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1 IV 국내금연진료지침 (2017) 천은미 이화여자대학교의과대학호흡기내과학교실 Smoking cessation is the most important strategy to prevent mortality and premature death. Smoking is well known as chronic relapsing disease due to nicotine addiction. Pharmacotherapy combined with counselling is an effective method to quit smoking. From 2015 the government started to support medical burden for smoking cessation. However, there was no qualified smoking cessation document for Korean clinicians. Korean smoking cessation group has worked to improve the concern about smoking cessation and to develop standardized korean guideline for smoking cessation since a study group launched as a part of research society of Korea Academy of Tuberculosis and Respiratory diseases. Clinical document of smoking cessation was developed in 2017 supported by the Korea Academy of Tuberculosis and Respiratory diseases. Devoted pulmonologists in regard to smoking cessation were participated in developing clinical document for smoking cessation. This clinical document included not only the evidence based standard method for smoking cessation but also updated topics such as electronic cigarettes (heat-not burn), and recent government policies. Clinical document was based on qualified published guidelines and updated journals. In addition, questions and answers regarding important subjects were added in part of Q & A. This clinical document for smoking cessation will be helpful to treat smokers and to get skills related to quitting smoking because this document encompasses a wide range of fundamental methods for smoking cessation considering clinical situation of our country. Most of manuscript was summarized from clinical document for smoking cessation developed by Korean smoking cessation group in Key Words: Smoking cessation, Guideline Corresponding author: Eun Mi Chun, M.D., Ph.D. Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Ewha Womans University, Mokdong Hospital, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul 07985, Korea Tel: , Fax: , cem@ewha.ac.kr 1. 서론 1) 담배의역사와종류담배는기원전 5,000년전부터농작물로재배되기시작할정도로오래되었으며콜럼버스 (Christopher Columbus) 에의해서구에알려졌다 1. 우리나라는임진왜란시기에일본으로부터담배가소개되었다. 담배의유해성에대하여 1964년미국연방보건총감 (U.S. Surgeon General) 은흡연이폐암발병의원인이된다고발표하였으며이연구결과이후미국에서는적극적인담배세인상과담배광고금지등의금연운동이본격화되었다 2. 15

