pissn: eissn: Allergy Asthma Respir Dis 4(1):14-21, January ORIGINAL ARTICLE 소아천식환

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1 pissn: eissn: ():4-2, January ORIGINAL ARTICLE 소아천식환자에서호기산화질소농도와노력성중간호기유량과의관계 임현욱, 김은지, 임창훈, 박상희, 정지태,,2 유영,2,3 고려대학교의과대학소아과학교실, 2 고려대학교안암병원천식환경보건센터, 3 고려대학교알레르기면역연구소 Relationships between fractional exhaled nitric oxide levels and FEF25% 75% in children with asthma Hyunwook Lim, Eunji Kim, Chang Hoon Lim, Sang Hee Park, Ji Tae Choung,,2 Young Yoo,2,3 Department of Pediatrics, Korea University College of Medicine, Seoul; 2 Environmental Health Center, Korea University Anam Hospital, Seoul; 3 Allergy Immunology Center, Korea University, Seoul, Korea Purpose: Fractional exhaled nitric oxide (FeNO) is considered an indirect marker of airway inflammation, and forced expiratory flow between 25% and 75% of vital capacity (FEF25% 75%) is widely used as a sensitive indicator of small airway obstruction in asthma. The aim of this study was to investigate relationships between FeNO and FEF25% 75% in children with asthma. Methods: A total of 8 children with asthma underwent spirometry and measurement of eosinophil markers. FeNO levels were measured, and skin prick tests to 3 common allergens were done. Study subjects were divided into 2 groups according to FEF25% 75% values (group, normal FEF25% 75% 65%pred, n= 90; group 2, impaired FEF25% 75% < 65%pred, n= 28). Results: The mean ( ± standard deviation, SD) age was not significantly different between groups and 2 (0.3 ± 2.8 years vs.. ± 3.4 years), and the sex ratio was also not significantly different between 2 groups. The geometric mean (range of SD) concentration of FeNO was significantly higher in group 2 than in group (25.8 ppb [ ppb] vs ppb [ ppb], P= 0.008). A significant inverse correlation between FeNO and FEF25% 75% was observed in group 2 (r= 0.493, P= 0.038), but not in group (r= 0.037, P= 0.749) after adjustment for confounders, such as atopy, age, sex, weight, and height. Conclusion: FeNO levels were higher in group of asthmatic children with impaired FEF25% 75% level. FeNO levels were inversely correlated with FEF25% 75% only in impaired small-airway obstruction group after adjustment for atopy. These results suggest that smallairway obstruction may relate more closely to airway inflammation in asthmatic children with impaired small-airway function. ( 206;4:4-2) Keywords: Asthma, Child, Spirometry, FeNO 서론천식은가역적인기도폐쇄, 기도과민성및만성적인기도염증을특징으로하는질환이다. 만성적인기도염증은크고작은기관지를침범하여광범위한기도폐쇄를조장하고천식의특징적현상인반복되는천명, 기침, 호흡곤란이나가슴답답함등을나타낸다. 