Smoking cessation/e-cigarettes

What every physician needs to know:

Over the past 50 years, smoking prevalence in the US has decreased from over 40% in the mid 1960s to around 15% in 2015. Much of this is attributable to increased public awareness regarding the effects of smoking; younger generations are much less likely to have smoked than their parents. Despite this, tobacco use remains a large burden in terms of overall mortality and cost. Nearly 500,000 people die annually in the US and an estimated $170 billion is spent annually on healthcare for diseases directly related to tobacco use. To combat this immense burden on society, clinicians over the last 20 years have greatly increased their rates of smoking cessation counseling and use of cessation aids, whether in the form of nicotine replacement therapy (NRT) or pharmacological agents.

As a result, a large number of different pharmacological and nicotine replacement therapies have been developed and studied in recent years. The most studied and utilized agents are nicotine patches, nicotine gum/lozenges, bupropion SR and varenicline. Each of these therapies have been shown to increase success rates 2-3 fold over placebo, with a combination of 2 or more agents leading to the greatest benefit. Despite earlier concerns due to the neuropsychiatric effects of pharmacotherapy, newer studies have demonstrated both their efficacy and safety.

Initial Approach to Smoking Cessation

Although ultimately the responsibility lies with the patient in terms of quitting, physicians play an important role in helping patients through the process. A number of recent studies have shown that roughly 2/3 of current smokers were either ready to quit or had made attempts to quit, but only 6% succeeded in sustained cessation. This number may seem daunting, but a number of techniques and aids are available at the physician’s disposal, including reassuring the patient that most people who successfully quit had to try an average of anywhere from 6 to 30 times.

The first step lies in meeting with the patient and opening the discussion regarding cessation. A standardized model is recommended by the Agency for Healthcare Research and Quality (AHRQ), focusing on the 5 A’s (Ask, Advise, Assess, Assist, Arrange) at every office visit including the first.

Ask – The physician must take a thorough history of the patient’s tobacco use history. Careful attention should be paid to duration and frequency of use, type of tobacco products used and previous attempts at cessation (including the number and duration).
Advise – The physician should then briefly advise the patient on the dangers of cigarette smoking and the benefits of cessation in a clear and firm manner. Even very brief counseling such as this has been shown to be effective in helping to aid cessation.
Assess – The next step is in assessing the patient’s readiness to quit. It may seem obvious, but a smoker who is unwilling to stop is also very unlikely to stop. A large percentage of patients are willing to quit but feel overwhelmed at the prospect. At each visit, the physician should reinforce the dangers of smoking to the patient who is in the pre-contemplative phase. For those who are willing but feel the task is too difficult or who have relapsed, the patient should be encouraged to continue and reminded that few succeed on their first attempt but perseverance is important.
Assist – For those patients ready to attempt, the physician should begin by advising the patient to set a quit date. Next a thorough survey of timing of cigarette use, triggers (stressors, people, situations, alcohol use) and pitfalls in previous cessation attempts should be performed. Together with the patient, a discussion should be held on strategies to avoid these pitfalls and situations. Next, physical and emotional effects of nicotine withdrawal should be discussed–cravings, sleep difficulties, weight gain and irritability are common. Remind the patient that these are temporary and subside over time. Finally, options regarding nicotine replacement therapy or pharmacotherapy should be discussed with the patient. A number of options exist and will be discussed in the following sections.
Arrange – Most importantly, patients should be scheduled for routine follow-up to assess their progress. It is important to congratulate patients for even attempting to quit. For patients who have relapsed, it is important to continue to encourage them and to give consideration for additional or alternate therapies.

Nicotine Replacement Therapy

Nicotine replacement therapies come in many forms. Most are easily accessible without a prescription. Most patients are familiar with patches and nicotine gum/lozenges, but alternate forms exist, such as nicotine inhalers, lozenges and nasal sprays. NRT is safe and well-tolerated in patients and results in lower serum levels of nicotine compared to smoking. Cardiovascular disease is not a contraindication to use of NRT. Before starting, the patient should be reminded that nicotine replacement therapy can mitigate some of the symptoms of withdrawal, but will not completely eliminate them.

Compared to placebo, nicotine replacement therapy (NRT) results in a two to three-fold increased likelihood of cessation when used correctly. No studies have demonstrated the superiority of one method of NRT delivery to another, but a number of studies have demonstrated increased efficacy when both long and short acting delivery methods are used, i.e. patches and gum.

Should the patient relapse and smoke while on NRT, they should be encouraged not to stop their routine–many believe that they should stop NRT if they begin smoking while on the patch, as this could result in toxicity, but the risk is low. Instead, they should be encouraged to continue their regimen and continue their cessation attempt.

