ESTxENDS Trial-Substudy on Oxidative Stress Induced by Electronic Nicotine Delivery Systems (ENDS) Measured in Urine

--\> This is a substudy of the main ESTxENDS trial (NCT03589989). Oxidative stress outcomes should be considered secondary outcomes of the main smoking cessation outcome formulated in NCT03589989. Cigarette smoking is the leading cause of preventable death in Switzerland and still more than a quarter of the Swiss population smokes cigarettes. Recently, electronic nicotine delivery systems (ENDS; also called vaporizer or electronic cigarette) have become popular with smokers who want to stop smoking or reduce their exposure to inhaled chemicals since ENDS use appears to be safer than tobacco smoking. Smoking induces inflammation leading to acute and chronic oxidative stress, both evidenced in in vitro and in vivo studies. Tobacco-smoke contains free reactive radicals that generate reactive oxygen species (ROS). Afterwards ROS in turn induce oxidative stress, which likely plays a key role in causing airways and related pathologies linked to tobacco-smoke exposure. Acute and chronic oxidative stress can be measured by quantifying two biomarkers in urine samples: 8-iso-prostaglandin F2α (8-isoprostane) and 8-Oxo-2'-deoxyguanosine (8-OHdG). 8-isoprostane, a marker of lipoperoxidation, results mainly from the non-enzymatic action of free radical attack on arachidonic fatty acids. 8-OHdG is a marker of DNA oxidation caused by ROS, and a predictor of lung cancer. Oxidative stress between smokers who quit (with or without ENDS) and those who use ENDS for a long time have not yet been assessed in the setting of a randomized controlled trial (RCT). This study will therefore test the efficacy of ENDS for cigarette smoking cessation, the safety of ENDS on adverse events, the exposure to inhaled chemicals and the effect of ENDS on health-related outcomes, in particular by measuring oxidative stress in urine samples. For the main ESTxENDS trial (NCT03589989), cigarette smokers motivated to quit smoking cigarettes will be included. Participants in the intervention group will re