Abstract  RATIONALE: Several studies have linked long-term exposure to particulate air pollution with increased cardiopulmonary mortality; only two have also examined incident circulatory disease. OBJECTIVES: To examine associations of individualized long-term exposures to particulate and gaseous air pollution with incident myocardial infarction (MI) and stroke, as well as all-cause and cause-specific mortality. METHODS: We estimated long-term residential air pollution exposure for over 100,000 participants in the California Teachers Study, a prospective cohort of female public school professionals. We linked geocoded residential addresses with inverse distance-weighted monthly pollutant surfaces for two measures of particulate matter and for several gaseous pollutants. We examined associations between exposure to these pollutants and risks of incident MI and stroke, and of all-cause and cause-specific mortality, using Cox proportional hazards models. MEASUREMENTS AND MAIN RESULTS: We found elevated hazard ratios linking long-term exposure to fine particulate matter (PM2.5, scaled to an increment of 10 µg/m3) with mortality from ischemic heart disease (IHD) (1.20, 95% C.I. 1.02-1.41) and, particularly among post-menopausal women, incident stroke (1.19, 95% C.I. 1.02-1.38). Long-term exposure to particulate matter less than 10 µm aerodynamic diameter (PM10) was associated with elevated risks for IHD mortality (1.06, 95% C.I. 0.99-1.14) and incident stroke 1.06 (95% CI: 1.00-1.13), while nitrogen oxides were associated with elevated risks for cardiovascular as well as IHD mortality. CONCLUSIONS: Long-term exposures to PM2.5 and PM10 were associated with increased risks of incident stroke and death from IHD; exposures to nitrogen oxides were associated with all cardiovascular as well as IHD mortality.

Abstract  Background: A growing body of research suggests that prenatal exposure to air pollution may be harmful to fetal development. We assessed the association between exposure to air pollution during pregnancy and anthropometric measures at birth in four areas within the Spanish Children's Health and Environment (INMA) mother and child cohort study. Methods: Exposure to ambient nitrogen dioxide (NO2) and benzene was estimated for the residence of each woman (n = 2,337) for each trimester and for the entire pregnancy. Outcomes included birth weight, length, and head circumference. The association between residential outdoor air pollution exposure and birth outcomes was assessed with linear regression models controlled for potential confounders. We also performed sensitivity analyses for the subset of women who spent more time at home during pregnancy. Finally, we performed a combined analysis with meta-analysis techniques. Results: In the combined analysis, an increase of 10 µg/m3 in NO2 exposure during pregnancy was associated with a decrease in birth length of -0.9 mm [95% confidence interval (CI), -1.8 to -0.1 mm]. For the subset of women who spent ≥ 15 hr/day at home, the association was stronger (-0.16 mm; 95% CI, -0.27 to -0.04). For this same subset of women, a reduction of 22 g in birth weight was associated with each 10-µg/m3 increase in NO2 exposure in the second trimester (95% CI, -45.3 to 1.9). We observed no significant relationship between benzene levels and birth outcomes. Conclusions: NO2 exposure was associated with reductions in both length and weight at birth. This association was clearer for the subset of women who spent more time at home.

Abstract  This work explored the association between nitrogen dioxide (NO(2)) and PM(2.5) components with changes in cardiovascular function in an adult non-smoking cohort. The cohort consisted of 65 volunteers participating in the US EPA's Detroit Exposure and Aerosol Research Study (DEARS) and a University of Michigan cardiovascular sub-study. Systolic and diastolic blood pressure (SBP, DBP), heart rate (HR), brachial artery diameter (BAD), brachial artery flow-mediated dilatation (FMD) and nitroglycerin-mediated arterial dilatation (NMD) were collected by in-home examinations. A maximum of 336 daily environmental and health effect observations were obtained. Daily potassium air concentrations were associated with significant decreases in DBP (-0.0447 mmHg/ng/m(3) ± 0.0132, p = 0.0016, lag day 0) among participants compliant with the personal monitoring protocol. Personal NO(2) exposures resulted in significant changes in BAD (e.g., 0.0041 mm/ppb ± 0.0019, p = 0.0353, lag day 1) and FMD (0.0612 ± 0.0235, p = 0.0103, lag day 0) among other findings.

