Prospective Health Outcomes and Inflammatory Biomarkers Associated with e-Cigarette Use

与电子烟使用相关的预期健康结果和炎症生物标志物

基本信息

批准号：
10226191
负责人：
Peter Castaldi
金额：
$ 51.27万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
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：
2019-09-15 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10226191
关键词：
Acute Adaptive Immune System Address Antibodies Antibody Response Autoantibodies B-Lymphocytes Biological Biological Markers Blood Cells Chronic Obstructive Airway Disease Cigarette Smoker Clinical Control Groups Controlled Study Data Disease Electronic Nicotine Delivery Systems Electronic cigarette Elements Evaluation Genomics Goals Grant Health Human Immunologic Receptors Individual Inflammation Inflammatory Inflammatory Response Link Longitudinal Studies Lung Machine Learning Measures Methods Molecular Mouse Strains Oropharyngeal Outcome Pattern Performance Phenotype Population Positioning Attribute Process Proteomics Pulmonary Emphysema Pulmonary Function Test/Forced Expiratory Volume 1 Questionnaires Recording of previous events Respiratory Signs and Symptoms Smoker Spirometry Surrogate Endpoint T cell response T-Lymphocyte T-cell receptor repertoire Testing United States Food and Drug Administration Visit X-Ray Computed Tomography adaptive immune response authority biomarker discovery biomarker panel candidate marker chest computed tomography cohort combustible cigarette design electronic cigarette use genome-wide health assessment lung injury novel novel strategies patient population phenotypic data predictive modeling prospective public health relevance random forest response biomarker study population targeted sequencing tool transcriptome sequencing transcriptomics young adult

项目摘要

Project Summary. This project is designed to identify validated biomarkers for use in the assessment of electronic nicotine delivery systems (ENDS) by the FDA. Since the introduction of ENDS, commonly referred to as e-cigarettes, there has been a large increase in ENDS use among young adults and older traditional cigarette smokers who also use ENDS (dual users). Since 2016, the Food and Drug Administration (FDA) has had regulatory authority over ENDS, and there is an acute need for ENDS-related biomarkers that can be used as validated surrogate endpoints for evaluation of new ENDS products. With the goal of validated biomarker discovery in two independent cohorts, the COPDGene and UCSD ENDS studies, we propose to identify ENDS-related inflammatory biomarkers in ENDS only and dual users and relate these biomarkers to five-year lung health outcomes. COPDGene is an ongoing, longitudinal study of >6,000 current and former traditional cigarette (t-cig) smokers enriched for chronic obstructive pulmonary disease (COPD) with detailed longitudinal lung phenotyping data (including chest CT), genome-wide blood RNA-seq, and proteomic data. The UCSD ENDS Study is a controlled study of young ENDS only users and controls with detailed assessment of inflammatory biomarkers in the oropharynx, airways and blood. Biomarkers used as validated surrogate measures must be 1) associated with ENDS use, 2) predictive of health outcomes, and 3) have a strong biological rationale. We hypothesize that inflammatory biomarkers of ENDS use will be predictive of five-year lung health effects. In Aim 1 of this proposal, discovery of inflammatory transcriptomic and proteomic biomarkers of ENDS exposure will be performed in subjects from the COPDGene five-year study visit, and biomarkers will be validated in two independent sets of subjects from the COPDGene ten-year visit and the UCSD ENDS Study. In Aim 2 we will identify antibody-specific adaptive immune response biomarkers of ENDS exposure using adaptive immune receptor repertoire sequencing (AIRR-seq). Auto-antibodies are biomarkers that are associated with the degree of lung damage in COPD. AIRR-seq is a powerful tool for inflammatory biomarker discovery that characterizes an individual’s decades-long history of antibody responses. In Aim 3 we will use machine learning predictive models to relate ENDS-associated biomarker panels to five-year lung health outcomes from COPDGene. The investigative team for this grant is well-positioned to identify novel inflammatory biomarkers of ENDS use. The COPDGene and UCSD cohorts have the detailed lung phenotyping and molecular characterization necessary to discover and clinically validate biomarkers in two important populations of ENDS users, i.e. ENDS only and dual users.

项目摘要。该项目旨在确定经过验证的生物标志物用于评估 FDA的电子尼古丁输送系统（末端）。自从引入目的以来，通常被称为电子烟，年轻人和年龄较大的年轻人的目的使用量大大增加传统的吸烟者也使用末端（双用户）。自2016年以来，食品和药物管理局（FDA）对目的具有监管权，并且对终点相关的生物标志物有急需可以用作经过验证的替代端点，以评估新目的产品。有目标在两个独立队列中的经过验证的生物标志物发现，COPDGENE和UCSD结束了研究，我们建议仅在目的中识别与末端相关的炎症生物标志物以及双重用户及相关这些生物标志物达到五年的肺健康成果。科普丁是一项持续的纵向研究 > 6,000名当前和以前的传统香烟（T-cig）吸烟者富含慢性阻塞性肺疾病（COPD），具有详细的纵向肺表型数据（包括胸部CT），全基因组血液 RNA-seq和蛋白质组学数据。 UCSD结束研究是对年轻目的的对照研究，只有用户和对照对口咽，气道和血液中炎症生物标志物的详细评估。用作经过验证的替代测量的生物标志物必须为1）与目的相关联，2）预测健康结果和3）具有强大的生物学原理。我们假设炎症生物标志物目的的使用将预测五年的肺部健康影响。在本提案的目标1中，发现末端暴露的炎症转录组和蛋白质组学生物标志物将在来自的受试者中进行 Copdgene五年研究访问，生物标志物将在两组独立的科目中进行验证从Copdgene十年访问和UCSD结束研究中。在AIM 2中，我们将确定特定于抗体的使用自适应免疫受体库的自适应免疫响应生物标志物暴露测序（AIRR-SEQ）。自动抗体是与肺损害程度相关的生物标志物在COPD中。 airr-seq是炎症生物标志物发现的强大工具，该发现是一个人的角色数十年的抗体反应史。在AIM 3中，我们将使用机器学习预测模型与 COPDGENE的终端相关生物标志物面板与五年的肺部健康成果。调查这笔赠款的团队有很好的位置，可以识别新型炎症生物标志物的使用。 Copdgene UCSD队列具有发现的详细肺表型和分子表征。并在临床上验证了两个重要用户的生物标志物，即仅结束和双重用户。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Deleterious Association of Inhalant Use on Sleep Quality during the COVID-19 Pandemic.

DOI：
10.3390/ijerph182413203
发表时间：
2021-12-15
期刊：
International journal of environmental research and public health
影响因子：
0
作者：
Gunge D;Marganski J;Advani I;Boddu S;Chen YJE;Mehta S;Merz W;Fuentes AL;Malhotra A;Banks SJ;Crotty Alexander LE
通讯作者：
Crotty Alexander LE

Just When We Thought Nothing Could Be Worse Than Smoking Tobacco, Vaping e-Hookah Proves Us Wrong.

就在我们认为没有什么比吸烟更糟糕的时候，电子水烟却证明我们错了。