pissn: 2288-0402 eissn: 2288-0410 Allergy Asthma Respir Dis 6 Suppl 1:S9-20, September 2018 https://doi.org/10.4168/aard.2018.6.s1.s9 REVIEW 한국소아알레르기역학연구의과거와미래 이은, 1 이소연, 2 양현종, 3 홍수종 2 1 전남대학교의과대학전남대학교병원소아청소년과, 2 울산대학교의과대학서울아산병원소아청소년과, 3 순천향대학교의과대학순천향대학교서울병원소아청소년과 Epidemiology of allergic diseases in Korean children Eun Lee, 1 So-Yeon Lee, 2 Hyeon-Jong Yang, 3 Soo-Jong Hong 2 1 Department of Pediatircs, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju; 2 Department of Pediatrics, Environmental Health Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul; 3 Department of Pediatrics, Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Seoul, Korea In order to overcome a certain disease, it is necessary to confirm the prevalence, natural course and risk factors of the disease. The Korean Academy of Pediatric Allergy and Respiratory Disease has become the mainstream and has been paying a great deal of attention to the epidemiologic research of allergic diseases in Korean children since 1995. In this review, we would like to summarize the International Study of Asthma and Allergies in Childhood epidemiology study in Korea, the cohort study for allergic diseases, and the national medical big data. New epidemiological studies are needed to clarify the relationships between allergic diseases and factors such as air pollution, climate changes, microbiome, and diet, which are likely to be new risk factors for allergic diseases. Based on these epidemiological studies, we hope to find ways to overcome pediatric allergic diseases in Korea and also to share epidemiologic techniques and manpower. (Allergy Asthma Respir Dis 2018;6 Suppl 1:S9-20) Keywords: Epidemiology, Allergic diseases, Child 서론질환을극복하기위해서는질환의발생과정을이해하는것이필수적이며, 이를위해서는질환의유병률, 자연경과및위험인자를확인하는것이필요하다. 국내소아알레르기질환의유병률이높기에이를극복하기위하여대한소아알레르기호흡기학회가주축이되어소아알레르기질환역학연구에많은관심을기울여왔다. 따라서, 대한소아알레르기호흡기학회를주축으로시작되어공유한많은경험들은현재활발히진행되고있는소아알레르기질환관련다양한역학연구의밑바탕이되었다고할수있다. 물론이러한단면적인역학연구가가진한계점이있고, 이를극복또는보완하기위하여코호트연구를구성하거나국외다른연구와연대를할수도있으며국가대규모의료자료를이용할수도있다. 하지만, 이들연구또한장단점및한계가있어각연구가가진장점을최대한활용하면서단점을극복한가장효율적인연구를통하여 확보된훌륭한연구성과들이소아알레르기질환의극복을위하여한걸음더나아가는데큰역할을할것으로생각한다. 이연구에서는한국 International Study of Asthma and Allergies in Childhood (ISAAC) 역학연구, 국내소아코호트연구및국가보건의료빅데이터활용역학연구에대해정리해봄으로써, 미래우리나라소아알레르기질환극복을위해한걸음더나아갈수있는방법을모색해볼수있을것으로기대한다. 한국 ISAAC 역학연구 1. 한국 ISAAC 역학연구의역사 : 1995, 2000, 2005, 2008, 2010, 2015 년시행된역학연구알레르기질환에대한관심과중요도가증가하여체계적이며효율적인알레르기질환의관리를위하여알레르기질환유병률과위험인자에대한자료가요구되었다. 이에한국을포함한전세계가 Correspondence to: Soo-Jong Hong https://orcid.org/0000-0003-1409-2113 Department of Pediatrics, Childhood Asthma Atopy Center, Environmental Health Center, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea Tel: +82-2-3010-3379, Fax: +82-2-473-3725, E-mail: sjhong@amc.seoul.kr 이논문은대한소아알레르기호흡기학회 30주년기념논문임. Received: December 21, 2017 Revised: January 22, 2018 Accepted: January 24, 2018 S9 2018 The Korean Academy of Pediatric Allergy and Respiratory Disease The Korean Academy of Asthma, Allergy and Clinical Immunology This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/). http://www.aard.or.kr
Allergy Asthma Respir Dis Lee E, et al. Epidemiology of allergic diseases 표준화된방법을통하여첫번째알레르기질환의역학조사를시행하였는데, 한국에서첫역학조사는대한소아알레르기호흡기학회가주관이되어 한국어린이, 청소년의알레르기질환에관한전국적역학조사 가 1995년에처음시행되었다 (Table 1). 1 5년후 2000년에두번째전국규모의소아알레르기질환역학연구가진행되었다. 두 ISAAC 연구에서는서울과지방의 8개도시 ( 안산, 울산, 수원, 제주, 창원, 청주, 춘천, 전주 ) 의 68개학교에서 6 12세초등학생및 12 15세중학생을대상으로지면설문지 (written questionnaire) 및중학생에서천식과관련된비디오설문을추가로시행하였다. 초등학생은학부모가답변을작성하고, 중학생은본인이지면설문지에답변을작성하였다. 알레르기질환의유병률및위험요인을확인하고, 지역적인차이를확인한전세계적인연구에한국도동참 하였다는의의가있었다. 이를토대로이후로시행된 ISAAC 연구를통하여한국알레르기질환의역학자료를확보하게되었다. 2005년에는 1995년과 2000년에시행된 ISAAC 연구의연장선상으로, 이전연구에참여한서울지역학교에국한되어 ISAAC 연구가시행되었다. 2008년에는 아토피없는서울 프로젝트일환으로서울지역에국한되어알레르기질환의단면역학연구가시행되었다. 2010년에는전국에서모집단의대표성을확보할수있도록표본을설계하고, 초등학교 1학년과중학교 1학년을대상으로 알레르기질환에대한전국역학조사 가시행되었다. 