pissn: 2288-0402 eissn: 2288-0410 1(1):41-49, March 2013 http://dx.doi.org/10.4168/aard.2013.1.1.41 ORIGINAL ARTICLE 인천과아산지역소아청소년의흡입알레르겐감작률및다항원감작과알레르기질환발병과의관계 김형영 1, 서주희 2, 정영호 3,4, 이은 3,4, 양송이 3,4, 하미나 5, 권호장 5, 임종한 6, 김환철 6, 이기재 7, 박인호 8, 임영욱 9, 이종현 10, 김예니 11, 최연희 12, 유지숙 13, 김정선 14, 유승도 15, 이보은 15, 홍수종 3,4 1 고신대학교의과대학소아청소년과학교실, 2 원자력병원소아청소년과, 울산대학교의과대학서울아산병원 3 소아청소년과, 4 소아천식아토피센터, 5 단국대학교의과대학예방의학교실, 6 인하대학교병원직업환경의학과, 7 한국방송통신대학교자연과학대학정보통계학과, 8 부경대학교자연과학대학통계학과, 9 연세대학교환경공해연구소, 10 ( 주 ) 네오엔비즈환경안전보호연구소, 11 국립서울병원소아청소년진료소청소년정신과, 12 경북대학교치의학전문대학원예방치과학교실, 13 단국대학교의과대학소아청소년과학교실, 14 국립암센터암역학예방연구부, 15 국립환경과학원환경보건연구과 Sensitization rates to inhalant allergens in children and adolescents of Incheon and Asan area and the relationship between polysensitization and prevalence of allergic diseases Hyung Young Kim 1, Ju-Hee Seo 2, Young-Ho Jung 3,4, Eun Lee 3,4, Song I Yang 3,4, Mina Ha 5, Ho-Jang Kwon 5, Jong-Han Lim 6, Hwan-Chul Kim 6, Kee Jae Lee 7, Inho Park 8, Young-Wook Lim 9, Jong-Hyun Lee 10, Yeni Kim 11, Youn-Hee Choi 12, Jeesuk Yu 13, Jeongseon Kim 14, Seung-Do Yu 15, Bo-Eun Lee 15, Soo-Jong Hong 3,4 1 Department of Pediatrics, Kosin University College of Medicine, Busan; 2 Department of Pediatrics, Korea Cancer Center Hospital, Seoul; 3 Department of Pediatrics, 4 Childhood Asthma Atopy Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul; 5 Department of Preventive Medicine, Dankook University College of Medicine, Cheonan; 6 Department of Occupational and Environmental Medicine, Inha University Hospital, Incheon; 7 Department of Information Statistics, Korean National Open University, College of Natural Science, Seoul; 8 Department of Statistics, Bukyong National University, College of Natural Science, Busan; 9 Institute for Environmental Research, Yonsei University, Seoul; 10 Institute of Environmental Safety and Protection, Neo Environmental Business Co., Bucheon; 11 Department of Adolescent Psychiatry, National Center for Child and Adolescent Psychiatry, Seoul National Hospital, Seoul; 12 Department of Preventive Dentistry, Kyungpook National University, School of Dentistry, Daegu; 13 Department of Pediatrics, Dankook University College of Medicine, Cheonan; 14 Cancer Epidemiology Branch, National Cancer Center, Goyang; 15 Department of Environmental Health Research, National Institute of Environmental Research, Incheon, Korea Purpose: Sensitization to allergens is considered as major mechanism of allergy and related to the development of allergic diseases. The objective of this study was to evaluate overall sensitization rates of inhalant allergens and the relationship between polysensitization and prevalence of allergic diseases in children and adolescents. Methods: A cross-sectional pilot study of 122 elementary school students, 114 middle school students, and 115 high school students from Incheon and Asan was conducted by using the International Study of Asthma and Allergies in Childhood (ISSAC) questionnaire. The skin prick tests were performed with 14 common inhalant allergens on 339 students. Results: The inhalant allergen that has a significantly different sensitization rate according to age was Dermatophagoides farinae. And the inhalant allergen that has significantly different sensitization rate according to region was Japanese hop. In addition, girls have higher sensitization rate to any mold allergens than boys. In case of having sensitization more than two allergens, the risks of diagnosis of asthma and allergic rhinitis on questionnaire were increased. Asthma is related to sensitization of dog or cat and allergic rhinitis is related to sensitization of house