
==== Front
JMIR Res Protoc
JMIR Res Protoc
ResProt
JMIR Research Protocols
1929-0748
JMIR Publications Toronto, Canada

v13i1e60325
39230946
10.2196/60325
Protocol
Protocol
Patterns of Use of e-Cigarettes and Their Respiratory Effects: Protocol for an Umbrella Review
Leung Tiffany
La Rosa Giusy Rita Maria DDS, PhD https://orcid.org/0000-0001-5127-5299
1Department of Clinical and Experimental Medicine University of Catania Via Santa Sofia, 89 Catania, 95123 Italy 39 095 478 1124 giusy.larosa@unict.it

Polosa Riccardo MD, PhD 12https://orcid.org/0000-0002-8450-5721

O’Leary Renée PhD 2https://orcid.org/0000-0001-7412-045X

1 Department of Clinical and Experimental Medicine University of Catania Catania Italy
2 Center for the Acceleration of Harm Reduction University of Catania Catania Italy
Corresponding Author: Giusy Rita Maria La Rosa giusy.larosa@unict.it
2024
4 9 2024
13 e603257 5 2024
19 7 2024
24 7 2024
25 7 2024
©Giusy Rita Maria La Rosa, Riccardo Polosa, Renée O’Leary. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 04.09.2024.
2024
https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Research Protocols, is properly cited. The complete bibliographic information, a link to the original publication on https://www.researchprotocols.org, as well as this copyright and license information must be included.

Background

Electronic nicotine delivery systems (ENDS)—e-cigarettes or vapes—have been shown to substantially reduce or eliminate many toxins compared with cigarette smoke, but simultaneously ENDS use also produces their own unique toxins. Yet the patterns of use among people who use ENDS are not homogeneous. Some people who use ENDS also smoke cigarettes (dual use). Other people who formerly smoked cigarettes are completely substituting ENDS (exclusive use). A small number of people who have never smoked cigarettes are using ENDS (naïve use of nicotine). Each of these patterns of use results in different exposures to toxins. Unfortunately, epidemiological studies routinely group together any ENDS use regardless of other tobacco use.

Objective

This umbrella review primarily aims to present all the evidence available on the respiratory effects of ENDS use by adults based on their pattern of use: dual use, exclusive use, and naïve use. With each of these patterns of use, are there benefits, no changes, or harmful effects on respiratory functioning? Our objective is to provide clinicians with a detailed analysis of how different patterns of ENDS use impact respiratory functioning and to point to the best sources of evidence.

Methods

This umbrella review follows the Methods for Overviews of Reviews framework and the PRIOR (Preferred Reporting Items for Overviews of Reviews) statement. Systematic reviews published since 2019 will be searched across 4 databases and 3 gray literature sources. Additional searches will include citation chasing, references lists, and referrals from respiratory specialists. The quality of included reviews will be evaluated using the AMSTAR2 (A Measurement Tool to Assess Systematic Reviews) checklist. We will document biases in 3 areas: protocol deviations, biases from the Oxford Catalogue of Bias, and internal data discrepancies. Two reviewers will independently conduct the search and quality assessments. Our analysis will focus on reviews rated as moderate or high confidence by AMSTAR2. We will use the Vote Counting Direction of Effect method to manage expected data heterogeneity, assessing whether ENDS use is beneficial or detrimental, or has no effect on respiratory functions based on the pattern of use.

Results

The review is expected to be completed by December 2024. The database search was concluded in April 2024, and data extraction and bias assessment were completed in June 2024. The analysis phase is planned to be completed by October 2024.

Conclusions

A thorough and comprehensive assessment of the evidence will better inform the contentious debate over the respiratory effects of ENDS providing much needed clarity by linking their effects to specific usage patterns. This analysis is particularly crucial in understanding the risks associated with continued cigarette smoking.

