pissn: eissn: Allergy Asthma Respir Dis 3(4): , July REVIEW 소아알레르기질환에서류코트리엔

Size: px

Start display at page:

Download "pissn: eissn: Allergy Asthma Respir Dis 3(4): , July REVIEW 소아알레르기질환에서류코트리엔"

자현 백
5 years ago
Views:

1 pissn: eissn: (4): , July REVIEW 소아알레르기질환에서류코트리엔조절제의역할 최봉석 1, 손명현 2, 김규언 2 1 경북대학교의학전문대학원소아과학교실, 2 연세대학교의과대학소아과학교실및알레르기연구소 The role of leukotriene modifier in pediatric allergic disease Bong Seok Choi 1, Myung Hyun Sohn 2, Kyu-Earn Kim 2 1 Department of Pediatrics, Kyungpook National University School of Medicine, Daegu; 2 Department of Pediatrics and Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea Leukotriene (LT) modifiers are composed of leukotriene receptor antagonists and 5-lipoxygenase inhibitors. LTs, C4, D4, and E4 are collectively termed cysteinyl LTs and best are the characterized receptors for cyslts are cyslt1 and cyslt2. cyslt1 ligation mediates sustained bronchial contraction, mucosal secretion, and edema, which are central to the pathogenesis of asthma. cyslt2 ligation is thought to contribute to edema, inflammation, and tissue fibrosis in asthma. LT modifiers attenuate bronchoconstriction responses and exert anti-inflammatory effects, reflected by reduced eosinophil counts in the peripheral blood, sputum, and bronchoalveolar lavage fluid of asthmatic patients. Inhaled corticosteroids are generally superior to LT modifiers as a first-line controller. However, LT modifiers are easy to administer, have good compliance, and have excellent safety. LT modifiers are recommended for asthmatic children aged 5 years as a first-line controller. The Japanese Guideline for Childhood Asthma recommends LT modifiers, as a firstline controller prior to inhaled corticosteroid for children aged < 2 years. LT modifiers can improve asthma control as add-on therapy with ICS. They can also be effective for exercise-induced asthma. LT modifiers are recommended for the treatment of allergic rhinitis in combination with H1-antihistamines or as a first-line drug for patients who cannot or do not wish to use intranasal corticosteroids. LT modifiers can also be considered for add-on therapy in the treatment of chronic urticaria, atopic dermatitis, and other allergic diseases. ( 2015;3: ) Keywords: Leukotriene antagonist, Asthma, Allergic rhinitis, Atopic dermatitis, Urticaria 서론류코트리엔조절제에는류코트리엔수용체길항제 (leukotriene receptor antagonist) 와류코트리엔생성억제제 (5-lipoxygenase inhibitors) 가있다. 류코트리엔수용체길항제에는 zafirlukast, montelukast, pranlukast가있으며 1995년부터임상에서사용되기시작하였다. 