RESUMO
RATIONALE: Exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with adverse effects on the respiratory system. However, the association between internal levels of PAH metabolites and lung function levels remains unclear. OBJECTIVES: We investigated the relationships between urinary PAH metabolite concentrations and lung function levels in a general Chinese population. METHODS: Lung function and 12 urinary PAH metabolites were measured in 2,747 participants from the Wuhan-Zhuhai cohort in China. Associations between urinary PAH metabolites and lung function were analyzed by linear mixed models. We also investigated associations among urinary PAH metabolite concentrations, traffic exposure time, and dietary PAH exposure. MEASUREMENTS AND MAIN RESULTS: We found significant associations between increased levels of urinary PAH metabolites and reduced lung function. Each 1-U increase in log-transformed levels of 2-hydroxynaphthalene, 9-hydroxyfluorene, 2-hydroxyfluorene, 4-hydroxyphenanthrene, 9-hydroxyphenanthrene, 3-hydroxyphenanthrene, 1-hydroxyphenanthrene, 2-hydroxyphenanthrene, 1-hydroxypyrene, or total urinary PAH metabolites was associated with a 23.79-, 19.36-, 41.76-, 36.87-, 33.47-, 27.37-, 39.53-, 34.35-, 25.03-, or 37.13-ml reduction in FEV1, respectively (all P < 0.05). Each 1-U increase in 2-hydroxynaphthalene, 2-hydroxyfluorene, 4-hydroxyphenanthrene, 1-hydroxyphenanthrene, 2-hydroxyphenanthrene, or total urinary PAH metabolites was associated with a 24.39-, 33.90-, 27.15-, 28.56-, 27.46-, or 27.99-ml reduction in FVC, respectively (all P < 0.05). The total urinary PAH metabolites concentration was positively associated with both traffic exposure time and dietary PAH exposure among nonsmokers. CONCLUSIONS: Total and specific urinary PAH metabolites were associated with lung function reduction in a general Chinese population. Further studies are needed to investigate the potential mechanism by which PAHs induces lung function reduction.
Assuntos
Pneumopatias/induzido quimicamente , Pneumopatias/urina , Pulmão/fisiopatologia , Hidrocarbonetos Policíclicos Aromáticos/urina , China , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: To investigate the effects of the urinary metabolite profiles of background exposure to the atmospheric pollutants polycyclic aromatic hydrocarbon (PAH) and Framingham risk score (FRS), which assesses an individual's cardiovascular disease risk, on heart rate variability (HRV). METHODS: The study conducted from April to May 2011 in Wuhan, China, included 1978 adult residents with completed questionnaires, physical examinations, blood and urine samples, and 5-min HRV indices (including SD of all normal to normal intervals (SDNN), root mean square successive difference (rMSSD), low frequency (LF), high frequency (HF) and their ratio (LF/HF), and total power) obtained from 3-channel Holter monitor. 12 urinary PAH metabolites were measured by gas chromatography-mass spectrometry. FRS was calculated by age, sex, lipid profiles, blood pressure, diabetes and smoking status. Linear regression models were constructed after adjusting for potential confounders. RESULTS: Elevated total concentration of hydroxynaphthalene (ΣOHNa) was significantly associated, in a dose-responsive manner, with decreased SDNN and LF/HF (ptrend=0.014 and 0.007, respectively); elevated total concentration of hydroxyfluorene (ΣOHFlu) was significantly associated with reduced SDNN, LF and LF/HF (ptrend=0.027, 0.003, and <0.0001, respectively); and elevated total concentration of all PAH metabolites (ΣOH-PAHs) was associated with decreased LF and LF/HF (ptrend=0.005 and <0.0001, respectively). Moreover, increasing quartiles of FRS were significantly associated with decreased HRV indices, except LF/HF (all ptrend<0.0001). Interestingly, individuals in low-risk subgroups had greater decreases in SDNN, LF and LF/HF in relation to ΣOH-PAHs, ΣOHNa and ΣOHFlu than those in high-risk subgroups (all p<0.05). CONCLUSIONS: Environmental PAH exposure may differentially affect HRV based on individual coronary risk profiles.
