Stage-Dependent Reorganization of Inflammatory Biomarker Networks During Acute Exacerbations of COPD

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are characterized by intensified systemic inflammation, yet the relationship between inflammatory biomarker profiles and underlying GOLD-defined airflow limitation severity remains incompletely understood. This exploratory cross-sectional study investigated inflammatory and hematological biomarkers across the spectrum of stable-state GOLD-defined airflow limitation severity in patients hospitalized for AECOPD. A total of 100 participants were included, comprising non-COPD controls and patients with mild-to-moderate (GOLD 1–2), severe (GOLD 3), and very severe (GOLD 4) COPD (n = 25/group). Absolute leukocyte count, C-reactive protein (CRP), erythrocyte sedimentation rate, interleukin-6 (IL-6), procalcitonin, and hemoglobin were analyzed using non-parametric statistics, ordinal logistic regression, and Spearman correlation analysis. Absolute leukocyte counts, CRP, IL-6, and procalcitonin differed significantly across the airflow limitation continuum (p < 0.05). Among all variables examined, CRP was the only biomarker independently associated with increasing GOLD-defined airflow limitation severity (OR = 1.15, 95% CI: 1.01–1.31, p = 0.034). Correlation analyses revealed stage-dependent alterations in biomarker interaction patterns, with strong CRP-centered associations observed in GOLD 1–2 progressively weakening in advanced disease stages. These findings suggest that COPD severity is associated not only with quantitative changes in inflammatory biomarkers but also with progressive reorganization of inflammatory biomarker relationships, supporting the potential value of CRP as a complementary marker of disease stratification during AECOPD.