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

Abstract

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.

Blood molecular biomarkers of the inflammatory phenotypes of asthma

“…Serum levels of EDN, which is a degranulation protein released by eosinophils, reportedly reflect eosinophil activation in adult and childhood asthma. EDN may better reflect asthma control status than the total eosinophil count, and may be a useful biomarker for asthma severity [6,7]. In the previous and current reports, EDN and periostin showed similar sensitivity and specificity for blood and sputum eosinophilia [4,7].…”

“…EDN may better reflect asthma control status than the total eosinophil count, and may be a useful biomarker for asthma severity [6,7]. In the previous and current reports, EDN and periostin showed similar sensitivity and specificity for blood and sputum eosinophilia [4,7]. Moreover, the ability to diagnose the eosinophilic inflammatory phenotype was enhanced by use of two biomarkers in combination [4].…”

Serum potential biomarkers according to sputum inflammatory cell profiles in adult asthmatics

“…Among 1,133 adult asthmatics [13] in Ajou University Medical Center (Suwon, Korea), 421 with available sputum profiles were enrolled in this study. All patients were consistent with the diagnosis of bronchial asthma and had been treated with maintenance medications, including medium-to-high doses of inhaled corticosteroids.…”

Blood eosinophils: In quest of a Holy Grail for personalized asthma treatment with biologicals

“…Therefore, more sensitive biomarkers, pathophysiological or clinical features for adequate treatment selection and indication, are highly welcome. Eosinophil activation markers such as eosinophil‐derived neurotoxin (EDN), eosinophil‐derived protein X (EDX), eosinophil cationic protein (ECP) and eosinophil extracellular traps (EET) may overcome certain problems and inaccuracies of PBE . Moreover, another possible IL5‐independent mechanism of eosinophil activation, such as the activation of inflammatory response by neutrophil autophagy and neutrophil extracellular DNA traps, should be considered .…”