Rationale

The bronchodilator response (BDR) has been previously associated with increased burden of childhood asthma. In this study, we aim to investigate whether BDR is linked to serum cytokine and chemokine levels in children with moderate-to-severe asthma (MSA).

Methods

Children (aged 6-18 years, n=145) with MSA were recruited in the SysPharmPediA cohort, for whom asthma control and positive BDR (? zFEV₁>0.78) were defined [Abdel-Aziz and Neerincx et al JPM 2021 & Quanjer et al Chest 2017]. Risk of uncontrolled asthma to BDR was estimated by logistic regression after adjusting for age, sex, race, country, and season of inclusion. A panel of 39 serum proteins were measured by Luminex. Proteins with <40% missing values and show <limit of detection (LOD) were imputed by LOD/?2. Children with and without positive BDR were compared for serum proteins by the Mann-Whitney U test with multiple testing correction. A similar analysis was done in children with and without blood eosinophilia (>300 cells/?L).

Results

Children with positive BDR (27%, median age=12.2 yrs) were more likely to have uncontrolled asthma (adj OR=2.7, 95% CI=1.1-7.4). Children with positive BDR showed significantly higher abundance of IL-4, IL-13, TNF-?, IL-7, IL-6, IL-10 and MMP-1 compared to those with no BDR (q<0.05). In contrast, children with blood eosinophilia (64%, median age=11.4 yrs) only had higher abundances of CCL18 and CCL22 (q<0.05).

Conclusion

In children with MSA, positive BDR is associated with elevated T2 and T1 inflammation markers. The findings suggest that BDR may be complementary to blood eosinophils, and could be used as a non-invasive clinical parameter in asthma phenotyping.