More than 2.5 Million Youth Reported E-Cigarette Use in 2022

Flavored products, disposable devices, and a wide variety of brands threaten the health of our nation’s youth

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A  study  released today from the U.S. Food and Drug Administration and the U.S. Centers for Disease Control and Prevention (CDC) found that 2.55 million U.S. middle and high school students reported current (past 30-day) e-cigarette use in 2022, which includes 14.1% of high school students and 3.3% of middle school students. Nearly 85% of those youth used flavored e-cigarettes and more than half used disposable e-cigarettes.

Among youth who currently used e-cigarettes, 14.5% reported their usual brand was Puff Bar, followed by Vuse (12.5%), Hyde (5.5%), and SMOK (4.0%); more than one fifth (21.8%) reported their usual brand was a brand other than the 13 listed in the survey.

The findings, published in the  Morbidity and Mortality Weekly Report , are based on data from the 2022 National Youth Tobacco Survey (NYTS), a cross-sectional, self-administered survey of U.S. middle (grades 6–8) and high (grades 9–12) school students, which was administered January 18–May 31, 2022. The study assessed current use (on one or more of the past 30 days) of e-cigarettes; frequency; and use by device type, flavors, and usual brand.

“This study shows that our nation’s youth continue to be enticed and hooked by an expanding variety of e-cigarette brands delivering flavored nicotine,” said Deirdre Lawrence Kittner, Ph.D., M.P.H., director of CDC’s Office on Smoking and Health. “Our work is far from over. It’s critical that we work together to prevent youth from starting to use any tobacco product – including e-cigarettes – and help all youth who do use them, to quit.”

Other Key Findings

  • Frequency of Use: Among youth who currently used e-cigarettes, more than one in four (27.6%) used them daily and more than four in 10 (42.3%) used them on 20 or more of the past 30 days.
  • Device Type: Among youth who currently used e-cigarettes, the most commonly used e-cigarette device type was disposable (55.3%), followed by prefilled or refillable pods or cartridges (25.2%), and tanks or mod systems (6.7%). Additionally, 12.8% reported not knowing the type of device used.
  • Flavored E-cigarettes: Among youth who currently used e-cigarettes, 84.9% used flavored e-cigarettes, i.e., with flavors other than tobacco, including 85.5% of high school and 81.5% of middle school students reporting use. Overall, the most used flavors were fruit (69.1%); candy, desserts, or other sweets (38.3%); mint (29.4%); and menthol (26.6%).

“Adolescent e-cigarette use in the United States remains at concerning levels, and poses a serious public health risk to our nation’s youth,” said Brian King, Ph.D., M.P.H., director of the FDA’s Center for Tobacco Products. “Together with the CDC, protecting our nation’s youth from the dangers of tobacco products—including e-cigarettes—remains among the FDA’s highest priorities, and we are committed to combatting this issue with the breadth of our regulatory authorities.”

Due to changes in methodology, including differences in survey administration and data collection procedures in recent years due to the COVID-19 pandemic, the ability to compare estimates from 2022 with those from prior NYTS waves is limited; differences between estimates might be due to changes in methodology, actual behavior, or both.

Addressing Youth Tobacco Product Use

Youth use of tobacco products in any form, including e-cigarettes—is unsafe. Such products contain nicotine, which is highly addictive and can harm the developing adolescent brain. Using nicotine during adolescence might also increase risk for future addiction to other drugs.

Since 2014, e-cigarettes have been the most used tobacco product among U.S. youth. As the tobacco product landscape continues to change, the sustained implementation of comprehensive tobacco prevention and control strategies at the national, state, and local levels, coupled with FDA regulations, is critical to prevent and reduce youth access to and use of e-cigarettes.

For additional information, including quit resources, visit:

  • Quick Facts on the Risks of E-cigarettes for Kids, Teens, and Young Adults | CDC
  • Smokefree.gov

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How bad is vaping for your health? We’re finally getting answers

As more of us take up vaping and concerns rise about the long-term effects, we now have enough data to get a grip on the health impact – and how it compares to smoking

By Graham Lawton

6 December 2023

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Klaus Kremmerz

AS THE old joke goes, when I read about the dangers of smoking, I gave up reading. If you are a vaper, you might feel like you want to stop reading now. Don’t: you need to know this.

I am a vaper. Like many others, I used to smoke and switched to vaping for health reasons. I plan to quit completely, but I haven’t managed it yet. I am sure vaping is better for me than smoking, but I am also sure it is worse than not vaping. I cough in the morning and feel massively addicted to the nicotine. I don’t even really know what I am inhaling. I worry that it will be hard to quit, that I am causing long-term damage to my body and that by vaping, I am susceptible to slipping back down the slope to cigarettes. I also have the same worries for the teenagers I see coming out of school and immediately enveloping themselves in sweet-smelling clouds.

Why does the UK want to ban disposable vapes and when will it happen?

As vaping has increased throughout the Western world, these fears have been repeated often. Part of last month’s King’s Speech in the UK focused on new legislation aiming to create a smoke-free generation in part by cracking down on youth vaping. Worldwide, there have been calls for tougher regulation and more investigation into vaping’s health effects as increasing numbers of children admit to taking up the habit.

But there hasn’t been a huge amount to say on whether fears over health effects are well-founded – until recently. Now, vaping…

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The electronic cigarette ( e-cigarette ), for many considered as a safe alternative to conventional cigarettes, has revolutionised the tobacco industry in the last decades. In e-cigarettes , tobacco combustion is replaced by e-liquid heating, leading some manufacturers to propose that e-cigarettes have less harmful respiratory effects than tobacco consumption. Other innovative features such as the adjustment of nicotine content and the choice of pleasant flavours have won over many users. Nevertheless, the safety of e-cigarette consumption and its potential as a smoking cessation method remain controversial due to limited evidence. Moreover, it has been reported that the heating process itself can lead to the formation of new decomposition compounds of questionable toxicity. Numerous in vivo and in vitro studies have been performed to better understand the impact of these new inhalable compounds on human health. Results of toxicological analyses suggest that e-cigarettes can be safer than conventional cigarettes, although harmful effects from short-term e-cigarette use have been described. Worryingly, the potential long-term effects of e-cigarette consumption have been scarcely investigated. In this review, we take stock of the main findings in this field and their consequences for human health including coronavirus disease 2019 (COVID-19).

Electronic nicotine dispensing systems (ENDS), commonly known as electronic cigarettes or e-cigarettes , have been popularly considered a less harmful alternative to conventional cigarette smoking since they first appeared on the market more than a decade ago. E-cigarettes are electronic devices, essentially consisting of a cartridge, filled with an e-liquid, a heating element/atomiser necessary to heat the e-liquid to create a vapour that can be inhaled through a mouthpiece, and a rechargeable battery (Fig.  1 ) [ 1 , 2 ]. Both the electronic devices and the different e-liquids are easily available in shops or online stores.

figure 1

Effect of the heating process on aerosol composition. Main harmful effects documented. Several compounds detected in e-cigarette aerosols are not present in e-liquid s and the device material also seems to contribute to the presence of metal and silicate particles in the aerosols. The heating conditions especially on humectants, flavourings and the low-quality material used have been identified as the generator of the new compounds in aerosols. Some compounds generated from humectants (propylene glycol and glycerol) and flavourings, have been associated with clear airways impact, inflammation, impairment of cardiovascular function and toxicity. In addition, some of them are carcinogens or potential carcinogens

The e-liquid typically contains humectants and flavourings, with or without nicotine; once vapourised by the atomiser, the aerosol (vapour) provides a sensation similar to tobacco smoking, but purportedly without harmful effects [ 3 ]. However, it has been reported that the heating process can lead to the generation of new decomposition compounds that may be hazardous [ 4 , 5 ]. The levels of nicotine, which is the key addictive component of tobacco, can also vary between the commercially available e-liquids, and even nicotine-free options are available. For this particular reason, e-cigarettes are often viewed as a smoking cessation tool, given that those with nicotine can prevent smoking craving, yet this idea has not been fully demonstrated [ 2 , 6 , 7 ].

Because e-cigarettes are combustion-free, and because most of the damaging and well-known effects of tobacco are derived from this reaction, there is a common and widely spread assumption that e-cigarette consumption or “vaping” is safer than conventional cigarette smoking. However, are they risk-free? Is there sufficient toxicological data on all the components employed in e-liquids ? Do we really know the composition of the inhaled vapour during the heating process and its impact on health? Can e-cigarettes be used to curb tobacco use? Do their consumption impact on coronavirus disease 2019 (COVID-19)? In the present review, we have attempted to clarify these questions based on the existing scientific literature, and we have compiled new insights related with the toxicity derived from the use of these devices.

Effect of e-cigarette vapour versus conventional cigarette exposure: in vivo and in vitro effects

Numerous studies have been performed to evaluate the safety/toxicity of e-cigarette use both in vivo and in in vitro cell culture.

One of the first studies in humans involved the analysis of 9 volunteers that consumed e-cigarettes , with or without nicotine, in a ventilated room for 2 h [ 8 ]. Pollutants in indoor air, exhaled nitric oxide (NO) and urinary metabolite profiles were analysed. The results of this acute experiment revealed that e-cigarettes are not emission-free, and ultrafine particles formed from propylene glycol (PG) could be detected in the lungs. The study also suggested that the presence of nicotine in e-cigarettes increased the levels of NO exhaled from consumers and provoked marked airway inflammation; however, no differences were found in the levels of exhaled carbon monoxide (CO), an oxidative stress marker, before and after e-cigarette consumption [ 8 ]. A more recent human study detected significantly higher levels of metabolites of hazardous compounds including benzene, ethylene oxide, acrylonitrile, acrolein and acrylamide in the urine of adolescent dual users ( e-cigarettes and conventional tobacco consumers) than in adolescent e-cigarette -only users (Table 1 ) [ 9 ]. Moreover, the urine levels of metabolites of acrylonitrile, acrolein, propylene oxide, acrylamide and crotonaldehyde, all of which are detrimental for human health, were significantly higher in e-cigarette -only users than in non-smoker controls, reaching up to twice the registered values of those from non-smoker subjects (Table 1 ) [ 9 ]. In line with these observations, dysregulation of lung homeostasis has been documented in non-smokers subjected to acute inhalation of e-cigarette aerosols [ 10 ].

Little is known about the effect of vaping on the immune system. Interestingly, both traditional and e-cigarette consumption by non-smokers was found to provoke short-term effects on platelet function, increasing platelet activation (levels of soluble CD40 ligand and the adhesion molecule P-selectin) and platelet aggregation, although to a lesser extent with e-cigarettes [ 11 ]. As found with platelets, the exposure of neutrophils to e-cigarette aerosol resulted in increased CD11b and CD66b expression being both markers of neutrophil activation [ 12 ]. Additionally, increased oxidative stress, vascular endothelial damage, impaired endothelial function, and changes in vascular tone have all been reported in different human studies on vaping [ 13 , 14 , 15 , 16 , 17 ]. In this context, it is widely accepted that platelet and leukocyte activation as well as endothelial dysfunction are associated with atherogenesis and cardiovascular morbidity [ 18 , 19 ]. In line with these observations the potential association of daily e-cigarettes consumption and the increased risk of myocardial infarction remains controversial but benefits may occur when switching from tobacco to chronic e-cigarette use in blood pressure regulation, endothelial function and vascular stiffness (reviewed in [ 20 ]). Nevertheless, whether or not e-cigarette vaping has cardiovascular consequences requires further investigation.

More recently, in August 2019, the US Centers for Disease Control and Prevention (CDC) declared an outbreak of the e-cigarette or vaping product use-associated lung injury (EVALI) which caused several deaths in young population (reviewed in [ 20 ]). Indeed, computed tomography (CT scan) revealed local inflammation that impaired gas exchange caused by aerosolised oils from e-cigarettes [ 21 ]. However, most of the reported cases of lung injury were associated with use of e-cigarettes for tetrahydrocannabinol (THC) consumption as well as vitamin E additives [ 20 ] and not necessarily attributable to other e-cigarette components.

On the other hand, in a comparative study of mice subjected to either lab air, e-cigarette aerosol or cigarette smoke (CS) for 3 days (6 h-exposure per day), those exposed to e-cigarette aerosols showed significant increases in interleukin (IL)-6 but normal lung parenchyma with no evidence of apoptotic activity or elevations in IL-1β or tumour necrosis factor-α (TNFα) [ 22 ]. By contrast, animals exposed to CS showed lung inflammatory cell infiltration and elevations in inflammatory marker expression such as IL-6, IL-1β and TNFα [ 22 ]. Beyond airway disease, exposure to aerosols from e-liquids with or without nicotine has also been also associated with neurotoxicity in an early-life murine model [ 23 ].

Results from in vitro studies are in general agreement with the limited number of in vivo studies. For example, in an analysis using primary human umbilical vein endothelial cells (HUVEC) exposed to 11 commercially-available vapours, 5 were found to be acutely cytotoxic, and only 3 of those contained nicotine [ 24 ]. In addition, 5 of the 11 vapours tested (including 4 that were cytotoxic) reduced HUVEC proliferation and one of them increased the production of intracellular reactive oxygen species (ROS) [ 24 ]. Three of the most cytotoxic vapours—with effects similar to those of conventional high-nicotine CS extracts—also caused comparable morphological changes [ 24 ]. Endothelial cell migration is an important mechanism of vascular repair than can be disrupted in smokers due to endothelial dysfunction [ 25 , 26 ]. In a comparative study of CS and e-cigarette aerosols, Taylor et al . found that exposure of HUVEC to e-cigarette aqueous extracts for 20 h did not affect migration in a scratch wound assay [ 27 ], whereas equivalent cells exposed to CS extract showed a significant inhibition in migration that was concentration dependent [ 27 ].

In cultured human airway epithelial cells, both e-cigarette aerosol and CS extract induced IL-8/CXCL8 (neutrophil chemoattractant) release [ 28 ]. In contrast, while CS extract reduced epithelial barrier integrity (determined by the translocation of dextran from the apical to the basolateral side of the cell layer), e-cigarette aerosol did not, suggesting that only CS extract negatively affected host defence [ 28 ]. Moreover, Higham et al . also found that e-cigarette aerosol caused IL-8/CXCL8 and matrix metallopeptidase 9 (MMP-9) release together with enhanced activity of elastase from neutrophils [ 12 ] which might facilitate neutrophil migration to the site of inflammation [ 12 ].

In a comparative study, repeated exposure of human gingival fibroblasts to CS condensate or to nicotine-rich or nicotine-free e-vapour condensates led to alterations in morphology, suppression of proliferation and induction of apoptosis, with changes in all three parameters greater in cells exposed to CS condensate [ 29 ]. Likewise, both e-cigarette aerosol and CS extract increased cell death in adenocarcinomic human alveolar basal epithelial cells (A549 cells), and again the effect was more damaging with CS extract than with e-cigarette aerosol (detrimental effects found at 2 mg/mL of CS extract vs. 64 mg/mL of e-cigarette extract) [ 22 ], which is in agreement with another study examining battery output voltage and cytotoxicity [ 30 ].

All this evidence would suggest that e-cigarettes are potentially less harmful than conventional cigarettes (Fig.  2 ) [ 11 , 14 , 22 , 24 , 27 , 28 , 29 ]. Importantly, however, most of these studies have investigated only short-term effects [ 10 , 14 , 15 , 22 , 27 , 28 , 29 , 31 , 32 ], and the long-term effects of e-cigarette consumption on human health are still unclear and require further study.

figure 2

Comparison of the degree of harmful effects documented from e-cigarette and conventional cigarette consumption. Human studies, in vivo mice exposure and in vitro studies. All of these effects from e-cigarettes were documented to be lower than those exerted by conventional cigarettes, which may suggest that e-cigarette consumption could be a safer option than conventional tobacco smoking but not a clear safe choice

Consequences of nicotine content

Beyond flavour, one of the major issues in the e-liquid market is the range of nicotine content available. Depending on the manufacturer, the concentration of this alkaloid can be presented as low , medium or high , or expressed as mg/mL or as a percentage (% v/v). The concentrations range from 0 (0%, nicotine-free option) to 20 mg/mL (2.0%)—the maximum nicotine threshold according to directive 2014/40/EU of the European Parliament and the European Union Council [ 33 , 34 ]. Despite this normative, however, some commercial e-liquids have nicotine concentrations close to 54 mg/mL [ 35 ], much higher than the limits established by the European Union.

The mislabelling of nicotine content in e-liquids has been previously addressed [ 8 , 34 ]. For instance, gas chromatography with a flame ionisation detector (GC-FID) revealed inconsistencies in the nicotine content with respect to the manufacturer´s declaration (average of 22 ± 0.8 mg/mL vs. 18 mg/mL) [ 8 ], which equates to a content ~ 22% higher than that indicated in the product label. Of note, several studies have detected nicotine in those e-liquids labelled as nicotine-free [ 5 , 35 , 36 ]. One study detected the presence of nicotine (0.11–6.90 mg/mL) in 5 of 23 nicotine-free labelled e-liquids by nuclear magnetic resonance spectroscopy [ 35 ], and another study found nicotine (average 8.9 mg/mL) in 13.6% (17/125) of the nicotine-free e-liquids as analysed by high performance liquid chromatography (HPLC) [ 36 ]. Among the 17 samples tested in this latter study 14 were identified to be counterfeit or suspected counterfeit. A third study detected nicotine in 7 of 10 nicotine-free refills, although the concentrations were lower than those identified in the previous analyses (0.1–15 µg/mL) [ 5 ]. Not only is there evidence of mislabelling of nicotine content among refills labelled as nicotine-free, but there also seems to be a history of poor labelling accuracy in nicotine-containing e-liquids [ 37 , 38 ].

