pissn: 2288-0402 eissn: 2288-0410 Allergy Asthma Respir Dis 3(1):47-53, January 2015 http://dx.doi.org/10.4168/aard.2015.3.1.47 ORIGINAL ARTICLE 흡입알레르겐에대한피부단자시험과혈청특이 IgE (ImmunoCAP system) 의비교 남영희, 전동섭, 이수걸 동아대학교의과대학내과학교실 Comparison of skin prick test and serum specific IgE measured by ImmunoCAP system for various inhalant allergens Young-Hee Nam, Dong-Sub Jeon, Soo-Keol Lee Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea Purpose: It appears that much of the discordance between skin prick test (SPT) and ImmunoCAP in clinical practice. We investigated the comparison and correlation between SPT and ImmunoCAP for inhalant allergens. Methods: A total of 1,400 patients who were tested SPT and ImmunoCAP were recruited from June 2011 to May 2014 in Dong-A University Hospital, and the results of two assays were compared for 17 inhalant allergens. For SPT, mean wheal size 3 mm or allergen/histamine 1 at 15 minutes, and the result of ImmunoCAP of 0.35 ku/l was considered positive, respectively. Results: Of the study subjects, bronchial asthma was 29.3%, rhinitis 36.8%, atopic dermatitis 0.6%, and chronic urticaria 4.3%. The agreement rate of between two assays was 77.4%. When ImmunoCAP was compared with SPT as the reference, the sensitivity, specificity was 75.5% and 80.0%, respectively. Significant correlation was observed (r= 0.59), and birch, mugwort, Japanese hop, house dust mites, and cockroach showed very strong correlation (r> 0.7). Conclusion: The agreement, sensitivity, and specificity between SPT and ImmunoCAP was various according to allergens. We should determine the clinical relevance of the allergen sensitization using both SPT and ImmunoCAP not alone with combination of clinical symptoms. (Allergy Asthma Respir Dis 2015;3:47-53) Keywords: Allergens, Skin tests, Immunoglobulin E 서론알레르기질환의유병률이전세계적으로증가함에따라, 환자들의삶의질이떨어지고, 사회경제적부담이증가하고있어공공보건에서매우중요한문제로인식되고있다. 1) 알레르기질환은알레르겐에대한특이 IgE를생성하는것을특징으로하며, 알레르겐감작은이후알레르기질환발생에있어서중요한위험인자로알려져있어이를확인하고감시하는것은매우중요하다. 자세한병력청취와신체검사를시행하고, 피부반응시험, 혈청검사및필요한경우유발검사를통해알레르기질환을진단한다. 알레르겐특이 IgE 는체내검사 (in vivo) 와체외검사 (in vitro) 를통해확인할수있다. 2) 피부단자시험 (skin prick test) 은 in vivo 검사로검사방법이간단하고, 짧은시간내에검사를안전하게시행할수있어널리이용되고있다. 3) 피부반응정도가혈청총 IgE, 특이 IgE 뿐만아니라기관지유발시험과도높은일치율을보이고있다. 4,5) 그러나, 항히스타민제를복용하거나피부묘기증, 심한습진이있는환자는시행하기힘들며, 검사자에따라판독결과에차이가나거나, 제조회사에따라알레르겐추출물질 (extract) 이다양하여검사결과가달라질수있는단점이있다. 3,6) 환자의혈청에서특이 IgE를확인하는 in vitro 검사는 radio-allergosrobent test (RAST), multiple allergen simul- Correspondence to: Soo-Keol Lee Department of Internal Medicine, Dong-A University College of Medicine, 32 Daesingongwon-ro, Seo-gu, Busan 602-714, Korea Tel: +82-51-240-2810, Fax: +82-51-242-5852, E-mail: skleeai@dau.ac.kr Received: June 26, 2014 Revised: August 28, 2014 Accepted: September 1, 2014 2015 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/). 47 http://www.aard.or.kr
