A Role for Alveolar Exhaled Nitric Oxide Measurement in the Diagnosis of Hepatopulmonary Syndrome.

Abstract

The authors sought to characterize predominantly alveolar exhaled nitric oxide (eNO) in hepatopulmonary syndrome (HPS) compared with non-HPS, changes after liver transplantation, and diagnostic properties. HPS is defined by liver disease, intrapulmonary vascular dilatations (IPVDs), and hypoxemia. Rat models and small human studies suggest that NO overproduction may cause IPVDs. A retrospective review of the Canadian HPS Database (2007 to 2017) and prospective eNO measurement (main outcome) in healthy controls (measurement expiratory flow, 200 mL/s). HPS was defined as: (1) liver disease; (2) contrast echocardiography consistent with IPVDs; and (3) partial pressure of arterial oxygen <70 mm Hg with alveolar-arterial gradient >20 mm Hg; subclinical HPS as criteria (1) and (2) only; and no HPS as criterion (1) only. Current smokers and subjects with asthma or pulmonary hypertension were excluded. A linear mixed effects model was used to compare eNO between groups and before and after transplantation. eNO was 10.4±0.7 ppb in HPS (n=26); 8.3±0.6 ppb in subclinical HPS (n=38); 7.1±1.0 ppb in no HPS (n=15); and 5.6±0.7 ppb in controls (n=30) (P<0.001). eNO decreased from 10.9±0.8 ppb preliver to 6.3±0.8 ppb postliver transplant (n=6 HPS, 6 subclinical HPS) (P<0.001). eNO <6 ppb was 84.4% (73.1% to 92.2%) sensitive and ≥12 ppb was 78.1% (69.4% to 85.3%) specific for HPS (vs. subclinical HPS). HPS subjects have higher alveolar eNO than non-HPS subjects, levels normalize with liver transplantation. Applying eNO cutoff values may aid in HPS diagnosis.