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Impact of vaping on respiratory health

Linked editorial.

Protecting children from harms of vaping

• Related content
• Peer review
• Andrea Jonas , clinical assistant professor
• Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, Stanford University, Stanford, CA, USA
• Correspondence to A Jonas andreajonas{at}stanford.edu

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 Teens and young adults have seen the biggest uptake in use of vape pens, which have superseded conventional cigarettes as the preferred modality of nicotine consumption.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.

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.

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

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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Restricted airways, scarred lung tissue found among vapers

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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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NIH-funded studies show damaging effects of vaping, smoking on blood vessels

Combining e-cigarettes with regular cigarettes may increase health risks     

Long-term use of electronic cigarettes, or vaping products, can significantly impair the function of the body’s blood vessels, increasing the risk for cardiovascular disease. Additionally, the use of both e-cigarettes and regular cigarettes may cause an even greater risk than the use of either of these products alone. These findings come from two new studies supported by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health (NIH).  

The findings, which appear today in the journal Arteriosclerosis, Thrombosis, and Vascular Biology , add to growing evidence that long-term use of e-cigarettes can harm a person’s health. Researchers have known for years that tobacco smoking can cause damage to blood vessels. However, the effects of e-cigarettes on cardiovascular health have been poorly understood. The two new studies – one on humans, the other on rats – aimed to change that.

“In our human study, we found that chronic e-cigarettes users had impaired blood vessel function, which may put them at increased risk for heart disease,” said Matthew L. Springer, Ph.D., a professor of medicine in the Division of Cardiology at the University of California in San Francisco, and leader of both studies. “It indicates that chronic users of e-cigarettes may experience a risk of vascular disease similar to that of chronic smokers.” 

In this first study, Springer and his colleagues collected blood samples from a group of 120 volunteers that included those with long-term e-cigarette use, long-term cigarette smoking, and those who didn't use. The researchers defined long-term e-cigarette use as more than five times/week for more than three months and defined long-term cigarette use as smoking more than five cigarettes per day.

They then exposed each of the blood samples to cultured human blood vessel (endothelial) cells in the laboratory and measured the release of nitric oxide, a chemical marker used to evaluate proper functioning of endothelial cells. They also tested cell permeability, the ability of molecules to pass through a layer of cells to the other side. Too much permeability makes vessels leaky, which impairs function and increases the risk for cardiovascular disease.

The researchers found that blood from participants who used e-cigarettes and those who smoked caused a significantly greater decrease in nitric oxide production by the blood vessel cells than the blood of nonusers. Notably, the researchers found that blood from those who used e-cigarettes also caused more permeability in the blood vessel cells than the blood from both those who smoked cigarettes and nonusers. Blood from those that used e-cigarettes also caused a greater release of hydrogen peroxide by the blood vessel cells than the blood of the nonusers. Each of these three factors can contribute to impairment of blood vessel function in people who use e-cigarettes, the researchers said.

In addition, Springer and his team discovered that e-cigarettes had harmful cardiovascular effects in ways that were different from those caused by tobacco smoke. Specifically, they found that blood from people who smoked cigarettes had higher levels of certain circulating biomarkers of cardiovascular risks, and the blood people who used e-cigarettes had elevated levels of other circulating biomarkers of cardiovascular risks.

“These findings suggest that using the two products together, as many people do, could increase their health risks compared to using them individually,” Springer said.  “We had not expected to see that.”

In the second study, the researchers tried to find out if there were specific components of cigarette smoke or e-cigarette vapor that were responsible for blood vessel damage. In studies using rats, they exposed the animals to various substances found in tobacco smoke or e-cigarettes. These included nicotine, menthol (a cigarette additive), the gases acrolein and acetaldehyde (two chemicals found in both tobacco smoke and e-cigarette vapors), and inert carbon nanoparticles to represent the particle-like nature of smoke and e-cigarette vapor.

Using special arterial flow measurements, the researchers demonstrated that blood vessel damage does not appear to be caused by a specific component of cigarette smoke or e-cigarette vapor. Instead, they said, it appears to be caused by airway irritation that triggers biological signals in the vagus nerve that somehow leads to blood vessel damage, possibly through an inflammatory process. The vagus is a long nerve extending from the brain that connects the airway to the rest of the nervous system and plays a key role in heart rate, breathing, and other functions. The researchers showed that detaching the nerve in rats prevented blood vessel damage caused by tobacco smoke, demonstrating its key role in this process. 

“We were surprised to find that there was not a single component that you could remove to stop the damaging effect of smoke or vapors on the blood vessels,” Springer said. “As long as there’s an irritant in the airway, blood vessel function may be impaired.”   

The finding has implications for efforts to regulate tobacco products and e-cigarettes, as it underscores how difficult it is to pinpoint any one ingredient in them that is responsible for blood vessel damage. “What I like to tell people is this: Just breathe clean air and avoid using these products,” Springer said.

Lisa Postow, Ph.D., an NHLBI program officer in NHLBI’s Division of Lung Diseases, agreed that the study results “provide further evidence that exposure to e-cigarettes could lead to harmful cardiovascular health effects.” She added that more data is needed to fully understand the health effects of e-cigarettes. The NIH and others are continuing to explore this area.

Research reported in the e-cigarette study was funded by NHLBI grants U54HL147127, P50HL120163, and R01HL120062 and the U.S. Food and Drug Administration Center for Tobacco Products (FDA CTP); and grant P50CA180890 from the National Cancer Institute at the NIH and FDA CTP. Research reported in the cigarette smoke/-vagal nerve study was supported by NHLBI grants R01HL120062 and U54HL147127 and FDA CTP and grant P50CA180890 from the National Cancer Institute at the NIH and FDA CTP. For additional funding details, please see the full journal articles.

Study: Chronic e-cigarette use impairs endothelial function on the physiological and cellular levels. Arteriosclerosis, Thrombosis, and Vascular Biology.  DOI: 10.1161/ATVBAHA.121.317749

Study:  Impairment of Endothelial Function by Cigarette Smoke is not Caused by a Specific Smoke Constituent, but by Vagal Input from the Airway. Arteriosclerosis, Thrombosis, and Vascular Biology. DOI: 10.1161/ATVBAHA.122.318051

About the National Heart, Lung, and Blood Institute (NHLBI):  NHLBI is the global leader in conducting and supporting research in heart, lung, and blood diseases and sleep disorders that advances scientific knowledge, improves public health, and saves lives. For more information, visit  www.nhlbi.nih.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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Study Links E-Cigarette Use with Higher Risk of Heart Failure

Large study adds to growing body of evidence that vaping may harm the heart.

Apr 02, 2024

Contact: Nicole Napoli , [email protected], 202-669-1465

WASHINGTON (Apr 02, 2024) -

People who use e-cigarettes are significantly more likely to develop heart failure compared with those who have never used them, according to one of the largest prospective studies to date investigating possible links between vaping and heart failure. The findings are being presented at the American College of Cardiology’s Annual Scientific Session.

Heart failure is a condition affecting more than 6 million U.S. adults in which the heart becomes too stiff or too weak to pump blood as effectively as it should. It can often lead to debilitating symptoms and frequent hospitalizations as people age. Electronic nicotine products, which include e-cigarettes, vape pens, hookah pens, personal vaporizers and mods, e-cigars, e-pipes and e-hookahs, deliver nicotine in aerosol form without combustion. Since they were first introduced in the U.S. in the late 2000s, electronic nicotine products have often been portrayed as a safer alternative to smoking, but a growing body of research has led to increased concern about potential negative health effects.

“More and more studies are linking e-cigarettes to harmful effects and finding that it might not be as safe as previously thought,” said Yakubu Bene-Alhasan, MD, a resident physician at MedStar Health in Baltimore and the study’s lead author. “The difference we saw was substantial. It’s worth considering the consequences to your health, especially with regard to heart health.”

For the study, researchers used data from surveys and electronic health records in All of Us, a large national study of U.S. adults run by the National Institutes of Health, to analyze associations between e-cigarette use and new diagnoses of heart failure in 175,667 study participants (an average age of 52 years and 60.5% female). Of this sample, 3,242 participants developed heart failure within a median follow-up time of 45 months.

The results showed that people who used e-cigarettes at any point were 19% more likely to develop heart failure compared with people who had never used e-cigarettes. In calculating this difference, researchers accounted for a variety of demographic and socioeconomic factors, other heart disease risk factors and participants’ past and current use of other substances, including alcohol and tobacco products. The researchers also found no evidence that participants’ age, sex or smoking status modified the relationship between e-cigarettes and heart failure.

Breaking the data down by type of heart failure, the increased risk associated with e-cigarette use was statistically significant for heart failure with preserved ejection fraction (HFpEF)—in which the heart muscle becomes stiff and does not properly fill with blood between contractions. However, this association was not significant for heart failure with reduced ejection fraction (HFrEF)—in which the heart muscle becomes weak and the left ventricle does not squeeze as hard as it should during contractions. Rates of HFpEF have risen in recent decades, which has led to an increased focus on determining risk factors and improving treatment options for this type of heart failure.

The findings align with previous studies conducted in animals, which signaled e-cigarette use can affect the heart in ways that are relevant to the heart changes involved in heart failure. Other studies in humans have also shown links between e-cigarette use and some risk factors associated with developing heart failure. However, previous studies attempting to assess the direct connection between e-cigarette use and heart failure have been inconclusive, which Bene-Alhasan said is due to the inherent limitations of the cross-sectional study designs, smaller sample sizes and the smaller number of heart failure events seen in previous research.

Researchers said the new study findings point to a need for additional investigations of the potential impacts of vaping on heart health, especially considering the prevalence of e-cigarette use among younger people. Surveys indicate that about 5% to 10% of U.S. teens and adults use e-cigarettes. In 2018, the U.S. Surgeon General called youth e-cigarette use an epidemic and warned about the health risks associated with nicotine addiction.

“I think this research is long overdue, especially considering how much e-cigarettes have gained traction,” Bene-Alhasan said. “We don’t want to wait too long to find out eventually that it might be harmful, and by that time a lot of harm might already have been done. With more research, we will get to uncover a lot more about the potential health consequences and improve the information out to the public.”

Bene-Alhasan also said e-cigarettes are not recommended as a tool to quit smoking, since many people may continue vaping long after they quit smoking. The U.S. Centers for Disease Control and Prevention recommends a combination of counseling and medications as the best strategy for quitting smoking.

Researchers said that the study’s prospective observational design allows them to infer, but not conclusively determine, a causal relationship between e-cigarette use and heart failure. However, with its large sample size and detailed data on substance use and health information, Bene-Alhasan said the study is one of the most comprehensive studies to assess this relationship to date.

