Saliva cotinine and recent smoking--evidence for a nonlinear relationship

Cotinine concentration in various body fluids is considered to be among the most useful markers of nicotine exposure currently available. Despite the prevailing consensus concerning cotinine's usefulness, cotinine's large intrasubject variability has led some to question the value of a single-point measurement. Several individual differences (for example, age, race, sex, and so forth) may affect cotinine excretion, and a peculiar nonlinearity between the number of cigarettes smoked and cotinine concentration has been reported previously in the literature. The purpose of this investigation was to examine the nature of the association between cotinine and reported number of cigarettes smoked after adjustment for the relationship between cotinine and age, a key individual difference known to affect drug absorption, distribution, metabolism, excretion, and tissue sensitivity. The authors examined the relationship between saliva cotinine and daily cigarette consumption in 116 smokers (mean age = 37.4 years; average number of cigarettes smoked daily = 20.1) who logged each cigarette into a hand-held computer as part of a study on the accuracy of recall. The Pearson correlation between saliva cotinine and the logged number of cigarettes smoked in the previous 17 hours (the time window corresponding to the half-life of cotinine) accounted for significantly more of the variance in cotinine than did the average logged number of cigarettes smoked daily during 5 days. Age was also significantly associated with cotinine levels. Further examination of the relationship between cotinine and amount smoked in the previous 17 hours revealed evidence for a significant nonlinear component. Inclusion of both age and a cubic nonlinear component of daily cigarette consumption resulted in further significant improvement in the amount of variance accounted for in cotinine levels. These results suggest that adjustments forage and the inclusion of a nonlinear component for cigarette consumption will result in more precise use of cotinine as a validation tool for existing differences in smoking levels.