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A land use regression model for predicting ambient concentrations of nitrogen dioxide in Hamilton, Ontario, Canada.

This paper reports on the development of a land use regression (LUR) model for predicting the intraurban variation of traffic-related air pollution in Hamilton, Ontario, Canada, an industrial city at the western end of Lake Ontario. Although land use regression has been increasingly used to characterize exposure gradients within cities, research to date has yet to test whether this method can produce reliable estimates in an industrialized location. Ambient concentrations of nitrogen dioxide (NO2) were measured for a 2-week period in October 2002 at > 100 locations across the city and subsequently at 30 of these locations in May 2004 to assess seasonal effects. Predictor variables were derived for land use types, transportation, demography, and physical geography using geographic information systems. The LUR model explained 76% of the variation in NO2. Traffic density, proximity to a highway, and industrial land use were all positively correlated with NO2 concentrations, whereas open land use and distance from the lake were negatively correlated with NO2. Locations downwind of a major highway resulted in higher NO2 levels. Cross-validation of the results confirmed model stability over different seasons. Our findings demonstrate that land use regression can effectively predict NO2 variation at the intraurban scale in an industrial setting. Models predicting exposure within smaller areas may lead to improved detection of health effects in epidemiologic studies.

Air Pollutants, Occupational↗

Air pollution involving nitrogen dioxide exposure and wheezing bronchitis in children.

BACKGROUND: A population-based case-control study was performed in Stockholm to assess the influence of air pollution on the occurrence of severe wheezing bronchitis in children. METHODS: The study included 197 children aged 4 months to 4 years, who were hospitalized because of breathing difficulties with wheezing, and 350 population controls. Information on potential risk factors for childhood wheezing and a residential history was obtained at home interview with parents. Outdoor nitrogen dioxide (NO2) concentrations at home addresses and day care centres from birth on were estimated from validated models, mainly using data on traffic intensity from municipal registers. RESULTS: The risk of wheezing bronchitis was related to time-weighted mean outdoor NO2 exposure in girls (P = 0.02), but not in boys. A gas stove in the home appeared to be a risk factor primarily for girls. All analyses controlled for parental asthma and maternal smoking, which were independent risk factors for wheezing bronchitis. CONCLUSIONS: The results suggest that exposure to combustion products containing NO2 may be of particular importance for the development of wheezing bronchitis in girls.

Air Pollutants↗

Synthesis of environmental evidence: nitrogen dioxide epidemiology studies.

The use of meta-analysis is becoming more common in the medical literature, but it is not common in the environmental literature. Although meta-analysis cannot combine a group of poorly executed, conflicting studies to get an unequivocal answer, there are certain situations where it can be helpful. The inability of studies to produce similar results may be a function of the power of the studies rather than a reflection of their quality. The literature on the effects of nitrogen dioxide on the odds of respiratory illness in children is such an example. Three quantitative methods for the synthesis of this evidence are presented. Although the methods produce slightly different results, the conclusion from all three methods is that the increase in the odds of respiratory illness in children exposed to a long-term increase of 30 micrograms/m3 (comparable to the increase resulting from exposure to a gas stove) is about 20 percent. This estimated increase is not sensitive to the method of analysis.

Air Pollution↗

Predictors of concentrations of nitrogen dioxide, fine particulate matter, and particle constituents inside of lower socioeconomic status urban homes.

Air pollution exposure patterns may contribute to known spatial patterning of asthma morbidity within urban areas. While studies have evaluated the relationship between traffic and outdoor concentrations, few have considered indoor exposure patterns within low socioeconomic status (SES) urban communities. In this study, part of a prospective birth cohort study assessing asthma etiology in urban Boston, we collected indoor and outdoor 3-4 day samples of nitrogen dioxide (NO2) and fine particulate matter (PM2.5) in 43 residences across multiple seasons from 2003 to 2005. Homes were chosen to represent low SES households, including both cohort and non-cohort residences in similar neighborhoods, and consisted almost entirely of multiunit residences. Reflectance analysis and X-ray fluorescence spectroscopy were performed on the particle filters to determine elemental carbon (EC) and trace element concentrations, respectively. Additionally, information on home characteristics (e.g. type, age, stove fuel) and occupant behaviors (e.g. smoking, cooking, cleaning) were collected via a standardized questionnaire. The contributions of outdoor and indoor sources to indoor concentrations were quantified with regression analyses using mass balance principles. For NO2 and most particle constituents (except outdoor-dominated constituents like sulfur and vanadium), the addition of selected indoor source terms improved the model's predictive power. Cooking time, gas stove usage, occupant density, and humidifiers were identified as important contributors to indoor levels of various pollutants. A comparison between cohort and non-cohort participants provided another means to determine the influence of occupant activity patterns on indoor-outdoor ratios. Although the groups had similar housing characteristics and were located in similar neighborhoods, cohort members had significantly higher indoor concentrations of PM2.5 and NO2, associated with indoor activities. We conclude that the effect of indoor sources may be more pronounced in high-density multiunit dwellings, and that future epidemiological studies in these populations should explicitly consider these sources in assigning exposures.

