Special issue of \u3ci\u3eAtmospheric Environment\u3c/i\u3e on findings from EPA’s Particulate Matter Supersites Program

In July 1997, the US Environmental Protection Agency (EPA) issued new National Ambient Air Quality Standards (NAAQS) for fine particulate matter (PM2.5, atmospheric particles with aerodynamic diameters less than 2.5 μm). The PM2.5 NAAQS was developed by the EPA based on the results of numerous epidemiological studies that found persistent associations between outdoor concentrations of particulate matter (PM) and significant adverse health effects. However, considerable uncertainty existed concerning mechanisms by which various classes of particles might cause adverse health effects, as well as more detailed information on the composition and concentrations of ambient fine PM, that would be critical in implementing the new standards

Personal and Ambient Air Pollution is Associated with Increased Exhaled Nitric Oxide in Children with Asthma

BACKGROUND: Research has shown associations between pediatric asthma outcomes and airborne particulate matter (PM). The importance of particle components remains to be determined. METHODS: We followed a panel of 45 schoolchildren with persistent asthma living in Southern California. Subjects were monitored over 10 days with offline fractional exhaled nitric oxide (Fe(NO)), a biomarker of airway inflammation. Personal active sampler exposures included continuous particulate matter < 2.5 μm in aerodynamic diameter (PM(2.5)), 24-hr PM(2.5) elemental and organic carbon (EC, OC), and 24-hr nitrogen dioxide. Ambient exposures included PM(2.5), PM(2.5) EC and OC, and NO(2). Data were analyzed with mixed models controlling for personal temperature, humidity and 10-day period. RESULTS: The strongest positive associations were between Fe(NO) and 2-day average pollutant concentrations. Per interquartile range pollutant increase, these were: for 24 μg/m(3) personal PM(2.5), 1.1 ppb Fe(NO) [95% confidence interval (CI), 0.1–1.9]; for 0.6 μg/m(3) personal EC, 0.7 ppb Fe(NO) (95% CI, 0.3–1.1); for 17 ppb personal NO(2), 1.6 ppb Fe(NO) (95% CI, 0.4–2.8). Larger associations were found for ambient EC and smaller associations for ambient NO(2). Ambient PM(2.5) and personal and ambient OC were significant only in subjects taking inhaled corticosteroids (ICS) alone. Subjects taking both ICS and antileukotrienes showed no significant associations. Distributed lag models showed personal PM(2.5) in the preceding 5 hr was associated with Fe(NO). In two-pollutant models, the most robust associations were for personal and ambient EC and NO(2), and for personal but not ambient PM(2.5). CONCLUSION: PM associations with airway inflammation in asthmatics may be missed using ambient particle mass, which may not sufficiently represent causal pollutant components from fossil fuel combustion

Air Pollution Particulate Matter Amplifies White Matter Vascular Pathology and Demyelination Caused by Hypoperfusion

Cerebrovascular pathologies are commonly associated with dementia. Because air pollution increases arterial disease in humans and rodent models, we hypothesized that air pollution would also contribute to brain vascular dysfunction. We examined the effects of exposing mice to nanoparticulate matter (nPM; aerodynamic diameter ≤200 nm) from urban traffic and interactions with cerebral hypoperfusion. C57BL/6 mice were exposed to filtered air or nPM with and without bilateral carotid artery stenosis (BCAS) and analyzed by multiparametric MRI and histochemistry. Exposure to nPM alone did not alter regional cerebral blood flow (CBF) or blood brain barrier (BBB) integrity. However, nPM worsened the white matter hypoperfusion (decreased CBF on DSC-MRI) and exacerbated the BBB permeability (extravascular IgG deposits) resulting from BCAS. White matter MRI diffusion metrics were abnormal in mice subjected to cerebral hypoperfusion and worsened by combined nPM+BCAS. Axonal density was reduced equally in the BCAS cohorts regardless of nPM status, whereas nPM exposure caused demyelination in the white matter with or without cerebral hypoperfusion. In summary, air pollution nPM exacerbates cerebrovascular pathology and demyelination in the setting of cerebral hypoperfusion, suggesting that air pollution exposure can augment underlying cerebrovascular contributions to cognitive loss and dementia in susceptible elderly populations

Augmentation of arginase 1 expression by exposure to air pollution exacerbates the airways hyperresponsiveness in murine models of asthma

Abstract Background Arginase overexpression contributes to airways hyperresponsiveness (AHR) in asthma. Arginase expression is further augmented in cigarette smoking asthmatics, suggesting that it may be upregulated by environmental pollution. Thus, we hypothesize that arginase contributes to the exacerbation of respiratory symptoms following exposure to air pollution, and that pharmacologic inhibition of arginase would abrogate the pollution-induced AHR. Methods To investigate the role of arginase in the air pollution-induced exacerbation of airways responsiveness, we employed two murine models of allergic airways inflammation. Mice were sensitized to ovalbumin (OVA) and challenged with nebulized PBS (OVA/PBS) or OVA (OVA/OVA) for three consecutive days (sub-acute model) or 12 weeks (chronic model), which exhibit inflammatory cell influx and remodeling/AHR, respectively. Twenty-four hours after the final challenge, mice were exposed to concentrated ambient fine particles plus ozone (CAP+O3), or HEPA-filtered air (FA), for 4 hours. After the CAP+O3 exposures, mice underwent tracheal cannulation and were treated with an aerosolized arginase inhibitor (S-boronoethyl-L-cysteine; BEC) or vehicle, immediately before determination of respiratory function and methacholine-responsiveness using the flexiVent®. Lungs were then collected for comparison of arginase activity, protein expression, and immunohistochemical localization. Results Compared to FA, arginase activity was significantly augmented in the lungs of CAP+O3-exposed OVA/OVA mice in both the sub-acute and chronic models. Western blotting and immunohistochemical staining revealed that the increased activity was due to arginase 1 expression in the area surrounding the airways in both models. Arginase inhibition significantly reduced the CAP+O3-induced increase in AHR in both models. Conclusions This study demonstrates that arginase is upregulated following environmental exposures in murine models of asthma, and contributes to the pollution-induced exacerbation of airways responsiveness. Thus arginase may be a therapeutic target to protect susceptible populations against the adverse health effects of air pollution, such as fine particles and ozone, which are two of the major contributors to smog