The Effects of a Standardized Research E-Cigarette On The Human Lung: A Clinical Trial With Bronchoscopic Biomarkers
标准化研究电子烟对人肺的影响:支气管镜生物标志物的临床试验
基本信息
- 批准号:9476111
- 负责人:
- 金额:$ 63.69万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-09-15 至 2019-08-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAerosolsAffectAnimalsBiochemicalBiological AssayBiological MarkersBloodBreathingBronchoscopyCell CountCell Culture TechniquesCellsChemicalsChronic Obstructive Airway DiseaseCigaretteClinical TrialsClinical Trials DesignCotinineCross-Sectional StudiesDataDecision MakingElectronic cigaretteExhalationFeasibility StudiesFlavoringFundingFutureGene ExpressionGoalsHumanIn VitroInflammationInflammatoryInflammatory ResponseIntentionIrrigationLaboratoriesLaboratory StudyLungLung InflammationLung diseasesMalignant neoplasm of lungMarketingMeasuresMessenger RNAMethodsMicroRNAsNasal EpitheliumNational Institute of Drug AbuseNicotineNitric OxideNoseOrganParticipantPathogenesisPathway interactionsPeer ReviewPilot ProjectsProtocols documentationPublic HealthPulmonary InflammationQuality ControlRNARandomizedRandomized Clinical TrialsRegulationResearchResearch InfrastructureRisk ReductionRunningSafetySamplingScienceSmokeSmokerSmokingStandardizationSurrogate MarkersTimeTobaccoToxic effectToxicant exposureUnited States Food and Drug AdministrationUnited States National Institutes of HealthUniversitiesUrineauthoritybiobankcigarette smokingcigarette smokingcytokinedata integrationdesignenvironmental tobacco smoke exposurehuman datain vivoinnovationmRNA Expressionmetabolomicsmultiple omicsnever smokernicotine replacementprimary outcomesmoking cessationtreatment effecturinaryvoltage
项目摘要
Abstract
The use of electronic cigarettes (e-cigs) is increasing rapidly. Yet, little is known about the potential lung toxicity
for inhaling e-cig aerosols relative to smoking. The FDA has deemed regulatory authority over e-cigs and needs
data to determine how to regulate their designs and constituents. It is plausible that e-cig aerosol constituents
(carriers, flavor, and byproducts of these) induce an inflammatory response in the lung, but there is no direct
evidence for this, and what the magnitude of the effect is, if any. While there may be numerous ongoing
laboratory in vitro and in vivo studies to assess e-cig exposure and toxicity, these utilize indirect methods for
assessing lung toxicity. There also are ongoing human studies that focus on the effect of e-cig use on smoking-
related biomarkers of exposure, but these usually assess biofluids outside the lung (e.g., blood and urine). It is
unknown how any of these studies may relate to lung toxicity, e.g., the target organ, and thus there is a critical
research gap. To assess human lung toxicity from e-cig use, we propose to conduct a clinical trial of 128 smokers
to assess inflammatory responses in the lung via serial bronchoscopy. To do this, we will exploit an extraordinary
opportunity for study e-cig toxicity by employing the new NIDIA standardized research e-cig (SREC). Subjects
will be randomized to continued cigarette smoking (control), one of two e-cig use conditions (complete
substitution with the nicotine SREC or dual use with planned smoking reduction), or complete substitution with
nicotine replacement therapy (NRT). Each group will be 32 subjects and the trial will be 5 weeks (a 1 week run-
in period, followed by 4 weeks of the experimental condition). Primary outcomes will be lung biomarkers (cell
counts, cytokines, exhaled nitric oxide, RNA and microRNA gene expression, and untargeted metabolomics).
