Eosinophil Cationic Protein (ECP)/Eosinophil-derived Neurotoxin (EDN) 농도와 천식 아동의 성장 상태 사이의 연관성

박미정,허경,김효빈,김창근 대한소아내분비학회 2007 Annals of Pediatirc Endocrinology & Metabolism Vol.12 No.2

목 적 : 천식은 흔히 볼 수 있는 만성 질환의 하나로 천식환아의 성장에 있어 성장지연이나 비만을 야기시킨다고 알려져 있으나 그 기전은 확실하지 않다. 이에 저자들은 천식을 가진 환아들을 대상으로 신체 계측을 통해 성장 상태를 평가하여 성장 지연 유무를 확인하고 비만도를 측정하였으며 EDN, ECP 수치와 혈중 호산구수를 측정하여 성장상태와의 상관성을 알아보고자 하였다. 방 법 : 천식으로 입원한 아동 90명(남아 57명, 여아 33명, 4-16세)을 를 대상으로 입원 당시 신장과 체중을 측정하여 각각의 표준편차 점수치를 구하였고 혈중 EDN, ECP 농도와의 연관성을 알아보았다. 결 과 : 1) 대상아동의 평균 신장표준편차 점수(height SDS)는 0.33±0.85, 체중 SDS는 0.23±1.20였다. 2) 체중 SDS가 -2에서 -1인 저체중군 환아는 7.8%, -1에서 1인 정상 체중군은 71.1%, 1에서 2인 과체중군은 21.1%였고, 신장 SDS가 -2에서 -1인 저신장군 환아는 2.2%, -1에서 1인 정상 신장군 75.5%, 1에서 2인 고신장군은 22.2% 였다. 3) 신장 SDS는 혈청ECP 농도(r=-0.27, P=0.01) 및 EDN 농도(r=-0.27, P=0.009)와 유의한 음의 상관성이 있었다. 체중 SDS는 ECP와 유의한 음의 상관관계에 있었다(r= -0.20, P=0.05). 4) ECP 수치가 높은 군은 ECP 수치가 정상인 군에 비해 신장 SDS가 유의하게 낮았으며(0.21±0.82 vs 0.63 ±0.85, P<0.01), 체중 SDS 또한 ECP수치가 높은 군이 정상인 군에 비해 유의하게 낮았다(0.03±1.07 vs 0.76±1.37, P<0.06). EDN 수치가 높은 군은 EDN 수치가 정상인 군에 비해 신장 SDS가 유의하게 낮았다(0.27±0.85 vs 0.45±0.80, P<0.009). 결 론 : 천식 아동에서 ECP와 EDN 수치가 높을수록 키와 체중의 저하를 보였다. Purpose : Short statue or obesity has been reported in asthmatic children, but the results are inconsistent. Recently eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN) levels has been known as important markers of airway inflammation and reflect asthma severity as well. The aim of this study is to evaluate the growth status and to analyze the possible relation with serum EDN and ECP levels. Methods : A total of 90 children (57 boys and 33 girls, 4 to 16 years old) who had been admitted for bronchial asthma were included. To standardize the data for age and sex, standard deviation scores (SDS) were calculated for height and weight. Values less than -2 SDS below the mean were considered to be extremely low, -1 SDS to 1 SDS as normal, values higher than 2 SDS considered very high. Serum EDN and ECP levels were measured. Results : The mean height SDS was 0.33±0.85 and weight SDS was 0.23±1.20. The prevalence of short stature was 2.2%, normal stature 75.5%, and tall stature 22.2%. The prevalence of underweight was 7.8%, normal weight 71.1%, and overweight 21.1%. Height SDS was negatively correlated with serum ECP (r=-0.27, P=0.01) and EDN (r=-0.27, P=0.009) and weight SDS was negatively correlated with serum ECP (r=-0.20, P=0.05). Height SDS were significantly lower in high ECP and EDN groups compared to normal ECP and EDN groups (P<0.01 and P<0.009, respectively). Weight SDS was lower in high ECP group compared to normal ECP group (P<0.05). Conclusion : Growth (height and weight) was inversely correlated with serum EDN and ECP levels. These results suggest that high ECP and EDN levels might be related with growth retardation of asthmatic children.