Abstract  BACKGROUND: Epidemiologic studies have demonstrated that exposure to road traffic is associated with adverse cardiovascular outcomes. OBJECTIVES: To identify specific traffic-related air pollutants that are associated with the risk of coronary heart disease (CHD) morbidity and mortality to support evidence-based environmental policy making. METHODS: This population-based cohort study included a 5-year exposure period and a 4-year follow-up period. All residents aged 45-85 years who resided in Metropolitan Vancouver during the exposure period and without known CHD at baseline were included in this study (n = 452,735). Individual exposures to traffic-related air pollutants including black carbon, fine particles (aerodynamic diameter ≤2.5 µm; PM2.5), NO2, and NO were estimated at subjects' residences using land use regression models and integrating changes in residences during the exposure period. CHD hospitalizations and deaths during the follow-up period were identified from provincial hospitalization and death registration records. RESULTS: An interquartile range elevation in the average concentration of black carbon (0.94×10-5/m filter absorbance, equivalent to approximately 0.75 µg/m3 elemental carbon) was associated with a 3% increase in CHD hospitalization (95% confidence interval, 1-5%) and a 6% increase in CHD mortality (3-9%) after adjustment for age, sex, preexisting comorbidity, neighborhood socioeconomic status, and co-pollutants (PM2.5 and NO2). There were clear linear exposure-response relationships between black carbon and coronary events. CONCLUSIONS: Long-term exposure to traffic-related fine particulate air pollution, indicated by black carbon, may partly explain the observed associations between exposure to road traffic and adverse cardiovascular outcomes.

Abstract  The authors investigated the association of early-life exposure to indoor air pollution with neuropsychological development in preschoolers and assessed whether this association differs by glutathione-S-transferase gene (GSTP1) polymorphisms. A prospective, population-based birth cohort was set up in Menorca, Spain, in 1997–1999 (n = 482). Children were assessed for cognitive functioning (McCarthy Scales of Children's Abilities) and attention-hyperactivity behaviors (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) at age 4 years. During the first 3 months of life, information about gas appliances at home and indoor nitrogen dioxide concentration was collected at each participant's home (n = 398, 83%). Genotyping was conducted for the GSTP1 coding variant Ile105Val. Use of gas appliances was inversely associated with cognitive outcomes (β coefficient for general cognition = –5.10, 95% confidence interval (CI): –9.92, –0.28; odds ratio for inattention symptoms = 3.59, 95% CI: 1.14, 11.33), independent of social class and other confounders. Nitrogen dioxide concentrations were associated with cognitive function (a decrease of 0.27 point per 1 ppb, 95% CI: –0.48, –0.07) and inattention symptoms (odds ratio = 1.06, 95% CI: 1.01, 1.12). The deleterious effect of indoor pollution from gas appliances on neuropsychological outcomes was stronger in children with the GSTP1 Val-105 allele. Early-life exposure to air pollution from indoor gas appliances may be negatively associated with neuropsychological development through the first 4 years of life, particularly among genetically susceptible children.

Abstract  Studies on health effects of air pollutants ideally define exposure through the collection of air samples in the participants' homes. Concentrations derived from these samples are then considered as an estimate for the average concentration of air pollutants in the homes. Conclusions drawn from such studies therefore depend very much on the validity of the measured air pollution concentrations. In this paper we analysed repeated BTEX and NO(2) measurements with a time period of several months lying between the two conducted home visits. We investigated the variability of their concentrations over time by determining correlation coefficients and calculating within- and between-home variances. Our population consisted of 631 homes of participants from two cohort studies within the framework of the German study on Indoor Factors and Genetics in Asthma. Air pollutants were measured using passive samplers both indoors and outdoors. The measured BTEX concentrations were poorly correlated, with Pearson's correlation coefficient r ranging from -0.19 to 0.27. Additionally, a considerable seasonal effect could be observed. A higher correlation was found for the NO(2) concentrations with r ranging between 0.24 and 0.55. For the BTEX, the between-home variance was bigger than the within-home variance, for NO(2) both variances were of about the same order. Our results indicate that in a setting of moderate climate like in Germany, the variability of BTEX and NO(2) concentrations over time is high and a single measurement is a poor surrogate for the long-term concentrations of these air pollutants.