Several biochemical measures to assess compliance will be employed. A biorepository of urine and nasal
samples will be created for future studies to compare non-invasive biomarkers with lung biomarkers. The
infrastructure for this trial is already established under an FDA- and IRB approved protocol. This study is
significant because it will focus on lung inflammation, a plausible effect on the lungs of e-cig use, and the impact
for switching to e-cigs or dual use, versus complete cessation with NRT. Such data are needed as soon as
possible to assist the FDA in the regulation of e-cigs, including nicotine content. The study is innovative by using
a clinical trial design using serial bronchoscopy, incorporating inflammation biomarkers with metabolomic and
gene expression data, and uses an integrative, complementary and comprehensive approach through multiple
‘omics assays (gene expression – mRNA and miRNA, metabolomics, cell infiltrates and cytokine levels). This
study has considerable public health impact because it will provide experimental evidence in humans of target
organ effects.
摘要
电子烟(e-cigs)的使用正在迅速增加。然而,对潜在的肺毒性知之甚少
用于吸入相对于吸烟的电子烟气溶胶。FDA认为电子烟的监管机构和需求
数据,以确定如何规范其设计和成分。电子烟气溶胶成分似乎是合理的
(载体,香料和这些副产物)诱导肺部炎症反应,但没有直接的
这一点的证据,以及影响的大小,如果有的话。虽然可能有许多正在进行的
实验室体外和体内研究评估电子烟暴露和毒性,这些研究利用间接方法,
评估肺毒性。也有正在进行的人体研究,重点是电子烟对吸烟的影响-
相关的暴露生物标志物,但这些通常评估肺外的生物流体(例如,血液和尿液)。是
尚不清楚这些研究与肺毒性的关系,例如,靶器官,因此有一个关键的
研究差距。为了评估使用电子烟对人类肺部的毒性,我们建议对128名吸烟者进行临床试验。
通过连续支气管镜检查评估肺部炎症反应。为了做到这一点,我们将利用一个非凡的
通过采用新的NIDA标准化研究电子烟(SREC)研究电子烟毒性的机会。科目
将被随机分配到继续吸烟(对照),两种电子烟使用条件之一(完成)
用尼古丁SREC替代或计划减少吸烟的双重用途),或完全替代
尼古丁替代疗法(NRT)每组将有32名受试者,试验将持续5周(1周运行-
阶段,随后是4周的实验条件)。主要结果将是肺生物标志物(细胞
计数、细胞因子、呼出的一氧化氮、RNA和microRNA基因表达以及非靶向代谢组学)。
将采用几种生物化学措施来评估依从性。尿液和鼻腔的生物储存库
将为未来的研究创建样本,以比较非侵入性生物标志物与肺生物标志物。的
本试验的基础设施已根据FDA和IRB批准的方案建立。本研究
重要的是,它将重点关注肺部炎症,电子烟使用对肺部的合理影响,以及
转换为电子烟或两用,而不是完全停止使用NRT。这些数据需要尽快,
这可能有助于FDA监管电子烟,包括尼古丁含量。本研究的创新之处在于,
使用连续支气管镜检查的临床试验设计,将炎症生物标志物与代谢组学和
基因表达数据,并通过多种方法使用综合,互补和全面的方法,
组学分析(基因表达- mRNA和miRNA、代谢组学、细胞浸润和细胞因子水平)。这
这项研究具有相当大的公共卫生影响,因为它将为人类提供目标的实验证据。
器官效应。
项目成果
期刊论文数量(0)
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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Peter G. Shields其他文献
Biochemical and molecular epidemiology of cancer.
癌症的生化和分子流行病学。
- DOI:
- 发表时间:
1991 - 期刊:
- 影响因子:0
- 作者:
Haruhiko Sugimura;Ainsley Weston;Neil E. Caporaso;Peter G. Shields;Elise D. Bowman;Metcalf Ra;Curtis C. Harris - 通讯作者:
Curtis C. Harris
Suppression of de novo antibody responses against SARS-CoV2 and the Omicron variant after mRNA vaccination and booster in patients with B cell malignancies undergoing active treatment, but maintenance of pre-existing antibody levels against endemic viruses.