2 (1) 담배의종류 1 일반담배 : 담배의형태는엽궐련 (cigar) 과담뱃대 (pipe), 지궐련 (cigarette) 과점막을통해니코틴을전달하는무연담배 (smokeless tobacco) 가있다. 2 전자담배 : 전자담배는 2004 년개발된이후전세계적으로사용이증가하고있다. 니코틴을포함한액상용액 (e-liquid) 을배터리를이용하여무화기 (atomizer) 를통해에어로졸형태로흡입하는 액상형전자담배 와 2014 년 11 월필립모리스사에서아이코스 (I Quit Ordinary Smoking, IQOS) 라는이름으로시판되는두종류가있으며, 국내에서도 KT&G 의릴과같이판매되고있다. 일반형궐련형담배는태울때온도가 도고온인데반해아이코스나릴은 300 도전후의저온으로담배를찌는방식으로니코틴을흡입한다 (Heat-not- burn tobacco). 일반형궐련담배와액상형전자담배의유해성분함유량을비교한연구에서는액상용액에서의니코틴함량은일반담배와비슷하였으며액상성분에의한여러예상하지못한부작용이발생할가능성을제시하였다. 또한전자담배의사용으로청소년이나비흡연자들이본격적으로흡연을하게되는기회가증가한다고보고하였다. 아이코스와같은찌는형태의궐련형전자담배도니코틴은일반담배의 80% 이상, 발암물질인포름알데히드도 70% 이상으로유사하며일부발암물질은더높은것으로보고되었다 3. 전자담배를이용한금연효과에대해서는무작위대조군연구에서는대조군에비해 6 개월금연성공률이각각유의한차이가없었으며메타분석에서는전자담배를사용하는흡연자가전자담배비사용군에비해서오히려금연성공에대해오즈비가 0.72 (95% CI, ; p<0.05) 로낮게나타났다 4,5. 2) 니코틴중독기전 니코틴중독은금연실패의가장중요한원인이다. 니코틴은 α4β2 니코틴아세틸콜린수용체에선택적으로작용하여뇌에서도파민분비를증가시킨다. 니코틴부족에의한금단증상은신체적증상과정서적증상으로구별되며서맥, 구역, 식욕증가와우울감, 불안, 좌절감, 자극민감성, 주의력감소등의증상을보일수있다 6. 3) 우리나라의흡연현황과금연정책정부는 2020 년까지성인남성흡연율을 29% 까지감소시키는것을목표로하고정책을추진하고있다. 국내성인남성흡연율은 1998 년 66.3% 에서 2015 년 39.3% 로지속적으로감소하고있다 년부터는공중이용시설에서금연을시행하였으며, 2015년에는담뱃값을 2,500 원에서 4,500 원으로크게인상하였다. 2015년부터는건강보험공단에서상담과약물치료를전액지원하는금연치료프로그램을시행하고있고, 2017년에는매년 3회 (12주씩 3회, 36주 ) 까지가능하다. 금연진료에참여하는금연교육은교육사이트 or.kr 에서가능하다. 대한결핵및호흡기학회산하금연연구회에서는 2017년호흡기학회지원으로국내최초의료인을위한체계적인금연지침서를개발하였으며 2018년에는금연치료에관한스마트폰에서사용가능한앱 (app) 을개발하여의료진뿐아니라금연에관심이있는흡연자도금연치료에쉽게접할수있도록하고있다. 4) 금연에서의의사의역할환자진료시매번환자의흡연력을확인하고, 흡연자이면서금연의사가있다면 5As (Ask, Advice, Assess, Assist, Arrange) 에따라금연을적극적으로유도한다. 현재금연의사가없으면 5Rs (Relevance, Risk, Rewards, Roadblocks, Repetition) 를통해차후방문에금연할수있도록유도한다 7. 16

3 2. 금연치료의비약물학적접근 1) 상담과약물치료의병행 흡연자의 70% 는매년금연을시도하고자한다. 그러나도움없이혼자서금연을시도한경우는 75% 가일주일이내에실패한다. 효과적인금연을위해서는약물학적방법과비약물학적방법을동시에사용하는것이좋은결과를가져올수있다 8. 메타분석에서는약물치료와함께상담을시행하였을때에는약물치료만시행한경우와비교하여성공률이약 1.4 배높았고 (95% CI, ), 상담횟수에비례하여금연성공률이높았으며상담시간은 90 분에서 300 분까지가가장효과적이다. 또한상담만시행한경우와비교하더라도약물치료 - 상담병행요법에서금연성공률이약 1.7 배 (95% CI, ) 높았다 9. 2) 금연중운동요법과식이요법 남자보다여자에게서, 흡연량이많았거나, 젊을수록금연후체중이증가하는경향이높다. 금연후 1 년이상의장기간추적결과체중변화의원인은금연자체로인한영향이아닌금연후의신체활동감소에기인한기초대사율감소, 미각회복과탄수화물섭취증가등이대부분이다. 금연을할때급격한체중증가도금연실패의중요한원인이기때문에성공적인금연을위해서는초기부터체중관리가필요하다. 금연중체중증가가동반되는데주기적인운동을병용할경우체중조절과더불어금단증상완화에도도움을줄수있다. 주 3 회이상 30 분이상의중강도이상운동을 3 개월이상규칙적으로하는것이금연성공에도움이된다 10. 체중조절을위한식이요법으로는과일과야채의섭취를자주할수록체중관리효과와더불어금연성공률이높아진다 11. 금연중담배가생각나서입이심심할때마다껌, 은단등으로대치하거나당근, 오이, 다시마, 미역등의음식물을대치하면체중조절과금연에도움이된다. 3) 금단증상및흡연욕구대처법흡연자는금연첫날부터수주동안발생하는심한금단증상이일시적이고몸이회복되고있다는신호라는것을인지하고, 초조감, 욕구불만, 안절부절불안감은산책, 심호흡, 명상을통해조절하며, 수면전이완운동을통해불면증을해소한다 12. 가능한흡연구역을피하고, 흡연하는주변사람들에게흡연을자제해줄것을부탁한다. 식후에흡연생각이나지않도록, 양치를하거나심호흡이나명상, 요가와같은이완요법을적극적으로이용한다. 3. 금연약물요법 1) 니코틴대체제니코틴은흡연자의뇌속에 7초만에도달하며 1개피로도수용체의 80% 를충족시킨다. 이러한과정이반복되면서니코틴수용체수는증가하게되고담배요구량은계속늘게된다. 흡연자들의뇌속에는비흡연자보다비정상적으로많은니코틴수용체가존재하며흡연욕구를만족시키기위해더많은니코틴이필요하게된다 13. 니코틴대체제는담배보다천천히니코틴을뇌에전달하면서니코틴수용체를포화시켜수용체수를점차줄이고금연후 3개월째에는정상니코틴수용체수에가까워지게된다. 니코틴대체제는금연의지가있는사람이나없는사람모두에게제1차금연보조제로권장되며 6개월까지금연효과가증가되나 6개월이상은권고되지않는다. 2) 부프로피온서방정 1997년미국식품의약국 (Food and Drug Administration, FDA) 에의해금연치료제로최초로승인된경구약 17

