Electronic cigarettes: assessing the efficacy and the adverse effects through a systematic review of published studies

To investigate the efficacy and the adverse effects (AEs) of the electronic cigarette, we performed a systematic review of published studies.

Published: 9 August 2014

Positive: Yes

Link to publication: http://jpubhealth.oxfordjournals.org/content/early/2014/08/09/pubmed.fdu055.short

doi: 10.1093/pubmed/fdu055

Authors:

Maria Rosaria Gualano
Stefano Passi
Fabrizio Bert
Giuseppe La Torre
Giacomo Scaioli
Roberta Siliquini


Summary

Methods We selected experimental and observational studies examining the efficacy (as reduction of desire to smoke and/or number of cigarettes smoked and/or quitting or as reduction of nicotine withdrawal symptoms) and the safety of EC (AEs self-reported or clinical/laboratory). The following search engines were used: PubMed, ISI Web of Knowledge and Cochrane Controlled Trials Register.

Results Finally, six experimental studies and six cohort studies were included. In the prospective 12-month, randomized controlled trial, smoking reduction was documented in 22.3 and 10.3% at Weeks 12 and 52, respectively (P < 0.001 versus baseline). Moreover, two cohort studies reported a reduction in the number of cigarette/day (from 50 to 80%) after the introduction of the EC. ‘Mouth and throat irritation’, ‘nausea’, ‘headache’ and ‘dry cough’ were the most frequently AEs reported.


Conclusions

The use of the EC can reduce the number of cigarettes smoked and withdrawal symptoms, but the AEs reported are mainly related to a short period of use. Long-term studies are needed to evaluate the effects of the EC usage after a chronic exposure.

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Biochemically verified smoking cessation and vaping beliefs among vape store customers

To evaluate biochemically verified smoking status, and electronic nicotine delivery systems (ENDS) use behaviors and beliefs among a sample of customers from vapor stores (stores specializing in ENDS).

Published: Not yet (as of 13 February 2015)

Positive: Yes

Publication link: http://onlinelibrary.wiley.com/doi/10.1111/add.12878/abstract

doi: 10.1111/add.12878

Authors:

Alayna P. Tackett
William V. Lechner
Ellen Meier
DeMond M. Grant
Leslie M. Driskill
Noor N. Tahirkheli2
Theodore L. Wagener


Summary

Design, Setting, Participants

A cross-sectional survey of 215 adult vapor store customers at four retail locations in the Midwestern United States; a subset of participants (n=181) also completed exhaled carbon monoxide (CO) testing to verify smoking status.

Measurements

Outcomes evaluated included ENDS preferences, harm beliefs, use behaviors, smoking history and current biochemically verified smoking status.

Findings

Most customers reported starting ENDS as a means of smoking cessation (86%), using newer generation devices (89%), vaping non-tobacco/non-menthol flavors (72%), and using e-liquid with nicotine strengths of ≤20 mg/ml (72%). There was a high rate of switching (91.4%) to newer generation ENDS among those who started with a first generation product. Exhaled CO readings confirmed that 66% of the tested sample had quit smoking. Among those who continued to smoke, mean cigarettes per day decreased from 22.1 to 7.5 (p <.001). People who reported vaping longer (OR=4.7, 95% CI = 2.0–10.8), using newer generation devices (OR=3.0, 95% CI = 1.0–8.4) and using non-tobacco and non-menthol flavors (OR=2.6, 95% CI = 1.1–6.1) were more likely to have quit smoking.


Conclusions

Among vapor store customers in the US who use electronic nicotine delivery devices to stop smoking, vaping longer, using newer generation devices, and using non-tobacco and non-menthol flavored e-liquid appear to be associated with higher rates of smoking cessation. Continuer la lecture de Biochemically verified smoking cessation and vaping beliefs among vape store customers

Comparison of select analytes in aerosol from e-cigarettes with smoke from conventional cigarettes and with ambient air

Highlights

• The e-cigarettes contained and delivered mostly glycerin and/or PG and water.
• Aerosol nicotine content was 85% lower than the cigarette smoke nicotine.
• The levels of HPHCs in aerosol were consistent with the air blanks (<2 μg/puff).
• Mainstream cigarette smoke HPHCs (∼3000 μg/puff) were 1500 times higher than e-cigarette HPHCs.
• No significant contribution of tested HPHC classes was found for the e-cigarettes.

