3.1 The chemical composition of ATPs3.1.1 The chemical composition of dokha

Dokha is a blend of tobacco leaves with an array of spices, herbs, barks, dried fruits, or dried flowers and has gained its name from the pipe used to smoke the blend, the “midwakh” [12]. The array of available flavors misrepresents midwakh as a healthier cigarette counterpart among young people population. In fact, a few studies have investigated the role of toxicants and heavy metals in midwakh smoking-related diseases [27, 28]. Yet, studies that did analyze the chemical composition of midwakh report non-negligible findings [28]. As mentioned, midwakh is composed of fine dried green tobacco leaves collected without major processing. They retain high amounts of carbon monoxide, nicotine, and tar [29].

Additionally, midwakh is often smoked without a filter and rarely with a resin filter causing toxicants such as tar, carbon monoxide, hydrogen cyanide (HCN), nitrosamines, volatile organic compounds, and toxic heavy metals to immediately enter the lungs [29,30,31]. Tar, the sticky, aerosol residue of tobacco combustion, contains most of the toxic, carcinogenic, and mutagenic agents in tobacco [29]. Midwakh (dokha) has strikingly higher nicotine and tar levels than conventional cigarettes. A recent study reports that nicotine in different midwakh brands falls between 23.82 and 52.80 mg/g [29]. Furthermore, midwakh has 55.62% higher tar concentrations than cigarettes [29, 30]. CNS depressants and carcinogens such as acrylonitrile, benzene, and acrylamide have also been detected in midwakh [28, 29]. Moreover, concentrations of trace metals such as lead, cobalt, aluminum, nickel, copper, chromium, manganese, iron, potassium, calcium, zinc, magnesium, and strontium are markedly higher in midwakh than in cigarettes [27,28,29].

Alarmingly, metal content in midwakh is unregulated. A chemical analysis of midwakh smoke identified over 400 organic compounds including 22 irritants; 5 toxic compounds such as cycloheptatriene, 2-methylfuran, and m-xylene; and at least 3 carcinogens including benzene [28]. A midwakh tobacco brand was shown to have concentrations of aluminum, boron, cobalt, copper, lead, and zinc at 421.2 μg/g, 219.8 μg/g, 25.1 μg/g, 24.0 μg/g, 468.6 μg/g, and 342.7 μg/g, respectively [28]. These metals are in quantities equal or higher than in cigarettes. Interestingly, polycyclic aromatic hydrocarbons (PAHs), which are usually formed during incomplete combustion, were also detected in midwakh samples [31]. Two PAHs, naphthalene, and anthracene were found in trace amounts in raw dokha tobacco, while 12 PAHs were found in midwakh smoke at concentrations surpassing those detected in cigarettes [31].

3.1.2 The chemical composition of e-cigarettes

Formerly produced as a tobacco cessation facilitator, e-cigarettes are noncombustible electronic nicotine delivery systems containing flavoring agents [24, 25]. While e-cigarettes advanced from first-generation pods with disposable e-liquid cartridges to third-generation e-cigarettes with a refillable e-liquid tank and then to fourth-generation Joel brand, e-cigarette smoking essentially involves heating and aerosolizing an “e-liquid” made of nicotine, propylene glycol (PG), vegetable glycerine (VG), and flavor compounds using a battery-mediated device [32]. This resistance heating is done through a metallic coil, which is commonly Kanthal, comprised of iron, chromium, and aluminum or nichrome, a coil consisting of nickel and chromium [32]. Consequently, due to the thermal degradation of the e-liquid, e-cigarette gas and particle emissions consist of aerosolized PG, VG, flavors, nicotine, free radicals, and various carbonyls, and an array of hydroxycarbonyls were reported [32]. Carbonyl compounds including acetaldehyde and formaldehyde, which normally form after heating, have also been detected in e-cigarette vapor, in lower levels than cigarette smoke [33].

