Prevalence and Clinical Correlates of Thirdhand Smoke Exposure in a Pediatric Patient Population

儿科患者群体中三手烟暴露的患病率和临床相关性

基本信息

批准号：
10436539
负责人：
E. Melinda Mahabee-Gittens
金额：
$ 1.49万
依托单位：
CINCINNATI CHILDRENS HOSP MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-01-07 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10436539
关键词：
5 year old Adult Affect Area Aryl Hydrocarbon Receptor Biochemistry Biological Markers Black race Blood specimen Caribbean region Child Clinical Communication Research Cotinine CpG dinucleotide Cytosine DNA Methylation Ethics Female Gene Expression Genetic Transcription Goals Grant Guanine Health Laboratories Latina Measures Molecular Biology Morbidity - disease rate Mothers Nicotine Not Hispanic or Latino Outcome Patients Pattern Peer Review Prevalence Reporting Research Research Technics Sampling Scientist Site Smoker Specimen Handling Statistical Data Interpretation Swab Techniques Tobacco use Training Transcriptional Regulation base career career development clinical effect clinically relevant epigenome fetal tobacco exposure gene repression genome-wide health care service utilization inorganic phosphate methylation pattern non-smoker patient population pediatric patients pediatrician postnatal prenatal racial diversity research and development symposium thirdhand smoke tobacco smoke exposure undergraduate student

项目摘要

There is unequivocal evidence that tobacco smoke exposure (TSE) is associated with clinical morbidity and increased healthcare utilization in children. Our team has observed that 91% of smokers’ children have high rates of TSE as assessed with cotinine, a metabolite of nicotine and a measure of recent TSE. In order to provide clinicians with an accurate assessment of their patients’ long-term TSE and associated clinical effects, biomarkers are needed that can demonstrate this clinically relevant information. Our overarching hypothesis is that DNA methylation (DNAm) may serve as a biomarker of long-term postnatal TSE in children. This hypothesis is based on research indicating that DNAm results in gene expression and transcription regulation. Specifically, children with prenatal TSE have lower DNAm levels of the aryl hydrocarbon receptor repression (AHRR) gene cytosine-[phosphate]-guanine (CpG) dinucleotide cg05575921 compared to children with no prenatal TSE; these patterns are similar to those seen in adult smokers. However, there are a paucity of studies examining DNAm and postnatal TSE and they are limited by the: use of blood samples only, lack of inclusion of racially diverse children, and lack of inclusion of children with high TSE levels. To bridge these critical gaps, this diversity supplement will expand our understanding of the use of buccal swabs to analyze DNAm patterns and will elucidate the DNAm patterns present in racially diverse children with high TSE levels. To accomplish this, we will examine DNAm patterns from buccal swabs of Black, Non-Hispanic female children, 0-5 years of age whose mothers are active smokers; child samples will be compared to buccal samples from their mothers, and also matched with a group of children who have no TSE. The overall objective is to measure genome-wide gene expression and DNAm and to identify and compare differentially methylated CpGs in children of smokers and their mothers, and children of nonsmokers, focusing on loci implicated by previous studies (Aim 1) and to examine the association between DNAm levels compared to cotinine levels and maternal-reported TSE patterns in children, maternal-reported tobacco use patterns, and child illness types (Aim 2). This supplement will greatly facilitate the career goals of the candidate, Ms. Olivia Gittens, a Latina and Caribbean undergraduate student. Ms. Gittens’s career goal is to be an independent clinician- scientist studying how potentially modifiable prenatal and postnatal exposures affect young children’s epigenomes and associated clinical outcomes. To support her career development, during this grant period she will obtain training on: 1) laboratory techniques and handling of specimens, 2) research techniques in biochemistry and molecular biology, 3) statistical analyses and interpretation of results, 4) research communication through peer review and academic conferences, and 5) ethics in research and career development. Training in these areas will help prepare Ms. Gittens for an impactful research career.

有明确的证据表明烟草烟雾暴露（TSE）与临床发病率和我们的团队观察到，91% 的吸烟者儿童的医疗保健利用率较高。使用可替宁（一种尼古丁代谢物）评估 TSE 率，并作为近期 TSE 的衡量标准。为婴儿提供对其患者的长期 TSE 和相关临床效果的准确评估，我们需要生物标志物来证明这一临床相关信息。 DNA 甲基化 (DNAm) 可能作为儿童长期产后 TSE 的生物标志物。该假设基于表明 DNAm 导致基因表达和转录调控的研究。具体来说，患有产前 TSE 的儿童具有较低的芳基碳氢化合物受体抑制 DNAm 水平 (AHRR) 基因胞嘧啶-[磷酸]-鸟嘌呤 (CpG) 二核苷酸 cg05575921 与没有的儿童相比产前 TSE；这些模式与成年吸烟者相似，但很少。检查 DNAm 和产后 TSE 的研究，它们受到以下限制：仅使用血液样本，缺乏包容不同种族的儿童，以及缺乏高 TSE 水平的儿童的包容。关键差距，这种多样性补充将扩大我们对使用口腔拭子进行分析的理解 DNAm 模式，并将阐明 TSE 水平高的不同种族儿童中存在的 DNAm 模式。为了实现这一目标，我们将检查非西班牙裔黑人女性口腔拭子的 DNAm 模式母亲经常吸烟的 0-5 岁儿童样本将与口腔样本进行比较；总体目标是测量全基因组基因表达和 DNAm，并识别和比较差异甲基化吸烟者及其母亲的孩子以及非吸烟者的孩子的 CpG，重点关注与先前的研究（目标 1）并检查 DNAm 水平与可替宁水平相比之间的关联和母亲报告的儿童 TSE 模式、母亲报告的烟草使用模式和儿童疾病类型（目标 2）。该补充材料将极大地促进候选人 Olivia Gittens 女士的职业目标。吉滕斯女士的职业目标是成为一名独立的临床医生—— 科学家研究潜在可改变的产前和产后暴露如何影响幼儿表观基因组和相关的临床结果，以支持她的职业发展，在此资助期间。她将获得以下方面的培训：1）实验室技术和标本处理，2）研究技术生物化学和分子生物学，3）统计分析和结果解释，4）研究通过同行评审和学术会议进行沟通，以及 5) 研究和职业道德这些领域的培训将有助于吉滕斯女士为有影响力的研究生涯做好准备。