Researchers uncovered an association between vaping and mental fog


Two new studies from the University of Rochester Medical Center (URMC) have uncovered an association between vaping and mental fog.

Both adults and kids who vape were more likely to report difficulty concentrating, remembering, or making decisions than their non-vaping, non-smoking peers. It also appeared that kids were more likely to experience mental fog if they started vaping before the age of 14.

While other studies have found an association between vaping and mental impairment in animals, the URMC team is the first to draw this connection in people. Led by Dongmei Li, Ph.D., associate professor in the Clinical and Translational Science Institute at URMC, the team mined data from two major national surveys.

“Our studies add to growing evidence that vaping should not be considered a safe alternative to tobacco smoking,” said study author Li.

The studies, published in the journals Tobacco Induced Diseases and Plos One, analyzed over 18,000 middle and high school student responses to the National Youth Tobacco Survey and more than 886,000 responses to the Behavioral Risk Factor Surveillance System phone survey from U.S. adults. Both surveys ask similar questions about smoking and vaping habits as well as issues with memory, attention and mental function.

Both studies show that people who smoke and vape – regardless of age – are most likely to report struggling with mental function.

Behind that group, people who only vape or only smoke reported mental fog at similar rates, which were significantly higher than those reported by people who don’t smoke or vape.

The youth study also found that students who reported starting to vape early – between eight and 13 years of age – were more likely to report difficulty concentrating, remembering, or making decisions than those who started vaping at 14 or older.

“With the recent rise in teen vaping, this is very concerning and suggests that we need to intervene even earlier,” said Li. “Prevention programs that start in middle or high school might actually be too late.”

Adolescence is a critical period for brain development, especially for higher-order mental function, which means tweens and teens may be more susceptible to nicotine-induced brain changes.

While e-cigarettes lack many of the dangerous compounds found in tobacco cigarettes, they deliver the same amount or even more nicotine.

While the URMC studies clearly show an association between vaping and mental function, it’s not clear which causes which. It is possible that nicotine exposure through vaping causes difficulty with mental function.

But it is equally possible that people who report mental fog are simply more likely to smoke or vape – possibly to self-medicate.

Li and her team say that further studies that follow kids and adults over time are needed to parse the cause and effect of vaping and mental fog.

E-Cigarette Toxicology
Tobacco smoke is a complex aerosol which includes condensed liquid droplets (the particulate fraction or tar) suspended in a mixture of volatile and semivolatile compounds and combustion gases (the gas fraction). The gas phase of cigarette smoke includes nitrogen (N2), oxygen (O2), carbon dioxide (CO2), CO, acetaldehyde, methane, hydrogen cyanide (HCN), nitric acid, acetone, acrolein, ammonia, methanol, hydrogen sulfide (H2S), hydrocarbons, gas phase nitrosamines, and carbonyl compounds.

Constituents in the particulate phase include carboxylic acids, phenols, water, nicotine, terpenoids, tobacco-specific nitrosamines (TSNAs), polycyclic aromatic hydrocarbons (PAHs), and catechols. Studies are now emerging that the aerosol generated from e-cigarettes also contains many of these same toxic compounds and varying size distribution of PM not unlike that of cigarette smoke.

However, many of these compounds- and the associated PM – are present in e-cigarette aerosols at lower amounts than conventional cigarette smoke. Another consideration is the pH of the resultant aerosol, which will determine the fraction of total nicotine that is biologically available in the unprotonated form. The pH of e-cigarette aerosols varies from 4.85–9.6, whereas the pH of smoke from flue-cured tobaccos found in most cigarettes is acidic (pH 5.5–6.0). [43,70].

E-cigarette aerosols that are more alkaline (pH 6.5 or higher) results in nicotine existing primarily in the free-base form (unprotonated) which crosses the cell membrane for more rapid absorption. The long-term effect of exposure to-e-cigarette aerosols with a high pH is not known but might suggest that users will get their daily intake of nicotine faster than tobacco smokers, leading thus to reduction in vaping frequency and exposure to aerosols. Below, we further compare and contrast cigarette smoke toxicology with that of emerging data from e-cigarette aerosols.

Ultra Fine Particles (UFP)
PM can be classified according to their size: PM10: coarse particles less than 10 µm in diameter; PM2.5: fine particles less than 2.5 µm; and PM0.1: ultrafine particles (UFPs) smaller than 100 nm. Of these, PM0.1 has the potential to exert significant harm, as particles of this size can escape broncho-mucociliary action and scavenging by alveolar macrophages.