Trial Registration

PROSPERO CRD42024540034; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=540034

International Registered Report Identifier (IRRID)

DERR1-10.2196/60325

dual use
electronic nicotine delivery systems
naïve use
respiratory
smoking cessation
umbrella review
ext-peer-revThe proposal for this study was reviewed and funded by the Center of Excellence for the Acceleration of Harm Reduction, University of Catania.
==== Body
pmcIntroduction

Background

Electronic nicotine delivery systems (ENDS)—e-cigarettes or vapes—have been shown to substantially reduce or eliminate many toxins compared with cigarette smoke [1,2]. Although limited in number, ENDS use does produce their own unique toxins, such as metal exposure [3], and others that are present in tobacco smoke, such as carbonyls, although at much lower levels [4]. In terms of risk, most e-cigarette analyses show the cancer potencies of ENDS to be less than 1% of that of cigarette smoke [5]. Furthermore, the lung cancer risk from vaping is estimated to be 5 orders of magnitude lower than smoking [6].

Yet the patterns of use among people who use ENDS are not homogeneous. Some people who use ENDS also smoke cigarettes (dual use). Other people who formerly smoked cigarettes are completely substituting ENDS (exclusive use). A small number of people who have never smoked cigarettes are using ENDS (naïve use of nicotine). Unfortunately, epidemiological studies routinely group together any ENDS use regardless of other tobacco use [7], and this grouping together of populations with different patterns of use confounds the findings of studies [3].

For each of these discrete groups, ENDS exposure will have differing effects on their respiratory health and functioning. In dual use, ongoing exposure to tobacco smoke, even from as few as 1 or 2 cigarettes a day, continues to generate high risks for tobacco-related diseases [8-10]. Daily use of cigarettes and less than daily use of ENDS is the most common pattern of dual use, but there are differing patterns [11,12]. For exclusive use, smoking history (smoking career) may have already impacted respiratory functioning [9], regardless of the subsequent reduction in exposure to toxins. Advocates of tobacco harm reduction stress complete abstinence from cigarettes to obtain potential benefits from ENDS use [3]. Although the numbers of nicotine-naïve individuals using ENDS are small (for example, 0.6% to 0.7% of English adults who never smoked use ENDS [3]), evidence on the respiratory effects of ENDS use by these individuals is crucial for their health care and their lifestyle choices. Data on the effects of naïve use contribute to the research by identifying potential risks or harms of vaping that are not a consequence of prior smoking history [3].

Numerous systematic reviews have examined the respiratory effects of ENDS use with varying conclusions [13-16]. For instance, one systematic review found that vaping increases sensitive measures of airway resistance but does not appear to affect standard measurements of lung function test (eg, forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC], or the FEV1/FVC ratio) [14]. However, this review primarily focused on the acute effects of vaping. Another review by Alqahtani et al [15] highlighted the heterogeneity and inconsistencies in existing studies, underscoring the need for further research using robust study designs. Given the diverse findings and methodological differences in the existing literature, conducting an umbrella review is essential for a comprehensive and critical synthesis of the current evidence.

Research Question

The primary purpose of our umbrella review is to present all the evidence available on the respiratory effects of ENDS use by adults based on their pattern of use: dual use with continued cigarette smoking, exclusive use after abstaining from cigarettes, and use by adults who have never smoked cigarettes. With each of these patterns of use, are there benefits, no changes, or harmful effects on respiratory functioning? Our secondary purpose is to identify the higher quality systematic reviews through a rigorous assessment of both their conduct and reporting. Our objective is to provide clinicians with a detailed analysis of how different patterns of ENDS use impact respiratory functioning and to point to the best sources of evidence.

Methods

Overview

Our umbrella review was developed with the Methods for Overviews of Reviews (MOoR) framework [17,18] and the PRIOR (Preferred Reporting Items for Overviews of Reviews) statement [19].

Population, Intervention, Comparator, and Outcomes Criteria

The PICO (Population, Intervention, Comparator, and Outcome) criteria below define the scope of our umbrella review.

Population: adults (≥18 years old) who smoke cigarettes, adults who have quit smoking, and adults who have never smoked (<100 cigarettes lifetime)

Intervention: ENDS use

Comparator: within-subject changes, control group or arm (including placebo), or longitudinal cohort

