Health effects and known pathology associated with the use of E-cigarettes

Abstract

In recent years, new nicotine delivery methods have emerged, and many users are choosing electronic cigarettes (e-cigarettes) over traditional tobacco cigarettes. E-cigarette use is very popular among adolescents, with more than 3.5 million currently using these products in the US. Despite the increased prevalence of e-cigarette use, there is limited knowledge regarding the health impact of e-cigarettes on the general population. Based on published findings by others, E-cigarette is associated with lung injury outbreak, which increased health and safety concerns related to consuming this product. Different components of e-cigarettes, including food-safe liquid solvents and flavorings, can cause health issues related to pneumonia, pulmonary injury, and bronchiolitis. In addition, e-cigarettes contain alarmingly high levels of carcinogens and toxicants that may have long-lasting effects on other organ systems, including the development of neurological manifestations, lung cancer, cardiovascular disorders, and tooth decay. Despite the well- documented potential for harm, e-cigarettes do not appear to increase susceptibility to SARS-CoV- 2 infection. Furthermore, some studies have found that e-cigarette users experience improvements in lung health and minimal adverse effects. Therefore, more studies are needed to provide a definitive conclusion on the long-term safety of e-cigarettes. The purpose of this review is to inform the readers about the possible health-risks associated with the use of e-cigarettes, especially among the group of young and young-adults, from a molecular biology point of view.

Keywords: AEC, airway epithelial cells; AM, alveolar macrophages; BAL, bronchial alveolar lavage; CC16, Clara cell protein 16; CM, cardiomyocyte; CNS, central nervous system; COPD, chronic obstructive pulmonary disease; CS, cigarette smoke; CSC, Cancer Stem Cell; CYP, cytochrome P450; E-cigarettes; E2F1, E2F transcription factor 1; EMT, epithelial-to-mesenchymal transition; ENDS, electronic nicotine delivery system; EVALI; EVALI, e-cigarette or vaping product use-associated lung injury; FDA, Food and Drug Administration; FOXO3, forkhead box O3; HNSCC, head and neck squamous cancer cells; HUVEC, human umbilical vein endothelial cells; Health risks; IL, interleukin; LDL, low-density lipoprotein; MCP-1, monocyte chemoattractant protein-1; MMP9, matrix metallopeptidase 9; MPP, Mycoplasma pneumoniae pneumonia; NET, neutrophil extracellular traps; NK, natural killer; NOX, NADPH oxidase; NQO-1, NAD(P)H quinone dehydrogenase 1; Nicotine; Nrf2, nuclear factor erythroid 2-related factor 2; OGG1/2, 8-oxoguanine glycosylase; OS, oxidative stress; Oct4,, Octamer-binding transcription factor 4; PAFR, platelet-activating factor receptor; PAHs, polycyclic aromatic hydrocarbons; PG, propylene glycol; ROS, reactive oxygen species; Sox2,, SRY (sex determining region Y)-box 2; THC, Tetrahydrocannabinol; TNF‐α, tumor necrosis factor alpha; VAPI, vaping-associated pulmonary injury; VG, vegetable glycerin; Vaping; XPC, xeroderma pigmentosum complementation group C; Yap1, Yes associated protein 1; ZEB, zinc finger E-box binding homeobox; ZO-1, zonula occludens-1; e-cigarettes, electronic cigarettes; e-liquid, e-cigarette liquid; e-vapor, e-cigarette vapor; iPSC-EC, induced pluripotent stem cell-derived endothelial cells; pAMPK, phospho-AMP-activated protein kinase.

Graphical abstract

Fig. 1

Comparison of nicotine delivery systems. Schematic representation of commercially available vaping devices and their different components. The delivery systems of nicotine in vaping devices are very different from traditional cigarettes that generate smoke by combustion of tobacco and are inhaled through a filter . Tank e-cigarettes are battery-powered devices that deliver a charge to the metal coil when the activation “on/off button” is pressed, which heats the e-liquid in the cartridge, generating vapor that is inhaled through the mouthpiece , . On the other hand, single-use e-cigarettes do not utilize a mechanical ‘on’ trigger but activate vapor production through the user’s suction on a disposable, combined cartridge, and mouthpiece , .

Fig. 2

Summary of the clinical manifestations related to e-cigarette use. In the lungs vaping causes hypoxic respiratory failure, bilateral opacity, lipoid pneumonias, interstitial lung disease, bronchiolitis and diffuse alveolar hemorrhages . Furthermore, increased production of CYP that metabolically activate PAHs from the e-vapor, has been linked to lung cancer by promoting ROS production and enhancing genotoxicity . Vaping causes neurological disorders like seizures, syncope and tremors, disrupts the integrity of the BBB in the brain and increases the risk of developing a stroke , , , , , . E-vapor could also induce changes in the embryonic brain that may contribute to future cognitive and behavioral abnormalities, like deficits in short-term memory . Many e-cigarette brands contain acidified nicotine salts which result in delivery of high nicotine levels and potentially create dependence . Impact of vaping on the cardiovascular system includes transient elevation of blood pressure, arterial stiffness, tachycardia, angiogenesis and dyslipidemia , , , , , , . Additionally, vascular endothelial cells exposed to e-liquid showed decreased viability and higher production of ROS, leading to overall dysfunction . Vaping also has detrimental effects in the oral cavity including black and hairy tongue, oral mucosal lesions, nicotine stomatitis, uvulitis, tonsillitis, laryngitis, periodontal and gingivitis disease , , , , , , , , , , , , , .

Fig. 3

Main molecular mechanisms mediating e-cigarette pulmonary pathology. E-cigarette use has been demonstrated to elicit molecular responses in various cell types of the respiratory system. The effects of e-vapor exposure in AEC are 1) elevated ROS production which can lead to decreased antimicrobial efficiency, enhancing pneumococcal adhesion , 2) dehydration and osmotic stress leading to airway constriction , , and 3) increased cytokine secretion such as IL-6 and IL-8 . E-vapor exposure also leads to increased secretion of the mucin MUC5AC by mucus secretory goblet cells . Lipid profiles in AM are altered in response to e-vapor exposure , , . Morphological changes in these cells showed a shift toward phospholipid secretion, leading to opsonization impairment . E-vapor exposure also leads to reduction of neutrophilic ROS production which decreases NET formation , . However, some studies have shown an increase of NET formation after e-vapor exposure , , highlighting the need to further study the effect of e-cigarettes on neutrophils.