Nitric oxide and carbon monoxide diffusing capacity of the lung

Abstract

The single breath diffusion capacity of the lung for carbon monoxide (DLCO) is measure for gas uptake by the lung, and consists of a membrane and a vascular component. Nitric oxide (NO) binds 400 times faster to hemoglobin than carbon monoxide, thus the uptake of NO by the blood is very large. Therefore the diffusion capacity of the lung for nitric oxide (DLNO) should reflect the alveolocapillary membrane diffusing capacity only, and should not be influenced by the vascular component. In this thesis some studies with DLCO and DLNO were performed. The KCO is defined as the DLCO divided by the alveolar volume (VA) determined by single breath helium dilution. The interpretation of the KCO is difficult, especially when a restriction is present. The diagnostic value of the KCO appeared to have limited value next to the DLCO. Due to its single breath nature, the DLCO measures only easy accessible lung parts; therefore in patients with chronic obstructive pulmonary disease (COPD) only the non-emphysematous lung volume is measured. The DLNO is independent of hemoglobin concentration, and independent on capillary blood volume, therefore the DLNO is a better index for the function of the alveolocapillary membrane than the DLCO. The DLNO/DLCO ratio can point to the location of the decreased diffusing capacity. The KNO is independent of VA, and therefore is a better index for the diffusion capacity per unit lung volume than the KCO. In a large group of heavy smokers the DLNO performed slightly better in detecting emphysema (defined by low attenuation areas on high resolution computed tomography (HRCT) scan) than the DLCO and the FEV1/FVC ratio. The correlation between pulmonary function measures (FEV1, FEV1/FVC ratio and DLCO) and emphysema on HRCT was weak: normal pulmonary function tests are useful in excluding emphysema, but many subjects with a normal HRCT scan have abnormal pulmonary function tests. The DLNO/DLCO ratio in heavy smokers was significantly higher compared to normal subjects, which is consistent with a vascular based reduction of gas-exchange parameters. In subjects with COPD, HRCT scanning, spirometry and diffusion capacity are complementary approaches, and measure different pathophysiological entities