Supplementary material 13 to: Electronic cigarettes for smoking cessation

Lindson N, Livingstone-Banks J, Butler AR, McRobbie H, Bullen CR, Hajek P, Wu AD, Begh R, Theodoulou A, Notley C, Rigotti NA, Turner T, Fanshawe T, Hartmann-Boyce J
https://doi.org/10.1002/14651858.CD010216.pub10

The material in this section has been supplied by the author(s) for publication under a Licence for Publication and the author(s) are solely responsible for the material. Cochrane has reviewed this material, but Cochrane has not copyedited, formatted or proofread. Cochrane accordingly gives no representations or warranties of any kind in relation to, and accepts no liability for any reliance on or use of, such material.

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Carbon monoxide data not contributing to meta-analyses

Randomized and crossover trials, nicotine EC v comparator group [1]

Study ID

Intervention/ comparator

Time point

Data

Between-group difference[2] (↑ higher in EC/higher dose EC arm; ↔ equivocal; ↓ lower in EC/higher dose arm)

Czoli 2019

Nicotine EC v traditional cigarette

1 week

Compared to baseline (dual use):

EC -41%

Traditional cigarette +21%

George 2019

Nicotine EC v non-nicotine EC v traditional cigarette

4 weeks

eCO measured but not reported in detail. Lowest tertile of CO at end of study was in those with “best compliance with EC and least dual use”

NE

Katz 2025

Nicotine EC v combustible cigarettes

2 weeks

Meier 2017

Nicotine EC v non-nicotine EC

1 week

Randomized crossover trial. eCO: Naturalistic (whilst smoking, no EC) mean 11.4 (SE 1.3), Nicotine EC 11.6 (SE 1.3), Non-nicotine EC 10.2 (SE 1.3)

NCT03113136

Low Wattage EC (LWe) v High Wattage EC v combustible cigarettes

4 and 12 weeks

“At 4 and 12 weeks, the CO levels were reduced in dual users of combustible tobacco and e-cigarettes (LWe or HWe), compared to exclusive combustible tobacco users.”

Tseng 2016

Nicotine EC v non-nicotine EC

1 and 3 weeks

No between-group difference in eCO was observed at any time point, no further data available

Walele 2018*

Nicotine EC versus conventional cigarette

2 weeks

“At baseline, eCO was at 20.3 ppm (±8.4) in EVP subjects and at 21.3 ppm (±9.2) in CC subjects. In the EVP group, eCO levels dropped to 7.4 ppm at Week 1 and were between 7.6 and 9.0 ppm from Week 2 to EoS (eCO levels in non-smokers are typically ≤6 ppm (Bedfront, 2016)). In the CC group, eCO remained at levels close to baseline during the whole study (21.3–23.3 ppm).”

Walker 2020

Nicotine EC + NRT v non-nicotine EC + NRT v NRT only

6 months

20% nicotine EC arm; 10% non-nicotine EC arm; 4% NRT only arm had eCO < 8ppm at follow-up

Yingst 2020

Nicotine EC (36 mg/ml; refillable) versus nicotine EC (24 mg/ml; cig-a-like)

1 week

N = 17

“CO significantly decreased from baseline during the button-operated ENDS use period from 24.1 ppm (SD = 12.2) to 18.4 ppm (SD = 13.8) (p = .03), but did not significantly decrease during the cigalike use period (22.4 ppm (SD = 12.8) vs. 18.1 ppm (SD = 13.8) (p = .07)). Total CO reduction was not different between ENDS devices (p= .75).”

Studies in which all groups received nicotine EC with no between-group difference in concentration

Study ID

Time point

Data

Direction over time[3] (↓ decline; ↔ equivocal; ↑ increase)

Caponnetto 2013b*

1 year

eCO reported graphically, “smoking reduction with “Categoria” e-Cigarette use was associated to a substantial decrease in the level of eCO”. In figure, reductions from baseline in all groups, but particularly pronounced in people who quit smoking or reduced cigarette consumption by >50%

Caponnetto 2021*

24 weeks

In the 37 completers, mean change in CO from baseline -24.74 ppm (from 33.23 (SD 10.97) at baseline to 9.29 (SD 8.61) at follow-up)

Coffey 2020

4 weeks

Baseline (n=1022): mean eCO 13.94; 4 week follow-up (n=567): mean eCO 5.05. “Of those who provided a reading on both occasions (n = 567), mean CO dropped significantly from 13.9 to 5.05 ppm (paired t = 28.3, p < .001).”

