Association of blood inflammatory phenotypes and asthma burden in children with moderate-to-severe asthma

• Published in: ERJ open research p. 222
• Main Authors: Bahmani, Amir Hossein Alizadeh, Vijverberg, Susanne J.H., Hashimoto, Simone, Wolff, Christine, Almqvist, Catarina, Bloemsma, Lizan D., Brandstetter, Susanne, Corcuera-Elosegui, Paula, Gorenjak, Mario, Harner, Susanne, Hedman, Anna M., Kabesch, Michael, López-Fernández, Leyre, Kraneveld, Aletta D., Neerincx, Anne H., Pino-Yanes, Maria, Potočnik, Uroš, Sardón-Prado, Olaia, Dierdorp, Barbara S, Dekker, Tamara, Metwally, Nariman K. A., Duitman, Jan Willem, Lutter, René, Brinkman, Paul, Abdel-Aziz, Mahmoud I., Maitland-van der Zee, Anke H.
• Format: Journal Article
• Language: English
• Published: 01.08.2024
• ISSN: 2312-0541; 2312-0541
• DOI: 10.1183/23120541.00222-2024

Background Underlying immunological mechanisms in children with moderate-to-severe asthma are complex and unclear. We aimed to investigate the association between blood inflammatory parameters and asthma burden in children with moderate-to-severe asthma. Methods Blood inflammatory parameters (eosinophil(E) and neutrophil(N) counts and inflammatory mediators using multiplex immunoassay technology) were measured in children (6–17 years) with moderate-to-severe asthma from SysPharmPediA cohort across four European countries. Based upon low(L)/high(H) blood(B) eosinophil (LBE/HBE: </≥0.3×10 9 /L, respectively) and neutrophil counts (LBN/HBN: </≥4×10 9 /L, respectively), mixed(HBE-HBN), eosinophilic(HBE-LBN), neutrophilic(LBE-HBN), and paucigranulocytic(LBE-LBN) phenotypes were defined. Inflammatory mediator profiles and burden of disease (asthma control status, exacerbations and school days missed in the past year) were compared between phenotypes using adjusted logistic regression models. Results Among 126 included children (41% girls and mean( sd ) age of 11.94(2.76)), 22%, 44%, 11%, and 23% were classified as mixed, eosinophilic, neutrophilic, and paucigranulocytic phenotypes respectively. Neutrophilic children had lowest lung function (FEV 1 %predicted pre-salbutamol) compared to other groups. Children with mixed asthma were most often uncontrolled and had highest asthma-related school absence in the past year. Interleukin-6(IL-6) and matrix metalloproteinase-9(MMP-9) levels were significantly higher in patients with mixed or neutrophilic asthma, while tissue inhibitor of metalloproteinase-2(TIMP-2) was lower in patients with neutrophilic asthma compared to eosinophilic or paucigranulocytic asthma. Interleukin-5(IL-5) was increased in eosinophilic group compared to neutrophilic and paucigranulocytic groups, irrespective of the chosen cut-off for eosinophilia. Conclusion Differences in asthma burden-related clinical expression and distinct blood inflammatory mediator profiles were found between phenotypes, highlighting implications for optimizing personalized treatment and management strategies in children with moderate-to-severe asthma.