Abstract  Short-term effects of air pollution on common morbidity are largely unknown. The authors explored links between daily levels of air pollution (nitrogen dioxide, ozone, and particulate matter less than 10 lm in diameter (PM10)) and medical home visits made for diverse reasons in Bordeaux, France, during 2000–2006. Daily numbers of visits were obtained from a network of general practitioners. The excess relative risk (ERR) of a visit for each indicator associated with increased pollutant levels was estimated by fitting a Poisson regression model, controlling for well known confounding factors and temporal trends. Positive and significant associations were found between air pollution and most health indicators. A 10-lg/m3 increase in PM10 levels was associated with increases in visits for upper and lower respiratory diseases (ERRs were 1.5% (95% confidence interval (CI): 0.3, 2.7) and 2.5% (95% CI: 0.5, 4.4), respectively), headache and asthenia (ERR = 3.5%, 95% CI: 1.3, 5.9), and skin rash and conjunctivitis (ERR= 3.2%, 95% CI: -0.2, 6.8). Significant associations were also found between nitrogen dioxide and ozone and several health indicators. Distributed-lag models showed no harvesting effect, and some effects persisted up to 15 days after exposure increased. These results suggest that considering only the most severe effects of air pollution leads to underestimation of its impact on public health.

Abstract  Objective: The prevalence of adverse respiratory outcomes among children has been frequently associated with measurements of traffic-related exposures, and other data suggest asthma severity is worsened with residence near heavy traffic. We examined the association between neighbourhood traffic burden and repeated acute respiratory illnesses that required emergency department visits and/or hospitalisation for children with a primary or secondary diagnosis of asthma (89% acute bronchitis or pneumonia). Methods: This is a hospital-based longitudinal study of a southern California urban catchment area around two adjacent children’s hospitals. Subjects’ home addresses were geocoded and linked to nearby traffic data. Recurrent event proportional hazard analysis was used to estimate the hazard of repeated hospital encounters. Results: We found living within 300 metres of arterialroads or freeways increased risk of repeated hospital encounters in 3297 children age 18 years or less. At highest risk were children in the top quintile of traffic density (HR=1.21; 95% CL 0.99 to 1.49) and those who had 750 metres or more of arterial road and freeway length within 300 metres of their residence (HR=1.18; 95% CL 0.99 to 1.41). Associations between repeated hospital encounters and residence near heavy traffic were stronger in females than males and in children without insurance or who required government sponsored insurance than children with private insurance. The gender disparity was most notable among infants (age 0) and children ages 6–18 years. Conclusions: Results suggest exposure to traffic-related air pollution increases asthma severity as indicated by hospital utilisation. The finding in infants suggests this is an especially vulnerable population, although the validity of asthma diagnosis at this age is unknown. Females and children who do not have private insurance may also be more vulnerable to air pollution from traffic.

Abstract  BACKGROUND: Many studies have shown that exposures to air pollution are associated with cardiovascular events although the mechanism remains to be clarified. To identify whether exposures to ambient particles act on autonomic function via the lipid/endothelial metabolism pathway, we evaluated whether the effects of particulate matter < 2.5 microm in aerodynamic diameter (PM2.5) on heart rate variability (HRV) were modified by gene polymorphisms related to those pathways. METHODS: We used HRV and gene data from the Normative Aging Study and PM2.5 from a monitor located a kilometer from the examination site. We fitted a mixed model to investigate the associations between PM2.5 and repeated measurements of HRV by gene polymorphisms of apolipoprotein E (APOE), lipoprotein lipase (LPL) and vascular endothelial growth factor (VEGF) adjusting for potential confounders chosen a priori. RESULTS: A 10-microg/m(3) increase of PM2.5 in the two days before the examination was associated with 3.8% [95% confidence interval (CI): 0.2%, 7.4%], 7.8% [95 CI: 0.4%, 15.3%] and 10.6% [95% CI: 1.8 %, 19.4%] decreases of the standard deviation of normal-to-normal intervals, the low frequency and the high frequency, respectively. Overall, carriers of wild type APOE, LPL and VEGF genes had stronger effects of particles on HRV compared to those with hetero- or homozygous types. Variations of LPL-N291S, LPL-D9N and APOE-G113C significantly modified effects of PM2.5 on HRV. CONCLUSION: Associations between PM2.5 and HRV were modified by gene polymorphisms of APOE, LPL and VEGF and biological metabolism remains to be identified.

