Production of Endogenous Nitric Oxide in Chronic Obstructive Pulmonary Disease and Patients with Cor Pulmonale

Abstract

Exhaled nitric oxide (NO) production in stable chronic obstructive pulmonary disease (COPD) has been loosely related to the severity of illness, being significantly reduced in the most severe cases. Pulmonary hypertension is associated with lower NO output from the lung. In this study expired NO was measured in patients with severe stable COPD with or without cor pulmonale (CP). Echocardiographic estimates of right heart function, lung function, diffusion capacity, respiratory muscle strength, and arterial blood gases were obtained in 34 consecutive patients with stable COPD (mean age, 68 +/- 7 yr). Expired NO was measured by chemiluminiscence to obtain fractional exhaled concentrations at peak (FENOp) and at plateau (FENOpl) points of the single-breath curve and resting NO output (V NO). All measurements of expired NO output, FENOp, FENOpl and V NO showed a negative correlation with both systolic pulmonary artery pressure (Pspa) (r = -0.51, -0.63, and -0.63, respectively, p < 0.01 for all) and right ventricle wall dimension (r = -0.41, -0.59, and -0.43, respectively, p < 0.05 for all), but not with any measurement of lung function. When the patients were divided according to the Pspa using a cutoff limit of 35 mm Hg, those subjects with CP showed lower FENOp (13.2 +/- 4.0 versus 36.7 +/- 30.8 ppb, p < 0.05), FENOpl (5.7 +/- 1.9 versus 8.9 +/- 4.7 ppb, p < 0.05), and V NO (69. 2 +/- 5.6 versus 107.6 +/- 14.6 nl/ min, p = 0.02) than did those with a normal resting Pspa. NO production from the airways was significantly lower and inversely related to development of CP in patients with severe COPD. Impaired endothelial release may account for the reduced levels of expired NO.

Pulmonary hypertension in chronic obstructive pulmonary disease

“…There is some evidence, however, that the concentration of NO in expired air is lower in patients with more severe COPD. CLINI et al [93] investigated the relationship between expired NO and right-ventricular function in a group of 34 patients with COPD, showing that echocardiographic estimates of Ppa and right-ventricular function were significantly correlated with expired NO concentration. Patients with right-ventricular dysfunction had lower NO concentration in expired air, suggesting that these patients might have either an impaired release or reduced diffusion of NO from the endothelium into the airways [93].…”

“…It should be noted, however, that the exact origin of NO in expired air is uncertain. Nonetheless, the idea that markers of endothelial function could be analysed in expired air and this might provide information about pulmonary vascular function [93] is attractive and should deserve further investigation.…”

Pulmonary Diseases and the Heart

“…The hypoxic pulmonary vasoconstrictor response is an important adaptive mechanism in human physiology, shunting blood away from hypoxic regions toward better-ventilated areas of the lung, thus improving ventilation-perfusion matching within the lung. Pulmonary vascular remodeling in response to hypoxia is also mediated by a number of other factors including nitric oxide, 9 endothelin, 10 serotonin, and hypoxia inducible factor-1. The role of inflammatory mediators has become increasingly accepted.…”

Measurement of Exhaled Nitric Oxide Using End Tidal Value during Normal Breathing

“…Indeed Hyde et al [25] suggested that changes in NO in the exhaled gas represents changes in diffusing capacity rather than changes in NO production in the airways. Clini et al [40] came to similar conclusions. Production of NO from lung tissue into the alveolar space is likely to increase during inflammatory conditions such as asthma, which can lead to increase NO in the exhaled air.…”