These particles also penetrate deep into the respiratory tract (i.e., the alveolus) where they can be absorbed by the blood stream [71]. Smoking one cigarette exposes the human respiratory tract to between 10,000 and 40,000 μg PM (≈1012 particles per cigarette) [72] with a mean diameter <1 μm. Some studies indicate that e-cigarette aerosols contain less PM than cigarette smoke [73].

On the contrary, other studies state these aerosols contains high levels of UFP [74], reaching values of more than 2 × 105 particles/cm3 [75]. Such discrepancies can be due to differences in the parameters used during the study (e.g., type of e-cigarette, brand, flavor, and voltage).

However, PM from e-cigarettes evaporate within 10–20 s, and immediately after the vaping period, the aerosol concentration reaches initial background levels. On the contrary, PM emitted from cigarette smoke was lower in concentration but had a much longer lifetime (1.4 h). It was suggested therefore that the majority of e-cigarette aerosols are composed of volatile material, probably PG and/or VG [76].

The size and level of particulates in e-cigarette vapors have a bimodal particle size distribution of UFPs and submicron particles (96–175 nm) [77], with power and coil resistance greatly affecting e-cigarette aerosol count and mass distribution of particles [78]. This differs in comparison to that of a typical combustion cigarette, as the generation of particles in e-cigarette aerosols is smaller than those found in the smoke of combustible cigarettes [79].

This can be of concern as UFP can deposit deep in the lung and long-term exposure to UFP is associated with chronic inflammatory diseases such as COPD [71]. A dosimetry study estimated that an average of 6.25 × 1010 particles is deposited in the pulmonary tree after a single puff from an e-cigarette, with the highest deposition densities found in the lobar bronchi [80].

The effects of particles found in e-cigarette aerosols on the lung function remains unknown although PM and UFP are associated with cancer, cardiovascular, and respiratory diseases and cause epigenetic modifications, including alterations in the expression of noncoding RNAs. Such epigenetics changes can lead to dysregulation in genes expression [71,81]. Future studies should focus on identifying the nature of inhaled UFP from e-cigarettes and their negative impact on health.

Formaldehyde, acetaldehyde, and acrolein are three toxic low-molecular weight aldehydes present in cigarette smoke (700–800 μg/cigarette in mainstream smoke) as well as e-cigarette aerosols (8.2 to 40.4 μg/10 puffs) [82]. While the concentration of aldehydes in e-cigarette aerosols depends on the voltage of the battery and the temperature of the heating-coil, the quantity of these is variable between devices.

However, studies suggest that the level of aldehydes in e-cigarette aerosols can approach those from traditional cigarettes if the e-cigarette device is used at higher power settings (i.e., 5.0 V and more) or during dry puff conditions. Dry puff occurs when the atomizer heats up but does not have enough e-liquid to vaporize. In this case, the levels of aldehydes can increase up to 344.6 µg for formaldehyde and 206.3 µg for acetaldehyde [83].

Noteworthy is findings that there is production of carbonyls from thermal decomposition of PEG 400 and MCT. Also when heated to 230 °C, PEG 400 produced formaldehyde and acetaldehyde, two carcinogenic compounds, at levels that exceeded those produced by PG. PEG 400 and PG produced as much as 1.12% of the daily exposure limit/one inhalation, nearly the same exposure as smoking one cigarette. MCT and VG also produced low levels of aldehydes (approximately 33 times less than PEG 400) [84].

PAHs are organic compounds composed of multiple aromatic rings that contain mainly carbon and hydrogen. PAHs are produced from the incomplete combustion of organic compounds and thus are present in smoke from forest fires, wood, and cigarettes. Exposure to PAHs activates the aryl hydrocarbon receptor (AhR) which induces the expression of xenobiotic metabolizing enzymes (XMEs). These XMEs, such as cytochrome P450 1A1 and 1B1 (CYP1A1 and CYP1B1, respectively) are important in the metabolism and clearance of most PAHs [85]. Many PAHs are toxic and/or carcinogens.