dust mites. However, atopic dermatitis is not related to sensitization of any inhalant allergens. Conclusion: The sensitization rates of inhalant allergens may differ among age, gender, and region in children and adolescents of Incheon and Asan area. The polysensitized children and adolescents with inhalant allergens showed higher prevalences of allergic diseases such as asthma and allergic rhinitis on questionnaire than monosensitized group. ( 1(1):41-49, 2013) Keywords: Inhalant allergens, Skin prick test, Sensitization, Polysensitization Correspondence to: Soo-Jong Hong Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea Tel: +82-2-3010-3379, Fax: +82-2-473-3725, E-mail: sjhong@amc.seoul.kr This study was financially supported by the National Institute of Environmental Research. Received: January 9, 2013 Revised: March 15, 2013 Accepted: March 22, 2013 41 2013 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/). http://www.aard.or.kr
Kim HY, et al. Sensitization rates to inhalant allergens and effect of polysensitization 서론알레르기질환은최근수십년간국내는물론전세계적으로유병률이증가하고있으며소아질환에서도높은유병률을보이고있다. 1-4) 이러한알레르기질환을진단하는데있어알레르겐에대한특이 immunoglobulin E (IgE) 항체의존재를규명하기위해서시행하는피부단자시험 (skin prick test) 은안전하고, 경제적이며, 수행하기쉽고높은재현성을가진진단법으로알려져있다. 5) 알레르겐에대한감작이알레르기질환의발병과관련이있으며, 이와같은사실은알레르기질환의유병률증가와도관련이있을것으로여겨진다. 6,7) 국내에서도알레르겐감작과관련된여러연구가있었으나대부분알레르기질환진단을받은경우이거나알레르기관련증상들로병원에내원한환자들을대상으로한연구가주를이루었다. 8-11) 최근에와서국내의일반인구, 특히소아를대상으로하여알레르겐감작과관련한연구가활발히이루어지고있다. 12-16) 알레르겐에감작되는경우단일항원감작 (monosensitization) 과다항원감작 (polysensitization) 으로구분될수있는데, 17,18) 국내에서도알레르기관련증상을보이거나천식으로진단된소아들을대상으로단일항원감작군과다항원감작군사이의차이점을비교한연구가있었다. 19,20) 하지만, 국내에서소아청소년시기의일반인구를대상으로단일항원감작군과다항원감작군간의알레르기질환발병률의차이및알레르기지표차이를비교한연구는없었다. 본연구는인천과아산지역의초등학교, 중학교및고등학교학생들을대상으로흡입알레르겐감작률과분포를조사하고, 다항원감작과알레르기질환발병과의관계및비감작군, 단일항원감작군, 그리고다항원감작군간의총 IgE와폐기능차이여부를조사해보고자하였다. 대상및방법 1. 대상본연구는향후 어린이청소년환경노출과건강실태조사 를위한예비연구로서도시와농촌에해당하는곳으로임의적인방법을통해인천과아산을조사지역으로선정하였다. 각지역별로초등학교, 중학교및고등학교 1개교씩포함하였고각학교별로한학년당한학급을임의로선정하여해당학급의학생을표본조사하였다. 그리하여초등학교 1학년부터고등학교 3학년에이르기까지총 351명을대상으로 2011 년 12월부터 2012년 5월까지조사를진행하였다. 이들중최근 1주일이내에감기약이나항히스타민제를복용한경우혹은불특정한이유로피부단자시험에서히스타민투여에팽진이생기지않은 12명은피부단자시험과관련한연구결과에서제외되었다. 2. 설문조사알레르기질환과관련된설문조사에서한국형 International Study of Asthma and Allergies in Childhood (ISAAC) 설문지를이용하여알레르기질환의유병률을조사하였다. 각질환별로다음과같은 5 가지기준으로유병률을평가하였는데, 1) 평생증상유무, 2) 지난 12개월간증상유무, 3) 지금까지알레르기질환진단유무, 4) 평생치료유무, 그리고 5) 지난 12개월간치료유무가평가기준이었다. 그가운데, 설문조사에서알레르기질환의진단유무는 지금까지의사로부터천식 ( 또는알레르기비염또는아토피피부염 ) 이라고진단받은적이있습니까? 라는각각의질문으로평가하였다. 3. 피부단자시험과혈청총 IgE 농도피부단자시험은대상자의팔의전박부에검사를요하는알레르기항원용액과양성대조액 ( 히스타민 ), 음성대조액 ( 생리식염수 ) 을한방울씩떨어뜨린후가는주사바늘로점적부위를살짝찔러검사액이표피에도달하도록하고 15분뒤팽진과발적을측정하여판독하였다. 양성반응의판정기준은항원에대한팽진의평균직경이 3 mm 이상이고동시에양성대조액과비교하여같거나큰경우로정의하였다. 사용하는원인항원 (Allergopharma, Reinbek, Germany) 으로는국내에서흔한흡입알레르겐으로다음과같이구성되었다. 알레르기항원은 5개의그룹으로분류하였는데, 1그룹은집먼지진드기 (Dermatophagoides pteronyssinus, Dermatophagoides farinae) 2종류, 2그룹은동물털 (cat hair, dog hair) 2종류, 3 그룹은화분 ( 잔디꽃가루, alder, birch, oak, Japanese hop, ragweed, mugwort) 7종류, 4그룹은곰팡이항원 (Alternaria, Aspergillus) 2종류, 5그룹은바퀴로하였고, 총 14종을대상으로하였다. 한그룹안에서여러개의알레르겐에대한감작은단일항원감작으로, 두가지이상그룹에서각각한가지이상감작된경우는다항원감작으로정의하였고, 17-20) 흡입알레르기항원가운데 1종이상감작된경우를아토피로정의하였다. 혈청총 IgE 농도는 ImmunoCAP 검사 (Phadia, Uppsala, Sweden) 로측정하였다. 4. 폐기능검사폐기능검사는미국호흡기학회 (American Thoracic Society) 에서권유하는기준에따라시행하였다. 운동전안정상태에서 portable micro-spirometer (microspiro HI-298, Chest Co., Tokyo, Japan) 를이용하여노력성폐활량 (forced vital capacity, FVC), 1초간노력성호기량 (forced expiratory volume in one second, FEV 1), 노력성호기중간유량 (mean forced expiratory flow during the middle half of FVC, FEF 25-75%) 등을측정하였다. FEV 1 은성별및연령에기준한예측치 (%) 로표시하였다. 42 http://dx.doi.org/10.4168/aard.2013.1.1.41