2 천식환자에서기도폐쇄의정도를측정하기위해일반적으로 사용되는폐활량검사는 초간노력성호기량 (forced expiratory volume in second, FEV ), 노력성폐활량 (forced vital capacity) 과노력성중간호기유량 (forced expiratory flow between 25% and 75%, FEF 25% 75%) 등이있다. 초간노력성호기량은천식에서기도폐쇄가있을때심한정도를나타낼수있으나, 주로대기도의폐쇄를반영하고, 조절이잘되고있는천식환아에서는정상으로나타나는경우도많아소아천식의진단이나중증도의평가에는제한적인면 Correspondence to: Young Yoo Department of Pediatrics, Korea University Anam Hospital, 73 Inchon-ro, Seongbuk-gu, Seoul 0284, Korea 206 The Korean Academy of Pediatric Allergy and Respiratory Disease Tel: , Fax: , yoolina@korea.ac.kr The Korean Academy of Asthma, Allergy and Clinical Immunology This study was supported in part by grants from the Environmental Health Center for Childhood Asthma This is an Open Access article distributed under the terms of the Creative (204) and the Allergy Immunology Center, Korea University, Korea. Commons Attribution Non-Commercial License Received: June 22, 205 Revised: August 24, 205 Accepted: September 2, 205 ( 4

2 임현욱외 호기산화질소농도와노력성중간호기유량과의관계 이있다. 3 반면노력성중간호기유량은소기도폐쇄를시사하는가장예민한지표라는연구가있고, 4 특히증상이없는천식환아에서도기도폐쇄유무를판단하는정확한지표로알려져있다. 5 산화질소 (nitic oxide) 는호흡기상피세포에서기원하는내생적전달자로감염이나염증이있을때활성화된산화질소합성효소 (inducible nitric oxide synthase) 에의해만들어진다. 6 천식환자에서호기산화질소농도 (fractional exhaled nitric oxide) 는증가되어있고 7 기도의호산구성염증을잘반영하여, 8,9 염증정도를판단하고감시하는좋은방법으로알려져있다. 또한호기산화질소농도의측정은유도객담이나기관지폐포세척액내의염증측정에비해비침습적이고간단하여소아천식환자의기도염증측정을위한간접적인방법으로각광받고있다. 0 천식환자에서만성염증과기도폐쇄와의연관성을연구하기위해소기도의폐쇄를좀더잘반영하는노력성중간호기유량과호기산화질소농도와의관계를알아보는연구들이있었으나일부에서는유의한상관관계를보이고있고, -3 다른연구에서는그렇지않는등 4 일관성없는결과를보이고있다. 이러한이전연구들은기도염증과기도폐쇄의관계를전체천식환자에서알아보았으며현재까지대상자들을소기도폐쇄의유무로구분하여비교한연구는아니었다. 이에저자들은소아천식환자에서소기도폐쇄의간접지표인노력성중간호기유량과기도염증의지표인호기산화질소농도와의관계를알아보고, 소기도폐쇄의유무에따라노력성중간호기유량과기도염증과의상관관계를알아보고자하였다. 대상및방법. 연구대상 202년 3월부터 203년 월까지고려대학교안암병원소아알레르기호흡기클리닉에서천식으로진단받은 6 8세환아 8명을대상으로하였다. National Asthma Education and Prevention Program 가이드라인에 5 따라분류한결과경증간헐성천식 45명 (38.%), 경증지속성천식 37명 (3.4%), 중등증지속성천식이 36명 (30.5%) 이었다. 피부단자시험을시행한 05명의대상자중, 아토피는 85명 (8.0%), 비아토피는 20명 (9.0%) 이었다. 천식의진단은반복적인기침, 천명, 호흡곤란, 가슴답답함등의천식의전형적인증상을보이면서기관지확장제투여후 초간노력성호기량이 2% 이상증가하거나메타콜린유발시험에서 PC 20 (provocative concentration causing a 20% fall in FEV ) 가 6 mg/ml 미만인경우로정의하였다. 6 대상자들의면밀한의무기록분석을통해폐쇄성세기관지염이나기관지폐이형성증등기도과민성을보일수있는만성폐질환자를배제하였다. 대상자들은증상이없는상태에서검사를진행하였고, 연구한달이내에급성호흡기감염이있거나, 주 일이내에흡입용스테로이드, 류코트리엔조절제등을사용한경우연구대상에서제외하였다. 2. 연구방법 ) 대상군본연구에서는노력성중간호기유량을소기도폐쇄유무를기준으로각각 군 (normal FEF 25% 75% 65%pred) 과 2군 (impaired FEF 25% 75%<65%pred) 으로나누어두군에서호기산화질소농도, 폐기능검사수치와호산구지표등을비교하였다. 7 2) 폐기능검사폐기능검사는미국흉부학회 (American Thoracic Society, ATS) 의지침 8 에따라폐기능측정기 (022 digital spirometer, VIASYS, Palm Springs, CA, USA) 를이용하여측정하였다. 초간노력성호기량, 노력성폐활량, 노력성중간호기유량을측정하였고, 각각의추정정상치는한연구 9 를참고하였다. 