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1 pissn: eissn: (6): , November ORIGINAL ARTICLE 소아에서혈청 25-hydroxyvitamin D 와알레르기비염의연관성 윤서희, 김정윤, 김윤희, 박영아, 설인숙, 김민정, 김경원, 손명현, 김규언 연세대학교의과대학소아과학교실, 알레르기연구소 Association between the serum 25-hydroxyvitamin D level and allergic rhinitis in Korean children Seo Hee Yoon, Jung Yoon Kim, Yoon Hee Kim, Young A Park, In Suk Sol, Min Jung Kim, Kyung Won Kim, Myung Hyun Sohn, Kyu-Earn Kim Department of Pediatrics, Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea Purpose: Vitamin D is known to play an important role in the regulation of the immune system and in the prevention of allergic disease. Herein, we examined the association between vitamin D and allergic rhinitis (AR) in children. Methods: A total of 72 aeroallergen-proven AR and 57 healthy control subjects who visited Severance Children s Hospital between 2012 and 2014 were evaluated. The mean serum 25-hydroxyvitamin D (25(OH)D) level was measured in all subjects to evaluate their vitamin D status. Results: The mean serum 25(OH)D levels was significantly lower in patients with AR than in controls (19.5 ± 6.4 ng/ml vs ± 5.8 ng/ml, P = 0.013). The incidence of AR is higher in the 25(OH)D-insufficient group (15 20 ng/ml) and in the 25(OH)D-deficient group ( 15 ng/ml) compared with the 25(OH)D-sufficient group ( > 20 ng/ml) (40.3% vs. 84.4% vs. 22.2%, P< 0.001). There was no significant difference in the serum 25(OH)D level between subgroups with mild and moderate-to-severe AR symptoms (19.8 ± 6.5 vs ± 6.3, P= 0.596). After adjusting for confounding factors, the lower serum vitamin D level groups had increased odds of AR compared with the 25(OH)D-sufficient group (odds ration [95% confidence interval]; 3.67 [ ] in the 25(OH)D-insufficient group; P= and 6.04 [ ] in the 25(OH)D-deficient group; P= 0.012). Conclusion: The serum vitamin D levels were significantly lower in children with AR compared with healthy controls. Therefore, lower serum level of 25(OH)D may be associated with the development of AR. ( 2016:4: ) Keywords: Allergic rhinitis, Vitamin D, Childhood 서론알레르기비염 (allergic rhinitis, AR) 은비점막이흡입항원에노출된후재채기, 맑은콧물, 코막힘, 코의가려움, 후비루등의증상이유발되는 IgE 항체매개성 (IgE-mediated) 만성염증성질환이다. 1,2 알레르기비염은전세계인구의 40%, 3 미국성인인구의 10% 30% ( 소아는 40%), 4 유럽전체인구의약 23% 5 의유병률을보이며꾸준한증가추세를보이고있다. 