Identification of Clinical Phenotypes in Young Patients with Acute Exacerbations of Chronic Obstructive Pulmonary Disease: A Multicenter Cohort Study

INTRODUCTION: Despite the rising recognition of chronic obstructive pulmonary disease (COPD) in younger adults (20-50 years), the clinical heterogeneity of this population during acute exacerbations (AECOPD) remains undefined, obscuring precision risk stratification and personalized management. METHODS: This study analyzed data from a nationwide, multicenter, prospective cohort across 10 tertiary hospitals in China (September 2017-July 2021). From 13,993 eligible patients, we identified 334 young AECOPD cases. Unsupervised K-means clustering was applied using nine biomarkers of inflammation, hematologic function, and structural lung damage. To contextualize its clinical relevance, the disease severity of the identified high-risk phenotype was benchmarked against the elderly AECOPD cohort (n = 13,659). RESULTS: Cluster analysis identified two distinct phenotypes. The "Systemic Inflammatory Phenotype" (n = 179) was characterized by a pervasive inflammatory state (elevated C-reactive protein, neutrophils, white blood cell, procalcitonin, and fibrinogen) and significantly worse lung function. In contrast, the "Eosinophilic Phenotype" (n = 155) exhibited an eosinophil-predominant profile. Critically, the systemic inflammatory phenotype experienced a more severe hospital course, with significantly higher rates of invasive mechanical ventilation (3.9% vs. 0.0%, p = 0.017), noninvasive ventilation (23.5% vs. 10.3%, p = 0.003), and ICU admission (6.7% vs. 1.3%, p = 0.026). Notably, the overall disease severity of this high-risk phenotype was comparable to the elderly AECOPD cohort. CONCLUSION: We identified a high-risk systemic inflammatory phenotype among young AECOPD inpatients, demonstrating clinical acuity on par with elderly patients. These findings challenge the conventional age-centric risk paradigm and advocate for a shift toward phenotype-driven assessment to enable early identification and targeted management of young AECOPD patients at the greatest risk.