Characterizing ECOPD Phenotypes: Associations with In-Hospital Outcomes and Immunoinflammatory Mechanisms.

Wang, Q; Wang, L; Zhang, L; Zhao, C; Liu, Y; Liu, L; Yuan, L; Feng, M; Wang, G; Li, L; Zhang, S; Yuan, Y; Kang, D; Zhang, X

Characterizing ECOPD Phenotypes: Associations with In-Hospital Outcomes and Immunoinflammatory Mechanisms.

Wang, Q Wang, L Zhang, L Zhao, C Liu, Y Liu, L Yuan, L Feng, M Wang, G Li, L Zhang, S Yuan, Y Kang, D Zhang, X

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Publisher:: Dove Medical Press
Publication Type:: Journal Article
Citation:: International Journal of COPD, 2025, 20, (0), pp. 1613-1624
Issue Date:: 2025

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Field	Value	Language
dc.contributor.author	Wang, Q
dc.contributor.author	Wang, L
dc.contributor.author	Zhang, L
dc.contributor.author	Zhao, C
dc.contributor.author	Liu, Y
dc.contributor.author	Liu, L
dc.contributor.author	Yuan, L
dc.contributor.author	Feng, M
dc.contributor.author	Wang, G
dc.contributor.author	Li, L
dc.contributor.author	Zhang, S
dc.contributor.author	Yuan, Y
dc.contributor.author	Kang, D
dc.contributor.author	Zhang, X
dc.date.accessioned	2026-07-01T07:51:37Z
dc.date.available	2025-05-04
dc.date.available	2026-07-01T07:51:37Z
dc.date.issued	2025
dc.identifier.citation	International Journal of COPD, 2025, 20, (0), pp. 1613-1624
dc.identifier.issn	1176-9106
dc.identifier.issn	1178-2005
dc.identifier.uri	http://hdl.handle.net/10453/195508
dc.description.abstract	BACKGROUND: Hospitalization due to exacerbations of chronic obstructive pulmonary disease (ECOPD) is linked to substantial mortality rates. OBJECTIVE: This study aimed to identify the clinical and inflammatory phenotypes of patients with ECOPD, as well as to examine their associations with in-hospital outcomes. We sought to explore the underlying mechanisms that contribute to the relationship between ECOPD phenotypes and these outcomes. METHODS: A k-means cluster analysis was conducted on 20,890 recruited patients hospitalized for ECOPD. Logistic regression analyses were utilized to evaluate the associations between the identified phenotypes and in-hospital outcomes, such as mortality, invasive mechanical ventilation (IMV), and intensive care unit (ICU) admission. Additionally, a mediation analysis was performed to elucidate the immunoinflammatory mechanisms underlying the relationship between ECOPD phenotypes and in-hospital outcomes. RESULTS: Three distinct phenotypes were identified: Cluster 1 (n=4,944, 23.67%) exhibited a "Female Eosinophilic Phenotype", Cluster 2 (n=10,814, 51.77%) displayed a "Male Eosinophilic Phenotype", and Cluster 3 (n=5,132, 24.57%) presented as an "Geriatric Multimorbidity-Associated Neutrophilic Systemic Inflammatory Phenotype". Clusters 2 and 3 were associated with higher risks of in-hospital mortality (adjusted odds ratio [ORadj]=1.88 and 17.07, respectively) and IMV (ORadj=2.52 and 7.59, respectively) compared to Cluster 1. Patients in Cluster 3 also experienced an extended hospital stay (median of 13 days) and an increased risk of ICU admission (ORadj=7.72). Additionally, blood eosinophils, neutrophils, CRP, and albumin played a mediating role in the relationship between ECOPD phenotypes and the composite outcome. CONCLUSION: Our study identified three phenotypes stratified by sex, multimorbidity burden, and inflammatory endotypes, which advanced threshold definition for eosinophilic exacerbations and provided prognostic insights for ECOPD management.
dc.format	Electronic-eCollection
dc.language	eng
dc.publisher	Dove Medical Press
dc.relation.ispartof	International Journal of COPD
dc.relation.isbasedon	10.2147/COPD.S505016
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	1102 Cardiorespiratory Medicine and Haematology
dc.subject.classification	Respiratory System
dc.subject.classification	3201 Cardiovascular medicine and haematology
dc.subject.mesh	Aged
dc.subject.mesh	Aged, 80 and over
dc.subject.mesh	Cluster Analysis
dc.subject.mesh	Disease Progression
dc.subject.mesh	Eosinophils
dc.subject.mesh	Female
dc.subject.mesh	Hospital Mortality
dc.subject.mesh	Hospitalization
dc.subject.mesh	Humans
dc.subject.mesh	Intensive Care Units
dc.subject.mesh	Male
dc.subject.mesh	Middle Aged
dc.subject.mesh	Neutrophils
dc.subject.mesh	Phenotype
dc.subject.mesh	Prognosis
dc.subject.mesh	Pulmonary Disease, Chronic Obstructive
dc.subject.mesh	Respiration, Artificial
dc.subject.mesh	Risk Assessment
dc.subject.mesh	Risk Factors
dc.subject.mesh	Sex Factors
dc.subject.mesh	Time Factors
dc.subject.mesh	Humans
dc.subject.mesh	Pulmonary Disease, Chronic Obstructive
dc.subject.mesh	Male
dc.subject.mesh	Female
dc.subject.mesh	Phenotype
dc.subject.mesh	Aged
dc.subject.mesh	Hospital Mortality
dc.subject.mesh	Middle Aged
dc.subject.mesh	Risk Factors
dc.subject.mesh	Disease Progression
dc.subject.mesh	Aged, 80 and over
dc.subject.mesh	Intensive Care Units
dc.subject.mesh	Neutrophils
dc.subject.mesh	Respiration, Artificial
dc.subject.mesh	Risk Assessment
dc.subject.mesh	Prognosis
dc.subject.mesh	Eosinophils
dc.subject.mesh	Sex Factors
dc.subject.mesh	Hospitalization
dc.subject.mesh	Time Factors
dc.subject.mesh	Cluster Analysis
dc.subject.mesh	Eosinophils
dc.subject.mesh	Neutrophils
dc.subject.mesh	Humans
dc.subject.mesh	Pulmonary Disease, Chronic Obstructive
dc.subject.mesh	Disease Progression
dc.subject.mesh	Prognosis
dc.subject.mesh	Respiration, Artificial
dc.subject.mesh	Hospitalization
dc.subject.mesh	Hospital Mortality
dc.subject.mesh	Cluster Analysis
dc.subject.mesh	Risk Assessment
dc.subject.mesh	Risk Factors
dc.subject.mesh	Sex Factors
dc.subject.mesh	Phenotype
dc.subject.mesh	Time Factors
dc.subject.mesh	Aged
dc.subject.mesh	Aged, 80 and over
dc.subject.mesh	Middle Aged
dc.subject.mesh	Intensive Care Units
dc.subject.mesh	Female
dc.subject.mesh	Male
dc.subject.mesh	Humans
dc.subject.mesh	Pulmonary Disease, Chronic Obstructive
dc.subject.mesh	Male
dc.subject.mesh	Female
dc.subject.mesh	Phenotype
dc.subject.mesh	Aged
dc.subject.mesh	Hospital Mortality
dc.subject.mesh	Middle Aged
dc.subject.mesh	Risk Factors
dc.subject.mesh	Disease Progression
dc.subject.mesh	Aged, 80 and over
dc.subject.mesh	Intensive Care Units
dc.subject.mesh	Neutrophils
dc.subject.mesh	Respiration, Artificial
dc.subject.mesh	Risk Assessment
dc.subject.mesh	Prognosis
dc.subject.mesh	Eosinophils
dc.subject.mesh	Sex Factors
dc.subject.mesh	Hospitalization
dc.subject.mesh	Time Factors
dc.subject.mesh	Cluster Analysis
dc.title	Characterizing ECOPD Phenotypes: Associations with In-Hospital Outcomes and Immunoinflammatory Mechanisms.
dc.type	Journal Article
utslib.citation.volume	20
utslib.location.activity	United Kingdom
utslib.for	1102 Cardiorespiratory Medicine and Haematology
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Science
utslib.copyright.status	open_access	*
pubs.consider-herdc	true
dc.rights.license	This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by-nc/4.0/
dc.date.updated	2026-07-01T07:51:34Z
pubs.issue	0
pubs.publication-status	Published
pubs.volume	20
utslib.citation.issue	0

