Effect of exposure to 43 ppm nitric oxide and 3.6 ppm nitrogen dioxide on rabbit lung

Summary Continuous exposure of rabbits to 43 ppm nitric oxide and 3.6 ppm nitrogen dioxide for 6 days did not cause morphological changes in the lungs when compared to specimens from nonexposed rabbits. This is not in accordance with previously reported findings.Supported by a grant from Commission of the European Communities, Environmental Research Programme, Contract No.: 031-74-1 ENV DK     

Individual exposure to nitrogen dioxide and adverse pregnancy outcomes in Kaunas study

Several epidemiological studies have found some evidence suggesting that exposure to air pollutants during pregnancy increases the risk of adverse birth outcomes. In this cohort study, we assessed individual maternal exposure to nitrogen dioxide (NO₂) during pregnancy and examined the association between the exposure and pregnancy outcomes, such as low birth weight (LBW), term low birth weight (TLBW), small for gestational age (SGA) and preterm birth (PB). 3292 women living in Kaunas city, Lithuania, data and their singleton newborns were included in the study. Exposure to NO₂ was assigned to each individual subject during pregnancy based on residential address using an AIRVIRO dispersion model and geographic information system (GIS). The results of the logistic regression analysis showed that LBW risk increased statistically significantly with increasing exposure to NO₂. Increased maternal exposure to NO₂ tended to increase the risk for TLBW, SGA and PB.     

妊娠期大气二氧化氮暴露与孕妇维生素D缺乏症的关联

目的 孕妇维生素D缺乏症与妊娠期糖尿病、妊娠期高血压、孕妇贫血以及胎儿生长受限和早产等不良妊娠结局密切相关。本研究旨在探讨妊娠期大气二氧化氮（nitrogen dioxide,NO2）暴露与孕妇维生素D缺乏症的关联。方法 选取2013年5月-至2014年５月,在某市妇幼保健院建卡的孕妇作为初始研究对象。按照入选和排除标准最终纳入3244名孕妇进入本研究。通过问卷调查收集孕妇的一般人口学信息;利用环境监测站点的数据模拟孕妇在妊娠期间大气NO2的暴露水平;采用酶联免疫吸附法检测孕晚期孕妇血清中25（OH）D的浓度。结果 孕妇在孕早期、中期、晚期以及整个孕期NO2暴露水平的中位数分别为:39.52、36.84、28.09以及31.90μg/m3。孕晚期血清中25(OH)D浓度的平均值为42.09nmol/L。多元线性回归分析的结果显示,孕中期、孕晚期以及整个孕期NO2的暴露水平每增加10μg / m3,孕妇血清中25（OH）D的水平分别降低2.224nmol/L（95%CI:-2.777,-1.671）,2.240nmol/L（95%CI:-2.665,-1.816）以及5.299 nmol/L（95%CI:-6.481,-4.177）。多元logistic回归分析的结果显示,随着孕中期、孕晚期以及整个孕期NO2的暴露水平的增加,孕妇VD缺乏症发生的风险增加,其OR值分别为1.338（95%CI:1.225,1.461）,1.347（95%CI:1.259,1.442）以及2.049（95%CI:1.709～2.456）。结论 孕期NO2暴露是孕妇维生素D缺乏症发生的一个危险因素。在制订维生素D缺乏症的防控措施时需要考虑孕期NO2的暴露。     

Effect of lung damage by acute exposure to nitrogen dioxide on lung immunity in the rat

