Abstract  The ubiquitous gas, carbon monoxide (CO), is of substantial biological importance, but apart from its affinity for reduced transition metals, particularly heme-iron, it is surprisingly nonreactive—as is the ferrouscarbonyl—in living systems. CO does form strong complexes with heme proteins for which molecular O2 is the preferred ligand and to which are attributed diverse physiological, adaptive, and toxic effects. Lately, it has become apparent that both exogenous and endogenous CO produced by heme oxygenase engender a prooxidant milieu in aerobic mammalian cells which initiates signaling related to reactive oxygen species (ROS) generation. ROS signaling contingent on CO can be segregated by CO concentration-time effects on cellular function, by the location of heme proteins, e.g., mitochondrial or nonmitochondrial sites, or by specific oxidation-reduction (redox) reactions. The fundamental responses to CO involve overt physiological regulatory events, such as activation of redox-sensitive transcription factors or stress-activated kinases, which institute compensatory expression of antioxidant enzymes and other adaptations to oxidative stress. In contrast, responses originating from highly elevated or protracted CO exposures tend to be nonspecific, produce untoward biological oxidations, and interfere with homeostasis. This brief overview provides a conceptual framework for understanding CO biology in terms of this physiological-pathological hierarchy.

Abstract  The cellular effects of carbon monoxide (CO) are produced primarily by CO binding to iron or other transition metals, which may also promote prooxidant activities of the more reactive gases, oxygen and nitric oxide. We tested the hypothesis that prooxidant effects of CO deregulate the calcium-dependent mitochondrial pore transition (MPT), which disrupts membrane potential and releases apoptogenic proteins. Rats were exposed to either CO (50 ppm) or hypobaric hypoxia (HH) for 1, 3, or 7 days, and liver mitochondria harvested to study protein expression and sensitivity to MPT by calcium and oxidants. Both exposures induced hypoxia-sensitive protein expression: hypoxia-inducible factor 1α (HIF-1α), heme oxygenase-1 (HO-1), and manganese SOD (SOD2), but SOD2 induction was greater by CO than by HH, especially at 7 days. Relative to HH, CO also caused significant early mitochondrial oxidative and nitrosative stress shown by decreases in GSH/GSSG and increases in protein 3-nitrotyrosine (3-NT) and protein mixed disulfide formation. This altered MPT sensitivity to calcium through an effect on the “S-site,” causing loss of pore protection by adenine nucleotides. By 7 days, despite continued CO, nitrosative stress decreased and adenine nucleotide protection was restored to preexposure levels. This is the first evidence of functional mitochondrial pore stress caused by CO independently of its hypoxic effect, as well as a compensatory response exemplifying a mitochondrial phenotype shift. The implications are that cellular CO can activate or deactivate mitochondria for initiation of apoptosis in vivo.

Abstract  The biochemical paradigm for carbon monoxide (CO) is driven by the century-old Warburg hypothesis: CO alters O2-dependent functions by binding heme proteins in competitive relation to 1/oxygen partial pressure ( PO2). High PO2 thus hastens CO elimination and toxicity resolution, but with more O2, CO-exposed tissues paradoxically experience less oxidative stress. To help resolve this paradox we tested the Warburg hypothesis using a highly sensitive gas-reduction method to track CO uptake and elimination in brain, heart, and skeletal muscle in situ during and after exogenous CO administration. We found that CO administration does increase tissue CO concentration, but not in strict relation to 1/PO2. Tissue gas uptake and elimination lag behind blood CO as predicted, but 1/PO2 vs. [CO] fails even at hyperbaric PO2. Mechanistically, we established in the brain that cytosol heme concentration increases 10-fold after CO exposure, which sustains intracellular CO content by providing substrate for heme oxygenase (HO) activated after hypoxia when O2 is resupplied to cells rich in reduced pyridine nucleotides. We further demonstrate by analysis of CO production rates that this heme stress is not due to HO inhibition and that heme accumulation is facilitated by low brain PO2. The latter becomes rate limiting for HO activity even at physiological PO2, and the heme stress leads to doubling of brain HO-1 protein. We thus reveal novel biochemical actions of both CO and O2 that must be accounted for when evaluating oxidative stress and biological signaling by these gases.