For example, naphthalene is one of the most abundant PAHs (average intake rate by inhalation is 19 μg/day) [86] and is a respiratory toxicant as well as a possible human carcinogen (group 2B) [87]. In cigarette smoke, more than 500 PAHs are generated [88], and findings in animal models indicate that deleterious health effects are mediated by the AhR [85]. Benzo[a]pyrene (B[a]P) is another PAH present in cigarette smoke (<10 ng/cigarette) and is a group 1 carcinogen [89]. The type and amount of PAHs in e-cigarette aerosol is less than that of tobacco smoke [90].

In one study, Margham et al., examined the presence of 16 PAHs in different e-cigarette aerosols including dibenz[a,e]pyrene, naphthalene, and chrysene; the levels of these PAHs were 99.7% lower in e-cigarette aerosol compared to smoke from research cigarettes [91]. Overall, this suggests that e-cigarettes may pose less risk than tobacco because of the reduction in exposure to PAHs. Despite this, the presence of some of these PAHs in e-cigarette aerosols may also mean that vaping is not completely risk free.

E-liquids can contain traces of many inorganic elements and toxic metals such as sodium, bromine, gold, scandium, iron, and cobalt. The concentrations are much less than the respective ones in cigarette smoke, and thus, the risk associated with exposures could be very low. However, long-term studies are required to evaluate if these metals can accumulate in the lung and cause adverse effect after long-periods of exposure [92].

Moreover, in e-cigarettes, heating coils are usually made of nichrome (combination of nickel (Ni) and chromium (Cr)) and stainless steel. Toxic metals from heated coils can leach into vaping aerosols [91] and is the reason why Ni and Cr are present in e-cigarette aerosols but not the e-liquids [93,94]. This suggests that the Cr and Ni emission are higher than smoke from tobacco cigarettes.

Analysis of cigarette smoke showed that emission levels were not quantifiable. However, Cr and Ni levels in e-cigarette aerosol were 50 ng in the first 100 puffs [91]. Ni and Cr are toxic for human and classified as a group 1 carcinogen by the International Agency for Research on Cancer (IARC); inhalation of these metals is associated with chronic bronchitis and reduced lung function [95]. In addition to Ni and Cr, copper and zinc are also detected in e-cigarette aerosols (0.2 µg generated from 100 puffs).

Cadmium (Cd), a metal present in tobacco, is also found in aerosols but not in e-liquids. Analysis of four different e-cigarettes showed that the concentration of Cd in the e-cigarette aerosol is lower than in tobacco smoke (0.002 µg/15 puffs vs 0.056 µg/15 puffs, respectively) [96]. Cadmium accumulates in the lung of smokers, and although there is an association between Cd exposure and an increased risk of lung cancer, studies are inconclusive due to confounding factors such as the presence of other metals [97].

Other Toxicants
Aerosols generated from e-cigarettes also contain TSNAs and volatile organic compounds (VOCs) [10,43,45]. Among the VOCs found in e-cigarette aerosols, benzene is a main one, being classified as a known human carcinogen. Benzene is typically found in the air due to emissions from burning oil and motor vehicle exhaust.

Cigarette smoke is also a major source for benzene, accounting for nearly half of all human exposures. A comparative study evaluated the emission of benzene in e-cigarette aerosols. In this study, benzene was not detected in JUUL. However, in two refill tank systems, benzene was formed from solvents (PG and glycerol) and additives (benzoic acid and benzaldehyde).

Levels of benzene ranged between 1.8 μg/m3 and 5000 μg/m3, depending on the power settings and additives. Despite being much less than what is observed in traditional cigarettes (200,000 μg/m3), the concentrations of benzene found in e-cigarette aerosol still raises concern, especially considering that chronic, repeated exposure to benzene from e-cigarette aerosols might not be of negligible risk [62].

TSNAs are also present in trace amounts in e-cigarette aerosols. TSNAs are among the most important carcinogens in cigarette smoke and are formed during the curing process from nicotine and other tobacco alkaloids [98]. Total levels of TSNAs typically range from 200 to 1600 ng/cigarette [99]. Among the seven present in tobacco smoke, nicotine-derived nitrosamine ketone (NNK) and N-nitrosonornicotine (NNN) are regarded as the most carcinogenic [100]. Other TSNAs include N′-nitrosoanatabine (NAT) and N-nitrosoanabasine (NAB) [101].