영유아천식 악화시 Eosinophil-derived Neurotoxin 및 Eosinophil Cationic Protein 농도와 기도벽 비후 사이의 연관성

김효빈 ( Hyo Bin Kim ),최준기 ( Jun Gi Choi ),윤운기 ( Un Ki Youn ),마영수 ( Young Soo Ma ),신보문 ( Bo Moon Shin ),김정숙 ( Joung Sook Kim ),김창근 ( Chang Keun Kim ),Rachel Fletcher 대한소아알레르기 및 호흡기학회 2007 소아알레르기 및 호흡기학회지 Vol.17 No.2

Eosinophil-derived neurotoxin: a novel biomarker for diagnosis and monitoring of asthma

김창근 대한소아청소년과학회 2013 Clinical and Experimental Pediatrics (CEP) Vol.56 No.1

Asthma is associated with increased levels of eosinophils in tissues, body fluids, and bone marrow. Elevated levels of eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) have been noted in asthma patients. Higher levels of EDN and ECP are also associated with exacerbated asthmatic conditions. Thus, EDN, along with ECP, may aid the diagnosis and monitoring of asthma. Several groups have suggested that EDN is more useful than ECP in evaluating disease severity. This may partially be because of the recoverability of EDN (not sticky, 100% recovery rate), as ECP is a sticky and more highly charged protein. In terms of clinical utility, EDN level is a more accurate biomarker than ECP when analyzing the underlying pathophysiology of asthma. As a monitoring tool, EDN has shown good results in children with asthma as well as other allergic diseases. In children too young to fully participate in lung function tests, EDN levels may be useful as an alternative measurement of eosinophilic inflammation. EDN can also be used in adult patients and in multiple specimen types (e.g.,serum, sputum, bronchoalveolar lavage fluid, and nasal lavage fluid). These results are repeatable and reproducible. In conclusion, EDN may be a novel biomarker for the diagnosis, treatment, and monitoring of asthma/allergic disease.

Eosinophil-derived neurotoxin: a novel biomarker for diagnosis and monitoring of asthma

Kim, Chang-Keun The Korean Pediatric Society 2013 Clinical and Experimental Pediatrics (CEP) Vol.56 No.1

Asthma is associated with increased levels of eosinophils in tissues, body fluids, and bone marrow. Elevated levels of eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) have been noted in asthma patients. Higher levels of EDN and ECP are also associated with exacerbated asthmatic conditions. Thus, EDN, along with ECP, may aid the diagnosis and monitoring of asthma. Several groups have suggested that EDN is more useful than ECP in evaluating disease severity. This may partially be because of the recoverability of EDN (not sticky, 100% recovery rate), as ECP is a sticky and more highly charged protein. In terms of clinical utility, EDN level is a more accurate biomarker than ECP when analyzing the underlying pathophysiology of asthma. As a monitoring tool, EDN has shown good results in children with asthma as well as other allergic diseases. In children too young to fully participate in lung function tests, EDN levels may be useful as an alter native measurement of eosinophilic inflammation. EDN can also be used in adult patients and in multiple specimen types (e.g., serum, sputum, bronchoalveolar lavage fluid, and nasal lavage fluid). These results are repeatable and reproducible. In conclusion, EDN may be a novel biomarker for the diagnosis, treatment, and monitoring of asthma/allergic disease.

조산아 기관지폐이형성증의 발생에서 호산구 활성화 표지자

최선희 ( Sun-hee Choi ),정성훈 ( Sung-hoon Chung ),이경석 ( Kyung-suk Lee ),배종우 ( Chong-woo Bae ),나영호 ( Yeong-ho Rha ) 대한천식알레르기학회 2022 Allergy Asthma & Respiratory Disease Vol.10 No.1

Purpose: Eosinophil-derived neurotoxin (EDN) is not the only a marker for eosinophil activation, but also acts as an alarm protein. Very few studies have examined the potential role of eosinophils in the development of bronchopulmonary dysplasia (BPD). This study aims to address the roles of eosinophil and EDN in the early phase of BPD development. Methods: Patients were preterm neonates with respiratory distress syndrome (RDS) born at 36 weeks of gestation or less. Blood and urine samples were collected to measure total eosinophil count in the blood, serum eosinophil cationic protein (ECP), serum EDN, and urinary EDN during the first week of life. Results: Fifty-two preterms were recruited, of whom 43 infants were analyzed. Comparisons were made between the RDS (n=16) and non-RDS groups (n=27) and between the BPD (n=6) and non-BPD groups (n=26). There were no differences between RDS and non-RDS group in total eosinophil count, serum ECP, serum EDN, or urinary EDN, except when compared by gestational age, birth weight and prenatal dexamethasone use. Urinary EDN was increased significantly in the BPD group compared to the non-BPD group. Conclusion: We demonstrated the roles of eosinophil and EDN in the development of BPD and suggest that urinary EDN may be utilized as a noninvasive factor predicting the development of BPD. (Allergy Asthma Respir Dis 2022;10:40-44)

