Circulating nitric oxide products do not solely reflect nitric oxide release in cirrhosis and portal hypertension.

BACKGROUND: Patients with cirrhosis often develop a systemic vasodilatation and a hyperdynamic circulation with activation of vasoconstrictor systems such as the renin-angiotensin-aldosterone system (RAAS), and vasopressin. Increased nitric oxide (NO) synthesis has been implicated in the development of this state of vasodilation and pulmonary dysfunction including increased exhaled NO concentrations. Circulating metabolites (NO(x)) may affect the systemic and pulmonary NO-generation. However, the relations of these abnormalities to the haemodynamic changes remain unclear. AIMS: The aims of the present study were to measure changes in exhaled NO in relation to circulating NO(x), RAAS, and haemodynamics. METHODS: Twenty patients (eight child class A and 12 class B patients) underwent a liver vein catheterization with determination of splanchnic and systemic haemodynamics. Circulating NO(x) and exhaled NO were determined in the supine and sitting positions and related to haemodynamics, RAAS and lung diffusing capacity (D(L)CO). Eight matched healthy individuals served as controls. RESULTS: All patients with cirrhosis had portal hypertension. We found no significant difference in exhaled NO between patients and controls and no changes from the supine to the sitting position. Exhaled NO in the patients correlated significantly with plasma volume, heart rate and D(L)CO. NO(x) concentrations were not significantly increased in the patients. NO(x) correlated with portal pressure and haemodynamic indicators of vasodilatation, but not with exhaled NO concentrations. CONCLUSION: In patients with moderate cirrhosis, exhaled NO is normal. Circulating NO(x) do not seem to reflect pulmonary and systemic NO release, but NO(x) seems to reflect systemic and splanchnic haemodynamic changes in cirrhosis.

Exhaled nitric oxide measure using multiple flows in clinically relevant subgroups of COPD.

Although there is widespread interest in fractional exhaled nitric oxide (FeNO) as a non-invasive, time and cost effective biomarker for assessing airway inflammation in chronic obstructive pulmonary disease (COPD), its usefulness is still controversial. We examined the FeNO levels in clinically meaningful subgroups of COPD in a group of 91 COPD patients with FEV(1) 17-77% of predicted. Multiple flow rates FeNO at 10, 30, 50, 100 and 200 mL/s were measured and a two-compartment model was used to estimate the diffusion Capacity (D), alveolar NO concentration (Calv) and airway wall NO concentration (Caw). All patients had spirometry, assessment of symptoms with questionnaires and low-dose CT scan as well as assessment of weight and body composition. We examined the following subgroups of COPD: Patients with 1) Severe emphysema, 2) Chronic bronchitis, 3) Frequent exacerbations, 4) Loss of lean body mass and 5) Low fat-free mass index. We used advanced non-linear mixed model adjusted for age and gender. The modelled differences in D, Calv or Caw among COPD subgroups were small and not statistically significant. The analysis showed significant effects of current smoking on Caw and of gender on D and Calv. The results were the same if the advanced non-linear mixed model was substituted by more standard analysis techniques. This study questions the relevance of using FeNO as a biomarker to evaluate local inflammation in COPD and points to a need for developing novel non-invasive biomarkers for research laboratory work and daily clinical practice.