The Single-Breath Diffusing Capacity of CO and NO in Healthy Children of European Descent

Rationale: The diffusing capacity (D-L) of the lung can be divided into two components: the diffusing capacity of the alveolar membrane (Dm) and the pulmonary capillary volume (Vc). D-L is traditionally measured using a single-breath method, involving inhalation of carbon monoxide, and a breath hold of 8-10 seconds (D-L,(CO)). This method does not easily allow calculation of Dm and Vc. An alternative single-breath method (D-L,(CO),(NO)), involving simultaneous inhalation of carbon monoxide and nitric oxide, and traditionally a shorter breath hold, allows calculation of Dm and Vc and the D-L,(NO)/D-L,(CO) ratio in a single respiratory maneuver. The clinical utility of Dm, Vc, and D-L,(NO)/D-L,(CO) in the pediatric age range is currently unknown but also restricted by lack of reference values. Objectives: The aim of this study was to establish reference ranges for the outcomes of D-L,(CO),(NO) with a 5 second breath hold, including the calculated outcomes Dm, Vc, and the D-L,(NO)/D-L,(CO) ratio, as well as to establish reference values for the outcomes of the traditional D-L,(CO) method, with a 10 second breath hold in children. Methods: D-L,(CO),(NO) and D-L,(CO) were measured in healthy children, of European descent, aged 5-17 years using a Jaeger Masterscreen PFT. The data were analyzed using the Generalized Additive Models for Location Scale and Shape (GAMLSS) statistical method. Measurements and Main Results: A total of 326 children were eligible for diffusing capacity measurements, resulting in 312 measurements of D-L,(CO),(NO) and 297 of D-L,(CO), respectively. Reference equations were established for the outcomes of D-L,(CO),(NO) and D-L,(CO), including the calculated values: Vc, Dm, and the D-L,(NO)/D-L,(CO) ratio. Conclusion: These reference values are based on the largest sample of children to date and may provide a basis for future studies of their clinical utility in differentiating between alterations in the pulmonary circulation and changes in the alveolar membrane in pediatric patients.