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

项目总结/摘要 拟议的K 01应用程序旨在为Nancy Jao博士提供，有指导的研究， 培训必要过渡到一个独立的临床科学家与烟草监管相关的程序 研究。FDA长期以来一直表示有兴趣禁止薄荷脑作为可燃物的特征香料 由于其在促进烟草产品的开始和使用以及增加吸烟人数方面的作用， 与吸烟有关的死亡吸烟引起的炎症是吸烟引起炎症的主要途径。 导致吸烟者心血管疾病（CVD）发病率和死亡率增加。升高 炎症的生物标志物可以早期检测到，即使在无症状的个体中，作为亚临床指标 CVD风险。基础科学研究表明，薄荷醇调味品会导致炎症增加， 反应和功能障碍超出了吸烟的影响。然而，目前尚不清楚薄荷醇香烟是否 (MC)与非薄荷醇相比，使用薄荷醇可能会提高吸烟者的炎症生物标志物， 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， 戒烟或改用不可燃产品的人，是否会减少炎症还不清楚。 对于那些谁从MC转换到NMC吸烟。在研究1中，我们的目的是评估生物标志物的差异， MC和NMC吸烟者之间的全身炎症和CVD风险， 烟草与健康人口评估研究（PATH）。在研究2中，我们的目标是研究如何切换 从MC到NMC吸烟可能会影响全身炎症，吸烟行为和主观的生物标志物 与吸烟有关的反应。将招募MC吸烟者（N=68）进行为期五周的研究，其中一周为 MC吸烟基线（1期），随后4周转换为研究提供的品牌匹配 NMC（第2阶段）。全身性炎症的生物标志物（例如，hsCRP，白细胞介素细胞因子）和烟草 暴露（例如，可替宁，一氧化碳）将在术前、术中和术后从血样中进行分析 切换还将收集生态瞬时评估（EMA）方法，以衡量 吸烟和吸烟相关的主观反应。本课题的研究意义重大，直接针对 FDA有兴趣了解香料对烟草使用的健康影响的影响。在整个 五年奖，饶博士将由一个令人印象深刻的导师团队指导（1）转化研究， 烟草使用的生物行为和健康影响，特别是与炎症和CVD生物标志物相关的影响 风险;（2）纵向研究方法和先进的统计分析，包括PATH的使用 研究数据集和EMA方法;（3）设计和实施人体临床试验研究， 烟草监管影响。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使用的心血管健康危害， 特别是对于那些可能继续使用可燃香烟的人，如果FDA实施MC禁令。

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.