Developing Personalized Smoking Treatment in the Southern Community Cohort Study

摘要 吸烟会增加患多种癌症的风险，占所有癌症死亡人数的30%以上，占80% 死于肺癌的人数。与吸烟有关的疾病负担在社会经济和种族/民族方面存在差异 20年来，黑人和白人之间的癌症存活率差距一直未能弥合。改进的战略 对于服务不足的群体来说是必要的。使用生物数据个性化标准护理，以1)提高准确性 或2)测量尼古丁代谢速度来为药物治疗选择提供信息是一种 在低收入少数吸烟者中有希望但研究不足的方法。这种基于生物信息的个人化 治疗可以增加戒烟的动力，提高吸烟相关健康的准确性，从而使吸烟者受益 风险感知，或通过其他机制。接受基于基因的肺癌风险评估的吸烟者， Respiragene(由Young博士开发，顾问)更有可能接受肺癌筛查，使用尼古丁 替代疗法(NRT)和戒烟。另一种有前景的个性化干预工具是尼古丁 代谢物比率(核磁共振)，反映两种尼古丁代谢物(3‘-羟基可替宁/可替宁)比率的生物标志物。 与CYP2A6基因的活性非常接近。核磁共振被认为是新兴的生物标记物 尼古丁代谢，可以分为“快/正常”和“慢”两类。来自廷代尔博士(顾问)的试验数据 显示核磁共振为戒烟药物治疗的选择提供信息，从而使“快速/正常”代谢物是两倍 与“慢”代谢剂相比，使用varenicline戒烟的可能性一样大。这两种有希望的干预措施 已经在社区接受医疗保健的脆弱吸烟者中进行了研究。综合起来，这些初步的 在南方社区队列研究(SCCS)中，数据为个性化吸烟治疗设定了一个引人注目的阶段。 我们的总体目标是利用SCCS和外展核心社区咨询委员会(CAB) 指导开发两种个性化戒烟护理(PC)干预措施：PC-Respiragene 和PC-核磁共振图谱。PC-Respiragene和PC-核磁共振植根于行为改变的原始模型，该模型反映了 对戒烟动机的多方面看法。两者都将根据Low的态度和信念量身定做 社会经济地位(定义为人口的大多数&100%联邦贫困水平) 美国东南部，那里的烟草使用率非常高。目标1将调查居住在SCCS的吸烟者 田纳西州和密西西比州评估对吸烟相关健康风险认知的态度和信念，个性化 吸烟治疗和是否愿意参加PC戒烟试验(n=1647)。AIM 2将利用驾驶室投入 开发PC-Respiragene和PC-核磁共振，供SCCS中不同的、低SES社区吸烟者使用。目标3 将进行三臂随机对照试验(N=75)吸烟者，以试验PC-Respiragene和PC-核磁共振干预的可行性 并在6点确定生物化学验证的戒烟和肺癌筛查的初步估计 几个月与基于指南的护理(GBC)相比。这些目标的实现将为个性化的大规模RCT奠定基础 在SCCS中戒烟。

SUMMARY Cigarette smoking increases the risk of multiple cancers, accounting for more than 30% of all cancer deaths and 80% of deaths from lung cancer. Disparities exist in smoking-related disease burden by socioeconomic and racial/ethnic status, and the cancer survival gap between blacks and whites has failed to close in 2 decades. Improved strategies are needed for underserved groups. Personalizing standard care with biological data to 1) enhance accuracy of lung cancer risk or 2) measure speed of nicotine metabolism to inform pharmacotherapy choice is a promising yet understudied approach in low income minority smokers. Such biologically-informed personalized treatment could benefit smokers by increasing motivation to quit, improving the accuracy of smoking-related health risk perceptions, or via other mechanisms. Smokers undergoing the gene-based lung cancer risk assessment, Respiragene (developed by Dr. Young, consultant) were more likely to undergo lung cancer screening, use nicotine replacement therapy (NRT) and quit smoking. Another promising tool for personalized intervention is the nicotine metabolite ratio (NMR), a biomarker reflecting the ratio of two nicotine metabolites (3'hydroxycotinine/cotinine) that closely approximates CYP2A6 gene activity. The NMR is considered the emerging biomarker of choice to measure nicotine metabolism, which can be dichotomized as “fast/normal” vs “slow.” Trial data from Dr. Tyndale (consultant) show that NMR informs choice of smoking cessation pharmacotherapy such that “fast/normal” metabolizers are twice as likely to quit smoking on varenicline compared to “slow” metabolizers. Neither of these promising interventions have been studied in vulnerable smokers receiving health care in the community. Taken together, these preliminary data set a compelling stage for personalized treatment of smoking in the Southern Community Cohort Study (SCCS). Our overarching aim is to leverage the SCCS and the Outreach Core Community Advisory Board (CAB) to guide the development of two personalized care (PC) interventions for smoking cessation: PC-Respiragene and PC-NMR. PC-Respiragene and PC-NMR are rooted in the PRIME Model of behavior change which reflects a multi-faceted view of motivation for tobacco cessation. Both will be tailored to attitudes and beliefs of low socioeconomic status (defined as majority of the population < 100% federal poverty level) smokers in the southeastern US, where tobacco use prevalence is very high. Aim 1 will survey SCCS smokers residing in Tennessee and Mississippi to assess attitudes and beliefs on smoking-related health risk perceptions, personalized smoking treatment, and willingness to join a smoking cessation trial of PC (n=1647). Aim 2 will leverage CAB input to develop PC-Respiragene and PC-NMR for use among diverse, low SES community smokers in the SCCS. Aim 3 will conduct a 3-arm RCT (N=75) SCCS smokers to pilot PC-Respiragene and PC-NMR interventions for feasibility and determine preliminary estimates of biochemically-validated smoking cessation and lung cancer screening at 6 months vs. guideline based care (GBC). Completion of these aims will lay groundwork for a large RCT of personalized smoking cessation in the SCCS.