本文選題：哮喘兒童 + 空氣污染��； 參考：《中國疾病預(yù)防控制中心》2017年博士論文

【摘要】：目的大量流行病學(xué)研究資料表明室內(nèi)外空氣污染物可誘發(fā)并加劇哮喘癥狀,然而具體機制尚未完全闡明。體外細胞及動物高濃度空氣污染暴露實驗結(jié)果提示,空氣污染對哮喘的激發(fā)作用與炎癥反應(yīng)、氧化應(yīng)激及IgE表達調(diào)控通路相關(guān),但目前仍缺少充分的人群研究證據(jù)支持。因此,本研究擬通過對北京市哮喘兒童室內(nèi)、外空氣污染物連續(xù)監(jiān)測,綜合評價其對空氣污染物暴露水平;并通過對直接反映呼吸道炎癥、氧化應(yīng)激的生物標志物以及外周血血清中IgE表達調(diào)控相關(guān)信號分子的監(jiān)測,建立暴露-效應(yīng)相關(guān)關(guān)系,探討空氣污染物在兒童哮喘激發(fā)中的作用。方法1.以60名北京市哮喘兒童(男性,漢族,年齡5-14歲)為研究對象,通過統(tǒng)一的調(diào)查問卷收集調(diào)查對象年齡,藥物治療、家庭室內(nèi)裝修,被動吸煙、調(diào)查期間飲食、室內(nèi)霉斑、過敏史、疾病史、家族遺傳史等一般信息;2.通過對調(diào)查對象家庭室內(nèi)PM2.5、黑碳、苯、甲苯、二甲苯、甲醛連續(xù)監(jiān)測,以及對家庭附近空氣質(zhì)量監(jiān)測點PM2.5、PM10、NO2、S02監(jiān)測數(shù)據(jù)的收集,綜合評價其空氣污染物暴露水平。苯、甲苯、二甲苯的測定采用二次熱解吸-氣相色譜法,甲醛的測定采樣AHMT分光光度法,PM2.5質(zhì)量濃度的測定采用重量法,PM2.5中黑碳的測定采用多波長吸收法;室外環(huán)境空氣污染物濃度數(shù)據(jù)來源于北京環(huán)境保護監(jiān)測中心空氣質(zhì)量實時發(fā)布平臺;3.以哮喘兒童呼出氣中一氧化氮(FeNO)以及呼出氣冷凝液(EBC) pH作為反映哮喘兒童呼吸道炎癥的生物標志。FeNO的測定采用電化學(xué)法(離線監(jiān)測),EBC pH的測定采用微電極電位分析法;4.以呼出氣冷凝液中8-異前列烷(EBC8-ISO)作為反映哮喘兒童呼吸道氧化應(yīng)激狀態(tài)的生物標志。哮喘兒童EBC8-ISO濃度采用尿素濃度校正;8-ISO及尿素的測定方法為LC-MS/MS法;5.通過測定外周血血清中IgE表達調(diào)控的兩條信號通路的相關(guān)信號分子,研究空氣污染對哮喘兒童IgE信號通路激發(fā)作用。信號分子的測定采用ELISA試劑盒法;6.采用分層分析和多元線性回歸模型進行混雜因素的控制,綜合分析空氣污染對兒童哮喘的激發(fā)作用。結(jié)果1.調(diào)查期間,調(diào)查對象室內(nèi)PM2.5、BC、甲醛、苯、甲苯、間對-二甲苯、鄰二甲苯的濃度分別為 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日時間加權(quán)平均濃度分別為101.3±87.6μg/m3、152.8±88.4μg/m3、48.6±39.8 μg/m3、63.1±27.7μg/m3;同期室內(nèi)、外PM2.5的7日時間加權(quán)平均濃度間存在顯著相關(guān)關(guān)系(r=0.697, P0.001 ),室內(nèi)外 PM2.5 濃度比值(I/O ratio)為 0.86±0.39 (P25-P75 為 0.62-1.01)。2.在校正了年齡、哮喘類型、季節(jié)等因素影響后,對全部調(diào)查對象的分析發(fā)現(xiàn),FeNO與室內(nèi)空氣中苯、室外環(huán)境空氣中PM2.5、S02、N02間均存在顯著正相關(guān)關(guān)系;對未使用糖皮質(zhì)激素(ICS)的調(diào)查對象的單獨分析發(fā)現(xiàn),FeNO與室外環(huán)境空氣中PM2.5、S02、N02間均存在顯著正相關(guān)關(guān)系,而在使用ICS組該相關(guān)關(guān)系均不顯著。3.在校正了年齡、哮喘類型、季節(jié)等因素影響后,對全部調(diào)查對象的分析發(fā)現(xiàn),EBC pH與室外環(huán)境空氣中N02存在顯著的正相關(guān)關(guān)系,按照是否使用ICS分層后,該相關(guān)關(guān)系僅存在于服用ICS組;EBC pH與室內(nèi)所有監(jiān)測的空氣污染物均無顯著相關(guān)關(guān)系。4.在校正了年齡、哮喘類型、季節(jié)等因素影響后,沒有發(fā)現(xiàn)室內(nèi)、外環(huán)境空氣污染物與EBC 8-ISO相關(guān)關(guān)系。5.同一調(diào)查對象的FeNO與EBC 8-ISO間存在顯著正相關(guān)關(guān)系,表明呼吸道炎癥與氧化應(yīng)激關(guān)系密切。6.在血清中,兩條IgE表達調(diào)控通路內(nèi)信號分子間存在顯著地正相關(guān)關(guān)系;在校正了年齡、哮喘類型、被動吸煙等因素影響后,本研究沒有觀察到空氣污染物對信號分子水平的影響。結(jié)論室內(nèi)、外空氣污染物監(jiān)測結(jié)果表明,研究對象處于較高的空氣污染物暴露水平;哮喘兒童對室內(nèi)、外空氣污染物的暴露可以造成或加劇呼吸道炎癥;使用ICS藥物可以控制或降低空氣污染物對哮喘兒童造成的呼吸道炎癥;血清中IgE表達調(diào)控通路信號分子水平可能不是反映空氣污染對兒童哮喘激發(fā)作用的理想指標。
[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.
【學(xué)位授予單位】：中國疾病預(yù)防控制中心
【學(xué)位級別】：博士
【學(xué)位授予年份】：2017
【分類號】：R725.6

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