Several studies have reported that certain TSNA have been detected in e-cigarette aerosols, but the levels are considerably lower than in tobacco cigarettes (0.8 ng to 28.3 ng/e-cigarette aerosols (150 puffs) [100]. For this reason, the FDA recently announced its intention to regulate TSNAs in e-cigarettes [100]. With the rise of vaping as alternative of smoking, it is important to monitor the levels of TSNAs in the body as a result of the use of e-cigarettes. Additional studies on the potential risk of these TSNAs would enhance our understanding the health concerns of long-term exposure to TSNAs from e-cigarette aerosols.

Cellular Alterations from E-cigarette Exposure
Toxicity caused by e-liquids and the resultant aerosol that is generated may be the result of numerous factors including the composition of the e-liquid, the temperature, dose, duration, and the cell type. Cells within the respiratory epithelium represent the first line of defense against pathogens and inhaled toxicants, including those in cigarette smoke and e-cigarette aerosols. The lower respiratory tract (from the trachea through to the alveoli) is lined with more than 50 different cell types, most of which are epithelial [102].

Approximately half of the epithelial cells are ciliated and interspersed with basal cells, goblet cells (which produce mucin), and Clara cells, a non-ciliated secretory cell that produces Clara cell secretory protein (CCSP). The gas-exchanging alveoli consist of an epithelial layer and extracellular matrix surrounded by capillaries.

There are three major types of cells within the alveoli: type I pneumocytes which play role in gas exchange; type II pneumocytes which release pulmonary surfactants to lower surface tension; and alveolar macrophages, phagocytic cells that play major role in host defense [102,103].

Epithelial injury can serve as an initiating factor for a variety of lung diseases such as cancer and COPD. It is well known that smoking reduces the integrity of the epithelium barrier, thereby increasing the permeability of the respiratory epithelium, and impair host defense to reduce bacterial clearance. Moreover, cigarette smoke incites lung inflammation, induces oxidative stress, and causes DNA damage [104].

Studies are now emerging that indicate e-cigarettes also decrease cell integrity and induce inflammation, two effects that may be independent of the type of vaping device, cell type, as well as the presence of flavors and other components of e-liquids (e.g., solvents and nicotine) [102,105,106,107,108].

Chronic inflammation is thought to drive the development and progression of lung cancer and COPD [109]. Exposure to cigarette smoke causes airway inflammation and activates a molecular signaling cascade resulting in the production of cytokines and chemokines such as interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and IL-8 [110].

Cigarette smoke increases permeability of the respiratory epithelium and causes mucous overproduction. This pro-inflammatory milieu in the lung leads to consecutive recruitment of immune cells. Neutrophils and macrophages are among the first cells recruited, but other immune cells such CD8+ T cells are also increased. Accumulation of these immune cells leads to further release of pro-inflammatory cytokines, chemotactic factors, reactive oxygen species (ROS), and proteases, thereby perpetuating this inflammatory response [110,111].

The inflammation-promoting effects of tobacco smoke inhalation are undisputed, and emerging evidence indicates that e-cigarette aerosols also promote inflammation in the respiratory system, albeit at lower levels. For instance, mice exposed to tobacco flavored e-cigarette aerosols containing nicotine had an increase in pro-inflammatory cytokine and chemokine secretion [112] as well as increased infiltration of neutrophils and macrophages [113].

Similar to cigarette smoke, after a 3-day exposure to e-cigarette aerosols, there were higher levels of Muc5ac [113], a predominant gel-forming mucin that is induced during allergy, and it also increased in the airways of smokers and e-cigarette users [114]. In addition, the levels of neutrophil extracellular traps (NETs) and the neutrophilic enzymes elastase and matrix metalloproteinase-9 (MMP-9) that are associated with the development of COPD, are significantly elevated in e-cigarette users [114].

One variable that may impact the potential adverse effects of e-cigarettes is the device settings. Users tend to increase heating element parameters by regulating battery voltage and electrical resistance of the coil. Indeed, a survey study on 522 adults showed that, on average, the user sets the power of their devices to 28.3 ± 24.2 W [115].

These variables as well as puff topography (e.g., puff duration, inter-puff interval, and number of puffs) affect aerosol generation and nicotine delivery and thus could impact the potential health effects of e-cigarettes, including the level of inflammation. For example, PG and glycerol aerosols generated by an e-cigarette device operating at more than 40 W (considered to be high wattage) induced the release of IL-6 and IL-8 by human bronchial epithelial [116].

