Urinary eosinophil‐derived neurotoxin is associated with reduced lung function in pediatric asthma

Author:

Omony Jimmy12ORCID,Thölken Clemens3,Salimi Azam4,Laubhahn Kristina25ORCID,Illi Sabina12,Weckmann Markus67,Grychtol Ruth89,Rabe Klaus Friedrich10ORCID,Thiele Dominik611,Foth Svenja1213,Weber Stefanie1213,Brinkmann Folke67,Kopp Matthias Volkmar6714,Hansen Gesine89,Renz Harald415ORCID,von Mutius Erika125,Schaub Bianca25ORCID,Skevaki Chrysanthi413,

Affiliation:

1. Institute for Asthma and Allergy Prevention (IAP), Helmholtz Zentrum Munich German Research Center for Environmental Health (GmbH) Munich Germany

2. German Center for Lung Research (DZL) Comprehensive Pneumology Center Munich (CPC‐M) Munich Germany

3. Center for Synthetic Microbiology (SYNMIKRO) Philipps‐University Marburg Marburg Germany

4. Institute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics University of Marburg Marburg Germany

5. Department of Paediatric Allergology, Dr von Hauner Children's Hospital Ludwig Maximilians University Munich Germany

6. German Center for Lung Research (DZL) Airway Research Center North (ARCN) Großhansdorf Germany

7. University Children's Hospital Luebeck Germany

8. Department of Paediatric Pneumology, Allergology and Neonatology Hannover Medical School Hannover Germany

9. German Center for Lung Research (DZL) Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH) Hannover Germany

10. German Center for Lung Research (DZL) LungenClinic Grosshansdorf GmbH, Airway Research Center North (ARCN) Grosshansdorf Germany

11. Institute of Medical Biometry and Statistics (IMBS) University Medical Center Schleswig‐Holstein Luebeck Germany

12. University Children's Hospital Marburg, University of Marburg Marburg Germany

13. German Center for Lung Research (DZL) University of Giessen, Marburg Lung Center (UGMLC) Giessen Germany

14. Department of Pediatric Respiratory Medicine, Inselspital, University Children's Hospital of Bern University of Bern Bern Switzerland

15. Kilimanjaro Christian Medical University College (KCMUCo) Moshi Tanzania

Abstract

AbstractIntroductionEosinophil‐derived neurotoxin (EDN) is a biomarker for eosinophilic activation. Urinary (u) EDN may allow non‐invasive monitoring of asthma, but clinical recommendations are lacking. We assessed the potential of uEDN as a marker of disease activity in pediatric asthma.MethodsWe assessed urine samples of 371 children from the German ALLIANCE study cohort, from which we had: 169 preschool wheezers (<6 years), 80 asthmatics (≥6 years), and 122 healthy controls using the ImmunoCAP™ EDN Assay. Creatinine (Cr)‐adjusted uEDN values were analyzed using correlations, association tests, (non) parametric statistics, multiple linear, and multivariable regression.ResultsuEDN/uCr values were higher in atopic versus non‐atopic preschool‐aged subjects (p = .035) and associated with the sum of allergen‐specific IgE in younger (r = 0.24, p = .003), and older subjects (r = 0.23, p = .043). uEDN/uCr was marginally a good determinant for atopy (p = .078, for subjects aged <6 years, and p = .058 for subjects ≥6 years). Children with the T2‐high phenotype had higher uEDN/uCr (p < .001) versus T2‐low—irrespective of using uEDN/uCr or blood eosinophils in combination to allergen sIgE for disease phenotyping. uEDN/uCr significantly correlated with reduced lung function among asthmatics (FEV1 z‐scores: r = −0.30, p = .007, and FEV1/FVC z‐scores: r = −0.24, p = .038). Using multivariable modeling, uEDN/uCr was an independent determinant of FEV1 (p = .038), and to a lesser extent, FEV1/FVC (p = .080).ConclusionsuEDN/uCr may serve as a non‐invasive biomarker for clinical features such as lung function in pediatric asthma. We highlight the utility of uEDN/uCr as a biomarker that can be easily assessed using widely available robust diagnostic immunoassays.

Funder

Deutsche Forschungsgemeinschaft

Publisher

Wiley

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