Transfer factor (diffusing capacity) standardized for alveolar volume: validation, reference values and applications of a new linear model to replace KCO (TL/VA)

Abstract

Transfer factor (diffusing capacity) standardized for alveolar volume: validation, reference values and applications of a new linear model to replace KCO (TL/VA). D.J. Chinn, J.E. Cotes, R. Flowers, A-M. Marks, J.W. Reed. ERS Journals Ltd 1996.ABSTRACT: Transfer factor (TL) varies with alveolar volume (VA), but not in the manner implied by the carbon monoxide transfer coefficient (KCO (TL/VA)). This paper considers two other simple models (one linear and one exponential) which might standardize TL for VA, and asks the questions: 1) Is either model valid? 2) What are appropriate reference values? and 3) Will the model be useful?The relationship of TL to VA within subjects at different depths of inspiration, and between subjects having lungs of different sizes, were measured and compared. The subjects were asymptomatic, nonsmoking, Caucasian adults, including 31 males assessed in the laboratory and 503 male and female participants in population studies.The linear partial regression coefficients of TL on VA (L corrected for body temperature, atmospheric pressure and water saturation (BTPS)) standardized for height (H) in metres, were similar within-and between-subjects; the coefficients applied over a wide range of values for VA. Inclusion of VA·H -2 as a covariate in the reference equation for transfer factor, in addition to age and height, improves the accuracy of prediction of normal transfer factor compared with current reference values; its use suggests that some of the differences between published values is due to the volume term. The equations can be used clinically, and eliminate the need for carbon monoxide transfer coefficient. Eur Respir J., 1996Respir J., , 9, 1269Respir J., -1277 When an individual subject performs measurements of transfer factor (TL, which is also called diffusing capacity) by the single-breath method, the result is found to vary with the depth of inspiration, and hence with the alveolar volume (VA) during breatholding. This was first observed by KROGH [1] who, in 1915, reported that "with increasing lung volumes above mean capacity, the permeability factor k (i.e. diffusing capacity per unit lung volume) remained practically constant". Based on this observation the carbon monoxide transfer coefficient (KCO), hereafter designated TL/VA, has been equated with transfer factor standardized for alveolar volume. However, subsequent studies, reviewed by STAM and coworkers [2], have shown that between functional residual capacity and total lung capacity, TL/VA was not constant; instead, it was negatively correlated with alveolar volume. On this account, the usefulness of TL/VA as a means for standardizing TL has been questioned [3,4].The Krogh model (TL/VA) can be represented as TL= mVA, where m is a constant. It is invalid because m is not independent of VA. In this paper, two other simple models are considered, an exponential model of the form TL=mVA δ , and a linear model which can be represented as TL=mVA + c ( fig. 1). To be valid, the parameters of the equations should be independe...

In defence of the carbon monoxide transfer coefficientKCO(TL/VA)

“…After standardization for age, height and sex, Chinn et al [1] found a very similar relation between TL,CO and VA measured at full inflation in their population study (i.e. an inverse relationship between KCO and VA) to that found with submaximal inflation in an individual.…”

“…The objection of Chinn et al [1] to the use of TL/VA is that "VA was the largest single contributor to the variance in TL/VA"; unfortunately, this gives the misleading impression that TL/VA is derived from TL,CO by dividing TL by VA, whereas TL/VA and VA are the two primary measurements used to obtain TL,CO. An unambiguous way to rephrase this objection would be to say that the rate constant for CO uptake varies with VA, as shown (within an individual) by Krogh [3] in 1915, and confirmed by all subsequent authors.…”

“…The variation in KCO with VA in normal subjects has been investigated extensively since 1959 [4]; in 1994, Stam et al [5] suggested that in restrictive lung disease values of TL,CO and KCO should be compared with reference values both at the patient's predicted total lung capacity (TLC) and at the lung volume equal to the patient's actual TLC; this suggestion has been endorsed subsequently [1,6,7]. The novelty in the approach of Chinn et al [1] rests on the development of reference values for TL,CO and KCO, which include a term for VA (at TLC) as well as a height term, i.e.…”

“…The novelty in the approach of Chinn et al [1] rests on the development of reference values for TL,CO and KCO, which include a term for VA (at TLC) as well as a height term, i.e. they take into account variation in TLC at a standard height.…”

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].…”