23 February 2025
Grazia Caci a, Arielle Selya b c, Giusy Rita Maria La Rosa d, Lucia Spicuzza c d e, Jaymin B. Morjaria f, Giulio Geraci h, Riccardo Polosa
Introduction
Electronic cigarettes (ECs) are increasingly used for smoking cessation and harm reduction among adults who smoke1, 2, 3, as they mimic the smoking experience without the production of harmful combustion or smoke5, 6. While ECs produce significantly lower exposures to harmful substances than tobacco cigarettes7, 8, 9 and are associated with lower nicotine dependence levels10, 11, concerns remain about dependence12 and health effects resulting from long-term EC use13, especially by youth and tobacco-naïve individuals. EC toxicity likely varies by product-specific characteristics, including flavorings, though again, being noncombustible products, are categorically less toxic13, 14.
While data are not yet available for health outcomes requiring long-term cumulative exposures (e.g., ∼30 years for lung cancer), respiratory outcomes can plausibly develop over short- to medium-term durations (considered here as ∼1-5 years). Previous systematic and/or scoping reviews have reported that EC use is associated with lower toxic exposures than cigarettes12, 14, 15, 16, but that there are some risks of respiratory irritation16, mild adverse events12, and acute respiratory changes14, 15. However, none of these previous reviews robustly accounted for the confounding effect of prior cigarette smoking or focused specifically on individuals without an established smoking history, and the acute respiratory effects have unknown clinical significance, making the unique, clinical respiratory effects of ECs unclear form existing reviews.
Focusing on individuals without established smoking habits (“never-smoking”), therefore, is particularly informative for examining possible respiratory risks unique to EC use, as it avoids confounding by cigarette smoking history. However, EC use by never-smoking individuals is relatively rare17, 18, 19, 20. Although the proportion of EC users who are smoking-naïve appears to be increasing as population-level nicotine consumption shifts from smoking to vaping, especially among younger age groups21, this group nevertheless contributes very little to the evidence base at present. Accordingly, our group previously performed a narrative review and critical appraisal focusing on evidence among never-smoking adolescents and adults22, concluding that there is some evidence of coughing or wheezing symptoms but that EC use is unlikely to pose significant or clinically-meaningful respiratory harms over the medium term. However, these studies had important limitations, including an over-representation of US data (especially from the Population Assessment of Tobacco and Health (PATH)), inadequate controls for confounding (e.g. other combustible tobacco use), and limited follow-up durations.
Here, we extend this prior narrative review22 through a formal systematic review aimed at synthesizing existing evidence on possible respiratory outcomes prospectively associated with EC use in never-smoking individuals. Due to the small number of qualifying studies, we considered all available respiratory outcomes (self-reported diagnoses, respiratory symptoms, and lung function tests).