2 2015년에는전국단위에서표본모집단을선정하였던한국아동패널연구의한부분으로, 연구원이직접각가정을방문하여 ISAAC 설문지를이용한역학조사가시행되었다. 3 Table 1. Summary of International Study of Asthma and Allergies in Childhood studies in Korea Year Age (yr) (n) No. of enrolled schools or hospitals Areas 1995 1,30 (phase I) 2000 1,30 (phase III) 2005 8 (phase III) 6 7 (n= 25,117) 12 15 (n= 14,946) 6 7 (n= 27,831) 12 15 (n= 15,214) 10 Elementary schools & 10 middle schools in Seoul 24 Elementary schools & 24 elementary schools (a total of 68 schools) 10 Elementary schools & 10 middle schools in Seoul 24 Elementary schools & 24 middle schools (a total of 68 schools) 6 7 (n= 7,131) 10 Elementary schools & 10 middle schools only in Seoul involved in ISAAC study in 1995 and 2000 2008 6 11 (n= 5,036), 12 14 (n= 4,607) 2010 2,6 6 7 (n= 4,003), 12 15 (n= 4,112) Seoul, Ansan, Ulsan, Suwon, Jeju, Changwon, Cheongju, Chuncheon, Jeonju (9 cities) Seoul, Ansan, Ulsan, Suwon, Jeju, Changwon, Cheongju, Chuncheon, Jeonju (9 cities) Seoul 5 Elementary schools, 5 middle schools Seoul 45 Elementary schools & 40 middle schools Seoul, Gyeonggi-do, Incheon, Daejeon, Chungcheongnam, Chungcheongbuk-do, Gwangju, Jeollanam-do, Jeollabuk-do, Gyeongsangnam-do, Gyeongsangbuk-do, Daegu, Busan, Ulsan (15 cities), 2015 6 7 years of age 16 Regional hospitals in Korea Seoul, Incheon, Gyeonggi-do, Daejeon, Chungcheonbuk-do, Gangwon-do, Gwangju, Jeollanam-do, Daegu, Gyeongsangbuk-do, Busan, Ulsan, Gyeonsangnam-do (15 cities) Table 2. Temporal difference in the prevalence of asthma and risk factors of asthma in elementary school children in Korean Year Area Age (yr) Wheeze, ever Wheeze, last 12 months, risk factors Prevalence (%) Asthma diagnosis, ever Asthma treatment, Risk factors 1995 1 Nationwide 6 7 17.0 9.5 7.7 3.2 Fever in infancy, antibiotics in infancy 12 13 13.9 8.5, living in Seoul 2.7 1.0 2000 1 Nationwide 6 7 13.0 4.4 9.1 3.3 12 13 12.8 9.3, obesity, ETS 5.3 1.8 2005 31 Seoul 6 12 13.0 5.5 7.6 3.0 NA 2008 31 Seoul 6 12 11.7 5.6 7.9 2.7 Young age, male, family history of allergic diseases, antibiotics in infancy, parental asthma history, moving to a new house, visible mold at home in infancy 2010 2 Nationwide 6 7 19.0 10.1 10.2 3.9 NA 12 13 15.6 8.5 7.4 1.7 2015 3 Nationwide 6 7 15.9 3.5 5.8 2.3 NA ETS, environmental tobacco smoke; NA, not applicable. S10 https://doi.org/10.4168/aard.2018.6.s1.s9
이은외 한국소아알레르기역학연구 Allergy Asthma Respir Dis 2. 알레르기질환별유병률및위험요인 1) 천식 (1) 유병률천식은기관지에알레르기염증을동반하는소아청소년기의가장흔한만성질환중하나이며, 학교활동이나일상생활에지장을주는주요질환이다. 천식의유병률은지난 30여년간지속적으로증가하였다가최근에는더증가하지는않거나약간의감소추세를보이고있다. 국내의경우, ISAAC 연구에따른국내소아천식의유병률은 지난 12개월동안의천명증상 은 1995년의 9.5% 에서 2015 년의 3.5% 로감소추세를보이고있다 (Table 2). 1,3 또한 지난 12개월동안천식치료 로확인된천식유병률은 1995년 3.2% 에서 2015년의 2.3% 로유병률이더증가하지않고있음을확인할수있었다. 2,3 (2) 위험요인알레르기질환은환경적요인과유전적소인이복합적으로관여하는다인자성 (multifactorial) 질환으로소아청소년천식의유병률증가와지역간차이의원인에대해서는아직명확히밝혀져있지않다. 부모의천식, 아토피피부염, 알레르기비염, 남아, 2세이전의세기관지염, 영아기의항생제사용, 영아기의실내곰팡이노출, 새집으로이사, 그밖에다양한유전적다형성, 간접흡연, 애완동물과비만등이천식발생에영향을주는것으로보인다. 국내 ISAAC 연구결과에서보이는국내소아청소년의천식위험인자로는 1995년에는영유아시기의발열및영유아시기의항생제복용력과관련이있는것으로확인되었고, 1 2008년에시행된 ISAAC 연구에서는천식외의다른알레르기질환의동반여부, 알레르기질환의가족력, 영아기의항생제사용, 2세이전의세기관지염병력, 영아기의가정내곰팡이존재가소아천식의발생과연관이있는것으로확인되었다. 4 소아청소년의천식위험요인에대해 서는연구마다차이를보이는데, 메타연구등을통한포괄적인연구를통해다양한결과에대해보다체계적으로접근할수있을것으로생각한다. 천식관리지침의개발과적극적인치료, 효과적인치료제의적절한사용등의료인의노력은물론, 전국적인천식줄이기운동의결과로환자와보호자의관심이늘어나면서더욱체계적인예방과관리가가능해짐에따라천식의유병률이증가추세를벗어나유지또는감소하는경향을보이는것으로추정한다. 2) 알레르기비염 (1) 유병률비염은알레르기질환중에서상대적으로많은관심을받지는못하여왔지만, 지난 20여년간국내소아알레르기비염의유병률은지속적으로증가하고있어최근들어많은관심을받게되었다 (Table 3). 1,3,4 지난 12개월동안의증상 으로확인된알레르기비염의유병률은 1995년의 31.0% 에비해, 2010년 43.6% 로증가추이를보였다. 1 이는과거에비해소아에서도적극적으로알레르기비염관련진단과치료에대한관심이증가하는것과연관이있을수있다. 알레르기비염으로인한의료 사회비용증가는국가적으로많은부담이되고있으며, 최근에는학동전기소아에서도알레르기비염증상을많이호소하고있어알레르기비염의시작이과연언제부터인지, 자연경과는어떠한지, 진단적인새로운지표는없는지, 그원인은무엇인지등에관련한적극적인연구가더필요한실정에서역학연구의중요성이부각되고있다. (2) 위험요인알레르기비염역시부모의알레르기의유전적소인, 면역학적요인, 환경적요인이복합적으로작용하여발생한다. 