Abstract  This report describes a unique collaboration among investigators from Europe, the United States, and Canada using existing data from three geographic areas and supported by HEI in collaboration with the European Commission. APHENA offered a large and diverse data set with which to address methodological as well as scientific issues about the relationships between PM10, ozone, and mortality and morbidity that were the subject of lively debates at the time the project was launched. Drs. Katsouyanni and Samet and their colleagues undertook a rigorous examination of time-series methods used to model the relationship between daily PM10 and ozone concentrations and daily mortality and hospital admissions. They sought to develop a standardized approach to the analysis of time series data at the city and regional level, to assess the consistency between relative rates of mortality and hospital admissions across Europe and North America when estimated using a common analytic protocol, and to explore possible explanations for any remaining variation in the results that analytic differences could not explain.

Abstract  Relatively little is known about exposures to traffic-related particulate matter at schools located in dense urban areas. The purpose of this study was to examine the influences of diesel traffic proximity and intensity on ambient concentrations of fine particulate matter (PM(2.5)) and black carbon (BC), an indicator of diesel exhaust particles, at New York City (NYC) high schools. Outdoor PM(2.5) and BC were monitored continuously for 4-6 weeks at each of 3 NYC schools and 1 suburban school located 20 kilometers upwind of the city. Traffic count data were obtained using an automated traffic counter or video camera. BC concentrations were 2-3 fold higher at urban schools compared with the suburban school, and among the 3 urban schools, BC concentrations were higher at schools located adjacent to highways. PM(2.5) concentrations were significantly higher at urban schools than at the suburban school, but concentrations did not vary significantly among urban schools. Both hourly average counts of trucks and buses and meteorological factors such as wind direction, wind speed, and humidity were significantly associated with hourly average ambient BC and PM(2.5) concentrations in multivariate regression models. An increase of 443 trucks/buses per hour was associated with a 0.62 mug/m(3) increase in hourly average BC at a NYC school located adjacent to a major interstate highway. Car traffic counts were not associated with BC. The results suggest that local diesel vehicle traffic may be important sources of airborne fine particles in dense urban areas and consequently may contribute to local variations in PM(2.5) concentrations. In urban areas with higher levels of diesel traffic, local, neighborhood-scale monitoring of pollutants such as BC, which compared to PM(2.5), is a more specific indicator of diesel exhaust particles, may more accurately represent population exposures.

Abstract  The study was undertaken to investigate whether regular cooking with biomass aggravates systemic inflammation and oxidative stress that might result in increase in the risk of developing cardiovascular disease (CVD) in rural Indian women compared to cooking with a cleaner fuel like liquefied petroleum gas (LPG). A total of 635 women (median age 36 years) who cooked with biomass and 452 age-matched control women who cooked with LPG were enrolled. Serum interleukin-6 (IL-6), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α) and interleukin-8 (IL-8) were measured by ELISA. Generation of reactive oxygen species (ROS) by leukocytes was measured by flow cytometry, and erythrocytic superoxide dismutase (SOD) was measured by spectrophotometry. Hypertension was diagnosed following the Seventh Report of the Joint Committee. Tachycardia was determined as pulse rate >100 beats per minute. Particulate matter of diameter less than 10 and 2.5 μm (PM₁₀ and PM₂.₅, respectively) in cooking areas was measured using real-time aerosol monitor. Compared with control, biomass users had more particulate pollution in indoor air, their serum contained significantly elevated levels of IL-6, IL-8, TNF-α and CRP, and ROS generation was increased by 37% while SOD was depleted by 41.5%, greater prevalence of hypertension and tachycardia compared to their LPG-using neighbors. PM₁₀ and PM₂.₅ levels were positively associated with markers of inflammation, oxidative stress and hypertension. Inflammatory markers correlated with raised blood pressure. Cooking with biomass exacerbates systemic inflammation, oxidative stress, hypertension and tachycardia in poor women cooking with biomass fuel and hence, predisposes them to increased risk of CVD development compared to the controls. Systemic inflammation and oxidative stress may be the mechanistic factors involved in the development of CVD.

Abstract  Air pollution is a serious environmental problem. Elderly subjects show increased cardiac morbidity and mortality associated with air pollution exposure. Mexico City (MC) residents are chronically exposed to high concentrations of fine particulate matter (PM(2.5)) and PM-associated lipopolysaccharides (PM-LPS). To test the hypothesis that chronic exposure to urban pollution produces myocardial inflammation, female Balb-c mice age 4 weeks were exposed for 16 months to two distinctly different polluted areas within MC: southwest (SW) and northwest (NW). SW mice were given either no treatment or chocolate 2g/9.5mg polyphenols/3 times per week. Results were compared to mice kept in clean air. Key inflammatory mediator genes: cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and the LPS receptor CD14 (cluster of differentiation antigen 14) were measured by real-time polymerase chain reaction. Also explored were target NFκB (nuclear factor κB), oxidative stress and antioxidant defense genes. TNF-α, IL-6, and COX-2 were significantly increased in both NW and SWMC mice (p=0.0001). CD14 was up-regulated in SW mice in keeping with the high exposures to particulate matter associated endotoxin. Chocolate administration resulted in a significant down-regulation of TNF-α (p<0.0001), IL-6 (p=0.01), and IL-1β (p=0.02). The up-regulation of antioxidant enzymes and the down-regulation of potent oxidases, toll-like receptors, and pro-apoptotic signaling genes completed the protective profile. Exposure to air pollution produces up-regulation of inflammatory myocardial genes and endotoxin plays a key role in the inflammatory response. Regular consumption of dark chocolate may reduce myocardial inflammation and have cardioprotective properties in the setting of air pollution exposures.