Abstract  AIM: Carbon monoxide (CO) in blood as assessed by the COHb% is a marker of the cardiovascular (CV) risk in smokers. Non-smokers exposed to tobacco smoke similarly inhale and absorb CO. The objective in this population-based cohort study has been to describe inter-individual differences in COHb% in never smokers and to estimate the associated cardiovascular risk. METHODS: Of the 8,333 men, aged 34-49 years, from the city of Malmö, Sweden, 4,111 were smokers, 1,229 ex-smokers, and 2,893 were never smokers. Incidence of CV disease was monitored over 19 years of follow up. RESULTS: COHb% in never smokers ranged from 0.13% to 5.47%. Never smokers with COHb% in the top quartile (above 0.67%) had a significantly higher incidence of cardiac events and deaths; relative risk 3.7 (95% CI 2.0-7.0) and 2.2 (1.4-3.5), respectively, compared with those with COHb% in the lowest quartile (below 0.50%). This risk remained after adjustment for confounding factors. CONCLUSION: COHb% varied widely between never-smoking men in this urban population. Incidence of CV disease and death in non-smokers was related to COHb%. It is suggested that measurement of COHb% could be part of the risk assessment in non-smoking patients considered at risk of cardiac disease. In random samples from the general population COHb% could be used to assess the size of the population exposed to second-hand smoke.

Abstract  This study represented an initial attempt, by means of cross-sectional investigation, to determine the effects of chronic exposure to high altitude on pulmonary gas exchange. Single-breath DLco and its components were determined at rest and during muscular work in two groups of healthy, non-smoking, sea level natives who had initiated 1-16 yr of residence at 3,100 m altitude either during physical maturation (at age 10±4 yr) or as adults (at age 26±4 yr). The relative degree of acclimatization achieved in these lowland residents was assessed through their comparison both with normal sea-level values and with two additional groups of short-term sojourners and natives to 3.100 m. DLco at rest and work was significantly elevated above normal and above sojourner values in both groups of resident lowlanders at 3,100 m. The high DLco in the native to 3,100 m was closely approximated in the younger resident lowlander at rest, but only during exercise in the adult resident lowlander. The high DLco at rest and during exercise in the resident lowlanders was not attributable to differences in Hb concentration or in alveolar lung volume: and was accompanied primarily by an increased estimated Dmco and to a lesser extent by an expanded Vc. The interpretation and implications of these findings were limited by the low quantitative capability of Vc and Dmco estimates and by the cross-sectional nature of the study. Nevertheless, the higher than normal DLco and Dmco in the non-native, long-term resident of 3,100 m was substantial, highly significant statistically, and consistent over a wide range of metabolic rates at rest and work. These data provide, then, a reasonable rationale upon which longitudinal experiments may be based to determine the true effects of chronic hypoxia on pulmonary gas exchange in man.

Abstract  Being the most common cause of death from poisoning worldwide, cardiovascular manifestations of acute carbon monoxide (CO) poisoning have been subject of various studies but current evidence about effects of chronic CO exposure on atherosclerosis is limited which is very common. We aimed to investigate association of chronic CO exposure with atherosclerosis by measuring carotid intima-media thickness (CIMT) and high-sensitivity C-reactive protein (hs-CRP). Forty healthy male non-smoker indoor barbecue workers (mean age; 33.0 ± 9.0 years) working in different restaurants for at least three years and 48 age-matched healthy men (mean age; 34.3 ± 6.6 years) enrolled in the study. Clinical characteristics of indoor barbecue workers and control group were comparable in terms of body mass index, blood pressure, and lipid profile. However, carboxyhemoglobin (COHb) (6.4 ± 1.5% vs. 2.0 ± 1.1%), hs-CRP (2.7 ± 2.0 mg/L vs. 1.1 ± 0.8 mg/L) and CIMT (1.1 ± 0.3 mm vs. 0.9 ± 0.1 mm) were higher in indoor barbecue workers (p < 0.001 for each). In Pearson correlation analysis, CIMT was correlated with COHb concentration (r = 0.635, p < 0.001) and hs-CRP level (r = 0.466, p < 0.001). Among indoor barbecue workers, the years worked (years exposed to CO) are correlated with COHb, hs-CRP and CIMT. In multivariate analysis, COHb concentration is the only independent predictor of CIMT (β = 0.571, p < 0.001). The increased CIMT and hs-CRP in indoor barbecue workers suggest that chronic CO exposure may increase the risk of atherosclerotic cardiovascular events.

