pissn: 2288-0402 eissn: 2288-0410 2(4):272-276, September 2014 http://dx.doi.org/10.4168/aard.2014.2.4.272 ORIGINAL ARTICLE 전형적인알레르기증상으로내원한 6 세미만소아환자에서항원감작패턴 : 단일기관연구 윤정원 1, 이상민 1, 김준환 2, 김나연 2, 백지현 2, 백혜성 3, 지혜미 2, 김형윤 4, 최선희 5, 김기은 2, 염혜영 6, 한만용 2, 김진택 7, 신윤호 2 1 명지병원소아청소년과, 2 차의과학대학교소아과학교실, 3 한림대학교강동성심병원소아청소년과, 4 분당제생병원소아청소년과, 5 경희대학교의과대학소아과학교실, 6 서울의료원소아청소년과, 7 가톨릭대학교의과대학소아과학교실 Sensitization patterns to common allergens in Korean children younger than 6 years of age presenting with typical symptoms or signs of allergic diseases: a single center study Jung Won Yoon 1, Sang Min Lee 1, Joon Hwan Kim 2, Na Yeon Kim 2, Ji Hyeon Baek 2, Hey-Sung Baek 3, Hye Mi Jee 2, Hyeung Yoon Kim 4, Sun Hee Choi 5, Ki Eun Kim 2, Hye Yung Yum 6, Man Yong Han 2, Jintack Kim 7, Youn Ho Shin 2 1 Department of Pediatrics, Myongji Hospital, Goyang; 2 Department of Pediatrics, CHA University School of Medicine, Pocheon; 3 Department of Pediatrics, Hallym University Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul; 4 Department of Pediatrics, Bundang Jaesaeng Hospital, Seongnam; 5 Department of Pediatrics, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul; 6 Department of Pediatrics, Seoul Medical Center, Seoul; 7 Department of Pediatrics, The Catholic University of Korea School of Medicine, Seoul, Korea Purpose: Population studies have reported that sensitization to inhalant allergens is rare in young children; however, most subjects in those studies had little or no symptoms or signs highly suggestive of allergic diseases. The aim of the present study was to assess the prevalence of sensitization to inhalant allergens in young children with symptoms and/or signs of allergic disease. Methods: We analyzed the results of all specific IgE tests performed at our hospital laboratory in children younger than 6 years presenting with symptoms and/or signs highly suggestive of allergic diseases between 2008 and 2013. Specific IgE tests for Dermatophagoides pteronyssinus, Dermatophagoides farinae, Alternaria alternata, German cockroach, cat dander, egg white or egg yolk, milk, peanut, and soybean were performed on 295 children; a specific IgE concentration 0.35 or 0.2 IU/mL was considered positive. We also compared allergen sensitization rates using the two cutoff values. Results: One hundred eighty-one children (61.4%) were positive to at least 1 allergen tested and 53 children (18.9%) were positive to at least 1 inhalant allergen when a specific IgE concentration 0.35 