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.

项目概要/摘要 拟议的 K01 应用程序旨在为 Nancy Jao 博士提供指导研究和 转变为具有烟草监管相关计划的独立临床科学家所需的培训 研究。 FDA 长期以来一直表示有兴趣禁止薄荷醇作为可燃物中的特征香料 卷烟因其在促进烟草制品的开始和使用以及增加吸烟数量方面的作用 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。海拔高度 即使在无症状个体中，也可以早期检测到炎症生物标志物，作为亚临床指标 CVD 风险。基础科学研究表明，薄荷醇调味料会导致炎症增加 吸烟影响之外的反应和功能障碍。但目前尚不清楚薄荷醇卷烟是否 与非薄荷醇相比，使用 MC 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）的使用。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，炎症是否会减少尚不清楚 对于那些从 MC 吸烟转向 NMC 吸烟的人。在研究 1 中，我们旨在评估生物标志物的差异 全国代表性、纵向研究中 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 (PATH) 研究。在研究 2 中，我们旨在研究如何切换 从 MC 到 NMC 吸烟可能会影响全身炎症、吸烟行为和主观症状的生物标志物 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，其中为期一周 MC 吸烟的基线（第一阶段），然后是四个星期改用研究提供的、品牌匹配的药物 NMC（第二阶段）。全身炎症的生物标志物（例如 hsCRP、白细胞介素细胞因子）和烟草 将在之前、期间和之后对血液样本中的暴露情况（例如可替宁、一氧化碳）进行分析 交换。还将收集生态瞬时评估（EMA）方法来衡量生态模式 吸烟和与吸烟相关的主观反应。拟议的研究意义重大且直接针对 FDA 有兴趣了解香料对烟草使用对健康的影响。整个 五年奖后，饶博士将受到一支令人印象深刻的导师团队的指导，从事 (1) 的转化研究 烟草使用的生物行为和健康影响，特别是与炎症和心血管疾病生物标志物相关的影响 风险; (2) 纵向研究方法和高级统计分析，包括 PATH 的利用 研究数据集和 EMA 方法； (3) 人体临床试验研究的设计和实施 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 使用对心血管健康的危害， 特别是对于那些在 FDA 实施 MC 禁令后可能继续使用可燃卷烟的人。