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 建议的K01应用程序旨在为Nancy Jao博士提供有指导的研究和 进行必要的培训，以转变为具有烟草监管相关计划的独立临床科学家 研究的成果。FDA长期以来一直表示有兴趣禁止薄荷醇作为可燃物中的一种特征性风味 卷烟，因为它在促进烟草产品的启动和使用以及增加烟草产品的数量方面发挥了作用 与吸烟有关的死亡。吸烟引起的炎症是吸烟的主要途径 导致吸烟者心血管疾病(CVD)发病率和死亡率增加。中的高程 炎症的生物标志物可以作为亚临床指标及早发现，甚至在无症状的个体中也是如此。 心血管疾病风险。基础科学研究表明，薄荷醇调味料会导致炎症增加 除吸烟影响外的反应和功能障碍。然而，目前还不清楚薄荷醇香烟 与非薄荷醇相比，(MC)的使用可能会提高吸烟者炎症的生物标志物，并增加心血管疾病的风险 香烟(NMC)的使用。此外，尽管预计MC禁令将改善吸烟者的健康状况 那些戒烟或改用非可燃产品的人，炎症是否会减少还不得而知 对于那些从MC改用NMC吸烟的人。在研究1中，我们旨在评估不同生物标志物之间的差异 全国范围内MC和NMC吸烟者的全身炎症和心血管疾病风险--具有代表性的、纵向的 烟草与健康人口评估(PATH)研究。在研究2中，我们的目标是检查切换 从MC到NMC，吸烟可能会影响全身炎症、吸烟行为和主观方面的生物标志物 与吸烟有关的反应。MC吸烟者(N=68)将被招募进行为期五周的研究，为期一周 MC吸烟的基线(阶段1)，然后四周切换到研究提供的品牌匹配 NMC(第二阶段)。全身炎症的生物标志物(如hsCRP、白细胞介素型细胞因子)和烟草 暴露(如可替宁、一氧化碳)将在之前、期间和之后从血液样本中分析 正在切换。还将收集生态瞬时评估(EMA)方法来衡量 吸烟与吸烟相关的主观反应。提出的研究具有重要的意义和直接的针对性。 FDA有兴趣了解调味品对烟草使用对健康的影响。在整个过程中 五年奖，Jao博士将在(1)翻译研究方面得到一个令人印象深刻的指导团队的指导 烟草使用的生物行为和健康影响，特别是与炎症和心血管疾病的生物标记物有关的影响 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；以及(3)设计和实施人类临床试验研究 烟草监管方面的影响。了解MC使用对这些敏感的亚临床生物标志物的影响 在CVD诊断之前可以帮助FDA识别和量化MC使用对心血管健康的危害， 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。