Effect Of NO2 Exposure Research Articles

Effect of NO2 exposure on airway inflammation and oxidative stress in asthmatic mice

Nitrogen dioxide (NO2) is a widespread air pollutant. Epidemiological evidence indicates that NO2 is associated with an increase of incidence rate and mortality of asthma, but its mechanism is still unclear. In this study, we exposed mice to NO2 (5 ppm, 4 h per day for 30 days) intermittently to investigate the development and potential toxicological mechanisms of allergic asthma. We randomly assigned 60 male Balb/c mice to four groups: saline control, ovalbumin (OVA) sensitization, NO2 alone, and OVA+NO2 groups. The involved mechanisms were found from the perspective of airway inflammation and oxidative stress. The results showed that NO2 exposure could aggravate lung inflammation in asthmatic mice, and airway remodeling was characterized by significant thickening of the airway wall and infiltration of inflammatory cells. Moreover, NO2 would aggravate the airway hyperresponsiveness (AHR), which is characterized by significantly elevated inspiratory resistance (Ri) and expiratory resistance (Re), as well as decreased dynamic lung compliance (Cldyn). In addition, NO2 exposure promoted pro-inflammatory cytokines (IL-6 and TNF-α) and serum immunoglobulin (IgE) production. The imbalance of Th1/Th2 cell differentiation (IL-4 increased, IFN-γ reduced, IL-4/IFN-γ significantly increased) played a key role in the inflammatory response of asthma under NO2 exposure. In a nutshell, NO2 exposure could promote allergic airway inflammation and increase asthma susceptibility. The levels of ROS and MDA among asthmatic mice exposed to NO2 increased significantly, while GSH levels sharply decreased. These findings may provide better toxicological evidence for the mechanisms of allergic asthma risk due to NO2 exposure.

Short-Term Effects of Low-Level Ambient Air NO2 on the Risk of Incident Stroke in Enshi City, China.

Previous studies found that exposure to ambient nitrogen dioxide (NO2) was associated with an increased risk of incident stroke, but few studies have been conducted for relatively low NO2 pollution areas. In this study, the short-term effects of NO2 on the risk of incident stroke in a relatively low-pollution area, Enshi city of Hubei Province, China, were investigated through time-series analysis. Daily air-pollution data, meteorological data, and stroke incidence data of residents in Enshi city from 1 January 2015 to 31 December 2018 were collected. A time-series analysis using a generalised additive model (GAM) based on Poisson distribution was applied to explore the short-term effects of low-level NO2 exposure on the risk of incident stroke and stroke subtypes, as well as possible age, sex, and seasonal differences behind the effects. In the GAM model, potential confounding factors, such as public holidays, day of the week, long-term trends, and meteorological factors (temperature and relative humidity), were controlled. A total of 9122 stroke incident cases were included during the study period. We found that NO2 had statistically significant effects on the incidence of stroke and ischemic stroke, estimated by excess risk (ER) of 0.37% (95% CI: 0.04–0.70%) and 0.58% (95% CI: 0.18–0.98%), respectively. For the cumulative lag effects, the NO2 still had a statistically significant effect on incident ischemic stroke, estimated by ER of 0.61% (95% CI: 0.01–1.21%). The two-pollutant model showed that the effects of NO2 on incident total stroke were still statistically significant after adjusting for other air pollutants (PM2.5, PM10, SO2, CO, and O3). In addition, the effects of NO2 exposure on incident stroke were statistically significant in elderly (ER = 0.75%; 95% CI: 0.11–1.40%), males (ER = 0.47%; 95% CI: 0.05–0.89%) and cold season (ER = 0.83%; 95% CI: 0.15–1.51%) subgroups. Our study showed that, as commonly observed in high-pollution areas, short-term exposure to low-level NO2 was associated with an increased risk of incident stroke, including ischemic stroke. Males and elderly people were more vulnerable to the effects of NO2, and the adverse effects might be promoted in the cold season.

