Abstract  Background. Concerns regarding the health impact of urban air pollution on asthmatic children are pronounced along the US-Mexico border due to rapid population growth near busy border highways and roads. Objectives. We conducted the first binational study of the impacts of air pollution on asthmatic children in Ciudad Juarez, Mexico and El Paso, TX, and compared different exposure metrics to assess acute respiratory response. Methods. We recruited 58 asthmatic children from two schools in Ciudad Juarez and two schools in El Paso. A marker of airway inflammation (exhaled nitric oxide [eNO]), respiratory symptoms surveys, and pollutant measurements (indoor and outdoor 48-hr size-fractionated particulate matter, 48-hr black carbon, and 96-hr nitrogen dioxide) were collected at each school for 16 weeks. We examined associations between the pollutants and respiratory response using generalized linear mixed models. Results. We observed small but consistent associations between eNO and numerous pollutant metrics, with estimated increases in eNO ranging from 1 to 3% per interquartile range increase in pollutant concentrations. Effect estimates from models using school-based concentrations were generally stronger than corresponding estimates based on concentrations from ambient air monitors. Particles, both traffic- and non-traffic-related, were typically more robust predictors of eNO than nitrogen dioxide, for which associations were highly sensitive to model specification. Associations differed significantly across the four school-based cohorts, consistent with heterogeneity in pollutant concentrations and cohort characteristics. Models examining respiratory symptoms were consistent with the null. Conclusions. The results indicate adverse effects of air pollution on the subclinical respiratory health of asthmatic children in this region, and provide preliminary support for the use of air pollution monitors close to schools to track exposure and potential health risk in this population.

Abstract  The scientific literature suggests that ambient levels of nitrogen dioxide increase susceptibility to respiratory infections. However, this association has not been conclusively demonstrated. The epidemiologic data regarding this relationship are inconclusive because these studies have used parameters of "acute respiratory illness" that are not necessarily related to infectious episodes. Previous animal studies have used either mortality after bacterial infection with virulent bacteria or decreased rate of intrapulmonary killing of bacteria with low virulence. Studies using appropriate bacterial and viral challenge organisms, with morbidity as an endpoint, provide a better basis for extrapolation to humans. The investigations in animals suggest a relationship between nitrogen dioxide and increased susceptibility to respiratory infection, but studies in which functional parameters of host resistance to such infections have been used are few. The aim of this work was to determine the threshold level of acute nitrogen dioxide exposure that would induce increased susceptibility to, and increased severity of, viral and bacterial infections. Physiologic parameters of host resistance to respiratory infections were used as endpoints. A composite picture was developed of dose-response relationships between nitrogen dioxide and the impairment of a spectrum of defense parameters in the murine respiratory tract against viral and bacterial challenges. The salient findings of this study are as follows: (1) the intrapulmonary killing of Staphylococcus aureus was impaired at 5 ppm of nitrogen dioxide; (2) this effect was found at 2.5 ppm or less when nitrogen dioxide exposure was superimposed on lungs predisposed to lowered resistance through immunosuppression with corticosteroids; (3) the adverse effect of nitrogen dioxide occurred at lower concentrations when exposure followed bacterial challenge; and (4) during the course of murine Sendai virus infection, exposure to nitrogen dioxide for four hours per day did not alter the infection in the lungs, but rather it enhanced lung pathology. The implications of these findings are that the antibacterial defenses of the lungs are susceptible to the inhibiting effects of short acute exposures of lower concentrations of nitrogen dioxide when the lungs are predisposed by bacteria present or, even more so, by immunosuppression. The alveolar macrophage phagocytic system is the defense component of the lungs that is most susceptible to the adverse effects of nitrogen dioxide. The finding that nitrogen dioxide increases virus-associated lung damage suggests that the increased severity of the disease process results from the proliferation of the virus to high titers, rather than from alterations of the infective process.

