Acute effects of electronic and tobacco cigarettes on vascular and respiratory function in healthy volunteers:a cross-over study

Objectives: To assess the acute effects of nicotine-containing electronic cigarettes versus tobacco smoking on vascular and respiratory function and circulating microparticles, particularly platelet microparticles (PMPs, biomarker of haemostasis/thrombosis) and endothelial microparticles (EMPs, biomarker of endothelial function). Methods: Heart rate (HR), blood pressure, reactive hyperaemia index (RHI, microvascular reactivity), augmentation index (arterial stiffness) and respiratory function were assessed in 20 smokers immediately before and after electronic cigarettes use and tobacco smoking. The number of microparticles was determined by flow cytometry using counting beads as a reference. Labelling with Annexin-V was used to detect the total microparticle fraction. EMPs were characterized as CD31+CD42− and PMPs as CD31+CD42+. Results: HR increased after electronic cigarettes use and tobacco smoking (P < 0.001), whereas blood pressure remained unchanged (P > 0.05). RHI (P = 0.006), augmentation index (P = 0.010) but not augmentation index standardized to HR 75 bpm (P > 0.05) increased with electronic cigarettes use but not with tobacco smoking. Following tobacco smoking, there was a significant increase in total microparticles (P < 0.001), EMPs (P < 0.001) and PMPs (P < 0.001). In contrast, electronic cigarettes were only associated with an increase in PMPs (P < 0.001), with no significant changes in the total microparticle fraction or EMPs (all P > 0.05). Peak expiratory flow significantly decreased following electronic cigarettes use (P = 0.019). Conclusion: Our results demonstrate that acute exposure to tobacco smoking as well as electronic cigarettes influences vascular and respiratory function. Where tobacco smoking significantly increased microparticle formation, indicative of possible endothelial injury, electronic cigarettes use induced vasoreactivity and decreased peak expiratory flow. These findings suggest that both electronic cigarettes and tobacco smoking negatively impact vascular function

Nicotine delivery to users from cigarettes and from different types of e-cigarettes

BACKGROUND: Delivering nicotine in the way smokers seek is likely to be the key factor in e-cigarette (EC) success in replacing cigarettes. We examined to what degree different types of EC mimic nicotine intake from cigarettes. METHODS: Twelve participants (‘dual users’ of EC and cigarettes) used their own brand cigarette and nine different EC brands. Blood samples were taken at baseline and at 2-min intervals for 10 min and again at 30 min. RESULTS: Eleven smokers provided usable data. None of the EC matched cigarettes in nicotine delivery (C (max) = 17.9 ng/ml, T (max) = 4 min and AUC(0–>30) = 315 ng/ml/min). The EC with 48 mg/ml nicotine generated the closest PK profile (C (max) = 13.6 ng/ml, T (max) = 4 min, AUC(0–>30) = 245 ng/ml/min), followed by a third generation EC using 20 mg/ml nicotine (C (max) = 11.9 ng/ml, T (max) = 6 min, AUC(0–>30) = 232 ng/ml/min), followed by the tank system using 20 mg/ml nicotine (C (max) = 9.9 ng/ml, T (max) = 6 min, AUC(0–>30) = 201 ng/ml/min). Cig-a-like PK values were similar, ranging from C (max) 7.5 to 9.7 ng/ml, T (max) 4-6 min, and AUC(0–>30) 144 to 173 ng/ml/min. Moderate differences in e-liquid nicotine concentrations had little effect on nicotine delivery, e.g. the EC with 24 mg/ml cartridge had the same PK profile as ECs with 16 mg/ml cartridges. Using similar strength e-liquid, the tank EC provided significantly more nicotine than cig-a-like ECs. CONCLUSIONS: EC brands we tested do not deliver nicotine as efficiently as cigarettes, but newer EC products deliver nicotine more efficiently than cig-a-like brands. Moderate variations in nicotine content of e-liquid have little effect on nicotine delivery. Smokers who are finding cig-a-like EC unsatisfactory should be advised to try more advanced systems

Acute electronic cigarette use: nicotine delivery and subjective effects in regular users

Rationale Electronic cigarettes are becoming increasingly popular among smokers worldwide. Commonly reported reasons for use include the following: to quit smoking, to avoid relapse, to reduce urge to smoke, or as a perceived lower-risk alternative to smoking. Few studies, however, have explored whether electronic cigarettes (e-cigarettes) deliver measurable levels of nicotine to the blood. Objective This study aims to explore in experienced users the effect of using an 18-mg/ml nicotine first-generation e-cigarette on blood nicotine, tobacco withdrawal symptoms, and urge to smoke. Methods Fourteen regular e-cigarette users (three females), who are abstinent from smoking and e-cigarette use for 12 h, each completed a 2.5 h testing session. Blood was sampled, and questionnaires were completed (tobacco-related withdrawal symptoms, urge to smoke, positive and negative subjective effects) at four stages: baseline, 10 puffs, 60 min of ad lib use and a 60-min rest period. Results Complete sets of blood were obtained from seven participants. Plasma nicotine concentration rose significantly from a mean of 0.74 ng/ml at baseline to 6.77 ng/ml 10 min after 10 puffs, reaching a mean maximum of 13.91 ng/ml by the end of the ad lib puffing period. Tobacco-related withdrawal symptoms and urge to smoke were significantly reduced; direct positive effects were strongly endorsed, and there was very low reporting of adverse effects. Conclusions These findings demonstrate reliable blood nicotine delivery after the acute use of this brand/model of e-cigarette in a sample of regular users. Future studies might usefully quantify nicotine delivery in relation to inhalation technique and the relationship with successful smoking cessation/harm reduction