Published: 24 October 2014

Positive: Yes

Link to publication: http://www.sciencedirect.com/science/article/pii/S0273230014002505

Authors:

Rana Tayyarah
Gerald A. Long

Remarks: From Lorillard tobacco company


Summary

Leading commercial electronic cigarettes were tested to determine  bulk composition. The e-cigarettes and conventional cigarettes were evaluated using machine-puffing to compare nicotine delivery and relative yields of chemical constituents. The e-liquids tested were found to contain humectants, glycerin and/or propylene glycol, (⩾75% content); water (<20%); nicotine (approximately 2%); and flavor (<10%). The aerosol collected mass (ACM) of the e-cigarette samples was similar in composition to the e-liquids. Aerosol nicotine for the e-cigarette samples was 85% lower than nicotine yield for the conventional cigarettes. Analysis of the smoke from conventional cigarettes showed that the mainstream cigarette smoke delivered approximately 1500 times more harmful and potentially harmful constituents (HPHCs) tested when compared to e-cigarette aerosol or to puffing room air. The deliveries of HPHCs tested for these e-cigarette products were similar to the study air blanks rather than to deliveries from conventional cigarettes; no significant contribution of cigarette smoke HPHCs from any of the compound classes tested was found for the e-cigarettes. Thus, the results of this study support previous researchers’ discussion of e-cigarette products’ potential for reduced exposure compared to cigarette smoke.


Conclusion

The purpose of this study was to determine content and delivery of e-cigarette ingredients and to compare e-cigarette aerosol to conventional cigarettes with respect to select HPHCs for which conventional cigarette smoke is routinely tested. Routine analytical methods were adapted and verified for e-cigarette testing. Aerosol collection was conducted using conventional smoking machines and an intense puffing regime. As machine puffing cannot, and is not intended to, mimic human puffing, results of this study are limited to the scope of the comparisons made between the e-cigarette and conventional cigarette products tested.

The main ingredients for the e-cigarettes tested were consistent with disclosed ingredients: glycerin and/or propylene glycol (⩾75%), water (⩽18%), and nicotine (∼2%). Machine-puffing of these products under a standardized intense regime indicated a direct transfer of these ingredients to the aerosol while maintaining an aerosol composition similar to the e-liquid. Nicotine yields to the aerosol were approximately 30 μg/puff or less for the e-cigarette samples and were 85% lower than the approximately 200 μg/puff from the conventional cigarettes tested.

