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

汽油和柴油发动机排放的碳烟微粒(颗粒物，PM)与儿童的一系列不利健康影响有关。调查研究中最一致的发现是，儿童长期暴露在空气污染中会增加他们患过敏性哮喘的风险，并降低他们的呼吸道功能。因此，更多的哮喘病例发生在高煤烟暴露的社区，生活在这些社区的儿童需要更长的时间才能强行呼出空气(肺功能)。到目前为止，煤烟是如何损害儿童肺部的还不清楚。部分原因是从儿童肺部深处提取细胞样本非常困难，部分原因是无法测量儿童长期接触煤烟颗粒的情况。我们最近开发了一种新的方法，既可以测量长期接触煤烟的情况，又可以从儿童呼吸道深处提取细胞样本。这种方法要求儿童在呼吸到咸雾后咳出一块块的细胞。在这些塞子内有称为呼吸道巨噬细胞的大细胞，其正常功能是吸收吸入肺部的烟尘。测量巨噬细胞中的煤烟量是一个很好的标记物，可以衡量一个孩子在过去几个月中接触到煤烟的情况。除了清除烟尘，动物研究强烈表明，呼吸道巨噬细胞和另一种称为树突状细胞的细胞类型，参与了哮喘的发生和正常肺生长的调节。因此，呼吸道巨噬细胞和树突状细胞的细微变化很可能是吸入煤烟对健康不利影响的关键。我们推测，吸入煤烟会影响呼吸道巨噬细胞和树突状细胞，使它们释放更多的组织破坏性物质，并刺激这些呼吸道细胞支持肺部更多的过敏反应。在这项拟议的研究中，我们将测量健康儿童巨噬细胞中的煤烟量，并将每个儿童的巨噬细胞煤烟量与呼吸道巨噬细胞和树突状细胞的数量和功能进行比较。我们将专注于动物模型中已知的细胞变化，以增加发生哮喘的风险，减少呼吸道的生长。将使用流式细胞术对呼吸道巨噬细胞和树突状细胞进行分析--这是一种适合于分析少量细胞的技术。我们还将使用便携式烟尘监测来评估儿童在当地环境中走动时接触最多的地方。为了控制可能影响肺细胞的其他因素(例如性别和年龄)，以及一些儿童将无法产生足够的下呼吸道细胞进行详细分析，这项研究需要招募大量的受试者。总共有400名儿童将在36个月的时间里接受研究，其中250人不止一次。我们将从参加细胞体验中心的健康儿童中招募人才，这是一个嵌入在我们怀特查佩尔研究所的亲身实践的多媒体资源。到目前为止，已有3万多名儿童参观了该中心。参加我们中心的儿童主要生活在伦敦东区--欧洲空气污染最严重的地区之一。我们将通过开发关于空气污染和肺细胞的多媒体教育演示来吸引儿童。利用这一资源，我们正在最大限度地发挥这项研究对贫困城市儿童生活的影响的潜力。这项研究将是第一次关注空气污染对儿童产生长期影响的机制。所有这些技术在伦理上都是儿童可以接受的，我们的初步结果表明，我们可以从幼儿诱导痰样本中的少量细胞中识别出呼吸道巨噬细胞和树突状细胞。我们预计，这项研究的结果将加强煤烟导致儿童肺部疾病的论点，并将为环境如何影响哮喘的发展和正常的肺生长提供新的见解。

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.