Utility of serum HMGB1 in chronic obstructive pulmonary disease with pulmonary hypertension: A single-centre analysis

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) with pulmonary hypertension (PH) worsen outcomes, yet reliable prognostic biomarkers remain lacking.

We aimed to determine the prognostic value of serum high-mobility group Box 1 (HMGB1) in individuals experiencing AECOPD with concurrent PH and to examine its relationship with inflammatory and vascular markers.

Total 127 patients were divided into AECOPD-non-PH group (n = 71) and AECOPD-PH group (n = 56). Serum levels of HMGB1, interleukin-6 (IL-6), endothelin-1, tumour necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF) were measured. Predictive performance was evaluated using receiver operating characteristic and multiple logistic regression analyses.

The AECOPD-PH group had significantly higher serum HMGB1, endothelin-1 and PaCO₂ than the AECOPD-non-PH group. The combination of HMGB1, endothelin-1 and PaCO₂ demonstrated superior diagnostic accuracy for PH, with an area under the curve of 0.751. HMGB1 levels correlated positively with IL-6 (ρ=0.295, p = 0.001) and TNF-α (ρ=0.302, p = 0.001), but negatively with VEGF (ρ=-0.232, p = 0.009). In risk stratification, HMGB1 ≥ 38.24 ng/mL predicted intermediate-high risk PH with 69.2% sensitivity, 64.7% specificity and an area under the curve of 0.700.

Serum HMGB1 was moderately associated with PH in patients with AECOPD, demonstrating its utility in risk assessment. However, these findings are specific to the acute exacerbation setting and should not be extrapolated to stable-phase COPD-associated PH; further studies in stable COPD populations are warranted.