Testing of the e-cigarette aerosol indicates little or no detectable levels of the HPHC constituents tested. Overall the cigarettes yielded approximately 3000 μg/puff of the HPHCs tested while the e-cigarettes and the air blanks yielded <2 μg. Small but measurable quantities of 5 of the 55 HPHCs tested were found in three of the e-cigarette aerosol samples at 50–900 times lower levels than measurable in the cigarette smoke samples. Overall, the deliveries of HPHCs tested for the e-cigarette products tested were more like the study air blanks than the deliveries for the conventional cigarettes tested. Though products tested, collection parameters, and analytical methods are not in common between this study and others, the results are very consistent. Researchers have reported that most or all of the HPHCs tested were not detected or were at trace levels. Burstyn (2014) used data from approximately 50 studies to estimate e-cigarette exposures compared to workplace threshold limit values (TLV) based on 150 puffs taken over 8 h. The vast majority of the analytes were estimated as ≪1% of TLV and select carbonyls were estimated as <5% of TLV. Cheng (2014) reviewed 29 publications reporting no to very low levels of select HPHCs relative to combustible cigarettes, while noting that some of the tested products exhibited considerable variability in their composition and yield. Goniewicz et al. (2014) tested a range of commercial products and reported quantifiable levels for select HPHCs in e-cigarette aerosols at 9- to 450-fold lower levels than those in cigarette smoke that in some instances were on the order of levels determined for the study reference (a medicinal nicotine inhaler). Laugesen, 2009 and Theophilus et al., 2014 have presented results for commercial e-cigarette product liquids and aerosols having no quantifiable levels of tested HPHCs, or extremely low levels of measurable constituents relative to cigarette smoke. Additionally, findings from several recent studies indicate that short-term use of e-cigarettes by adult smokers is generally well-tolerated, with significant adverse events reported relatively rarely (Etter, 2010, Polosa et al., 2011, Polosa et al., 2014, Caponnetto et al., 2013, Dawkins and Corcoran, 2014 and Hajek et al., 2014). Thus, the results obtained in the aforementioned studies and in the present work broadly support the potential for e-cigarette products to provide markedly reduced exposures to hazardous and potentially hazardous smoke constituents in smokers who use such products as an alternative to cigarettes.

Additional research related to e-cigarette aerosol characterization is warranted. For example, continued characterization of major components and flavors is needed. Establishment of standardized puffing regimes and reference products would greatly aid sharing of knowledge between researchers. Continued methods’ refinement may be necessary for improved accuracy for quantitation of analytes at the low levels determined in this study. To that end, it is critical that negative controls and steps to avoid sample contamination be included when characterizing e-cigarette aerosol since analytes are on the order of what has been measured in the background levels of a laboratory setting. Though researchers have reported quantification of select analytes, great care must be taken when interpreting results at such trace levels.

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Hidden Formaldehyde in E-Cigarette Aerosols

Not a study per se, but a letter to the editor of the NEJM. This letter has been totally debunked, and is proved to have no value whatsoever (except for mouses who vape).

Published: 22 January 2015

Positive: No

Link to publication: http://www.nejm.org/doi/full/10.1056/NEJMc1413069

Comment from the author: http://www.nytimes.com/2015/01/27/opinion/joe-nocera-is-vaping-worse-than-smoking.html?_r=0

Comment from Clive Bates: http://www.clivebates.com/?p=2706

Comment from Dr Farsalinos: http://www.ecigarette-research.org/research/index.php/whats-new/whatsnew-2015/191-form-nejm

Comment from Dr Michael Siegel: http://tobaccoanalysis.blogspot.be/2015/01/new-study-reports-high-levels-of.html

Comment from Pr Hajek: http://www.sciencemediacentre.co.nz/2015/01/22/formaldehyde-in-e-cigarettes-expert-responds/

Comment from Pr Dautzenberg (in French): http://www.sciencesetavenir.fr/sante/20150126.OBS0840/e-cigarette-ce-n-est-pas-une-etude-c-est-une-lettre-torchon.html

Authors:

R. Paul Jensen, B.S.
Wentai Luo, Ph.D.
James F. Pankow, Ph.D.
Robert M. Strongin, Ph.D.
David H. Peyton, Ph.D.


Letter

To the Editor:

E-cigarette liquids are typically solutions of propylene glycol, glycerol, or both, plus nicotine and flavorant chemicals. We have observed that formaldehyde-containing hemiacetals, shown by others to be entities that are detectable by means of nuclear magnetic resonance (NMR) spectroscopy,1 can be formed during the e-cigarette “vaping” process. Formaldehyde is a known degradation product of propylene glycol that reacts with propylene glycol and glycerol during vaporization to produce hemiacetals. These molecules are known formaldehyde-releasing agents that are used as industrial biocides.5 In many samples of the particulate matter (i.e., the aerosol) in “vaped” e-cigarettes, more than 2% of the total solvent molecules have converted to formaldehyde-releasing agents, reaching concentrations higher than concentrations of nicotine. This happens when propylene glycol and glycerol are heated in the presence of oxygen to temperatures reached by commercially available e-cigarettes operating at high voltage. How formaldehyde-releasing agents behave in the respiratory tract is unknown, but formaldehyde is an International Agency for Research on Cancer group 1 carcinogen.4