IU/mL was considered positive. The children were more likely to have asthma or allergic rhinitis when they were sensitized to any inhalant allergen, particularly. The prevalence of sensitization to inhalant allergens increased with age (P< 0.001). There was no significant difference in the prevalence of polysensitization among different age groups, but sensitization to both inhalant and food allergens significantly increased with age. Conclusion: Our results suggest that specific IgE tests to common inhalant allergens, particularly the, may be considered when performing blood screening tests for young children presenting with symptoms and/or signs of allergic diseases. ( 2014;2:272-276) Keywords: Allergens, Child, Sensitization 서론 전세계적으로알레르기질환이증가하고있다. 알레르기질환을 일으키는위험인자는다양하다. 그중흡입항원에대한감작은소 아천식, 알레르기비염발생에있어서중요한위험인자이고, 1-4) 연 Correspondence to: Youn Ho Shin Department of Pediatrics, CHA Gangnam Medical Center, CHA University School of Medicine, 566 Nonhyeon-ro, Gangnam-gu, Seoul 135-913, Korea Tel: +82-2-3468-3032, Fax: +82-2-3468-3697, E-mail: epirubicin13@gmail.com Received: January 2, 2014 Revised: April 21, 2014 Accepted: May 11, 2014 령이증가함에따라서흡입항원에대한감작률이증가한다고알려 져있다. 1,2,5,6) 이와반대로, 식품항원에대한감작률은생후첫 1 년 동안흔하지만, 연령이증가함에따라감소하는경향을보인다. 2,7,8) 일반인을대상으로한대규모집단연구에서 1 세소아의흡입항원 에대한감작률이 1.5% 3% 정도로낮다고보고하였고, 7,9) 다른연 2014 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/3.0/). 272 http://www.aard.or.kr
윤정원외 알레르기증상소아환자에서항원감작 구는 2세소아의흡입항원감작률을 5% 라고보고하였다. 4) 이런연구들을바탕으로학동전기소아의흡입항원감작률이낮다고생각되어왔으며, 많은임상의들은학동기와영유아에서흡입항원에대한검사를시행하지않는경향이있었다. 이에반해, 2009년발표된유럽코호트연구는 352명의 3개월영아를대상으로흡입항원에대한검사를시행하였을때, 최소 1개이상의흡입항원에대한감작률이 9.4% 라고보고하였다. 10) 또한최근서울지역에위치한유치원생을대상으로한우리나라연구도 3세에 Dermatophagoides farinae에대한감작률이 10.5% 이고 3 6세소아에서흡입항원에대한총감작률은 38.6% 라고보고하였다. 11) 하지만, 3세미만영유아에서흡입항원에대한특이 IgE를측정하고알레르기질환의증상, 징후와의연관성을규명한국내연구는미미하다. 특히, 지금까지발표된연구들은대부분건강한일반소아를대상으로하는대규모집단연구들이었다. 이들연구들은대규모인구집단에서알레르기항원감작의변화를확인하는데는중요한의미가있지만, 알레르기질환을시사하는증상이나징후가있는소아가병의원에내원하였을때이런연구결과들을직접적으로활용하는데는어려움이있다. 따라서이번연구의목적은알레르기증상이나징후가있는 0 5 세소아에서흡입및식품알레르기항원감작률을확인하고, 연령별분포와질환과의관계를보고자하였다. 대상및방법 1. 연구대상이번연구는알레르기증상이나징후가발생하여 2008년 1월부터 2013년 3월까지차의과학대학교강남차병원소아청소년과를방문한환자중알레르기검사를시행받은 0 5세환자 295명의의무기록을후향적으로검토하여진행하였다. 이번연구는차의과학대학교강남차병원의료윤리위원회의심사를통과하였다. 2. 연구방법알레르기증상이나징후중특정식품을섭취하였을때발진이나구토, 설사등의소화기증상이발생한경우, 또는식품이피부에접촉하였을때그부위에발진이생긴경우식품알레르기로정의하였다. 12) 알레르기비염은이전에의사에의해진단받았거나감기에걸리지않았을때에도재채기, 맑은콧물, 코막힘또는간지러움등의증상을보인경우진단하였다. 13) 천식은지난 12개월이내에반복되는천명, 기침, 숨참같이전형적인천식이의심되는증상이있는경우, 또는흡입스테로이드나베타항진제에대해효과가있는경우진단하였다. 14) 습진은반복재발하는피부병변과간지러움을동반하는경우진단하였다. 