Outcome: any self-reported or clinically measured change in respiratory function

Respiratory function outcomes include both respiratory symptoms and test measurements. The symptoms include breathlessness, dyspnea, breathing difficulties, wheeze, cough, sputum, and phlegm. Tests include spirometry (ie, FEV1, FVC, forced expiratory flow at 25%-75% of forced vital capacity, peak expiratory flow, and FEV1/FVC%), airway resistance, impulse oscillometry, impaired mucociliary clearance, and lung function (ie, total lung capacity, residual volume, and expiratory reserve volume). Other outcomes include but are not limited to computed tomography findings of emphysema, airway remodeling, and small airway loss; respiratory-related quality of life and exercise limitations; incidence or prevalence of respiratory disease; and exacerbations of previous respiratory disease. Finally, outcomes include health care resource utilization for respiratory disease–related ambulatory care, emergency department visits, and hospitalization [14]. Other respiratory outcomes not in this list will be added as reported. E-cigarette or vaping use–associated lung injury (EVALI) data, if available, will be evaluated as a separate class of outcome.

Search and Selection Processes

Databases for the search include Scopus (Elsevier), MEDLINE (via PubMed), Cochrane Database of Systematic Reviews, International Prospective Register of Systematic Reviews (PROSPERO), and Epistemonikos, and the gray literature databases MedNar, National Technical Information Service, and WorldWideScience.org.

We will include systematic reviews published from 2019. Restricting the time frame is justified by 2 main reasons. First, these systematic reviews included the latest primary studies conducted with the most advanced devices. Second, these devices have evolved significantly over time, leading to considerable changes in their designs, making older models outdated and no longer available in the market [20,21]. A newer style model is the single-use disposables that were introduced to the market in 2019 [22]. The modifications in newer models have played a role in reducing exposure to silicon and solder [21], while alterations in ENDS liquids exhibit potential for lowering carbonyl emissions [23]. Therefore, it is imperative that our findings and conclusions are grounded in the most up-to-date evidence derived from tests conducted with these newer models.

Terms such as “electronic nicotine,” “e-cigarette,” and “vaping” will be combined with respiratory-related keywords such as “respiratory,” “lungs,” and “pulmonary” using Boolean operators (ie, OR for synonyms and AND for combining intervention and outcome). Title, abstract, and keywords fields will be selected for the search. For each database, the search terms and syntax will be adjusted according to the database-specific requirements, such as MeSH (Medical Subject Headings) terms for PubMed. A filter for detecting only systematic reviews will be applied where possible. As an example, the search strategy for the Scopus database is as follows: TITLE-ABS-KEY ( (“e-cig*” OR “vaping” OR “e-cigarette” OR “vapers” OR “Electronic nicotine delivery systems”) AND (“respiratory” OR “pulmonary” OR “lungs” OR “breathlessness” OR “dyspnea” OR “wheeze” OR “cough” OR “sputum” OR “phlegm” OR “spirometry”) AND (“systematic review” OR “meta-analysis”) ) AND PUBYEAR > 2018 AND PUBYEAR < 2025. Each search will be meticulously documented by screenshots of the database pages displaying the search syntax and the number of results, and all retrieved records will be exported into an EndNote library, where duplicates will be identified and removed. Two researchers will independently screen the records for all PICO criteria in the title and abstract (or summary); publications lacking any PICO criterion will be excluded. Discrepancies in the exclusions will be decided by the project leader, and the interrater agreement reported.

After the database searches are completed, we will conduct a second round of secondary searches. One search will be a citation chase (snowball search) in Google Scholar. The second search will be a check of the references of the included systematic reviews. These 2 searches will be conducted by 2 reviewers independently. Secondary search publications will be included or excluded based on the full paper criteria. Finally, the list of included systematic reviews will be checked by two experts in respiratory diseases.

Inclusion and Exclusion Criteria

After the title and abstract exclusion process, a full paper review will be conducted by 2 researchers independently for the inclusion and exclusion criteria shown in Table 1.

Table 1 Inclusion and exclusion criteria.a

Criteria	Inclusion	Exclusion	
Article type	Systematic review with a minimum search of 2 databases

	All other study designs

	
Language	All languages

	Reviews for which translation is unavailable

	
Publisher	Academic journals

Government reports

Medical organizations

	Predatory journals (not indexed in PubMed or Directory of Open Access Journals)

Conference abstracts

	
Primary study designs	Clinical trials (randomized or nonrandomized)

Experimental studies

Longitudinal cohort studies

	Cross-sectional study data

Surveys

Case studies

Qualitative studies

Animal studies

In vitro studies

	
Population	Adults who smoke cigarettes, adults who have quit smoking, and adults who have never smoked

	Youth

	
Data	Changes in disease symptoms

Clinical test measurements

Self-reported health status

	Passive or second-hand exposure

Only 1 primary study from included study designs

	
Bias assessment of primary studies	Individual primary studies assessed with any method

	No bias assessment of individual primary studies

Inappropriate bias tool

	
Analysis-synthesis method	Meta-analysis

Tabulation

Narrative assessment

	Solely summary of individual primary studies

	
aStudies excluded at the full paper examination will be listed in an appendix and will note the reason for exclusion.

