Friday, 22 January 2021

Three Years Later: The NASEM report on E-cigarettes

This week marks three years since the US National Academies of Sciences, Engineering and Medicine (NASEM) released a report commissioned by the U.S. FDA on the "Public Health Consequences of E-cigarettes." Since then, this report has often been cited as a definitive source for questions about the safety of e-cigarettes, and is a primary source for Health Canada's encouragement to smokers to switch to e-cigarettes. 

Thirty-six months later, however, the conclusions in this report are increasingly stale-dated. The panel of scientists who wrote the report looked only at evidence available before August 2017 - and for some key issues (like heart and lung diseases) there were virtually no published studies available for them to consider.

Since then there has been a marked growth in scientific evidence about these products. Of the approximately 7,000 studies on e-cigarettes listed in the U.S. National Library of Medicine, more than half (57%) were published after 2017. From today's vantage point, the NASEM report tells less than half the story. 

In general, these more recent studies have provided evidence on health hazards where there previously had been none and have strengthened those links that had already been identified. Newer studies have also dashed the hopes inferred from the NASEM report that these products could be effective for population-wide smoking cessation.

1. The NASEM report, even in 2018, did not provide all we needed to know to regulate e-cigarettes

The NASEM report was a weighty tome of nearly 800 pages. Perhaps because of its weight, many mistakenly considered it encyclopaedic, containing all the information one would need to know about e-cigarettes. 

But there were key aspects of the e-cigarette issue which were not addressed by this report. Notably it did not consider nor predict that there would be an explosion of vaping among young people in Canada and the United States. ( By 2019, there were 700,000 vapers in Canada under the age of 25, one-half of all vapers). 

The report did not analyze the behaviour of tobacco and vaping industries. It did not predict that the tobacco industry would come to dominate the vaping market, or consider the evidence that would predict the impact of their doing so. It did not analyze the impact of the industry developing  nicotine salt products, or anticipate that these higher-nicotine versions would soon domiate the market and accelerate the addiction of (mostly young) people to nicotine. 

It did not predict or analyze the imapct of e-cigarettes becoming a consumer product used for recreational drug purposes as much as to avoid smoking cigarettes, or that the marketing of these as consumer products would result in their not proving effective at helping people quit smoking.  It dismissed the likelihood that the e-cigarette could increase harm, and did not forecast that the prevalence of nicotine use  among young people would increase  dramatically as a result. 

2. The NASEM report has been misinterpreted as endorsing e-cigarettes

Perhaps spurred on by the hope that e-cigarettes would be an effective mass smoking cessation aid, some seized on just a few of the NASEM conclusions that seemed to suggest some benefit of
e-cigarettes to guide policy, but ignored the others. A careful reading of the whole report and the analysis behind its 47 conclusions would have led to a more cautious approach. 

3. Five adverse health outcomes where NASEM concluded "no available evidence" in 2017: an update

The NASEM panel qualified its conclusions by level of evidence: conclusive, substantial, moderate, limited, insufficient and no available evidence. The five areas where they found "no available evidence" illustrate the current limitations of using the NASEM report for policy development:

Cardiovascular disease
"There is no available evidence whether or not e-cigarette use is associated with clinical cardiovascular outcomes (coronary heart disease, stroke, and peripheral artery disease) and subclinical atherosclerosis (carotid intima-media thickness and coronary artery calcification)." (NASEM, Conclusion 9-1).  

The evidence void identified in NASEM has been addressed by several groups of researchers. These include a comprehensive review of preclinical and clinical studies, identifying pathways by which "chronic e-cigarette use could increase the development of CVD.", as well as review of experimental studies of effects on animals, human tissue and humans ("Most studies suggest potential for cardiovascular harm from electronic cigarette use."). Clinical tests have found the vascular effects of e-cigarettes to be the same as tobacco. A cross-sectional study of 450,000 people, representative of the USA population found that  "dual use of e-cigarettes + combustible cigarettes was associated with 36% higher odds of cardiovascular disease."

While longitudinal studies are still lacking, current evidence that e-cigarette use increases the risk of heart disease would now likely be considered moderate or substantial.

"There is no available evidence whether or not e-cigarette use is associated with intermediate cancer endpoints in humans. This holds true for e-cigarette use compared with use of combustible tobacco cigarettes and e-cigarette use compared with no use of tobacco products." (NASEM, Conclusion 10-1)

Many people believe that the fact that e-cigarettes have fewer carcinogens than cigarettes makes them safer. While fewer cancers may result from vaping than from smoking cigarettes, the risk of cancer is not necessarily reduced in lockstep with the reduction in numbers and amounts of carcinogens. There is no safe level of exposure to carcinogens.

