A systematic review of the effects of e-cigarette use on lung function

Our systematic review was conducted following a protocol developed prior to initiating the review, which was registered on the PROSPERO register of systematic reviews (CRD42021227121)10. This systematic review is reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines11.

Search strategy and study selection

Using a search strategy (Supplementary Tables 15) developed by an experienced health sciences librarian (G.G.), we systematically searched EMBASE, MEDLINE, and PsycINFO databases via Ovid, the Cochrane CENTRAL database, and the Web of Science Core from 2004 (the year of the first e-cigarette patent) until July 12, 2021. We additionally conducted a gray literature search by searching the websites of key governmental and public health organizations (the World Health Organization, Health Canada, the US Centers for Disease Control and Prevention, the US Food and Drug Administration, the Canadian Center on Substance Use and Addiction, the European Centre for Disease Prevention and Control, and the European Public Health Association). Additional articles were identified by manually searching the reference lists of included publications as well as SCOPUS and Google Scholar (first ten pages). Articles were included if they reported quantitative primary data on changes in lung function associated with vaping, defined as the use of any device that functions by transforming an e-liquid to an aerosol using metal coils, among human participants of any age. Studies of cells and those conducted in animals were excluded. Studies using heat-not-burn devices were also excluded, as these do not meet the above definition of vaping. Eligible studies included randomized controlled trials (RCTs), non-randomized studies of interventions (NRSIs), and cohort studies; cross-sectional studies and case reports were excluded. We included studies that used non-users of both vaping devices and conventional cigarettes as a comparison group and those that used a pre- and post-design in which individuals acted as their own controls. Inclusion was not restricted by language or country of publication. Abstracts and conference proceedings were included if sufficient data could be extracted from these publications.

Search results were downloaded from databases into reference management software (EndNote X9) or manually added (e.g., for gray literature results). Duplicates were removed in EndNote and entries were uploaded to Covidence (Veritas Health Innovation, Melbourne, Australia), a systematic review software. Two reviewers (L.H. and K.H.) independently screened the titles and abstracts of all identified publications for eligibility. Citations considered potentially eligible by either reviewer, based on the pre-specified review inclusion/exclusion criteria (Supplementary Table 6), were retrieved for full-text screening and assessed for inclusion. The reasons for exclusion after full-text review were annotated in Covidence and any disagreements were resolved by consensus or a third reviewer (A.H-L.).

Data extraction

Two independent reviewers (L.H and K.H.) extracted methodological, demographic, and outcome data from included studies in duplicate; disagreements were detected in Covidence and were resolved by consensus or, if necessary, by a third reviewer (A.H-L.). Extracted data included study characteristics (first author, journal, year of publication, years(s) of data collection, funding, data source, study design, recruitment strategy, duration of follow-up, country of origin, sample size); population characteristics (sex, gender, age, race, ethnicity, socioeconomic status, dose/frequency of e-cigarette use, conventional cigarette smoking status, smoked cannabis use); and vaping behavior, including the type of vaping device used (e.g., disposable e-cigarette vs. pod device such as JUUL), vaping products used (e.g., nicotine cartridges exclusively vs. THC cartridges exclusively vs. dual use of nicotine and THC products), and source of the vaping product (informal [i.e., friends, family members, or dealers] vs. commercial [i.e., vape shops, stores, dispensaries]).

Initially, extracted outcomes of primary interest were respiratory signs and symptoms, as these are important to patients and are the early signs of respiratory disease. Secondary outcomes included: findings on lung function; Computed tomography (CT) findings of emphysema, airway remodeling, and small airway loss; respiratory-related quality of life and exercise limitations; incidence and/or prevalence of respiratory disease as well as exacerbations of previous respiratory disease; and health care resource use including respiratory disease-related ambulatory care, emergency department visits, and hospitalization. Given the limited number of studies available and the heterogeneity of the data extracted from these studies, no meta-analysis was conducted.

Risk of bias

The risk of bias in included publications was assessed independently by two reviewers (L.H. and K.H.), and discrepancies were resolved by consensus or, if necessary, by a third reviewer (A.H-L.). The risk of bias of included non-randomized studies (pre-post studies, NRSI with non-vaping reference group, cohort study) was assessed using the Risk of Bias in Non-randomized Studies—of Interventions (ROBINS-I) tool12. The ROBINS-I tool evaluates intervention-specific outcomes for a study through seven domains which assess the risk of bias pre-intervention, at-intervention, and post-intervention. For each outcome of interest extracted from an included study, the risk of bias within each domain was reported as “low”, “moderate”, “serious”, or “critical”. Included RCTs were assessed using the Cochrane Collaboration’s Tool for Assessing Risk of Bias (ROB V1)13. Similar to ROBINS-I, this tool evaluates the risk of bias through the assessment of five domains; for each outcome of interest extracted from an included study, the risk of bias for each domain was reported as “low risk of bias”, “high risk of bias”, or “unclear risk of bias.” All eligible publications were included in the qualitative synthesis regardless of their assessed risk of bias.

Reporting summary

Further information on research design is available in the Nature Research Reporting Summary linked to this article.

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