Exposure to nitrogen dioxide (NO₂) damages Type I alveolar epithelial cells and the epithelium of the terminal bronchiole. Because an intact epithelium may help control the number of inhaled particles that are cleared by the pulmonary lymphatics, damage to the alveolar epithelium could alter the antigen load to the lung-associated lymph nodes (LALN). To determine the effects of lung damage by NO₂ inhalation on lung immunity, we exposed adult, male rats to 26 ppm NO₂ for 24 hr at various time intervals before and after intratracheal immunization with 10⁸ sheep red blood cells (SRBC). Seven days after immunization, we determined the number of anti-SRBC antibody-forming cells (AFC) in the LALN, cervical lymph nodes, and spleen. The immunologic response to SRBC was limited to the LALN, with few or no AFC in either the cervical lymph nodes or spleen. A fivefold increase in the number of IgG anti-SRBC $\text{AFC}\text{10}{}^6$ LALN cells was evident in rats immunized 1 day after NO₂ exposure. The increase was followed by a slight suppression of the IgG response when rats were immunized 3 days after exposure, returning to normal levels by 7 days after exposure. Histopathological examination of lung tissues showed a slight respiratory bronchiolitis which was followed by a bronchiolar epithelial cell hyperplasia and Type II cell hyperplasia in the adjacent alveoli. Based on these observations, it appears that the fluctuations observed in the LALN response may be the result of damage and subsequent repair of bronchiolar and alveolar epithelium following NO₂ inhalation.     

Indoor nitrogen dioxide pollution and respiratory symptoms of schoolchildren

Summary The influence of indoor nitrogen-dioxide exposure on respiratory symptoms of schoolchildren was investigated in a case-control study. The election method used was useful in obtaining symptomatic children, but insufficient in defining cases and controls without additional information. No relationship between indoor NO₂ and respiratory symptoms was found. Bias may have been present, especially because of the high mobility of the study population. Attempts to estimate historical exposure were inaccurate. Therefore the results do not exclude that an association between indoor NO₂ and respiratory symptoms exists.     

The German view: effects of nitrogen dioxide on human health--derivation of health-related short-term and long-term values

The presented overview concerning health relevant effects caused by nitrogen dioxide (NO2) resumes the current state of results from animal experiments and human studies (epidemiology and short-term chambers studies). NO2 concentrations applied in animal experiments were mostly considerably higher than in ambient air. Therefore, short- and long-term limit values were derived from human data. Experimental studies conducted with humans demonstrate effects after short-term exposure to concentrations at or above 400 microg NO2/m3. Effects on patients with light asthma could not be observed after short-term exposure to concentrations below 200 microg/m3. On basis of epidemiological long-term studies a threshold below which no effect on human health is expected could not be specified. Two short-term limit values have been proposed to protect public health: a 1-h value of 100 microg/m3 and a 24-h mean value of 50 microg/m3. Due to the limitations of epidemiological studies to disentangle effects of single pollutants, a long-term limit value cannot be easily derived. However, applying the precautionary principle, it is desirable to adopt an annual mean of 20 microg NO2/m3 as a long-term mean standard to protect public health.     

Estimation of occupational and nonoccupational nitrogen dioxide exposure for Korean taxi drivers using a microenvironmental model

Occupational and nonoccupational personal nitrogen dioxide (NO(2)) exposures were measured using passive samplers for 31 taxi drivers in Asan and Chunan, Korea. Exposures were also estimated using a microenvironmental time-weighted average model based on indoor, outdoor and inside the taxi area measurements. Mean NO(2) indoor and outdoor concentrations inside and outside the taxi drivers' houses were 24.7+/-10.7 and 23.3+/-8.3 ppb, respectively, with a mean indoor to outdoor NO(2) ratio of 1.1. Mean personal NO(2) exposure of taxi drivers was 30.3+/-9.7 ppb. Personal NO(2) exposures for drivers were more strongly correlated with interior vehicle NO(2) levels (r = 0.89) rather than indoor residential NO(2) levels (r = 0.74) or outdoor NO(2) levels (r = 0.71). The main source of NO(2) exposure for taxi drivers was considered to be occupational driving. Interestingly, the NO(2) exposures for drivers' using LPG-fueled vehicles (26.3+/-1.3 ppb) were significantly lower than those (38.1+/-1.3 ppb) using diesel-fueled vehicle (P <0.01). Since drivers spent most of their time inside their vehicle and indoors at home, a microenvironmental model was used to estimate the personal NO(2) exposure with indoor and outdoor NO(2) levels of the residence, and interior vehicle NO(2) levels (P <0.001). Some subpopulations, such as professional drivers, might be exposed to high NO(2) levels because they drive diesel-using vehicles outdoors in Korea.     