Abstract  Ultrafine particles (UFPs) have emerged as a potentially important environmental health concern as they are produced in large numbers by vehicle emissions and may contribute to previously reported associations between traffic pollution and acute cardiovascular morbidity. This review examines recent epidemiological evidence of UFP exposures and selected physiological outcomes that may be modified as part of the underlying causal pathway(s) linking particulate air pollution and acute cardiovascular morbidity. Outcomes examined included changes in heart rate variability (HRV) (autonomic function), ST-segment depression (myocardial ischemia), QT-interval (ventricular repolarization), and endothelial vasomotor function. Twenty-two studies were reviewed in total: 10 prospective panel studies and 12 randomized cross-over studies. Sixteen studies identified a significant relationship between UFPs and at least one of the above outcomes and current evidence generally supports the biological plausibility of a relationship between UFPs and acute cardiovascular morbidity. However, discrepancies were apparent in the direction of observed associations, particularly for HRV and ventricular repolarization. Reasons for these discrepancies may include differences in particle composition, time-point of clinical evaluation, and population susceptibilities. Nevertheless, evidence to date suggests that UFPs have a measureable impact on physiological measures known to be altered in cases of acute cardiovascular morbidity. Moving forward, expanded use of personal exposure measures is recommended for prospective panel studies to minimize exposure misclassification. In addition, effort should be made to include more women in studies of the acute cardiovascular effects of UFPs as findings to date generally reflect responses in men.

Abstract  Two methods were used to distinguish airborne engineered nanomaterials from other airborne particles in a facility that produces nano-structured lithium titanate metal oxide powder. The first method involved off-line analysis of filter samples collected with conventional respirable samplers at each of seven locations (six near production processes and one outdoors). Throughout most of the facility and outdoors, respirable mass concentrations were low (<0.050 mg/m(3)) and were attributed to particles other than the nanomaterial (<10% by mass titanium determined with inductively coupled plasma atomic emission spectrometry). In contrast, in a single area with extensive material handling, mass concentrations were greatest (0.118 mg m(-3)) and contained up to 39% +/- 11% lithium titanium, indicating the presence of airborne nanomaterial. Analysis of the filter samples collected in this area by transmission electron microscope and scanning electron microscope revealed that the airborne nanomaterial was associated only with spherical aggregates (clusters of fused 10-80 nm nanoparticles) that were larger than 200 nm. This analysis also showed that nanoparticles in this area were the smallest particles of a larger distribution of submicrometer chain agglomerates likely from welding in an adjacent area of the facility. The second method used two, hand-held, direct-reading, battery-operated instruments to obtain a time series of very fine particle number (<300 nm), respirable mass, and total mass concentration, which were then related to activities within the area of extensive material handling. This activity-based monitoring showed that very fine particle number concentrations (<300 nm) had no apparent correlation to worker activities, but that sharp peaks in the respirable and total mass concentration coincided with loading a hopper and replacing nanomaterial collection bags. These findings were consistent with those from the filter-based method in that they demonstrate that airborne nanoparticles in this facility are dominated by "incidental" sources (e.g., welding or grinding), and that the airborne "engineered" product is predominately composed of particles larger than several hundred nanometers. The methods presented here are applicable to any occupational or environmental setting in which one needs to distinguish incidental sources from engineered product.

