pissn: eissn: Allergy Asthma Respir Dis 6(4): , July ORIGINAL ARTICLE 소아구강알레르

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1 pissn: eissn: (4): , July ORIGINAL ARTICLE 소아구강알레르기증후군의원인과임상특성 박영아, 1 정경욱, 2 김윤희, 1 설인숙, 1 김경원, 1 손명현, 1 이수영, 2 김규언 3 1 연세대학교의과대학소아과학교실및알레르기연구소, 2 아주대학교의과대학소아과학교실, 3 소화아동병원 Etiology and clinical feature of oral allergy syndrome in children Young A Park, 1 Kyung-Uk Jeong, 2 Yoon Hee Kim, 1 In Suk Sol, 1 Kyung Won Kim, 1 Myung Hyun Sohn, 1 Soo Young Lee, 2 Kyu-Earn Kim 3 1 Department of Pediatrics and Institute of Allergy, Yonsei University College of Medicine, Seoul; 2 Department of Pediatrics, Ajou University College of Medicine, Suwon; 3 Sowha Children s Hospital, Seoul, Korea Purpose: Oral allergy syndrome (OAS) is a unique allergic reaction to fresh fruits or vegetables, which is caused by cross-reactivity between foods and pollens. This study was conducted to investigate the clinical feature of OAS and relevant pollen allergens as well as the association between them in Korean children. Methods: This single-center study included 290 children who were sensitized to pollens at Severance Hospital, and the clinical characteristics of children with and without OAS were compared. A multicenter study included 97 children who were diagnosed with OAS at 3 hospitals between January 2008 and June The details of clinical features were collected by retrospective medical record reviews using a standardized case report form. The relevant pollen allergens were identified by skin prick tests and/or serum specific IgE levels. Results: The most commonly sensitized allergen was Japanese hop in pollen-sensitized children. Children with OAS were most commonly sensitized to birch and oak, and 12.4% of the pollen-sensitized children had OAS in the single center. The number of children who were newly diagnosed with OAS has increased over the past 7 years. The most common causative food of OAS was apple. More than 60% of patients with OAS had oral allergic reactions to multiple foods. Conclusion: OAS may be relatively common in pollen-sensitized children. OAS should be considered in children with allergic disease and sensitization to pollens. ( 2018;6: ) Keywords: Oral allergy syndrome, Pediatric allergy, Pollen sensitization 서론구강알레르기증후군 (oral allergy syndrome) 은식품알레르기의한아형으로, 과일또는채소와같은음식물을먹은직후에접촉한부위인입술, 구강, 인두부위에가려움증, 혈관부종, 홍반이나타나는것이특징이다. 1 이것은식물성식품과꽃가루항원이구조적으로연관이되어나타나는교차반응 (cross reactivity) 에의한것 으로, 꽃가루-식품알레르기증후군 (pollen-food allergy syndrome) 이라고불리기도한다. 