A comparison of the serum levels of nicotine from e-cigarette or conventional cigarette consumption has been recently reported [ 39 ]. Participants took one vape from an e-cigarette , with at least 12 mg/mL of nicotine, or inhaled a conventional cigarette, every 20 s for 10 min. Blood samples were collected 1, 2, 4, 6, 8, 10, 12 and 15 min after the first puff, and nicotine serum levels were measured by liquid chromatography-mass spectrometry (LC–MS). The results revealed higher serum levels of nicotine in the conventional CS group than in the e-cigarette group (25.9 ± 16.7 ng/mL vs. 11.5 ± 9.8 ng/mL). However, e-cigarettes containing 20 mg/mL of nicotine are more equivalent to normal cigarettes, based on the delivery of approximately 1 mg of nicotine every 5 min [ 40 ].

In this line, a study compared the acute impact of CS vs. e-cigarette vaping with equivalent nicotine content in healthy smokers and non-smokers. Both increased markers of oxidative stress and decreased NO bioavailability, flow-mediated dilation, and vitamin E levels showing no significant differences between tobacco and e-cigarette exposure (reviewed in [ 20 ]). Inasmuch, short-term e-cigarette use in healthy smokers resulted in marked impairment of endothelial function and an increase in arterial stiffness (reviewed in [ 20 ]). Similar effects on endothelial dysfunction and arterial stiffness were found in animals when they were exposed to e-cigarette vapor either for several days or chronically (reviewed in [ 20 ]). In contrast, other studies found acute microvascular endothelial dysfunction, increased oxidative stress and arterial stiffness in smokers after exposure to e-cigarettes with nicotine, but not after e-cigarettes without nicotine (reviewed in [ 20 ]). In women smokers, a study found a significant difference in stiffness after smoking just one tobacco cigarette, but not after use of e-cigarettes (reviewed in [ 20 ]).

It is well known that nicotine is extremely addictive and has a multitude of harmful effects. Nicotine has significant biologic activity and adversely affects several physiological systems including the cardiovascular, respiratory, immunological and reproductive systems, and can also compromise lung and kidney function [ 41 ]. Recently, a sub-chronic whole-body exposure of e-liquid (2 h/day, 5 days/week, 30 days) containing PG alone or PG with nicotine (25 mg/mL) to wild type (WT) animals or knockout (KO) mice in α7 nicotinic acetylcholine receptor (nAChRα7-KO) revealed a partly nAChRα7-dependent lung inflammation [ 42 ]. While sub-chronic exposure to PG/nicotine promote nAChRα7-dependent increased levels of different cytokines and chemokines in the bronchoalveolar lavage fluid (BALF) such as IL-1α, IL-2, IL-9, interferon γ (IFNγ), granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemoattractant protein-1 (MCP-1/CCL2) and regulated on activation, normal T cell expressed and secreted (RANTES/CCL5), the enhanced levels of IL-1β, IL-5 and TNFα were nAChRα7 independent. In general, most of the cytokines detected in BALF were significantly increased in WT mice exposed to PG with nicotine compared to PG alone or air control [ 42 ]. Some of these effects were found to be through nicotine activation of NF-κB signalling albeit in females but not in males. In addition, PG with nicotine caused increased macrophage and CD4 + /CD8 + T-lymphocytes cell counts in BALF compared to air control, but these effects were ameliorated when animals were sub-chronically exposed to PG alone [ 42 ].

Of note, another study indicated that although RANTES/CCL5 and CCR1 mRNA were upregulated in flavour/nicotine-containing e-cigarette users, vaping flavour and nicotine-less e-cigarettes did not significantly dysregulate cytokine and inflammasome activation [ 43 ].

In addition to its toxicological effects on foetus development, nicotine can disrupt brain development in adolescents and young adults [ 44 , 45 , 46 ]. Several studies have also suggested that nicotine is potentially carcinogenic (reviewed in [ 41 ]), but more work is needed to prove its carcinogenicity independently of the combustion products of tobacco [ 47 ]. In this latter regard, no differences were encountered in the frequency of tumour appearance in rats subjected to long-term (2 years) inhalation of nicotine when compared with control rats [ 48 ]. Despite the lack of carcinogenicity evidence, it has been reported that nicotine promotes tumour cell survival by decreasing apoptosis and increasing proliferation [ 49 ], indicating that it may work as a “tumour enhancer”. In a very recent study, chronic administration of nicotine to mice (1 mg/kg every 3 days for a 60-day period) enhanced brain metastasis by skewing the polarity of M2 microglia, which increases metastatic tumour growth [ 50 ]. Assuming that a conventional cigarette contains 0.172–1.702 mg of nicotine [ 51 ], the daily nicotine dose administered to these animals corresponds to 40–400 cigarettes for a 70 kg-adult, which is a dose of an extremely heavy smoker. We would argue that further studies with chronic administration of low doses of nicotine are required to clearly evaluate its impact on carcinogenicity.

In the aforementioned study exposing human gingival fibroblasts to CS condensate or to nicotine-rich or nicotine-free e-vapour condensates [ 29 ], the detrimental effects were greater in cells exposed to nicotine-rich condensate than to nicotine-free condensate, suggesting that the possible injurious effects of nicotine should be considered when purchasing e-refills . It is also noteworthy that among the 3 most cytotoxic vapours for HUVEC evaluated in the Putzhammer et al . study, 2 were nicotine-free, which suggests that nicotine is not the only hazardous component in e-cigarettes [ 24 ] .

The lethal dose of nicotine for an adult is estimated at 30–60 mg [ 52 ]. Given that nicotine easily diffuses from the dermis to the bloodstream, acute nicotine exposure by e-liquid spilling (5 mL of a 20 mg/mL nicotine-containing refill is equivalent to 100 mg of nicotine) can easily be toxic or even deadly [ 8 ]. Thus, devices with rechargeable refills are another issue of concern with e-cigarettes , especially when e-liquids are not sold in child-safe containers, increasing the risk of spilling, swallowing or breathing.

These data overall indicate that the harmful effects of nicotine should not be underestimated. Despite the established regulations, some inaccuracies in nicotine content labelling remain in different brands of e-liquids . Consequently, stricter regulation and a higher quality control in the e-liquid industry are required.

Effect of humectants and their heating-related products

In this particular aspect, again the composition of the e-liquid varies significantly among different commercial brands [ 4 , 35 ]. The most common and major components of e-liquids are PG or 1,2-propanediol, and glycerol or glycerine (propane-1,2,3-triol). Both types of compounds are used as humectants to prevent the e-liquid from drying out [ 2 , 53 ] and are classified by the Food and Drug Administration (FDA) as “Generally Recognised as Safe” [ 54 ]. In fact, they are widely used as alimentary and pharmaceutical products [ 2 ]. In an analysis of 54 commercially available e-liquids , PG and glycerol were detected in almost all samples at concentrations ranging from 0.4% to 98% (average 57%) and from 0.3% to 95% (average 37%), respectively [ 35 ].

With regards to toxicity, little is known about the effects of humectants when they are heated and chronically inhaled. Studies have indicated that PG can induce respiratory irritation and increase the probability of asthma development [ 55 , 56 ], and both PG and glycerol from e-cigarettes might reach concentrations sufficiently high to potentially cause irritation of the airways [ 57 ]. Indeed, the latter study established that one e-cigarette puff results in a PG exposure of 430–603 mg/m 3 , which is higher than the levels reported to cause airway irritation (average 309 mg/m 3 ) based on a human study [ 55 ]. The same study established that one e-cigarette puff results in a glycerol exposure of 348–495 mg/m 3 [ 57 ], which is close to the levels reported to cause airway irritation in rats (662 mg/m 3 ) [ 58 ].

Airway epithelial injury induced by acute vaping of PG and glycerol aerosols (50:50 vol/vol), with or without nicotine, has been reported in two randomised clinical trials in young tobacco smokers [ 32 ]. In vitro, aerosols from glycerol only-containing refills showed cytotoxicity in A549 and human embryonic stem cells, even at a low battery output voltage [ 59 ]. PG was also found to affect early neurodevelopment in a zebrafish model [ 60 ]. Another important issue is that, under heating conditions PG can produce acetaldehyde or formaldehyde (119.2 or 143.7 ng/puff at 20 W, respectively, on average), while glycerol can also generate acrolein (53.0, 1000.0 or 5.9 ng/puff at 20 W, respectively, on average), all carbonyls with a well-documented toxicity [ 61 ]. Although, assuming 15 puffs per e-cigarette unit, carbonyls produced by PG or glycerol heating would be below the maximum levels found in a conventional cigarette combustion (Table 2 ) [ 51 , 62 ]. Nevertheless, further studies are required to properly test the deleterious effects of all these compounds at physiological doses resembling those to which individuals are chronically exposed.

Although PG and glycerol are the major components of e-liquids other components have been detected. When the aerosols of 4 commercially available e-liquids chosen from a top 10 list of “ Best E-Cigarettes of 2014” , were analysed by gas chromatography-mass spectrometry (GC–MS) after heating, numerous compounds were detected, with nearly half of them not previously identified [ 4 ], thus suggesting that the heating process per se generates new compounds of unknown consequence. Of note, the analysis identified formaldehyde, acetaldehyde and acrolein [ 4 ], 3 carbonyl compounds with known high toxicity [ 63 , 64 , 65 , 66 , 67 ]. While no information was given regarding formaldehyde and acetaldehyde concentrations, the authors calculated that one puff could result in an acrolein exposure of 0.003–0.015 μg/mL [ 4 ]. Assuming 40 mL per puff and 15 puffs per e-cigarette unit (according to several manufacturers) [ 4 ], each e-cigarette unit would generate approximately 1.8–9 μg of acrolein, which is less than the levels of acrolein emitted by a conventional tobacco cigarette (18.3–98.2 μg) [ 51 ]. However, given that e-cigarette units of vaping are not well established, users may puff intermittently throughout the whole day. Thus, assuming 400 to 500 puffs per cartridge, users could be exposed to up to 300 μg of acrolein.

In a similar study, acrolein was found in 11 of 12 aerosols tested, with a similar content range (approximately 0.07–4.19 μg per e-cigarette unit) [ 68 ]. In the same study, both formaldehyde and acetaldehyde were detected in all of the aerosols tested, with contents of 0.2–5.61 μg and 0.11–1.36 μg, respectively, per e-cigarette unit [ 68 ]. It is important to point out that the levels of these toxic products in e-cigarette aerosols are significantly lower than those found in CS: 9 times lower for formaldehyde, 450 times lower for acetaldehyde and 15 times lower for acrolein (Table 2 ) [ 62 , 68 ].

Other compounds that have been detected in aerosols include acetamide, a potential human carcinogen [ 5 ], and some aldehydes [ 69 ], although their levels were minimal. Interestingly, the existence of harmful concentrations of diethylene glycol, a known cytotoxic agent, in e-liquid aerosols is contentious with some studies detecting its presence [ 4 , 68 , 70 , 71 , 72 ], and others finding low subtoxic concentrations [ 73 , 74 ]. Similar observations were reported for the content ethylene glycol. In this regard, either it was detected at concentrations that did not exceed the authorised limit [ 73 ], or it was absent from the aerosols produced [ 4 , 71 , 72 ]. Only one study revealed its presence at high concentration in a very low number of samples [ 5 ]. Nevertheless, its presence above 1 mg/g is not allowed by the FDA [ 73 ]. Figure  1 lists the main compounds detected in aerosols derived from humectant heating and their potential damaging effects. It would seem that future studies should analyse the possible toxic effects of humectants and related products at concentrations similar to those that e-cigarette vapers are exposed to reach conclusive results.

Impact of flavouring compounds

The range of e-liquid flavours available to consumers is extensive and is used to attract both current smokers and new e-cigarette users, which is a growing public health concern [ 6 ]. In fact, over 5 million middle- and high-school students were current users of e-cigarettes in 2019 [ 75 ], and appealing flavours have been identified as the primary reason for e-cigarette consumption in 81% of young users [ 76 ]. Since 2016, the FDA regulates the flavours used in the e-cigarette market and has recently published an enforcement policy on unauthorised flavours, including fruit and mint flavours, which are more appealing to young users [ 77 ]. However, the long-term effects of all flavour chemicals used by this industry (which are more than 15,000) remain unknown and they are not usually included in the product label [ 78 ]. Furthermore, there is no safety guarantee since they may harbour potential toxic or irritating properties [ 5 ].

With regards to the multitude of available flavours, some have demonstrated cytotoxicity [ 59 , 79 ]. Bahl et al. evaluated the toxicity of 36 different e-liquids and 29 different flavours on human embryonic stem cells, mouse neural stem cells and human pulmonary fibroblasts using a metabolic activity assay. In general, those e-liquids that were bubblegum-, butterscotch- and caramel-flavoured did not show any overt cytotoxicity even at the highest dose tested. By contrast, those e-liquids with Freedom Smoke Menthol Arctic and Global Smoke Caramel flavours had marked cytotoxic effects on pulmonary fibroblasts and those with Cinnamon Ceylon flavour were the most cytotoxic in all cell lines [ 79 ]. A further study from the same group [ 80 ] revealed that high cytotoxicity is a recurrent feature of cinnamon-flavoured e-liquids. In this line, results from GC–MS and HPLC analyses indicated that cinnamaldehyde (CAD) and 2-methoxycinnamaldehyde, but not dipropylene glycol or vanillin, were mainly responsible for the high cytotoxicity of cinnamon-flavoured e-liquids [ 80 ]. Other flavouring-related compounds that are associated with respiratory complications [ 81 , 82 , 83 ], such as diacetyl, 2,3-pentanedione or acetoin, were found in 47 out of 51 aerosols of flavoured e-liquids tested [ 84 ] . Allen et al . calculated an average of 239 μg of diacetyl per cartridge [ 84 ]. Assuming again 400 puffs per cartridge and 40 mL per puff, is it is possible to estimate an average of 0.015 ppm of diacetyl per puff, which could compromise normal lung function in the long-term [ 85 ].

The cytotoxic and pro-inflammatory effects of different e-cigarette flavouring chemicals were also tested on two human monocytic cell lines—mono mac 6 (MM6) and U937 [ 86 ]. Among the flavouring chemicals tested, CAD was found to be the most toxic and O-vanillin and pentanedione also showed significant cytotoxicity; by contrast, acetoin, diacetyl, maltol, and coumarin did not show any toxicity at the concentrations assayed (10–1000 µM). Of interest, a higher toxicity was evident when combinations of different flavours or mixed equal proportions of e-liquids from 10 differently flavoured e-liquids were tested, suggesting that vaping a single flavour is less toxic than inhaling mixed flavours [ 86 ]. Also, all the tested flavours produced significant levels of ROS in a cell-free ROS production assay. Finally, diacetyl, pentanedione, O-vanillin, maltol, coumarin, and CAD induced significant IL-8 secretion from MM6 and U937 monocytes [ 86 ]. It should be borne in mind, however, that the concentrations assayed were in the supra-physiological range and it is likely that, once inhaled, these concentrations are not reached in the airway space. Indeed, one of the limitations of the study was that human cells are not exposed to e-liquids per se, but rather to the aerosols where the concentrations are lower [ 86 ]. In this line, the maximum concentration tested (1000 µM) would correspond to approximately 80 to 150 ppm, which is far higher than the levels found in aerosols of some of these compounds [ 84 ]. Moreover, on a day-to-day basis, lungs of e-cigarette users are not constantly exposed to these chemicals for 24 h at these concentrations. Similar limitations were found when five of seven flavourings were found to cause cytotoxicity in human bronchial epithelial cells [ 87 ].

Recently, a commonly commercialized crème brûlée -flavoured aerosol was found to contain high concentrations of benzoic acid (86.9 μg/puff), a well-established respiratory irritant [ 88 ]. When human lung epithelial cells (BEAS-2B and H292) were exposed to this aerosol for 1 h, a marked cytotoxicity was observed in BEAS-2B but not in H292 cells, 24 h later. However, increased ROS production was registered in H292 cells [ 88 ].

Therefore, to fully understand the effects of these compounds, it is relevant the cell cultures selected for performing these assays, as well as the use of in vivo models that mimic the real-life situation of chronic e-cigarette vapers to clarify their impact on human health.

The e-cigarette device

While the bulk of studies related to the impact of e-cigarette use on human health has focused on the e-liquid components and the resulting aerosols produced after heating, a few studies have addressed the material of the electronic device and its potential consequences—specifically, the potential presence of metals such as copper, nickel or silver particles in e-liquids and aerosols originating from the filaments and wires and the atomiser [ 89 , 90 , 91 ].