Abstract  Ambient particulate matter (PM) can increase the incidence of arrhythmia. However, the arrhythmogenic mechanism of PM is poorly understood. This study investigated the arrhythmogenic mechanism of PM. In Sprague-Dawley rats, QT interval was increased from 115.0±14.0 to 142.1±18.4ms (p=0.02) after endotracheal exposure of DEP (200μg/ml for 30min, n=5). Ventricular premature contractions were more frequently observed after DEP exposure (100%) than baseline (20%, p=0.04). These effects were prevented by pretreatment of N-acetylcysteine (NAC, 5mmol/L, n=3). In 12 Langendorff-perfused rat hearts, DEP infusion of 12.5μg/ml for 20min prolonged action potential duration (APD) at only left ventricular base increasing apicobasal repolarization gradients. Spontaneous early afterdepolarization (EAD) and ventricular tachycardia (VT) were observed in 8 (67%) and 6 (50%) hearts, respectively, versus no spontaneous triggered activity or VT in any hearts before DEP infusion. DEP-induced APD prolongation, EAD and VT were successfully prevented with NAC (5mmol/L, n=5), nifedipine (10μmol/L, n=5), and active Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) blockade, KN 93 (1μmol/L, n=5), but not by thapsigargin (200nmol/L) plus ryanodine (10μmol/L, n=5) and inactive CaMKII blockade, KN 92 (1μmol/L, n=5). In neonatal rat cardiomyocytes, DEP provoked ROS generation in dose dependant manner. DEP (12.5μg/ml) induced apoptosis, and this effect was prevented by NAC and KN 93. Thus, this study shows that in vivo and vitro exposure of PM induced APD prolongation, EAD and ventricular arrhythmia. These effects might be caused by oxidative stress and CaMKII activation.

Abstract  OBJECTIVES: The aim of this study was to determine the concentrations of respirable flour dusts and gliadin as well as gliadin-specific serum antibodies in exposed workers of Hamadan wheat flour mill factories.

METHODS: Blood samples from 95 exposed workers and 80 air samples from flour packing, husk packing, flour production and wheat unloading areas were collected. Respirable flour dust density was measured by a gravimetric method, and dust gliadin concentration as well as serum antibodies were determined by enzyme-linked immunosorbent assays.

RESULTS: The Time-weighted average (TWA) flour dust density was higher in all factories (1.56-4.68 mg/m(3)) compared with the threshold limit value (0.5 mg/m(3)) of ACGIH and showed a positive correlation with the gliadin concentration (p<0.05). Additionally, the respirable dust and gliadin concentrations were significantly higher at flour packing workstations compare with the other work areas. Moreover, the mean serum gliadin-specific IgA and IgG and total IgE antibodies were remarkably higher in exposed mill workers compared with the controls (p<0.05).

CONCLUSION: We clearly demonstrated that workers in Hamadan flour mills are in exposed to a hazardous level of respirable flour dust, receiving the highest level of dust and gliadin in flour packing areas. Furthermore, dust-exposed workers showed upper levels of serum antibodies indicating exposure to higher amounts of allergens than controls.

Abstract  Military personnel deployed in the Middle East have emphasized concerns regarding high levels of dust generated from blowing desert sand and the movement of troops and equipment. Airborne particulate matter levels (PM(10); PM < 10 μm) in the region may exceed 1500 μg/m(3), significantly higher than the military exposure guideline (MEG) of 50 μg/m(3). Increases in PM(10) have been linked to a rise in incidences of asthma, obstructive pulmonary disease, lung cancer, and cardiovascular diseases. Male Sprague-Dawley rats received a single intratracheal (IT) instillation of 1, 5, or 10 mg of Middle East PM(10) collected at a military occupied site in Kuwait, silica (positive control), or titanium dioxide (TiO(2); negative control) suspended in 400 μl sterile saline, or saline alone (vehicle control). Twenty-four hours, 3 d, 7 d and 6 mo postexposure (n = 15/group), organs including lung were evaluated for histopathological changes and for particle contaminants. Bronchoalveolar fluid (BALF) was also analyzed for cellular and biochemical parameters, including cytokines and chemokines. Instillation of silica resulted in early, pronounced, sustained inflammation indicated by significant increases in levels of total protein and neutrophils, and activities of lactate dehydrogenase activity and β-glucuronidase activity. Lower magnitude and transient changes using the same markers were observed in animals exposed to TiO(2) and Middle East PM(10). The results suggest that for acute exposures, this Middle East PM(10) is a nuisance-type dust with relatively low toxicity. However, since average deployment of military personnel to the Middle East is 180 d with potential for multiple follow-on tours, chronic exposure studies are needed to fully understand the pulmonary effects associated with Middle East PM exposure.