국내 ISAAC 연구 Table 3. Temporal difference in the prevalence of allergic rhinitis (AR) and risk factors of allergic rhinitis in elementary school children in Korean Year Area Age (yr) AR symptom*, ever AR symptoms*, Prevalence (%) AR, diagnosis, ever AR treatment, Risk factors 1995 1 Nationwide 6 7 37.7 31.0 15.5 11.8 NA 12 13 36.8 30.0 7.7 5.0 2000 1 Nationwide 6 7 35.4 29.7 20.4 15.1 NA 12 13 40.6 34.5 13.6 8.3 2005 31 Seoul 6 12 39.6 35.1 26.4 19.4 NA 2008 4 Seoul 6 12 39.4 35.8 34.1 26.1 Presence of other allergic diseases, family history of allergic diseases, antibiotics in infancy, acute bronchiolitis before 2 years of age, mold exposure at home in infancy 2010 2 Nationwide 6 7 46.5 43.6 37.0 28.6 NA 12 13 47.9 42.6 29.8 20.2 2015 3 Nationwide 6 7 49.9 46.6 45.2 31.8 NA NA, not applicable. *Sneezing, runny nose, or nasal stuffness distinct from respiratory symptoms. https://doi.org/10.4168/aard.2018.6.s1.s9 S11
Allergy Asthma Respir Dis Lee E, et al. Epidemiology of allergic diseases Table 4. Temporal difference in the prevalence of atopic dermatitis (AD) and risk factors of atopic dermatitis in elementary school children in Korean Year Area Age (yr) Itchy eczema, ever Itchy eczema, Prevalence (%) AD diagnosis, ever AD treatment, 1995 1 Nationwide 6 7 15.3 7.3 16.6 8.2 Young age, living in Seoul 12 13 7.2 3.9 7.3 4.4 Obesity Risk factors 2000 1 Nationwide 6 7 17.0 10.7 24.9 11.9 Young age, male, living in industrial area, prematurity, parental history of atopic dermatitis, parental history of allergic diseases 12 13 9.3 6.1 12.8 7.4 Obesity, living in industrial area, prematurity, parental history of atopic dermatitis, parental history of allergic diseases 2005 31 Seoul 6 12 24.3 16.0 29.2 14.5 NA 2008 7 Seoul 6 11 24.3 18.0 31.3 14.5 Family history of allergic diseases, moving to a new home, mold exposure at home in recent 12 mo 12 14 16.0 10.8 22.1 8.3 Female, family history of allergic diseases, mold exposure at home in infancy or recent 12 mo 2010 2,6 Nationwide 6 7 27.0 20.6 35.6 15.3 Atopy, family history of allergic diseases, moving to a new home, current mold exposure 12 13 19.9 13.1 24.2 8.9 Female, atopy, family history of allergic diseases, moving to a new home, current mold exposure 2015 3 Nationwide 6 7 15.8 12.7 20.0 10.8 NA NA, not applicable. 에서는부모의알레르기질환력, 알레르기비염외알레르기질환의존재, 영아기의항생제사용, 2세이전의세기관지염병력, 영아기에가정내곰팡이노출이알레르기비염의위험요인으로조사되었다. 2 이외에도남아, 부모의사회경제수준, 대기오염의증가및기후변화로인한화분알레르기의증가가유병률의증가와연관이있다. 그러나이러한위험요인은기존에사용해왔던 ISAAC 설문항에는포함되어있지않기때문에, 기후변화및화분알레르기와연관된요인과알레르기비염의상관성을확인할수있는다양한역학후속연구가필요하다. 3) 아토피피부염 (1) 유병률아토피피부염의유병률은지난 20여년간지속적으로증가하고있다 (Table 4). 1,3,5,6 지난 12개월동안증상 여부로확인한 6 7세소아의아토피피부염유병률은 1995년의 8.8% 에서 2015년 12.7% 로증가추세를보였다. 일부조절되지않는심한아토피피부염은이후발생하는알레르기비염과천식의발생이증가하는알레르기행진을보이는경우가많아, 아토피피부염의적극적인치료및관리가필요한상황이다. 향후주기적인역학연구를통해원인이무엇인지규명하여효과적인예방및관리가이루어질수있는근거가마련되어야할것이다. (2) 위험요인국내역학연구에서는부모의아토피피부염여부, 부모의알레르 기질환여부, 집안내곰팡이노출, 여아, 새집으로이사등이아토피피부염발생과연관이있는것으로조사되었다. 1,6,7 최근에는피부장벽이상이아토피피부염발생기전으로주목을받고있다. 식생활과주거문화의변화, 산모의임신중스트레스, 미세먼지등대기오염문제, 그리고간접흡연등환경요인과최근에는장내마이크로바이옴이나혈액내비타민 D 등이아토피피부염발생과연관이있다. 최근연구에서는 6개월이전의이유식시작, 이유식초기에알레르기항원성이높은식이를시작하는것이아토피피부염을포함한알레르기질환발생예방에도움이된다는연구결과들이있어, 향후역학연구에서는보다새로운사회여건에맞는다양한위험요인과의연관성을확인할수있는새로운위험인자설문항을발굴할필요가있을것으로생각하며, 이를통하여아토피피부염의복합적인발생원인을규명하는데도움이될수있을것이다. 4) 식품알레르기 (1) 유병률국내에서시행된 ISAAC 설문지에근거한역학조사자료에서, 전국초등학생의식품알레르기진단유병률은 1995년 4.6%, 2000년 5.2% 였으며, 서울지역초등학생의경우는 2005년 6.4%, 2008년 5.5%, 2012년 6.6% 로전체적으로유병률이증가하는경향을보였다 (Table 5). 1,8 보다정확한식품알레르기유병률을확인하기위해서는일반소아인구를대상으로설문지를통한조사가아닌경구유발시험등보다정확한식품알레르기진단방법을통한대규모식품알레르기유병률조사가필요하다. S12 https://doi.org/10.4168/aard.2018.6.s1.s9
