Health assessment across biological length scales for personal pollution exposure and its mitigation (INHALE)

为了评估污染对室外/室内城市环境中个人健康的影响，我们将开发一种基于物理的多尺度方法，从细胞、肺、人(由绿色基础设施包围)到邻里尺度，跨越生物长度尺度。我们将研究污染物的生物物理成分，这些成分决定了它们的细胞命运，它们对细胞和组织造成损害的可能性，以及这与健康结果之间的关系。我们将使用呼吸道模型来评估颗粒沉积和对人体健康的影响，并将污染颗粒通过个人追踪到细胞水平。分析的重点将放在一个人周围的直接微环境(约20米)上。综合模型还将代表各种干预情景(例如，路边树篱或哮喘患者等高危人群的药物治疗)，以评估暴露减少和健康结果的相应变化。这些暴露的生物参数将与80名参与者的心肺对污染的反应相结合，使用心肺、体力活动和个人细颗粒物暴露监测器。我们将在邻里尺度上对污染和空气流动进行数值模拟，并将以污染对健康影响为中心的方法应用于建模、传感器放置和环境管理的所有方面。因此，任何缓解策略都可以设计为将污染对健康的影响降至最低。我们将模拟颗粒物在附近的扩散及其微观物理，重点放在绿色基础设施及其缓解污染的能力上，例如树篱可以减少重金属污染。我们将在超细胞水平上检测金属和有机颗粒的物理效应和功能化学，以确定它们对细胞新陈代谢和健康的干扰。我们将使用模型来预测细胞命运的结果，这样我们就可以将污染颗粒的生物潜力(比如说)反向传播到个人和邻里尺度。因此，在每个长度尺度上，建模都将是关键。

To assess the impact of pollution on personal health in outdoor/indoor urban environments, we will develop a physics-based multi-scale approach across biological length scales from the cell, lung, person (surrounded by green infrastructure) up to the neighbourhood scale. We will examine the biophysical components of pollutants that determine their cellular fate, their potential for cell and tissue damage and how this relates to health outcomes. We will use airway models to assess particle deposition and effects on people's health as well as trace the pollution particles through an individual person down to the cellular level. The focus of the analysis will be on the immediate micro-environment (~20m) around a person. The integrated modelling will also represent various intervention scenarios (e.g. roadside hedges or medication for at-risk people such as asthmatics) to assess reduced exposure and corresponding changes in health outcomes. These biologic parameters of exposure will be integrated with the cardio-respiratory response to pollution in 80 participants using a combination of cardio-respiratory, physical activity and personal fine particles exposure monitors. We will numerically model the pollution and air flows at the neighbourhood scale and apply an approach centred on the impact of pollution on health to all aspects of modelling, sensor placement and management of the environment. Thus, any mitigation strategies can be designed to minimize the impact of pollution on health.We will model the dispersion of particles and their micro-physics within the neighbourhood with an emphasis on green infrastructure and their ability to mitigate pollution e.g. hedges can reduce heavy metal pollution. We will examine the physical effects and functional chemistry of the metals and organic components of particles at the ultracellular level to determine their interference to cell metabolism and health. We will use modelling to predict the outcomes of cell fate, so that we can back propagate biological potential of pollution particles (say) through to the individual and into the neighbourhood scale. Thus, modelling will be key at each length scale.