialization and urbanization in China. Whether the prevalence of respiratory diseases changed is still lack of evidence. The objective of this study is to assess potential changes in children's respiratory disease prevalence and associated household environmental factors in Wuhan over a 25-year time interval. METHODS: Two cross-sectional studies in the Period 1 (1993 to 1996) and Period 2 (2017 to 2018) were compared in this research. Elementary school children in period 1 (N=2,517) and in period 2 (N=3,152) were recruited in Wuhan, China. The respiratory health condition, home environmental factors, and family socioeconomic status of each subject were acquired through questionnaire survey using the same protocols in both periods. We used the Chi-square test to analyze the difference of household environmental factors (focused on three indoor air quality determinants) and children's respiratory health condition between two periods. Logistic regression models were used to assess the impacts of household environmental determinants on children's respiratory diseases and symptoms between the two studies, by adjusting a set of covariates. RESULTS: The three indoor air quality determinants have reduced substantially in prevalence from period 1 to period 2: environment tobacco smoke (ETS) from 86.6% to 45.9%, household coal use from 47.6% to 4.9%, and kitchen smoke from 58.9% to 7.3%. The prevalence of certain respiratory symptoms in children significantly decreased, such as cough with colds (51.1% to 41.6%) and phlegm with colds (22.3% to 17.7%). The prevalence of asthma was 2.5% and 2.4% and that of bronchitis was 27.1% and 29.8% in both periods. Coal use was a risk factor for asthma in period 1 (OR =2.34, 95% CI: 1.30-4.23), while it was not significantly associated with prevalence of asthma in period 2 (OR =0.60, 95% CI: 0.08-4.51). CONCLUSIONS: Household indoor air quality determinants and respiratory health condition of children in Wuhan has been improved over the last 25 years. At present, kitchen smoke is an important factor affecting the prevalence of wheeze whatever child has a cold or not and reducing exposure to ETS could be beneficial to protect children to be less likely to develop bronchitis.

Changes in children's lung function over two decades in relation to socioeconomic, parental and household factors in Wuhan, China.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The exposures and health effects of benzene, toluene and naphthalene for Chinese chefs in multiple cooking styles of kitchens.

Commercial cooking has higher intensity and more severe instantaneous cooking pollution from volatile organic chemicals compared to home cooking, making health risk assessment of occupational exposure for chefs a priority. In this study, chefs from three cooking styles of kitchens, including steaming, frying, and grilling, were selected to investigate the external and internal exposures, health risks and effects of several typical aromatic hydrocarbons (benzene, toluene and naphthalene). Naphthalene was found to be the most concentrated contaminant in air samples among the different kitchens, while benzene had the lowest concentration. The concentration of toluene in frying kitchens was significantly higher than that in steaming kitchens. Air concentrations of toluene in frying kitchens, as well as benzene concentrations in grilling kitchens exceeded the standard level according to indoor air quality standard (GB/T18883-2002). Regarding the metabolites of pollutants in urine, the content of S-benzylmercapturic acids (S-BMA) for frying chefs was significantly higher than that for other cooking styles of chefs, which was consistent with the relatively higher air concentrations of toluene. There was a good correlation between internal and external exposure of the pollutants. The level of oxidative stress was influenced by 2-hydroxynaphthalene (2-OHN) and S-BMA, indicating the potential health risks of these occupational exposed chefs. This study indicates the need to improve the monitoring of typical aromatic hydrocarbons, as well as to investigate their potential health effects in large-scale groups, and improve the ventilation in kitchens.

Nitrated Polycyclic Aromatic Hydrocarbons and Arachidonic Acid Metabolisms Relevant to Cardiovascular Pathophysiology: Findings from a Panel Study in Healthy Adults.