Abstract  While the pulmonary toxicity of NO2 is clearly established, the mechanism by which it is removed from inspired air is poorly understood. Uptake is most likely dependent on chemical reaction since, despite limited per se gaseous NO2 aqueous solubility, uptake proceeds rapidly without ready saturation. We utilized an isolated perfused rat lung model to characterize the effect of dose rate on uptake and transformation. Dose rate was varied via alterations in inspired concentration, tidal volume, and ventilation frequency. Dose equaled the total amount inhaled, uptake the amount removed from inspired air, and transformation the amount of NO2- that accumulated in the perfusate. We found a linear proportionality between both inspired concentration (4-20 ppm) and minute ventilation (45-130 ml/min) and uptake. Fractional uptakes (65%) were similar for all groups. Regression of combined concentration and minute ventilation data yielded a linear relationship between total inspired dose (25-330 micrograms NO2) and both uptake (r2 = 0.99) and transformation (r2 = 0.98). Testing of the functional descriptions resulted in measured uptakes and transformation that fell within a few percentage points of those predicted. We conclude that in acutely exposed isolated lungs (1) NO2 uptake is dependent on total inhaled dose rather than on the variables which serve to affect dose rate, (2) transformation is related to both total inspired dose and uptake, and (3) uptake is more accurately described using a regression equation rather than by use of fractional uptakes.

Abstract  A murine infectivity model was used to test the effect of exposure to atmospheres containing 290 +/- 50 microgram/m3 of respirable sized ferrous sulfate (FeSO4) particles (0.4 micron mass median aerodynamic diameter) and 1.0 ppm nitrogen dioxide (NO2) prior to infection with aerosols of Staphylococcus aureus or group C streptococci. Exposure to these combined pollutants for 24 or 48 hr did not impair pulmonary inactivation of S. aureus. Exposure to FeSO4 or NO2 for 48 hr, or to both pollutants for 24 or 48 hr, resulted in significant decreases in inactivation of inhaled group C streptococci. Mortality studies following pollutant exposure demonstrated earlier, but not an increased number of deaths. These studies demonstrate the importance of the test organism in assessing air quality standards with the infectivity model and enhanced toxicity and prolongation of exposure to relatively low levels of submicron-size particles of FeSO4 and NO2.

Abstract  It has been reported (J. Clin. Invest. 57: 301-307, 1976) that inhalation of nitrogen dioxide (NO2) will enhance the bronchial reactivity of asthmatics. This study was designed to evaluate the respiratory effect of a 1-h exposure of normal subjects and of atopic asthmatics to 0.1 parts per million (ppm) NO2. Fifteen normal and 15 asthmatic subjects were exposed to air and to NO2 in a randomized double-blind crossover design. Exposure to either atmosphere was bracketed by bronchial inhalation challenge using aerosolized metacholine chloride solutions. Plethysmographic measurements of specific airway resistance (sRaw) and the forced random noise impedance spectrum (5-30 Hz) were obtained immediately after each methacholine dose. Following acute exposure to NO2, there was a slight but not significant increase in mean base-line sRaw in both normals and asthmatics. The overall base-line resistive properties of the respiratory system determined by forced random noise excitation were not significantly affected by NO2 inhalation either. Finally, there was no change in bronchial response to methacholine challenge in either group. These findings indicate that 0.1 ppm NO2 exposure for 1 h without exercise had no demonstrable airways effects in either young atopic asthmatics with mild disease or young normal subjects.

Abstract  The acute influence of NO2 on mechanics of breathing and respiratory gas exchange was investigated in a total of 111 subjects, aged 25 to 74 years, with chronic nonspecific lung disease (CNSLD). They breathed NO2-air mixtures containing 0.5 to 8.0 ppm NO2 for up to 15 to 60 min. Additionally in nine subjects the protective action of atropine, meclastine, and orciprenaline was investigated. While the alveolar PO2 remained constant during inhalation of 5 and 4 ppm NO2, a significant decrease of the arterial PO2 and a corresponding increase of the arterial to alveolar PO2 gradients occurred. Inhalation of 2 ppm NO2 had not such an effect. Inhalation of NO2 at concentrations down to 1.5 ppm resulted in a significant increase of airway resistance. Lower concentrations had no significant effect. Prolongation of the exposure period from 15 to 60 min at a NO2 concentration of 5 ppm did not result in a more pronounced disturbance of the respiratory gas exchange for oxygen beyond the extent observed after exposure to 5 ppm NO2 for 15 min. Meclastine, in comparison with orciprenaline and atropine, showed a pronounced protective effect on the negative impact of NO2 on respiratory gas exchange and airway resistance. It is concluded that NO2 may act by release of histamine, causing a bronchiolar, alveolar, and interstitial edema, thus differing from irritant air pollutants like SO2, where reflex bronchoconstriction causes in some bronchitics dramatic increases of airway resistance at similar low concentrations.