For more information about the health effects of e-cigarettes, visit CardioSmart.org/StopSmoking .

Bene-Alhasan will present the study, “Electronic Nicotine Product Use Is Associated with Incident Heart Failure - The All of Us Research Program,” on Sunday, April 7, 2024, at 3:15 p.m. ET / 19:15 UTC in Hall B4-5.

ACC.24  will take place April 6-8, 2024, in Atlanta, bringing together cardiologists and cardiovascular specialists from around the world to share the newest discoveries in treatment and prevention. Follow  @ACCinTouch ,  @ACCMediaCenter  and  #ACC24  for the latest news from the meeting.

The American College of Cardiology  (ACC) is the global leader in transforming cardiovascular care and improving heart health for all. As the preeminent source of professional medical education for the entire cardiovascular care team since 1949, ACC credentials cardiovascular professionals in over 140 countries who meet stringent qualifications and leads in the formation of health policy, standards and guidelines. Through its world-renowned family of  JACC  Journals, NCDR registries, ACC Accreditation Services, global network of Member Sections, CardioSmart patient resources and more, the College is committed to ensuring a world where science, knowledge and innovation optimize patient care and outcomes. Learn more at  ACC.org .

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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

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.

Is CBD a wonder drug or waste of money? Here's what the evidence says

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…

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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.

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.

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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A systematic review of the effects of e-cigarette use on lung function

• Lucy Honeycutt 1 ,
• Katherine Huerne 1 , 2 ,
• Alanna Miller 1 ,
• Erica Wennberg 1 ,
• Kristian B. Filion 1 , 3 ,
• Roland Grad 1 , 4 ,
• Andrea S. Gershon 5 ,
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• Genevieve Gore 6 ,
• Andrea Benedetti 3 , 7 ,
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• Mark J. Eisenberg   ORCID: orcid.org/0000-0002-1296-0661 1 , 3 , 9  

npj Primary Care Respiratory Medicine volume  32 , Article number:  45 ( 2022 ) Cite this article

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• Epidemiology

Given the increasing use of e-cigarettes and uncertainty surrounding their safety, we conducted a systematic review to determine the effects of e-cigarettes on measures of lung function. We systematically searched EMBASE, MEDLINE, and PsycINFO databases via Ovid, the Cochrane CENTRAL database, and the Web of Science Core from 2004 until July 2021, identifying 8856 potentially eligible studies. A total of eight studies (seven studying immediate effects and one long-term effects, 273 total participants) were included. The risk of bias was assessed using the Risk of Bias in Non-randomized Studies—of Interventions (ROBINS-I) and Cochrane risk of bias tools. These studies suggest that vaping increases airway resistance but does not appear to impact forced expiratory volume in one second (FEV 1) , forced vital capacity (FVC), or FEV 1 /FVC ratio. However, given the limited size and follow-up duration of these studies, larger, long-term studies are required to further determine the effects of e-cigarettes on lung function.

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Introduction.

The first electronic cigarette (e-cigarette) was patented and marketed in 2004 1 . Since then, e-cigarette use (or “vaping”) has grown exponentially across the globe 2 . As the use of vaping devices evolves with policy, the consequences of vaping on health are becoming an increasingly important public health issue. E-cigarettes are being studied for harm reduction in individuals who use cigarettes and as a smoking cessation aid, as they are believed to be less harmful to health than smoking 3 . However, there is increasing evidence demonstrating adverse respiratory effects of vaping compared to vaping abstinence. In particular, an outbreak of E-Cigarette and Vaping-Associated Lung Illness (EVALI) brought the short-term respiratory consequences of vaping into question, especially if cannabis or THC-containing products are used 4 . Other short-term respiratory changes that have been linked to vaping include increased airway resistance 5 , breathing difficulty 6 , and transient lung inflammation 7 . Vaping has also been associated with chronic respiratory conditions such as asthma 8 and chronic bronchitis 9 . Despite these reports, the short- and long-term respiratory safety of vaping is still largely unknown. Several small studies have examined the effects of e-cigarettes on lung function, including measures such as forced expiratory volume in one second (FEV 1 ), forced vital capacity (FVC), and airway resistance. However, no evidence syntheses have been completed on this topic. Therefore, we conducted a systematic review to determine the effects of vaping on measures of lung function.

Our systematic review was conducted following a protocol developed prior to initiating the review, which was registered on the PROSPERO register of systematic reviews ( CRD42021227121 ) 10 . This systematic review is reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines 11 .

Search strategy and study selection

Using a search strategy (Supplementary Tables 1 – 5 ) developed by an experienced health sciences librarian (G.G.), we systematically searched EMBASE, MEDLINE, and PsycINFO databases via Ovid, the Cochrane CENTRAL database, and the Web of Science Core from 2004 (the year of the first e-cigarette patent) until July 12, 2021. We additionally conducted a gray literature search by searching the websites of key governmental and public health organizations (the World Health Organization, Health Canada, the US Centers for Disease Control and Prevention, the US Food and Drug Administration, the Canadian Center on Substance Use and Addiction, the European Centre for Disease Prevention and Control, and the European Public Health Association). Additional articles were identified by manually searching the reference lists of included publications as well as SCOPUS and Google Scholar (first ten pages). Articles were included if they reported quantitative primary data on changes in lung function associated with vaping, defined as the use of any device that functions by transforming an e-liquid to an aerosol using metal coils, among human participants of any age. Studies of cells and those conducted in animals were excluded. Studies using heat-not-burn devices were also excluded, as these do not meet the above definition of vaping. Eligible studies included randomized controlled trials (RCTs), non-randomized studies of interventions (NRSIs), and cohort studies; cross-sectional studies and case reports were excluded. We included studies that used non-users of both vaping devices and conventional cigarettes as a comparison group and those that used a pre- and post-design in which individuals acted as their own controls. Inclusion was not restricted by language or country of publication. Abstracts and conference proceedings were included if sufficient data could be extracted from these publications.

Search results were downloaded from databases into reference management software (EndNote X9) or manually added (e.g., for gray literature results). Duplicates were removed in EndNote and entries were uploaded to Covidence (Veritas Health Innovation, Melbourne, Australia), a systematic review software. Two reviewers (L.H. and K.H.) independently screened the titles and abstracts of all identified publications for eligibility. Citations considered potentially eligible by either reviewer, based on the pre-specified review inclusion/exclusion criteria (Supplementary Table 6 ), were retrieved for full-text screening and assessed for inclusion. The reasons for exclusion after full-text review were annotated in Covidence and any disagreements were resolved by consensus or a third reviewer (A.H-L.).

Data extraction

Two independent reviewers (L.H and K.H.) extracted methodological, demographic, and outcome data from included studies in duplicate; disagreements were detected in Covidence and were resolved by consensus or, if necessary, by a third reviewer (A.H-L.). Extracted data included study characteristics (first author, journal, year of publication, years(s) of data collection, funding, data source, study design, recruitment strategy, duration of follow-up, country of origin, sample size); population characteristics (sex, gender, age, race, ethnicity, socioeconomic status, dose/frequency of e-cigarette use, conventional cigarette smoking status, smoked cannabis use); and vaping behavior, including the type of vaping device used (e.g., disposable e-cigarette vs. pod device such as JUUL), vaping products used (e.g., nicotine cartridges exclusively vs. THC cartridges exclusively vs. dual use of nicotine and THC products), and source of the vaping product (informal [i.e., friends, family members, or dealers] vs. commercial [i.e., vape shops, stores, dispensaries]).

Initially, extracted outcomes of primary interest were respiratory signs and symptoms, as these are important to patients and are the early signs of respiratory disease. Secondary outcomes included: findings on lung function; Computed tomography (CT) findings of emphysema, airway remodeling, and small airway loss; respiratory-related quality of life and exercise limitations; incidence and/or prevalence of respiratory disease as well as exacerbations of previous respiratory disease; and health care resource use including respiratory disease-related ambulatory care, emergency department visits, and hospitalization. Given the limited number of studies available and the heterogeneity of the data extracted from these studies, no meta-analysis was conducted.

Risk of bias

The risk of bias in included publications was assessed independently by two reviewers (L.H. and K.H.), and discrepancies were resolved by consensus or, if necessary, by a third reviewer (A.H-L.). The risk of bias of included non-randomized studies (pre-post studies, NRSI with non-vaping reference group, cohort study) was assessed using the Risk of Bias in Non-randomized Studies—of Interventions (ROBINS-I) tool 12 . The ROBINS-I tool evaluates intervention-specific outcomes for a study through seven domains which assess the risk of bias pre-intervention, at-intervention, and post-intervention. For each outcome of interest extracted from an included study, the risk of bias within each domain was reported as “low”, “moderate”, “serious”, or “critical”. Included RCTs were assessed using the Cochrane Collaboration’s Tool for Assessing Risk of Bias (ROB V1) 13 . Similar to ROBINS-I, this tool evaluates the risk of bias through the assessment of five domains; for each outcome of interest extracted from an included study, the risk of bias for each domain was reported as “low risk of bias”, “high risk of bias”, or “unclear risk of bias.” All eligible publications were included in the qualitative synthesis regardless of their assessed risk of bias.

Reporting summary

Further information on research design is available in the Nature Research Reporting Summary linked to this article.

As our search did not identify studies which focused on the broad outcomes detailed above, we chose to limit our focus to studies on lung function. Our database searches identified 14,307 potentially eligible studies (Fig. 1 ). After duplicates were removed, 8856 titles and abstracts were assessed. After this initial screening, 44 full texts were retrieved and reviewed in further detail, yielding eight studies eligible for inclusion.

PRISMA flow diagram of included studies assessing the effect of e-cigarettes on lung function.

Study and participant characteristics

Of the eight included studies (273 total participants), seven 14 , 15 , 16 , 17 , 18 , 19 , 20 involved short-term exposure to e-cigarettes with immediate outcome assessment, and the remaining study followed vapers and non-vapers over 3.5 years 21 (Table 1 ). This prospective cohort study examined 21 participants (12 nonsmokers and nine vapers) at means of 12 (standard deviation: 1), 24 (2), and 42 (2) months after baseline 21 . Of the seven short-term studies, four were NRSIs (three pre-post studies 14 , 15 , 16 and one NRSI with a non-vaping reference group 20 ) and three were RCTs 17 , 18 , 19 . Among these seven studies, two included 70–80 participants 14 , 15 and five included 10–30 participants 16 , 17 , 18 , 19 , 20 . Exposures varied in terms of e-cigarettes, e-liquids, and vaping session timings. Most studies did not expand on their definition of “non-smoker/non-vaper” 15 , 16 , 18 , 19 , 20 , 21 , but two studies clarified that these participants were never-smokers 14 , 17 . One of these two studies further elaborated that participants had no exposure to tobacco products or e-cigarettes 17 . Few studies gave detailed information on the type of e-cigarette used. Three studies reported a specific brand or product (Blu 17 , eGo 16 , Joytech elips-C series 18 , Puff bar 20 ). Polosa et al. listed some of the various e-cigarettes used by participants throughout the longitudinal study, including standard refillable (eGo style products) and more advanced refillable (Provari, Innokin, Joytech, eVIC, Avatar Puff) 21 . The remaining studies did not report a specific brand, though one study described the e-cigarette used as a “1 st generation e-cigarette popular in Greece” 15 . All studies clarified whether the e-cigarettes used during the study contained nicotine.

