Nicotine - Retracted Studies, Papers, and Articles

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How Mistakes Can Happen

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

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.

Addiction / Dependence / Use

2023: Comments RE: Biochemical Validation of Dependence on JUUL and Other E-Cigarettes Among Youth

  • "Readers may be interested to know that there is now a comment to the Pierce et al paper from Shiffman and Hannon. The commenters raise questions about the conclusions drawn by the original authors and report alternative analyses of the same dataset." (Gitchell)
  • "To this last point, Pierce and Strong’s response now reports a relevant analysis, and it directly contradicts their assertion in the original paper: they demonstrate that dependence among JUUL users in each age cohort was not different from dependence in users of other ENDS brands (though the trend is evidently for lower dependence among JUUL users)."
  • Referring To: John P. Pierce, Eric C. Leas, David R. Strong; Biochemical Validation of Dependence on JUUL and Other E-Cigarettes Among Youth. Pediatrics April 2023; 151 (4): e2022059158. 10.1542/peds.2022-059158

2014: Comments RE: Electronic Cigarettes and Conventional Cigarette Use Among US Adolescents

  • "In a cross-sectional study, the observed relationship between e-cigarette use and higher and more sustained levels of smoking does not imply causation. Moreover, such studies do not take into account other population characteristics, which may play a crucial role when determining potential causation.2,3 Although the authors acknowledged this limitation in the text, they ended up drawing a conclusion that misleads the public into thinking e-cigarettes are leading to smoking initiation and addiction among adolescents." (Farsalinos, Polosa)
  • "Although Dutra and Glantz highlighted an important trend in e-cigarette use among our nation’s youth, failing to consider e-cigarette use in the context of other tobacco products may place undue emphasis on e-cigarettes, overshadowing the importance of the current use of multiple tobacco products as well as experimentation with cigars, smokeless tobacco, and hookah in this population." (Delnevo, Bover Manderski,Giovino)
  • Referring to: Dutra LM, Glantz SA. Electronic Cigarettes and Conventional Cigarette Use Among US Adolescents: A Cross-sectional Study. JAMA Pediatr. 2014;168(7):610–617. doi:10.1001/jamapediatrics.2013.5488

Cardiovascular

2024: Comments RE: Electronic Cigarette Use and Myocardial Infarction

  • "The research question posed is an important one, since the number of people who have never smoked and who report using e-cigarettes appears to have increased in recent years. However, we are concerned that the methods used in the Alzahrani study [1] make the reported findings highly suspect and the conclusion reached unlikely. This includes: 1) temporality concerns; 2) measurement, diagnosis, and biological plausibility concerns; 3) sample size concerns; 4) model design concerns; and 5) uncareful language." (Foxon, Polosa, Niaura, Cummings, Siegel, Benowitz)
  • Tweetorial
  • Referring to: Alzahrani T (November 06, 2023) Electronic Cigarette Use and Myocardial Infarction. Cureus 15(11): e48402. doi:10.7759/cureus.48402

2022: Comments RE: 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: Comments RE: 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." (Rodu)
  • 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.

2020: Comments RE: 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.” (Britton)
  • “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.” (Hajek)
  • "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.” (Shahab)
  • 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: Comments RE: 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, Singh, Delnevo)
  • See also: 2018
    • "Of concern,however, is the fact that 95% of EC users were also former or current tobacco cigarette (TC) smokers, and the timing of the MI relative to onset of EC use is unknown. (Middlekauff, Gornbein)
  • 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.

Cessation

2024: Comments RE: Declines in cigarette smoking among US adolescents and young adults: indications of independence from e-cigarette vaping surge

  • "However, the authors’ conclusions are based on questionable methodological decisions and flawed analyses. Most notably:
    • A. The joinpoint analysis of declining cigarette smoking is incorrectly conducted, in a way that obscures more rapid declines in current cigarette smoking after 2002;
    • B. Rather than conducting a standard analysis (i.e., a weighted and adjusted analysis of e-cigarette use and smoking trends), authors instead base their conclusions on tallying states that meet certain ad hoc and stringent criteria for (unadjusted) e-cigarette use and smoking trends; and
    • C. Analyses focus on an inappropriately narrow time window that does not fully capture the relevant dynamics. Together these flaws substantially underestimate the degree to which e-cigarettes may have displaced or offset cigarette smoking among youth and young adults.
    • Moreover, the conclusion that e-cigarette uptake is independent of the declines in cigarette smoking runs counter to a large and varied body of evidence that e-cigarettes substitute for or displace cigarettes. The authors only discuss two such papers, attempting to undermine their conclusions using some of the same flaws that underlie their own analyses, and neglect to mention the larger body of evidence. Together, this yields an article that could cause readers to hold a distorted view of the available evidence on these important issues." (Selya, Gitchell, Foxon, Sembower, Niaura)
  • Referring to: Pierce JP, Luo M, McMenamin SB, et alDeclines in cigarette smoking among US adolescents and young adults: indications of independence from e-cigarette vaping surgeTobacco Control Published Online First: 08 November 2023. doi: 10.1136/tc-2022-057907