Abstract  The association between particulate air pollution and asthma medication use and symptoms was assessed in a panel study of 53 adult asthmatics in Erfurt, Germany in winter 1996/1997. Number concentrations of ultrafine particles, 0.01-0.1 microm in diameter (NC0.01-0.1), mean 17,300.cm-3, and mass concentrations of fine particles 0.01-2.5 microm in diameter (MC0.01-2.5), mean 30.3 microg.m-3, were measured concurrently. They were not highly correlated (r=0.45). The associations between ambient particle concentrations and the prevalence of inhaled 'beta'2-agonist, corticosteroid use and asthma symptoms, were analysed separately with logistic regression models, adjusting for trend, temperature, weekend, holidays, and first order autocorrelation of the error. Cumulative exposures over 14 days of ultrafine and fine particles were associated with corticosteroid use. 'Beta'2-agonist use was associated with 5-day mean NC0.01-0.1 and MC0.01-2.5. The prevalence of asthma symptoms was associated with ambient particle concentrations. The results suggest that reported asthma medication use and symptoms increase in association with particulate air pollution and gaseous pollutants such as nitrogen dioxide.

Abstract  Adult male volunteers were exposed to nitrogen dioxide (NO2) at 1.0 ppm in purified air under conditions simulating ambient photochemical smog exposures (2-hr exposure with intermittent light exercise at 31 degrees C and 35% relative humidity). Sham exposures to purified air alone served as controls. Exposure effects were assessed by pulmonary physiological tests and by a standardized clinical evaluation. No statistically physiological changes attributable to NO2 exposure were found except for a marginal loss in forced vital capacity after exposure on two successive days (1.5% mean decrease, P less than .05). Reported respiratory and other symptoms were slightly increased with exposure as compared to control, but the change was not significant. Short-term toxicity of NO2 at peak ambient concentrations appears to be substantially less than that of ozone in healthy people, but adverse NO2 effects in diseased people or in long-term exposures cannot be ruled out at present.

Abstract  A study was carried out to determine the interrelationship between the inhalation of nitrogen dioxide (0.4 +/- 0.50 ppm), lung metastases development from circulating cancer cells, and death rate from such metastases. C57 BL/6J mice were used in these experiments. Animals were divided into control and NO2-exposed groups, and were exposed to filtered air and 0.4 ppm of NO2, respectively. Following 12 weeks of exposure, all animals were infused intravenously with syngeneic, viable B16 melanoma cells. The results indicate that a subpopulation of NO2-exposed animals showed a significant increase in mortality rate during the early part of the experiment. The interpretation is that animals especially sensitive to the NO2 insult developed extensive metastases at an early stage. The question raised is whether or not the progression of human cancer is influenced by the inhalation of noxious pollutants in the ambient atmosphere.

Abstract  The effects of NO2 on immune reponses of mice were investigated. Mice were exposed to various concentrations of NO2 in inhalation chambers. After exposure the following parameters were measured: phagocytosis of polystyrene beads by both peritoneal and alveolar macrophages, production of antibody-forming cells from mice immunized with sheep erythrocytes, lymphocyte blastogenesis of splenic cells, and susceptibility to influenza virus. The production of antibody-forming cells was reduced in mice that were exposed to 5 ppm NO2. The serum antibody titers, phagocytosis, and other immune parameters measured were not affected. Exposure to NO2 did not affect mortality to influenza virus. These data indicate that certain immune parameters were altered by exposure to NO2 however, NO2 does not appear to be a major immunosuppressive factor at the concentrations tested.

Abstract  As part of the EU-funded SAVIAH project, a regression-based methodology for mapping traffic-related air pollution was developed within a GIS environment. Mapping was carried out for NO2 in Amsterdam, Huddersfield and Prague. In each centre, surveys of NO2, as a marker for traffic-related pollution, were conducted using passive diffusion tubes, exposed for four 2-week periods. A GIS was also established, containing data on monitored air pollution levels, road network, traffic volume, land cover, altitude and other, locally determined, features. Data from 80 of the monitoring sites were then used to construct a regression equation, on the basis of predictor environmental variables, and the resulting equation used to map air pollution across the study area. The accuracy of the map was then assessed by comparing predicted pollution levels with monitored levels at a range of independent reference sites. Results showed that the map produced extremely good predictions of monitored pollution levels, both for individual surveys and for the mean annual concentration, with r2 ~ 0À79-0À87 across 8-10 reference points, though the accuracy of predictions for individual survey periods was more variable. In Huddersfield and Amsterdam, further monitoring also showed that the pollution map provided reliable estimates of NO2 concentrations in the following year (r2~0À59-0À86 for n=20).