In a comparative study, Cirillo. S. et al. used two identical devices containing the same e-liquid (PG/VG ratio, nicotine concentration, and flavors) but equipped with two different coils (1.5 and 0.25 ohm) to obtain total wattages of 8 ± 2 W and 40 ± 5 W, respectively. Aerosols generated at higher wattage induced a much more robust inflammatory response in rats compared to aerosols generated at lower wattage [117], suggesting that device characteristics are key factors that affect inflammation induced by e-cigarette aerosols.

Although in vitro and animal studies indicate that there are respiratory irritants in e-cigarette liquids capable of eliciting pulmonary inflammation, especially at high wattage, other parameters such as the fraction of exhaled nitric oxide (FeNO), a noninvasive marker of airway inflammation, and serum C-reactive protein (CRP), a nonspecific marker of systemic inflammation, are minimally affected by exposure to e-cigarettes [118,119].

Nitric oxide (NO) is a gas produced by many inflammatory cells due to the enzymatic activity of inducible nitric oxide synthase (iNOS). NO plays an important role as an antiviral molecule [120] and reduces the activity of macrophages, T lymphocytes, dendritic cells, mast cells, neutrophils, and natural killer (NK) cells [121]. FeNO is a test that measures the level of NO in parts per billion (PPB) in the exhaled air from the lung, is considered a marker of airway inflammation, and therefore is often used to determine the level of inflammation in allergic and eosinophilic asthma patients [122].

The extent to which NO is altered by e-cigarette exposure is controversial. Although individuals exposed to e-cigarettes had reduced FeNO immediately post vaping, which implies a reduction of lung inflammation [118], a separate study by Boulay et al. found no significant difference in FeNO or serum CRP after exposure to a laboratory made mixture of PG and glycerin [119].

Some effects may be due to nicotine itself. Interestingly, nicotine can both promote and reduce inflammation. By acting through nAChRs on immune cells, nicotine inhibits the function of the transcription factor nuclear factor-κβ (NF-κB) by increasing the phosphorylation of signal transducer and activator of transcription 3 (STAT3) [123,124].

Conversely, nicotine can activate immune cells by increasing their chemotactic activity, migration, and interaction with endothelial cells, resulting in a heightened inflammatory response [125]. Thus, numerous studies demonstrate that vaping causes an inflammation that is similar to that caused by cigarette smoke inhalation but probably to less of an extent. However, to be able to make definitive conclusions, more studies are required to better characterize the inflammatory response in the lung after long-term exposure to e-cigarettes.

Oxidative Stress
The pro-inflammatory effects of e-liquid aerosols may be mediated, at least partially, by ROS generation. ROS are chemically reactive species that contain a radical oxygen such as superoxide anion (O2−), hypochlorite (ClO−), peroxynitrite (ONOO−), and hydroxyl (•OH) or a non-radical oxygen such as hydrogen peroxide (H2O2). In the cell, ROS are generated during mitochondrial oxidative metabolism and serve as important signaling molecules in cell proliferation and survival.

ROS are also produced by the cells in response to xenobiotics, damage, and infections (mostly by neutrophils and macrophages) as a mechanism of defense [126,127]. Excessive ROS levels leads to oxidative stress, which is defined as an imbalance between the production of ROS and their elimination by antioxidants enzymes (e.g., superoxide dismutase (SOD) and glutathione peroxidase (GPX)).

In cigarette smoke, ROS are produced during the combustion process (120–150 nmol of ROS) [127]. Characterization of ROS in e-cigarette aerosols is more limited, and results are often contradictory. For instance, a recent study reported that ROS levels varies between 1.2–8.9 nmol/puff (with H2O2 accounting for 12–68% of total ROS) and that the amount ROS is dependent on the e-cigarette brand, flavor, and puffing regime.

Moreover, ROS production increased eight times as the voltage increased from the 3.7 V to 5.7 V [128]. In addition, cigarette smoke and e-cigarette aerosols also induce ROS production by the cells themselves. Different e-cigarettes and JUUL pod flavors generated significant amounts of cellular ROS and mitochondrial superoxide production in bronchial epithelial cells and monocytes, resulting in increased inflammatory mediators such as IL-6, IL-8, and prostaglandin E2 (PGE2) [46,52].

Moreover, e-cigarette aerosol-induced ROS is capable of triggering apoptosis and programmed necrosis that reduces overall cell viability [129]. Other cell death machinery is perturbed by e-cigarette aerosols including autophagy, a process by which proteins and other cellular components are recycled in order to maintain cellular homeostasis.