Here we present results of an analysis of commercial e-liquid vaporized with the use of a “tank system” e-cigarette featuring a variable-voltage battery. The aerosolized liquid was collected in an NMR spectroscopy tube (10 50-ml puffs over 5 minutes; 3 to 4 seconds per puff). With each puff, 5 to 11 mg of e-liquid was consumed, and 2 to 6 mg of liquid was collected. At low voltage (3.3 V), we did not detect the formation of any formaldehyde-releasing agents (estimated limit of detection, approximately 0.1 μg per 10 puffs). At high voltage (5.0 V), a mean (±SE) of 380±90 μg per sample (10 puffs) of formaldehyde was detected as formaldehyde-releasing agents. Extrapolating from the results at high voltage, an e-cigarette user vaping at a rate of 3 ml per day would inhale 14.4±3.3 mg of formaldehyde per day in formaldehyde-releasing agents. This estimate is conservative because we did not collect all of the aerosolized liquid, nor did we collect any gas-phase formaldehyde. One estimate of the average delivery of formaldehyde from conventional cigarettes is approximately 150 μg per cigarette,3 or 3 mg per pack of 20 cigarettes. Daily exposures of formaldehyde associated with cigarettes, e-cigarettes from the formaldehyde gas phase, and e-cigarettes from aerosol particles containing formaldehyde-releasing agents are shown in Figure 1.

Inhaled formaldehyde has a reported slope factor of 0.021 kg of body weight per milligram of formaldehyde per day for cancer (http://oehha.ca.gov/risk/pdf/TCDBcas061809.pdf). Among persons with a body weight of 70 kg, the incremental lifetime cancer risk associated with long-term cigarette smoking at 1 pack per day may then be estimated at 9×10−4. If we assume that inhaling formaldehyde-releasing agents carries the same risk per unit of formaldehyde as the risk associated with inhaling gaseous formaldehyde, then long-term vaping is associated with an incremental lifetime cancer risk of 4.2×10−3. This risk is 5 times as high (as compared with the risk based on the calculation of Miyake and Shibamoto shown in Figure 1), or even 15 times as high (as compared with the risk based on the calculation of Counts et al. shown in Figure 1) as the risk associated with long-term smoking. In addition, formaldehyde-releasing agents may deposit more efficiently in the respiratory tract than gaseous formaldehyde, and so they could carry a higher slope factor for cancer.

 

 

 

 

 

Vapors Produced by Electronic Cigarettes and E-Juices with Flavorings Induce Toxicity, Oxidative Stress, and Inflammatory Response in Lung Epithelial Cells and in Mouse Lung

The aerosols produced by vaporizing ENDS e-liquids exhibit oxidant reactivity suggesting oxidants or reactive oxygen species (OX/ROS) may be inhaled directly into the lung during a “vaping” session. These OX/ROS are generated through activation of the heating element which is affected by heating element status (new versus used), and occurs during the process of e-liquid vaporization.

Published: 6 February 2015

Positive: No

Link to publication: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0116732

DOI: 10.1371/journal.pone.0116732

Authors

Chad A. Lerner
Isaac K. Sundar
Hongwei Yao
Janice Gerloff
Deborah J. Ossip
Scott McIntosh
Risa Robinson
Irfan Rahman