The included RCTs ( n  = 3) 17 , 18 , 19 had an unclear risk of bias, with each study demonstrating an unclear risk of bias in 3+ domains (Table 2 ). This was primarily due to missing information in the manuscripts required to make an adequate judgment, such as a lack of detail surrounding randomization. The risk associated with the blinding of participants and personnel was judged to be low for all 3 included RCTs. These studies were not blinded, and one was placebo-controlled. However, it was judged that this lack of blinding would not influence measures of lung function. Of the included non-randomized studies ( n  = 5) 14 , 15 , 16 , 20 , 21 , four 14 , 15 , 16 , 20 were judged to be at moderate risk of bias and one 21 was found to have a serious risk of bias (Table 3 ). The most consistent source of bias in these studies was bias due to confounding, with only one 16 study judged to have a low risk of bias due to confounding. Of the remaining four studies, three 14 , 15 , 20 were found to have a moderate risk of bias due to confounding and one 21 was found to be at serious risk of bias due to confounding, with important confounding variables not accounted for in the design or analysis.

Effects of E-cigarette use on lung function

Seven studies 14 , 15 , 16 , 17 , 18 , 19 , 20 reported immediate measures of lung function after short-term exposure to e-cigarettes (Table 4 ), including FEV 1 , FVC, and FEV 1 /FVC. Two studies, Boulay et al. and Staudt. et al. suggested no changes in FEV 1 or FEV 1 /FVC after vaping among nonsmokers 17 , 19 . Kizhakke Puliyakote et al. observed lower baseline FEV 1 and FEV 1 /FVC values among nonsmokers compared to vapers 20 . Coppeta et al. found a decrease in FEV 1 and FEV 1 /FVC among nonsmokers after 1 min of vaping; however, these values returned to baseline after 15 min 16 .

Airway resistance and specific airway conductance after 10 min of vaping were measured in two 14 , 15 of the seven short-term studies (Table 4 ). Both Palamidas et al. 2013 and 2017 suggested that vaping increased airway resistance and decreased specific airway conductance among nonsmokers and smokers with and without respiratory disease. Oxygen saturation was assessed in four studies 15 , 17 , 19 , 20 . Three studies suggested no changes after vaping, with only Palamidas et. al. 2017 suggesting decreased oxygen saturation following vaping among smokers with and without asthma 15 .

Long-term changes (3.5 years) in lung function measurements were assessed in only one small ( n  = 21) study (Polosa 2017) 21 . This study suggested that FEV 1 , FVC, FEV 1 /FVC, and forced mid-expiratory flow (FEF 25-75 ) did not change over time among vapers and non-vapers (Table 5 ).

This systematic review was designed to determine the effect of vaping on measures of lung function. We found that there were only eight studies in the literature assessing this issue, all of which were small, and only one examined longer-term outcomes (3.5 years follow-up). In general, these studies suggest that there are no acute changes associated with vaping. However, airway resistance and conductance may be influenced by e-cigarettes, with two studies reporting changes in these values in multiple population subgroups. It is important to note that there were few studies available for this systematic review and that most of these studies focused on the acute effects of vaping; therefore, these results are suggestive but not definitive, and future research must be conducted in this area. Furthermore, three of the included studies had an unclear risk of bias, four had a moderate risk of bias, and one had a serious risk of bias, which further limits the interpretation of this review’s findings.

In addition to the limitations above, this review lacks subgroup analyses or a meta-analysis. This is due to the heterogeneity of the included studies, both in terms of study design and outcomes. Few studies were eligible for this review due to the variation in study designs and definitions of e-cigarettes and smoking status. For example, some studies included both conventional cigarette smokers and nonsmokers in their definition of “non-vapers” and did not analyze data separately based on conventional smoking status. Other studies used a “sham” vaping session for controls where either an e-cigarette with an empty cartridge (i.e., without e-liquid) or second-hand smoke were used. More commonly, studies were conducted on smokers only, without nonsmokers as a comparison group. Future studies could analyze subgroups based on both smoking and vaping status to allow for a more detailed quantitative analysis.

E-cigarettes are becoming more popular for recreational use and are being studied for harm reduction among smokers as a smoking cessation aid, as they are believed to be less harmful to health than smoking. However, there are limited data available and virtually no long-term studies assessing how prolonged e-cigarette use could impact lung function. As the use of vaping devices evolves and becomes more widespread, the health consequences of vaping are becoming an increasingly important public health issue. This is a knowledge gap that must be addressed. Knowledge of the safety of e-cigarettes, particularly their long-term safety, will inform public health policy and e-cigarette regulations, as well as the guidance clinicians, offer to their patients on smoking harm reduction. For these policies, regulations, and guidelines to be developed, we must understand how e-cigarettes can influence one’s health. This includes establishing the effects of e-cigarettes on clinical outcomes such as respiratory symptoms (cough, dyspnea), measures of lung function, and risk of developing respiratory disease. Further research is required to elucidate the short- and long-term consequences of vaping to determine whether e-cigarettes are truly a “safer” alternative to traditional cigarettes for smoking cessation or for recreational use. Future studies should be long-term, have large sample sizes, and may include different types of e-cigarettes as well as conventional cigarettes for comparison. In addition, it is important for future research to include clinical outcomes as described above. This will allow for better translation of the research findings to help inform clinical decision-making.

Data availability

No additional data were available, as this study is a knowledge synthesis that relied on aggregate, published results available in the public domain. Any inquiries should be directed to the corresponding author.

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Acknowledgements

The authors would like to thank Jenna Glidden and Andrea Hebert-Losier for their assistance with study screening, data abstraction, and risk of bias assessment. The authors would also like to thank Francesca Frati, who peer-reviewed the search strategy. This work was funded by the Canadian Institutes for Health Research (#HEV-172891). The funder of the study had no role in study design, data collection, data analysis, data interpretation, writing of the report, or decision to submit for publication. Dr. Filion is supported by a Senior Research Scholar award from the Fonds de recherche du Québec – Santé and a William Dawson Scholar award from McGill University. Dr. Thombs was supported by a Tier 1 Canada Research Chair.

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G.G. performed the search. L.H. and K.H. screened studies, extracted data, and performed a risk of bias assessment of included studies. L.H. drafted the manuscript. All authors contributed to the study design and interpretation of results, revised the manuscript for important intellectual content, and approved the final version of the manuscript. M.J.E. supervised the study and is the guarantor.

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Correspondence to Mark J. Eisenberg .

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Honeycutt, L., Huerne, K., Miller, A. et al. A systematic review of the effects of e-cigarette use on lung function. npj Prim. Care Respir. Med. 32 , 45 (2022). https://doi.org/10.1038/s41533-022-00311-w

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Latest Cochrane Review finds high certainty evidence that nicotine e-cigarettes are more effective than traditional nicotine-replacement therapy (NRT) in helping people quit smoking

A Cochrane review  has found the strongest evidence yet that e-cigarettes, also known as ‘vapes’, help people to quit smoking better than traditional nicotine replacement therapies, such as patches and chewing gums.

New evidence published today in the Cochrane Library finds high certainty evidence that people are more likely to stop smoking for at least six months using nicotine e-cigarettes, or ‘vapes’, than using nicotine replacement therapies, such as patches and gums. Evidence also suggested that nicotine e-cigarettes led to higher quit rates than e-cigarettes without nicotine, or no stop smoking intervention, but less data contributed to these analyses. The updated Cochrane review includes 78 studies in over 22,000 participants – an addition of 22 studies since the last update in 2021.

Smoking is a significant global health problem. According to the World Health Organisation (WHO), in 2020, 22.3% of the global population used tobacco, despite it killing up to half of its users. Stopping smoking reduces the risk of lung cancer, heart attacks and many other diseases. Though most people who smoke want to quit, many find it difficult to do so permanently. Nicotine patches and gum are safe, effective and widely used methods to help individuals quit.

E-cigarettes heat liquids with nicotine and flavourings, allowing users to ‘vape’ nicotine instead of smoking. Data from the review showed that i f six in 100 people quit by using nicotine replacement therapy, eight to twelve would quit by using electronic cigarettes containing nicotine. This means an additional two to six people in 100 could potentially quit smoking with nicotine containing electronic cigarettes.

Dr Jamie Hartmann-Boyce, Associate Professor at the University of Oxford, Editor of the Cochrane Tobacco Addiction Group, and an author of the new publication, said:

“Electronic cigarettes have generated a lot of misunderstanding in both the public health community and the popular press since their introduction over a decade ago. These misunderstandings discourage some people from using e-cigarettes as a stop smoking tool. Fortunately, more and more evidence is emerging and provides further clarity. With support from Cancer Research UK, we search for new evidence every month as part of a living systematic review. We identify and combine the strongest evidence from the most reliable scientific studies currently available. For the first time, this has given us high-certainty evidence that e-cigarettes are even more effective at helping people to quit smoking than traditional nicotine replacement therapies, like patches or gums.”

In studies comparing nicotine e-cigarettes to nicotine replacement treatment, significant side effects were rare. In the short-to-medium term (up to two years), nicotine e-cigarettes most typically caused throat or mouth irritation, headache, cough, and feeling nauseous. However, these effects appeared to diminish over time.

Dr Nicola Lindson, University Research Lecturer at the University of Oxford, Cochrane Tobacco Addiction Group’s Managing Editor, and author of the publication said:

“ E-cigarettes do not burn tobacco; and as such they do not expose users to the same complex mix of chemicals that cause diseases in people smoking conventional cigarettes. E-cigarettes are not risk free, and shouldn’t be used by people who don’t smoke or aren’t at risk of smoking. However, evidence shows that nicotine e-cigarettes carry only a small fraction of the risk of smoking. In our review, we did not find evidence of substantial harms caused by nicotine containing electronic cigarettes when used to quit smoking. However, due to the small number of studies and lack of data on long-term nicotine-containing electronic cigarette usage – usage over more than two years – questions remain about long-term effects.”

The researchers conclude that more evidence, particularly about the effects of newer e-cigarettes with better nicotine delivery than earlier ones, is needed to assist more people quit smoking. Longer-term data is also needed.

