Optimizing the calculation of D M,CO and V C via the single breath single oxygen tension DL CO/NO method

Abstract

Alveolar-capillary membrane conductance (DM,CO) and pulmonary-capillary blood volume (VC) are calculated via lung diffusing capacity for carbon monoxide (DLCO) and nitric oxide (DLNO) using the single breath, single oxygen tension (single-FiO2) method. However, two calculation parameters, the reaction rate of carbon monoxide with blood (θCO) and the DM,NO/DM,CO ratio (α-ratio), are controversial. This study systematically determined optimal θCO and α-ratio values to be used in the single-FiO2 method that yielded the most similar DM,CO and VC values compared to the ‘gold-standard’ multiple-FiO2 method. Eleven healthy subjects performed single breath DLCO/DLNO maneuvers at rest and during exercise. DM,CO and VC were calculated via the single-FiO2 and multiple-FiO2 methods by implementing seven θCO equations and a range of previously reported α-ratios. The RP θCO equation (Reeves and Park, Respiration physiology 88:1–21, 1992.) and an α-ratio of 4.0–4.4 yielded DM,CO and VC values that were most similar between methods. The RP θCO equation and an experimental α-ratio should be used in future studies.

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

“…However, as can be seen in Table 2, the single breath method tends to yield higher DLNO/DLCO ratios than that of the rebreathe method (presently, mean 5.39 ± 0.43 for single breath vs. 3.58 ± 0.59 for rebreathe), such that approaching the asymptote is not usually an issue. The observation that DLNO/DLCO is slightly higher using the single breath method is found in our laboratory and others (Ceridon et al, 2010; Ceridon et al, 2011; Coffman et al, 2016; Zavorsky and Lands, 2005; Zavorsky and Murias, 2006). …”

“…From both of these studies, our laboratory has concluded that the θ CO equation described by Reeves and Park is ideal, while the optimal α value is dependent on the technique used; ~2.26 for rebreathe and ~4.40 for single breath. This difference can be understood by recognizing that the single breath method, in our laboratory and others, often yields DLNO values somewhat higher than the rebreathe method (Ceridon et al, 2010; Ceridon et al, 2011; Coffman et al, 2016; Snyder et al, 2007; Zavorsky et al, 2014; Zavorsky and Murias, 2006; Zavorsky et al, 2004). Of note, while this inconsistency in DLNO values between the two methods in not completely understood, it is not the focus of this manuscript.…”

“…We have simultaneously assessed DLCO and DLNO using the single-breath technique at rest and during submaximal exercise in two separate studies in our laboratory (Coffman et al, 2016). In the first study, DLCO and DLNO were measured in duplicate at rest and during cycle exercise at 80W in 11 healthy subjects (Table 1, #5).…”

“…While some groups may argue that there is no gold standard in the case of Dm CO and V C , we feel it is important that the finite θ NO calculations be validated against a method that does not utilize NO. We have performed such optimizations on our calculations, which assume an infinite θ NO , using both the single breath and rebreathe techniques (Ceridon et al, 2010; Coffman et al, 2016). We feel it is important that those groups that are invested in the use of a finite θ NO apply a similar method, where the θ NO value would be systematically varied with respect to the other two required assumptions (the θ CO equation and Krogh coefficient) of the finite θ NO calculations.…”

“…While there exists a theoretical value for α that is based on the molecular weights and solubilities in water of both NO and CO (termed the Krogh coefficient), numerous studies utilizing an infinite θ NO have experimentally determined that α is actually greater than 1.97 (Magini et al, 2013; Tamhane et al, 2001). Accordingly, we have previously experimentally determined the best θ CO equation and α value to be used, for both the rebreathe and single breath techniques (Ceridon et al, 2010; Coffman et al, 2016), by systematically comparing the resulting Dm CO and V C values against those obtained via the original multiple O 2 tension method. From both of these studies, our laboratory has concluded that the θ CO equation described by Reeves and Park is ideal, while the optimal α value is dependent on the technique used; ~2.26 for rebreathe and ~4.40 for single breath.…”