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

  • Multiple Comments, many linking to more information
    • "The most obvious issue is that the result is based on studies that have no bearing on whether e-cigarettes are effective or not. This is because vapers who successfully quit smoking were excluded and only those who failed to do so were retained. The studies were not at fault, they were just not set up to evaluate quit rates in smokers who try and not try vaping. The fault is with misinterpreting their results. The letter in LRM referenced above provides more details." (Hajek)
  • Expert Reaction
    • “Publication of this study represents a major failure of the peer review system in this journal.” (West)
    • "The current paper represents the latest attempt to bring together the existing literature on e-cigarettes for smoking cessation. While its breadth is to be commended, its conclusions (that e-cigarettes don’t work for smoking cessation) are at best tentative and at worst incorrect. The main reason for this is that attempting to directly compare the results of a body of literature that uses such a wide range of study designs and includes such variable (and often poorly defined) populations and outcomes is difficult, if not impossible. Some of the observational studies included in the review, in particular, suffer from a range of limitations that don’t allow us to reliably assess whether e-cigarettes help smokers quit." (Bauld)
    • “Evidence from practice in England shows that two out of three smokers who combined e-cigarettes with additional expert support from a local stop smoking service quit successfully and while dual use is a complex issue, many vapers report using an e-cigarette to cut down and ultimately quit." (O'Connor)
    • “This review is grossly misleading in my opinion. There are several problems with the way studies were selected and used, but the main flaw is simple, though not easy to spot. The studies that are presented as showing that vaping does not help people quit only recruited people who were currently smoking and asked them if they used e-cigarettes in the past. This means that people who used e-cigarettes and stopped smoking were excluded. The same approach would show that proven stop-smoking medications do not help or even undermine quitting." (Hajek)
    • “This review is not scientific. The information included about two studies that I co-authored is either inaccurate or misleading. In addition, the authors have not included all previous studies they could have done in their meta-analysis. I believe the findings should therefore be dismissed. I am concerned at the huge damage this publication may have – many more smokers may continue smoking and die if they take from this piece of work that all evidence suggests e-cigarettes do not help you quit smoking; that is not the case." (McNeill)
  • Who will be duped by error-strewn ‘meta-analysis’ of e-cigarette studies?
    • "There are multiple challenges with interpreting the e-cigarette studies routinely appearing in the scientific literature – and over-interpretation is all too easy or even deliberate." (Bates)
  • Legacy Foundation (now Truth Initiative) submission to the FDA
    • "While the majority of the studies we reviewed are marred by poor measurement of exposures and unmeasured confounders, many of them have been included in a meta-analysis that claims to show that smokers who use e-cigarettes are less likely to quit smoking compared to those who do not.[73] This meta- analysis simply lumps together the errors of inference from these correlations. As described in detail above, quantitatively synthesizing heterogeneous studies is scientifically inappropriate and the findings of such meta-analyses are therefore invalid."
    • "Findings from the studies with the strongest methodologies suggest that e-cigarettes are effective in helping adult smokers to quit or to reduce their cigarette consumption and that rates of smoking cessation with e-cigarettes are similar to rates of cessation with nicotine replacement therapy."
  • Correspondence
    • "There are other problems—such as selective inclusion of studies, and selective reporting of data from studies that were included —and limitations the authors acknowledge in the text but ignore in their conclusions. Detailed criticism of the methods is, however, not needed, because lumping incongruous studies together—which were mostly not designed to evaluate the efficacy of e-cigarettes, and contain no useful information on this topic unless misinterpreted—makes no scientific sense in the first place." (Hajek, McRobbie, Bullen)
  • Sunday Science Lesson: What is “meta-analysis”? (and why was Glantz’s inherently junk?)
    • "Glantz’s meta-analysis is not just junk science because of details about the studies, though those are problems in themselves. It is junk science because there are probably not even two of the studies in his collection that are similar enough to average together, let alone all of them." (Phillips)
  • Referring to: 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.

