New results from surveys on vaping and tobacco issues.

This week two surveys were reported with information on nicotine-related behaviours.  One was by the B.C.-based Research Co, the other by the Toronto-based Centre for Addiction and Mental Health. 

This post reports on these results.

CAMH Student Survey

The  Ontario Student Drug Use and Mental Health Survey  (OSDUHS) [1]  has been conducted by CAMH every second year for an impressive 45 years. The Ontarians who were contemplating high school graduation when it was first in the field in 1977 will now be preparing for retirement! 

Questions on tobacco use were included in the first survey in 1977 and questions on e-cigarette use were added in 2015. Unlike many surveys which use past-month use as the main indicator (e.g. 'current smoking'), this survey focuses on use during the past 12 months.

As would be expected the questions on the survey and the manner of collecting data have evolved over the decades. The impact of COVID-19 restrictions triggered significant changes between 2019 and 2021 and resulted in a drastically reduced response rate. This cycle of the survey had the smallest sample size in the survey's history. The authors warn "because of the significant changes to the methodology in 2021, caution is warranted when comparing these estimates with those from previous OSDUHS cycles." 

In 2019 - 14,142 students in grades 7 to 12 from 992 classes in 263 schools in 47 school boards participated in the survey between November of 2018 and June 2019. [2] 

In 2021 -  2,225 students in grades 7 to 12 from 122 schools in 31 school boards completed the survey online (from any location at any time) between March and June 2021.

The survey found  significant reductions in vaping and dridnking, but not for using tobacco, cannabis or opioids

The caution on comparisons should be kept in mind when reviewing the decline in many indicators of concern. The survey found a statistically significant decrease in vaping and alcohol, but the drop in past-year cigarette smoking (from 5% to 4.1%) and cannabis use (from 22.0% to 17.0%) was not statistically significant. 

The survey found that many Ontario high school students think it is easy to get access to nicotine. 

Just over one-half (56%) of students reported it they thought it is "fairly easy" or "very easy" to get e-cigarettes, and just under one-half (45%) had that view for tobacco.

The survey paints an asymptotic approach to ending  youth tobacco smoking, and a return to higher rates of nicotine use.

Each successive wave of the OSDUHS since 1995 has shown a decrease in the percentage of students in grades 7 - 11 who have smoked in the past year, but the rate of decline is slowing.

Even with the reported declines in vaping behaviour, overall nicotine use in 2021 appears to be greater than it was in 2005, when 14.4% of  high school students smoked cigarettes (and alternative product use, like hookah and cigarillos, had not yet emerged as a measurable problem).

Historic data, shown below, is available for grades 7 to 11 for the years 1977 to 2017 and for grades 7 to 12 for the years 1995 to 2021. [3] 

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RESEARCHco

Research Co has conducted four waves of its survey on vaping:  in August 2018, October 2019, September 2020 and April 2022. The poll was not taken in 2021. The company describes the methods as follows: "Results are based on an online study conducted from April 16 to April 18, 2022, among 1,000 adults in Canada. The data has been statistically weighted according to Canadian census figures for age, gender and region. The margin of error, which measures sample variability, is +/- 3.1 percentage points, nineteen times out of twenty."

This survey found vaping on the rise.

. Like the Ontario student survey, it also identifies past-year behaviour instead of the more usual past-month use. The question asked is: "Have you used an electronic cigarette or e-cigarette (vaping) in the past 12 months?"). 

Research Co found an increase in e-cigarette use in 2022 when compared with 2 years earlier -  in all regions and for all ages except those over 55 years of age. 

Support for regulatory controls remains strong, albeit decreasing with time.

This survey has asked about public support for certain restrictions on vaping marketing, with some questions asked in several years and others asked on only one or two waves. In 2021 the survey found:

* Three times as many Canadians support as oppose restrictions on allowing e-cigarette manufacturers to make relative risk claims. In comparison with earlier survey waves, overall support for such restrictions was lower, largely because a greater number of respondents were "not sure" of their position. Excluding "not sure", in 2021, 74% of respondents agreed with restricting references to e-cigarettes as being  healthier. 

* Social acceptance of e-cigarettes has not much changed. Levels of agreement to the statement "I would  not consider dating a person who used electronic cigarettes" remain much as they were in 2019 (at about half of all respondents and 58% of those who stated an opinion).