폐활량측정의정도관리는 ATS/European Respiratory Society의지침 8,20 을참고하여시행하였다. 노력성폐활량과 초간노력성호기량의절대적차이값이 5% 미만인경우신뢰성있는값으로인정하여 3회측정치중최고치를각각선택하였다. 3) 호기산화질소농도측정호기산화질소농도의측정은미국흉부학회의지침 2 에따라상용측정기 (NIOX Mino, Aerocrine AB, Solna, Sweden) 를이용하여측정하였다. 모든대상자는검사 2시간전부터양상추, 딸기, 라스베리, 당근, 시금치및콜라등의음식과운동을제한하였고편안하게앉은상태에서검사를진행하였다. 대상자들은마우스피스를물고총폐활량까지들이쉰후 50 ml/sec의속도에따라불어내었고, 호기중에 0 20 cmh 2O의압력이유지되게하여피검자의구개범인두공이닫히게하여비강내산화질소가호기중에섞이지않게하였으며호기산화질소농도의측정값은 parts per billion (ppb) 으로표시하였다. 4) 혈액호산구지표측정대상자의정맥혈을채취하여백혈구수와백혈구감별계산을알아낸후호산구수를측정하였다. 호산구양이온단백농도는면역학적검사방법을통해대상자의혈청을항호산구양이온단백결합브롬화시안활성스폰지메트릭스 (anti-eosinophil cationic protein [ECP]-binding cyanogen bromide-activated cellulose spongelike matrix) 가들어있는 ImmunoCAP (Phadia AB, Uppsala, Sweden) 에넣고검체내호산구양이온단백과항원항체면역반응을일으키게한후, 이를항호산구양이온단백효소결합체 (anti-ecp enzyme conjugate) 와기질과의반응을이용해농도를 5

3 Lim H, et al. Relationships between FeNO levels and FEF25%-75% 정량화하였다. 22 5) 피부단자시험피부단자시험은대상자의전완전부에 3종의주요흡입항원 (Dermatopagoides pteronyssinus, Dermatophagoides farinae, Alternaria, Aspergillus, cockroach, cat, dog, oak, alder, ragweed, mugwort, rye grass, hazel) 과양성대조액 ( 히스타민 ) 및음성대조액 ( 생리식염수 ) 을한방울씩떨어뜨린후 26게이지바늘을상피깊이까지찔러검사액이도달하도록하였다. 이후검사액을서로섞이지않게닦아내고, 5분이지난뒤팽진을관찰하였다. 팽진의최장축과최장축의수직이등분선의길이를측정하여평균직경을기록하였다. 각항원에대해팽진의평균직경이 3 mm 이상이면서동시에양성대조보다큰경우를양성으로판정하였고, 한개이상의항원에대해양성반응을보이는경우를아토피로정의하였다. 6) 통계분석두군간의연속변수의평균비교는 t-test를이용하였고, 결과값은평균 ± 표준편차로표시하였다. 호산구분율, 호산구양이온단백, 호기산화질소농도는정규분포를따르지않아자연로그를취한다음기하평균 ( 표준편차의범위 ) 값으로나타내었다. 두군에서성별, 아토피유무등빈도분석은 chi-square 검사를시행하였다. 호기산화질소농도와폐기능검사수치와의상관관계는편상관관계를이용하여교란변수 ( 아토피유무, 성별, 나이, 몸무게, 키 ) 를통제하여분석하였다. 통계는 IBM SPSS Statistics ver (IBM Co., Armonk, NY, USA) 을이용하였고 P-value가 0.05 미만일경우통계적으로유의한것으로판단하였다. 결과. 대상자의특성및폐기능검사결과대상자총 8명중남아가 77명 (65.3%) 이었고, 연령 ( 평균 ± 표준편차 ) 은 0.5±2.9세였으며, 피부단자시험을시행한 05명중에서아토피는 85명 (80.9%) 이었다. 폐기능검사결과 초간노력성호기량예측치의평균 ± 표준편차는 88.3%±5.3%, 노력성폐활량예측치의평균 ± 표준편차는 95.5%±4.5%, 초간호기유량 / 노력성폐활량의평균 ± 표준편차는 84.9%±4.5% 그리고노력성중간호기유량예측치의평균 ± 표준편차는 85.7%±27.0% 였다. 군 (normal FEF 25% 75% 65%pred) 과 2군 (impaired FEF 25% 75% < 65%pred) 에서나이 ( 평균 ± 표준편차 ) (군, 0.3±2.8세 ; 2군,. ±3.4세 ; P = 0.229), 남아의비율 (군, 64.4%; 2군, 67.9%; P = 0.823) 및아토피빈도는 (군, 79.3%; 2군, 86.9%; P = 0.553) 차이가없었다. 군에서천식중증도는경증간헐성이 36명 (4.%), 경증지속성이 28명 (30%), 중등증지속성은 26명 (28.9%), 중증지속성천식은 0명 Table. Clinical characteristics in children with asthma Characteristic Group (n= 90) Group 2 (n= 28) Total (n= 8) P-value Age (yr) 0.3± 2.8.± ± Boys 58 (64.4) 9 (67.9) 77 (65.3) Atopy 65 (79.3) 20 (86.9) 85 (80.9) Body mass index (kg/m 2 ) (0.0%) 이었고, 2 군에서는각각 9 명 (35.7%), 9 명 (2.4%), 0 명 (42.9%), 0 명 (0.0%) 으로두군간에유의한차이는없었다 (P = 0.43). 