Female↗

Effect of nitrogen dioxide on the EPR property of lithium octa-n-butoxy 2,3-naphthalocyanine (LiNc-BuO) microcrystals.

Lithium octa-n-butoxy-naphthalocyanine (LiNc-BuO) is a stable free radical that can be detected by electron paramagnetic resonance (EPR) spectroscopy. Previously we have reported that microcrystals of LiNc-BuO exhibit a single sharp EPR peak, whose width varies linearly with the partial pressure of paramagnetic molecules such as oxygen and nitric oxide. In this report, we present the effect of nitrogen dioxide (NO2), which is also a paramagnetic molecule, on the EPR properties of LiNc-BuO. The gas-sensing property of LiNc-BuO is attributed to the open molecular framework of the crystal structure which is arranged with wide channels capable of accommodating large molecules such as NO2. The EPR linewidth of LiNc-BuO was highly sensitive to the partial pressure of NO2 in the gas mixture. The line-broadening was quick and reversible in the short-term for low concentration of NO2. However, the EPR signal intensity decreased with time of exposure, apparently due to a reaction of NO2 with LiNc-BuO crystals to give diamagnetic products. The results suggested that LiNc-BuO may be a useful probe for the determination of trace amounts of NO2 using EPR spectroscopy.

Electron Spin Resonance Spectroscopy↗

Nitrogen dioxide (silo gas) poisoning in pigs.

Toxic silo gases are a potential danger to livestock housed in close proximity to silos. On the fourth day of ensiling, five fattening pigs were found dead in a pen adjoining a grass silo. Post mortem examination revealed extensive lung damage and methaemoglobinaemia. A dense reddish-brown gas was concentrated at floor level to a height of 1 m in the pen and had diffused into adjoining pens, where dry and suckling sows and litters were showing signs of respiratory distress and weakness. The gas was identified as a mixture of nitrogen dioxide and dinitrogen tetroxide. These gases may be produced in the early stages of silage making. In this case, they had accumulated in a slurry channel below the silo and leaked through an adjoining wall into the piggery. The production and toxicological effects of silo gases are discussed.

Animals↗

Investigations into the relations between respiratory illness in children, gas cooking and nitrogen dioxide in the U.K.

In 1977 an association was reported between the prevalence of respiratory illness and use of gas for cooking at home in a national sample of six to 11 year olds living in England and Scotland (p less than .10). Other variables such as social class and number of cigarette smokers at home did not seem to explain the association. As the gas cooker is an unflued appliance emitting a variety of pollutants during gas combustion it was suggested that indoor air pollution might explain the finding. Nitrogen dioxide (NO2) was suspected so a series of studies was conducted to investigate the distribution of levels of NO2 in the home, the relative contribution of sources of NO2 to indoor exposure and the relation between respiratory illness in six to 11 year olds and levels of NO2 in the home. The gas cooker was found to be one of the main sources of NO2 in the home. Winter weekly averages in kitchens with gas cookers had a mean of 112.2 ppb (n = 428, range 5-317 ppb). Levels in electric cooking kitchens were significantly lower (n = 87, mean 18 ppb, range 6-188 ppb). Studies of health indicated a relation between respiratory illness and bedroom levels of NO2 over the range 4-169 ppb (p .10). Results for living room levels of NO2 suggested a similar but non-significant relationship (p greater than .10). No relation was found for kitchen levels of NO2. For schoolchildren any effect on health from indoor NO2 is likely to be weak. However other sections of the population such as infants and the elderly who may spend more time indoors and are particularly susceptible to respiratory illness need to be studied to assess fully the impact that NO2 may be having on health.