Serum Levels of Eosinophil-Derived Neurotoxin: A Biomarker for Asthma Severity in Adult Asthmatics

이영수,이지호,양은미,권은미,정창규,김수진,최영우,조유숙,김창근,박해심 대한천식알레르기학회 2019 Allergy, Asthma & Immunology Research Vol.11 No.3

Purpose: Eosinophilic inflammation is a key component of severe asthma (SA). However, there has been no reliable serum biomarker for the eosinophilic inflammation of SA. We hypothesized that serum eosinophil-derived neurotoxin (EDN) could predict the eosinophilic inflammation of SA in adult asthmatics. Methods: Severe asthmatics (n = 235), nonsevere asthmatics (n = 898), and healthy controls (n = 125) were enrolled from Ajou University Hospital, South Korea. The serum levels of EDN and periostin were measured by enzyme-linked immunosorbent assay and compared between severe and nonsevere asthmatics. Their associations with total eosinophil count (TEC) and clinical parameters were evaluated; clinical validation of the K-EDN kit for the measurement of serum EDN was evaluated. Results: Severe asthmatics were older and had longer disease duration with significantly lower levels of forced expiratory volume in 1 second and methacholine PC20 than nonsevere asthmatics. Significant differences were found in TEC or sputum eosinophil count (%) between the groups. The serum levels of EDN and periostin were significantly higher in severe asthmatics than in nonsevere asthmatics and in healthy controls (all P < 0.05). Although significant correlations were found between serum EDN levels measured by the 2 kits (ρ = 0.545, P < 0.0001), higher correlation coefficients between serum EDN levels measured by the K-EDN kit and TEC were higher (ρ = 0.358, P < 0.0001) than those between serum EDN levels measured by the MBL kit and TEC (ρ = 0.319, P < 0.0001) or serum periostin level (ρ = 0.222, P < 0.0001). Multivariate regression analysis demonstrated that serum EDN levels measured by the K-EDN kit predicted the phenotype of SA (P = 0.003), while 2 other biomarkers did not. Conclusions: The serum EDN level may be a useful biomarker for assessing asthma severity in adult asthmatics.

만성 기침 환자의 천식 진단을 위한 호산구 탈과립 단백의 효용성

김예진 ( Ye Jin Kim ),김효빈 ( Hyo Bin Kim ),김창근 ( Chang Keun Kim ),( Zak Callaway ) 대한천식알레르기학회 2010 천식 및 알레르기 Vol.30 No.4

Background: Chronic cough is a common non-specific symptom and has various causes including asthma. Objective: The aims of this study were to compare eosinophilic degranulation in the airways between chronic cough patients with and without asthma and to evaluate correlations between sputum eosinophils and eosinophilic degranulation proteins. Method: Thirty-seven patients with chronic cough and 9 normal individuals (control group) were enrolled. Patients with chronic cough were divided into 2 groups based on positivity for bronchial hyperresponsiveness (BHR): those with asthma (asthma group, n=18) and those without asthma (non-asthma group, n=19). Sputum levels of eosinophil- derived neurotoxin (EDN) and major basic protein (MBP) levels were measured, and eosinophil counts were performed in all patients. Result: Sputum % eosinophils were increased in both the asthma and non-asthma groups compared to the control group. However, sputum EDN/MBP levels were increased only in the asthma group compared to the non-asthma and control groups. Sputum % eosinophils correlated positively with sputum EDN/MBP levels in the asthma group, but not in the Non-asthma group. Conclusion: Increased EDN/MBP levels and significant correlations between % eosinophils and EDN/MBP levels were observed only in the asthma group, suggesting that eosinophil degranulation proteins could be a marker for identifying chronic cough due to asthma. (Korean J Asthma Allergy Clin Immunol 2010;30:293-298)

Montelukast Reduces Serum Levels of Eosinophil-Derived Neurotoxin in Preschool Asthma

김창근,Zak Callaway,박진성,Hisashi Nishimori,Tikatoshi Ogino,Mizuho Nagao,다카오후지사와 대한천식알레르기학회 2018 Allergy, Asthma & Immunology Research Vol.10 No.6

