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Final report
TOverall objectives of the project:
Breathing elevated concentrations of microscopic air pollution particles has been shown to
have adverse effects on respiratory and cardiac health. Consequently, the concentrations
of these particles in the air we breathe are regulated within the member states of the
European Union. The air quality standards are based on the concentration of particles in
the air, yet it is clear that not all particles are alike. For example in a recent children’s
health study, allergic and respiratory symptoms were found to be greatest in children who
attended schools near busy roads despite overall particle concentrations being similar
across all of the schools examined. This observation suggested that traffic related particles
might be especially detrimental to health.
In the current study we examined whether this
was true by collecting particles from sites throughout Europe, including four of the schools
from the ISAAC II children’s health study, where there were clear differences in traffic. We
wished to examine whether there were differences in composition of particles collected
from sites with heavy versus low traffic, or between sites with differences in diesel and
gasoline engine use. In addition, we attempted to demonstrate that any difference in
particle composition would affect their capacity to cause inflammation or damaging
oxidation reactions in the lung using a range of experimental models. The capacity of these
ambient particles to cause toxicity was compared with fresh gasoline and diesel particles,
collected under controlled conditions.
Experimental approach and working method:
To address these issues we collected airborne particles, of differing size from various sites
throughout Europe: five sites in the Netherlands, four schools and one road tunnel, two sites
in Germany, and one site each in Italy and Sweden. Particle sampling was performed in the
majority of sites on at least four occasions over a year The sites were selected for clear
differences in traffic density and type. Particles were chemically analyzed prior to testing in a
range of models. These experimental models examined the hypothesis that the health effects
of inhaled particles are related to their capacity to elicit inflammatory responses in the lung,
which in turn is stimulated by their capacity to cause oxidation reactions, which itself is a
function of their composition. After screening all the particles a small subset that displayed
contrasts in their pro-inflammatory, pro-oxidant and compositional characteristics were
tested to determine their capacity to cause inflammation. A smaller number of samples were
tested in humans by adding the particles to the airways and examining their capacity to cause
inflammation. Further human studies were performed by exposing healthy (young and elderly
adults), asthmatic subjects and patients with chronic obstructive pulmonary disease (COPD)
to controlled diesel exhaust exposures. Similar to the previous studies airway and systemic
inflammation was assessed in these subjects. Finally, attempts were made to link the
chemical and toxicological results obtained in this study with the previously observed health
effects observed in the children respiratory health study at the four school sites in the
Netherlands.
Achievements and results:
1. We found that the pro-oxidant and pro-inflammatory characteristics of ambient
particles varied considerably between different sites when particles were compared at
an equal mass. This was related to differences in particle composition.
2. The activity of particles at a particular site varied considerably throughout a year, but
despite this there were still clear differences between particles from different sites.
3. Generally particles from sites with high traffic were more active than those from low
traffic sites.
4. Whilst certain studies have suggested that particles with an aerodynamic diameter
between 0.1-2.5um might drive most of the reported health effects we found that
larger particles in the range 2.5-10um were also highly reactive.
5. We found that healthy subjects displayed airway inflammation when exposed to fresh
diesel exhaust particles, despite these having a low activity compared with ambient
material. (
6. We derived preliminary evidence that particle activity, not just ambient
concentration, could be related to the magnitude of respiratory and allergic symptoms
in children attending schools near busy roads.
7. This study is the first to successfully integrate the disciplines of particle toxicity with
epidemiological health effect assessment.
Progress report 2002 - 2003
This aim of this project is to improve understanding of the adverse effects of ambient and motor engine generated particles. Particles, collected in a high volume sampling campaign across Europe will be extensively characterised by chemical composition, size, number and metal content. These data will then be used to interpret the effects the particles have in a range of experimental models, including in vitro, cell culture, animal and human challenge experiments. In summary, the overall objectives of this research project are:
To assess the toxicological and inflammatory potential of ambient suspended particles (collected sites across Europe with contrasting traffic intensity) in comparison with diesel and gasoline engine particles. To relate these findings, made in in-vitro and in-vivo animal and human studies, to the physico-chemical characteristics of particulates. To relate these data to the previously demonstrated effects of exhaust emissions on human airways. To undertake a comparison of these new data in relation to the population based epidemiological findings of adverse health effects of ambient particles.
Results and milestones
Work package I was directed at collection and characterization of ambient and engine particulate matter (PM). This was achieved using high volume samplers which sampled European ambient PM from several sites in Munich, Rome, the Netherlands and Northern Sweden. Additionally, diesel engine and gasoline particulates have been sampled. The particulates were then physically and chemically characterised in detail. These particles have subsequently been forwarded to other partner members for them to evaluate their chemical and biomedical reactions within subsequent work packages.
Work package II. This work package was directed towards toxicological screening of the PM using in-vitro techniques. The groups in London, Edinburgh and Rome used different techniques to clarify oxidative, pro-inflammatory and DNA-transcription related actions induced by the sampled PM. It was demonstrated that particles sampled from different places showed large differences in their capacity to produce reactive responses in these models. Additionally, not only the fine particles but also slightly more coarse particles produced such effects.
Work package III was directed towards evaluating the mechanisms by which the chemical and biological mediated by the air pollution particles. The involvement of oxidative stress pathways and certain transcription factor and DNA associated mechanisms have been shown. Complementary in-depth work is currently ongoing.
Work package IV. The preparation for the overall toxicity and PM composition evaluation is under progress. The completion of this work package is one of the final stages and outcomes of the project, as it rests on the delivery of all the experimental and descriptive data.
Work packages V and VI included diesel engine exhaust exposures in human subjects. It has been demonstrated that certain groups of asthmatics respond with different acute inflammatory response as compared with healthy subjects. A detailed investigation of the reasons behind this is ongoing. People with Chronic Obstructive Pulmonary Disease (COPD) have been investigated in terms of respiratory and cardiovascular responses, and compared with an age matched elderly group of non-smokers. This is intended to yield new information about how the elderly healthy and respiratory severly ill individual may respond to diesel engine exhaust associated air pollution.
Work package VII. This final work combines all generated data and will try to explain through what physical and chemical characteristics ambient and motor engine PM cause adverse biomedical effects.
Future actions. The final experimental work and full evaluation of the data is due during this last year of the project.
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