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The role of inhalation behaviors as predictors of nicotine uptake was examined in the Pennsylvania Adult Smoking Study (2012-2014), a study of 332 adults whose cigarette smoking was measured in a naturalistic environment (e.g., at home) with portable handheld topography devices. Piecewise regression analyses showed that levels of salivary cotinine, trans-3'-hydroxycotinine, and total salivary nicotine metabolites (cotinine + trans-3'-hydroxycotinine) increased linearly up to a level of about 1 pack per day (20 cigarettes per day (CPD)) (P &lt; 0.01). Total daily puff volume (TDPV; in mL) (P &lt; 0.05) and total daily number of puffs (P &lt; 0.05), but not other topographical measures, increased linearly with CPD up to a level of about 1 pack per day. The mean level of cotinine per cigarette did not change above 20 CPD and was 36% lower in heavy smokers (≥20 CPD) than in lighter smokers (&lt;20 CPD) (15.6 ng/mL vs. 24.5 ng/mL, respectively; P &lt; 0.01). Mediation models showed that TDPV accounted for 43%-63% of the association between CPD and nicotine metabolites for smokers of &lt;20 CPD. TDPV was the best predictor of nicotine metabolite levels in light-to-moderate smokers (1-19 CPD). In contrast, neither CPD, total daily number of puffs, nor TDPV predicted nicotine metabolite levels above 20 CPD (up to 40 CPD). Finally, although light smokers are traditionally considered less dependent on nicotine, these findings suggest that they are exposed to more nicotine per cigarette than are heavy smokers due to more frequent, intensive puffing.

Comparison of Puff Volume With Cigarettes per Day in Predicting Nicotine Uptake Among Daily Smokers