Allergy Asthma Respir Dis Nam YH, et al. Comparison of skin prick test and ImmunoCAP for inhalant allergens taneous test (MAST), ImmunoCAP system 등이있다. RAST는방사성물질에노출의위험이있고, 피부단자시험에비해민감도가낮아최근에는거의시행하지않고있다. 7,8) MAST는피부단자시험에비해민감도와상관관계가낮고, 혈청이많이필요하며, 검사시간이길다는단점이있다. 9,10) ImmunoCAP은이전의검사에비해민감도, 특이도가높고, 피부단자시험과일치율이높아현재널리이용되고있다. 11-13) 하지만, ImmunoCAP과피부단자시험결과가일치하지않는보고도있어, 피부단자시험과 in vitro 검사의임상적연관성을최적화하려는다양한시도가진행되었다. 13-15) Immuno- CAP과피부단자시험을비교한국내연구가있지만, 집먼지진드기 16), 곰팡이 17) 등일부항원혹은몇몇항원만을비교하였거나, 환자대상수가적어다양한항원에대한비교연구는부족한실정이다. 14,18,19) 본연구에서는흔한흡입알레르겐에대해피부단자시험과 ImmunoCAP 결과를비교하고, 두검사간의상관성을확인하고자하였다. 대상및방법 1. 연구대상 2011년 6월부터 2014년 5월까지동아대학교병원알레르기클리닉을방문하여피부단자시험을시행한환자 1,400명을대상으로의무기록을이용하여후향적으로분석하였다. 2. 연구방법흡입알레르겐총 24종, 수목꽃가루 (tree mix, birch, alder, beech, oak, Japanese cedar), 목초꽃가루 (grass mix, rye grass, timothy grass, orchard grass, Bermuda grass), 잡초꽃가루 (ragweed, mugwort, Japanese hop), 곰팡이 (Alternaria, Aspergillus fumiatus, Cladosporium, Candida albicans), 집먼지진드기 (Dermatophagoides pteronyssinus, Dermatophagoides farinae), 동물상피 (cat dander, dog hair), 긴털가루진드기 (Tyrophagus putrescentiae), 바퀴벌레 (cockroach) 등에대해피부단자시험을시행하였다. Japanese cedar는 Lofarma (Milan, Italy) 사, Alternaria, cat dander, dog hair 는 Bencard (Breford, UK) 사의제품을사용하였고, 나머지알레르겐은 Allergopharma (Reinbeck, Germany) 사의제품을사용하였다. 양성대조액은히스타민 (1 mg/ml), 음성대조액은생리식염수를사용하여 15분후팽진크기와발적유무를확인하였다. 팽진의평균크기가 3 mm보다크거나, 히스타민에비해같거나클때 (allergen/histamine, A/H 1) 를양성으로판정하였다. 혈청총 IgE, 알레르겐특이 IgE를 ImmunoCAP system (Phadia AB, Uppsala, Sweden) 으로측정하였다. 특이 IgE는 0.35 ku/l 이상인경우양성으로판정하였다. 환자의피부단자시험결과와병력을통하여원인으로의심되는 알레르겐에대하여 ImmunoCAP 을이용하여혈청특이 IgE 를측 정하였다. 24 개의알레르겐중혈청특이 IgE 를측정한 17 개알레르 겐에대해피부단자시험과 ImmunoCAP 결과를비교하여일치율 을확인하였다. 팽진의평균크기가 3 mm 보다클때 ( 팽진크기기 준 ), A/H 1 인경우 (A/H 기준 ) 를각각기준값 (reference value) 으 로하여피부단자시험에대한 ImmunoCAP 의민감도, 특이도를 구하고, 팽진의평균크기와혈청특이 IgE 수치를비교하여상관관 계를확인하였다. 피부단자시험과 ImmunoCAP 의비교는 17 개알 레르겐각각에대한결과를확인하여이들의평균값으로하였다. 3. 통계학적분석 통계분석은 SPSS ver. 12.0 (SPSS Inc., Chicago, IL, USA) 을이용 하여분석하였다. 모든측정치는평균 ± 표준편차또는백분율로 나타내었다. 두군간의비교는 Fisher exact test, Mann-Whitney U test 를이용하였다. 피부단자시험과혈청특이 IgE 수치사이의상 관관계는 Spearman 상관분석, 두검사간의일치도는 Kappa 분석 을이용하였다. 