Abstract  Environmental tobacco smoke (ETS) and ambient air fine particulate matter (PM(2.5)) are both complex mixtures that have important adverse effects on the cardiovascular system. Although exposures to these complex mixtures have been studied individually, direct comparisons between the two has not been performed. In this study, the authors employed a novel, noninvasive ultrasound biomicroscopy method (UBM) to assess the effects of long-term, low-concentration inhalations of side-stream smoke (SS) and concentrated ambient PM(2.5) (CAPs) on plaque progression. ApoE(-/-) mice (n = 8/group) on high-fat chow (HFC), or normal chow (NC), were exposed to SS (PM = 450 microg/m(3)) or filtered air (FA) for 6 h/day, 5 days/week, for 6 months; CAPs exposure was at 134 microg/m(3) (NC only). Mortality during the SS exposure was greater in the HFC than in the NC, and SS significantly enhanced the effects of diet. No mortality was observed in CAPs-exposed mice. At 4 and 6 months, SS produced the greatest change in plaque area in the left common carotid artery (CCA) in HFC as compared to FA or NC, but not in the brachiocephalic artery. In contrast, CAPs exposure significantly enhanced plaque areas in brachiocephalic and left CCA at 3 and 6 months of exposure. The effect of SS was comparable in magnitude to that produced by CAPs at an average PM(2.5) mass concentration that was only 30% as high. In light of the employment of the same animal model, uniform inhalation exposure protocols, time schedules, a noninvasive monitoring protocol, and a parallel study design, these findings have broad applicability.

Abstract  PURPOSE: To investigate whether New York State employees who responded to the World Trade Center disaster were more likely to report asthma or lower respiratory symptoms (LRS; cough, wheeze, chest tightness, shortness of breath) than non-exposed employees, 2 years post-September 11.

METHODS: Participants (578 exposed, 702 non-exposed) completed mailed questionnaires in 2003. A unique exposure assessment method was used; exposure scores were divided at the mean (at/below, above). Poisson regression was used.

RESULTS: Exposure was associated with LRS, but not asthma. Participants with exposure scores at/below the mean had a twofold increased risk of most LRS. Those with scores above the mean had a three to fourfold increased risk. For scores above the mean, the magnitude of effect was consistently higher for smoke exposure.

CONCLUSIONS: Moderately exposed responders may experience health impacts from exposures in later stages of a disaster. Exposure to smoke may have had a greater lower respiratory impact than resuspended dust.

Abstract  CONTEXT: Diesel exhaust (DE) is an important component in traffic-related air pollution, associated with adverse health effects. DE generated at idling has been demonstrated to induce inflammation in human airways, in terms of inflammatory cell recruitment, enhanced expression of vascular endothelial adhesion molecules, cytokines, mitogen-activated protein kinases, and transcription factors in the bronchial epithelium.

OBJECTIVE: This study aimed to investigate airway inflammatory responses in healthy subjects exposed to DE generated during transient speed and engine load under the urban part of the European Transient Cycle.

METHODS: Fifteen healthy subjects were exposed to DE at an average particulate matter concentration of 270 µg/m(3) and filtered air for 1 h. Bronchoscopy with endobronchial mucosal biopsy sampling and airway lavage was performed 6 h postexposure. Results: Compared with filtered air, DE exposure caused an increased expression of the vascular endothelial adhesion molecules P-selectin and vascular cell adhesion molecule-1 (P  =  0.036 and P  =  0.030, respectively) in bronchial mucosal biopsies, together with increased numbers of bronchoalveolar lavage eosinophils (P  =  0.017).

CONCLUSIONS: DE generated under urban running conditions increased bronchial adhesion molecule expressions, together with the novel finding of bronchoalveolar eosinophilia, which has not been shown after exposure to DE at idling. Variations in airway inflammatory response to DE generated under diverse running condition may be related to differences in exhaust composition.

Abstract  Epidemiological studies typically using wide size range mass metrics (e.g. PM(10)) have demonstrated associations between airborne particulate matter and several adverse health outcomes. This approach ignores the fact that mass concentration may not correlate with regional lung dose, unlike the case of trace gases. When using measured particle size distributions as the basis for calculating regional lung dose, PM(10) mass concentration is found to be a good predictor of the mass dose in all regions of the lung, but is far less predictive of the surface area and particle number dose. On the other hand, measurements of particle number do not well predict mass dose, indicating that the chosen particle metric is likely to determine the health outcomes detectable by an epidemiological study. Consequently, epidemiological studies using mass metrics (PM(2.5) and PM(10)) may fail to recognise important health consequences of particulate matter exposure, leading to an underestimate of the public health consequences of particle exposure.

