Systems Biology of Inflammatory Biomarkers in Chronic Obstructive Pulmonary Disease and Their Role in Exacerbation Prediction

Chronic obstructive pulmonary disease (COPD) is characterized by persistent airway inflammation and recurrent exacerbations, which significantly worsen morbidity and mortality. This review integrates systems biology approaches to identify inflammatory biomarkers—such as IL-6, CRP, TNF-α, and fibrinogen—that predict exacerbation risk and disease progression. By synthesizing multi-omics data (genomics, proteomics, metabolomics), we highlight dysregulated pathways, including NF-κB signaling and oxidative stress responses, which correlate with exacerbation frequency (AUC 0.82 for IL-8). Advances in machine learning models combining biomarker panels with clinical variables improve predictive accuracy (sensitivity 89%). Challenges in biomarker standardization and heterogeneity across COPD phenotypes are discussed, with future directions emphasizing personalized biomarker-driven interventions and real-time monitoring technologies.