Respiratory symptoms among never-established smokers who vape: a multiregional cross-sectional survey of 1,519 adults

Background E-cigarettes have emerged as a widespread alternative to combustible tobacco, yet evidence on their respiratory impact among adults without an established smoking history remains limited. The present study examined respiratory symptom frequency among exclusive e-cigarette users compared with adults without established smoking or vaping histories. Methods A cross-sectional, internet-based survey was conducted across six world regions. Data were collected between May 2023 and December 2024. Participants comprised 1,519 adults without an established cigarette-smoking history (hereafter, never-established smokers), including 1,005 past-7-day exclusive e-cigarette users (NSV) and 514 comparison participants with no established vaping history and no past-7-day vaping (NSNV). Respiratory symptoms were assessed using the Respiratory Symptom Experience Scale (RSES). Linear regression models estimated mean differences in RSES scores between groups, adjusting for age, sex, body mass index (BMI), education, and employment status, with a sensitivity analysis additionally adjusting for recruitment region. Results NSV had higher mean RSES scores than NSNV (adjusted β = 0.20, 95% CI 0.14–0.26; p < 0.001), with adjusted means of 1.64 and 1.44, respectively. Additional adjustment for recruitment region slightly attenuated the association (β = 0.18, 95% CI 0.12–0.24; p < 0.001). There was no evidence that the association differed by sex or age group. Refillable-device users had lower symptom scores than disposable-device users (β = −0.11, 95% CI − 0.20 to − 0.03; p = 0.006), but did not differ significantly from pre-filled pod users (β = −0.08, 95% CI − 0.20 to 0.03; p = 0.16). Among NSV, participants with at least two years of cumulative vaping had higher scores than those with less than two years of use (β = 0.10, 95% CI 0.03–0.17; p = 0.004), whereas scores did not differ significantly across vaping-frequency categories (omnibus p = 0.121). Conclusions NSV reported modestly more frequent respiratory symptoms than NSNV. However, both the adjusted mean difference and the upper limit of its 95% confidence interval were below the previously reported minimal clinically important difference of 0.57. These cross-sectional findings do not provide evidence of a clinically meaningful difference in respiratory symptom frequency, although causality cannot be established. Clinical trial number Not applicable.