The relationship between indoor nitrogen dioxide concentration levels and personal exposure: a pilot study

Summary A small, personal monitoring study was performed in a subpopulation (14 families) of a case-control study on the relationship between indoor nitrogen-dioxide exposure and respiratory diseases of schoolchildren. Mothers, schoolchildren and pre-schoolchildren were asked to carry duplicate Palmes diffusion tubes during one week. Simultaneously nitrogen-dioxide concentrations were measured in the kitchen, living room, bedroom, outdoors and—for a few participants—at school and at work. Information on time activity patterns was gathered by means of a self administered diary. Several models for estimating exposure were constructed and tested against measured exposure. The personal exposure of the participants could well be explained by models containing indoor concentrations. Models with time-weighted average concentrations did not explain personal exposure better than models containing indoor concentrations. A calculated time-weighted average exposure was found to underestimate measured personal exposure by an average 20%, probably because the average concentration in a location does not necessarily reflect the actual exposure in that location. Personal exposure of mothers and children was very similar and highly correlated, indicating that the personal exposure of the mother might be a reasonable estimate for the exposure of the child.     

Effect of chronic exposure to nitrogen dioxide on collagen content in lung and skin of guinea pigs

The influence of nitrogen dioxide on the connective tissue of guinea pigs was studied after 180 days (8 hours per day) of exposure at a concentration of 2 mg/m³. The long-term exposure induced a decrease of total collagen content in lung tissue, and an increase in skin as well as an increase of collagen catabolite levels in blood serum and urine. The increase of soluble fractions of collagen and the decrease of insoluble ones was found in skin of the exposed animals. Morphological studies showed nitrogen dioxide-induced emphysema and damage in bronchioli of the lungs and some degenerative skin changes. The results obtained suggest the inhibition of collagen maturation and/or activation of its catabolism as the main mechanism of nitrogen dioxide-induced connective tissue damage.     

糖皮质激素治疗二氧化氮致大鼠急性肺水肿实验初步研究

目的 探讨糖皮质激素对二氧化碳(NO2)所致大鼠急性肺水肿的治疗效果.方法 将SD大鼠随机分为空白对照组、染毒组及大、中、小剂量糖皮质激素治疗组,每组6只.空白对照组予净空气平衡30 min,染毒组及大、中、小剂量糖皮质激素治疗组在NO2染毒后分别给予生理盐水2.5 mg/kg和地塞米松6.0、3.0、1.0 mg/kg.测定大鼠肺湿干重比(W/D),用ELISA法测定血浆心房利尿钠肽(ANP)含量、全血超氧化物歧化酶(SOD)活力及血浆中白细胞介素-6(IL-6)、IL-10、肿瘤坏死因子-α(TNF-α)、γ-干扰素(IFN-γ)的含量.结果 与空白对照组比较,大、中、小剂量激素治疗组及染毒组大鼠肺W/D明显升高,差异有统计学意义(P<0.05);与染毒组比较,大、中、小剂量激素治疗组大鼠肺W/D明显降低,差异有统计学意义(P<0.05).与空白对照组比较,大、中、小剂量激素治疗组及染毒组大鼠全血中SOD活力明显降低,差异有统计学意义(P<0.05);与染毒组比较,大、中、小剂量激素治疗组全血中SOD活力无明显改变,差异无统计学意义(P>0.05).与空白对照组比较,染毒组大鼠血浆中ANP含量明显升高,差异有统计学意义(P<0.05);与染毒组比较,大、中、小剂量激素治疗组大鼠血浆中ANP含量明显降低,差异有统计学意义(P<0.05).与染毒组[(68.55±27.84)pg/ml]比较,大、中、小剂量激素治疗组大鼠血浆中TNFα含量[分别为(27.04±8.19)、(40.10±9.09)、(39.76±9.60)pg/ml]明显降低,差异有统计学意义(P<0.05).与染毒组[(29.29±9.31)pg/ml]比较,大、中剂量激素治疗组大鼠血浆中IL-6含量[分别为(15.97±6.18)、(19.69±5.52)pg/ml]降低,差异有统计学意义(P<0.05).与染毒组[(44.38±9.19)pg/ml]比较,大、中、小剂量激素治疗组大鼠血浆中IL-10含量[(23.24±5.14)、(27.78±8.17)、(33.29±10.42)pg/ml]降低,差异有统计学意义(P<0.05).与染毒组[(30.83±6.82)pg/ml]比较,大、中剂量激素治疗组大鼠血浆中IFN-γ含量[分别为(7.21±4.55)、(19.23±4.35)pg/ml]降低,差异有统计学意义(P<0.05).结论 大、中、小剂量糖皮质激素均具有改善肺泡壁和毛细血管的通透性及非特异性的抗炎作用,对肺水肿有明显的治疗作用,在降低炎性因子方面,以大、中剂量激素治疗组效果更为明显.     

