Airway macrophage (AM) phagocytosis is impaired in severe asthma. Prostaglandin (PG) E2 and D2 are increased in severe asthma and suppress AM phagocytic function in vitro. In this study, we sought ...evidence for PG-mediated impairment of phagocytosis of inhalable carbonaceous particulate matter (PM) by AM in children with severe asthma compared with mild asthmatics and healthy controls.
AM were obtained from children with asthma and healthy controls using induced sputum. AM carbon area (μm(2)) was assessed by image analysis. In a subgroup of asthmatics, urinary PGE2 and PGD2 metabolites were measured by high-performance liquid chromatography, and PM exposure at the home address was modelled. Phagocytosis of PM by human monocyte-derived macrophages and rat AM was assessed in vitro by image analysis.
AM carbon was 51% lower in children with moderate-to-severe asthma (n=36) compared with mild asthmatics (n=12, p<0.01) and healthy controls (n=47, p<0.01). There was no association between modelled PM exposure and AM carbon in 33 asthmatics who had a urine sample, but there was an inverse association between AM carbon and urinary metabolites of PGE2 and D2 (n=33, rs=-0.40, p<0.05, and rs=-0.44, p<0.01). PGE2 10(-6) M, but not PGD2 10(-6) M, suppressed phagocytosis of PM10 by human macrophages in vitro (p<0.05 vs control). PGE2 10(-6) M also suppressed phagocytosis of PM10 by rat AM in vitro (p<0.01 vs control).
Phagocytosis of inhaled carbonaceous PM by AMs is impaired in severe asthma. PGE2 may contribute to impaired AM phagocytic function in severe asthma.
Background: Adverse cardiorespiratory health is associated with exposure to ambient particulate matter (PM). The highest PM concentrations in London occur in proximity to waste transfer stations ...(WTS), sites that experience high numbers of dust-laden, heavy-duty diesel vehicles transporting industrial and household waste. Objective: Our goal was to quantify the contribution of WTS emissions to ambient PM mass concentrations and oxidative potential. Methods: PM with a diameter < 10 μm (PM₁₀) samples were collected daily close to a WTS. PM₁₀ mass concentrations measurements were source apportioned to estimate local versus background sources. PM oxidative potential was assessed using the extent of antioxidant depletion from a respiratory tract lining fluid model. Total trace metal and bioavailable iron concentrations were measured to determine their contribution to PM oxidative potential. Results: Elevated diurnal PM₁₀ mass concentrations were observed on all days with WTS activity (Monday—Saturday). Variable PM oxidative potential, bioavailable iron, and total metal concentrations were observed on these days. The contribution of WTS emissions to PM at the sampling site, as predicted by microscale wind direction measurements, was correlated with ascorbate (r = 0.80; p = 0.030) and glutathione depletion (r = 0.76; p = 0.046). Increased PM oxidative potential was associated with aluminum, lead, and iron content. Conclusions: PM arising from WTS activity has elevated trace metal concentrations and, as a consequence, increased oxidative potential. PM released by WTS activity should be considered a potential health risk to the nearby residential community.
Air Pollution and Asthma Pfeffer, Paul E.; Mudway, Ian S.; Grigg, Jonathan
Chest,
April 2021, 2021-04-00, Letnik:
159, Številka:
4
Journal Article
Recenzirano
There is global concern regarding the harmful impact of polluted air on the respiratory health of patients with asthma. Multiple epidemiologic studies have shown ongoing associations between high ...levels of air pollution and poor early life lung growth, development of allergic sensitization, development of asthma, airway inflammation, acutely impaired lung function, respiratory tract infections, and asthma exacerbations. However, studies have often yielded inconsistent findings, and not all studies have found significant associations; this may be related to both variations in statistical, measurement, and modeling methodologies between studies as well as differences in the concentrations and composition of air pollution globally. Overall, this variation in findings suggests we still do not fully understand the effects of ambient pollution on the lungs and on the evolution and exacerbation of airway diseases. There is clearly a need to augment epidemiologic studies with experimental studies to clarify the underlying mechanistic basis for the adverse responses reported and to identify the key gaseous and particle-related components within the complex air pollution mixture driving these outcomes. Some progress toward these aims has been made. This article reviews studies providing an improved understanding of causal pathways linking air pollution to asthma development and exacerbation. The article also considers potential strategies to reduce asthma morbidity and mortality through regulation and behavioral/pharmacologic interventions, including a consideration of pollutant avoidance strategies and antioxidant and/or vitamin D supplementation.
Exposure to particulate matter (PM) air pollution especially derived from traffic is associated with increases in cardiorespiratory morbidity and mortality. In this study, we evaluated the ability of ...novel vehicle cabin air inlet filters to reduce diesel exhaust (DE)-induced symptoms and markers of inflammation in human subjects.
Thirty healthy subjects participated in a randomized double-blind controlled crossover study where they were exposed to filtered air, unfiltered DE and DE filtered through two selected particle filters, one with and one without active charcoal. Exposures lasted for one hour. Symptoms were assessed before and during exposures and lung function was measured before and after each exposure, with inflammation assessed in peripheral blood five hours after exposures. In parallel, PM were collected from unfiltered and filtered DE and assessed for their capacity to drive damaging oxidation reactions in a cell-free model, or promote inflammation in A549 cells.
