Endotypes identified by cluster analysis in asthmatics and non-asthmatics and their clinical characteristics at follow-up: the case-control EGEA study.


Journal

BMJ open respiratory research
ISSN: 2052-4439
Titre abrégé: BMJ Open Respir Res
Pays: England
ID NLM: 101638061

Informations de publication

Date de publication:
12 2020
Historique:
received: 08 05 2020
revised: 05 10 2020
accepted: 28 10 2020
entrez: 3 12 2020
pubmed: 4 12 2020
medline: 25 11 2021
Statut: ppublish

Résumé

Identifying relevant asthma endotypes may be the first step towards improving asthma management. We aimed identifying respiratory endotypes in adults using a cluster analysis and to compare their clinical characteristics at follow-up. The analysis was performed separately among current asthmatics (CA, n=402) and never asthmatics (NA, n=666) from the first follow-up of the French EGEA study (EGEA2). Cluster analysis jointly considered 4 demographic, 22 clinical/functional (respiratory symptoms, asthma treatments, lung function) and four blood biological (allergy-related, inflammation-related and oxidative stress-related biomarkers) characteristics at EGEA2. The clinical characteristics at follow-up (EGEA3) were compared according to the endotype identified at EGEA2. We identified five respiratory endotypes, three among CA and two among NA: CA1 (n=53) with active treated adult-onset asthma, poor lung function, chronic cough and phlegm and dyspnoea, high body mass index, and high blood neutrophil count and fluorescent oxidation products level; CA2 (n=219) with mild asthma and rhinitis; CA3 (n=130) with inactive/mild untreated allergic childhood-onset asthma, high frequency of current smokers and low frequency of attacks of breathlessness at rest, and high IgE level; NA1 (n=489) asymptomatic, and NA2 (n=177) with respiratory symptoms, high blood neutrophil and eosinophil counts. CA1 had poor asthma control and high leptin level, CA2 had hyper-responsiveness and high interleukin (IL)-1Ra, IL-5, IL-7, IL-8, IL-10, IL-13 and TNF-α levels, and NA2 had high leptin and C reactive protein levels. Ten years later, asthmatics in CA1 had worse clinical characteristics whereas those in CA3 had better respiratory outcomes than CA2; NA in NA2 had more respiratory symptoms and higher rate of incident asthma than those in NA1. These results highlight the interest to jointly consider clinical and biological characteristics in cluster analyses to identify endotypes among adults with or without asthma.

Sections du résumé

BACKGROUND
Identifying relevant asthma endotypes may be the first step towards improving asthma management. We aimed identifying respiratory endotypes in adults using a cluster analysis and to compare their clinical characteristics at follow-up.
METHODS
The analysis was performed separately among current asthmatics (CA, n=402) and never asthmatics (NA, n=666) from the first follow-up of the French EGEA study (EGEA2). Cluster analysis jointly considered 4 demographic, 22 clinical/functional (respiratory symptoms, asthma treatments, lung function) and four blood biological (allergy-related, inflammation-related and oxidative stress-related biomarkers) characteristics at EGEA2. The clinical characteristics at follow-up (EGEA3) were compared according to the endotype identified at EGEA2.
RESULTS
We identified five respiratory endotypes, three among CA and two among NA: CA1 (n=53) with active treated adult-onset asthma, poor lung function, chronic cough and phlegm and dyspnoea, high body mass index, and high blood neutrophil count and fluorescent oxidation products level; CA2 (n=219) with mild asthma and rhinitis; CA3 (n=130) with inactive/mild untreated allergic childhood-onset asthma, high frequency of current smokers and low frequency of attacks of breathlessness at rest, and high IgE level; NA1 (n=489) asymptomatic, and NA2 (n=177) with respiratory symptoms, high blood neutrophil and eosinophil counts. CA1 had poor asthma control and high leptin level, CA2 had hyper-responsiveness and high interleukin (IL)-1Ra, IL-5, IL-7, IL-8, IL-10, IL-13 and TNF-α levels, and NA2 had high leptin and C reactive protein levels. Ten years later, asthmatics in CA1 had worse clinical characteristics whereas those in CA3 had better respiratory outcomes than CA2; NA in NA2 had more respiratory symptoms and higher rate of incident asthma than those in NA1.
CONCLUSION
These results highlight the interest to jointly consider clinical and biological characteristics in cluster analyses to identify endotypes among adults with or without asthma.

Identifiants

pubmed: 33268339
pii: 7/1/e000632
doi: 10.1136/bmjresp-2020-000632
pmc: PMC7713177
pii:
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: IP reports personal fees from AGIRàdom, and other fees from ASTRA ZENECA and NOVARTIS outside the submitted work. JJ reports personal fees from ALK and Thermofischer, and grants and personal fees from Novartis and Astra Zeneca outside the submitted work.