Child↗

Nitrogen dioxide exposure from domestic gas cooking and airway response in asthmatic women.

BACKGROUND: Previous studies have not found a consistent association between exposure to domestic cooking using gas appliances and exacerbation of asthma. We investigated the immediate airflow response to acute exposure from single episodes of gas cooking, and peak airflow variability from continued exposure to repeated episodes of gas cooking in a group of non-smoking asthmatic women. METHODS: Sixteen adult non-smoking women with mild to severe persistent asthma were studied. The acute short term level of nitrogen dioxide (NO2) during gas cooking episodes and the mean exposure to NO2 from repeated gas cooking episodes were measured over a 2 week period, as well as proxy measures of frequency of cooking on each day and the length of time spent cooking each day. Their asthma status was monitored using peak expiratory flow rates (PEFR) before and after cooking, 2 week self-recorded serial readings of PEFR, respiratory symptom severity score, and use of rescue bronchodilators for acute asthma attacks. RESULTS: Cooking was significantly associated with an immediate mean fall in PEFR of 3.4% (p=0.015, paired t test). The acute short term NO2 level during cooking was significantly correlated with the fall in PEFR (r=-0.579; p=0.019). The frequency of cooking over a 2 week period was positively correlated with the mean exposure to NO2 (r=0.529; p=0.042). Continued exposure to NO2 over a 2 week period was associated significantly with increased frequency of rescue bronchodilator usage for asthma attacks (r=0.597; p=0.031). However, it was negatively associated with PEFR variability (r=-0.512; p=0.051) and respiratory symptom severity score (r= -0.567; p=0.043), probably due to the masking effects of bronchodilator treatment. CONCLUSIONS: Acute short term exposure to NO2 from single episodes of gas cooking is associated with immediate airflow limitation. Continued exposure from repeated episodes of gas cooking in asthmatic women is associated with greater use of rescue bronchodilators.

Adult↗

Effects of nitrogen dioxide on respiratory tract clearance in the ferret.

During growth and development, young children are periodically exposed to relatively high concentrations of various air contaminants, including tobacco smoke and environmental pollutants generated by fossil fuel use. The effects of these exposures on respiratory function and lung development are difficult to determine because of interindividual variation and lack of accurate dosimetry. To provide information on the effects of chronic exposure to a common indoor and outdoor pollutant during lung development, a study was performed to assess the effects of exposure to two concentrations of nitrogen dioxide (NO2; 0.5 or 10 ppm) on tracer particle clearance from the airways of ferrets exposed during postnatal respiratory tract development. Separate groups of ferrets were exposed nose-only to the test atmospheres or clean air 4 h/d, 5 d/wk, for either 8 or 15 wk. Those animals exposed for 8 wk were subsequently housed in a filtered air environment until the particle clearance measurements commenced at 3 wk prior to the end of the 15-wk exposure protocol. Radiolabeled (51Cr) tracer particles were deposited in the respiratory tract of all animals by inhalation, and the clearance rates from the head and thoracic regions were separately monitored for 18 d. No significant effects of the NO2 exposure on head airways clearance were seen. In contrast, the rates of particle clearance from the thorax of both the 8- and 15-wk groups exposed to 10 ppm NO2 were significantly reduced, and did not differ from each other. Thoracic clearance was also reduced in animals exposed to 0.5 ppm, but the rate was not significantly different from that of the clean air exposed controls. These results show that NO2 at moderate concentrations caused highly significant changes in the deep lung of the juvenile ferret, and suggest that impairment of the clearance function may be only slowly recovered after chronic exposure.

Animals↗

Fluctuations of inspired concentrations of nitric oxide and nitrogen dioxide during mechanical ventilation.

