Predictive Value and Clinical Correlation of Baseline FeNO Levels for Balloon Pulmonary Angioplasty Efficacy in Patients with Inoperable chronic thromboembolic pulmonary hypertension

Background Balloon pulmonary angioplasty (BPA) has been confirmed to improve ventilatory efficiency and pulmonary gas exchange in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH), yet the underlying mechanisms driving these improvements remain poorly elucidated. Nitric oxide (NO), as a key endothelium-derived vasodilator, plays a critical role in regulating pulmonary vascular tone and endothelial function. Against this backdrop, the present study aimed to investigate the dynamic changes in fractional exhaled nitric oxide (FeNO) levels following BPA and clarify its correlation with a panel of clinical and functional parameters in this patient population. Methods A prospective cohort of 57 patients diagnosed with inoperable CTEPH was recruited from Shanghai Pulmonary Hospital Affiliated to Tongji University. Comprehensive clinical assessments, including measurements of FeNO, N-terminal pro-brain natriuretic peptide (NT-proBNP), pulmonary function tests (PFT), transthoracic echocardiography (TTE), cardiopulmonary exercise testing (CPET), and right heart catheterization (RHC), were conducted both before BPA treatment and after the completion of the intervention course. Results Patients were stratified into two subgroups based on baseline FeNO levels: FeNO < 25 ppb (n = 46) and FeNO ≥ 25 ppb (n = 11). Key findings were as follows: 1. FeNO levels increased significantly in the FeNO < 25 ppb group after BPA (P < 0.001), whereas no statistically significant change was observed in the FeNO ≥ 25 ppb group (P = 0.110). 2. In the FeNO < 25 ppb group, notable improvements were achieved in pulmonary function, cardiac structure and function, hemodynamic indices, and cardiopulmonary exercise capacity post-BPA; in contrast, the FeNO ≥ 25 ppb group exhibited improvements in cardiac function, hemodynamics, and cardiopulmonary exercise capacity, but no significant changes in pulmonary function parameters. 3. Correlation analysis revealed that baseline FeNO levels in the FeNO < 25 ppb group were negatively correlated with post-treatment changes in diffusing capacity of the lung for carbon monoxide (DLCO) and mean pulmonary artery pressure (mPAP), and positively correlated with baseline left ventricular end-systolic diameter (LVES); for the FeNO ≥ 25 ppb group, baseline FeNO levels were negatively correlated with baseline DLCO values. 4. No significant differences in baseline pulmonary function and cardiac function were detected between the two subgroups; however, the FeNO < 25 ppb group presented with higher baseline mPAP, pulmonary vascular resistance (PVR), and VE/VCO2 slope (SLOPE), as well as lower baseline oxygen uptake efficiency slope (OUES). Moreover, the magnitude of improvements in LVED, LVES, and mPAP was more pronounced in the FeNO < 25 ppb group. Conclusion FeNO levels can serve as a reliable predictive biomarker for treatment response to BPA in CTEPH patients. Those with lower baseline FeNO levels tend to be more suitable candidates for BPA and achieve more comprehensive clinical benefits, while patients with higher FeNO levels may require adjunctive therapeutic strategies to optimize their treatment outcomes.