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E-cigarettes, smoking and

health

A Literature Review Update

Stephanie Byrne,

Emily Brindal, Gemma Williams, Kim Anastasiou, Anne Tonkin, Samantha

Battams and Malcolm Riley

22 June 2018

Prepared for: Department of Industry, Innovation and Science

HEALTH & BIOSECURITY

CSIRO

Citation

Byrne S, Brindal E, Williams G, Anastasiou KM, Tonkin A, Battams S and Riley MD (2018), E-cigarettes, smoking and health. A Literature Review Update. CSIRO, Australia.

Copyright

© Commonwealth Scientific and Industrial Research Organisation 2018. To the extent permitted by law, all rights are reserved and no part of this publication covered by copyright may be reproduced or copied in any form or by any means except with the written permission of CSIRO.

Important disclaimer

CSIRO advises that the information contained in this publication comprises general statements based on scientific research. The reader is advised and needs to be aware that such information may be incomplete or unable to be used in any specific situation. No reliance or actions must therefore be made on that information without seeking prior expert professional, scientific and technical advice. To the extent permitted by law, CSIRO (including its employees and consultants) excludes all liability to any person for any consequences, including but not limited to all losses, damages, costs, expenses and any other compensation, arising directly or indirectly from using this publication (in part or in whole) and any information or material contained in it. CSIRO is committed to providing web accessible content wherever possible. If you are having difficulty with accessing this document please contact csiroenquiries@csiro.au.

Byrne S, Brindal E, Williams G, Anastasiou KM, Tonkin A, Battams S and Riley MD (2018), E-cigarettes, smoking and health. A Literature Review

Update. CSIRO, Australia. | iii

Foreword

This report was funded by the Australian Commonwealth Department of Industry, Innovation and

Science. It was produced

by a team led by the Commonwealth Scientific and Industrial Research Organisation (CSIRO), and included external scientist consultants. The terms of reference for the task were specifically to: Review all available evidence applicable to the impacts of the use of e-cigarettes, personal vaporisers and nicotine on individual and population health. This is addressed in Part 1 of the report. Review all available evidence applicable to the use of e-cigarettes, personal vaporisers and nicotine on rates of smoking. This is addressed in

Part 2 of the report.

Assess the impacts on health of allowing the use of e-cigarettes and personal vaporisers in countries where they have been permitted. This is addressed in Part 3 of the report. Review the impact of e-cigarettes and personal vaporisers on individual health as an al ternative to smoking. This is addressed in Part 4 of the report. Identify any potential for e-cigarettes to reduce rates of smoking in Australia. This is addressed in

Part 5 of the report.

Compare rates of tobacco smoking in countries where e-cigarettes and similar smoking alternatives are available with rates in countries where such products are not available.

This is addressed in

Part 6 of the report.

In the course of the review, scientific literature relating to the use of e-cigarettes (for example use

within population groups, and motivation for use) was reviewed and this contextual information is included in Part 7 of the report. Extensive tables describing the studies reviewed are positioned at the end of each part of this report. CSIRO

Executive Summary

Part 1: Review all available evidence applicable to the impacts of the use of e-cigarettes, personal vaporisers and nicotine on individual and population health.

Health risks of e-cigarettes - human studies

Because of the lack of long-term studies, there continues to be no evidence that e-cigarette use is associated with clinical cardiovascular disease. Carcinogenic compounds and carcinogenic metabolites arising from e-cigarette use are demonstrated to be present in e-cigarette users, and arise through e-cigarette use in animal studies. However the risk of the development of cancer or other health effects from the levels arising from e-cigarettes use is unclear. The use of e-cigarettes may impair lung function however the independent effect of e-cigarettes is unclear because of potential confounding by conventional cigarette smoking. Case studies have suggested that e-cigarette use interferes with, or delays, wound healing. While these reports are suggestive, evidence from case studies should be verified using appropriately designed studies.

Health risks of e-cigarettes - injuries

It is clear that e-cigarettes can explode and cause serious projectile and thermal injuries. Intentional or accidental ingestion of e-fluids can cause serious injury or death.

Health risks of e-cigarettes - animal studies

E-cigarette vapour can cause significant damage to frog embryos, rats and mice. Adverse outcomes include increased release of pro-inflammatory cytokines, emphysematous lung destruction, renal, hepatic and heart fibrosis among rodents exposed to e-cigarettes vapours or IV e-cigarette liquids compared with those exposed to room air. E-cigarette vapour exposure also had significant effects on the offspring of exposed pregnant mice and frog embryos including increased release of pro-inflammatory cytokines, sleep disturbances and craniofacial defects. The implications of animal studies for human health is speculative.

Health risks of e-cigarettes - in vitro studies

In vitro studies on e-cigarette vapour, liquid and extracts indicate the potential for human health risks including cell death, increased oxidative stress, reduced lung function, changes in inflammatory response, altered gene expression and increase of cellular ri sk factors for cardiovascular disease.

Byrne S, Brindal E, Williams G, Anastasiou KM, Tonkin A, Battams S and Riley MD (2018), E-cigarettes, smoking and health. A Literature Review

Update. CSIRO, Australia. | v

There is a lack of clarity about the direct implications of the in vitro findings for human health. Conclusion: the evidence available suggests that regular use of e-cigarettes is likely to have adverse health consequences. There is a lack of clarity about the magnitude of adverse health effects, and the quantity of e-cigarette use required to trigger adverse health effects. Part 2: Review all available evidence applicable to the use of e-cigarettes, personal vaporisers and nicotine on rates of smoking. Gateway Effect - use of e-cigarettes leading to initiation of conventional cigarette smoking The evidence for a strong positive relationship between use of e-cigarettes and later cigarette smoking amongst youth continues to accumulate. The evidence is consistent in observational studies and across different countries. A plausible biological pathway from use of e-cigarettes to conventional cigarette smoking operates through developing addiction to nicotine.