The standard particle filter employed in this study reduced PM10 mass concentrations within the exposure chamber by 46%, further reduced to 74% by the inclusion of an active charcoal component. In addition use of the active charcoal filter was associated by a 75% and 50% reduction in NO2 and hydrocarbon concentrations, respectively. As expected, subjects reported more subjective symptoms after exposure to unfiltered DE compared to filtered air, which was significantly reduced by the filter with an active charcoal component. There were no significant changes in lung function after exposures. Similarly diesel exhaust did not elicit significant increases in any of the inflammatory markers examined in the peripheral blood samples 5 hour post-exposure. Whilst the filters reduced chamber particle concentrations, the oxidative activity of the particles themselves, did not change following filtration with either filter. In contrast, diesel exhaust PM passed through the active charcoal combination filter appeared less inflammatory to A549 cells.
A cabin air inlet particle filter including an active charcoal component was highly effective in reducing both DE particulate and gaseous components, with reduced exhaust-induced symptoms in healthy volunteers. These data demonstrate the effectiveness of cabin filters to protect subjects travelling in vehicles from diesel exhaust emissions.
Numerous epidemiological studies have shown health effects related to short- and long-term exposure to elevated levels of ambient particulate matter (PM). It is not clear however which specific ...characteristics (e.g., size, components) or sources of PM are responsible for the observed effects.
The aim of RAPTES (Risk of Airborne Particles: a Toxicological–Epidemiological hybrid Study) was to investigate which specific physical, chemical or oxidative characteristics of ambient PM are associated with adverse effects of PM on health. This was done by performing experimental exposure of human volunteers to air pollution at several real-world settings that had high contrast and low correlation between several PM characteristics.
For this goal, eight sites in the Netherlands that differed in local PM emission sources were chosen for extensive air pollution characterization. Measurement sites included an underground train station, three different road traffic sites, an animal farm, a sea harbor, a site located in the vicinity of steelworks, and an urban background site. Five- to six-hours average concentration measurements at each site were made between June 2007 and October 2009. We measured PM
10, PM
2.5, particle number concentration (PNC), oxidative potential of PM, absorbance, endotoxin content, as well as elemental and chemical composition of PM, and gaseous pollutants concentrations. This paper presents a detailed characterization of particulate air pollution at the sampling sites.
We found significant differences in all PM characteristics between the sites. The underground train station, compared to each outdoor location, had substantially higher concentrations of nearly all PM characteristics. The average PM
10 and PM
2.5 mass concentrations at the underground train station were 394 μg m
−3 and 137 μg m
−3, respectively, which was 14.1 and 7.6 times higher than the urban background. The sum of the concentrations of trace metals in fine and coarse PM was nearly 20 times above the outdoor levels. Elemental carbon (EC) was elevated at the underground site in the fine but also in the coarse mode, in contrast to the traffic sites where EC was predominantly found in fine PM. The highest concentrations and contrasts in PNC were at the traffic sites (between 45,000 and 80,000 particles cm
−3), which was several times higher than measured at any other site. Correlations of PNC with metals, PM
10, PM
2.5 and absorbance were low to moderate, while correlations between PM
10, PM
2.5 and the metals Cu and Fe were high. After excluding the underground train station data, correlations between PM10, EC and metals decreased whereas the correlation between PNC and EC increased.
We conclude that we were able to successfully identify and characterize real-world situations with very different particle characteristics. High contrast and low correlations between PM characteristics, as well as consistency of these differences across sampling campaigns, provide a good basis for identifying health relevant PM characteristics in the upcoming analysis.
► We successfully identified and characterized real-world situations with very different PM characteristics. ► Underground train station had the highest concentrations of almost every PM characteristic. ► Correlations between PM characteristics were low enough to investigate their independent health effects.
Objectives Vitamin C is an important low-molecular weight antioxidant at the air-lung interface. Despite its critical role as a sacrificial antioxidant, little is known about its transport into the ...respiratory tract lining fluid (RTLF), or the underlying airway epithelial cells. While several vitamin C transporters have been identified, such as sodium-ascorbate cotransporters (SVCT1/2) and glucose transporters (GLUTs), the latter transporting dehydroascorbate, knowledge of their protein distribution within the human lung is limited, in the case of GLUTs or unknown for SVCTs. Setting and participants Protein expression of vitamin C transporters (SVCT1/2 and GLUT1-4) was examined by immunohistochemistry in endobronchial biopsies, and by FACS in airway leucocytes from lavage fluid, obtained from 32 volunteers; 16 healthy and 16 mild asthmatic subjects. In addition, antioxidant concentrations were determined in RTLF. The study was performed at one Swedish centre. Primary and secondary outcome measures The primary outcome measure was to establish the location of vitamin C transporters in the human airways. As secondary outcome measures, RTLF vitamin C concentration was measured and related to transporter expression, as well as bronchial epithelial inflammatory and goblet cells numbers. Results Positive staining was identified for SVCT1 and 2 in the vascular endothelium. SVCT2 and GLUT2 were present in the apical bronchial epithelium, where SVCT2 staining was predominately localised to goblet cells and inversely related to RTLF vitamin C concentrations. Conclusions This experimental study is the first to demonstrate protein expression of GLUT2 and SVCT2 in the human bronchial epithelium. A negative correlation between SVCT2-positive goblet cells and bronchial RTLF vitamin C concentrations suggests a possible role for goblet cells in regulating the extracellular vitamin C pool.
