key: cord-0015081-31ohj4xl
authors: Kim, Jae Yeol
title: Directions and Challenges in Smoking Cessation Treatment
date: 2020-12-02
journal: Tuberc Respir Dis (Seoul)
DOI: 10.4046/trd.2020.0150
sha: 3cb102e39654476b4845670af3aede7d2d746431
doc_id: 15081
cord_uid: 31ohj4xl

Raising the tax on tobacco-related products is the most effective and sustainable intervention for smoking cessation. The 2015 tobacco-tax increase resulted in a decreased smoking rate among Korean adult men. However, participation in the government-sponsored smoking-cessation programs developed after the 2015 tobacco tax increase has declined sharply since 2018. The popularity of electronic cigarettes (e-cigarettes) seems to be an important factor in this decline. Indeed, the market share of e-cigarettes has increased steadily since 2007, when the e-cigarette was introduced in Korea as a vaporizer. The introduction of the tobacco-heating device IQOS in 2017 resulted in the skyrocketing popularity of e-cigarettes, especially among the young generation of Koreans. The U.S. Food and Drug Administration (FDA) authorized marketing of IQOS as a “reduced exposure” tobacco product on July 7, 2020, further complicating smoking-cessation efforts. The agency announced that IQOS produces fewer or lower levels of some toxins than combustible cigarettes. However, FDA authorization does not mean that these products are safe. There is no evidence that reducing the harmful chemical components leads to health benefits. Clinicians need to maintain the position that those who smoke, regardless of tobacco-product type, should be counseled for smoking cessation and prescribed appropriate proven pharmacologic agents.

tronic toothbrushes) were provided as incentives. However, this special treatment was terminated on January 1, 2019 3 . In the first year of introduction, this program registered more than 200,000 smokers; the number of participants increased to more than 400,000 in 2017. However, the number of participating smokers has sharply decreased since 2018 ( Figure  2 ) 4 . Not only smoking cessation counseling and pharmacologic treatment by medical doctors but also other services for quitting smoking, such as smoking cessation clinics at public health centers, phone consultation for smoking cessation, online services for smoking cessation, and visiting services for smoking cessation have experienced rapid decline in participation since 2018 5 . Increased tolerance to the raised prices of cigarettes and the popularity of electronic cigarettes (ecigarettes) are seen as important factors for the loss of interest in these programs. In the face of the increased prices of cigarettes, smokers are seeking ways to continue smoking, such as switching to cheaper products or reducing other expenses 6 . This explains the dramatic rise in sales of e-cigarettes in Korea since 2015. E-cigarettes were relatively more economical compared with combustible cigarettes because they were excluded from the tax increase. In addition, companies that produced e-cigarettes actively marketed their products by describing them as less harmful to people' s health.

An e-cigarette is a battery-powered electronic device that vaporizes a nicotine-containing solution 7 . Instead of burning tobacco, the user inhales aerosolized substances-vapor. This type of e-cigarette is called a closed system vaporizer (CSV), and the use of a CSV is popularly known as "vaping. " Although tobacco companies have been developing nicotine aerosol-generation devices since as early as 1963, the modern e-cigarette was invented in 2003 by the Chinese pharmacist Hon Lik 8 . Hon's father died in 2004 from lung cancer. Hon himself was a heavy smoker, smoking one to two packs per day. His father' s death was the main influence for him to develop e-cigarettes. In 2003, he formulated the idea of using a high-frequency piezoelectric ultrasound-emitting element to vaporize a nicotine-containing solution. This vapor, similar to cigarettes, would then be inhaled to deliver nicotine to consumers. He filed his first patent in China in 2003, and then in the United States and the European Union. The first e-cigarette was manufactured using ultrasound technology a year later in Beijing, China. The first e-cigarette model, named "Ruyan, " consisted of three parts: a battery, a plastic cartridge containing a nicotine solution, and a heating element composed of an ultrasonic atomizer.

The use of CSVs has increased sharply worldwide, including Korea. According to the 11th Korea Youth Risk Behavior Webbased Survey conducted in 2015, 9.8% of teenagers used CSVtype e-cigarettes 9 . However, the entrance of heated tobacco products (HTPs) changed the picture of the global e-cigarette market. HTPs heat, rather than combust, processed tobacco in a controlled fashion. HTPs are rapidly gaining market share in some countries, such as Japan and South Korea, and have been introduced in more than 50 countries as of May 2020 10 . IQOS was introduced to Korea as the first type of HTP in 2017. According to a study that evaluated more than 6,000 subjects aged ≥19 years who participated in the Korea National Health and Nutrition Examination Survey (KNHANES), those who 

In Korea, the market share of e-cigarettes has increased steadily after the tobacco tax increase in 2015 ( Figure  3 ). In recent data, from the first half of 2020, 182,000,000 packs of e-cigarettes have been sold (180,000,000 packs of HTPs+2,000,000 packs of CSVs), accounting for 10.5% of the total sales of tobacco products (1,740,000,000 packs). The share of e-cigarettes was 11.1% in the same period last year (decrease of 0.57%). The sales of HTPs decreased by 6.6% and that of CSVs plummeted by 80.3% 3 . The plunge in sales of CSVs may have been affected by the warning against the use of CSVs announced by the Korean government in October 2019, which came after the report of vaping-associated acute lung injury in the United States.

