Baseline Type 2 Biomarker Levels and Clinical Remission Predictors in Children with Asthma
Authors: Chen Mengmeng , Li Congcong , Yang Qiuyan , Zhang Huijie , Zhang Yanli , Wang Na , Dong Jingcheng 
Published: April 2024

Abstract

Background
Little study investigates the association between baseline type 2 biomarker levels and clinical features in children diagnosed with asthma. Characterizing clinical remission in Th2-high asthma could offer valuable insights into asthma prognosis.
Objectives
The study aims to investigate the association of baseline type 2 biomarker levels and clinical features in children with asthma, and to identify predictors of clinical remission of asthma in children.
Methods
A total of 172 children with baseline age of 6.87 ± 3.04 (mean ± SD) years were enrolled in the study including 119 with physician-diagnosed asthma who regularly attended a pediatric asthma center and 53 control subjects with no respiratory symptoms. Clinical tests included lung function examination, Fraction of exhaled NO (FeNO), total IgE, blood eosinophil, and skin test. Serum Th2 biomarkers were examined by ELISA. The enrolled patients have readjusted into Th2-high asthma according to clinical eosinophil count and total IgE, and Th2-high asthma subjects were further classified into acute attack asthma, persistent asthma, and clinical remission according to the recent GINA guidelines and clinical evaluation. To verify our results, the concentration of TSLP levels was measured in BALF, serum, and lung tissue by ELISA in mouse models.
Results
Compared with asthma and control groups, eosinophil counts and blood eosinophils (%) were significant, whereas, no correlation was observed between asthma subjects and controls including Th2 biomarkers, gender, or ages. Positive correlations were observed between Th2 inflammatory biomarkers (TSLP, TRAC IL-5, IL-13, and Periostin) at baseline. Th2-high asthma (n = 110) was defined based on clinical measurement of IgE > 100 IU/ml and a blood eosinophil count ≥ 140 cells/µl. Among those Th2-high asthma subjects, there were 48 in acute exacerbation (43.6%), and 36 in clinical remission (32.7%), 26 were clinical asthma persistence (23.6%). Lung function and serum TSLP had marked significance among the three categories. Compared with clinical remission asthmatic subjects and controls, serum TSLP levels were significantly higher in subjects experiencing acute exacerbation and subjects defined as asthma persistence. Spearman’s correlation outlined that serum TSLP levels were related to Total IgE (IU/mL), FEV1/FVC ratio, and FEF25-75, pred %. Multivariate logistic regression analysis demonstrated that serum TSLP levels were associated with clinical remission in Th2-high asthma children (OR = 1.009; 95% CI, 1.0087–1.0086 P = 0.023<0.05). It is also revealed that serum TSLP levels may help evaluate clinical remission in Th2-high asthma when using ROC curves analysis (AUC = 0.5887, 95% CI: 0.5052 to 0.7038, P < 0.05). A cutoff value of 373.363 pg/mL was found with the highest clinical sensitivity and specificity. PPV, and NPV were 100%, 39.1%, and 59.4%, 100% in two groups, respectively. However, there were no positive results in the analysis of multivariable logistic regression in determining the predictors of persistence in Th2-high asthma. In BALF mouse, TSLP concentration had no statistically significant change in the acute and remission stages when compared to the control, but it did increase noticeably in the chronic stage (P < 0.001).