Association between short-term exposure to ambient nitrogen dioxide and the risk of conjunctivitis in Hefei, China: A time-series analysis

BackgroundConjunctivitis, one of the most common ocular surface diseases, can be caused by many contributors. However, the important role of air pollution has been inadequately evaluated, particularly in countries with poor air quality. This study aims to explore the possible association of short-term ambient nitrogen dioxide (NO2) exposure with the risk of outpatient visits for conjunctivitis. MethodsA total of 43,462 conjunctivitis patients from January 1, 2014 to December 31, 2018 were identified from the Department of Ophthalmology of The Second Affiliated Hospital of Anhui Medical University, Hefei, China. Such data were linked to the daily mean concentration of NO2 at ten fixed air quality monitoring stations. A distributed lag nonlinear model (DLNM) combined with a quasi-Poisson generalized linear regression model was employed to assess the association between NO2 exposure and the risk of outpatient visits for conjunctivitis. Stratified analyses were also performed on the basis of gender, age group and season. ResultsThe association of NO2 exposure with the risk of outpatient visits for conjunctivitis was statistically significant. In the single-day lags (lag 0 to lag 11) analysis, the largest effect estimates were observed at lag 0. In the moving average exposure lags (lag 0–1 to lag 0–11) analysis, the cumulative effects were stronger than the single-day lag effects. The stratified analyses suggested that the effect of NO2 exposure was more pronounced in females and patients aged 19–65 years and in the cold season. ConclusionsThis study confirms the evidence that short-term NO2 exposure is associated with an increased risk of conjunctivitis outpatient visits. Our research encourages individuals to avoid outdoor activities on severe air pollution days and the government is obliged to adopt more stringent environmental policies to alleviate the effects of air pollution on human health, particularly for individuals at risk of developing conjunctivitis.

Gestational exposures to outdoor air pollutants in relation to low birth weight: A retrospective observational study

Findings for impacts of outdoor air pollutants on birth outcomes were controversial. We performed a retrospective observational study in 2527 preschoolers of Shanghai, China and investigated associations of duration-averaged concentrations of outdoor sulphur dioxide (SO2), nitrogen dioxide (NO2), and particulate matter with an aerodynamic diameter ≤ 10 μm (PM10) in different months and trimesters of gestation, with preterm birth (PB), low birth weight (LBW), term low birth weight (T-LBW), and small for gestational age (SGA). Daily concentrations of outdoor air pollutants were collected in each residence-located district. Parents reported health information. In the multivariate logistic regression analyses, exposures to outdoor NO2 were consistently associated with the higher odds of LBW and T-LBW. These associations were generally stronger for early months than for later months of the gestation. Adjusted odds ratios generally were larger in multi-pollutant model than in single-pollutant model. Exposure to NO2 in the first month of the gestation was significantly associated with T-LBW (adjusted OR, 95%CI: 1.91, 1.02–3.58 for increment of interquartile range (18.5 μg/m3); p-value = 0.044) in multi-pollutant model. This association was stronger in girls, renters, and children whose mothers ≥30 years-old, with household dampness-related exposures, and with parental smoking during pregnancy. Our results indicate that exposure to NO2 during gestation perhaps is a risk factor for LBW and T-LBW, and effects of NO2 exposures could be greater during early periods than during later periods of gestation.

Effects of nitrogen dioxide exposure on the risk of eye and adnexa diseases among children in Shenzhen, China: an assessment using the generalized additive modeling approach

ABSTRACT This study aimed to assess the relationship between nitrogen dioxide (NO2) exposure and the risk of eye and adnexa diseases (EADs) among children in Shenzhen, China. Information about the daily number of outpatients with EADs and the concentration of air pollutants and meteorological data were collected. A generalized additive model was used to assess the effect of NO2 exposure on the risk of EADs during outpatient visits. An increase in NO2 level by 10 μg/m3 was related to an increase in the daily number of outpatients by 5.43% (95% confidence interval [CI]: 2.25%, 8.70%) at lag0, by 4.35% (95% CI: 1.15%, 7.66%) at lag1, and by 3.21% (95% CI: 0.05%, 6.47%) at lag3. In addition, the relationship between NO2 exposure and the risk of dacryoadenitis was the strongest, with an estimated value of 15.0% (95% CI: 7.99%, 22.5%) at lag0. Moreover, the association between NO2 exposure and the risk of EADs among children in Shenzhen was confirmed in this study. Therefore, the government should introduce stringent environmental policies to control air pollution and protect human health, particularly that of the vulnerable population.