COVID

2022: Comments RE: Does Vaping Increase the Risk of COVID-19 Transmission and Make Individuals Who Vape Susceptible to Infection and Prone to Severe Illness? A Review

  • "It is important to state that there is no empiric evidence of transmission of the SARS-CoV-2 virus or any other pathogen through vaping expirations. None of the sources cited by the authors on this issue (references cited in the first paragraph above) provide such evidence, they merely speculate about it in very vague general terms.
  • Given the lack of experimental detection, the potential plausibility and scope of this pathogen transmission should be discussed through well structured models based on the theory and data of pathogen transmission mechanisms. Unfortunately, the authors missed three extensive articles in which we undertook this task (links to the articles). (Sussman)
  • Referring to: Singhal S, Degano C, Berenbaum E, Keller-Olaman S. Does Vaping Increase the Risk of COVID-19 Transmission and Make Individuals Who Vape Susceptible to Infection and Prone to Severe Illness? A Review. J Can Dent Assoc. 2022 Jan;88:m1. PMID: 35881057.

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

  • Multiple Comments:
    • "This article is getting severe criticism on Twitter. This thread summarises one issue and links to threads on other, more classic, problems." (Brown) Further comments by the same author (Brown) point out some errors in tables.
    • "The authors surveyed and controlled for socioeconomic factors, ethnicity and compliance with confinement precautions, but not for other risk behaviors besides smoking or vaping (such as alcohol drinking, substance usage, unprotected sex). The lack of this important comparative context further weakens the conclusions of this study." (Sussman)
    • "Flaws in the paper itself are only one part of the problem that needs to be addressed by the authors. The other is the public relations offensive mounted on the back of the paper once it was published in the Journal of Adolescent Health on August 11." "Unsurprisingly, such an incendiary claim generated considerable media coverage, even though there is no basis for it in fact or evidence." "Finally, there was a political dimension. On the same day as the article was published, August 11, 2020, Illinois Congressman Raja Krishnamoorthi, Chairman of the Subcommittee on Economic and Consumer Policy, found time to write a press release and letter to the Commissioner of the Food and Drug Administration, Dr. Stephen Hahn demanding FDA "clear the market of e-cigarettes" in response to the study." (Bates)
  • See Also:Qeios 1
    • "In this brief peer review, we argue that the data reported by Gaiha et al (https://doi.org/10.1016/j.jadohealth.2020.07.002) regarding associations between vaping and COVID-19 testing are so suspect that any conclusions drawn from it cannot be relied upon. We discuss six main areas of concern and conclude that the paper should be retracted." (Gitchell, Kleykamp, Niaura, Shiffman, Cummings, Sweanor, Abrams)
  • Qeios 2
    • "In a recent study, Gaiha et al. examined the association between e-cigarette use and COVID-19 in an online cross-sectional study of people aged 13-24 years conducted from May 6 to May 14, 2020. We have noticed serious issues in population weighting, response bias and biological implausibility. The suggested conclusions and interpretation of the study findings cannot be considered reliable. These issues raise the question of retracting the study." (Farsalinos, Niaura)
  • 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.

Diabetes and Prediabetes

2022: Comments RE: 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: Comments RE: 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.

EVALI (coming soon)

Gateway

2022: Comments RE: Impact of the e-cigarette era on cigarette smoking among youth in the United States: A population-level study

  • "The present re-analysis shows that the report of a gateway effect in the NYTS data by Harrell et al. is not supported by these data when appropriate statistical methodology is applied." (Foxon)
  • Referring to: Harrell MB, Mantey DS, Chen B, Kelder SH, Barrington-Trimis J. Impact of the e-cigarette era on cigarette smoking among youth in the United States: A population-level study. Prev Med. 2022 Nov;164:107265. doi: 10.1016/j.ypmed.2022.107265. Epub 2022 Sep 22. PMID: 36152819; PMCID: PMC10381788.