Abstract  Both blood viscosity and carbon monoxide (CO) has been associated with cardiovascular diseases (CVDs). In order to investigate the effects of chronic low-level CO exposure on the determinants of blood viscosity (hematocrit, plasma viscosity, erythrocyte deformability, and erythrocyte aggregation), 10 men exposed to CO at work for at least 6 months and 10 healthy controls were included in the study. Plasma viscosity was determined by a cone-plate viscometer, erythrocyte deformability and erythrocyte aggregation by laser-assisted optical rotational cell analyzer. Mean plasma viscosity of the group exposed to CO (1.4 +/- 0.1 mPa.sn) was significantly higher than that of the controls (1.2 +/- 0.06 mPa.sn) (p < .05). Plasma fibrinogen level of the CO group (275 +/- 11 mg/dL) was slightly higher than that of the controls (263 +/- 14 mg/dL). The rise in plasma viscosity by chronic low-level CO exposure may be the mechanism of CO-induced increase in the risk for CVDs.

Abstract  We examined the associations between gaseous pollutants and hospitalization for chronic obstructive pulmonary diseases (COPD) among elderly people living in Vancouver, British Columbia, Canada, a city in which ambient air pollution levels are relatively low. We regressed the logarithm of daily counts of acute COPD hospitalization during the 5-year period from 1994 to 1998 on the daily mean levels of each pollutant, after accounting for seasonal and subseasonal fluctuations, non-Poisson dispersion, and weather variables. Nitrogen dioxide and carbon monoxide were significantly associated with hospitalization for COPD, and the magnitude of effects was increased slightly with increasing days of exposure averaging, with the relative risk for a 7-day average being 1.11 (95%CI: 1.04, 1.20) and 1.08 (1.02, 1.13) for nitrogen dioxide and carbon monoxide, respectively. There was no significant association between either sulfur dioxide or ozone and COPD hospitalization. The combined relative risk for all four gaseous pollutants on COPD hospitalization was 1.21. The effects of gaseous pollutants on COPD hospitalization were not significant after adjustment for PM10, although its inclusion did not have a marked effect on the point estimates for relative risks. Nitrogen dioxide has a significant impact on COPD hospitalization. Further studies are needed to separate the effects of single pollutants from the combined effects of the complex mixture of air pollutants in urban atmospheres.

Abstract  Two studies at three sites in the UK provided confirmation that systematic positive bias in NO2 diffusion tube measurement occurred because of changes to "within-tube" chemistry, rather than eddy diffusion at the mouth of the tube. In the first study in Cambridge, UK, sampler overestimation for 1 and 2 week exposures was compared to corresponding time-averaged monitor measurements (NO-NO2-NOx, O3) and weather variables. Noninearity between sampler and monitor NO2 measurements was interpreted in terms of spatial and temporal variations in relative and absolute availability of NO, NO2 and O3 at the site. A maximum overestimation occurred for an exposure mean NO2/NOx approximately 0.5. The separate contributions of reduced NO2 photolysis and eddy diffusion were compared in Study II using samplers of two materials, acrylic and quartz, and of different lengths (40, 55, 71 and 120 mm) at three sites: Norwich background, Cambridge intermediate, London kerbside. For compared sites, NO2 measured by acrylic samplers was significantly higher than for equivalent quartz samplers. For quartz samplers [NO2]mean was only just above the monitor at Norwich and London; sampler/monitor NO2 = 1.04 (P = 0.59) and 1.01(P = 0.76), respectively. For acrylic samplers the order of [NO2]mean was 40 mm > 120 mm > 71 mm > or = 55 mm. Excepting 40 mm samplers, this accords with a chemical bias where co-diffusing NO and 03 molecules in longer tubes have more time to react to form excess NO2. Bias in 40 mm samplers is discussed. Eddy diffusion is negligible for standard samplers because [NO2]mean was equivalent for 55 mm and 71 mm acrylic samplers and close to monitor NO2 for 71 mm quartz tubes. Both studies showed that sampler accuracy was dependent on location. Significantly, overestimation was greatest (approximately 3-4 ppb) where the NO2 annual mean was approximately 20 ppb, close to the UK and EU air quality standard of 21 ppb.