2,3 구강알레르기증후군은성인에서관찰되는가장흔한식품알레르기이며, 꽃가루알레르기가있는성인에서는 8% 50% 로연구대상및지역에따라다양한유병률을보인다. 4,5 꽃가루에대한감작률은나이에따라증가하는경향을보이기때문에구강알레르기증후군은성인에비해소아에서는낮은빈도를보인다. 3,6,7 국내에서는꽃가루감작이있는성인의약 35% 에 Correspondence to: Sooyoung Lee Department of Pediatrics, Ajou University School of Medicine, 206 World cup-ro, Yeongtong-gu, Suwon 16499, Korea Tel: , Fax: , jsjs87@ajou.ac.kr Co-correspondence to: Myung Hyun Sohn Department of Pediatrics and institute of allergy, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea Tel: , Fax: , MHSOHN@yuhs.ac This study was supported by the Outstanding Fellow Research Grant of the Korean Academy of Pediatric Allergy and Respiratory Disease Received: December 1, 2017 Revised: April 13, 2018 Accepted: April 20, 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 (

2 Park YA, et al. Oral allergy syndrome in pollen-sensitized children 서구강알레르기증상이있었다는보고가있으나, 8 소아에서의구강알레르기증후군의유병률에대한연구는부족한상황이다. 1980년대꽃가루알레르기의유병률은약 15% 20% 였으나, 2013 년서울및경기지역거주성인에서꽃가루알레르기는 58.3% 로꾸준한증가를보였다. 9,10 국내소아알레르기환자에서꽃가루감작률은 2009년에 6.2% 로 1990년대와비교하였을때증가추세를보였으며, 꽃가루에대해감작이시작되는연령도낮아졌다. 11 이연구에서는최근소아에서의꽃가루감작률을확인하고, 꽃가루항원에감작이있는소아에서구강알레르기증상의유무에따른임상양상을비교하고자하였다. 또한소아구강알레르기증후군환자의원인식품과임상양상을확인하고자하였다. 대상및방법 반한부종이나홍반이관찰되는경우로정의하였다. 12 3) 알레르기피부단자시험알레르기피부단자시험에포함된꽃가루항원은수목 ( 떡갈나무 [oak], 일본삼나무 [Japanese cedar], 자작나무 [birch], 소나무 [pine], 개암나무 [hazelnut], 아카시아나무 [acacia]), 목초 ( 우산잔디 [bermuda grass], 오리새 [orchard grass], 겨이삭 [red top], 큰조아재비 [timothy]), 잡초 ( 돼지풀 [ragweed], 미역취 [golden rod], 환삼덩굴 [Japanese hop], 산쑥 [sagebrush]) 이며, Allergopharma Ltd. (Reinbek, Germany) 시약을사용하였다. 0.9% 생리식염수와히스타민용액 (1 mg/ml) 을각각음성과양성대조군으로사용하였고양성반응의기준은검사 15분후형성된팽진 (wheal) 의크기가 3 mm 이면서양성대조군보다큰경우로정의하였다 대상 1) 단일기관연구꽃가루감작이확인된소아중에서, 구강알레르기증후군증상이동반된경우는증상이없는소아와어떤임상양상의차이를보이는지알아보기위하여단일기관연구를시행하였다. 2008년 1월부터 2013년 12월까지세브란스병원소아청소년과에서알레르기피부단자시험을시행한 18세미만의소아총 1,097명중꽃가루에양성반응을보인 290명을대상으로하였다. 꽃가루에감작이확인된 290명중구강알레르기증후군진단을받은 36명과구강알레르기증상이없는 254명으로나누어임상양상을비교하였다. 2) 다기관연구구강알레르기증후군의임상양상을분석하고자, 다기관연구를시행하였다. 2008년 1월부터 2013년 12월까지세브란스병원에서진단을받은 36명과 2008년 1월부터 2014년 6월 30일까지강남세브란스병원, 아주대학교병원에서진단을받은 18세미만의소아 22 명, 39명을각각포함하여, 총 97명을대상으로하였다. 2. 방법 1) 자료의수집후향적의무기록자료수집을통해서피부단자시험및구강알레르기증후군의진단연령, 성별, 임상증상, 알레르기질환의병력에대한정보를확인하였다. 이연구는해당 3개병원연구심의위원회 (Institutional Review Board) 의심의를통과하였다 ( , , AJIRB-MED-MDB-14). 2) 구강알레르기증후군의진단구강알레르기증후군은병력청취를통하여진단하였으며, 가공하지않은과일이나야채섭취후입술이나구강내가려움증을동 4) 혈액호산구수와혈청총 IgE 측정모든대상자는말초혈액을채취하여말초혈액총호산구수와혈청총 IgE를측정하였다. 혈액내호산구수는말초혈액을채취하여 NE-8000 (Sysmes, Kobe, Japan) 을이용하여계수하였다. 