두군에서 초간노력성호기량예측치의평균 ± 표준편차 ( 군, 93.6%±0.6%; 2 군, 7.2%±5.9%; P < 0.00), 노력성폐활량예측 치의평균 ± 표준편차 ( 군, 97.7% ±2.%; 2 군, 88.2%±8.9%; P = 0.07), 초간노력성호기유량 / 노력성폐활량의평균 ± 표준편 차 ( 군, 88.2%±4.9%; 2 군, 74.5%±8.2%; P < 0.00), 노력성중간호 기유량예측치의평균 ± 표준편차 ( 군, 97.5%±7.7%; 2 군, 47.8% ±3.4%; P<0.00) 는모두 2 군에서유의하게낮았다. 호기산화질 소농도의기하평균 ( 표준편차의범위 ) 은 2 군에서 37.2 ppb ( ppb) 으로 군의 25.8 ppb ( ppb) 보다유의하게높았 다 (P = 0.006) (Table ). 대상자를정상 초간노력성호기량군 (FEV %pred, 80%) 과 비정상 초간노력성호기량군 (FEV %pred, < 80%) 으로나누어분 석한결과 군에서호기산화질소농도 ( 기하평균 [ 표준편차의범 위 ]) 는각각 25.4 ppb ( ppb) 와 32.2 ppb ( ppb) 로 유의한차이가없었고 (P = 0.277), 2 군에서도각각 37.9 ppb ( ppb) 와 37.0 ppb ( ppb) 로유의한차이가없었다 (P = 0.878). 2. 전체대상자에서호기산화질소농도와폐기능및호산구 지표와의관계 9.4± ± ± FEV %pred 93.6± ± ± 5.3 < 0.00 FVC %pred 97.7± ± ± FEV/FVC 88.2± ± ± 4.5 < 0.00 FEF25%-75% %pred 97.5± ± ± 27.0 < 0.00 Eosinophil (%) 3.6 (.3 9.8) 4.2 ( ) 3.7 (.5 9.3) ECP (μg/l) 7.6 ( ) 7.2 ( ) 7.5 ( ) ( ) 37.2 ( ) 28.2 ( ) Valus are presented as mean± standard deviation, number (%), or geometric mean (range). Group, normal FEF25% 75% group (FEF25% 75% 65%pred); group 2, impaired FEF25% 75% group (FEF25% 75% < 65%pred); FEV, forced expiratory volume in second; FVC, forced vital capacity; FEF25% 75%, forced expiratory flow between 25% and 75% of vital capacity; ECP, eosinophil cationic protein; FeNO, fractional exhaled nitric oxide. 전체대상자에서호기산화질소농도는노력성중간호기유량예 측치 (r = 0.2, P = 0.035) 와유의한음의상관관계가있으나, 초 간노력성호기량예측치 (r = 0.44, P = 0.54) 와는유의한상관관 계가없었다 (Fig. ). 호기산화질소농도는호산구분율 (r = 0.342, 6

4 임현욱외 호기산화질소농도와노력성중간호기유량과의관계,000 r= 0.44, P= 0.54,000 r= 0.049, P= FEV %pred (%) A FVC %pred (%) B,000 r= 0.95, P= 0.053,000 r= 0.2, P= FEV/FVC (%) C FEF25% 75% %pred (%) D Fig.. FeNO values do not correlate with FEV %pred (r= 0.44, P= 0.54; A), FVC %pred (r= 0.049, P= 0.627; B) and FEV/FVC (r= 0.95, P= 0.053; C), but show significantly inverse correlation with FEF25% 75% %pred (r= 0.2, P= 0.035; D) in total asthmatic children. FeNO, fractional exhaled nitric oxide; FEV, forced expiratory volume in second; FVC, forced vital capacity; FEF25% 75%, forced expiratory flow between 25% and 75% of vital capacity. P<0.00) 및호산구양이온단백농도와 (r = 0.200, P = 0.033) 모두유의한양의상관관계를보였다. 3. 군에서호기산화질소농도와폐기능및호산구지표와의관계 군에서호기산화질소농도는 초간노력성호기량예측치 (r = 0.08, P = 0.878) 및노력성중간호기유량예측치 (r = 0.037, P = 0.749) 와유의한상관관계가없었다 (Fig. 2). 호기산화질소농도는호산구분율 (r = 0.398, P<0.00) 및호산구양이온단백농도와 (r = 0.240, P = 0.026) 유의한양의상관관계를보였다. 4. 2군에서호기산화질소농도와폐기능및호산구지표와의관계 2군에서호기산화질소농도는 초간노력성호기량 / 노력성폐활량 (r = 0.566, P = 0.04) 및노력성중간호기유량예측치와유의한음의상관관계를보였다 (r = 0.493, P = 0.038) (Fig. 3). 호기산화질소농도는호산구분율 (r = 0.207, P = 0.30) 및호산구양이온단백 (r = 0.23, P = 0.236) 과유의한상관관계를보이지않았다. 