Purpose: Several markers for eosinophilic inflammation have been proposed to predictresponse to asthma treatment. However, definitive criteria for treatment decisions have notyet been established. We investigate a potentially useful relatively non-invasive biomarker,eosinophil-derived neurotoxin (EDN), to predict favorable responses to budesonide ormontelukast, common treatment for children with asthma. Methods: Young children (1 to 6 years old) were enrolled in this randomized, parallel,2-group, open-label trial. Criteria for eligibility included: 1) being symptomatic during therun-in period; and 2) having a serum EDN (sEDN) level ≥ 53 ng/mL, with positive specificimmunoglobulin E to house dust mite. Eligible patients were randomly placed into 2 groups:the BIS group received budesonide inhalation suspension (BIS) 0.5 mg once daily; the MONTgroup received montelukast 4 mg once daily. Ineligible patients were invited to receivemontelukast 4 mg once daily (OBS group). Treatment period was 12 weeks. Results: Asthma control days increased significantly in the BIS and MONT groups (P < 0.000)over the 12-week study period. There was no significant change in sEDN in the BIS group butthere was a significant decrease in the MONT group (P < 0.000). Patients in the OBS groupwith high EDN levels (> 53 ng/mL) showed a significant decrease due to MONT treatment(P = 0.023). Rescue medication usage significantly decreased in the BIS and MONT groups(P < 0.000). Conclusions: EDN is a useful relatively non-invasive biomarker for predicting responses tomontelukast and budesonide treatment of preschool children with beta2-agonist responsiverecurrent wheeze and multiple-trigger wheeze (Trial registry at UMIN Clinical Trials Registry,UMIN000008335).

마이코플라스마 폐렴의 호산구성 기도 염증과 천식의 병인과의 연관성

최준기 ( Jun Gi Choi ),고지연 ( Ji Yeon Koh ),김효빈 ( Hyo Bin Kim ),김창근 ( Chang Geun Kim ) 대한소아알레르기호흡기학회(구 대한소아알레르기 및 호흡기학회) 2009 소아알레르기 및 호흡기학회지 Vol.19 No.1

목적: 기도 내 호산구의 활성화와 탈과립 현상이 마이코플라스마 폐렴과 어떻게 관련이 있는지를 알아보고자 하였다. 이를 위해 호산구의 활성도를 나타내는 염증성 매개체인 EDN과 ECP를 마이코플라스마 폐렴 환자의 객담 및 혈청에서 측정하여 그 면역학적 기전을 알아보고자 하였다. 방법: 마이코플라스마 폐렴 환자 40명의 급성기와 회복기, 안정기 천식군 20명, 정상 대조군 20명을 대상으로 하여, 유도 객담 검사 및 혈액을 체취한 후 EDN, ECP를 측정하여 세 군간의 차이를 분석하였다. 결과: 마이코플라스마 폐렴군 급성기의 혈청 EDN, ECP 농도는 안정기 천식군과 유의한 차이를 보이지 않을 만큼 증가되어 있었고, 회복기의 혈청 EDN 농도는 천식군에 비하여 의미 있게 낮아진 소견을 보였다. 마이코플라스마 폐렴군 급성기의 객담 EDN 농도는 안정기 천식군과 유의한 차이를 보이지 않을 만큼 증가되어 있었고, 회복기의 객담 EDN 농도는 안정기 천식군에 비하여 의미 있게 낮아진 소견을 보였다. 마이코플라스마 폐렴군 급성기의 객담 ECP 농도는 안정기 천식군과 유의한 차이를 보이지 않을 만큼 증가되어 있었고, 회복기의 객담 ECP 농도는 안정기 천식군의 값에 비하여 낮아진 경향을 보였지만 통계적으로 의미 있는 차이는 보이지 않았다. 결론: 호산구의 탈과립과 활성화를 나타내는 호산구염증 매개체가 마이코플라스마 폐렴의 급성기에는 증가하고 회복기에는 감소하는 결과를 보임으로써, 호산구의 탈과립이 마이코플라스마 폐렴의 병태생리학적 기전에서 중요한 역할을 함을 보여주었다. Purpose: To investigate whether airway eosinophilic degranulation develops in Mycoplasma pneumonia (M. pneumonia), and to elucidate the association between M. pneumonia and asthma. Methods: Forty patients with M. pneumonia, 20 stable asthma patients (stable asthma) and 20 normal controls were recruited from October 2005 to February 2007. In the M. pneumonia, blood and induced sputum sampling were collected at admission (acute stage) and 6 to 8 weeks later (convalescent stage). Eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) levels in sputum and serum were measured in all 3 groups. Results: Serum levels of EDN and ECP in the acute stage of M. pneumonia were comparable to those in the stable asthma group. However, in the convalescent stage of M. pneumonia, EDN and ECP levels were significantly lower than in the stable asthma (P<0.01 and P<0.05, respectively). Sputum levels of EDN and ECP levels in the acute stage of M. pneumonia were comparable to those in the stable asthma. Sputum EDN levels in the convalescent stage of M. pneumonia were significantly lower than those in the stable asthma (P<0.05), and sputum ECP levels were lower than those in the stable asthma, which was not statistically significant. Conclusion: Eosinophilic degranulation may play an important role in the pathogenesis of M. pneumonia, which suggests the association between M. pneumonia and asthma. [Pediatr Allergy Respir Dis(Korea) 2009;19:63-70]