4 물로서초기에항우울제로개발되어금연치료제로도사용되고있다. 부프로피온서방정은항우울제효과로인해니코틴금단증상과연관된우울감을감소시켜주므로우울증이동반된흡연자에게효과적이다. 적응증은니코틴대체제에실패한환자나니코틴을사용하지않는치료를선호하는환자와식욕억제효과가있어금연후체중증가를염려하는환자에게추천된다 14. 부프로피온서방정복용법은금연시작 1 주일전에 150 mg 을 1 일 1 회아침에복용하기시작하여 3 일간복용후 4 일째부터는 150 mg 을 1 일 2 회복용한다. 부프로피온서방정은 6 개월까지처방할수있다. 흔한부작용은불면증, 두통, 구갈이다. 간질의병력, 식이조절장애가있거나 14 일이내에모노아민산화효소억제제 (monoamine oxidase inhibitor) 를복용한경우는금기사항이다. 3) 바레니클린바레니클린은 α4β2 니코틴수용체에선택적효현제로서도파민을분비하여, 금단증상을완화하며동시에부분적길항작용도하게되어, 니코틴수용체에니코틴이결합하는것을차단한다 15. 바레니클린은니코틴대체제, 부프로피온에비해금연율이유의하게높았다 16. 또한무작위배정연구에서 1 mg과 0.5 mg을비교한결과용량을감량한그룹이표준용량을쓴그룹과비교했을때금연율의차이가없고, 부작용은적게나타난것으로확인되어, 용량을감량할필요가있는경우용량을줄여지속적으로복용하는것이중요하다 17. 금연의지는있으나금단증상이심하여점진적으로금연하고자하는흡연자는바레니클린투여후첫 4주이내에흡연량을 50% 감소시키고, 다음 4주이내에 50% 를감소시키며 12주에완전히금연하여총 6개월바레니클린을복용하는점진적금연법이도움이된다 18. 바레니클린을 3 6개월, 혹은 1년까지장기복용하는것에대한안전성은확립되어있다 19. 바레니클린복용법은 1 3일동안 0.5 mg을 1일 1회사용후 4 7일동안 0.5 mg을 1일 2회복용하고 8일부터투약종료일까지 1 mg 씩 1일 2회복용한다. 투여기간은기본 12주이며, 금연의유지를위해서는추가로 12주간더투여할수있다. 부작용으로는오심이가장흔하여 30 50% 로부프로피온서방정에비해높다. 오심증상이심할경우는약제감량이도움이된다. 오심은치료시작 1주정도면호전되며불면증은복용자의복용첫 4주이내에나타나고불면증상이있는경우저녁약을취침시간보다는이른저녁시간에복용할것을권고한다. 바레니클린은경중등도의만성폐쇄성폐질환환자에서지속적인금연성공률을높이는데효과적이었고, 부작용역시낮은비율로나타났다 20. 대규모무작위비교연구에의하면바레니클린은심혈관계질환을가진흡연자에서위약과비교하여 주동안지속적으로금연율이높았으며심혈관계질환을가진환자와기존의정신과적질환이있는경우에도위약에비해부작용에유의한차이가없었다 21,22. 바레니클린으로금연경험이있는환자가다시금연을위해사용할때에도처음사용하는흡연자의금연율과비슷한성적을보였다 23. 4) 금연약제병용치료금단증상이삼한경우는니코틴패치와니코틴껌이나로렌즈등을병합사용하거나경구보조제인부프로피온 (bupropion) 이나바레니클린 (varenicline) 을같이병용하면효과를볼수있다. 4. 특수한상황에서의금연 1) 여성및임산부성인여성의흡연율은 2005년 5.7%, 2014년 5.7% 로 10년간유사하며, 20대가 9.1% 로가장높은흡연율을보인다. 또한흡연하는친구가있거나, 가족이흡연하는경우는흡연율이높았다

5 임산부및수유부는약물치료보다금연상담과심리적지지요법이권고된다. 임신은금연을위한좋은동기부여가된다. 임산부에서는금연약물치료에대한연구가부족하여안정성이검증되지않아집중적인금연상담과심리적지지가우선적으로권고된다 25. 2) 청소년 12세에서 18세청소년들의흡연율은감소하고있으나국내청소년흡연율은아직높다. 흡연자중 50% 정도가청소년기에흡연을시작하였고, 청소년기에흡연을시작하면중증흡연자가될가능성이높다는연구도있다 26. 메타분석결과상담치료가간단한권고만하거나치료를하지않은군에비해금연성공률이 2배높았다 27. 청소년흡연자에게도약물치료에대한검증된연구결과가없어상담이우선적으로선택되며약물치료는권고되지않는다. References 1. Seo MK. Women's smoking behavior: Factors and policy options. Health Welfare Policy Forum 2011;172: Smith SS, Jorenby DE, Leischow SJ, Nides MA, Rennard SI, Johnston JA, et al. Targeting smokers at increased risk for relapse: treating women and those with a history of depression. Nicotine Tob Res 2003;5: Copeland AL, Martin PD, Geiselman PJ, Rash CJ, Kendzor DE. Smoking cessation for weight-concerned