Concerns on nitrated polycyclic aromatic hydrocarbons (nitro-PAHs) in the environment have mainly arisen from their mutagenic and carcinogenic effects. The objective of this study is to investigate whether nitro-PAH exposures are associated with biomarkers of cardiovascular pathophysiology. In a panel study design, urines and blood samples were collected up to four times with a 2-week interval from 89 healthy adults. We measured 1-naphthylamine, 2-naphthylamine, 9-aminophenanthrene, 2-aminofluorene, and 1-aminopyrene as biomarkers of nitro-PAH exposures. We measured three urinary metabolites of arachidonic acid (AA) including 20-hydroxyeicosatetraenoic acid (20-HETE) from the cytochrome P450 (CYP) pathway, 8-isoprostane from the nonenzymatic pathway, and 11-dehydro-thromboxane B2 (11-dhTXB2) from the cyclooxygenase (COX) pathway. Urinary malondialdehyde, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and 6-sulfatoxymelatonin (aMT6s) were measured to reflect systemic oxidative stress. Plasma concentrations of the soluble P-selectin and von Willebrand factor (vWF) were measured as biomarkers of platelet activation and endothelial dysfunction. We found that increased urinary concentrations of amino-PAHs were significantly associated with increased 20-HETE, 11-dhTXB2, and 8-OHdG and with decreased 8-isoprostane and aMT6s. Increased amino-PAHs were positively associated with P-selectin and vWF, respectively. These results suggest that exposure to nitro-PAHs increases systemic oxidative stress and alters AA metabolism toward CYP and COX pathways, leading to an increased cardiovascular disease risk.

Single-cell transcriptomics uncovers phenotypic alterations in the monocytes in a Chinese population with chronic cadmium exposure.

BACKGROUND: Cadmium is the most prevalent form of heavy metal contaminant globally and its exposure rises serious health concern. Chronic exposure to cadmium causes immune disturbances. However, few studies have addressed how it affects circulating immune cells, one of the most essential elements for the host defense system, at both population and molecular level. Therefore, this is the first single-cell transcriptomic analysis of the response of the human circulating immune system to plasma cadmium level. METHODS: We conducted a cross-sectional study in Hunan province, which has the highest level of cadmium land contamination in China. A total of 3283 individuals were eligible for analyzing the association between plasma cadmium levels and the monocyte counts and its subgroups. Another 780 individuals were assigned for validation. Thirty propensity-matched individuals without chronic disease from the lowest- and highest-quartile groups according to serum cadmium levels were selected for single-cell RNA sequencing (scRNA-seq) and flow cytometry analyses. Moreover, the monocyte phenotypic alterations in the heavy metal-exposed population were validated with a cecal ligation and puncture sepsis mouse model. RESULTS: From August 2016 to July 2017, we conducted a cross-sectional study to identify phenotypic alterations in peripheral immune cells in cadmium polluted areas in China. Monocyte percentages were negatively associated with plasma cadmium levels in multivariable linear regression analysis. Peripheral blood mononuclear cell scRNA-seq revealed that the CD14+ monocyte subset was dramatically reduced in the highest-quartile cadmium-exposed group. Moreover, we assessed different hallmarks of immune cell dysfunction-such as host defense capability, apoptotic signaling, cellular diversity and malignant gene expression in monocytes. Importantly, cadmium induced phenotypic alterations in the immune system were validated in the cecal ligation and puncture sepsis mouse model, in which chronic exposure to cadmium not only increased the death rate but also decreased monocyte numbers and the ability to clear bacterial infections. CONCLUSION: This transcriptomic analysis provides molecular information about how the most important hallmarks of immune cell dysfunction are affected by plasma cadmium level. The significant phenotypic alterations in monocytes serving as early indicators of increased susceptibility to infectious and malignant diseases.

Metabolomic and Transcriptomic Analysis of MCF-7 Cells Exposed to 23 Chemicals at Human-Relevant Levels: Estimation of Individual Chemical Contribution to Effects.

BACKGROUND: Humans are constantly being exposed to various xenobiotics at relatively low concentrations. To date, limited evidence is available to ascertain whether a complex xenobiotic mixture at human-relevant levels causes any health effect. Moreover, there is no effective method to pinpoint the contribution of each chemical toward such an effect. OBJECTIVES: This study aims to understand the responses of cells to a mixture containing 23 xenobiotics at human-relevant levels and develop a feasible method to decipher the chemical(s) that contribute significantly to the observed effect. METHODS: We characterized the metabolome and transcriptome of breast cancer cells (MCF-7) before and after exposure to the mixture at human-relevant levels; preexposure levels were derived from existing large-scale biomonitoring data. A high-throughput metabolomics-based "leave-one-out" method was proposed to understand the relative contribution of each component by comparing the metabolome with and without the particular chemical in the mixture. RESULTS: The metabolomic analysis suggested that the mixture altered metabolites associated with cell proliferation and oxidative stress. For the transcriptomes, gene ontology terms and pathways including "cell cycle," "cell proliferation," and "cell division" were significantly altered after mixture exposure. The mixture altered genes associated with pathways such as "genotoxicity" and "nuclear factor erythroid 2-related factor 2 (Nrf2)." Through joint pathways analysis, metabolites and genes were observed to be well-aligned in pyrimidine and purine metabolisms. The leave-one-out results showed that many chemicals made their contributions to specific metabolic pathways. The overall metabolome pattern of the absence of 2,4-dihyroxybenzophenone (DHB) or bisphenol A (BPA) showed great resemblance to controls, suggesting their higher relative contribution to the observed effect. DISCUSSION: The omics results showed that exposure to the mixture at human-relevant levels can induce significant in vitro cellular changes. Also, the leave one out method offers an effective approach for deconvoluting the effects of the mixture. https://doi.org/10.1289/EHP6641.

