Effect of Menthol to Non-Menthol Cigarette Switching on Subclinical Inflammatory Biomarkers of Cardiovascular Health: Simulating a Menthol Cigarette Ban

薄荷醇向非薄荷醇香烟转换对心血管健康亚临床炎症生物标志物的影响：模拟薄荷醇香烟禁令

• 批准号: 10693276
• 负责人: Nancy Chia Lei Jao
• 金额: $ 17.77万
• 依托单位: ROSALIND FRANKLIN UNIV OF MEDICINE & SCI
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10693276
• 关键词: Accounting; Adult; Affect; Area; Award; Basic Science; Biological Markers; Blood specimen; C-reactive protein; Carbon Monoxide; Cardiovascular Diagnostic Techniques; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Cessation of life; Cigarette; Cigarette Smoker; Clinical; Clinical Trials; Confounding Factors (Epidemiology); Cotinine; Data; Data Collection; Data Set; Development; Disease; Doctor of Philosophy; Early Diagnosis; Ecological momentary assessment; Evaluation; Fibrinogen; Flavoring; Functional disorder; Goals; Health; Health Hazards; Human; Individual; Inflammation; Inflammatory; Inflammatory Response; Intake; Interleukins; Measures; Menthol; Mentors; Mentorship; Methodology; Methods; Morbidity - disease rate; Outcome; Participant; Pathway interactions; Pattern; Phase; Policies; Population; Population Assessment of Tobacco and Health; Prevalence; Regulation; Research; Research Methodology; Research Priority; Role; Scientist; Smoker; Smoking; Smoking Behavior; Statistical Data Interpretation; Stress; Structure; Time; Tobacco; Tobacco use; Training; Translational Research; United States Food and Drug Administration; biobehavior; cardiovascular disorder risk; cardiovascular health; career; cigarette smoking; combustible cigarette; craving; cytokine; design; follow-up; health disparity; improved; interest; mortality; non-cigarette tobacco product; programs; recruit; response; smoking cessation; systemic inflammatory response; tobacco exposure; tobacco flavor; tobacco products; tobacco regulatory science

PROJECT SUMMARY/ABSTRACT The proposed K01 application is designed to provide Nancy Jao, Ph.D., with the mentored research and training necessary to transition into an independent clinical scientist with a tobacco regulatory relevant program of research. The FDA has long indicated interest in banning menthol as a characterizing flavor in combustible cigarettes due to its role in facilitating the initiation and use of tobacco products and increasing the number of smoking-related deaths. Smoking-induced inflammation is a leading pathway by which cigarette smoking contributes to increased cardiovascular disease (CVD) morbidity and mortality in smokers. Elevations in biomarkers of inflammation can be detected early, even in asymptomatic individuals, as a subclinical indicator of CVD risk. Basic science studies have shown that menthol flavoring can cause increases in inflammatory response and dysfunction beyond the effects of smoking. However, it is unknown whether menthol cigarette (MC) use may elevate biomarkers of inflammation in smokers and increase CVD risk compared to non-menthol cigarette (NMC) use. Additionally, while it is expected that a MC ban will improve health outcomes for smokers who quit or switch to non-combustible products, it is unknown whether there will be reductions in inflammation for those who switch from MC to NMC smoking. In Study 1, we aim to evaluate differences in biomarkers of systemic inflammation and CVD risk between MC and NMC smokers in nationally-representative, longitudinal Population Assessment of Tobacco and Health (PATH) Study. In Study 2, we aim to examine how switching from MC to NMC smoking may impact biomarkers of systemic inflammation, smoking behavior, and subjective responses related to smoking. MC smokers (N=68) will be recruited for a five-week study, with one-week of baseline of MC smoking (Phase 1), followed by four weeks of switching to study-provided, brand-matched NMCs (Phase 2). Biomarkers of systemic inflammation (e.g., hsCRP, interleukin cytokines) and tobacco exposure (e.g., cotinine, carbon monoxide) will be analyzed from blood samples before, during, and after switching. Ecological momentary assessment (EMA) methods will also be gathered to measure patterns of smoking and smoking-related subjective responses. The proposed research is significant and directly targets FDA's interest in understanding the impact of flavorings on the health effects of tobacco use. Throughout the five-year award, Dr. Jao will be mentored by an impressive mentorship team in (1) translational research in biobehavioral and health effects of tobacco use, particularly relating to biomarkers of inflammation and CVD risk; (2) longitudinal research methods and advanced statistical analyses, including utilization of the PATH study dataset and EMA methodology; and (3) design and implementation of human clinical trial studies with tobacco regulatory implications. Understanding the impact of MC use on these sensitive subclinical biomarkers prior to CVD diagnosis can help the FDA identify and quantify cardiovascular health hazards of MC use, particularly for those who may continue to use combustible cigarettes if a MC ban is implemented by the FDA.

项目摘要/摘要 拟议的K01应用程序旨在向Nancy Jao，Ph.D.提供指导的研究和 通过烟草监管相关计划过渡到独立临床科学家所需的培训 研究。 FDA长期以来一直表明禁止薄荷醇作为可燃的味道的兴趣 由于香烟在促进烟草产品的启动和使用中的作用，并增加了数量 与吸烟有关的死亡。吸烟引起的炎症是吸烟的领先途径 有助于增加吸烟者的心血管疾病（CVD）发病率和死亡率。高程 即使在无症状的个体中，也可以尽早检测到炎症的生物标志物作为亚临床指标 CVD风险。基础科学研究表明，薄荷醇调味剂会导致炎症增加 反应和功能障碍超出了吸烟的影响。但是，尚不清楚Menthol香烟是否 （MC）使用可能会提高吸烟者炎症的生物标志物，并增加CVD风险 香烟（NMC）使用。此外，虽然预计MC禁令将改善吸烟者的健康状况 谁退出或切换到非燃烧产品，尚不清楚炎症是否会减少 对于那些从MC转向NMC吸烟的人。在研究1中，我们旨在评估生物标志物的差异 MC和NMC吸烟者之间的全身性炎症和CVD风险在国家代表性的纵向中 烟草和健康（PATH）研究的人群评估。在研究2中，我们旨在检查如何切换 从MC到NMC吸烟可能会影响系统性炎症，吸烟行为和主观的生物标志物 与吸烟有关的反应。 MC吸烟者（n = 68）将招募为期五周的研究，其中一周为一周 MC吸烟的基线（第1阶段），然后切换到研究提供了四个星期 NMC（第2阶段）。系统性炎症的生物标志物（例如HSCRP，白介素细胞因子）和烟草 接触（例如，可替宁，一氧化碳）将从血液样本中分析 交换。还将收集生态瞬时评估（EMA）方法，以测量 吸烟和与吸烟有关的主观反应。拟议的研究很重要，直接针对 FDA有兴趣了解调味料对烟草使用的健康影响的影响。整个 五年奖，Jao博士将由一名令人印象深刻的指导团队指导（1）翻译研究 烟草使用的生物行为和健康影响，特别是与炎症和CVD的生物标志物有关 风险; （2）纵向研究方法和高级统计分析，包括路径的利用 研究数据集和EMA方法论； （3）设计和实施人类临床试验研究 烟草监管含义。了解MC使用对这些敏感亚临床生物标志物的影响 在CVD诊断之前，可以帮助FDA识别并量化MC使用的心血管健康危害， 特别是对于那些如果FDA实施MC禁令，可能会继续使用可燃香烟的人。