15) 두드러기는다양한크기, 개수, 분포를보이면서소양감을동반하고 24시간이내소실되는팽진이 있는경우진단하였다. 16) 총 IgE 농도와항원특이 IgE 농도는 ImmunoCAP (Phadia AB, Uppsala, Sweden) 으로측정하였으며, 항원특이 IgE는 0.35 IU/mL 이상인경우양성으로정의하였고, 기준이 0.2 IU/mL 이상인경우와각각의감작률에대해비교하였다. 17) 검사항원항목은주요알레르기항원 10종 (house dust mite [Dermatophagoides pteronyssinus, D. farinae], Alternaria alternata, German cockroach, cat dander, milk, egg [egg white or egg yolk], peanut, and soybean) 에대하여시행하였다. 식품항원중한가지이상에대해서양성인경우를식품항원양성, 흡입항원중한가지이상에대해서양성인경우를흡입항원양성, 식품과흡입항원모두에대해서양성을보인경우를 both allergens 양성, 식품과흡입항원에상관없이최소한두가지이상의항원에대해서양성을보인경우를다항원감작 (polysensitization) 으로정의하였다. 3. 통계분석모든연속변수는정규분포를따르는경우평균 ± 표준편차로표시하였으며총 IgE 농도는정규분포를하지않아로그화하여분석하였다. 각군간의유의성검정은카이제곱검정과 t-검정을이용하였으며, 연령에따른분율의비교는우도비경향분석법을이용하였다. 알레르기질환의진단위험도는로지스틱회귀분석을이용하였다. P 값은 0.05 미만인경우를통계적으로유의한것으로판단하였다. 수집된자료의통계분석은 IBM SPSS Statistics ver. 19.0 (IBM Co., Armonk, NY, USA) 를이용하였다. 결과연구대상자는모두알레르기증상이나징후가있는 6세미만의환자 295명이었고, 임상적특성은 Table 1과같다. 환자는평균연령 2.3±1.6세이고여자의비율은 41.7% 였다. ImmunoCAP 검사결과 0.35 IU/mL 이상을양성으로정의하였을때최소한한개이상의검사항원에대해양성반응을보인환자의비율은 181명 (61.4%) 이었다. 검사시행당시환자의임상적진단은식품알레르기가 123명 (41.7%) 으로가장많았으며, 다음으로습진 (114 명, 38.6%), 천식 (59 명, 20.0%), 비염 (54명, 18.3%), 두드러기 (47명, 15.9%) 가차지하였다. 이중두가지이상의진단을받은경우는 30.5% 였다. 혈청특이 IgE 검사에서흡입항원중집먼지진드기가 17.9% 로가장높은감작률을나타냈으며, 흡입항원과식품항원에대한감작률을비교하였을때식품항원에대한감작률이더높았다 (Table 2). 또한이번연구에서는항원에대한감작기준을비교하였다. 0.2 IU/ ml와 0.35 IU/mL를양성으로정의한경우흡입항원에대한감작률은각각 50% 와 18.9%, 식품항원에대한감작률은각각 80% 와 http://dx.doi.org/10.4168/aard.2014.2.4.272 273
Yoon JW, et al. Sensitization patterns in young children with typical allergic symptoms or signs 56.0% 였다. 개별항원에대한감작률은 Fig. 1 에제시하였다. 그중 곰팡이와바퀴벌레항원은 0.2 IU/mL 이상을양성으로정의한경 우각각 40% 와 43% 의높은감작률을나타내었고, 0.35 IU/mL 이 Table 1. Clinical characteristics of the study subjects (n= 295) Characteristic Value Female sex 123 (41.7) Age (yr) 2.3± 1.6 Diagnosis Eczema Allergic rhinitis Bronchial asthma Food allergy Urticaria Combined allergic diseases 114 (38.6) 54 (18.3) 59 (20.0) 123 (41.7) 47 (15.9) 90 (30.5) Positive serum specific IgE tests* 181 (61.4) Log total IgE 1.67± 0.69 Values are presented as number (%) or mean± standard deviation. *A specific IgE concentration 0.35 IU/mL was considered positive. Table 2. Prevalence of positive serum specific IgE tests in children younger than 6 years Tested allergens No.