한국에서는 1998년부터 pranlukast (Onon, Ono Pharmaceutical Co., Osaka, Japan) 를시작으로 montelukast (Singulair, MSD, Haarlem, The Netherlands), zafirukast (Accolate, Astra Zeneca, London, UK) 등이발매되었다. 류코트리엔생성억제제에는 zileuton (Zyflo, Abbott Laboratories, Chicago, IL, USA) 이있으며 1996년미국에도입되었고현재국내에는유통되지않는다. 본종 설에서는류코트리엔과수용체에대한기초적인사항들과여러알레르기질환에서류코트리엔조절제의역할에대하여알아보았다. 류코트리엔의합성경로류코트리엔 (leukotriene, LT) 이라는이름은생성물이최초로밝혀진것이백혈구에서였고, 세개의이중결합구조 (-triene) 를가지고있음에기인하였으며이후백혈구이외의다른면역세포들에서도발견되고있다. 세포막내의 phospholipid는 phospholipase A 2 에의해 arachidonic acid (AA) 로대사된다. AA는세포질내로유리되어 cyclooxygenase pathway를통해 prostaglandin이나 thromboxane을형성하거나 5-lipoxygenase pathway를거쳐 LT를형성한다. Correspondence to: Kyu-Earn Kim Department of Pediatrics, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonju-ro, Gangnam-gu, Seoul , Korea Tel: , Fax: , kekim@yuhs.ac 2015 The Korean Academy of Pediatric Allergy and Respiratory Disease This study was supported by a grant of the Korea Health Technology R&D Project through the Korea Health The Korean Academy of Asthma, Allergy and Clinical Immunology Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant This is an Open Access article distributed under the terms of the Creative number : HI11C1404). Commons Attribution Non-Commercial License Received: February 7, 2015 Revised: February 24, 2015 Accepted: February 24, 2015 (

2 Choi BS, et al. Leukotriene modifiers for allergic disease 5-lipoxygenase pathway에서 AA는 5-lipoxygenase (5-LO) 에의해 5-hydroperoxyeicosatetraenoic acid를거쳐 LTA 4 를형성한다. 이과정에 5-LO activating protein이필요하다. 1) LTA 4 는류코트리엔 B 4 또는 cysteinyl leukotriene (cyslt) 인 LTC 4 로전환되며이는 LTD 4, LTE 4 로전환된다 (Fig. 1). 류코트리엔수용체및류코트리엔의생물학적활성 cyslt의수용체는 cyslt 1, cyslt 2 로분류된다. cyslt 1 은 LTD 4 와가장강하게결합하고 LTC 4, LTE 4 순의결합력을보이며지속적인기관지수축및점액분비, 부종등천식의병인에중심적인역할을한다. cyslt 2 는 LTC 4 와 LTD 4 에비슷하게가장강한결합력을보이며 LTE 4 가다음순서의결합력을보인다. cyslt 2 작용에대해서는상대적으로잘알려져있지않으나염증, 부종, 조직섬유화등에관여하는것으로생각한다. 2) LTB 4 의수용체에는 BLT 1 과 BLT 2 가있다. LTB 4 는주로 BLT 1 을통해호중구및기타백혈구의동원및활성화를보인다. BLT 2 는낮은친화도의수용체로역할은아직잘알려져있지않다. 최근기도개형 (airway remodeling) 에 cyslt가관여한다는보고들이있다. 천식소아에서호기가스분석상 cyslt 농도가기저막두께와비례하는것으로보고되었으며 cyslt가상피세포에서점액분비를증가시키고 interleukin-13 에의한평활근의증식에중요한역할을한다는보고도있다. 3) 류코트리엔길항제의개요및각약제별특징 1. 류코트리엔수용제길항제 1) Montelukast Montelukast는정제및츄정, 과립등의형태가있으며경구투여한다. 하루에한번복용하며 cyslt 1 수용체길항제로작용한다. 반감기는 시간이며간에서대사되고 CYP3A4, CYP2C9와연관되며담도로배설된다. 일반적으로생후 6개월이후부터사용한다. 2) Pranlukast cyslt 1 수용체길항제로반감기는 1.5시간이며하루 2회경구로복용한다. 간에서대사되고 CYP3A4가연관되며 1세미만에서는아직안전성이확립되지않았다. 3) Zafirlukast cyslt 1 수용체길항제로작용하며미국시장에서처음으로도입된류코트리엔수용체길항제이다. 