Abstract  A simple method is suggested for calculating the time it takes ozone to traverse a biological region, such as a bilayer or a cell, and comparing this time to the halflife of ozone within that region. For a bilayer the calculations suggest that most of the ozone reacts within a bilayer, but a fraction may exit unreacted. For the lung lining fluid layer (LLFL), the calculations show that ozone cannot cross this layer without reacting where the LLFL is thicker than about 0.1 ?m. However, since the LLFL varies from 20 to 0.1 ?m in thickness with patchy areas in the lower airways that are virtually uncovered, some ozone could reach underlying cells, particularly in the lower airways. For cells (such as alveolar type I epithelial cells), the calculations show that ozone reacts within the cell too rapidly to pass through and exit unreacted from the other side. These calculations have implications for ozone toxicity. In vivo, the toxicity of ozone is suggested to result from the effects of a cascade of products that are produced in the reactions of ozone with primary target molecules that lie close to the air/tissue boundary. These products, which have a lower reactivity and longer lifetime than ozone itself, can transmit the effects of ozone beyond the air/tissue interface. The variation in thickness of the LLFL may modulate the species causing damage to the cells below it. In the lower airways, where the LLFL is thin and patchy, more cellular damage may be caused by ozone itself; in the upper airways where the LLFL is thicker, secondary products (such as aldehydes and hydrogen peroxide) may cause most of the damage. In vitro studies must be designed in an attempt to model the lung physiology. For example, if cells in culture are studied, and if the cells are exposed to ozone while under a supporting medium solution that contains ozone-reactive substances, then the cells may be damaged by products that are formed in the reactions of ozone with the cell medium rather than by ozone itself.

Abstract  Antioxidants located in the lining layer of the respiratory tract may be important in determining sensitivity of lung tissues to inhaled pollutants. This study addressed species differences in the amounts of ascorbic acid (AH2), glutathione (GSH), uric acid (UA), and alpha-tocopherol (AT) in bronchoalveolar lavage (BAL) fluid and cells of humans, guinea pigs, and rats. Protein and lipid phosphorus (lipid P) were used as normalizing factors. More than 90% of the lavageable AH2, UA, GSH, protein, and lipid P was present in the extracellular fraction of BAL in rats and guinea pigs, while over 95% of the lavageable AT was located in the BAL cells. BAL fluid AH2/protein in rats was 7- to 9-fold higher than in humans and guinea pigs. However, human BAL fluid had 2- to 8-fold higher UA/protein, GSH/protein, and AT/protein ratios than rats and guinea pigs. In BAL cells, rats had higher AH2/protein and AT/protein ratios than guinea pigs and humans, and both rats and guinea pigs had higher GSH and AT/protein ratios than humans. Individual variability among humans in the BAL fluid and cellular antioxidants was generally greater than in the laboratory animals. These data demonstrate that some large species differences exist in BAL fluid and cellular antioxidants which could affect susceptibility to oxidant pollutants.