* (%) House dust mites Mold (Alternaria alternata) Cockroach Cat dander Milk Egg (egg white or egg yolk) Peanut Soybean Values are presented as number (%). *No. of serum specific IgE 0.35 IU/mL. 53/280 (18.9) 50/280 (17.9) 1/107 (0.9) 4/100 (4.0) 2/19 (10.5) 164/293 (56.0) 105/284 (37.0) 131/283 (46.3) 29/211 (13.7) 25/195 (12.8) Table 3. Distribution of children sensitized to inhalant allergens, food allergens, both allergens, or polysensitization according to age groups in the children younger than 6 years Allergen 0 < 2 yr (n= 155) 2 <4 yr (n=84) 4 <6 yr (n=56) P-value Mono Poly Total Mono Poly Total 11 (7.1) 0 (0) 11 (7.1) 40 (25.8) 54 (34.8) 94 (60.6) 15 (17.9) 2 (2.4) 17 (20.2) 20 (23.8) 28 (33.3) 48 (57.1) 23 (41.1) 2 (3.6) 25 (44.6) 10 (17.9) 12 (21.4) 22 (39.3) < 0.001 0.102 < 0.001 0.508 0.187 0.025 9 (5.8) 14 (16.7) 13 (23.2) 0.001 55 (35.5) 35 (41.2) 19 (33.9) 0.559 Log total IgE 1.55± 0.64 1.68± 0.64 2.00± 0.79 < 0.001 Values are presented as number (%) or mean± standard deviation. include (Dermatophagoides pteronyssinus and Dermatophagoides farinae), Alternaria alternata, German cockroach, and cat dander and food allergens include milk, egg (egg white or egg yolk), peanut, and soybean. 상을양성으로정의한경우 4% 와 1% 로낮은감작률을나타냈다. 이는대부분의환자가 0.2 0.35 IU/mL 사이의수치를보였기때문 에, 0.35 IU/mL 이상을양성으로정의한경우상대적으로낮은감 작률을나타냈다 (Fig. 1). 연령에따른항원의감작률을보면, 연령이증가함에따라흡입 항원에대한감작률은증가 (P<0.001), 식품항원에대한감작률은 감소 (P = 0.025), 식품, 흡입항원모두에감작된분율은증가하였다 (P = 0.001). 식품또는흡입항원종류와상관없이최소한두개이상 의항원에대해양성을보인다항원감작인경우연령에따른감작 률의차이는없었다 (P = 0.559) (Table 3, Fig. 2). 연령이증가함에따 라총 IgE 농도가증가하였고 (1.55±0.64 IU/mL vs. 1.68±0.64 IU/ ml vs. 2.00±0.79 IU/mL; P<0.001), 남자의총 IgE 농도가여자의 총 IgE 농도보다유의하게높았다 (1.79±0.74 IU/mL vs. 1.51± 0.60 IU/mL; P = 0.001). 최소한한개이상의흡입항원에감작된경우와집먼지진드기에 House dust mites Molds Cockroach Cat dander Milk Egg Peanut Soybean 0.35 IU/mL 0.2 IU/mL 0 20 40 60 80 100 Sensitization rate by two cutoff levels (%) Fig. 1. Allergen sensitization rates according to the two cutoffs. Sensitization rate (%) 70 60 50 40 30 20 10 0 0 <2 2 <4 4 <6 Age (yr) Fig. 2. Changing patterns of the percentage of children with sensitization to inhalant allergens, food allergens, both allergens, and polysensitization according to age. 274 http://dx.doi.org/10.4168/aard.2014.2.4.272
윤정원외 알레르기증상소아환자에서항원감작 Table 4. Association between allergic diseases and serum specific IgE levels higher than or equal to 0.35 IU/mL to various allergens Allergic disease Asthma (n= 59) Allergic rhinitis (n= 54) Eczema (n= 114) Tested allergens Sensitization, n (%) 29 (49.2) 13 (22.0) 16 (29.6) 16 (29.6) 25 (46.3) 20 (37.0) 9 (16.7) 15 (13.2) 14 (12.3) 72 (63.2) 48 (42.1) 36 (31.6) 감작된경우천식진단위험이증가하였다 (odd ratio [OR], 2.69; 95% confidence interval [CI], 1.39 5.21; P = 0.003 and OR, 3.00, 95% CI, 1.54 5.85; P = 0.001). 