Transfer factor standardized for alveolar volume.

The interesting article by CHINN et al. [1] explored the relationship of transfer factor (TL) or diffusing capacity to alveolar volume (VA) within normal subjects at different depths of inspiration and between normal subjects having lungs of different sizes, and found that the ratio TL/VA (often called the carbon monoxide transfer coefficient (KCO)) varied with VA itself (i.e. lung size) as well as age, height and gender. The authors claimed, with justification, that inclusion of VA·height-2 in reference equations improves the accuracy of predictions for TL. Some support for their findings that TL/VA is less in those with larger lungs (standardized for height) comes from a paper by BRUDIN et al. [2], in which extravascular tissue density (g lung per unit thoracic volume) was measured with positron emission tomography (PET) in normal subjects lying supine at functional residual capacity (FRC) + tidal volume (VT)/2. Tissue density was inversely correlated with lung size. A link between tissue density and TL/VA is not unreasonable, supporting the notion that larger lungs are relatively "hyperexpanded". Nevertheless, I take issue with CHINN et al. [1] when they say (at the end of the Abstract): "The equations can be used clinically and eliminate the need for the carbon monoxide transfer coefficient (KCO)". There is a popular misconception that TL is divided by VA to "correct" for volume, i.e. the alveolar volume "seen" by the marker gas (CO). In fact, TL is derived from (TL/VA) × VA; TL/VA in this context being: (loge (COo/COt)/BHT)/pb' where o and t refer to alveolar CO concentrations at (approximately) the beginning and end of the breathholding time (BHT), and Pb' is the barometric pressure minus water vapour pressure. Therefore, the components of TL are TL/VA (or KCO) and VA. In the clinical interpretation of a low TL, it is helpful to know whether this is due to a low KCO or a low VA, or both. Consider two instances where, without airflow obstruction, TL was 60% of reference values. In the first instance, there could be a low KCO and normal VA, which would be compatible with a diagnosis of pulmonary vasculitis or hepatopulmonary syndrome; and in the second instance, there could be a high KCO and low VA, which would suggest pneumonectomy or another cause of "loss of units". In pathological states, an increase in TL/VA (or KCO) can be caused either by an increase in blood volume (secondary to increased blood flow per unit VA), the reason for the high KCO in "pneumonectomy", or by a decrease in the expansion of the lung. Attempts have been made to "correct" TL/VA (KCO) and TL for a reduction in VA. As I have implied above, the correction factor will be different for a generalized reduction in alveolar expansion on the one hand, and a "loss of alveolar units" on the other. In clinical practice, there is no simple solution. For this and other reasons, I believe inspection both of KCO and VA values is essential in understanding the reasons for a low TL value.