Adverse symptoms attributed to e-cigarettes over six months among participants of a randomized controlled trial testing nicotine freebase e-cigarettes for smoking cessation – Secondary analysis of the ESTxENDS trial

Abstract Introduction People smoking tobacco cigarettes and switching to e-cigarettes report adverse symptoms attributed to e-cigarettes. We aimed at assessing the proportions and changes over 6 months in self-reported symptoms among participants of a large randomized controlled trial (RCT) testing e-cigarettes for smoking cessation. Method We included participants from the intervention group of the Efficacy, Safety and Toxicology of ENDS (ESTxENDS) RCT. They received e-cigarettes, free-base nicotine e-liquids and smoking cessation counseling, phone follow-up at 1-,2-,4-,8-weeks and a visit at 6 months after target quit date. A set of pre-defined adverse symptoms experienced while vaping or smoking were systematically assessed at each contact. We used descriptive statistics and mixed models to report proportion of symptoms over time in exclusive e-cigarette users. We assessed the effect of symptoms on smoking re-initiation and the effect of duration of exclusive e-cigarette use on the resolution of symptoms in marginal structural models (MSM). Results The intervention group included 622 participants, with a mean age of 40 (SD: 14) and 53% identified as men. After one week, the most commonly reported adverse symptoms among the 405 exclusive e-cigarette users were dry mouth (34%,95 CI: 29%-39%), mouth/throat irritation (23%,19%-27%), and cough (25%,21%-29%). After 6 months, 256 exclusive e-cigarette users reported dry mouth (18%,14%-23%), mouth/throat irritation (11%,7%-15%), and cough (12%,8%-16%). MSM revealed mouth/throat irritation led to smoking re-initiation, but continuing exclusive e-cigarette use resolved dry mouth in many. Conclusions Adverse symptoms attributed to e-cigarettes are reported by fewer exclusive e-cigarette users over time. While continued e-cigarette use led to less dry mouth, mouth/throat irritation symptoms seemed to resolve because people experiencing symptoms switched back to smoking tobacco, while continuous exclusive e-cigarette users had less symptoms.