women: group vs. individually tailored, dietary, and weight-control follow-up sessions. Addict Behav 2006;31: Marcus BH, Albrecht AE, King TK, Parisi AF, Pinto BM, Roberts M, et al. The efficacy of exercise as an aid for smoking cessation in women: a randomized controlled trial. Arch Intern Med 1999;159: Ginzel KH, Maritz GS, Marks DF, Neuberger M, Pauly JR, Polito JR, et al. Critical review: nicotine for the fetus, the infant and the adolescent? J Health Psychol 2007;12: Bader P, McDonald P, Selby P. An algorithm for tailoring pharmacotherapy for smoking cessation: results from a Delphi panel of international experts. Tob Control 2009;18: Fiore MC. Treating tobacco use and dependence: an introduction to the US Public Health Service Clinical Practice Guideline. Respir Care 2000;45: Shiffman S, Brockwell SE, Pillitteri JL, Gitchell JG. Use of smoking-cessation treatments in the United States. Am J Prev Med 2008;34: Stead LF, Lancaster T. Behavioural interventions as adjuncts to pharmacotherapy for smoking cessation. Cochrane Database Syst Rev 2012;12:CD Marcus BH, Lewis BA, Hogan J, King TK, Albrecht AE, Bock B, et al. The efficacy of moderate-intensity exercise as an aid for smoking cessation in women: a randomized controlled trial. Nicotine Tob Res 2005;7: Williamson DF, Madans J, Anda RF, Kleinman JC, Giovino GA, Byers T. Smoking cessation and severity of weight gain in a national cohort. N Engl J Med 1991;324: Department of Family and Community Medicine, University of Toronto. Smoking cessation guidelines: how to treat your patient's tobacco addiction. Toronto, CA: A Pegasus Healthcare International Publication; Cunningham JA, Kushnir V, Selby P, Tyndale RF, Zawertailo L, Leatherdale ST. Effect of mailing nicotine patches on tobacco cessation among adult smokers: a randomized clinical trial. JAMA Intern Med 2016;176: Aubin HJ. Tolerability and safety of sustained-release bupropion in the management of smoking cessation. Drugs 2002;62 Suppl 2: Rollema H, Chambers LK, Coe JW, Glowa J, Hurst RS, Lebel LA, et al. Pharmacological profile of the alpha4beta2 nicotinic acetylcholine receptor partial agonist varenicline, an effective smoking cessation aid. Neuropharmacology 2007;52: Cahill K, Stevens S, Perera R, Lancaster T. Pharmacological interventions for smoking cessation: an overview 19