김형영외 흡입항원감작률과다항원감작의영향 5. 통계방법 수집된자료의통계분석은 IBM SPSS ver. 18.0 (IBM Co., Armonk, NY, USA) 을이용하였으며각항원별로비교그룹 ( 연령별, 지역별, 성별 ) 간의비교는카이제곱검정을이용하였다. FEV 1 은성 별과키를토대로한정상예측치에대한비율로표시하여통계에 적용하였고, 총 IgE 는로그값을구하여분석하였다. FEV 1 과총 IgE 에대하여세군간의비교는 analysis of variance test 를이용하였 고, 이중각군사이의차이가의미있는지확인하기위한다중비 Table 1. Subjects characteristics Characteristic Value No. of respondents Age (yr) 13.05± 3.28 351 Elementary school students 9.22± 1.71 122 Middle school students 13.51± 0.81 114 High school students 16.65± 0.66 115 Sex (M/F) Elementary school students 61/61 122 Middle school students 52/62 114 High school students 86/29 115 Body mass index (kg/m 2 ) 19.93± 3.05 343 Elementary school students 17.78± 3.39 121 Middle school students 20.16± 2.86 113 High school students 22.52± 3.27 109 Survey area and school grade 351 Asan/elementary 59 (16.8) Asan/middle 55 (15.7) Asan/high 58 (16.5) Incheon/elementary 63 (17.9) Incheon/middle 59 (16.8) Incheon/high 57 (16.2) Parental history of allergic diseases (asthma or AR or AD) 150 (42.7) 351 Parental history of asthma 16 (4.6) 351 Parental history of AR 134 (38.2) 351 Parental history of AD 27 (7.7) 351 Educational degree of parents ( university graduate) 185 (53.8) 344 Economic status (monthly income) 338 Low ( 2,999 thousand won) 87 (25.7) Middle (3,000 4,999 thousand won) 153 (45.3) High ( 5,000 thousand won) 98 (29.0) Environmental tobacco smoking 113 (32.6) 347 No of allergen sensitization 339 Nonsensitization 172 (50.7) Monosensitization 128 (37.8) Polysensitization* 39 (11.5) Values are presented as mean± standard deviation or number (%). AR, allergic rhinitis; AD, atopic dermatitis. *More than two sensitizations on skin prick test. 교방법으로 Bonferroni 보정을이용하였다. 알레르기질환진단위 험도는로지스틱회귀분석을이용하였으며, P 값이 0.05 미만인경 우를통계적으로의미있는것으로판정하였다. 1. 대상군의인구학적특성 결과 이연구에등록된대상자는총 351 명으로, 인천에서 179 명, 아산 에서 172 명이모집되었다. 초등학생 (7 12 세 ) 122 명, 중학생 (13 15 세 ) 114 명, 고등학생 (16 18 세 ) 115 명이었고각학년별로비슷한비 율의명수로구성되었으며, 남자가 56.7% 였다. 알레르겐감작에따 른분류에서비감작 172 명 (50.7%), 단일항원감작 128 명 (37.8%), 다 항원감작 39 명 (11.5%) 이었다 (Table 1). 2. 피부단자시험양성률 초등학생및중학생, 그리고고등학생을비교했을때흡입알레 르겐감작률의차이를보이는항원은북아메리카집먼지진드기 (D. farinae) 였다 (Table 2). 지역별로차이를보이는항원은환삼덩굴 Table 2. Sensitization rates to common inhalant allergens according to age Variable 7 12 yr (n= 122) 13 15 yr (n= 114) 16 18 yr (n= 115) Total (n= 351) P-value Any allergens 52 (44.1) 56 (50.0) 59 (54.1) 167 (49.3) 0.129 Dermatophagoides pteronyssinus 43 (36.4 46 (41.1) 45 (41.3) 134 (39.5) 0.451 Dermatophagoides farinae 42 (35.6) 49 (43.8) 54 (49.5) 145 (42.8) 0.034 Cockroach 0 (0) 0 (0) 0 (0) 0 (0) NA Grasses* 2 (1.7) 0 (0) 3 (2.8) 5 (1.5) 0.597 Alder* 0 (0) 0 (0) 1 (0.9) 1 (0.3) 0.322 Birch* 1 (0.8) 2 (1.8) 4 (3.7) 7 (2.1) 0.167 Oak* 0 (0) 0 (0) 1 (0.9) 1 (0.3) 0.322 Japanese hop 8 (6.8) 6 (5.4) 6 (5.5) 20 (5.9) 0.679 Mugwort* 4 (3.4) 2 (1.8) 4 (3.7) 10 (2.9) 1.000 Ragweed* 0 (0) 0 (0) 2 (1.8) 2 (0.6) 0.103 Dog* 3 (2.5) 1 (0.9) 2 (1.8) 6 (1.8) 0.806 Cat* 8 (6.8) 3 (2.7) 3 (2.8) 14 (4.1) 0.136 Alternaria* 2 (1.7) 2 (1.8) 4 (3.7) 8 (2.4) 0.390 Aspergillu* 1 (0.8) 1 (0.9) 1 (0.9) 3 (0.9) 1.000 Dog or cat* 9 (7.6) 4 (3.6) 5 (4.6) 18 (5.3) 0.307 At least 1 indoor allergen 48 (40.7) 52 (46.4) 54 (49.5) 154 (45.4) 0.179 At least 1 pollen allergen 10 (8.5) 9 (7.9) 15 (13.8) 34 (10.0) 0.193 At least 1 mold allergen*, 2 (1.7) 3 (2.7) 4 (3.7) 9 (2.7) 0.416 Polysensitization II 12 (10.2) 10 (8.9) 17 (15.6) 39 (11.5) 0.091 Values are presented as number (%). NA, not available. *Fisher s exact test. Indoor allergens include D. pteronyssinus, D. farinae, cockroach, dog, and cat. Pollen allergens include grass, alder, birch, oak, Japanese hop, mugwort, and ragweed. Mold allergens include Alternaria and Aspergillus. II More than two sensitizations on skin prick test. http://dx.doi.org/10.4168/aard.2013.1.1.41 43
