ERS technical standard: Global Lung Function Initiative reference values for exhaled nitric oxide fraction ( <i>F</i> <sub> ENO <sub>50</sub> </sub> )
Marieann Högman, Cole Bowerman, Luis Chávez, Holger Dressel, Andreï Malinovschi, Thomas Radtke, Sanja Stanojevic, Irene Steenbruggen, Steve Turner, Anh Tuan Dinh‐Xuan
Abstract
Background Elevated exhaled nitric oxide fraction at a flow rate of 50 mL·s −1 ( F ENO 50 ) is an important indicator of T-helper 2-driven airway inflammation and may aid clinicians in the diagnosis and monitoring of asthma. This study aimed to derive Global Lung Function Initiative reference equations and the upper limit of normal for F ENO 50 . Methods Available individual F ENO 50 data were collated and harmonised using consensus-derived variables and definitions. Data collected from individuals who met the harmonised definition of “healthy” were analysed using the generalised additive models of location, scale and shape (GAMLSS) technique. Results Data were retrospectively collated from 34 782 individuals from 34 sites in 15 countries, of whom 8022 met the definition of healthy (19 sites, 11 countries). Overall, height, age and sex only explained 12% of the between-subject variability of F ENO 50 (R 2 =0.12). F ENO device was neccessary as a predictor of F ENO 50 , such that the healthy range of values and the upper limit of normal varied depending on which device was used. The range of F ENO 50 values observed in healthy individuals was also very wide, and the heterogeneity was partially explained by the device used. When analysing a subset of data in which F ENO 50 was measured using the same device and a stricter definition of health (n=1027), between-site heterogeneity remained. Conclusion Available F ENO 50 data collected from different sites using different protocols and devices were too variable to develop a single all-age reference equation. Further standardisation of F ENO devices and measurement are required before population reference values might be derived.