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. 2011 Mar;13(3):202-8.
doi: 10.1093/ntr/ntq237. Epub 2011 Jan 21.

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

Maciej Lukasz Goniewicz  1 , Mark D Eisner, Eduardo Lazcano-Ponce, Wioleta Zielinska-Danch, Bartosz Koszowski, Andrzej Sobczak, Christopher Havel, Peyton Jacob, Neal L Benowitz
Affiliations

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

Maciej Lukasz Goniewicz et al. Nicotine Tob Res. 2011 Mar.

Abstract

Objectives: 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.

Methods: Cotinine and NNAL were measured in urine of 373 active smokers and 228 passive smokers.

Results: 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%).

Conclusions: 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.

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Figures

Figure 1.
Figure 1.
Distribution of urine cotinine concentrations with receiver operating characteristics of the optimal cutoff point among passive and active smokers. The dashed line is drawn at the optimal ROC cutoff point.
Figure 2.
Figure 2.
Distribution of urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) concentrations with receiver operating characteristics (ROC) of the optimal cutoff point among passive and active smokers. The dashed line is drawn at the optimal ROC cutoff point.
Figure 3.
Figure 3.
Distribution of the urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL)/cotinine ratio with receiver operating characteristics (ROC) of the optimal cutoff point among passive and active smokers. The dashed line is drawn at the optimal ROC cutoff point.
See this image and copyright information in PMC

References

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