Effect of exposure of children to particulate matter air pollution on airway macrophages and dendritic cells.

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Microscopic particles of soot (particulate matter, PM) from petrol and diesel engine emissions are linked to a wide range of adverse health effects in children. The most consistent findings in survey studies are that long-term exposure of children to air pollution increases their risk of developing allergic asthma and reduces the function of their airways. Thus more cases of asthma occur in high soot-exposed communities, and children living in these communities take longer to forcibly breathe out air (lung function). To date, how soot damages children's lungs in unknown. In part this is because sampling cells from deep inside children's lungs has been very difficult, and in part, because measuring long-term exposure of individual children to sooty particles has been impossible. We recently developed a new method that both measures long-term exposure to soot and samples cells from deep inside the airways of children. This method involves children coughing up plugs of cells after breathing a salty mist. Within these plugs are large cells called airway macrophages whose normal function is to take up soot that is breathed into the lung. Measuring the amount of soot in macrophages is a very good marker of an individual child's exposure to soot over the preceding months. In addition to removing soot, animal studies strongly suggest that airway macrophages, and another cell type called dendritic cells, are involved in the development of asthma and the regulation of normal lung growth. It is therefore very likely that subtle changes in airway macrophages and dendritic cells are key to the adverse health effects of inhaled soot. We speculate that breathing in soot affects airway macrophages and dendritic cells so that they release more tissue damaging substances, and stimulates these airway cells to support more allergic reactions in the lung. In this proposed study, we will measure the amount of soot in macrophages of healthy children, and for each child, compare the amount of macrophage soot to the number and function of airway macrophages and dendritic cells. We will focus on cellular changes that are known from animal models to enhance risk of developing asthma and reduce the growth of the airways. Airway macrophages and dendritic cells will be analysed using flow cytometry - a technique that suited to the analysis of small numbers of cells. We will also use portable soot monitoring to assess where children are exposed most when they move around their local environment. In order to control for other factors that may affect lung cells (e.g. gender and age), and that some children will not be able to produce sufficient lower airway cells for detailed analysis, this study needs to recruit a large number of subjects. In total, 400 children will be studied, 250 more than once, over a 36 month period. We will recruit from healthy children attending the Centre of the Cell experience, a hands-on multimedia resource that is embedded within our Institute at Whitechapel. To date, over 30,000 children have visited the Centre. Children attending our Centre mainly live in the East End of London - one of the worst areas for air pollution in Europe. We will engage with children by developing an multi-media educational presentation on air pollution and lung cells. Using this resource, we are maximising the study's potential to impact on the lives of deprived urban children. This study will be the first that focuses on the mechanisms for the long-term effects of air pollution in children. All the techniques are ethically acceptable in children, and we have preliminary results that show we can identify both airway macrophages and dendritic cells from the small number of cells in induced sputum samples from young children. We envisage that the study's results will strengthen the argument that soot causes lung diseases in childhood, and will provide new insights into how the environmental affects asthma development and normal lung growth.