혈청총 IgE, 항원특이 IgE는 CAP radioallergosorbent technique (Uni- CAP, Pharmacia and Upjohn, Uppasala, Sweden) 을이용하여측정하였다. 5) 알레르기비염, 알레르기천식, 아토피피부염병력청취에서반복되는콧물, 코막힘, 재채기등의특징적인알레르기비염의임상증상이있고, 흡입항원에대한혈청특이 IgE 항체또는피부단자시험양성인경우에알레르기비염으로진단하였다. 14 천식은기침이나호흡곤란의증상을동반하며, 기관지확장제사용후 1초노력호기량 (forced expiratory volume in 1 second) 이 12% 이상증가한경우나메타콜린과만니톨을이용한기관지유발시험에서기도과민성이있는경우 ( 메타콜린, PC mg/ml; 만니톨, PD mg) 에진단하였다. 15 아토피피부염은임상적으로특징적인피부소견이있는경우의사의판단하에진단하였다. 16 6) 통계분석통계분석은 IBM SPSS Statistics ver (IBM Co., Armonk, NY, USA) 을이용하였다. 정규분포를보이는측정값은평균과표준편차 (mean±standard deviation) 로표시하였으며, 비정규분포를보이는측정값은중앙값과사분위간범위 (median [interquartile range]) 로표시하였다. 두군간분석에서는 Student t-test 또는 chi-square test를적용하였고, 비정규분포를보이는측정값에대하여는 Mann-Whitney test를적용하였다. P값이 0.05 미만일때 220

3 박영아외 소아알레르기증후군 통계적으로유의한것으로판단하였다. 결과 1. 꽃가루감작률과구강알레르기증후군유무에따른비교 ( 단일기관연구 ) 2008년 1월부터 2013년 12월까지세브란스병원에서피부반응시험을시행한소아청소년은 1,097명이었고, 이중에서꽃가루에양성반응을보인소아는 290명으로 26.4% 였다. 꽃가루에양성을보인단일기관의소아 290명의평균연령은 10.19±2.81세이고, 이중 225명 (77.6%) 은알레르기비염, 118명 (40.7%) 은천식, 37명 (12.8%) 은아토피피부염, 18명 (6.2%) 은알레르기결막염을진단받았다 (Fig. 1). 꽃가루에양성반응을보인 290명에서가장높은감작률을보인꽃가루는환삼덩굴 (120 명, 41.4%) 이었다. 그다음에이어, 떡갈나무 (37.2%), 자작나무 (36.9%), 산쑥 (29.0%), 미역취 (26.6%), 아카시아 (23.8%) 순서로높은감작률을보였다 (Fig. 2). 꽃가루에감작이확인된대상자 290명중 36명 (12.4%) 이구강알레르기증후군진단을받았다. 평균연령은 10.06±3.10세이며, 가장어린환자의연령은 5세였다. 꽃가루에감작이확인된대상자중에서구강알레르기증상이있는군은구강알레르기증상이없는군에비하여여성의비율이높았다 (P = 0.013). 두군에서나이, 혈청호산구수, 혈청총 IgE 수치는통계적으로유의한차이를보이지않았다 (Table 1). 구강알레르기증상이있는 36명에서가장높은감작률을보인꽃가루는자작나무와떡갈나무 ( 각각 23명, 63.9%) 이고, 환삼덩굴 (36.1%), 아카시아 (23%), 산쑥 (23%) 의순서로높은빈도를보였다 (Fig. 2). 알레르기질환의동반빈도는알레르기비염이가장많았고, 그다음으로천식, 아토피피부염순서이며, 꽃가루감작이확인된전체환자에서보이는빈도와비슷한양상을보였다 (Fig. 1). Chronic urticaria Allergic conjunctivitis Atopic dermatitis Asthma Pollen-sensitized children Oral allergy syndrome 2. 구강알레르기증후군의임상양상 ( 다기관연구 ) 세기관에서구강알레르기증후군을진단받은전체 97명의평균연령은 9.52±0.35세이고, 가장어린소아는 3세였다. 2008년에구강알레르기증후군진단을받은소아는 6명, 2009년에 7명, 2010년에 4명이었고, 2012년에는 20명, 2013년 22명, 2014년 28명으로뚜렷 Fig. 1. Distribution of allergic diseases in pollen-sensitized children (n = 290) and distribution of combined other allergic diseases in children with oral allergy syndrome (n= 36) in a single center. (%) Allergic rhinitis Japanese hop Birch (%) Oak Sagebrush Goldenrod Fig. 2. Sensitization rates to pollen allergens. The most common sensitized allergens were Japanese hop followed by birch, oak, sagebrush in pollen-sensitized children (n= 290). Birch and oak were the most commonly sensitized allergens in children with oral allergy syndrome (n= 36) in a single center. Acacia Timothy grass Pollen-sinsitized