이은외 한국소아알레르기역학연구 Allergy Asthma Respir Dis Table 5. Temporal difference in the prevalence of food allergy and risk factors of food allergy in elementary school children in Korean Year Area Age (yr) Food allergy symptoms, ever Symptoms in the Prevalence (%) Food allergy diagnosis, ever Food allergy treatment, 1995 1 Nationwide 6 7 10.9 6.5 4.2 2.7 NA 12 13 11.3 7.4 3.8 2.0 2000 1 Nationwide 6 7 8.9 5.7 4.7 2.6 NA 12 13 12.6 8.6 5.1 2.1 Risk factors 2005 8 Seoul 6 12 12.0 7.6 6.4 2.8 Presence of other allergic diseases, antibiotics in infancy, presence of mold at home in infancy 2008 8 Seoul 6 12 11.2 7.4 5.5 2.4 2010 32 Nationwide 6 7 19.0 10.1 10.2 3.9 NA 12 13 15.6 8.5 7.4 1.7 2015 3 Nationwide 6 7 17.12 3.2 NA NA NA NA, not applicable. Table 6. Temporal difference in the prevalence of bronchial hyperresponsiveness and risk factors of bronchial hyperresponsiveness in elementary school children in Korean Variable Criteria of PC20 (mg/ml) Prevalence (%) 2005 2006*,9 2009 2010*,9 2010*,33 2015,3 PC20 < 16 36.0 20.9 19.5 25.8 PC20 <8 21.6 12.9 11.3 17.2 PC20 <4 9.7 5.6 4.2 10.0 Characteristics of each study No. of subjects 1,208 1,208 1,151 559 Age (yr) 5 7 9 11 5 13 6 7 Region Nationwide Nationwide Seoul Nationwide Risk factor NA NA NA Combined atopic dermatitis, current dog ownership NA, not applicable; PC20, provocation concentration causing a 20% fall in forced expiratory volume in 1 second. *Methacholine provocation test. Provocholine challenge test. (2) 위험요인국내 ISAAC 연구에서는알레르기질환존재, 영아기항생제사용, 영아기가정내곰팡이노출등이식품알레르기발생과연관이있는것으로확인되었다. 8 식품알레르기발생은장내마이크로바이옴의변화, 이유식시작시기, 낮은혈중비타민 D 농도, 항생제노출, 식단의변화와연관이있는것으로보고되고있지만, 아직정확한요인이명확히밝혀져있지않아향후추적역학연구를통한원인규명이필요하다. 5) 기관지과민성 (1) 유병률기관지과민성의측정은객관적으로천식을진단하는중요한방법중하나이다. 일반소아를대상으로한기관지과민성의유병률에대한국내연구결과가거의없었으나, 최근관련된연구들이보고되고있다. 2009년과 2010년에조사한전국초등학생 5 6학년을 대상으로한메타콜린기관지유발시험에서 PC 20 (provocation concentration causing a 20% fall in forced expiratory volume in 1 second)<8 mg/ml로정의한기관지과민성은 12.9% 였고, 2010년서울지역초등학생에서는 11.3% 였다. 9 2005년과 2006년에시행한전국초등학생 1, 2학년대상에서메타콜린기관지유발시험에서는 PC 20 < 8 mg/ml인경우가 21.6% 였고 2015년전국초등학생 1학년대상의프로보콜린기관지유발시험에서 17.2% 였다 (Table 6). 3,9 기관지과민성은나이가들수록감소하고, 10 여아에서는사춘기이후로기관지과민성이증가하는경향을보여, 11 기관지과민성의민감도나자연경과는연령과성별에따라차이를보일수있어결과해석시연령및성별의고려가필요하다. (2) 위험요인기관지과민성은부모의천식병력, 본인의알레르기비염존재, 낮은연령, 낮은폐기능, 아토피가있는경우, 말초혈액내호산구수 https://doi.org/10.4168/aard.2018.6.s1.s9 S13
Allergy Asthma Respir Dis Lee E, et al. Epidemiology of allergic diseases Table 7. Temporal difference in sensitization rates on skin prick tests Sensitization rate in each year (%) 2005 2008 2010 34 2015 3 Number of allergens used in each study 18 18 18 18 Sensitization rate to at least 1 inhalant allergen, n (%) 588 (30.1) 234 (37.7) 3,753 (47.9) 290 (45.6) Most commonly sensitized aeroallergen 7 yr: Der p (23.5%), 12 yr: Der p (33.0%) Characteristics of each study 7 yr: Der p (31.4%) 6 7 yr: Der f (32.4%), 12 13 yr: Der p (42.7%) 7 yr: Der p (37.1%) Number of subjects 3,280 621 7,829 642 Age (yr) 6 12 6 12 6 7, 12 13 6 7 Region Nationwide Seoul Nationwide Nationwide Der f, Dermatophagoides farina; Der p, Dermatophagoides pteronyssinus. 증가의동반, 남아에서더흔하게동반된다. 3,9,10 어린연령및폐기능감소가동반된경우, 기관지과민성의정도가더심한것으로알려져있다. 9 근래에는미세먼지, 이산화질소, 이산화황, 오존등대기오염의정도와관련이보고되고있어향후역학연구를통하여기관지과민성의추가적인위험요인및장기적인예후에대한연구가필요할것으로생각한다. 6) 피부감작 (1) 유병률피부반응시험에서의양성률, 즉아토피는연구대상자에따라차이가있지만, 국내 ISAAC 연구방법으로 2005년에시행된 어린이 청소년의환경노출및건강실태조사 에서는 7세때한개이상의항원에감작된비율이 30.1% 에서 2015년아동패널연구에서동일연령대소아에서의 45.6% 로증가하는추이를보였다 (Table 7). 가장흔한항원은집먼지진드기였다. (2) 위험요인국내 ISAAC 연구에서의피부반응감작의위험요인에대한연구는부족한상황으로, 향후이에대한연구가필요한실정이다. 2010년에시행된유병률조사에서는남아에서, 연령이증가하면서감작률이증가하는것으로조사되었다. 11 2009년 ISAAC 연구방법으로시행된 어린이의환경노출에의한건강영향조사 에서는낮은소득수준, 간접흡연노출, 심한자동차매연에의노출이피부감작과관련이있었다. 12 3. ISAAC 연구및국가자료를이용한연구의알레르기질환의유병률차이알레르기질환의유병률은연구방법및자료에따라차이가있다. 동일시기에시행된 ISAAC 연구와국민건강보험공단자료에서아토피피부염진단코드로확인한아토피피부염유병률을비교해보면유병률에큰차이가있다. 예를들면, 2008년도서울에서시행된아토피프리 (free) 사업에서는 6 11세의 의사진단아토피피부 염 유병률은 31.3%, 2010 년 ISAAC 설문지를이용한역학연구에서는 6 7세에서 29.8% 인것에비하여 (Table 7), 국민건강보험공단자료에서는 6세때아토피피부염의유병률이 7.6% 로차이가크게있었다. 13 2008 2011 년에시행된국민건강영양조사에서는 6 11 세의경우, 아토피피부염의유병률이 15.0% 19.1% 로확인되었다. 5 조사방법에따라이러한큰차이를보이는이유로는역학조사에서사용하는설문조사내용과사용하는진단의기준, 연령, 치료가필요한중증군과치료를받지않은경증군의차이와같은대상군차이등다양한원인이있기에이를고려한해석이필요하다. 그리고아토피피부염을제외한다른알레르기질환의경우, 국가자료를이용한연구에서는특정연령별로질환유병률에대한자료가부족하여향후이에대한연구가필요하다. 