Abstract
Background/Objectives: Chronic Obstructive Pulmonary Disease (COPD) exacerbations affect health and mortality, yet current risk assessments based on previous events have limitations and are less preventative. This study used metabolomics to assess if amino acid profiles are linked to higher COPD exacerbation risk, compared to an amino acid-based panel to standard risk stratification methods, and explored its clinical decision-making and prevention potential. Methods: This prospective cohort study measured plasma concentrations of 19 amino acids in 88 individuals with COPD using ultra-performance liquid chromatography. Participants were observed for 2.5 years to track occurrences of moderate and severe COPD exacerbations. Results: During follow-up, 44 participants (50%) had an exacerbation. Tyrosine and hsCRP were independently linked to exacerbations in multivariable analysis and formed the basis of the “COPDAE score.” This score independently predicted future exacerbations after adjusting for Global Initiative for Chronic Obstructive Lung Disease (GOLD) classifications. A COPDAE score above 1.73 correlated with lower event-free survival in several subgroups: GOLD group A (log-rank = 13.7, p < 0.001), groups A and B (log-rank = 5.0, p = 0.025), and groups A and C (log-rank = 15.2, p < 0.001). Conclusions: Tyrosine and hsCRP together form a biomarker panel to assess and stratify COPD exacerbation risk. This score can help identify stable patients at risk, even with mild symptoms or few prior events, enabling earlier, more personalized interventions.