Michelle Mitchell, chief executive at Cancer Research UK, said:

“We welcome this report which adds to a growing body of evidence showing that e-cigarettes are an effective smoking cessation tool. We strongly discourage those who have never smoked from using e-cigarettes, especially young people. This is because they are a relatively new product and we don’t yet know the long term health effects. While the long term effects of vaping are still unknown, the harmful effects of smoking are indisputable – smoking causes around 55,000 cancer deaths in the UK every year. Cancer Research UK supports balanced evidence-based regulation on e-cigarettes from UK governments which maximises their potential to help people stop smoking, whilst minimising the risk of uptake among others.”

• Read the full Cochrane review and plain language summary 
• Learn more about Cochrane Tobacco Addition Group
• Science Media Centre: Expert reaction to cochrane review on electronic cigarettes for smoking cessation

 Hartmann-Boyce J, Lindson N, Butler AR, McRobbie H, Bullen C, Begh R, Theodoulou A, Notley C, Rigotti NA, Turner T, Fanshawe TR, Hajek P. Electronic cigarettes for smoking cessation. Cochrane Database of Systematic Reviews 2022, Issue 11. Art. No.: CD010216. DOI: 10.1002/14651858.CD010216.pub7

This work was supported by Cancer Research UK [A ref. A29845]

To speak to a team member about this project please contact Dr. Hartmann-Boyce, [email protected] or Dr. Lindson, [email protected] .

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Can vaping cause changes in our cells?

20 March 2024

You may have seen recent media coverage of a study that looked at changes in different types of cells from people who smoked and people who vaped. In this article, we take a closer look at what the researchers did, what they found and what the results of the study could mean.  

Does this study show that vaping causes cancer?  

No. The type of change that this study looked at is different from changes to a cell’s DNA sequence (mutations) . This study shows that some changes were there but not what they might be doing.  So, we don’t have enough information yet to understand what these findings mean in terms of any potential health effects.  

E-cigarettes haven’t been around for long enough for us to know what their longer-term health effects could be . So, vaping isn’t risk-free and children and people who have never smoked shouldn’t vape. But research overall still finds that legal vaping is far less harmful than smoking and can help people who smoke to stop.  

What did the researchers do?

The researchers looked at chemical ‘marks’ that add information to the genetic code in our DNA. This is called epigenetics. It’s a bit like highlighting or adding notes to a page in a book – the words themselves don’t change, but we read them differently. The epigenetic marks affect how our cells ‘read’ the instructions in their genes.  

Epigenetic changes ‘turn on’ or ‘turn off’ genes. They’re a way for cells to respond to what’s happening around them by following the instructions from the right gene(s). Epigenetic changes can be temporary and reverse when they’re no longer needed, whereas genetic mutations in our DNA tend to be permanent.   

In this study, the researchers looked into a type of epigenetic change called methylation, i n which a small molecule (made up of one carbon atom and three hydrogen atoms, a ‘methyl group’) gets attached to some of the building blocks of DNA. In particular, they focused on methylation in different types of cells in people who smoked but also looked at it in a small number of people who vaped and another small group of people who used smokeless tobacco.  

What did the study find?

The study found methylation changes in cells taken from people who smoked, including cheek (which are directly exposed to smoke), cervical (which aren’t) and blood cells. The kind of changes seen varied depending on the type of cell. As mentioned above, epigenetic changes can be temporary, enabling cells to respond to their environment and then stop when the response is no longer needed. The researchers found variation in methylation patterns depending on how long someone had smoked for, and some changes were only seen in samples from people who currently smoked and not in people who had stopped smoking.   

The researchers also compared methylation changes in cell DNA samples from people who vaped with those from people who smoked. They found some similarities between the kinds of changes seen in people who vaped and people who smoked.  

What does it mean?

This research is at an early stage, so we don’t have enough information yet to understand what the findings mean. For example, the study looked at some changes that were seen in cell DNA samples, not how the cells with those changes were behaving compared to cells without the changes.  

When two things occur together, it could mean that:  

• one is causing the other;   
• they could also be there by chance; or   
• they could both be caused by a third factor that we don’t know yet.   

So, the epigenetic changes could be part of our cells’ response to cigarette smoke or e-cigarette vapour, they could be unrelated or they could be caused by something else that was affecting both the study participants who smoked and the participants who vaped.   

There were also some limitations to what the study was able to do, for example, participants who vaped may have smoked in the past, so we can’t be completely sure that the changes seen weren’t caused by previous smoking.   

Should I stop vaping?

If you used to smoke and are vaping to help you to stay off tobacco, the most important thing is not to go back to smoking. So, if you’re thinking of stopping vaping, make sure you only do so if you think you won’t start smoking again. If you think there’s a risk that you’ll smoke if you stop vaping, talk to your free local stop smoking service, GP or pharmacist for advice on stopping vaping or switching to an alternative stop smoking tool.  

Because vaping isn’t risk free, it’s important that children and people who have never smoked don’t start to vape. By contrast, however, decades of research have proven the harmful effects of smoking, which kills one person every five minutes in the UK. Research so far has found that e-cigarettes are far less harmful than smoking and can help people to stop. So, if you smoke and want to stop , e-cigarettes are an option.   

What could epigenetics research mean in the future?

Epigenetics is an interesting area of research and we look forward to seeing what future studies can tell us about cancer and how it develops.   

What are the UK governments doing about smoking and vaping?

In October 2023, the UK Government announced plans to create the first ever smokefree generation by raising the age of sale of tobacco as well as action to tackle youth vaping . Today, those plans are being introduced in Parliament as the Tobacco and Vapes Bill.  

Under the Bill, anyone born on or after 1 January 2009 will never legally be able to be sold tobacco.  

As an individual who once believed in the promise of vaping as a safer alternative to smoking, I embarked on a journey that ultimately led me to a profound realization: prioritizing my health over convenience was paramount.

It’s undeniable that traditional tobacco products wreak havoc on our bodies, causing irreversible damage to our lungs and increasing the risk of life-threatening diseases like cancer. In my quest for a healthier alternative, I turned to vaping, hoping to break free from the chains of tobacco addiction.

However, my experience with vaping proved to be far from the panacea I had envisioned. Despite its touted benefits, vaping failed to satisfy my cravings and instead left me feeling depleted and unwell. Dehydration, coupled with a lack of essential nutrients from improper eating habits, took its toll on my body, manifesting in alarming symptoms such as liver pain and debilitating fatigue.

Concerned for my well-being, I sought medical advice and underwent a liver scan, revealing unsettling fatty deposits in my liver—a stark reminder of the detrimental effects of vaping on my health. Faced with this sobering reality, I made a conscious decision to reclaim control of my life and pursue a healthier lifestyle.

Quitting vaping marked the beginning of a remarkable transformation. Freed from the shackles of addiction, I experienced a newfound sense of vitality and vigor. The burden of liver pain lifted, replaced by an abundance of energy and vitality that I had long forgotten.

Today, I stand as living testimony to the power of resilience and determination in overcoming adversity. By embracing the simple pleasures of life and relinquishing the harmful habits that once held me captive, I have unlocked a world of boundless possibilities.

To those who may find themselves ensnared by the allure of vaping or any other harmful habit, I implore you to heed this cautionary tale. Embrace the gift of life with gratitude and reverence, for it is a precious treasure to be cherished and nurtured.

In closing, let us remember that true fulfillment lies not in succumbing to the temptations of vice, but in embracing the purity of existence and breathing the air as nature intended. As I bask in the radiance of newfound health and vitality, I invite you to join me on this transformative journey towards a brighter, healthier future.

Yours in health and healing,

I think until there is solid proof that vaping is as bad as cigarettes then people should stop putting fake news on the internet. Smoking contains over 7000 toxins, including tar that they use on the roads , vaping has about 5 substances in and is actually around 95% safer than smoking . My Dr adviced me to switch to vaping to quit the cancer sticks , which I did , my breathing has improved loads and my horrid,rattly smokers cough I had for years had gone , I no longer get out of breath just walking up the stairs. I agree if people have never smoked then they shouldn’t just start vaping and kids shouldn’t do it either . But my Dr said the nail thing in vapes is nicotine, which is not harmful at all , it’s just addictive. We breath in toxins every time we leave the house , with all the car fumes and pollution that’s in the air . The reason the government don’t want people quitting smoking and start vaping is because there’s millions weeks millions of pounds to be made in smoking and killing millions of people a year . There is no money to be made in the vaping . What’s more important, people’s health or money … The government are the most untrustworthy ,lying snakes on the planet. And until there is concrete proof people should vape to quit the cancer sticks.

Every way of smoking, including vaping, is, in my layman understanding, a huge cancer risk. After all, you inhale smoke with plenty of dangerous ingredients that go right up your brain, down your throat and also down your lungs and no one could ever convince me that this is healthy or free of any cancer danger. There are other articles on this (great) website, which clearly explain that the greatest dangers of developing cancer are drinking alcohol and smoking. Luckily, I have never smoked anything in my entire life and I have no interest in starting this, in fact I am very disgusted if someone on the streets is smoking and I have to pass by or even walk behind that person, which makes me holding my breath until I got away, yet, from my observation while walking the streets, when somebody is vaping the clouds are way thicker and the smell seems to go way farther than the smell of burning tobacco. To me, those are clearly warning signs that vaping may even be far more dangerous, also when it comes to cancer development, than smoking cigarettes, although I highly advise to stay away from any kind of smoking anyway. And I would not be surprised if later studies will finally figure out that vaping is indeed coming with a far greater risk than smoking cigarettes, although, again, my layman advise is to just stay away from smoking anything, no matter what it is.

WOAH! This shared a lot of info about how bad vaping is!

Cancer research has a responsibility to protect the public, not the Corporations pushing Vapes on the population under the guise of “safer than cigarettes”. This is akin to saying there is no evidence that walking across the motorway with a blindfold on is unsafe because there is no evidence to suggest you would get run over (as no one has carried out a real study to confirm or deny this)

This nanny state will not stop me vaping it saved me from smoking and your never stop children smoking just like cannabis

Nobody has ever asked my husband about his vaping – e-cigarette use despite having lung cancer🙀 what is going on?

Methyl is not a molecule (the closest molecule to it is methane). It is usually called a group (or, maybe, a moiety).

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RESOURCES INFORMATION LIBRARY

Research, data & articles.

This resource is collection of the best and latest research on vaping and other reduced-harm products, medical journal articles, as well as journalistic pieces organized by topic that contain valuable data, information, and perspectives on tobacco harm reduction, vaping, and safer nicotine products.

Our intention is update this resource with additional sources as they become available, so please check back often.

