Divergent effects of urban particulate air pollution on allergic airway responses in experimental asthma: a comparison of field exposure studies.
ABSTRACT BACKGROUND: Increases in ambient particulate matter of aerodynamic diameter of 2.5 mum (PM2.5) are associated with asthma morbidity and mortality. The overall objective of this study was to test the hypothesis that PM2.5 derived from two distinct urban U.S. communities would induce variable responses to aggravate airway symptoms during experimental asthma. METHODS: We used a mobile laboratory to conduct community-based inhalation exposures to laboratory rats with ovalbumin-induced allergic airways disease. In Grand Rapids exposures were conducted within 60 m of a major roadway, whereas the Detroit was located in an industrial area more than 400 m from roadways. Immediately after nasal allergen challenge, Brown Norway rats were exposed by whole body inhalation to either CAPs or filtered air for 8 h (7:00 AM - 3:00 PM). Both ambient and concentrated PM2.5 was assessed for mass, size fractionation, and major component analyses, and trace element content. Sixteen hours after exposures, bronchoalveolar lavage fluid (BALF) and lung lobes were collected and evaluated for airway inflammatory and mucus responses. RESULTS: Similar CAPs mass concentrations were generated in Detroit (542 mug/m3) and Grand Rapids (519 mug/m3). Exposure to CAPs at either site had no effects in lungs of non-allergic rats. In contrast, asthmatic rats had 200% increases in airway mucus and had more BALF neutrophils (250% increase), eosinophils (90%), and total protein (300%) compared to controls. Exposure to Detroit CAPs enhanced all allergic inflammatory endpoints by 30-100%, whereas inhalation of Grand Rapids CAPs suppressed all allergic responses by 50%. Detroit CAPs were characterized by high sulfate, smaller sized particles and were derived from local combustion sources. Conversely Grand Rapids CAPs were derived primarily from motor vehicle sources. CONCLUSIONS: Despite inhalation exposure to the same mass concentration of urban PM2.5, disparate health effects can be elicited in the airways of sensitive populations such as asthmatics. Modulation of airway inflammatory and immune responses is therefore dependent on specific chemical components and size distributions of urban PM2.5. Our results suggest that air quality standards based on particle speciation and sources may be more relevant than particle mass to protect human health from PM exposure.
Article: Regulation of cytokine production in human alveolar macrophages and airway epithelial cells in response to ambient air pollution particles: further mechanistic studies.[show abstract] [hide abstract]
ABSTRACT: In order to better understand how ambient air particulate matter (PM) affect lung health, the two main airway cell types likely to interact with inhaled particles, alveolar macrophages (AM) and airway epithelial cells have been exposed to particles in vitro and followed for endpoints of inflammation, and oxidant stress. Separation of Chapel Hill PM 10 into fine and coarse size particles revealed that the main proinflammatory response (TNF, IL-6, COX-2) in AM was driven by material present in the coarse PM, containing 90-95% of the stimulatory material in PM10. The particles did not affect expression of hemoxygenase-1 (HO-1), a sensitive marker of oxidant stress. Primary cultures of normal human bronchial epithelial cells (NHBE) also responded to the coarse fraction with higher levels of IL-8 and COX-2, than induced by fine or ultrafine PM. All size PM induced oxidant stress in NHBE, while fine PM induced the highest levels of HO-1 expression. The production of cytokines in AM by both coarse and fine particles was blocked by the toll like receptor 4 (TLR4) antagonist E5531 involved in the recognition of LPS and Gram negative bacteria. The NHBE were found to recognize coarse and fine PM through TLR2, a receptor with preference for recognition of Gram positive bacteria. Compared to ambient PM, diesel PM induced only a minimal cytokine response in both AM and NHBE. Instead, diesel suppressed LPS-induced TNF and IL-8 release in AM. Both coarse and fine ambient air PM were also found to inhibit LPS-induced TNF release while silica, volcanic ash or carbon black had no inhibitory effect. Diesel particles did not affect cytokine mRNA induction nor protein accumulation but interfered with the release of cytokine from the cells. Ambient coarse and fine PM, on the other hand, inhibited both mRNA induction and protein production. Exposure to coarse and fine PM decreased the expression of TLR4 in the macrophages. Particle-induced decrease in TLR4 and hyporesponsiveness to LPS may be related to LPS tolerance induced by low levels of LPS.Toxicology and Applied Pharmacology 10/2005; 207(2 Suppl):269-75. · 4.45 Impact Factor