BACKGROUND: Nitric oxide (NO) is a very reactive agent with potentially toxic oxidation products such as nitrogen dioxide (NO2). Therefore, during NO inhalation a constant inspired concentration and accurate measurement of NO and NO2 concentrations are essential. The objective of this study was to test the NO concentrations at various positions along the inspiratory limb of the breathing circuit using a recently developed system to administer NO in phase with inspiratory flow during mechanical ventilation (Servo 300 NO-A, Siemens, Sweden). Furthermore, we tested whether an active heating system would interfere with inspired NO concentrations. RESULTS: A sharp decline in the NO concentration was found between the respirator's inspiratory outlet and more distal points along the inspiratory limb of the circuit. This finding was most evident when an active heating system was mounted between those points. CONCLUSIONS: The concentrations of NO and NO2 should be measured as near to the patient as possible, as significant fluctuations of these concentrations might be found along the inspiratory limb of the respiratory circuit especially when an active heating system is used.

Journal Article↗

Suppression of nitric oxide oxidation to nitrite by curcumin is due to the sequestration of the reaction intermediate nitrogen dioxide, not nitric oxide.

Curcumin, a phytochemical with antioxidant and other cytoprotective properties, has been reported to reduce nitrite formation during nitric oxide (NO) oxidation in solution. This decrease in nitrite production was attributed to the direct sequestration of NO by curcumin. In this report, we confirm that curcumin inhibits nitrite formation from DEA/NO-derived NO in a concentration-dependent manner. However, curcumin over a concentration range of 3-50 microM had no effect on the concentration of free NO (0.5 microM) in solution at 37 degrees C as assessed using an NO electrode. We conclude that the inhibitory effect of curcumin on the oxidation of NO to nitrite is due to its known sequestration of the reaction intermediate nitrogen dioxide (NO(2)). The ability of curcumin to sequester NO(2), but not NO, suggests that curcumin may be useful for separating the actions of NO(2) from those of NO in various biological systems.

Antioxidants↗

Outdoor air concentrations of nitrogen dioxide and sulfur dioxide and prevalence of wheezing in school children.

We report analysis of data on outdoor air pollution and respiratory symptoms in children collected in the Czech part of the international Small Area Variations in Air pollution and Health (SAVIAH) Project, a methodological study designed to test the use of geographical information systems (GIS) in studies of environmental exposures and health at small area level. We collected the following data in two districts of Prague: (1) individual data on 3,680 children (response rate 88%) by questionnaires; (2) census-based socio-demographic data for small geographical units; (3) concentrations of nitrogen dioxide (NO2) and sulfur dioxide (SO2) measured by passive samplers in three 2-week surveys at 80 and 50 locations, respectively. We integrated all data into a geographical information system. Modeling of NO2 and SO2 allowed estimation of exposure to outdoor NO2 and SO2 at school and at home for each child. We examined the associations between air pollution and prevalence of wheezing or whistling in the chest in the last 12 months by logistic regression at individual level, weighted least squares regression at small area (ecological) level and multilevel modeling. The results varied by the level of analysis and method of exposure estimation. In multilevel analyses using individual data, odds ratios per 10 microg/m3 increase in concentrations were 1.16 (95% CI = 0.95-1.42) for NO2, and 1.08 (95% CI = 0.97-1.21) for SO2. While mapping of spatial distribution of NO2 and SO2 in the study area appeared valid, the interpolation from outdoor to personal exposures requires consideration.

Air Pollutants↗

Peroxynitrite-derived carbonate and nitrogen dioxide radicals readily react with lipoic and dihydrolipoic acid.

Alpha-lipoic acid (LA) and dihydrolipoic acid (DHLA) may have a role as antioxidants against nitric oxide-derived oxidants. We previously reported that peroxynitrite reacts with LA and DHLA with second-order rate constants of 1400 and 500 M(-1) s(-1), respectively, but indicated that these direct reactions are not fast enough to protect against peroxynitrite-mediated damage in vivo. Moreover, the mechanism of the reaction of peroxynitrite with LA has been recently challenged (J. Biol. Chem.279:9693-9697; 2004). Pulse radiolysis studies indicate that LA and DHLA react with peroxynitrite-derived nitrogen dioxide (*NO2) (k2 = 1.3 x 10(6) and 2.9 x 10(7) M(-1) s(-1), respectively) and carbonate radicals (CO(3-)) (k2 = 1.6 x 10(9) and 1.7 x 10(8) M(-1) s(-1), respectively). Carbonate radical-mediated oxidation of LA led to the formation of the potent one-electron oxidant LA radical cation. LA inhibited peroxynitrite-mediated nitration of tyrosine and of a hydrophobic tyrosine analog, N-t-BOC L-tyrosine tert-butyl ester (BTBE), incorporated into liposomes but enhanced tyrosine dimerization. Moreover, while LA competitively inhibited the direct oxidation of glutathione by peroxynitrite, it was poorly effective against the radical-mediated thiol oxidation. The mechanisms of reaction defined herein allow to rationalize the biochemistry of peroxynitrite based on direct and free radical-mediated processes and contribute to the understanding of the antioxidant actions of LA and DHLA.

