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

• 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
• 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

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 提高儿童的医疗保健利用率。我们的团队观察到，91%的吸烟者的孩子患有高血压症 可替宁是尼古丁的一种代谢物，也是近期TSE的一种衡量指标。为了 为临床医生提供对患者长期TSE和相关临床效果的准确评估， 需要能够证明这一临床相关信息的生物标志物。我们最重要的假设是 DNA甲基化(DNaM)可作为儿童出生后长期TSE的生物标志物。这 假说是基于研究表明dNaM导致基因表达和转录调节。 具体地说，患有产前tse的儿童芳香烃受体阻遏的dNaM水平较低。 (AHRR)基因胞嘧啶-[磷酸]-鸟氨酸(CpG)二核苷酸cg05575921与无 产前TSE；这些模式类似于成年吸烟者的情况。然而，有一种稀缺的 检查dNaM和出生后TSE的研究受到以下限制：仅使用血液样本，缺乏 纳入不同种族的儿童，以及没有纳入TSE水平较高的儿童。为了弥合这些 关键差距，这一多样性补充将扩大我们对口腔拭子使用分析的理解 DNaM模式，并将阐明在具有高TSE水平的种族多样性儿童中存在的dNaM模式。 为了做到这一点，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；儿童样本将与口腔样本进行比较 来自他们母亲的样本，也与一组没有TSE的儿童匹配。总体目标 是测量全基因组的基因表达和dNaM，并识别和比较差异甲基化 吸烟者及其母亲的子女和不吸烟者的子女中的CPGS，重点关注与 以前的研究(目标1)，并检查dNaM水平与可替宁水平之间的关系 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)。这份补充材料将极大地促进候选人奥利维亚·吉滕斯女士的职业目标。 拉丁裔和加勒比海本科生。吉滕斯女士的职业目标是成为一名独立的临床医生- 研究潜在可改变的产前和产后暴露如何影响幼儿的科学家 表观基因组和相关的临床结果。以支持她的事业发展，在这段资助期间 她将接受以下方面的培训：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 通过同行评议和学术会议进行交流，以及5)研究和职业道德 发展。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。