Abstract  Concrete grinding exposes workers to unacceptable levels of crystalline silica dust, known to cause diseases such as silicosis and possibly lung cancer. This study examined the influence of major factors of exposure and effectiveness of existing dust control methods by simulating field concrete grinding in an enclosed workplace laboratory. Air was monitored during 201 concrete grinding sessions while using a variety of grinders, accessories, and existing dust control methods, including general ventilation (GV), local exhaust ventilation (LEV), and wet grinding. Task-specific geometric mean (GM) of respirable crystalline silica dust concentrations (mg/m³ for LEV:HEPA-, LEV:Shop-vac-, wet-, and uncontrolled-grinding, while GV was off/on, were 0.17/0.09, 0.57/0.13, 1.11/0.44, and 23.1/6.80, respectively. Silica dust concentrations (mg/m³ using 100-125 mm (4-5 inch) and 180 mm (7 inch) grinding cups were 0.53/0.22 and 2.43/0.56, respectively. GM concentrations of silica dust were significantly lower for (1) GV on (66.0%) vs. off, and (2) LEV:HEPA- (99.0%), LEV:Shop-vac- (98.1%) or wet- (94.4%) vs. uncontrolled-grinding. Task-specific GM of respirable suspended particulate matter (RSP) concentrations (mg/m³ for LEV:HEPA-, LEV:Shop-vac-, wet-, and uncontrolled grinding, while GV was off/on, were 1.58/0.63, 7.20/1.15, 9.52/4.13, and 152/47.8, respectively. GM concentrations of RSP using 100-125 mm and 180 mm grinding cups were 4.78/1.62 and 22.2/5.06, respectively. GM concentrations of RSP were significantly lower for (1) GV on (70.2%) vs. off, and (2) LEV:HEPA- (98.9%), LEV:Shop-vac- (96.9%) or wet- (92.6%) vs. uncontrolled grinding. Silica dust and RSP were not significantly affected by (1) orientation of grinding surfaces (vertical vs. inclined); (2) water flow rates for wet grinding; (3) length of task-specific sampling time; or, (4) among cup sizes of 100, 115 or 125 mm. No combination of factors or control methods reduced an 8-hr exposure level to below the recommended criterion of 0.025 mg/m³ for crystalline silica, requiring further refinement in engineering controls, administrative controls, or the use of respirators.

Abstract  This study presents different research techniques linked together to improve our understanding of the particulate matter (PM) impacts on health. PM samples from the exhaust of different vehicles were collected by a versatile aerosol concentration enrichment system (VACES). Waterborne PM samples were collected with this technique, thus retaining the original physicochemical characteristics of aerosol particles. PM samples originated from a gasoline Euro 3 car and two diesel cars complying with the Euro 2 and Euro 4 standards, respectively. The Euro 2 diesel car operated consecutively on fossil diesel and biodiesel. The Euro 4 car was also retrofitted with a diesel particle filter. In total, five vehicle configurations and an equal number of samples were examined. Each sample was intratracheally instilled to 10 mice at two different dose levels (50 and 100 μL). The mice were analyzed 24 h after instillation for acute lung inflammation by bronchoalveolar lavage and also for hematological changes. Results show that a moderate but still significant inflammatory response is induced by PM samples, depending on the vehicle. Several organic and inorganic species, including benz(a)anthracene, chrysene, Mn, Fe, Cu, and heavy polycyclic aromatic hydrocarbons (PAHs), as well as the reactive oxygen species content of the PM suspensions are correlated to the observed responses. The study develops conceptual dose-response functions for the different vehicle configurations. These demonstrate that inflammatory response is not directly proportional to the mass dose level of the administered PM and that the relative toxicity potency depends on the dosage level.

Abstract  A deeper understanding of how the physical properties of particles regulate specific biological responses is becoming a crucial requirement for their successful biomedical application. To provide insights on their design and application, J774A.1 cells are exposed to particles with different diameters (430 nm, 1.9 μm and 4.8 μm), and the size effects on a series of cellular responses in macrophages are evaluated. Cellular uptake study demonstrates that nanosized particles accumulate in the cells at a faster rate, and with a higher surface area. Once the data are converted into the expression of particle volume, the maximum value is found with 1.9 μm particles instead of nanoparticles. Moreover, the uptake intermediates are also trapped, and the steps of particle internalization include filopodia sensing, skeleton rearrangement, and morphology change. Subsequent cellular trafficking reveals that only nanosized particles transport via lysosomal pathway, which is consistent with their uptake mechanisms. Furthermore, nanosized particles prefer to promote the secretion of Th1-specific molecule signals (e.g. IFN, IL-12) rather than immune suppressors. All these results, along with a couple of surprises, are discussed in the view of clinical practice. They are expected, in principle, to establish the basis of new design concepts for particle-based biomedical applications.