* Twice as many support banning flavours as oppose. Levels of agreement to "Banning certain flavours of vaping products, such as cannabis and "confectionery”" were lower in 2022 than when assessed in 2020, but overall agreement among those with an opinion is two-thirds (67%).

* Support for advertising restrictions remains high.  Levels of agreement to "Restricting the use of testimonials and "lifestyle" advertising for vaping products" were slightly lower in 2022 than in 2020, when federal measures were just being implemented. In 2022, three-quarters (76.5%) of those with an opinion expressed agreement with this policy.

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Sources:

[1] CAMH. Findings from the 2021 Ontario Student Drug Use and Health Survey. https://www.camh.ca/-/media/files/pdf---osduhs/2021-osduhs-report-pdf.pdf

[2] CAMH. Detailed Findings from the 2019 Ontario Student Drug Use and Health Survey. https://www.camh.ca/-/media/files/pdf---osduhs/drugusereport_2019osduhs-pdf.pdf?la=en&hash=7F149240451E7421C3991121AEAD630F21B13784

[3] CAMH. Detailed Findings from the 2019 Ontario Student Drug Use and Health Survey. 1977-2017
https://www.champlainpathways.ca/wp-content/uploads/2018/01/Detailed_DrugUseReport_2017OSDUHS.pdf

[4] Tables for Poll conducted by Research Co. on Vaping in Canada - April 26, 2022
https://researchco.ca/wp-content/uploads/2022/04/Tables_Vaping_CAN_26Apr2022.pdf

[5] Tables for Poll conducted by Research Co. on Vaping in Canada - October 2020
https://researchco.ca/wp-content/uploads/2020/10/Tables_Smoking_CAN_27Oct2020.pdf

[6] Tables for Poll conducted by Research Co. on Vaping in Canada - November 2019
https://researchco.ca/wp-content/uploads/2019/11/Tables_Vaping_CAN_13Nov2019.pdf

[7] Tables for Poll conducted by Research Co. on Vaping in Canada - November 2018
https://researchco.ca/wp-content/uploads/2018/11/Tables_Vaping_21Nov2018.pdf

The First Four Years: The legislative review of the Tobacco and Vaping Products Act.

May 23, 2022 marks four years since Royal Assent was given to the legislation that turned the Tobacco Act into the Tobacco and Vaping Products Act. On that day, the Minister of Health is obliged by law to submit to both the Senate and the House of Commons a report on the "review of the provisions and operation of this Act."

This is no minor obligation placed on the Minister. It is one of only two statutory obligations for specific actions by the Minister under this act (the other one, regarding public disclosure of information is not in force until the department prepares regulations). There are significant potential consequences for non-compliance: if the Minister fails to conduct a review or fails to submit it to Parliament, h/she is liable to a $25,000 fine (section 3 and section 48). 

This was not a voluntary undertaking of the government. Provisions for this 'legislative review' were not included in the bill as it was originally submitted to Parliament, but were introduced by (opposition) Senator Judith Seidman during the Committee's final clause-by-clause discussion on April 13, 2017. 

As Senator Seidman explained, a mandatory report from government was a way to protect Canadians in the face of many unknown issues surrounding the legalization of vaping products. 

 "Under the circumstances, with so much science unknown, we don't know if vaping is effective for cessation. We hear a lot of dual usage. We don't know if it will renormalize smoking for young people. We don't know what kinds of toxins vapors are really exposed to. We do not even know how to measure a lot of those toxins. We're not really sure about second-hand exposure and how to measure that.

All things considered, everything is so unknown that I really feel it's important to keep tabs on this as parliamentarians. We're opening the door to something. We need to be able to feel secure in ourselves that we're doing the right thing and that we're able to monitor."

Legislative reviews are a new tool for accountability and program improvement.

The requirement for a ministerial report to Parliament on significant issues of public concern is not unique to tobacco. The Cannabis Act, which was studied by Parliament around the same time as the TVPA, also had reporting requirements introduced during clause-by-clause study. That review is required to be presented to Parliament in March 2023. 

Statutory reporting requirements are an emerging tool for federal government accountability and in recent years have been included in many different policy areas. Among these are  requirements to report on progress towards climate change goals (due the end of 2023), on laws aimed at reducing the number of Indigenous children in care ( due after 2025), on the state of palliative care (due 2024), on food safety (after 2024). 