children Oral allergy syndrome Orchard grass Ragweed Bermuda grass Table 1. Comparison of children with or without oral allergy syndrome (OAS) in a single center (n= 290) Variable OAS (n= 36, 12.4%) Non-OAS (n= 254, 87.6%) P-value Male sex 20 (55.6) 191 (75.2) Age (yr) 10.06± ± Eosinophil count (/μl) 340 (275) 390 (380) Serum total IgE (ku/l) 317 (421) 401 (666) Asthma 14 (38.9) 104 (40.9) Allergic rhinitis 24 (66.7) 201 (79.1) Values are presented as number (%), mean± standard deviation, or median (interquartile range). No. of patients Year Fig. 3. Yearly incidence of oral allergy syndrome showing an increasing tendency (n= 97, multicenter study)

4 Park YA, et al. Oral allergy syndrome in pollen-sensitized children Table 2. Food that caused oral allergy syndrome (n= 97, multicenter study) Causative food No. of patients (%) Apple 59 (60.8) Peach 34 (35.1) Kiwi 26 (26.8) Watermelon 17 (17.5) Plum 11 (11.3) Oriental melon 10 (10.3) Pear 10 (10.3) Melon 9 (9.3) Banana 8 (8.2) Cherry 8 (8.2) Pineapple 8 (8.2) 한증가추세를보였다 (Fig. 3). 모든소아는피부단자시험이나항원특이 IgE 검사에서꽃가루에감작이확인되었다. 집먼지진드기에감작이확인된소아는 62명 (63.9%), 고양이비듬에는 21명 (21.6%), 개털에는 20명 (20.6%), 곰팡이에는 6명 (6.2%) 이었다. 일부대상은꽃가루외흡입항원에대한감작여부를확인하지않았다. 구강알레르기증후군의가장흔한원인음식은사과 (59명, 60.8%) 이고, 그다음에이어복숭아 (34명, 35.1 %), 키위 (26명, 26.8%) 가많았다 (Table 2). 구강알레르기증상이있는소아중에서한가지과일에만증상이있는소아는 32명 (33.0%) 이고, 7명 (7.2%) 은 5가지이상의음식에증상이있었다. 자작나무에감작이확인된소아중 52 명 (74.3%) 이사과에구강알레르기증상을보였으며, 34.3% 는복숭아, 24.3% 는키위, 11.4% 는자두에증상이있었다 (Table 3). 돼지풀에감작이확인된소아중 15.6% 는수박에구강알레르기증상이있었고, 잔디에감작이확인된소아중 15.2% 는참외에증상이있었다. 고찰이연구에서알레르기질환이있는소아청소년의꽃가루감작률은 26.4% 이고, 꽃가루중에서환삼덩굴 (41.4%) 이가장높은감작률을보였다. 꽃가루알레르기가있는소아의 12.4% 가구강알레르기증후군진단을받았으며, 여아의비율이높았다. 구강알레르기증후군으로진단된소아에서가장높은감작률을보인꽃가루는자작나무 (74.3%) 이고, 원인식품은사과가 59% 로가장많았다. 우리나라학동기소아의나무감작률은 9.8%, 잡초감작률은 2.0% 를보인최근보고와비교하였을때, 17 이번연구는알레르기질환이있는소아청소년을대상으로하였기때문에꽃가루감작률이뚜렷하게높다. 환삼덩굴은알레르기질환이있는국내성인의감작률이 1999년에 27.5% 에서 2008년에 36.9% 로증가하는양상을보 Table 3. Association between pollen and causative food in oral allergy syndrome (n= 97, multicenter study) Pollen Food No. of patients (%) Birch (n= 70) Apple 52 (74.3) 였고, 18 이후기후변화의영향으로국내환삼덩굴꽃가루의항원성 이증가하고있다는보고가있었다 년이후에진행된이연 구에서, 알레르기질환이있는소아의 41.4% 가환삼덩굴에감작이 확인되었고, 꽃가루중에서가장높은감작률을보였다. 이연구를 통해국내소아에서환삼덩굴감작률이증가함을확인할수있었 으며, 향후국내꽃가루알레르기에서환삼덩굴을주요원인항원 으로고려해야할것이다. 꽃가루알레르기가있는소아의 12.4% 가구강알레르기증상을 보였다. 과거의연구들은구강알레르기증후군의유병률을매우다 양하게보고하였다. 