A randomized controlled study in healthy participants to explore the exposure continuum when smokers switch to a tobacco heating product or an E-cigarette relative to cessation

Abstract

Background: Cigarette smoking is associated with a number of diseases, such as cancer and cardiovascular diseases. Recently, there has been an increase in the use of electronic cigarettes (ECs) and tobacco-heating products (THPs) as an alternative to cigarettes, which may reduce the health burden associated with smoking. However, an exposure continuum when smokers switch to ECs or THPs compared to complete smoking cessation is not well established.

Methods: 148 healthy smokers were randomized to either continue smoking cigarettes, switch to using the glo THP or a prototype EC, or completely quit any nicotine or tobacco product use for 5 days, after a 2-day baseline period. During this study breath and 24-h urine samples were collected for Biomarker of Exposure (BoE) analysis.

Results: After a 5-day switching period BoE levels showed a substantial significant decrease in levels from baseline in the groups using the glo THP, the prototype EC, and having quit all nicotine and tobacco use. On an exposure continuum, smokers who completely quit nicotine had the lowest levels of assessed BoEs, followed by those who switched to the EC and then those who switched to glo THP use. Participants who continued to smoke had the highest levels of BoEs.

Conclusions: THP or EC use over a 5-day period resulted in significant reductions in exposure to smoke toxicants, in some cases to levels similar to those for nicotine cessation. These results show that on an exposure continuum, nicotine cessation gives the greatest reduction in exposure to tobacco smoke toxicants, closely followed by the EC and the glo THP. These significant reductions in exposure to toxicants suggest that the glo THP and EC have the potential to be Reduced Risk Products.

Study registration: ISRCTN80651909.

Keywords: Biomarker of exposure; Harm reduction; Smoking; Tobacco heating product; e-Cigarette.

Graphical abstract

Fig. 1

Study design schematic. Participants completed a two-day baseline period during which they continued to smoke combustible cigarettes before being randomised to one of the five study arms in the exposure period.

Fig. 2

Biomarker of Exposure (BoEs) changes between baseline and Days 6 to 7. Data are mean values expressed as the percentage change from the baseline value. All data, except for eCO, were calculated using biomarker levels from 24-h urine collections at baseline and on Days 6 to 7. eCO levels were calculated from data captured at baseline and on Day 6 to 7. eCO - exhaled carbon monoxide; TNeq - total nicotine equivalents (nicotine, cotinine, 3-hydroxycotinine and their glucuronide conjugates); 1-OHP - 1-hydroxypyrene; 2-AN - 2-aminonaphthalene; 3-HPMA - 3-hydroxypropylmercapturic acid; 4-ABP - 4-aminobiphenyl; CEMA - 2-cyanoethylmercapturic acid; HEMA - 2-hydroxyethylmercapturic acid; S-PMA - S-phenylmercapturic acid; HMPMA - 3-hydroxy-1-methylpropylmercapturic acid; MHBMA - monohydroxybutenyl-mercapturic acid; NNAL - 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol; NNN - N-nitrosonornicotine; o-tol - o-toluidine; AAMA - N-acetyl-S-(2-carbamoylethyl)cysteine; GAMA - N-acetyl-S-(2-hydroxy-2-carbamoylethyl)cysteine.