Prevalence of respiratory diseases in relation to smoking rate in adults living in four Chinese cities: a comparison between 2017-2018 and 1993-1996.

BACKGROUND: The sustained high prevalence of smoking in China has contributed substantially to the burden of chronic diseases, including respiratory diseases. This study compared the prevalence of smoking and respiratory diseases in Chinese adults between two time periods spanning over 25 years. METHODS: Cross-sectional surveys were performed in four Chinese cities of Chongqing, Lanzhou, Wuhan, and Guangzhou in 1993-1996 (Period 1) and in 2017-2018 (Period 2). Participants completed questionnaires asking smoking status, the presence of asthma and chronic bronchitis, education attainment and household characteristics. Logistic regression models were used to estimate the odds ratios of disease prevalence with regard to active smoking status for men and passive smoking status for women. RESULTS: Prevalence of asthma, prevalence of chronic bronchitis, and smoking rate, all decreased from Period 1 to Period 2. We observed strong evidence that active smoking increased prevalence for both asthma and chronic bronchitis in men during Period 1, with spatial heterogeneity and modifying effect by college-level education. Home exposure to passive smoking was associated with increased odds of having chronic bronchitis among female participants in Chongqing during Period 2, although the association was not statistically significant. CONCLUSIONS: The prevalence for asthma and chronic bronchitis were lower in 2017-2018 compared to 25 years ago in the same four Chinese cities. Decreased smoking rate may have contribution to the improvement of these respiratory diseases. Male smokers, especially those without college-level education, showed higher prevalence of chronic bronchitis compared to nonsmokers during Period 1.

Respiratory health effects of residential individual and cumulative risk factors in children living in two cities of the Pearl River Delta Region, China.

BACKGROUND: Indoor environment is complex, with many factors potentially interacting with each other to affect health. However, previous studies have usually focused on effect of a single factor. Assessment of the combined effects of multiple factors can help with understanding the overall health risk. METHODS: A cross-sectional study was conducted among 2,306 school children in Guangzhou and Shenzhen. Questionnaire data on respiratory symptoms and diseases were collected along with sociodemographic and residential environmental information. A subset of children (N=987) were measured for their lung function. A random forest algorithm was applied to screen the top-ranked indoor environmental exposure variables and to form a composite index for cumulative risk of indoor pollution (CRIP). Logistic regressions were conducted to analyze the independent effect of single indoor environmental risk factors and the combined effect of CRIP on children's respiratory health. Multiple linear regressions were used to examine the independent and combined effects of indoor environmental exposure on lung function. RESULTS: We found that home dampness and molds as well as environmental tobacco smoke (ETS) were significantly and independently associated with increased prevalence of children's respiratory symptoms and diseases and with reduced lung function. A higher CRIP level was significantly associated with increased risk of cough with cold (OR =1.37, 95% CI: 1.05-1.79) and wheeze (OR =2.71, 95% CI: 1.16-6.34). A higher CRIP level was also associated with reduced lung function measured as FVC, FEV1, PEF, FEF25%, FEF25-75% and VC. CONCLUSIONS: In children living in the subtropical region of the Pearl River Delta, home dampness and the presence of mold as well as ETS were individual risk factors for children's respiratory health. The composite CRIP index was associated with respiratory symptoms and lung function, suggesting the utility of this index for predicting the combined effects of multiple risk factors.

Changes in children's asthma prevalence over two decades in Lanzhou: effects of socioeconomic, parental and household factors.