Abstract  BACKGROUND: The Democratic National Convention (DNC) in Boston, Massachusetts in 2004 provided an opportunity to evaluate the impacts of a localized and short-term but potentially significant change in traffic patterns on air quality, and to determine the optimal monitoring approach to address events of this nature. It was anticipated that the road closures associated with the DNC would both influence the overall air pollution level and the distribution of concentrations across the city, through shifts in traffic patterns. METHODS: To capture these effects, we placed passive nitrogen dioxide badges at 40 sites around metropolitan Boston before, during, and after the DNC, with the goal of capturing the array of hypothesized impacts. In addition, we continuously measured elemental carbon at three sites, and gathered continuous air pollution data from US EPA fixed-site monitors and traffic count data from the Massachusetts Highway Department. RESULTS: There were significant reductions in traffic volume on the highway with closures north of Boston, with relatively little change along other highways, indicating a more isolated traffic reduction rather than an across-the-board decrease. For our nitrogen dioxide samples, while there was a relatively small change in mean concentrations, there was significant heterogeneity across sites, which corresponded with our a priori classifications of road segments. The median ratio of nitrogen dioxide concentrations during the DNC relative to non-DNC sampling periods was 0.58 at sites with hypothesized traffic reductions, versus 0.88 for sites with no changes hypothesized and 1.15 for sites with hypothesized traffic increases. Continuous monitors measured slightly lower concentrations of elemental carbon and nitrogen dioxide during road closure periods at monitors proximate to closed highway segments, but not for PM2.5 or further from major highways. CONCLUSION: We conclude that there was a small but measurable influence of DNC-related road closures on air quality patterns in the Boston area, and that a low-cost monitoring study combining passive badges for spatial heterogeneity and continuous monitors for temporal heterogeneity can provide useful insight for community air quality assessments.

Abstract  Multipollutant models are frequently used to differentiate roles of multiple pollutants in epidemiologic studies of ambient air pollution. In the presence of differing levels of measurement error across pollutants under consideration, however, they can be biased and as misleading as single-pollutant models. Their appropriate interpretation depends on the relationships among the pollutant measurements and the outcomes in question. In situations where two or more pollutant variables may be acting as surrogates for the etiologic agent(s), multipollutant models can help identify the best surrogate, but the risk estimates may be influenced by inclusion of a second variable that is not itself an independent risk factor for the outcome in question. In this paper, these issues will be illustrated in the context of an ongoing study of emergency visits in Atlanta. Emergency department visits from 41 of 42 hospitals serving the twenty-county Atlanta metropolitan area for the period 1993-2004 (n=10,206,389 visits) were studied in relation to ambient pollutant levels, including speciated particle measurements from an intensive monitoring campaign at a downtown station starting in 1998. Relative to our earlier publications, reporting results through 2000, the period for which the speciated data are now available is now tripled (six years in length). Poisson generalized linear models were used to examine outcome counts in relation to three-day moving average concentrations of pollutants of a priori interest (ozone, nitrogen dioxide, carbon monoxide, sulfur dioxide, oxygenated hydrocarbons, PM10, coarse PM, PM2.5, and the following components of PM2.5: elemental carbon, organic carbon, sulfate, water-soluble transition metals.) In the present analysis, we report results for two outcome groups: a respiratory outcomes group and a cardiovascular outcomes group. For cardiovascular visits, associations were observed with CO, 3 NO2, and PM2.5 elemental carbon and organic carbon. In multipollutant models, CO was the strongest predictor. For respiratory visits, associations were observed with ozone, PM10, CO and NO2 in single-pollutant models. In multipollutant models, PM10 and ozone persisted as predictors, with ozone the stronger predictor. Caveats and considerations in interpreting the multipollutant model results are discussed.