Kim HY, et al. Sensitization rates to inhalant allergens and effect of polysensitization Table 3. Sensitization rates to common inhalant allergens according to region Variable Asan (n= 172) Incheon (n= 179) P-value Any allergens 83 (48.3) 84 (46.9) 0.959 Dermatophagoides pteronyssinus 63 (37.5) 71 (41.5) 0.449 Dermatophagoides farinae 67 (39.9) 78 (45.6) 0.286 Cockroach 0 (0) 0 (0) NA Grasses* 4 (2.4) 1 (0.6) 0.212 Alder* 0 (0) 1 (0.6) 1.000 Birch* 6 (3.6) 1 (0.6) 0.066 Oak* 0 (0) 1 (0.6) 1.000 Japanese hop* 16 (9.5) 4 (2.3) 0.005 Mugwort* 6 (3.6) 4 (2.3) 0.540 Ragweed* 1 (0.6) 1 (0.6) 1.000 Dog* 2 (1.2) 4 (2.3) 0.685 Cat* 5 (3.0) 9 (5.3) 0.414 Alternaria* 5 (3.0) 3 (1.8) 0.499 Aspergillus* 2 (1.2) 1 (0.6) 0.621 Dog or cat 6 (3.6) 12 (7.0) 0.157 At least 1 indoor allergen 73 (43.5) 81 (47.4) 0.469 At least 1 pollen allergen 24 (14.3) 10 (5.8) 0.010 At least 1 mold allergen*, 6 (3.6) 3 (1.8) 0.334 Polysensitization II 21 (12.5) 18 (10.5) 0.762 Values are presented as number (%). NA, not available. *Fisher s exact test. Indoor allergens include D. pteronyssinus, D. farinae, cockroach, dog, and cat. Pollen allergens include grass, alder, birch, oak, Japanese hop, mugwort, and ragweed. Mold allergens include Alternaria and Aspergillus. II More than two sensitizations on skin prick test. Table 4. Sensitization rates to common inhalant allergens according to gender Variable Male (n= 199) Female (n= 152) P-value Any allergens 98 (51.6) 69 (46.3) 0.335 Dermatophagoides pteronyssinus 77 (40.5) 57 (38.3) 0.671 Dermatophagoides farinae 87 (45.8) 58 (38.9) 0.205 Cockroach 0 (0) 0 (0) NA Grasses* 3 (1.6) 2 (1.3) 1.000 Alder* 1 (0.5) 0 (0) 1.000 Birch* 4 (2.1) 3 (2.0) 1.000 Oak* 1 (0.5) 0 (0) 1.000 Japanese hop 11 (5.8) 9 (6.0) 0.923 Mugwort* 7 (3.7) 3 (2.0) 0.522 Ragweed* 1 (0.5) 1 (0.7) 1.000 Dog* 3 (1.6) 3 (2.0) 1.000 Cat 8 (4.2) 6 (4.0) 0.933 Alternaria* 2 (1.1) 6 (4.0) 0.145 Aspergillus* 0 (0) 3 (2.0) 0.084 Dog or cat 10 (5.3) 8 (5.4) 0.966 At least 1 indoor allergen 91 (47.9) 63 (42.3) 0.303 At least 1 pollen allergen 21 (11.1) 13 (8.7) 0.479 At least 1 mold allergen*, 2 (1.1) 7 (4.7) 0.046 Polysensitization II 23 (12.1) 16 (10.7) 0.376 Values are presented as number (%). NA, not available. *Fisher s exact test. Indoor allergens include D. pteronyssinus, D. farinae, cockroach, dog, and cat. Pollen allergens include grass, alder, birch, oak, Japanese hop, mugwort, and ragweed. Mold allergens include Alternaria and Aspergillus. II More than two sensitizations on skin prick test. (Japanese hop) 이었으며, 화분항원들가운데한가지라도양성인경우에도지역별차이를보였다 (Table 3). 성별로차이를보이는항원은각항원별로는존재하지않았으나, 여자에서곰팡이항원들가운데한가지라도양성인경우가많았다 (Table 4). 알레르기질환 ( 천식이나알레르기비염 ) 유무에따라차이를보이는항원은집먼지진드기였고아토피와다항원감작에서도차이를보였다 (Table 5). 3. 알레르겐감작과설문지상에서의알레르기질환진단과의관련성 1) 천식진단 (Table 6) 초등학생에서는어느항원한가지에라도감작된경우 (P = 0.034) 와북아메리카집먼지진드기 (P = 0.033) 및동물털 (P = 0.01) 등의실내항원에감작된경우에천식진단의위험이증가하였고, 다항원감작인경우 (P = 0.012) 에천식진단의위험이증가하였다. 중학생및고등학생에서는특정항원에대한감작이천식진단의위험을증가시키지못하였다. 전체대상군에서는어느한가지동물의털에라도감작된경우 (P = 0.011) 와다항원감작인경우 (P = 0.044) 에천식진단의위험이증가하였다. 2) 알레르기비염진단 (Table 7) 초등학생및중학생에서는어느항원한가지에라도감작된경우및집먼지진드기에감작된경우에알레르기비염진단의위험이증가하였다. 고등학생에서는유럽집먼지진드기 (D. pteronyssinus) 에감작된경우 (P = 0.036) 와다항원감작인경우 (P = 0.048) 에알레르기비염진단의위험이의미있게증가하였다. 전체대상군으로비교한경우에도같은양상의결과를보였다. 3) 아토피피부염진단 (Table 8) 초등학생, 중학생및고등학생에서각항원의감작과아토피피부염진단과의관련성은없었고, 다항원감작인경우에도아토피피부염진단의위험이유의하게증가하지않았다. 4. 항원감작수에따른 log ( 총 IgE) 와 FEV 1 의비교 (Fig. 1) 혈청총 IgE를검사한대상자는 329명 (93.7%) 이었고, log ( 총 IgE) 는비감작군이 3.4±1.1, 단일항원감작군은 4.8±1.0, 다항원감작군에서는 5.1±1.0으로비감작군이단일항원감작군 (P < 0.001) 및다항원감작군 (P<0.001) 보다의미있게낮은결과를보였으나, 단일항원감작군과다항원감작군사이에차이는없었다. 44 http://dx.doi.org/10.4168/aard.2013.1.1.41