6 한국의경우, 제5차국민건강영양조사보고서에따르면 19세이상성인의유병률은 13.6% 였고, 년전국소아청소년들을무작위추출하여조사한현증 알레르기비염유병률은 29.0% 였다. 8 알레르기비염은종종학교와직장에서의업무수행능력을저하시키거나수면에지장을초래하여삶의질과생산력을저하시키고, 천식의발생가능성을높이는위험인자로도알려져있어상당한경제적, 사회적부담을초래하는질병으로서주의가필요하다. 1,4,9 최근많은연구들이비타민 D (Vitamin D) 가칼슘항상성과뼈의무기질화등의전통적역할외에당뇨병이나암, 신경계, 심혈관계등의다양한질환의병리생태에관여하고있음을보고하였다 특히비타민 D는 T 림프구항원수용체의신호전달과활성화에중요한역할을하는것으로밝혀져, 후천면역과알레르기면역반 Correspondence to: Myung Hyun Sohn Department of Pediatrics, Institute of Allergy, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea Tel: , Fax: , MHSOHN@yuhs.ac Received: June 10, 2016 Revised: September 23, 2016 Accepted: September 23, 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 Yoon SH, et al. Vitamin D and allergic rhinitis in children 응에관련함도알려지고있다 또한비타민 D의체내수준을평가할때가장많이사용하는지표 16 인혈청 25-hydroxyvitamin D (25(OH)D) 가정상인보다천식이나알레르기비염환자들에서저하되어있음이보고되어체내비타민 D 부족이알레르기질환의발생위험인자들중하나가아닌가추정되고있다 소아의경우, 성인에비해알레르기질환과비타민 D의연관성을조사한연구가적고 20,21 특히국내에서소아알레르기비염과비타민 D에대한연구는매우드문상황이다. 22 따라서본저자들은알레르기비염을진단받은소아청소년과건강한대조군에서혈청비타민 D를비교하여알레르기비염과의연관성을조사해보고자하였다. 대상및방법 and Upjohn Diagnostics AB, Uppsala, Sweden) 면역형광효소법으로측정하였다. 혈청특이 IgE 검사는집먼지진드기 2종 (Dermatophagoides pteronyssinus [Der p], Dermatophagoides farinae [Der f]), 바퀴벌레, 곰팡이류 (Aspergillus fumigatus, Alternaria alternaria), 동물털또는상피세포 (cat fur, dog hair), 화분류 ( 쑥, 돼지풀, 참나무, 자작나무, 환삼덩굴 ) 등의흡입항원을 Phadia ImmunoCAP (ImmunoDiagnostics, Uppsala, Sweden) 을통해검사하였다. Phadia ImmunoCAP 검사는혈청특이 IgE 항체가 0.35 kua/l 이상인경우를양성으로정의하였고, 말초혈액호산구및백혈구숫자는자동화분석기기 (automatic hematology analyzer; ADVIA 2120, Siemens Healthcare Diagnostics, IL, USA) 를통해각각측정하였다 대상 2012년 1월부터 2014년 4월까지세브란스병원소아청소년과를방문한 3 18세소아청소년중알레르기비염으로진단받은 72명과건강검진을위해내원한건강한 57명, 총 129명을대상으로연구를실시하였다. 알레르기비염은콧물, 재채기, 코막힘, 소양감의증상이있으면서흡입항원에대한혈청특이 IgE 항체또는피부반응검사 (skin prick test) 가양성인경우로정의하였다. 1 알레르기비염군은 Allergic Rhinitis and its Impact on Asthma (ARIA) 가이드라인의분류에따라빈도 ( 간헐성또는지속성 ) 와중증도 ( 경증또는중등도-중증 ) 로군을나누어비교하였고, 모든대상자들을혈청 25(OH)D 농도에따라부족군 ( 15 ng/ml), 불충분군 (15 20 ng/ml), 충분군 ( >20 ng/ml) 세군으로나누어분석하였다. 23,24 대상자제외기준은혈중비타민 D 농도에영향을줄수있는전신질환 ( 구루병, 골다공증, 류마티스관절염, 궤양성대장염, 크론병, 갑상선질환등 ) 이나알레르기결막염외알레르기질환 ( 예, 천식이나아토피피부염 ) 을가지고있는경우, 또체내비타민 D 농도에영향을줄수있는약물이나보충제를먹고있는경우 ( 예, barbiturates, sulfasalazine, ketoconazole, 비타민 D 또는칼슘보충제 ) 로선정하였다. 본연구는세브란스병원연구심의위원회 (Institutional Review Board, IRB) 의승인을받았으며 ( 승인번호 : ) 모든참가대상자와보호자의동의를받은후실시하였다. 