Abstract  BACKGROUND: Consistent evidence has indicated that air pollution increases the risk of cardiovascular diseases. The underlying mechanisms linking air pollutants to increased cardiovascular risk are unclear. OBJECTIVES: We investigated the association between the pollution levels and changes in such global coagulation tests as the prothrombin time (PT) and the activated partial thromboplastin time (APTT) in 1218 normal subjects from the Lombardia Region, Italy. Plasma fibrinogen and naturally occurring anticoagulant proteins were also evaluated. METHODS: Hourly concentrations of particulate (PM10) and gaseous pollutants (CO, NO2, SO2, and O3) were obtained from 53 monitoring sites covering the study area. Generalized additive models were applied to compute standardized regression coefficients controlled for age, gender, body mass index, smoking, alcohol, hormone use, temperature, day of the year, and long-term trends. RESULTS: The PT became shorter with higher ambient air concentrations at the time of the study of PM10 (coefficient = -0.06; P < 0.05), CO (coefficient = -0.11; P < 0.001) and NO2 (coefficient =-0.06; P < 0.05). In the 30 days before blood sampling, the PT was also negatively associated with the average PM10 (coefficient = -0.08; P < 0.05) and NO2 (coefficient = -0.08; P < 0.05). No association was found between the APTT and air pollutant levels. In addition, no consistent relations with air pollution were found for fibrinogen, antithrombin, protein C and protein S. CONCLUSIONS: This investigation shows that air pollution is associated with changes in the global coagulation function, suggesting a tendency towards hypercoagulability after short-term exposure to air pollution. Whether these changes contribute to trigger cardiovascular events remains to be established.

Abstract  #Human activities, particularly habitat destruction and species introductions, are resulting in increased homogenization of once unique biogeographic regions. In the southeastern United States, extensive endemism occurs among highland fish species that have specialized ecologies, are adapted to cool, clear, nutrient-poor conditions, and are sediment-intolerant. Highland streams flow into lower elevation systems, which are often inhabited by more widespread, generalist fish species adapted to warmer, more turbid, fine-sediment-rich, and nutrient-rich conditions. Common land use practices, such as deforestation, degrade stream habitats and reduce habitat diversity, which is often correlated with taxonomic and ecological diversity. Habitat homogenization can thus cause assemblage homogenization via loss of native species and addition of nonindigenous species. However, midpoints in the homogenization process may be characterized by constant or even increased species diversity because generalist, sediment-tolerant, ônativeö species invade from downstream areas. Perusal of a species list for a river system would not reveal such invasions because lists seldom discriminate between upstream and downstream assemblages in a drainage. Traditional metrics often used in biological assessment, such as species richness (a diversity) and evenness, should not include invasive species, whether native or exotic. Greater attention should be paid to the actual species present and their ecological requirements, and to changes in overlap in species occurrence among regions. Aquatic ecosystem integrity can degrade despite apparent increases in species diversity.

Abstract  Some 60% of coastal rivers and bays in the U.S. have been moderately to severely degraded by nutrient pollution. Both nitrogen (N) and phosphorus (P) contribute to the problem, although for most coastal systems N additions cause more damage. Globally, human activity has increased the flux of N and P from land to the oceans by 2-fold and 3-fold, respectively. For N, much of this increase has occurred over the past 40 years, with the increase varying by region. Human activity has increased the flux of N in the Mississippi River basin by 4-fold, in the rivers of the northeastern U.S. by 8-fold, and in the rivers draining to the North Sea by more than 10-fold. The sources of nutrients to the coast vary. For some estuaries, sewage treatment plants are the largest single input; for most systems nonpoint sources of nutrients are now of relatively greater importance, both because of improved point source treatment and control (particularly for P) and because of increases in the total magnitude of nonpoint sources (particularly for N) over the past three decades. For P, agricultural activities dominate nonpoint source fluxes. Agriculture is also the major source of N in many systems, including the flux of N down the Mississippi River, which has contributed to the large hypoxic zone in the Gulf of Mexico. For both P and N, agriculture contributes to nonpoint source pollution both through losses at the field scale, as soils erode away and fertilizer is leached to surface and ground waters, and from losses from animal feedlot operations. In the U.S. N from animal wastes that leaks directly to surface waters or is volatilized to the atmosphere as ammonia may be the single largest source of N that moves from agricultural operations into coastal waters. In some regions, including the northeastern U.S., atmospheric deposition of oxidized N from fossil-fuel combustion is the major flux from nonpoint sources. This atmospheric component of the N flux into estuaries has often been underestimated, particularly with respect to deposition onto the terrestrial landscape with subsequent export downstream. Because the relative importance of these nutrient sources varies among regions and sites, so too must appropriate and effective mitigation strategies. The regional nature and variability of nutrient sources require that nutrient management efforts address large geographic areas.