김형영외 흡입항원감작률과다항원감작의영향 Table 5. Sensitization rates to common inhalant allergens between children with asthma or allergic rhinitis and the others Variable AS or AR (-) (n= 188) AS or AR (+) (n= 160) P-value Any allergens 72 (40.4) 95 (60.1) < 0.001 Dermatophagoides pteronyssinus 54 (30.3) 80 (50.6) < 0.001 Dermatophagoides farinae 61 (34.3) 84 (53.2) < 0.001 Cockroach 0 (0) 0 (0) NA Grasses* 3 (1.7) 2 (1.3) 1.000 Alder* 1 (0.6) 0 (0) 1.000 Birch* 2 (1.1) 5 (3.2) 0.260 Oak* 1 (0.6) 0 (0) 1.000 Japanese hop 7 (3.9) 13 (8.2) 0.097 Mugwort* 4 (2.2) 6 (3.8) 0.525 Ragweed* 1 (0.6) 1 (0.6) 1.000 Dog* 1 (0.6) 5 (3.2) 0.103 Cat 6 (3.4) 8 (5.1) 0.438 Alternaria* 3 (1.7) 5 (3.2) 0.482 Aspergillus* 2 (1.1) 1 (0.6) 1.000 Dog or cat 7 (3.9) 11 (7.0) 0.218 At least 1 indoor allergen 65 (36.5) 89 (56.3) < 0.001 At least 1 pollen allergen 14 (7.9) 20 (12.7) 0.146 At least 1 mold allergen*, 4 (2.2) 5 (3.2) 0.740 Polysensitization II 12 (7.8) 27 (14.8) < 0.001 Values are presented as number (%). AS, asthma; AR, allergic rhinitis; NA, not available. *Fisher s exact test. Indoor allergens include D. pteronyssinus, D. farinae, cockroach, dog, and cat. Pollen allergens include grass, alder, birch, oak, Japanese hop, mugwort, and ragweed. Mold allergens include Alternaria and Aspergillus. II More than two sensitizations on skin prick test. 폐기능검사는 339명 (96.6%) 에서시행하였고, FEV 1 은비감작군이 98.9%±11.2%, 단일항원감작군은 100.9%±15.3%, 다항원감작군은 95.2%±12.9% 로다항원감작군이단일항원감작군보다낮은값을보였으나통계학적차이는없었다 (P = 0.056). FEV 1 이외의다른폐기능검사수치들모두에서세군사이에차이가없었다. 고찰본연구를통하여주요흡입알레르겐에대한연령별, 지역별및성별로감작률의차이를보이는항원들을확인할수있었다. 연령별로는나이가증가할수록집먼지진드기감작률이증가하였고, 그중에서북아메리카집먼지진드기의감작률이유의하게증가함을알수있었다. 지역별로는아산에서환삼덩굴의감작률이유의하게높았고, 성별차이점으로는여자에서곰팡이항원감작률이높게확인되었다. 단일항원과다항원감작이연령에따라서알레르기질환진단의위험에미치는차이점이있는지여부도이번연구를통하여알수있었다. 국내에서알레르기와관련된증상및질환을가진환자에게가장흔한흡입알레르겐은집먼지진드기로주요항원은유럽집먼지진드기와북아메리카집먼지진드기로알려져있으며, 9,21) 일반인구를대상으로한연구결과에서도동일한결과를보여준다. 12,14) 초등학생과중학생을대상으로전국적인역학조사와초 중 고학생을대상으로인천, 제주, 그리고울산에서실시한다기관연구를보면집먼지진드기항원에대한감작률은연령이증가함에따라증가하는경향을보였고, 14,15) 본연구에서도북아메리카집먼지진드기의 Table 6. Relationship between allergen sensitization and diagnosis of asthma on questionnaire Variable Allergen sensitization Elementary (10/122) Middle (9/114) High (8/115) Total (27/351) aor (95% CI) P-value aor (95% CI) P-value aor (95% CI) P-value aor (95% CI) P-value Any allergens 7.74 (1.16 51.96) 0.034 0.89 (0.19 4.31) 0.888 0.54 (0.10 3.00) 0.482 1.50 (0.64 3.53) 0.355 Dermatophagoides pteronyssinus 5.02 (0.97 25.90) 0.054 0.59 (0.12 3.00) 0.523 1.21 (0.21 6.95) 0.835 1.36 (0.59 3.16) 0.468 Dermatophagoides farinae 5.85 (1.15 29.64) 0.033 0.96 (0.20 4.64) 0.963 0.68 (0.12 3.80) 0.655 1.58 (0.67 3.71) 0.292 Dog or cat 9.71 (1.72 54.97) 0.010 1.29 (0.05 34.54) 0.878 3.27 (0.17 63.96) 0.436 5.06 (1.44 17.75) 0.011 At least 1 indoor allergen* 9.03 (1.35 60.58) 0.024 1.12 (0.23 5.40) 0.884 0.68 (0.12 3.80) 0.655 1.76 (0.75 4.14) 0.198 At least 1 pollen allergen 1.62 (0.17 15.52) 0.676 1.23 (0.12 12.89) 0.860 1.63 (0.21 12.70) 0.640 1.60 (0.48 5.30) 0.442 At least 1 mold allergen NA NA NA NA 10.03 (0.43 233.98) 0.151 1.39 (0.15 12.97) 0.774 No of allergen sensitization Nonsensitization 1 (ref) 1 (ref) 1 (ref) 1 (ref) Monosensitization 5.11 (0.66 39.62) 0.119 0.84 (0.16 4.54) 0.843 0.20 (0.02 2.24) 0.192 1.07 (0.41 2.83) 0.890 Polysensitization 16.99 (1.88 153.82) 0.012 1.10 (0.08 14.45) 0.942 1.52 (0.22 10.73) 0.673 3.11 (1.03 9.37) 0.044 Data were calculated by logistic regression multivariate analysis. aor, adjusted by age, sex, body mass index, environmental tobacco smoke, monthly income, and history of parental asthma; OR, odds ratio; NA, not available. *Indoor allergens include D. pteronyssinus, D. farinae, cockroach, dog, and cat. Pollen allergens include grass, alder, birch, oak, Japanese hop, mugwort, and ragweed. Mold allergens include Alternaria and Aspergillus. More than two sensitizations on skin prick test. http://dx.doi.org/10.4168/aard.2013.1.1.41 45