Other important components in the aerosols include silicate particles from the fiberglass wicks or silicone [ 89 , 90 , 91 ]. Many of these products are known to cause abnormalities in respiratory function and respiratory diseases [ 89 , 90 , 91 ], but more in-depth studies are required. Interestingly, the battery output voltage also seems to have an impact on the cytotoxicity of the aerosol vapours, with e-liquids from a higher battery output voltage showing more toxicity to A549 cells [ 30 ].

A recent study compared the acute effects of e-cigarette vapor (with PG/vegetable glycerine plus tobacco flavouring but without nicotine) generated from stainless‐steel atomizer (SS) heating element or from a nickel‐chromium alloy (NC) [ 92 ]. Some rats received a single e-cigarette exposure for 2 h from a NC heating element (60 or 70 W); other rats received a similar exposure of e-cigarette vapor using a SS heating element for the same period of time (60 or 70 W) and, a final group of animals were exposed for 2 h to air. Neither the air‐exposed rats nor those exposed to e-cigarette vapor using SS heating elements developed respiratory distress. In contrast, 80% of the rats exposed to e-cigarette vapor using NC heating units developed clinical acute respiratory distress when a 70‐W power setting was employed. Thus, suggesting that operating units at higher than recommended settings can cause adverse effects. Nevertheless, there is no doubt that the deleterious effects of battery output voltage are not comparable to those exerted by CS extracts [ 30 ] (Figs.  1 and 2 ).

E-cigarettes as a smoking cessation tool

CS contains a large number of substances—about 7000 different constituents in total, with sizes ranging from atoms to particulate matter, and with many hundreds likely responsible for the harmful effects of this habit [ 93 ]. Given that tobacco is being substituted in great part by e-cigarettes with different chemical compositions, manufacturers claim that e -cigarette will not cause lung diseases such as lung cancer, chronic obstructive pulmonary disease, or cardiovascular disorders often associated with conventional cigarette consumption [ 3 , 94 ]. However, the World Health Organisation suggests that e-cigarettes cannot be considered as a viable method to quit smoking, due to a lack of evidence [ 7 , 95 ]. Indeed, the results of studies addressing the use of e-cigarettes as a smoking cessation tool remain controversial [ 96 , 97 , 98 , 99 , 100 ]. Moreover, both FDA and CDC are actively investigating the incidence of severe respiratory symptoms associated with the use of vaping products [ 77 ]. Because many e-liquids contain nicotine, which is well known for its powerful addictive properties [ 41 ], e-cigarette users can easily switch to conventional cigarette smoking, avoiding smoking cessation. Nevertheless, the possibility of vaping nicotine-free e-cigarettes has led to the branding of these devices as smoking cessation tools [ 2 , 6 , 7 ].

In a recently published randomised trial of 886 subjects who were willing to quit smoking [ 100 ], the abstinence rate was found to be twice as high in the e-cigarette group than in the nicotine-replacement group (18.0% vs. 9.9%) after 1 year. Of note, the abstinence rate found in the nicotine-replacement group was lower than what is usually expected with this therapy. Nevertheless, the incidence of throat and mouth irritation was higher in the e-cigarette group than in the nicotine-replacement group (65.3% vs. 51.2%, respectively). Also, the participant adherence to the treatment after 1-year abstinence was significantly higher in the e-cigarette group (80%) than in nicotine-replacement products group (9%) [ 100 ].

On the other hand, it is estimated that COPD could become the third leading cause of death in 2030 [ 101 ]. Given that COPD is generally associated with smoking habits (approximately 15 to 20% of smokers develop COPD) [ 101 ], smoking cessation is imperative among COPD smokers. Published data revealed a clear reduction of conventional cigarette consumption in COPD smokers that switched to e-cigarettes [ 101 ]. Indeed, a significant reduction in exacerbations was observed and, consequently, the ability to perform physical activities was improved when data was compared with those non-vapers COPD smokers. Nevertheless, a longer follow-up of these COPD patients is required to find out whether they have quitted conventional smoking or even vaping, since the final goal under these circumstances is to quit both habits.

Based on the current literature, it seems that several factors have led to the success of e-cigarette use as a smoking cessation tool. First, some e-cigarette flavours positively affect smoking cessation outcomes among smokers [ 102 ]. Second, e-cigarettes have been described to improve smoking cessation rate only among highly-dependent smokers and not among conventional smokers, suggesting that the individual degree of nicotine dependence plays an important role in this process [ 97 ]. Third, the general belief of their relative harmfulness to consumers' health compared with conventional combustible tobacco [ 103 ]. And finally, the exposure to point-of-sale marketing of e-cigarette has also been identified to affect the smoking cessation success [ 96 ].

Implication of e-cigarette consumption in COVID-19 time

Different reports have pointed out that smokers and vapers are more vulnerable to SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infections or more prone to adverse outcomes if they suffer COVID-19 [ 104 ]. However, while a systematic review indicated that cigarette smoking is probably associated with enhanced damage from COVID-19, a meta-analysis did not, yet the latter had several limitations due to the small sample sizes [ 105 ].

Interestingly, most of these reports linking COVID-19 harmful effects with smoking or vaping, are based on their capability of increasing the expression of angiotensin-converting enzyme 2 (ACE2) in the lung. It is well known that ACE2 is the gate for SARS-CoV-2 entrance to the airways [ 106 ] and it is mainly expressed in type 2 alveolar epithelial cells and alveolar macrophages [ 107 ]. To date, most of the studies in this field indicate that current smokers have higher expression of ACE2 in the airways (reviewed by [ 108 ]) than healthy non-smokers [ 109 , 110 ]. However, while a recent report indicated that e-cigarette vaping also caused nicotine-dependent ACE2 up-regulation [ 42 ], others have revealed that neither acute inhalation of e-cigarette vapour nor e-cigarette users had increased lung ACE2 expression regardless nicotine presence in the e-liquid [ 43 , 110 ].

In regard to these contentions, current knowledge suggests that increased ACE2 expression is not necessarily linked to enhanced susceptibility to SARS-CoV-2 infection and adverse outcome. Indeed, elderly population express lower levels of ACE2 than young people and SARS-CoV-2/ACE2 interaction further decreases ACE2 expression. In fact, most of the deaths provoked by COVID-19 took place in people over 60 years old of age [ 111 ]. Therefore, it is plausible that the increased susceptibility to disease progression and the subsequent fatal outcome in this population is related to poor angiotensin 1-7 (Ang-1-7) generation, the main peptide generated by ACE2, and probably to their inaccessibility to its anti-inflammatory effects. Furthermore, it seems that all the efforts towards increasing ACE2 expression may result in a better resolution of the pneumonic process associated to this pandemic disease.

Nevertheless, additional complications associated to COVID-19 are increased thrombotic events and cytokine storm. In the lungs, e-cigarette consumption has been correlated to toxicity, oxidative stress, and inflammatory response [ 32 , 112 ]. More recently, a study revealed that while the use of nicotine/flavour-containing e-cigarettes led to significant cytokine dysregulation and potential inflammasome activation, none of these effects were detected in non-flavoured and non-nicotine-containing e-cigarettes [ 43 ]. Therefore, taken together these observations, e-cigarette use may still be a potent risk factor for severe COVID-19 development depending on the flavour and nicotine content.

In summary, it seems that either smoking or nicotine vaping may adversely impact on COVID-19 outcome. However, additional follow up studies are required in COVID-19 pandemic to clarify the effect of e-cigarette use on lung and cardiovascular complications derived from SARS-CoV-2 infection.

Conclusions

The harmful effects of CS and their deleterious consequences are both well recognised and widely investigated. However, and based on the studies carried out so far, it seems that e-cigarette consumption is less toxic than tobacco smoking. This does not necessarily mean, however, that e-cigarettes are free from hazardous effects. Indeed, studies investigating their long-term effects on human health are urgently required. In this regard, the main additional studies needed in this field are summarized in Table 3 .

The composition of e-liquids requires stricter regulation, as they can be easily bought online and many incidences of mislabelling have been detected, which can seriously affect consumers’ health. Beyond their unknown long-term effects on human health, the extended list of appealing flavours available seems to attract new “never-smokers”, which is especially worrying among young users. Additionally, there is still a lack of evidence of e-cigarette consumption as a smoking cessation method. Indeed, e-cigarettes containing nicotine may relieve the craving for smoking, but not the conventional cigarette smoking habit.

Interestingly, there is a strong difference of opinion on e-cigarettes between countries. Whereas countries such as Brazil, Uruguay and India have banned the sale of e-cigarettes , others such as the United Kingdom support this device to quit smoking. The increasing number of adolescent users and reported deaths in the United States prompted the government to ban the sale of flavoured e-cigarettes in 2020. The difference in opinion worldwide may be due to different restrictions imposed. For example, while no more than 20 ng/mL of nicotine is allowed in the EU, e-liquids with 59 mg/dL are currently available in the United States. Nevertheless, despite the national restrictions, users can easily access foreign or even counterfeit products online.

In regard to COVID-19 pandemic, the actual literature suggests that nicotine vaping may display adverse outcomes. Therefore, follow up studies are necessary to clarify the impact of e-cigarette consumption on human health in SARS-CoV-2 infection.

In conclusion, e-cigarettes could be a good alternative to conventional tobacco cigarettes, with less side effects; however, a stricter sale control, a proper regulation of the industry including flavour restriction, as well as further toxicological studies, including their chronic effects, are warranted.

Availability of data and materials

Not applicable.

Abbreviations

Angiotensin-converting enzyme 2

Angiotensin 1-7

Bronchoalveolar lavage fluid

Cinnamaldehyde

US Centers for Disease Control and Prevention

Carbon monoxide

Chronic obstructive pulmonary disease

Coronavirus disease 2019

Cigarette smoke

Electronic nicotine dispensing systems

e-cigarette or vaping product use-associated lung injury

Food and Drug Administration

Gas chromatography with a flame ionisation detector

Gas chromatography-mass spectrometry

Granulocyte–macrophage colony-stimulating factor

High performance liquid chromatography

Human umbilical vein endothelial cells

Interleukin

Interferon γ

Liquid chromatography-mass spectrometry

Monocyte chemoattractant protein-1

Matrix metallopeptidase 9

α7 Nicotinic acetylcholine receptor

Nickel‐chromium alloy

Nitric oxide

Propylene glycol

Regulated on activation, normal T cell expressed and secreted

Reactive oxygen species

Severe acute respiratory syndrome coronavirus 2

Stainless‐steel atomizer

Tetrahydrocannabinol

Tumour necrosis factor-α

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Acknowledgements

The authors gratefully acknowledge Dr. Cruz González, Pulmonologist at University Clinic Hospital of Valencia (Valencia, Spain) for her thoughtful suggestions and support.

This work was supported by the Spanish Ministry of Science and Innovation [Grant Number SAF2017-89714-R]; Carlos III Health Institute [Grant Numbers PIE15/00013, PI18/00209]; Generalitat Valenciana [Grant Number PROMETEO/2019/032, Gent T CDEI-04/20-A and AICO/2019/250], and the European Regional Development Fund.

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Marques, P., Piqueras, L. & Sanz, MJ. An updated overview of e-cigarette impact on human health. Respir Res 22 , 151 (2021). https://doi.org/10.1186/s12931-021-01737-5

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Impact of vaping on respiratory health

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  • Andrea Jonas , clinical assistant professor
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Widespread uptake of vaping has signaled a sea change in the future of nicotine consumption. Vaping has grown in popularity over the past decade, in part propelled by innovations in vape pen design and nicotine flavoring. Teens and young adults have seen the biggest uptake in use of vape pens, which have superseded conventional cigarettes as the preferred modality of nicotine consumption. Relatively little is known, however, about the potential effects of chronic vaping on the respiratory system. Further, the role of vaping as a tool of smoking cessation and tobacco harm reduction remains controversial. The 2019 E-cigarette or Vaping Use-Associated Lung Injury (EVALI) outbreak highlighted the potential harms of vaping, and the consequences of long term use remain unknown. Here, we review the growing body of literature investigating the impacts of vaping on respiratory health. We review the clinical manifestations of vaping related lung injury, including the EVALI outbreak, as well as the effects of chronic vaping on respiratory health and covid-19 outcomes. We conclude that vaping is not without risk, and that further investigation is required to establish clear public policy guidance and regulation.

Abbreviations

BAL bronchoalveolar lavage

CBD cannabidiol

CDC Centers for Disease Control and Prevention

DLCO diffusing capacity of the lung for carbon monoxide

EMR electronic medical record

END electronic nicotine delivery systems

EVALI E-cigarette or Vaping product Use-Associated Lung Injury

LLM lipid laden macrophages

THC tetrahydrocannabinol

V/Q ventilation perfusion

Introduction

The introduction of vape pens to international markets in the mid 2000s signaled a sea change in the future of nicotine consumption. Long the mainstay of nicotine use, conventional cigarette smoking was on the decline for decades in the US, 1 2 largely owing to generational shifts in attitudes toward smoking. 3 With the advent of vape pens, trends in nicotine use have reversed, and the past two decades have seen a steady uptake of vaping among young, never smokers. 4 5 6 Vaping is now the preferred modality of nicotine consumption among young people, 7 and 2020 surveys indicate that one in five US high school students currently vape. 8 These trends are reflected internationally, where the prevalence of vape products has grown in both China and the UK. 9 Relatively little is known, however, regarding the health consequences of chronic vape pen use. 10 11 Although vaping was initially heralded as a safer alternative to cigarette smoking, 12 13 the toxic substances found in vape aerosols have raised new questions about the long term safety of vaping. 14 15 16 17 The 2019 E-cigarette or Vaping product Use-Associated Lung Injury (EVALI) outbreak, ultimately linked to vitamin E acetate in THC vapes, raised further concerns about the health effects of vaping, 18 19 20 and has led to increased scientific interest in the health consequences of chronic vaping. This review summarizes the history and epidemiology of vaping, and the clinical manifestations and proposed pathophysiology of lung injury caused by vaping. The public health consequences of widespread vaping remain to be seen and are compounded by young users of vape pens later transitioning to combustible cigarettes. 4 21 22 Deepened scientific understanding and public awareness of the potential harms of vaping are imperative to confront the challenges posed by a new generation of nicotine users.

Sources and selection criteria

We searched PubMed and Ovid Medline databases for the terms “vape”, “vaping”, “e-cigarette”, “electronic cigarette”, “electronic nicotine delivery”, “electronic nicotine device”, “END”, “EVALI”, “lung injury, diagnosis, management, and treatment” to find articles published between January 2000 and December 2021. We also identified references from the Centers for Disease Control and Prevention (CDC) website, as well as relevant review articles and public policy resources. Prioritization was given to peer reviewed articles written in English in moderate-to-high impact journals, consensus statements, guidelines, and included randomized controlled trials, systematic reviews, meta-analyses, and case series. We excluded publications that had a qualitative research design, or for which a conflict of interest in funding could be identified, as defined by any funding source or consulting fee from nicotine manufacturers or distributors. Search terms were chosen to generate a broad selection of literature that reflected historic and current understanding of the effects of vaping on respiratory health.

The origins of vaping

Vaping achieved widespread popularity over the past decade, but its origins date back almost a century and are summarized in figure 1 . The first known patent for an “electric vaporizer” was granted in 1930, intended for aerosolizing medicinal compounds. 23 Subsequent patents and prototypes never made it to market, 24 and it wasn’t until 1979 that the first vape pen was commercialized. Dubbed the “Favor” cigarette, the device was heralded as a smokeless alternative to cigarettes and led to the term “vaping” being coined to differentiate the “new age” method of nicotine consumption from conventional, combustible cigarettes. 25 “Favor” cigarettes did not achieve widespread appeal, in part because of the bitter taste of the aerosolized freebase nicotine; however, the term vaping persisted and would go on to be used by the myriad products that have since been developed.