Assuntos
Poluentes Atmosféricos/efeitos adversos , Doenças Cardiovasculares , Exposição Ambiental/efeitos adversos , Frequência Cardíaca/efeitos dos fármacos , Coração/efeitos dos fármacos , Hidrocarbonetos Policíclicos Aromáticos/efeitos adversos , Adulto , Poluentes Atmosféricos/farmacologia , Poluentes Atmosféricos/urina , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , China , Relação Dose-Resposta a Droga , Eletrocardiografia Ambulatorial , Exposição Ambiental/análise , Feminino , Fluorenos/efeitos adversos , Fluorenos/farmacologia , Fluorenos/urina , Coração/fisiopatologia , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Naftalenos/efeitos adversos , Naftalenos/farmacologia , Naftalenos/urina , Hidrocarbonetos Policíclicos Aromáticos/farmacologia , Hidrocarbonetos Policíclicos Aromáticos/urina , Características de Residência , Fatores de RiscoRESUMO
BACKGROUND: Particulate air pollution has been recognized to be associated with a wide range of adverse health effects, including increased mortality, morbidity, exacerbation of respiratory conditions. However, earlier physiological or pathological changes or long-term bodies' reaction to air pollutants have not been studied in depth in China. The Wuhan-Zhuhai (WHZH) cohort study is designed to investigate the association between air pollutants exposure and physiological or pathological reactions on respiratory and cardiovascular system. METHODS/DESIGN: The cohort is a community-based prospective study that includes 4812 individuals aged 18-80 years. The collections of data were conducted from April to May 2011 in Wuhan city and in May 2012 in Zhuhai city. At baseline, data on demographic and socioeconomic information, occupational history, family disease history, lifestyle, cooking mode, daily travel mode, physical activity and living condition have been collected by questionnaires. Participants underwent an extensive physical examination, including anthropometry, spirometry, electrocardiography, and measurements of blood pressure, heart rate, exhaled nitric oxide and carbon monoxide. Potential conditions in the lung, heart, liver, spleen, and skin were synchronously performed. In addition, samples of morning urine, fasting blood serum and plasma were collected during physical health examination. DNA were extracted and were stored at -80°C. Environment concentrations of particulate matter and chemicals were determined for 15 days in each of four seasons. Participants are followed for physiological or pathological changes or incidence of cardiopulmonary diseases every 3 years. DISCUSSION: The results obtained in WHZH cohort study may increase a better understanding of the relationship between particulate air pollution and its components and possible health damages. And the potential mechanisms underlying the development of cardiopulmonary diseases has implications for the development of prevention and treatment strategies.
Assuntos
Doenças Cardiovasculares/epidemiologia , Exposição Ambiental/estatística & dados numéricos , Material Particulado , Doenças Respiratórias/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Poluentes Atmosféricos , Pressão Sanguínea , Testes Respiratórios , Monóxido de Carbono/análise , Doenças Cardiovasculares/fisiopatologia , China/epidemiologia , Estudos de Coortes , Culinária , Eletrocardiografia , Meio Ambiente , Feminino , Frequência Cardíaca , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/análise , Estudos Prospectivos , Doenças Respiratórias/fisiopatologia , Estações do Ano , Espirometria , Inquéritos e Questionários , Adulto JovemRESUMO
Environmental exposure to crystalline silica (CS) particles is common and occurs during natural, industrial, and agricultural activities. Prolonged inhalation of CS particles can cause silicosis, a serious and incurable pulmonary fibrosis disease. However, the underlying mechanisms remain veiled. Herein, we aim to elucidate the novel mechanisms of interleukin-11 (IL-11) driving fibroblast metabolic reprogramming during the development of silicosis. We observed that CS exposure induced lung fibrosis in mice and activated fibroblasts, accompanied by increased IL-11 expression and metabolic reprogramming switched from mitochondrial respiration to glycolysis. Besides, we innovatively uncovered that elevated IL-11 promoted the glycolysis process, thereby facilitating the fibroblast-myofibroblast transition (FMT). Mechanistically, CS-stimulated IL-11 activated the extracellular signal-regulated kinase (ERK) pathway and the latter increased the expression of hypoxia inducible factor-1α (HIF-1α) via promoting the translation and delaying the degradation of the protein. HIF-1α further facilitated glycolysis, driving the FMT process and ultimately the formation of silicosis. Moreover, either silence or neutralization of IL-11 inhibited glycolysis augmentation and attenuated CS-induced lung myofibroblast generation and fibrosis. Overall, our findings elucidate the role of IL-11 in promoting fibroblast metabolic reprogramming through the ERK-HIF-1α axis during CS-induced lung fibrosis, providing novel insights into the molecular mechanisms and potential therapeutic targets of silicosis.