또한흡입, 식품항원모두에대해감 작되었을때천식진단의위험이높았으나 (OR, 2.62; 95% CI, 1.24 5.55; P = 0.012), 다항원감작인경우에는천식진단의위험을증가 시키지않았다. 최소한한개이상의흡입항원에감작된경우와집 먼지진드기에감작된경우알레르기비염진단위험이증가하였다 (OR, 2.15; 95% CI, 1.09 4.26; P = 0.028 and OR, 2.38; 95% CI, 1.19 4.73; P = 0.014). 식품항원에감작된경우습진진단의위험도 가증가하였다 (OR, 1.62; 95% CI, 1.00 2.62; P = 0.049) (Table 4). 고찰 OR (95% CI) 2.69 (1.39 5.21) 3.00 (1.54 5.85) 0.74 (0.42 1.32) 0.77 (0.42 1.41) 2.62 (1.24 5.55) 2.15 (1.09 4.26) 2.38 (1.19 4.73) 0.68 (0.37 1.24) 1.01 (0.55 1.85) 1.59 (0.70 3.60) 0.57 (0.30 1.09) 0.56 (0.29 1.10) 1.62 (1.00 2.62) 1.43 (0.88 2.32) 0.67 (0.31 1.41) 이번연구는알레르기증상이나징후를주소로내원한 6 세미만 소아환자에서흡입항원에대한감작률이높고, 연령이증가할수록 감작률이증가하는것을확인하였다. 또한 0 2 세매우어린연령에 서다항원감작률이높고, 흡입항원, 특히집먼지진드기에대한감 작이천식, 알레르기비염과연관성이높은것을확인하였다. P-value 0.003 0.001 0.307 0.399 0.012 0.028 0.014 0.208 0.988 0.271 0.091 0.093 0.049 0.146 0.290 include (Dermatophagoides pteronyssinus and Dermatophagoides farinae), Alternaria alternata, German cockroach, and cat dander and food allergens include milk, egg (egg white or egg yolk), peanut, and soybean. OR, odd ratios; CI, confidence interval. 3 세에서 6 세사이의일반소아를대상으로이루어진다기관연 구에서는흡입항원에대한혈청특이 IgE 검사에서높은양성률 (38.6%) 을보였고, 집먼지진드기가가장높은감작률을보였다고 보고하였다. 11) 이번연구에서는 0 5 세사이소아에서흡입항원에 대한혈청특이 IgE 검사감작률이 17.9% 였으며, 4 세이상 6 세미만 의소아에서는 45% 였다. 흡입항원에대해서양성을나타낸경우, 그원인으로집먼지진드기가 94% 이상을차지하였다. 이번연구는 알레르기증상이나징후를주소로병원에내원한환자를대상으로했다는점에서높은감작률을예측할수있었으나, 0 2세어린연령의환자 (52.5%) 가포함되었다는것을고려하였을때, 흡입항원에대한감작률이다른연구 4,7,9,11) 보다높은것을확인하였다. 국내에서시행한전국적인역학조사와다기관연구에서는, 알레르기증상이나징후를보이는환자에서가장흔하게감작된항원은집먼지진드기이며, 연령이증가함에따라집먼지진드기감작률이증가하는경향을보고하였다. 18,19) 이번연구에서도연령이증가함에따라흡입항원에대한감작이증가하였으며, 특히집먼지진드기에대한혈청특이 IgE 농도가유의하게증가하였다. 연령증가와바퀴벌레및곰팡이항원은유의한상관성을나타내지않았는데, 검사를시행한환자의수가적어서그경향을분석하기에어려움이있었다. 또한감작기준을 0.2 IU/mL으로하였을경우검사를시행한환자에서는 30% 40% 정도의비교적높은감작률을보였으나, 이들대부분이 0.2 0.35 IU/mL 사이의수치를나타냈기때문에 0.35 IU/mL 이상을양성기준으로하는경우에는감작률이감소하였다. 연령증가와바퀴벌레, 곰팡이항원사이의상관관계를분석하기위해서는많은수의환자를대상으로한전향적인연구가필요할것으로생각된다. 다른연구 6) 에서와달리성별에따른감작률은흡입항원과식품항원모두에서차이를보이지않았으며, 총 IgE의농도에서만유의한차이를보였다. 집먼지진드기는아토피발생에중요한항원으로생각되어왔고집먼지진드기에대해영유아초기에감작된경우또는감작된과거력이있는경우추후천식발생과연관이있다고보고한연구가있다. 20-22) 이번연구에서도흡입항원, 특히집먼지진드기가천식, 알레르기비염발생위험도를증가시키는것을확인할수있었다. 이번연구에서중요한결과는각연령대에서다항원감작이비슷한정도로발생하였고, 연령이증가함에따라식품, 흡입항원에모두양성인비율이증가하였고, 식품, 흡입항원에모두양성인경우는천식발생위험도를증가시켰다는것이다. 이번연구결과는천식뿐만아니라다른알레르기증상이나징후를주소로병원에내원하여알레르기검사를시행하는경우에도다양한식품, 흡입항원에대한검사를시행하는것이중요할수있음을시사한다. 천명이발생한영아를대상으로한다른연구에서는단일항원감작이발생한후다항원감작이발생한다고보고하였고, 23) 다항원감작을예방하기위해서단일항원에대한면역치료가유용할것이라고보고하였다. 24) 이번연구는알레르기증상이나징후를주소로병원에내원한소아환자들을대상으로했고, 이전연구들은천명이있는소아들을대상으로하는등대상군이다르기때문에결과에차이가있었을것으로생각된다. 이번연구는후향적으로의무기록을검토하였기때문에질환의중증도와감작률사이의연관성을확인할수없었고, 증례수가적다는제한점이있다. 또한알레르기증상이나징후를주소로병원 http://dx.doi.org/10.4168/aard.2014.2.4.272 275