Antioxidants↗

Nitrogen dioxide as an oxidizing agent of 8-oxo-7,8-dihydro-2'-deoxyguanosine but not of 2'-deoxyguanosine.

The redox reactions of guanine and its widely studied oxidation product, the 8-oxo-7,8-dihydro derivative, are of significant importance for understanding the mechanisms of oxidative damage in DNA. Employing 2'-deoxyguanosine 5'-monophosphate (dGMP) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) in neutral aqueous solutions as model systems, we have used nanosecond laser flash photolysis to demonstrate that neutral radicals, dGMP(-H)(*), derived by the one-electron oxidation and deprotonation of dGMP, can oxidize nitrite anions (NO2(-)) to the nitrogen dioxide radical (*)NO2. In turn, we show that (*)NO2 can give rise to a one-electron oxidation of 8-oxo-G, but not of dGMP. The one-electron oxidation of dGMP was initiated by a radical cation generated by the laser pulse-induced photoionization of a pyrene derivative with enhanced water solubility, 7,8,9,10-tetrahydroxytetrahydrobenzo[a]pyrene (BPT). The dGMP(-H)(*) neutral radicals formed via deprotonation of the dGMP(*)(+) radical cations and identified by their characteristic transient absorption spectrum (lambda(max) approximately 310 nm) oxidize nitrite anions with a rate constant of (2.6 +/- 0.3) x 10(6) M(-1) s(-1). The 8-oxo-dG is oxidized by (*)NO2 with a rate constant of (5.3 +/- 0.5) x 10(6) M(-1) s(-1). The 8-oxo-dG(-H)(*) neutral radicals thus generated are clearly identified by their characteristic transient absorption spectra (lambda(max) approximately 320 nm). The rate constant of 8-oxo-dG oxidation (k(12)) by the (*)NO2 one-electron oxidant (the (*)NO2/NO2(-) redox potential, E degrees approximately 1.04 V vs NHE) is lower than k(12) for a series of oxidizing aromatic radical cations with known redox potentials. The k(12) values for 8-oxo-dG oxidation by different aromatic radical cations derived from the photoionization of their parent compounds depend on the redox potentials of the latter, which were in the range of 0.8-1.6 V versus NHE. The magnitude of k(12) gradually decreases from a value of 2.2 x 10(9) M(-1) s(-1) (E degrees = 1.62 V) to 5.8 x 10(8) M(-1) s(-1) (E degrees = 1.13 V) and eventually to 5 x 10(7) M(-1) s(-1) (E degrees = 0.91 V). The implications of these results, including the possibility that the redox cycling of the (*)NO2/NO2(-) species can be involved in the further oxidative damage of 8-oxo-dG in DNA in cellular environments, are discussed.

DNA Damage↗

Comparison of two administration techniques of inhaled nitric oxide on nitrogen dioxide production.

The purpose of this study was to verify whether, compared with the introduction of the NO-N2 mixture at the air inlet of the ventilator (classical method), a direct injection of NO-N2 into the inspiratory line of the ventilator circuit with a new injection device (new method), would reduce NO2 formation by reducing contact time between O2 and NO. The effect of two FIO2(0.21 and 0.90) and NO concentrations on NO2 production was determined. In the classical method, NO and O2 were mixed with an air/oxygen blender before the gas mixture entered the ventilator. In the new method, NO was injected directly into the respiratory line with the injection system. Nitric oxide and nitrogen dioxide gases were measured using a chemiluminescence analyzer. For a FI02 of 0.90 and 90 ppm of NO2, the amount of NO2 produced was decreased from 8.9 +/- 0.8 ppm (mean +/- SD) with the classical injection system to 4.4 +/- 0.2 ppm with the new injection system (P = 0.0039, Mann-Whitney test), and NO2 production was decreased from 4.5 +/-0.2 ppm to 2.1 +/- 0.4 ppm (P = 0.02) at 60 ppm of NO. However, at a FIO2, no difference was found in the amount of NO2 produced. We conclude that, compared with the classical method of NO administration, the new NO injection system reduces considerably the concentration of inhaled NO2 when a high FIO2 and a high concentration of NO are used.

