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Background: Wheezing is common in early life, but most children stop wheezing by school age. However, the prediction of course of wheezing through childhood is difficult., Objective: To investigate whether urinary EPX (a marker of eosinophil activation) in children at age 3 years may be useful for the prediction of wheeze persistence and future asthma diagnosis., Methods: U-EPX was measured at age 3 years (radioimmunoassay) in 906 participants in the population-based birth cohort. Children attended follow-ups to age 16 years. We investigate the discriminative ability of u-EPX and other factors in predicting asthma diagnosis at age 16 using receiver operating characteristic [ROC] curves., Results: Of 613 children with follow-up information at age 16, 511 had data on u-EPX at age 3 and asthma diagnosis at age 16 years; of those; 133 (21.7%) had asthma. Based on longitudinal data, children were assigned to wheeze clusters: No wheeze (NWZ), early transient (ETW), late-onset (LOW), intermittent (INT) and persistent wheeze (PEW). U-EPX levels differed significantly between different wheeze clusters (p = .003), with clusters characterised with persistent symptoms having higher u-EPX. In the whole cohort, the best performing classification model for asthma diagnosis at age 16 years included sex, u-EPX, sensitisation and wheeze (area under the curve (AUC) = 0.82, 95% CI: 0.76-0.88). u-EPX and allergic sensitisation alone had similar predictive power (AUC [95%CI]: 0.64 [0.58-0.71] and 0.65 [0.60-0.71]). The best performing classification model for asthma prediction among children with doctor-confirmed wheeze in the first 3 years included child's u-EPX and sensitisation at age 3 years, sex, gestational age and maternal atopy (AUC: 0.76, 95%CI: 0.67-0.85)., Conclusions: Early-life u-EPX may be a useful non-invasive marker for asthma prediction in adolescence., (© 2024 The Author(s). Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)