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.