Abstract:

BACKGROUND: Hospitalization due to exacerbations of chronic obstructive pulmonary disease (ECOPD) is linked to substantial mortality rates. OBJECTIVE: This study aimed to identify the clinical and inflammatory phenotypes of patients with ECOPD, as well as to examine their associations with in-hospital outcomes. We sought to explore the underlying mechanisms that contribute to the relationship between ECOPD phenotypes and these outcomes. METHODS: A k-means cluster analysis was conducted on 20,890 recruited patients hospitalized for ECOPD. Logistic regression analyses were utilized to evaluate the associations between the identified phenotypes and in-hospital outcomes, such as mortality, invasive mechanical ventilation (IMV), and intensive care unit (ICU) admission. Additionally, a mediation analysis was performed to elucidate the immunoinflammatory mechanisms underlying the relationship between ECOPD phenotypes and in-hospital outcomes. RESULTS: Three distinct phenotypes were identified: Cluster 1 (n=4,944, 23.67%) exhibited a "Female Eosinophilic Phenotype", Cluster 2 (n=10,814, 51.77%) displayed a "Male Eosinophilic Phenotype", and Cluster 3 (n=5,132, 24.57%) presented as an "Geriatric Multimorbidity-Associated Neutrophilic Systemic Inflammatory Phenotype". Clusters 2 and 3 were associated with higher risks of in-hospital mortality (adjusted odds ratio [ORadj]=1.88 and 17.07, respectively) and IMV (ORadj=2.52 and 7.59, respectively) compared to Cluster 1. Patients in Cluster 3 also experienced an extended hospital stay (median of 13 days) and an increased risk of ICU admission (ORadj=7.72). Additionally, blood eosinophils, neutrophils, CRP, and albumin played a mediating role in the relationship between ECOPD phenotypes and the composite outcome. CONCLUSION: Our study identified three phenotypes stratified by sex, multimorbidity burden, and inflammatory endotypes, which advanced threshold definition for eosinophilic exacerbations and provided prognostic insights for ECOPD management.

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http://hdl.handle.net/10453/195508