扩散法被动式二氧化氮个体监测器的研制

研制了一种应用分子扩散法原理测量ＮＯ２的个体监测器。用三乙醇胺浸渍的滤纸作为ＮＯ２吸收介质，采样后用Ｓａｌｔｚｍａｎ比色法分析。采样器在温度－１０～３５℃，风速２０～２５０ｃｍ／ｓ，相对温度１０％～８０％的范围内使用，采样速度单面为７４ｍｌ／ｍｉｎ；把壳体改进为双面暴露的采样，采样速度为１５０ｍｌ／ｍｉｎ，相对标准差为１０％。与有泵的采样方法（溶液吸收管和化学发光仪器）相比较，总准确度为±２２％。与日本同类产品相比较，测定结果是一致的。本监测器最小可测浓度为０．０１３ｍｇ／ｍ３（２４ｈ采样），可广泛应用于室内空气污染和个体接触量的监测。     

Immunologic response in vaccinated mice during long-term exposure to nitrogen dioxide.

Swiss albino mice were continuously exposed to either 2 ppm NO₂, 0.5 ppm NO₂ with daily 1-hour peaks of 2 ppm NO₂, 5 days a week, or to filtered air. After a 12-week exposure the mice were vaccinated with A₂/Taiwan influenza virus vaccine and the exposures to the various environmental conditions continued for an additional 28 weeks. At 2 weeks after vaccination, the serum neutralizing (SN) antibody titers and SN seroconversion rates were depressed to a various extent in mice exposed to NO₂. At 4 weeks after the vaccination and later, the SN antibody titers did not differ significantly among the various groups.Nonvaccinated mice exposed to NO₂ for 12 weeks showed a marked decrease in concentrations (mg/ml) of serum IgA, and an increase in serum IgM, IgG₁ and IgG₂ immunoglobulins. When concentrations of immunoglobulins were adjusted for age of mice after vaccination, a significant elevation was observed in serum IgM, IgG₁ and IgG₂ of mice exposed to NO₂ as compared to controls. During the 2-week period immediately following the vaccination, exposure to NO₂ appeared to be the predominant factor influencing the percentage concentration of the four serum immunoglobulins.     

职业接触二硫化碳对血脂水平的影响

时40名慢性二硫化碳中毒患者脂蛋白及血脂进行检测分析,提示二硫化碳能诱导高脂蛋白血症及高脂血症。     

Respiratory health effects of nitrogen dioxide exposure and current guidelines

This article reviews (i) the role of nitrogen dioxide (NO2) in respiratory diseases, including asthma, and (ii) appraises whether current guidelines for NO2 confer an adequate margin of safety for asthmatics. Medline and Excerpta Medica (1966-1997) were searched to retrieve original epidemiological studies which examined the relationship between NO2 and respiratory diseases including asthma. Previously reported reviews of controlled clinical studies were also utilised. The results of this search were then related to current NO2 guidelines. The review of 23 outdoor and 36 indoor studies suggests that respiratory effects are associated with levels of NO2 that may be encountered in common domestic and outdoor settings. Meta-analyses of studies among the general population of children demonstrate a 20% increase in respiratory problems, including increases of asthma by 20%, and wheezing by 12% in households with gas cookers. Epidemiological evidence also indicates that hourly NO2 values of 80 ppb are likely to cause respiratory symptoms in the general population of children. Such levels are frequently present in domestic and school settings. Critical appraisal of the epidemiological evidence indicates the need for a revision of NO2 guidelines to protect both asthmatics and the general population, especially children.     