Fig 1

Timeline of vape pen invention to widespread use (1970s-2020)

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The forerunner of the modern vape pen was developed in Beijing in 2003 and later introduced to US markets around 2006. 26 27 Around this time, the future Juul Laboratories founders developed the precursor of the current Juul vape pen while they were students at the Stanford Byers-Center for Biodesign. 28 Their model included disposable cartridges of flavored nicotine solution (pods) that could be inserted into the vape pen, which itself resembled a USB flash drive. Key to their work was the chemical alteration of freebase nicotine to a benzoate nicotine salt. 29 The lower pH of the nicotine salt resulted in an aerosolized nicotine product that lacked a bitter taste, 30 and enabled manufacturers to expand the range of flavored vape products. 31 Juul Laboratories was founded a decade later and quickly rose to dominate the US market, 32 accounting for an estimated 13-59% of the vape products used among teens by 2020. 6 8 Part of the Juul vape pen’s appeal stems from its discreet design, as well as its ability to deliver nicotine with an efficiency matching that of conventional cigarettes. 33 34 Subsequent generations of vape pens have included innovations such as the tank system, which allowed users to select from the wide range of different vape solutions on the market, rather than the relatively limited selection available in traditional pod based systems. Further customizations include the ability to select different vape pen components such as atomizers, heating coils, and fluid wicks, allowing users to calibrate the way in which the vape aerosol is produced. Tobacco companies have taken note of the shifting demographics of nicotine users, as evidenced in 2018 by Altria’s $12.8bn investment in Juul Laboratories. 35

Vaping terminology

At present, vaping serves as an umbrella term that describes multiple modalities of aerosolized nicotine consumption. Vape pens are alternatively called e-cigarettes, electronic nicotine delivery systems (END), e-cigars, and e-hookahs. Additional vernacular terms have emerged to describe both the various vape pen devices (eg, tank, mod, dab pen), vape solution (eg, e-liquid, vape juice), as well as the act of vaping (eg, ripping, juuling, puffing, hitting). 36 A conventional vape pen is a battery operated handheld device that contains a storage chamber for the vape solution and an internal element for generating the characteristic vape aerosol. Multiple generations of vape pens have entered the market, including single use, disposable varieties, as well as reusable models that have either a refillable fluid reservoir or a disposable cartridge for the vape solution. Aerosol generation entails a heating coil that atomizes the vape solution, and it is increasingly popular for devices to include advanced settings that allow users to adjust features of the aerosolized nicotine delivery. 37 38 Various devices allow for coil temperatures ranging from 110 °C to over 1000 °C, creating a wide range of conditions for thermal degradation of the vape solution itself. 39 40

The sheer number of vape solutions on the market poses a challenge in understanding the impact of vaping on respiratory health. The spectrum of vape solutions available encompasses thousands of varieties of flavors, additives, and nicotine concentrations. 41 Most vape solutions contain an active ingredient, commonly nicotine 42 ; however, alternative agents include tetrahydrocannabinol (THC) or cannabidiol (CBD). Vape solutions are typically composed of a combination of a flavorant, nicotine, and a carrier, commonly propylene glycol or vegetable glycerin, that generates the characteristic smoke appearance of vape aerosols. Some 450 brands of vape now offer more than 8000 flavors, 41 a figure that nearly doubled over a three year period. 43 Such tremendous variety does not account for third party sellers who offer users the option to customize a vape solution blend. Addition of marijuana based products such as THC or CBD requires the use of an oil based vape solution carrier to allow for extraction of the psychoactive elements. Despite THC vaping use in nearly 9% of high schoolers, 44 THC vape solutions are subject to minimal market regulation. Finally, a related modality of THC consumption is termed dabbing, and describes the process of inhaling aerosolized THC wax concentrate.

Epidemiology of vaping

Since the early 2000s, vaping has grown in popularity in the US and elsewhere. 8 45 Most of the 68 million vape pen users are concentrated in China, the US, and Europe. 46 Uptake among young people has been particularly pronounced, and in the US vaping has overtaken cigarettes as the most common modality of nicotine consumption among adolescents and young adults. 47 Studies estimate that 20% of US high school students are regular vape pen users, 6 48 in contrast to the 5% of adults who use vape products. 2 Teen uptake of vaping has been driven in part by a perception of vaping as a safer alternative to cigarettes, 49 50 as well as marketing strategies that target adolescents. 33 Teen use of vape pens is further driven by the low financial cost of initiation, with “starter kits” costing less than $25, 51 as well as easy access through peer sales and inconsistent age verification at in-person and online retailers. 52 After sustained growth in use over the 2010s, recent survey data from 2020 suggest that the number of vape pen users has leveled off among teens, perhaps in part owing to increased perceived risk of vaping after the EVALI outbreak. 8 53 The public health implications of teen vaping are compounded by the prevalence of vaping among never smokers (defined as having smoked fewer than 100 lifetime cigarettes), 54 and subsequent uptake of cigarette smoking among vaping teens. 4 55 Similarly, half of adults who currently vape have never used cigarettes, 2 and concern remains that vaping serves as a gateway to conventional cigarette use, 56 57 although these results have been disputed. 58 59 Despite regulation limiting the sale of flavored vape products, 60 a 2020 survey found that high school students were still predominantly using fruit, mint, menthol, and dessert flavored vape solutions. 48 While most data available surround the use of nicotine-containing vape products, a recent meta-analysis showed growing prevalence of adolescents using cannabis-containing products as well. 61

Vaping as harm reduction

Despite facing ongoing questions about safety, vaping has emerged as a potential tool for harm reduction among cigarette smokers. 12 27 An NHS report determined that vaping nicotine is “around 95% less harmful than cigarettes,” 62 leading to the development of programs that promote vaping as a tool of risk reduction among current smokers. A 2020 Cochrane review found that vaping nicotine assisted with smoking cessation over placebo 63 and recent work found increased rates of cigarette abstinence (18% v 9.9%) among those switching to vaping compared with conventional nicotine replacement (eg, gum, patch, lozenge). 64 US CDC guidance suggests that vaping nicotine may benefit current adult smokers who are able to achieve complete cigarette cessation by switching to vaping. 65 66

The public health benefit of vaping for smoking cessation is counterbalanced by vaping uptake among never smokers, 2 54 and questions surrounding the safety of chronic vaping. 10 11 Controversy surrounding the NHS claim of vaping as 95% safer than cigarettes has emerged, 67 68 and multiple leading health organizations have concluded that vaping is harmful. 42 69 Studies have demonstrated airborne particulate matter in the proximity of active vapers, 70 and concern remains that secondhand exposure to vaped aerosols may cause adverse effects, complicating the notion of vaping as a net gain for public health. 71 72 Uncertainty about the potential chronic consequences of vaping combined with vaping uptake among never smokers has complicated attempts to generate clear policy guidance. 73 74 Further, many smokers may exhibit “dual use” of conventional cigarettes and vape pens simultaneously, further complicating efforts to understand the impact of vape exposure on respiratory health, and the role vape use may play in smoking cessation. 12 We are unable to know with certainty the extent of nicotine uptake among young people that would have been seen in the absence of vaping availability, and it remains possible that some young vape pen users may have started on conventional cigarettes regardless. That said, declining nicotine use over the past several decades would argue that many young vape pen users would have never had nicotine uptake had vape pens not been introduced. 1 2 It remains an open question whether public health measures encouraging vaping for nicotine cessation will benefit current smokers enough to offset the impact of vaping uptake among young, never smokers. 75

Vaping lung injury—clinical presentations

Vaping related lung injury: 2012-19.

The potential health effects of vape pen use are varied and centered on injury to the airways and lung parenchyma. Before the 2019 EVALI outbreak, the medical literature detailed case reports of sporadic vaping related acute lung injury. The first known case was reported in 2012, when a patient presented with cough, diffuse ground glass opacities, and lipid laden macrophages (LLM) on bronchoalveolar lavage (BAL) return in the context of vape pen use. 76 Over the following seven years, an additional 15 cases of vaping related acute lung injury were reported in the literature. These cases included a wide range of diffuse parenchymal lung disease without any clear unifying features, and included cases of eosinophilic pneumonia, 77 78 79 hypersensitivity pneumonitis, 80 organizing pneumonia, 81 82 diffuse alveolar hemorrhage, 83 84 and giant cell foreign body reaction. 85 Although parenchymal lung injury predominated the cases reported, additional cases detailed episodes of status asthmaticus 86 and pneumothoraces 87 attributed to vaping. Non-respiratory vape pen injury has also been described, including cases of nicotine toxicity from vape solution ingestion, 88 89 and injuries sustained owing to vape pen device explosions. 90

The 2019 EVALI outbreak

In the summer of 2019 the EVALI outbreak led to 2807 cases of idiopathic acute lung injury in predominantly young, healthy individuals, which resulted in 68 deaths. 19 91 Epidemiological work to uncover the cause of the outbreak identified an association with vaping, particularly the use of THC-containing products, among affected individuals. CDC criteria for EVALI ( box 1 ) included individuals presenting with respiratory symptoms who had pulmonary infiltrates on imaging in the context of having vaped or dabbed within 90 days of symptom onset, without an alternative identifiable cause. 92 93 After peaking in September 2019, EVALI case numbers steadily declined, 91 likely owing to identification of a link with vaping, and subsequent removal of offending agents from circulation. Regardless, sporadic cases continue to be reported, and a high index of suspicion is required to differentiate EVALI from covid-19 pneumonia. 94 95 A strong association emerged between EVALI cases and the presence of vitamin E acetate in the BAL return of affected individuals 96 ; however, no definitive causal link has been established. Interestingly, the EVALI outbreak was nearly entirely contained within the US with the exception of several dozen cases, at least one of which was caused by an imported US product. 97 98 99 The pattern of cases and lung injury is most suggestive of a vape solution contaminant that was introduced into the distribution pipeline in US markets, leading to a geographically contained pattern of lung injury among users. CDC case criteria for EVALI may have obscured a potential link between viral pneumonia and EVALI, and cases may have been under-recognized following the onset of the covid-19 pandemic.

CDC criteria for establishing EVALI diagnosis

Cdc lung injury surveillance, primary case definitions, confirmed case.

Vape use* in 90 days prior to symptom onset; and

Pulmonary infiltrate on chest radiograph or ground glass opacities on chest computed tomography (CT) scan; and

Absence of pulmonary infection on initial investigation†; and

Absence of alternative plausible diagnosis (eg, cardiac, rheumatological, or neoplastic process).

Probable case

Pulmonary infiltrate on chest radiograph or ground glass opacities on chest CT; and

Infection has been identified; however is not thought to represent the sole cause of lung injury OR minimum criteria** to exclude infection have not been performed but infection is not thought to be the sole cause of lung injury

*Use of e-cigarette, vape pen, or dabbing.

†Minimum criteria for absence of pulmonary infection: negative respiratory viral panel, negative influenza testing (if supported by local epidemiological data), and all other clinically indicated infectious respiratory disease testing is negative.

EVALI—clinical, radiographic, and pathologic features

In the right clinical context, diagnosis of EVALI includes identification of characteristic radiographic and pathologic features. EVALI patients largely fit a pattern of diffuse, acute lung injury in the context of vape pen exposure. A systematic review of 200 reported cases of EVALI showed that those affected were predominantly men in their teens to early 30s, and most (80%) had been using THC-containing products. 100 Presentations included predominantly respiratory (95%), constitutional (87%), and gastrointestinal symptoms (73%). Radiological studies mostly featured diffuse ground glass opacities bilaterally. Of 92 cases that underwent BAL, alveolar fluid samples were most commonly neutrophil predominant, and 81% were additionally positive for LLM on Oil Red O staining. Lung biopsy was not required to achieve the diagnosis; however, of 33 cases that underwent tissue biopsy, common features included organizing pneumonia, inflammation, foamy macrophages, and fibrinous exudates.

EVALI—outcomes

Most patients with EVALI recovered, and prognosis was generally favorable. A systematic review of identified cases found that most patients with confirmed disease required admission to hospital (94%), and a quarter were intubated. 100 Mortality among EVALI patients was low, with estimates around 2-3% across multiple studies. 101 102 103 Mortality was associated with age over 35 and underlying asthma, cardiac disease, or mental health conditions. 103 Notably, the cohorts studied only included patients who presented for medical care, and the samples are likely biased toward a more symptomatic population. It is likely that many individuals experiencing mild symptoms of EVALI did not present for medical care, and would have self-discontinued vaping following extensive media coverage of the outbreak at that time. Although most EVALI survivors recovered well, case series of some individuals show persistent radiographic abnormalities 101 and sustained reductions in DLCO. 104 105 Pulmonary function evaluation of EVALI survivors showed normalization in FEV 1 /FVC on spirometry in some, 106 while others had more variable outcomes. 105 107 108

Vaping induced lung injury—pathophysiology

The causes underlying vaping related acute lung injury remain interesting to clinicians, scientists, and public health officials; multiple mechanisms of injury have been proposed and are summarized in figure 2 . 31 109 110 Despite increased scientific interest in vaping related lung injury following the EVALI outbreak, the pool of data from which to draw meaningful conclusions is limited because of small scale human studies and ongoing conflicts due to tobacco industry funding. 111 Further, insufficient time has elapsed since widespread vaping uptake, and available studies reflect the effects of vaping on lung health over a maximum 10-15 year timespan. The longitudinal effects of vaping may take decades to fully manifest and ongoing prospective work is required to better understand the impacts of vaping on respiratory health.

Fig 2

Schematic illustrating pathophysiology of vaping lung injury

Pro-inflammatory vape aerosol effects

While multiple pathophysiological pathways have been proposed for vaping related lung injury, they all center on the vape aerosol itself as the conduit of lung inflammation. Vape aerosols have been found to harbor a number of toxic substances, including thermal degradation products of the various vape solution components. 112 Mass spectrometry analysis of vape aerosols has identified a variety of oxidative and pro-inflammatory substances including benzene, acrolein, volatile organic compounds, and propylene oxide. 16 17 Vaping additionally leads to airway deposition of ultrafine particles, 14 113 as well as the heavy metals manganese and zinc which are emitted from the vaping coils. 15 114 Fourth generation vape pens allow for high wattage aerosol generation, which can cause airway epithelial injury and tissue hypoxia, 115 116 as well as formaldehyde exposure similar to that of cigarette smoke. 117 Common carrier solutions such as propylene glycol have been associated with increased airway hyper-reactivity among vape pen users, 31 118 119 and have been associated with chronic respiratory conditions among theater workers exposed to aerosolized propylene glycol used in the generation of artificial fog. 120 Nicotine salts used in pod based vape pen solutions, including Juul, have been found to penetrate the cell membrane and have cytotoxic effects. 121

The myriad available vape pen flavors correlate with an expansive list of chemical compounds with potential adverse respiratory effects. Flavorants have come under increased scrutiny in recent years and have been found to contribute to the majority of aldehyde production during vape aerosol production. 122 Compounds such as cinnamaldehyde, 123 124 2,5-dimethylpyrazine (chocolate flavoring), 125 and 2,3-pentanedione 126 are common flavor additives and have been found to contribute to airway inflammation and altered immunological responses. The flavorant diacetyl garnered particular attention after it was identified on mass spectrometry in most vape solutions tested. 127 Diacetyl is most widely associated with an outbreak of diacetyl associated bronchiolitis obliterans (“popcorn lung”) among workers at a microwave popcorn plant in 2002. 128 Identification of diacetyl in vape solutions raises the possibility of development of a similar pattern of bronchiolitis obliterans among individuals who have chronic vape aerosol exposure to diacetyl-containing vape solutions. 129

Studies of vape aerosols have suggested multiple pro-inflammatory effects on the respiratory system. This includes increased airway resistance, 130 impaired response to infection, 131 and impaired mucociliary clearance. 132 Vape aerosols have further been found to induce oxidative stress in lung epithelial cells, 133 and to both induce DNA damage and impair DNA repair, consistent with a potential carcinogenic effect. 134 Mice chronically exposed to vape aerosols developed increased airway hyper-reactivity and parenchymal changes consistent with chronic obstructive pulmonary disease. 135 Human studies have been more limited, but reveal increased airway edema and friability among vape pen users, as well as altered gene transcription and decreased innate immunity. 136 137 138 Upregulation of neutrophil elastase and matrix metalloproteases among vape users suggests increased proteolysis, potentially putting those patients at risk of chronic respiratory conditions. 139

THC-containing products

Of particular interest during the 2019 EVALI outbreak was the high prevalence of THC use among EVALI cases, 19 raising questions about a novel mechanism of lung injury specific to THC-containing vape solutions. These solutions differ from conventional nicotine based products because of the need for a carrier capable of emulsifying the lipid based THC component. In this context, additional vape solution ingredients rose to attention as potential culprits—namely, THC itself, which has been found to degrade to methacrolein and benzene, 140 as well as vitamin E acetate which was found to be a common oil based diluent. 141

Vitamin E acetate has garnered increasing attention as a potential culprit in the pathophysiology of the EVALI outbreak. Vitamin E acetate was found in 94% of BAL samples collected from EVALI patients, compared with none identified in unaffected vape pen users. 96 Thermal degradation of vitamin E acetate under conditions similar to those in THC vape pens has shown production of ketene, alkene, and benzene, which may mediate epithelial lung injury when inhaled. 39 Previous work had found that vitamin E acetate impairs pulmonary surfactant function, 142 and subsequent studies have shown a dose dependent adverse effect on lung parenchyma by vitamin E acetate, including toxicity to type II pneumocytes, and increased inflammatory cytokines. 143 Mice exposed to aerosols containing vitamin E acetate developed LLM and increased alveolar protein content, suggesting epithelial injury. 140 143

The pathophysiological insult underlying vaping related lung injury may be multitudinous, including potentially compound effects from multiple ingredients comprising a vape aerosol. The heterogeneity of available vape solutions on the market further complicates efforts to pinpoint particular elements of the vape aerosol that may be pathogenic, as no two users are likely to be exposed to the same combination of vape solution products. Further, vape users may be exposed to vape solutions containing terpenes, medium chain triglycerides, or coconut oil, the effects of which on respiratory epithelium remain under investigation. 144

Lipid laden macrophages

Lipid laden alveolar macrophages have risen to prominence as potential markers of vaping related lung injury. Alveolar macrophages describe a scavenger white blood cell responsible for clearing alveolar spaces of particulate matter and modulating the inflammatory response in the lung parenchyma. 145 LLM describe alveolar macrophages that have phagocytosed fat containing deposits, as seen on Oil Red O staining, and have been described in a wide variety of pulmonary conditions, including aspiration, lipoid pneumonia, organizing pneumonia, and medication induced pneumonitis. 146 147 During the EVALI outbreak, LLM were identified in the alveolar spaces of affected patients, both in the BAL fluid and on both transbronchial and surgical lung biopsies. 148 149 Of 52 EVALI cases reported in the literature who underwent BAL, LLM were identified in over 80%. 19 100 101 148 149 150 151 152 153 Accordingly, attention turned to LLM as not only a potential marker of lung injury in EVALI, but as a possible contributor to lung inflammation itself. This concern was compounded by the frequent reported use of oil based THC vape products among EVALI patients, raising the possibility of lipid deposits in the alveolus resulting from inhalation of THC-containing vape aerosols. 154 The combination of LLM, acute lung injury, and inhalational exposure to an oil based substance raised the concern for exogenous lipoid pneumonia. 152 153 However, further evaluation of the radiographic and histopathologic findings failed to identify cardinal features that would support a diagnosis of exogenous lipoid pneumonia—namely, low attenuation areas on CT imaging and foreign body giant cells on histopathology. 155 156 However, differences in the particle size and distribution between vape aerosol exposure and traditional causes of lipoid pneumonia (ie, aspiration of a large volume of an oil-containing substance), could reasonably lead to differences in radiographic appearance, although this would not account for the lack of characteristic histopathologic features on biopsy that would support a diagnosis of lipoid pneumonia.

