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

被引:62
作者
Lee, Youngsoo [1 ]
Lee, Ji-Ho [2 ]
Yang, Eun-Mi [1 ]
Kwon, EunMi [3 ]
Jung, Chang-Gyu [4 ]
Kim, Su-Chin [1 ]
Choi, Youngwoo [1 ]
Cho, You Sook [5 ]
Kim, Chang-Keun [3 ]
Park, Hae-Sim [1 ]
机构
[1] Ajou Univ, Dept Allergy & Clin Immunol, Sch Med, 164 Worldcup Ro, Suwon 16499, South Korea
[2] Yonsei Univ, Dept Pulmonol & Allergy, Wonju Coll Med, Wonju, South Korea
[3] Inje Univ, Asthma & Allergy Ctr, Dept Pediat, Sanggye Paik Hosp, Seoul, South Korea
[4] Keimyung Univ, Dept Allergy, Sch Med, Daegu, South Korea
[5] Univ Ulsan, Asan Med Ctr, Dept Allergy & Clin Immunol, Coll Med, Seoul, South Korea
关键词
Eosinophil-derived neurotoxin; asthma; biomarkers; SPUTUM CELL COUNTS; CHILDHOOD ASTHMA; CLUSTER-ANALYSIS; PERIOSTIN; INFLAMMATION; DISEASE; IDENTIFICATION; EXACERBATIONS; ASSOCIATION; MEPOLIZUMAB;
D O I
10.4168/aair.2019.11.3.394
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
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 (rho = 0.545, P < 0.0001), higher correlation coefficients between serum EDN levels measured by the K-EDN kit and TEC were higher (rho = 0.358, P < 0.0001) than those between serum EDN levels measured by the MBL kit and TEC (rho = 0.319, P < 0.0001) or serum periostin level (rho = 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.
引用
收藏
页码:394 / 405
页数:12
相关论文
共 49 条
[1]   The ENFUMOSA cross-sectional European multicentre study of the clinical phenotype of chronic severe asthma [J].
Abraham, B ;
Antó, JM ;
Barreiro, E ;
Bel, EHD ;
Bonsignore, G ;
Bousquet, J ;
Castellsague, J ;
Chanez, P ;
Cibella, F ;
Cuttitta, G ;
Dahlén, B ;
Dahlén, SE ;
Drews, N ;
Djukanovic, R ;
Fabbri, LM ;
Folkerts, G ;
Gaga, M ;
Gratziou, C ;
Guerrera, G ;
Holgate, ST ;
Howarth, PH ;
Johnston, SL ;
Kanniess, F ;
Kips, JC ;
Kerstjens, HAM ;
Kumlin, M ;
Magnussen, H ;
Nijkamp, FP ;
Papageorgiou, N ;
Papi, A ;
Postma, DS ;
Pauwels, RA ;
Rabe, KF ;
Richter, K ;
Roldaan, AC ;
Romagnoli, M ;
Roquet, A ;
Sanjuas, C ;
Siafakas, NM ;
Timens, W ;
Tzanakis, N ;
Vachier, I ;
Vignola, AM ;
Watson, L ;
Yourgioti, G .
EUROPEAN RESPIRATORY JOURNAL, 2003, 22 (03) :470-477
[2]   Induced sputum cell counts in healthy adults [J].
Belda, J ;
Leigh, R ;
Parameswaran, K ;
O'Byrne, PM ;
Sears, MR ;
Hargreave, FE .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2000, 161 (02) :475-478
[3]   IL-17 mRNA in sputum of asthmatic patients: linking T cell driven inflammation and granulocytic influx? [J].
Bullens, Dominique M. A. ;
Truyen, Els ;
Coteur, Liesbeth ;
Dilissen, Ellen ;
Hellings, Peter W. ;
Dupont, Lieven J. ;
Ceuppens, Jan L. .
RESPIRATORY RESEARCH, 2006, 7 (1)
[4]  
Castro M, 2015, LANCET RESP MED, V3, P355, DOI [10.1016/S2213-2600(15)00042-9, 10.1016/S2213-2600(15)00119-8]
[5]   Strategy aimed at reduction of sputum eosinophils decreases exacerbation rate in patients with asthma [J].
Chlumsky, J. ;
Striz, I. ;
Terl, M. ;
Vondracek, J. .
JOURNAL OF INTERNATIONAL MEDICAL RESEARCH, 2006, 34 (02) :129-139
[6]   Biological function of eosinophil extracellular traps in patients with severe eosinophilic asthma [J].
Choi, Youngwoo ;
Duy Le Pham ;
Lee, Dong-Hyun ;
Lee, So-Hee ;
Kim, Seung-Hyun ;
Park, Hae-Sim .
EXPERIMENTAL AND MOLECULAR MEDICINE, 2018, 50 :1-8
[7]   TH2 and TH17 inflammatory pathways are reciprocally regulated in asthma [J].
Choy, David F. ;
Hart, Kevin M. ;
Borthwick, Lee A. ;
Shikotra, Aarti ;
Nagarkar, Deepti R. ;
Siddiqui, Salman ;
Jia, Guiquan ;
Ohri, Chandra M. ;
Doran, Emma ;
Vannella, Kevin M. ;
Butler, Claire A. ;
Hargadon, Beverley ;
Sciurba, Joshua C. ;
Gieseck, Richard L. ;
Thompson, Robert W. ;
White, Sandra ;
Abbas, Alexander R. ;
Jackman, Janet ;
Wu, Lawren C. ;
Egen, Jackson G. ;
Heaney, Liam G. ;
Ramalingam, Thirumalai R. ;
Arron, Joseph R. ;
Wynn, Thomas A. ;
Bradding, Peter .
SCIENCE TRANSLATIONAL MEDICINE, 2015, 7 (301)
[8]   International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma [J].
Chung, Kian Fan ;
Wenzel, Sally E. ;
Brozek, Jan L. ;
Bush, Andrew ;
Castro, Mario ;
Sterk, Peter J. ;
Adcock, Ian M. ;
Bateman, Eric D. ;
Bel, Elisabeth H. ;
Bleecker, Eugene R. ;
Boulet, Louis-Philippe ;
Brightling, Christopher ;
Chanez, Pascal ;
Dahlen, Sven-Erik ;
Djukanovic, Ratko ;
Frey, Urs ;
Gaga, Mina ;
Gibson, Peter ;
Hamid, Qutayba ;
Jajour, Nizar N. ;
Mauad, Thais ;
Sorkness, Ronald L. ;
Teague, W. Gerald .
EUROPEAN RESPIRATORY JOURNAL, 2014, 43 (02) :343-373
[9]   Phase 3 Study of Reslizumab in Patients With Poorly Controlled Asthma Effects Across a Broad Range of Eosinophil Counts [J].
Corren, Jonathan ;
Weinstein, Steven ;
Janka, Lindsay ;
Zangrilli, James ;
Garin, Margaret .
CHEST, 2016, 150 (04) :799-810
[10]   Lebrikizumab Treatment in Adults with Asthma [J].
Corren, Jonathan ;
Lemanske, Robert F., Jr. ;
Hanania, Nicola A. ;
Korenblat, Phillip E. ;
Parsey, Merdad V. ;
Arron, Joseph R. ;
Harris, Jeffrey M. ;
Scheerens, Heleen ;
Wu, Lawren C. ;
Su, Zheng ;
Mosesova, Sofia ;
Eisner, Mark D. ;
Bohen, Sean P. ;
Matthews, John G. .
NEW ENGLAND JOURNAL OF MEDICINE, 2011, 365 (12) :1088-1098