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

有明确的证据表明，烟草烟雾暴露（TSE）与临床发病率相关， 提高儿童的医疗保健利用率。我们的研究小组观察到，91%的吸烟者的孩子有很高的 使用尼古丁代谢物可替宁和近期TSE指标评估的TSE发生率。为了 为临床医生提供患者长期TSE和相关临床效应的准确评估， 需要能够证明这种临床相关信息的生物标志物。我们的首要假设是 DNA甲基化（DNAm）可作为儿童长期出生后TSE的生物标志物。这 该假设基于研究表明DNA m会导致基因表达和转录调节。 具体来说，产前TSE患儿的芳香烃受体抑制的DNA m水平较低， （AHRR）基因胞嘧啶-[磷酸]-鸟嘌呤（CpG）二核苷酸cg05575921与无 产前TSE;这些模式与成年吸烟者相似。然而， 检查DNAm和产后TSE的研究受到以下限制：仅使用血液样本，缺乏 包括种族多样性儿童，以及缺乏包括高TSE水平的儿童。弥补这些 关键的差距，这种多样性补充将扩大我们的理解使用口腔拭子分析 DNAm模式，并将阐明存在于不同种族的儿童高TSE水平的DNAm模式。 为此，我们将检测来自非西班牙裔黑人女性口腔拭子的DNAm模式， 母亲为主动吸烟者的0 - 5岁儿童;儿童样本将与口腔样本进行比较。 从他们的母亲身上提取样本，并与一组没有TSE的儿童进行匹配。总体目标 是测量全基因组基因表达和DNAm，并鉴定和比较差异甲基化的 吸烟者及其母亲的子女和非吸烟者的子女中的CpG，重点关注与吸烟有关的基因座。 之前的研究（目的1），并检查与可替宁水平相比，DNA m水平之间的关联 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）。这一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， 拉丁美洲和加勒比海本科生。吉滕斯女士的职业目标是成为一名独立的临床医生- 科学家研究潜在的可改变的产前和产后暴露如何影响幼儿的 表观基因组和相关的临床结果。为了支持她的职业发展，在此资助期间， 她将接受以下培训：1）实验室技术和处理标本，2） 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; 5）研究和职业道德 发展这些领域的培训将有助于Gittens女士为有影响力的研究生涯做好准备。

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.