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

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 [OR 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.