Abstract  Prolonged intermittent exposure to subanesthetic concentrations of nitrous oxide (N2O) can impair spermatogenesis in the LEW/f mai rat. USP purity standards state that N2O used for medical purposes may contain other oxides of nitrogen such as NO and NO2 as impurities at concentrations up to one part per million (ppm) each. The question thus arises as to whether prolonged exposure to N2O may be associated with adverse health effects from oxides of nitrogen other than N2O, particularly NO2. NO2 has demonstrated biological toxicity at concentrations as low as 0.3 ppm. In this study, rats were exposed to filtered air with and without 1 ppm NO2 for 7 hr/day, 5 days/week, for 21 days. No gross or light microscopy abnormality was found in the testes of NO2-exposed rats. Serum vitamin B12 levels were within normal limits. The findings indicate that NO2 exposure under the test conditions does not in itself impair spermatogenesis or alter B12 levels.

Abstract  Epidemiologic studies support an association among elevated levels of nitrogen dioxide (NO2), increased respiratory symptoms, and alterations in lung function. To determine if low level NO2 inhalation potentiates exercise-induced bronchospasm, 15 asthmatic subjects, defined by airway constriction with cold air provocation, inhaled 0.30 ppm (560 micrograms/m3) NO2 for 30 min. All asthmatics inhaled either air or 0.30 ppm NO2 via a mouthpiece for 20 min at rest followed by 10 min of exercise on a bicycle ergometer at a workload of 300 kpm/min, producing a 3-fold or greater increase in minute ventilation. Our studies showed 72 +/- 2 (SE)% deposition of inhaled NO2 at rest and 87 +/- 1% deposition with exercise (p less than 0.001). Nitrogen dioxide inhalation at rest resulted in no significant change in pulmonary function. Nitrogen dioxide inhalation plus exercise compared to control (air) exposure plus exercise produced significantly greater reductions in FEV (p less than 0.01) and partial expiratory flow rates at 60% of total lung capacity (p less than 0.05). One hour after completion of NO2 exposure and exercise, pulmonary function had returned to baseline values. To determine if NO2 exposure caused increased reactivity to a known bronchoconstrictor, asthmatic subjects inhaled cold air (range: -11 +/- 2 degrees C) at 3 successive rates of isocapnic ventilation. The response to cold air was expressed as the respiratory heat exchange required to reduce the FEV by 10% (PD10RHE). Prior NO2 exposure potentiated the fall in FEV, PD10RHE, and specific airway conductance (p less than 0.05) after isocapnic cold air hyperventilation, compared to the control exposure. These data indicate that 0.30 ppm NO2 inhalation potentiates exercise-induced bronchospasm and airway hyperreactivity after cold air provocation in asthmatic subjects.

Abstract  The nitrogen dioxide (NO2) diurnal cycle found in urban communities usually consists of a low basal concentration upon which are superimposed higher concentration peaks or spikes of short duration. Various components of this environmental exposure mode were examined to assess effects of urban exposure profiles on susceptibility to infectious pulmonary disease. Mice were exposed to NO2 peaks of 4.5 ppm for 1, 3.5, or 7 h, challenged with Streptococcus sp. either immediately or 18 h postexposure, and then observed for mortality. When the streptococcal challenges were immediately after NO2 exposure, the mortality rate was directly related to the length of peak exposure, whether or not a basal exposure was used, and all peak lengths significantly increased mortality. When the challenge was delayed for 18 h after the peak exposure, spiked exposures of 3.5 and 7 h increased mortality to the same degree. If a 1-h peak exposure to 4.5 ppm was superimposed twice daily upon a continuous basal NO2 concentration of 1.5 ppm, there was a suggestive trend toward increased mortality near the end of the second week of exposure when challenge occurred immediately after the morning spike. Studies were also conducted to examine interactions with ozone (O3) and NO2, since urban air typically contains both of these oxidants. Using various combinations of basal and spiked exposure levels of NO2 and O3, synergistic results were obtained for streptococcal-induced mortality.

