Standardisation and application of the single-breath determination of nitric oxide uptake in the lung

Abstract

Diffusing capacity of the lung for nitric oxide (), otherwise known as the transfer factor, was first measured in 1983. This document standardises the technique and application of single-breath This panel agrees that 1) pulmonary function systems should allow for mixing and measurement of both nitric oxide (NO) and carbon monoxide (CO) gases directly from an inspiratory reservoir just before use, with expired concentrations measured from an alveolar "collection" or continuously sampled rapid gas analysers; 2) breath-hold time should be 10 s with chemiluminescence NO analysers, or 4-6 s to accommodate the smaller detection range of the NO electrochemical cell; 3) inspired NO and oxygen concentrations should be 40-60 ppm and close to 21%, respectively; 4) the alveolar oxygen tension ( ) should be measured by sampling the expired gas; 5) a finite specific conductance in the blood for NO (θNO) should be assumed as 4.5 mL·min·mmHg·mL of blood; 6) the equation for 1/θCO should be (0.0062· +1.16)·(ideal haemoglobin/measured haemoglobin) based on breath-holding and adjusted to an average haemoglobin concentration (male 14.6 g·dL, female 13.4 g·dL); 7) a membrane diffusing capacity ratio (/) should be 1.97, based on tissue diffusivity.

The blood transfer conductance for nitric oxide: Infinite vs. finite θ NO

“…However, studies in our laboratory and others have suggested that a value greater than 1.97 should be used when converting Dm NO to Dm CO (Magini et al, 2013; Tamhane et al, 2001). For this reason, we are wary of the conclusion by the recent task force that a value of 1.97 should be utilized (Zavorsky et al, 2017). Below, we have calculated an ‘effective α’ for the finite method (see below) which can be used to directly convert DLNO to Dm CO as the α ratio does for the infinite method.…”

“…While we respect the work of the recent ERS task force, we believe their findings are premature as no study has been designed to calculate an exact θ NO in vivo in humans, and we are also uncomfortable with their conclusions regarding the correct Dm NO /Dm CO (a-) ratio. Additionally, the ERS task force has not presented any new evidence for use of a finite θ NO beyond the evidence discussed above (Zavorsky et al, 2017). Therefore at this time, we suggest the continued use of the assumption that θ NO is infinite until further optimization of the finite θ NO method can be performed.…”

“…Finally, a 2016 study in humans measured DLCO and DLNO while participants breathed 15% and 21% oxygen and attempted to estimate θ NO ; however, this study was not designed to precisely calculate θ NO and therefore only suggests the continued use of the 4.5 ml CO /min/mmHg/ml blood value (Guenard et al, 2016). Based on only these three studies, a recent task force has recommended use of a finite θ NO for calculation of Dm CO and V C (Zavorsky et al, 2017). Furthermore, to the best of our knowledge, there have been no studies optimizing θ NO to the multiple O2 tension method, a method which does not utilize NO, or any other method.…”

“…There remains significant uncertainty as to the correct specific blood transfer conductance for nitric oxide (NO) with hemoglobin (θ NO ) when studying lung diffusing capacity even in light of the ERS task force findings (Zavorsky et al, 2017). Specifically, there is currently a debate as to whether to assume an infinite or finite θ NO when calculating alveolar-capillary membrane conductance (Dm CO ) and pulmonary-capillary blood volume (V C ) from measures of lung diffusing capacity for CO (DLCO) and NO (DLNO).…”

“…While our laboratory has consistently held the original assumption that θ NO is effectively infinite, other groups have begun applying a finite value for θ NO of 4.5 ml CO /min/mmHg/ml blood measured via an in vitro study and supported by animal and human studies not designed to calculate an exact θ NO value (Borland and Cox, 1991; Borland et al, 2010; Guenard et al, 2016; Zavorsky et al, 2014). Based on this limited work, a task force has recently recommended the use of a finite θ NO ; however, we believe these recommendations, including those concerning θ NO and also the correct Dm NO /Dm CO ratio, are premature (Zavorsky et al, 2017). In this manuscript, we will begin by summarizing the evolution of, and the scientific reasoning behind, the original assumption that θ NO is effectively infinite.…”