Gelatinase-associated lipocalin: a marker of neutrophilic inflammation in uncontrolled childhood asthma

Bronchial asthma is among the most common chronic respiratory diseases in pediatrics, with about half of children with asthma experiencing uncontrolled disease progression. Markers of eosinophilic endotype in asthma are well studied, but the neutrophilic endotype, especially in children, has not been sufficiently researched, and reliable serum/plasma markers of the neutrophilic pattern of inflammation in asthma are unknown. Our objective was to determine diagnostic value of neutrophil gelatinase-associated lipocalin (NGAL) levels in blood plasma, and its dependence on clinical asthma control in children. 132 children with asthma aged 6-17 years (mean age 12.5±3.5 years; 81 boys/51 girls) were examined. The degree of asthma control was assessed using the Asthma Control Test questionnaire. The following groups were determined: controlled asthma cases (n = 21); partially controlled asthma (n = 47), and uncontrolled asthma patients (n = 64). NGAL concentration in blood plasma was determined using an automated immunoassay. Statistical analysis included the Kruskal-Wallis test, Mann-Whitney U test, Spearman's correlation analysis, and ordinal logistic regression. The NGAL levels In children with uncontrolled asthma were significantly higher than in controlled and partially controlled asthma groups (p = 0.043). NGAL levels showed a positive correlation with absolute number of peripheral blood neutrophils (r = 0.272; p < 0.001), and showed no association with markers of eosinophilic asthma endotype (total IgE, eosinophils). At the same time, we did not find any differences in NGAL concentration depending on the asthma severity (Kruskal–Wallis test p = 0.420), or clinical phases of the disease, i.e., 103 (63-185) ng/mL in remission stage (n = 46); 105 (66.8-156) ng/mL in exacerbation in presence of viral infection (n = 14); in exacerbation free of viral infection (n = 72), 138 (90.5-207) ng/mL. This difference was insignificant (p = 0.310 by Kruskal-Wallis test). Ordinal logistic regression showed that an increase in NGAL levels by every 10 ng/mL was associated with the likelihood of failed asthma control by 5% (OR = 1.05; 95% CI: 1.01-1.09; p = 0.022). regardless of gender, age, and disease severity. Plasma NGAL concentration is an independent biomarker of uncontrolled asthma in children, reflecting a predominantly neutrophilic inflammation pattern. NGAL may be used as a screening tool for early diagnostics of children at risk of losing asthma control and requiring further treatment adjustment.