4. ISAAC 연구및국가자료연구의한계및향후연구방향 ISAAC 연구는지면설문지를이용하여대규모역학연구가가능하다는장점이있지만, 원래 ISAAC 연구의목적이특정연령대소아를대상으로국가간비교를위한설문조사에서시작한것이기때문에, 목적이외에다른용도로사용시에는한계점을가지고있다. 특히지면설문지만으로특정질환의유무를확인하는것에는증상의주관적인부분으로특정질환을진단하게되거나회상치우침의한계로인해정확한유병률조사가어려운부분이있다. 반면에직접진찰을하더라도진찰당시에질환을가지고있지않은경우라면그것도제한점이될수있기에어떤방법이더정확한방법이다라고정의하기에는어려움이있지만연구목적에맞게설계되고해석할필요가있다. ISAAC 연구가전국규모의소아청소년을포함한연구라고할지라도, 국내전체소아청소년을모두포함하지못함으로써, 선택비뚤어짐이있을수있다. 또한, 일부연구에서는특정연령대만을포함하므로, 국내전체소아청소년의자료로확대하기에는제한점이있다. 이러한한계점을극복하기위한대안으로서, 국민건강영향평가자료및심평원자료를이용하기도하지만, 이러한국가자료를이용한연구에서도국내의료여건에서진단명오류, 증상이있으나병원을내원하지않은대상자의제외 S14 https://doi.org/10.4168/aard.2018.6.s1.s9
이은외 한국소아알레르기역학연구 Allergy Asthma Respir Dis 등한계가있다. ISAAC 연구결과를토대로알레르기질환의위험요인을확인함으로써효과적인알레르기질환의예방과관리에도움이될수있지만, ISAAC 연구또한설문지를이용한단면연구로서인과관계를확인하기에는한계점이분명히있다. 이는현재진행중인출생코호트연구를통해해결의실마리를찾는데도움이될것이다. 또한, 질환의유병률조사를위해서는보다정확한질환의정의, 일반화할수있는대표성을가진대상자의선정및보다향상된연구디자인적용이필요하고, 특히동일인을대상으로시간의흐름에따른추적연구를한다면매우중요한자료를확보할수있을것이다. 국내소아코호트연구 1. MOthers and Children s Environmental Health MOthers and Children s Environmental Health (MOCEH) 연구는우리나라에서처음으로시도된병원과지역사회기반출생코호트연구로서환경노출의영향을중요타겟으로기획되었으며, 2006년부터 2010년까지서울, 충청, 울산세지역에서 1,751명의산모를등록하여진행하였다 (Table 8). 14 주요가설로는대기오염, 중금속, 호르몬교란물질등이아이들의성장, 발달, 질환발생에어떤영향을주는지보고자하였다. 환경노출에대한조사로는설문지 ( 식이설문포함 ), 실내외환경측정 (PM 10, PM 2.5, NO 2, HCHO, VOCs) 을하였고, 생체지표로서소변에서 1-hydroxypyrene, 2-naphthol, hippuric acid, cotinine, 호르몬교란물질 (bisphenol A, phthalate), malondialdehyde와유전자변이로 GSTM1/T1을대상군일부에서측정하였고, 혈액에서중금속 ( 납, 수은, 카드뮴 ), 중성지방, 콜레스테롤, folate를측정하였다. 주요타겟결과로는자궁내성장, 미숙아, 저체중아와같은임신관련, 출생후키, 체중등의성장, 아이의정신발달, 알레르기질환을보고자하였다. 알레르기질환에대한조사는 ISAAC 설문지를이용하여 6 24개월, 3 5세에각각평가하였고알레르기와관련된생체지표로 IgE, 호산구, interleukin-10 측정을 3 5세에일부에서시행하였다. 알레르기질환과관련된주요연구결과로는생후 6개월에측정한실내유기화학물질의농도가높을수록 3세아토피피부염위험도가증가하고 15 제대혈카드뮴이높은경우 6개월아토피피부염발생이증가한다는 16 결과를보고하였다. 2. COhort for Childhood Origin of Asthma and allergic diseases COhort for Childhood Origin of Asthma and allergic diseases (COCOA) 연구는우리나라에서알레르기질환연구를목표로처음으로시작된병원과지역사회기반출생코호트이다. 2007년 11 월부터 2016년 12월까지서울지역의 5개대학병원과 8개의보건소 에서 3,004명의산모를등록하여향후 20년간추적할계획으로연구를진행중이다. 17 현재최장 10세아이들이추적되고있으며, 현재추적률이약 80% 정도에이르고있다. 임신중, 생후초기의실내외환경, 스트레스, 식이, 마이크로바이옴이아이들의알레르기질환발생을유발한다는가설을설정하여, 이러한요인들이어떻게알레르기질환발생에영향을주는지규명하고있으며, 특히개개인의유전적감수성에따라이러한영향이어떻게변화하는지에대해서도연구하고있다. 노출에대한조사로는설문지 (6개월, 1세이후매년 ), 실내환경조사 ( 임신중, 7 8세 ), 실외대기오염환경조사 (giographic information system 기반으로임신중부터매년 ), 산모정신건강조사 ( 엄마의산전, 산후스트레스평가 ), 아이의정신발달검사 (6개월, 1, 2, 3, 4, 6, 8, 9, 10세 ), 산모와아이의식이조사 ( 설문지 ), 마이크로바이옴 ( 분변, 피부 ), 제대혈, 태반, 산모와아이의혈액및소변검사, 폐기능과관련하여 impulse oscillometry, fractional exhaled nitric oxide, 폐기능검사, 기관지유발시험을, 알레르기검사로는 1세, 3세에 UniCAP 검사, 3세, 6세에피부반응시험을시행하고있다. 알레르기질환에대한평가는 6개월, 1세이후매년설문지와함께소아알레르기분과전문의사에의해이루어지고있다. 알레르기질환이외에도정신건강발달, 신체발달에대한평가도함께시행하여산모의스트레스가출생후아이의아토피피부염발생위험도를증가시킨다는연구결과를보고하였다. 18 3. Panel Study on Korean Children 아동패널연구 (Panel Study on Korean Children) 는영유아성장및발달에적합한육아환경조성을위하여 2008년부터시작된전국단위의병원기반출생코호트이다. 2단계층화무작위추출로선별된 30개의산부인과병원에서 2,150명의산모를모집하여진행중이다. 육아환경조성을위한추적조사를시행하고있기에, 구체적인질환관련가설이나타겟질환이없는제한점이있다. 설문조사를기반으로하고있으며설문조사자가개별인터뷰를통해조사하고있으며설문응답률이 98% 에이를정도로설문응답충실도가높으며추적관찰률또한약 80% 정도로높다. 알레르기질환과관련된조사로서 2015 년에아동패널대상군에서소아호흡기알레르기질환검사참고치조사를위해 ISAAC 설문조사를시행하였고, 폐기능검사, 기관지유발시험, 피부반응시험을병원에서시행하였으며알레르기질환에대한의사평가와진찰이함께이루어졌다. 4. Korea Children s ENvironmental Health Study plan 임신및아동기에환경및환경오염노출이아이의성장, 발달및질환발생에미치는영향을평가하고자시작된전국단위병원기반출생코호트연구이다. 2013년부터시작하여핵심코호트에포함될임신부 5,000명을함께모집중이다. 주요가설은임신-출산, https://doi.org/10.4168/aard.2018.6.s1.s9 S15