Administration, Inhalation↗

Toxicity of nitrogen dioxide: an introduction.

Many questions, needed to advance our understanding of the mechanism of injury from high-level NO2, remain unanswered to date. This is partly due to the limited interest in the toxicity of high-level exposures, and partly due to the public pressure and interest to study the effects of low- (environmental) levels. However, the effects of exposure to high-level NO2 are of great interest to the military since high levels of NO2 may be found in combat situations. It is also important to the civilian section in occupational settings where accidents may occur as in silo filler accidents. To fill this gap in knowledge, the Department of Respiratory Research, Division of Medicine at Walter Reed Army Institute of Research took the initiative and convened a panel of experts in a symposium to discuss in depth the effects of exposure to high-level nitrogen dioxide. The symposium goals were to address the issues beginning from the chemistry of NO2 molecule, to the dosimetry of its uptake (isolated lung), to the biological effects of exposure in vivo in small animals (rats), large animals (sheep), and finally in the most relevant species, humans.

Animals↗

Ambient nitrogen dioxide and distance from a major highway.

The primary objective of this pilot study was to measure the variation of ambient nitrogen dioxide (NO(2)) concentration with increasing distance from a major highway in Montréal, Canada, in order to assess the validity of distance from the roadways as a surrogate for exposure to traffic-related air pollution in epidemiologic studies. A total of 31 two-sided Ogawa passive samplers (using triethanolamine-impregnated filters as an absorbent) were installed for 7 days in groups of two or three along an axis perpendicular to a major highway where traffic density exceeds 100000 vehicles/day. Distances ranged from 0 to 1310 m from the highway. Concentrations of NO(2) ranged from 11.9 to 29.3 ppb, and decreased significantly with increasing logarithmic distance from the highway (P<0.0001). Concentrations of NO(2) were also significantly lower upwind than downwind relative to the highway (P=0.0012). These findings indicate that distance from highways may be a valid surrogate for traffic-related air pollution.

Journal Article↗

Personal exposure to nitrogen dioxide (NO2) and the severity of virus-induced asthma in children.

BACKGROUND: A link between exposure to the air pollutant nitrogen dioxide (NO2) and respiratory disease has been suggested. Viral infections are the major cause of asthma exacerbations. We aimed to assess whether there is a relation between NO2 exposure and the severity of asthma exacerbations caused by proven respiratory viral infections in children. METHODS: A cohort of 114 asthmatic children aged between 8 and 11 years recorded daily upper and lower respiratory-tract symptoms, peak expiratory flow (PEF), and measured personal NO2 exposures every week for up to 13 months. We took nasal aspirates during reported episodes of upper respiratory-tract illness and tested for infection by common respiratory viruses and atypical bacteria with RT-PCR assays. We used generalised estimating equations to assess the relation between low (<7.5 microg/m3), medium (7.5-14 microg/m3 ), and high (>14 microg/m3) tertiles of NO2 exposure in the week before or after upper respiratory-tract infection and the severity of asthma exacerbation in the week after the start of an infection. FINDINGS: One or more viruses were detected in 78% of reported infection episodes, and the medians of NO2 exposure were 5 (IQR 3.6-6.3), 10 (8.7-12.0), and 21 microg/m3 (16.8-42.9) for low, medium, and high tertiles, respectively. There were significant increases in the severity of lower respiratory-tract symptom scores across the three tertiles (0.6 for all viruses [p=0.05] and >2 for respiratory syncytial virus [p=0.01]) and a reduction in PEF of more than 12 L/min for picornavirus (p=0.04) for high compared with low NO2 exposure before the start of the virus-induced exacerbation. INTERPRETATION: High exposure to NO2 in the week before the start of a respiratory viral infection, and at levels within current air quality standards, is associated with an increase in the severity of a resulting asthma exacerbation.

Air Pollutants↗