在接受积极治疗的 B 细胞恶性肿瘤患者中进行 mRNA 疫苗接种和加强接种后,可抑制针对 SARS-CoV2 和 Omicron 变体的从头抗体反应,但维持针对地方性病毒的现有抗体水平。
- DOI:
10.1101/2022.03.17.22272389 - 发表时间:
2022 - 期刊:
- 影响因子:0
- 作者:
Joseph H. Azar;John P. Evans;M. Sikorski;K. Chakravarthy;Selah McKenney;I. Carmody;C. Zeng;Rachael Teodorescu;No;Jamie L. Hamon;D. Bucci;M. Velegraki;Chelsea M Bolyard;Kevin P. Weller;Sarah;Reisinger;S. Bhat;K. Maddocks;R. Gumina;N. Anastasia;Vlasova;E. Oltz;L. Saif;D. Chung;J. Woyach;Peter G. Shields;Shan;Zihai Li;M. Rubinstein - 通讯作者:
M. Rubinstein
Detection and quantification of 8-hydroxydeoxyguanosine adducts in peripheral blood of people exposed to ionizing radiation.
电离辐射暴露人群外周血中 8-羟基脱氧鸟苷加合物的检测和定量。
- DOI:
- 发表时间:
1993 - 期刊:
- 影响因子:10.4
- 作者:
Vincent L. Wilson;B. Taffe;Peter G. Shields;Andrew C. Povey;Curtis C. Harris - 通讯作者:
Curtis C. Harris
Tryptophan hydroxylase gene variant and smoking behavior.
色氨酸羟化酶基因变异与吸烟行为。
- DOI:
- 发表时间:
2001 - 期刊:
- 影响因子:0
- 作者:
C. Lerman;C. Lerman;Neil E. Caporaso;A. Bush;Yun;J. Audrain;D. Main;Peter G. Shields - 通讯作者:
Peter G. Shields
Lack of association of tyrosine hydroxylase genetic polymorphism with cigarette smoking.
酪氨酸羟化酶遗传多态性与吸烟缺乏关联。
- DOI:
10.1097/00008571-199712000-00012 - 发表时间:
1997 - 期刊:
- 影响因子:0
- 作者:
C. Lerman;Peter G. Shields;D. Main;J. Audrain;Joan Roth;Neil R. Boyd;Neil E. Caporaso - 通讯作者:
Neil E. Caporaso
Peter G. Shields的其他文献
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{{ truncateString('Peter G. Shields', 18)}}的其他基金
The Ohio State University Tobacco Center of Regulatory Science (OSU-TCORS)
俄亥俄州立大学烟草监管科学中心 (OSU-TCORS)
- 批准号:
10666066 - 财政年份:2023
- 资助金额:
$ 63.69万 - 项目类别:
Project 1: Urban and Rural Male Youth Cohort Study of Tobacco Use
项目1:城乡男性青少年烟草使用队列研究
- 批准号:
9333246 - 财政年份:2017
- 资助金额:
$ 63.69万 - 项目类别:
Project 2: Understanding Adolescent Trajectories, Exposures and Suscep
项目 2:了解青少年轨迹、暴露和 Suscep
- 批准号:
9333247 - 财政年份:2017
- 资助金额:
$ 63.69万 - 项目类别:
Project 4: Comprehension of Health Risks in More and Less Arousing Affe
项目四:在或多或少引发的情感中理解健康风险
- 批准号:
9333249 - 财政年份:2017
- 资助金额:
$ 63.69万 - 项目类别:
Project 1: Urban and Rural Male Youth Cohort Study of Tobacco Use p138-171
项目1:城乡男性青少年烟草使用队列研究 p138-171
- 批准号:
8595671 - 财政年份:2013
- 资助金额:
$ 63.69万 - 项目类别:
Core D: Developmental/Pilot Research Core p367-377
核心 D:发展/试点研究核心 p367-377
- 批准号:
8595688 - 财政年份:2013
- 资助金额:
$ 63.69万 - 项目类别:
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