Summary

Abstract

Oxidative stress and inflammatory response are the key events in the pathogenesis of chronic airway diseases. The consumption of electronic cigarettes (e-cigs) with a variety of e-liquids/e-juices is alarmingly increasing without the unrealized potential harmful health effects. We hypothesized that electronic nicotine delivery systems (ENDS)/e-cigs pose health concerns due to oxidative toxicity and inflammatory response in lung cells exposed to their aerosols. The aerosols produced by vaporizing ENDS e-liquids exhibit oxidant reactivity suggesting oxidants or reactive oxygen species (OX/ROS) may be inhaled directly into the lung during a “vaping” session. These OX/ROS are generated through activation of the heating element which is affected by heating element status (new versus used), and occurs during the process of e-liquid vaporization. Unvaporized e-liquids were oxidative in a manner dependent on flavor additives, while flavors containing sweet or fruit flavors were stronger oxidizers than tobacco flavors. In light of OX/ROS generated in ENDS e-liquids and aerosols, the effects of ENDS aerosols on tissues and cells of the lung were measured. Exposure of human airway epithelial cells (H292) in an air-liquid interface to ENDS aerosols from a popular device resulted in increased secretion of inflammatory cytokines, such as IL-6 and IL-8. Furthermore, human lung fibroblasts exhibited stress and morphological change in response to treatment with ENDS/e-liquids. These cells also secrete increased IL-8 in response to a cinnamon flavored e-liquid and are susceptible to loss of cell viability by ENDS e-liquids. Finally, exposure of wild type C57BL/6J mice to aerosols produced from a popular e-cig increase pro-inflammatory cytokines and diminished lung glutathione levels which are critical in maintaining cellular redox balance. Thus, exposure to e-cig aerosols/juices incurs measurable oxidative and inflammatory responses in lung cells and tissues that could lead to unrealized health consequences.


Conclusions

In conclusion, we showed that 1) OX/ROS are generated by vaporizing ENDS/e-cig e-liquids/e-juices and are further influenced by the state of the heating element, 2) differences in OX/ROS reactivity in e-liquids prior to vaporization is associated with e-liquid flavor, 3) e-liquids can mediate effects on lung cell morphology and affect viability, 4) e-cig aerosols can modulate levels of oxidative stress and inflammation markers in both lung cells and mouse lungs, and 5) e-cig aerosols affect in vivo in lung glutathione redox physiology implicating oxidative stress. These data clearly demonstrate the lung toxicity and hazards of exposure to ENDS/e-cigarettes.

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Dependence levels in users of electronic cigarettes, nicotine gums and tobacco cigarettes

 

  • Little is known about the addictiveness of electronic cigarettes (e-cigarettes).
  • We assessed dependence in daily users of e-cigarettes.
  • We found that e-cigarettes users were less addicted to e-cigarettes than smokers were addicted to tobacco cigarettes and nicotine gum users to the nicotine gum.

Published: 18 December 2014

Positive: Yes

Link to publication: http://www.drugandalcoholdependence.com/article/S0376-8716%2814%2901986-3/abstract#.VND5EhP-1Qw.twitter

DOI: http://dx.doi.org/10.1016/j.drugalcdep.2014.12.007

Authors

Jean-François Etter
Thomas Eissenberg


Summary

Objective

To assess dependence levels in users of e-cigarettes, and compare them with dependence levels in users of nicotine gums and tobacco cigarettes.

Design

Self-reports from cross-sectional Internet and mail surveys. Comparisons of: (a) 766 daily users of nicotine-containing e-cigarettes with 30 daily users of nicotine-free e-cigarettes; (b) 911 former smokers who used the e-cigarette daily with 451 former smokers who used the nicotine gum daily (but no e-cigarette); (c) 125 daily e-cigarette users who smoked daily (dual users) with two samples of daily smokers who did not use e-cigarettes (2206 enrolled on the Internet and 292 enrolled by mail from the general population of Geneva). We used the Fagerström test for nicotine dependence, the nicotine dependence syndrome scale, the cigarette dependence scale and versions of these scales adapted for e-cigarettes and nicotine gums.