Since 2017, researchers have found that e-cigarette aerosol contains carcinogens that damage DNA, that e-cigarettes deregulate genes associated with cancer, and that e-cigarette vapour induces cancer in mice. Because of the long lag time between exposure and later cancer, some cancer researchers are calling for tighter regulation

Respiratory diseases
"There is no available evidence whether or not e-cigarettes cause respiratory diseases in humans." (NASEM, Conclusion 11-1). 

As we recently reported there have been many recent studies of e-cigarettes and respiratory diseases.  They include studies with strong methodologies like meta-analysis and examination of longitudinal data.  

Far from no evidence, the newer evidence linking vaping to respiratory disease would likely now be considered substantial or conclusive.

Pregnancy Outcomes
"There is no available evidence whether or not e-cigarettes affect pregnancy outcomes." (NASEM, Conclusion 11-1).

Subsequent to the NASEM report, other reviews of the evidence have concluded that nicotine consumed from e-cigarettes was similar to that consumed from combustible cigarettes and that "the ideal situation for both mother and fetus would involve complete cessation of all nicotine-containing products."  After following large populations of U.S. women during pregnancy, researchers have recently concluded that e-cigarette use  "is not a safer alternative to [conventional cigarette] smoking during pregnancy."

An updated version of NASEM would likely conclude there is limited evidence that e-cigarettes negatively affect pregnancy outcomes. 

Dual Use
"There is no available evidence whether or not long-term e-cigarette use among smokers (dual use) changes morbidity or mortality compared with those who only smoke combustible tobacco cigarettes." (NASEM, Conclusion 18-3).

Dual use of e-cigarettes and combustible cigarettes is very prevalent - four in 10 Canadian vapers also smokes cigarettes (only 25% are former smokers). Research subsequent to NASEM by researchers using data from heart studies and general population studies have concluded that using both e-cigarettes and conventional cigarettes is likely more harmful than only smoking.

4. More recent scientific evaluations found more evidence to support precautionary approach. 

The NASEM report was commissioned by the American Food and Drug Administration in 2016.  Last year health reviews were published that had subsequently been commissioned by other health authorities, including the World Health Organization, the European Union, and governments in Ireland, the Netherlands, Australia and Spain.

In February 2020, the World Health Organization concluded "ENDS [electronic nicotine delivery systems] on their own are associated with increased risk of cardiovascular diseases and lung disorders and adverse effects on the development of the fetus during pregnancy. ENDS are undoubtedly harmful, should be strictly regulated, and, most importantly, must be kept away from children."

In September 2020, based on evidence available up to April 2019, the European Union's Scientific Committee on Health, Environmental and Emerging Risks (SCHEER) found evidence linking e-cigarette use to respiratory disease, heart disease, to adolescent smoking and to addiction.

In June 2020 the Irish Health Research Board reported that "e-cigarettes were not more effective for smoking cessation than approved nicotine replacement therapies (NRTs), which questions the need for e-cigarettes as a smoking cessation intervention. In the second review, we found that e-cigarettes were associated with initiation of conventional cigarette smoking among adolescents, which identifies a potentially serious harm."

In April 2020, the Trimbos Institute reported to the Dutch government that "Newer studies provide more and more indications that the use of an e-cigarette could lead to damage to the respiratory tract and the cardiovascular system."

Reviews on the impact of e-cigarettes on tobacco use conducted for the government of Australia by that country's National Centre for Epidemiology and Public Health concluded that e-cigarettes did not help people quit smoking, but did increase the probability of a young person starting to smoke. In its own review, the Australian Ministry of Health felt that current evidence on the direct health harms associated with e-cigarettes justified taking a precautionary approach.  

A 2020 Spanish Health Department report states that the adverse short-term effects on the respiratory system are similar to those of cigarette smoking.

5. Federal advice to Canadians is not keeping up with science

The Canadian government has not yet commissioned an independent review of the evidence assessing the public health impact of e-cigarettes, although it reports that it does in-house reviews. 

Currently, its advice to use cigarettes as cessation products and on the risks of vaping does not include references to research conducted after 2017. Its main messages on health effects do not specify health risks other than those associated with nicotine. 

Health Canada's advice on the health risks of vaping
does not identify risks other than those related to nicotine