마이코플라스마 폐렴의 호산구성 기도 염증과 천식의 병인과의 연관성

최준기,김효빈,고지연,김창근 대한 소아알레르기 호흡기학회 2009 Allergy Asthma & Respiratory Disease Vol.19 No.1

Purpose : To investigate whether airway eosinophilic degranulation develops in Mycoplasma pneumonia (M. pneumonia), and to elucidate the association between M. pneumonia and asthma. Methods : Forty patients with M. pneumonia, 20 stable asthma patients (stable asthma) and 20 normal controls were recruited from October 2005 to February 2007. In the M. pneumonia, blood and induced sputum sampling were collected at admission (acute stage) and 6 to 8 weeks later (convalescent stage). Eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) levels in sputum and serum were measured in all 3 groups. Results : Serum levels of EDN and ECP in the acute stage of M. pneumonia were comparable to those in the stable asthma group. However, in the convalescent stage of M. pneumonia, EDN and ECP levels were significantly lower than in the stable asthma (P<0.01 and P<0.05, respectively). Sputum levels of EDN and ECP levels in the acute stage of M. pneumonia were comparable to those in the stable asthma. Sputum EDN levels in the convalescent stage of M. pneumonia were significantly lower than those in the stable asthma (P<0.05), and sputum ECP levels were lower than those in the stable asthma, which was not statistically significant. Conclusion : Eosinophilic degranulation may play an important role in the pathogenesis of M. pneumonia, which suggests the association between M. pneumonia and asthma. 목 적 : 기도 내 호산구의 활성화와 탈과립 현상이 마이코플라스마 폐렴과 어떻게 관련이 있는지를 알아보고자 하였다. 이를 위해 호산구의 활성도를 나타내는 염증성 매개체인 EDN과 ECP를 마이코플라스마 폐렴 환자의 객담 및 혈청에서 측정하여 그 면역학적 기전을 알아보고자 하였다. 방 법 : 마이코플라스마 폐렴 환자 40명의 급성기와 회복기, 안정기 천식군 20명, 정상 대조군 20명을 대상으로 하여, 유도 객담 검사 및 혈액을 체취한 후 EDN, ECP를 측정하여 세 군간의 차이를 분석하였다. 결 과 : 마이코플라스마 폐렴군 급성기의 혈청EDN, ECP 농도는 안정기 천식군과 유의한 차이를 보이지 않을 만큼 증가되어 있었고, 회복기의 혈청 EDN 농도는 천식군에 비하여 의미 있게 낮아진 소견을 보였다. 마이코플라스마 폐렴군 급성기의 객담 EDN 농도는 안정기 천식군과 유의한 차이를 보이지 않을 만큼 증가되어 있었고, 회복기의 객담 EDN 농도는 안정기 천식군에 비하여 의미 있게 낮아진 소견을 보였다. 마이코플라스마 폐렴군 급성기의 객담 ECP 농도는 안정기 천식군과 유의한 차이를 보이지 않을 만큼 증가되어 있었고, 회복기의 객담 ECP 농도는 안정기 천식군의 값에 비하여 낮아진 경향을 보였지만 통계적으로 의미있는 차이는 보이지 않았다. 결 론 : 호산구의 탈과립과 활성화를 나타내는 호산구염증 매개체가 마이코플라스마 폐렴의 급성기에는 증가하고 회복기에는 감소하는 결과를 보임으로써, 호산구의 탈과립이 마이코플라스마 폐렴의 병태생리학적 기전에서 중요한 역할을 함을 보여주었다.