e-cigarettes: ?another resource to decrease smoking

 e-cigarettes may help with smoking cessation (see smoking cessation ecigs NEJM2024 in dropbox, or DOI: 10.1056/NEJMoa2308815)

 

Details:

-- 1246 participants participated in this open-label, controlled trial of adults who smoked at least 5 cigarettes per day for at least 12 months and wanted to quit within 3 months. This was a Swiss study with 5 sites, with recruitment from July 2018 to June 2021

-- patients were recruited through free and paid advertisements in the lay press and on social media, and by advertising in healthcare facilities and on public transport

-- exclusion criteria included pregnant or breast-feeding women, as well as people who used nicotine replacement therapy (NRT) or other smoking cessation drug or e-cigarettes in the prior three months

-- all participants were asked to specify a target quit date and then had a baseline visit scheduled a week before that date

-- participants were also invited to an in-person clinic visit 6 months after the target date, with a subsequent phone call from one of the trial nurses to collect data by phone in those who missed that on-site visit

-- nurses and participants were both aware of which group the participants were enrolled in, which was determined through a random selection process

 

-- control group: standard smoking cessation counseling (including cognitive behavioral therapy, motivational interviewing), and shared decision-making for the smoking cessation medications and NRT, which was adapted to the level of nicotine dependence of the participants

    -- there was also counseling by telephone at the participant’s target quit date, and at weeks 2, 3, 4, and 8 after their target quit date.

    -- this group also received $50 at the baseline visit that could be used for any purpose, including the purchase of NRT 

 

-- intervention group: standard smoking cessation counseling (including the optional use of NRT, an in-person session, and 5 telephone calls) adapted to the context of the intervention, as well as e-cigarette kits of 6 flavors (2  tobacco, 1 menthol, and 3 fruity), and for 4 nicotine concentrations (19.6 mg, 11 mg, 6 mg, and 0 mg per mL)

    -- the e-cigarette liquids contained propylene glycol, vegetable glycerin, medical-quality free-base nicotine, alcohol, and flavoring

 

-- median age 38, 47% female, 73% employed, highest educational level attained: obligatory schools or no formal schooling 8%/secondary education 46%/tertiary education 47%

-- median age when smoking was started=16yo, median number of cigarettes per day=15, at least one previous attempt to quit smoking in 85%, Fagerstrom Test for Nicotine Dependence score=4.3

    -- the Fagerstrom Test for Nicotine Dependence has 6 questions to evaluate the quantity of cigarette consumption, the compulsion to use, and dependence. The scores range from 0 to 10, higher numbers suggest greater dependence

-- median expired CO level: 20 ppm

 

--At baseline visit patients completed questionnaires and had some tests, including assessing demographics, smoking history and smoking status, expired carbon monoxide level, withdrawal symptoms, and respiratory symptoms

 

-- primary outcome: continuous abstinence from tobacco smoking at 6 months, as measured by personal reports of no cigarette smoking after their target quit date, with chemical validation by anabasine level (a chemical found in the tobacco plant) <3ng/mL. If the anabasine data were not available, abstinence was validated by an exhaled CO level <9 ppm

 

Results:

-- time from baseline visit to target quit date: 6 days

-- intervention group: e-cigarettes used by 96% in the intervention group; in addition 7% used NRT, 0.5% varenicline or bupropion

-- control group: 64% used NRT, 4% e-cigarettes, 4% the smoking cessation drugs

  

-- 6-month data were available for 91% of participants (64% obtained at follow-up visit and 23% by phone call/email/mailed questionnaire)

    -- biochemically-validated, continuous abstinence from smoking:

        -- intervention group: 180 of 622 participants (28.9%)

        -- control group: 102 of 624 business months (16.3%)

            -- 71% more likely to be continuously abstinent with intervention, adjusted relative risk 1.71 (1.39-2.12), with the absolute difference between the groups of 12.6% (8.0-17.2)

 

-- secondary outcomes (basically not much different from the primary outcome), comparing the control group to the intervention group:

    -- continuous abstinence without chemical validation: 23.4% versus 38.1%, difference of 14.7%, adjusted relative risk aRR 1.57 (1.32-1.85)

    -- sustained abstinence allowing a two-week grace period, with biochemical validation: 17.6% versus 30.7%, difference 13.1%, aRR 1.70 (1.39-2.08)