Goniewicz 2017

2 weeks

Report significant decline in eCO from baseline (P < 0.05) at 1 and 2 weeks

Hickling 2019

6 weeks[4]

Reduction from mean eCO (ppm) 25.67 (SD 17.16, n = 45) at baseline to 22.09 (SD 15.93, n = 45) at 6 weeks. At 24 weeks, no change (mean 26, SD 16.78, n = 31)

↓ 6 weeks

↔ 24 weeks

Hoeppner 2024

3 months

Baseline: 23.8, 3 months: 28.9, change from baseline: +5.1

Ikonomidis 2018[5]

1 month

Reductions in eCO in people using EC + conventional cigarettes (baseline mean 15 ppm, SD 0.6, n = 24; 1 month mean 12.5, SD 0.6, n = 24); people using EC only (baseline mean 13.9, SD 0.7, n = 42; 1 month mean 4.2, SD 0.6, n = 42); “noncompliant” group (baseline mean 18.5, SD 0.7, n = 4, 1 month mean 15.1, SD 0.6, n = 4). (Slight increase in controls (given no intervention): baseline mean 15.3, SD 1, n = 20; 1 month mean 16.4, SD 0.7, n = 20.)

Martner 2019

4 weeks

Reported for individual participants (n = 12), no averages given. “Following baseline, five participants showed immediate reductions in CO and high levels of EC use. Three showed more gradual reductions in CO and gradual increases in EC use. Two participants showed initial, but brief, reductions in CO and high levels of EC use, and two failed to appreciably reduce CO levels and showed relatively low EC use.” (data for other participants lost or withdrawn)

NE

McRobbie 2015

4 weeks

Mean change from baseline in eCO (ppm): -12 (95% CI -16 to -8), n = 33. Point estimate for reduction same in abstinent and smoking participants at 4 weeks

Pacifici 2015

1, 4, 8 months

At one month, EC users showed a significant decline in eCO; there was no significant change in non-EC users (people who had opted not to use the EC provided). At four and eight months, exhaled CO had declined in EC and non-EC users.

Pericot-Valverde 2025

8 weeks

Baseline: 21.5, 8 weeks: 14.8, change from baseline: -7.5

Polosa 2011*

2 years

Significant reduction in the average eCO across the whole cohort of 23.5 to 8 ppm at 24 months (P = 0.011)

Polosa 2014b*

6 months

Measured eCO, report results graphically by group; at 24 weeks, CO appears to have significantly reduced amongst quitters and people reducing cigarette consumption by at least 50%, and appears to have remained stable in people who continued smoking at least half as many cigarettes as they had at baseline

↓ quitters and people reducing cigarette consumption

↔ people who continued smoking at least half as many cigarettes as they had at baseline

Pratt 2016

4 weeks

Baseline mean eCO 27.27 ppm (n = 19, no SD provided). At week 4, mean 15.21 (n = 19)

Pulvers 2018

4 weeks

Significant change in eCO (P < 0.001). Baseline mean 14.3 ppm, SD 12.7, n= 40. 4 weeks: mean 8.9, SD 8.35, n = 40.

Scheibein 2020

4, 8, 12 weeks

Week 1 (baseline): 21.89 (14.41) ppm, n = 23

Week 4: 13.78 (8.76) ppm, n = 17

Week 8: 15.78 (7.41) ppm, n = 12

Week 12: 15.56 (10.29) ppm, n = 9

Sifat 2024

8 weeks

EC + incentives arm: baseline: 14.57, 8 weeks: 8.69, change from baseline: -7.23

EC arm: baseline: 14.07, 8 weeks: 8.86, change from baseline: -4.57

Smith 2020

1 week

Study arms varied by PG/VG ratio. Reduced eCO in all groups. Combined mean: baseline 33.1 (SD 18.3), n = 30; 1 week 26.5 (SD 16.1), n = 28)

Strasser 2016

10 days

Randomized to 4 different brands of EC (similar nicotine content). eCO reductions in all arms. Blu: Baseline mean 19.2 (SD 9.8, n = 6), day 10 mean 3.2 (2.2, n = 5)). Green smoke: Baseline 21.6 (8.8, n = 6), day 10 mean 4.0 (3.4, n = 5). V2: baseline mean 22.0 (8.1, n = 6), day 10 mean 4.8 (3.5, n = 5). White cloud: baseline mean 15.5 (3.5, n = 6); day 10 mean 1.5 (0.7, n = 2)

Valentine 2018

8 weeks

Data provided in figures only, estimated baseline mean eCO (ppm) 9.3, SD 7.1, n = 50. 8 weeks: 8.5, 95% CI 7.1 to 9.9, n = 31

Van Staden 2013*

2 weeks

Smokers who switched to EC had significant reduction in arterial (1.95%, 95% CI 0.47 to 3.44; P = 0.01) and venous (1.87%, 95% CI 0.38 to 3.36; P = 0.02) carboxyhaemoglobin levels.

Walele 2018*[6]

2 years

“The mean (±SD) eCO level in all subjects at Month 1 was 8.7 ppm (±6.5), and steadily decreased to reach 4.1 ppm (±3.1) at Month 24.”

[1] eCO: exhaled carbon monoxide; NS: not specified

[2] NE: not estimable

[3] NE: not estimable

[4] EC provided for 6 weeks; eCO measured at weeks 1 - 10 and 24

[5] Acute cross-over trial followed by ‘chronic phase’ so treated as cohort for purposes of this review

[6] Short term RCT (see first table); all participants then given nicotine EC hence inclusion in this table, as well