5. 아토피유무에따른호기산화질소농도와폐기능및호산구지표와의관계아토피군과비아토피군에서나이의평균 ± 표준편차는 군과 2 군에서각각 0.7±2.8세와 0.0±2.9세 (P = 0.338), 남아의비율은 67.0% 와 50.0% (P = 0.54), 신체비만지수의평균 ± 표준편차는 9.8±3.7 kg/m 2 와 9.6±4.8 kg/m 2 (P = 0.843) 으로두군간에유의한차이는없었다. 아토피군과비아토피군에서의호산구분율의기하평균 (표준편차의범위 ) 은 2.4% (2.3% 2.5%) 와.5% (.4%.6%) (P = 0.00), 호산구양이온단백농도의기하평균 ( 표준편차의범위 ) 은 20.6 μg/ L ( μg/l) 와 7.9 μg/l ( μg/l) (P<0.00), 호기산화질소농도의기하평균 (표준편차의범위 ) 은 3.7 ppb ( ppb) 와 7.8 ppb ( ppb) (P = 0.003) 로유의하게아토피군에서높았다 (Table 2). 아토피군에서호기산화질소농도는호산구분율이나 (r = 0.459, P<0.00) 호산구양이온단백농도와 (r = 0.382, P<0.00) 유의한양의상관관계를보였고비아토피군에서호기산화질소농도는호산구분율과유의한양의상관관계를보였다 (r = 0.549, P = 0.05). 7

5 Lim H, et al. Relationships between FeNO levels and FEF25%-75%,000 r= 0.08, P= 0.878,000 r= 0.072, P= FEV %pred (%) A FVC %pred (%) B,000 r= 0.04, P= 0.367,000 r= 0.037, P= FEV/FVC (%) C FEF25% 75% %pred (%) D Fig. 2. FeNO values show significant correlation with neither FEV %pred (r= 0.08, P= 0.878; A), FVC %pred (r= 0.072, P= 0.534; B), FEV/FVC (r= 0.04, P= 0.367; C) nor FEF25% 75% %pred (r= 0.037, P= 0.749; D) in children with group (normal FEF25% 75%, 65%pred). FeNO, fractional exhaled nitric oxide; FEV, forced expiratory volume in second; FVC, forced vital capacity; FEF25% 75%, forced expiratory flow between 25% and 75% of vital capacity. 군과 2군을각각아토피유무별로나누어호기산화질소농도의평균을비교한결과 군에서는아토피군이 30.3 ppb ( ppb) 으로, 비아토피군의 6.2 ppb ( ppb) 보다유의하게높았으나 (P = 0.002), 2군에서는아토피군 36.4 ppb ( ppb) 와비아토피군 35.8 ppb ( ppb) 사이에유의한차이는없었다 (P = 0.942). 고찰본연구의결과호기산화질소농도가노력성중간호기유량예측치가낮은 2군에서 군보다유의하게높게나타났다. 아토피유무, 성별, 나이, 몸무게, 키등의영향인자보정후전체대상자의호기산화질소농도는노력성중간호기유량예측치와유의한음의상관관계를보였다. 호기산화질소농도가 군에서는모든폐활량검사항목들과유의한상관관계가없었던반면, 2군에서는 초간노력성호기량 / 노력성폐활량, 노력성중간호기유량예측치와유의한음의상관관계를보였다. 전체대상자에서호기산화질소농도와노력성중간호기유량예 측치는유의하게음의상관관계를보여, 과거연구들과,7 비슷한결과를보였다. 한편천식환아 80명을대상으로시행한과거연구 0 에서는호기산화질소농도가 초간노력성호기량, 초간노력성호기량 / 노력성폐활량예측치와상관관계를보이지않았고, 아토피천식환아 450명을대상으로시행한또다른연구 3 에서도호기산화질소농도는 초간노력성호기량예측치, 노력성폐활량예측치, 초간노력성호기량 / 노력성폐활량, 노력성중간호기유량예측치모두와유의한상관관계를보이지않았다. 이와같이호기산화질소농도와폐기능검사항목과의관계가연구에따라차이를보이는이유는폐기능검사결과가상대적으로성인천식환자에비해소아천식환자에서재현성이떨어지고, 중증지속성소아천식환자에서도 초간노력성호기량은비교적정상범위를보일수있어 3 기도폐쇄를덜예민하게반영하기때문으로볼수있다. 또한각연구별로대상환자들의천식중증도와스테로이드흡입치료의기간에차이가있으며, 폐기능검사는오랜기간진행되었던만성염증에의한기도폐쇄를반영하는생리적지표인반면 23 호기산화질소농도는측정당시의호산구염증정도를나타내는지표이다. 24 따라서두지표가천식의서로다른면을반영한다는점에서한시점에서 8