A retrospective cohort study of long-term nitrogen dioxide exposure and incident hypertension

Objective: To investigate the effect of long-term exposure of nitrogen dioxide on the incidence of hypertension. Methods: From March to December 2009, 37 386 eligible residents from four cities in northern China (Tianjin, Shenyang, Taiyuan, and Rizhao) were enrolled in a follow-up study by using the random cluster sampling method. Demographic characteristics, lifestyle, history of diseases, and self-report situation of hypertension were collected by using questionnaire. Based on the average annual concentration of NO2 during the period from the cohort to the onset of hypertension as an estimate of exposure, the effect of NO2 exposure on hypertension was analyzed by employing Cox proportional hazards model. The interactions between NO2 exposure and different characteristics (age, sex, body mass index, smoking, alcohol consumption, education, economy, exercise, and fruit intake) were also examined. Results: The baseline age of residents was (43.74±13.78) years, and the body mass index (BMI) was (22.56±2.92) kg/m(2). During an average follow-up time of 11.40 years, 2 619 (7.0%) new cases of hypertension were reported. The overall mean environmental pollution levels during the study period for the entire cohort was (40.74±17.07) μg/m(3). After adjusting for age, sex, BMI, family history of hypertension, socio-economic information, and lifestyle, the hazard ratio (HR) of incident hypertension with a 10 μg/m(3) increase of NO2 was 1.21 (95%CI: 1.18-1.25). Compared with residents aged 60 years and over (HR=1.19, 95%CI: 1.14-1.26), former and current smoking (HR=1.20, 95%CI: 1.14-1.25), and high-frequency fruit consumption (HR=1.17, 95%CI: 1.13-1.21), residents younger than 60 years (HR=1.28, 95%CI: 1.25-1.32), non-smoker (HR=1.23, 95%CI: 1.19-1.27), and low-frequency fruit consumption (HR=1.27, 95%CI: 1.20-1.35) had stronger interaction effect with NO2 (all P values for interaction<0.05). Conclusion: NO2 exposure may lead to the onset of hypertension, which has a stronger effect on people younger than 60 years old, without smoking history and with low-frequency fruit consumption.

Effects of NO2 exposure on daily mortality in São Paulo, Brazil

BackgroundRecent reports have suggested that air pollution mixtures represented by nitrogen dioxide (NO2) may have effects on human health, which are independent from those of particulate matter mass. We evaluate the association between NO2 and daily mortality among elderly using one- and multipollutant models. MethodsThis study was a daily time series of non-accidental and cause-specific mortality among the elderly living in São Paulo, Brazil, between 2000 and 2011. Effects of NO2, particulate matter smaller than 10µm (PM10), carbon monoxide (CO) and ozone (O3) were estimated in Poisson generalized additive models. The single lag effect at lags 0 and 1 days and the cumulative effect from 0 to lag 10 days were evaluated in one-, two-, three- and four-pollutant models. The cumulative risk index (CRI) recently proposed to analyze associations with health of multiple correlated pollutants was additionally estimated for each multipollutant model. ResultsAn association between NO2, PM10, CO and O3 exposures and non-accidental and cause-specific deaths was found in one-pollutant models. NO2 effects remained significant in multipollutant models for non-accidental and circulatory deaths. The estimated CRIs suggested that circulatory deaths were mainly associated with NO2, and respiratory deaths mainly with CO and O3, regardless the lag. For non-accidental deaths, multipollutant models were associated with the highest CRI, with the main pollutants depending on the chosen lag. ConclusionsThe results suggest that air pollution mixtures represented by NO2 have an effect on non-accidental and circulatory mortality, which is independent from PM10, CO and O3. The CRI was always larger than the risks associated with single pollutants.