Autophagy is induced in response to cellular stress such as nutrient deprivation, oxidative stress, DNA damage, protein aggregates, damaged organelles, or pathogens, whereby it functions as a cytoprotective response [130]. E-cigarette exposure, similar to cigarette smoke, induces autophagy in human bronchial epithelial cells and murine lungs [131]. Nicotine inhalation was also linked with reduced cell viability via induction of cellular apoptosis/senescence through ROS-mediated autophagy [132].

Aldehydes also cause release of proinflammatory cytokines, proteases, and ROS in pulmonary and endothelial cells. These findings are of potential importance, as emphysema, the component of COPD characterized by alveolar loss, is mechanistically attributed to aberrant activation of these various cell death pathways [133]. In conclusion, vaping can induce cellular responses similar to those caused by smoking (e.g., oxidative stress and cell death), which are mechanistically linked to emphysema.

DNA Damage

Lung cancer is a leading cause of preventable death in the world, and the role of cigarette smoke in the etiology of lung cancer is well established. Many chemicals present in cigarette smoke such as the aldehydes and PAHs induce DNA adducts [134]. Several studies suggest that exposure to e-cigarettes also induces DNA damage [46,135,136,137,138], possibly because of increased oxidative stress [137,139].

However, the extent to which e-cigarette aerosols cause DNA damage is incongruent, with at least one study reporting that e-cigarette aerosols do not induce damage as measured by assessment of DNA double-stranded breaks [140]. This discrepancy may arise from differences in e-cigarette products and/or methodology (e.g., technique used to evaluate DNA damage, cell type, and/or method for generating the aerosol).

E-liquids—as well as nicotine alone—may inhibit DNA repair mechanisms. At least five major DNA repair mechanisms exist, including base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), homologous recombination (HR), and nonhomologous end joining (NHEJ) [141].

Current evidence exists that e-cigarette aerosols impair DNA repair by reducing the level of xeroderma pigmentosum C (XPC) and 8-Oxoguanine glycosylase (OGG1/2) involved in NER and BER, respectively [112,136]. While emerging cell-based evidence indicates the possibility of DNA damage, these same data add to the difficulty in drawing conclusions and highlight the need for further studies to assess the link between long-term use of e-cigarettes and cancer.

Host Defense
Traditional cigarette smoke exposure increases susceptibility to influenza and other respiratory infections such as tuberculosis and pneumonia [142,143] through numerous effects on host defense mechanisms. Smoking impacts both innate and adaptive immunity.

Innate immunity is nonspecific defense mechanisms including physical barriers (e.g., epithelium of the skin and lungs) and various immune cells such as macrophages and NK cells. Macrophages are phagocytic cells that engulf and digest cellular debris along with foreign substances such as microbes. Exposure to smoke inhibits the phagocytotic function of macrophages [144,145,146].

The cytolytic capacity NK cells, for which the primary function is to destroy virus-infected cells and to limit the spread of tumors, is attenuated by cigarette smoke [147]. Similarly, there is growing evidence that e-cigarette exposure decreases host defense mechanisms [51,107,148,149] by decreasing the phagocytic ability of macrophages, resulting in reduced bacterial clearance [142,149].

Moreover, e-liquid vapors decrease the production of the antiviral protein SPLUNC1 by epithelial cells and thus increase susceptibility to infection by rhinovirus, a respiratory virus that is the primary cause of the common cold [51]. Moreover, long-term exposure (3 months) of mice to e-cigarettes downregulates the antiviral immune response (secretion of interferon γ (IFN-γ)) by lung-resident macrophages against influenza virus [150]. Influenza is an acute respiratory infection associated with a significant morbidity and mortality. Influenza affects 10–20% of patients annually in developed countries, and there is increased susceptibility among smokers.

Adaptive immunity, defined by the presence of B and T lymphocytes, is also negatively affected by cigarette smoke, as numerous studies have shown that smoking increases the number of CD8+ T cells which may lead to emphysematous lung destruction [146]. There are currently no experimental studies on the effect of vaping on adaptative immune function in response to infections.

The sole report in humans indicates that vaping decreases the expression of immune genes in nasal scrape biopsies including chemokine (C-X-C Motif) ligand 2 (CXCL2), chemokine (C-X3-C Motif) receptor 1 (CX3CR1), as well as cluster of differentiation 28 (CD28). [151].