2. 방법 1) 혈청 25(OH)D, 혈청총 IgE, 특이 IgE 측정, 말초혈액호산구수측정연구시작시점에서모든피험자에게혈청 25(OH)D 와말초혈액백혈구수 (white blood cells), 총호산구수 (total eosinophil counts) 를측정하였다. 혈청 25(OH)D는 gamma counter (COBRA II, Packard, Meriden, CT, USA) 장비를이용하여 radioimmunoassay 법으로측정하였고, 총 IgE 농도는 CAP system FEIA (Pharmacia 2) 알레르기피부단자검사알레르기피부단자검사는집먼지진드기 2종 (Der p, Der f), 동물털또는상피세포 (cat fur, dog hair), 화분류 (grass mixture, tree pollen mixture, 쑥, 돼지풀 ), 진균류 (Aspergillus fumigatus, Alternaria alternata) 등우리나라에서흔한흡입항원들의추출물 (Allergopharma, Reinbek, Germany; Hollister-Stier, Spokane, WA, USA; Bencard, London, England) 을이용해환자의등에표준화된방법으로시행하였다. 히스타민용액 (1 mg/ml) 을양성대조군과 0.9% 생리식염수를음성대조군으로사용하였고검사 15분뒤형성된팽진 (wheal) 의크기가 3 mm면서히스타민의팽진보다클경우를양성으로판정하였다 통계분석통계적분석은 IBM SPSS Statistics ver (IBM Co., Armonk, NY, USA) 을사용하여분석하였다. 결과들은평균 ± 표준편차 (standard deviation, SD) 로나타내었으며, 빈도분석에는연속형자료의경우 t 검정이나 Mann-Whitney 검정을, 범주형자료의경우카이제곱검정 (chi-square test) 이나 Fisher 의정확한검정으로분석하였다. 상관분석을통해혈청 25(OH)D와총호산구수, 백혈구수, 나이, 체질량지수 (body mass index, BMI) 사이의연관성을알아보았으며, 비타민 D 농도에따른알레르기비염의발생위험률은이분형로지스틱회귀분석으로비차비 (odds ratios, ORs) 를구해알아보았다. 비차비와 95% 신뢰구간 (confidence interval, CI) 은나이, 채혈한계절, 성별, BMI를보정하여도출하였다. 통계적유의성은 P<0.05일때로정의하였다. 결과 1. 대상자특성연구에참여한총 129명의대상자중, 알레르기비염군은모두

3 윤서희외 비타민 D 와소아알레르기비염 Table 1. Clinical and demographic characteristics of the allergic rhinitis and control groups Characteristic 명이었고 ( 남자 46 명, 63.9%) 건강한대조군은 57 명 ( 남자 34 명, 59.7%) 이었다. 알레르기비염군과대조군의평균나이는각각 9.0± 3.2 세와 8.4±3.5 세였으며, 두군간에성별과평균나이는통계적 으로유의한차이는없었다 (Table 1). 총호산구수는대조군보다 알레르기비염군에서유의하게높은것으로나타났다 (369± /µl vs. 210± /µl, P<0.001) (Table 1). 2. 계절별혈청비타민 D 농도비교 채혈당시계절 27,28 에따른혈청 25(OH)D 의평균값은각각봄 (3 5 월 ) 20.91±6.70 ng/ml, 여름 (6 8 월 ) 24.2±5.7 ng/ml, 가을 (9 11 월 ) 21.3±5.4 ng/ml, 겨울 (12 2 월 ) 17.2±5.4 ng/ml 로겨울 이가장낮고여름이가장높았다 (P<0.001). 3. 알레르기비염군과대조군사이혈청비타민 D 농도비교 알레르기비염군과정상대조군사이의평균혈청 25(OH)D 농도 는각각 19.5±6.4 ng/ml 와 22.3±5.8 ng/ml 로, 알레르기비염군 에서보다유의하게낮았다 (P = 0.013) (Fig. 1A). 또한혈청 25(OH) D 수치에따라모든대상자를비타민 D 충분, 불충분, 부족군으로 나누었을때, 23 각군에서 AR 은비타민충분군에서는 16 명 (32.0%), 불충분군에서는 29 명 (61.7%), 부족군에서는 27 명 (84.4%) 으로, 혈 청 25(OH)D 가감소함에따라알레르기비염환자수는늘어나는 경향을보였다 ( 선형대선형결합 linear by linear association test, P<0.001) (Table 1). Allergic rhinitis (n= 72) Control (n= 57) P-value Age (yr) 9.0± ± Male sex 46 (63.9) 34 (59.6) BMI (kg/m 2 ) 17.8± ± WBC (/μl) 7,084± 1,953 6,880± 1, TEC (/μl) 369± ± 149 < (OH)D (ng/ml) 19.5± ± Serum vitamin D status Sufficient (> 20 ng/ml) 16 (32.0) 34 (68.0) Insufficient (15 20 ng/ml) 29 (61.7) 18 (38.3) < Deficient ( 15 ng/ml) 27 (84.4) 5 (15.6) Values are presented as mean± standard deviation or number (%). 