One Canadian province has included a mandatory review of its tobacco laws for over a decade. When Quebec adopted a new Tobacco Act in 1998, it included obligations (which have been continued in section 77) for the Minister to present an implementation report by October 2005 (176 pages), October 2010, and November 2020 . 

The Quebec reports provide legislators with information on the results, as well as an explanation of areas where reforms are needed.  They have served to accelerate legislative change.  

In the conclusion to its most recent report, for example, the Quebec Ministry of Health signals that actions (including legislative change) are needed to address problems that challenge governments across Canada. Among the concerns raised by the ministry are the persistence of disparities in tobacco use, the incentives that manufacturers give to retailers to promote sales, the growing similarities between the vaping and tobacco markets, and others. It recommends that measures be expanded to address price and accessibility, to enhance the power of enforcement officials, more controls on vaping products, and others.

In launching a consultation on its legislative review, Health Canada has tightened the focus of its review. 

Last month, Health Canada released a discussion paper and opened a 5-week consultation on the legislative review. The consultation period ends at midnight April 27, 2022 -- less than a month before the statutory deadline for the department to present its report to Parliament. 

Through the discussion paper the department confirmed that it is intending to provide Parliament with a partial review of the "provisions and operations of the act", and will focus only on 5 topic areas. For each of these, public views are sought with reference to 1) the sufficiency of current measures, 2) the availability of additional measures and 3) the state of evidence to support additional action. These topics are: 

• Protecting young persons and non-users of tobacco products from inducements to use vaping products
• Protect the health of young persons and non-users of tobacco products from exposure to and dependence on nicotine that could result from the use of vaping products
• Protecting the health of young persons by restricting access to vaping products
• Preventing the public from being deceived or misled with respect to the health hazards of using vaping products
• Enhancing public awareness of health hazards

Apparently excluded from this review will be a review or report on "provisions and operation" of legislative measures addressing tobacco use, adult vaping, enforcement, industry reporting, product regulation, etc. 

The public consultation has triggered yet another skirmish with industry front-groups

The public consultation is not a required step in the legislative review, although such consultations are required for other policy developments. 

This is the fourth federal consultation on youth-related vaping issues in the past 14 months (the others were on taxation, ending June 2021; flavour restrictions, ending September 2021, and nicotine concentration, ending March 2021). Other consultations have taken place since the TVPA was introduced -- including a 2019 consultation on Reducing Youth Access and Appeal of Vaping Products, consultations on Vaping Product Labelling in 2019, consultations on the Regulation of Vaping Products in 2017 and targetted consultations on relative risk statements in 2018. At this point it is not obvious that the department will be provided with information that is not already at hand as a result of these previous exercises.

Predictably, Rights4Vapers (the group led by vape store owners and  whose campaign against flavour restrictions was funded by the head of the Vaping Industry Trade Association) is driving submissions to the consultation process. This agency puts great emphasis on the numbers of responses it generates, and uses the results of these mobilization efforts to challenge public health regulations.   

The legislative review of the TVPA will set important precedents.

The TVPA is one of the first modern laws for which a legislative review must be tabled in parliament. How the Minister of Health addresses his responsibilities under the Tobacco and Vaping Products Act will set the standard for the same obligations under the Cannabis Act. How Parliament responds if the Minister files a partial or late report (as is signalled in the discussion document) will similarly set the precedent for other legislative reviews.

An opportunity not to be missed.

The new requirement for a legislative review of Canada's tobacco law has enormous potential to improve the lives of Canadians by accelerating the end of the tobacco epidemic and its new variant, vaping. Providing Parliamentarians and the public with a detailed and honest accounting of the challenges facing government on this important file and a vision for legislative and policy enhancements could be the springboard for the next generation of tobacco laws in Canada.

• Physicians for a Smoke-Free Canada submission to Health Canada's consultation on the legislative review can be found here. 

Finland and China break new ground on regulating the vaping market

Last week two countries advanced major reforms to regulatory controls on the vaping market. On April 13th, Finland finalized changes to its Tobacco Act, a day after China finalized its first regulatory standard for e-cigarettes. This post describes some of the measures these governments are putting in place.

Finland is set to be the third country to require plain packaging of e-cigarettes

Israel pioneered
plain packaging
of e-cigarettes

In just over a year, on May 1, 2023, all brand images and logos will be prohibited on vaping product packaging in Finland, and the health ministry says that more controls will be made by regulation ( "separate provisions on the technical details related to the layout of packages and products will be issued by a decree.")

