Effect of Immediate vs Gradual Reduction in Nicotine Content of Cigarettes on Biomarkers of Smoke Exposure A Randomized Clinical Trial
Effect of Immediate vs Gradual Reduction in Nicotine Content of Cigarettes on Biomarkers of Smoke Exposure A Randomized Clinical Trial
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DOI：
10.1001/jama.2018.11473
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发表时间：
2018-09-04
影响因子：
120.7
通讯作者：
Donny, Eric C.
中科院分区：
文献类型：
--
作者：
Hatsukami, Dorothy K.;Luo, Xianghua;Donny, Eric C.
重要性在美国销售的所有香烟中，将尼古丁降低到最低或非成瘾水平的最佳时间方法尚未确定。为了确定将尼古丁含量立即与逐渐降低到非常低的水平以及与通常尼古丁水平香烟相比对毒物暴露的生物标志物的影响。在10个美国研究中心进行了一项平行设计研究，包括2周的基线吸烟和20周的干预。于2014年7月至2016年9月招募了30天内无戒烟意向的每日吸烟者志愿者样本，末次随访于2017年3月完成。干预（1）立即将尼古丁降至每克卷烟0.4mg;（2）每克香烟尼古丁含量由15.5mg逐渐降至0.4mg，每月更换5次;或（3）维持每克烟草香烟15.5mg尼古丁。主要结果和测量烟雾毒物暴露的3种共同主要生物标志物的组间差异：呼气一氧化碳（CO）、尿3-羟丙基巯基尿酸（3-HPMA，丙烯醛的代谢物）和尿菲四醇（PheT，多环芳烃的指示物）计算为20周干预的浓度-时间曲线下面积。（平均年龄45岁; 549名女性[44%]; 958名[77%]完成了试验），在立即减少组与逐渐减少组中观察到的CO暴露水平显著较低（平均差异，-4.06 ppm [95% CI，-4.89至-3.23]; P < .0055），3-HPMA（几何平均值比，0.83 [95%CI，0.77至0.88]; P < .0055）和PheT（几何平均值比，0.88 [95%CI，0.83至0.93]; P < .0055）。与对照组相比，立即减少组的CO暴露水平显著降低（平均差异，-3.38 [95% CI，-4.40至-2.36]; P < .0055），3-HPMA（几何平均值比，0.81 [95%CI，0.75至0.88]; P < .0055）和PheT（几何平均值比，0.86 [95%CI，0.81至0.92]; P < .0055）。逐渐减少组与对照组之间的CO无显著差异（平均差异，0.68 [95%CI，-0.31至1.67]; P = 0.18），3-HPMA（几何均值比，0.98 [95% CI，0.91 - 1.06]; P = 0.64）和PheT（几何平均数比，0.98 [95% CI，0.92 - 1.04];结论和相关性在吸烟者中，与逐渐减少相比，立即减少香烟中的尼古丁会导致吸烟暴露生物标志物随时间的显著下降或对照组，逐渐减少和对照组之间没有显著差异。
IMPORTANCE The optimal temporal approach for reducing nicotine to minimally or nonaddictive levels in all cigarettes sold in the United States has not been determined.OBJECTIVES To determine the effects of immediate vs gradual reduction in nicotine content to very low levels and as compared with usual nicotine level cigarettes on biomarkers of toxicant exposure.DESIGN, SETTING, AND PARTICIPANTS A double-blind, randomized, parallel-design study with 2 weeks of baseline smoking and 20 weeks of intervention was conducted at 10 US sites. A volunteer sample of daily smokers with no intention to quit within 30 days was recruited between July 2014 and September 2016, with the last follow-up completed in March 2017.INTERVENTIONS (1) Immediate reduction to 0.4mg of nicotine per gram of tobacco cigarettes; (2) gradual reduction from 15.5mg to 0.4mg of nicotine per gram of tobacco cigarettes with 5 monthly dose changes; or (3) maintenance on 15.5mg of nicotine per gram of tobacco cigarettes.MAIN OUTCOMES AND MEASURES Between-group differences in 3 co-primary biomarkers of smoke toxicant exposure: breath carbon monoxide (CO), urine 3-hydroxypropylmercapturic acid (3-HPMA, metabolite of acrolein), and urine phenanthrene tetraol (PheT, indicator of polycyclic aromatic hydrocarbons) calculated as area under the concentration-time curve over the 20 weeks of intervention.RESULTS Among 1250 randomized participants (mean age, 45 years; 549 women [44%]; 958 [77%] completed the trial), significantly lower levels of exposure were observed in the immediate vs gradual reduction group for CO (mean difference, -4.06 parts per million [ppm] [95% CI, -4.89 to -3.23]; P < .0055), 3-HPMA (ratio of geometric means, 0.83 [95% CI, 0.77 to 0.88]; P < .0055), and PheT (ratio of geometric means, 0.88 [95% CI, 0.83 to 0.93]; P < .0055). Significantly lower levels of exposure were observed in the immediate reduction vs control group for CO (mean difference, -3.38 [95% CI, -4.40 to -2.36]; P < .0055), 3-HPMA (ratio of geometric means, 0.81 [95% CI, 0.75 to 0.88]; P < .0055), and PheT (ratio of geometric means, 0.86 [95% CI, 0.81 to 0.92]; P < .0055). No significant differences were observed between the gradual reduction vs control groups for CO (mean difference, 0.68 [95% CI, -0.31 to 1.67]; P = .18), 3-HPMA (ratio of geometric means, 0.98 [95% CI, 0.91 to 1.06]; P = .64), and PheT (ratio of geometric means, 0.98 [95% CI, 0.92 to 1.04]; P = .52).CONCLUSIONS AND RELEVANCE Among smokers, immediate reduction of nicotine in cigarettes led to significantly greater decreases in biomarkers of smoke exposure across time compared with gradual reduction or a control group, with no significant differences between gradual reduction and control.