25(OH)D, 25-hydroxyvitamin D; BMI, body mass index; WBC, white blood cell; TEC, total eosinophil count. Mean serum 25(OH)D (ng/ml) Mean serum 25(OH)D (ng/ml) Fig. 1. Comparison of serum vitamin D levels according to the presence of allergic rhinitis (A) and the Allergic Rhinitis and its Impact on Asthma (ARIA) classification (B). (A) The box plots show the significant difference in the mean 25-hydroxyvitamin D (25(OH)D) levels between the allergic rhinitis and control group. (B) No significant differences were observed among the ARIA classification subgroups. Allergic rhinitis was classified on the basis of the ARIA 2008 guideline. Data are expressed as mean± standard deviation. 성반응을보인경우는 44 명 (61.1%) 이었다. 감작된항원을실내와 실외항원으로구별했을때실내항원에만감작된환아는 48 명 (66.7%), 실외항원에만감작된환아는 4 명 (5.6%), 양쪽모두감작된 경우는 20 명 (27.8%) 으로, 세개의군에서평균 25(OH)D 농도차이 는관찰되지않았다 (P = 0.188) (Table 2). 감작된항원개수에따라 단일항원감작군과두개이상감작된다중항원감작군으로분류 하여비교하였을때 25(OH)D 농도차이또한관찰되지않았다 (data not shown). Allergic rhinitis Mild/ Intermittent Mild/ Persistent P= Subjects P= Controls Moderatesevere/ Intermittent Allergic rhinitis subgroups Moderatesevere/ Persistant A B 4. 알레르기비염군에서감작항원에따른혈청비타민 D 농도비교알레르기비염군에서가장많은빈도로감작된흡입항원은 Der f (88.9%) 와 Der p (76.4%) 였다. 적어도세개이상의흡입항원에양 5. 알레르기비염군에서중증도에따른혈청비타민 D 농도비교알레르기비염군을 ARIA 가이드라인에따라분류하면 18명 (25.0%) 은경증 / 간헐성, 30명 (41.7%) 은경증 / 지속성, 15명 (20.8%) 은중등도-중증 / 간헐성, 그리고 9명 (12.5%) 은중등도-중증 / 지속성군 425

4 Yoon SH, et al. Vitamin D and allergic rhinitis in children Table 2. Comparison of vitamin D status according to the types of sensitized inhalation antigen Variable Inhalation antigen Indoor* Outdoor Both No. of patients 48 (66.7) 4 (5.6) 20 (27.8) P-value 25(OH)D (ng/ml) 19.5± ± ± Values are presented as number (%) or mean± standard deviation. 