Ascorbic Acid Prevents Vascular Endothelial Dysfunction Induced by Electronic Hookah (Waterpipe) Vaping

Background Electronic hookah (e‐hookah) vaping has increased in popularity among youth, who endorse unsubstantiated claims that flavored aerosol is detoxified as it passes through water. However, e‐hookahs deliver nicotine by creating an aerosol of fine and ultrafine particles and other oxidants that may reduce the bioavailability of nitric oxide and impair endothelial function secondary to formation of oxygen‐derived free radicals. Methods and Results We examined the acute effects of e‐hookah vaping on endothelial function, and the extent to which increased oxidative stress contributes to the vaping‐induced vascular impairment. Twenty‐six healthy young adult habitual hookah smokers were invited to vape a 30‐minute e‐hookah session to evaluate the impact on endothelial function measured by brachial artery flow‐mediated dilation (FMD). To test for oxidative stress mediation, plasma total antioxidant capacity levels were measured and the effect of e‐hookah vaping on FMD was examined before and after intravenous infusion of the antioxidant ascorbic acid (n=11). Plasma nicotine and exhaled carbon monoxide levels were measured before and after the vaping session. Measurements were performed before and after sham‐vaping control experiments (n=10). E‐hookah vaping, which increased plasma nicotine (+4.93±0.92 ng/mL, P <0.001; mean±SE) with no changes in exhaled carbon monoxide (−0.15±0.17 ppm; P =0.479), increased mean arterial pressure (11±1 mm Hg, P <0.001) and acutely decreased FMD from 5.79±0.58% to 4.39±0.46% ( P <0.001). Ascorbic acid infusion, which increased plasma total antioxidant capacity 5‐fold, increased FMD at baseline (5.98±0.66% versus 9.46±0.87%, P <0.001), and prevented the acute FMD impairment by e‐hookah vaping (9.46±0.87% versus 8.74±0.84%, P =0.002). All parameters were unchanged during sham studies. Conclusions E‐hookah vaping has adverse effects on vascular function, likely mediated by oxidative stress, which overtime could accelerate development and progression of cardiovascular disease. Registration URL: https://ClinicalTrials.gov . Unique identifier: NCT03690427.

Effects of flavourants and humectants on waterpipe tobacco puffing behaviour, biomarkers of exposure and subjective effects among adults with high versus low nicotine dependence

IntroductionFlavourants and humectants in waterpipe tobacco (WT) increase product appeal. Removal of these constituents, however, is associated with increased intensity of WT puffing, likely due to reduced nicotine delivery efficiency. To clarify the potential public health outcomes of restrictions on flavourants or humectants in WT, we evaluated the effects of these constituents on puffing behaviours, biomarkers of exposure and subjective effects among adults with high versus low WT dependence.MethodsN=39 high dependence and N=49 low dependence WT smokers (Lebanese Waterpipe Dependence Scale scores >10 = high dependence) completed four smoking sessions in a cross-over experiment. Conditions were preferred flavour with humectant (+F+H), preferred flavour without humectant (+F-H), unflavoured with humectant (−F+H) and unflavoured without humectant (−F−H). Measures of puff topography, plasma nicotine and expired carbon monoxide (eCO) boost, and subjective effects were assessed.ResultsLevel of WT dependence modified the effect of WT condition on average flow rate, average puff volume and eCO boost. Although, overall, participants puffed the +F+H WT least intensely and −F−H WT most intensely, this association was strongest among WT smokers with high dependence. Participants preferred smoking the +F+H WT and achieved the largest plasma nicotine boost in that condition.DiscussionFindings underscore the complexity of setting product standards related to flavourants and humectants in WT. Future research evaluating whether WT smokers with high dependence would quit or reduce their WT smoking in response to removal of flavourants or humectants from WT is necessary to appreciate the full public health effects of such policies.

