空气污染对哮喘儿童IgE信号通路激发作用研究

发布时间：2018-07-12 13:16

本文选题：哮喘儿童 + 空气污染　；参考：《中国疾病预防控制中心》2017年博士论文

【摘要】：目的大量流行病学研究资料表明室内外空气污染物可诱发并加剧哮喘症状,然而具体机制尚未完全阐明。体外细胞及动物高浓度空气污染暴露实验结果提示,空气污染对哮喘的激发作用与炎症反应、氧化应激及IgE表达调控通路相关,但目前仍缺少充分的人群研究证据支持。因此,本研究拟通过对北京市哮喘儿童室内、外空气污染物连续监测,综合评价其对空气污染物暴露水平;并通过对直接反映呼吸道炎症、氧化应激的生物标志物以及外周血血清中IgE表达调控相关信号分子的监测,建立暴露-效应相关关系,探讨空气污染物在儿童哮喘激发中的作用。方法1.以60名北京市哮喘儿童(男性,汉族,年龄5-14岁)为研究对象,通过统一的调查问卷收集调查对象年龄,药物治疗、家庭室内装修,被动吸烟、调查期间饮食、室内霉斑、过敏史、疾病史、家族遗传史等一般信息;2.通过对调查对象家庭室内PM2.5、黑碳、苯、甲苯、二甲苯、甲醛连续监测,以及对家庭附近空气质量监测点PM2.5、PM10、NO2、S02监测数据的收集,综合评价其空气污染物暴露水平。苯、甲苯、二甲苯的测定采用二次热解吸-气相色谱法,甲醛的测定采样AHMT分光光度法,PM2.5质量浓度的测定采用重量法,PM2.5中黑碳的测定采用多波长吸收法;室外环境空气污染物浓度数据来源于北京环境保护监测中心空气质量实时发布平台;3.以哮喘儿童呼出气中一氧化氮(FeNO)以及呼出气冷凝液(EBC) pH作为反映哮喘儿童呼吸道炎症的生物标志。FeNO的测定采用电化学法(离线监测),EBC pH的测定采用微电极电位分析法;4.以呼出气冷凝液中8-异前列烷(EBC8-ISO)作为反映哮喘儿童呼吸道氧化应激状态的生物标志。哮喘儿童EBC8-ISO浓度采用尿素浓度校正;8-ISO及尿素的测定方法为LC-MS/MS法;5.通过测定外周血血清中IgE表达调控的两条信号通路的相关信号分子,研究空气污染对哮喘儿童IgE信号通路激发作用。信号分子的测定采用ELISA试剂盒法;6.采用分层分析和多元线性回归模型进行混杂因素的控制,综合分析空气污染对儿童哮喘的激发作用。结果1.调查期间,调查对象室内PM2.5、BC、甲醛、苯、甲苯、间对-二甲苯、邻二甲苯的浓度分别为 55.3±29.9μg/m3、3.8±1.4 μg/m3、62.2±42.7μg/m3、13.1±15.9μg/m3、18.7±16.7μg/m3、7.9±7.9μg/m3、3.1±5.0μg/m3,室外PM2.5、PM10、SO2、NO2的7日时间加权平均浓度分别为101.3±87.6μg/m3、152.8±88.4μg/m3、48.6±39.8 μg/m3、63.1±27.7μg/m3;同期室内、外PM2.5的7日时间加权平均浓度间存在显著相关关系(r=0.697, P0.001 ),室内外 PM2.5 浓度比值(I/O ratio)为 0.86±0.39 (P25-P75 为 0.62-1.01)。2.在校正了年龄、哮喘类型、季节等因素影响后,对全部调查对象的分析发现,FeNO与室内空气中苯、室外环境空气中PM2.5、S02、N02间均存在显著正相关关系;对未使用糖皮质激素(ICS)的调查对象的单独分析发现,FeNO与室外环境空气中PM2.5、S02、N02间均存在显著正相关关系,而在使用ICS组该相关关系均不显著。3.在校正了年龄、哮喘类型、季节等因素影响后,对全部调查对象的分析发现,EBC pH与室外环境空气中N02存在显著的正相关关系,按照是否使用ICS分层后,该相关关系仅存在于服用ICS组;EBC pH与室内所有监测的空气污染物均无显著相关关系。4.在校正了年龄、哮喘类型、季节等因素影响后,没有发现室内、外环境空气污染物与EBC 8-ISO相关关系。5.同一调查对象的FeNO与EBC 8-ISO间存在显著正相关关系,表明呼吸道炎症与氧化应激关系密切。6.在血清中,两条IgE表达调控通路内信号分子间存在显著地正相关关系;在校正了年龄、哮喘类型、被动吸烟等因素影响后,本研究没有观察到空气污染物对信号分子水平的影响。结论室内、外空气污染物监测结果表明,研究对象处于较高的空气污染物暴露水平;哮喘儿童对室内、外空气污染物的暴露可以造成或加剧呼吸道炎症;使用ICS药物可以控制或降低空气污染物对哮喘儿童造成的呼吸道炎症;血清中IgE表达调控通路信号分子水平可能不是反映空气污染对儿童哮喘激发作用的理想指标。
[Abstract]:Objective a large number of epidemiological studies have shown that indoor and outdoor air pollutants can induce and exacerbate asthma symptoms, but the specific mechanisms have not yet been fully elucidated. The results of high concentration air pollution exposure experiments in vitro and in vitro results suggest that the effect of air pollution on asthma is related to inflammatory response, oxidative stress and the regulation of IgE expression, but the effect of air pollution on asthma is related. There is still lack of sufficient evidence support. Therefore, this study intends to evaluate the air pollutants exposure level by continuous monitoring of indoor and external air pollutants in Beijing asthmatic children, and to regulate the regulation of IgE expression in the peripheral blood serum by directly reflecting the respiratory inflammation, the oxidative stress biomarkers and the peripheral blood serum. The monitoring of signal molecules and the establishment of exposure effect correlation to explore the role of air pollutants in the stimulation of children's asthma. Method 1. 60 Beijing asthmatic children (male, Han, age 5-14 years old) were selected as the research subjects. The years of age, drug treatment, family interior decoration, passive smoking, investigation period were collected through a unified questionnaire. General information on diet, indoor mildew, allergy history, disease history, family genetic history, and other general information; 2. through the continuous monitoring of indoor PM2.5, black carbon, benzene, toluene, xylene, formaldehyde, and the collection of PM2.5, PM10, NO2, S02 monitoring data on the air quality monitoring point near family, comprehensive evaluation of the exposure level of air pollutants. Benzene, toluene, The determination of xylene by two times pyrolysis absorption gas chromatography, formaldehyde determination sampling AHMT spectrophotometric method, PM2.5 mass concentration determination by weight method, PM2.5 