성별, 나이, 총 IgE 항체치를교란변수 (confounding factor) 로보고, 이들을통제하여상관관계를다시확인하였다. P<0.05 인경우통계학적으로유의하다고판단하였다. 1. 연구대상 결과 총 1,400 명의환자의평균연령은 45.36±17.27 세, 여자가 743 명 (53.1%) 이었다. 평균혈청총 IgE 항체치는 308.68±644.15 ku/l 이 었다. 천식으로진단받은환자 410 명 (29.3%), 알레르기비염 515 명 (36.8%), 아토피피부염 9 명 (0.6%), 만성두드러기 60 명 (4.3%) 등이었 다 (Table 1). Table 1. Clinical characteristics of study subjects (n= 1,400) Characteristic Value Female sex 743 (53.1) Age (yr) 45.36± 17.27 Total IgE (ku/l) 308.68± 644.15 Disease BA 410 (29.3) AR 515 (36.8) BA with AR 154 (11.0) Atopic dermatitis 9 (0.6) Chronic urticaria 60 (4.3) Food allergy 28 (2.0) Others 555 (39.6) Values are presented as number (%) or mean± standard deviation. AR, allergic rhinitis; BA, bronchial asthma. 48 http://dx.doi.org/10.4168/aard.2015.3.1.47
남영희외 흡입알레르겐에대한피부단자시험과 ImmunoCAP 의비교 Allergy Asthma Respir Dis 2. 피부단자시험팽진크기를기준으로하였을때, 759명 (54.2%) 이양성반응을보였다. 양성반응을보인알레르겐개수에따라 1 5개 : 573명 (41%), 6 10개 : 133명 (9.5%), 11 개이상 : 34명 (2.4%) 이었다 (Fig. 1). D. farinae 가가장높은양성률을보였고 (35.5%), D. pteronyssinus, T. putrescentiae, tree mix, cat dander 등의순으로나타났다. A/H 기준일때는 657명 (46.9%) 이양성반응을보였다. 양성반응을보인알레르겐개수는 1 5개 : 534명 (38.1%), 6 10 개 : 88명 (6.3%), 11개이상 : 35명 (2.5%) 이었고 (Fig. 1), D. farinae 가가장높은양성률 (30.5%) 을보였다. 두가지기준으로피부단자시험결과를비교하였을때평균일치율은 96.5% 이고, Alternaria가가장일치율이높았고 (98.1%), D. farinaeentiae가가장낮았다 (77.7%) (Table 2). 3. 혈청특이 IgE 총 17개알레르겐중에서 oak (51.9%), cat dander (50%) 가양성률이가장높았고, Alternaria (25.4%) 가가장낮은양성률을보였다 (Table 2). 4. 피부단자시험과 ImmunoCAP 비교 1) 연관성 : 일치율, 민감도, 특이도팽진크기기준일때일치율은 77.3% ( 양성일치율, 30.2%; 음성일치율, 47.0%) 이고, D. pteronyssinus 89.4% 로가장높고, dog hair 57.3% 로가장낮았다. Kappa 계수는 0.52였고, birch, mugwort, D. pteronyssinus 는 0.7 이상의높은일치도를보였다. 민감도는 72.6%, 특이도 82.5% 였다. A/H 기준일때, 일치율은 77.5% ( 양성일치율, Table 2. Positive rate of skin prick test and ImmunoCAP (n= 1,400) Allergen Mean wheal 3 mm A/H 1 Agreement (%) ImmunoCAP Tree mix 195 (13.9) 171 (12.2) 91.5 Birch 153 (10.9) 139 (9.9) 93.4 102/214 (47.2) Alder 151 (10.8) 136 (9.7) 93.6 Beech 133 (9.5) 106 (7.6) 93.7 97/208 (46.6) Oak 131 (9.4) 97 (6.9) 93.6 27/52 (51.9) Japanese cedar 48 (3.4) 33 (2.4) 97.5 21/54 (38.9) Grass mix 57 (4.1) 46 (3.3) 97.1 Rye grass 44 (3.1) 34 (2.4) 97.4 22/68 (32.4) Timothy grass 59 (4.2) 38 (2.7) 96.7 Orchard grass 51 (3.6) 40 (2.9) 97.3 Bermuda grass 39 (2.8) 28 (2) 97.7 16/41 (39.0) Ragweed 59 (4.2) 45 (3.2) 97 41/121 (33.9) Mugwort 116 (8.3) 94 (6.7) 94. 