Nicotine - Retracted Studies, Papers, and Articles

How Mistakes Can Happen

2022: Cross‑sectional e‑cigarette studies are unreliable without timing of exposure and disease diagnosis

• "Studies based on cross-sectional data with no information on age of e-cigarette initiation and age of diagnosis invariably overestimate associations by including cases that were diagnosed before e-cigarette exposure. Although the authors of those studies did not make causal claims in the reports, university media releases and subsequent media articles invariably misled the public to believe that e-cigarette use increases risk for diseases."
• Citation: Rodu B, Plurphanswat N. Cross-sectional e-cigarette studies are unreliable without timing of exposure and disease diagnosis. Intern Emerg Med. 2023 Jan;18(1):319-323. doi: 10.1007/s11739-022-03141-3. Epub 2022 Nov 25. PMID: 36434423.

2022: Analysis of common methodological flaws in the highest cited e-cigarette epidemiology research

• Conclusion: "Our critical appraisal reveals common, preventable flaws, the identification of which may provide guidance to researchers, reviewers, scientific editor, journalists, and policy makers. One striking result of the review is that a large portion of the high-ranking papers came out of US-dominated research institutions whose funders are unsupportive of a tobacco harm reduction agenda..."
• Citation: Hajat C, Stein E, Selya A, Polosa R; CoEHAR study group. Analysis of common methodological flaws in the highest cited e-cigarette epidemiology research. Intern Emerg Med. 2022 Apr;17(3):887-909. doi: 10.1007/s11739-022-02967-1. Epub 2022 Mar 24. Erratum in: Intern Emerg Med. 2022 Aug;17(5):1561. PMID: 35325394; PMCID: PMC9018638.
• Article: Researchers Expose the Pitiful Quality of Highly Cited Vaping Studies

2022: A Critical Review of Recent Literature on Metal Contents in E-Cigarette Aerosol

• Abstract: "The inhalation of metallic compounds in e-cigarette (EC) aerosol emissions presents legitimate concerns of potential harms for users. We provide a critical review of laboratory studies published after 2017 on metal contents in EC aerosol, focusing on the consistency between their experimental design, real life device usage and appropriate evaluation of exposure risks. All experiments reporting levels above toxicological markers for some metals (e.g., nickel, lead, copper, manganese) exhibited the following experimental flaws: (i) high powered sub-ohm tank devices tested by means of puffing protocols whose airflows and puff volumes are conceived and appropriate for low powered devices; this testing necessarily involves overheating conditions that favor the production of toxicants and generate aerosols that are likely repellent to human users; (ii) miscalculation of exposure levels from experimental outcomes; (iii) pods and tank devices acquired months and years before the experiments, so that corrosion effects cannot be ruled out; (iv) failure to disclose important information on the characteristics of pods and tank devices, on the experimental methodology and on the resulting outcomes, thus hindering the interpretation of results and the possibility of replication"
• Citation: Soulet S, Sussman RA. A Critical Review of Recent Literature on Metal Contents in E-Cigarette Aerosol. Toxics. 2022 Aug 29;10(9):510. doi: 10.3390/toxics10090510. PMID: 36136475; PMCID: PMC9506048.

2022: Critical Review of the Recent Literature on Organic Byproducts in E-Cigarette Aerosol Emissions

• Abstract: "We review the literature on laboratory studies quantifying the production of potentially toxic organic byproducts (carbonyls, carbon monoxide, free radicals and some nontargeted compounds) in e-cigarette (EC) aerosol emissions, focusing on the consistency between their experimental design and a realistic usage of the devices, as determined by the power ranges of an optimal regime fulfilling a thermodynamically efficient process of aerosol generation that avoids overheating and “dry puffs”. The majority of the reviewed studies failed in various degrees to comply with this consistency criterion or supplied insufficient information to verify it. Consequently, most of the experimental outcomes and risk assessments are either partially or totally unreliable and/or of various degrees of questionable relevance to end users. Studies testing the devices under reasonable approximation to realistic conditions detected levels of all organic byproducts that are either negligible or orders of magnitude lower than in tobacco smoke. Our review reinforces the pressing need to update and improve current laboratory standards by an appropriate selection of testing parameters and the logistical incorporation of end users in the experimental design."
• Citation: Soulet S, Sussman RA. Critical Review of the Recent Literature on Organic Byproducts in E-Cigarette Aerosol Emissions. Toxics. 2022 Nov 22;10(12):714. doi: 10.3390/toxics10120714. PMID: 36548547; PMCID: PMC9787926.