 Finland is also imposing restrictions on the shape of vaping liquid containers ("The refill container must not differ from other refill containers in shape, color, surface, color of the label or other appearance, and the appearance of the refill container must not promote the sale of the product.")  

Israel was the first country to require plain packaging of vaping products, implementing the measure in early 2020. Denmark passed legislation later that year, which comes into force this October. (The Netherlands has initiated legislation which is not yet finalized).

These are measures that are not currently in development in Canada. Although Health Canada's Forward Regulatory Plan that was released this time last year indicated regulations were being developed to "place certain limits on what promotional elements can appear on vaping product packages", this initiative was dropped in this year's Departmental Plan.

There are other measures that Finland has put in place which are not yet established in Canada. These include:

• Finland has banned flavours other than tobacco since 2016 (the first among a growing number of countries to do so)
• Finland requires retailers to implement "self-monitoring" plans to prevent sales to youth.
• Manufacturers must provide pre-notification 6 months before introducing products to market. 
• Manufacturers of cigarettes and e-cigarettes must pay regulatory fee based on sales volume.  (joining a growing number of countries which are now requiring this measure) 

China pioneers technical standards for e-cigarette manufacturers.

Although the e-cigarette is widely accepted as a Chinese innovation, it is only recently that the Chinese government has brought the e-cigarette market under public authority. Last November e-cigarettes were brought under the control of China's state tobacco monopoly. Soon afterwards consultations were launched to inform the development of the rules that would be imposed on this newly-regulated industry. Draft regulations were circulated at the World Trade Organization in early December, with a second consultation initiated in March. The final version (GB 41700-2022) was adopted on April 8 and comes into force on October 1, 2022. (The formal version is not yet downloadable, but photocopies are circulating on the web).  

China is adopting some product standards that are already in place in many other countries. These include:

• a maximum concentration of 20 mg/ml of nicotine (now in place in 41 countries)
• a ban on flavours other than tobacco flavour (adopted by 5 other countries)
• a ban on additives that a mutagenic, carcinogenic or reproductive toxins (in place in the EU)
• reporting and labelling requirements
• ban on colouring ingredients in vaping liquids

It is also introducing measures that are less common elsewhere, including:

• a ban on e-cigarettes that do not contain nicotine
• a ban on refillable e-cigarettes
• a maximum of 200 mg of nicotine per e-cigarette
• maximum concentration of certain compounds (e.g. heavy metals, arsenic, 2,3-Butanedione)
• a maximum level of nicotine that is released per puff 
• a maximum temperature for aerosolizing liquids (a stunning 350 degrees celsius!)
• a ban on additives that do not appear on the "white list" of 101 chemicals 
• a ban on additives that increase health risks
• a ban on additives that are not technically necessary or that are used in greater quantity than required

To implement some of these requirements (such as maximum nicotine release per puff and maximum temperatures), Chinese authorities have established testing protocols and standards, which are included by reference or as appendices to the new standard.  

Three different countreis with three different "white lists" for additives.

Although many countries have prohibited the use of certain categories of additives, such as colouring agents or reproductive toxins, only a few have moved towards prohibiting all additives other than those which are specifically permitted for us.

Health Canada is a proponent of this approach. In its proposed flavour restrictions, published 10 months ago, it identified 82 exempted flavouring additives (40 for tobacco-flavours, and 42 for menthol-mint flavours) and proposed to prohibit all others. The Netherlands National Institute for Public Health and the Environment (RIVM) also promoted this approach, and proposed a list of 23 flavouring additives that could be approved for use as part of its proposed ban on all non-tobacco flavours. The "White List" in China's regulation (currently accessible in the draft version of the regulation) includes 101 chemicals. There is only a modest overlap in these lists: of the 182 chemicals identified in these lists, only 22 are identified by more than one country. (A combined list can be accessed here).

With its October 1, 2023 implementation date, it appears likely that China will be the first to implement a flavouring ingredient "white list".  The Netherlands has indicating that its flavour restrictions are delayed until at least January 2023 and Health Canada has not made public its implementation timeline.

A first ban on open systems and emission rates

Last  year, in its 8th report to the World Health Organization, the WHO study group on tobacco product regulation (TOBReg) recommended that governments should prohibit e-cigarettes "in which the user can control device features and liquid ingredients (that is, open systems)" and those "with a higher abuse liability than conventional cigarettes, for example by restricting the emission rate or flux of nicotine." China appears to be the first country to put such restrictions into effect. 