CD28 is co-stimulatory signal required for T-cell activation, and the chemokines and their receptors play a critical role in the activation and recruitment of immune cells to sites of infection and inflammation [152,153]. Overall, these studies suggest that e-cigarettes can disturb the immune response, and future studies to address whether use of e-cigarettes increase the susceptibility to infections are needed.

Epigenetic Modifications
Epigenetics refers to changes in gene expression that do not involve changes in the DNA sequence and includes histone modifications, microRNA (miRNAs) and long noncoding RNAs (lncRNAs), and DNA methylation [71]. Cigarette smoke is now well established to cause epigenetic modifications. Smoke-induced DNA methylation is a possible mechanism behind smoke-induced diseases such as cancer.

DNA methylation is also associated with vaping, with in utero e-cigarette exposure of mice leading to abnormalities in DNA methylation that was associated with a higher abnormal inflammatory environment in the lung of both the mothers and offspring [154]. Cigarette smoke also induces histone modifications and changes miRNAs levels in vitro as well as in vivo after smoke exposure and in individuals with COPD [155,156,157,158].

miRNAs are small noncoding RNAs that function in posttranscriptional regulation of genes expression by silencing mRNA expression, and their dysregulation is implicated in a number of smoke-related diseases [159,160]. There is now evidence that e-cigarette exposure alters the expression of 578 miRNAs in human lung epithelial cells, although the functional significance of these miRNAs and their contribution in the cytoxicity of e-cigarettes remains unknown [161].

Cigarette smoke also alters lncRNA expression such as Hox transcript antisense intergenic RNA (HOTAIR), colon cancer-associated transcript-1 (CCAT1), and metastasis associated in lung adenocarcinoma transcript 1 (MALAT1). LncRNAs are transcripts with lengths exceeding 200 nucleotides that are not translated into protein but function to control transcription and posttranscriptional mRNA processing. Similar to miRNAs, these functions often involve complementary base pairing with the target mRNA [162].

There is currently little information on e-cigarettes and lncRNA, although a recent report indicates that exposure to e-cigarettes alters the expression of long noncoding, antisense, small nucleolar, and miscRNAs [163]. Thus, it is possible that e-cigarettes regulate the expression of numerous genes partially through epigenetic mechanisms.


E-cigarette use is rising rapidly among both smokers and nonsmokers. The chemical composition of the aerosol produced by e-cigarettes varies depending on parameters such as the device, voltage used, and the composition of e-liquid. Compared to tobacco smoke, many of the compounds found in e-cigarette aerosols are considered toxic or carcinogenic, including aldehydes, heavy metals, and TSNAs. Present studies suggest that even short-term e-cigarette use causes similar effects as tobacco smoke including cellular inflammation, apoptosis, oxidative stress, and DNA damage (Figure 1).

These pathological processes are an important driver of many respiratory diseases such as COPD. Clearly, there is much about the effect of vaping that we do not know, including whether vaping causes decline in lung function similar to smoke, how vaping might lead to respiratory diseases, and which group of users are at highest risk?

Although for current smokers e-cigarettes can be viewed as a “lesser of evils”, the effect of e-cigarette products on respiratory health may not be known for many years. Therefore, long-term epidemiological, toxicological, and clinical studies are required to build a more solid body of evidence, allowing us to reach more definitive conclusions on the potential harms of e-cigarette use.

Until we know more on the effects of e-cigarettes on pulmonary health, we must take into account age, current and prior cigarette smoking, the presence of preexisting lung conditions such as asthma and COPD, and the potential for other pulmonary complications when considering the risk versus benefit equilibrium of e-cigarette use.

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Figure 1
The known and unknown health effects of vaping in comparison to cigarette smoke. The major toxic effects of compounds found in cigarette smoke (Right lung) and in vaping aerosols (Left lung) are lunginflammation, oxidative stress, cell death, impaired immune response, DNA damage and epigeneticmodifications. The respiratory diseases caused by cigarette smoke (lung cancer, COPD [emphysema and/orobstruction of airways]) are not yet established to be caused by vaping (represented by question marks in theleft lung). The presence of lipid-laden macrophages is a feature predominantly associated with vaping products containing THC and has been a feature of EVALI.

reference link :

More information: Catherine Xie et al, Association of electronic cigarette use with self-reported difficulty concentrating, remembering, or making decisions in US youth, Tobacco Induced Diseases (2020). DOI: 10.18332/tid/130925


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