Assuntos
Fibroblastos , Interleucina-11 , Reprogramação Metabólica , Fibrose Pulmonar , Dióxido de Silício , Animais , Camundongos , Fibroblastos/efeitos dos fármacos , Glicólise , Interleucina-11/metabolismo , Reprogramação Metabólica/efeitos dos fármacos , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismo , Dióxido de Silício/toxicidade , Silicose/metabolismoRESUMO
Short-term exposures to outdoor air pollutants have been associated with lower lung function, but the results are inconsistence. The effects of different pollutant levels on lung function changes are still unclear. We quantified the effects of outdoor air pollution exposure (NO2, PM10, O3, and PM2.5) on lung function among 1,694 female non-smokers from the Wuhan-Zhuhai Cohort in China by using linear mixed model. We further investigated the associations in the two cities with different air quality levels separately to quantify the effects of different pollutant level exposure on lung function. We found the moving averages of NO2, PM10, and PM2.5 concentrations were significantly associated with reduced FVC. In city at high pollutant level, the moving average of NO2, PM10, O3, and PM2.5 exposures were significantly associated with both FVC and FEV1 reductions. In the low-level air pollution city, PM10 (Lag03-Lag05) and O3 concentrations (Lag01-Lag03) were significantly associated with reduced FVC, while PM10 (Lag03-Lag05), O3 (Lag0-Lag03), and PM2.5 (Lag04-Lag06) exposure were significantly associated with reduced FEV1. Our results suggest that outdoor air pollution is associated with short-term adverse effects on lung function among female non-smokers. The adverse effects may persist for longer durations within 7 days at higher air pollutant levels.
Assuntos
Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , Pulmão/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , China , Exposição Ambiental/efeitos adversos , Feminino , Volume Expiratório Forçado , Humanos , Modelos Lineares , Pulmão/efeitos dos fármacos , Pessoa de Meia-Idade , Dióxido de Nitrogênio/análise , Ozônio/análise , Material Particulado/efeitos adversos , Testes de Função Respiratória , Fumar , Fatores de Tempo , Capacidade Vital , Adulto JovemRESUMO
Indoor air pollutants from environmental tobacco smoke and cooking fume can induce oxidative stress and inflammatory response, which generate oxidatively damaged DNA in human body. Among 2224 adults, levels of FENO and urinary 8-oxodG were measured using a nano coulomb nitric oxide analyzer and a high performance liquid chromatography system with electrochemical detector, respectively. Association between aging with higher FENO levels and urinary 8-oxodG levels were analyzed using multiple linear regression analysis. Nonsmoking women aged 64 years and over, with higher FENO (≥ 25 part per billion) and self-catering but without passive smoking had a higher risk of increased urinary 8-oxodG (â³% of urinary 8-oxodG: 81.3 %, 95 % CI: 27.4-158.0 %) levels, particularly these elderly women with using liquefied petroleum gas for cooking, had a higher risk for increased urinary 8-oxodG levels (â³% of urinary 8-oxodG: 100.2 %, 95 % CI: 95 % CI: 35.3-196.3 %), compared with those aged less than 64 years, with lower FENO (< 25 part per billion). Cooking activity aggravated aging-related the aging-induced in urinary 8-oxodG excretion among nonsmoking women aged 64 years and over but without passive smoking.
Assuntos
Desoxiguanosina/análogos & derivados , Óxido Nítrico/metabolismo , 8-Hidroxi-2'-Desoxiguanosina , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Cromatografia Líquida de Alta Pressão , Culinária , Dano ao DNA , Desoxiguanosina/urina , Expiração , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxirredução , Estresse Oxidativo , Risco , Poluição por Fumaça de Tabaco/efeitos adversosRESUMO
OBJECTIVE: To investigate indoor factors affecting fractional exhaled nitric oxide (FeNO) in community residents. METHODS: A total of 2404 adults (865 men, 1539 women, mean age 51.7 ± 13.3 years) were recruited to the study. Factors affecting FeNO were analyzed by multiple linear regression analysis. RESULTS: Participants without a kitchen exhaust fan/hood had higher FeNO (GM: 10.21%, 95% CI: 4.18%-16.59%). Participants engaged in home cooking who used only liquefied petroleum gas had higher FeNO (GM: 5.75%, 95% CI: 0.10%-11.73%) compared to those using natural gas for residential (home) cooking. CONCLUSION: Nonuse of a kitchen exhaust fan/hood and use of liquefied petroleum gas among persons engaged in home cooking were associated with higher FeNO levels.