Kim HY, et al. Sensitization rates to inhalant allergens and effect of polysensitization Table 7. Relationship between allergen sensitization and diagnosis of allergic rhinitis on questionnaire Variable Allergen sensitization Elementary (57/122) Middle (60/114) High (36/115) Total (153/351) aor (95% CI) P-value aor (95% CI) P-value aor (95% CI) P-value aor (95% CI) P-value Any allergens 2.70 (1.15 6.38) 0.023 3.25 (1.34 7.85) 0.009 2.61 (0.96 7.11) 0.060 2.44 (1.51 3.94) < 0.001 Dermatophagoides pteronyssinus 3.37 (1.39 8.19) 0.007 2.73 (1.12 6.63) 0.027 2.95 (1.07 8.11) 0.036 2.49 (1.54 4.02) < 0.001 Dermatophagoides farinae 2.48 (1.05 5.88) 0.039 3.50 (1.44 8.56) 0.006 2.53 (0.93 6.87) 0.069 2.47 (1.53 4.01) < 0.001 Dog or cat 2.10 (0.48 9.23) 0.326 0.74 (0.09 6.29) 0.785 1.27 (0.15 10.54) 0.822 1.43 (0.53 3.85) 0.484 At least 1 indoor allergen* 2.82 (1.20 6.63) 0.018 2.77 (1.16 6.63) 0.022 2.53 (0.93 6.87) 0.069 2.36 (1.47 3.80) < 0.001 At least 1 pollen allergen 1.27 (0.31 5.17) 0.737 6.35 (0.72 56.17) 0.096 2.19 (0.60 7.99) 0.235 2.04 (0.93 4.46) 0.076 At least 1 mold allergen 1.17 (0.06 22.98) 0.916 NA NA 8.41 (0.57 123.10) 0.120 2.78 (0.60 12.83) 0.190 No of allergen sensitization Nonsensitization 1 (ref) 1 (ref) 1 (ref) 1 (ref) Monosensitization 2.51 (0.99 6.38) 0.053 2.88 (1.14 7.31) 0.026 2.17 (0.73 6.45) 0.164 2.19 (1.31 3.66) 0.003 Polysensitization 3.34 (0.85 13.12) 0.084 5.53 (0.98 31.24) 0.053 3.84 (1.01 14.64) 0.048 3.43 (1.60 7.38) 0.002 Data were calculated by logistic regression multivariate analysis. aor, adjusted by age, sex, body mass index, environmental tobacco smoke, monthly income, and history of parental asthma; OR, odds ratio; NA, not available. *Indoor allergens include D. pteronyssinus, D. farinae, cockroach, dog, and cat. Pollen allergens include grass, alder, birch, oak, Japanese hop, mugwort, and ragweed. Mold allergens include Alternaria and Aspergillus. More than two sensitizations on skin prick test. Table 8. Relationship between allergen sensitization and diagnosis of atopic dermatitis on questionnaire Allergen sensitization Elementary (36/122) Middle (29/114) High (24/115) Total (89/351) aor (95% CI) P-value aor (95% CI) P-value aor (95% CI) P-value aor (95% CI) P-value Any allergens 2.11 (0.82 5.42) 0.122 0.82 (0.32 2.12) 0.681 2.09 (0.74 5.94) 0.167 1.42 (0.84 2.40) 0.195 Dermatophagoides pteronyssinus 2.16 (0.83 5.62) 0.113 0.55 (0.20 1.49) 0.239 1.11 (0.39 3.15) 0.844 1.03 (0.61 1.76) 0.911 Dermatophagoides farinae 2.17 (0.84 5.61) 0.111 0.78 (0.30 2.03) 0.612 1.68 (0.60 4.68) 0.323 1.32 (0.78 2.24) 0.303 Dog or cat 1.12 (0.20 6.26) 0.895 1.05 (0.10 11.07) 0.965 1.72 (0.23 12.64) 0.596 1.44 (0.48 4.30) 0.519 At least 1 indoor allergen* 1.88 (0.74 4.81) 0.187 0.85 (0.33 2.18) 0.729 1.68 (0.60 4.68) 0.323 1.28 (0.76 2.16) 0.359 At least 1 pollen allergen 1.92 (0.42 8.84) 0.401 0.49 (0.07 3.26) 0.460 3.21 (0.91 11.33) 0.069 1.65 (0.74 3.67) 0.225 At least 1 mold allergen NA NA 2.08 (0.08 55.16) 0.662 5.20 (0.53 50.83) 0.157 1.13 (0.22 5.72) 0.881 No of allergen sensitization Nonsensitization 1 (ref) 1 (ref) 1 (ref) 1 (ref) Monosensitization 2.53 (0.93 6.89) 0.070 0.91 (0.34 2.47) 0.857 1.69 (0.53 5.35) 0.374 1.46 (0.84 2.56) 0.181 Polysensitization 1.04 (0.19 5.86) 0.962 0.48 (0.07 3.19) 0.450 3.09 (0.82 11.74) 0.097 1.26 (0.53 2.98) 0.597 Data were calculated by logistic regression multivariate analysis. aor, adjusted by age, sex, body mass index, environmental tobacco smoke, monthly income, and history of parental asthma; OR, odds ratio; NA, not available. *Indoor allergens include D. pteronyssinus, D. farinae, cockroach, dog, and cat. Pollen allergens include grass, alder, birch, oak, Japanese hop, mugwort, and ragweed. Mold allergens include Alternaria and Aspergillus. More than two sensitizations on skin prick test. 