HPHC - Harmful and Potentially Harmful Constituents

2023: Comments RE: Arsenic and arsenic species in MOD, POD, and disposable POD electronic cigarette aerosols: a pilot study

  • The article has several serious shortcomings
    • REPRODUCIBILITY AND LACK OF CRUCIAL INFORMATION.
    • INAPPROPRIATE AIRFLOW FOR SUB-OHM DEVICES.
    • ERRONEOUS CONCENTRATION VALUES
    • STORAGE (Sussman)
  • Referring to: Tehrani MW, Ahererra AD, Tanda S, Chen R, Borole A, Goessler W, Rule AM. Arsenic and arsenic species in MOD, POD, and disposable POD electronic cigarette aerosols: a pilot study. Journal of Environmental Exposure Assessment. 2023; 2(2): 9. http://dx.doi.org/10.20517/jeea.2023.03

2022: Comments RE: Should IQOS Emissions Be Considered as Smoke and Harmful to Health? A Review of the Chemical Evidence

  • The reader may find the following commentary on Uguna & Snape by Chris Snowdon of interest. It includes a scientific review of the paper by Roberto Sussman that provides a convincing rebuttal of the author's assertions that heated tobacco products generate smoke. (Bates)
  • Referring to: Uguna CN, Snape CE. Should IQOS Emissions Be Considered as Smoke and Harmful to Health? A Review of the Chemical Evidence. ACS Omega. 2022 Jun 22;7(26):22111-22124. doi: 10.1021/acsomega.2c01527. PMID: 35811880; PMCID: PMC9260752.

2022: Comments RE: Evidence for the coupling of refill liquids content and new particle formation in electronic cigarette vapors

  • "Conclusion. This study might be a correct and rigorous examination of various processes of the particulate phase of e-cigarette aerosol that are strictly valid under the abnormal overheating testing conditions. The study does not prove that such processes can occur in low powered devices, or even in high powered devices under the recommended power ranges and airflow rates normally used by consumers. The utility to assess the safety profile of e-cigarettes requires the devices to be tested under the best approximation possible to realistic usage. Unfortunately, this study failed to comply with this important consistency condition." (Sussman)
  • Referring to: Dada O, Castillo K, Hogan M, Chalbot MG, Kavouras IG. Evidence for the coupling of refill liquids content and new particle formation in electronic cigarette vapors. Sci Rep. 2022 Nov 3;12(1):18571. doi: 10.1038/s41598-022-21798-w. PMID: 36329089; PMCID: PMC9633786.

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

  • Multiple Comments
    • "Users will operate the equipment in a way that does not lead to harsh dry puff conditions, with associated high VA formation. This is a key human control feedback that does not exist in laboratory equipment. So experiments that just standardise power settings or volume consumption must take care to validate these are realistic proxies for human use for a particular device. In this paper, many of the coil, power and volume settings combinations were not realistic. That could have been avoided through engaging with people with real practical expertise." (Bates)
    • "In reality, as power to the coil increases, liquid consumption also increases. In real-world scenarios, human users regulate both power and liquid flow to minimise the risk of dry-puff conditions and therefore avoiding increases in VA emissions." (Barnes)
  • 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: Comments RE: Hidden formaldehyde in e-cigarette aerosols

  • "The problem for the authors is that cancer is a human condition and their calculation is based exposures measured by a lab machine in conditions that no humans would be able to tolerate." (Bates)
  • See also: PubPeer 2015-2017
    • "Although Jensen et al. mentioned in the 2015 NEJM research letter that the health risks of formaldehyde hemiacetal inhalation are unknown ("How formaldehyde-releasing agents behave in the respiratory tract is unknown..."), they made a calculation that the formaldehyde-attributable cancer risk from e-cigarette use is 5 to 15 times higher than from long-term smoking. These two statements are clearly contradictory, and the calculation of any cancer risk from formaldehyde hemiacetal emissions is invalid since no such risk has been established for these compounds." (Farsalinos)
  • See also: replication study
    • "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." (Farsalinos, Voudris, Spyrou, Poulas)
  • See also 2015: Researchers call for retraction of NEJM paper showing dangers of e-cigarettes
    • Links to the efforts to have the referenced paper retracted.
  • 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.

Respiratory

2023: Comments RE: E-cigarette vapor exposure in utero causes long-term pulmonary effects in offspring

  • Given all these shortcomings (opaqueness, unrealistic airflow and nicotine, likely overexposure of mice), the results of this study are not reliable to assess potential harms from exposure to e-cigarette aerosol. (Sussman)
  • Aslaner DM, Alghothani O, Saldana TA, Ezell KG, Yallourakis MD, MacKenzie DM, Miller RA, Wold LE, Gorr MW. E-cigarette vapor exposure in utero causes long-term pulmonary effects in offspring. Am J Physiol Lung Cell Mol Physiol. 2022 Dec 1;323(6):L676-L682. doi: 10.1152/ajplung.00233.2022. Epub 2022 Oct 11. PMID: 36218276; PMCID: PMC9722245.