Assuntos
Testes Respiratórios , Habitação , Óxido Nítrico/metabolismo , Adolescente , Adulto , Contagem de Células Sanguíneas , China , Estudos de Coortes , Culinária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Adulto JovemRESUMO
Exposure to particulate matter (e.g., PM2.5) may result in DNA damage, a major culprit in mutagenesis and environmental toxicity. DNA damage levels may vary among individuals simultaneously exposed to PM2.5, however, the genetic determinants are still unclear. To explore whether PM2.5 exposure and genetic variants contribute to the alteration in DNA damage, we recruited 328 subjects from three independent cohorts (119 from Zhuhai, 123 from Wuhan and 86 from Tianjin) in southern, central and northern China with different PM2.5 exposure levels. Personal 24-h PM2.5 exposure levels and DNA damage levels of peripheral blood lymphocytes were evaluated. Genotyping were performed using Illumina Human Exome BeadChip with 241,305 single nucleotide variants (SNVs). The DNA damage levels are consistent with the PM2.5 exposure levels of each cohort. A total of 35 SNVs were consistently associated with DNA damage levels among the three cohorts with pooled P values less than 1.00×10(-3) after adjustment for age, gender, smoking status and PM2.5 exposure levels, of which, 18 SNVs together with gender and PM2.5 exposure levels were independent factors contributing to DNA damage. Gene-based test revealed 3 genes significantly associated with DNA damage levels (P=5.11×10(-3) for POLH, P=2.88×10(-3) for RIT2 and P=2.29×10(-2) for CNTN4). Gene ontology (GO) analyses indicated that the identified variants were significantly enriched in DNA damage response pathway. Our findings highlight the importance of genetic variation as well as personal PM2.5 exposure in modulating individual DNA damage levels.
Assuntos
Povo Asiático/genética , Dano ao DNA , Variação Genética , Material Particulado/toxicidade , Idoso , China , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Tamanho da PartículaRESUMO
Exposure to particulate matter 2.5 (PM2.5) may result in DNA damage. Histone variant H2AX phosphorylation plays a central role in the response to damaged chromatin. In the current study, we investigated whether H2AX gene polymorphisms account for PM2.5-modulated DNA damage levels. A total of 307 healthy urban residents were collected from three cities in southern, central, and northern China, Zhuhai, Wuhan, and Tianjin, respectively. The dust mass concentrations of PM2.5 were detected by Gilian 5000 pumps, and the DNA damage levels were measured using comet assay. Seven potentially functional single nucleotide polymorphisms (SNPs) of H2AX gene were selected and genotyped by Illumina Infinium(®) BeadChip. We found that three SNPs (rs10790283 G > A, rs604714 C > A and rs7759 A > G) were significantly associated with DNA damage levels (adjusted P = 0.002, 0.018 and 0.027, respectively). Significant interactions (P < 0.05) were observed between certain genetic polymorphisms and PM2.5-modulated DNA damage levels. These results suggested that genetic variations of H2AX might be associated with the DNA damage levels in urban residents with different exposure to PM2.5. Further studies with large sample size in independent populations merit validating these findings.
Assuntos
Povo Asiático/estatística & dados numéricos , Dano ao DNA , Etnicidade/estatística & dados numéricos , Histonas/genética , Material Particulado/toxicidade , Polimorfismo de Nucleotídeo Único , China , Ensaio Cometa , Predisposição Genética para Doença , Variação Genética , Genótipo , Histonas/fisiologia , Humanos , Linfócitos/química , Tamanho da Partícula , Material Particulado/análise , População UrbanaRESUMO
The switching defective/sucrose nonfermenting (SWI/SNF) related, matrix associated, actin dependent regulators of chromatin (SMARC) are components of human SWI/SNF like chromatin remodeling protein complexes, which are essential in the process of DNA damage repair. In this study, we hypothesized that genetic variants in SMARC genes may modify the capacity of DNA repair to damage. To test this hypothesis, we genotyped a total of 20 polymorphisms in five key SMARC genes (SMARCA5, SMARCC2, SMARCD1, SMARCD2, SMARCD3) to evaluate their associations with DNA damage levels in 307 subjects. The DNA damage levels were measured with comet assay. The multiple linear regression was used to assess the relationship between each polymorphism and DNA damage levels in additive model. We found that the genotypes of rs6857360 (ß=0.23, 95% CI=0.06-0.40, P=0.008) in SMARCA5, rs6919 (ß=0.20, 95% CI=0.05-0.34, P=0.008) and rs2727280 (ß=0.18, 95% CI=0.04-0.33, P=0.013) in SMARCD2, and rs17173769 (ß=-0.27, 95% CI=-0.52 to -0.01, P=0.045) in SMARCD3 were significantly associated with DNA damage levels. After combining these four polymorphisms, we found that the more unfavorable alleles the subjects carried, the heavier DNA damage they suffered, suggesting a locus-dosage effect between combined genotypes and DNA damage levels (P for trend=0.006). These findings suggest that genetic variants in SMARC genes may contribute the individual variations of DNA damage levels in Chinese population. Further larger and functional studies are warranted to confirm our findings.