Abstract Rationale Emerging evidence suggests potential respiratory effects associated with electronic cigarette (e-cigarette) use (vaping). However, existing studies have several limitations, including inadequate consideration of dynamic transitions between e-cigarette and combustible cigarette use, insufficient control for smoking history, and a lack of systematic analysis of recurrent respiratory episodes. Objective To evaluate the associations between e-cigarette use and incident respiratory diseases, accounting for time-varying exposures and recurrent episodes. Methods This study included 13,442 adults aged 18 to 75 who participated from Wave 1 to 5 (2013 to 2019) in the Population Assessment of Tobacco and Health (PATH) Study and reported no history of any respiratory symptoms at enrollment. E-cigarette and cigarette use (yes or no) were assessed each wave and modeled as time-varying exposures (vapers=1520 and smokers=5360 at enrollment). Smoking history was defined as a lifetime consumption of 100 cigarettes or more at enrollment, while e-cigarette history was defined as a lifetime use of e-cigarettes. Self-reported respiratory disease outcomes included chronic obstructive pulmonary disease (first-onset events=322; recurrent episodes=537), chronic bronchitis (first-onset events=451; recurrent episodes=599), emphysema (first-onset events=119; recurrent episodes=160), and asthma (first-onset events=514; recurrent episodes=814). Survey-weighted time-varying Cox models were used to analyze first onset of respiratory diseases, and LWYY Cox models to assess recurrent episodes. Models were stratified by both smoking history and vaping history, adjusting for sex, age, race, body mass index, education, poverty, and time-varying combustible cigarette use. Sensitivity analyses were conducted among those who reported no history of regular e-cigarette use at enrollment (N = 953 excluded). Results In recurrence models, e-cigarette use was significantly associated with elevated risk of COPD (hazard ratio HR=1.65, 95% confidence interval CI: 1.16, 2.36) and showed suggestive associations with emphysema (HR = 1.57, 95% CI: 0.97, 2.56) and bronchitis (HR = 1.34, 95% CI: 0.93, 1.94). Despite the uncertainty due to limited events, the directions of vaping effects in onset and recurrence models showed strong consistency. Sensitivity analyses yielded similar results. Conclusion This study presents the impacts of e-cigarette use on incident respiratory diseases, particularly COPD, which is independent of cigarette use. Employing an innovative design, this study incorporated time-varying exposures and recurrent episodes in the models, thereby more accurately capturing dynamic transitions of tobacco products and reflecting respiratory disease burden. This enhances the clinical relevance of our findings, providing meaningful evidence supporting immediate public health interventions and stricter e-cigarette regulation. Further research with longer follow up periods and larger sample sizes are needed. This abstract is funded by: None
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