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.
Purpose
The World Health Organisation (WHO) recently ranked air pollution as the major environmental cause of premature death. However, the significant potential health and societal costs of poor ...mental health in relation to air quality are not represented in the WHO report due to limited evidence. We aimed to test the hypothesis that long-term exposure to air pollution is associated with poor mental health.
Methods
A prospective longitudinal population-based mental health survey was conducted of 1698 adults living in 1075 households in South East London, from 2008 to 2013. High-resolution quarterly average air pollution concentrations of nitrogen dioxide (NO
2
) and oxides (NO
x
), ozone (O
3
), particulate matter with an aerodynamic diameter < 10 μm (PM
10
) and < 2.5 μm (PM
2.5
) were linked to the home addresses of the study participants. Associations with mental health were analysed with the use of multilevel generalised linear models, after adjusting for large number of confounders, including the individuals’ socioeconomic position and exposure to road-traffic noise.
Results
We found robust evidence for interquartile range increases in PM
2.5
, NO
x
and NO
2
to be associated with 18–39% increased odds of common mental disorders, 19–30% increased odds of poor physical symptoms and 33% of psychotic experiences only for PM
10
. These longitudinal associations were more pronounced in the subset of non-movers for NO
2
and NO
x
.
Conclusions
The findings suggest that traffic-related air pollution is adversely affecting mental health. Whilst causation cannot be proved, this work suggests substantial morbidity from mental disorders could be avoided with improved air quality.
BACKGROUND: Specific characteristics of particulate matter (PM) responsible for associations with respiratory health observed in epidemiological studies are not well established. High correlations ...among, and differential measurement errors of, individual components contribute to this uncertainty. OBJECTIVES: We investigated which characteristics of PM have the most consistent associations with acute changes in respiratory function in healthy volunteers. METHODS: We used a semiexperimental design to accurately assess exposure. We increased exposure contrast and reduced correlations among PM characteristics by exposing volunteers at five different locations: an underground train station, two traffic sites, a farm, and an urban background site. Each of the 31 participants was exposed for 5 hr while exercising intermittendy, three to seven times at different locations during March— October 2009. We measured PM₁₀ , PM₂.₅, particle number concentrations (PNC), absorbance, elemental/organic carbon, trace metals, secondary inorganic components, endotoxin content, gaseous pollutants, and PM oxidative potential. Lung function FEV₁ (forced expiratory volume in 1 sec), FVC (forced vital capacity), FEF₂₅_₇₅ (forced expiratory flow at 25-75% of vital capacity), and PEF (peak expiratory flow) and fractional exhaled nitric oxide (FENQ) were measured before and at three time points after exposure. Data were analyzed with mixed linear regression. RESULTS: An interquartile increase in PNC (33,000 particles/cm³) was associated with an 11% 95% confidence interval (CI): 5, 17% and 12% (95% CI: 6, 17%) FENO increase over baseline immediately and at 2 hr postexposure, respectively. A 7% (95% CI: 0.5, 14%) increase persisted until the following morning. These associations were robust and insensitive to adjustment for other pollutants. Similarly consistent associations were seen between FVC and FEV₁ with PNC, NO₂ (nitrogen dioxide), and NOX (nitrogen oxides). CONCLUSIONS: Changes in PNC, NO₂, and NOX were associated with evidence of acute airway inflammation (i. e., FENO) and impaired lung function. PM mass concentration and PM₁₀ oxidative potential were not predictive of the observed acute responses.
Particulate matter (PM) pollutant exposure, which induces oxidative stress and inflammation, and vitamin D insufficiency, which compromises immune regulation, are detrimental in asthma.
Mechanistic ...cell culture experiments were undertaken to ascertain whether vitamin D abrogates PM-induced inflammatory responses of human bronchial epithelial cells (HBECs) through enhancement of antioxidant pathways.
Transcriptome analysis, PCR and ELISA were undertaken to delineate markers of inflammation and oxidative stress; with comparison of expression in primary HBECs from healthy and asthmatic donors cultured with reference urban PM in the presence/absence of vitamin D.