Recent work suggests that LLM reflect a non-specific marker of vaping, rather than a marker of lung injury. One study found that LLM were not unique to EVALI and could be identified in healthy vape pen users, as well as conventional cigarette smokers, but not in never smokers. 157 Interestingly, this work showed increased cytokines IL-4 and IL-10 among healthy vape users, suggesting that cigarette and vape pen use are associated with a pro-inflammatory state in the lung. 157 An alternative theory supports LLM presence reflecting macrophage clearance of intra-alveolar cell debris rather than exogenous lipid exposure. 149 150 Such a pattern would be in keeping with the role of alveolar macrophages as modulating the inflammatory response in the lung parenchyma. 158 Taken together, available data would support LLM serving as a non-specific marker of vape product use, rather than playing a direct role in vaping related lung injury pathogenesis. 102

Clinical aspects

A high index of suspicion is required in establishing a diagnosis of vaping related lung injury, and a general approach is summarized in figure 3 . Clinicians may consider the diagnosis when faced with a patient with new respiratory symptoms in the context of vape pen use, without an alternative cause to account for their symptoms. Suspicion should be especially high if respiratory complaints are coupled with constitutional and gastrointestinal symptoms. Patients may present with non-specific markers indicative of an ongoing inflammatory process: fevers, leukocytosis, elevated C reactive protein, or elevated erythrocyte sedimentation rate. 19

Fig 3

Flowchart outlining the procedure for diagnosing a vaping related lung injury

Vaping related lung injury is a diagnosis of exclusion. Chest imaging via radiograph or CT may identify a variety of patterns, although diffuse ground glass opacities remain the most common radiographic finding. Generally, patients with an abnormal chest radiograph should undergo a chest CT for further evaluation of possible vaping related lung injury.

Exclusion of infectious causes is recommended. Testing should include evaluation for bacterial and viral causes of pneumonia, as deemed appropriate by clinical judgment and epidemiological data. Exclusion of common viral causes of pneumonia is imperative, particularly influenza and SARS-CoV-2. Bronchoscopy with BAL should be considered on a case-by-case basis for those with more severe disease and may be helpful to identify patients with vaping mediated eosinophilic lung injury. Further, lung biopsy may be beneficial to exclude alternative causes of lung injury in severe cases. 92

No definitive therapy has been identified for the treatment of vaping related lung injury, and data are limited to case reports and public health guidance on the topic. Management includes supportive care and strong consideration for systemic corticosteroids for severe cases of vaping related lung injury. CDC guidance encourages consideration of systemic corticosteroids for patients requiring admission to hospital, or those with higher risk factors for adverse outcomes, including age over 50, immunosuppressed status, or underlying cardiopulmonary disease. 100 Further, given case reports of vaping mediated acute eosinophilic pneumonia, steroids should be implemented in those patients who have undergone a confirmatory BAL. 77 79

Additional therapeutic options include empiric antibiotics and/or antivirals, depending on the clinical scenario. For patients requiring admission to hospital, prompt subspecialty consultation with a pulmonologist can help guide management. Outpatient follow-up with chest imaging and spirometry is recommended, as well as referral to a pulmonologist. Counseling regarding vaping cessation is also a core component in the post-discharge care for this patient population. Interventions specific to vaping cessation remain under investigation; however, literature supports the use of behavioral counseling and/or pharmacotherapy to support nicotine cessation efforts. 66

Health outcomes among vape pen users

Health outcomes among chronic vape pen users remains an open question. To date, no large scale prospective cohort studies exist that can establish a causal link between vape use and adverse respiratory outcomes. One small scale prospective cohort study did not identify any spirometric or radiographic changes among vape pen users over a 3.5 year period. 159 Given that vaping remains a relatively novel phenomenon, many users will have a less than 10 “pack year” history of vape pen use, arguably too brief an exposure period to reflect the potential harmful nature of chronic vaping. Studies encompassing a longer period of observation of vape pen users have not yet taken place, although advances in electronic medical record (EMR) data collection on vaping habits make such work within reach.

Current understanding of the health effects of vaping is largely limited to case reports of acute lung injury, and health surveys drawing associations between vaping exposure and patient reported outcomes. Within these limitations, however, early work suggests a correlation between vape pen use and poorer cardiopulmonary outcomes. Survey studies of teens who regularly vape found increased frequencies of respiratory symptoms, including productive cough, that were independent of smoking status. 160 161 These findings were corroborated in a survey series identifying more severe asthma symptoms and more days of school missed owing to asthma among vape pen users, regardless of cigarette smoking status. 162 163 164 Studies among adults have shown a similar pattern, with increased prevalence of chronic respiratory conditions (ie, asthma or chronic obstructive pulmonary disease) among vape pen users, 165 166 and higher risk of myocardial infarction and stroke, but lower risk of diabetes. 167

The effects of vaping on lung function as determined by spirometric studies are more varied. Reported studies have assessed lung function after a brief exposure to vape aerosols, varying from 5-60 minutes in duration, and no longer term observational cohort studies exist. While some studies have shown increased airway resistance after vaping exposure, 130 168 169 others have shown no change in lung function. 137 170 171 The cumulative exposure of habitual vape pen users to vape aerosols is much longer than the period evaluated in these studies, and the impact of vaping on longer term respiratory heath remains to be seen. Recent work evaluating ventilation-perfusion matching among chronic vapers compared with healthy controls found increased ventilation-perfusion mismatch, despite normal spirometry in both groups. 172 Such work reinforces the notion that changes in spirometry are a feature of more advanced airways disease, and early studies, although inconsistent, may foreshadow future respiratory impairment in chronic vapers.

Covid-19 and vaping

The covid-19 pandemic brought renewed attention to the potential health impacts of vaping. Studies investigating the role of vaping in covid-19 prevalence and outcomes have been limited by the small size of the populations studied and results have been inconsistent. Early work noted a geographic association in the US between vaping prevalence and covid-19 cases, 173 and a subsequent survey study found that a covid-19 diagnosis was five times more likely among teens who had ever vaped. 174 In contrast, a UK survey study found no association between vaping status and covid-19 infection rates, although captured a much smaller population of vape pen users. 175 Reports of nicotine use upregulating the angiotensin converting enzyme 2 (ACE-2) receptor, 176 which serves as the binding site for SARS-CoV-2 entry, raised the possibility of increased susceptibility to covid-19 among chronic nicotine vape pen users. 177 178 Further, vape use associated with sharing devices and frequent touching of the mouth and face were posited as potential confounders contributing to increased prevalence of covid-19 in this population. 179

Covid-19 outcomes among chronic vape pen users remain an open question. While smoking has been associated with progression to more severe infections, 180 181 no investigation has been performed to date among vaping cohorts. The young average age of chronic vape pen users may prove a protective factor, as risk of severe covid-19 infection has been shown to increase with age. 182 Regardless, a prudent recommendation remains to abstain from vaping to mitigate risk of progression to severe covid-19 infection. 183

Increased awareness of respiratory health brought about by covid-19 and EVALI is galvanizing the changing patterns in vape pen use. 184 Survey studies have consistently shown trends toward decreasing use among adolescents and young adults. 174 185 186 In one study, up to two thirds of participants endorsed decreasing or quitting vaping owing to a combination of factors including difficulty purchasing vape products during the pandemic, concerns about vaping effects on lung health, and difficulty concealing vape use while living with family. 174 Such results are reflected in nationwide trends that show halting growth in vaping use among high school students. 8 These trends are encouraging in that public health interventions countering nicotine use among teens may be meeting some measure of success.

Clinical impact—collecting and recording a vaping history

Vaping history in electronic medical records.

Efforts to prevent, diagnose, and treat vaping related lung injury begin with the ability of our healthcare system to identify vape users. Since vaping related lung injury remains a diagnosis of exclusion, clinicians must have a high index of suspicion when confronted with idiopathic lung injury in a patient with vaping exposure. Unlike cigarette use, vape pen use is not built into most EMR systems, and is not included in meaningful use criteria for EMRs. 187 Retrospective analysis of outpatient visits showed that a vaping history was collected in less than 0.1% of patients in 2015, 188 although this number has been increasing. 189 190 In part augmented by EMR frameworks that prompt collection of data on vaping history, more recent estimates indicate that a vaping history is being collected in up to 6% of patients. 191 Compared with the widespread use of vaping, particularly among adolescent and young adult populations, this number remains low. Considering generational trends in nicotine use, vaping will likely eventually overcome cigarettes as the most common mode of nicotine use, raising the importance of collecting a vaping related history. Further, EMR integration of vaping history is imperative to allow for retrospective, large scale analyses of vape exposure on longitudinal health outcomes at a population level.

Practical considerations—gathering a vaping history

As vaping becomes more common, the clinician’s ability to accurately collect a vaping history and identify patients who may benefit from nicotine cessation programs becomes more important. Reassuringly, gathering a vaping history is not dissimilar to asking about smoking and use of other tobacco products, and is summarized in box 2 . Collecting a vaping history is of particular importance for providers caring for adolescents and young adults who are among the highest risk demographics for vape pen use. Adolescents and young adults may be reluctant to share their vaping history, particularly if they are using THC-containing or CBD-containing vape solutions. Familiarity with vernacular terms to describe vaping, assuming a non-judgmental approach, and asking parents or guardians to step away during history taking will help to break down these barriers. 192

Practical guide to collecting a vaping history

Ask with empathy.

Young adults may be reluctant to share history of vaping use. Familiarity with vaping terminology, asking in a non-judgmental manner, and asking in a confidential space may help.

Ask what they are vaping

Vape products— vape pens commonly contain nicotine or an alternative active ingredient, such as THC or CBD. Providers may also inquire about flavorants, or other vape solution additives, that their patient is consuming, particularly if vaping related lung injury is suspected.

Source— ask where they source their product from. Sources may include commercially available products, third party distributors, or friends or local contacts.

Ask how they are vaping

Device— What style of device are they using?

Frequency— How many times a day do they use their vape pen (with frequent use considered >5 times a day)? Alternatively, providers may inquire how long it takes to deplete a vape solution cartridge (with use of one or more pods a day considered heavy use).

Nicotine concentration— For individuals consuming nicotine-containing products, clinicians may inquire about concentration and frequency of use, as this may allow for development of a nicotine replacement therapy plan.

Ask about other inhaled products

Clinicians should ask patients who vape about use of other inhaled products, particularly cigarettes. Further, clinicians may ask about use of water pipes, heat-not-burn devices, THC-containing products, or dabbing.

The following provides a practical guide on considerations when collecting a vaping history. Of note, collecting a partial history is preferable to no history at all, and simply recording whether a patient is vaping or not adds valuable information to the medical record.

Vape use— age at time of vaping onset and frequency of vape pen use. Vape pen use >5 times a day would be considered frequent. Alternatively, clinicians may inquire how long it takes to deplete a vape solution pod (use of one or more pods a day would be considered heavy use), or how frequently users are refilling their vape pens for refillable models.

Vape products— given significant variation in vape solutions available on the market, and variable risk profiles of the multitude of additives, inquiring as to which products a patient is using may add useful information. Further, clinicians may inquire about use of nicotine versus THC-containing vape solutions, and whether said products are commercially available or are customized by third party sellers.

Concurrent smoking— simultaneous use of multiple inhaled products is common among vape users, including concurrent use of conventional cigarettes, water pipes, heat-not-burn devices, and THC-containing or CBD-containing products. Among those using marijuana products, gathering a history regarding the type of product use, the device, and the modality of aerosol generation may be warranted. Gathering such detailed information may be challenging in the face of rapidly evolving product availability and changing popular terminology. Lastly, clinicians may wish to inquire about “dabbing”—the practice of inhaling heated butane hash oil, a concentrated THC wax—which may also be associated with lung injury. 193

Future directions

Our understanding of the effects of vaping on respiratory health is in its early stages and multiple trials are under way. Future work requires enhanced understanding of the effects of vape aerosols on lung biology, such as ongoing investigations into biomarkers of oxidative stress and inflammation among vape users (clinicaltrials.gov NCT03823885 ). Additional studies seek to elucidate the relation between vape aerosol exposure and cardiopulmonary outcomes among vape pen users ( NCT03863509 , NCT05199480 ), while an ongoing prospective cohort study will allow for longitudinal assessment of airway reactivity and spirometric changes among chronic vape pen users ( NCT04395274 ).

Public health and policy interventions are vital in supporting both our understanding of vaping on respiratory health and curbing the vaping epidemic among teens. Ongoing, large scale randomized controlled studies seek to assess the impact of the FDA’s “The Real Cost” advertisement campaign for vaping prevention ( NCT04836455 ) and another trial is assessing the impact of a vaping prevention curriculum among adolescents ( NCT04843501 ). Current trials are seeking to understand the potential for various therapies as tools for vaping cessation, including nicotine patches ( NCT04974580 ), varenicline ( NCT04602494 ), and text message intervention ( NCT04919590 ).

Finally, evaluation of vaping as a potential tool for harm reduction among current cigarette smokers is undergoing further evaluation ( NCT03235505 ), which will add to the body of work and eventually lead to clear policy guidance.

Several guidelines on the management of vaping related lung injury have been published and are summarized in table 1 . 194 195 196 Given the relatively small number of cases, the fact that vaping related lung injury remains a newer clinical entity, and the lack of clinical trials on the topic, guideline recommendations reflect best practices and expert opinion. Further, published guidelines focus on the diagnosis and management of EVALI, and no guidelines exist to date for the management of vaping related lung injury more generally.

Summary of clinical guidelines

  • View inline

Conclusions

Vaping has grown in popularity internationally over the past decade, in part propelled by innovations in vape pen design and nicotine flavoring. Teens and young adults have seen the biggest uptake in use of vape pens, which have superseded conventional cigarettes as the preferred modality of nicotine consumption. Despite their widespread popularity, relatively little is known about the potential effects of chronic vaping on the respiratory system, and a growing body of literature supports the notion that vaping is not without risk. The 2019 EVALI outbreak highlighted the potential harms of vaping, and the consequences of long term use remain unknown.

Discussions regarding the potential harms of vaping are reminiscent of scientific debates about the health effects of cigarette use in the 1940s. Interesting parallels persist, including the fact that only a minority of conventional cigarette users develop acute lung injury, yet the health impact of sustained, longitudinal cigarette use is unquestioned. The true impact of vaping on respiratory health will manifest over the coming decades, but in the interval a prudent and time tested recommendation remains to abstain from consumption of inhaled nicotine and other products.

Questions for future research

How does chronic vape aerosol exposure affect respiratory health?

Does use of vape pens affect respiratory physiology (airway resistance, V/Q matching, etc) in those with underlying lung disease?

What is the role for vape pen use in promoting smoking cessation?

What is the significance of pulmonary alveolar macrophages in the pathophysiology of vaping related lung injury?

Are particular populations more susceptible to vaping related lung injury (ie, by sex, demographic, underlying comorbidity, or age)?

Series explanation: State of the Art Reviews are commissioned on the basis of their relevance to academics and specialists in the US and internationally. For this reason they are written predominantly by US authors

Contributors: AJ conceived of, researched, and wrote the piece. She is the guarantor.

Competing interests: I have read and understood the BMJ policy on declaration of interests and declare the following interests: AJ receives consulting fees from DawnLight, Inc for work unrelated to this piece.

Patient involvement: No patients were directly involved in the creation of this article.

Provenance and peer review: Commissioned; externally peer reviewed.