하루 2회복용하며아직 12세이상에서만허가를받은상태이다. 반감기는 10시간정도이며간에서대사되고 CYP2C9가연관되며담도로배설된다. 2. 류코트리엔생성억제제 5-LO 억제제로는 zileuton 한가지만임상적으로유용하나현재국내에는유통되지않고있다. 12세이상에서사용가능하며반감 5-Lipoxygenase Arachidonic acid 15-Lipoxygenase 5-HPETE 5-HETE 5-Lipoxygenase LTA4 12-Lipoxygenase and 15-Lipoxygenase 15S-Epoxytetraene LTA4-hydrolase Glutathione-S-transferase LTB4 LTC4 Gamma-glutamyl transpeptidase LXA4 LXB4 Cysteinyl-leukotrienes LTD4 Dipeptidase LTE4 Fig. 1. Major pathways for leukotriene and lipoxin formation. 5-HPETE, 5-hydroperoxyeicosatetraenoic acid; 5-HETE, 5-hydroxyeicosatetraenoicacid; LT, leukotriene; LX, lipoxins

3 최봉석외 알레르기질환에서의류코트리엔조절제 기는 2.5시간이다. 간에서대사되고 CYP1A2, CYP2C9, CYP3A4 와연관되며신장으로배설된다. 천식에서의류코트리엔조절제여러연구들에서류코트리엔조절제는기관지수축반응을감소시키는것으로보고되었으며, 4) 천식환자의말초혈액, 객담, 기관지세척액에서호산구수를감소시키는항염증효과도보인다. 5) 많은경우들에서천식의장기적인관리에효과적이며투여 1 2주내에천식의악화빈도를줄이기도한다. 6) 1. 1차조절제로서의류코트리엔조절제만성천식환자를대상으로한위약대조연구에서류코트리엔조절제인 5-LO 억제제및류코트리엔수용체길항제는폐기능, 주간및야간증상, 삶의질, 속효성완화제의사용, 급성악화등의개선효과를보였다. 7) 류코트리엔수용체길항제와 5-LO 억제제를 1 차조절제로직접비교한전향적연구에서는경증-중등증의천식환자를대상으로하였으며 12주투여후비교시 zileuton 투여군이최대호기속도, 증상점수에서 montelukast 투여군보다더좋은결과를보였다. 8) 천식의 1차조절제로는흡입용스테로이드제가류코트리엔조절제보다일반적으로우위에있으며폐기능의개선이나염증의조절 등의면에서더나은효과를보이며이는소아에서도유사한결과를보인다. 9) 그러나류코트리엔조절제는투여가간편하여순응도가높고안전성이우수한장점이있다. 스테로이드제에대한거부감이심하거나흡입용스테로이드제로인한쉰목소리등의부작용이심한경우, 알레르기비염이동시에있는경우, 흡입기에대한순응도가떨어지는경우, 아스피린과민성천식등의경우류코트리엔조절제가좋은대안이될수있다. 대한소아알레르기호흡기학회의 2008 소아 청소년천식진료가이드라인에서는 0 5세소아의 step 2 유지치료에서저용량의흡입용스테로이드제또는류코트리엔조절제를선호약제로추천하고있으며 6세이상에서는대체약제로추천하고있다 (Fig. 2) 년일본소아천식가이드라인에서는 2세미만의소아의 step 2 치료에서저용량흡입스테로이드제보다류코트리엔조절제를기본약물로권고하고있다. 6) 2. 병합요법에서의류코트리엔조절제저농도흡입용스테로이드제단독으로천식이잘조절되지않는경우류코트리엔조절제의추가는폐기능및천식조절을개선시키며 10) 개선정도는흡입용스테로이드제를두배증량한것과유사한것으로보고되었다. 11) 흡입용스테로이드제단독으로조절이불충분한천식환자에서류코트리엔조절제를추가한경우와지속성 β2 항진제를추가한경우를비교한몇몇연구에서는류코트리엔조 0-5 세 Step 1 Step 2 Step 3 Step 4 Step 5 Preferred SABA prn Low-dose ICS or LTM Medium-dose ICS or Low-dose ICS LABA or LTM High-dose ICS or Medium-dose ICS LABA or LTM Alternative Theophylline Theophylline Theophylline Quick-Relief Medication Each step: Patient Education & Environmental Control - 증상이있으면 SABA 치료가요구된다. - 바이러스호흡기감염 : SABA 를 4-6 시간마다흡입해야한다. 1 일이상규칙적흡입치료가요구될때에는전문의에게의뢰해야한다. 심한증상의악화혹은병력의경우단기간의경구스테로이드를사용해야한다. - 주의 : SABA 의빈번한사용이필요한경우는 step up 을고려해야한다. High-dose ICS oral corticosteroid or Anti-lgE 6 세이상 Step 1 Step 2 Step 3 Step 4 Step 5 Preferred SABA prn Low-dose ICS Alternative Quick-Relief Medication LTM or Theophylline Medium-dose ICS or Low-dose ICS LABA or LTM or Theophylline Each step: Patient Education & Environmental Control High-dose ICS or Medium-dose ICS LABA or LTM or Theophylline High-dose ICS oral corticosteroid or Anti-lgE - 증상이있으면 20 분간격으로 3 회까지 SABA 치료를할수있다. 