The more common therapies are discussed below:

Patches – Slow release patches are available over the counter, and come in different dosages–21 mg, 14 mg and 7 mg. For those who smoke > 10 cigarettes a day, one 21 mg patch is applied daily for 6 weeks, followed by a taper to 14 mg for 2 weeks, then 7 mg for 2 weeks. For those that smoke < 10 cigarettes a day, the recommended starting dose is 14 mg for 6 weeks, then 7 mg for 2 weeks. No difference has been found between wearing the patch continuously or removing it while sleeping.
Gum – 2 mg and 4 mg varieties exist and are available over the counter. Gum should primarily be used for breakthrough cravings that occur while using patches. Patients should be instructed not to chew the gum continuously, but instead to chew the gum briefly and then place it in the cheek or under the tongue to allow for slow absorption.
Lozenges – Similar to nicotine to gum, 2 mg and 4 mg varieties exist in mint and cherry flavors over the counter. Lozenges should be used in the same manner as gum–for breakthrough cravings. Nicotine lollipops are also available.
Nicotine Inhalers – Nicotine inhalers have not been studied as extensively as other short acting NRTs. A number of prescription-only devices have been studied and are no more effective than other forms of NRT.
Nasal Sprays – Less commonly used compared to other NRTs due to rhinitis–occurs in up to 90% of users.

Pharmacotherapy

In the last 20 years, a number of pharmacological agents have been studied as smoking cessation aids. Varenicline and bupropion have emerged as the two most commonly used agents. Despite their demonstrated efficacy, the public and physicians have been reluctant to use these agents due to concerns for neuropsychiatric side-effects. Newer data, however, has shown that many of the effects may be secondary to the withdrawal effects of nicotine rather than the medications themselves.

Commonly Used Agents:

Chantix/Varenicline – A partial agonist of the nicotinic receptor, varenicline is hypothesized to work in a two-fold manner: by binding to the receptor and mitigating withdrawal effects and by blocking binding of nicotine to the receptor preventing any buzz which would normally occur. From 2009-2016, varenicline carried a blackbox warning due to concerns for increased suicidality, however, this was removed as more recent, larger studies demonstrate that varenicline carries no increased risk for depression or suicidality compared to placebo. Compared with placebo, varencline increases the likelihood of cessation two to three-fold, with studies showing similar efficacy to nicotine replacement therapy. Women have higher success rates with this medication, up to 45%, as compared with bupropion. On initiating varenicline, the patient should be instructed to attempt cessation 1 week after the initiation and continue medication for at least 12 weeks. The main side effects are nausea, vivid dreams and rash.
Zyban/Bupropion – A norepinephrine/dopamine reuptake inhibitor, bupropion’s theoretical mechanism of action is to increase levels of dopamine in the brain to mitigate the psychiatric effects of nicotine withdrawal. Similar to varenicline, bupropion also carried a blackbox warning due to concerns for increased suicidality, but this has since been removed as similar studies have shown no increased risk. As with varenicline, bupropion should be started 1 week prior to the patient’s planned quit date and continued for at least 12 weeks. Compared head-to-head with varenicline, bupropion is less efficacious and has success rates similar to patches alone. The main side effects reported are insomnia and appetite suppression. For patients with increased risk of seizure, bupropion is contraindicated as it lowers the seizure threshold.

Less Commonly Used Agents:

Clonidine – An α2 agonist, clonidine decreases sympathetic outflow from the CNS–how this affects nicotine cravings is unclear. Clonidine is rarely used for smoking cessation and is limited by numerous side effects: orthostatic hypotension, depression, xerostomia and rebound hypertension for higher doses. Its efficacy is lower than the other pharmacological agents and NRT monotherapy. Use for smoking cessation is off-label.
Nortriptyline – A tricyclic antidepressant, nortriptyline increases CNS concentrations of serotonin and norepinephrine–how this affects nicotine cravings is unclear. Like clonidine, nortriptyline is rarely used for smoking cessation due to its side effect profile and limited efficacy compared to varenicline, bupropion or combination NRT.

Are E-cigarettes an Efficacious Tool for Smoking Cessation?

Several trials and a large meta analysis have been performed in recent years with mixed results. A study published in 2016 reviewed 38 large studies and concluded that e-cigarette use was associated with a 28% decrease in likelihood of smoking cessation. The most recent survey in the U.K. found a rise in vaping from 700,000 in 2012 to 2.9 million in 2017, and the primary reason ex-smokers (52% of vapers) give for using e-cigarettes is to help them stop smoking, while current smokers (45% of vapers) use e-cigarettes principally to decrease their cigarette smoke intake.

Currently, however, both the USPSTF and American Thoracic Society (ATS) have released statements citing insufficient evidence to make recommendations regarding e-cigarette use as a smoking cessation tool. Additionally, no studies exist as to the effects of e-cigarette usage with conventional smoking cessation aids, either NRT or pharmacotherapy. E-cigarettes are rapidly evolving, with newer generation devices having improved nicotine delivery, thus newer studies on more modern devices may find that these drug delivery devices have efficacy in the arena of smoking cessation. Future studies are needed to continue assessing e-cigarette efficacy in smoking cessation.

Are E-cigarettes Useful as a Harm Reduction Technique for Refractory Smokers?