    -- sustained abstinence allowing up to 5 cigarettes, with biochemical validation: 17.5% versus 35.2%, difference 17.7%, aRR 1.96 (1.61-2.38)

    -- abstinence within previous 7 days, with biochemical validation: 21.3% versus 39.4% difference 18.1% adjusted relative risk 1.74 (1.47-2.07)

    -- abstinence within previous 7days, without biochemical validation: 32.1% versus 53.4%, difference 21.3%, adjusted relative risk 1.56 (1.37-1.77)

 

-- respiratory symptoms, per participant report, comparing intervention group vs control group:

    -- no cough: 41% intervention group versus 34% in control group

    -- no phlegm: 62% versus 51%

    -- no chest tightness: 73% versus 72%

    -- not feeling breathless: 34% versus 30%

    -- no limitation in home activities: 95% versus 93%

    -- confidence in leaving home: 96% versus 95%

    -- sound sleep: 92% versus 90%

    -- having a lot of energy: 40% versus 39%

-- withdrawal symptoms: angry/irritable, nervous/anxious, depressed mood, difficulty concentrating, increased appetite/hunger/weight gain, insomnia/sleeping problems, restless, craving to smoke: all were marginally more in the control group. Overall it was 6.2% in the control group versus 5.3% in the intervention group

 

-- safety issues:

    -- one person died during the trial in the control group

    -- 4% in the intervention group and 5% in the control group had a serious adverse event, not significant statistically

    -- overall 44% in the intervention group and 37% in the control group reported adverse events, relative risk 1.19 (1.04-1.37), p=0.01

        -- the major differences were musculoskeletal issues in 13 vs 9 participants (mostly “bone issues”); psych 11 vs 6 participants (mostly depression)

 

Commentary:

-- a prior systematic review/meta-analysis synthesized results from 6 studies that were graded as low or very low risk of bias (https://bmjopen.bmj.com/content/bmjopen/11/2/e044222.full.pdf ). Although the authors of the current study stated that that trial “showed that e-cigarettes were more effective for tobacco smoking cessation than nicotine-replacement therapy”, in fact the study found that e-cigarettes were no more effective than NRT

    -- though I certainly do not check all references to articles, I do try to look at ones that have major impact, at least to make sure that the stated conclusions reflected the reality of these articles. And, perhaps surprisingly, it is not so rare that I find significantly contrary information in the article itself, even in NEJM

-- there was also a Cochrane review on this subject, noting that e-cigarette seem to stop smoking longterm (vs placebo e-cigarettes), and decrease the number of cigarettes smoked in those unable to quit, but there were few trials, low event rates, and wide confidence intervals, all decreasing the certainty of their results (as they noted): https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD010216.pub2/full 

 

-- This current study found that e-cigarettes were associated with greater abstinence from smoking than standard counseling, though many who did abstain from smoking continued using the e-cigarettes at the 6-month mark (unclear from the study if the patients who continued to vape had cut back on the intensity of vaping, a useful outcome to know)

 

-- one major concern is the toxicity of the components of e-cigarettes: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9386787/ .  There are several components that are of concern:

    -- flavoring compounds: studies have found that around 150 flavoring chemicals are used in the 7000 unique e-liquid flavors. Flavoring chemicals are associated with a range of adverse pulmonary effects when in high concentrations. Diacetyl and cinnamaldehyde are particularly toxic. Cell-based assays have suggested that flavorants can impair innate immunity defenses and potentially contribute to respiratory problems

    -- propylene glycol and glycerin: non-toxic at room temperatures but with heat there are potentially dangerous thermal degradation products, including traces of acetaldehyde, acetone, formaldehyde, methylgloxal, and propionaldehyde with heated propylene glycol; and formaldehyde, acetaldehyde, and acrolein as with heated glycerol. The concern is that chronic exposure could be deleterious

-- but the perspective here is that there about 600 ingredients in cigarettes, and that when they are burned there more than 7000 chemicals released. More than 70 of these chemicals are known to cause cancer (https://www.fda.gov/tobacco-products/products-ingredients-components/chemicals-cigarettes-plant-product-puff#:~:text=Is%20there%20more%20than%20nicotine,7%2C000%20chemicals%20in%20cigarette%20smoke.&text=More%20than%2070%20of%20those%20chemicals%20are%20linked%20to%20cancer. )