Effects of acute nitrogen dioxide exposure on cellular immunity after lung immunization

The effects of acute NO2 exposure on antigen-specific cell-mediated lung immunity in Fischer 344 rats were evaluated. Animals were exposed for 24 hr to either room air or 5, 10, or 26 ppm NO2 before intratracheal immunization with 10(8) sheep red blood cells (SRBC). Cellular immunity was evaluated by antigen-specific lymphocyte stimulation assays of pooled lymphoid cell suspensions from either the thoracic lymph nodes or spleens. Elevated cellular immunity was observed after exposure to NO2. The ability of the 26 ppm NO2 exposure to increase cellular immunity seemed to parallel, and in some cases even exceed, that seen in control animals immunized with SRBC mixed with 2 X 10(7) heat-killed Bacillus Calmette-Guerin. These results support the theory that lung damage, and/or alterations of regulatory populations of immune cells, induced by agents such as NO2 can be responsible for the production of abnormally elevated immune responses to antigens deposited in the damaged lung.     

长期大气二氧化氮暴露与心脑血管住院风险的因果关联研究

目的探讨长期大气二氧化氮(NO2)暴露与心脑血管住院的因果关联。方法依托我国"基于社区人群的健康队列"广州市子队列, 将2015年在广州市35个社区招募的36 271名成年参与者纳入研究, 收集基本人口学特征、生活行为方式、NO2暴露及心脑血管住院结局信息。采用基于逆概率加权的边际结构模型估计发病风险比(HR)及其95%CI。结果截至2020年12月31日共随访203 822人年, 调查对象的年龄为(50.9±17.8)岁, 心脑血管住院率为8.7%。2015-2020年, 研究对象年均NO2污染暴露为48.7 μg/m3。NO2长期暴露每增加10 μg/m3, 心脑血管、心血管及脑血管住院的HR值(95%CI)分别为1.33(1.16～1.52)、1.36(1.16～1.60)及1.25(1.00～1.55)。分层分析结果提示未婚/已婚、文化程度为初中/高中、高运动频率以及从未吸烟/当前吸烟人群可能更加易感。结论长期大气NO2暴露可增加心脑血管住院风险。     

纳米二氧化钛经口暴露对小鼠肝脏的影响

目的 探讨纳米二氧化钛(TiO2 NPs)经口暴露后对小鼠肝脏的影响。方法 60只健康雄性ICR小鼠随机分为对照组、TiO2 NPs (10、50、100) mg/kg·BW染毒组,连续灌胃30 d后,颈椎脱臼处死小鼠,计算小鼠肝脏系数,观察小鼠肝脏组织病理学切片,测定肝组织匀浆中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST),超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH - PX)、总抗氧化能力(T - AOC)活力以及丙二醛(MDA)含量。结果 与对照组相比,各染毒组小鼠肝脏系数差异无统计学意义(P＞0.05);病理学切片观察各染毒组肝脏组织均可见不同程度肝组织损伤;随着TiO2 NPs染毒剂量的增加,ALT、AST活力以及MDA含量在50、100 mg/kg·BW组升高,SOD活性在100 mg/kg·BW组降低,GSH - PX活性在50、100 mg/kg·BW组降低,T - AOC水平在10、50、100 mg/kg·BW组均降低,差异均具有统计学意义(P＜0.05)。结论 经口暴露TiO2 NPs,可使小鼠肝脏发生氧化应激反应,造成肝脏氧化损伤,并最终导致小鼠肝脏组织结构及功能破坏,具有一定的肝脏毒性作用。     