How the new federal tax on vaping products will affect prices (and affordability)

Three hundred and fifty-four days ago, a budget was presented to the Canadian parliament that proposed  tax on vaping products to be applied in 2022, [1] and invited  "input from industry and stakeholders on these proposals to help ensure the effective imposition and collection of excise duties on vaping products." 

Yesterday the details on this tax were made clear in the 2022 federal budget [2] The budget was accompanied by a ways and means motion with the necessary changes to the Excise Act, effective October 1, 2022. [3]

This post looks at the evolution of this tax proposal and at the impact it will have on some vaping liquid prices. 

Finance Canada has adjusted the tax to increase the rate for larger containers.

In 2021 the federal proposal read as follows: "The proposed framework would impose a single flat rate duty on every 10 millilitres (ml) of vaping liquid or fraction thereof, within an immediate container (i.e., the container holding the liquid itself). This rate could be in the order of $1.00 per 10 ml or fraction thereof, and the excise duty would be calculated and imposed based on the volume of the smallest immediate container holding the liquid."

In 2022, the proposed tax read as follows: "Budget 2022 proposes to implement the previously announced excise duty on vaping products, effective as of October 1, 2022. The proposed federal excise duty rate would be $1.00 per 2 ml, or fraction thereof, for containers with less than 10 ml of vaping liquid. For containers with more than 10 ml, the applicable federal rate would be $5.00 for the first 10 mL, and $1.00 for every additional 10 ml, or fraction thereof."

The difference can be illustrated examining three product categories:

• e-liquid pods for devices like JUUL,  VUSE or STLTH, 
• disposable devices like Allo, 
• e-liquid bottles designed to be used in refillable containers or tanks. 

For all products, the tax is applied on the basis of the volume of liquid:  the cost of the unit, the strength or type of nicotine is not a factor. Pods (which are often sold in packages of 2 or 4 units) will bear a tax of $1 per pod (unchanged since 2021). Mid-volume disposables will bear a tax of $1 per 2 ml (higher than last year). Containers with more than 10 ml will be taxed at a considerably higher rate than proposed last year (because of a minimum $5 per 10 ml).

Provincial governments are invited to participate and share 

The federal government is continuing to extend an offer to provinces to participate in a joint vaping tax program in which the tax revenues would be split. Importantly, this is identifying as something to be managed to achieve public health goals  ("The overall tax burden on vaping products will be regularly reviewed to ensure that important public health objectives are being met."). This cooperative approach is currently in place for cannabis, as seen in the Quebec-Canadian agreement here, but has not been negotiated for tobacco.

The new tax will recover an estimated $10 to $50 per month from Canadian vapers.

There is wide variability among devices and users, which makes it difficult to compare the price of a “unit dose” of nicotine from vaping with those from tobacco. Nonetheless, studies of vapers have found typical consumption of 22 ml to 63 ml per week (3 ml to 10 ml per day),[4] with daily JUUL users consuming 10 pods per month.[5] A JUUL pod has been found to deliver to the human body the equivalent amount of nicotine as a package of cigarettes.[6] Health Canada’s surveys report that spending on devices and liquids averages $53 for devices-components each month and $52 for liquids,[7] giving an average daily cost of about $3.25.

On the basis of those reports, the proposed tax will trigger a monthly increase in cost of:

• $10 for the typical JUUL user [5]; $30 for someone who consumers 1 pod per day 
• $13 (for 3 ml/day user) to $50 (for 10 ml/day user purchasing 60 ml bottles) [4]

Finance Canada predicts that the vaping tax will generate $145 million in revenues in a full calendar year, or roughly $100 per year for each of Canada's 1.4 million vapers. In addition to this specific (volume-based) tax, the government will also receive revenues from the ad valorem (percentage) goods and services tax.

Even in provinces which currently tax vaping products, these will remain much cheaper than cigarettes

Currently 4 provinces impose taxes on vaping liquids.[8] Three impose ad valorem taxes:  British Columbia (20% in lieu of PST), Newfoundland (20% in addition to HST) and Saskatchewan (20% in lieu of PST). One imposes a specific tax (Nova Scotia, $0.50/ml).  

The imposition of an additional federal tax will NOT make e-liquids more expensive than the equivalent volume of cigarettes. 