Jump to Topic…

Science // Smoking Cessation Science // Harm Reduction Science // Health Effects Science // Flavors Science // Youth Usage Science // Smokeless Tobacco Science // Regulatory Effects News // Smoking Cessation News // Harm Reduction News // COVID-19 News // EVALI News // Youth Usage News // Social Justice News // Taxes News // Tobacco Control

Highlighted Resources

These resources are some of the highest rated, latest research on vaping.

Balancing Consideration of the Risks and Benefits of E-Cigarettes

Nicotine without smoke: tobacco harm reduction, electronic cigarettes for smoking cessation, a randomized trial of e-cigarettes versus nicotine-replacement therapy, educational videos, recommended videos, what vaping did.

Vaping: what people are getting wrong | The Economist

Vaping: a more balanced message | Michigan Public Health

Why bans of low-risk nicotine alternatives to smoking in lmic's will do more harm than good, vaping demystified.

The E-Cigarette Summit 2019, London | Ethan Nadelman Presentation

Why Health Groups Lie About Vaping

Vaporized: U.K. Government Promotes Vaping As Smoking Cessation Tool | CNBC Prime

Marc Slis, Vape Shop Owner - Michigan Testimony

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Stop Smoking Start Vaping

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Velvet Glove, Iron Fist

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The Cigarette Century

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The Cigarette

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Cigarette Wars

Cassandra Tate

Sander L. Gilman & Zhou Xun

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For Smokers Only

Ashes to Ashes

Richard Kluger

Say Why To Drugs

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Scientific Research / Articles

Smoking cessation, harm reduction, health effects, youth usage, smokeless tobacco, regulatory effects, news media / blog articles, social justice, tobacco control.

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• Help & Support

Where There’s Smoke: New Research Publication Lights Fire about Dangers of Vaping

by Stacey Sturner | January 12, 2023

• E-Cigarettes

The American Journal of Preventive Medicine recently published a new paper, titled “ Cigarette-E-cigarette Transitions and Respiratory Symptom Development ,” which assessed the respiratory health effects of 16 tobacco product transitions, including from non-use to e-cigarette use.

Funded in part by the American Lung Association, the study suggests e-cigarette initiation among nonusers and subsequent cigarette smoking may cause significant lung health impacts. These results reinforce the urgency for robust e-cigarette regulations, as well as demonstrate that additional research is needed to better determine the specific harms of e-cigarettes.

“The topline finding that e-cigarette initiation among nonusers is associated with increased respiratory morbidity is an important point to emphasize given continued high rates of e-cigarette usage among youth and young adult never smokers in the U.S.,” stated Andrew Stokes, PhD , assistant professor of global health at the Boston University School of Public Health and senior author of the paper. “It adds to our body of scientific evidence urgently calling for the public health intervention in support of more stringent regulatory e-cigarette standards.”

Dr. Stokes was a 2020-2022 recipient of the Lung Association’s Public Policy Research Award, which aims to empower scientists who are impacting lung health. In February 2022, he likewise served as senior author of a paper published in the  American Journal of Respiratory and Critical Care Medicine , revealing young adults who use e-cigarettes are more likely to develop respiratory issues within one year of vaping.

The latest study, like the one published in February, used data from the Food and Drug Administration’s (FDA) Population Assessment of Tobacco and Health (PATH) cohort, a longitudinal study tracking changes in tobacco use over time among participants. Among 33,231 observations from 13,528 unique participants, the study authors found that nonusers who started e-cigarette use had 62% greater rate of wheezing.

Albert Rizzo, MD, Chief Medical Officer of the Lung Association, added, “Anything that can be done to help curb the e-cigarette epidemic is an important step forward. This research further amplifies our organization’s warning against e-cigarette use due to the resulting health ramifications. It’s a mission-critical public policy initiative, now and always.”

“What is exceedingly clear is that e-cigarette initiation among nonusers is associated with increased respiratory morbidity,” continued Dr. Stokes. “We’re just starting to scratch the surface in our systematic identification of behavioral patterns most closely tied to respiratory events.”

The Lung Association has called on the FDA to end the sale of all flavored tobacco products, including flavored e-cigarettes. Flavors attract youth and the high levels of nicotine found in many e-cigarettes quickly hook kids. States including California and Massachusetts, as well as Washington, D.C. and multiple other cities have passed legislation to end the sale of flavored tobacco products in their states.

In addition, the Lung Association has called on federal officials to do more to ensure youth who are addicted to vaping and other tobacco products have resources to help them end their addiction.

To learn more about e-cigarette risks or a list of proven-effective cessation programs available to help youth and adults quit all tobacco products for good, please visit: Lung.org/quit-smoking .

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Blog last updated: August 25, 2023

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

Related content:

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."

• e-cigarette

View the discussion thread.

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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• Clinical Trials on the Effects of Vaping

Home / Resources / Clinical Trials on the Effects of Vaping

What is Vaping?

Vaping refers to inhaling and exhaling aerosolized particles from an e-cigarette. An e-cigarette is an electronic device filled with a nicotine-based liquid that is vaporized when the device is used.

Vaping was initially hailed as an important innovation. It was believed smokers could use e-cigarettes as an alternative to tobacco. This would reduce exposure to nicotine, tar, and other hazardous substances.

What’s more, many smokers considered vaping soothing, giving them “something to do with their hands” and a way to react in stressful situations where they would usually smoke. Some people succeeded in using vaping as a stepping stone to quit smoking.

With that said, the long term effects of vaping have not been fully studied. While many individuals view vaping as a step in the right direction to eliminate smoking, more research needs to be compiled on the effects it can have on individuals and society as a whole.

What Conditions is Vaping Associated With?

The unique condition associated with vaping is referred by the new medical acronym EVALI.

It stands for E-Cigarette or Vaping Associated Lung Injury.

As of October 22, 2019, 34 known deaths were associated with EVALI. The median age of victims was 45 and 59% of them were men.

In total, nearly 2,300 cases of EVALI were reported to the CDC by November 20, 2019. All 50 states have been affected except Alaska.

Samples of lung tissue taken from victims have tested positive for high amounts of vitamin E acetate, a toxin in some vaping products. Vitamin E acetate is believed to be safe when used in nutritional supplements or skincare products, but not when ingested.

Lung damage caused by EVALI can cause symptoms similar to pneumonia. Damage to the lungs makes it difficult for the body to take in oxygen and distribute it throughout the body.

EVALI is distinct from, but related to, bronchiolitis obliterans – also known as popcorn lung. This is an inflammatory condition that affects the tiniest airways within the lungs. Inflammation can lead to scarring that blocks airways, causing coughing and shortness of breath.

What Research Currently Exists Around Vaping?

The association between vaping and EVALI is already an established scientific fact. However, it is not yet clear exactly what risk factors contribute to the development of EVALI.

Current research focuses on finding a definitive answer for what chemicals or other factors may be responsible for EVALI. This will help the medical community understand why some e-cigarette enthusiasts are affected and others are not, paving the way for effective treatment.

Why Are Further Vaping Clinical Trials Important?

Vaping clinical trials will be essential to the long-term health and quality of life of those affected by EVALI or popcorn lung. Evidence of disease has been found in teens as well as elderly adults.

Unfortunately, there is no treatment capable of reversing the lung damage caused by EVALI. As with other pervasive lung disorders, such as COPD, therapies are likely to focus on preserving healthy lung function.

Current Vaping Clinical Trials

This is the current list of active vaping clinical trials on record with  ClinicalTrials.gov .

Patients are advised to watch this space carefully, since new clinical resources for vaping health are being developed rapidly.

Conditions: Substance Use Disorder; Alcohol Use Disorder Sponsors: National Institute on Drug Abuse (NIDA) Recruiting

Conditions: Nicotine Use Disorder Interventions: Behavioral: CBT-MI Sponsors: Overcome Recruiting

Conditions: Vaping Teens; Healthy Volunteers Interventions: Behavioral: Mindfulness-based Stress Reduction (MBSR) Program Sponsors: National Institute on Drug Abuse (NIDA) Recruiting

Conditions: Cigarette Smoking; Nicotine Vaping Interventions: Other: All nicotine/ tobacco products at market price; Other: Nicotine vaping products at 1/2 market price; Other: Heated tobacco products at 1/2 market price.; Other: Nicotine pouch products at 1/2 market price. Sponsors: Virginia Polytechnic Institute and State University; Medical University of South Carolina; University of Waterloo; National Cancer Institute (NCI) Recruiting

Conditions: Smoking Cessation; Vaping Cessation Interventions: Drug: Cytisinicline Sponsors: Achieve Life Sciences Recruiting

Conditions: Coronary Artery Disease Interventions: Behavioral: Smoking cessation; Behavioral: Switching to E-cigarette Sponsors: Samsung Medical Center Recruiting

Conditions: Vaping Interventions: Behavioral: Discussion of point-of-care ultrasound lung findings Sponsors: Medical University of South Carolina Recruiting

Conditions: Vaping; Adolescent Behavior; Communication Research Interventions: Other: Tailored Sponsors: Abramson Cancer Center at Penn Medicine; University of Florida Recruiting

Conditions: Vaping; Pregnancy Related; Pediatric Respiratory Diseases Sponsors: University College Dublin; Royal College of Surgeons, Ireland Recruiting

Conditions: Vaping; Electronic Cigarette Use Interventions: Other: Vaping Sponsors: Laval University; Ministere de la Sante et des Services Sociaux Recruiting

Conditions: Tobacco Use Disorder; Nicotine Dependence Interventions: Behavioral: Counseling; Behavioral: Contingency management; Behavioral: Text-based support Sponsors: Medical University of South Carolina; National Cancer Institute (NCI) Recruiting

Conditions: E Cigarette Use Interventions: Behavioral: adapted vaping cessation intervention Sponsors: Veterans Medical Research Foundation; University of California Recruiting

It is not yet known whether EVALI represents a widespread health risk that could affect millions of users or is isolated to certain products or practices. Whatever the case, thousands of people face severe health effects right now.

Today’s vaping clinical trials will be essential to the health of former and future e-cigarette users. Being aware of the potential risks of vaping – and making family and friends aware of those risks – is advisable as more information becomes available.