Variable Voltage, Tank-Style ENDS Do Not Always Deliver Nicotine

Objectives: In this paper, we characterize the nicotine delivery profile of a variable voltage, tank-style electronic nicotine delivery system (ENDS). Methods: Ten cigarette smokers (8 men, 2 women) completed this within-subject study assessing effects of 2 device power settings (15 W, 45 W) and 3 liquid nicotine concentrations (0, 3, and 6 mg/ml) using a tank-style ENDS. Participants completed one directed (10 puffs) and one ad libitum use period for each condition, with blood sampled throughout. Results: Plasma nicotine concentration did not increase significantly at 15 W regardless of liquid nicotine concentration. At 45 W, mean plasma nicotine increased (not significantly compared to 0 mg/ml) from 2.24 ng/ml (SD = 0.2) at baseline to 3.4 ng/ml (SD = 0.6) in the 3 mg/ml condition. In the 6 mg/ml, 45 W condition, mean plasma nicotine increased significantly (compared to 0 mg/ml) from 2.0 ng/ml (SD=0) at baseline to 5.96 ng/ml (SD = 1.3) after 10 puffs. In general, puf duration and volume decreased as device power and nicotine concentration increased. Conclusions: Despite using a variable wattage, tank-style device, nicotine delivery was minimal. These results, when combined with results from other studies using tank-style devices, highlight ENDS performance heterogeneity. Regulation may play a role in standardizing ENDS nicotine delivery.

Differential effects of tobacco cigarettes and electronic cigarettes on endothelial function in healthy young people

In our study of otherwise healthy young people, baseline flow-mediated dilation (FMD), a predictor of atherosclerosis and increased cardiovascular risk, was not different among tobacco cigarette (TC) smokers or electronic cigarette (EC) vapers who had refrained from smoking, compared with nonsmokers. However, acutely smoking one TC impaired FMD in smokers, whereas vaping a similar EC “dose” (as estimated by change in plasma nicotine levels) did not. Finally, although it is reassuring that acute EC vaping did not acutely impair FMD, it would be premature and dangerous to conclude that ECs do not lead to atherosclerosis or increase cardiovascular risk.

Acute effects of JUUL and IQOS in cigarette smokers

BackgroundJUUL is an electronic cigarette that aerosolises a nicotine-containing liquid, while IQOS heats tobacco to produce an aerosol. Both are marketed to smokers, but their effects have seldom been examined in this population.MethodsEighteen cigarette smokers (13 men) with no JUUL or IQOS experience completed a within-subject, laboratory study assessing nicotine delivery and subjective effects after controlled (10 puffs, ~30 s interpuff interval) and ad libitum (90 min) use of JUUL, IQOS or own-brand (OB) cigarettes.ResultsJUUL increased mean plasma nicotine concentration significantly from 2.2 (SD=0.7) ng/mL to 9.8 (4.9) ng/mL after 10 puffs and to 11.5 (9.3) ng/mL after ad libitum use. IQOS increased mean plasma nicotine significantly from 2.1 (0.2) ng/mL to 12.7 (6.2) ng/mL after 10 puffs and to 11.3 (8.0) ng/mL after ad libitum use. OB increased mean plasma nicotine significantly from 2.1 (0.2) ng/mL to 20.4 (11.4) ng/mL after 10 puffs and to 21.0 (10.2) ng/mL after ad libitum use. Mean OB plasma nicotine concentration was significantly higher than JUUL and IQOS. OB increased expired carbon monoxide concentration, but IQOS and JUUL did not. ‘Craving a cigarette/nicotine’ and ‘Urges to smoke’ were reduced significantly for all products following the directed bout.ConclusionsAmong smokers, JUUL and IQOS delivered less nicotine than cigarettes. Also, in this sample, IQOS and OB reduced abstinence symptoms more effectively than JUUL. Additional work with experienced JUUL and IQOS users is needed, as their nicotine delivery profiles and subjective experiences may differ.

