This single-centre observational analysis examined the potential role of serum HMGB1 (high-mobility group Box 1) as a biomarker in patients presenting with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) who also had pulmonary hypertension (PH). The investigators sought to determine whether HMGB1 related to concurrent inflammatory and vascular mediators and whether it had predictive or diagnostic utility for PH and for stratifying PH risk during acute exacerbation.
The study population comprised 127 patients admitted with AECOPD. Participants were categorized into two groups based on the presence or absence of PH: AECOPD-non-PH (n = 71) and AECOPD-PH (n = 56). Key clinical and laboratory variables were compared between groups, and relationships among biomarkers were assessed using correlation analyses. Diagnostic performance and predictive value were evaluated using receiver operating characteristic (ROC) analysis and multivariable logistic regression where reported.
A total of 127 patients with AECOPD were enrolled and divided into AECOPD-non-PH (71 patients) and AECOPD-PH (56 patients). Serum concentrations of several circulating mediators were measured: HMGB1, interleukin-6 (IL-6), endothelin-1, tumour necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF). Arterial blood gas data including PaCO2 were included in comparative analyses. The investigators used ROC curves to assess diagnostic accuracy and reported correlations between HMGB1 and other measured biomarkers.
Measured biomarkers included HMGB1, IL-6, endothelin-1, TNF-α and VEGF. Compared with the AECOPD-non-PH group, the AECOPD-PH group showed significantly higher serum HMGB1 and endothelin-1 as well as higher PaCO2.
Correlation analysis demonstrated that HMGB1 levels were positively associated with inflammatory cytokines: IL-6 (Spearman ρ = 0.295, p = 0.001) and TNF-α (ρ = 0.302, p = 0.001). In contrast, HMGB1 correlated negatively with VEGF (ρ = -0.232, p = 0.009). These relationships indicate that higher circulating HMGB1 during AECOPD coincided with higher levels of pro-inflammatory cytokines and lower VEGF, a finding the authors report without inferring causation.
The investigators evaluated the diagnostic accuracy of individual and combined markers for identifying PH in the AECOPD population using ROC analysis. A model combining HMGB1, endothelin-1 and PaCO2 achieved better discrimination for PH than single markers alone, with an area under the curve (AUC) reported as 0.751. This combined approach was presented as demonstrating superior diagnostic performance in this cohort of patients experiencing acute exacerbations.
For risk stratification among patients with PH during AECOPD, the authors identified a serum HMGB1 cutoff. An HMGB1 concentration ≥ 38.24 ng/mL predicted intermediate–high risk pulmonary hypertension with a sensitivity of 69.2% and specificity of 64.7%, and an AUC of 0.700. These operating characteristics indicate moderate discrimination for identifying higher-risk PH within the acute exacerbation setting.
The authors concluded that serum HMGB1 was moderately associated with pulmonary hypertension in the context of AECOPD and that HMGB1, particularly when considered alongside endothelin-1 and PaCO2, may have clinical utility for diagnostic and risk-assessment purposes during acute exacerbations. HMGB1’s positive correlations with IL-6 and TNF-α and its negative correlation with VEGF support its association with inflammation and vascular mediator profiles in this setting.
The publication explicitly cautions that these findings apply to the acute exacerbation phase and should not be extrapolated to stable COPD-associated PH without further study. The authors recommended additional research in stable COPD populations to determine whether HMGB1 has similar diagnostic or prognostic value outside the acute exacerbation setting. Details such as the criteria used to define PH, the timing of sample collection relative to exacerbation onset, methods for measuring biomarkers, and multivariable model covariates were not reported in the abstract and therefore cannot be restated here.
Overall, in this single-centre cohort, serum HMGB1 demonstrated moderate associations with PH and with other inflammatory and vascular markers during AECOPD, and it may contribute to combined-marker approaches for identifying PH and stratifying its risk in the acute care context.