Nitric oxide and carbon monoxide lung transfer in patients with advanced liver cirrhosis

In advanced cirrhosis, decreased lung transfer for carbon monoxide (TLCO) and increased alveolar-arterial oxygen tension difference (PA-aO2 ≥15 mmHg while breathing ambient air) are frequently detected. Pulmonary membrane diffusion capacity for CO (DmCO) and pulmonary capillary blood volume (Vcap) can be derived from the simultaneous measurement of TLCO and lung transfer for nitric oxide (TLNO). Measurements of single-breath TLNO and TLCO were performed in 49 cirrhotic patients with advanced liver cirrhosis and in 35 healthy controls to derive Vcap, DmCO, and TLNO:TLCO ratio. Twenty-five patients had increased PA-aO2, of whom 11 had hepatopulmonary syndrome (HPS). Compared with controls, non-HPS patients with normal PA-aO2 had a significant ∼10% decrease in TLCO, DmCO, and Vcap but similar TLNO:TLCO ratios. Compared with non-HPS patients with normal PA-aO2, non-HPS patients with increased PA-aO2 had lower Vcap and higher TLNO:TLCO ratio but similar DmCO. HPS patients had lower Vcap and higher TLNO:TLCO ratios than both subgroups of non-HPS patients. In cirrhotic patients, TLNO:TLCO ratios correlated positively, and TLCO (percentage of the predicted value) and Vcap (percentage of the predicted value) correlated negatively with PA-aO2 ( r 2 = 0.25, P = 0.0003, r 2 = 0.48, P < 0.0001 and r 2 = 0.57, P < 0.0001, respectively). We concluded that, in cirrhotic patients, lower TLCO and increased PA-aO2 are associated with lower Vcap. In addition, high TLNO:TLCO ratios in patients with increased PA-aO2 suggest a decreased thickness of the capillary blood layer in these patients.