| Shahab et al., 2017b (221) | Cross-sectional study, using unspecified EC or NRT products for ≥ 6 months | Smokers (n = 37)Dual use NRT (n = 36)Dual use EC (n = 36)NRT (n = 36)EC (n = 36) | NNAL, 3HPMA, AAMA, CYMA, MHBMA3, HEMA were expressed as proportions of levels in the smoker arm. Significantly lower levels of all biomarkers were observed for EC only users (2.9–43.5% decrease) that were similar to those in NRT only users. NRT and EC dual users presented similar biomarker levels to the smoking group |
| Lorkiewicz et al., 2019 (216) | Cross-sectional study, using unspecified ECs or smokeless products | No tobacco (n = 12)ECs (n = 12)smokers (n = 12)smokeless tobacco (n = 12) | The EC users showed higher levels of xylene, cyanide, styrene, ethylbenzene, and acrolein metabolites than non-tobacco users, but lower levels for toluene and acrolein metabolites. Levels of VOC metabolites in the smokeless tobacco group were similar to those in the non-tobacco group |
| Czoli et al., 2019 (214) | Three-period crossover design where dual users (smoked ≥ 5 cigarettes per day and used an EC at least once a day for the past 7 days) to either EC > smoking > no tobacco or smoking > EC > no tobacco, with each condition lasting for 7 days | Dual users (n = 48) | 1-HOP was significantly higher during the smoking period than during dual use but was lower during EC use. NNAL levels decreased significantly from dual use, by 30% during EC use and by 35% during cessation but did not change during smoking |
| Hecht et al., 2015 (226) | Cross-sectional study comparing biomarker levels in smoker to ECs switchers (≥ 2 months) with those in smokers from three previously published studies (Carmella et al. 2009; Hatsukami et al. 2010; Zarth et al. 2014) | EC users (n = 28) | All biomarkers (1-HOP, total NNAL, 3HPMA, 2HPMA, HMPMA, and SPMA) were significantly lower in EC users than in smokers |
| Mcrobbie et al., 2015 (217) | Switching study in which smokers switched to ECs or dual use | EC users (n = 16)Dual use (n = 18) | 3HPMA in urine showed significant reductions at 4 weeks after switching compared with baseline (ECs 79%, dual use 60%) |
| Goniewicz et al., 2017 (215) | Switching study in which smokers switched to ECs dual use for 2 weeks then ECs only for 2 weeks | Smokers switching to ECs (n = 20) | Significant reductions were seen after 2 weeks in urine biomarkers of exposure to NNAL and eight VOC metabolite levels (50–69%) and fluorene (42–82%), butnot in those for pyrene, phenanthrene, and naphthalene |
| Cravo et al. 2016 (225) | Parallel study in which smokers were randomly assigned in a ratio of 3:1 to switch to an EC (tobacco or menthol flavour) or continue smoking for 12 weeks | Switch to EC (n = 306)continue smoking (n = 102) | After 12 weeks, 3-HPMA, S-PMA and total NNAL in urine were reduced by around 30% compared with baseline in those who switched to ECs, whereas noreductions were among those who continued smoking |
| O’Connell et al., 2016 (245)D’Ruiz et al., 2017 (232)D’Ruiz et al., 2016 (356) | Parallel study of smokers switching to ECs or dual use during 6 days in clinic | Rechargeable EC tobacco flavour (n = 15)rechargeable EC cherry flavour (n = 15)disposable EC cherryflavour (n = 15)dual use with rechargeable EC tobacco flavour (n = 15)dual use with rechargeable EC cherry flavour (n = 15)dual use with disposable EC cherry flavour (n = 15)cessation (n = 15) | Biomarkers: all urine biomarker measures (total NNAL, 3-HPMA, HMPMA, CEMA, 1-OHP, NNN, MHBMA, S-PMA) were significantly reduced compared to baseline in all groups, except MHBMA in the cherry disposable dual use group; levels in dual users were significantly higher than those in the cessation groupSpirometry: small changes seen in FVC from baseline to Day 5 (!0.5% to 3.1%) but were significant for tobacco and cherry rechargeable EC only users, while FEV1changes (!1.5% to 6.0%) were significant increases for the tobacco and cherry rechargeable EC only users and cherry rechargeable dual usersExhaled CO: reduced across all study groups, by around 89% in EC only and cessation groups and around 26% in dual user groupsExhaled FeNO: increased by 45.8–63.4% in EC only groups and 55%in the cessation group, but not in dual user groups (differences from the tobacco rechargeable and cherry disposable EC only groups were significant)Systolic blood pressure: changes varied across groups, but significant reductions in mornings seen for cherry flavour dual users, and in rechargeable tobaccoEC only usersDiastolic blood pressure: reduced significantly in mornings forrechargeable tobacco dual users and cherry rechargeable EC only usersHeart rate: reductions observed in the cessation group, rechargeable tobacco EC only group and rechargeable cherry product EC only and dual use groups |