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Small study looks at chronic e-cigarette users, seeing partial improvement once they stop

Chronic use of e-cigarettes, commonly known as vaping, can result in small airway obstruction and asthma-like symptoms, according to researchers at Harvard-affiliated Massachusetts General Hospital.

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In the first study to microscopically evaluate the pulmonary tissue of e-cigarette users for chronic disease, the team found in a small sample of patients fibrosis and damage in the small airways, similar to the chemical inhalation damage to the lungs typically seen in soldiers returning from overseas conflicts who had inhaled mustard or similar types of noxious gases. The study was published in  New England Journal of Medicine Evidence .

“All four individuals we studied had injury localized to the same anatomic location within the lung, manifesting as small airway-centered fibrosis with constrictive bronchiolitis, which was attributed to vaping after thorough clinical evaluations excluded other possible causes,” says lead author Lida Hariri, an associate professor of pathology at Harvard Medical School and a pathologist and physician investigator at MGH. “We also observed that when patients ceased vaping, they had a partial reversal of the condition over one to four years, though not complete due to residual scarring in the lung tissue.”

A huge increase in vaping, particularly among young adults and adolescents, has occurred in the United States, with studies showing about 9 percent of the population and nearly 28 percent of high school students are e-cigarette users. Unlike cigarette smoking, however, the long-term health risks of chronic vaping are largely unknown.

In order to determine the underlying pathophysiology of vaping-related symptoms, the MGH team examined a cohort of four patients, each with a three- to eight-year history of e-cigarette use and chronic lung disease. All patients underwent detailed clinical evaluation, including pulmonary function tests, high resolution chest imaging, and surgical lung biopsy. Constrictive bronchiolitis, or narrowing of the small airways due to fibrosis within the bronchiolar wall, was observed in each patient. So was significant overexpression of MUC5AC, a gel-forming protein in the mucus layer of the airway that has been seen in airway cell and sputum samples of individuals who vape. In addition, three of the four patients had evidence of mild emphysema consistent with their former combustible cigarette smoking history, though researchers concluded this was distinct from the findings of constrictive bronchiolitis seen in the patient cohort.

Because the same type of lung damage was observed in all patients, as well as partial improvement in symptoms after e-cigarette usage was stopped, researchers concluded that vaping was the most likely cause after thorough evaluation and exclusion of other possible causes. “Our investigation shows that chronic pathological abnormalities can occur in vaping exposure,” says senior author David Christiani, a professor of medicine at HMS and a physician investigator at Mass General Research Institute. “Physicians need to be informed by scientific evidence when advising patients about the potential harm of long-term vaping, and this work adds to a growing body of toxicological evidence that nicotine vaping exposures can harm the lung.”

A hopeful sign from the study was that three of the four patients showed improvements in their pulmonary function tests and high-resolution computed tomography (HRCT) chest imaging after they ceased vaping. “While there is growing evidence to show that vaping is a risky behavior with potential long-term health consequences for users,” says Hariri, “our research also suggests that quitting can be beneficial and help to reverse some of the disease.”

The study was funded by the National Institutes of Health.

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News releases.

News Release

Tuesday, December 15, 2020

Study finds surge of teen vaping levels off, but remains high in early 2020

Findings are from the annual Monitoring the Future survey

Findings released today from the most recent Monitoring the Future (MTF) survey of substance use behaviors and related attitudes among teens in the United States indicate that levels of nicotine and marijuana vaping did not increase from 2019 to early 2020, although they remain high. The annual MTF survey is conducted by the University of Michigan’s Institute for Social Research, Ann Arbor, and is funded by the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health.

In the four years since the survey began including questions on nicotine and marijuana vaping, use of these substances among teens have increased to markedly high levels From 2017 to 2019, the percentage of teenagers who said they vaped nicotine in the past 12 months roughly doubled for eighth graders from 7.5% to 16.5%, for 10th graders from 15.8% to 30.7%, and for 12th graders from 18.8% to 35.3%. In 2020, the rates held steady at a respective 16.6%, 30.7%, and 34.5%. 

“The rapid rise of teen nicotine vaping in recent years has been unprecedented and deeply concerning since we know that nicotine is highly addictive and can be delivered at high doses by vaping devices, which may also contain other toxic chemicals that may be harmful when inhaled,” said NIDA Director Nora D. Volkow, M.D. “It is encouraging to see a leveling off of this trend though the rates still remain very high.”

Past-year vaping of marijuana also remained steady in 2020, with 8.1% of eighth graders, 19.1% of 10th graders, and 22.1% of 12th graders reporting past-year use, following a two-fold increase over the past two years. Additionally, daily marijuana vaping significantly decreased among 10th graders from 3% in 2019 to 1.7% in 2020.

Survey results also showed that reported use of JUUL vaping devices (also known as e-cigarettes), which contain nicotine and were previously the most popular brand among teens, significantly decreased from 2019 to 2020 among the older two grades. In 10th graders, past 12-month use of JUUL vaping devices decreased from 28.7% in 2019 to 20% in 2020 and in 12th graders, it decreased from 28.4% in 2019 to 22.7% in 2020.

The MTF survey is given annually to students in eighth, 10th, and 12th grade who self-report their substance use behaviors over various prevalence periods: daily, past 30 days, past 12 months and lifetime. The survey also documents students’ perception of harm, disapproval of use, and perceived availability of drugs. The survey results are released the same year the data are collected.

From February 11 through March 14, 2020, the MTF survey investigators collected 11,821 surveys in 112 schools before data collection stopped prematurely due to the COVID-19 pandemic. While the completed surveys from early 2020 represent about 25% of the sample size of a typical year’s data collection, the results were gathered from a broad geographic and representative sample, so the data were statistically weighted to provide national numbers. Estimates from MTF may differ from other government surveys due to differences in study population, questionnaire language and other factors. Study investigators are working with schools to deploy the survey in early 2021 to gather data that will reflect substance use during the COVID-19 pandemic and related periods of social distancing.

MTF researchers also conducted an in-depth analysis of a subset of the 2020 MTF data, combining 10th and 12th graders into a sample of 8,660 high schoolers, which was published today in JAMA Pediatrics . The percentage of combined 10th and 12th graders who said they vaped nicotine in the past 30 days, past 12 months, or over the course of their lifetime were similar from 2019 to 2020, at 22%, 32%, and 41% respectively. Similarly, in this group, daily, or near daily (20 or more occasions in the past 30 days), nicotine vaping declined from 9% to 7% from 2019 to 2020. Overall, investigators concluded nicotine vaping for participants in these two grades remained steady despite decreases in use of previously popular brands like JUUL because teens moved to use of other vaping device brands, such as disposable, single use vaping devices. This and other data on trends in vaping brands used, perceived availability of vaping devices, and perceived risk of vaping from this subset of teens were published today in the same study.

Other highlights:

  • The use of marijuana (in all forms, including smoking and vaping), the most commonly used illicit drug by adolescents, did not significantly change in any of the three grades for lifetime use, past 12-month use, past 30-day use, and daily use from 2019–2020.
  • Alcohol use has not significantly changed over the past five years. However, across all grades, alcohol use in the past 12 months has leveled off from its historical gradual decline.
  • Past year non-medical use of amphetamines among eighth graders increased from 3.5% in 2017 to 5.3% in 2020. However, 10th and 12th graders reported recent lows in past year use at 4.3% for both grades and significant 5-year declines.
  • Among eighth graders, past 12-month use of inhalants has increased from 3.8% in 2016 to 6.1% in 2020, a 64% proportional increase, unlike 12th graders, who reported an all-time low use of inhalants.
  • Cigarette smoking in the last 30 days did not significantly change from 2019 to 2020. In all three grades, prevalence has dropped at least four-fold since the mid-1990s and is at or near historic lows.
  • Past year use of over-the-counter cough medicine among eighth graders has gradually increased over the past five years, from 1.6% in 2015 to 4.6% in 2020, its highest rate since 2006.
  • The percent of students reporting past year use of other drugs remains relatively low among 12th graders: 3.9% for LSD; 2.4% for synthetic cannabinoids; 2.9% for cocaine; 1.8% for MDMA (ecstasy); 1.4% for methamphetamine; and 0.3% for heroin.

Detailed tables of the 2020 MTF data can be found online here .

The subset analysis of 10 th and 12 th grader nicotine vaping data published today in JAMA Pediatrics is titled Trends in Use and Perceptions of Nicotine Vaping Among U.S. Youth; National Estimates 2017–2020 .

NIDA has provided grant (DA001411) funding for the MTF survey since its inception in 1975. For additional information on the MTF Survey, including an infographic, NIDA Director’s blog, and other related information, go to: NIDA’s Monitoring the Future webpage .

Follow Monitoring the Future 2020 news on Twitter at @NIDAnews or join the conversation by using: #MTF2020. Information on all drugs can be found on NIDA’s website .

About the National Institute on Drug Abuse (NIDA): NIDA is a component of the National Institutes of Health, U.S. Department of Health and Human Services. NIDA supports most of the world’s research on the health aspects of drug use and addiction. The Institute carries out a large variety of programs to inform policy, improve practice, and advance addiction science. For more information about NIDA and its programs, visit www.drugabuse.gov .

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov .

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On December 17, a data processing error was found, which misrepresented the scope of the decreases in daily or near-daily vaping of nicotine, marijuana, and just flavoring. The release has been updated to reflect the correct data. 

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Vaping in adolescents: epidemiology and respiratory harm

Eric stephen hamberger.

a Division of Pediatric Pulmonology and Sleep Medicine, Department of Pediatrics, UCLA, Los Angeles

Bonnie Halpern-Felsher

b Division of Adolescent Medicine, Department of Pediatrics, Stanford University, Palo Alto, California, USA

Purpose of review

This review highlights epidemiologic changes in e-cigarette use in adolescents, discusses recent advances in aerosolized nicotine delivery, and provides and updated profile of research related to the lung-specific harm of e-cigarettes.

Recent findings

In the past decade, nicotine-containing e-cigarettes have emerged as the most popular tobacco and nicotine delivery modality among adolescents in the United States. 1 The surge in popularity of these devices has coincided with an outbreak of vaping-related lung injury, bringing e-cigarette use to national attention, and creating a great deal of confusion regarding their potential for respiratory harm. Newer pod-based devices and formulations of e-liquids have resulted in products appeal to youth and deliver nicotine with increasing efficiency. E-liquid aerosols are associated with direct harm to respiratory epithelium and have been shown to alter pulmonary function, inflammation, mucociliary clearance, and lung histology.

Although the long-term harms of regular e-cigarette use are unknown, numerous studies including early longitudinal data suggest e-cigarette use is associated with incidence of respiratory disease, independent of concurrent traditional cigarette use. Improved understanding and recognition of harm will contribute to the basis of further studies examining the role of e-cigarettes on chronic respiratory disease and will inform future prevention education.

INTRODUCTION: E-CIGARETTE USE IN ADOLESCENTS IN THE UNITED STATES

Since their introduction to the United States tobacco market in 2007, e-cigarettes have gained widespread popularity among adolescents. Although they were originally developed as a tobacco cessation tool, vaping has become pervasive among middle and high school students, with epidemic rates of e-cigarette use observed starting in 2017. Although combustible cigarette use among youth began a precipitous decline since the late 1990s, e-cigarette use among high school students surpassed combustible tobacco use for the first time in 2014, a trend that continued to widen into 2020 [ 1 ].

Monitoring the future surveys of over 43 000 students throughout the US report yearly rises in nicotine vaping among middle and high school students since 2016, the largest increase of which occurred between 2017 and 2018. During this time period, past-12-month use of electronic cigarettes nearly doubled among 12th graders, from 11% to 21%, representing the greatest increase in use of any substance recorded in all Monitoring the Future data [2 ▪▪ ]. By 2019, 35% of 12th graders reported past-12-month use of e-cigarettes, with approximately 1 in 4 reporting past-30-day use, and 1 in 9 reporting daily use [ 3▪▪ ].

Following the 2018 Monitoring the Future report, the US Surgeon General Dr Jerome Adams and the then FDA Commissioner Dr Scott Gotlieb declared e-cigarette use among adolescents an ‘epidemic.’ Despite national attention, vaping among adolescents continued to rise in the United States. JUUL, a pod-based e-cigarette that uses its proprietary cartridge-based nicotine controlled approximately 70% of the US e-cigarette market at that time. The rapid rise in prevalence of Juul pods, which contain the amount of nicotine found in 1.5–2 packs of cigarettes [ 4 ], was attributed to the rise in adolescent e-cigarette usage and resultant numbers of youth addicted to nicotine.

Over 60% of middle and high school students participating in the 2019 National Youth Tobacco Survey named JUUL as their primary e-cigarette brand, with the next highest brand SMOK named by 7.8% of participants. Flavored e-cigarettes were preferred by 59% and 72% of middle and high school exclusive e-cigarette users, respectively, with the most common categories being fruit (66.1%), ‘mint or menthol’ (57.3%), and ‘candy, desserts, or other treats’ (34.9%). Mint or menthol flavors were shown to have the greatest increase in overall use, tripling from 2016 to 2019, and nearing popularity of fruit-based flavors by 2019 [ 1 ].

SMOKING CESSATION, INITIATION, AND RISK PERCEPTION

The focus of e-cigarette use has been divided into two subtypes of users: active smokers seeking to quit traditional cigarettes, and recreational users. In the former, e-cigarettes have been acknowledged by many as an effective tool for smoking cessation. When compared to other forms of nicotine-replacement therapy (NRT), e-cigarettes have been found to be modestly effective at best in helping smokers achieve abstinence from cigarettes.

A 2013 study published in The Lancet showed similar rates of abstinence in adult smokers using e-cigarettes compared to nicotine patches, with abstinence defined as use of fewer than 6 cigarettes smoked in the 6-month follow-up period. The overall rate of abstinence reached a rate of 7.3% in the e-cigarette group [ 5 ]. However the question of whether e-cigarettes could provide long-term abstinence remained unanswered. A 2019 randomized controlled trial published in The New England Journal of Medicine attempted to address this question by comparing one-year abstinence rates in smokers assigned to either nicotine-containing e-cigarettes or other forms of NRT such as patches or gum, both in conjunction with cognitive behavioral support. This study reported 18% abstinence in the e-cigarette group compared to 9.9% in the NRT group, suggesting that e-cigarettes may be more effective than other forms of NRT when combined with individualized therapy [ 6▪ ]. However, 80% of users in the e-cigarette group who reported abstinence continued to vape at 52 weeks compared to 9% of successful NRT-group participants. As such, people were more likely to switch from one tobacco product (cigarettes) to another (e-cigarettes), rather than quit nicotine and tobacco altogether. A recent study by Gomajee et al. [ 7 ] has suggested that continued use of e-cigarettes by former smokers is associated with reinitiation of cigarette smoking.

With regard to recreational users, a specific focus on youth vaping culture has emphasized the potential for nicotine addiction in youth who have never smoked traditional cigarettes [ 8 ]. Monitoring the Future data from 2019 showed a two-fold likelihood of ever-use of e-cigarettes compared to combustibles and five-fold prevalence of past-month use among 12th graders [ 9▪▪ ]. The relationship between vaping and cigarette smoking initiation has been a subject of scrutiny in recent years, with numerous studies reporting a correlation between e-cigarette exposure and uptake of cigarette smoking among adolescents and young adults [ 10 – 12 ]. A 2018 report from the National Academies of Sciences, Engineering, and Medicine states, ‘There is substantial evidence that e-cigarette use increases risk of ever using combustible tobacco cigarettes among youth and young adults’ [ 13 ]. Nonetheless, a causative relationship between e-cigarette use and smoking initiation remains unclear. A 2019 analysis of youth tobacco trends challenge this assertion, citing an acceleration in the decline of past-30-day smoking after 2014 that coincides with a rise in youth vaping nationally [ 14 ]. However, it is unlikely that the reduction in cigarette use in the United States is because of the increase in e-cigarette use, especially since the decline in cigarette use among adolescents began in the 1990s, well before e-cigarettes came on the US market.

In adolescents, flavors, marketing, and lower perceived risk are thought to play a key role in initiation of vaping, due in large part to unfamiliarity with newer products and lack of prevention education. Adolescent responses in a 2015 survey-based study by Roditis et al. [ 15 ] embodied many common misperceptions about e-cigarettes, with some participants believing that aerosols from e-liquids are less addictive than traditional cigarettes and others stating that e-liquids do not contain any nicotine. In a 2018 study examining perceived health risks of pod-based devices, short-term and long-term health risks did not differ between pod-based and other e-cigarette devices [ 16 ]. However, risk perceptions among adults in two national surveys between 2012 and 2017 showed an increase in perceived harm, suggesting that risk perception will continue to improve over time [ 17 ].

