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E-cigarettes: an evidence update <br /> <br />71 <br /> <br />As in every new field, methodological problems limit the usefulness of some of the data <br />collected so far. Two problems in particular are prominent. <br /> <br />1) Almost all studies used prescribed puffing regimes, sometimes derived from <br />observations of smokers rather than vapers. We described above the evidence that <br />puffing schedules have a major influence on nicotine delivery to vapour. Puffing <br />schedules that do not correspond with vapers’ behaviour are thus unlikely to provide <br />realistic nicotine delivery data. Only three studies allowed vapers to puff ad-lib on first <br />use. <br /> <br />2) Regarding the question of the speed of nicotine delivery, all existing studies started <br />blood sampling only after five minutes of vaping. Cigarettes provide peak nicotine <br />plasma levels very quickly (eg peak arterial nicotine concentrations of around 20ng/ml <br />nicotine are reached within 20 seconds of starting to puff on an cigarette [107]). Data <br />collected so far do not allow an appraisal of whether EC are approaching cigarettes in <br />this key parameter. <br />Despite these limitations, the studies above have generated several strands of useful <br />information on how much nicotine vapers obtain over t ime and how this compares with <br />nicotine intake from cigarettes. <br /> <br />Cotinine is a metabolite of nicotine with a long half-life which shows nicotine exposure <br />over time. Cotinine data are thus not influenced by the laboratory puffing schedules. <br />Some studies suggest that experienced vapers can, over time, reach nicotine levels <br />comparable to those obtained from smoking [108-110], although others have found <br />plasma or salivary cotinine levels that are still lower than those observed in daily <br />smokers [111-113]. <br /> <br />Cigalike EC deliver lower levels of nicotine than cigarettes [114-116], especially to <br />novice users [117-119]. Vapers obtain slightly more nicotine from them with practice, <br />but nicotine delivery is comparatively low and slow [115]. Experienced users can obtain <br />a rise in blood nicotine concentration of between 8 and 16ng/ml [120, 121]. Tank <br />systems deliver nicotine more efficiently than cigalikes and somewhat faster [120, 122, <br />123]. <br /> <br />Overall, the data indicate that within five minutes of use of a cigalike EC, blood nicotine <br />levels can rise by approximately 5ng/ml. For comparison, after chewing a piece of 2mg <br />nicotine chewing gum, peak plasma concentrations of 3 –5ng/ml are observed within <br />approximately 30 minutes [124, 125]. For experienced users of tank systems the <br />increase in blood nicotine concentration within five minutes of use can be 3–4 times <br />higher. <br />