6 and network meta-analysis. Cochrane Database Syst Rev 2013;(5):CD Fouz-Rosón N, Montemayor-Rubio T, Almadana-Pacheco V, Montserrat-García S, Gómez-Bastero AP, Romero- Muñoz C, et al. Effect of 0.5 mg versus 1 mg varenicline for smoking cessation: a randomized controlled trial. Addiction 2017;112: Ebbert JO, Hughes JR, West RJ, Rennard SI, Russ C, McRae TD, et al. Effect of varenicline on smoking cessation through smoking reduction: a randomized clinical trial. JAMA 2015;313: Tonstad S, Tønnesen P, Hajek P, Williams KE, Billing CB, Reeves KR; Varenicline Phase 3 Study Group. Effect of maintenance therapy with varenicline on smoking cessation: a randomized controlled trial. JAMA 2006;296: Tashkin DP, Rennard S, Hays JT, Ma W, Lawrence D, Lee TC. Effects of varenicline on smoking cessation in patients with mild to moderate COPD: a randomized controlled trial. Chest 2011;139: Anthenelli RM, Benowitz NL, West R, St Aubin L, McRae T, Lawrence D, et al. Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial. Lancet 2016;387: Benowitz NL, Pipe A, West R, Hays JT, Tonstad S, McRae T, et al. Cardiovascular safety of varenicline, bupropion, and nicotine patch in smokers: a randomized clinical trial. JAMA Intern Med 2018;178: Gonzales D, Hajek P, Pliamm L, Nackaerts K, Tseng LJ, McRae TD, et al. Retreatment with varenicline for smoking cessation in smokers who have previously taken varenicline: a randomized, placebo-controlled trial. Clin Pharmacol Ther 2014;96: Ministry of Health and Welfare. Korea health statistics 2014: Korea National Health and Nutrition Examination Survey [Internet] [cited 2017 May 8]. Available from: Patnode CD, Henderson JT, Thompson JH, Senger CA, Fortmann SP, Whitlock EP. Behavioral counseling and pharmacotherapy interventions for tobacco cessation in adults, including pregnant women: a review of reviews for the U.S. preventive services task force. Rockville, MD: Agency for Healthcare Research and Quality (US); Cho KS. Prevalence of hardcore smoking and its associated factors in Korea. Health and Social Welfare Review 2013;33: Stanton A, Grimshaw G. Tobacco cessation interventions for young people. Cochrane Database Syst Rev 2013; (8):CD

흡연자의 3분의 2 이상은금연을원하며 50% 이상의흡연자가 1년이내에금연을시도하지만대부분금연에실패하며 6% 미만에서만 1년경과후금연상태를유지한다 4. 금연을시도하는경우절반이상이첫주이내에포기하며니코틴중독이조기금연실패의가장중요한원인이다 5. 니코틴은흡연시중독을유발하는물질로

흡연자의 3분의 2 이상은금연을원하며 50% 이상의흡연자가 1년이내에금연을시도하지만대부분금연에실패하며 6% 미만에서만 1년경과후금연상태를유지한다 4. 금연을시도하는경우절반이상이첫주이내에포기하며니코틴중독이조기금연실패의가장중요한원인이다 5. 니코틴은흡연시중독을유발하는물질로 VI 금연치료의비약물요법과약물요법 천은미 이대목동병원호흡기내과 Smoking cessation is the leading preventable cause of morbidity and mortality. All smokers must be encouraged and assisted to quit smoking by health care participants.