• https://www.centeronaddiction.org/e-cigarettes/recreational-vaping/what-vaping
• https://www.drugabuse.gov/publications/drugfacts/vaping-devices-electronic-cigarettes
• https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html
• https://www.cdc.gov/media/releases/2019/p1028-first-analysis-lung-injury-deaths.html
• https://rarediseases.info.nih.gov/diseases/9551/bronchiolitis-obliterans
• https://www.cdc.gov/mmwr/volumes/68/wr/mm6841e3.htm?s_cid=mm6841e3_w

Other Resources

• Guide to Clinical Trials for Alcohol
• Guide to Clinical Trials for Asbestos
• Clinical Trial Guide for Seniors and the Elderly
• Guide to Clinical Trials for Minorities
• Clinical Trial Guide for Parents and Children
• Guide to Clinical Trials for Pets
• Guide To Keeping Your Health Records Secure
• Clinical Trials on the Effects of Bullying
• Clinical Trials on the Positive Effects of Gardening and Experiencing Nature
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• What is Clinical Research?
• Research Studies for Money

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Claims vaping may expose teens to brain-damaging toxic metals, fact-checked

A new study concludes that "e-cigarette use during adolescence may increase the likelihood of metal exposure - but how worried should we be.

A new study suggests that teenagers who vape a lot could be harming their brain and organ development – because they may be absorbing damaging amounts of lead and uranium.

The finding has raised further concerns about the safety of e-cigarettes, which are used by nearly one in ten children aged 11 to 15 , even though it is illegal to sell the products to anyone under 18.

This is triple the number that vaped three years ago, as marketing tactics such as using bright colours and exotic flavours – which the government now plans to restrict – are thought to have attracted many children towards vaping.

Following previous concerns that the nicotine found in vapes could be harming the developing adolescent brain, and that e-cigarettes could be causing depression and potentially even increasing the risk of cancer , researchers from the University of Nebraska Medical Center have found a potential link to heavy metals.

What did the study find?

Their study, published in the journal Tobacco Control , involved 200 teenagers who ­vaped and who gave urine samples to be tested for heavy metals.

They were categorised as occasional vapers, meaning they had an average of 0.9 puffs a day, intermittent vapers (7.9 puffs a day) and frequent users (27 puffs).

The researchers found that the lead levels in the children’s urine were 30 per cent higher among frequent vapers than in the occasional vaping group – while their uranium levels were twice as high.

No statistically significant differences were found in urinary cadmium levels between the three groups regardless of their vaping frequency.

Scientists not involved in the study said the findings were cause for concern and raised some important issues that need to be further researched.

But they said that the study did not, in itself, prove that vaping increases the level of heavy metals in a person – or what health risks are posed by the amounts that were measured, whatever their source.

What were the shortcomings of the study?

Experts argue that the sample size is fairly small – at 200 people – and, crucially, that the vapers could have been exposed to lead and uranium in all sorts of other ways, such as diet, local water supplies or a proximity to heavy industry.

The study only found an ‘association’ between vaping and the presence of these heavy metals in the participant’s urine, rather than proving cause and effect.

Furthermore, the study didn’t have a ‘control’ group of people who didn’t vape, meaning it cannot tell us anything about the absolute increase in exposure to heavy metals from e-cigarette among the participants, only about relative exposure among less and more frequent vapers.

The scientists were keen to stress that they were not encouraging teenagers to take up vaping – except maybe if it was as a replacement for tobacco smoking.

But rather they are arguing that you can’t draw the firm conclusion that e-cigarettes push up lead and uranium levels in the body.

What have the experts said?

Professor Kevin McConway, Emeritus Professor of Applied Statistics at Open University, said: “This research can’t establish that the higher levels of lead and uranium in the urine of participants who said they vaped more often were actually caused by their vaping.

“It’s possible that that was the cause, or at least part of it – but there are several alternative explanations.”

He explains that the participants not only had different frequencies of vaping but would have differed in many other ways.

And some of these differences – for example in food and drink consumption and proximity to natural deposits, which are also potential sources of the metals – could account for at least some, if not all, of the differing levels of lead and uranium.

So even though the researchers took account of other potential factors, such as age, sex, ethnicity and exposure to secondhand tobacco smoke, there were other factors they couldn’t ‘control’ for.

The researchers behind the study point out that the “sources and pathways of uranium exposure in this contest are not well understood and would require further research to elucidate”.

“Uranium or its compounds could potentially be present in e-cigarette aerosols or e-liquids, either as contaminants or byproducts of the heating process,” they added.

In other words, the researchers aren’t saying that they actually know that there is any uranium in the vapes at all. They point out that uranium in urine could come from other sources and the same is likely to apply to lead.

So some of the difference could be down to where people live, for example, which was not taken directly into account.

Another limitation of the study is that the data came from one set of answers about vaping frequency and one set of urine measurements, made at roughly the same time, so there’s no way of knowing how metal levels in the urine might change over time as vaping levels change.

Professor Lion Shahab, Co-Director of the UCL Tobacco and Alcohol Research Group, said: “This is a well-conducted study [but it] cannot tell us anything about absolute increase in exposure to heavy metals from e-cigarette use in this population, only about relative exposure among less and more frequent e-cigarette users.

“It is also difficult to translate these results into clinically meaningful effects. However, on the basis of such studies we know that e-cigarettes expose users to much lower levels of harmful substances than cigarettes but to higher levels than fresh air, so the best advice remains: if you smoke, vaping is much safer; if you don’t smoke, don’t vape.”

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New Study Targets Marketing of Vaping Products, Influence on Young Adults

With nicotine and cannabis vaping on the rise among young adults, Cal State Fullerton public health researcher Joshua Yang is studying how exposure to new and emerging products affects use.

Yang is directing the three-year study “Influence of Emerging Alternative Products on Transitions in Nicotine and Cannabis Product Use.” The research is funded by a $1.2 million grant from the Regents of the University of California, Office of the President.

“Though cigarette smoking among young adults has been declining in the United States, the use of electronic nicotine delivery systems is particularly high,” said Yang, professor of public health.

The purpose of his study is to determine the effects of exposure to and engagement with electronic nicotine delivery systems and cannabis electronic vaporizers, or vapes, on young adults’ transitions in using tobacco and cannabis vaping products, Yang said.

“Due to the health consequences associated with vaping both tobacco and cannabis, there is an urgent need to improve our understanding of the factors that lead young adults to transition to using these products,” said Yang, whose research interests include alternative tobacco products, such as e-cigarettes, and tobacco control.

His research project focuses on young adults who only vape nicotine and whether exposure to new and emerging nicotine and cannabis products, such as those with new flavors or product designs, leads to other tobacco or cannabis product use. 

With projections for continued growth in the vaping market and expansion of the legalization of recreational marijuana, exposure to cannabis vapes is likely to continue increasing, Yang added.

Yang said the study’s results could be used to inform prevention of vaping, improve interventions for nicotine and cannabis vaping addiction, provide helpful information for cessation protocols and implement policies to better regulate the marketing of these products, especially to teens and young adults.

The study focuses on three specific research areas, including using technical tools to identify popular new and emerging products and brands as they are introduced to the market in near real time .  

Yang explained that vapes are a relatively new method of using cannabis, with the rate of cannabis vaping increasing among young adults.

“This past year, we’ve been studying online retailers selling nicotine and cannabis products marketed to young adults. Next, we’ll compare last year’s products with this year’s products,” Yang said.

This fall, Yang plans to conduct an online survey of California young adults, ages 18 to 25, to assess how emerging product engagement and other factors influence their transition from using only nicotine vapes to other products like cannabis vapes. 

The final stage of his study will focus on in-depth interviews of survey respondents to better understand changes in substance use patterns, such as transitioning to cannabis vaping. Public health student researchers will assist in analyzing the data.

“The working hypothesis is that exposure to and engagement with emerging tobacco, nicotine and cannabis products act on product use patterns through multiple interactive pathways, including through exposure to online marketing,” Yang said.

“Through this research, we hope to understand whether greater exposure to new and emerging products results in higher engagement and use.”

Contact: Debra Cano Ramos [email protected]

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August 28, 2024

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UK doctors urge government to act over 'vaping epidemic'

Leading UK doctors urged the government Wednesday to pass legislation to tackle "a vaping epidemic," in particular among young people, by banning disposable e-cigarettes and all flavors apart from tobacco.

The call came alongside the publication of a British Medical Association (BMA) report which it said was a "blueprint" for the "bold actions needed."

The previous Conservative government unveiled plans earlier this year to eventually phase out smoking, alongside banning disposable e-cigarettes and restricting their flavors and packaging.

The new Labour administration—which swept to power early last month—has revived the draft legislation but is yet to detail its exact approach.

The BMA report noted that vape use among children and young people has increased almost six-fold in the last decade.

It implored the government not to "shy away from taking brave action" in order to "stem the trend."

"There is no denying we are living in a vaping epidemic," Professor David Strain, chair of the BMA's board of science, said in comments accompanying the report's release.

He noted one in 10 ten adults now vape, while calling the six-fold increase in those aged between 11 and 17 who now vape "far more worrying."

"As a doctor, I understand the role vapes can play in helping people to stop smoking, but they have no rightful place in our children and young people's lives," Strain added.

"An industry so obviously targeting children with colors, flavors and branding, to push a product that can lead to nicotine addiction and potential further harms cannot be allowed to happen any longer."

The report recommends banning all disposable vape and non-tobacco flavor sales, as well as using imagery, coloring and branding on packaging and devices.

That would mirror current restrictions on cigarettes.

The BMA also wants curbs on advertising and marketing, and rules keeping vapes behind retail counters and not on display.

Meanwhile, it is recommending government education campaigns on the dangers of vapes to reduce their appeal, especially among youngsters.

"We are calling on ministers to take bold and brave actions that will make a real difference," Penelope Toff, the BMA's public health medicine committee head, said.

A Department of Health and Social Care spokesperson said marketing vapes to children and young people was "utterly unacceptable."

The spokesperson said planned legislation will outlaw the practice while "regulating flavors , packaging, and changing how and where they are displayed in shops."

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An updated overview of e-cigarette impact on human health

Patrice marques.

1 Department of Pharmacology, Faculty of Medicine, University of Valencia, Avda. Blasco Ibañez 15, 46010 Valencia, Spain

2 Institute of Health Research INCLIVA, University Clinic Hospital of Valencia, Valencia, Spain

Laura Piqueras

3 CIBERDEM-Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders, ISCIII, Av. Monforte de Lemos 3-5, 28029 Madrid, Spain

Maria-Jesus Sanz

Associated data.

Not applicable.

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.

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 ​ (Table1) 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 ​ (Table1) 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 ].