25(OH)D, 25-hydroxyvitamin D. *Indoor allergens include; house dust, Dermatophagoides pteronyssinus, Dermatophagoides farinae, cockroach, Aspergillus fumigatus, Alternaria alternata, cat fur, dog hair. Outdoor allergens include; ragweed, mugwort, oak, birch, alder, hop Japanese, bermuda grass, grass mixture, tree pollen mixture. Table 3. Correlation between 25(OH)D and other factors Factor 25(OH) D Correlation (r) P-value Age < Total eosinophil count Total IgE White blood cell Body mass index (OH)D, 25-hydroxyvitamin D. Table 4. Risk of allergic rhinitis according to the vitamin D status Characteristic Serum vitamin D status Allergic rhinitis Unadjusted OR (95% CI) P-value Adjusted OR* (95% CI) P-value Sufficient (> 20 ng/ml) 1 (reference) 1 (reference) Insufficient (15 19 ng/ml) 2.03 ( ) ( ) Deficient ( 15 ng/ml) 4.03 ( ) ( ) (OH)D, 25-hydroxyvitamin D; OR, odds ratio; CI, confidence interval. *Adjusted for age, sex, seasons, total eosinophil count and body mass index. 에속하였다. 평균 25(OH)D 수치는중등도 -중증/ 지속성군에서가장낮았지만, 모든군사이에통계학적유의한차이는관찰되지않았다 (P = 0.321) (Fig. 1B). 또한알레르기비염환자군을다시증상의지속기간으로나누었을때지속성군에서간헐성군보다평균 25(OH)D 수치는낮았지만통계적유의성은없었고 (18.6±5.7 vs. 20.6±7.1, P = 0.186), 질환의중증도로경증군과중등도-중증군을나누었을때두군간혈청 25(OH)D 농도의유의한차이또한보이지않았다 (19.8±6.5 vs. 19.0±6.3, respectively, P = 0.596). 6. 혈청비타민 D 농도와다른임상지표간의상관관계알레르기비염군에서나이가증가함에따라혈청 25(OH)D 의수치는감소하는상관관계를보였다 (r = 0.319, P<0.001). 총호산구수, 백혈구수, 체질량지수는혈청 25(OH)D 농도와유의한상관성이관찰되지않았다 (Table 3). 총호산구수와혈청총 IgE 사이는양의상관관계 (r = 0.463, P<0.001) 를보였다. 7. 비타민 D 부족과알레르기비염과의연관성나이, 계절, 성별, 체질량지수를보정한후비타민 D-불충분군그리고부족군과충분군끼리알레르기비염환자수를비교해보았을때, 충분군에비해불충분군과부족군에서각각약 4배 (OR, 3.67; 95% CI, ; P = 0.014), 6배 (OR, 6.04; 95% CI, ; P = 0.012) 로알레르기비염에대한위험성이증가하였다 (Table 4). 그외 BMI의증가에따라알레르기비염에대한위험성은 1.3 배가증가하였다 (OR, 1.29; 95% CI, ; P = 0.003). 고찰이번연구에서는소아알레르기비염환자에서 25(OH)D 수치가정상대조군보다유의하게낮았고, 비타민 D에영향을미칠수있는요인들을보정한후에도혈청비타민 D 부족군과불충분군에서충분군보다알레르기비염의위험도가유의하게높아짐을확인할수있었다. 혈청비타민 D 수치와알레르기비염의관계를보고한다른연구들도비슷한결과를보여주고있는데, 국내제4기국민건강영양조사 ( ) 자료에따르면 18세이상의성인 8,012명에서혈청 25(OH)D 수치가저하될수록알레르기비염의유병률은높아지는것으로나타났고, 29 Arshi 등 20 도이란의건강한인구와비교했을때알레르기비염환자들에게서심각한비타민 D 결핍이더많다고보고하였다. 또한최근미국에서실시된코호트연구에서어머니가임신제 1, 2분기에하루음식으로섭취한비타민 D 100 IU당자녀가학동기알레르기비염을앓을위험도가각각 21% 와 20% 씩감소하는것이밝혀져비타민 D 부족과알레르기비염이밀접한연관이있음을알수있었다. 30 비타민 D가알레르기비염의발병에관여하는기전으로는우선선천면역계에서비타민 D는호흡기상피세포와피부의내인성항균성펩타이드발현을증가시켜외부항원에대한장벽을강화시킨 426

