Diagnostic Performance Evaluation of the Novel Index Combining Urinary Cotinine and 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol in Smoking Status Verification and Usefulness for Trend Monitoring of Tobacco Smoking Exposure

During the last decade in Korea, urinary cotinine concentrations in non-current smokers have decreased, making it difficult to distinguish secondhand smoke (SHS) exposure from nonsmokers because of overlapping values between non-current smokers with and without SHS exposure. Additionally, the importance of smoking status verification to avoid misclassification is increasing with the increased use of e-cigarettes. We developed a novel index combining urinary cotinine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and evaluated its diagnostic performance for the classification of smoking status using the KNHANES VII dataset. A total of 10,116 and 5575 Korean participants aged >19 years with measured urinary cotinine concentrations were enrolled in a training set and validation set, respectively. When using 4.0 as the cutoff value for distinguishing current smokers from non-current smokers, urinary cotinine center dot NNAL showed a better diagnostic performance than urinary cotinine or urinary NNAL. Among e-cigarette users, urinary cotinine center dot NNAL showed more accurate classification rates than urinary NNAL. Furthermore, urinary cotinine center dot NNAL had measurable values in non-current smokers, whereas urinary cotinine had unmeasurable values in one-fourth of all participants. This study shows that urinary cotinine center dot NNAL might be a useful biomarker for smoking status verification and trend monitoring of tobacco smoking exposure with increased use of e-cigarettes.