Abstract  A survey of 344 streams in the Appalachian Mountain region of Virginia that support reproducing populations of native brook trout (Salvelinus fontinalis) was conducted in the spring of 1987. The surveyed streams represent about 76% of the identified trout streams in the region. Relative to commonly applied sensitivity criteria, 93% of the streams are sensitive (alkalinity ≤ 200 μeq L−1), 49% of the streams are extremely sensitive (alkalinity ≤ 50 μeqL−1) and 10% of the streams are currently acidic (alkalinity ≤ 0.0 μeq L−1). Sulfate is the dominant anion in the streams, but all catchments associated with the streams are retaining significant amounts of atmospherically deposited sulfur (median retention=68%). Estimates of past and potential future acidification were obtained using a simple linear model relating changes in concentrations of base cations to changes in concentrations of sulfate. Sulfate concentration changes were determined as the difference between currently observed concentrations and estimated past and future steady state concentrations. Changes in concentrations of base cations were calculated, assuming base cation increase factors equal to 0.4 and 0.8 times the sulfate increase. The median historical alkalinity loss for the sampled population is estimated as 29 and 9 μeq L−1 for the two assumed factors, with 3 and 0% of the streams estimated to have had historical alkalinities < 0.0 μeq L−1. The median future alkalinity loss is estimated as 90 and 30 μeq L−1 for the two assumed factors, with 88 and 32% of the streams estimated to have future alkalinities < 0.0 μeq L−1.

Abstract  Nitrous acid is a significant photochemical precursor of the hydroxyl radical the key oxidant in the degradation of most air pollutants in the troposphere. The sources of nitrous acid in the troposphere, however, are still poorly understood. Recent atmospheric measurements revealed a strongly enhanced formation of nitrous acid during daytime via unknown mechanisms. Here we expose humic acid films to nitrogen dioxide in an irradiated tubular gas flow reactor and find that reduction of nitrogen dioxide on light-activated humic acids is an important source of gaseous nitrous acid. Our findings indicate that soil and other surfaces containing humic acid exhibit an organic surface photochemistry that produces reductive surface species, which react selectively with nitrogen dioxide. The observed rate of nitrous acid formation could explain the recently observed high daytime concentrations of nitrous acid in the boundary layer, the photolysis of which accounts for up to 60 per cent of the integrated hydroxyl radical source strengths. We suggest that this photo-induced nitrous acid production on humic acid could have a potentially significant impact on the chemistry of the lowermost troposphere.

Abstract  Nitrogen oxides are trace gases that critically affect atmospheric chemistry and aerosol formation1. Vegetation is usually regarded as a sink for these gases, although nitric oxide and nitrogen dioxide have been detected as natural emissions from plants2, 3. Here we use in situ measurements to show that solar ultraviolet radiation induces the emission of nitrogen oxide radicals (NOx) from Scots pine (Pinus sylvestris) shoots when ambient concentrations drop below one part per billion. Although this contribution is insignificant on a local scale, our findings suggest that global NOx emissions from boreal coniferous forests may be comparable to those produced by worldwide industrial and traffic sources.