6 임현욱외 호기산화질소농도와노력성중간호기유량과의관계,000 r= 0.066, P= 0.795,000 r= 0.79, P= FEV %pred (%) A FVC %pred (%) B,000 r= 0.566, P= 0.04,000 r= 0.493, P= FEV/FVC (%) C FEF25% 75% %pred (%) D Fig. 3. FeNO values do not correlate with inversely correlate with with FEV %pred (r= 0.066, P= 0.795; A) or FVC %pred (r= 0.79, P= 0.477; B), but show significant FEV/FVC (r= 0.566, P= 0.04; C), and FEF25% 75% %pred (r= 0.493, P= 0.038; D) in children with group 2 (impaired FEF25% 75%, < 65%pred). FeNO, fractional exhaled nitric oxide; FEV, forced expiratory volume in second; FVC, forced vital capacity; FEF25% 75%, forced expiratory flow between 25% and 75% of vital capacity. Table 2. Comparison of clinical characteristics between atopy and nonatopy group Characteristic Atopy group (n= 85) Nonatopy group (n= 20) P-value Age (yr) 0.7± ± Boys 55 (67.0) 0 (50.0) 0.54 Body mass index (kg/m 2 ) 9.8± ± FEV %pred 88.0± ± FVC %pred 95.5± ± FEV/FVC 94.8± ± FEF25%-75% %pred 85.± ± Eosinophil (%) 2.4 ( ).5 (.36.57) 0.00 ECP (μg/l) 20.6 (8.3 5.) 7.9 ( ) < ( ) 7.8 ( ) Valus are presented as mean± standard deviation, number (%), or geometric mean (range). FEV, forced expiratory volume in second; FVC, forced vital capacity; FEF25% 75%, forced expiratory flow between 25% and 75% of vital capacity; ECP, eosinophil cationic protein; FeNO, fractional exhaled nitric oxide. 의호기산화질소농도측정이만성적인폐기능의생리적변화를직 접적으로설명하기에는한계가있다. 본연구에서소아천식환자의폐기능지표중노력성중간호기유 량예측치를 65% 기준으로이상을 군, 미만을 2군으로나누어비교한결과 2군에서유의하게더높은호기산화질소를보였으나, 정상과비정상 초간노력성호기량으로비교한결과두군에서호기산화질소농도의유의한차이가없어서호기산화질소농도가대기도폐쇄보다는소기도폐쇄와더욱밀접한관련이있는것으로생각된다. 군에서호기산화질소농도는 초간노력성호기량과유의한음의상관관계를보였던반면, 다른폐활량검사항목들과는유의한상관관계를보이지않았고, 2군에서는호기산화질소가 초간노력성호기량 / 노력성폐활량, 노력성중간호기유량와유의한음의상관관계를보였다. 아토피등의교란변수를보정후에도 2군에서호기산화질소가노력성중간호기유량과유의한음의관계를보였고, 2 군을아토피유무별로나눈후호기산화질소농도를비교한결과유의한차이가없었다. 따라서나이, 몸무게, 키, 성별과더불어아토피유무는호기산화질소농도와노력성중간호기유량의상관관계에끼치는영향은유의하지않았다. 아토피성천식환아에서유의하게비아토피성천식환아보다호산구분율, 호산구양이온단백이높았고, 호기산화질소농도도마 9

7 Lim H, et al. Relationships between FeNO levels and FEF25%-75% 찬가지로아토피성천식환아에서높은결과는이전연구들 25,26 과 비슷하다. 호기산화질소는호산구분율, 호산구양이온단백과관 련이있어호산구성염증반응의정도를잘반영하기때문에 27 아토 피성천식환아에서호기산화질소농도가더높은것이설명된다. 이번연구의한계점은노력성중간호기유량이소기도폐쇄를정 량적으로측정하는직접적인지표가아닌간접적인지표라는점 과, 소기도의호기산화질소농도를직접측정하지못하였기때문 에대기도의호기산화질소가섞여있을가능성을배제할수없다 는점이다. 호기산화질소농도는측정시호기속도와반비례하여 호기속도가빠를수록폐포의호기산화질소농도를반영하고호기 속도가느릴수록대기도내의호기산화질소농도를반영하는것으 로알려져있다. 28 본연구에서호기산화질소농도측정시소기도 의호기산화질소반영을위해호기속도를증가시켜볼수있었지 만, 재현성이가장좋다고알려진속도 29 로검사를진행하였다. 호기산화질소농도와폐기능검사수치는서로의종속관계로정 의할수없는천식의독립적인특징을나타내는지표이기때문에 두지표들의직접적인연관성을정량적으로분석하지못하였다. 천 식조절단계나중증도에따른분석이안된점도추가적인한계점 으로생각된다. 따라서두지표간의직접적인연관성은추가적인 연구가필요하다. 이번연구의대상자는대부분흡입용스테로이드나류코트리엔 조절제로치료받다가검사 주일전에치료를중단하였다. 이는기 도내에염증은해소시킬수있으나기도폐쇄등의축적된생리적 인변화를완전히정상화시키는데는제한적이다. 따라서추후연 구에서는천식조절제치료를한번도받지않은환자군을대상으 로호기산화질소농도와폐기능검사수치간의관계를알아보고, 천식의중등도및조절정도에따른분석을곁들인다면보다의미 있는결과를얻을수있을것이다. 결론적으로소아천식환자에서소기도폐쇄가있는군이호기 산화질소농도가더높게나타났고, 소기도폐쇄가있는군에서호 기산화질소농도와노력성중간호기유량은아토피유무, 키, 몸무 게와성별등의영향인자를보정후에도유의한음의상관관계를 보였다. 