Allergy Asthma Respir Dis Lee E, et al. Epidemiology of allergic diseases Table 8. Characteristics of cohort studies in Korea children Study name Geographic area Study design Participants Enrollment period Duration of followup (yr) Objective Exposure assessment MOCEH (MOthers and Children s Environmental Health) 14,16 Seoul, Cheonan, Ulsan Birth cohort 1,751 2006 2010 5 The association between children health and environment (air pollution, heavy metals, environmental hormone, etc.) Questionnaires, heavy metal, GIS, urine biomarker, lipid profiles COCOA (COhort for Childhood Origin of Asthma and allergic diseases) 17,18 Seoul Birth cohort 3,004 2007 2016 20 The following 5 environmental variables contribute causally to the development and natural course of allergic diseases: (1) perinatal indoor factors (i.e., house-dust mite, bacterial endotoxin, tobacco smoking, and particulate matters 2.5 and 10), (2) perinatal outdoor pollutants, (3) maternal prenatal psychosocial stress and the child's neurodevelopment, (4) perinatal nutrition, and (5) perinatal microbiome. Questionnaires, SPT, IOS, FeNO, spirometry, metacholine challenge test, indoor environment measurement, GIS, microbiome, cord blood, placenta PSKC (Panel Study on Korean Nationwide Birth cohort 2,150 2008? Study on the development of child care environment suitable for infant Children) 18 growth and development Questionnaires, SPT, IOS, FeNO, spirometry, metacholine challenge test K-CENHS (Korea Children s ENvironmental Health Study plan) Nationwide Birth cohort Recruitment period 2013 2016 20 Effect of exposure to environmental and environmental pollution during pregnancy and childhood on child growth, development, and disease occurrence Indoor environment measurement, GIS, smoking, heavy metal, endocrine disrupter CHEER (Children s Health and Nationwide Cohort 2,631 2005, Environmental Research) 19-22 7 years 6 The effect of environmental factors (air pollution, heavy metals, environmental hormone, etc) on the health of children in school age among urban, industrial, country area Questionnaires, heavy metal, SPT, spirometry, metacholine challenge test, GIS KOREA (KOrean childhood cohort from early REcurrent wheezing to Asthma) 23 Seoul, Gyeonggi-do Cohort 593 2009 2014? For the standardization of examination for diagnosis and treatment of asthma in school children and phenotypes for preschool wheezing Questionnaires, SPT, IOS, FeNO, spirometry, metacholine challenge test GIS, giographic information system; ISAAC, International study of asthma and allergies in childhood; SPT, skin prick test; IOS, impulse oscillometry system; FeNO, fractional exhaled nitric oxide. Outcome assessment of allergic diseases ISAAC questionnaires Doctor diagnosis. ISAAC questionnaires ISAAC questionnaires, Doctor diagnosis ISAAC questionnaires ISAAC questionnaires Doctor diagnosis. ISAAC questionnaires S16 https://doi.org/10.4168/aard.2018.6.s1.s9
이은외 한국소아알레르기역학연구 Allergy Asthma Respir Dis 알레르기, 성장-발달및내분비, 신경인지발달, 사회성및정서발달분야에대한환경요인이미치는영향이며, 노출변수로대기오염, 실내공기오염, 내분비장애물질, 중금속, 농약, 부유세균, 산모흡연을조사한다. 조사기간은 2016년부터 2036년까지 20년간이며임신-출산기, 영유아기, 학동기이전, 학동기, 청소년기의 5단계로나누어장기계획을수립하여단계별환경유해인자와건강결과에대한분석을할예정이다. 5. Children s Health and Environmental Research 환경적인자가학동기어린이의건강에미치는영향을규명하기위한연구로서어린이의환경오염물질노출이건강에미치는영향에대한광범위한연구를목적으로 2005년부터 2010년까지 6년에걸쳐대도시, 산업단지, 농어촌을포함한전국 10개도시의 33개초등학교에서총 7,059 명을조사하였고, 그중 2,631명에대해서는 1, 2학년에모집하여 2년간격으로 2차례추적조사 (2년, 4년후 ) 를시행한소아알레르기전문가가직접참여한학동기소아코호트연구이다. 환경오염수준과노출특성, 환경관련성질환특히소아알레르기질환의유병상태를비교하는단면조사연구이지만 2년간격으로추적조사를실시하였기때문에코호트연구이기도하다. 설문조사 ( 식이설문포함 ), 실외환경조사, 중금속노출, 폐기능검사, 기관지유발시험, 피부반응시험등을시행하였고알레르기질환은 ISAAC 설문을통해평가하였다. 알레르기질환과관련하여, 뒤늦게시작되고 (late onset), 아토피성향이강하고, 낮은사회경제적상태에있는학동기아이들이잘조절되지않는지속성천식의표현형을가지는경우가많았다는결과 19 와아토피표현형이학동기천식과기관지과민성발생에예측인자로작용할수있다는결과 20 를보고한바있다. 또한도로와의거리가가까운집에거주하는경우기관지과민성증가에영향을주고, 21 세기관지염의과거력이있는아이들에서대기오염에대한노출이폐기능감소, 기관지과민성에영향을주어천식발생을증가시킬수있음을보여주었다. 22 6. KOrean childhood cohort from early REcurrent wheezing to Asthma 기존에국내에서거의연구되지못하였던, 학동전기천식진단과치료를위한검사표준화를위해조성된병원기반질환코호트로 2009년부터 2014년까지 593명의 2 4세의재발성천명환자를모집하여 6 7세까지추적관찰하였던연구이다. 학동전기재발성천명을발생시점, 증상지속여부에따라여러가지표현형으로나누고이에따른예후를조사하여한국인에적절한표현형에따른진단과치료방법을구축하고자한연구로서설문조사, 알레르기검사와함께유전자검사, 마이크로바이옴, 폐기능검사, 호기산화질소, 기관지유발시험, impulse oscillometry 등을조사하여천식표현형 과관련된조기진단및치료바이오마커를발굴하고자하였다. 