5 57/143 (39.9) Japanese hop 78 (5.6) 55 (3.9) 96.1 19/47 (40.4) Alternaria 30 (2.1) 17 (1.2) 98.1 9/21 (42.9) A. fuminatus 68 (4.9) 31 (2.2) 95.4 17/67 (25.4) Cladosporium 51 (3.6) 27 (1.9) 96.7 Candida albicans 101 (7.2) 64 (4.6) 93.6 D. pteronyssinus 466 (33.3) 408 (29.1) 79.5 399/1,034 (38.6) D. farinae 497 (35.5) 427 (30.5) 77.7 460/997 (46.1) Cat dander 194 (13.9) 148 (10.6) 90.3 39/78 (50.0) Dog hair 142 (10.1) 77 (5.5) 91.3 33/68 (48.5) Cockroach 155 (11.1) 79 (5.6) 90.2 5/15 (33.3) T. putrescentiae 270 (19.3) 170 (12.1) 83 3/9 (33.3) Values are presented as number (%) unless otherwise indicate. A/H, allergen/histamine; A. fuminatus, Aspergillus fuminatus; D. pteronyssinus, Dermatophagoides pteronyssinus; D. farinae, Dermatophagoides farinae; T. putrescentiae, Tyrophagus putrescentiae. 800 700 600 641 743 Mean wheal size 3 mm A/H 1 No of subjects 500 400 300 200 100 0 148 139 171 151 118 104 82 56 74 64 35 31 30 22 32 15 22 13 14 7 34 23 15 7 4 5 0 1 2 3 4 5 6 7 8 9 10 11-15 16-20 21-25 No. of allergens with positive results for SPT Fig. 1. Distribution of subjects according to the number of allergens with positive results for skin prick test (SPT). A/H, allergen/histamine. http://dx.doi.org/10.4168/aard.2015.3.1.47 49
Allergy Asthma Respir Dis Nam YH, et al. Comparison of skin prick test and ImmunoCAP for inhalant allergens Table 3. The agreement between skin prick test and ImmunoCAP Allergen Mean wheal 3 mm A/H 1 Agreement (%) Agreement (%) Kappa P-value Positive Negative Total Positive Negative Total Birch 36.9 49.1 86.0 0.717 < 0.001 35 51.9 86.9 0.734 < 0.001 Beech 31.7 48.1 79.8 0.589 < 0.001 27.4 50.5 77.9 0.546 < 0.001 Oak 38.5 40.4 78.9 0.578 < 0.001 34.6 44.2 78.8 0.581 < 0.001 Japanese cedar 20.4 51.9 72.3 0.389 0.003 16.7 53.7 70.4 0.33 0.01 Rye grass 25.0 60.3 85.3 0.664 < 0.001 20.6 64.7 85.3 0.638 < 0.001 Bermuda grass 22.0 56.1 78.1 0.511 0.001 9.8 53.7 63.5 0.145 0.281 Ragweed 22.3 62.0 84.3 0.63 < 0.001 19.0 64.5 83.5 0.592 < 0.001 Mugwort 34.3 51.7 86.0 0.712 < 0.001 30.1 54.5 84.6 0.673 < 0.001 Japanese hop 38.3 44.7 83.0 0.664 < 0.001 36.2 53.2 89.4 0.781 < 0.001 Alternaria 23.8 42.9 66.7 0.31 0.154 14.3 57.1 71.4 0.364 0.031 A. fumiatus 9.0 61.2 70.2 0.18 0.139 9.0 64.2 73.2 0.231 0.055 D. pteronyssinus 31.1 58.3 89.4 0.773 < 0.001 27.9 58.9 86.8 0.711 < 0.001 D. farinae 33.5 49.1 82.6 0.647 < 0.001 29.4 50.5 79.9 0.586 < 0.001 Cat dander 42.3 26.9 69.2 0.385 < 0.001 41.0 32.1 73.1 0.462 < 0.001 Dog hair 38.2 19.1 57.3 0.157 0.15 36.8 33.8 70.6 0.413 0.001 Cockroach 