2022: Comments RE: 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: Comments RE: 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. https://doi.org/10.1016/j.amepre.2019.10.014

2022: Comments RE: 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: Comments RE: 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: Comments RE: 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?)." (Bates)
  • 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: Comments RE: Are Electronic Cigarette Users at Risk for Lipid-mediated Lung Injury?

  • "The problem is that vegetable glycerin (glycerol) is not a lipid it is an alcohol. It cannot cause the lipoid pneumonia symptoms mentioned." (Bates)
  • "Endogenous lipoid pneumonia from VG (or PG) inhalation is a speculation and implausible...The experience in the US over the past several months clearly shows that the culprit for the acute lung intoxication cases are black market THC oils which were sold as THC oils, not e-cigarette products." (Farsalinos)
  • "visual assessment of lung HRCT scans showed no pathological findings in people vaping daily for more than 3.5 years. In particular, no CT features compatible with early signs of COPD (i.e. parenchymal micronodules, ground-glass opacity, or macroscopic emphysema) or lipoid pneumonia or popcorn lung disease were present." (Polosa)
  • Referring to: Eissenberg T, Maziak W. Are Electronic Cigarette Users at Risk for Lipid-mediated Lung Injury? Am J Respir Crit Care Med. 2020 Apr 15;201(8):1012-1013. doi: 10.1164/rccm.201910-2082LE. PMID: 31917600; PMCID: PMC7159422.

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

  • Multiple Comments:
    • "One of the essential criteria of causal inference is that exposure to the cause precedes disease onset. Three of the diseases Glantz studies — COPD, chronic bronchitis and emphysema — take decades to become clinically apparent and would have been present, even though undiagnosed, in many of his cases long before his study began in 2014, and indeed even before e-cigarettes first became available in the US in about 2007. His findings are also flawed by the fact that most vapers have smoked, and since smoking is a strong cause of chronic lung disease, vapers inevitably carry an increased risk of lung disease long after quitting smoking. Glantz claims to have allowed for this statistically but his approach is simplistic: he lacks the detail of lifetime duration and intensity of smoking required. On these grounds alone his conclusion is specious." (Britton)
    • "Donald Kenkel and colleagues at Cornell University conducted a replication of the analysis using econometric techniques...When we use a more flexible empirical specification, among respondents who had never smoked combustible tobacco, we find no evidence that current or former e-cigarette use is associated with respiratory disease. The statistical associations between e-cigarette use and respiratory disease are driven by e-cigarette users who are also current or former smokers of combustible tobacco. A striking feature of the data is that almost all e-cigarette users were either current or former smokers of combustible tobacco." (Bates)
  • 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: Comments RE: Electronic-cigarette smoke induces lung adenocarcinoma and bladder urothelial hyperplasia in mice

  • Multiple comments:
    • “The comparison between mice breathing vapour and mice breathing air is not statistically significant. There is no sample size justification and no power calculation. There is no message to the public here – I suspect these results are just noise.” (Britton)
    • “The study has unclear relevance for human vapers. Rodents were exposed to what are for them huge concentrations of chemicals that bear no resemblance to human exposure from vaping. Several animals in fact died during these exposures. The authors assigned the effects they observed to a carcinogen NNK – but NNK has been measured before in human vapers, and it is known that exposure from vaping is either negligible or none.” (Hajek)
  • 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: Comments RE: Electronic Cigarette Use in US Adults at Risk for or with COPD: Analysis from Two Observational Cohorts

  • "​It is literally true that they "find no evidence...", but that is because this study is completely ill-suited to drawing any policy conclusions about e-cigarettes and COPD. Despite hinting at the limitations of cross-sectional data, the authors draw a negative-sounding conclusion without addressing the key question of how respiratory health changes for a given smoker who uses e-cigarettes to quit or cut down once they are ill from smoking or as a way of preventing COPD." (Bates)
  • 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.