Abstract  Evolution has resorted to nitric oxide (NO), a tiny, reactive radical gas, to mediate both servoregulatory and cytotoxic functions. This article reviews how different forms of nitric oxide synthase help confer specificity and diversity on the effects of this remarkable signaling molecule.

Abstract  Swiss Webster mice were exposed to either 4.8 ppm (9024 microgram/m3) nitrogen dioxide (NO2), 0.45 ppm (882 microgram/m3) ozone (O3), or their combination intermittently (8 hr daily) for 7 days, and the effects were studied in the lung by a series of physical and biochemical parameters, including lung weight, DNA and protein contents, oxygen consumption, sulfhydryl metabolism, and activities of NADPH generating enzymes. The results show that exposure to NO2 caused relatively smaller changes than O3, and that the effect of each gas alone under the conditions of exposure was not significant for most of the parameters tested. However, when the two gases were combined, the exposure caused changes that were greater and significant. Statistical analysis of the data shows that the effects of combined exposure were more than additive, i.e., they might be synergistic. The observations suggest that intermittent exposure to NO2 or O3 alone at the concentration used may not cause significant alterations in lung metabolism, but when the two gases are combined the alterations may become significant.

Abstract  U.S. Environmental Protection Agency. This paper discusses the legal and scientific reasons for separating personal exposure to PM into ambient and nonambient components. It then demonstrates by several examples how well-established models and data typically obtained in exposure field studies can be used to estimate both individual and community average expo-sure to ambient-generated PM (ambient PM outdoors plus ambient PM that has infiltrated indoors), indoor-generated PM, and personal activity PM. Ambient concentrations are not highly correlated with personal exposure to nonambient PM or total PM but are highly correlated with personal exposure to ambient-generated PM. Therefore, ambient concentrations may be used in epidemiology as an appropriate surrogate for personal exposure to ambient-generated PM. Suggestions are offered as to how exposure to ambient-generated PM may be obtained and used in epidemiology and risk assessment. Implications: Exposure analysts historically have sought to determine the total personal exposure to PM of all types in all environments. The lack of correlation between this parameter and ambient PM concentration has been considered an impediment to epidemiologic studies seeking to find an association between ambient PM concentrations and health outcomes. For community, time-series epidemiology, it is necessary only that the community average personal exposure to ambient-generated PM be correlated with the ambient PM concentration. If everyone spent the same amount of time outside and in each microenvironment each day, and the air exchange rate and any forced-air ventilation that resulted in particle removal was a constant, and PM concentrations were uniform across the community, a high correlation would be expected between the PM concentration measured by a community-based PM monitor and the personal exposure of each individual to ambient-generated PM. Also, a high correla-tion would be expected between ambient concentration and the exposure surrogate of interest in epidemiology, the community average personal exposure to ambient-generated PM. For short-term panel studies, time-series should be determined for all classes of PM. For cohort studies of long-term effects, consideration must be given to the influence of possible variations in exposures to nonambient-generated PM because of differences among cities in time-location patterns (fractions of time spent outdoors), average air exchange rates, and average concentrations of indoor-generated and personal activity PM.

Abstract  Mice were exposed to 0.5 ppm nitrogen dioxide (NO2) for 6, 18, and 24 hours daily. The lung alveoli were expanded in all mice exposed to NO2 from three to 12 months, with the highest degree of involvement at 12 months; thus the number of expanded alveoli appeared to increase with exposure time. The general impression was of early bronchiolar inflammation with reduction of distal airway size and a concomitant expansion of alveoli. The overall lesions appeared to be consistent with the development of early focal emphysema. Examination of the heart, liver, kidney, and spleen did not reveal any unique pathology. Mice exposed to NO2 and challenged with Klebsiella pneumoniae exhibited a marked reduction in functional lung tissue.