33.3 33.3 66.6 0.4 0.053 26.7 60.0 86.7 0.7 0.007 T. putrescentiae 33.3 44.4 77.7 0.571 0.058 11.1 44.4 55.5 0 > 0.9 Mean 30.2 47.0 77.3 25.0 52.5 77.5 A/H, allergen/histamine; A. fuminatus, Aspergillus fuminatus; D. pteronyssinus, Dermatophagoides pteronyssinus; D. farinae, Dermatophagoides farinae; T. putrescentiae, Tyrophagus putrescentiae. Kappa P-value Table 4. The sensitivity and specificity of ImmunoCAP compared with skin prick test as the reference Allergen Mean wheal 3 mm A/H 1 Sensitivity (%) Specificity (%) Sensitivity (%) Specificity (%) Birch 90.8 82.7 97.4 81.0 Beech 85.7 76.3 90.5 72.4 Oak 83.3 75.0-44.2 71.9 Japanese cedar 68.8 73.7 69.2 70.7 Rye grass 77.3 89.1 87.5 84.6 Bermuda grass 81.8 76.7 57.1 64.7 Ragweed 84.4 84.3 92.0 81.2 Mugwort 80.3 90.2 84.3 84.8 Japanese hop 72.0 95.5 85.0 92.6 Alternaria 62.5 69.2 100 66.7 A.fumiatus 40.0 78.8 46.2 79.6 D. pteronyssinus 91.0 88.7 91.7 84.7 D. farinae 87.7 79.5 89.6 75.1 Cat dander 64.7 77.8 69.6 78.1 Dog hair 54.2 65.0 67.6 74.2 Cockroach 50.0 100 80.0 90.0 T. putrescentiae 60.0 100 33.3 66.7 Mean 72.6 82.5 78.3 77.6 A/H, allergen/histamine; A. fuminatus, Aspergillus fuminatus; D. pteronyssinus, Dermatophagoides pteronyssinus; D. farinae, Dermatophagoides farinae; T. putrescentiae, Tyrophagus putrescentiae. Table 5. Correlation between mean wheal size of skin prick test and serum specific IgE levels measured by ImmunoCAP system Allergen Correlation (r) P-value Correlation (*r) P-value Birch 0.725 < 0.001 0.385 < 0.01 Beech 0.675 < 0.001 0.534 < 0.01 Oak 0.634 < 0.001 0.552 < 0.01 Japanese cedar 0.43 0.001 0.529 < 0.01 Rye grass 0.67 < 0.001 0.517 < 0.01 Bermuda grass 0.571 < 0.001-0.125 0.469 Ragweed 0.598 < 0.001 0.417 NA Mugwort 0.715 < 0.001 0.255 0.003 Japanese hop 0.735 < 0.001 0.464 0.002 Alternaria 0.414 0.062 0.61 0.009 A. fumiatus 0.231 0.06 0.428 0.001 D. pteronyssinus 0.787 < 0.001 0.464 < 0.01 D. farinae 0.779 < 0.001 0.506 < 0.01 Cat dander 0.521 < 0.001 0.062 0.6 Dog hair 0.395 0.001 0.387 0.002 Cockroach 0.786 0.001 0.627 0.029 T. putrescentiae 0.44 0.236 0.175 0.744 A/H, allergen/histamine; A. fuminatus, Aspergillus fuminatus; D. pteronyssinus, Dermatophagoides pteronyssinus; D. farinae, Dermatophagoides farinae; T. putrescentiae, Tyrophagus putrescentiae; NA, not available. *r means partial correlation coefficient adjusted by sex, age, and total IgE levels. 50 http://dx.doi.org/10.4168/aard.2015.3.1.47