The use of e-cigarettes with higher

concentrations of nicotine is observed to have a stronger association to later conventional cigarette use. A positive association is observed between the initiation of conventional smoking following use of non-nicotine e-cigarettes (however it is much weaker than the association with nicotine containing e-cigarettes). This highlights the possibility for other causal mechanisms besides the development of nicotine addiction linking e-cigarette use to the initiation of cigarette smoking. There is insufficient evidence to draw any conclusion about whether the use of e-cigarettes results in the use of other substances such as marijuana. Almost all investigations of 'gateway effect' focus on young people.

Smoking cessation

Observational studies indicate that e-cigarettes are preferred as a smoking cessation method in some, but not all, populations. There is good evidence from clinical trials that e-cigarettes may reduce withdrawal symptoms in smokers after a short period of cigarette abstinence.

The results of the trials

have limited application because most trials are short term. There is currently no evidence that quit rates for smoking have decreased as a result of e-cigarette use. Long-term success with cessation was not measured in trials. Results from randomised controlled trials indicate that nicotine-containing e-cigarettes are more effective at reducing the amount of conventional smoking than nicotine-free e-cigarettes or no e-cigarettes. There is limited evidence comparing the effectiveness of e-cigarettes for smoking cessation with other smoking cessation methods. CSIRO Conclusion: In many countries where appropriate evidence is availabl e, it appears that e-cigarette use occurs with cigarette use. However the evidence is consistent in suggesting that use of e-cigarettes by non-smoking youth predicts future smoking. While many smokers and former smokers state a preference for e-cigarettes as a smoking cessation method, the effectiveness of this method compared with other smoking cessation methods is not known. Part 3: Assess the impacts on health of allowing the use of e-cigarettes and personal vaporisers in countries where they have been permitted. Country-level difference in impact on health of e-cigarettes is difficult to demonstrate because: o the use of e-cigarettes is low in all countries, o diseases and health conditions often have a long latent period, while the history of use of e-cigarettes is relatively short o diseases and health conditions are often due to multiple factors combined, and it is hard to disentangle the independent effects of these determinants which may be changing at different rates in different parts of the population. The United States (US) accounted for 56% of the global e-cigarette market in 2015. US studies show that t here is no apparent change in the trend of age-adjusted Chronic Obstructive Pulmonary Disease deaths in the US over the period of 2000-2014, and no change in the trend for the prevalence of age-adjusted hypertension from 1999-2016. There is no break in the trend towards more former smokers, measured by the Quit ratio (the ratio of former smokers to ever smokers) in the US which is slowly increasi ng over

2005-2016.

Population modelling of the health impacts of e-cigarettes is greatly hampered by lack of knowledge of the health effects of e-cigarettes. Models which have been developed give a positive or a negative overall health impact of e-cigarettes on a population depending on the parameters used. The health impact for a population will vary according to the prevalence of conventional smokers in the population. Conclusion: based on the current evidence it is not possible to determine whether e- cigarettes have a positive or a negative effect on health in countries where they are permitted.

Byrne S, Brindal E, Williams G, Anastasiou KM, Tonkin A, Battams S and Riley MD (2018), E-cigarettes, smoking and health. A Literature Review

Update. CSIRO, Australia. | vii

Part 4: Review the impact of e

-cigarettes and personal vaporisers on individual health as an alternative to smoking. There is some evidence that blood pressure of smokers is lowered over a month when e-cigarettes are used instead of conventional cigarettes. In the short-term, there is evidence of small improvements in lung function in smokers who use e-cigarettes. The level of specific carcinogenic compounds and resulting metabolites is lower in humans after e-cigarette use compared to conventional cigarette use. The range of toxic compounds arising from normal use is not the same for e-cigarettes and conventional cigarettes. For e-cigarettes, potentially toxic compounds also arise from the e-fluid which varies in composition, and from the heating elements (which typically contribute metal vapour for example). Nicotine absorption and nicotine dependency for e-cigarettes users appears to depend on how the e-cigarettes are used. This is probably because the way in which the devices are used in terms of puffs and intensity can determine the amounts of nicotine inhaled, in addition to the nicotine concentration of the e-fluid. Conclusion: when e-cigarettes are used by smokers instead of conventional cigarettes there is evidence for improvement in individual health. However, use of e-cigarettes may also introduce independent health risks, and 'dual use' (using both e-cigarettes and conventional cigarettes) is popular. Part 5: Identify any potential for e-cigarettes to reduce rates of smoking in

Australia.

The prevalence of regular smoking in Australia has been declining since at least 1945, from very high levels, particularly in men. The most recent national data indicates that 14% of Australian adults are current regular smokers. E-cigarette use in Australia has generally increased from 2013 and 2016, however the prevalence of current regular use is below 8% amongst all adolescent and adult age groups. People who have used e-cigarettes on one or more occasions over their lifetime are termed 'ever users'. Among 'ever users' of e-cigarettes, the largest percentage is people who have used e-cigarettes only once or twice. This group is larger than current users and ex-users for all age groups, but is particularly large in adolescents and younger adults. E-cigarette use beyond once or twice is very uncommon amongst people who are not current or ex cigarette smokers. CSIRO The most common reason for using e-cigarettes among adolescents and younger adults is 'out of curiosity', while among older adults the reasons for use are more likely to be related to tobacco smoking (to cease smoking, to reduce the number of cigarettes smoked, or to avoid recommencing smoking).

Conclusion: It is

a critical research question to determine the effectiveness of e-cigarettes compared to other smoking cessation methods among Australian smokers generally, and alsoquotesdbs_dbs10.pdfusesText_16

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