Abstract  Recent studies suggest that DNA oxidative damage be related to the chemical constituents of ambient particles. The purpose of this study was to examine whether particulate polycyclic aromatic hydrocarbons (PAHs) and quinone-structure chemicals increase body burden of oxidative stress in human exposed to heavy traffic volume. We recruited two nonsmoking security guards who worked at a university campus gate near a heavily trafficked road. Each subject wore a personal air sampler for 24h per day to estimate exposures to 24 PAHs and anthraquinone (AnQ) in PM(2.5). Daily pre- and post-work shift spot urines were collected for 29d from each subject. Urine samples were analyzed for 8-hydroxy-2'-deoxyguanosine (8-OHdG). Additionally, using 19 organic tracers other than 24 PAHs and AnQ, a receptor source apportionment model of chemical mass balance was applied to determine the contributions of sources on the PM: gasoline vehicle, diesel vehicle, coal burning, vegetable debris, cooking, natural gas and biomass burning. The relationship among urinary 8-OHdG, individual PAH, and AnQ was demonstrated as follows: the average urinary concentration of 8-OHdG was increased more than three times after 8-h work-shift than those before the work shift. All the 24 PAH and AnQ levels were positively and significantly associated with the post-work urinary 8-OHdG. The results from source apportionment suggest vehicular emission to be the dominant source of personal exposure to PM(2.5). Our finding indicates that personal air exposures to 24 individual PAHs and AnQ originating from traffic emissions are important in increasing oxidative burdens in human body.

Abstract  Commuting by bike has a clear health enhancing effect. Moreover, regular exercise is known to improve brain plasticity, which results in enhanced cognition and memory performance. Animal research has clearly shown that exercise upregulates brain-derived neurotrophic factor (BDNF - a neurotrophine) enhancing brain plasticity. Studies in humans found an increase in serum BDNF concentration in response to an acute exercise bout. Recently, more evidence is emerging suggesting that exposure to air pollution (such as particulate matter (PM)) is higher in commuter cyclists compared to car drivers. Furthermore, exposure to PM is linked to negative neurological effects, such as neuroinflammation and cognitive decline. We carried-out a cross-over experiment to examine the acute effect of exercise on serum BDNF, and the potential effect-modification by exposure to traffic-related air pollution. Thirty eight physically fit, non-asthmatic volunteers (mean age: 43, 26% women) performed two cycling trials, one near a major traffic road (Antwerp Ring, R1, up to 260,000 vehicles per day) and one in an air-filtered room. The air-filtered room was created by reducing fine particles as well as ultrafine particles (UFP). PM10, PM2.5 and UFP were measured. The duration (∼20min) and intensity of cycling were kept the same for each volunteer for both cycling trials. Serum BDNF concentrations were measured before and 30min after each cycling trial. Average concentrations of PM10 and PM2.5 were 64.9μg/m(3) and 24.6μg/m(3) in cycling near a major ring way, in contrast to 7.7μg/m(3) and 2.0μg/m(3) in the air-filtered room. Average concentrations of UFP were 28,180 particles/cm(3) along the road in contrast to 496 particles/cm(3) in the air-filtered room. As expected, exercise significantly increased serum BDNF concentration after cycling in the air-filtered room (+14.4%; p=0.02). In contrast, serum BDNF concentrations did not increase after cycling near the major traffic route (+0.5%; p=0.42). Although active commuting is considered to be beneficial for health, this health enhancing effect could be negatively influenced by exercising in an environment with high concentrations of PM. Whether this effect is also present with chronic exercise and chronic exposure must be further elucidated.

Abstract  Exposure to particulate matter is a risk factor for respiratory and cardiovascular diseases. However, the mechanisms underlying these effects are not well understood. Here, we compared the impact of diesel exhaust particles (DEP) on airway resistance, inflammation and oxidative stress in normal mice, or mice made hypertensive by implanting osmotic minipump infusing angiotensin II. On day 13 after the onset of infusion, angiotensin II induced significant increase in heart rate (P < 0.05) and systolic blood pressure (P < 0.0001). On the same day, mice were intratracheally instilled with either DEP (15 mu g/mouse) or saline. Twenty-four hour later, the measurement of airway reactivity to methacholine (0-10 mg/ml) in vivo by a forced oscillation technique showed a significant and dose dependent increase in airway resistance in normotensive mice exposed to DEP compared to those exposed to saline. In hypertensive mice, there was no difference in airway resistance in DEP versus saline exposed mice. However, following exposure to DEP, airway resistance significantly increased in normotensive versus hypertensive mice. Bronchoalveolar lavage (BAL) fluid analysis showed a significant increase in macrophage numbers in normotensive mice exposed to DEP compared to those exposed to saline, and to hypertensive mice exposed to DEP. Neutrophil numbers were significantly increased in both normotensive and hypertensive mice exposed to DEP compared with their respective control groups. Superoxide dismutase activity was significantly decreased following DEP exposure in both normotensive and hypertensive mice compared to their respective controls. However, total proteins, a marker for increase of epithelial permeability, and malondialdehyde, a reflection of lipid peroxidation, were only increased in normotensive mice exposed to DEP. Therefore, our data suggest that DEP do not aggravate airway resistance and inflammation in angiotensin II-induced hypertensive mice. On the contrary, at the dose of DEP and time point investigated, airway resistance, inflammation and oxidative stress are increased in normotensive compared to hypertensive mice. (C) 2012 Published by Elsevier Ireland Ltd.