2016: "Popcorn Lung" Comments RE: Comment on “Flavoring Chemicals in E-Cigarettes: Diacetyl, 2,3-Pentanedione, and Acetoin in a Sample of 51 Products, Including Fruit-, Candy-, and Cocktail-Flavored E-Cigarettes”

    • "Over the past five years, we have published the results of several studies in which diacetyl and 2,3-pentanedione levels were measured in various consumer products..."
    • "..."hundreds of consumer products (e.g., tea, coffee, citrus juices, butter) contain naturally occurring diacetyl and 2,3-pentanedione...several studies have shown that airborne diketones associated with these products are easily detectable..."
    • "Unless one assumes that unflavored coffee beans pose a serious risk of “popcorn lung,” a rare and oftentimes lethal disease, then one should agree that exposures to airborne diketone levels above the NIOSH and ACGIH OELs are not necessarily indicative of respiratory risk."
    • "Similarly, we measured concentrations of naturally occurring diacetyl and 2,3-pentanedione in mainstream cigarette smoke at levels (200–400 ppm and 30–50 ppm, respectively) that are hundreds of thousands of times higher than the NIOSH and ACGIH OELs, yet cigarette smoking is not associated with “popcorn lung”. Also, as others have noted, diketone exposures from traditional cigarettes are higher than those associated with e-cigarette use, hence switching from tobacco to e-cigarettes may result in reduced diketone exposure."
    • "Ironically, suggesting that diketone levels in e-cigarettes are potentially dangerous could actually lead to higher diketone exposures in the smoking population if smokers decide not to switch to e-cigarettes due to as yet unfounded health concerns." (Pierce, Abelmann, Finley) For further information, see authors response to the comments above.
  • See Also: 2016: On the Vapor Trail: Examining the Chemical Content of E-Cigarette Flavorings
    • "The 51 e-juices sampled make up a very small proportion of all the products sold, and there is variability in the chemical content of specific products as well as how those chemicals are delivered by different devices. The authors therefore acknowledge that it is impossible to extrapolate their results to all the other products on the market. Importantly, this study did not assess levels of diacetyl, 2,3-pentanedione, and acetoin in actual users, much less health effects. So it’s premature to assume that exposure to these chemicals via e-cigarettes causes health problems." (Arnold)
  • See Also: 2015: Is the Harvard E-Cigarette Buttery Flavor Study Credible?
    • "As I advised previously, vapers should only use liquids that are certified to be free of buttery flavors that are suspected respiratory toxicants. However, laboratory investigations of e-cigarettes should use validated methods to assure credibility. The results of the Harvard Buttery Flavor Study do not meet this standard." (Rodu)
  • See Also: 2015: A new study finds diacetyl in e-cigarettes but exaggerates risks and fails to discuss about smoking
    • "In conclusion, the article is creating false impressions and exaggerates the potential risk from diacetyl and acetyl propionyl exposure through e-cigarettes. They failed to mention that these chemicals are present in tobacco cigarette smoke and violated a classical toxicological principle that the amount determines the toxicity and the risk." (Farsalinos)
  • See Also: 2015: New Study Finds that Average Diacetyl Exposure from Vaping is 750 Times Lower than from Smoking
    • "Nevertheless, it is disingenuous and actually damaging to the public's health to spread the message that vaping causes fatal lung disease or even that it appears to increase the risk for popcorn lung. And it is especially disingenuous and damaging to send these messages to the public without telling us that smoking produces exposure to diacetyl that is on average about 750 times higher than vaping." (Siegel)
  • Referring to: Allen JG, Flanigan SS, LeBlanc M, Vallarino J, MacNaughton P, Stewart JH, Christiani DC. Flavoring Chemicals in E-Cigarettes: Diacetyl, 2,3-Pentanedione, and Acetoin in a Sample of 51 Products, Including Fruit-, Candy-, and Cocktail-Flavored E-Cigarettes. Environ Health Perspect. 2016 Jun;124(6):733-9. doi: 10.1289/ehp.1510185. Epub 2015 Dec 8. PMID: 26642857; PMCID: PMC4892929.

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

  • "The mice were severely overdosed with nicotine, up to the lethal levels for mice, and a huge amount above what any human vaper would get...Regarding the relevance to human health, nicotine poisoning poses normally no risk to vapers or smokers because if nicotine concentrations start to rise above their usual moderate levels, there is an advance warning in the form of nausea which makes people stop nicotine intake long before any dangerous levels can accrue. (Mice in these types of experiments do not have that option)." (Hajek)
  • Referring to: 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: Comments RE: Exposure to Electronic Cigarettes Impairs Pulmonary Anti-Bacterial and Anti-Viral Defenses in a Mouse Model

  • " In other words, to obtain the same exposure in humans the e-cig user should take 11000 – 13000 puffs per day. Assuming 8 hours of sleep per day, in order to acquire such a high number of puffs e-cig users would need to take 11-13 puffs per minute and thus practically take an e-cig puff with each breath. In conclusion we recommend that the results of the discussed study should be interpreted with caution and that more studies with more realistic levels of e-liquid exposure should be conducted." (Mukhin, Rose)
  • 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

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

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

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