Urine levels of metabolites of hazardous compounds in e-cigarette -only users versus dual users and non-smokers

The concentrations of metabolites were normalised to creatinine values. PMA  phenylmercapturic acid (metabolite of benzene), HEMA  2-hydroxyethylmercapturic acid (metabolite of ethylene oxide), CNEMA  2 cyanoethylmercapturic acid (metabolite of acrylonitrile), 3-HPMA  3 hydroxypropylmercapturic acid (metabolite of acrolein), 2-HPMA  2-hydroxypropylmercapturic acid (metabolite of propylene oxide), AAMA  2-carbamoylethylmercapturic acid (metabolite of acrylamide), HMPMA  3-hydroxy-1-methylpropylmercapturic acid (metabolite of crotonaldehyde)

*P < 0.05 or **P < 0.01 versus e-cigarette –only users’ group. Data adapted from Rubinstein et al. [ 9 ]

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 – 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 – 29 ]. Importantly, however, most of these studies have investigated only short-term effects [ 10 , 14 , 15 , 22 , 27 – 29 , 31 , 32 ], and the long-term effects of e-cigarette consumption on human health are still unclear and require further study.

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 – 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 ​ (Table2) 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.

Content comparison of the most common carbonyl compounds from e-cigarettes versus conventional tobacco cigarettes consumption

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 – 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 ​ (Table2) 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 – 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 – 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 – 91 ].

Other important components in the aerosols include silicate particles from the fiberglass wicks or silicone [ 89 – 91 ]. Many of these products are known to cause abnormalities in respiratory function and respiratory diseases [ 89 – 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 ​ and2 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 – 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 ​ Table3 3 .

Future research needed in the impact of e-cigarette -consumption in human health

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.

Acknowledgements

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

Abbreviations

Authors' contributions

All authors discussed and agreed to the scope of the manuscript and contributed to the development of the manuscript at all stages. All authors read and approved the final manuscript.

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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The authors of the manuscript declare no conflicts of interest and take sole responsibility for the writing and content of the manuscript. None of the authors have been involved in legal or regulatory matters related to the contents of this paper.

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The BMA urges Government to take action to stop a growing ‘epidemic’ of vaping

Press release from the BMA

The BMA is calling on the Government to stop what it calls a “growing epidemic of vape use in the UK”. With vape use among children and young people increasing almost six-fold in the last decade 1 , a BMA report released today indicates that one of the most dominant factors influencing this rise is the widespread availability of disposable vapes. Within the report, the professional association for doctors across the UK lays out a series of bold actions needed to stem the trend of increased vaping, particularly among children and young people, and those who have never smoked. While the previous Conservative government introduced the Tobacco and Vapes Bill earlier this year which set out proposals around regulating the sale of vapes, this was not carried forward into the new parliamentary session. The new Labour Government re-introduced a Bill aimed at tackling smoking and youth vaping during the King’s Speech in July, but so far there are no details of any measures that will be taken. In today’s report “Taking our breath away: why we need stronger regulation of vapes” 2 , the BMA sets out its blueprint for what legislation should include to tackle rising vape use, especially among children and young people. Recommendations include: Banning the commercial sale of all disposable vapes, on the grounds of disproportionate and harmful use by children and young people and their adverse impact on the environment. Banning all non-tobacco vape flavours. Prohibiting the use of all imagery, colouring and branding for both the packaging and vape device, similar to current restrictions on cigarettes. Further restrictions on all advertising and marketing; and ensure vapes are kept behind the counter and not on display in shops and retail outlets. Government education campaigns for the public on the dangers of vapes to reduce appeal, especially among children and young people. While the BMA recognises that vapes can be a useful tool in helping some people to stop smoking cigarettes, they offer a less dangerous rather than a risk-free alternative, with the World Health Foundation having declared them harmful. Vaping can lead to nicotine addiction, with nicotine having the potential to cause health problems such as high blood pressure and increased risk of COPD. Further, some e-cigarettes have been found to contain other harmful substances such as lead. When combined with the rising number of children and young people trying and smoking vapes, the BMA says the Government must not shy away from taking brave action. Professor David Strain, chair of the BMA’s board of science, said: “There is no denying we are living in a vaping epidemic. Vape usage has risen hugely in the last decade, with one in 10 ten adults now vaping. “However, far more worrying, is the increase in young people who vape, with almost six times more 11-17 year-olds vaping now compared with ten years ago. “As a doctor, I understand the role vapes can play in helping people to stop smoking, but they have no rightful place in our children and young people’s lives and when it comes to protecting their health, we cannot afford to gamble. “An industry so obviously targeting children with colours, flavours and branding, to push a product that can lead to nicotine addiction and potential further harms cannot be allowed to happen any longer. “And with two vapes thrown away every second in the UK, the environmental impact of this epidemic is disastrous.” Dr Penelope Toff, chair of the BMA’s public health medicine committee, added: “The last Government made significant progress putting forward a bill that included a ban on disposable vapes, and plans to regulate flavours and marketing. This new Government must now ensure these measures are carried through into legislation – and it would do well to go even further. “We are calling on ministers to take bold and brave actions that will make a real difference, like banning all vape flavours other than tobacco, so that the grip these products have on our children and young people is released, while still ensuring they remain an option to help some people stop smoking. “Likewise, there is no reason why they should need colourful branding and displays; they should be relegated to behind the shop counter, in plain packaging, like cigarettes have been for years. “While this Government has rightly pledged to tackle smoking and vaping, the test will be in how it acts. As we await details, we have put together this blueprint of the actions that are crucial right now to stop this serious public health threat in its tracks.” Ends

Notes to editors

The BMA is a professional association and trade union representing and negotiating on behalf of all doctors in the UK. A leading voice advocating for outstanding health care and a healthy population. An association providing members with excellent individual services and support throughout their lives.

• 7.6% of 11-17 year olds are now vaping regularly or occasionally, compared to 1.3% in 2014. 11% of adults in Great Britain currently use vapes, compared to 4.2% in 2014.   Source: ASH .
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News Release

Thursday, August 29, 2024

Cannabis and hallucinogen use among adults remained at historic highs in 2023

Vaping among younger adults and binge drinking among mid-life adults also maintained historically high levels, NIH-supported study shows.

Past-year use of cannabis and hallucinogens stayed at historically high levels in 2023 among adults aged 19 to 30 and 35 to 50, according to the latest findings  from the  Monitoring the Future survey . In contrast, past-year use of cigarettes remained at historically low levels in both adult groups. Past-month and daily alcohol use continued a decade-long decline among those 19 to 30 years old, with binge drinking reaching all-time lows. However, among 35- to 50-year-olds, the prevalence of binge drinking in 2023 increased from five and 10 years ago. The Monitoring the Future study is conducted by scientists at the University of Michigan’s Institute for Social Research, Ann Arbor, and is funded by the National Institutes of Health.

Reports of vaping nicotine or vaping cannabis in the past year among adults 19 to 30 rose over five years, and both trends remained at record highs in 2023. Among adults 35 to 50, the prevalences of nicotine vaping and of cannabis vaping stayed steady from the year before, with long-term (five and 10 year) trends not yet observable in this age group as this question was added to the survey for this age group in 2019.

For the first time in 2023, 19- to 30-year-old female respondents reported a higher prevalence of past-year cannabis use than male respondents in the same age group, reflecting a reversal of the gap between sexes. Conversely, male respondents 35 to 50 years old maintained a higher prevalence of past-year cannabis use than female respondents of the same age group, consistent with what’s been observed for the past decade.

“We have seen that people at different stages of adulthood are trending toward use of drugs like cannabis and psychedelics and away from tobacco cigarettes,” said Nora D. Volkow, M.D., director of NIH’s National Institute on Drug Abuse (NIDA). “These findings underscore the urgent need for rigorous research on the potential risks and benefits of cannabis and hallucinogens – especially as new products continue to emerge.”

Since 1975, the Monitoring the Future study has annually surveyed substance use behaviors and attitudes among a nationally representative sample of teens. A longitudinal panel study component of Monitoring the Future conducts follow-up surveys on a subset of these participants (now totaling approximately 20,000 people per year), collecting data from individuals every other year from ages 19 to 30 and every five years after the participants turn 30 to track their drug use through adulthood. Participants self-report their drug use behaviors across various time periods, including lifetime, past year (12 months), past month (30 days), and other use frequencies depending on the substance type. Data for the 2023 panel study were collected via online and paper surveys from April 2023 through October 2023.

Full data summaries and data tables showing the trends below, including breakdowns by substance, are available in the report . Key findings include:

Cannabis use in the past year and past month remained at historically high levels for both adult age groups in 2023. Among adults 19 to 30 years old, approximately 42% reported cannabis use in the past year, 29% in the past month, and 10% daily use (use on 20 or more occasions in the past 30 days). Among adults 35 to 50, reports of use reached 29%, 19%, and 8%, respectively. While these 2023 estimates are not statistically different from those of 2022, they do reflect five- and 10-year increases for both age groups.

Cannabis vaping in the past year and past month was reported by 22% and 14% of adults 19 to 30, respectively, and by 9% and 6% of adults 35 to 50 in 2023. For the younger group, these numbers represent all-time study highs and an increase from five years ago.

Nicotine vaping among adults 19 to 30 maintained historic highs in 2023. Reports of past-year and past-month vaping of nicotine reached 25% and 19%, respectively. These percentages represent an increase from five years ago, but not from one year ago. For adults 35 to 50, the prevalence of vaping nicotine remained steady from the year before (2022), with 7% and 5% reporting past-year and past-month use.

Hallucinogen use in the past year continued a five-year steep incline for both adult groups, reaching 9% for adults 19 to 30 and 4% for adults 35 to 50 in 2023. Types of hallucinogens reported by participants included LSD, mescaline, peyote, shrooms or psilocybin, and PCP.

Alcohol remains the most used substance reported among adults in the study. Past-year alcohol use among adults 19 to 30 has showed a slight upward trend over the past five years, with 84% reporting use in 2023. However, past month drinking (65%), daily drinking (4%), and binge drinking (27%) all remained at study lows in 2023 among adults 19 to 30. These numbers have decreased from 10 years ago. Past-month drinking and binge drinking (having five or more drinks in a row in the past two week period) decreased significantly from the year before for this age group (down from 68% for past month and 31% for binge drinking reported in 2022).

Around 84% of adults 35 to 50 reported past-year alcohol use in 2023, which has not significantly changed from the year before or the past five or 10 years. Past-month alcohol use and binge drinking have slightly increased over the past 10 years for this age group; in 2023, past-month alcohol use was at 69% and binge drinking was at 27%. Daily drinking has decreased in this group over the past five years and was at its lowest level ever recorded in 2023 (8%).

Additional data: In 2023, past-month cigarette smoking, past-year nonmedical use of prescription drugs, and past-year use of opioid medications (surveyed as “narcotics other than heroin”) maintained five- and 10-year declines for both adult groups. Among adults 19 to 30 years old, past-year use of stimulants (surveyed as “amphetamines”) has decreased for the past decade, whereas for adults 35 to 50, past-year stimulant use has been modestly increasing over 10 years. Additional data include drug use reported by college/non-college young adults and among various demographic subgroups, including sex and gender and race and ethnicity.