Data Extraction

For efficiency, the data extraction and quality assessments of a systematic review (including its supplementary materials and protocol) will be conducted concurrently.

The specific items for data extraction will be chosen by the research team and pilot-tested on 2 systematic reviews. The planned data items are included in Textbox 1. For systematic reviews that include multiple study designs, data will be selected solely from those that fulfill the inclusion criteria. One researcher will perform the data extraction, and a second reviewer will 100% cross-check it.

Data items for the data extraction.

Bibliographic information

Funders and conflicts of interest

Databases searched and dates

Secondary searches performed

Inclusion-exclusion criteria of the systematic reviews

Population demographics

Intervention description including the electronic nicotine delivery system device and nicotine strength

Outcome definition and measurement

Primary studies with their bias assessments

Narrative assessment (if applicable)

Data analyses (including sensitivity analyses)

Meta-analyses

Any subgroup analyses

GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) or authors’ assessment of confidence in the evidence

Limitations identified by the systematic review authors

Conclusions quoted

Quality Assessment

We will use the AMSTAR2 (A Measurement Tool to Assess Systematic Reviews) checklist [24] to assess the quality of the systematic reviews and identify the higher quality ones. The review team will designate AMSTAR2 item 7 (a list of excluded studies) as a noncritical weakness and not a critical flaw because PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) [25], a widely used reporting standard, does not require an excluded studies list. Two reviewers will independently complete the checklist, and the project leader will decide any unresolved discrepancies. For the overall confidence rating, the project leader will score its confidence rating as high, moderate, low, or critically low as per the AMSTAR2 criteria except for item 7 as noted above.

A second quality assessment of the reviews will be an examination for reporting biases in 3 areas. The first will be unreported deviations from the protocol. The second will be a checklist of reporting biases drawn from the Oxford Catalogue of Bias [26]: spin bias of nonsignificant findings, omitted findings, one-sided reference bias, framing by over- or underemphasis of outcomes, and overreliance on P values (as compared with clinical relevance). The third examination will check for internal data reporting discrepancies within the systematic review publication with the checklist proposed by Puljak et al [27].

We expect that this umbrella review will include a systematic review of ENDS substitution of cigarette smoking that we published with coauthors [16]. To preclude the possibility of bias, 2 neutral third-party reviewers will conduct the AMSTAR2 and reporting bias assessments for this systematic review.

The search processes and results will be displayed in a PRIOR flow diagram. A study table will report the systematic reviews, a second table will display their AMSTAR2 scoring and rating, and a third table will record reporting biases. A citation matrix will list all the primary studies included in the systematic reviews. Analyses will be presented based on the pattern of use: dual use, exclusive use, and naïve use. Subgroup analyses are planned for populations with asthma or chronic obstructive pulmonary disease.

Planned Analyses

In our review, heterogeneity presents a challenge to select the appropriate method of analysis. The evidence base of primary studies is expected to be highly heterogeneous. Particularly notable are the variations in ENDS devices, nicotine strengths, the duration of the intervention, and the duration of follow-up. Heterogeneity occurs also between the systematic reviews, primarily from differences in their inclusion and exclusion criteria. Heterogeneity also arises from earlier and later search dates resulting in different primary studies analyzed in the systematic reviews.

For these reasons, a statistical meta-analysis will most likely not be feasible. Our analysis method will be a Vote Counting Direction of Effect, which is appropriate for heterogeneous data [28]. This analysis will indicate if ENDS use is beneficial, detrimental, or has no effect on respiratory functions. To reduce the risk of bias for the synthesis, only systematic reviews rated at AMSTAR2 moderate or high confidence will be analyzed. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) or bias description rating of the findings made in the systematic reviews will be included in the Vote Counting Direction of Effect.