Transcriptome analysis identified over 500 genes significantly perturbed by PM-stimulation, including multiple pro-inflammatory cytokines. Vitamin D altered expression of a subset of these PM-induced genes, including suppressing IL6. Addition of vitamin D suppressed PM-stimulated IL-6 production, although to significantly greater extent in healthy versus asthmatic donor cultures. Vitamin D also differentially affected PM-stimulated GM-CSF, with suppression in healthy HBECs and enhancement in asthmatic cultures. Vitamin D increased HBEC expression of the antioxidant pathway gene G6PD, increased the ratio of reduced to oxidised glutathione, and in PM-stimulated cultures decreased the formation of 8-isoprostane. Pre-treatment with vitamin D decreased CXCL8 and further decreased IL-6 production in PM-stimulated cultures, an effect abrogated by inhibition of G6PD with DHEA, supporting a role for this pathway in the anti-inflammatory actions of vitamin D.
In a study using HBECs from 18 donors, vitamin D enhanced HBEC antioxidant responses and modulated the immune response to PM, suggesting that vitamin D may protect the airways from pathological pollution-induced inflammation.
Implementation of regulatory standards has reduced exhaust emissions of particulate matter from road traffic substantially in the developed world. However, nonexhaust particle emissions arising from ...the wear of brakes, tires, and the road surface, together with the resuspension of road dust, are unregulated and exceed exhaust emissions in many jurisdictions. While knowledge of the sources of nonexhaust particles is fairly good, source-specific measurements of airborne concentrations are few, and studies of the toxicology and epidemiology do not give a clear picture of the health risk posed. This paper reviews the current state of knowledge, with a strong focus on health-related research, highlighting areas where further research is an essential prerequisite for developing focused policy responses to nonexhaust particles.
•Largest study to characterise personal BC exposure for professional drivers.•Participants exposures were 2.6 times higher at work compared to not at work.•Professional drivers experienced high peaks ...in exposure (>100 µg/m3) while driving.•Tunnels, location, day of week and time of shift were determinants of BC exposure.•Driving with windows closed significantly reduced drivers’ exposure.
Professional drivers working in congested urban areas are required to work near harmful traffic related pollutants for extended periods, representing a significant, but understudied occupational risk. This study collected personal black carbon (BC) exposures for 141 drivers across seven sectors in London. The aim of the study was to assess the magnitude and the primary determinants of their exposure, leading to the formulation of targeted exposure reduction strategies for the occupation. Each participant’s personal BC exposures were continuously measured using real-time monitors for 96 h, incorporating four shifts per participant. ‘At work’ BC exposures (3.1 ± 3.5 µg/m3) were 2.6 times higher compared to when ‘not at work’ (1.2 ± 0.7 µg/m3). Workers spent 19% of their time ‘at work driving’, however this activity contributed 36% of total BC exposure, highlighting the disproportionate effect driving had on their daily exposure. Taxi drivers experienced the highest BC exposures due to the time they spent working in congested central London, while emergency services had the lowest. Spikes in exposure were observed while driving and were at times greater than 100 µg/m3. The most significant determinants of drivers’ exposures were driving in tunnels, congestion, location, day of week and time of shift. Driving with closed windows significantly reduced exposures and is a simple behaviour change drivers could implement. Our results highlight strategies by which employers and local policy makers can reduce professional drivers’ exposure to traffic-related air pollution.
As the incidence of respiratory and allergic symptoms has been reported to be increased in children attending schools in close proximity to busy roads, it was hypothesised that PM from roadside ...schools would display enhanced oxidative potential (OP). Two consecutive one-week air quality monitoring campaigns were conducted at seven school sampling sites, reflecting roadside and urban background in London. Chemical characteristics of size fractionated particulate matter (PM) samples were related to the capacity to drive biological oxidation reactions in a synthetic respiratory tract lining fluid. Contrary to hypothesised contrasts in particulate OP between school site types, no robust size-fractionated differences in OP were identified due high temporal variability in concentrations of PM components over the one-week sampling campaigns. For OP assessed both by ascorbate (OP(AA) m(-3)) and glutathione (OP(GSH) m(-3)) depletion, the highest OP per cubic metre of air was in the largest size fraction, PM(1.9-10.2). However, when expressed per unit mass of particles OP(AA) µg(-1) showed no significant dependence upon particle size, while OP(GSH) µg(-1) had a tendency to increase with increasing particle size, paralleling increased concentrations of Fe, Ba and Cu. The two OP metrics were not significantly correlated with one another, suggesting that the glutathione and ascorbate depletion assays respond to different components of the particles. Ascorbate depletion per unit mass did not show the same dependence as for GSH and it is possible that other trace metals (Zn, Ni, V) or organic components which are enriched in the finer particle fractions, or the greater surface area of smaller particles, counter-balance the redox activity of Fe, Ba and Cu in the coarse particles. Further work with longer-term sampling and a larger suite of analytes is advised in order to better elucidate the determinants of oxidative potential, and to fuller explore the contrasts between site types.