Unlike their conventional counterpart, no precise protocols have been established to test e-cigarettes, yet chemical analyses have been carried out, whereby 46 volatile and semi-volatile compounds were detected in e-liquid formulations and 55 compounds were found in e-cigarette aerosols [34]. A study investigating the presence of carbonyl compounds, volatile organic compounds (VOCs), tobacco-specific nitrosamines (TSNAs), and metals revealed that all tested e-cigarette samples contained three carbonyls with reported toxic properties: formaldehyde, acetaldehyde, and acrolein [35]. Almost all samples contained the volatile organic compounds toluene and m, p-xylene, and all generated vapors containing nickel, and lead, with some vapor samples containing traces of the carcinogenic nitrosamines: N′-nitrosonornicotine (NNN) and 4-(methylonitrosoamino)-1-(3-pirydyl)-l-butanone (NNK) [35].

An elemental analysis of thirty-six inorganic chemical elements revealed that e-cigarette aerosols include a variety of elements encompassing heavy metals at concentrations significantly higher than in conventional cigarettes [36]. Further analysis showed that e-cigarette fluid and aerosol contain nickel, chromium, copper, zinc, silver, and lead [37]. In order to compare metal concentrations in e-liquids from the refilling dispenser, e-liquids in the tank, and the inhaled aerosol, an analysis was carried out using samples from the devices of daily e-cigarette users. It revealed that concentrations of most metals were significantly higher in samples collected from tanks and the aerosols to be inhaled by the consumer than those from the refilling dispenser [37]. Concentrations of chromium, copper, nickel, lead, and zinc were also more than 25 times higher than in the dispenser samples, and the concentrations of aluminum, cadmium, and antimony were between 2.30 and 4.65 times higher in the tank and between 1.60 and 3.58 times higher in the aerosol in comparison with the dispenser samples [37].

Flavoring compounds contain diacetyl and various aldehydes including benzaldehyde, vanillin, ethyl vanillin, and cinnamaldehyde noting that many of the employed flavorants have been deemed as safe food additives. However, their consumption through inhalation has not been designated as safe by the Federal Food, Drug, and Cosmetic Act (FFDCA). Aldehydes are reactive and can produce adducts by forming covalent bonds with nucleic acids, cellular proteins, and other biomolecules [38]. Interestingly, detected concentrations of aldehydes vary greatly among commercial e-cigarettes liquids and can be as high as 34% as in the case of cinnamaldehyde in cinnamon flavored e-liquids [39]. Acetoin, diacetyl, and its structural analogue 2,3-pentanedione are used in various food flavorings such as butter, caramel, and strawberry, but they are also commonly employed in e-cigarette flavors with strong appeal such as cupcake, cotton candy, and Blue Water Punch [40]. In their study of 51 e-cigarette flavors, Allen et al. disclose that at least one of these three compounds was detected in 47 of different flavor samples, and that diacetyl, a chemical compound correlated with various severe respiratory pathologies in microwave popcorn-processing plant workers, was observed in concentrations above the laboratory limit in 39 of these flavors [40] (Table 1).

Table 1 The chemical composition of dokha [28,29,30,31] and e-cigarettes [32,33,34,35,36,37,38,39,40]3.2 The health effects of ATPs3.2.1 The health effects of dokha

Unlike the effects of tobacco smoking on health that have been very well documented, the effects of ATP consumption are poorly studied. Various authors report a scarcity in studies investigating the health effects of midwakh consumption [41,42,43]. One report shows that midwakh smoking has serious effects on blood pressure like other forms of smoking [12]. Notably, midwakh contains higher concentrations of nicotine and tar than other tobacco products [43, 44]. Since nicotine levels in midwakh (23.83–52.80 mg/g) are much higher than those in cigarettes (0.5–19.5 mg/g), they are expected to impose harmful health effects [29]. The alkaloid, nicotine, can permeate the blood-brain barrier; bind to nicotinic receptors in the central nervous system, promote adrenaline release; and, consequently, stimulate cardiac contractility and constrict blood vessels [44]. In chronic use, excessive sympathetic stimulation leads to continuous elevation of heart rate and cardiac output, causing flow turbulence and potentially damage to blood vessel lining [44].