高浓度二氧化氮致大鼠急性肺水肿模型的建立

目的 建立高浓度二氧化氮(NO2)染毒SD大鼠致急性肺水肿的模型.方法 将SD大鼠随机分为对照组(8只)和染毒组(30只),染毒组以(6747.47±215.24)mg/m3 NO2通过动式染毒柜染毒90 s后以净空气平衡换气30 min;对照组大鼠入染毒柜以净空气平衡30 min.染毒组分别在6、12、18、24 h拍摄大鼠胸片,各时间点取6只大鼠留取血样后处死,取肺组织做病理检查,进行肺湿/干系数测定.检测全血红细胞膜超氧化物歧化酶(SOD)活力和血浆中心钠素(ANP)浓度.结果 染毒组大鼠均在24 h内发生肺水肿,胸片显示,斑片云雾状阴影,12 h时加重,18 h时斑片影加深,遍及全肺,呈现"白肺"状,24 h后无明显恢复.HE染色显示,染毒组6 h肺泡间隙增大,泡内有少量嗜伊红液体渗出,12 h后肺泡融合,泡内嗜伊红液体增多,18 h后肺泡及组织中充满嗜伊红液体,至24 h时无恢复.染毒组6、12、18、24 h肺湿/干系数分别为5.60±0.20、6.89±0.25、8.03±0.47、7.81±0.45,与对照组(4.72±0.06)比较,差异均有统计学意义(P＜0.01);染毒组12、18、24 h肺湿/干系数与6 h相比,差异均有统计学意义(P＜0.01);染毒后18、24 h肺湿/干系数与12 h相比,差异有统计学意义(P＜0.01).与对照组比较,染毒组6、12、18、24 h红细胞膜SOD活力均明显降低,差异有统计学意义(P＜0.01).染毒组18、24 h血浆中ANP浓度分别为(136.66±35.37)、(134.10±60.41)ng/ml,明显高于对照组[(31.31±13.06)ng/ml]、染毒组6、12 h[分别为(34.71±13.42)、(47.98±7.86)ng/ml],差异均有统计学意义(P＜0.01).结论 高浓度NO2以动式染毒柜染毒SD大鼠复制急性肺水肿模型是可行的.

Abstract：

Objective To establish the rats model of acute pulmonary edema induced by inhalation of high concentrations of nitrogen dioxide (NO2). Methods 38 SD rats were divided into the experimental group ( n=30 ) and the control group ( n=8 ). 30 rats in the experimental group were exposed to (6747.47±2 5.24) mg/m3 NO2 in the exposure system. At the time point of 6, 12, 18, 24 h, chest X-ray examination was taken for the experimental group And at each time point, 6 rats were sacrificed after taking blood samples. After sacrificing,the lung of rats was taken for pathological examination and calculated lung wet/dry weight ratio. Erythrocyte superoxide dismutase (SOD) activity and plasma atrial natriuretic peptide (ANP) concentration of blood samples were detected. Results Acute pulmonary edema was successfully induced by exposure to NO2 in 30 rats within 24 hours. There were some cloudy shadows without clear edge on the chest X-ray. To the time point of 12 hours, shadows combined with each other, and to the time point of 18 hours, the whole lung became "white"on the X-ray. The situation stabilized but not improved at the time point of 24 hours. HE staining of the lung tissue showed that to the time point of 6 hours, the alveolar gap increased and small amount of eosinophilic liquid leaked into alveolar. To the time point of 12 hours, alveolar combined with each other and eosinophilic liquid increased in amount. To the time point of 18 hours, the whole alveolar was filled with eosinophilic liquid and the situation stabilized till the time point of 24 hours. Wet/dry weight ratio of the experimental group at each time point were 5.6±0.20、6.89±0.25、8.03±-0.47、7.81 ± 0.45. There was significant difference compared with the control group which was 4.72 ± 0.06 (P＜0.01). There was statistical difference between 12,18,24 h and 6 h time points (P＜0.01). Moreover, statistical difference was observed between 18,24 h and 12 h time points for wet/dry weight ratio (P＜0.01). The erythrocvte SOD activity reduced significantly. Compared with the control group, there was a statistical difference (P＜0.01) at each time point. After exposure of 18 and 24hours, plasma A NP concentration ( 136.66± 35.37) and ( 134.10±60.41 ) ng/ml respectively, which were higher than (31.31 ± 13.06 ) ng/ml of control group and ( 34.71 ± 13.42 ) ng/ml of 6 hours time point and (47.98 ± 7.86 )ng/ml. The differences were significant (P＜0.01),Conclusion High concentrations of NO2 can induce acute pulmonary edema model successfully in SD rats.