E-cigarette use and combustible tobacco cigarette smoking uptake among non-smokers, including relapse in former smokers: umbrella review, systematic review and meta-analysis

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Abstract
Combustible tobacco smoking is a leading cause of death and disability worldwide. E-cigarettes are promoted for smoking cessation, but evidence on how their use relates to smoking uptake is limited. We searched PubMed, Scopus, Web of Science, PsychINFO (Ovid), Medline (Ovid) and Wiley Cochrane Library in April 2020. Studies of non-smokers - never, not current, and former smokers - with a baseline measure of e-cigarette use and an outcome measure of combustible smoking uptake were included. Of 6,225 studies identified, 3 systematic reviews (incorporating 13 primary research studies) and 12 additional studies were included in umbrella and top-up systematic reviews, respectively. All 25 studies found increased risk of smoking uptake with e-cigarette exposure, although magnitude varied substantially. Using a random-effects model, comparing e-cigarette users versus non-e-cigarette users, among never-smokers at baseline the odds ratio (OR) for smoking initiation was 3.25 (95%CI 2.61-4.05, I 2 85.7%) and among non-smokers at baseline the OR for current smoking was 2.87 (95%CI 1.97-4.19, I 2 90.1%). Among former smokers, smoking relapse was higher in e-cigarette users versus non-users (OR=2.40, 95% CI 1.50-3.83, I 2 12.3%). Across multiple settings, non-smokers who use e-cigarettes are consistently more likely than non-e-cigarettes users to initiate combustible cigarette smoking and become current smokers; risk magnitude varied, with an average of around three times the odds. Former smokers using e-cigarettes have over twice the odds of relapse as non-e-cigarettes users. This study is the first to our knowledge to review and pool data on the latter topic.
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