경우감작률이초등학생, 중학생, 고등학생에서 35.6%, 43.8%, 49.5% 로통계적으로유의하게증가하는경향을보였다 (Table 2). 집먼지진드기를제외한그외흡입알레르겐가운데오리나무 (alder), 자작나무 (birch), 떡갈나무 (oak), 오리새풀 (orchard grass), 우산잔디 (bermuda grass), 큰조아재비 (timothy), 쑥 (mugwort), 돼지풀 (ragweed), 환삼덩굴 (Japanese hop), Alternaria, Aspergillus 등다수의화분항원과곰팡이항원에서연령별감작률의차이를보였던국내연구와달리, 14) 본연구에서는연령에따른감작률의차이가없었는데이는전체연구대상자의수가적음에따른화분및곰 팡이항원에대한감작에양성인숫자가작아서초래되는결과로여겨져직접적인비교를하기어려웠다. 그러나대상군수나조사방법의차이외에생활환경의차이, 조사지역의차이, 또는기후변화등으로인한감작패턴의차이나조기감작의문제등다양한새로운가능성을생각해보아야할것으로생각한다. 본연구에서는성별에따른흡입알레르겐의감작률차이가각항원별로는없었으나한가지이상의곰팡이항원에대한감작률이여자에서높았다. 앞서언급한국내연구에서는유럽집먼지진드기, 북아메리카집먼지진드기, 실외곰팡이항원등에서남자의감작률 46 http://dx.doi.org/10.4168/aard.2013.1.1.41
김형영외 흡입항원감작률과다항원감작의영향 10 * * 140 ** 8 120 Log (total lge) 6 4 %predicted FEV1 100 2 80 0 60 Nonsensitization Monosensitization Polysensitization A Nonsensitization Monosensitization Polysensitization B Fig. 1. Comparison of total immunoglobulin E (IgE, A), forced expiratory volume in 1 second (FEV1, B) in nonsensitized, monosensitized and polysensitized groups. *P< 0.05. **P< 0.1. 이높았고, 12) 다른연구에서도초등학생및중학생에서집먼지진드기를비롯한다수의화분항원과곰팡이항원감작률이남아에서더높은결과를보였는데, 14) 이와같이남아에서높은차이를보이는이유는명확하게알려져있지않다. 그러나본연구에서는그대상군수가적어성별의차이를보이지않을가능성이많다고추정되어향후더많은대상군에서의연구가필요할것으로기대된다. 지역별차이에따른흡입알레르겐감작률의차이는여러국내연구들을통해서도밝혀진바있으며, 13-15) 각지역의기후및지리환경적인영향에따른결과로해석할수있겠다. 특히제주지역의귤응애 (Citrus red mite) 및일본삼나무 (Japanese cedar) 와같이그외지역과다른식생분포에따라알레르기질환의원인알레르겐이큰차이를보이는경우가있다. 8,12) 본연구에서인천과아산, 두지역간에감작률의차이를보였던흡입알레르겐은환삼덩굴이었다. 환삼덩굴은가을철중부지역의주요잡초알레르겐으로알려져있고, 22) 최근 10년간경기남부지역의화분알레르겐의감작률변화를조사한연구에서감작률이뚜렷하게증가한대표적인알레르겐이었다. 11) 본연구상에서인천과아산, 두지역간에수목및잡초의지리적분포에차이가있을가능성이있지만, 화분알레르겐의분포차이를설명할만한객관적이고과학적인자료는없어서아산지역이인천지역에비해환삼덩굴의감작률이높은이유를명확하게설명하기에는제한이따른다. 또한환삼덩굴에감작된수가적어서환삼덩굴이두지역간의뚜렷한차이를보이는흡입알레르겐이라고단정하기엔제약이따르며이는조사대상자수를충분히확보하여재검증할필요가있을것으로보인다. 그러나이러한차이는지역또는시기별항원감작의차이에대한새로운관심의시작이될수도있을것으로생각된다. 단일항원과다항원감작군을비교한국내연구는드물뿐만아니라대부분알레르기질환을가진환자들을대상으로한연구이다. 19,20) 이처럼다항원감작과관련된국내외보고들이거의없어서 이러한현상이유사한알레르겐에대한교차반응의결과인지, 같은환경에서발견되는알레르겐에대한동시감작의결과인지, 감작군의아토피성향의다른표현형일뿐인지등아직그이유가확실하게밝혀져있지않다. 20,23) 이전의국내외연구들의결과를보면단일항원감작군보다다항원감작된경우총 IgE, eosinophil cationic protein, 식품항원에대한감작률이증가하였고, 천식증상이더심하고폐기능검사에서 FEV 1 이감소하며면역치료에대한효과가떨어지는점에서두군사이에임상적특징이다르다는것을시사한다고하였다. 19,20) 고등학생을대상으로한국내연구에서는피부단자시험에서한가지항원에양성일때보다두가지이상의항원에서양성을보일때기도과민성이유의하게더증가하는결과를나타냈다. 24) 본연구에서다항원감작을보일때알레르기질환의유병률에영향을미치는지여부를조사한결과, 설문지조사상에서천식과알레르기비염의발병위험이증가하였으나아토피피부염은관련이없었다. 이는다양한발병기전이복잡하게얽혀있는알레르기질환들중에서도, 알레르겐감작이외의유전적요인에의한피부장벽이상 25-27) 과같은다른요소가아토피피부염발병에영향을미칠수있다는점, 게다가실제로흡입알레르겐감작과아토피피부염사이에직접적인인과관계가적을가능성, 그리고연령이증가하면서증상이점차소실되는소아아토피피부염의일반적인자연경과로인해설문지상에서의아토피피부염의진단력이실제현증아토피피부염질환상태를반영하지못하고있을가능성등의이유로다항원감작에의한영향이천식및알레르기비염과는다르게나왔을개연성이있을수있겠다. 28) 이전의국내연구와비교해볼때단일항원감작군과다항원감작군사이에보였던총 IgE나 FEV 1 의의미있는차이는확인할수없었고, 총 IgE의경우비감작군이단일항원감작군및다항원감작군과의미있는차이를보였으나단일항원과다항원감작군사 http://dx.doi.org/10.4168/aard.2013.1.1.41 47