As a component of our analyses, we will calculate the overlap of primary studies between the systematic reviews. This analysis is necessary to determine if certain primary studies are overrepresented and therefore would result in these studies being overweighted in the findings. We will apply the corrected coverage area calculation [29] to determine which, if any, primary studies could skew the findings of our umbrella review.

Respiratory functioning outcomes (see PICO above) will be ranked in importance for clinical care by a respiratory physician.

A sensitivity analysis will compare findings in the analyses with those from the systematic reviews rated at low confidence. If necessary, a sensitivity analysis will compare results from commercially funded systematic reviews (including tobacco industry, vape companies, pharmaceutical companies, and medical equipment manufacturers) with all others.

The observations of reporting biases will be reported in a table. The impact of reporting biases on the research literature will be explored in the Discussion and will contribute to our recommendations for future research

If 10 or more systematic reviews are included, publication bias will be investigated with a tabulation of the conclusions of the systematic reviews on the respiratory effects of ENDS usage.

Any deviations from the protocol will be reported in the published umbrella review.

Results

The protocol has been registered in PROSPERO (CRD42024540034), and the umbrella review is expected to be completed by December 2024, followed by the submission of the review for journal publication. The database search was concluded in April 2024, and data extraction and bias assessments were completed in June 2024. The analysis phase is planned to be completed by October 2024.

Discussion

This will be the first umbrella review to provide a comprehensive overview of respiratory symptoms in ENDS users. Based on the current evidence, exclusive ENDS use is expected to significantly improve respiratory outcomes after completely switching away from cigarette smoking. In contrast, dual use with concurrent tobacco cigarette consumption may experience less improvement than exclusive ENDS use. Additionally, we anticipate a deterioration or no effect on respiratory symptoms in naïve use of vapes.

This umbrella review is expected to have a potential significant impact thanks to its methodological rigor, grounded in the MOoR framework and the PRIOR statement. However, the scarcity of data on the respiratory health effects of ENDS in never smokers is a possible limitation that may affect the robustness of the study findings.

Methodological rigor is crucial in a highly polarized research field [30-32]. A rigorous and comprehensive evaluation of the evidence will clarify some of the key controversies surrounding the respiratory impacts of ENDS, correlating their effects with specific usage patterns, particularly the risks associated with ongoing cigarette smoking.

The intention is to widely disseminate the publication of the study protocol and the completed review through articles in peer-reviewed journals and conference presentations. The link to the publication will be shared via our email list to hundreds of academic experts in the field and to general media with a press release. Dissemination will also occur via social media platforms.

A summary of the results will be available on the study website for public access. The anonymized data will be available to researchers on reasonable request.

This investigator-initiated study is sponsored by ECLAT srl, a research-based spin-off company of the University of Catania, with the help of a grant from the Global Action to End Smoking (formerly known as Foundation for Smoke-Free World), an independent, US nonprofit 501(c)(3) grantmaking organization, accelerating science-based efforts worldwide to end the smoking epidemic. The funders had no role in the design of the study; the collection, analysis, and interpretation of data; or the writing of the manuscript. The contents, selection, and presentation of facts as well as any opinions expressed in this umbrella review are the sole responsibility of the authors and under no circumstances shall be regarded as reflecting the positions of the funder.

Abbreviations

AMSTAR2 A Measurement Tool to Assess Systematic Reviews

ENDS electronic nicotine delivery systems

EVALI e-cigarette or vaping use–associated lung injury

FEV1 forced expiratory volume in 1 second

FVC forced vital capacity

GRADE Grading of Recommendations, Assessment, Development, and Evaluations

MOoR Methods for Overviews of Reviews

PICO Population, Intervention, Comparator, and Outcome

PRIOR Preferred Reporting Items for Overviews of Reviews

PRISMA Preferred Reporting Items for Systematic Reviews and Meta-Analyses

PROSPERO International Prospective Register of Systematic Reviews

Data Availability

Data sharing is not applicable to this study as no datasets were generated or analyzed during this study.

Authors' Contributions: GRMLR contributed to the conceptualization, writing of the original draft, and the reviewing and editing of the manuscript. RO was involved in the conceptualization, writing of the original draft, and the reviewing and editing of the manuscript. RP contributed to the conceptualization, secured funding, and participated in the reviewing and editing of the manuscript.