| Sakamaki-Ching et al., 2020 (222) | Cross-sectional study of age and gender matched participants, assessing spot urine samples from EC users, smokers and non-smokers for metals (antimony, cadmium, copper, indium, lead, nickel, rubidium, selenium, silver, titanium, and zinc), metal exposure, and BOPH | EC users (n = 20)smokers (n = 13)non-smokers (n = 20) | Metals: biomarkers for seleniumwere significantly higher in ECusers than in non-smokers or smokers with means 54.0, 41.8, and 39.7 μg/g creatinine, respectively, and were significantly increased for zinc in EC userscompared to non-smokers (584.5 vs413.6 mg/g creatinine) but not compared to smokers (470.7 mg/g creatinine)Metal exposure: metallothionein was significantly greater in ECusers than in non-smokers (mean 3761 vs1129 pg/mg creatinine) but similar to that in smokers (4096 pg/mg creatinine)BOPH: concentrations were increased in EC users when compared to non-smokers but not smokers (8-OHdG 442.8 vs221.6 and 388 ng/mg creatinine; 8-isoprostane 750.8 vs411.2 and 784.2 ng/mg creatinine) |
| Campagna et al., 2016 (357)Cibella et al., 2016 (229) | Longitudinal study (52 weeks) of smokers switching to ECs with different concentrations of nicotine | 2.4% nicotine (n = 49)1.8% nicotine (n = 50)0% nicotine (n = 40) | 82 participants continued smoking, 34 significantly reduced thenumber of cigarettes smoked, and 18 quit smoking after switchingExhaled CO: decreased significantly in quitters and smokers whoreduced cigarette consumption from week 12Exhaled FeNO: increased significantly in quitters from week 12FEV1, FVC and FEV1/FVC ratio: not affected by smoking status (continued, reduced, or quit)FEF25–75%: significantly increased among quitters |
| Polosa et al., 2016 (220) | Retrospective chart review study of changes in respiratory outcomes over 2 years in patients with COPD who were daily EC users (without combustible cigarettes) or smokers, matched for age and sex | Baseline COPD GOLDstage 1 (smokers n = 3; EC users n = 2)stage 2 (smokers n = 5; EC users n = 6)stage 3 (smokers n = 11; EC users n = 10)stage 4 (smokers n = 5; EC users n = 6) | FEV1, FVC and ratio FEV1/FVC ratio did not change from baseline values in either EC users or smokers, whereas COPD exacerbations were reduced and 6-min walking test scores increased compared with baseline in the EC users group but not the smoking group |
| Pulvers et al., 2018 (358) | Switch study of smokers switching to an EC for 30 days with choice of seven flavours and two nicotine concentrations (12 or 24 mg/mL) | Smokers (n = 37) | Cigarette consumption: decreased significantly from mean 24.8 days to 14.0 days per month and mean 8.7 to 4.4 cigarettes per day, with six participants quitting, 21 becoming dual users and the remaining 10 sporadic EC only usersBiomarkers: NNAL, PMA, CNEMA decreased significantly from baseline, whereas HEMA, MMA, 3-HPMA, 2-HPMA, AAMA and HPMMA did notExhaled CO: decreased significantlySmoking dependence: decreased significantly from baseline |
| Aherrera et al., 2017 (218) | Cross sectional study of nickel and chromium concentrations in EC users | EC users (n = 59) | Concentrations in urine, saliva, and breath: were below the limit of detection for nickel in 4.7%, 3.2% and 3.1% of samples, respectively, and for chromium in 7.8%, 1.6% and 56.3% of samplesWeekly consumption, time to first vape, voltage of device, number of coil changes per month, and levels in aerosol, dispenser, and tank had effectsNickel concentrations in urine were associated with time to first vape, coil changes, and concentrations in aerosol; in saliva were only associated with concentrations in aerosol and in tank, and in breath showed no associationsChromium in saliva was associated with cotinine in urine and concentrations in aerosol, tank, and dispenser |
| Wieslander et al., 2001 (231) | Symptoms study after experimental exposure of healthy non-asthmatic volunteers to propylene glycol mist for 1 min | Healthy volunteers (n = 27) | Symptom VAS ratings: showed significant increase of ocular irritation, throat irritation, and dyspnoea but no effects on solvent smell or other symptomsLung function: FEV1, FVC, FEV1/FVC ratio, PEF did not change significantly from before to after exposureTear film stability: break-up time decreased significantly after exposure from 38 to 28 sDose response: throat dryness was 47% in the low exposure groupbut 100% in the high exposure group, where VAS ratings were also higher |