Yoon JW, et al. Sensitization patterns in young children with typical allergic symptoms or signs 에내원한환자를대상으로하였기때문에정상군이없다는한계 점이있다. 이를규명하기위해서추후정상군을포함한대규모전 향적연구가필요할것으로사료된다. 결론적으로, 이번연구는알레르기증상이나징후를주소로병 원에내원한경우어린연령에서도흡입항원감작발생률이높은 것을확인하였다. 또한어린연령에서도다항원감작이발생하며, 식품, 흡입항원모두에대해감작된경우천식진단의위험이증가 하는것을확인하였다. 따라서알레르기증상이나징후를주소로 병원에내원하는환자에서는 0 5 세어린연령에서도흡입항원 ( 특 히집먼지진드기 ) 에대한특이 IgE 검사를시행하는것을고려해 야하고, 동시에다양한식품, 흡입항원에대한특이 IgE 검사도시 행해야할것으로사료된다. REFERENCES 1. Illi S, von Mutius E, Lau S, Niggemann B, Gruber C, Wahn U, et al. Perennial allergen sensitisation early in life and chronic asthma in children: a birth cohort study. Lancet 2006;368:763-70. 2. Hoffmann-Petersen B, Host A, Larsen KT, Bergstein KR, Thomsen ML, Braendholt V, et al. Prevalence of IgE sensitization in Danish children with suspected asthma. Pediatr Allergy Immunol 2013;24:727-33. 3. Porsbjerg C, von Linstow ML, Ulrik CS, Nepper-Christensen S, Backer V. Risk factors for onset of asthma: a 12-year prospective follow-up study. Chest 2006;129:309-16. 4. Arshad SH, Tariq SM, Matthews S, Hakim E. Sensitization to common allergens and its association with allergic disorders at age 4 years: a whole population birth cohort study. Pediatrics 2001;108:E33. 5. Govaere E, Van Gysel D, Massa G, Verhamme KM, Doli E, De Baets F. The influence of age and gender on sensitization to aero-allergens. Pediatr Allergy Immunol 2007;18:671-8. 6. Baatenburg de Jong A, Dikkeschei LD, Brand PL. High prevalence of sensitization to aeroallergens in children 4 yrs of age or younger with symptoms of allergic disease. Pediatr Allergy Immunol 2009;20:735-40. 7. Kulig M, Bergmann R, Klettke U, Wahn V, Tacke U, Wahn U. Natural course of sensitization to food and inhalant allergens during the first 6 years of life. J Allergy Clin Immunol 1999;103:1173-9. 8. Roberts G, Peckitt C, Northstone K, Strachan D, Lack G, Henderson J, et al. Relationship between aeroallergen and food allergen sensitization in childhood. Clin Exp Allergy 2005;35:933-40. 9. Douwes J, van Strien R, Doekes G, Smit J, Kerkhof M, Gerritsen J, et al. Does early indoor microbial exposure reduce the risk of asthma? The Prevention and Incidence of Asthma and Mite Allergy birth cohort study. J Allergy Clin Immunol 2006;117:1067-73. 