Association between electronic cigarette use and respiratory outcomes among people with no established smoking history: a comprehensive review and critical appraisal.

Nicotine consumption in many countries is shifting away from combustible cigarettes and toward electronic cigarettes (ECs). Understanding the overall population-level impact requires weighing their possible benefits (e.g., for smoking cessation/switching) vs harms (e.g., long-term health risks). However, current evidence on health risks is limited by the absence of long-term data and confounding by prior cigarette smoking history. Focusing on short- to medium-term respiratory outcomes associated with EC use among people who never smoked (PWNS) is informative. We perform a narrative review and critical appraisal of studies examining the prospective association between exclusive EC use and respiratory outcomes among PWNS (either true never-smoking or never-established smoking). We included 12 studies with prospective designs that examine a range of respiratory outcomes subsequent to EC use among PWNS. Eight studies did not find statistically significant differences in respiratory risk associated with baseline EC use. The remaining five studies reported a significant association in at least one analysis, but in four of these studies, associations were not robust across models. Limitations included overreliance on data from the U.S. Population Assessment of Tobacco and Health, uncertain directionality (i.e., pre-existing respiratory conditions were not always ruled out), confounding by other combustible tobacco use, and small sample sizes. All but one study lacked clear and statistically significant evidence of self-reported respiratory diagnoses associated with EC use among PWNS, or showed a tenuous association with mild respiratory symptoms. This has favorable implications for ECs' population health impact; however, small sample sizes and statistical biases limit this evidence. A formal systematic review on this topic is forthcoming.