Development and validation of a woodsmoke biomarker in urine

描述（由申请人提供）：人类暴露于高水平的木材烟雾与不良健康影响相关，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10万人暴露于野火、规定燃烧和农田燃烧产生的高水平木材烟雾中。7万至8万参与野火灭火的人也有大量的职业接触到木材烟雾。暴露评估方法不完善，导致暴露分类错误，阻碍了调查木材烟雾暴露与不良健康影响之间的关系。因此，职业暴露限值的设定和社区影响驱动的管理火灾指南受到缺乏暴露反应数据的影响。本提案的主要目标是开发人类暴露于木材烟雾的生物标志物。初步研究表明，木材烟雾暴露后，尿液中一些取代甲氧基化酚类化合物的含量增加。我们的假设是，在摄入或吸入木材烟雾燃烧产物后观察到的尿中甲氧基酚的剂量依赖性增加可以定量地与环境木材烟雾有关，从而为评估职业和环境暴露人群的木材烟雾暴露提供生物标志物基础。为了验证这一假设，我们计划测量从野火战士收集的尿液样本中的甲氧基酚水平，这些消防员的职业暴露于木材烟雾中。消防员暴露于细颗粒（PM2.5）， CO和左旋葡聚糖（LG，一种木材烟雾特异性示踪剂）将被表征。尿甲氧基酚将通过GC/MS技术测定木材烟雾暴露前后（轮班前和轮班后）。将开发回归模型，以预测肌酸酐校正的尿中特定甲氧基酚浓度的交叉移位变化与木材烟雾暴露（PM2.5， CO， LG）的测量之间的关联。我们将通过评估木材烟雾暴露-生物标志物反应关系中的受试者内部和受试者之间的差异来评估甲氧基酚摄取、代谢和尿排泄的个体间差异的影响。此外，燃料类型对暴露于特定甲氧基酚的影响，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了探讨。一个经过验证的木烟暴露生物标志物将有助于研究木烟暴露对人类的不利影响，并可用于评估在家庭和职业环境中减少木烟暴露的干预措施的有效性。本研究提出了与哮喘和慢性阻塞性肺病、室内环境、暴露评估方法和控制技术/个人防护装备相关的NORA研究重点。环境和职业接触木材烟雾会对呼吸系统健康造成不利影响。我们建议测量人类尿液中的木材烟雾化学物质，以确定一个人吸入了多少木材烟雾。这些改进的烟雾暴露措施将帮助我们更好地了解烟雾暴露与健康问题之间的联系，因此将指导制定充分保护公众健康的暴露标准的卫生政策。

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.