This can be illustrated for two product categories - pre-filled cartridges (eg 1.9 ml VUSE cartridge, $7) and bottled e-liquids (eg 30 ml DVINE, $15). The comparison for a  VUSE cartridge is made with the price of a package of 20 cigarettes, based on a combined whole-sale retail cost of $3.80 and taxes currently in place.[9] The cost of a bottle of 30 ml liquid is compared with 3 packages of 20 cigarettes. 

Even in Nova Scotia and Newfoundland, which have the highest taxes on vaping products, the price of a package of cigarettes is more expensive than a pre-filled cartridge. Because Nova Scotia also implements a specific tax, the pattern is somewhat different for a bottle of 30 ml. Quebec has dramatically lower tobacco taxes than other provinces, which results in it having the smallest gap between capsules and tobacco prices.

Even after these taxes are imposed, e-liquids will remain affordable for too many young Canadians

Minimum wages ranging from  $11.81 to $16 across Canada. Using the estimates of post-tax prices for vaping pods and vaping liquids, it will take a minimum wage earner between half an hour and an hour to earn enough to purchase a taxed e-liquid pod, and between 3 and 6 minutes to purchase a ml of e-liquid.

References

[1] Government of Canada. Federal Budget. April 2021. 

[2] Government of Canada. Federal Budget. April 2022. 

[3] Notice of Ways and Means Motion to amend the Excise Act, 2001 and Other Related Texts

[4] Smets, J When Less is More: Vaping Low-Nicotine vs. High-Nicotine E-Liquid is Compensated by Increased Wattage and Higher Liquid Consumption. International Journal of Environmental Research and Public Health, 2019.

[5] Leavens, E et al. JUUL electronic cigarette use patterns, other tobacco product use, and reasons for use among ever users: Results from a convenience sample. Addictive Behaviours, 2019.

[6] Prochaska, J. et al. Nicotine delivery and cigarette equivalents from vaping a JUUL pod. Tobacco Control. 2021.

[7] Environics. Vapers Online Survey to Measure Attitudes and Behaviours Regarding Vaping Over Time. POR 098-19

[8] Physicians for a Smoke-Free Canada. At-a-glance: Provincial restrictions on vaping products. January 2022

[9] Physicians for a Smoke-Free Canada Taxes on cigarettes in Canadian jurisdictions. April 2022

A report commissioned by the Australian government reviews the evidence on the health outcomes of e-cigarettes.

 

This week the Australian National Centre for Epiemiology and Population Health released an updated systematic review of the health impacts from  the use of e-cigarettes. The report (Electronic cigarettes and health outcomes: systematic review of global evidence) was commissioned by the Australian Department of Health.

This post presents the key findings from this review.

A "top up" from previous reviews.

In preparing this report, the researchers prepared "an umbrella review of evidence from major national and international independent reviews with a “top-up” systematic review of evidence published since the NASEM review." Their methods followed established protocols and were guided by the  e-cigarette working group of the National Health and Medical Research Council.

As shown in their summary table, shown below, there is still not much evidence on many key issues (grey areas), and many of the studies are not helpful in establishing causation (red areas). This representation is a helpful reminder that  'no evidence about harm' cannot be read as 'evidence of no harm'.

The key findings of this Australian report and their conclusion, as presented in their executive summary, are pasted below. 

Dependence and abuse liability

• Among non-smokers, there is substantial evidence that e-cigarette use results in dependence on e-cigarettes.
• Among smokers, there is limited evidence that e-cigarette use results in dependence on e-cigarettes. There is limited evidence that e-cigarettes have lower abuse liability than combustible cigarettes and limited evidence that ecigarettes have a higher abuse liability than nicotine replacement therapy products among smokers.
•  Among smokers, there is insufficient evidence whether abuse liability risk is influenced by flavour and nicotine concentration variations. 

Cardiovascular health outcomes

• There is no available evidence on the effect of e-cigarette use on the risk of clinical cardiovascular disease outcomes, such as myocardial infarction, stroke or cardiovascular mortality.
• There is no available evidence on e-cigarette use and the risk of subclinical atherosclerosis-related outcomes such as carotid intima-media thickness and coronary artery calcification.
• Among non-smokers, there is insufficient evidence that e-cigarette use is related to other cardiovascular outcomes, including: increased blood pressure, heart rate, autonomic control and arterial stiffness; reduced endothelial function, hand microcirculation and cardiac function/geometry; and cardiac device interference.
• Among smokers, there is moderate evidence that use of e-cigarettes increases heart rate, systolic blood pressure, diastolic blood pressure and arterial stiffness acutely after use; and limited evidence that use increases endothelial dysfunction, and that long term use after switching from combustible cigarette smoking decreases blood pressure.

