High Throughput Methods to Measure Disparities in Childhood Exposure to Tobacco

描述(由申请人提供)： 儿童在子宫内通过母亲吸烟和在儿童时期因二手烟(SHS)不由自主地接触到烟草。接触SHS与重要的健康问题有关，如低出生体重、哮喘诱发、哮喘加重、耳朵和下呼吸道感染增加，以及婴儿猝死综合症。值得注意的是，SHS的暴露和SHS对健康的影响因种族、民族和SES而异。因此，努力消除儿童接触SHS对于缩小健康差距至关重要。由于儿童避免吸烟的选择有限，因此需要采取有效的公共卫生措施，以识别有风险的儿童，增加父母戒烟，并实施家庭吸烟限制，特别是针对少数族裔家庭。一种准确的、非侵入性的客观测量SHS的方法将提高国家评估儿童和少数民族烟草暴露风险的能力，他们在研究中往往代表不足。干血斑点被称为评估有毒物质暴露的“金矿”。它们很容易获得，而且可以获得数千个样本来评估整个人群的暴露水平。对干血迹中烟草成分的分析将提供一个机会，在人口层面上客观地衡量烟草暴露情况。该项目的目标是通过测量可替宁(烟草暴露的生物标记物)来研究儿童暴露于SHS的差异。我们建议(1)建立高通量液相色谱串联质谱(LC/MS/MS)方法来定量干血斑点中的可替宁；(2)通过应用高通量可替宁检测方法来估计美国人群因种族暴露而宫内烟草毒物暴露的流行率(n~2900)；以及(3)通过应用高通量可替宁检测方法来估计6-36个月龄儿童中因种族暴露而SHS暴露的比率(n~3400)。这一应用程序采用了一支在烟草研究(包括量化尼古丁代谢物的分析方法)、儿科流行病学和健康差异研究方面拥有专业知识的多学科团队。该提案非常适合于为期两年的“GO”赠款机制，因为它能够迅速获得现有的重要资源--新生儿和儿童的干血斑点，这将产生数千个个体样本。高通量测量干血斑中的可替宁的方法将提供做以下所有事情的机会：扩大对不同社区的风险评估的范围，准确地测量SHS暴露，增加对儿童SHS暴露的识别，将SHS暴露的生物标记物测量转移到临床领域，解决与烟草相关的健康差距，并为卫生保健政策的变化提供信息。所开发的方法将为未来的流行病学和临床研究计划提供重要的资源，这些计划有可能通过减少SHS暴露而改善儿童的健康--SHS是对公共健康的重要威胁。 公共卫生相关性： 该项目将有助于减少烟草对儿童健康影响方面的差异。我们将通过创建一种强大的工具来实现这一目标，该工具可以客观地测量二手烟暴露，特别适合在年轻人和少数族裔人群中使用，并在来自不同人群的婴儿和儿童的干血迹的大样本中测试该方法。

DESCRIPTION (provided by applicant): Children are involuntarily exposed to tobacco both in utero through maternal smoking and during childhood from secondhand smoke (SHS). SHS exposure is associated with important health problems such as low birth- weight, asthma induction, asthma exacerbation, increased ear and lower respiratory infections, and sudden infant death syndrome. Notably, SHS exposure and the health effects of SHS vary by race, ethnicity and SES. Therefore, efforts to eliminate childhood exposure to SHS are critical for the reduction of health disparities. Because children have limited options for avoiding exposure, effective public health measures are needed to identify children at risk, increase parental smoking cessation, and implement home smoking restrictions, particularly with respect to minority households. An accurate, noninvasive method to objectively measure SHS would increase the nation's capacity to assess tobacco exposure risk in small children and minorities, who are often under-represented in research. Dried blood spots have been called a "gold mine" for assessing toxic exposures. They are obtained easily, and thousands of samples can be available to assess exposure levels across a population. Analysis of tobacco constituents in dried blood spots would afford an opportunity to objectively measure tobacco exposure on a population level. The goal of this project is to study disparities in childhood exposure to SHS by measuring cotinine, a biomarker of tobacco exposure. We propose to (1) develop high throughput liquid chromatography tandem mass spectrometry (LC/MS/MS) methods to quantify cotinine in dried blood spots; (2) estimate the U.S. population prevalence of in utero tobacco toxicant exposure by race by applying high throughput cotinine assay methods to extant dried blood spots collected during routine neonatal screening (n~2900); and (3) estimate the rate of SHS exposure in children ages 6-36 months by race by applying high throughput cotinine assay methods to extant dried blood spots collected to screen for lead exposure (n~3400). This application employs a multidisciplinary team with expertise in tobacco research (including the analytical methods to quantify nicotine metabolites), pediatric epidemiology, and health disparities research. The proposal is well-suited to the two-year "GO" grant mechanism because of the ability to rapidly access the important resource of extant dried blood spots from neonates and children that will yield thousands of individual samples. High throughput methods to measure cotinine in dried blood spots will provide opportunities to do all of the following: increase the reach of risk assessment into diverse communities, accurately measure SHS exposure, increase identification of childhood SHS exposure, move biomarker measurement of SHS exposure into the clinical arena, address tobacco-related health disparities, and inform changes in health care policy. The methods developed will provide an important resource to future epidemiological and clinical research initiatives that have potential to improve the health of children by reducing SHS exposure -- an important threat to public health. PUBLIC HEALTH RELEVANCE: This project will contribute to reducing disparities in health effects from tobacco among children. We will accomplish this goal by creating a powerful tool to objectively measure secondhand smoke exposure that is especially suited to use in young and minority populations and test the method in a large sample of dried blood spots from a diverse population of infants and children.