European reference equations for CO and NO lung transfer

Abstract

The aim of the present study was to calculate reference equations for carbon monoxide and nitric oxide transfer, measured in two distinct populations.The transfer factor of the lung for nitric oxide (TL,NO) and carbon monoxide (TL,CO) were measured in 303 people aged 18-94 yrs. Measurements were similarly made in two distant cities, using the single-breath technique. Capillary lung volume (Vc) and membrane conductance, the diffusing capacity of the membrane (Dm), for carbon monoxide (Dm,CO) were derived.The transfer of both gases appeared to depend upon age, height, sex and localisation. The rate of decrease in both transfers increased after the age of 59 yrs. TL,NO/alveolar volume (VA) and TL,CO/VA were only age-dependent. The mean TL,NO/TL,CO was 4.75 and the mean Dm/Vc was 6.17 min ; these parameters were independent of any covariate. Vc and Dm,CO calculations depend upon the choice of coefficients included in the Roughton-Forster equation. Values of 1.97 for Dm,NO/Dm,CO ratio and 12.86 min?kPa -1 for 1/red cell CO conductance are recommended.The scatter of transfer reference values in the literature, including the current study, is wide. The present results suggest that differences might be due to the populations themselves and not the methods alone.KEYWORDS: Ageing, capillary lung volume, carbon monoxide, diffusion, nitric oxide, pollution T he measurement of the transfer of gases through the lung is one of the few tests aimed at investigating alveolar function. The 1957 model and equation of ROUGHTON and FORSTER [1] permitted the transfer of carbon monoxide through the aveolocapillary structure to be split into two resistances, one for the alveolar membrane (1/membrane conductance, the diffusing capacity of the membrane (Dm), for carbon monoxide (Dm,CO)) and the other for the blood reacting with the gas (1/HCOVc), where HCO is the red cell conductance at a concentration, set by the pioneers of the method, of 14.9 g?dL -1 [2] and Vc the capillary lung volume:where TL,CO is the transfer factor of the lung for carbon monoxide. The first technique used to solve this equation with two unknowns, Dm and Vc, was to measure two transfers of CO, one under conditions of normoxia the other under hyperoxia. Breathing O 2 , by reducing HCO, lowers the TL,CO. GUENARD et al.[3] first published measurements of Dm and Vc using transfer factor of the lung for nitric oxide (TL,NO) and TL,CO and assuming HNO to be infinity, i.e. TL,NO5Dm,NO.The transfer of CO is dependant upon both Dm and Vc with HCO as a finite value.The relationship between Dm for nitric oxide (Dm,NO) and Dm,CO introduces a constant a: Dm,NO5aDm,CO. Therefore, the measurement of NO transfer alone permits the calculation of Dm,CO and, by introducing the latter into the CO transfer equation, of Vc.Most published reference values for Dm and Vc have been derived from the first two-step technique; one used the NO/CO method in a population of 127 healthy adults with a mean¡SD age of ,40¡12 yrs [4] and another focused on NO transfer in a population of 1...

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“…Using 2.42 instead of 1.97 would have decreased Dm and increased Vc by 23%, and thus introduced an unlikely discrepancy between the two measurements. We therefore preferred to use 1.97 as previously reported in our reference equations (3).…”

“…The coefficient relating DLNO and Dm was set at 1.97 according to the solubility and molecular weights of both gases (3). To solve the Roughton and Forster equation (37), we used an equation proposed by Forster (17) expressing the conductance of CO with hemoglobin ( CO) as a function of capillary PO2:…”

“…Hemoglobin concentrations were measured from venous blood samples, and Vc and DL CO values were corrected accordingly for an inspired PO2 of 150 mmHg and for standard concentrations of hemoglobin of 14.6 g/dl for men and 13.4 g/dl for women (29). The percent predicted values were calculated using previously reported equations (3).…”

Reply to commentary on: Confusion in reporting pulmonary diffusion capacity for nitric oxide and the alveolar-capillary membrane conductance for nitric oxide

“…In fact as breath hold time is increased, NO expiratory concentration reduces, reaching the detection limit of the NO analyser. This is an issue when using electrochemical sensors, as we 1 and others did, 2,5,8 and not with a highsensitivity chemiluminescence NO analyser as other authors did. 10,11 As regards the membrane diffusion for carbon monoxide (DmCO), membrane diffusion for nitric oxide (DmNO) and capillary volume (Vcap), we prefer to call the capillary volume Vcap and not Vc as frequently done to avoid confusion with the vital capacity, and we do not agree with the Zavorsky and Borland critique.…”

“…However, we recognise that our DLNO values in normal subjects, obtained in a sizeable number of subjects, are lower than those previously reported by Zavorsky et al 2 In any case the apparatus we used (Jaeger/Vyasis PFT Masterscreen) was calibrated for gas analysis using automated procedures and the linearity of analysers was factory checked. The formula used is: Concerning breath hold time, we used 4 s, which is the same as Aguilaniu et al 8 used whose data were the basis of the normal standards for European equations for carbon monoxide (CO) and nitric oxide (NO). Anyway, with a longer breath hold time we would expect an underestimation of DLNO, as reported by Dressler et al, 9 and not an overestimation as suggested by Zavorsky and Borland.…”