Development and validation of a woodsmoke biomarker in urine

描述(由申请人提供)：人类暴露在高水平的木烟中与不良健康影响有关，包括肺功能受损、哮喘、呼吸系统疾病和心血管疾病。仅在美国，每年就有超过10万人暴露在因野火、规定燃烧和农田焚烧而产生的高水平林烟中。参与野地灭火的7万至8万人也会在工作中接触大量的林烟。由于暴露评估方法不充分，导致暴露错误分类，阻碍了调查木材烟雾暴露与有害健康影响之间的关系。因此，为受控火灾制定职业暴露限值和社区影响驱动的指导方针时，缺乏暴露反应数据。这项提议的主要目标是开发人类接触木烟的生物标记。初步工作表明，接触木烟后，尿液中许多取代甲氧基酚类化合物的水平会增加。我们的假设是，摄入或吸入木烟燃烧产物后尿甲氧基酚的剂量依赖性增加可能与环境木烟以定量方式相关，从而为评估职业和环境暴露人群的木烟暴露提供了生物标志物基础。为了验证这一假设，我们计划测量从职业暴露于木烟的野火战士身上收集的尿样中甲氧基酚的水平。消防员暴露在细颗粒物(PM2.5)、一氧化碳和左旋葡聚糖(LG，一种木烟特定示踪剂)中的特征将得到表征。采用GC/MS技术，在接触木烟前后(班前和班后)测定尿甲氧基酚。将开发回归模型，以预测特定甲氧基酚的肌酐校正尿液浓度与木材烟雾暴露(PM2.5、CO、Lg)测量之间的交叉变化之间的关系。我们将通过评估受试者内部和受试者之间的木材烟雾暴露-生物标记物反应关系的差异来评估个体间甲氧基苯酚摄取、代谢和尿液排泄的差异的影响。此外，还将探讨燃料类型对特定甲氧基酚暴露的影响，从而对尿甲氧基酚生物标志物与烟雾暴露之间的关系进行探讨。一个经过验证的木烟暴露生物标志物将有助于对调查木烟暴露对人类不利影响的研究进行暴露评估，并可用于评估减少家庭和职业环境中木烟暴露的干预措施的有效性。这项拟议的研究涉及Nora与哮喘和COPD、室内环境、暴露评估方法和控制技术/个人防护设备相关的研究重点。环境和职业暴露在木材烟雾中会对呼吸健康造成不利影响。我们建议测量人类尿液中的木烟化学物质，以确定一个人吸入了多少木烟。这些改善的烟雾暴露指标将有助于我们更好地了解烟雾暴露与健康问题之间的联系，从而指导卫生政策制定充分保护公众健康的暴露标准。

DESCRIPTION (provided by applicant): Exposure of humans to high levels of woodsmoke is associated with adverse health effects including impaired lung function, asthma, respiratory disease and cardiovascular disease. In the US alone, more than 100,000 people annually are exposed to elevated woodsmoke levels from wildfires, prescribed burns and agricultural field burning. 70,000 - 80,000 people involved in wildland fire fighting also receive substantial occupational exposure to woodsmoke. Investigating the relationship between woodsmoke exposure and adverse health effects is hindered by inadequate methods of exposure assessment, which lead to exposure misclassification. Consequently, the setting of occupational exposure limits and community-impact-driven guidelines for managed fires suffers from a lack of exposure-response data. The primary objective of this proposal is to develop biological markers of human exposure to woodsmoke. Preliminary work has shown that levels of a number of substituted methoxylated phenolic compounds are increased in urine following woodsmoke exposure. It is our hypothesis that the dose- dependent increase in urinary methoxyphenols observed following ingestion or inhalation of woodsmoke combustion products can be related in a quantitative manner to environmental woodsmoke, and thereby provide a biomarker basis for assessment of woodsmoke exposure in occupationally and environmentally exposed populations. To test this hypothesis, we plan to measure methoxyphenol levels in urine samples collected from wildfire fighters who have elevated occupational exposure to woodsmoke. Firefighter exposures to fine particles (PM2.5), CO and levoglucosan (LG, a woodsmoke-specific tracer) will be characterized. Urinary methoxyphenols will be determined before and after woodsmoke exposure (pre- and post-shift), by using GC/MS techniques. Regression models will be developed to predict the associations between cross-shift changes in creatinine-corrected urinary concentrations of specific methoxyphenols and measurements of woodsmoke exposure (PM2.5, CO, LG). We shall evaluate the effect of inter-individual variation in methoxyphenol uptake, metabolism and urinary excretion by assessing within and between subject variance in the woodsmoke exposure-biomarker response relationship. Additionally, the influence of fuel type upon exposure to specific methoxyphenols, and consequently upon the relationship between urinary methoxyphenol biomarkers and smoke exposure will be explored. A validated biomarker of woodsmoke exposure will facilitate exposure assessment for studies investigating adverse effects of woodsmoke exposure in humans, and could be used to evaluate the effectiveness of interventions to reduce woodsmoke exposure in domestic and occupational settings. This proposed study addresses NORA research priorities related to asthma and COPD, indoor environment, exposure assessment methods and control technology/personal protective equipment. Environmental and occupational exposures to wood smoke cause adverse respiratory health effects. We propose to measure woodsmoke chemicals in human urine in order to determine how much wood smoke an individual has breathed in. These improved measures of smoke exposure will help us to better understand the link between smoke exposures and health problems, and hence will guide health policy in the setting of exposure standards that are adequately protective of public health.