단기간의경구스테로이드치료도고려할수있다. - 주의 : 1 주일에 2 일이상 SABA 치료가요구될때는천식조절이잘안되고있다는것을의미하며 step up 을고려해야한다. Fig. 2. Stepwise approach for asthma management in childhood. SABA, short acting β2 agonist; prn, pro re nata; ICS, inhaled corticosteroid; LTM, leukotriene modifier; LABA, long acting β2 agonist (2008 Guideline for childhood asthma. Korean Academy of Pediatric Allergy and Respiratory Disease)

4 Choi BS, et al. Leukotriene modifiers for allergic disease 절제가염증의조절에서우위에있었으며지속성 β2 항진제는폐기능개선의측면에서우위를보였다. 12) 3. 운동유발성천식에서의류코트리엔조절제운동유발성천식환자의객담및호기가스에서 cyslt의농도가높게보고되었으며한연구에서는 4 8주동안매일 montelukast를투여한후 salmeterol을감량하여도운동유발성기관지수축에대한예방효과가지속되는것으로보고하였다. 13) 8 12세의운동유발성천식환아를대상으로한국내연구에서도 montelukast를 2개월투여한후임상증상의개선및운동유발검사소견의호전을보고하였다. 14) 미국식약청은 2007년 15세이상의운동유발성천식환자의예방에 montelukast의사용을승인하였고 2시간전에사용하도록권고하였다. 15) 알레르기비염에서의류코트리엔조절제류코트리엔은비점막혈관평활근의이완작용을보이며혈관투과성증가와호산구의이동을촉진한다. 코막힘은 LTC4 농도와연관성이높은것으로알려져있으며재채기와코가려움증은히스타민농도와관련된다. 이러한이유로류코트리엔조절제는코막힘에효과적일수있으며장기복용시에더효과가증가한다. 콧물과재채기에대해서는투여 4주내에항히스타민제에근접한효과를보인다. 16) 류코트리엔조절제는비강내스테로이드제보다는알레르기비염에덜효과적인것으로알려져있다. 17) 항히스타민제와의효과비교에서는다소상반된결과들을보이며 2010년 The Allergic Rhinitis and its Impact on Asthma (ARIA) 가이드라인에서는항히스타민제를우선적으로추천하고있다. Montelukast와 2세대항히스타민제 ( 예, loratadine, fexofenadine) 의병합요법은각약물의단독요법보다증상조절에더효과적일수있다. 18) 알레르기비염에서일차적으로추천되는약제는비강내스테로이드제이나비강내스프레이를사용하기힘들거나거부하는환자의경우류코트리엔조절제단독이나항히스타민제와의병합요법을추천할수있다. 19) 또한류코트리엔조절제는천식과알레르기비염이동시에있는경우유용하게사용되며알레르기결막염의경우에도증상완화에어느정도효과를보인다. 20) 류코트리엔조절제는항히스티민제와달리졸림등의부작용은보이지않는다. 아토피피부염에서의류코트리엔조절제상피세포에서도호중구에서유래한 LTA 4 를 LTB 4, LTC 4 로전환시킬수있으며, cysteinyl LT는혈관투과성을증가시키고피부혈관을확장시킨다. 21) 아토피피부염환자에서추출한호염기구및호산구에서다량의 cysteinyl LT의분비를보이며 22) 아토피피부염환 자에서혈중호염기구의활성화및 LTC 4 분비능의증가를보인다. 23) 전신적인 cysteinyl LT 생산정도의지표로삼는뇨중 LTE 4 의증가여부는아토피피부염환자에서다양한결과를보인다. 24) 아토피피부염환자에서류코트리엔조절제에대한효과도상반된결과를보인다. 중등증-중증아토피피부염소아를대상으로한무작위이중맹검위약대조시험에서는 montelukast를투여한군에서가려움증, 수면장애, 항히스타민제와국소스테로이드제의사용빈도감소를보였다. 25) 반면 16 60세의아토피피부염환자를대상으로한이중맹검위약대조시험에서는 montelukast 투여군이위약군과큰차이를보이지않았다. 26) 만성두드러기에서의류코트리엔조절제류코트리엔은두드러기의병인에도관련될것으로생각되어왔다. 활성화된비만세포는히스타민외에도류코트리엔을생산및분비하며 LTD 4 를피내주사하면심한팽진과발적을보인다. 27) 유럽알레르기학회의 2013년두드러기치료가이드라인 28) 에서는만성두드러기의치료를위해 2세대항히스타민제를 1차적으로투여하며 2주이상증상이지속되는경우 4배까지증량해보고 1 4주동안증상지속시 omalizumab, ciclosporin A, montelukast 등의추가치료를추천하고있다. 류코트리엔조절제는두드러기에서투여후효과를보일때까지의기간은다양하여길면수주가걸리기도한다. 29) 류코트리엔조절제가만성두드러기환자에서항히스타민제나위약에비해큰효과가없었다는보고들도있으나항히스타민제와류코트리엔조절제의병합요법은항히스타민제단독요법보다효과적인것으로보고된다. 