 

-- over the past several years, I have personally suggested e-cigarettes to patients who are unable to decrease or stop their smoking with the usual combination of aids (nicotine patches/gum, bupropion, varenicline, counseling, cognitive behavioral therapy). Several people have been able to switch completely to e-cigarettes, initially vaping frequently but being able to decrease the vaping quite significantly over a few months, some quitting all nicotine completely. In fact i have not had a patient who was unable to decrease their vaping significantly over time

-- there was even one systematic review and meta-analysis suggesting that smoking even one cigarette a day confers 50% of the risk of cardiovascular disease as smoking 20 cigarettes per day: https://gmodestmedblogs.blogspot.com/2018/01/smoking-just-one-cigarette-one-too-many.html )

-- there is also concern that in teenagers e-cigarettes may be a gateway drug to smoking regular cigarettes: https://gmodestmedblogs.blogspot.com/2019/02/e-cigs-nicotine-as-gateway-drug.html

-- but, i think the clinical bottom-line is that cigarettes are the most deleterious modifiable cardiovascular risk factor, they are perhaps the most addictive substance, and there are so many very severe adverse health effects even beyond the cardiovascular ones: lots of cancers, pulmonary disease, infections (esp pulmonary ones), risk of diabetes, osteoporosis, pregnancy complications, peptic ulcer disease, periodontal disease, cataracts and macular degeneration, postoperative complications, and overall mortality (and, i suspect i am leaving out some.....)

 

Limitations:

-- this is not a blinded controlled study, which introduces a risk of bias

-- the study coordinators used the $50 cash voucher for those in the control group as a means to allay their disappointment with not being in the e-cigarette group

    -- but they have no information in terms of how these participants actually interpreted the voucher; and there also may well have been additional out-of-pocket costs for getting the NRT, which could have been a disincentive

        – in fact, in the study there was a huge difference in the actual adherence to the meds in the 2 groups: 64% used NRT in the control group versus 96% using e-cigarettes in the intervention group. And, this difference might well have seriously affected the validity of their results

-- though a 6-month trial is reasonably standard in the cigarette smoking cessation literature, it does not necessarily predict long-term smoking cessation. This study will continue with follow-up at 12, 24, and 60 months

    -- also, there was much more interaction between the study nurses and the intervention group vs control group that might also have affected the results (more touches leading to better outcomes in the intervention groiup?)

-- the patients we see in clinic are very unlikely to be able to get the intensity of the nursing involvement that was in the study design, which might also significantly limit the results we might get in the community

-- we do not have any information of the trajectory of vaping: what was the initial consumption and dose of nicotine? how did that track over the length of the study? it would be useful to know if it decreased significantly over time, with less exposure to the addictive nicotine and the potentially toxic components of e-cigarettes

 

So:

-- the overriding good news is that the number of people smoking cigarettes in the US has decreased substantially over the last few decades.

    -- per a report by statista in 2023:

 

-- But, it does seem that nicotine is so addictive and is associated with so many whole-body serious problems that e-cigarettes seem to be a reasonable option to help people decrease their use of regular cigarettes, if the usual pharmacologic/nonpharmacologic approaches are unsuccessful.

-- and there are huge societal benefits to decreasing smoking: smoking exposure can lead to many bad health outcomes in nonsmokers, many costs for families to take care of relatives with smoking-related illnesses (psychological/social as well as financial), the disruptive effects on the community (loss of community members, decreased participation in the workforce, higher health insurance costs because of costly treatments), etc.

 

a few past blogs on this:

-- a gradual decrease in cigarettes beginning 2 weeks before the quit date seems to work better than an abrupt stop of NRT at the quit date: https://gmodestmedblogs.blogspot.com/2016/03/abrupt-vs-gradual-smoking-cessation.html

-- the American Thoracic Societty guidelines for smoking cessation, promoting varenicline as a primary approach: https://gmodestmedblogs.blogspot.com/2020/07/guidelines-smoking-cessation-meds.html 

-- a study suggesting that it takes 20-30 years of smoking cessation to normalize mortality rates: https://gmodestmedblogs.blogspot.com/2024/01/smoking-cessation-20-30yrs-to-normalize.html 

 

 

geoff

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