black carbon determination using multi wavelength absorption method; outdoor environmental air pollutant concentration data from the Beijing environmental protection monitoring center air quality real-time publishing platform; 3. Using nitric oxide (FeNO) and exhaled gas condensate (EBC) pH as a biomarker to reflect respiratory inflammation in children with asthma,.FeNO was measured by electrochemical method (off-line monitoring), EBC pH was measured by microelectrode potential analysis, and 4. of 8- isoprost (EBC8-ISO) in exhaled gas condensate as a reflection of asthma children Biological markers of oxidative stress in respiratory tract. The concentration of EBC8-ISO in children with asthma was corrected by urea concentration; LC-MS/MS method was used for the determination of 8-ISO and urea; 5. the stimulating effect of air pollution on the IgE signaling pathway in children with asthma was investigated by measuring the two signal molecules regulated by IgE expression in the serum of the peripheral blood. ELISA kit method was used for the determination of the children. 6. the control of mixed factors was carried out by stratified analysis and multiple linear regression model. The effect of air pollution on children's asthma was synthetically analyzed. Results during the 1. investigation, the concentrations of PM2.5, BC, formaldehyde, benzene, toluene, xylene and o-xylene were 55.3 + 29.9 mu g/m3,3., respectively. 8 + 1.4 mu g/m3,62.2 + 42.7 mu g/m3,13.1 + 15.9 mu g/m3,18.7 + 7.9 mu g/m3,3.1 + 5 mu g/m3, the weighted average concentration of outdoor PM2.5, PM10, SO2 and NO2 in 7 days is 101.3 + 87.6 mu g/m3152.8 + 88.4 micron g/m3,48.6 + 39.8 + 27.7. The correlation (r=0.697, P0.001), indoor and outdoor PM2.5 concentration ratio (I/O ratio) was 0.86 + 0.39 (P25-P75 0.62-1.01).2. in the correction of age, asthma type, season and other factors, the analysis of all subjects found that FeNO and indoor air benzene, PM2.5, S02, N02 between the ambient air was significant positive correlation; A single analysis of the subjects who did not use Glucocorticoid (ICS) found that there was a significant positive correlation between FeNO and PM2.5, S02, and N02 in the air of outdoor environment, while in the ICS group, there was no significant.3. in the correction of age, asthma type, season and other factors. The analysis of all subjects was found, EBC pH and room There was a significant positive correlation of N02 in the ambient air. After the use of ICS, the correlation was only in the ICS group, and there was no significant correlation between EBC pH and all the indoor air pollutants monitored indoors. After the correction of age, asthma type, season and other factors, there was no indoor air pollutants and E. There is a significant positive correlation between the FeNO and EBC 8-ISO of the same subjects of BC 8-ISO correlation, indicating that respiratory inflammation and oxidative stress are closely related to.6. in the serum, and there is a significant positive correlation between the signal molecules within the two IgE expression regulation pathways, and after the influence of factors such as age, asthma type, passive smoking, etc. The study did not observe the effect of air pollutants on the level of signal molecules. Conclusion indoor air pollutants monitoring results show that the subjects are at higher levels of air pollution exposure, and exposure to indoor and external air pollutants can cause or aggravate the inflammation of the respiratory tract in asthmatic children; the use of ICS drugs can control or reduce the empty space. The airway inflammation of asthma children is caused by air pollutants, and the level of IgE signaling pathway in serum may not be an ideal indicator to reflect the effect of air pollution on children's asthma.
【学位授予单位】：中国疾病预防控制中心
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R725.6

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