Abstract  Mice were exposed to 0.5 ppM NO2 and then challenged with Klebsiella pneumoniae and killed after 14 days. Although NO2 exposure was conducted from 7 days to 12 months, significant differences from control group were noted only after 3 months exposure. Groups with less exposure had higher, but not significantly so, mortality than did controls. Exposure to NO2 for 6, 18, or 24 hr/day increased half-life clearance after 12 months. Only 24 hr/day exposure increased half-life clearance after only 6 months exposure. The effect of NO2 on bacterial clearance half-time was more an arithmetical progression than logarithmic.

Abstract  A preliminary testing of eight guinea pigs for D-2,3-diphosphoglycerate (2, 3DPG) content of red blood cells, half of which had been exposed to continuous 0.36 ppm nitrogen dioxide for one week, showed a significant increase (P < .05)for the exposed animals.

Abstract  The major aspects that must be considered in studies of the health effects of environmental pollutants are: the direct damage due to the exposure, the role of pre-existing disease, and effects of the exposure on the response to secondary stresses. In experimental studies at concentrations of air pollutants found in urban environments frank toxicological responses are rarely observed. However, exposure to a secondary stress, i.e. respiratory challenge with infectious bacteria, can exacerbate the response of the experimental host. Changes in the resistance to respiratory infections provide a highly sensitive experimental animal model system, which is increasingly used in studies of health effects of air pollutants. This model indicates the impairment of the basic defense mechanisms of the respiratory system by the combined exposure to low concentrations of pollutants and the superimposed bacterial infection. Changes in the resistance to respiratory infections were studied in various species of laboratory animals. S. pyogenes and K. pneumoniae are the bacteria of choice to induce the pulmonary infection. Included in the studies are short-term single and multiple exposures as well as long-term exposures to gaseous pollutants such as O3 and NO2 and particulate pollutants such as sulfates and nitrates. Changes in the resistance are measured as excess mortalities and reduced survival time as compared to those in infected animals not exposed to the pollutants. Other parameters measured ranged from changes in the immune response to changes in retention rates of bacteria in lungs.

Abstract  Many epidemiological studies have shown positive short-term associations between health and current levels of outdoor air pollution. The aim of this study was to investigate the association between air pollution and the number of visits to accident and emergency (A&E) departments in London for respiratory complaints. A&E visits include the less severe cases of acute respiratory disease and are unrestricted by bed availability. Daily counts of visits to 12 London A&E departments for asthma, other respiratory complaints, and both combined for a number of age groups were constructed from manual registers of visits for the period 1992-1994. A Poisson regression allowing for seasonal patterns, meteorological conditions and influenza epidemics was used to assess the associations between the number of visits and six pollutants: nitrogen dioxide, ozone, sulphur dioxide, carbon monoxide, and particles measured as black smoke (BS) and particles with a median aerodynamic diameter of <10 Ám (PM10). After making an allowance for the multiplicity of tests, there remained strong associations between visits for all respiratory complaints and increases in SO2: a 2.8% (95% confidence interval (CI) 0.7-4.9) increase in the number of visits for a 18 Ág x (-3) increase (10th-90th percentile range) and a 3.0% (95% CI 0.8-5.2) increase for a 31 Ág x m(-3) increase in PM10. There were also significant associations between visits for asthma and SO2, NO2 and PM10. No significant associations between O3 and any of the respiratory complaints investigated were found. Because of the strong correlation between pollutants, it was difficult to identify a single pollutant responsible for the associations found in the analyses. This study suggests that the levels of air pollution currently experienced in London are linked to short-term increases in the number of people visiting accident and emergency departments with respiratory complaints.

Abstract  Current pollution limits indicating potential harm to human health caused by nitrogen dioxide have prompted a variety of studies on the cytotoxicity and genotoxicity of nitrogen dioxide (NO₂) in vitro. The present study focuses on toxic effects of NO₂ at the WHO defined 1-h limit value of 200 μg NO₂/m(3) air, equivalent to 0.1 ppm NO₂. Nasal epithelial mucosa cells of 10 patients were cultured as an air-liquid interface and exposed to 0.1 ppm NO₂ for 0.5 h, 1 h, 2 h and 3 h and synthetic air as negative control. After exposure, analysis of genotoxicity was performed by the alkaline single cell microgel electrophoresis (comet) assay and by the micronucleus test. Depression of proliferation and cytotoxic effects were checked by the micronucleus assay and the trypan blue exclusion assay. The experiments demonstrated significant DNA fragmentation even at the shortest exposure duration of half an hour in the comet assay. The amount of DNA fragmentation significantly increased with extended NO₂ exposure durations. The amount of DNA fragmentation increased with extended exposure durations to synthetic air at a significantly lower level as compared to NO₂ exposure. Micronucleus inductions were seen only at the longest exposure duration of 3h. There were no changes in proliferation seen in the micronucleus assay under any experimental setup. Moreover, no signs of necrosis, apoptosis or changes in viability were detected. Data demonstrate genotoxicity of NO₂ at concentrations found in the urban atmosphere during short exposure durations. DNA alterations in the micronucleus assay at an exposure time of 3h indicate a significant DNA alteration possibly being hazardous to humans.