Conflicts of Interest: GRMLR is currently a research fellow at the University of Catania and, at the time of drafting this paper, was supported by ECLAT srl, a University of Catania spin-off that has received funding from the Global Action to End Smoking (formerly known as Foundation for Smoke-Free World). RO is supported by a contract with ECLAT, srl. ECLAT has received funding from the Global Action to End Smoking (formerly known as Foundation for Smoke-Free World). She declares no conflicts of interest. RP is a full tenured professor of internal medicine at the University of Catania (Italy) and medical director of the Institute for Internal Medicine and Clinical Immunology at the same university. He has received grants from U-BIOPRED and AIR-PROM, Integral Rheumatology & Immunology Specialists Network, Global Action to End Smoking (formerly known as Foundation for Smoke-Free World), Pfizer, GlaxoSmithKline, CV Therapeutics, NeuroSearch A/S, Sandoz, Merk Sharp & Dohme, Boehringer Ingelheim, Novartis, Arbi Group srl, Duska Therapeutics, Forest Laboratories, and Ministero dell Universita’ e della Ricerca Bando PNRR 3277/2021 (CUP E63C22000900006) and 341/2022 (CUP E63C22002080006), funded by NextGenerationEU, the European Union economic recovery package. He is founder of the Center for Tobacco Prevention and Treatment at the University of Catania and the Center of Excellence for the Acceleration of Harm Reduction at the same university. He receives consultancy fees from Pfizer, Boehringer Ingelheim, Duska Therapeutics, Forest Laboratories, CV Therapeutics, and Sermo Inc. He is being paid textbook royalties from Elsevier. He is also involved in a patent application for ECLAT Srl. He is a pro bono scientific advisor for Lega Italiana Anti Fumo and the International Network of Nicotine Consumers Organizations. He is chair of the European Technical Committee for Standardization on “Requirements and test methods for emissions of electronic cigarettes” (CEN/TC 437; WG4).
==== Refs
1 Goniewicz ML Smith DM Edwards KC Blount BC Caldwell KL Feng J Wang L Christensen C Ambrose B Borek N van Bemmel D Konkel K Erives G Stanton CA Lambert E Kimmel HL Hatsukami D Hecht SS Niaura RS Travers M Lawrence C Hyland AJ Comparison of nicotine and toxicant exposure in users of electronic cigarettes and combustible cigarettes JAMA Netw Open 2018 1 8 e185937 10.1001/jamanetworkopen.2018.5937 30646298 2718096 30646298
2 National Academies of Sciences, Engineering, and Medicine Public Health Consequences of E-Cigarettes 2018 Washington, DC National Academies Press
3 McNeill A Simonavicius E Brose L Taylor E East K Zuikova E NIHR Maudsley Biomedical Research Centre (BRC), Addictions, Nicotine Research Group Nicotine Vaping in England: An Evidence Update Including Health Risks and Perceptions 2022 London King's College
4 Strongin RM E-cigarette chemistry and analytical detection Annu Rev Anal Chem (Palo Alto Calif) 2019 12 1 23 39 10.1146/annurev-anchem-061318-115329 30848928 30848928
5 Stephens WE Comparing the cancer potencies of emissions from vapourised nicotine products including e-cigarettes with those of tobacco smoke Tob Control 2017 053808 10.1136/tobaccocontrol-2017-053808 28778971 tobaccocontrol-2017-053808
6 Scungio M Stabile L Buonanno G Measurements of electronic cigarette-generated particles for the evaluation of lung cancer risk of active and passive users J Aerosol Sci 2018 115 1 11 10.1016/j.jaerosci.2017.10.006
7 Gordon T Karey E Rebuli ME Escobar YNH Jaspers I Chen LC E-cigarette toxicology Annu Rev Pharmacol Toxicol 2022 62 301 322 10.1146/annurev-pharmtox-042921-084202 10.1146/annurev-pharmtox-042921-084202 34555289
