Air pollution effects on inflammation, cardiovascular risk factors and cardiovascular events - role of source-specific PM and PM components

在上一个项目阶段，我们研究了总体细颗粒物（PM）和来自不同排放源的PM对普通人群先天免疫系统炎症标志物、心血管危险因素和心脏代谢疾病的影响。我们最重要的发现是，短期和长期暴露于细颗粒物与全身炎症反应、血糖控制受损和2型糖尿病风险升高相关，长期PM与动脉血压升高和亚临床动脉粥样硬化相关。我们研究的第一个初步证据也表明了通过适应性免疫系统的另一个途径，这在以前的长期流行病学研究中还没有被研究过。源特定的分析往往会显示出增加的毒性，新鲜的本地交通排放相比，整体PM，而这是迄今为止无法观察到的本地行业特定的PM。在这项更新提案中，我们的目标是通过以下方式推进我们的研究：（1）利用建模的成分数据加强暴露评估，并将情景模拟从仅包括本地源扩展到包括交通和工业的区域源。(2)我们希望利用扩大的海因茨Nixdorf回忆研究（HNR）健康数据库，其中包括10年的随访，以调查特定来源的PM对心血管和脑血管事件发生率的影响，以及对心血管危险因素的扩展分析。(3)此外，我们的初步分析表明，适应性免疫系统参与了对PM的慢性炎症反应的产生。毒理学证据支持这一新发现。我们的目标是遵循这一新的空气污染研究途径，并调查来源特异性PM与游离轻链和意义不明的单克隆丙种球蛋白病（MGUS）的关系。我们希望能够为解决细颗粒空气污染对特定来源和特定成分健康影响的紧迫问题做出贡献，并通过这一点为更有效和高效的预防措施做出贡献。

During the previous project phase we investigated the impact of overall fine particulate matter (PM) and PM from different emission sources on inflammatory markers of the innate immune system, cardiovascular risk factors and cardiometabolic disease in the general population. Our most important finding is that short- and long-term exposure to fine PM are associated with a systemic inflammatory response, impaired glucose control, and an elevated risk of type 2 diabetes mellitus, and that long-term PM is associated with increased arterial blood pressure and subclinical atherosclerosis. First preliminary evidence from our study also suggests an additional pathway via the adaptive immune system, which has not been examined in long-term epidemiological studies before. Source-specific analyses tend to show an increased toxicity of fresh local traffic emissions in comparison to overall PM, while this could not be observed so far for local industry-specific PM. In this renewal proposal, we aim to advance our research by (1) enhancing the exposure assessment with modeled constituent data and by extending the scenario simulations from including only local sources to including also regional sources of traffic and industry. (2) We want to make use of the enlarged Heinz Nixdorf Recall Study (HNR) health data base, which now incorporates 10 years of follow-up, to investigate source-specific PM effects on incidence of cardiovascular and cerebrovascular events as well as extended analyses on cardiovascular risk factors. (3) Moreover, our preliminary analyses have pointed to an involvement of the adaptive immune system in the generation of chronic inflammatory responses to PM. This novel finding has been supported by toxicological evidence. We aim to follow this new avenue of air pollution research and investigate the associations of source-specific PM with free light chains and monoclonal gammopathy of undetermined significance (MGUS). We expect to be able to contribute to the pressing questions on source-specific and constituent-specific health effects of fine PM air pollution and through this contribute to more effective and efficient preventive measures.