| Goniewicz et al., 2018 (219) | Cross-sectional analysis of population in longitudinal Population Assessment of Tobacco and Health (PATH) study for biomarker concentrations | Smokers (n = 2411)EC users (n = 247)dual users (n = 792)never tobacco users (n = 1655) | NNAL: concentrations were significantly lower in never-smokers than in EC users and in both groups compared with smokers (geometric mean 0.921 vs4.887 and 203.5 pg/mg creatinine), whereas dual users had higher levels than smokers (262.2 pg/mg creatinine)Other tobacco specific nitrosamines: NAT, NAB, and NNN in EC users were above the limit of quantification for 12%, 15% and 34%of samples, respectively and were all higher than those in never tobacco users but significantly lower than those in smokersMetal exposure: beryllium wasfound only in 3–9% of samples; cadmium was higher in EC users than in never tobacco users (0.193 vs 0.149 ng/mg creatinine) but lower than in smokers and dual users (0.277 and 0.280 ng/mg creatinine, respectively); lead was elevated in EC users compared to never users (0.432 vs 0.351 ng/mg creatinine) but was highest in smokers and dual users (0.500 and 0.479 ng/mg creatinine, respectively); strontium differed only between dual users and smokers (130.5 vs 113.7 ng/mg creatinine); and no differences in concentrations between groups were found for cobalt, manganese or thalliumTobacco alkaloids: anabasine and anatabine concentrations were significantly lower in EC users than in dual users or smokers but similar to those in never tobacco usersTotal inorganic arsenic: significantly higher in EC users than in smokers and dual users (0.053 vs 0.048 and 0.045 ug/mg creatinine) but not different to never tobacco users (0.054 ug/mg creatinine)PAHs: of seven biomarkers of PAHexposure only 1-hydroxypyrene was elevated in EC users compared to never tobacco users, while all were significantly higher in smokers and five were higher in dual usersVOCs: of 20 biomarkers four were significantly elevated in EC users compared with never tobacco users (AMCA 1.5 times, BMA 1.1 times, CYHA 1.3 times, and CYMA 3.0 times*), although CYHA could only be detected in 3% of never tobacco users and 14% of EC users; 17 biomarkers were higher in smokers than in EC users by 1.4–31.0 times |
| Oliveri et al., 2020 (234) | Cross-sectional observational study comparing biomarkers of exposure and BOPH in ex-smoker (≥10 cigarettes per day for ≥10 years) EC users (≥6 months) with current smokers | Smokers (n = 62)ex-smoker EC users (n = 132) | Biomarkers of exposure: concentrations of total NNAL, nicotine equivalents, 3HPMA, and COHb were lower in EC users than smokersBOPH: of white blood cells, HDL cholesterol, 11-dehydrothromboxane B2, 8-epi-prostaglandin F2α, and sICAM-1, lower concentrations were found in EC users for 11-dehydrothromboxane B2 (471.4 vs 664.8 ng/g creatinine), 8-epi-prostaglandin F2α (288.6 vs374.1 ng/g creatinine), and sICAM-1 (224.5 vs266.4 ng/mL), although differences for the latter were observed only for cartridge based ECs and not tank-base ECs |
| Piper et al., 2019 (227) | Baseline assessments for longitudinal observational cohort study (2 years) of smokers versus EC dual users | Smokers (n = 166)dual users (n = 256) | In dual users, lower mean valueswere seen than in smokers for smoking duration (22.1 vs25.6 years), daily cigarette consumption (12.5 vs15.8), Fagerström nicotine dependence (4.15 vs 4.81), smoking within 30 min of waking (79.4% vs67.3%), and levels of NNAL (453.31 vs 340.99 pg/mL), whereas smoking starting age, motivation to quit, exhaled CO, the Wisconsin Inventory of Smoking Dependence Motives, and cotinine biomarkers did not differ significantly |
| Round et al., 2019 (223) | Randomized, controlled, open-label, forced switch parallel group study in smokers of menthol and non-menthol cigarettes who switched to an EC or nicotine gum, to measure biomarkers of exposure after 5 days | Smoker to EC (n = 38)smoker to nicotine gum (n = 39)menthol smoker to menthol EC (n = 40)menthol smoker to nicotine gum (n = 41) | In all switching groups, total nicotine equivalents in urine, cotinine in plasma, and all biomarkers of tobacco smoke exposure decreased except for 3-OH-B[a]P in the smoker to nicotine gum group (reductions were ECs 30.4–95.5%, menthol ECs 35.7–97.7%, and nicotine gum 20–99.2%) |
| Song et al., 2020 | Cross-sectional study of lung inflammation, measured by cell counts, cytokines, genome-wide gene expression and DNA methylation in bronchoalveolar lavage and brushings, in never smokers, EC users and smokers | Never-smokers (n = 42)EC users (n = 15)smokers (n = 16) | Most inflammatory cell counts and cytokine concentrations in EC users were intermediate between those of smokers and never-smokers, while most biomarkers were similar to those for never smokers, as were differential gene expression and DNA methylation |
