Identification of Clinical Phenotypes in Young Patients with Acute Exacerbations of COPD: A Multicenter Cohort Study

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.

This study analyzed data from a nationwide, multicenter, prospective cohort across 10 tertiary hospitals in China (Sep 2017-Jul 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).

Cluster analysis identified two distinct phenotypes. The "Systemic Inflammatory Phenotype" (n=179) was characterized by a pervasive inflammatory state (elevated CRP, neutrophils, WBC, PCT, 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), non-invasive 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 were comparable to the elderly AECOPD cohort.

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 towards phenotype-driven assessment to enable early identification and targeted management of young AECOPD patients at the greatest risk.