Electronic cigarettes for smoking cessation

Background Electronic cigarettes (ECs) are handheld electronic vaping devices which produce an aerosol formed by heating an e‐liquid. Some people who smoke use ECs to stop or reduce smoking, but some organizations, advocacy groups and policymakers have discouraged this, citing lack of evidence of efficacy and safety. People who smoke, healthcare providers and regulators want to know if ECs can help people quit and if they are safe to use for this purpose. This is an update of a review first published in 2014. Objectives To examine the effectiveness, tolerability, and safety of using electronic cigarettes (ECs) to help people who smoke achieve long‐term smoking abstinence. Search methods We searched the Cochrane Tobacco Addiction Group's Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and PsycINFO to 1 February 2021, together with reference‐checking and contact with study authors. Selection criteria We included randomized controlled trials (RCTs) and randomized cross‐over trials in which people who smoke were randomized to an EC or control condition. We also included uncontrolled intervention studies in which all participants received an EC intervention. To be included, studies had to report abstinence from cigarettes at six months or longer and/or data on adverse events (AEs) or other markers of safety at one week or longer. Data collection and analysis We followed standard Cochrane methods for screening and data extraction. Our primary outcome measures were abstinence from smoking after at least six months follow‐up, adverse events (AEs), and serious adverse events (SAEs). Secondary outcomes included changes in carbon monoxide, blood pressure, heart rate, blood oxygen saturation, lung function, and levels of known carcinogens/toxicants. We used a fixed‐effect Mantel‐Haenszel model to calculate the risk ratio (RR) with a 95% confidence interval (CI) for dichotomous outcomes. For continuous outcomes, we calculated mean differences. Where appropriate, we pooled data from these studies in meta‐analyses. Main results We included 56 completed studies, representing 12,804 participants, of which 29 were RCTs. Six of the 56 included studies were new to this review update. Of the included studies, we rated five (all contributing to our main comparisons) at low risk of bias overall, 41 at high risk overall (including the 25 non‐randomized studies), and the remainder at unclear risk. There was moderate‐certainty evidence, limited by imprecision, that quit rates were higher in people randomized to nicotine EC than in those randomized to nicotine replacement therapy (NRT) (risk ratio (RR) 1.69, 95% confidence interval (CI) 1.25 to 2.27; I2 = 0%; 3 studies, 1498 participants). In absolute terms, this might translate to an additional four successful quitters per 100 (95% CI 2 to 8). There was low‐certainty evidence (limited by very serious imprecision) that the rate of occurrence of AEs was similar) (RR 0.98, 95% CI 0.80 to 1.19; I2 = 0%; 2 studies, 485 participants). SAEs occurred rarely, with no evidence that their frequency differed between nicotine EC and NRT, but very serious imprecision led to low certainty in this finding (RR 1.37, 95% CI 0.77 to 2.41: I2 = n/a; 2 studies, 727 participants). There was moderate‐certainty evidence, again limited by imprecision, that quit rates were higher in people randomized to nicotine EC than to non‐nicotine EC (RR 1.70, 95% CI 1.03 to 2.81; I2 = 0%; 4 studies, 1057 participants). In absolute terms, this might again lead to an additional four successful quitters per 100 (95% CI 0 to 11). These trials mainly used older EC with relatively low nicotine delivery. There was moderate‐certainty evidence of no difference in the rate of AEs between these groups (RR 1.01, 95% CI 0.91 to 1.11; I2 = 0%; 3 studies, 601 participants). There was insufficient evidence to determine whether rates of SAEs differed between groups, due to very serious imprecision (RR 0.60, 95% CI 0.15 to 2.44; I2 = n/a; 4 studies, 494 participants). Compared to behavioral support only/no support, quit rates were higher for participants randomized to nicotine EC (RR 2.70, 95% CI 1.39 to 5.26; I2 = 0%; 5 studies, 2561 participants). In absolute terms this represents an increase of seven per 100 (95% CI 2 to 17). However, this finding was of very low certainty, due to issues with imprecision and risk of bias. There was no evidence that the rate of SAEs differed, but some evidence that non‐serious AEs were more common in people randomized to nicotine EC (AEs: RR 1.22, 95% CI 1.12 to 1.32; I2 = 41%, low certainty; 4 studies, 765 participants; SAEs: RR 1.17, 95% CI 0.33 to 4.09; I2 = 5%; 6 studies, 1011 participants, very low certainty). Data from non‐randomized studies were consistent with RCT data. The most commonly reported AEs were throat/mouth irritation, headache, cough, and nausea, which tended to dissipate with continued use. Very few studies reported data on other outcomes or comparisons and hence evidence for these is limited, with confidence intervals often encompassing clinically significant harm and benefit. Authors' conclusions There is moderate‐certainty evidence that ECs with nicotine increase quit rates compared to ECs without nicotine and compared to NRT. Evidence comparing nicotine EC with usual care/no treatment also suggests benefit, but is less certain. More studies are needed to confirm the size of effect, particularly when using modern EC products. Confidence intervals were for the most part wide for data on AEs, SAEs and other safety markers, though evidence indicated no difference in AEs between nicotine and non‐nicotine ECs. Overall incidence of SAEs was low across all study arms. We did not detect any clear evidence of harm from nicotine EC, but longest follow‐up was two years and the overall number of studies was small. The evidence is limited mainly by imprecision due to the small number of RCTs, often with low event rates. Further RCTs are underway. To ensure the review continues to provide up‐to‐date information, this review is now a living systematic review. We run searches monthly, with the review updated when relevant new evidence becomes available. Please refer to the Cochrane Database of Systematic Reviews for the review's current status