Effect of Early-Life Exposure to Metal Mixtures on Lung Function and Mitochondrial DNA in Children
生命早期接触金属混合物对儿童肺功能和线粒体 DNA 的影响
基本信息
- 批准号:10609404
- 负责人:
- 金额:$ 54.8万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-04-02 至 2025-03-31
- 项目状态:未结题
- 来源:
- 关键词:AdultAffectAgeAnimalsArsenicBangladeshBiologicalBiological MarkersBiosensorBloodBronchodilator AgentsCadmiumChildChild HealthChildhoodCollectionDataData CorrelationsDevelopmentDiseaseElderlyEnvironmental PollutantsExposure toGoalsHealthHealth PolicyHumanImpairmentIndividualInfrastructureInterventionLeadLifeLinkLongitudinal StudiesLungLung diseasesManganeseMeasurableMeasurementMeasuresMediatingMediationMetal exposureMetalsMethodsMitochondriaMitochondrial DNAModelingOutcomeOxidative StressPhysiologicalPredispositionPregnancyPregnant WomenProcessPropertyProspective cohortPublic HealthPulmonary Function Test/Forced Expiratory Volume 1Pulmonary function testsResearchRiskRisk FactorsSamplingStructureSuperfundTimeTooth structureToxic effectTreesUniversitiesVital capacityagedblood-based biomarkercapsulecostcost efficientdeciduous toothearly childhoodearly life exposureglobal healthimprovedin uteroinnovationlung developmentmetal poisoningmitochondrial DNA alterationmitochondrial dysfunctionnoveloxidationoxidative DNA damageoxidative damageprenatalprogramspulmonary functionrepairedresponsestatisticstime usetooltoxic metal
项目摘要
PROJECT SUMMARY
Exposure to harmful toxic metals in utero and during early life is a global health problem. Although millions of
children worldwide are exposed to multiple metals at those times, we still lack convincing evidence of the
impact of metal exposure, particularly mixtures of metals, on childhood lung function. Indeed, most studies
investigated metals individually, but in real life, pregnant women and their children are exposed to many metals
simultaneously, and their combined effects are often unpredictable. Because the human lung develops through
a sequence of highly choreographed processes, ideally, human studies would continuously measure levels of
multiple metals to identify relevant windows of susceptibility.
In this study, we will obtain weekly measurements of multiple metal exposures simultaneously by using
a highly innovative method to measure metal levels in deciduous teeth. Like trees, teeth develop in layers that
trap metals at concentrations commensurate with exposure levels. Hence, each layer is like a time capsule that
contains metal levels from the time it was formed. We will use a validated method to measure 14 metals in
teeth. We can assess exposures cumulatively, as well as at discrete week-by-week developmental windows,
starting prenatally as early as gestational weeks 13-16 up to the time of tooth collection (~6 years). In order to
develop a noninvasive and inexpensive biomarker for later-life lung function, we will combine our analyses of
these metal assessments in teeth with novel blood-based biomarkers that leverage the unique properties of the
mitochondrial DNA (mtDNA), a cumulative biosensor of metal-induced oxidative DNA damage. Our goal is to
use tooth-based, time-specific measures of metals to assess their effects on lung function individually or as a
mixture. We hypothesize that metals adversely affect lung function and that the effects of metal exposures on
children’s lungs are associated with the cumulative damage measured in blood mtDNA.
We can time- and cost-effectively conduct this research by leveraging the infrastructure of the Health
Effects of Arsenic Longitudinal Study (HEALS), a well-characterized prospective cohort of 35,000 adults and
their children in Araihazar, Bangladesh. The proposed study will include 600 children ages 6-10 years. We will
collect at least one deciduous tooth sample from each child and conduct standard lung function tests and
obtain blood mtDNA measures twice, 2 years apart.
We anticipate that findings from this innovative and cost-efficient study will generate information on the
impact of in utero and early-life exposure to multiple metals on pulmonary function in children. Information
generated from this study will appreciably improve our understanding of lung function in response to
environmental metal exposure and ultimately will inform strategies to improve lung function in children.
项目总结
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Muhammad F Parvez其他文献
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{{ truncateString('Muhammad F Parvez', 18)}}的其他基金
Effect of Early-Life Exposure to Metal Mixtures on Lung Function and Mitochondrial DNA in Children
生命早期接触金属混合物对儿童肺功能和线粒体 DNA 的影响
- 批准号:
10133073 - 财政年份:2019
- 资助金额:
$ 54.8万 - 项目类别:
Effect of Early-Life Exposure to Metal Mixtures on Lung Function and Mitochondrial DNA in Children
生命早期接触金属混合物对儿童肺功能和线粒体 DNA 的影响
- 批准号:
9905524 - 财政年份:2019
- 资助金额:
$ 54.8万 - 项目类别:
Effect of Early-Life Exposure to Metal Mixtures on Lung Function and Mitochondrial DNA in Children
生命早期接触金属混合物对儿童肺功能和线粒体 DNA 的影响
- 批准号:
10377354 - 财政年份:2019
- 资助金额:
$ 54.8万 - 项目类别:
Arsenic Exposure, Impaired Respiratory Function, and Immunosuppression
砷暴露、呼吸功能受损和免疫抑制
- 批准号:
9087230 - 财政年份:2015
- 资助金额:
$ 54.8万 - 项目类别:
Arsenic Exposure, Impaired Respiratory Function, and Immunosuppression
砷暴露、呼吸功能受损和免疫抑制
- 批准号:
9238773 - 财政年份:2015
- 资助金额:
$ 54.8万 - 项目类别:
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