Cancer

• There is no available evidence on the relationship of e-cigarette use to invasive cancer risk.
• There is no available evidence on the relationship of e-cigarette use to the risk of precancer/subclinical cancer outcomes. 

Respiratory health outcomes

• There is conclusive evidence that the use of e-cigarettes can cause respiratory disease (EVALI) among smokers and non-smokers. Current evidence from the largest study to date is that this lung injury is chiefly related to e-cigarettes delivering THC, with half of cases related to THC in conjunction with vitamin E acetate, and 14% in patients reporting the use of nicotine-delivering products only, indicating that the latter products can cause EVALI.
• There is insufficient evidence on the relationship of e-cigarette use to other clinical respiratory outcomes, including asthma, bronchitis and COPD in smokers and no available evidence in non-smokers.
• There is insufficient evidence for a reduction in respiratory exacerbations and disease progression among adult healthy, asthmatic and COPD smokers who switch to exclusive or dual-use of e-cigarettes.
• There is limited evidence in non-smokers and insufficient evidence in smokers that e-cigarettes have acute (up to two hours post-exposure) effects on spirometry parameters.
• There is limited evidence that e-cigarette use increases respiratory resistance and impedance in healthy and asthmatic smokers up to 30 minutes post-exposure.
• There is insufficient evidence on the effect of e-cigarettes on exhaled breath outcomes among smokers and non-smokers (healthy and asthmatic).
• There is insufficient evidence on the relationship of e-cigarette use to other respiratory measures (sinonasal symptoms, airway hyperresponsiveness) in smokers and no available evidence in non-smokers.

Oral health

• There is no available evidence on the relationship of e-cigarette use to clinical or intermediate/subclinical oral health outcomes in exclusive e-cigarette users, independent of the effect of smoking.
• There is insufficient evidence of reduced plaque, gingival and papillary bleeding in smokers switching to e-cigarette use
• In populations including exclusive e-cigarette users, dual users, and non-smokers (never and former smokers), there is insufficient evidence as to the relationship of e-cigarette use to increased gum disease, bone loss around the teeth and any periodontal disease. 

Developmental and reproductive effects

• There is no available evidence as to how use of e-cigarettes affects the development of children or adolescents.
• There is insufficient evidence as to how e-cigarette use relates to pregnancy and foetal outcomes, such as low birthweight, preterm birth, Apgar score and small-forgestational-age birth, among exclusive e-cigarette users and dual users.
• There is no available evidence as to how use of e-cigarettes affects other reproductive outcomes.

Burns and injuries

• There is conclusive evidence that e-cigarettes can cause burns and injuries, which can be severe and can result in death.

Poisoning

• There is conclusive evidence that intentional or accidental exposure to nicotine eliquids can lead to poisoning, which can be severe and can result in death. A significant number of accidental poisonings occur in children under the age of six.
• There is conclusive evidence that use of e-cigarettes can result in nicotine toxicity. 

Mental health effects

• There is no available evidence as to how e-cigarette use affects clinical mental health outcomes. 
• There is insufficient evidence as to the relationship of e-cigarette use to depressive symptoms and no available evidence regarding their effects on alternative subclinical mental health measures.

 Environmental hazards with health implications

• There is conclusive evidence that e-cigarette use results in increased airborne particulate matter in indoor environments.
• There is limited evidence that e-cigarette use results in increased concentrations of airborne nicotine and of nicotine and cotinine on indoor surfaces.
• There is insufficient evidence that e-cigarette use results in increased air levels of carbon dioxide, carbon monoxide, propylene glycol, volatile organic compounds and carbonyls.
• There is substantial evidence that e-cigarettes can cause fires and environmental waste and insufficient evidence as to the extent that these present a hazard to human health. 

Neurological outcomes 

• There is conclusive evidence that the use of e-cigarettes can lead to seizures.
• There is limited evidence that injuries due to e-cigarette explosions can lead to nerve damage.
• There is no available evidence as to how the use of e-cigarettes affects the risk of other clinical neurological outcomes.