남영희외 흡입알레르겐에대한피부단자시험과 ImmunoCAP 의비교 Allergy Asthma Respir Dis 25.0%; 음성일치율, 52.5%), 민감도 78.3%, 특이도 77.6% 였다. Kappa 계수 0.5였고, birch, Japanese hop, D. pteronyssinus, cockroach 가높은값을보였다 (Tables 3, 4). 두가지기준에대한일치율, 민감도, 특이도의평균은각각 77.4% ( 양성일치율 : 27.6%, 음성일치율 : 49.8%), 75.5%, 80.0% 였다. 2) 상관성 17개알레르겐모두양의상관관계를보였으며, Alternaria, A. fumiagtus, T. putrescentiae 를제외하고모두통계학적으로유의한상관관계를보였다. Birch, mugwort, Japanese hop, D. pteronyssinus, D. farina, cockroach는상관계수 (r) 0.7로강한양의상관관계를보였다. 교란변수를통제하고분석한결과에서는 Bermuda grass, ragweed, cat dander, T. putrescentiae 를제외한 13개알레르겐에서유의한상관관계를확인하였지만, 교란변수통제전보다 (r = 0.59) 약한상관관계 (r = 0.40) 를보였다 (Table 5). 고찰본연구에서는최근 3년간부산에위치한 3차대학병원에서시행한피부단자시험결과를확인하였다. 기관지천식, 알레르기비염등의호흡기알레르기환자뿐만아니라, 피부알레르기, 음식알레르기, 알레르기질환과관련이없는만성기침및호흡곤란을호소하는환자등을대상으로하여연구를시행하였다. 따라서부산지역성인환자들을대상으로흡입알레르겐에대한감작률을확인할수있었다. 집먼지진드기 (29.1% 35.5%) 가가장높은감작률을보였으며, 이는본연구그룹에서 10년전에시행한연구결과와비슷하였다 (24.9% 35.5%). 20) 그외 T. putrescentiae (15.7%), tree mix (13.1%), cat dander (12.2%) 순으로높은감작률을보였고, 두연구에서각각의알레르겐에대해비슷한감작률을보였다. 서울, 경기, 제주지역에서시행한국내연구에서도집먼지진드기, T. putrescentiae가가장높은감작률을보였다. 21) 피부단자시험은일반적으로팽진의평균크기 3 mm 이거나, A/H 1인경우를양성판정기준으로사용하고있다. 본연구에서는두가지기준으로각각알레르겐에대한양성률을확인하였으며, 이들사이의일치율은 96.5% 로매우높은일치도를보였다. 팽진의크기 ( 3 mm) 기준이일부알레르겐에대해서는적합하지않아, 새로운기준을고려해야한다는연구가있지만, 22) 본연구에서는집먼지진드기 (78.6%), T. putrescentiae (83%) 를제외하고대부분의알레르겐에서 90% 이상의높은일치율을보였다. ImmunoCAP은 paper 대신 cyanogen bromide-activated cellulose carrier로구성된고체상 (solid phase) 을이용하여혈청내특이 IgE를연속적이며표준화된단위 (ku/l) 로측정한다. 기존의 paper disc 방식인 RAST에비해알레르겐결합능이 3배이상높아검체 와쉽게결합하고, 20분이내에알레르겐-항체결합이평형상태에도달한다. 23,24) 이전의여러연구에서 RAST에비해민감도, 특이도가높았다. 23,25,26) MAST의단점을보완한 MAST-immunoblot 검사와 ImmunoCAP를비교한국내연구에서는알레르겐에따라큰차이를보였다. 14) MAST-immunoblot 은민감도 11.1% 75%, 특이도 78.3% 98.6% 였고, ImmunoCAP은 5.6% 71.2%, 81.3% 98.8% 로두검사에서비슷한결과를보였다. 본연구에서는피부단자시험을시행한환자중알레르기질환이의심되는환자에게피부단자시험과병력을통해의심되는알레르겐에대해 ImmunoCAP 검사를시행하였다. 두검사사이의일치율과피부단자시험결과를기준으로 ImmunoCAP 의민감도, 특이도를비교하고, 두검사간의상관관계를확인하였다. 팽진크기기준일때, 17개흡입알레르겐에대한 ImmunoCAP 의일치율은 77.3%, A/H 기준일때 77.5% 로비슷하였지만, 민감도는각각 72.6%, 78.3%, 특이도각각 82.5%, 77.6% 이었다. 피부단자시험의팽진크기를기준으로할때 ImmunoCAP 의특이도가높고, A/H 기준으로할때민감도가높았다. 알레르겐마다차이가있지만, birch, D. pteronyssinus는민감도가높고, cockroach, Japanese hop은특이도가높았다. 만성비염환자를대상으로시행한연구에서 13) 피부단자시험에대한 ImmunoCAP의민감도는 50% 80% 로, 53가지알레르겐중 mountain cedar 86.2% 를제외하고모두 80% 보다낮았다. 특이도는대부분 80% 보다높고, 일치율은 80.6% 이었다. 알레르기의심환자를대상으로한독일 27) 과중국 28) 의연구에서일치율 80%, 81%, 민감도 82.8% (67.4% 98.8%), 87.2% (87% 87.8%) 특이도 78.7% (72.2% 85.1%) 4.1% (53.0% 87.2%) 이었다. 국내연구에서 14) 두검사의일치율은 95.2% 였다. 