Kinetic of NO2 uptake by Phleum pratense pollen: Chemical and allergenic implications

Phleum pratense pollen was exposed to NO2 in a reactor allowing a continuous analysis of NO2 concentration by FTIR. The uptake coefficient of NO2 on pollen was calculated postulating a first order kinetic reaction and a value of (1.1 ± 0.1) × 10−7 was determined. NO2 uptake was faster when the pollen water content was increased and when the pollen was pre-treated with ozone. The effect of NO2 exposure on pollen allergic properties was investigated by quantifying Th2- and Th1-associated chemokines in a model of human dendritic cells. Cellular analysis clearly showed that cells exposed to fumigated pollen favored the production of chemokines known to promote Th2-cell responses. Altogether these data demonstrate that NO2 uptake by pollen directly correlates with increased Th2 response in human cells, and are in favor of the involvement of NO2 pollution in the increase of allergic diseases.

Mechanistic Study of the Effect of Sulphur Dioxide and Nitrogen Dioxide Exposure of ASC/T, Whetlerised BPL and Whetlerised Chlorinated BPL Activated Carbons on the Chemisorption of Hydrogen Cyanide from Air

Three activated carbons, ASC/T, Whetlerised BPL and Whetlerised chlorinated BPL (BPL/C) (4.5 %w/w chlorine/carbon) were tested extensively on their adsorption behaviour towards HCN in air, before and after exposure to SO2 and NO2 in air at pressures from 2 to 500 mbar. Whetlerite impregnation solutions of carefully controlled compositions were made up to treat the BPL and BPL/C. ASC/T and the resulting Whetlerised carbons BPL/W and BPL/WC were examined. Nitrogen isotherm data were obtained for these carbons before and after exposure to SO2 and NO2. The carbons were also analysed by ICP-AES and AAS for total Cr, and by alkaline extraction then spectrophotometric analysis using diphenylcarbazide reagent, for the determination of CrVI. The ASC/T, BPL/W and BPL/WC were challenged by 2 mg/l HCN in air at 22°C/80% relative humidity (RH) before and after exposure to SO2 and NO2. Surface area, microporous volume N2 adsorption energy and pore size distribution data were obtained for the range of carbons from the nitrogen isotherms. Adsorption rate constants, adsorption capacity and adsorption site densities for HCN and (CN)2 were obtained. Analysis of the results for all three carbons shows that the principal effects of SO2 and NO2 are in reducing the fraction of Cr as CrVI and in blocking the micropore adsorption sites for HCN and (CN)2. There is little obvious correlation between SO2 or NO2 loading and the N2 adsorption rate constants and N2 adsorption energies. There is an overall reduction in microporous area and volume on exposure of ASC/T to both SO2 and, to a lesser but still marked degree, to NO2. The biggest reduction is in the fraction of pores &lt;5 Å radius. It is thought that the reduction in breakthrough time and the related adsorption capacity for HCN and (CN)2 is due to chemical reduction of the CrVI by SO2 on the carbons giving sulphate or sul-phuric acid species, both blocking the microporous structure and reducing the ability of CrVI to oxidise the copper cyanide complexes to oxamide. Analogous mechanisms are proposed to explain the lesser but nonetheless marked effect of NO2 exposure. These findings are consistent with earlier work in the authors' laboratory and that reported elsewhere.

Nitrogen dioxide exposure increases airway contractile response to histamine by decreasing histamine N-methyltransferase activity in guinea pigs.