BACKGROUND: The prevalence of childhood asthma may have changed with rapid economic development. This study aims to ascertain potential changes in asthma prevalence in relation to changes in socioeconomic, parental and household factors, based on a comparison between two periods spanning over 20 years in Lanzhou, a large northwestern city of China. METHODS: Cross-sectional studies using the same protocols were performed in Lanzhou, China in 1994-1995 (Period I) and in 2017 (Period II). Children of 6-12 years old from elementary schools were selected by a multistage sampling method. Information on the presence of asthma and asthma-related symptoms of children, socioeconomic status, feeding methods, parental illness and behavior patterns, as well as household characteristics, were collected through a questionnaire survey. Logistic regression models were used to estimate odds ratios of asthma prevalence with regard to socioeconomic, parental and household factors, respectively. RESULTS: Significant prevalence reductions were observed for paternal smoking, household coal use, and parental asthma, while the prevalence increased significantly for children sleeping in their own rooms or own beds, ventilation use during cooking, and parental occupation and education level after 22 years. In children, the prevalence of ever-diagnosed asthma decreased from 3.2% in period I to 1.5% in Period II (P<0.001); the prevalence of wheeze also decreased from 15.4% to 9.3% (P<0.001). Passive smoking (OR =1.531, 95% CI: 1.032-2.270) and poor household ventilation (OR =1.709, 95% CI: 1.208-2.416) were significantly associated with an increased prevalence of wheeze in Period I, whereas household mold (OR =2.112, 95% CI: 1.203-3.811) was significantly associated with prevalence of wheeze. Parental asthma history was associated with increased prevalence of asthma and asthma-related symptoms. Breastfeeding was significantly associated with reduced risk of asthma in period II children. CONCLUSIONS: The prevalence of asthma and that of asthma-related symptoms were lower in 2017 than in 1994-1995 in school children living in Lanzhou. In 2017 with increased urbanization and industrialization, breastfeeding became a significant protective factor and household mold was a significant risk factor for asthma diagnosis and asthma-related symptoms. Promoting breastfeeding and household mold control is recommended to reduce the risk of childhood asthma in contemporary Lanzhou.

[Effectiveness of tibio-talo-calcaneal arthrodesis with full thread headless compression screws via combined minimal incisions].

Objective: To investigate the effectiveness of tibio-talo-calcaneal arthrodesis with full thread headless compression screws via combined minimal incisions. Methods: Between January 2012 and December 2016, 36 patients (36 feet) with ankle diseases underwent tibio-talo-calcaneal arthrodesis with parallel double thread headless compression screws via minimal anterior and lateral oblique incisions. There were 14 males and 22 females with an average age of 53.8 years (range, 18-76 years). There were 19 cases of left feet and 17 cases of right feet. There were 21 cases of talar necrosis, 7 cases of post-traumatic arthritis, 3 cases of rheumatoid arthritis, 2 cases of tuberculosis infection (inactive), 1 case of talar absence, 1 case of Charcot's disease, and 1 case of pigmented villonodular synovitis of ankle and subtalar joints. Preoperative American Orthopaedic Foot and Ankle Society (AOFAS) score and visual analogue scale (VAS) score were 53.7±2.5 and 5.9±0.2, respectively. The operation time was recorded and the wound healing and complications were observed. The bone healing was assessed by X-ray film and CT scanning. The function and pain of joint were evaluated by AOFAS and VAS scores. Results: The mean operation time was 49.8 minutes (range, 33-82 minutes). Incision infection occurred in 1 patient (2.8%) at 3 weeks after operation, and recovered after debridement. The other incisions healed by first intention without complications. Thirty-five patients were followed up with an average of 18.5 months (range, 12-29 months). Imaging examination showed fusion of the ankle and subtalar joints with an average fusion time of 10.9 weeks (range, 8-15 weeks). After 1 year, the AOFAS score (84.7±0.6) and VAS score (0.3±0.1) were significantly higher than preoperative scores ( t=12.596, P=0.000; t=30.393, P=0.000). Conclusion: It is an effective surgical method of tibio-talo-calcaneal arthrodesis with full thread headless compression screws via combined minimal incisions for end-stage ankle disease because of the less complications incidence and the higher postoperative fusion rate.

Indoor black carbon of outdoor origin and oxidative stress biomarkers in patients with chronic obstructive pulmonary disease.