Références

Eur Respir J. 2011 Aug;38(2):310-7
pubmed: 21233270
Curr Allergy Asthma Rep. 2015 Jul;15(7):38
pubmed: 26143394
Am J Respir Crit Care Med. 2013 Dec 1;188(11):1303-12
pubmed: 24180417
Am J Epidemiol. 2007 Sep 1;166(5):552-60
pubmed: 17615091
Eur Respir J. 2017 Dec 28;50(6):
pubmed: 29284685
Clin Exp Allergy. 1999 Dec;29 Suppl 4:17-21
pubmed: 10641560
Am J Respir Crit Care Med. 2019 Feb 15;199(4):433-445
pubmed: 30525902
Annu Rev Med. 2020 Jan 27;71:289-302
pubmed: 31689153
Front Pediatr. 2019 Mar 19;7:68
pubmed: 30941334
Nat Immunol. 2015 Jan;16(1):45-56
pubmed: 25521684
Am J Respir Crit Care Med. 1997 Oct;156(4 Pt 2):S123-9
pubmed: 9351592
Am J Respir Crit Care Med. 2018 Jan 1;197(1):22-37
pubmed: 28910134
Lancet. 2018 Jan 27;391(10118):350-400
pubmed: 28911920
J Allergy Clin Immunol. 2016 Jul;138(1):61-75
pubmed: 26851968
Allergy. 2019 Sep;74(9):1649-1659
pubmed: 30865306
Respir Res. 2019 Sep 6;20(1):203
pubmed: 31492144
J Allergy (Cairo). 2013;2013:785835
pubmed: 24288549
J Allergy Clin Immunol. 2018 Jan;141(1):442-445
pubmed: 28987809
R J. 2016 Aug;8(1):289-317
pubmed: 27818791
J Allergy Clin Immunol. 2019 Jul;144(1):1-12
pubmed: 31277742
Nat Med. 2012 May 04;18(5):716-25
pubmed: 22561835
Pharmacol Ther. 2018 Jan;181:169-182
pubmed: 28842273
Pulm Ther. 2016;2:19-41
pubmed: 27512723
Allergy. 2019 Oct;74(10):1835-1851
pubmed: 30953574
Nat Rev Immunol. 2006 Oct;6(10):772-83
pubmed: 16998510
Eur Respir J. 2016 Oct;48(4):1040-1051
pubmed: 27492832
Thorax. 2009 May;64(5):374-80
pubmed: 19131450

Auteurs

Rachel Nadif (R)

Université Paris-Saclay, UVSQ, Univ. Paris-Sud, INSERM, Equipe d'Epidémiologie Respiratoire Intégrative, CESP, 94807 Villejuif, France rachel.nadif@inserm.fr.

Mickael Febrissy (M)

Université de Paris, LIPADE, Paris, France.

Miora Valérie Andrianjafimasy (MV)

Université Paris-Saclay, UVSQ, Univ. Paris-Sud, INSERM, Equipe d'Epidémiologie Respiratoire Intégrative, CESP, 94807 Villejuif, France.

Nicole Le Moual (N)

Université Paris-Saclay, UVSQ, Univ. Paris-Sud, INSERM, Equipe d'Epidémiologie Respiratoire Intégrative, CESP, 94807 Villejuif, France.

Frederic Gormand (F)

CHU de Lyon, Pneumology Department, Lyon, France.

Jocelyne Just (J)

Service d'Allergologie, APHP, Hôpital Trousseau, Sorbonne Université, Paris, France.

Isabelle Pin (I)

Univ. Grenoble Alpes, INSERM, CNRS, Team of Environmental Epidemiology Applied to Reproduction and Respiratory Health, IAB, 38000 Grenoble, France.
CHU de Grenoble-Alpes, Pédiatrie, Grenoble, France.

Valerie Siroux (V)

Univ. Grenoble Alpes, INSERM, CNRS, Team of Environmental Epidemiology Applied to Reproduction and Respiratory Health, IAB, 38000 Grenoble, France.

Régis Matran (R)

Université de Lille Nord de France, Lille, France.
CHU de Lille, Laboratoire de Biochimie et Biologie Moléculaire, Pôle de Biologie Pathologie Génétique, Lille, France.

Orianne Dumas (O)

Université Paris-Saclay, UVSQ, Univ. Paris-Sud, INSERM, Equipe d'Epidémiologie Respiratoire Intégrative, CESP, 94807 Villejuif, France.

Mohamed Nadif (M)

Université de Paris, CNRS, Centre Borelli, 75005 Paris, France.

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