Changes in biomarkers after 180 days of tobacco heating product use: a randomised trial

The aim of this study was to investigate whether biomarkers of exposure (BoE) and potential harm (BoPH) are modified when smokers switch from smoking cigarettes to exclusive use of a tobacco heating product (THP) in an ambulatory setting. Participants in this randomised, controlled study were healthy volunteer smokers assigned either to continue smoking or switch to a THP, and a control group of smokers who abstained from cigarette smoking. Various BoE and BoPH related to oxidative stress, cardiovascular and respiratory diseases, and cancer were assessed at baseline and up to 180 days. In continuing smokers, BoE and BoPH remained stable between baseline and day 180, while THP users’ levels of most BoE reduced significantly, becoming similar to those in controls abstaining from cigarette smoking. Also at 180 days, significant changes in numerous BoPH, including total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol, 8-epi-prostaglandin F2α type III, fractional concentration of exhaled nitric oxide and white blood cell count, were directionally consistent with lessened health impact. Our findings support the notion that the deleterious health impacts of cigarette smoking may be reduced in smokers who completely switch to using THPs. Supplementary Information The online version contains supplementary material available at 10.1007/s11739-021-02798-6.

not CEVal-compliant at Day 90, thus the analysis was performed on n = 97 participants.
2 Urinary markers at Day 180 (NNN,TNeq, A Of the 59 participants in the Day 180 PP population, 6 were excluded from the analysis (urine collection issues affecting baseline and/or Day 180 visit) thus the analysis was performed on n = 53 participants.

B
Of the 127 participants in the Day 180 PP population, 21 were excluded from the analysis (1 x prohibited medication affecting baseline and/or Day 180 visit, 20 x urine collection issues affecting baseline and/or Day 180 visit). Of the remaining participants, 21 were not CEVal-compliant at Day 180, thus the analysis was performed on n = 85 participants.

WBC at Day 180
A Of the 59 participants in the Day 180 PP population, 3 were excluded from the analysis (baseline and/or Day 180 samples not received at lab) thus the analysis was performed on n = 56 participants.

B
Of the 127 participants in the Day 180 PP population, 7 were excluded from the analysis (1 x prohibited medication affecting baseline and/or Day 180 visit, 6 x baseline and/or Day 180 samples not received at lab). Of the remaining participants, 27 were not CEVal-compliant at Day 180, thus the analysis was performed on n = 93 participants.

FeNO at Day 180
A Of the 59 participants in the Day 180 PP population, 5 were excluded from the analysis (baseline and/or Day 180 assessment not performed by site) thus the analysis was performed on n = 54 participants.

B
Of the 127 participants in the Day 180 PP population, 6 were excluded from the analysis (1 x prohibited medication affecting baseline and/or Day 180 visit, 5 x baseline and/or Day 180 assessment not performed). Of the remaining participants, 28 were not CEVal-compliant at Day 180, thus the analysis was performed on n = 93 participants.
eCO at Day 120/Day 150 A Of the 63 participants in the Day 90 PP population, 1 was excluded from the analysis since they were withdrawn prior to their Day 120 visit, thus the analysis was performed on n = 62 participants.