Article: Residential proximity to a major roadway is associated with features of asthma control in children.[show abstract] [hide abstract]
ABSTRACT: While several studies suggest that traffic-related air pollutants are detrimental for respiratory health, few studies have examined relationships between residential proximity to a major roadway and asthma control in children. Furthermore, a major limitation of existing research is reliance on self-reported outcomes. We therefore determined the spatial relationship between the distance from a major roadway and clinical, physiologic and inflammatory features of asthma in a highly characterized sample of asthmatic children 6-17 years of age across a wide range of severities. We hypothesized that a closer residential proximity to a major roadway would be associated with increased respiratory symptoms, altered pulmonary function and a greater magnitude of airway and systemic inflammation. 224 children 6-17 years with confirmed asthma completed questionnaires and underwent spirometry, plethysmography, exhaled nitric oxide determination, exhaled breath condensate collection and venipuncture. Residential distance from a major roadway was determined by mapping the geographic coordinates of the residential address in Geographic Information System software. The distance between the home address and the nearest major roadway was calculated according to the shortest distance between the two points (i.e., "as the crow flies"). Asthmatic children living in closer proximity to a major roadway had an increased frequency of wheezing associated with increased medication requirements and more hospitalizations even after controlling for potential confounders. These children also had increased airway resistance, increased airway inflammation reflected by a lower breath condensate pH, and higher plasma EGF concentrations. These findings suggest that closer residential proximity to a major roadway is associated with poorer asthma control in school-age children. Assessment of residential proximity to major roadways may be useful in the clinical evaluation of asthma in children.PLoS ONE 01/2012; 7(5):e37044. · 4.09 Impact Factor
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ABSTRACT: A systematic approach was used to quantify the metals present in particulate matter emissions associated with on-road motor vehicles. Consistent sampling and chemical analysis techniques were used to determine the chemical composition of particulate matter less than 10 microm in aerodynamic diameter (PM10*) and particulate matter less than 2.5 microm in aerodynamic diameter (PM2.5), including analysis of trace metals by inductively coupled plasma mass spectrometry (ICP-MS). Four sources of metals were analyzed in emissions associated with motor vehicles: tailpipe emissions from gasoline- and diesel-powered vehicles, brake wear, tire wear, and resuspended road dust. Profiles for these sources were used in a chemical mass balance (CMB) model to quantify their relative contributions to the metal emissions measured in roadway tunnel tests in Milwaukee, Wisconsin. Roadway tunnel measurements were supplemented by parallel measurements of atmospheric particulate matter and associated metals at three urban locations: Milwaukee and Waukesha, Wisconsin, and Denver, Colorado. Ambient aerosol samples were collected every sixth day for one year and analyzed by the same chemical analysis techniques used for the source samples. The two Wisconsin sites were studied to assess the spatial differences, within one urban airshed, of trace metals present in atmospheric particulate matter. The measurements were evaluated to help understand source and seasonal trends in atmospheric concentrations of trace metals. ICP-MS methods have not been widely used in analyses of ambient aerosols for metals despite demonstrated advantages over traditional techniques. In a preliminary study, ICP-MS techniques were used to assess the leachability of trace metals present in atmospheric particulate matter samples and motor vehicle source samples in a synthetic lung fluid.Research report (Health Effects Institute) 04/2006;