In July 2019, the Wisconsin Department of Health Services and Illinois Department of Public Health received reports regarding rapid increase in visits to the emergency department owing to lung injury that was possibly associated with the use of e-cigarettes. In a preliminary report, they analyzed 53 cases, most of whom were young (median age, 19 years; range, 16-53 years), male (44/53, 83%), and white (82%). Many of them (83%) had a history of vaping cartridges containing cannabis products, either alone or in combination with other products. Meanwhile, 17% used products containing nicotine only. More than two-thirds of the cases showed hypoxia at presentation, which indicated extensive pulmonary infiltration. Of the patients, 83% had an abnormal chest radiograph at presentation, usually in the form of bilateral, ground-glass opacity. In the initial reports, the mortality rate was 2% (1/53). The final report noted 98 cases and two deaths 12 . The number of cases peaked in September 2019, and as of February 18, 2020, 2,807 e-cigarette or vaping product-use associated lung injury (EVALI) cases had been reported, with 68 deaths 13 . The exact cause of EVALI has not been determined, although the vitamin E acetate and tetrahydrocannabinol in the products are highly suspected to be the culprits. Upon learning of reports of EVALI cases in the United States, the Korean government issued a strong warning against the use of CSVs in October 2019, which remains in effect. CSV products sold in the Korean market have been analyzed, and no product has been found to contain cannabis components. Vitamin E acetate was detected in three of 112 products, but only at a minimal concentration (0.03-0.12 ppm). An animal study showed that the concentration of vitamin E acetate would need to be ≥3.12 mg/kg to provoke significant pulmonary toxicity 14 . At present, Korea does not have a confirmed case of EVALI.

The U.S. Food and Drug Administration (FDA) authorized the marketing of Philip Morris Products S.A. ' s "IQOS Tobacco Heating System" as a modified risk tobacco product (MRTP) as of July 7, 2020. The products authorized for sale include the IQOS device, Marlboro Heatsticks, Marlboro Smooth Menthol Heatsticks, and Marlboro Fresh Menthol Heatsticks. This announcement permits the marketing of MRTPs as containing a reduced level of or presenting a reduced exposure to a substance, to benefit the health of the population. Although the U.S. FDA has stressed that this action does not imply that IQOS is safe nor "FDA approved," this decision has a huge impact on the behavior of current or potential consumers of HTPs. The issue of the relative safety of HTPs would be hotly debated in the future.

Pharmacologic Treatment

By smoking cigarettes, a person inhales an estimated 7,000 compounds, including numerous toxic components, such as benzene, formaldehyde, benzopyrene, carbon monoxide, ac- www.e-trd.org rolein, and even metals. These materials cause injury through inflammation, irritation, asphyxiation, carcinogenesis, and other mechanisms, with the respiratory tract being the first system to be hit. Undoubtedly, smoking causes and aggravates various respiratory diseases, including chronic obstructive pulmonary disease (COPD), lung cancer, bronchitis, and asthma 16 .

In South Korea, pneumonia ranked tenth among all causes of death in 2004; its rank climbed to the third position, after malignancies and cardiovascular diseases in 2019 17 . Smoking is the second most important risk factor after congestive heart failure in patients hospitalized with community-acquired pneumonia in South Korea 18 . Given this context, Korean hospitals provide counseling and pharmacologic treatment to smokers who are hospitalized for pneumonia. The percentage of community-acquired pneumonia patients with a history of smoking within a 1-year period who are offered smoking cessation counseling is reported to be as high as 92.2% 19 . In the case of COPD, smoking cessation is one of the most important interventions for disease management. It is also the only way of slowing the decline rate of forced expiratory volume in 1 second and improving survival 20 . Regarding lung cancer, smoking is an important factor for its development and outcomes. Cigarette smoking status is reported as an independent predictor of mortality in patients with lung cancer 21 .

Smoking increases the risk of all-cause mortality in a doseresponse manner 22 . Pharmacotherapy and nicotine replacement reliably increase the long-term smoking abstinence rates.

The smoking cessation promotion program developed after the 2015 tobacco tax increase in South Korea covers the cost of pharmacologic agents. Physicians can choose between varenicline and bupropion. Varenicline has shown a superior smoking cessation effect compared with a nicotine substitute or sustained-release bupropion in many prospective controlled studies [23] [24] [25] . In the initial period of introduction of varenicline, cardiovascular adverse effects, and neuropsychiatric symptoms, such as abnormal dreams, have been raised as safety issues. However, a subsequent study found no risk of serious cardiovascular adverse events during or after varenicline treatment 26 . Varenicline, bupropion, and nicotine patch are well tolerated and effective in adults with psychotic, anxiety, and mood disorders 27 . Thus, varenicline can be used as the most effective anti-smoking drug by most smokers, including those with psychiatric disorders, cardiovascular diseases, and COPD.

The tobacco tax increase in 2015 was helpful for the decrease of the smoking rate below 40% among adult males for the first time in Korean history. Financial resources secured by tobacco tax increase were diverted to multiple programs to promote smoking cessation. However, the loss of enthusiasm for smoking cessation was evident since 2018. The skyrocketing popularity of new type of cigarettes, HTPs and CSVs especially among young generation was also an important factor for the loss of interest in these programs. However, the ultimate health benefits of e-cigarettes and their role as intermediary agents before final quitting of smoking have not been established scientifically yet. As clinicians, we need to adhere to proven ways of the counseling and pharmacologic treatment for smoking cessation.

Jae Yeol Kim serves as editor-in-chief of the Tuberculosis of Respiratory Diseases, but has no role in the decision to publish this article.

No funding to declare.

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