Abstract  BACKGROUND: Children spend a significant amount of time in school. Little is known about the role of allergen exposure in school environments and asthma morbidity.

OBJECTIVES: The School Inner-City Asthma Study (SICAS) is a National Institutes of Health (NIH)-funded prospective study evaluating the school/classroom-specific risk factors and asthma morbidity among urban children.

METHODS/RESULTS: This article describes the design, methods, and important lessons learned from this extensive investigation. A single center is recruiting 500 elementary school-aged children, all of whom attend inner-city metropolitan schools. The primary hypothesis is that exposure to common indoor allergens in the classroom will increase the risk of asthma morbidity in children with asthma, even after controlling for home allergen exposures. The protocol includes screening surveys of entire schools and baseline eligibility assessments obtained in the spring prior to the academic year. Extensive baseline clinical visits are being conducted among eligible children with asthma during the summer prior to the academic school year. Environmental classroom/school assessments including settled dust and air sampling for allergen, mold, air pollution, and inspection data are collected twice during the academic school year and one home dust sample linked to the enrolled student. Clinical outcomes are measured every 3 months during the academic school year.

CONCLUSION: The overall goal of SICAS is to complete the first study of its kind to better understand school-specific urban environmental factors on childhood asthma morbidity. We also discuss the unique challenges related to school-based urban research and lessons being learned from recruiting such a cohort.

Abstract  BACKGROUND: Exposure to particulate matter (PM) air pollution may be an important environmental factor leading to exacerbations of inflammatory illnesses in the GI tract. PM can gain access to the gastrointestinal (GI) tract via swallowing of air or secretions from the upper airways or mucociliary clearance of inhaled particles.

METHODS: We measured PM-induced cell death and mitochondrial ROS generation in Caco-2 cells stably expressing oxidant sensitive GFP localized to mitochondria in the absence or presence of an antioxidant. C57BL/6 mice were exposed to a very high dose of urban PM from Washington, DC (200 μg/mouse) or saline via gastric gavage and small bowel and colonic tissue were harvested for histologic evaluation, and RNA isolation up to 48 hours. Permeability to 4 kD dextran was measured at 48 hours.

RESULTS: PM induced mitochondrial ROS generation and cell death in Caco-2 cells. PM also caused oxidant-dependent NF-κB activation, disruption of tight junctions and increased permeability of Caco-2 monolayers. Mice exposed to PM had increased intestinal permeability compared with PBS treated mice. In the small bowel, colocalization of the tight junction protein, ZO-1 was lower in the PM treated animals. In the small bowel and colon, PM exposed mice had higher levels of IL-6 mRNA and reduced levels of ZO-1 mRNA. Increased apoptosis was observed in the colon of PM exposed mice.

CONCLUSIONS: Exposure to high doses of urban PM causes oxidant dependent GI epithelial cell death, disruption of tight junction proteins, inflammation and increased permeability in the gut in vitro and in vivo. These PM-induced changes may contribute to exacerbations of inflammatory disorders of the gut.

Abstract  We demonstrate that there is great variation in the size range and chemical composition of metalliferous particulate matter (PM) present within petrochemical complex chimney stacks. Cascade impactor PM samples from seven size ranges (17, 14, 5, 2.5, 1.3, 0.67, and 0.33 μm) were collected from inside stacks within the San Roque complex which includes the largest oil refinery in Spain. SEM analysis demonstrates the PM to be mostly carbonaceous and aluminous fly ash and abundant fine metalliferous particles. The metals with the most extreme concentrations averaged over all size ranges were Ni (up to 3295 μg m(-3)), Cr (962 μg m(-3)), V (638 μg m(-3)), Zn (225 μg m(-3)), Mo (91 μg m(-3)), La (865 μg m(-3)), and Co (94 μg m(-3)). Most metal PM are strongly concentrated into the finest fraction (<0.33 μm), although emissions from some processes, such as purified terephthallic acid (PTA) production, show coarser size ranges. The fluid catalytic cracking stack shows high concentrations of La (>200 μg m(-3) in PM(0.67-1.3)), Cr and Ni in a relatively coarse PM size range (0.7-14 μm). Our unique database, directly sampled from chimney stacks, confirms that oil refinery complexes such as San Roque are a potent source of a variety of fine, deeply inhalable metalliferous atmospheric PM emissions.