Through the Looking-glass: Revisiting Smoking and Health

Abstract

Whether electronic (e)-cigarettes can contribute to tobacco harm reduction has been a point of contention. This discordance, in part, stems from the growing population that uses them. Despite the ideal scenario in which only former smokers will vape e-cigarettes to aid in smoking cessation, there is the reality that many are incompletely switching to e-cigarettes and become dual users of both inhalants. Additionally, people who never previously smoked are also using e-cigarettes. The health effects must be evaluated for all these groups. Glantz et al. conducted a meta-analysis and systematic review of population studies to compare pooled odds ratios (ORs) associated with different disease outcomes (i.e. cardiovascular disease, stroke, metabolic dysfunction, asthma, COPD, and oral disease) in relation to smoking and vaping use patterns. In support of tobacco harm reduction, e-cigarette use was associated with decreased risk for asthma, COPD, and oral disease. However, in support of harm promotion, all inhalant use patterns were significantly associated with increased risk for all disease outcomes compared to never smokers and never vapers, with the exception of stroke. Most notably, dual use of both combustible tobacco and e-cigarettes was significantly associated with higher risk across all disease outcomes relative to combustible cigarettes. Though longitudinal studies are needed to establish causality, by recommending e-cigarettes, there may actually be more harm imposed than good.

Editorial

January 11, 2024 marked the 60^th anniversary of the initial United States Surgeon General Report, “Smoking and Health”, that inexorably linked cigarette smoking and lung cancer ¹. Similar to the old Virginia Slims slogan, “you’ve come a long way, baby”, smoking rates have diminished greatly since the release of that first report². However, smoking still represents the leading cause of preventable deaths³. Numerous countries have enacted policies aimed at decreasing conventional cigarette use such as inclusion of warning labels on tobacco products, limiting advertising, and imparting bans on products. Such measures have contributed to significant reductions in cigarette use. However, as countries continue to grapple with the high burden of disease that results from cigarette smoking, a new quandary has arisen: Can electronic (e)-cigarettes help reduce harm?

E-cigarettes were introduced into consumer markets just under 20 years ago⁴. Since then, some countries have banned these nicotine delivery devices, some have limited them, and others have embraced them. Meanwhile, e-cigarette use (vaping) has grown worldwide⁵. E-cigarette users include prior smokers, never-smokers, and concurrent cigarette and e-cigarette (dual) users. Defining the health effects, and potential harm reduction, for these inhalant users involves answering two questions: 1) How does sole e-cigarette and dual use compare to sole cigarette smoking? and 2) How do disease outcomes compare for cigarette smokers, e-cigarette vapers, and dual users relative to never-users?

To address these questions, Drs. Glantz, Nguyen, and Oliveira da Silva performed a systematic review and meta-analysis of population studies centered on health outcomes in the setting of smoking, e-cigarette vaping, and dual use of both forms of tobacco⁶. The authors pooled odds ratios (ORs) for different disease outcomes if there were at least 5 or more studies identified for the disease: cardiovascular disease, stroke, metabolic dysfunction, asthma, chronic obstructive pulmonary disease (COPD), and oral disease. Because dual use of combustible tobacco and e-cigarettes is the most common pattern of use, and has the least published data, this meta-analysis is most notable for bringing to light the risks of dual use.

Considerations for cigarette smokers

When compared to cigarette smoking, e-cigarette users have a lower risk of asthma (OR=0.84) and COPD (OR=0.53). However, e-cigarette use was similar to conventional smoking for risk of the other disease outcomes. In contrast, dual use of both combustible cigarettes and e-cigarettes was significantly associated with higher odds for all disease outcomes: cardiovascular (OR=1.23), stroke (OR=1.26), metabolic dysfunction (OR=1.22), asthma (OR=1.20), COPD (OR=1.41), and oral disease (OR=1.27). These findings corroborate what has been seen in basic science research studies, where exposure of cells and mammals to both the chemicals within combustible tobacco (>7,000) and those within e-cigarette aerosols (94–139) lead to additive or synergistic adverse effects⁷.

Considerations for never smokers/never vapers

Not surprisingly, use of combustible cigarettes was associated with significantly increased risk for all disease outcomes relative to never smokers / never vapers (OR range: 1.27–2.99). Sole use of e-cigarettes was also associated with higher risk for all disease outcomes (OR range: 1.24–1.47). This finding is consistent with what has been seen across basic and translational science studies, where e-cigarette chemicals are damaging at the organ system, cellular, and molecular levels. Most shockingly, dual use of both inhalants was associated with the highest risk across all disease outcomes (OR range: 1.49–3.29).

In the common pursuit of decreasing morbidity and mortality associated with cigarette smoking, dissenting viewpoints have arisen as to whether switching to or adding in e-cigarettes may reduce harm across disease outcomes. What we must keep in mind is that the potential for harm versus benefit is highly dependent on the population and disease outcome being discussed. For never smokers and vulnerable populations, the consensus is clear that e-cigarettes are not safe. When considering the benefits for a cigarette smoker, completely switching from cigarettes to e-cigarettes may be associated with reduced risk of asthma and COPD; however, this may not hold true for other disease outcomes, and the risks for asthma and COPD in e-cigarette vapers are still elevated in comparison to non-use. Because dual use has the most harmful health outcomes, and those who try to use e-cigarettes to diminish or quit smoking frequently become dual users, we must consider that recommending e-cigarettes to decrease cigarette consumption may actually lead to increased harm.

An important note on many of the studies included in the meta-analysis by Glantz et al. is that they did not account for duration or intensity of smoking and e-cigarette vaping. Another limitation was that the majority of odds ratios included in the meta-analysis were cross-sectional (80%) and derived from data obtained through US-based surveys (85%). Overall, more data are needed, particularly longitudinal population studies in multiple populations, that would allow for causality between exposures and disease outcomes to be assessed.

As discussed by Glantz et al., the conclusion on whether e-cigarettes may exhibit carcinogenic effects may be too early to make, as we are still in the early days of e-cigarette and dual use research. Remember, cigarette smoking was popular for over 80 years before the link to cancer was made¹, and e-cigarettes have been popular for less than 10 years. Since data from bench scientists demonstrates that e-cigarette aerosols are DNA damaging and pro-carcinogenic^8–10, we would do well to heed the cancer signal emerging.

Conclusion

Great strides have been made in reducing smoking over the past 60 years. To maintain this momentum, promoting smoking and vaping cessation among users and preventing uptake of either inhalants among non-users remain the ultimate goals. While complete switching by smokers to e-cigarettes may be associated with reduced risk for certain disease outcomes, it is certainly not harmless. Further, incomplete switching that results in dual use of combustible cigarettes and e-cigarettes will increase risk for disease compared to sole combustible cigarettes, leading to harm promotion. More studies are needed to establish causality and to better define overall health effects. However, this comes at the trade-off of time when the clock is already ticking for those who are already vaping and dual using both forms of tobacco.