The dangers of smoking are very well established. Even still, some continue to smoke. While we have seen a dramatic decrease in smoking rates in the last 50 years, close to 1 in 6 adults still continues to smoke. Despite their best efforts, some are unable to stop smoking, which has led many to look towards e-cigarettes as a possibly safer alternative. Clinicians are now faced with the challenge of advising these patients on the use of e-cigarettes. On one side of the coin, e-cigarettes produce smaller amounts of toxic compounds compared to tobacco smoke – this has led some to argue that they confer less risk to human health. However, the lack of data on the effects of long-term use, and conflicting studies regarding whether current smokers can use e-cigarettes effectively to wean off of conventional tobacco products, makes the future of e-cigarettes as a harm reduction tool unclear.

Who is Using E-cigarettes?

E-cigarette use continues to rise each year, with the greatest increase seen in youth and young adults (ages 12-24). Between 2011 and 2014, use in adolescents and young adults increased 650% and 890% respectively. As of 2014, nearly 3 million middle/high school students (nearly 1 in 6) reported using e-cigarettes in the month prior to reporting. The use of e-cigarettes in this age range has also exceeded the use of conventional tobacco products two fold, with a significant number (60%) reporting co-use of tobacco and e-cigarettes. In the U.K. 2.9 million adults are using e-cigarettes, with 52% of users being ex-smokers, 45% being current smokers, and 3% being non-smokers.

How do E-cigarettes Work?

While significant variation exists among e-cigarettes, the underlying mechanism is the same for all devices. All use an electric current to heat a coil around a wick. The wick is saturated with a solution of propylene glycol, vegetable glycerin, flavorings and a variable amount of nicotine – usually called e-liquid or e-juice. As the coil is heated, the solution is vaporized and inhaled.

Several variations of the pattern exist and can be broken into 3 categories:

Cartridge based–the most common and popular form. Each cartridge is disposable and screws into a small battery. Many are designed to be similar in size and appearance to cigarettes.
Tank based–generally more powerful than cartridge systems. Tank based devices are interchangeable and significant variation exists between products.
Direct dripping–the most powerful of the e-cigarette devices. A wick is placed in large coil with solution dripped directly on coils. Even more variation exists with direct dripping devices as they tend to be custom built.

Because of the incredible level of variation, it is difficult to study the overall composition of vapor produced from different devices. Most studies support that non-nicotine toxin production is highest in direct dripping devices, followed by tank based, then cartridge based devices. Additionally, until recently, the production of e-liquid was unregulated and often contained additives/adulterants which were known to be irritating or toxic or known carcinogens.

What are the Short-term Effects of E-cigarette Use?

A number of adverse effects have been reported in the literature related to e-cigarette use. Earlier literature was centered around case reports of lipoid pneumonia and diffuse giant cell granulomatous reactions which resolved with cessation. Apart from these case reports, newer literature has begun to elucidate some of the underlying pathophysiology in short-term use. A number of studies have demonstrated that e-cigarette vapor adversely affects airway epithelial permeability and ciliary function predisposing the user to infection. It has also been shown to produce pro-inflammatory cytokines such as IL-6 and IL-8. Furthermore, known carcinogens, specifically formaldehyde and nitrosamines, have been found in e-cigarette vapor–albeit at lower levels than in tobacco smoke. E-cigarette vapor also induces virulence factors in airway colonizers such as S. aureus. Clinically, e-cigarette vapor tends to induce the same immediate effects that cigarettes do: a temporary reduction in FEV1, throat and oropharyngeal irritation and cough.

While not its intended method of use, there are an increasing number of reports of toxic ingestions of e-liquid ingestion by children. As a result, action at the federal level has been taken to regulate sale and manufacture of e-liquid and some states have enacted laws requiring e-liquid to be in child safe containers.

What are the Long-term Effects of E-cigarette Use?

Given their relatively recent development and adoption, the long-term effects of chronic use have yet to be determined fully. What is known so far is that e-cigarette vapor contains compounds which affect the lungs in ways similar to tobacco smoke. The difficulty in assessing long-term effects lies in the considerable variety of different e-cigarette devices as discussed above. Some devices, such as the direct dripping method, tend to use much higher currents leading to higher temperatures and thus greater toxin production. Furthermore, many people co-use e-cigarettes with tobacco smoke–the effects of simultaneous use has not yet been studied.

Does Use of E-cigarettes in Non-Smokers Lead to Smoking?

This remains an area of hot debate–a number of short-term studies have suggested that young adults in particular are at risk for e-cigarettes as a gateway into smoking. As is the case with other issues regarding e-cigarettes, long-term data is lacking. There is, however, a parallel in the use of non-combustible nicotine products like snus. In Sweden, the use of snus, a form of smokeless tobacco has greatly exceeded the use of cigarettes and other combustible tobacco products. Over the last 30 years, the incidence of smoking continues to fall despite an increase in snus usage. While smokeless tobacco is fraught with its own health risks and its use should not be condoned as a safer alternative to smoking, the data from Sweden suggests that usage of one form of nicotine use may not act as a gateway for smoking.

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