2017: Carbonyl Emissions in E-cigarette Aerosol: A Systematic Review and Methodological Considerations

• Importantly, control for the generation of dry puffs was not performed in the vast majority of studies, particularly in studies using variable power devices, which could result in testing conditions and reported carbonyl levels that have no clinical relevance or context.
• Citation: Farsalinos KE, Gillman G. Carbonyl Emissions in E-cigarette Aerosol: A Systematic Review and Methodological Considerations. Front Physiol. 2018 Jan 11;8:1119. doi: 10.3389/fphys.2017.01119. PMID: 29375395; PMCID: PMC5769337.

2017: E-cigarettes emit very high formaldehyde levels only in conditions that are aversive to users: A replication study under verified realistic use conditions

• The high levels of formaldehyde emissions that were reported in a previous study were caused by unrealistic use conditions that create the unpleasant taste of dry puffs to e-cigarette users and are thus avoided.
• Citation: Farsalinos KE, Voudris V, Spyrou A, Poulas K. E-cigarettes emit very high formaldehyde levels only in conditions that are aversive to users: A replication study under verified realistic use conditions. Food Chem Toxicol. 2017 Nov;109(Pt 1):90-94. doi: 10.1016/j.fct.2017.08.044. Epub 2017 Aug 31. PMID: 28864295.

2015: E-cigarettes generate high levels of aldehydes only in 'dry puff' conditions

• Electronic cigarettes produce high levels of aldehyde only in dry puff conditions, in which the liquid overheats, causing a strong unpleasant taste that e-cigarette users detect and avoid.
• Citation: Farsalinos KE, Voudris V, Poulas K. E-cigarettes generate high levels of aldehydes only in 'dry puff' conditions. Addiction. 2015 Aug;110(8):1352-6. doi: 10.1111/add.12942. Epub 2015 May 20. PMID: 25996087.

Post-Publication Criticism

• Note: Dates denote when comments were published, not the paper's publication date.

2022: The association between e-cigarette use and asthma among never combustible cigarette smokers: behavioral risk factor surveillance system (BRFSS) 2016 & 2017

• "The study by Osei et al. used the Behavioral Risk Factor Surveillance Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with any disease. Therefore, it is deficient and unreliable." (Rodu)
• Referring to: Osei AD, Mirbolouk M, Orimoloye OA, Dzaye O, Uddin SMI, Dardari ZA, DeFilippis AP, Bhatnagar A, Blaha MJ. The association between e-cigarette use and asthma among never combustible cigarette smokers: behavioral risk factor surveillance system (BRFSS) 2016 & 2017. BMC Pulm Med. 2019 Oct 16;19(1):180. doi: 10.1186/s12890-019-0950-3. PMID: 31619218; PMCID: PMC6796489.

2022: Association Between E-Cigarette Use and Chronic Obstructive Pulmonary Disease by Smoking Status: Behavioral Risk Factor Surveillance System 2016 and 2017

• "The study by Osei et al. is deficient and unreliable, because it used the Behavioral Risk Factor Surveillance Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with chronic obstructive pulmonary disease (COPD)." (Rodu)
• Referring to: Osei, A. D., Mirbolouk, M., Orimoloye, O. A., Dzaye, O., Uddin, S. M. I., Benjamin, E. J., Hall, M.E., DeFilippis, A.P., Bhatnagar, A., Biswal, S.S., Blaha, M. J. (2020). Association Between E-Cigarette Use and Chronic Obstructive Pulmonary Disease by Smoking Status: Behavioral Risk Factor Surveillance System 2016 and 2017. American Journal of Preventive Medicine. doi:10.1016/j.amepre.2019.10.014

2022: E-cigarette use is associated with a self-reported diagnosis of prediabetes in never cigarette smokers: Results from the behavioral risk factor surveillance system survey

• "The results by Atuegwu et al. are deficient and unreliable, because the authors used the Behavioral Risk Factor Surveillance Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with any disease." (Rodu)
• Referring to: Atuegwu NC, Perez MF, Oncken C, Mead EL, Maheshwari N, Mortensen EM. E-cigarette use is associated with a self-reported diagnosis of prediabetes in never cigarette smokers: Results from the behavioral risk factor surveillance system survey. Drug Alcohol Depend. 2019 Dec 1;205:107692. doi: 10.1016/j.drugalcdep.2019.107692. Epub 2019 Oct 28. PMID: 31707269; PMCID: PMC6893144.