30) 안정성류코트리엔조절제는비교적안전하며부작용이거의없는것으로보고되고있다. Zafirlukast나 montelukast를복용한소수 (<2%) 에서아나필락시스, 혈관부종, 현기증, 소화불량, 근력약화, 간효소치증가등을보였다. Montelukast를복용한환자들의시판후조사 (postmarketing surveillance) 에서극히일부에서자살충동이나행동, 정서변화등을보인것으로보고되었으나이후진행된연구들에서는자살충동의증가를보이지않았다 ) Zileuton은두통, 소화불량, 근육통, 백혈구감소증, 간효소치증가, 수면장애, 행동변화등의부작용이있을수있으며상대적으로다른약제들보다중한부작용을보일수있어투여중에간효소치의모니터링을요할수있다. Churg-Strauss 증후군은스테로이드의존성천식환자에서드물게보고되었으며대부분의경우경구스테로이드제를감량하는중에발생하여기저에있던 Churg- Strauss 증후군이스테로이드제감량으로인해드러났을가능성이 258

5 최봉석외 알레르기질환에서의류코트리엔조절제 제시되고있다. 34) 결론 류코트리엔조절제는현재알레르기질환에서널리사용되고있 는약제로여러연구들을통하여그효과와안전성이입증되었으 며천식및알레르기비염등에서보조적인치료제로추천된다. 아 직적응증으로승인받지는못하였으나, 아토피피부염, 만성두드러 기등의다른알레르기질환에서도추가치료약물로고려해볼수 있는등그활용영역이넓어지고있다. REFERENCES 1. Peters-Golden M, Brock TG. 5-lipoxygenase and FLAP. Prostaglandins Leukot Essent Fatty Acids 2003;69: Okunishi K, Peters-Golden M. Leukotrienes and airway inflammation. Biochim Biophys Acta 2011;1810: Parameswaran K, Radford K, Fanat A, Stephen J, Bonnans C, Levy BD, et al. Modulation of human airway smooth muscle migration by lipid mediators and Th-2 cytokines. Am J Respir Cell Mol Biol 2007;37: Leigh R, Vethanayagam D, Yoshida M, Watson RM, Rerecich T, Inman MD, et al. Effects of montelukast and budesonide on airway responses and airway inflammation in asthma. Am J Respir Crit Care Med 2002; 166: Terashima T, Amakawa K, Matsumaru A, Yamaguchi K. Correlation between cysteinyl leukotriene release from leukocytes and clinical response to a leukotriene inhibitor. Chest 2002;122: Hamasaki Y, Kohno Y, Ebisawa M, Kondo N, Nishima S, Nishimuta T, et al. Japanese Guideline for Childhood Asthma Allergol Int 2014;63: Nelson H, Kemp J, Berger W, Corren J, Casale T, Dube L, et al. Efficacy of zileuton controlled-release tablets administered twice daily in the treatment of moderate persistent asthma: a 3-month randomized controlled study. Ann Allergy Asthma Immunol 2007;99: Kubavat AH, Khippal N, Tak S, Rijhwani P, Bhargava S, Patel T, et al. A randomized, comparative, multicentric clinical trial to assess the efficacy and safety of zileuton extended-release tablets with montelukast sodium tablets in patients suffering from chronic persistent asthma. Am J Ther 2013;20: Castro-Rodriguez JA, Rodrigo GJ. The role of inhaled corticosteroids and montelukast in children with mild-moderate asthma: results of a systematic review with meta-analysis. Arch Dis Child 2010;95: Phipatanakul W, Greene C, Downes SJ, Cronin B, Eller TJ, Schneider LC, et al. Montelukast improves asthma control in asthmatic children maintained on inhaled