NICOTINE DELIVERY AND MODERN DEVICES

An inherent problem in early vaping research arises from an evolving and largely heterogenous e-cigarette market. Although traditional cigarettes may contain small variations in nicotine content and packaging, combustible products are fairly homogenous. Vaping devices, on the other hand, have substantial differences in percentage nicotine content, formulation of nicotine (free-based vs. newer salt-based), e-liquid tank size, efficiency of nicotine delivery, device voltage, and other variables. Research continues to lag behind innovations in nicotine delivery. Although some products may contain a high concentration of nicotine, users may not achieve the same level of serum nicotine as they would from another device. Higher device voltage and alterations in solvent concentrations, for example, can produce drastically different aerosol delivery [ 18 ]. Such variations make research on dosage, nicotine concentration, addiction, perceived harm, flavors, and other factors extremely difficult.

A 2017 study found significant discrepancies in blood nicotine levels between different products among experienced e-cigarette users [ 19 ]. Blood nicotine levels in all e-cigarette products did not reach levels attained using combustible cigarettes; however, later generations of e-cigarette products such as Vuse and refillable e-cigarette brands resulted in significantly higher levels of serum nicotine when compared to first-generation ‘cig-a-likes’. The study suffered from large variations in vaping technique, user experience, and sample size. One study published in 2019 attempted to standardize vaping techniques between different devices and resulted in a similar pattern of greater serum concentrations after using advanced e-cigarettes when compared to first-generation devices [ 20 ]. A subsequent study by the same lead researchers showed greater and faster serum nicotine boosts in pod-based devices such as JUUL than both early generation cig-a-likes and advanced e-cigarette devices [ 21▪▪ ].

Pax Labs first received a US patent for its JUUL device in 2015 and has since overtaken its competitors as the dominant brand in the e-cigarette industry. The stated purpose of this patent was to allow for efficient plasma nicotine absorption while minimizing the harshness associated with inhalation of high concentrations of nicotine. By lowering the pH of e-liquids using a weak acid, users experience less bitterness allowing for nicotine concentrations 2–10 times greater than free-base nicotine contained in previous e-liquid formulations and resulting in greater plasma nicotine concentrations [ 22 ]. In addition to formula innovations, several elements of JUUL devices are attributed to their market dominance. Proprietary pods create a user-friendly experience as opposed to larger tank-based devices. They are also considerably smaller and easy to conceal. JUUL devices have the appearance of a USB flash drive. Design elements have drawn comparisons to popular tech products and has been referred to as the ‘iPhone of e-cigs’ [ 23 ].

RESPIRATORY HARM OF E-CIGARETTES

Most modern e-liquids contain three components: nicotine, a solvent, and a chemical flavorant. E-liquid solvents contain a propylene glycol and vegetable glycerin that determine properties of aerosolization based on the ratio of these components. Debate exists regarding the specific danger posed by solvents alone. Early studies of these components described propylene glycol as well tolerated when ingested; however, findings suggest that propylene glycol causes oral and nasal irritation, and minimal squamous cell metaplasia [ 24 ]. More recent studies have revealed potentially toxic effects in human cells [ 25 ].

Nicotine has long been known to have serious adverse effects to virtually every organ system, but can result in specific harm to lungs when inhaled [ 26 ]. Upon exposure to nicotine, parasympathetic ganglia are stimulated, causing bronchoconstriction and resulting in increased airway resistance in a dose-dependent manner and dysregulates central nervous system control of breathing through stimulation of nicotinic acetylcholine receptors [ 27 ]. Over time, nicotine can result in changes similar to chronic obstructive pulmonary disease by decreasing elastin and increasing volume of alveoli [ 26 ]. Similar findings were demonstrated in a 2016 study examining the effects of nicotine-containing e-liquids in the lung tissue of mice and humans. Pulmonary function testing of nicotine-exposed mice showed a FEF 50 /FVC ratio reduction from 23 to 15, suggesting small airway obstruction. Lung parenchyma analysis revealed morphology similar to emphysema with significant reduction in alveolar surface area and increase in alveolar volume [ 28 ].

Immune function may be significantly altered as well. Exposure to e-liquids has been shown to cause immunologic changes, resulting in significant derangements of the inflammasome, elevated macrophage numbers, and increased Caspase expression resulting in apoptosis [ 28 , 29 , 30▪ ]. Direct mucociliary dysfunction has been demonstrated through a variety of mechanisms in both in vitro and in vivo models [30 ▪ ], and nicotine-containing e-liquids have been shown to reduce ciliary beat frequency in human lung epithelial cells [ 28 ]. Aerosolized e-liquids result in acquired cystic fibrosis transmembrane conductance regulator dysfunction, indirectly impairing mucociliary clearance similar to combustible tobacco exposure [ 31▪ , 32 ].

The physiologic effects of flavors are highly variable given the enormous variety of available flavors in e-liquids. Artificial flavors can be chemically synthesized to replicate pleasing aromas or can be extracted directly from source components and thus properties of individual flavors determine specific toxicity to humans. Components in flavoring ingredients implicated to be harmful in humans include diacetyl and acetylpropionyl, which have been associated with toxic damage resulting in bronchiolitis obliterans [ 33 ]. Alpha-diketones have been shown in rodent studies to cause bronchial fibrosis with direct exposure [ 34 ]. It is important to note, however, that concentrations of these chemicals vary greatly depending on the flavorant itself and the method of synthesis or extraction, which can have drastically different effects on human lung tissue.

A 2018 study by Muthumalage et al. examined oxidative stress and inflammatory effects of common flavoring chemicals including acetoin, diacetyl, pentanedione, cinnamaldehyde, maltol, ortho-vanillin, and coumarin at various concentrations. Among these, cinnamaldehyde showed the greatest cytotoxic effect, although ortho-vanillin, pentanedione, and menthol derivatives also showed significant cytotoxicity. Expression of proinflammatory cytokine, Interleukin 8, known to play an important role the pathogenesis of cancer, was significantly increased when exposed to diacetyl, pentanedione, o-vanillin, maltol, coumarin, and cinnamaldehyde [ 35 ]. Cinnamaldehyde has been correlated with severe cytotoxicity in numerous other studies [ 25 , 36 , 37 ].

Long-term studies present a challenge in vaping research because of the relative novelty and evoling nature of these products. However, a 2019 longitudinal analysis examined the association of chronic respiratory disease (chronic obstructive pulmonary disease, chronic bronchitis, emphysema, or asthma) with e-cigarette use [ 38 ]. When controlled for combustible tobacco smoking, current e-cigarette use was associated with incidence of respiratory disease by a factor of a 1.29. This is among the first population-based longitudinal studies on the long-term harms of chronic e-cigarette use.

E-CIGARETTE OR VAPING PRODUCT USE-ASSOCIATED LUNG INJURY

Although not directly linked to commercial e-cigarette use, the recent epidemic of vaping-related illnesses merits discussion as it has brought e-cigarette use in adolescents to unprecedented levels of national attention. The e-cigarette or vaping product use-associated lung injury (EVALI) epidemic began in mid-2019 under mysterious circumstances, with seemingly random occurrences of acute respiratory failure in patients reporting recent vaping. By the end of 2019, more than 2500 EVALI cases had been reported from all 50 states, Washington, DC, Puerto Rico, and the US Virgin Islands, with 55 reported deaths [ 39▪ ]. Analysis of bronchial alveolar lavage fluid samples from 51 EVALI case patients revealed the presence of vitamin E-acetate in 94% of the samples [ 40 ]. Vitamin-E acetate is used as a diluent in THC-containing e-liquids sold primarily through illicit markets. To our knowledge, vitamin-E acetate is not a common ingredient or diluent in nonillicit commercially available e-liquids; however, more investigation is needed to verify this, and tests on the remaining samples from the remaining patients is sorely needed. Nonetheless, it is important to make the distinction between acute lung injury from illicit devices containing potentially fatal chemical adulterants and devices that pose a more insidious threat of nicotine addiction and long-term lung damage.

CONCLUSION: POPULATION-BASED BENEFITS VERSUS RISK

There now exists a divide between the potential risk of generation-wide nicotine addiction and the potential benefit of smoking cessation. A 2018 report by Public Health England (PHE) maintained that ‘vaping is at least 95% less harmful than smoking [cigarettes]’. Yet as recently as 2019, an update by PHE emphasizes risk reduction in adult smokers, while acknowledging the potential for youth initiation of e-cigarette [ 41 , 42 ]. This is in stark contrast to a 2019 report by the European Respiratory Society, that states ‘long-term effects of ECIG use are unknown, and there is therefore no evidence that ECIGs are safer than tobacco in the long term. Based on current knowledge, negative health effects cannot be ruled out [ 43 ].’ US organizations with vested interest in e-cigarette policy and youth lung health including the American Thoracic Society, the Centers for Disease Control and Prevention, the American Lung Association, and the American Association of Pediatrics, recommend alternative smoking cessation tools and advocate for tighter regulations and age restrictions for the purchase of e-cigarettes [ 44 , 45▪ , 46 , 47 ].

In recent years, a flood of data have emerged on nicotine-containing e-cigarette devices and their potential for respiratory harm and addiction. Much of the controversy surrounding e-cigarettes in adolescents stems from its relationship to traditional tobacco. Epidemiologic data in adolescents show a significant rise in e-cigarette use with concurrent decline in cigarette smoking within the past decade, however the decline in cigarette use started long before e-cigarettes entered the US market [ 2▪▪ ]. Further, the rate of rise in e-cigarette use among adolescents has far exceeded the already-low rate of traditional tobacco use. It stands to reason that the vast majority of adolescents in the present day would have never used combustible cigarettes, and thus comparisons of relative risk between the two products is not nearly as relevant to this population. Far more relevant is the observation that millions of adolescents are becoming addicted to nicotine at an unprecedented rate, using devices engineered to deliver aerosols with increasing efficiency, and undergoing a worldwide experiment in which the long-term effects are unknown.

  • Nicotine addiction among adolescents has experienced an unprecedented rise in the past decade due in large part to the emergence of electronic nicotine delivery systems known as e-cigarettes.
  • The rise in e-cigarette use has been attributed to numerous factors including small, sleek devices, technological advances in nicotine-salt formulations, and attractive flavors.
  • Respiratory harms associated with e-cigarette include changes to the inflammasome, delayed mucociliary clearance, impaired pulmonary function, and histologic alterations to the alveoli.
  • Although there are conflicting data on the efficacy of e-cigarettes as a smoking cessation tool, there is increasing evidence that inhalation of aerosolized e-liquids may have detrimental effects on lung health. Public misperception of harm plays a large role in increased use of e-cigarettes among youth.

Acknowledgements

We would like to thank Dr David Cornfield, Dr John Mark, and Dr MyMy Buu for their professional guidance and valued support. We would also like to thank Dr Cornfield for his invitation to review this topic.

Financial support and sponsorship

This work was supported by the Department of Pediatrics, Division of Pediatric Pulmonology and Sleep Medicine at UCLA, and the Department of Pediatrics, Division of Adolescent Medicine at Stanford University. Research reported in this study was made possible in part by grant number U54 HL147127 of the National Heart, Lung, and Blood Institute (NHLBI) and the Food and Drug Administration Center for Tobacco Products. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the Food and Drug Administration.

Conflicts of interest

There are no conflicts of interest.

REFERENCES AND RECOMMENDED READING

Papers of particular interest, published within the annual period of review, have been highlighted as:

▪ of special interest

▪▪ of outstanding interest

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New Study Reveals Young E-Cigarette Users Develop Wheezing, Other Respiratory Symptoms

CHICAGO, IL | February 8, 2022

A new study funded by the American Lung Association reveals that young adults who used e-cigarettes were more likely to develop respiratory issues within one year of vaping. The study, titled, “ Association of Electronic Cigarette Use with Respiratory Symptom Development among US Young Adults ,” will be published in the American Journal of Respiratory and Critical Care Medicine .

In the study, senior author  Andrew Stokes , Ph.D., from Boston University School of Public Health found that participants who used e-cigarettes had greater incidence of self-reported respiratory symptoms, such as wheezing, dry cough during sleeping and wheezing during exercise, within 12 months of use. These symptoms were reported regardless of former combustible cigarette use.

"The present study finds a significant prospective association of vaping with subsequent respiratory symptom development in a large, nationally representative cohort of young adults with no previous history of respiratory symptoms,” said Dr. Stokes. “This evidence highlights an urgent public health imperative for more robust regulatory standards at all levels of government to stop the youth vaping epidemic in its tracks."

Specifically, the study found that:

  • 32% greater odds of developing any respiratory symptom and 
  • 51% greater odds of developing wheezing in the chest. 
  • 20% greater odds of developing any respiratory symptom and 
  • 41% greater odds of developing wheezing in the chest. 

“This study provides more evidence that e-cigarettes are harmful to the lungs and that the U.S. Food and Drug Administration (FDA) needs to provide stronger public health protections from these products including removing all flavored products from the marketplace,” said Albert Rizzo, M.D., Chief Medical Officer for the American Lung Association. “This research adds further evidence that there is no safe e-cigarette and that vaping is harmful to your health.”

Additionally, the study reported that tobacco flavored e-cigarette users had 170% greater odds of developing any respiratory symptom compared to never users.

The Lung Association has called on the FDA to create a standard and define which chemicals should go into the tobacco flavored e-cigarettes. The organization recognizes that all flavors in e-cigarettes are additives and there is no “tobacco” flavor inherent in e-cigarettes.

This article used data from the PATH study (Population Assessment of Tobacco and Health), a longitudinal study tracking changes in tobacco use over time among participants. This article looked at young adults (aged 18-24 years) who were current or former e-cigarettes users and had no respiratory disease or symptoms prior to entering the study. 

Dr. Stokes is currently funded by the American Lung Association’s Public Policy Research Award, a new award empowering scientists to examine public policy issues that impact lung health. 

Learn more about the dangers of e-cigarettes at E-Cigarettes & Vaping | American Lung Association .

The American Lung Association is the leading organization working to save lives by improving lung health and preventing lung disease through education, advocacy and research. The work of the American Lung Association is focused on four strategic imperatives: to defeat lung cancer; to champion clean air for all; to improve the quality of life for those with lung disease and their families; and to create a tobacco-free future. For more information about the American Lung Association, which has a 4-star rating from Charity Navigator and is a Platinum-Level GuideStar Member, call 1-800-LUNGUSA (1-800-586-4872) or visit:  Lung.org.  To support the work of the American Lung Association, find a local event at  Lung.org/events.

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New Study Offers First Evidence Of Vaping's Long-Term Risks

Allison Aubrey - 2015 square

Allison Aubrey

The study finds that e-cigarettes are linked to increased risk of chronic lung diseases including emphysema, chronic bronchitis and COPD, as well as weakened immune defenses.

AUDIE CORNISH, HOST:

Fifty-two people have died, and more than 2,000 have been hospitalized this year because of lung injuries caused by vaping. The crisis has raised awareness about the larger problem of teen vaping. Now, while many of the worst cases have been linked to black market products that contain THC, new evidence suggests something more - that people who vape nicotine are more likely to get respiratory diseases, including chronic bronchitis and emphysema. NPR's Allison Aubrey reports.

ALLISON AUBREY, BYLINE: Early last year, one of the most comprehensive studies ever done pointed to evidence that teens who vape nicotine can experience increased coughing, wheezing and other short-term effects, such as asthma exacerbations. Now researchers are beginning to pin down the potential long-term risks. The new study finds that e-cigarettes are linked to an increased risk of chronic lung disease.

Stan Glantz, a professor of medicine at UC San Francisco, and his collaborators assessed data from a study of about 30,000 people, including smokers and people who vape.

STAN GLANTZ: We started out with people who didn't have any diagnosis of respiratory disease, and then we followed them forward in time for three years. And we said, is there an association between e-cigarette use and new respiratory disease?

AUBREY: During that time, people who used combustible products, such as cigarettes, had more than double the risk of being diagnosed with a respiratory disease, which is not surprising. But the more novel finding is that e-cigarettes had an independent effect. People in the study who only used e-cigarettes had about a 30% higher risk of developing chronic conditions, such as COPD, chronic bronchitis, emphysema or asthma. Glantz says the risks appear to be highest among adults who both vape and smoke, which often happens when people turn to vaping in an attempt to quit smoking but then aren't able to completely give up cigarettes.

GLANTZ: If you are a dual user - that is, if you're using cigarettes and e-cigarettes at the same time - these two risks multiply.

AUBREY: Given that e-cigarettes are relatively new, the long-term effects of vaping are just beginning to be understood, says Robert Tarran of the University of North Carolina, Chapel Hill. He says this study offers important evidence.

ROBERT TARRAN: I think it's fair to say that the new study adds to the body of evidence saying vaping e-cigarettes is harmful to the lungs.

AUBREY: It seems that e-cigarettes can harm the lungs in multiple ways. Vaping can lead to inflammation and tamp down immune defenses.

TARRAN: Vaping can do a lot to the lungs, so it can change inflammatory processes. And it actually seems to cause immunosuppression, so it leaves people more prone to infection.

AUBREY: He says it's not just the nicotine. There are other ingredients, including propylene glycol, glycerin and flavoring compounds, that may lead to harmful effects when heated and inhaled. Despite these risks, many argue that e-cigarettes still have a role to play in trying to help smokers reduce the risk of lung disease. Amy Fairchild is dean of the College of Public Health at The Ohio State University.