8 Hackshaw A Morris JK Boniface S Tang J Milenković D Low cigarette consumption and risk of coronary heart disease and stroke: meta-analysis of 141 cohort studies in 55 study reports BMJ 2018 360 j5855 10.1136/bmj.j5855 29367388 29367388
9 Oelsner EC Balte PP Bhatt SP Cassano PA Couper D Folsom AR Freedman ND Jacobs DR Kalhan R Mathew AR Kronmal RA Loehr LR London SJ Newman AB O'Connor GT Schwartz JE Smith LJ White WB Yende S Lung function decline in former smokers and low-intensity current smokers: a secondary data analysis of the NHLBI pooled cohorts study Lancet Respir Med 2020 8 1 34 44 10.1016/S2213-2600(19)30276-0 31606435 S2213-2600(19)30276-0 31606435
10 Inoue-Choi M Freedman ND Saito E Tanaka S Hirabayashi M Sawada N Tsugane S Usui Y Ito H Wang C Tamakoshi A Takeuchi T Kitamura Y Utada M Ozasa K Sugawara Y Tsuji I Wada K Nagata C Shimazu T Mizoue T Matsuo K Naito M Tanaka K Katanoda K Inoue M Low-intensity cigarette smoking and mortality risks: a pooled analysis of prospective cohort studies in Japan Int J Epidemiol 2022 08 10 51 4 1276 1290 10.1093/ije/dyab224 34718588 6414574 34718588
11 Baig SA Giovenco DP Behavioral heterogeneity among cigarette and e-cigarette dual-users and associations with future tobacco use: findings from the population assessment of tobacco and health study Addict Behav 2020 104 106263 10.1016/j.addbeh.2019.106263 32028096 S0306-4603(19)31047-0 32028096
12 Buu A Tong Z Cai Z Li R Yang JJ Jorenby DE Piper ME Subtypes of dual users of combustible and electronic cigarettes: longitudinal changes in product use and dependence symptomatology Nicotine Tob Res 2023 25 3 438 443 10.1093/ntr/ntac151 35738022 6615357 35738022
13 Larue F Tasbih T Ribeiro PAB Lavoie KL Dolan E Bacon SL Immediate physiological effects of acute electronic cigarette use in humans: a systematic review and meta-analysis Respir Med 2021 190 106684 10.1016/j.rmed.2021.106684 34808583 S0954-6111(21)00392-9 34808583
14 Honeycutt L Huerne K Miller A Wennberg E Filion KB Grad R Gershon AS Ells C Gore G Benedetti A Thombs B Eisenberg MJ A systematic review of the effects of e-cigarette use on lung function NPJ Prim Care Respir Med 2022 32 1 45 10.1038/s41533-022-00311-w 10.1038/s41533-022-00311-w 36273009 10.1038/s41533-022-00311-w 36273009
15 Alqahtani MM Alenezi FK Almeshari MA Alanazi AM Taleb ZB Kalan MEE Martinasek MP McNab RJ Culbreth R Alotaibi M Aljohani H Goodfellow LT Ismaeil TT Algarni SS Alotaibi TF Alqahtani MK Al-Ajel H Alwadeai KS Almutairi NS Ford E E-cigarette use and respiratory symptoms in adults: a systematic review and meta-analysis Tob Induc Dis 2023 21 168 10.18332/tid/174660 38098748 168 38098748
16 Qureshi MA Vernooij RWM La Rosa GRM Polosa R O'Leary R Respiratory health effects of e-cigarette substitution for tobacco cigarettes: a systematic review Harm Reduct J 2023 20 1 143 10.1186/s12954-023-00877-9 37794458 10.1186/s12954-023-00877-9 37794458
17 Lunny C Brennan SE McDonald S McKenzie JE Toward a comprehensive evidence map of overview of systematic review methods: paper 1—purpose, eligibility, search and data extraction Syst Rev 2017 6 1 231 10.1186/s13643-017-0617-1 29162130 10.1186/s13643-017-0617-1 29162130
18 Lunny C Brennan SE McDonald S McKenzie JE Toward a comprehensive evidence map of overview of systematic review methods: paper 2—risk of bias assessment; synthesis, presentation and summary of the findings; and assessment of the certainty of the evidence Syst Rev 2018 7 1 159 10.1186/s13643-018-0784-8 30314530 10.1186/s13643-018-0784-8 30314530