Objectives Increases in ambient particulate matter (PM) have been associated with an elevated risk of stroke, myocardial ischaemia and coronary heart disease, with activation of blood coagulation ...likely playing an important role. PM-mediated activation of two major activation pathways of coagulation provides a potential mechanism for the observed association between PM and cardiovascular disease. However, it remains unclear which specific characteristics and components of air pollution are responsible. Methods In order to investigate those characteristics and components, we semiexperimentally exposed healthy adult volunteers at five different locations with increased contrasts and reduced correlations among PM characteristics. Volunteers were exposed for 5 h, exercising intermittently, 3–7 times at different sites from March to October 2009. On site, we measured PM mass and number concentration, its oxidative potential (OP), content of elemental/organic carbon, trace metals, sulphate, nitrate and gaseous pollutants (ozone, nitrogen oxides). Before and 2 and 18 h after exposure we sampled blood from the participants and measured thrombin generation using the calibrated automated thrombogram. Results We found that thrombin generation increases in the intrinsic (FXII-mediated) blood coagulation pathway in relation to ambient air pollution exposure. The associations with NO2, nitrate and sulphate were consistent and robust, insensitive to adjustment for other pollutants. The associations with tissue factor-mediated thrombogenicity were not very consistent. Conclusions Ex vivo thrombin generation was associated with exposure to NO2, nitrate and sulphate, but not PM mass, PM OP or other measured air pollutants.
Context: Proximity to traffic, particularly to diesel-powered vehicles, has been associated with inducing and enhancing allergies. To investigate the basis for this association, we performed ...controlled exposures of allergic rhinitics to diesel exhaust (DE) at a dose known to be pro-inflammatory in healthy individuals.
Objective: We hypothesized that diesel-exhaust exposure would augment lower airway inflammation in allergic rhinitics.
Materials and methods: Fourteen allergic rhinitics were exposed in a double-blinded, randomized trial to DE (100 μg/m
3
PM
10
) and filtered air for 2 h on separate occasions. Bronchoscopy with endobronchial mucosal biopsies and airway lavage was performed 18 h post-exposure, and inflammatory markers were assessed.
Results: No evidence of neutrophilic airway inflammation was observed post-diesel, however, a small increase in myeloperoxidase was found in bronchoalveolar lavage (p = 0.032). We found no increases in allergic inflammatory cells. Reduced mast cell immunoreactivity for tryptase was observed in the epithelium (p = 0.013) parallel to a small decrease in bronchial wash stem cell factor (p = 0.033).
Discussion and conclusion: DE, at a dose previously shown to cause neutrophilic inflammation in healthy individuals, induced no neutrophilic inflammation in the lower airways of allergic rhinitics, consistent with previous reports in asthmatics. Although there was no increase in allergic inflammatory cell numbers, the reduction in tryptase in the epithelium may indicate mast cell degranulation. However, this occurred in the absence of allergic symptoms. These data do not provide a simplistic explanation of the sensitivity in rhinitics to traffic-related air pollution. The role of mast cells requires further investigation.
The aim of the study was to characterize ozone-induced antioxidant responses in the human airway, including the resident leukocyte population, bronchial mucosa, and respiratory-tract lining fluids. ...Fifteen healthy subjects were exposed to 0.2 ppm ozone for 2 h, with bronchial wash, bronchoalveolar lavage, and biopsy sampling performed 6 h postexposure. Nasal lavage was also performed at multiple time points pre- and postexposure to evaluate responses during the actual exposure period. During the ozone challenge significant losses of nasal lining fluid urate and vitamin C were observed, which resolved 6 h postexposure. At this time point, increased numbers of neutrophils and enhanced concentrations of total glutathione, vitamin C, and urate were seen in bronchial airway lavages. In bronchoalveolar lavage, increased concentrations of total glutathione, vitamin C, urate, α-tocopherol, and extracellular superoxide dismutase occurred 6 h post ozone. In alveolar leukocytes significant losses of glutathione were observed, whereas ascorbate concentrations in endobronchial mucosal biopsies were elevated after ozone at this time. These data demonstrate that ozone elicits a broad spectrum of airway antioxidant responses, with initial losses of vitamin C and urate followed by a phase of augmentation of low-molecular-weight antioxidant concentrations at the air-lung interface. The temporal association between the increased RTLF glutathione following ozone and the loss of this thiol from macrophages implies a mobilization to the lung surface, despite the absence of a quantitative association. We propose this constitutes an acute protective adaptation to ozone.
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