OBJECTIVES: We assessed relationships between indoor black carbon (BC) exposure and urinary oxidative stress biomarkers, 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA), in participants with chronic obstructive pulmonary disease (COPD). METHODS: Eighty-two participants completed in-home air sampling for one week prior to providing urine samples up to four times in a year. Weekly indoor and daily outdoor concentrations were used to estimate indoor daily lags and moving averages. There were no reported in-home BC sources, thus indoor levels closely represented outdoor BC infiltration. Mixed effects regression models with a random intercept for each participant were used to assess relationships between indoor BC and 8-OHdG and MDA, adjusting for age, race, BMI, diabetes, heart disease, season, time of urine collection, urine creatinine, and outdoor humidity and temperature. RESULTS: There were positive effects of BC on 8-OHdG and MDA, with the greatest effect the day before urine collection (6.9% increase; 95% CI 0.9-13.3%, per interquartile range: 0.22 µg/m3) for 8-OHdG and 1 to 4 days before collection (8.3% increase; 95% CI 0.03-17.3% per IQR) for MDA. Results were similar in models adjusting for PM2.5 not associated with BC and NO2 (10.4% increase, 95% CI: 3.5-17.9 for 8-OHdG; 8.1% increase, 95% CI: -1.1-18.1 for MDA). Effects on 8-OHdG were greater in obese participants. CONCLUSIONS: We found positive associations between BC exposure and 8-OHdG and MDA, in which associations with 8-OHdG were stronger in obese participants. These results suggest that exposure to low levels of traffic-related pollution results in lipid peroxidation and oxidative DNA damage in individuals with COPD.

Cardiopulmonary effects of overnight indoor air filtration in healthy non-smoking adults: A double-blind randomized crossover study.

BACKGROUND: More than 90% of the world's population lives in areas where outdoor air pollution levels exceed health-based limits. In these areas, individuals may use indoor air filtration, often on a sporadic basis, in their residences to reduce exposure to respirable particles (PM2.5). Whether this intervention can lead to improvements in health outcomes has not been evaluated. METHODS: Seventy non-smoking healthy adults, aged 19 to 26 years, received both true and sham indoor air filtration in a double-blinded randomized crossover study. Each filtration session was approximately 13 h long. True and sham filtration sessions were separated by a two-week washout interval. The study was carried out in a suburb of Shanghai. RESULTS: During the study period, outdoor PM2.5 concentrations ranged from 18.6 to 106.9 µg/m3, which overlapped with levels measured in Western Europe and North America. Compared to sham filtration, true filtration on average decreased indoor PM2.5 concentration by 72.4% to 10.0 µg/m3 and particle number concentration by 59.2% to 2316/cm3. For lung function measured immediately after the end of filtration, true filtration significantly lowered airway impedance at 5 Hz (Z5) by 7.1% [95% CI: 2.4%, 11.9%], airway resistance at 5 Hz (R5) by 7.4% [95% CI: 2.4%, 12.5%], and small airway resistance (R5-R20) by 20.3% [95% CI: 0.1%, 40.5%], reflecting improved airway mechanics especially for the small airways. However, no significant improvements for spirometry indicators (FEV1, FVC) were observed. True filtration also significantly lowered von Willebrand factor (VWF) by 26.9% [95% CI: 7.3%, 46.4%] 24 h after the end of filtration, indicating reduced risk for thrombosis. Stratified analysis in male and female participants showed that true filtration significantly decreased pulse pressure by 3.3% [95% CI: 0.8%, 7.4%] in females, and significantly reduced VWF by 42.4% [95% CI: 17.4%, 67.4%] and interleukin-6 by 22.6% [95% CI: 0.4%, 44.9%] in males. Effect modification analyses indicated that filtration effects in male and female participants were not significantly different. CONCLUSION: A single overnight residential air filtration, capable of reducing indoor particle concentrations substantially, can lead to improved airway mechanics and reduced thrombosis risk.

Respiratory and cardiovascular responses to walking down a traffic-polluted road compared with walking in a traffic-free area in participants aged 60 years and older with chronic lung or heart disease and age-matched healthy controls: a randomised, crossover study.

