An exploratory study investigating the physiochemical characteristics of ambient air particles responsible for the dysregulation of pulmonary genes

There is strong evidence that ambient air particulates that are breathed into the lung cause increased hospitalizations and deaths from cardio-respiratory disease. There is also evidence that they cause a general life-shortening and reduce lung development in children. In recent years the major source of such particles in urban areas is motor traffic and in particular the very small 'nanoparticles' which these emit as exhaust. Laboratory evidence and a small number of human volunteer studies indicate that it may be the total surface area of particles breathed in and/or the concentration of metals or chemicals on their surfaces which give rise to the observed health risk. Two major problems have impeded research progress in this important area. One is a biological issue in that previous studies have attempted to investigate hypothesized biological mechanisms of effect in a piecemeal fashion and mostly using conventional toxicological techniques. The second issue has related to technological problems in collecting and characterising ambient particles in the smallest (probably most important) size range. Our collaborative research group has been given Strategic Research Funding by the Higher Education Funding Council in Wales and we have obtained 'state of the art' equipment to collect and analyze particles down to nanoparticle sizes. Thus we now have the capability to address the second issue. Further our Research group has expanded to include skills and expertise in the new genetic and proteomic approaches to disease causation. This we can address the first issue by means of the holistic approach offered by the new generation of genetic/proteomic technologies. We propose a scoping study which by combining the expertise of investigators in a number of disciplines from biosciences through to epidemiology, will enable a fuller characterisation of the chemical composition and shape of these particulates, as well as investigating their biological effects through applying the new technologies developed as a result of the genetic revolution. The investigation will focus on the effects of particles of differing size and chemical constitution sampled from urban and rural environments on human tissue cultured in the laboratory. Analysis of the resulting genetic and protein factors will provide information which is currently lacking, about biological mechanisms of action of these particulates in humans. Our proposed research will be useful in a number of respects. The marriage of environmental with biological investigation will enable us to elucidate which kinds of particles (and their associated physico-chemistry) cause which kind of biological effects. This will not only indicate which causal pathways appear most promising for future research effect but also which kinds of particles in the environment environmental scientists should concentrate their research on with respect to health risks. Taken as whole this project is truly interdisciplinary bringing together scientists with expertise in areas ranging from the environment through to genetics. By combining these scientific disciplines this work should drive forward our understanding of the human health risks associated with air particulates. In addition, it will lay the groundwork for larger projects of this type to be undertaken as it will enable to the scientific methodologies to be fine tuned. Such projects will be important in determining future environmental policy with respect air particulates which are presently regarded by the European Union and World Health Organisation as very harmful to health.