Abstract  To evaluate the potential toxic and immunologic effects of nitrogen dioxide (NO2) exposure on cells from the lower respiratory tract, normal human alveolar macrophages obtained by bronchoalveolar lavage were exposed to increasing concentrations of NO2 using an in vitro exposure system. Alveolar macrophages exposed to 5, 10, or 15 ppm NO2 for 3 hr showed no difference in cell viability when compared to air-exposed macrophages. In addition, the spontaneous release of neutrophil chemotactic factor (NCF) was not changed by NO2 exposure, nor was there any effect on the ability of alveolar macrophages to release increased amounts of NCF following stimulation with activated zymosan. Furthermore, alveolar macrophages did not spontaneously release interleukin-1 (IL-1) following air or NO2 exposure. When stimulated with influenza virus both air- and NO2-exposed cells released increased amount of IL-1, but was no significant difference in the amount of IL-1 released by air- and NO2-exposed alveolar macrophages. Thus, although NO2 exposure is known to incite an inflammatory response in the lower respiratory tract, using the in vitro exposure system described in this study we were unable to demonstrate a direct toxic effect of NO2 on viability or any NO2-induced change in the release of the immunoregulatory molecules NCF and IL-1.

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  Background: A number of emergency department studies have corroborated findings from mortality and hospital admission studies regarding an association of ambient air pollution and respiratory outcomes. More refined assessment has been limited by study size and available air quality data. Methods: Measurements of 5 pollutants (particulate matter [PM10], ozone, nitrogen dioxide [NO2], carbon monoxide [CO], and sulfur dioxide [SO2]) were available for the entire study period (1 January 1993 to 31 August 2000); detailed measurements of particulate matter were available for 25 months. We obtained data on 4 million emergency department visits from 31 hospitals in Atlanta. Visits for asthma, chronic obstructive pulmonary disease, upper respiratory infection, and pneumonia were assessed in relation to air pollutants using Poisson generalized estimating equations. Results: In single-pollutant models examining 3-day moving averages of pollutants (lags 0, 1, and 2): standard deviation increases of ozone, NO2, CO, and PM10 were associated with 1–3% increases in URI visits; a 2 μg/m3 increase of PM2.5 organic carbon was associated with a 3% increase in pneumonia visits; and standard deviation increases of NO2 and CO were associated with 2–3% increases in chronic obstructive pulmonary disease visits. Positive associations persisted beyond 3 days for several of the outcomes, and over a week for asthma. Conclusions: The results of this study contribute to the evidence of an association of several correlated gaseous and particulate pollutants, including ozone, NO2, CO, PM, and organic carbon, with specific respiratory conditions.

Abstract  A mechanized wheel was constructed for use in evaluating the interaction of exercise and gaseous pollutants such as O3 and NO2. Immediately after the pollutant exposure, both exercised and nonexercised female mice (CD-1) were combined with controls, challenged with an aerosol of viable Streptococcus pyogenes (group C), and then observed over a 15-d period for incidence of mortality. Exposure to O3 at 196 micrograms/m3 (0.1 ppm) or 590 micrograms/m3 (0.3 ppm) while exercising yielded mortality rates that were significantly higher than those observed in the O3 groups that were not exercised. With exposure to NO2 at 5640 micrograms/m3 (3 ppm), exercise produced a significant enhancement in mortality over the other treatment groups. These studies show that exercise can affect the mortality observed in this model system and indicate the need for establishing safe exposure levels of pollutants as a function of the activity level of the exposed population.

