From the authors:
We are grateful to C. Borland for his comments on our review of the TLNO/TLCO ratio (the ratio of the transfer factor of the lung for nitric oxide versus carbon monoxide) [1] and its clinical applications. Undoubtedly, TLNO, on its own, has a role to play in accessing alveolar function in terms of the membrane diffusing capacity, DM. The calculation of pulmonary capillary volume (Vc), on the other hand, requires a value for ΘblCO, the specific conductance of blood for carbon monoxide, and there is some doubt about its correct value. The TLNO/TLCO ratio does not require knowledge of ΘblCO.
An important difference between TLNO and TLCO is that TLNO is not affected by changes in alveolar oxygen tension (PAO2). Thus, as Borland points out, the TLNO/TLCO ratio will fall if mean PAO2 falls because of its dependence on the DMCO/ΘblCO·Vc ratio and the increase in the value of ΘblCO. But, with the standard single breath technique, with a maximal inspiration and subsequent breath hold, there is not likely to be much variation in PAO2 in those units “accessible” to the inspired test gas, whose oxygen fraction is between 0.18 and 0.21 depending on the test gas composition. In routine lung function no corrections have been proposed for PAO2 inhomogeneity in the single breath TLCO test.
C. Borland argues that units with a high alveolar ventilation to perfusion (V′A/Q′) ratio have a high DM/Vc since pulmonary capillary blood flow (and presumably capillary volume) is low in relation to alveolar surface area and volume, and this will increase the TLNO/TLCO ratio. Because of its dependence on DMCO/ΘblCO·Vc, the TLNO/TLCO ratio will be further increased in high V′A/Q′ units by the rise in PAO2 and fall in ΘblCO; thus, a rise in TLNO/TLCO could be a marker for pathological processes involving the pulmonary circulation, including emphysema. We thank C. Borland for pointing this out. But, because of the nature of the single breath test, the rise in DM/Vc is likely to be more important than the fall in ΘblCO.
The converse, that low V′A/Q′ (poorly ventilated but overperfused) regions will have a low DM/Vc ratio seems less likely, since V′A/Q′ and DM/Vc ratios are not directly related. V′A/Q′ depends on the ratio of flow rates, measured during tidal breathing; DM/Vc ratios, on the other hand, measured at full inflation during a breath hold, reflect, more or less, the ratio of alveolar membrane to capillary and red cell surface areas. As we point out in our review [1], this surface area ratio decreases as lung expansion declines (equivalent to a fall in the ratio of transfer coefficients for NO versus CO) and is the reason for the fall in TLNO/TLCO in extrapulmonary restriction.
Finally, in cases of severe anaemia with very low haemoglobin levels, we take C. Borland’s point that TLNO may be reduced.
Footnotes
Conflict of interest: None declared.
- Received March 6, 2013.
- Accepted March 8, 2013.
- ©ERS 2014
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