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Updated: Jan 19, 2026
Measuring Nitrite and Nitrate, Metabolites in the Nitric Oxide Pathway, in Biological Materials using the Chemiluminescence Method
Published on: December 25, 2016
Repeatability and variation of the flow independent nitric oxide parameters
Tuomas Karvonen1, Lauri Lehtimäki1,2
1Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Introduction:
Fractional exhaled nitric oxide (FENO) is a non-invasive marker of airway inflammation. Measuring FENO at several flow rates enables the calculation of flow independent NO-parameters (alveolar NO concentration (CANO), bronchial flux of NO (JawNO), bronchial mucosal NO concentration (CawNO) and bronchial wall NO diffusion capacity (DawNO)) that are capable of partitioning the source and release mechanism of NO from the lower respiratory tract. However, the current literature on repeatability and normal variation of the NO-parameters is deficient, and this information is needed to develop the method towards clinical use.
Methods:
We calculated NO-parameters in 28 healthy subjects using two different mathematical methods and used three different study protocols to investigate: (i) repeatability of two consecutive measurements of NO-parameters, (ii) within-day variation of the NO-parameters over one working day and (iii) day-to-day variation of the NO-parameters between consecutive days during course of a working week.
Results:
JawNO was the most repeatable among the NO-parameters, whereas DawNO and CawNO were notably least repeatable. CANO was higher during the second consecutive measurement (1.22 versus 1.57 ppb, p = 0.017). Both investigated mathematical methods yielded equally repeatable results. JawNO was slightly higher in the afternoon compared to morning (716 versus 881 pl/s, p = 0.01), but other parameters showed no diurnal variation. Upper 95% limit for the day-to-day difference in the parameters in healthy subjects was about 1.2 ppb in CANO, 400 pl/s in JawNO, 92 ppb in CawNO and 16 pl/s/ppb in DawNO.
Conclusions:
This is the first study assessing short-time repeatability of the NO-parameters. Repeatability of the NO-parameters was good and day-to-day variation in NO-parameters was quite low. We recommend scheduling FENO-measurements at the same time of day, if possible, and in clinical use variation in NO-parameters above the normal limits found in this study suggest changes in the disease's activity.
