Impact of analysis interval on the multiple exhalation flow technique to partition exhaled nitric oxide

Exhaled nitric oxide (eNO) is elevated in asthmatics and is a purported marker of airway inflammation. By measuring eNO at multiple flows and applying models of eNO exchange dynamics, the signal can be partitioned into its proximal airway [J' aw NO (nl/sec)] and distal airway/alveolar contributions [CA(NO)(ppb)]. Several studies have demonstrated the potential significance of such an approach in children with asthma. However, techniques to partition eNO are variable, limiting comparisons among studies. The objective of this study is to examine the impact of the analysis interval (time or volume) on eNO plateau concentrations and the estimation of J' aw NO and CA(NO). In 30 children with mild to moderate asthma, spirometry and eNO at multiple flows (50, 100, and 200 ml/sec) were measured. The plateau concentration of eNO at each flow was determined using two different methods of analysis: (1) constant time interval and (2) constant volume interval. For both methods of analysis, a two-compartment model with axial diffusion was used to characterize J' aw NO and CA(NO). At a flow of 200 ml/sec, the time interval analysis predicts values for eNO that are smaller than the volume interval analysis. As a result, there are significant differences in CA(NO) between the methods of analysis (volume > time). When using the multiple flow technique to partition eNO, the method of analysis (constant time vs. constant volume interval) significantly affects the estimation of CA(NO), and thus potentially the assessment and interpretation of distal lung inflammation.