20,21 낮은유병률을보인이전보고에서, 구강알 레르기증상은약하고일시적인경우가많기때문에환자들이증 상을지나치거나, 의사에게진단받지못하는경우가많아실제보다 낮은유병률이조사되었을가능성이있다고저자들이강조하였 다. 3 구강알레르기증후군의가장확실한진단방법은이중맹검위 약대조식품유발시험 (double-blind, placebo-controlled oral food challenge) 이다. 22 아직다양한식품에대해표준화된프로토콜이 확립되어있지않고, 검사중부작용의위험성때문에식품유발시 험은임상적으로널리사용되지못하고있으며, 이를대체하는진 단법으로병력청취와피부단자시험, 혈청특이 IgE 검사등이활용 되고있다. 12,23 이중에서병력청취가구강알레르기증후군의진단 에가장중요한데, 소아의병력은부모에게서얻는경우가대부분 이다. 경미한구강알레르기증상을보이는소아의경우에는부모 가인지하기어렵기때문에, 특히소아를대상으로한이연구에서 확인된구강알레르기증후군의실제빈도는결과보다더높을가능 성도고려해야한다. 그러나, 알레르기질환이있는멕시코소아의 8.9%, 시드니소아의 14.7% 에서구강알레르기증상이있다는최근 보고는이연구의 12.4% 와유사한빈도를보여주고있어서, 이연 구결과는앞으로진행되는국내소아구강알레르기증후군연구의 참고자료가될수있을것이다. 6,7 Peach 24 (34.3) Kiwi 17 (24.3) Plum 8 (11.4) Ragweed (n= 32) Watermelon 5 (15.6) Grass (n= 33) Oriental melon 5 (15.2) 구강알레르기증후군의위험인자에대한연구는많지않은데, 꽃가루알레르기비염이있는환자중에서성별이여성일때, 혹은비 염증상중코가려움증의증상만동반한경우에구강알레르기증 상발생의위험이높다는보고가있다. 20 이번연구에서도구강알레 르기증후군은여아의비율이높았으며, 의무기록을조사한후향적 222

5 박영아외 소아알레르기증후군 연구의한계로알레르기비염의자세한증상비교는어려웠다. 전체소아 290명에서환삼덩굴이가장높은감작률을보였지만, 기존연구와마찬가지로구강알레르기증상이있는소아 36명에서는자작나무가가장높은감작률을보였다. 과거보고에서자작나무에감작이있는경우에는 50% 70% 에서구강알레르기증상이있다고알려져있으며, 사과, 복숭아, 개암, 샐러리, 감자, 살구, 땅콩등에증상이생길수있다. 5,24 자작나무에감작이확인된 70명중에서 52명이사과에구강알레르기증상이있었으나, 헤이즐넛, 샐러리, 살구, 땅콩등에증상을보인증례는없었다. 구강알레르기증후군은지역에따라다양한꽃가루분포의영향을받는다. 25 일본에서는일본삼나무가 60% 80% 의가장높은감작률을보이기때문에, 삼나무의주요항원인 Cry j 3와교차반응을보일수있는토마토에대한구강알레르기증후군보고가많다. 26,27 이연구대상소아에서토마토에구강알레르기증상이있는 7명은모두일본삼나무에감작이되어있지않았다. 잔디와연관된구강알레르기증상은스페인의보고가많은데, 스페인은자작나무및돼지풀에감작률이매우낮고잔디에대한감작률이높기때문이다. 잔디에감작이있는경우는복숭아에주로증상을보이는것으로알려져있지만, 28 이번연구에서는 33명중 5명이참외에서증상이있었고복숭아에는증상이보이지않았다. 돼지풀에감작이있는경우에는멜론, 바나나, 수박등에구강알레르기증상이생길수있는데, 29 이연구대상자들은주로수박 (15.6%) 에증상이있었다. 구강알레르기증후군은식품에대한기호와음식문화의영향을받기때문에지역이나연령에따른차이를보일수있다. 3 열대과일의소비가많은멕시코에서소아구강알레르기증상의가장흔한원인식품인파인애플은이연구대상자의약 8% 에서만증상을보였다. 7 해외에서는멜론이나아보카도와연관된구강알레르기증후군에대한보고가있고, 1 국내에서도최근성인에서쑥갓, 깻잎과연관된구강알레르기증상에대한보고가있었지만, 30 이연구에서이와같은증례는없었다. 이연구는수도권에위치한 3개의대학병원에서구강알레르기증후군진단을받은소아를대상으로하였기때문에일부지역의자료라는제한점이있다. 또한병력청취과정에서부모의회상오류나선택오류가개입하였을가능성이있다. 마지막으로, 구강알레르기증후군의원인식품에대해경구유발시험과같은객관적평가방법을시행하지않은제한점이있다. 구강알레르기증후군증상은대부분경미하나, 드물게심한전신반응으로진행할수있다. 1 구강알레르기증후군은식품제한으로예방이가능하고면역치료에도효과가있기때문에원인항원과식품을확인하는것이중요하다. 31 이연구는꽃가루감작이있는소아청소년에서구강알레르기증후군의원인식품과의연관성을분석했다는점에서의의를갖는다. 결론적으로이연구를통하여국내소아청소년에서꽃가루감작 률과구강알레르기증후군의유병률을확인하였고, 구강알레르기 증후군의빈도가점차증가하고있음을알수있었다. 앞으로체계 적인전향적조사를통한국내소아구강알레르기증후군의중증 도및꽃가루와관련된원인식품에대한대규모연구가필요할것 으로생각한다. REFERENCES 1. Mari A, Ballmer-Weber BK, Vieths S. The oral allergy syndrome: improved diagnostic and treatment methods. Curr Opin Allergy Clin Immunol 2005;5: Yagami T, Haishima Y, Nakamura A, Osuna H, Ikezawa Z. Digestibility of allergens extracted from natural rubber latex and vegetable foods. J Allergy Clin Immunol 2000;106: Ma S, Sicherer SH, Nowak-Wegrzyn A. A survey on the management of pollen-food allergy