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

Amir Hossein Alizadeh Bahmani; Susanne J H Vijverberg; Simone Hashimoto; Christine Wolff; Catarina Almqvist; Lizan D Bloemsma; Susanne Brandstetter; Paula Corcuera-Elosegui; Mario Gorenjak; Susanne Harner; Anna M Hedman; Michael Kabesch; Leyre López-Fernández; Aletta D Kraneveld; Anne H Neerincx; Maria Pino-Yanes; Uroš Potočnik; Olaia Sardón-Prado; Barbara S Dierdorp; Tamara Dekker; Nariman K A Metwally; Jan Willem Duitman; René Lutter; Paul Brinkman; Mahmoud I Abdel-Aziz; Anke H Maitland-van der Zee

doi:10.1183/23120541.00222-2024

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

Amir Hossein Alizadeh Bahmani, Susanne J H Vijverberg, Simone Hashimoto, Christine Wolff, Catarina Almqvist, Lizan D Bloemsma, Susanne Brandstetter, Paula Corcuera-Elosegui, Mario Gorenjak, Susanne Harner, Anna M Hedman, Michael Kabesch, Leyre López-Fernández, Aletta D Kraneveld, Anne H Neerincx, Maria Pino-Yanes, Uroš Potočnik, Olaia Sardón-Prado, Barbara S Dierdorp, Tamara DekkerNariman K A Metwally, Jan Willem Duitman, René Lutter, Paul Brinkman, Mahmoud I Abdel-Aziz, Anke H Maitland-van der Zee

Faculty of Science

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

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 and neutrophil counts and inflammatory mediators using multiplex immunoassay technology) were measured in children (6-17 years) with moderate-to-severe asthma from the SysPharmPediA cohort across four European countries. Based upon low/high blood eosinophil (LBE/HBE) counts of </≥0.3×10 9·L -1, respectively and low/high blood neutrophil (LBN/HBN) counts of </≥4×10 9·L -1, 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 the lowest lung function (forced expiratory volume in 1 s % predicted pre-salbutamol) compared with other groups. Children with mixed asthma were most often uncontrolled and had the highest asthma-related school absence in the past year. Interleukin (IL)-6 and matrix metalloproteinase-9 levels were significantly higher in patients with mixed or neutrophilic asthma, whereas tissue inhibitor of metalloproteinase-2 was lower in patients with neutrophilic asthma compared with eosinophilic or paucigranulocytic asthma. IL-5 was increased in eosinophilic group compared with the 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 optimising personalised treatment and management strategies in children with moderate-to-severe asthma.

Original language	English
Article number	00222-2024
Journal	ERJ Open Research
Volume	10
Issue number	6
DOIs	https://doi.org/10.1183/23120541.00222-2024
Publication status	Published - Nov 2024

Bibliographical note

Funding

The SysPharmPediA cohort is supported by ZonMW under project number 9 003 035 001; the Ministry of Education, Science, and Sport of the Republic of Slovenia with contract number C330\u201316\u2013500 106; the German Ministry of Education and Research with project number FKZ 031L0088; Instituto de Salud Carlos III through Strategic Action for Health Research; and European Community within the Active and Assisted Living Program framework with award numbers AC15/00015 and AC15/00058 under the frame of the ERACoSysMed JTC-1 call. Funding information for this article has been deposited with the Crossref Funder Registry.

Funders	Funder number
Instituto de Salud Carlos III
European Commission	AC15/00015, AC15/00058
ZonMw	9 003 035 001
Ministry of Education, Science, and Sport of the Republic of Slovenia	C330–16–500 106
Bundesministerium für Bildung und Forschung	FKZ 031L0088

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Alizadeh Bahmani, A. H., Vijverberg, S. J. H., Hashimoto, S., Wolff, C., Almqvist, C., Bloemsma, L. D., Brandstetter, S., Corcuera-Elosegui, P., Gorenjak, M., Harner, S., Hedman, A. M., Kabesch, M., López-Fernández, L., Kraneveld, A. D., Neerincx, A. H., Pino-Yanes, M., Potočnik, U., Sardón-Prado, O., Dierdorp, B. S., ... Maitland-van der Zee, A. H. (2024). Association of blood inflammatory phenotypes and asthma burden in children with moderate-to-severe asthma. ERJ Open Research, 10(6), Article 00222-2024. https://doi.org/10.1183/23120541.00222-2024

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title = "Association of blood inflammatory phenotypes and asthma burden in children with moderate-to-severe asthma",

abstract = "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 and neutrophil counts and inflammatory mediators using multiplex immunoassay technology) were measured in children (6-17 years) with moderate-to-severe asthma from the SysPharmPediA cohort across four European countries. Based upon low/high blood eosinophil (LBE/HBE) counts of 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 the lowest lung function (forced expiratory volume in 1 s \% predicted pre-salbutamol) compared with other groups. Children with mixed asthma were most often uncontrolled and had the highest asthma-related school absence in the past year. Interleukin (IL)-6 and matrix metalloproteinase-9 levels were significantly higher in patients with mixed or neutrophilic asthma, whereas tissue inhibitor of metalloproteinase-2 was lower in patients with neutrophilic asthma compared with eosinophilic or paucigranulocytic asthma. IL-5 was increased in eosinophilic group compared with the 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 optimising personalised treatment and management strategies in children with moderate-to-severe asthma.",

