The participant sample was 59% male, 96% Caucasian with an average age of 45.4 (SD=10.8) years old. On average, they had been smoking for 29.3 years (SD=11.2), smoked an average of 20.5 cigarettes per day (SD=8.4), with an average nicotine dependence score of 4.9 (SD=2.1). Most participants smoked a Light brand (55%) and non-menthol (71%) cigarette. This study sample is similar to the full clinical study sample, [n=568; (see 15)], but with a significantly greater proportion of Caucasians (84% in the full sample). Of the 142 who attended these initial intake sessions, 131 (92%) agreed to complete a smoking topography assessment with their own brand cigarettes; 14 withdrew prior to having assays completed, 5 had contaminated urine samples, and 3 had failed topography assessment. Topography session completers did not differ from non-completers on demographic or smoking variables.
Mean plasma NMR value was 0.395 (SD=0.20; range 0.012–1.246). Mean, standard deviation, lower and upper limits for quartiles were: 1) 0.192 (SD=0.06; 0.010–0.259); 2) 0.313 (SD=0.03; 0.260–0.357); 3) 0.410 (SD=.036; 0.358–0.477); 4) 0.668 (SD=0.21; 0.478–1.246) (additional data see ). Females were more likely to be in the highest NMR (faster metabolism; p=.02), consistent with prior reports that women metabolize nicotine faster than men (25
). NMR was non-significantly higher among participants who were older (p=.10), had higher nicotine dependence levels (p=.09), and who smoked non-menthol cigarettes (p=.10). Thus, these variables were included as covariates.
Mean (Standard Deviation), unless noted otherwise. Note: Reg.=Regular cigarette; Lt.=Light cigarette; U-Lt=Ultra-Light cigarette, based on Federal Trade Commission (FTC) cigarette classifications used at the time data was collected (FTC, 2000).
Mean total puff volume was 785.1 ml (SD=284.9; range 247.4–1776.1). There was an overall association of NMR quartiles with total puff volume (F=2.62, p=.05); smokers in the third quartile (p=.042) and fourth quartile (p=.016) exhibited significantly higher total puff volumes than those in the first quartile (; ). Faster metabolizers by CYP2A6 (*1/*1, n=89) genotype also had higher puff volumes than slower metabolizers (defined as any of *2, *4, *9, *12 variants, n=19); means were 816.8 ml (SD=292.0) vs. 643.3 ml (SD=206.9), respectively (F=6.04, p=.02) (results the same when the 5 non-European ancestry subjects were excluded).
Figure 1 Association of the NMR with total puff volume and NNAL. (A) NMR quartiles versus total puff volume (ml). Results are mean values +/− standard error (F=2.62, p=.05). Post-hoc comparisons indicate a significant difference between first and third (more ...)
Mean total NNAL was 1.47 pmol/mg creatinine (SD=0.79; range 0.10–4.2). There was a significant main effect of the NMR (F=3.59, p=.02); smokers in the third quartile (p=.001) and fourth quartile (p=.033) had higher total NNAL levels than those in the first quartile (; ). A similar, non-significant difference was seen in genotypic fast versus slow metabolizers (1.54 pmol/mg creatinine [SD=.92] vs. 1.34 pmol/mg creatinine [SD=.68]), p=.35). Results were unchanged when the nicotine dependence (FTND) covariate was replaced with smoking rate.
Linear regression analysis indicated a positive association between log-transformed NMR and total puff volume (beta=321.2, t=2.35, p=.024, R2 =.051); and log-transformed NMR and total NNAL (beta=.831, t=2.41, p=.02, R2 =.052). Stepwise regression analysis indicated that the total puff volume by daily cigarette consumption product was positively associated with total NNAL level (beta=2.538×10−5, t=2.94, p=.004), controlling for sex (p=.02), years smoking (p=.04), and menthol (p=.16); the overall model was significant [F(4,104)=4.85, p=.001, R2=.16).