e-cigs decrease adult smoking; but in kids??

A recent UK study found that e-cigarettes were more effective than nicotine replacement therapy in smokers who want to quit (see ecigs dec smoking nejm2019 in dropbox, or DOI: 10.1056/NEJMoa1808779).

Details:

--886 people were randomized into an e-cigarette starter pack (second-generation refillable e-cigarette with one bottle of nicotine liquid, 18mg/ml), with recommendation to purchase further e-liquids of the flavor and strength they want, vs 3-months of nicotine replacement products (including product combos, such as patches with gum, and the ability of patients to switch these products around). Product use started right after randomization [see blog at the end which found that starting nicotine patches 2-4 weeks before smoking cessation was more effective]

--median age 41, 48% female, 70% employed, 41% entitled to free prescriptions (this is a "marker of social disadvantage or poor health"), median 15 cigarettes/d, median expired CO level 20 ppm, score on Fagerstrom Test for Cigarette Dependence 4.6 (out of scale of 10, higher being more dependent), use of NRT in past in 75%, past use of e-cigs in 42%

--biweekly behavioral support for at least 4 weeks

--primary outcome: sustained abstinence for 1 year, validated biochemically at final visit by exhaled CO

--seconday outcomes: patient-reported treatment usage, and respiratory symptoms; smoking reduction from 26-52 weeks, abstinence at 4 weeks and at 26 weeks.

Results:

-- 79% completed the 52-week followup

--1-year abstinence rates:

    --e-cigs: 18.0% vs nicotine replacement therapy (NRT): 9.9%

        --relative risk 1.83 (1.30-2.58), p<0.001

        --absolute difference of 8.1/100, so number-needed-to-treat for sustained abstinence = 12

--in those abstinent at 52 weeks: 80% (63 of 79) on e-cigs were still using them, vs 9% (4 of 44) on NRT 

--secondary analyses:

    --abstinence between 26-52 weeks: 21% on e-cigs vs 12% NRT, 79% reduction with RR 1.79 (1.32-2.44)

    --abstinence at 4 weeks: 44% on e-cigs vs 30% NRT, 45% reduction with RR 1.45 (1.22-1.74)

    --abstinence at 26 weeks: 35% on e-cigs vs 25% NRT, 40% reduction with RR 1.40 (1.14-1.72)

--treatment adherence daily during first 4 weeks: 53% on e-cigs vs 10% on NRT

--cough: decreased from 55% baseline to 31% with e-cigs, and from 52% to 40% with NRT, 20% better with e-cigs than NRT, RR 0.8 (0.6-0.9)

--phlegm production decreased from 44% baseline to 25% with e-cigs, and from 43% to 37% with NRT, 30% better with e-cigs, RR 0.7 (0.6-0.9)

--no difference in wheezing or shortness of breath

--urge to smoke (scale 1 to 6, where 1=not at all, 6= all the time): e-cigs 2.6 vs NRT 3.0 at 1 week; 2.0 vs 2.3 at 4 weeks

--also decreases in irritability, restlessness, and inability to concentrate with e-cigs

--patient satisfaction: on a scale of 1-5, where 2=a little less than regular cigarettes, 3=the same, and 4=a little more:

    --helpfulness to quit, at 4 weeks: e-cigs 4.3 vs NRT 3.7

    --taste, at 4 weeks: e-cigs 3.5 vs NRT 3.1

    --satisfaction, at 4 weeks: e-cigs 2.7 vs NRT 2.3

--adverse effects:

    --throat or mouth irritation: 65.3% on e-cigs vs 51.2% on NRT

    --nausea: 37.9% on NRT vs 31.3% e-cigs

    --no serious adverse effect in either group felt to be related to e-cigs or NRT

Commentary:

--one major concern in the above study was that those on e-cigs continued to use them at the end of the study, vs stopping the NRT after 3 months or so.

    --Are there health risks to long-term use of e-cigs (there are definitely troubling components in e-cigs, such as ultrafine particles that can be inhaled deeply in the lungs, flavorants such as diacetyl (linked to serious lung disease), volatile organic compounds, and heavy metals (eg nickel, tin, lead); also, what will be the effects of new chemicals used in the future, such as new flavors, modifications of components, etc. And we know that evaluation and regulation on adding new chemicals is essentially nil: see http://gmodestmedblogs.blogspot.com/2019/02/breast-implants-and-lymphoma-medical.html )?

    -- it seems reasonable to assume that the components in e-cigs which might be toxic are less so than the 2-3000 components of regular cigarettes, some of which are known and documented carcinogens.

    --but we do need long-term studies (and, at least  good animal studies) for e-cigs to make sure there are no likely bad long-term effects.

    --and, of course, the other concern with regular cigarettes is COPD/destruction of lung tissue. several non-nicotine components of regular cigarettes can cause lung and airways destruction (see https://www.ncbi.nlm.nih.gov/books/NBK53021/ ). Is this a concern with long-term with e-cigs??

