Serum HMGB1 was moderately associated with PH in patients with AECOPD, demonstrating its utility in risk assessment, with the combination of HMGB1, endothelin-1 and PaCO2 showing superior diagnostic accuracy (AUC=0.751) for pulmonary hypertension.
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 pulmonary hypertension compared to individual markers.
Serum HMGB1 levels correlated positively with IL-6 and TNF-α, and negatively with VEGF.
A serum HMGB1 threshold of ≥38.24 ng/mL predicted intermediate-high risk pulmonary hypertension with moderate sensitivity and specificity.
The findings of serum HMGB1 utility are specific to the acute exacerbation setting and should not be extrapolated to stable-phase COPD-associated pulmonary hypertension.
This research suggests that a protein called HMGB1, measurable in the blood, may help identify which patients hospitalized for a flare-up (acute exacerbation) of chronic obstructive pulmonary disease (COPD) also have dangerous high blood pressure in their lungs (pulmonary hypertension). The study compared 71 COPD patients without pulmonary hypertension to 56 COPD patients with pulmonary hypertension, finding that those with pulmonary hypertension had notably higher blood levels of HMGB1. The researchers also found that HMGB1 levels were linked to higher levels of inflammation markers (IL-6 and TNF-α) and lower levels of a vascular growth factor (VEGF), suggesting HMGB1 may reflect both inflammatory and vascular changes occurring in this condition. When HMGB1 was combined with two other measurements—endothelin-1 (another blood marker) and PaCO2 (a measure of carbon dioxide in the blood)—the combined test was better at detecting pulmonary hypertension than any single marker alone, achieving an AUC of 0.751. A specific HMGB1 blood level cutoff of 38.24 ng/mL was identified that could flag patients at intermediate-to-high risk, correctly identifying about 69% of high-risk patients and correctly ruling out about 65% of lower-risk patients. This research suggests that measuring HMGB1 during a COPD flare-up could assist clinicians in assessing pulmonary hypertension risk, potentially helping to guide patient monitoring and care decisions. However, the study was conducted at a single center with a relatively small sample, and the authors caution that these findings apply only to patients during acute flare-ups—not to people with stable COPD—so further research in broader and more diverse populations is needed before this marker could be used routinely in clinical practice.
Lv Q, Yao R, Cheng M. (2026). Utility of serum HMGB1 in chronic obstructive pulmonary disease with pulmonary hypertension: A single-centre analysis.. Pulmonology. https://doi.org/10.1080/25310429.2026.2720837