In defence of the carbon monoxide transfer coefficientK_CO(T_L/V_A)

Abstract

In defence of the carbon monoxide transfer coefficient KCO (TL/VA). J.M.B.Hughes, N.B.Pride. #ERS Journals Ltd 2001. ABSTRACT: The carbon monoxide transfer factor (TL,CO) is the product of the two primary measurements during breath-holding, the CO transfer coefficient (KCO) and the alveolar volume (VA). KCO is essentially the rate constant for alveolar CO uptake (Krogh's kCO), and in healthy subjects, increases when VA is reduced by submaximal inflation, or when pulmonary blood flow increases. Recently, new reference values were proposed for clinical use which included the observed VA at full inflation; this was claimed to "eliminate the need for KCO".In this commentary, some mechanisms e.g. respiratory muscle weakness, lung resection, diffuse alveolar damage and airflow obstruction, which decrease or increase total lung capacity (TLC) are reviewed.Even when alveolar structure and function are normal, the change in KCO at a given VA varies according to the underlying pathophysiological mechanism. The advantages and disadvantages of normalizing KCO and TL,CO to predisease predicted TLC or to the patient's actual VA (using lack of expansion or loss of alveolar units models) are considered.Examination of carbon monoxide transfer coefficient and alveolar volume separately provides information on disease pathophysiology which cannot be obtained from their product, the carbon monoxide transfer factor. A few years ago, a paper in the European Respiratory Journal [1] concluded that: ". . . the use of TL/VA (the carbon monoxide (CO) transfer coefficient) cannot be justified on scientific grounds". Apart from one letter of disagreement [2], this view that TL/VA (or KCO) is a redundant and misleading measurement has not been challenged. This is surprising because measurements of TL/VA have continued to be published in respiratory journals.The single breath method for measuring CO uptake by the lung, which is used world-wide, was introduced by Krogh [3] in 1915; this measurement was termed diffusion constant. Subsequently the diffusion constant for CO was renamed the diffusing capacity (DL,CO) or the transfer factor (TL,CO), with the uptake being measured at total lung capacity (TLC). Krogh [3] pointed out that TL,CO was the product of two separate measurements, which potentially varied widely (and independently), the rate constant for CO removal from alveolar gas (called the permeability factor (kCO)) and the alveolar volume (VA).kCO is measured as the exponential decay in fractional concentration of CO over a period of breath-holding (BHT):where CO 0 and CO t are the alveolar CO concentrations at the start and finish of the breath-holding period. The units of kCO are s -1 or min -1 . The total CO transfer of the lung is calculated as:where PB and PH2O are the barometric pressure and the water vapour pressure (at 37 ‡C) which standardize for the driving pressure for CO uptake, i.e.the pressure of CO in the alveoli (PA,CO). VA is the alveolar volume measured at standard temperature and pressure, dry (STPD). In modern usag...

Standardisation of the single-breath determination of carbon monoxide uptake in the lung

“…As noted previously, DL,CO decreases as the lung deflates as a function of both membrane and capillary configuration changes [17][18][19][20][21][22][23][24][104][105][106][107][108][109][110][111]. The relationship is complex, however, and is probably nonlinear [108,110].…”

“…status postpneumonectomy), the reduction in DL,CO may be less than the reduction in VA (high DL,CO/VA); in others (e.g. pulmonary vascular disease), the reduction in DL,CO may be greater than the reduction in VA (low DL,CO/VA) [17]. In many disease states, however, the ratio of pathological reductions in DL,CO and VA may be quite variable and of unclear physiological or clinical significance.…”

“…As the lung inflates, DM increases (due to unfolding membranes and increasing surface area), while Vc effects are variable (due to differential stretching and flattening of alveolar and extra-alveolar capillaries) [10,[17][18][19][20][21][22][23][24]. The net effect of these changes is that DL,CO tends to increase as the lung inflates.…”

“…In many disease states, however, the ratio of pathological reductions in DL,CO and VA may be quite variable and of unclear physiological or clinical significance. Thus, although the DL,CO/VA relationship can be used to describe the relative reductions in CO uptake properties and alveolar gas volumes in lung disease [17,19,107,112], drawing more specific clinical or pathological conclusions based upon VA (or any other volume) adjustments should be made with caution. This is especially true if the adjustment leads to the implication that CO uptake properties of the lung are normal.…”

“…The capacity of the lung to exchange gas across the alveolarcapillary interface is determined by its structural and functional properties [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. The structural properties include the following: lung gas volume; the path length for diffusion in the gas phase; the thickness and area of the alveolar capillary membrane; any effects of airway closure; and the volume of blood in capillaries supplying ventilated alveoli.…”