The T_LNO/T_LCO ratio in pulmonary function test interpretation

To the Editor:

Hughes and van der Lee [1] provide an excellent review of transfer factor of the lung for nitric oxide (T_LNO)/transfer factor of the lung for carbon monoxide (T_LCO) and highlight this ratio as a new lung function test in its own right. Perhaps we “T_LNO enthusiasts” have overplayed T_LNO as a route to D_M (membrane diffusing capacity) and to V_c (lung capillary volume) over the past three decades rather than thinking of it as a part of this ratio. Hughes and van der Lee [1] have rightly argued that T_LNO/T_LCO reflects D_M/V_c and α, the ratio of nitric oxide/carbon monoxide diffusivity.

Because T_LCO is oxygen tension (P_O2) dependent and T_LNO is not, I would also emphasise the importance of alveolar P_O2 as a potential determinant of T_LNO/T_LCO in some of the studies they quote.

We found that T_LNO/T_LCO decreased from 4.5 to 3.8 in 10 healthy volunteers as alveolar oxygen per centwas decreased from 20 to 12% [2].This is entirely predictable from the review by Hughes and van der Lee [1] since specific conductance of blood for carbon monoxide (Θbl_CO) increases with hypoxia, as they predicted (equation 8).

Thus, in a healthy individual as breath hold time increases alveolar oxygen tension and, hence, T_LNO/T_LCO should fall. Again, on exercise, where most participants have used single breath or rebreathing methods, oxygen consumption rises with increasing workload, mean sampled alveolar P_O2 falls steeply and hence T_LNO/T_LCO should fall. In disease we might expect lung units of high D_M/V_c to also have high alveolar ventilation V′_A/perfusion (Q′) and, therefore, high P_O2. T_LNO/T_LCO will then increase as Θ_CO falls. This could contribute, along with increased D_M/V_c to increased T_LNO/T_LCO observed in heavy smokers, certain diffuse pulmonary diseases, pulmonary hypertension and pulmonary artery hypertension. This argument always supposes that it is units of high V′_A/Q′ that are being sampled. Conversely reduced lung expansion in restriction or in the obese would give low V′_A/Q′ and hence low T_LNO/T_LCO.

One final comment is that they state on a number of occasions that T_LNO is independent of haemoglobin. This is correct in the strictest sense: theoretically and in clinical practice lung nitric oxide transfer does not vary with the haematocrits routinely encountered [3, 4]. However, if seriously low haemoglobin concentrations (<8 g·dL⁻¹) are generated in the laboratory this can be shown to reduce the blood nitric oxide conductance [5].

• Received February 7, 2013.
• Accepted February 20, 2013.

• ©ERS 2014