Serum BDNF, PD-1, MMP-9 in AECOPD: prognostic value and a dual-axis risk model

To investigate longitudinal changes in neuroimmune biomarkers during acute exacerbations of chronic obstructive pulmonary disease (AECOPD), their modulation by standard therapy, and prognostic implications for 90-day outcomes.

In a prospective cohort, 266 hospitalized AECOPD patients were stratified into worsened (n = 53) and stable (n = 213) groups; 80 healthy individuals served as controls. Serum levels of BDNF, PD-1, MMP-9, and cytokines were assessed at admission (T1), pre-discharge (T2), and 90-day follow-up (T3). Mixed-effects models evaluated biomarker trajectories, while Cox regression examined correlations with clinical outcomes.

Compared with controls, AECOPD patients exhibited higher IL-6, TNF-α, PD-1, and MMP-9, alongside reduced BDNF and IL-10. Stable patients demonstrated partial biomarker normalization, whereas worsened patients retained a pro-inflammatory profile. Corticosteroids and antibiotics attenuated cytokine elevations, and oxygen therapy facilitated BDNF recovery. Low BDNF and high MMP-9 predicted spirometric decline, while elevated PD-1 and MMP-9 were associated with increased 90-day readmission risk. A dual-axis model incorporating neurotrophic and immune exhaustion markers outperformed GOLD classification for risk prediction.

Neuroimmune biomarkers capture recovery heterogeneity in AECOPD. The proposed dual-axis model improves prognostic accuracy and may inform personalized management strategies.