Results

Dependence ratings were slightly higher in users of nicotine-containing e-cigarettes than in users of nicotine-free e-cigarettes. In former smokers, long-term (>3 months) users of e-cigarettes were less dependent on e-cigarettes than long-term users of the nicotine gum were dependent on the gum. There were few differences in dependence ratings between short-term (≤3 months) users of gums or e-cigarettes. Dependence on e-cigarettes was generally lower in dual users than dependence on tobacco cigarettes in the two other samples of daily smokers.


Conclusions

Some e-cigarette users were dependent on nicotine-containing e-cigarettes, but these products were less addictive than tobacco cigarettes. E-cigarettes may be as or less addictive than nicotine gums, which themselves are not very addictive.

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

Study of mouse models for resistance to flu and pneumonia after 2 weeks being submitted to vapour 3 hours per day.

It shows that free radicals are present in the vapour, leading to reduced immunity to flu and pneumonia. But those radicals are only at a level equivalent to 1% of the one found in combustible cigarette smoke.

Published: 04 February 2015

Positive: N/A

Link to publication: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0116861#sec011

DOI: 10.1371/journal.pone.0116861

Comments from Jacques Le Houezec (in French): JLH Comments

Bernd Mayer’s point of view, with a set of studies debunking the results: http://www.bernd-mayer.com/electronic-cigarettes-airway-infections-update/

ECITA’s comments: http://www.ecita.org.uk/ecita-blog/new-study-mice-shows-remarkably-little-acute-toxicity-despite-major-methodology-problems

Authors:

Thomas E. Sussan
Sachin Gajghate
Rajesh K. Thimmulappa
Jinfang Ma
Jung-Hyun Kim
Kuladeep Sudini
Nicola Consolini
Stephania A. Cormier
Slawo Lomnicki
Farhana Hasan
Andrew Pekosz
Shyam Biswal


Summary

Electronic cigarettes (E-cigs) have experienced sharp increases in popularity over the past five years due to many factors, including aggressive marketing, increased restrictions on conventional cigarettes, and a perception that E-cigs are healthy alternatives to cigarettes. Despite this perception, studies on health effects in humans are extremely limited and in vivo animal models have not been generated. Presently, we determined that E-cig vapor contains 7×1011 free radicals per puff. To determine whether E-cig exposure impacts pulmonary responses in mice, we developed an inhalation chamber for E-cig exposure. Mice that were exposed to E-cig vapor contained serum cotinine concentrations that are comparable to human E-cig users. E-cig exposure for 2 weeks produced a significant increase in oxidative stress and moderate macrophage-mediated inflammation. Since, COPD patients are susceptible to bacterial and viral infections, we tested effects of E-cigs on immune response. Mice that were exposed to E-cig vapor showed significantly impaired pulmonary bacterial clearance, compared to air-exposed mice, following an intranasal infection with Streptococcus pneumonia. This defective bacterial clearance was partially due to reduced phagocytosis by alveolar macrophages from E-cig exposed mice. In response to Influenza A virus infection, E-cig exposed mice displayed increased lung viral titers and enhanced virus-induced illness and mortality. In summary, this study reports a murine model of E-cig exposure and demonstrates that E-cig exposure elicits impaired pulmonary anti-microbial defenses. Hence, E-cig exposure as an alternative to cigarette smoking must be rigorously tested in users for their effects on immune response and susceptibility to bacterial and viral infections.


Conclusions

In conclusion, E-cig exposure results in immunomodulatory effects that are similar to those observed after exposure to cigarette smoke. Since bacterial and viral exacerbations are major drivers of COPD disease progression, this study raises a concern that COPD patients who switch from cigarettes to E-cigs may not observe substantial improvement in their disease progression. Furthermore, popularity of E-cigs among teenagers is rapidly rising, which may lead to an emerging threat to public health with regards to recurrent bacterial or viral infections. Despite the common perception that E-cigs are safe, this study clearly demonstrates that E-cig use, even for relatively brief periods, may have significant consequences to respiratory health in an animal model; and hence, E-cigs need to be tested more rigorously, especially in susceptible populations.

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