Figure 1.

Graphical abstract

(A) Cigarette smoking addiction represents a complex and challenging interventional target. Cigarettes provide bolus nicotine delivery which accumulates over the course of a day causing a basal-bolus pharmacokinetic pattern, and flavorants from tobacco, menthol, additives, and the combustion process. Consumption is also integrated with habituated use rituals. Cigarettes elicit subjective responses which can be quantified by the Cigarette Evaluation Questionnaire (CEQ). The CEQ consists of 12 questions which segment into five latent categories: satisfaction, enjoyment of respiratory tract sensations, psychological reward, craving reduction, and aversion. Responses are reported on a rating scale of (0–6). The spider chart shown represents mean responses for each category after smoking a combusted cigarette.³ Responses to acute use of combusted cigarettes with nicotine content ranging from very low (0.4 mg, darkest blue) to typical (15.8 mg, red) show a dose-response impact on the CEQ.⁴

(B) Determinants of cessation efficacy can inform a personalized and adaptive interventional paradigm. A stop-smoking product aligned with personal choice and other predictive selection criteria can be tried during an initial pre-quit period. If initial response is below a minimal threshold, adjustments can be made, including change of dosing or flavor, combination with an adjunctive product, or switching to a better tolerated product. Provision of supportive care or digital closed loop technologies can further improve outcomes as well as accuracy of measuring initial response (i.e., reduction in exhaled CO in the pre-quit period).