Pub Date: Tuesday, Jun 21, 2022
Author: Neal L. Benowitz MD
Affiliation: University of California San Francisco
The American Heart Association working group has prepared a scientific statement on the cardiopulmonary consequences of vaping in adolescents. The conclusion that vaping among adolescents is not a good thing and should be prevented if possible is shared by most tobacco and health researchers and health professionals. The importance of determining the short- and long-term health consequences of vaping in adolescents is clear. But what do we really know about the health consequences of vaping in adolescents, and how do we balance concerns about the harm of vaping to adolescents with the potential benefits of vaping as a tool to reduce or eliminate combusted tobacco – mainly cigarette – smoking?
While vaping is still prevalent among adolescents, the prevalence has in fact decreased since 2019. Fortunately, over the past 10 years, despite the rising prevalence of e-cigarette use in adolescents, the prevalence of cigarette smoking has fallen to the lowest rates ever, with fewer than 6% of high school students having smoked a cigarette in the past 30 days and fewer than 3% being daily smokers1. This is a huge success for public health and portends a marked reduction of smoking-related disability and death in future years. Unfortunately, that benefit will not be realized for 30 years. This observation also calls into question whether adolescent e-cigarette use is a gateway to regular cigarette smoking.
The population health risk of vaping-related disease among adolescents depends on the prevalence and frequency of vaping. Many youths experiment with vaping but vape only occasionally, suggesting a low health risk for these individuals. Vaping for 20 or more days per months suggests a degree of dependence and a greater risk for harm. Data from the National Youth Tobacco Survey in 2020 found a past 30 day use prevalence of 19.6% for high school seniors and 4.7% for middle schoolers2. The overall prevalence of those who used 20 days or more per month was 7.6% for high school and 0.9% for middle schoolers. The same survey for 2021 found past 30-days of use in 11.3% of high school and 2.8% in middle school students, with 20 day or more use in 4.9% and 0.5% in the groups, respectively3. Some of the decline since 2019 may be due to reduced access or disease-related concerns during the COVID-19 pandemic, but in contrast smoking rates among adults have not declined. As will be discussed later, the population health risks to children need to be considered in the context of a potential benefit of e-cigarettes in promoting smoking cessation among adult smokers. Also of note is that there is a high degree of concordance of vaping nicotine and smoking marijuana among youth. The prevalence of marijuana use in many communities is higher than that of vaping. Any analysis of adverse health effects of nicotine vaping in youth need to consider the contributions of marijuana smoking or vaping.
E-cigarette liquids and aerosols have been reported to be harmful to cells and animals in numerous studies4. Such studies raise biologically plausible concerns about disease risk, but important limitations of such studies include the relevance of exposure conditions and doses of e-cigarette aerosol and difficulties in extrapolating findings of studies in cells and animals to humans.The most informative data regarding risk are human studies, which include acute exposure studies and epidemiology studies.
Short-term human studies of the effects of vaping on cardiovascular function most clearly demonstrate the well-known pharmacologic effects of nicotine5. Nicotine is a sympathomimetic drug that increases heart rate and blood pressure, increases myocardial work, reduces heart rate variability, can constrict some blood vessels and increases arterial stiffness. Reduced heart rate variability and increased arterial stiffness predict future cardiovascular events in general, presumably due to underlying vascular disease. But it is not clear that nicotine-induced changes in sympathetic tone have the same predictive value. Acutely, e-cigarette use impairs endothelial function, but when smokers switch from cigarettes to e-cigarettes their endothelial function is markedly improved6. Perhaps the greatest concern regarding cardiovascular health is the reported association between e-cigarette use and biomarkers of inflammation. Chronic inflammation is thought to be an important factor in the promotion of atherosclerotic vascular disease. Chronic nicotine exposure may be associated with other pathophysiological processes such as reducing insulin sensitivity and promoting an atherogenic lipid profile, but the degree to which these effects promote disease without smoke is unclear.
The strongest evidence for human disease risk relies on epidemiology studies, which unfortunately for most of the potential harmful effects of vaping will take many years. This reviewer is aware of no convincing epidemiology study that demonstrates an association between vaping and cardiovascular disease. E-cigarette epidemiology studies are difficult because most vapers who are at risk for cardiovascular disease are former or current cigarette smokers. Smokers may begin E-cigarette use because of smoking-related concerns about health. Another problem is variability in product use, with many people changing e-cigarette devices and liquids over time and/or using multiple tobacco products. There are many types of e-cigarette devices and liquids which differ considerably in generation of toxic chemicals and most likely in cardiopulmonary toxicity7.
There is substantial epidemiology on the cardiovascular effects of nicotine as delivered by smokeless tobacco. In Sweden, lifelong use of snus, a government-regulated low-carcinogen smokeless tobacco product, is widespread among men. Regular snus users take in as much nicotine per day as daily cigarette smokers. The cardiovascular epidemiology of snus use in Sweden finds no significant increase in myocardial infarction or stroke, but there is a small increase in fatal myocardial infarction or stroke, and in recurrent myocardial infarction in persistent snus users5. These effects may be explained at least in part by the arrhythmogenic effects of catecholamines released by nicotine.
