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

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 (eosino...

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Main Authors: 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
Format: Article
Language:English
Published: European Respiratory Society 2024-12-01
Series:ERJ Open Research
Online Access:http://openres.ersjournals.com/content/10/6/00222-2024.full
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author 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
author_facet 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
author_sort Amir Hossein Alizadeh Bahmani
collection DOAJ
description 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 </≥0.3×109·L−1, respectively and low/high blood neutrophil (LBN/HBN) counts of </≥4×109·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.
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spelling doaj-art-036f374c8b1946888ab889551931cee52025-01-14T09:50:22ZengEuropean Respiratory SocietyERJ Open Research2312-05412024-12-0110610.1183/23120541.00222-202400222-2024Association of blood inflammatory phenotypes and asthma burden in children with moderate-to-severe asthmaAmir Hossein Alizadeh Bahmani0Susanne J.H. Vijverberg1Simone Hashimoto2Christine Wolff3Catarina Almqvist4Lizan D. Bloemsma5Susanne Brandstetter6Paula Corcuera-Elosegui7Mario Gorenjak8Susanne Harner9Anna M. Hedman10Michael Kabesch11Leyre López-Fernández12Aletta D. Kraneveld13Anne H. Neerincx14Maria Pino-Yanes15Uroš Potočnik16Olaia Sardón-Prado17Barbara S. Dierdorp18Tamara Dekker19Nariman K.A. Metwally20Jan Willem Duitman21René Lutter22Paul Brinkman23Mahmoud I. Abdel-Aziz24Anke H. Maitland-van der Zee25 Department of Pulmonary Medicine, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands Department of Pulmonary Medicine, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands Department of Pulmonary Medicine, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands Department of Pediatric Pneumology and Allergy, University Children's Hospital Regensburg (KUNO), Regensburg, Germany Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden Department of Pulmonary Medicine, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands KUNO, University of Regensburg, Regensburg, Germany Division of Pediatric Respiratory Medicine, Hospital Universitario Donostia, San Sebastián, Spain Center for Human Molecular Genetics and Pharmacogenomics, Faculty of Medicine, University of Maribor, Maribor, Slovenia Department of Pediatric Pneumology and Allergy, University Children's Hospital Regensburg (KUNO), Regensburg, Germany Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden Department of Pediatric Pneumology and Allergy, University Children's Hospital Regensburg (KUNO), Regensburg, Germany Division of Pediatric Respiratory Medicine, Hospital Universitario Donostia, San Sebastián, Spain Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands Department of Pulmonary Medicine, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna, Santa Cruz de Tenerife, Spain Center for Human Molecular Genetics and Pharmacogenomics, Faculty of Medicine, University of Maribor, Maribor, Slovenia Division of Pediatric Respiratory Medicine, Hospital Universitario Donostia, San Sebastián, Spain Amsterdam Institute for Infection and Immunity, Inflammatory Diseases, Amsterdam, The Netherlands Amsterdam Institute for Infection and Immunity, Inflammatory Diseases, Amsterdam, The Netherlands Department of Pulmonary Medicine, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands Department of Pulmonary Medicine, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands Department of Pulmonary Medicine, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands Department of Pulmonary Medicine, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands Department of Pulmonary Medicine, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands Department of Pulmonary Medicine, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands 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 </≥0.3×109·L−1, respectively and low/high blood neutrophil (LBN/HBN) counts of </≥4×109·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.http://openres.ersjournals.com/content/10/6/00222-2024.full
spellingShingle 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
Association of blood inflammatory phenotypes and asthma burden in children with moderate-to-severe asthma
ERJ Open Research
title Association of blood inflammatory phenotypes and asthma burden in children with moderate-to-severe asthma
title_full Association of blood inflammatory phenotypes and asthma burden in children with moderate-to-severe asthma
title_fullStr Association of blood inflammatory phenotypes and asthma burden in children with moderate-to-severe asthma
title_full_unstemmed Association of blood inflammatory phenotypes and asthma burden in children with moderate-to-severe asthma
title_short Association of blood inflammatory phenotypes and asthma burden in children with moderate-to-severe asthma
title_sort association of blood inflammatory phenotypes and asthma burden in children with moderate to severe asthma
url http://openres.ersjournals.com/content/10/6/00222-2024.full
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