최근기도내마이크로바이옴의구성및기능은소아천식의자연경과에영향을미쳐다양한소아천식표현형을보일수있다는것을확인한바있다. 23 국가보건의료빅데이터활용역학연구 1. 국내빅데이터연구배경우리나라는 information technology 강국이라는명성에걸맞게어마어마한양의다양한국가빅데이터를보유하고있다. 국민건강보험공단빅데이터, 100만코호트, 국가건강검진자료, 영유아건강검진자료, 심평원의보건의료빅데이터, 요양기관평가자료, 입원환자데이터셋, 고령환자 소아청소년환자데이터셋, 질병관리본부의바이러스 세균질병감시정보, 국민건강영양조사, 지역사회건강조사, 한국인유전체역학조사사업자료 ( 당뇨병, 고혈압, 비만, 골다공증, 고지혈증, 대사증후군코호트 ), 안성 안산코호트, 농촌 도시기반코호트, 쌍둥이코호트, 국내이주자 / 국제협력코호트, 청소년건강행태온라인조사, 한국보건사회연구원의한국의료패널, 영아모성사망조사자료, 전국출산력및가족보건복지실태조사, 국가암정보센터의중앙암등록자료, 통계청의사망원인데이터등수없이많은의료 보건빅데이터를모두공개하고있으며, 여기에환경부의대기오염정보, 기상청동네예보와꽃가루예보등국내에서수집되는모든데이터가공개되고있다. 이들각각의보건의료빅데이터는구축목적에따라중요한데이터를보유하고있으나, 개인정보보호법으로인한데이터간의연계제한으로인해연구수행에큰제약이되고있다. 최근건강증진, 질병예방, 보건의료가치향상, 미래보건의료설계를목표로보건복지부, 행정자치부, 미래창조과학부, 산업통산자원부, 국민건강보험공단, 건강보험심사평가원, 국립암센터, 국립보건연구원, 한국보건의료연구원, 사회보장정보원, 한국보건산업진흥원등의공공기간을아우르는보건의료빅데이터추진단이구성되어, 국민건강증진을위한빅데이터연계연구가활성화될것으로기대된다. 국민보험공단의페디그리코호트 ( 모자연계코호트 ) 를통한산모의임신중질환과복약데이터, 영유아검진코호트를통한영유아기발달평가및질환발생, 국민건강영양조사의폐기능검사, 진단검사결과를연계할수있다면, 세계적으로가치있는후향적코호트구축이가능해질것이다. 2. 국가자료소개및연구현황공단과심평원빅데이터활용연구는주로천식에국한되어있으며, 소아영역의연구는주로국민건강영양조사데이터활용연구가주를이루고있다. https://doi.org/10.4168/aard.2018.6.s1.s9 S17
Allergy Asthma Respir Dis Lee E, et al. Epidemiology of allergic diseases Table 9. Advantage, disadvantage, and data sources of Korean healthcare big data Data sources Studies (No. of publication) Advantages Disadvantages Health Insurance Review and Assessment Service National Health Information Database of National Health Insurance Service National Health and Nutrition Examination Survey Korea Youth Risk Behavior Web-based Survey Asthma (9) Nationwide cohort from 2007 (98% of Korean population) Including information of inpatients, outpatients, and pharmacy Healthcare utilization, procedures, diagnoses, treatment, and payments Cost-effectiveness, and cost-benefit analysis; possible High external validity Asthma (26 articles), allergic rhinitis (3), atopic dermatitis (2), aller- Korean population) Nationwide cohort from 2002 (98% of gic diseases (2) Including information of inpatients, outpatients, and pharmacy Healthcare utilization, procedures, diagnoses, treatment, and payments Information of income level and residence Cost-effectiveness, and cost-benefit analysis; possible High external validity Asthma (14), allergic rhinitis (9), atopic dermatitis (23), allergic diseases (4), allergic sensitization (3), anaphylaxis (1) Cross-sectional design Questionnaire by interviewer Urinary cotinine levels Some of blood test, and lung function test Cross-sectional design Online survey No information of off-label or over-the-counter drugs and procedures Interference by policy and reimbursement No information of severity, laboratories, and image Shared identification number in neonates before confirmation of Resident Registration Number No linkage with family, income level, and residence Cost-utility analysis (Quality adjusted life years); impossible Low internal validity, discrepancy with real-practice No information of off-label or over-the-counter drugs and procedures Interference by policy and reimbursement Few information of severity, laboratories, and image Duplicated records in neonates before confirmation of Resident Registration Number Shared identification number in neonates before confirmation of Resident Registration Number No linkage with family Cost-utility analysis (Quality adjusted life years); impossible Low internal validity, discrepancy with real-practice False report (i.e., smoking) Cannot investigate causal pathway Cannot investigate cost-analysis Cannot investigate causal pathway Cannot investigate cost-analysis 1) 심사평가원, 국민보험공단보건의료빅데이터인구집단에서의특정약물부작용, 특정질환이나진료행태의추세분석, 국가정책의적정성또는효과판정수행에가장효과적인데이터이며, 무작위임상시험또는코호트연구수행이불가능하거나, 어려운경우인과관계규명의차선책으로선택될수있다. 24 심평원과공단데이터는기본적으로같은데이터이나 2007년도부터구축된심평원자료가거주지, 소득수준구분이없는것에반해공단데이터는 2002년부터구축되었고, 거주지와소득수준데이터를포함하고있는차이점이있다 (Table 9). (1) 장점유럽의빅데이터연구의경우입원, 외래, 약국데이터간의연계가불가능하여연구수행이제한적이거나, 25,26 대만과같이인구전수가아닌표본데이터만공개하는경우에비해 27 국내빅데이터는국내인구전수대상으로입원, 외래, 투약, 처치를모두포함하는국가기반후향적코호트구축이가능하다. 