알레르겐에따라매우다양한민감도와특이도를보였고, 양성률이가장높은 D. pteronyssinus, D. farinae 의피부단자시험에대한 ImmunoCAP의일치도, 민감도, 특이도는 D. pteronyssinus 74.%, 71.2%, 87.5%, D. farinae 70.7%, 68.2%, 81.3% 이었다. 4차국민건강영양조사를분석한연구에서는일치도가매우낮았다. 18) D. farinae, mugwort 는높은일치도를보였지만, cockroach, oak, dog dander는일치율이낮았고, Japanese hop는일치도수치가음의값을보였다. 본연구에서피부단자시험과 ImmunoCAP을정량적으로비교하여 r = 0.59로비교적높은상관관계를보였다. 나이가들수록피부단자시험에서피부반응이떨어지고, 29) 흡인알레르겐에대한감작률이감소한다. 20,30) 성별이아토피에영향을줄수있고, 16,31) 총 IgE 항체치가높을수록피부단자시험양성률이높다는연구결과가있다. 13,14) 따라서성별, 나이, 총 IgE 항체치를통제하였고, 통제전보다는감소한양상을보이지만대부분의알레르겐에서통계적으로의미있는상관관계를유지하였다. Wiliams 등 32) 은각각의알레르겐에서두검사가상관관계가있는것을확인하였고 (timothy, r = 0.87; ragweed, r = 0.76; Alternaria, r = 0.73; cat dander, r = 0.73; http://dx.doi.org/10.4168/aard.2015.3.1.47 51
Allergy Asthma Respir Dis Nam YH, et al. Comparison of skin prick test and ImmunoCAP for inhalant allergens D. farinae, r = 0.56) 8 개월뒤에다시시행한검사에서도상관관계 가잘유지되었다. 국내에서가장흔하고중요한알레르겐이며, 본 연구에서도양성률이가장높은집먼지진드기는 D. pteronyssinus r = 0.46, D. farinae r = 0.43 이었다. 22) 본연구에서는이보다높은상 관관계를보였으며, 국내의다른연구 28) 에서도 r = 0.663 으로외국 보다국내보고에서상관관계가높았다. 국내단일 3 차병원에서주 요흡입알레르겐 9 종에대해피부단자시험과 ImmunoCAP 을비 교하여매우높은민감도 92.9% 를보고하였고, 특히집먼지진드기, dog hair, cat dander 가높았다. 19) Receiver operating characteristic (ROC) 곡선에서민감도와특이도모두가장높은값을반영하는 index Q 도평균 0.79 로높았다. 하지만환자수가매우적었으며 (9 26 명 ), 두검사간의상관관계는확인하지않았다. 피부단자시험과 ImmunoCAP 은알레르겐에따라매우다양한 일치도, 민감도, 특이도를보였고, 결과가일치하지않는경우도높 은빈도로나타났다. 피부단자시험은피부의비만세포에결합한특 이 IgE 와알레르겐의반응을확인하고, 혈청검사는혈액내순환 하는특이 IgE 를측정하는데 27) 이러한측정방법의차이로검사결 과가일치하지않을수있다. ImmunoCAP 의 cyanogen bromide 는 cellulose allegro-sorbent 에결합하기위해서아미노기 (amino group) 가필요하다. 24) 단백질에비해탄수화물을많이포함한알레 르겐은 ImmunoCAP 의고체상과결합반응이덜일어나반응정 도가떨어질수있다. 나이가들수록피부반응이감소하고, 29) 알레 르겐에따라피부단자시험의양성판정기준을다르게고려해야하 거나, 22) 각각의검사에사용된알레르겐의추출물질이다른것등 을두검사결과가다른것에대한이유로생각할수있다. 본연구에서 ImmunoCAP 을전체환자를대상으로시행하지 못하였고, 일부알레르겐의경우대상환자수가적은한계점이있 어이러한점들을보완한추가적인연구가필요하리라생각된다. 피부단자시험과 ImmunoCAP 은흡입알레르겐에따라다양 한일치율, 민감도, 특이도를보였다. 대부분의알레르겐에서통계 적으로유의한양의상관관계를확인하였다. Birch, mugwort, Japanese Hop, 집먼지진드기는매우높은상관관계를보였으나, 그외 알레르겐에대해서는다양한정도의상관관계를보였다. 따라서, 환자의원인알레르겐을규명하고자할때알레르겐에따라피부단 자시험과 ImmunoCAP 을비교하여원인알레르겐을결정하는것 이바람직할것이다. REFERENCES 1. Meltzer EO, Blaiss MS, Derebery MJ, Mahr TA, Gordon BR, Sheth KK, et al. Burden of allergic rhinitis: results from the Pediatric Allergies in America survey. J Allergy Clin Immunol 2009;124(3 Suppl):S43-70. 2. Hamilton RG. Clinical laboratory assessment of immediate-type hypersensitivity. J Allergy Clin Immunol 2010;125(2 Suppl 2):S284-96. 3. Plebani M, Borghesan F, Faggian D. 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