To determine the mechanism responsible for nitrogen dioxide (NO2)-induced airway hyperresponsiveness, we examined the effects of NO2 exposure on the contractile response to histamine and the level of histamine N-methyltransferase (HMT) activity, a histamine-degrading enzyme, in guinea pig trachea in vitro. Guinea pigs were divided into seven groups. Each group received continuous NO2 exposure (2.0 ppm) for either 2, 6, 12, 24, 48, or 96 h. The remaining group did not receive NO2 exposure (control). HMT activity in trachea was decreased from the control value of 70.3 +/- 7.7 pmol/min/mg protein to 34.6 +/- 6.7 pmol/min/mg protein by 12 h exposures of NO2. However, 24 and 48 h exposures of NO2 did not significantly alter HMT activity. In contrast, HMT activity exceeded the control value by 96 h exposures of NO2 (85.5 +/- 5.1 pmol/min/mg protein). Twelve hour exposures of NO2 shifted the concentration-response curves to histamine to lower concentrations and significantly reduced the median effective concentration (EC50) of histamine (log M) from the control value of -5.16 +/- 0.09 to -6.15 +/- 0.14 (P < 0.01). In contrast, the EC50 concentration of histamine (log M) increased from the control value of -5.20 +/- 0.10 to -4.90 +/- 0.11 by 96 h exposures of NO2 (P < 0.05). However, NO2 exposure did not alter the contractile response to acetylcholine. Morphologically, tracheal epithelial cells had vacuoles after 12 h exposures of NO2, but denudation of the epithelium did not occur during this experiment. In situ hybridization for HMT mRNA demonstrated that the level of HMT mRNA increased dominantly in tracheal epithelial cells after 96 h exposures of NO2. The present results indicated that the decrease in the level of HMT activity in the trachea was closely associated with the increase in the airway contractile response to histamine, suggesting that NO2-induced transient airway hyperresponsiveness to histamine is due to the decreased capacity of histamine catabolism in airway.

Acute effect of nitrogen dioxide exposure on the functional activity of alpha-1-protease inhibitor in bronchoalveolar lavage fluid of normal subjects.

Nitrogen dioxide is one form of an oxidizing free radical that is sufficiently stable to exist in relatively high concentrations in ambient air and cigarette smoke. We examined the effect of NO2 exposure on the functional activity against pancreatic elastase of alpha-1-protease inhibitor (alpha 1PI) in bronchoalveolar lavage (BAL) fluid of nonsmoking subjects. Ten nonsmokers (mean age, 25 +/- 2 SE yr) were exposed to NO2 (3 or 4 ppm) for 3 h with intermittent exercise. Seven nonsmokers (mean age, 24 +/- 2 SE yr) underwent a similar protocol but were exposed to NO2-free air and served as control subjects. Bronchoalveolar lavage was performed 3.5 to 4 h after the end of exposure. Exposure to NO2 caused a 45% decrease in functional activity of alpha 1PI in BAL. There was no significant difference in immunoreactive alpha 1PI between the groups whether expressed as micrograms per 100 ml of recovered fluid or per milligram of albumin. This inactivation of alpha 1PI was not associated with any neutrophil migration into the air spaces of the lung. The "elastaselike" activity of BAL using synthetic elastinlike chromophore substrate succinyl-trialanine-nitroanilide showed no significant difference between the NO2-exposed group (221 +/- 39 SE ng/dl BAL) and the control group (196 +/- 61 SE ng/dl BAL). Assay for human leukocyte elastase (HLE) in concentrated BAL using the synthetic substrate Methoxysuc-Ala3-Pro-Val-aminomethylcoumarin did not detect any HLE activity in the BAL. These results showed that nonsmoking subjects exposed to relatively low concentrations of NO2 for a short time have a significant inactivation of alpha 1PI in the lower respiratory tract fluid than did nonsmoking control subjects.

Long-term NO2 exposure of mice in the presence and absence of vitamin E. I. Effect on body weights and lipofuscin pigments.

Mice on diets deficient in vitamin E, normal diets, diets with high supplements of vitamin E, and diets supplemented with N, N'-diphenyl-p-phenylenediamine (DPPD) were continuously exposed to 0.5 ppm or to 1.0 ppm nitrogen dioxide (NO2) or to filtered room air from weaning to 18 months of age. The effects of NO2 exposure on body weights, tissue weights, survival rates, and tissue organic solvent soluble lipofuscin (age) pigment concentrations were examined. Vitamin E deficiency resulted in lower body weights by 18 months of age; exposure to NO2 further increased this weight loss. With the exception of the kidney, tissue weights were not affected by NO2 exposure. Mice exposed to NO2 had lower survival rates than unexposed control animals. Tissue organic solvent soluble lipofuscin pigment (LFP) concentrations in the uterus, lung, spleen, kidney, liver, brain, and heart were not afffected by NO2 exposure. Only in the liver did vitamin E deficiency lead to an increase in LFP concentration; it did not occur in any of the other tissues examined.