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

Omony, Jimmy; Thölken, Clemens; Salimi, Azam; Laubhahn, Kristina; Illi, Sabina; Weckmann, Markus; Grychtol, Ruth; Rabe, Klaus Friedrich; Thiele, Dominik; Foth, Svenja; Weber, Stefanie; Brinkmann, Folke; Kopp, Matthias Volkmar; Hansen, Gesine; Renz, Harald; von Mutius, Erika; Schaub, Bianca; Skevaki, Chrysanthi (2024). Urinary eosinophil-derived neurotoxin is associated with reduced lung function in pediatric asthma. Pediatric allergy and immunology, 35(6) Wiley-Blackwell 10.1111/pai.14172

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INTRODUCTION

Eosinophil-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.

METHODS

We 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.

RESULTS

uEDN/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).

CONCLUSIONS

uEDN/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.

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