AMY FAIRCHILD: There is no question that vaping nicotine is not safe, but it is safer than inhaling burning tobacco.

AUBREY: This remains the key argument in favor of vaping - that it's less risky than smoking. But at a time when 1 in 4 high school seniors report vaping and are at risk of getting hooked on nicotine, the authors of the new paper argue the evidence pointing to the harms of e-cigarettes is starting to pile up.

Allison Aubrey, NPR News.

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Health Risks Of Vaping: Let's Stick To The Science And Speculate Less

Related articles.

most recent study on vaping

Despite increasing evidence that vaping is safer than smoking, uncertainty surrounds the long-term effects of electronic cigarette use. Many in the tobacco control field have used the lack of data to speculate about these unknown risks. Here's a better way to deal with the uncertainty.

most recent study on vaping

A growing body of evidence gathered over the last 15 years has shown that using an electronic cigarette ("vaping") is probably far safer than smoking and likely to help smokers quit their deadly habit forever. Certain segments of the public health establishment have reacted oddly to these results—they've ignored them and treated vaping as a serious threat. The American Heart Association, for example, has even called for e-cigarettes to be taxed and regulated as stringently as tobacco products are. [1]

Fortunately, this view doesn't seem to be as predominant as it once was; we're beginning to see more physicians, scientists, and public health organizations make statements based on the available science instead of what they think the evidence might show one day.

Consider this May 24 review article published in Prescriber : E-cigarettes: informing the conversation with patients  by Anna Kate Barton. The author, a clinical research fellow at the University of Edinburgh in the UK, helpfully outlined the history, anatomy, and science of e-cigarettes with the aim of helping doctors more knowledgeably discuss vaping with their patients. Compared to the typical news report about vaping —"Vaping is not better than smoking, and it still causes long-term lung damage"—Barton's article illustrated how we should talk about scientific issues when the evidence surrounding them is evolving. Let's consider a few examples.

Smoking cessation

What does the current evidence say about vaping and smoking cessation? ACSH has previously reported that vaping very likely helps smokers quit cigarettes, and maybe even nicotine , for good. Citing some of the same literature we have, Barton reached a similar conclusion about smoking cessation. While acknowledging the limitations of these studies ( discussed here ), she explained:

Patients using e-cigarettes also often report greater satisfaction and greater reduction in smoking than those using nicotine patches, and e-cigarettes are regarded as the most popular form of smoking cessation aid with smokers wishing to quit. Current position statements and the existing evidence base advocate their combination with stop smoking counseling, the most effective smoking cessation tool.

This comes down to a concept known as “ harm reduction .” Ideally, people would never take up smoking. But since they do, the goal should be to help them mitigate the risks when abstinence isn't feasible. More experts are beginning to embrace this approach in order to enhance smoking cessation campaigns, as Barton noted:

E-cigarettes as aids to smoking cessation are advocated by several organizations including Public Health England. This is based on the principle of risk-reduction – simply, e-cigarettes provide nicotine in a much safer form that traditional cigarettes. Although neither are entirely risk-free, e-cigarettes are generally accepted to confer less risk to both the user and passive smokers than traditional cigarettes.

Health risks of vaping

After contrasting the overall risk of vaping with smoking, Barton added that some preliminary studies have indeed associated e-cigarette use with various negative outcomes. For example, an onslaught of headlines in mid-2019 warned the public about an outbreak of “e-cigarette or vaping product use-associated lung injury” (EVALI). Under-reported at the time was the fact that the injury-causing devices were typically purchased illegally and contained THC or certain dangerous additives, which made them far more harmful than the nicotine-containing devices adult customers can legally purchase in licensed vape shops in the US and UK. Surveying the literature nearly two years later, we get a better sense of the problem:

Interestingly, 82% [of EVALI cases] reported use of THC-containing [vape] products. Vitamin E acetate is sometimes added as a condensing agent in e-liquid, particularly in those containing THC, and this has been associated with EVALI. As such, the CDC discourages use of THC-containing [vape products], particularly those sourced informally from family or friends.

The point, then, is that proper regulation and vigilance by individual users can minimize these types of injuries. The UK, where vaping has proven to be a similarly popular smoking cessation approach, “has not thus far experienced a similar epidemic of EVALI as the USA,” Barton added, though she mentioned two severe cases that apparently weren't related to THC or Vitamin E acetate .

About those long-term effects

Opponents of vaping often point to the dearth of research on its chronic health effects as a first line of criticism. This is a fair enough point, but I hasten to add that it cuts both ways. If we don't know the long-term effects of vaping, we don't know the long-term effects of vaping. “At present,” Barton observed in reference to chronic lung disease, “we can only reflect on potential consequences of 10–15 years of widespread e-cigarette use.”

But that's often not what tobacco control advocates do. “The long-term risks of exclusive use of e-cigarettes are not fully known,” The American Cancer Society claims, “but evidence is accumulating that e-cigarette use has negative effects on the cardiovascular system and lungs. Without immediate measures to stop epidemic use of these products, the long-term adverse health effects will increase.” Retired University of California, San Francisco tobacco researcher Stanton Glantz has even suggested that  e-cig users would “be better off just smoking.”

The impulse to reject anything tobacco-related is understandable. But we have to stick with the data we have, which suggests vaping is far safer than smoking, and wait for the long-term results to come in. What we can't do is minimize the existing evidence while simultaneously making statements about the future. Uncertainty is acceptable when we don't have enough evidence, as Barton wrote:

It seems unlikely that e-cigarettes will be without pathological consequences within the human lung and elsewhere, though when we will be able to prove or disprove this is less clear … Regular monitoring of suspected adverse events arising from e-cigarettes … will aid recognition of new complications in [the] future, though it is unlikely we will appreciate the full picture of any long-term harms until well into this century.

[1] The FDA classifies e-cigarettes as tobacco products, but this designation makes little sense. According to Nicotine and Tobacco Research , "If all products containing nicotine derived from tobacco were labeled as 'tobacco products' internationally, then nicotine-replacement therapies would be classified as tobacco products, which they are clearly not."

View the discussion thread.

most recent study on vaping

By Cameron English

Director of Bioscience 

Cameron English is a writer, editor and co-host of the Science Facts and Fallacies Podcast. Before joining ACSH, he was managing editor at the Genetic Literacy Project.

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Study: Vaping beats nicotine gum for smokers trying to quit

Whether it’s part of a New Year’s resolution or just following doctor’s orders, ditching cigarettes is easier said than done.

And while nicotine gum has long been available to help soothe the withdrawal cravings, a quitter could be better off vaping instead as a stop-gap, according to the results of a clinical trial published by the American Medical Association.

Smokers who turned to e-cigarettes to help them stop smoking were more likely to have stayed quit after 6 months than those who chewed gum, according to the research team, which included Queen Mary University in London and Peking University in Beijing.

The findings, which were carried in the journal JAMA Internal Medicine, showed 16% of the 1,100 people surveyed and who switched to e-cigarettes had stopped smoking after 6 months, compared with about 9% of those who tried nicotine chewing gum, which users often struggle with due to side effects such as nausea.

The researchers found no difference between using vapes and taking varenicline, a medication said to inhibit nicotine cravings.

But there is a downside: Those who took to vaping as a kind of halfway house were also likely 6 months later to be still vaping - which, the researchers, said, brings with it separate health concerns.

In contrast, those who took to the other quit methods covered by the trial - chewing nicotine gum or taking medication - were weaned off those methods a half year later.

According to a study published in the journal Nature in mid-February, some negative effects of smoking on the human immune system can linger long after someone quits.

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Study finds vaping renders frontline immune cells unable to move to meet threats

by University of Birmingham

Vaping

Inhaling vapor from an e-cigarette may be stopping frontline immune cells from working typically, as a new study shows that even moderate smoke exposure suppresses cell activity.

The findings are published in the Journal of Allergy and Clinical Immunology and suggest that inhaling e-cigarette smoke could be damaging neutrophils, the first line of defense in the human immune system. The findings are important as previous research has shown that damage caused to neutrophil by cigarette smoking can lead to long-term lung damage.

Researchers from the University of Birmingham took blood samples from healthy donors who had never smoked or vaped. The team then exposed neutrophils taken from the blood to 40 puffs of unflavored vape, which previous studies have shown is a low daily exposure; with half of the samples were exposed to nicotine-containing vapor while the rest to nicotine-free alternatives.

Results of the tests showed that in both the nicotine and non-nicotine groups, the neutrophils remained alive but were stuck in place, rendering them incapable of effectively tackling threats to the body.

Dr. Aaron Scott, associate professor in respiratory science at the University of Birmingham and lead author of the study said, "We found that after short, low-level exposure to e-cigarette vapor, the cells remain alive but can no longer move as effectively and are unable to carry out their normal protective functions. Interestingly, vapor from e-liquids which did not contain nicotine also had the same negative effects as vapor from e-liquids which did contain nicotine.

"E-cigarettes are a proven, lower harm, tool to help smokers quit smoking but our data adds to current evidence that e-cigarettes are not harmless and highlights the need for to fund longer-term studies in vapers."

Further experiments with neutrophils exposed to e-cigarette vapor suggest a build-up of a microfilament within the cells which are unable to re-arrange themselves properly is driving the suppression of the cells normal function.

Actin is usually found as small filaments within cells and rearrange themselves into a network to help a cell change its shape. This function is used by neutrophils so that they can move towards and surround threats to destroy them.

The team observed that there were high concentrations of the filament F-actin within the neutrophils that had been exposed to e-cigarette vapor, whether containing nicotine or not. The accumulation of the F-actin resulted in the immune cells being less able to move and function typically.

David Thickett, professor in respiratory medicine at the University of Birmingham, Clinical Lead for the University Hospitals Birmingham (UHB), NHS Foundation Trust, and a co-author of the paper said, "Neutrophils normally protect the lungs by moving from the blood to the site of possible harm before using a number of protective functions to protect the lung. The observed impact that e-cigarette vapor had on their mobility is therefore of significant concern, and if this were to happen in the body would make those who regularly use e-cigarettes at greater risk of respiratory diseases."

Professor Liz Sapey, director of the Institute of Inflammation and Aging at the University of Birmingham and honorary acute medicine and respiratory consultant physician at UHB, and a co-author of the paper said, "Smoking has a well-documented impact on neutrophils , and this study further shows the impact that e-cigarettes still have on the immune system. Neutrophils are heavily implicated in aging and chronic obstructive disease and their relationship with tissue damage , and the impact of vaping in suppressing neutrophil activity regardless of nicotine could have long term implications for health."

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First long-term study finds e-cigarettes significantly increase the risk of chronic lung disease

Researchers are reporting that the use of e-cigarettes significantly increases a person’s risk of developing chronic lung diseases like asthma, bronchitis, emphysema, or chronic obstructive pulmonary disease (COPD). The finding represents the first long-term study that links e-cigarettes to respiratory illness in a sample representative of the entire U.S. adult population. The study also found that people who used e-cigarettes and also smoked tobacco -- by far the most common pattern among adult e-cigarette users -- were at an even higher risk of developing chronic lung disease than those who used either product alone. The findings were published in the American Journal of Preventive Medicine and are based on an analysis of publicly available data from the Population Assessment of Tobacco and Health (PATH), which tracked e-cigarette and tobacco habits as well as new lung disease diagnoses in over 32,000 American adults from 2013 to 2016. The study is funded in part by the NHLBI.

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Smoking e-cigarettes a possible strategy in quitting tobacco cigarettes, study suggests

Vaping, combined with smoking-cessation counseling, may be more helpful than...

Vaping, combined with smoking-cessation counseling, may be more helpful than counceling alone, a new study suggests. Credit: AP/Robert F. Bukaty

A new study suggests that, for smokers who want to quit, e-cigarettes used in combination with smoking-cessation counseling may be more helpful than counseling alone.

Most smokers say they want to quit, but fewer than one in 10 succeed in quitting each year, according to the U.S. Centers for Disease Control and Prevention. The odds improve with conventional smoking-cessation therapy, which may include cognitive behavioral therapy, motivational interviewing and shared decision-making with a health care professional about smoking cessation drugs or nicotine-replacement therapies, experts say. 

Even then, at the end of the six-month study, only 38.5% of participants in a control group who used only those combined strategies were abstaining from tobacco cigarettes, said Dr. Reto Auer, lead author of the study, which was published Wednesday in the New England Journal of Medicine. For an intervention group that used the combined strategies along with an electronic nicotine-delivery system — commonly known as a vape or e-cigarette — the percentage of abstainers jumped to 59.6.

“This is wonderful news for smokers,” said Auer, a primary care physician and clinical researcher who teaches at the Institute of Primary Health Care at the University of Bern, Switzerland. “We found a significant increase in the proportion of people who quit smoking.”

That news comes with a big caveat, though. Former smokers “might not die” from that habit anymore, Auer said, but they may “continue to be in addictive behavior” if they replace tobacco cigarettes with e-cigarettes. The CDC says that e-cigarettes are safer than cigarettes, but not necessarily safe. The aerosol they use includes not just nicotine but heavy metals like lead, volatile organic compounds and cancer-causing agents.

The study was the largest yet comparing the effectiveness of e-cigarettes used in combination with smoking-cessation therapy with smoking-cessation therapy alone, Auer said.

It included 1,246 adult participants who were smoking at least five cigarettes a day but wanted to set a quit date. At regular intervals over six months, the control group got standard-of-care smoking-cessation counseling. The intervention group got the counseling plus two “e-cigarette starter kits” with a choice of free e-liquid flavors and nicotine concentrations. They were allowed to use the devices at will and replenish them.

While the difference between the number of control and intervention participants who quit smoking was significant, so was the difference in the number of those participants who were using e-cigarettes at the six-month mark.

Nearly half of the participants in the intervention group were using e-cigarettes exclusively, versus just 3% of those in the control group. There was also a stark difference among those who abstained from both tobacco and e-cigarettes. Just 11.2% of those in the intervention group achieved that feat, versus 35.5 % of those in the control group.

In New York, where a 2021 state Department of Health survey found that more than a fifth of high school students reported using e-cigarettes during the past month, experts reacted cautiously.

“You could argue that switching from cigarettes to vapes is good, because that’s harm reduction, but then you could make the argument that vaping in general is harmful,” said Northwell Health’s Dr. Richard Stumacher, associate chief medical officer for Northern Westchester Hospital and former head of pulmonary critical care there. “Lungs were designed to inhale only one thing, and that’s air. They’re designed to tolerate insults like smoke or other chemicals for a short period of time, not on an ongoing basis.”

Stumacher said e-cigarettes could be a tool for quitting. The rapid onset of nicotine they deliver mimics the experience of smoking more closely than most other nicotine replacement therapies now in use, making the devices potentially useful but carrying addictive risk.

As a tool, it needs to be used “with guidance, with someone who knows what they’re doing, with a product that’s vetted,” with an aim of reducing nicotine intake, he said. But the vaping industry is largely unregulated, and scientists need more time — “something on the order of 20-plus years” — to fully understand the potential damage that e-cigarette use may cause to the human body, Stumacher said.

Dr. Rachel Boykan, a pediatrician and professor of clinical pediatrics at the Renaissance School of Medicine at Stony Brook University, called the study results “promising” but said there were “inherent concerns with using these very high nicotine content devices to stop tobacco smoking.”

Long-term data already in the scientific literature suggest that “people don’t quit nicotine using these products,” she said. And, for young people, their use should be out of the question, she said. “We know nicotine interferes with brain function. It impacts cognitive development at a crucial time, it contributes to anxiety, depression, ADHD,” she said.

Tony Abboud, executive director of Vapor Technology Association, an industry group, said in a statement that the study joined a “growing body of research that proves how helpful and successful e-cigarettes can be to adults who would like to quit smoking.”

Some earlier research supports a measured approach, though. A 2021 American Journal of Public Health meta-analysis of 64 scientific papers about the association between e-cigarette use and smoking cessation concluded that the devices should not be approved as consumer products but might “warrant consideration as a prescription therapy.” 

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  1. Current evidence identifies health risks of e-cigarette use; long-term

    One recent analysis of the adult Population Assessment of Tobacco and Health (PATH) study found a statistically significant association between former or current e-cigarette use at the time participants enrolled in the study and the development of incident respiratory disease (chronic obstructive pulmonary disease/COPD, chronic bronchitis, emphy...

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  8. New study links vaping to increased respiratory symptoms in young

    New study links vaping to increased respiratory symptoms in young adults August 15, 2023 Young people who use electronic cigarettes or vape report increased respiratory symptoms, including wheezing and shortness of breath, compared to those who don't use e-cigarettes, according to a new study.

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  12. Vaping in adolescents: epidemiology and respiratory harm

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  17. People who vape had worrisome changes in cardiovascular function, even

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  18. Health Risks Of Vaping: Let's Stick To The Science And Speculate Less

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  25. Study finds vaping renders frontline immune cells unable to move to

    Study finds vaping renders frontline immune cells unable to move to meet threats. Inhaling vapor from an e-cigarette may be stopping frontline immune cells from working typically, as a new study ...

  26. First long-term study finds e-cigarettes significantly increase the

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