A study investigating the effects of midwakh smoking on male UAE medical students revealed a significant mean increase in systolic blood pressure of 12 ± 1 mmHg, 20 ± 2 bpm in heart rate, and a nonsignificant mean decrease in diastolic blood pressures of 1 ± 1 mmHg [43]. In other words, midwakh smoking appears to increase heart rate and systolic pressure significantly. Shaikh and colleagues report that immediately after smoking midwakh, there was an observed increase of 4 ± 1 breaths/min in respiratory rate by (2 ± 2 breaths/min) [43]. This is higher than the increase (in respiration rate) brought about by waterpipe smoking. Given that midwakh smokers smoke dokha an average of 12 times per day, they are exposed to markedly high levels of nicotine and tar, increasing their risk of lung cancer [44, 45]. While not considered a carcinogen, nicotine has been associated with bronchial epithelial cell apoptosis [46]. Midwakh analyses revealed high toxin levels and five central nervous system depressants in its smoke [28]. A growing number of seizure cases following midwakh consumption have also been reported in the literature. For example, after a sustained seizure following midwakh consumption for the first time, a 17-year-old male was rushed into an emergency unit and presented with confusion, tachycardia, tachypnea, and a blood pressure of 180/100 mm Hg [42].

Other similar cases were reported by Alsaadi and colleagues [47]. Remarkably, seven male adolescents, who were otherwise healthy, were admitted to hospital for new onset tonic-clonic seizures after a few minutes of smoking midwakh [47]. While further research is required to pinpoint the mechanisms behind midwakh-induced seizures, the high nicotine content in addition to the potential effects of the additives may have brought these about [47]. Ultimately, these few studies point to a substantial psychological and health risks that should be properly evaluated.

3.2.2 The health effects of e-cigarettes

E-cigarettes have been regarded as the less harmful alternative to cigarettes [48]. Since conventional cigarette smoking is typically completed in 8–10 puffs over a 5–8-min period, most e-cigarette smoking is intermittent throughout the day, leading to lower and more stable nicotine levels with no arterial spikes [49]. Some studies report that e-cigarette consumption poses low cardiovascular risk, at least when it comes to short-term use in healthy users [48, 49]. Yet, other studies investigating the longer cardiovascular repercussions of e-cigarette smoking are limited and controversial since novel compounds in e-cigarette vapor, such as flavorings and fragrances, are mostly untested, and their cardiovascular effects are unexamined [50, 51].

Interestingly, a meta-analysis including studies published in 2000-2017 reported negative effects of e-cigarettes on endothelial function, an increase in arterial stiffness, and a greater long-term risk for coronary events [51]. Despite the reported negative effects of e-cigarettes on heart rate, diastolic and systolic blood pressure, one study reported that switching from conventional smoking to e-cigarettes had positive effects on blood pressure regulation [52]. However, dual smokers of e-cigarettes and combustible cigarettes were 36% more likely to suffer from cardiovascular disease [52]. An inhalation toxicology analysis revealed an absence of oxidative stress and inflammation in mice exposed to e-vapor aerosols, while high urinary markers were detected in mice exposed to conventional cigarette smoke [53]. E-cigarette vapor aerosols produced smaller atherosclerotic plaques, affected systolic and diastolic cardiac function, and endothelial function in significantly less severity than conventional cigarettes [54].

A recent case report disclosed that an otherwise healthy patient without any previous cardiopulmonary comorbidities developed a sudden severe, acute cardiomyopathy with e-cigarette use [54]. Another study reports the association of daily e-cigarette use, but not former or occasional e-cigarette use, with higher risks of myocardial infarction in comparison with conventional cigarette use [55]. E-cigarettes also release various compounds displaying pulmonary toxicity such as volatile carbonyls, reactive oxygen species, furans, and metals [56]. A few comprehensive studies investigated the long-term effects of e-cigarettes compounds such as vaporized nicotine and its associated solvents, PG, and VG [57, 58]. E-cigarette aerosol inhalation has been reported to produce enhanced airway reactivity, airway obstruction, inflammation, and emphysema [58]. After exposure to e-cigarettes, airway irritation, mucus hypersecretion, inflammatory response, systemic changes, and altered respiratory function were observed [59, 60].

Moreover, e-cigarette exposure could lead to alteration in gene and protein expression, inhibition of ciliary beating, inhibition of cystic fibrosis transmembrane conductance regulator, and increased cytokine expression in bronchial epithelia [57]. Similarly, the nasal epithelia display inhibited ciliary beating and downregulation of immune genes, while the bronchi display increased stiffness and impaired vasoconstriction [57]. In fact, e-cigarette consumption is linked with aggravated pathology in asthma, cystic fibrosis, and chronic obstructive pulmonary disease patients [