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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\u00a0true 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\u00a0respiratory <jats:italic>diagnoses<\/jats:italic> associated with EC use among PWNS, or showed a tenuous association with mild respiratory <jats:italic>symptoms<\/jats:italic>. This has favorable implications for ECs\u2019 population health impact; however, small sample sizes and statistical biases limit this evidence. A formal systematic review on this topic is forthcoming.<\/jats:p>","DOI":"10.1007\/s11739-025-03894-7","type":"journal-article","created":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T10:08:46Z","timestamp":1740391726000},"page":"667-680","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Association between electronic cigarette use and respiratory outcomes among people with no established smoking history: a comprehensive review and critical appraisal"],"prefix":"10.1007","volume":"20","author":[{"given":"Arielle","family":"Selya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giusy Rita Maria","family":"La Rosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Spicuzza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaymin B.","family":"Morjaria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grazia","family":"Caci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8450-5721","authenticated-orcid":false,"given":"Riccardo","family":"Polosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,24]]},"reference":[{"key":"3894_CR1","unstructured":"National Academies of Sciences E, Medicine (2018) Public health consequences of E-cigarettes. 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PubPeer.\nhttps:\/\/pubpeer.com\/publications\/073593D85C242F942A6859CCFE70D0#1"}],"container-title":["Internal and Emergency Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11739-025-03894-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11739-025-03894-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11739-025-03894-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,19]],"date-time":"2025-04-19T05:04:31Z","timestamp":1745039071000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11739-025-03894-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,24]]},"references-count":40,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["3894"],"URL":"https:\/\/doi.org\/10.1007\/s11739-025-03894-7","relation":{},"ISSN":["1828-0447","1970-9366"],"issn-type":[{"value":"1828-0447","type":"print"},{"value":"1970-9366","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,24]]},"assertion":[{"value":"6 November 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 February 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 February 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"LS declares no conflict. GC declares no conflict. JBM has received honoraria for speaking and financial support to attend meetings\/advisory boards from Wyeth, Chiesi, Pfizer, MSD, Boehringer Ingelheim, Teva, GSK\/Allen & Hanburys, Napp, Almirall, AstraZeneca, Trudell, Cook Medical, Medela AG and Novartis. He has been an expert witness in a court case relating to the impact of smoking on illness severity, ITU admissions, and mortality from COVID-19 in South Africa in 2020. The entire proceeds of the work were donated to a number of charitable organizations. AS is an employee of Pinney Associates Inc (PA). Since October 2019, PA has been and continues to consult to Juul Labs Inc (JLI) on nicotine vapor products to advance tobacco harm reduction. In addition, as of October 2024, Pinney Associates consults to Philip Morris International (PMI) solely on US regulatory pathways for non-combustible, non-tobacco nicotine products. PA does not consult on combustible tobacco products. AS also individually provides consulting services on behavioral science to the Center of Excellence for the Acceleration of Harm Reduction (CoEHAR) through ECLAT Srl., which received funding from the Foundation for a Smokefree World (FSFW; now the Global Action to End Smoking (GAES). Neither\u00a0JLI nor PMI\u00a0had no role in, or oversight, of this study. GRMLR is currently a research fellow at the University of Catania. She declares no conflict of interest. RP is full tenured professor of Internal Medicine at the University of Catania (Italy) and Medical Director of the Institute for Internal Medicine at the same University. He has received the following EU and governmental competitive grants: U-BIOPRED, AIR-PROM, Integral Rheumatology & Immunology Specialists Network (IRIS), Ministero dell\u2019Universit\u00e0 e della Ricerca (MUR) PNRR 3277\/2021, PNRR 341\/2022, and PNRR 411\/2021 funded by NextGenerationEU of the European Commission. He has also received investigator-initiated grants from Foundation for a Smoke-Free World, Pfizer, GlaxoSmithKline, CV Therapeutics, NeuroSearch A\/S, Sandoz, Merk Sharp & Dohme, Boehringer Ingelheim, Novartis, Arbi Group Srl., Duska Therapeutics, and Forest Laboratories. He is the founder of the Center for Tobacco Prevention and Treatment (CPCT) and of the Center of Excellence for the Acceleration of Harm Reduction at Catania University. He has received consultancy fees from Pfizer, Boehringer Ingelheim, Duska Therapeutics, Forest Laboratories, CV Therapeutics, Sermo Inc., GRG Health, Clarivate Analytics, Guidepoint Expert Network, and GLG Group. He receives textbooks royalties from Elsevier and EDRA. He is also Chair of the European Technical Committee for Standardization on \u201cRequirements and test methods for emissions of electronic cigarettes\u201d (CEN\/TC 437; WG4) and scientific advisor of the non-profit Foundation RIDE2Med.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Research involving human participants and\/or animals"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed conse"}}]}}