corticosteroids. Ann Allergy Asthma Immunol 2003; 91: Baumgartner RA, Martinez G, Edelman JM, Rodriguez Gomez GG, Bernstein M, Bird S, et al. Distribution of therapeutic response in asthma control between oral montelukast and inhaled beclomethasone. Eur Respir J 2003;21: Bjermer L, Bisgaard H, Bousquet J, Fabbri LM, Greening AP, Haahtela T, et al. Montelukast and fluticasone compared with salmeterol and fluticasone in protecting against asthma exacerbation in adults: one year, double blind, randomised, comparative trial. BMJ 2003;327: Edelman JM, Turpin JA, Bronsky EA, Grossman J, Kemp JP, Ghannam AF, et al. Oral montelukast compared with inhaled salmeterol to prevent exercise-induced bronchoconstriction. A randomized, double-blind trial. Exercise Study Group. Ann Intern Med 2000;132: Kim JH, Min UK, Choi SO, Lee SG, Hong SJ. Clinical effect of montelukast in exercise-induced asthma. J Asthma Allergy Clin Immunol 2002; 22: Pearlman DS, van Adelsberg J, Philip G, Tilles SA, Busse W, Hendeles L, et al. Onset and duration of protection against exercise-induced bronchoconstriction by a single oral dose of montelukast. Ann Allergy Asthma Immunol 2006;97: Okubo K, Baba K. A double-blind non-inferiority clinical study of montelukast, a cysteinyl leukotriene receptor 1 antagonist, compared with pranlukast in patients with seasonal allergic rhinitis. Allergol Int 2008;57: Ratner PH, Howland WC 3rd, Arastu R, Philpot EE, Klein KC, Baidoo CA, et al. Fluticasone propionate aqueous nasal spray provided significantly greater improvement in daytime and nighttime nasal symptoms of seasonal allergic rhinitis compared with montelukast. Ann Allergy Asthma Immunol 2003;90: Cingi C, Gunhan K, Gage-White L, Unlu H. Efficacy of leukotriene antagonists as concomitant therapy in allergic rhinitis. Laryngoscope 2010; 120: Lieberman PL, Settipane RA. Azelastine nasal spray: a review of pharmacology and clinical efficacy in allergic and nonallergic rhinitis. Allergy Asthma Proc 2003;24: Cingi C, Ozlugedik S. Effects of montelukast on quality of life in patients with persistent allergic rhinitis. Otolaryngol Head Neck Surg 2010;142: Talbot SF, Atkins PC, Goetzl EJ, Zweiman B. Accumulation of leukotriene C4 and histamine in human allergic skin reactions. J Clin Invest 1985;76: Taşkapan MO. Zileuton and atopic dermatitis. Ann Allergy Asthma Immunol 2001;87: Ruzicka T, Ring J. Enhanced releasability of prostaglandin E2 and leukotrienes B4 and C4 from leukocytes of patients with atopic