Comparison of Urine Cotinine and the Tobacco-Specific Nitrosamine Metabolite 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanol (NNAL) and Their Ratio to Discriminate Active From Passive Smoking
Comparison of Urine Cotinine and the Tobacco-Specific Nitrosamine Metabolite 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanol (NNAL) and Their Ratio to Discriminate Active From Passive Smoking
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DOI：
10.1093/ntr/ntq237
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发表时间：
2011-03-01
影响因子：
4.7
通讯作者：
Benowitz, Neal L.
中科院分区：
文献类型：
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作者：
Goniewicz, Maciej Lukasz;Eisner, Mark D.;Benowitz, Neal L.
可替宁是区分主动吸烟与被动吸烟的最广泛使用的生物标志物。然而，当比较轻度或偶尔吸烟者与重度暴露的被动吸烟者时，可替宁水平存在重叠。4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁醇（NNAL）是一种烟草特有的亚硝胺，可在尿液中测量，半衰期比可替宁长得多。本研究的目的是确定区分主动吸烟者和被动吸烟者的最佳分界点，并比较使用可替宁、NNAL和尿中NNAL/可替宁比值的敏感性和特异性。检测了373例主动吸烟者和228例被动吸烟者的尿中可替宁和NNAL。几何平均可替宁水平为2.03 ng/ml（四分位间距：0.43-8.60）和1，043 ng/ml（658- 2，251），被动吸烟者和主动吸烟者的NNAL水平分别为5.80 pg/ml（2.28-15.4）和165 pg/ml（90.8-360）pg/ml。与主动吸烟者相比，被动吸烟者尿液中的NNAL/可替宁比值显著更高（2.85 vs. 0.16，p <0.01）。受试者工作特征分析确定了区分被动吸烟者与主动吸烟者的最佳截止点：可替宁为31.5 ng/ml（敏感性：97.1%，特异性：93.9%），NNAL为47.3 pg/ml（87.4%和96.5%），NNAL/可替宁比值为0.74 × 10 ~（-3）（分别为97.3%和87.3%），两者均为鉴别烟草烟雾暴露源的敏感而特异的生物标志物。当一个人持续暴露于烟草烟雾中时，测量生物标志物时，可替宁是最好的整体替代品。NNAL由于其半衰期长，在暴露和生物标志物测量之间存在延迟时特别有用。NNAL/可替宁比值在区分被动吸烟者与主动吸烟者时提供了与单独NNAL相比相似的灵敏度，但特异性较差。
Cotinine is the most widely used biomarker to distinguish active versus passive smoking. However, there is an overlap in cotinine levels when comparing light or occasional smokers versus heavily exposed passive smokers. 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is a tobacco-specific nitrosamine measurable in urine with a much longer half-life than cotinine. The aim of the study was to determine optimal cutoff points to discriminate active versus passive smokers and to compare sensitivity and specificity for the use of cotinine, NNAL, and the ratio of the NNAL/cotinine in urine.Cotinine and NNAL were measured in urine of 373 active smokers and 228 passive smokers.Geometric mean cotinine levels were 2.03 ng/ml (interquartile interval: 0.43-8.60) and 1,043 ng/ml (658-2,251) and NNAL levels were 5.80 pg/ml (2.28-15.4) and 165 pg/ml (90.8-360) pg/ml in passive and active smokers, respectively. NNAL/cotinine ratio in urine was significantly higher for passive smokers when compared with active smokers (2.85 vs. 0.16, p < .01). The receiver operating characteristics analysis determined optimal cutoff points to discriminate passive versus active smokers: 31.5 ng/ml for cotinine (sensitivity: 97.1% and specificity: 93.9%), 47.3 pg/ml for NNAL (87.4% and 96.5%), and 0.74 x 10(-3) for NNAL/cotinine ratio (97.3% and 87.3%).Both urine cotinine and NNAL are sensitive and specific biomarkers for discriminating the source of tobacco smoke exposure. Cotinine is the best overall discriminator when biomarkers are measured while a person has ongoing exposure to tobacco smoke. NNAL because of its long half-life would be particularly useful when there is a delay between exposure and biomarker measurement. The NNAL/cotinine ratio provides similar sensitivity but poorer specificity at discriminating passive versus active smokers when compared with NNAL alone.