Noninvasive urinary biomarkers 3-bromotyrosine and leukotriene E4 in assessing asthma control and flare-up in children: a case-control study.

UNLABELLED: To assess urinary biomarkers 3-bromotyrosine and leukotriene E4 (LTE4) levels in children with asthma and their association with asthma control and flare-up. This was a prospective study which applied a case-control design with 2:1 ratio. Children aged 3 to 15 years diagnosed with asthma according to the GINA 2022 guidelines were included. Measurements of urinary 3-bromotyrosine and LTE4 values were done using liquid chromatography-mass spectrometry. The asthma group (n = 146) had significantly higher urinary 3-bromotyrosine levels (22.58 ± 8.15 ng/mg creatinine) compared to healthy controls (n = 73) (14.53 ± 1.27 ng/mg creatinine, p < 0.001). Children with asthma flare-up exhibited significantly higher urinary 3-bromotyrosine levels (32.14 ± 7.76 ng/mg creatinine) compared to those with well-controlled asthma (17.16 ± 5.48 ng/mg creatinine, p < 0.001). Levels of 3-bromotyrosine decreased significantly after symptom control in hospitalized flare-up cases. Similarly, urinary LTE4 levels were significantly higher in the asthma group (308.40 ± 90.13 pg/mg creatinine) than controls (84.54 ± 18.27 pg/mg creatinine, p < 0.001). A significant difference in LTE4 levels was observed between well-controlled and flare-up cases. Urinary LTE4 levels also decreased following symptom control in hospitalized children. Both 3-bromotyrosine and LTE4 levels showed similar patterns of increase and decrease across asthma subgroups (well-controlled and flare-up). The Pearson's correlation coefficient between 3-bromotyrosine and LTE4 was r = 0.58 (p < 0.001). The ROC curve analysis demonstrated that both biomarkers moderately predict severity of asthma. The area under the curve for predicting flare-up was higher for LTE4.

CONCLUSION

Noninvasive urinary biomarkers, 3-bromotyrosine, and LTE4 were elevated in asthma and flare-up. Both biomarkers exhibited similar trends, with levels rising or falling according to asthma control status. The area under the curve to severity of asthma was higher for LTE4.

WHAT IS KNOWN: • Asthma in children is associated with airway inflammation; several inflammatory biomarkers correlate with disease activity. Non-invasive biomarkers are increasingly preferred in children because blood sampling and invasive procedures can be difficult. • Urinary biomarkers have been investigated in asthma, particularly markers related to oxidative stress, leukotriene metabolism, eosinophilic inflammation, and mast-cell activation.

WHAT IS NEW: • Demonstrates that both non-invasive urinary biomarkers, 3-bromotyrosine and LTE4, are significantly elevated in children with asthma compared with healthy controls, and their higher levels are associated with poor disease control and flare-up. Both 3-bromotyrosine and LTE4, levels showed similar patterns of increase and decrease across asthma subgroups. • The Pearson's correlation coefficient between 3-bromotyrosine and LTE4 was r=0.58. The area under the curve to severe flare-up was higher for LTE4. Biomarker levels decline after symptom control provides evidence that these markers reflect ongoing disease activity and might be useful in disease monitoring.