이는소기도폐쇄가있는소아천식환자에서소기도폐쇄 가기도염증의간접지표인호기산화질소농도와더욱밀접한관 계가있음을시사한다. REFERENCES. International consensus report on diagnosis and treatment of asthma. National Heart, Lung, and Blood Institute, National Institutes of Health. Bethesda, Maryland Publication no , March 992. Eur Respir J 992;5: Pyun BY. Guideline for the management of childhood asthma. J Korean Pediatr Soc 200;44: Bacharier LB, Strunk RC, Mauger D, White D, Lemanske RF Jr, Sorkness CA. Classifying asthma severity in children: mismatch between symptoms, medication use, and lung function. Am J Respir Crit Care Med 2004;70: McFadden ER Jr, Linden DA. A reduction in maximum mid-expiratory flow rate. a spirographic manifestation of small airway disease. Am J Med 972;52: Gibb ER, Thyne SM, Kaplan DN, Ly NP. Asthma, FEF25 75, and hospitalizations in children. Pediatr Allergy Immunol Pulmonol 203;26: Barnes PJ, Liew FY. Nitric oxide and asthmatic inflammation. Immunol Today 995;6: Alving K, Weitzberg E, Lundberg JM. Increased amount of nitric oxide in exhaled air of asthmatics. Eur Respir J 993;6: Jatakanon A, Lim S, Kharitonov SA, Chung KF, Barnes PJ. Correlation between exhaled nitric oxide, sputum eosinophils, and methacholine responsiveness in patients with mild asthma. Thorax 998;53: Mattes J, Storm van's Gravesande K, Reining U, Alving K, Ihorst G, Henschen M, et al. NO in exhaled air is correlated with markers of eosinophilic airway inflammation in corticosteroid-dependent childhood asthma. Eur Respir J 999;3: Ko HS, Chung SH, Choi YS, Choi SH, Rha YH. Relationship between exhaled nitric oxide and pulmonary function test in children with asthma. Korean J Pediatr 2008;5:8-7.. Choi BS, Jee HM, Park YH, Kim KW, Sohn MH, Kim KE. Relationship between exhaled nitric oxide concentration and pulmonary function/ airway hyperresponsiveness in asthmatic children. Pediatr Allergy Respir Dis 2009;9: Colon-Semidey AJ, Marshik P, Crowley M, Katz R, Kelly HW. Correlation between reversibility of airway obstruction and exhaled nitric oxide levels in children with stable bronchial asthma. Pediatr Pulmonol 2000; 30: Steerenberg PA, Janssen NA, de Meer G, Fischer PH, Nierkens S, van Loveren H, et al. Relationship between exhaled NO, respiratory symptoms, lung function, bronchial hyperresponsiveness, and blood eosinophilia in school children. Thorax 2003;58: Kim JO, Woo SI, Hahn YS. Relevance of exhaled nitric oxide levels to asthma control test scores and spirometry values in children with atopic asthma. Pediatr Allergy Respir Dis 20;2: National Asthma Education and Prevention Program. Expert Panel Report 3 (EPR-3): guidelines for the diagnosis and management of asthma-summary report J Allergy Clin Immunol 2007;20(5 Suppl):S Cockcroft DW. Bronchoprovocation methods: direct challenges. Clin Rev Allergy Immunol 2003;24: Ciprandi G, Tosca MA, Cirillo I, Lionetti E, Leonardi S, Miraglia Del Giudice M, et al. Impaired FEF25-75 may predict high exhaled nitric oxide values in children with allergic rhinitis and/or asthma. J Biol Regul Homeost Agents 202;26( Suppl):S Standardization of Spirometry, 994 Update. American Thoracic Society. Am J Respir Crit Care Med 995;52: Park CH, Kim HB, Jung YH, Lee E, Yang SI, Seo JH, et al. Predicted normal values of pulmonary function tests in normal Korean children. Allergy Asthma Respir Dis 204;2: Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, et al. Standardisation of spirometry. Eur Respir J 2005;26: Dweik RA, Boggs PB, Erzurum SC, Irvin CG, Leigh MW, Lundberg JO, et al. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med 20;84: Johansson SG, Yman L. In vitro assays for immunoglobulin E. Method- 20

8 임현욱외 호기산화질소농도와노력성중간호기유량과의관계 ology, indications, and interpretation. Clin Rev Allergy 988;6: del Giudice MM, Brunese FP, Piacentini GL, Pedulla M, Capristo C, Decimo F, et al. Fractional exhaled nitric oxide (FENO), lung function and airway hyperresponsiveness in naïve atopic asthmatic children. J Asthma 2004;4: Covar RA, Szefler SJ, Martin RJ, Sundstrom DA, Silkoff PE, Murphy J, et al. Relations between exhaled nitric oxide and measures of disease activity among children with mild-to-moderate asthma. J Pediatr 2003;42: Sampson AP. The role of eosinophils and neutrophils in inflammation. Clin Exp Allergy 2000;30 Suppl : Prasad A, Langford B, Stradling JR, Ho LP. Exhaled nitric oxide as a screening tool for asthma in school children. Respir Med 2006;00: Joseph-Bowen J, de Klerk N, Holt PG, Sly PD. Relationship of asthma, atopy, and bronchial responsiveness to serum eosinophil cationic proteins in early childhood. J Allergy Clin Immunol 2004;4: Paredi P, Kharitonov SA, Meah S, Barnes PJ, Usmani OS. A novel approach to partition central and peripheral airway nitric oxide. Chest 204; 45: Pedroletti C, Zetterquist W, Nordvall L, Alving K. Evaluation of exhaled nitric oxide in schoolchildren at different exhalation flow rates. Pediatr Res 2002;52:

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¼Û±âÇõ 223 Table 1. Results of FEV 1.0, Methacholine Challenge Test, and Exercise Provocation Test in Eight Patients Who Performed PFT Pts Tests 1 2 3 4 5 6 7 8 FEV 1.0 (%pred) 66.6 88.8 120 101 90.5 95.4 91.6