19 Gates M Gates A Pieper D Fernandes RM Tricco AC Moher D Brennan SE Li T Pollock M Lunny C Sepúlveda D McKenzie JE Scott SD Robinson KA Matthias K Bougioukas KI Fusar-Poli P Whiting P Moss SJ Hartling L Reporting guideline for overviews of reviews of healthcare interventions: development of the PRIOR statement BMJ 2022 378 e070849 10.1136/bmj-2022-070849 35944924 35944924
20 Traboulsi H Cherian M Abou Rjeili M Preteroti M Bourbeau J Smith BM Eidelman DH Baglole CJ Inhalation toxicology of vaping products and implications for pulmonary health Int J Mol Sci 2020 21 10 3495 10.3390/ijms21103495 32429092 ijms21103495 32429092
21 Williams M Talbot P Design features in multiple generations of electronic cigarette atomizers Int J Environ Res Public Health 2019 16 16 2904 10.3390/ijerph16162904 31416115 ijerph16162904 31416115
22 McEwen A McRobbie H Ross L Soar K Vaping: A Guide for Health and Social Care Professionals 2023 Dorset National Centre for Smoking Cessation and Training
23 de Falco B Petridis A Paramasivan P Troise AD Scaloni A Deeni Y Stephens WE Fiore A Reducing toxic reactive carbonyl species in e-cigarette emissions: testing a harm-reduction strategy based on dicarbonyl trapping RSC Adv 2020 10 36 21535 21544 10.1039/d0ra02138e 10.1039/d0ra02138e 35518766 d0ra02138e 35518766
24 Shea BJ Reeves BC Wells G Thuku M Hamel C Moran J Moher D Tugwell P Welch V Kristjansson E Henry DA AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both BMJ 2017 358 j4008 10.1136/bmj.j4008 28935701 28935701
25 Page MJ McKenzie JE Bossuyt PM Boutron I Hoffmann TC Mulrow CD Shamseer L Tetzlaff JM Akl EA Brennan SE Chou R Glanville J Grimshaw JM Hróbjartsson A Lalu MM Li T Loder EW Mayo-Wilson E McDonald S McGuinness LA Stewart LA Thomas J Tricco AC Welch VA Whiting P Moher D The PRISMA 2020 statement: an updated guideline for reporting systematic reviews BMJ 2021 372 n71 10.1136/bmj.n71 33782057 33782057
26 Catalogue of Bias Collaborative 2023-07-12 https://catalogofbias.org/
27 Puljak L Riva N Parmelli E González-Lorenzo M Moja L Pieper D Data extraction methods: an analysis of internal reporting discrepancies in single manuscripts and practical advice J Clin Epidemiol 2020 117 158 164 10.1016/j.jclinepi.2019.09.003 31541692 S0895-4356(19)30222-7 31541692
28 McKenzie JE Brennan SE Chapter 12: Synthesizing and presenting findings using other methods Cochrane Handbook for Systematic Reviews of Interventions 2023 2024-08-23 https://training.cochrane.org/handbook/current/chapter-12
29 Pieper D Antoine S Mathes T Neugebauer EAM Eikermann M Systematic review finds overlapping reviews were not mentioned in every other overview J Clin Epidemiol 2014 67 4 368 375 10.1016/j.jclinepi.2013.11.007 24581293 S0895-4356(13)00481-2 24581293
30 Balfour DJK Benowitz NL Colby SM Hatsukami DK Lando HA Leischow SJ Lerman C Mermelstein RJ Niaura R Perkins KA Pomerleau OF Rigotti NA Swan GE Warner KE West R Balancing consideration of the risks and benefits of e-cigarettes Am J Public Health 2021 111 9 1661 1672 10.2105/AJPH.2021.306416 34410826 34410826
31 Carroll DM Denlinger-Apte RL Dermody SS King JL Mercincavage M Pacek LR Smith TT Tripp HL White CM Polarization within the field of tobacco and nicotine science and its potential impact on trainees Nicotine Tob Res 2021 23 1 36 39 10.1093/ntr/ntaa148 32777049 5890529 32777049
32 Eisenkraft Klein D Hawkins B Schwartz R Understanding experts’ conflicting perspectives on tobacco harm reduction and e-cigarettes: an interpretive policy analysis SSM Qual Res Health 2022 2 100197 10.1016/j.ssmqr.2022.100197