The effect of flavoured and non-flavoured tobacco on subjective experience, topography and toxicant exposure among waterpipe smokers

IntroductionFlavoured waterpipe (WP) tobacco is a major factor in the resurgence of WP smoking and a main attractant of WP use among youth. Yet, evidence of the effects of limiting flavour on WP smoker’s experiences and exposures is limited. This study examined the impact of flavour manipulation on WP smokers’ toxicant exposure and smoking experiences.MethodA total of 144 WP smokers attended two, 45 min ad libitum smoking sessions (flavoured vs non-flavoured tobacco) in a crossover design study. Participants completed a battery of questions assessing subjective smoking experiences. Exhaled carbon monoxide (eCO) and plasma nicotine concentrations were measured before and after the smoking sessions. Puff topography was recorded throughout the smoking sessions.ResultsCompared with the non-flavoured WP tobacco, participants reported enhanced subjective smoking measures of satisfaction and enjoyment following smoking flavoured WP tobacco (ps <0.05). Although participants spent a longer time smoking flavoured tobacco, they took on average larger puffs while smoking the non-flavoured tobacco (ps <0.05). Greater levels of eCO were recorded following the non-flavoured tobacco session (p<0.05) compared with flavoured tobacco. No significant differences were observed in plasma nicotine concentrations between the two tobacco conditions. WP harm perception was higher among participants after smoking non-flavoured WP tobacco compared with their preferred flavour (p<0.05).ConclusionSmoking the flavoured tobacco product was associated with enhanced subjective experiences compared with the non-flavoured, suggesting a potential role for flavour regulation in reducing WP use. Mixed results were observed for toxicants exposure in relation to smoking flavoured compared with non-flavoured products suggesting the need for a more comprehensive assessment of the effects of other tobacco constituents and additives on toxicant exposure in WP smokers.

What factors reliably predict electronic cigarette nicotine delivery?

BackgroundThe ability of an electronic cigarette (e-cigarette) to deliver nicotine effectively may be dependent on features of the device, the liquid and the user. Some of these features have been examined in previous work (eg, liquid nicotine concentration and puff topography), while others have not (eg, nicotine dependence and demographic characteristics). The purpose of this secondary analysis is to examine such features as predictors of e-cigarette nicotine delivery using a relatively large sample.MethodsFour studies were combined in which e-cigarette-experienced users (n=63; 89% men; 75% white) and e-cigarette-naïve cigarette smokers (n=67; 66% men; 54% white) took 10 puffs from an eGo-style e-cigarette (~7.3 watts) filled with liquid that had a nicotine concentration of 18, 25 or 36 mg/mL. Thus, held constant across all studies were device features of battery/cartomiser style and power level and the topography parameters of puff number and interpuff interval. Blood was sampled before and after use, and puff topography was measured. Three general linear models were conducted to predict plasma nicotine concentrations (pre–post increase) for: (1) e-cigarette users only, (2) smokers only and (3) both groups combined. Predictor variables included puff duration, puff volume, liquid nicotine concentration, presession plasma nicotine concentration, nicotine dependence score (smokers only), gender and race.ResultsIn all models tested, longer puff durations and higher liquid nicotine concentrations were associated significantly with increased nicotine delivery (ps<0.05). For e-cigarette users only, higher presession nicotine concentration was associated significantly with increased nicotine delivery (p<0.05).ConclusionsPuff duration and liquid nicotine concentration may be among the more important factors to consider as regulators attempt to balance e-cigarette safety with efficacy. These findings should be interpreted in the context of devices with relatively low power output, a variable not studied here but likely also directly relevant to product regulation.