As reviewed in the AHA statement, the acute pulmonary effects of vaping include a small or no change in lung spirometry and in some but not all studies an increase in inflammatory biomarkers, such as expired nitric oxide. Gene expression studies show changes indicative of immunosuppression, possibly an effect of nicotine which activates the endogenous cholinergic anti-inflammatory system. Animal studies show an increased susceptibility to bacterial and viral infection, which could be a consequence of immune suppression.
As reviewed by the writing group, the strongest epidemiological evidence for vaping harm to adolescents is an increased incidence of wheezing and cough, which may be related to irritant effects of aerosol chemicals. Many epidemiology studies relating vaping to other respiratory disease have serious limitations. For example, the cited study by Mull that links vaping in adolescents to bronchiectasis was based on three adolescents who vaped both nicotine and THC8. As the scientific statement discusses, vaping THC oil contaminated with vitamin E acetate can cause acute lung injury (EVALI). Longitudinal analyses that link vaping and COPD, such as the cited Bhatta study are problematic because the diagnosis of COPD was self-reported and the vast majority of adult vapers were former or current cigarettes smokers9. E-cigarette use was reported as current or former, with no information on when e-cigarette use started, how much was vaped, or what devices were used. The majority of vapers who were never smokers are relatively young, and the development of COPD in these individuals after a few years of vaping is unlikely to be causally related to e-cigarette use. An important confounder was described in the COPDgene and SPIROMIC studies10. These investigators found that adults who used e-cigarettes were heavier, more dependent smokers who were less likely to quit smoking. The e-cigarette users showed a more rapid decline in lung function than non-users, but this effect was no longer significant when controlled for conventional cigarette use. While epidemiology studies need to be conducted, these studies demonstrate why definitive conclusions are problematic. It should also be noted that some studies report that when smokers with asthma or COPD switch to e-cigarettes, their symptoms improve11. In this reviewer’s opinion, there is not at this point in time convincing evidence that vaping causes chronic lung disease, although this possibility should certainly be examined in future research.
While concerns about adverse effects of vaping in youth are valid, they need to be in the context of reducing tobacco-related disease broadly. More than 34 million adults in the U.S currently smoke cigarettes, and more than 400,000 will die each year from smoking-induced disease. Smoking remains one of the major causes of premature morbidity and mortality and contributes to all of the 10 most common causes of death in the U.S. Quitting smoking as soon as possible will save the most lives. While most smokers want to quit, the absolute quit rates each year are low. Both randomized clinical trials and some population studies show that switching to e-cigarettes increase rates of smoking cessation12. The quitting rates with e-cigarette use appear to be higher than those with the use of nicotine replacement medication. The working group notes that the rate of quitting smoking among vapers in the general population is lower than that of a non-vaper13. This observation is driven by lower quit rates in people who continue to smoke and vape. Most likely this finding is related to smokers who vape being more dependent and/or to the use of e-cigarettes to sustain nicotine addiction in situations where smoking is prohibited. The successful use of e-cigarettes to quit requires an intention to quit and switching completely to e-cigarettes as soon as possible.
As mentioned in the AHA scientific statement, a mandated reduction of the nicotine content of cigarettes and other combustible products is being considered by the FDA, and has already been proposed as policy in New Zealand. Acceptance of a nicotine reduction policy, which could markedly reduce smoking prevalence, will be likely be greater if an acceptable alternative source of nicotine, such as e-cigarettes, is available.
The AHA statement concludes with a number of sound recommendations for reducing or preventing youth vaping. These include better measures to reduce youth access, including strict age verification at place of sale; prohibiting marketing of e-cigarettes to youth; and education of healthcare stakeholders, students and their parents regarding realistic concerns about e-cigarette use. The recommendation to limit access could be even stronger if e-cigarette sales were limited to adult-only tobacco specialty stores. Some of the recommendations of the AHA such as an e-cigarette flavor ban and limiting the nicotine content of e-liquids are controversial. While child-friendly flavors should be banned, there is concern that banning other flavors such as menthol would reduce use by smokers wishing to switch, particularly since tobacco flavorings are constant reminders to former smokers of cigarette smoking. While limiting the nicotine concentration of e-liquids might make products less addictive to youth, high nicotine liquids that are vaped with low wattage devices result in much less exposure to aerosol liquid and to thermal degradation products compared to that generated by higher wattage devices that must be used with lower nicotine liquids14. Thus, high nicotine e-cigarettes are likely to be less hazardous for smokers wanting to reduce their harm from cigarette smoking.
In conclusion, the AHA scientific statement raises important concerns about possible adverse health consequences of vaping in adolescents, recommends some way to reduce adolescent vaping, and provides guidance as to what future studies need to be done to characterize the risk. However, in the broad context of public health, we need to balance the concerns about risks to youth with the potential benefits for smoking cessation in adults15. As stated by former U.S. Surgeon General C. Everett Koop, “As we take every action to save our children from the ravages of tobacco, we should demonstrate that our commitment to those who are already addicted... will never expire.”
