颗粒物人体传输动力学行为、器官剂量分布规律与健康效应研究

Heavy particulate air pollution in China has an important adverse effect on human health. The particulate matters could be inhaled and thus harmful to the human lungs. The ultrafine particles could further penetrate the alveoli, be translocated to other organs by the blood circulation, and cause health effects to the whole body. However, it still remains a problem about how to quantitatively assess the effects of particulate matter on human health. This proposal suggested an idea and framework to show the evidence of particle health effects based on the dose distributions in human organs/tissues and biomarkers in human body..The main contents of this project include three aspects: (1) How the particles enter the body? We will use the computational fluid dynamics (CFD) to numerically model the airflow and particle transport and deposition in human lung, but extend the CFD method to stochastic individual path (SIP) in human lung in order to quickly predict the dose in human lungs; (2) How the body does to the particles? We suggest a new method of PBPK-h based on the traditional PBPK (Physiologically based pharmacokinetic modeling) method to consider the particle deposition in human blood, to simulate the particle transport and dose distributions in human organs and tissues; (3) What the particles do to the body? We intend to use the biomarker of DNA damage and inflammatory factors to establish the relationship between the health effect and particle dose in human body, i.e. dose-response curve. The transport dynamics and dose distributions of particles in human organs could be visualized and then the health effects of the particles could be evaluated by the biomarkers in human body based on the particle dose..In conclusion, we will use the human dose and biological markers as the evidences to illustrate the process of particle migration and transformation in the human body, to provide evidence for health effects and quantitatively evaluate and predict the effects of particles on human body.

颗粒物的健康危害已得到广泛认识，但如何科学定量评估颗粒物对人体的健康危害却成为难题。本项目提出以颗粒物“器官剂量”与“人体生物标志物”为证据的健康危害研究思路与框架。研究内容包括三方面：（1）颗粒物如何进入人体？提出基于随机单一路径SIP的肺部空气流动与颗粒物传输动力学行为CFD快速模拟与计算人体肺部颗粒物剂量方法。（2）身体如何处理颗粒物？提出基于生理学的颗粒物代谢动力学血液修正模型PBPK-h模拟与计算颗粒物器官剂量分布及其变化规律。（3）颗粒物对人体做了什么？拟采用尿液与血液中人体健康氧化损伤与炎性因子关键生物标志物建立颗粒物“剂量-健康效应关系”统计学模型。项目通过人体剂量与生物标志物关键技术手段，揭示颗粒物在人体内部的迁移转化过程与规律，提供健康危害证据，为定量评估与预测颗粒物人体健康危害奠定科学基础与理论依据。

颗粒物的健康危害已得到广泛认识，但如何科学定量评估颗粒物对人体的健康危害却成为难题。本项目提出了以颗粒物“器官剂量”与“生物标志物”为证据的健康危害研究思路与框架。研究内容主要包括三方面：1、颗粒物如何进入人体？提出基于随机单一路径SIP的肺部空气流动与颗粒物传输动力学行为CFD快速模拟与计算人体肺部颗粒物剂量方法。2、身体如何处理颗粒物？提出基于生理学的颗粒物代谢动力学血液修正模型PBPK-h模拟与计算颗粒物器官剂量分布及其变化规律。3、颗粒物对人体做了什么？采用氧化损伤与炎性因子关键生物标志物建立颗粒物“剂量-健康效应关系”并找到颗粒物健康损伤关键证据。..项目取得的重要结果：1、关于生命早期（孕期）污染暴露对出生后儿童疾病发生与发展的影响，被写入“国际共识声明”、美国胸科学会ATS官方报告、意大利儿童学会 “儿童急性中耳炎控制指南”、国际中耳炎学会ISOM最新进展等。2、受邀参加世界卫生组织WHO研究中心的哮喘疾病负担调查并制定未来十年研究对策。3、多篇论文入选国际权威期刊“最高被引”论文、封面论文、全球高被引ESI 1%。4、成果得到了许多国际权威院士在国际顶尖期刊（如Lancet等）高度评价与大篇幅正面报道。5、受国际权威期刊Expert Review of Clinical Immunology（影响因子IF=3.9）主编邀请撰写“空气污染与过敏性疾病：新发现”综述论文。..关键数据：发表国际SCI学术期刊论文31篇（其中JCR一区期刊23篇）、《科学通报》1篇。入选国际人工环境学会ISBE会士、国际室内空气质量与气候学会ISIAQ理事BOD。担任10本有影响力国际学术期刊编委会成员，包括Environment International（IF=8）客座编辑、Building and Environment（IF=4.8）、Indoor Air（IF=4.7）、Energy and Buildings（IF=4.6）等权威期刊编委。担任国际ISIAQ学会主办的国际学术会议Healthy Buildings 2019 Asia大会主席。获得湖南省自然科学奖二等奖（排名第一）、中国高被引学者。..成果科学意义：项目通过人体剂量与生物标志物关键技术手段，揭示颗粒物在人体内部的迁移转化过程与规律，提供健康危害证据，定量评估与预测了颗粒物人体健康危害。