Pulmonary hypertension (PH) commonly complicates acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and is associated with worse outcomes. Dysregulation of nitric oxide synthase pathways has been implicated in pulmonary vascular dysfunction. The relative balance between inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) may reflect vascular pathobiology relevant to PH, but the clinical utility of circulating iNOS, eNOS, or the eNOS/iNOS ratio in patients with AECOPD has not been well defined.
This retrospective observational study included 260 hospitalized AECOPD patients. PH status was determined by Doppler echocardiography: 138 patients had PH and 122 did not. Clinical data collected included demographics, smoking history, comorbidities (including hypertension), GOLD grade, pulmonary function indices, and arterial blood gas parameters.
Serum concentrations of iNOS and eNOS were measured using enzyme-linked immunosorbent assay (ELISA). The eNOS/iNOS ratio was computed from those measurements. In patients with PH, right ventricular–pulmonary arterial (RV–PA) coupling was evaluated using the TAPSE/PASP ratio (tricuspid annular plane systolic excursion divided by pulmonary artery systolic pressure). Statistical analyses included receiver operating characteristic (ROC) analysis to assess diagnostic performance, multivariate logistic regression to identify independent risk and protective factors for PH, and correlation analyses between NOS markers and hemodynamic indices.
Compared with AECOPD patients without PH, those with PH had significantly higher serum iNOS levels and significantly lower eNOS levels and eNOS/iNOS ratio (all P < 0.001). Similar trends were observed when patients were stratified by GOLD grade: patients with GOLD III–IV demonstrated higher iNOS and lower eNOS and eNOS/iNOS ratio than patients with GOLD I–II.
Among the tested markers, the eNOS/iNOS ratio demonstrated the best diagnostic performance for identifying PH in AECOPD. ROC analysis produced an area under the curve (AUC) of 0.86 for the ratio, with reported sensitivity of 83.33% and specificity of 74.59% for detecting PH in this cohort.
Multivariate logistic regression identified several independent risk and protective factors for PH in the studied AECOPD population. Independent risk factors included smoking, GOLD grade III–IV, hypertension, and elevated iNOS. Protective factors included higher FEV1% predicted, higher PaO2, higher eNOS, and a higher eNOS/iNOS ratio. These results suggest that both clinical features and circulating NOS markers independently relate to PH risk in AECOPD.
In patients with PH, serum iNOS correlated positively with pulmonary artery systolic pressure (PASP), whereas eNOS and the eNOS/iNOS ratio correlated negatively with PASP. Additional analysis explored relationships with RV–PA coupling measured by TAPSE/PASP: iNOS was negatively correlated with TAPSE/PASP, while eNOS and the eNOS/iNOS ratio were positively correlated. The eNOS/iNOS ratio showed the strongest positive association with TAPSE/PASP (r = 0.53, P < 0.001), indicating a link between circulating NOS balance and right ventricular–pulmonary arterial functional coupling.
The findings indicate that serum NOS imbalance—specifically a lower eNOS/iNOS ratio—is associated with PH in patients hospitalized for AECOPD and with measures of impaired RV–PA coupling. The eNOS/iNOS ratio demonstrated promising diagnostic accuracy in this cohort and could be considered a noninvasive biomarker to help identify COPD-related PH. Limitations inherent to the report include the retrospective design and reliance on Doppler echocardiography for PH categorization; details beyond what is reported in the source (for example, external validation, cutoff selection rationale, or longitudinal prognostic data) were not provided in the abstract.
The study was approved by Tianjin Chest Hospital (approval number #2024KY-025-01). As a retrospective analysis, informed written consent was waived. The authors declared no competing interests. The article is published under exclusive licence to the publisher, with standard disclaimers.