Abuse Liability of Cigarettes and Little Cigars in Adult Smokers

Objectives: Little cigars resemble cigarettes but are not subject to the US Food and Drug Administration's flavor restrictions on cigarettes. This within-subject laboratory study assessed the abuse liability of cigarettes and little cigars of varying flavors. Methods: Forty-eight adult cigarette smokers who also smoke little cigars or cigarillos completed 4 sessions that differed by tobacco product smoked: usual brand cigarette, unflavored, cherry, and menthol little cigars. Expired breath CO (COex), plasma nicotine, physiological measures, smoking topography, and subjective measures were assessed during and after each session. Results: Compared to usual brand cigarettes, little cigars were associated with smaller reductions in craving and lower subjective appeal. Minor changes in COex were observed despite less tobacco smoked in some of the little cigar sessions. Cherry flavored little cigars had the highest COex boost and subjective appeal relative to unflavored and menthol flavored little cigars. Conclusions: Generally, little cigars were rated as less appealing than cigarettes. However, cherry flavored little cigars had higher subjective appeal and produced a different smoking topography compared to the unflavored and menthol flavored little cigars. These data suggest some tobacco flavors may lead to an increased abuse liability and toxicant exposure relative to others.

P941Acute effects of electronic hookah smoking on endothelial function, inflammation and oxidative stress

Background Electronic nicotine delivery systems (ENDS) are a new rapidly growing global epidemic. More recently, electronic (e-) hookahs, have increased in popularity in the United States, with the greatest uptake by young female adults, who endorse marketing claims that these products are safer alternatives to traditional hookah tobacco smoking. Unlike other ENDS such as e-cigarettes, e-hookah bowls are used through traditional waterpipes, allowing the vapor–containing aerosolized nicotine, propylene glycol, glycerin, and flavorings–to pass through a water-filled basin, before it is inhaled through the user's mouth. Contributing to e-hookah bowls' popularity is the belief that e-hookah flavored smoke is detoxified as it passes through the water-filled basin, rendering e-hookah a safer tobacco alternative. However, an e-hookah bowl delivers flavored nicotine by creating a vapor of fine (<2.5 μm) and ultrafine particles (<0.1 μm) that could induce vascular toxicity. Purpose To test the acute effect of electronic hookah smoking on endothelial function, inflammation and oxidative stress. Methods In 17 healthy young adults who smoke hookah but not cigarettes (age 26±1 years, mean±SE; BMI 23.8±0.7 kg-m2), we measured brachial artery flow-mediated dilation (FMD) before and after a 30-minute e-hookah bowl smoking. To test for inflammatory mediation, pro-inflammatory cytokines hsCRP, TNF-α, and fibrinogen were collected before and after smoking. To test for oxidative stress mediation, on a separate day, the acute effect of e-hookah smoking on FMD was examined after intravenous infusion of Vitamin C, an effective antioxidant. Plasma nicotine levels were collected before and after the smoking session. The same measurements were performed before and after a subset of subjects (n=8) performed a sham-smoking control study. Results E-hookah smoking, which markedly increased plasma nicotine (Δ plasma nicotine: +6.07±1.87, p=0.018) and mean arterial pressure (Δ mean arterial pressure: +12±2 mm Hg, p<0.001), acutely decreased FMD from 8.04±0.68 to 6.14±0.52%Δ, p<0.001, indicating impaired endothelial function. While fibrinogen and TNF-α levels increased from 225.31±7.41 to 236.77±9.79, p=0.026 and from 0.80±0.04 to 0.87±0.05, p=0.036, respectively, hsCRP did not change (P=ns). Vitamin C administration prevented the acute FMD impairment by e-hookah smoking (P=ns). All parameters were unchanged during sham-control studies. Conclusions In contrast to the widespread popular belief that e-hookah is safe, the data herein show that each e-hookah session constitutes a potent vascular toxin acutely impairing endothelial function and inducing an inflammatory state. That the acute impairment in FMD with electronic hookah is restored with administration of the potent antioxidant Vitamin C suggest that elevated vascular oxidative stress as a key mechanism involved. These new data provide evidence to counter claims that e-hookah is a safer tobacco alternative. Acknowledgement/Funding This work was funded by the National Institutes of Health, National Heart, Lung, and Blood Institute 1R21HL145002-01 to MRH.