Abstract  Nitrogen dioxide and carbonate radical anion have received sporadic attention thus far from biological investigators. However, accumulating data on the biochemical reactions of nitric oxide and its derived oxidants suggest that these radicals may play a role in various pathophysiological processes. These potential roles are also indicated by recent studies on the high efficiency of urate and nitroxides in protecting cells and whole animals against the injury associated with conditions of excessive nitric oxide production. The high protective effects of these antioxidants are incompletely defined at the mechanistic level but some of them can be explained by their efficiency in scavenging peroxynitrite-derived radicals, particularly nitrogen dioxide and carbonate radical anion. In this review, we provide a framework for this hypothesis and discuss the potential sources and properties of these radicals that are likely to become increasingly recognized as important mediators of biological processes.

Abstract  The purpose of the present study was to examine the risk of stillbirth associated with ambient air pollution during pregnancy. Using live birth and fetal death data from New Jersey from 1998 to 2004, the authors assigned daily concentrations of air pollution to each birth or fetal death. Generalized estimating equation models were used to estimate the relative odds of stillbirth associated with interquartile range increases in mean air pollutant concentrations in the first, second, and third trimesters and throughout the entire pregnancy. The relative odds of stillbirth were significantly increased with each 10-ppb increase in mean nitrogen dioxide concentration in the first trimester (odds ratio (OR) = 1.16, 95% confidence interval (CI): 1.03, 1.31), each 3-ppb increase in mean sulfur dioxide concentration in the first (OR = 1.13, 95% CI: 1.01, 1.28) and third (OR = 1.26, 95% CI: 1.03, 1.37) trimesters, and each 0.4-ppm increase in mean carbon monoxide concentration in the second (OR = 1.14, 95% CI: 1.01, 1.28) and third (OR = 1.14, 95% CI: 1.06, 1.24) trimesters. Although ambient air pollution during pregnancy appeared to increase the relative odds of stillbirth, further studies are needed to confirm these findings and examine mechanistic explanations.

Abstract  The authors conducted a 2-year follow-up of 40 cardiovascular disease patients (mean age = 65.6 years (standard deviation, 5.8)) who underwent repeated measurements of cardiovascular response before and during the 2008 Beijing Olympics (Beijing, China), when air pollution was strictly controlled. Ambient levels of particulate matter with an aerodynamic diameter less than 2.5 µm (PM(2.5)), black carbon, nitrogen dioxide, sulfur dioxide, ozone, and carbon monoxide were measured continuously, with validation of concurrent real-time measurements of personal exposure to PM(2.5) and carbon monoxide. Linear mixed-effects models were used with adjustment for individual risk factors, time-varying factors, and meteorologic effects. Significant heart rate variability reduction and blood pressure elevation were observed in association with exposure to air pollution. Specifically, interquartile-range increases of 51.8 µg/m(3), 2.02 µg/m(3), and 13.7 ppb in prior 4-hour exposure to PM(2.5), black carbon, and nitrogen dioxide were associated with significant reductions in the standard deviation of the normal-to-normal intervals of 4.2% (95% confidence interval (CI): 1.9, 6.4), 4.2% (95% CI: 1.8, 6.6), and 3.9% (95% CI: 2.2, 5.7), respectively. Greater heart rate variability declines were observed among subjects with C-reactive protein values above the 90th percentile, subjects with a body mass index greater than 25, and females. The authors conclude that autonomic and vascular dysfunction may be one of the mechanisms through which air pollution exposure can increase cardiovascular disease risk, especially among persons with systemic inflammation and overweight.