이를통해인과관계분석뿐만아니라비용-효과분석이가능한장점이있다. (2) 단점역학연구를수행함에있어진단검사, 영상의학검사결과의부재, 특정암을제외한질환중증도자료부재, 실제임상과의불일치등 의단점이대두되고있다. 특히, 정책또는보험급여심사기준의변화에따른간섭이크게작용하여내적타당도의신뢰도가문제가된다. 28 또한특정질환에서의 OTC 약물 (over-the-counter), 성형수술또는시술과비급여약물정보부재또한중요한제한점이다. 2) 국민건강영양조사, 청소년건강행태온라인조사국민건강영양조사는 1998년부터시작되어현재제7기 (2016 2018) 조사가진행중이다. 제1기인 1998년에는 200조사구, 12,000 가구를대상으로조사를수행하였고, 제7기인 2016 2018년에는연간 192 조사구에서총 4,416가구의구성원을대상으로조사가진행되고있다. 지금까지살아오면서천식, 알레르기비염, 아토피피부염을의사로부터진단을받은적이있습니까?, 최근 1년동안천식의증상을관리하고치료하기위해서약을복용하거나흡입했습니까? 라는설문항목에대한보호자답변을통한알레르기질환을정의하고있다. (1) 장점국가수준의국민건강영양의단면조사연구를위한사업으로넓은범위의건강과영양측정을위해조사원에의한설문조사, 신체계측, 혈액및소변검사, 폐기능검사등폭넓은데이터를포함하고있다. 3개년도당약 1만가구를조사하면서전국을대표하는확 S18 https://doi.org/10.4168/aard.2018.6.s1.s9
이은외 한국소아알레르기역학연구 Allergy Asthma Respir Dis 률표본이될수있도록순환표본조사방식을도입하였다. (2) 단점설문기반조사의기본적인한계가발생하게되며그결과알레르기질환의과소추정문제가발생하게된다. 또한 지금까지살아오면서천식, 아토피피부염, 알레르기비염을의사로부터진단을받은적이있습니까? 설문진단항목한가지만사용하고있어알레르기질환에따라서는각유병률의과소또는과다추정문제가발생할수있으며, 조사원에의한대면설문으로인해설문의정확도가높아지는반면, 흡연과같이예민한항목의거짓보고가문제가된다. 29 보건의료빅데이터와달리치료약제와치료에대한반응항목이없고, 경제성분석이불가능한단점이있으며, 전형적인단면- 조사연구로인과관계분석이나비용-효과분석이불가능하다. 3. 국가기반빅데이터의장점과제한점과거코호트또는병원의무기록과의자유로운연계로양질의역학연구수행이가능했으나, 개인정보보호법시행이후실제임상데이터나코호트데이터와의연계가어렵고그로인한정보의부정확성이문제가되고있다. 특히, 공단또는심평원데이터의경우의무기록과검사결과의부재로인해과다추정또는과소추정의오류가발생할가능성이높다. 질병관리본부에서수행중인국민건강영양조사나청소년건강행태온라인조사의경우표본집단을대상으로하는전형적인단면조사연구로설문조사와일부검사결과로이루어져있으나, 노출과질병발생간의전후관계를특정화할수없는단점이있으며, 대면조사형식으로이루어져임산부또는청소년흡연과같은항목의설문조사결과의거짓보고로인한신뢰도저하의문제가있다. 4. 향후전망보건의료빅데이터추진단에서추진중인다양한빅데이터의연계와활용, 정보보호기술개발등을통해보다정확한빅데이터구축이가능할것으로생각된다. 심평원의의약품안전사용서비스 (drug utilization review) 와환경부의실시간대기오염데이터간의연계논의가현재활발히진행중이며, 소아빅데이터연구자들의염원이었던가계코호트 (Pedigree cohort) 가 2018년도공개될예정이어서보다정확하고신뢰할수있는빅데이터가구축될것으로희망한다. 결론초기 ISAAC 연구는전세계적인소아알레르기질환유병률의국가간비교및위험인자확인에주된목적이있었다. 그러나국내에서단면 ISAAC 연구를연속적으로시행할수있어서국내소아 알레르기질환의유병률과그변화를확인할수있었던것과이러 한연구과정을통해많은알레르기의사들이역학연구경험을쌓 게된것은매우큰성과라할수있다. 그러나최근연구에서중요 가설로대두되고있는위생가설, 대기오염, 실내공기오염, 기후변 화, 마이크로바이옴, 식이등새로운위험요인들을발굴하기위한 새로운형태의역학조사나설문개발, 실측조사등이필요할것으 로생각한다. 또한, 이미국내에존재하는다양한형태의알레르기 질환관련국가자료및기존의 ISAAC 역학연구의장점과연구성 과를반영하여바이어스를최소화함으로써보다정확한소아알레 르기질환유병률변화와원인규명이가능할것이다. 임신, 출산으로부터시작되는출생코호트는질병과노출에대 한반복측정이소아기부터청소년기를거쳐성인기까지연결가능 한연구이다. 따라서어린이의성장, 발달, 질환에대한환경노출에 대한효과를검증할수있는이상적인형태의연구이며같은노출 이라도노출되는시기나반복성에따라영향이달라질수있다. 궁 극적으로코호트연구를시작하고잘유지한다는것은매우어렵 고힘들기는하지만국내많은연구자들이같이참여하여경험을 공유함으로써미래의인력을양성할수있고, 나아가출생또는소 아기추적코호트를통해알레르기질환의발생원인규명을통하 여예방과관리, 치료타겟의발굴등이가능할것이며, 나아가우리 나라어린이의성장과발달에영향을미치는인자들을규명할수 있을것으로기대한다. 이러한기존의역학연구경험을바탕으로, 앞으로다양한목표 기반의단면조사역학연구, 코호트연구, 국가기반보건의료빅데 이터활용연구등이상호보완적으로활발히진행되어알레르기 질환에대한개인또는국가수준에서저감시키는방법이개발되고 발전되기를희망한다. REFERENCES 1. Hong SJ, Ahn KM, Lee SY, Kim KE. The prevalences of asthma and allergic diseases in Korean children. Korean J Pediatr 2008;51:343-50. 2. Lee Y, Choi J, Park MR, Kim J, Kim WK, Park YM, et al. Analysis of regional prevalence of allergic diseases in Korean school children. Allergy Asthma Respir Dis 2015;3:62-9. 3. Korea Centers for Disease Control and Prevention. Investigation of the reference ranges of respiratory and allergic diseases test based on disease diagnosis in nationwide randomized general pediatric population. Cheongju (Korea): Korea Centers for Disease Control and Prevention, 2015. 4. Kim WK, Kwon JW, Seo JH, Kim HY, Yu J, Kim BJ, et al. Interaction between IL13 genotype and environmental factors in the risk for allergic rhinitis in Korean children. J Allergy Clin Immunol 2012;130:421-6. 5. Lee JH, Han KD, Kim KM, Park YG, Lee JY, Park YM. Prevalence of atopic dermatitis in Korean children based on data from the 2008-2011 Korean National Health and Nutrition Examination Survey. Allergy Asthma Immunol Res 2016;8:79-83. 6. Park YM, Lee SY, Kim WK, Han MY, Kim J, Chae Y, et al. Risk factors of atopic dermatitis in Korean schoolchildren: 2010 international study of https://doi.org/10.4168/aard.2018.6.s1.s9 S19
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