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.