Sleep outcomes

• There is no available evidence as to the effect of e-cigarettes on clinical sleep outcomes.

Less serious adverse events

• There is moderate evidence that less serious adverse events – such as throat irritation, cough, dizziness, headache and nausea – occur with use of nicotine ecigarettes. 

Optical health

• There is no available evidence on the relation of e-cigarette use to clinical optical outcomes.
• There is insufficient evidence on the relation of e-cigarette use to corneal epithelial thickness or pre-corneal tear film stability and no evidence on other optical outcomes.

Wound healing

• There is no available evidence as to the effect of e-cigarette use on clinical or subclinical wound healing outcomes.

Olfactory outcomes

• There is no available evidence on the effect of e-cigarette use on clinical olfactory outcomes.
• There is insufficient evidence on the relationship between use of e-cigarettes and subclinical olfactory measures.

Endocrine outcomes

• There is no available evidence on the relationship of e-cigarette use to clinical endocrine outcomes and insufficient evidence regarding subclinical endocrine outcomes of prediabetes and insulin resistance.

Allergic diseases

• There is limited evidence that e-cigarette use can lead to contact dermatitis and no available evidence on other clinical allergy outcomes. 

Haematological outcomes

• There is no available evidence on the relationship of e-cigarette use to haematological outcomes.

 Smoking uptake

• There is strong evidence that never smokers who use e-cigarettes are on average around three times as likely than those who do not use e-cigarettes to initiate cigarette smoking.
• There is strong evidence that non-smokers who use e-cigarettes are also around three times as likely as those who do not use e-cigarettes to become current cigarette smokers.
• There is limited evidence that former smokers who use e-cigarettes are more likely to relapse and resume current smoking than former smokers who have not used e-cigarettes.

Smoking and nicotine cessation

• There is limited evidence that, in the clinical context, freebase nicotine e-cigarettes may be more efficacious for smoking cessation than existing NRT, and that nicotine e-cigarettes may be more efficacious than no intervention or usual care.
• Trials demonstrating efficacy were limited to products with freebase nicotine concentrations ≤20mg/mL. There is no evidence that nicotine salt products are efficacious for smoking cessation.
• There is insufficient evidence that freebase nicotine e-cigarettes are efficacious for smoking cessation, compared to non-nicotine e-cigarettes or that non-nicotine e-cigarettes are efficacious for smoking cessation compared to counselling or approved NRT.
• There is insufficient evidence that freebase nicotine e-cigarettes are efficacious outside the clinical setting.
• No evidence on nicotine salt products was located and their efficacy for smoking cessation is unknown.
• There is limited evidence that use of nicotine e-cigarettes for smoking cessation results in greater ongoing exposure to nicotine than approved NRT, through ongoing exclusive e-cigarette use or dual use if smoking continues.

Conclusions

There is strong or conclusive evidence that nicotine e-cigarettes can be harmful to health and uncertainty regarding their impacts on a range of important health and disease outcomes. Based on the current worldwide evidence, use of nicotine e-cigarettes increases the risk of a range of adverse health outcomes, including: poisoning; toxicity from inhalation (such as seizures); addiction; trauma and burns; lung injury; and smoking uptake, particularly in youth. Their effects on most other clinical outcomes are unknown, including those related to cardiovascular disease, cancer, respiratory conditions other than lung injury, mental health, development in children and adolescents, reproduction, sleep, wound healing, neurological conditions other than seizures, and endocrine, olfactory, optical, allergic and haematological conditions. Nicotine e-cigarettes are highly addictive, underpinning increasing and widespread use among children and adolescents in many settings. Less direct evidence indicates adverse effects of e-cigarettes on cardiovascular health markers, including blood pressure and heart rate, lung function and adolescent brain development and function. Environmental impacts include indoor air pollution, waste and fires. The commonest pattern of e-cigarette use is dual e-cigarette use and tobacco smoking, which is generally considered an adverse outcome. There is limited evidence of efficacy of freebase nicotine e-cigarettes as an aid to smoking cessation in the clinical setting. E-cigarettes may be beneficial in some smokers who use them to quit smoking completely and promptly, with uncertainty about their overall balance of risks and benefits for cessation. Current evidence supports national and international efforts to avoid ecigarette use in the general population, particularly in non-smokers and youth. Better evidence is needed on health impacts, the overall balance of quality, safety and efficacy of e-cigarettes as potential aids for smoking cessation, and effective regulatory options.