BACKGROUND: Long-term exposure to pollution can lead to an increase in the rate of decline of lung function, especially in older individuals and in those with chronic obstructive pulmonary disease (COPD), whereas shorter-term exposure at higher pollution levels has been implicated in causing excess deaths from ischaemic heart disease and exacerbations of COPD. We aimed to assess the effects on respiratory and cardiovascular responses of walking down a busy street with high levels of pollution compared with walking in a traffic-free area with lower pollution levels in older adults. METHODS: In this randomised, crossover study, we recruited men and women aged 60 years and older with angiographically proven stable ischaemic heart disease or stage 2 Global initiative for Obstructive Lung Disease (GOLD) COPD who had been clinically stable for 6 months, and age-matched healthy volunteers. Individuals with ischaemic heart disease or COPD were recruited from existing databases or outpatient respiratory and cardiology clinics at the Royal Brompton & Harefield NHS Foundation Trust and age-matched healthy volunteers using advertising and existing databases. All participants had abstained from smoking for at least 12 months and medications were taken as recommended by participants' doctors during the study. Participants were randomly assigned by drawing numbered disks at random from a bag to do a 2 h walk either along a commercial street in London (Oxford Street) or in an urban park (Hyde Park). Baseline measurements of participants were taken before the walk in the hospital laboratory. During each walk session, black carbon, particulate matter (PM) concentrations, ultrafine particles, and nitrogen dioxide (NO2) concentrations were measured. FINDINGS: Between October, 2012, and June, 2014, we screened 135 participants, of whom 40 healthy volunteers, 40 individuals with COPD, and 39 with ischaemic heart disease were recruited. Concentrations of black carbon, NO2, PM10, PM2.5, and ultrafine particles were higher on Oxford Street than in Hyde Park. Participants with COPD reported more cough (odds ratio [OR] 1·95, 95% CI 0·96-3·95; p<0·1), sputum (3·15, 1·39-7·13; p<0·05), shortness of breath (1·86, 0·97-3·57; p<0·1), and wheeze (4·00, 1·52-10·50; p<0·05) after walking down Oxford Street compared with Hyde Park. In all participants, irrespective of their disease status, walking in Hyde Park led to an increase in lung function (forced expiratory volume in the first second [FEV1] and forced vital capacity [FVC]) and a decrease in pulse wave velocity (PWV) and augmentation index up to 26 h after the walk. By contrast, these beneficial responses were attenuated after walking on Oxford Street. In participants with COPD, a reduction in FEV1 and FVC, and an increase in R5-20 were associated with an increase in during-walk exposure to NO2, ultrafine particles and PM2.5, and an increase in PWV and augmentation index with NO2 and ultrafine particles. In healthy volunteers, PWV and augmentation index were associated both with black carbon and ultrafine particles. INTERPRETATION: Short-term exposure to traffic pollution prevents the beneficial cardiopulmonary effects of walking in people with COPD, ischaemic heart disease, and those free from chronic cardiopulmonary diseases. Medication use might reduce the adverse effects of air pollution in individuals with ischaemic heart disease. Policies should aim to control ambient levels of air pollution along busy streets in view of these negative health effects. FUNDING: British Heart Foundation.

Individualized coracoid osteotomy and 3D congruent arc reconstruction of glenoid for the treatment of recurrent anterior shoulder dislocation.

BACKGROUND: The present study investigated individualized coracoid osteotomy for 3D congruent arc glenoid reconstruction and evaluated the clinical outcomes in recurrent anterior shoulder dislocation. METHODS: From January 2005 to July 2015, 78 patients with glenoid defect underwent coracoid and conjoint tendon transposition. The patients were divided into the individualized group (n = 34) and the non-individualized group (n = 44). All patients had CT data to reconstruct the shoulder model using Mimics software. In the individualized group, the individual coracoid osteotomy and bone fixation position parameters were measured from preoperative planification through simulating a 3D congruent arc glenoid reconstruction model. The non-individualized group underwent classic Bristow-Latarjet (B-L) procedure. The postoperative evaluation parameters included 3D congruent arc index, coracoid bone position, shoulder osteoarthritis index (Samilson-Prieto) and shoulder function score (Rowe, Constant-Murley score). RESULTS: The mean follow-up time was 51.0 months (ranging from 24 to 146). The individualized group got 3D congruent arc reconstruction of the glenoid by postoperative CT scanning. Bone position was more precise in the individual group than that in the B-L group. There was a lower incidence of shoulder osteoarthritis (Samilson-Prieto) in the individual group compared with that in the B-L group: 0 vs 13.6% (mild 6/44, P = 0.027), respectively. No significant difference was observed between the individual and B-L groups in rate of re-dislocation: 0 vs 4.5% (2/44, P = 0.315), respectively. The postoperative Rowe and Constant score was significantly improved but was not significantly different between the two groups. CONCLUSION: The individual procedure achieved 3D congruent arc glenoid reconstruction. The clinical effects in patients with medium glenoid defect were good, especially the low incidence of shoulder osteoarthritis in middle-term follow-up.