eczema. Acta Derm Venereol 1987;67: Hishinuma T, Suzuki N, Aiba S, Tagami H, Mizugaki M. Increased urinary leukotriene E4 excretion in patients with atopic dermatitis. Br J Dermatol 2001;144: Ehlayel MS, Bener A, Sabbah A. Montelukast treatment in children with moderately severe atopic dermatitis. Eur Ann Allergy Clin Immunol 2007; 39: Friedmann PS, Palmer R, Tan E, Ogboli M, Barclay G, Hotchkiss K, et al. A double-blind, placebo-controlled trial of montelukast in adult atopic eczema. Clin Exp Allergy 2007;37: Maxwell DL, Atkinson BA, Spur BW, Lessof MH, Lee TH. Skin responses to intradermal histamine and leukotrienes C4, D4, and E4 in patients with chronic idiopathic urticaria and in normal subjects. J Allergy Clin Immunol 1990;86: Zuberbier T, Aberer W, Asero R, Bindslev-Jensen C, Brzoza Z, Canonica GW, et al. The EAACI/GA(2) LEN/EDF/WAO Guideline for the definition, classification, diagnosis, and management of urticaria: the 2013 revision and update. Allergy 2014;69: Mora PM, Gonzalez Perez Mdel C, Jimenez Villarruel M, Rodriguez Castro E, Fogelbach GG. Therapeutic options in idiopathic chronic urticaria. Rev Alerg Mex 2005;52: Nettis E, Colanardi MC, Paradiso MT, Ferrannini A. Desloratadine in combination with montelukast in the treatment of chronic urticaria: a ran

6 Choi BS, et al. Leukotriene modifiers for allergic disease domized, double-blind, placebo-controlled study. Clin Exp Allergy 2004; 34: Philip G, Hustad C, Noonan G, Malice MP, Ezekowitz A, Reiss TF, et al. Reports of suicidality in clinical trials of montelukast. J Allergy Clin Immunol 2009;124:691-6.e Schumock GT, Stayner LT, Valuck RJ, Joo MJ, Gibbons RD, Lee TA. Risk of suicide attempt in asthmatic children and young adults prescribed leukotriene-modifying agents: a nested case-control study. J Allergy Clin Immunol 2012;130: Philip G, Hustad CM, Malice MP, Noonan G, Ezekowitz A, Reiss TF, et al. Analysis of behavior-related adverse experiences in clinical trials of montelukast. J Allergy Clin Immunol 2009;124: e Cho JH, Kim HJ, Moon JY, Jang SM, Kim HJ, Bae SW, et al. A case of Churg-Strauss syndrome in association with leukotriene modifier therapy when oral corticosteroids were withdrawn in an asthmatic patient. J Asthma Allergy Clin Immunol 2002;22:

ÀÇÇÐ°�ÁÂc00Ì»óÀÏ˘

ÀÇÇÐ°�ÁÂc00Ì»óÀÏ˘ Common Allergic Diseases in Children Sang - Il Lee, M.D. Department of pediatrics Sungkyunkwan University School of Medicine, Samsung Medical Center E - mail : silee@smc.samsung.co.kr Abstract Allergy