Ambient particulate matter (PM) exposure is associated with respiratory and cardiovascular morbidity and mortality. To what extent such effects are different for PM obtained from different sources or ...locations is still unclear. This study investigated the in vitro toxicity of ambient PM collected at different sites in the Netherlands in relation to PM composition and oxidative potential.
PM was sampled at eight sites: three traffic sites, an underground train station, as well as a harbor, farm, steelworks, and urban background location. Coarse (2.5-10 μm), fine (< 2.5 μm) and quasi ultrafine PM (qUF; < 0.18 μm) were sampled at each site. Murine macrophages (RAW 264.7 cells) were exposed to increasing concentrations of PM from these sites (6.25-12.5-25-50-100 μg/ml; corresponding to 3.68-58.8 μg/cm2). Following overnight incubation, MTT-reduction activity (a measure of metabolic activity) and the release of pro-inflammatory markers (Tumor Necrosis Factor-alpha, TNF-α; Interleukin-6, IL-6; Macrophage Inflammatory Protein-2, MIP-2) were measured. The oxidative potential and the endotoxin content of each PM sample were determined in a DTT- and LAL-assay respectively. Multiple linear regression was used to assess the relationship between the cellular responses and PM characteristics: concentration, site, size fraction, oxidative potential and endotoxin content.
Most PM samples induced a concentration-dependent decrease in MTT-reduction activity and an increase in pro-inflammatory markers with the exception of the urban background and stop & go traffic samples. Fine and qUF samples of traffic locations, characterized by a high concentration of elemental and organic carbon, induced the highest pro-inflammatory activity. The pro-inflammatory response to coarse samples was associated with the endotoxin level, which was found to increase dramatically during a three-day sample concentration procedure in the laboratory. The underground samples, characterized by a high content of transition metals, showed the largest decrease in MTT-reduction activity. PM size fraction was not related to MTT-reduction activity, whereas there was a statistically significant difference in pro-inflammatory activity between Fine and qUF PM. Furthermore, there was a statistically significant negative association between PM oxidative potential and MTT-reduction activity.
The response of RAW264.7 cells to ambient PM was markedly different using samples collected at various sites in the Netherlands that differed in their local PM emission sources. Our results are in support of other investigations showing that the chemical composition as well as oxidative potential are determinants of PM induced toxicity in vitro.
Background Diesel exhaust particles (DEPs) are a major component of particulate matter in Europe's largest cities, and epidemiologic evidence links exposure with respiratory symptoms and asthma ...exacerbations. Respiratory reflexes are responsible for symptoms and are regulated by vagal afferent nerves, which innervate the airway. It is not known how DEP exposure activates airway afferents to elicit symptoms, such as cough and bronchospasm. Objective We sought to identify the mechanisms involved in activation of airway sensory afferents by DEPs. Methods In this study we use in vitro and in vivo electrophysiologic techniques, including a unique model that assesses depolarization (a marker of sensory nerve activation) of human vagus. Results We demonstrate a direct interaction between DEP and airway C-fiber afferents. In anesthetized guinea pigs intratracheal administration of DEPs activated airway C-fibers. The organic extract (DEP-OE) and not the cleaned particles evoked depolarization of guinea pig and human vagus, and this was inhibited by a transient receptor potential ankyrin-1 antagonist and the antioxidant N-acetyl cysteine. Polycyclic aromatic hydrocarbons, major constituents of DEPs, were implicated in this process through activation of the aryl hydrocarbon receptor and subsequent mitochondrial reactive oxygen species production, which is known to activate transient receptor potential ankyrin-1 on nociceptive C-fibers. Conclusions This study provides the first mechanistic insights into how exposure to urban air pollution leads to activation of guinea pig and human sensory nerves, which are responsible for respiratory symptoms. Mechanistic information will enable the development of appropriate therapeutic interventions and mitigation strategies for those susceptible subjects who are most at risk.
PDF