Abstract  Background: Acute myocardial infarction (AMI) is the leading cause of death attributed to cardiovascular diseases. An association between traffic-related air pollution and AMI has been suggested, but the evidence is still limited. Objectives: to evaluate in a multi-centre study association between hospitalisation for first AMI and daily levels of traffic-related air pollution. Methods: We collected data on first AMI hospitalisations in 5 European cities. AMI registers were available in Augsburg and Barcelona; hospital discharge registers (HDRs) were used in Helsinki, Rome and Stockholm. NO2, CO and PM10 (particles <10 mu m) were measured at central monitoring sites. Particle number concentration (PNC), a proxy for ultrafine particles (<0.1 mu m), was measured for a year in each centre, and then modelled retrospectively for the whole study period. We used generalized additive models for statistical analyses. Age and 28-day fatality and season were considered as potential effect modifiers in the 3 HDR centres. Results: Nearly 27 000 cases of first AMI were recorded. There was a suggestion of an association of the same day CO and PNC levels with AMI: RR=1.005 (95% confidence interval: 1.000-1.010) per 0.2 mg/m3 and RR=1.005 (95%CI: 0.996-1.015) per 10000 particles/cm3, respectively. However, associations were only observed in the 3 cities with HDR, where power for city-specific analyses was higher. We observed in these cities the most consistent associations among fatal cases aged <75 years: RR at 1-day lag for CO=1.021 (95%CI: 1.000-1.048) per 0.2 mg/m3, for PNC= 1.058 (95% CI: 1.012-1.107) per 10000 particles/cm3, and for NO2=1.032 (95%CI: 0.998-1.066) per 8 mu g/m3. Effects of air pollution were more pronounced during the warm than the cold season. Conclusions: We found support for the hypothesis that exposure to traffic-related air pollution increases the risk of AMI. Most consistent associations were observed among fatal cases aged <75 years and in the warm season.

Abstract  #BACKGROUND: Cohort studies have reported increased risks of cardiopulmonary mortality from long-term air pollution exposure, but the evidence is limited and inconclusive. We studied the association between long-term exposure to source-specific air pollution and myocardial infarction (MI) in a case-control study of first-time MI cases and population controls age 45 to 70 years in Stockholm county in 1992 to 1994. METHODS: Home addresses during several decades were combined with historical emission databases and dispersion models to obtain annual mean levels of pollutants from traffic and heating during 30 years for 1397 cases and 1870 controls. Nitrogen dioxide (NO2), carbon monoxide (CO), and particulate matter with an aerodynamic diameter less than 10 microm (PM10) were used as indicators of traffic emissions and sulfur dioxide (SO2) as an indicator of emissions from residential heating. RESULTS: There was no association between long-term average air pollution exposure and overall MI, but an increased risk of fatal MI was suggested, especially for out-of-hospital death. After adjustment for cardiovascular risk factors, the odds ratio for fatal MI associated with a 5th to 95th percentile difference in 30-year average exposure was 1.51 (95% confidence interval = 0.96-2.16) for NO2, 1.22 (0.98-1.52) for CO, 1.39 (0.94-2.07) for PM10, and 1.24 (0.77-2.02) for SO2. For out-of-hospital death, the odds ratio related to NO2 exposure was 2.17 (1.05-4.51). CONCLUSIONS: This study provides some support for an association between long-term air pollution exposure and fatal cardiovascular disease.

Abstract  To clarify the health effects of ozone exposure in young children, the authors studied the association between air pollution and hospital admissions for acute respiratory problems in children less than 2 years of age during the 15-year period from 1980 to 1994 in Toronto, Canada. The daily time series of admissions was adjusted for the influences of day of the week, season, and weather. A 35% (95% confidence interval: 19%, 52%) increase in the daily hospitalization rate for respiratory problems was associated with a 5-day moving average of the daily 1-hour maximum ozone concentration of 45 parts per billion, the May-August average value. The ozone effect persisted after adjustment for other ambient air pollutants or weather variables. Ozone was not associated with hospital admissions during the September-April period. Ambient ozone levels in the summertime should be considered a risk factor for respiratory problems in children less than 2 years of age.