2022: The Association Between E-Cigarette Use and Prediabetes: Results From the Behavioral Risk Factor Surveillance System, 2016-2018

• "The study by Zhang et al. used the Behavioral Risk Factor Surveillance Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with any disease. Their results are deficient and unreliable, because a recent analysis by my research group provides definitive evidence that the vast majority of diseases reported by vapers in cross-sectional surveys had been diagnosed before survey participants initiated the behavior." (Rodu)
• Referring to: Zhang Z, Jiao Z, Blaha MJ, Osei A, Sidhaye V, Ramanathan M Jr, Biswal S. The Association Between E-Cigarette Use and Prediabetes: Results From the Behavioral Risk Factor Surveillance System, 2016-2018. Am J Prev Med. 2022 Jun;62(6):872-877. doi: 10.1016/j.amepre.2021.12.009. Epub 2022 Mar 3. PMID: 35597566.

2022: Tests for confounding with cigarette smoking in the association of E-cigarette use with respiratory disorder: 2020 National-Sample Data

• "The study by Wills et al. is deficient and unreliable, because it used the Behavioral Risk Factor Surveillance Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with chronic obstructive pulmonary disease (COPD)." (Rodu)
• Referring to: Wills TA, Choi K, Pokhrel P, Pagano I. Tests for confounding with cigarette smoking in the association of E-cigarette use with respiratory disorder: 2020 National-Sample Data. Prev Med. 2022 Aug;161:107137. doi: 10.1016/j.ypmed.2022.107137. Epub 2022 Jul 9. PMID: 35820496; PMCID: PMC9328844.

2022: Association Between E-Cigarette Use and Cardiovascular Disease Among Never and Current Combustible-Cigarette Smokers

• "The study by Osei et al. used the Behavioral Risk Factor Surveillance Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with cardiovascular disease. A recent analysis by my research group of data from the Population Assessment of Tobacco and Health, which contains this essential temporal information, provides definitive evidence that the results from Osei et al. are deficient and unreliable." (Rodu)
• Referring to: Osei AD, Mirbolouk M, Orimoloye OA, Dzaye O, Uddin SMI, Benjamin EJ, Hall ME, DeFilippis AP, Stokes A, Bhatnagar A, Nasir K, Blaha MJ. Association Between E-Cigarette Use and Cardiovascular Disease Among Never and Current Combustible-Cigarette Smokers. Am J Med. 2019 Aug;132(8):949-954.e2. doi: 10.1016/j.amjmed.2019.02.016. Epub 2019 Mar 8. PMID: 30853474.

2022: E-cigarette use and respiratory disorder in an adult sample

• "Their study used the Behavioral Risk Factor Surveillance Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with cardiovascular diseases." (Rodu)
• Referring to: Wills TA, Pagano I, Williams RJ, Tam EK. E-cigarette use and respiratory disorder in an adult sample. Drug Alcohol Depend. 2019 Jan 1;194:363-370. doi: 10.1016/j.drugalcdep.2018.10.004. Epub 2018 Nov 7. PMID: 30472577; PMCID: PMC6312492.

2022: Cardiovascular Outcomes Associated With Adult Electronic Cigarette Use

• "The study by Vindhyal et al. used the National Health Interview Survey, which contains no information about when participants started to smoke or vape, or when they were diagnosed with cardiovascular diseases."
• Referring to: Vindhyal MR, Okut H, Ablah E, Ndunda PM, Kallail KJ, Choi WS. Cardiovascular Outcomes Associated With Adult Electronic Cigarette Use. Cureus. 2020 Aug 8;12(8):e9618. doi: 10.7759/cureus.9618. PMID: 32923219; PMCID: PMC7478662.

2022: E-cigarette use and respiratory symptoms in residents of the United States: A BRFSS report

• "The problem with these studies is disentangling the effects of a smoking career (something more complicated than adjusting for current-, former-, never-smoking status) and subsequent vaping behaviour. Also, the relationships are complicated by reverse causation (was the vaping a response to smoking-induced respiratory symptoms?), a hard-to-define counterfactual (has the vaping displaced smoking or displaced abstinence?), and the fact that respiratory damage arises from cumulative exposure and vaping exposures may be adding incremental risk (would the subject have any symptoms if they hadn't smoked first?)."
• Referring to: Varella MH, Andrade OA, Shaffer SM, Castro G, Rodriguez P, Barengo NC, Acuna JM. E-cigarette use and respiratory symptoms in residents of the United States: A BRFSS report. PLoS One. 2022 Dec 1;17(12):e0269760. doi: 10.1371/journal.pone.0269760. PMID: 36454742; PMCID: PMC9714717.