5 윤서희외 비타민 D 와소아알레르기비염 다. 또한후천면역계에서비타민 D는수지상세포의성숙을억제하고표면수용체를감소시켜항원전달능력을저해하며, CD4+ T 세포에직접작용하여 interleukin-10- 분비 CD4+ 조절 T 세포의생산을촉진하여면역관용상태를유도하는것으로알려져있다. 31 위의연구결과들을종합해보면, 비타민 D가부족할때코점막을통해접하게되는외부항원에대한장벽이약화되고, 면역관용이감소하여항원감작과알레르기비염발생이증가할수있다. 최근상기연구결과들을토대로비타민 D 부족을개선하여알레르기비염치료에이용하려는연구들도보고되고있는데, Modh 등 32 은, 비타민 D가부족한알레르기비염환자들에게서비타민 D 보충후상당한임상적호전을가져왔음을보고하였다. 또한비타민 D 부족이있는알레르기비염환자들에게한해치료적목적의비타민 D 보충을제안하기도하였으나, 아직적절한비타민 D의체내농도와비타민 D 보충시기, 예방목적또는치료목적에따른최적화된용법및용량등에대한자료가부족하여이에대한추가적인연구가필요할것으로보인다. 33 이번연구에서는알레르기비염환자군을감작된항원종류와질병의중증도에따라분류하여비타민 D의차이가있는지를살펴보았다. 알레르기질환에서감작항원과비타민 D 농도를연구한연구들은적은편이나아토피환자들에게서비타민 D 부족시 (25(OH)D <30 ng/ml) 식품항원감작에대한위험성이증가한다는보고가있었고, 28 반대로 Lim 등 34 은혈청비타민 D 증가가집먼지진드기및바퀴벌레흡입항원감작과연관이있다고보고한바가있다. 일반인들을대상으로 에진행된미국국민건강영양조사 (National Health and Nutrition Examination Survey) 35 에서는소아청소년에서비타민 D 부족군 (25(OH)D<15 ng/ml) 이충분군 (25(OH)D>30 ng/ml) 보다돼지풀과참나무에대한감작위험성이유의하게증가하였음이관찰되었는데, 동물털 (dog), 곰팡이 (Alternaria) 같은실내항원에대한감작또한유의하게증가하는것이관찰되었다. 그러나실내항원중집먼지진드기 (Der p, Der f) 는유의한연관성을보이지않았다. 이번연구에서는실내항원단독감작군이나실외항원단독감작군그리고양쪽모두감작된군에서혈청비타민 D 농도차이는보이지않았고, 단일항원감작군과다중항원감작군사이혈청비타민 D 농도차이또한관찰되지않았다. 이번연구에서는조사대상자들중많은수가실내, 실외양쪽항원모두에감작이되어있어실내및실외항원종류별로미치는비타민 D 농도의영향을알아보기에어려움이있었고, 실외항원만감작된대상자가매우적어실외항원감작에대한결론을내리기에는한계가있었다. 이번연구에서는알레르기비염환자군을 ARIA 가이드라인에따라분류하여혈청 25(OH)D 와의연관성을살펴보았으나, 분류한군사이에혈청 25(OH)D 의유의한차이를발견할수없었다. 중등도가높고증상지속기간이긴중등도 -중증/ 지속성군에서 4개의 아군중혈청평균 25(OH)D 가가장낮았지만, 다른군들과유의한 차이를보이진않았다. ARIA 가이드라인에서는질환의중증도가 환자개개인의삶의질 (quality-of-life) 을저해하는지의여부로구 분되며, 증상의기간또한개인의주관적인보고로나누어지므로, 1 특정생물학적인표지자로뒷받침되어분류된것은아닌만큼가 이드라인에의해분류한질환의중증도와혈청비타민 D 사이의 연관성을밝히는것은어려울수있다고생각한다. 그외혈청비타민 D 농도에영향을줄수있는다양한인자들중 유일하게연령이혈청 25(OH)D 수치와음의상관관계를보였다. 이 것은연령이증가하면서체내의비타민 D 저장능력이감소하고피 부에서비타민 D3 를생산하는능력이감소하기때문으로추정된 다. 36,37 또한다른연구결과들과비슷하게혈청 25(OH)D 수치는체 질량지수와음의상관관계를보였는데, 이는비타민 D 가체지방에 침착되어비타민 D 의생체이용률 (bioavailability) 이떨어지기때문 으로제시되나, 통계적으로유의한결과를보이진않았다. 38 따라서 알레르기비염치료에서비타민 D 보충요법을적용할때나이와체 질량지수에대한고려가필요할것으로생각한다. 이번연구저자들은국내소아청소년에서혈청 25(OH)D 수치를 알레르기비염환자와정상인간에비교해보았다. 이번연구의결 과는 25(OH)D 수치에영향을주는인자들을교정하고난후에도 의미있는결과를보였으나, 다음과같은제한점들을가지고있다. 첫째, 소아에서적절한체내비타민 D 상태를나타내는혈청 25(OH)D 수치는아직확립되지않았고이를정립하는연구가필 요하며, 둘째, 대학병원을방문한환자들을대상으로하였기때문 에국내전체소아알레르기비염환자군을대표하기는어렵다고생 각된다. 셋째, 대상자수가적어더많은대상자에서의연구가필요 할것으로보인다. 결론으로이번연구저자들은소아알레르기비염환자들에게서 건강한대조군에비해혈청 25(OH)D 수치가낮다는것을확인하 였고, 혈청 25(OH)D 수치가높은환자군에비해부족하거나불충 분한환자군에서알레르기비염발생위험이높아진다는것을확인 하였다. 이번연구는소아청소년을대상으로알레르기비염과비타 민 D 의관계를분석하였고, 특히 ARIA 분류법에의해질환의중증 도와지속기간과비타민 D 의관계성을확인했다는점에서의의가 있다고생각한다. 추후일반인구를대상으로비타민 D 와알레르 기비염과의연관성을파악하는코호트연구등추가적인횡적연 구들이비타민 D 와알레르기비염간의원인 - 결과관계를파악하 는데필요할것으로보인다. REFERENCES 1. 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 Al

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