The 2023 survey year was the first time a cohort from the Monitoring the Future study reached 65 years of age; therefore, trends for the 55- to 65-year-old age group are not yet available.

“The data from 2023 did not show us many significant changes from the year before, but the power of surveys such as Monitoring the Future is to see the ebb and flow of various substance use trends over the longer term,” said Megan Patrick, Ph.D., of the University of Michigan and principal investigator of the Monitoring the Future panel study. “As more and more of our original cohorts – first recruited as teens – now enter later adulthood, we will be able to examine the patterns and effects of drug use throughout the life course. In the coming years, this study will provide crucial data on substance use trends and health consequences among older populations, when people may be entering retirement and other new chapters of their lives.”

View more information on data collection methods for the Monitoring the Future panel study and how the survey adjusts for the effects of potential exclusions in the report . Results from the related 2023 Monitoring the Future study of substance use behaviors and related attitudes among teens in the United States were released in December 2023, and 2024 results are upcoming in December 2024.

If you or someone you know is struggling or in crisis, help is available. Call or text 988   or chat at 988lifeline.org . To learn how to get support for mental health, drug or alcohol conditions visit  FindSupport.gov . If you are ready to locate a treatment facility or provider, you can go directly to  FindTreatment.gov or call  800-662-HELP (4357) .

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.nida.nih.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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Marijuana Is Too Strong Now

As weed has become easier to obtain, it has become harder to smoke.

Produced by ElevenLabs and News Over Audio (NOA) using AI narration.

Updated at 11:08 a.m. ET on August 29, 2024

A strange thing has happened on the path to marijuana legalization. Users across all ages and experience levels are noticing that a drug they once turned to for fun and relaxation now triggers existential dread and paranoia. “The density of the nugs is crazy, they’re so sticky,” a friend from college texted me recently. “I solo’d a joint from the dispensary recently and was tweaking just walking around.” (Translation for the non-pot-savvy: This strain of marijuana is not for amateurs.)

In 2022, the federal government reported that, in samples seized by the Drug Enforcement Administration, average levels of tetrahydrocannabinol, or THC—the psychoactive compound in weed that makes you feel high—had more than tripled compared with 25 years earlier, from 5 to 16 percent. That may understate how strong weed has gotten. Walk into any dispensary in the country, legal or not, and you’ll be hard-pressed to find a single product advertising such a low THC level. Most strains claim to be at least 20 to 30 percent THC by weight; concentrated weed products designed for vaping can be labeled as up to 90 percent.

For the average weed smoker who wants to take a few hits without getting absolutely blitzed, this is frustrating. For some, it can be dangerous. In the past few years, reports have swelled of people, especially teens, experiencing short- and long-term “marijuana-induced psychosis,” with consequences including hospitalizations for chronic vomiting and auditory hallucinations of talking birds . Multiple studies have drawn a link between heavy use of high-potency marijuana, in particular, and the development of psychological disorders, including schizophrenia , although a causal connection hasn’t been proved.

Read: Marijuana’s health effects are about to get a whole lot clearer

“It’s entirely possible that this new kind of cannabis—very strong, used in these very intensive patterns—could do permanent brain damage to teenagers because that’s when the brain is developing a lot,” Keith Humphreys, a Stanford psychiatry professor and a former drug-policy adviser to the Obama administration, told me. Humphreys stressed that the share of people who have isolated psychotic episodes on weed will be “much larger” than the number of people who end up permanently altered. But even a temporary bout of psychosis is pretty bad.

One of the basic premises of the legalization movement is that marijuana, if not harmless, is pretty close to it—arguably much less dangerous than alcohol. But much of the weed being sold today is not the same stuff that people were getting locked up for selling in the 1990s and 2000s. You don’t have to be a War on Drugs apologist to be worried about the consequences of unleashing so much super-high-potency weed into the world.

The high that most adult weed smokers remember from their teenage years is most likely one produced by “mids,” as in, middle-tier weed. In the pre-legalization era, unless you had a connection with access to top-shelf strains such as Purple Haze and Sour Diesel, you probably had to settle for mids (or, one step down, “reggie,” as in regular weed) most of the time. Today, mids are hard to come by.

The simplest explanation for this is that the casual smokers who pine for the mids and reggies of their youth aren’t the industry’s top customers. Serious stoners are. According to research by Jonathan P. Caulkins, a public-policy professor at Carnegie Mellon, people who report smoking more than 25 times a month make up about a third of marijuana users but account for about two-thirds of all marijuana consumption. Such regular users tend to develop a high tolerance, and their tastes drive the industry’s cultivation decisions.

The industry is not shy about this fact. In May, I attended the National Cannabis Investment Summit in Washington D.C., where investors used the terms high-quality and potent almost interchangeably. They told me that high THC percentages do well with heavy users—the dedicated wake-and-bakers and the joint-before-bed crowd. “Thirty percent THC is the new 20 percent,” Ryan Cohen, a Michigan-based cultivator, told me. “Our target buyer is the guy who just worked 40 hours a week and wants to get high as fuck on a budget.”

Smaller producers might conceivably carve out a niche catering to those of us who prefer a milder high. But because of the way the legal weed market has developed, they’re struggling just to exist. As states have been left alone to determine what their legal weed markets will look like, limited licensing has emerged as the favored apparatus. That approach has led to legal weed markets becoming dominated by large, well-financed “multistate operators,” in industry jargon.

Across the country, MSOs are buying up licenses, acquiring smaller brands, and lobbying politicians to stick prohibitions on home-growing into their legalization bills. The result is an illusion of endless choice and a difficult climate for the little guy. Minnesota’s 15 medical dispensaries are owned by two MSOs. All 23 of Virginia’s are owned by three different MSOs. Some states have tried to lower barriers to entry, but the big chains still tend to overpower the market. (Notable exceptions are California and Colorado, which have a longer history with legal marijuana licensing, and where the markets are less dominated by mega-chains.) Despite the profusion of stores in some states and the apparent variety of strains on the shelf, most people who walk into a dispensary will choose from a limited number of suppliers that maximize for THC percentage.

If the incentives of the market point to ever-higher concentrations of THC, one path to milder varieties would be government regulation. But legal weed exists largely in a regulatory vacuum.

Six years ago, my colleague Annie Lowrey observed that “the lack of federal involvement in legalization has meant that marijuana products are not being safety-tested like pharmaceuticals; measured and dosed like food products; subjected to agricultural-safety and pesticide standards like crops; and held to labeling standards like alcohol.” Very little has changed since she wrote that. Some states have limited THC percentages per serving for edibles, but only Vermont and Connecticut have potency caps on so-called flower, meaning the old-fashioned kind of weed that you smoke in leaf form. And then there’s the Wild West of legal hemp-derived THC products, which functionally have no potency limits at all.

Read: Congress accidentally legalized weed six years ago

Marijuana is still illegal under the federal Controlled Substances Act. States have been allowed to do their own thing, but the lack of federal legalization has meant a lack of federal regulation. In May, the Department of Justice officially proposed rescheduling marijuana from Schedule 1 under the CSA, where heroin is, to Schedule 3, where ketamine and anabolic steroids are. That change, if it happens, will dramatically expand medical -marijuana research and access, but it won’t affect the recreational market at all.

To establish an approach to marijuana legalization that protects consumers and gives them real choice and information about what they’re using, Congress would need to fully deschedule weed, not just reschedule it. Descheduling marijuana would circumvent the legal baggage of Schedule 3, allowing the federal government to ease into a nationally standardized set of health and safety regulations for recreational use, not just medical.

Such a change would ideally allow the federal government, particularly the Food and Drug Administration, the power to regulate marijuana in the same way they regulate other uncontrolled substances such as alcohol and tobacco—by overseeing packaging, advertising, and distribution. Sellers could be required to create clear, standardized nutrition-fact-style labels that indicate true THC percentage, recommended dosages, and professional suggestions for what to do in the case of a bad high. A full descheduling would also shorten the research knowledge gap, because private marijuana companies could run FDA-approved tests on their products and develop modern regulatory strategies that align with public-health standards.

The history of drug enforcement in America was long one of discriminatory, draconian enforcement. But the shift toward legal weed has tacked too far in the opposite direction. If marijuana is to be sold legally, consumers should know what they’re buying and have confidence that someone is making sure it’s safe. If we can agree as a society that getting high on weed shouldn’t be illegal, we can also agree that smoking weed shouldn’t involve dissociating at a house party or running into the middle of a snowstorm because you think imaginary bad guys are after you. The sad irony of legalization is that as weed has become easier to obtain, it has become harder to smoke.

Support for this project was provided by the William and Flora Hewlett Foundation.

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Vaping and smoked tobacco regulations published today

Goals to tackle youth vaping rates and secure a smokefree future for Aotearoa New Zealand have taken a significant step forward today with new vaping and smoked tobacco regulations released .

New vaping regulations include :

• New Specialist Vape Retailers (SVR) stores must be at least 300 metres away from schools and marae
• Vape products and their packaging must only have generic flavour descriptions
• Maximum allowable nicotine strength in single-use (disposable) vapes is reduced to 20mg/mL to make them less addictive for youth and non-smokers
• All vaping products must have removable batteries and child-safety mechanisms to improve their safety and better protect our young people.

A timeline of how the vaping regulations will be phased in is available on the Ministry of Health website.

In addition to legislative measures being implemented to address youth vaping, the Ministry of Health, Te Whatu Ora and Te Aka Whai Ora developed health promotion programme Protect Your Breath (PYB) to encourage young people to live vape free lives. This launched on social media and other places that reach young people late last year. A PYB youth-focused online mindfulness series launched in July and the Later Vaper Arcade – an interactive space where young people will be challenged to re-frame and re-position their thinking on vaping – is coming soon.

Smoked tobacco regulations provide:

• Finalised criteria that will be used to select approved smoked tobacco retailers for the smoked tobacco retail scheme. This has responsible people, business location, safety, security and training at the forefront of all considerations. The scheme takes effect from 1 July 2024 and will see the number of tobacco retailers drop to no more than 600.
• Finalised product testing requirements so that from 1 April 2025, we can ensure only very low-level nicotine products are being sold. Full strength cigarettes contain approximately 15-16mg/g of nicotine and low nicotine tobacco will have no more than 0.8mg/g, resulting in a significantly less addictive product.

The smoked tobacco retail scheme application process will open through the Ministry’s Health Advisory and Regulatory Platform (HARP) on 21 September 2023 and applicants wanting to be considered for a place on the scheme have until 12 November 2023 to submit an application.

More information on the Smoked Tobacco Retail Scheme will be available on the Ministry’s website soon. A smoked tobacco timeline is available on the Ministry’s website.

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