2020: Risk of Stroke With E-Cigarette and Combustible Cigarette Use in Young Adults

• “These findings arise from subgroup analysis involving multiple hypothesis tests and are therefore unreliable. Contrary to the authors’ claim, this study provides no evidence that vaping increases the risk of stroke accrued from smoking tobacco.”
• “While the paper itself is careful in interpreting the finding, the press release is grossly misleading. The study provides no justification for the claim that vaping increases the risk of stroke.”
• "While this paper highlights the need to continue studying the potential health effects of e-cigarette use, the results should be interpreted with caution as the observed associations may be simply due to unmeasured confounding and reverse causality.”
• Referring to: Parekh T, Pemmasani S, Desai R. Risk of Stroke With E-Cigarette and Combustible Cigarette Use in Young Adults. Am J Prev Med. 2020 Mar;58(3):446-452. doi: 10.1016/j.amepre.2019.10.008. Epub 2020 Jan 7. PMID: 31924460.

2020-2022: Association Between Electronic Cigarette Use and Myocardial Infarction

• Multiple comments:
  • "The study by Alzahrani et al. used data from the National Health Interview Survey, which contains no information about when participants started to smoke or vape, and when they were diagnosed with a myocardial infarction." (Rodu)
  • "E-cigarettes first appeared in the US at about 2009 and their use picked up from about 2013. In the cohorts from 2014 and 2016 that this study used, most participants with a history of MI can be expected to have had their MI before they tried e-cigarettes...The authors’ conclusions are thus misleading on an important public health issue. The article has been used e.g. to claim that vaping increases risk of cardiovascular disease by the WHO Director Ghebreyesus (DOI: 10.1016/S0140-6736(19)31730-1). The data that the paper reports show no such thing." (Hajek)
• See also: 2021
  • "Alzahrani and colleagues rightly point out that their models test for and thus demonstrate statistically independent effects of smoking and vaping, but if vaping and smoking are not actually independent contributors to identifying MI occurrence—that is, if the association between e-cigarette use and MI occurrence varies as a function of combustible cigarette use—then the main-effects model cannot be used to draw conclusions about the association between e-cigarette use and MI, independent of (or regardless of) one's history of combustible cigarette use." (Critcher, Siegel)
• See also: 2019
  • "As the debate on the risks−benefits of electronic-cigarettes continues, a rigorous evidence base is critical. Although determining whether the use of e-cigarettes carries excess risk for future MI is important, it is not possible through the analysis of cross-sectional data, such as the National Health Interview Survey data, from which temporality cannot be inferred. Equally important, we were unable to replicate the authors’ findings. Given the importance of this topic to public health, we request that the authors provide a full and comprehensive explanation for the discrepancies noted and temper their conclusions about “increased risk of myocardial infarction” to reflect the limitations of cross-sectional data." (Bover Manderski, Delnevo)
• See also: 2018
  • "Our findings show the well-established limitations of cross-sectional studies, which cannot justify any claims about causal inference, as mentioned in the conclusion by Alzahrani and colleagues.1 Therefore, the conclusion of their study is incorrect and should be revised." (Farsalinos, Niaura)
• Referring to: Alzahrani T, Pena I, Temesgen N, Glantz SA. Association Between Electronic Cigarette Use and Myocardial Infarction. Am J Prev Med. 2018 Oct;55(4):455-461. doi: 10.1016/j.amepre.2018.05.004. Epub 2018 Aug 22. Erratum in: Am J Prev Med. 2019 Oct;57(4):579-584. PMID: 30166079; PMCID: PMC6208321.

2020: Association Between Youth Smoking, Electronic Cigarette Use, and COVID-19

• See also: Qeios 1 and Qeios 2
• Referring to: Gaiha SM, Cheng J, Halpern-Felsher B. Association Between Youth Smoking, Electronic Cigarette Use, and COVID-19. J Adolesc Health. 2020 Oct;67(4):519-523. doi: 10.1016/j.jadohealth.2020.07.002. Epub 2020 Aug 11. PMID: 32798097; PMCID: PMC7417895.

2019-2020: Association of E-Cigarette Use With Respiratory Disease Among Adults: A Longitudinal Analysis

• Referring to: Bhatta DN, Glantz SA. Association of E-Cigarette Use With Respiratory Disease Among Adults: A Longitudinal Analysis. Am J Prev Med. 2020 Feb;58(2):182-190. doi: 10.1016/j.amepre.2019.07.028. Epub 2019 Dec 16. PMID: 31859175; PMCID: PMC6981012.