author = "\{Alizadeh Bahmani\}, \{Amir Hossein\} and Vijverberg, \{Susanne J H\} and Simone Hashimoto and Christine Wolff and Catarina Almqvist and Bloemsma, \{Lizan D\} and Susanne Brandstetter and Paula Corcuera-Elosegui and Mario Gorenjak and Susanne Harner and Hedman, \{Anna M\} and Michael Kabesch and Leyre L{\'o}pez-Fern{\'a}ndez and Kraneveld, \{Aletta D\} and Neerincx, \{Anne H\} and Maria Pino-Yanes and Uro{\v s} Poto{\v c}nik and Olaia Sard{\'o}n-Prado and Dierdorp, \{Barbara S\} and Tamara Dekker and Metwally, \{Nariman K A\} and Duitman, \{Jan Willem\} and Ren{\'e} Lutter and Paul Brinkman and Abdel-Aziz, \{Mahmoud I\} and \{Maitland-van der Zee\}, \{Anke H\}",

note = "Copyright {\textcopyright}The authors 2024.",

year = "2024",

month = nov,

doi = "10.1183/23120541.00222-2024",

language = "English",

volume = "10",

journal = "ERJ Open Research",

issn = "2312-0541",

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Alizadeh Bahmani, AH, Vijverberg, SJH, Hashimoto, S, Wolff, C, Almqvist, C, Bloemsma, LD, Brandstetter, S, Corcuera-Elosegui, P, Gorenjak, M, Harner, S, Hedman, AM, Kabesch, M, López-Fernández, L, Kraneveld, AD, Neerincx, AH, Pino-Yanes, M, Potočnik, U, Sardón-Prado, O, Dierdorp, BS, Dekker, T, Metwally, NKA, Duitman, JW, Lutter, R, Brinkman, P, Abdel-Aziz, MI & Maitland-van der Zee, AH 2024, 'Association of blood inflammatory phenotypes and asthma burden in children with moderate-to-severe asthma', ERJ Open Research, vol. 10, no. 6, 00222-2024. https://doi.org/10.1183/23120541.00222-2024

TY - JOUR

T1 - Association of blood inflammatory phenotypes and asthma burden in children with moderate-to-severe asthma

AU - Alizadeh Bahmani, Amir Hossein

AU - Vijverberg, Susanne J H

AU - Hashimoto, Simone

AU - Wolff, Christine

AU - Almqvist, Catarina

AU - Bloemsma, Lizan D

AU - Brandstetter, Susanne

AU - Corcuera-Elosegui, Paula

AU - Gorenjak, Mario

AU - Harner, Susanne

AU - Hedman, Anna M

AU - Kabesch, Michael

AU - López-Fernández, Leyre

AU - Kraneveld, Aletta D

AU - Neerincx, Anne H

AU - Pino-Yanes, Maria

AU - Potočnik, Uroš

AU - Sardón-Prado, Olaia

AU - Dierdorp, Barbara S

AU - Dekker, Tamara

AU - Metwally, Nariman K A

AU - Duitman, Jan Willem

AU - Lutter, René

AU - Brinkman, Paul

AU - Abdel-Aziz, Mahmoud I

AU - Maitland-van der Zee, Anke H

PY - 2024/11

Y1 - 2024/11

N2 - 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 and neutrophil counts and inflammatory mediators using multiplex immunoassay technology) were measured in children (6-17 years) with moderate-to-severe asthma from the SysPharmPediA cohort across four European countries. Based upon low/high blood eosinophil (LBE/HBE) counts of 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 the lowest lung function (forced expiratory volume in 1 s % predicted pre-salbutamol) compared with other groups. Children with mixed asthma were most often uncontrolled and had the highest asthma-related school absence in the past year. Interleukin (IL)-6 and matrix metalloproteinase-9 levels were significantly higher in patients with mixed or neutrophilic asthma, whereas tissue inhibitor of metalloproteinase-2 was lower in patients with neutrophilic asthma compared with eosinophilic or paucigranulocytic asthma. IL-5 was increased in eosinophilic group compared with the 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 optimising personalised treatment and management strategies in children with moderate-to-severe asthma.

AB - 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 and neutrophil counts and inflammatory mediators using multiplex immunoassay technology) were measured in children (6-17 years) with moderate-to-severe asthma from the SysPharmPediA cohort across four European countries. Based upon low/high blood eosinophil (LBE/HBE) counts of 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 the lowest lung function (forced expiratory volume in 1 s % predicted pre-salbutamol) compared with other groups. Children with mixed asthma were most often uncontrolled and had the highest asthma-related school absence in the past year. Interleukin (IL)-6 and matrix metalloproteinase-9 levels were significantly higher in patients with mixed or neutrophilic asthma, whereas tissue inhibitor of metalloproteinase-2 was lower in patients with neutrophilic asthma compared with eosinophilic or paucigranulocytic asthma. IL-5 was increased in eosinophilic group compared with the 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 optimising personalised treatment and management strategies in children with moderate-to-severe asthma.

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U2 - 10.1183/23120541.00222-2024

DO - 10.1183/23120541.00222-2024

M3 - Article

C2 - 39687398

SN - 2312-0541

VL - 10

JO - ERJ Open Research

JF - ERJ Open Research

IS - 6

M1 - 00222-2024

ER -

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

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