Association of blood inflammatory endotypes and asthma burden in moderate-to-severe pediatric asthma

<bold>Background:</bold> The complexity underlying immunological mechanisms in children with moderate to severe asthma is unclear. <bold>Aim:</bold> We aimed to investigate association of blood inflammatory parameters on asthma burden in children with moderate to severe asthma. <bold>Methods:</bold> Blood inflammatory parameters (eosinophil and neutrophil counts and inflammatory mediators) were measured in 126 children (6-17 years) with moderate-severe asthma from SysPharmPediA cohort across four European countries. Children were divided into mixed, eosinophilic, neutrophilic, and paucigranulocytic asthma based upon blood eosinophil (cut-offs: 0.3×10⁹/L or 0.5×10⁹/L) and neutrophil counts (cut-off: 4×10⁹/L). Inflammatory mediators and burden of disease (asthma control, exacerbations and school days missed in past year) were compared between groups. <bold>Results:</bold> Children with neutrophilic asthma had lowest lung function (FEV₁%predicted pre-salbutamol) compared to other blood inflammatory endotypes. Children with increased blood eosinophils and neutrophils (mixed group) were most often uncontrolled and had highest asthma-related school absence in past year. IL-6 and MMP-9 levels were higher in patients with mixed or neutrophilic asthma, while TIMP-2 was lower in patients with neutrophilic asthma compared to children with eosinophilic or paucigranulocytic asthma. IL-5 was increased in eosinophilic group compared to neutrophilic and paucigranulocytic groups. <bold>Conclusion:</bold> Different blood inflammatory endotypes can be identified in children with moderate to severe asthma while being on maintenance treatment. High blood neutrophil and eosinophil counts despite inhaled corticosteroid (ICS) use are associated with a higher asthma burden.