    --although one potential benefit of continued use of e-cigs could be a decrease in subsequent risk of relapse to regular cigarettes

    --it would be useful to have a trial with titration down of e-cigs (using less frequently, or less potent nicotine concentration) over time to see if smoking cessation continued without e-cigs and if there were later relapses

-- this study did find a pretty significant adherence difference of e-cigs over NRT, with the notable finding that in the first 4 weeks only 10% on NRT used them daily vs 53% on e-cigs.

-- other studies have had similar benefit of NRT and bupropion at 1 year (my sense from prior studies, including those with varenicline, is that they are mostly shorter than 1 year; and as in the above study, abstention at 1-year was much lower than at the 6-month mark, and therefore a better indicator of effectiveness)

-- i have had some pretty reasonable success with e-cigs when the traditional smoking cessation techniques and meds do not work, though a significant obstacle for some of my patients is their cost (not covered by any insurance)

--limitations of the study: the biggest one to me is whether increased legitimatization of e-cigs will lead to more kids using them

    --there was a very recent (11 Feb 2019) report from the CDC showing that among high school students in 2018, 27% (4.04 million) reported current use of any tobacco product, with e-cigs being the most commonly used (20.8%, 3.05 million); 7.2% of middle school students (840,000) also reported current tobacco use, with e-cigs being most commonly used (4.9%, 570,000). Overall cigarette smoking in US youth has steadily declined over the past 2 decades, but during 2017-8, current use of any tobacco product increased from 19.6% to 27.1% (38.3% increase) among high-school students and from 5.6% to 7.2% (28.6% increase) in middle-school students.  These increases were basically explained by huge increases in e-cig use: increased from 11.7% to 20.8% (77.8% increase in one year) among high-school students and from 3.3% to 4.9% (48.5% increase in one year) among middle-school students

    --a very extensive 2015 report  (see http://www.monitoringthefuture.org/pubs/monographs/mtf-overview2015.pdf , from the National Institute on Drug Abuse at the NIH on general drug use among adolescents, also noted the rapid ascension of e-cigs (though the current increase is much more profound), and that  fewer students saw e-cigs as being a “great health risk”. The most common reason for using them is “to see what it’s like”, and the second most common reason “because it tastes good”. Of note a small minority of 5-10% of the users stated that they used e-cigs  to stop regular cigarette smoking (see http://gmodestmedblogs.blogspot.com/2016/12/teen-drug-use-in-us-new-survey.html ). 

        --the concern with students is many-fold, including: adverse effects of nicotine itself to the developing brain, potential adverse effects to the body overall from long-term exposure to the chemicals in the e-cigs; and, being young, the length of their exposure to these products is likely to be quite extensive for many of them

    --other limitations of the current adult e-cig study: the carbon monoxide confirmation of non-smoking is valid for only the past 24 hours, patients were preselected as having no preference for e-cigs or NRT, the median cigarette use beforehand was 15/day and results may not be generalizable to those smoking much less or much more, this was a controlled study with a behavioral component that may not be available in real clinical situations, pregnant women were excluded

--a significant positive of the study is that they allowed combinations of NRT and switching between different ones, more replicating clinical practice and patient preferences

So, the overall public health effect of e-cigarettes is a bit unclear.  The current study in adults does show that they may be useful in helping current smokers quit, though the persistent use of them at the 1-year mark is troubling. My practice is to suggest them to current smokers when other non-pharmacologic and drug treatments have failed, and I have had several patients do quite well with that (and most ultimately stopping the e-cigs as well). This benefit might wane as the manufacturers develop more seductive flavors to entice continued e-cig usage and if there are then very long-term exposures.  But the really big public health issue is the dramatic (“epidemic”, per the FDA head) effect on the youth, with really very likely adverse long-term health effects. the recent FDA commissioner's report does articulate this problem, but is not aggressive enough in proposed regulation (see blog below).

Prior relevant blogs:

--http://gmodestmedblogs.blogspot.com/2018/11/fda-bans-some-flavored-tobacco-product.html reviews the recent position of the FDA on flavored tobacco products, noting serious concern about the potential problems in kids, proposing some pretty strong guidelines about limiting access for youth, but is quite limited in regulation for anyone 18yo and older. and minimal restrictions on what the manufacturers need to do

--https://blogs.bmj.com/bmjebmspotlight/2016/05/10/primary-care-corner-with-geoffrey-modest-md-e-cigarettes-as-a-tool-to-quitting-smokingharm-reduction/ an article in Addiction journal for e-cigarettes as a tool for quitting smoking/harm reduction

--https://blogs.bmj.com/bmjebmspotlight/2016/03/28/primary-care-corner-with-geoffrey-modest-md-abrupt-vs-gradual-smoking-cessation/ refers to an article finding that starting nicotine patches 2-4 weeks prior to smoking cessation doubled the long-term quit rate

geoff

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