2019: Electronic-cigarette smoke induces lung adenocarcinoma and bladder urothelial hyperplasia in mice

• Referring to: Tang MS, Wu XR, Lee HW, Xia Y, Deng FM, Moreira AL, Chen LC, Huang WC, Lepor H. Electronic-cigarette smoke induces lung adenocarcinoma and bladder urothelial hyperplasia in mice. Proc Natl Acad Sci U S A. 2019 Oct 22;116(43):21727-21731. doi: 10.1073/pnas.1911321116. Epub 2019 Oct 7. Erratum in: Proc Natl Acad Sci U S A. 2019 Nov 5;116(45):22884. PMID: 31591243; PMCID: PMC6815158.

2017: Electronic Cigarette Use in US Adults at Risk for or with COPD: Analysis from Two Observational Cohorts

• Referring to: Bowler RP, Hansel NN, Jacobson S, Graham Barr R, Make BJ, Han MK, O'Neal WK, Oelsner EC, Casaburi R, Barjaktarevic I, Cooper C, Foreman M, Wise RA, DeMeo DL, Silverman EK, Bailey W, Harrington KF, Woodruff PG, Drummond MB; for COPDGene and SPIROMICS Investigators. Electronic Cigarette Use in US Adults at Risk for or with COPD: Analysis from Two Observational Cohorts. J Gen Intern Med. 2017 Dec;32(12):1315-1322. doi: 10.1007/s11606-017-4150-7. Epub 2017 Sep 7. PMID: 28884423; PMCID: PMC5698219.

2017: "Juice Monsters": Sub-Ohm Vaping and Toxic Volatile Aldehyde Emissions

• Referring to: Soha Talih, Rola Salman, Nareg Karaoghlanian, Ahmad El-Hellani, Najat Saliba, Thomas Eissenberg, and Alan Shihadeh Chemical Research in Toxicology 2017 30 (10), 1791-1793 DOI: 10.1021/acs.chemrestox.7b00212

2017: Hidden formaldehyde in e-cigarette aerosols

• See also: PubPeer 2015-2017 and replication study
• Referring to: Jensen RP, Luo W, Pankow JF, Strongin RM, Peyton DH. Hidden formaldehyde in e-cigarette aerosols. N Engl J Med. 2015 Jan 22;372(4):392-4. doi: 10.1056/NEJMc1413069. PMID: 25607446.

2016-2020: E-cigarettes and smoking cessation in real-world and clinical settings: a systematic review and meta-analysis

• Kalkhoran S, Glantz SA. E-cigarettes and smoking cessation in real-world and clinical settings: a systematic review and meta-analysis. Lancet Respir Med. 2016 Feb;4(2):116-28. doi: 10.1016/S2213-2600(15)00521-4. Epub 2016 Jan 14. PMID: 26776875; PMCID: PMC4752870.

2016: Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner

• Garcia-Arcos I, Geraghty P, Baumlin N, Campos M, Dabo AJ, Jundi B, Cummins N, Eden E, Grosche A, Salathe M, Foronjy R. Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner. Thorax. 2016 Dec;71(12):1119-1129. doi: 10.1136/thoraxjnl-2015-208039. Epub 2016 Aug 24. PMID: 27558745; PMCID: PMC5136722.

2015: Exposure to Electronic Cigarettes Impairs Pulmonary Anti-Bacterial and Anti-Viral Defenses in a Mouse Model

• Referring to: Sussan TE, Gajghate S, Thimmulappa RK, Ma J, Kim J-H, Sudini K, et al. (2015) Exposure to Electronic Cigarettes Impairs Pulmonary Anti-Bacterial and Anti-Viral Defenses in a Mouse Model. PLoS ONE 10(2): e0116861. https://doi.org/10.1371/journal.pone.0116861

Retractions

2022: Original: Association of Smoking and E-Cigarette in Chronic Liver Disease: An NHANES Study

• 2023: Retraction Notice to “Association of Smoking and E-Cigarette in Chronic Liver Disease: An NHANES Study”
  • Media - Filter: Journal Retracts Study That Linked Vaping to Liver Disease

2022: Original: Cancer Prevalence in E-Cigarette Users: A Retrospective Cross-Sectional NHANES Study

• 2022: Retraction Notice to “Cancer Prevalence in E-Cigarette Users: A Retrospective Cross-Sectional NHANES Study”
  • Media - Reason: A Medical Journal Retracts a 2022 Study That Linked Vaping to Cancer

2019: Original: Electronic Cigarette Use and Myocardial Infarction Among Adults in the US Population Assessment of Tobacco and Health

• 2020: Retraction to: Electronic Cigarette Use and Myocardial Infarction Among Adults in the US Population Assessment of Tobacco and Health
  • PubPeer
  • Media - USA Today: A study claimed vaping doubles risk for heart attacks. It's been retracted for being 'unreliable'

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