Wold LE, Tarran R, Crotty Alexander LE, Hamburg NM, Kheradmand F, St. Helen G, PhD; Wu JC; on behalf of the American Heart Association Council on Basic Cardiovascular Sciences; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Hypertension; and Stroke Council. Cardiopulmonary consequences of vaping in adolescents: a scientific statement from the American Heart Association [published online ahead of print June 21, 2022]. Circ Res. doi: 10.1161/RES.0000000000000544
- Meza R, Jimenez-Mendoza E and Levy DT. Trends in Tobacco Use Among Adolescents by Grade, Sex, and Race, 1991-2019. JAMA Netw Open. 2020;3:e2027465.
- Wang TW, Neff LJ, Park-Lee E, Ren C, Cullen KA and King BA. E-cigarette Use Among Middle and High School Students - United States, 2020. MMWR Morb Mortal Wkly Rep. 2020;69:1310-1312.
- Park-Lee E, Ren C, Sawdey MD, Gentzke AS, Cornelius M, Jamal A and Cullen KA. Notes from the Field: E-Cigarette Use Among Middle and High School Students - National Youth Tobacco Survey, United States, 2021. MMWR Morb Mortal Wkly Rep. 2021;70:1387-1389.
- Tarran R, Barr RG, Benowitz NL, Bhatnagar A, Chu HW, Dalton P, Doerschuk CM, Drummond MB, Gold DR, Goniewicz ML, Gross ER, Hansel NN, Hopke PK, Kloner RA, Mikheev VB, Neczypor EW, Pinkerton KE, Postow L, Rahman I, Samet JM, Salathe M, Stoney CM, Tsao PS, Widome R, Xia T, Xiao D and Wold LE. E-Cigarettes and Cardiopulmonary Health. Function (Oxf). 2021;2:zqab004.
- Benowitz NL and Fraiman JB. Cardiovascular effects of electronic cigarettes. Nat Rev Cardiol. 2017;14:447-456.
- George J, Hussain M, Vadiveloo T, Ireland S, Hopkinson P, Struthers AD, Donnan PT, Khan F and Lang CC. Cardiovascular Effects of Switching From Tobacco Cigarettes to Electronic Cigarettes. J Am Coll Cardiol. 2019;74:3112-3120.
- Benowitz NL, St Helen G and Liakoni E. Clinical Pharmacology of Electronic Nicotine Delivery Systems (ENDS): Implications for Benefits and Risks in the Promotion of the Combusted Tobacco Endgame. J Clin Pharmacol. 2021;61 Suppl 2:S18-S36.
- Mull ES, Shell R, Adler B and Holtzlander M. Bronchiectasis associated with electronic cigarette use: A case series. Pediatr Pulmonol. 2020;55:3443-3449.
- Bhatta DN and Glantz SA. Association of E-Cigarette Use With Respiratory Disease Among Adults: A Longitudinal Analysis. Am J Prev Med. 2020;58:182-190.
- Bowler RP, Hansel NN, Jacobson S, Graham Barr R, Make BJ, Han MK, O'Neal WK, Oelsner EC, Casaburi R, Barjaktarevic I, Cooper C, Foreman M, Wise RA, DeMeo DL, Silverman EK, Bailey W, Harrington KF, Woodruff PG, Drummond MB, for C and Investigators S. Electronic Cigarette Use in US Adults at Risk for or with COPD: Analysis from Two Observational Cohorts. J Gen Intern Med. 2017;32:1315-1322.
- Morjaria JB, Mondati E and Polosa R. E-cigarettes in patients with COPD: current perspectives. Int J Chron Obstruct Pulmon Dis. 2017;12:3203-3210.
- Hartmann-Boyce J, McRobbie H, Lindson N, Bullen C, Begh R, Theodoulou A, Notley C, Rigotti NA, Turner T, Butler AR and Hajek P. Electronic cigarettes for smoking cessation. Cochrane Database Syst Rev. 2020;10:CD010216.
- Kalkhoran S and Glantz SA. E-cigarettes and smoking cessation in real-world and clinical settings: a systematic review and meta-analysis. Lancet Respir Med. 2016;4:116-28.
- Kosmider L, Kimber CF, Kurek J, Corcoran O and Dawkins LE. Compensatory Puffing With Lower Nicotine Concentration E-liquids Increases Carbonyl Exposure in E-cigarette Aerosols. Nicotine Tob Res. 2018;20:998-1003.
- Balfour DJK, Benowitz NL, Colby SM, Hatsukami DK, Lando HA, Leischow SJ, Lerman C, Mermelstein RJ, Niaura R, Perkins KA, Pomerleau OF, Rigotti NA, Swan GE, Warner KE and West R. Balancing Consideration of the Risks and Benefits of E-Cigarettes. Am J Public Health. 2021;111:1661-1672.
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-- The opinions expressed in this commentary are not necessarily those of the editors or of the American Heart Association --