syndrome in allergy practices. J Allergy Clin Immunol 2003;112: Katelaris CH. Food allergy and oral allergy or pollen-food syndrome. Curr Opin Allergy Clin Immunol 2010;10: Hoffmann-Sommergruber K, O'Riordain G, Ahorn H, Ebner C, Laimer Da Camara Machado M, Pühringer H, et al. Molecular characterization of Dau c 1, the Bet v 1 homologous protein from carrot and its cross-reactivity with Bet v 1 and Api g 1. Clin Exp Allergy 1999;29: Brown CE, Katelaris CH. The prevalence of the oral allergy syndrome and pollen-food syndrome in an atopic paediatric population in southwest Sydney. J Paediatr Child Health 2014;50: Bedolla-Barajas M, Kestler-Gramajo A, Alcalá-Padilla G, Morales-Romero J. Prevalence of oral allergy syndrome in children with allergic diseases. Allergol Immunopathol (Madr) 2017;45: Cho YS, Lim YJ, Lee JC, Kim SH, Lim MK, Yoo B, et al. Oral allergy syndrome in pollen - sensitized patients. J Asthma Allergy Clin Immunol 1998;18: Dreborg S. Food allergy in pollen-sensitive patients. Ann Allergy 1988; 61(6 Pt 2): Park HJ, Lee JH, Park KH, Kim KR, Han MJ, Choe H, et al. A six-year study on the changes in airborne pollen counts and skin positivity rates in Korea: Yonsei Med J 2016;57: Kim JH, Oh JW, Lee HB, Kim SW, Kang IJ, Kook MH, et al. Changes in sensitization rate to weed allergens in children with increased weeds pollen counts in Seoul metropolitan area. J Korean Med Sci 2012;27: Webber CM, England RW. Oral allergy syndrome: a clinical, diagnostic, and therapeutic challenge. Ann Allergy Asthma Immunol 2010;104: Yun YY, Ko SH, Park JW, Hong CS. IgE immune response to Ginkgo biloba pollen. Ann Allergy Asthma Immunol 2000;85: Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, Togias A, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy 2008;63 Suppl 86: Crapo RO, Casaburi R, Coates AL, Enright PL, Hankinson JL, Irvin CG, et al. Guidelines for methacholine and exercise challenge testing This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July Am J Respir Crit Care Med 2000; 161: Williams H, Stewart A, von Mutius E, Cookson W, Anderson HR; International Study of Asthma and Allergies in Childhood (ISAAC) Phase One and Three Study Groups. Is eczema really on the increase world

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386-390.hwp 386 HANYANG MEDICAL REVIEWS Vol. 29 No. 4, 2009 우리나라 미숙아의 통계와 의료비용 Statistics and Medical Cost of Preterm in Korea 윤혜선 을지대학교 노원을지병원 소아청소년과학교실 Hye Sun Yoon, M.D., Ph.D., Department of Pediatrics, Nowon