Abstract  There are no reported studies on the effects of ambient air pollution on emergency department (ED) attendances in Sydney, Australia. This study aimed to determine associations between ambient air pollutants and ED attendances for cardiovascular disease (CVD) in those aged 65+ years. We constructed daily time series of hospital ED attendances, air pollutants and meteorological factors for the Sydney metropolitan area from 1 January 1997 to 31 December 2001. We used generalised linear models to determine associations between daily air pollution and daily ED attendances and controlled for the effects of long-term trends, seasonality, weather and other potential confounders. Increased ED attendances for all CVD, cardiac disease and ischaemic heart disease were seen with 24-h particulate pollution, 1-h NO(2), 8-h CO and 24-h SO(2). Air pollutants were associated with decreased ED attendances for stroke. The effects of air pollutants on CVD, cardiac disease and stroke attendances were generally greater in the cool period compared to the warm period. The single-pollutant effects of CO, O(3), NO(2) and SO(2) were essentially unchanged in two-pollutant models. Although air pollution levels in Sydney are relatively low compared to similar cities, we have demonstrated associations between ambient air pollutants and ED attendances for CVD in people aged 65+ years. Our study adds to the growing evidence for the effects of ambient air pollution on CVD outcomes even at relatively low ambient concentrations.

Abstract  Objective: It is still unknown whether specific components in fine particles are associated with heart rate variability (HRV) reduction. Methods: We recruited 46 patients with or at risk for cardiovascular diseases to measure 24-hour HRV by ambulatory electrocardiographic monitoring. Fixed-site air-monitoring stations were used to represent participants' exposures to particles with aerodynamic diameters less than 10 ?m (PM10) and 2.5 ?m (PM2.5), and particulate components of sulfate, nitrate, organic carbon (OC) and elemental carbon, and gaseous pollutants. Results: We found that HRV reduction was associated with sulfate, OC, and PM2. 5 but not with the other five pollutants in single-pollutant models. Sulfate was found to remain in significant association with HRV reduction adjusting for OC and PM2.5 in three-pollutant models. Conclusions: Exposures to sulfate and OC in PM2.5were associated with HRV reduction in patients with or at risk for cardiovascular diseases.

Abstract  Objective: The authors conducted an investigation of the association between air pollution and arrhythmia. Methods: A prospective panel study (October 2000-April 2001) was conducted in Erfurt, Germany. Fifty-seven men with coronary heart disease were subjected to six 24-hour electrocardiogram recordings. Runs of supraventricular and ventricular tachycardia were associated with continuous ultrafine particle counts (UFP), accumulation mode particle counts (ACP), PM2,5, and gaseous pollutants. Poisson and linear regression models were applied adjusting for trend, weekday, and meteorologic data. Results: Elevated concentrations of UFP, ACP, PM2,5, and nitrogen dioxide increased the risk for supraventricular runs and the number of ventricular runs at almost all lags. Statistically significant associations were found predominantly in the previous 24 to 71 hours and with the 5-day moving average. Conclusion: Elevated concentrations of fine and ultrafine particle increased the risk of arrhythmia in men with coronary heart disease.

Abstract  The National Children's Study is considering a wide spectrum of airborne pollutants that are hypothesized to potentially influence pregnancy outcomes, neurodevelopment, asthma, atopy, immune development, obesity, and pubertal development. In this article we summarize six applicable exposure assessment lessons learned from the Centers for Children's Environmental Health and Disease Prevention Research that may enhance the National Children's Study: a) Selecting individual study subjects with a wide range of pollution exposure profiles maximizes spatial-scale exposure contrasts for key pollutants of study interest. b) In studies with large sample sizes, long duration, and diverse outcomes and exposures, exposure assessment efforts should rely on modeling to provide estimates for the entire cohort, supported by subject-derived questionnaire data. c) Assessment of some exposures of interest requires individual measurements of exposures using snapshots of personal and microenvironmental exposures over short periods and/or in selected microenvironments. d) Understanding issues of spatial-temporal correlations of air pollutants, the surrogacy of specific pollutants for components of the complex mixture, and the exposure misclassification inherent in exposure estimates is critical in analysis and interpretation. e) "Usual" temporal, spatial, and physical patterns of activity can be used as modifiers of the exposure/outcome relationships. f) Biomarkers of exposure are useful for evaluation of specific exposures that have multiple routes of exposure. If these lessons are applied, the National Children's Study offers a unique opportunity to assess the adverse effects of air pollution on interrelated health outcomes during the critical early life period.