10. Kjaer HF, Eller E, Andersen KE, Host A, Bindslev-Jensen C. The association between early sensitization patterns and subsequent allergic disease. The DARC birth cohort study. Pediatr Allergy Immunol 2009;20:726-34. 11. Kim EJ, Kwon JW, Lim YM, Yoon D, Seo JH, Chang WS, et al. Assessment of Total/Specific IgE Levels Against 7 Inhalant Allergens in Children Aged 3 to 6 Years in Seoul, Korea. Allergy Asthma Immunol Res 2013;5:162-9. 12. Sicherer SH, Sampson HA. Food allergy. J Allergy Clin Immunol 2010; 125(2 Suppl 2):S116-25. 13. Brozek JL, Bousquet J, Baena-Cagnani CE, Bonini S, Canonica GW, Casale TB, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 revision. J Allergy Clin Immunol 2010;126:466-76. 14. Bateman ED, Hurd SS, Barnes PJ, Bousquet J, Drazen JM, FitzGerald M, et al. Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J 2008;31:143-78. 15. Brenninkmeijer EE, Schram ME, Leeflang MM, Bos JD, Spuls PI. Diagnostic criteria for atopic dermatitis: a systematic review. Br J Dermatol 2008;158:754-65. 16. Zuberbier T, Asero R, Bindslev-Jensen C, Walter Canonica G, Church MK, Gimenez-Arnau A, et al. EAACI/GA(2)LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria. Allergy 2009;64:1417-26. 17. Depner M, Ege MJ, Genuneit J, Pekkanen J, Roponen M, Hirvonen MR, et al. Atopic sensitization in the first year of life. J Allergy Clin Immunol 2013;131:781-8. 18. Kim J, Hahm MI, Lee SY, Kim WK, Chae Y, Park YM, et al. Sensitization to aeroallergens in Korean children: a population-based study in 2010. J Korean Med Sci 2011;26:1165-72. 19. Park SH, Lim DH, Son BK, Kim JH, Song YE, Oh IB, et al. Sensitization rates of airborne pollen and mold in children. Korean J Pediatr 2012;55: 322-9. 20. Platts-Mills TA, Vervloet D, Thomas WR, Aalberse RC, Chapman MD. Indoor allergens and asthma: report of the Third International Workshop. J Allergy Clin Immunol 1997;100(6 Pt 1):S2-24. 21. Shin JW, Sue JH, Song TW, Kim KW, Kim ES, Sohn MH, et al. Atopy and house dust mite sensitization as risk factors for asthma in children. Yonsei Med J 2005;46:629-34. 22. Verhoeff AP, Van Strien RT, Van Wijnen JH, Brunekreef B. House dust mite allergen (Der p I) and respiratory symptoms in children: a case-control study. Clin Exp Allergy 1994;24:1061-9. 23. Fasce L, Tosca MA, Baroffio M, Olcese R, Ciprandi G. Atopy in wheezing infants always starts with monosensitization. Allergy Asthma Proc 2007;28: 449-53. 24. Frew AJ. 25. Immunotherapy of allergic disease. J Allergy Clin Immunol 2003;111(2 Suppl):S712-9. 276 http://dx.doi.org/10.4168/aard.2014.2.4.272