Kim HY, et al. Sensitization rates to inhalant allergens and effect of polysensitization 이에는차이가없었다. 이러한결과는전체연구대상자수및다항원감작군수가작아서생긴결과일수도있고그와반대로일반소아청소년인구를대표하는결과의단초를제공하는자료일수도있으므로, 이번예비조사결과를바탕으로일반소아청소년인구를대표할만한충분한연구대상자숫자확보를통한추후연구가필요할것으로보인다. 다만이결과는예비연구로서일반소아청소년을대상으로다항원감작군이갖는특징을제시하였다는데의미가있다고하겠다. 본연구에는몇가지제한점이있다. 첫째, 이번연구는 어린이청소년환경노출과건강실태조사 와관련된예비연구로서조사지역을선정하는데있어과학적이고객관적인선정방식을거치지못하고임의로선정하였기에인천과아산지역이도시와농촌을정확히대표하기어렵고, 또한소아청소년시기의일반인구를대표하기에는조사대상자의숫자가충분하지못한한계점이있다. 이로인해집먼지진드기를제외한다른흡입알레르겐에대한감작률을산출하여결과를도출하기에는제한이있었다. 둘째, 단면연구이기에흡입알레르겐감작과알레르기질환발병과의인과관계를명확히확인하기는어려웠다. 셋째, 알레르겐감작률을단지연령, 지역, 성에대한영향만을고려하였고사회경제적수준, 실내외대기오염수준의평가, 주거환경의차이, 알레르기질환의가족력등의변수를고려하지못하였다. 넷째, 알레르기질환유병률을의사의진단이나검사가아닌 ISAAC 설문지에의존하였기에실제알레르기질환유병률과차이를보일수있고설문조사가기억에의존할수밖에없으므로회상오류의가능성이있다. 하지만본연구는흡입알레르겐의감작률과분포뿐만아니라다항원감작과알레르기질환발병과의관계및비감작군, 단일항원감작군, 다항원감작군간의알레르기지표차이를소아청소년시기의일반인구를대상으로조사하였다는것이이전의연구들과차별화될수있는점이다. 따라서이번예비연구의결과를토대로향후연구대상을전국을대표할수있는소아청소년으로확대한다면더욱명확한결과를얻을수있을것으로보인다. 결론적으로본연구를통해인천과아산두지역의소아청소년을대상으로흡입알레르겐감작률을조사한결과, 연령증가에따라북아메리카집먼지진드기의감작률이의미있게증가하였다. 그리고감작된수가적어서해석에제한이따르나, 아산에서환삼덩굴의감작률이높았고여자가곰팡이항원감작률이높게나타났다. 또한다항원감작이천식과알레르기비염과관련이있어, 향후기후변화등환경적요인변화와환경노출에대한평가를추가한실태조사를통하여다항원감작의위험요인을밝혀낼수있다면유병률을비롯한소아청소년시기알레르기질환의이해를넓히고나아가예방을하는데도움이될것으로생각한다. 감사의글 본연구에직간접적으로협조를아끼지않은이유진연구원을 포함한공동연구원과실질적인도움을주신해당학교장및보건 교사, 학부모와단국대학교의료원환경보건센터연구원들께감사 드립니다. REFERENCES 1. Downs SH, Marks GB, Sporik R, Belosouva EG, Car NG, Peat JK. Continued increase in the prevalence of asthma and atopy. Arch Dis Child 2001;84:20-3. 2. Johnson CC, Ownby DR, Zoratti EM, Alford SH, Williams LK, Joseph CL. Environmental epidemiology of pediatric asthma and allergy. Epidemiol Rev 2002;24:154-75. 3. Kwon JW, Kim BJ, Song Y, Seo JH, Kim TH, Yu J, et al. Changes in the prevalence of childhood asthma in seoul from 1995 to 2008 and its risk factors. Allergy Asthma Immunol Res 2011;3:27-33. 4. Suh M, Kim HH, Sohn MH, Kim KE, Kim C, Shin DC. Prevalence of allergic diseases among Korean school-age children: a nationwide crosssectional questionnaire study. J Korean Med Sci 2011;26:332-8. 5. Dean T, Venter C, Pereira B, Arshad SH, Grundy J, Clayton CB, et al. Patterns of sensitization to food and aeroallergens in the first 3 years of life. J Allergy Clin Immunol 2007;120:1166-71. 6. Arbes SJ Jr, Gergen PJ, Vaughn B, Zeldin DC. Asthma cases attributable to atopy: results from the Third National Health and Nutrition Examination Survey. J Allergy Clin Immunol 2007;120:1139-45. 7. Chan-Yeung M, Hegele RG, Dimich-Ward H, Ferguson A, Schulzer M, Chan H, et al. Early environmental determinants of asthma risk in a highrisk birth cohort. Pediatr Allergy Immunol 2008;19:482-9. 8. Kim SH, Kang HR, Kim KM, Kim TB, Kim SS, Chang YS, et al. The sensitization rates of food allergens in a Korean population: a multi-center study. J Asthma Allergy Clin Immunol 2003;23:502-14. 9. Kim YJ, Han JE, Kang IJ. Change of inhalant allergen sensitization in children with allergic respiratory diseases during recent 10 years. Korean J Asthma Allergy Clin Immunol 2004;24:241-6. 10. Choi BS, Lee YJ, Baek JY, Kim KW, Sohn MH, Kim KE. Prevalence of sensitization to tyrophagus putrescentiae in children with allegic diseases. Pediatr Allergy Respir Dis 2010;20:107-13. 11. Lee JW, Choi GS, Kim JE, Jin HJ, Kim JH, Ye YM, et al. Changes in sensitization rates to pollen allergens in allergic patients in the southern part of gyeonggi province over the last 10 years. Korean J Asthma Allergy Clin Immunol 2011;31:33-40. 12. Jeon BH, Lee J, Kim JH, Kim JW, Lee HS, Lee KH. Atopy and sensitization rates to aeroallergens in children and teenagers in Jeju, Korea. Korean J Asthma Allergy Clin Immunol 2010;30:14-20. 13. Jung HH, Kwon JW, Lee SY, Seo JH, Song YH, Kim BJ, et al. Correlation between demographic characteristics and indoor allergen sensitization among Jeongeup countryside, Jeongeup city, and Seoul city in Korea. Korean J Asthma Allergy Clin Immunol 2010;30:277-84. 14. 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. 15. 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. 48 http://dx.doi.org/10.4168/aard.2013.1.1.41
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