Abstract  Previous studies of 2 h of exposure to NO2 at high urban atmospheric levels (i.e., 0.50-1.0 ppm), utilizing light-to-moderate exercise for up to 1 h have failed to demonstrate significant pulmonary dysfunction in healthy humans. To test the hypothesis that heavy sustained exercise would elicit pulmonary dysfunction on exposure to 0.60 ppm NO2 and/or enhance the effects of exposure to 0.30 ppm O3, 40 aerobically trained young adults (20 males and 20 females) completed 1 h of continuous exercise at work rates eliciting a mean minute ventilation of 70 and 50 l/min for the males and females, respectively. Exposures to filtered air, 0.60 ppm NO2, 0.30 ppm O3, and 0.60 ppm NO2 plus 0.30 ppm O3 were randomly delivered via an obligatory mouthpiece inhalation system. Treatment effects were assessed by standard pulmonary function tests and exercise ventilatory and subjective symptoms response. Two-way analysis of variance with repeated measures and post hoc analyses revealed a statistically significant (P less than 0.05) effect of O3 on forced expiratory parameters, specific airway resistance, exercise ventilatory response, and reported subjective symptoms of respiratory discomfort. In contrast, no significant effect of NO2 was observed nor was there any significant interaction of NO2 and O3 in combination. There were no significant differences between male and female responses to gas mixture treatments. It was concluded that inhalation of 0.60 ppm NO2 for 1 h while engaged in heavy sustained exercise does not elicit effects evidenced by measurement techniques used in this study nor evoke additive effects beyond those induced by 0.30 ppm O3 in healthy young adults.

Abstract  Nitrogen dioxide (NO2) is an important component of both outdoor and indoor air pollution. NO2 is a reactive gas that participates with sunlight, hydrocarbons, and oxygen in the formation of ozone and other photochemical oxidants. No2 may also react with aerosols to form nitrous and nitric acids. The principal source of NO2 in outdoor air is motor vehicle emissions, although power pants and fossil-fuel-burning industries also contribute lesser amounts of this gas.

Abstract  In the present study, changes of lipid peroxides, phospholipids and antioxidant levels in lungs of 4 animal species exposed to the combined gases of NO2 and O3 were compared. Male mice, hamster, rats and guinea pigs were used. Lipid peroxides were increased significantly in the lungs of mice and guinea pigs exposed to the combined gases, but not in hamsters and rats. Changes of α-tocopherol (VE) contents were slight. On the other hand, non-protein sulfhydryl (NPSH) contents were increased strikingly, especially in hamsters but were not increased in guinea pigs. Phosphatidylcholine (PC) contents were increased and phosphatidylethanolamine (PE) contents were decreased by the exposure to the combined gases, with the order guinea pig > mouse > rat. In hamsters no changes were seen. The changes of fatty acid composition in guinea pigs and mice were marked, the increases of palmitate and palmitolate and the decreases of polyunsaturated fatty acid were especially characteristic. These changes in phospholipid class and fatty acid composition may be a “a kind of adaptation phenomenon” to avoid further lipid peroxidation. On the other hand, the changes in hamsters and rats were small. The results show the existence of species differences in lipid peroxide formation by exposure to the combined gases of NO2 and O3. They were found to be related to the contents of antioxidants and the compositions of phospholipids and their fatty acids.

Abstract  Changes in lipid peroxide (thiobarbituric acid reactant) levels, in the content of non-protein sulfhydryls (NPSH) and total proteins, and in the activities of antioxidative protective enzymes were examined in the lungs of four animal species exposed to a mixture of NO2 and O3 for 2 weeks. Male mice, hamsters, rats and guinea pigs were used. Thiobarbituric acid (TBA) reactant levels were increased significantly in the lungs of mice and guinea pigs, but not in hamsters and rats. NPSH contents were increased markedly in hamsters, mice and rats, but not in guinea pigs. The activities of antioxidative protective enzymes also changed with the exposure. The most characteristic change was the significant increase in glutathione peroxidase (GPx-H2O2) activity in hamsters and rats - species which did not exhibit increases in their TBA reactant levels. The increase in this enzyme activity in mice was significant, but not very large. Furthermore, guinea pigs were genetically deficient in this enzyme, and the increase in glycolytic enzymes for regenerating NADPH was also lowest in guinea pigs. The glutathione S-transferase (GSH-Tase) activity in mice and guinea pigs was decreased by exposure to the combined gases. These results suggest that the increases in lipid peroxide levels in mice and guinea pigs may be due to a lesser ability to regenerate protective reducing substances, such as NPSH and NADPH, than that of hamsters and rats. Induction of protective enzyme activities on exposure to the combined gases was also poor in mice and guinea pigs.