Setting reference values for exhaled nitric oxide: a systematic review.

Background: The values obtained when the fraction of exhaled nitric oxide (FeNO) is measured are affected by several factors that are specific to the individual patient, making interpretation difficult, especially in the initial assessment of patients with respiratory symptoms.

Methods: Systematic review of studies on FeNO reference values and individual-specific factors that influence them.

Results: From 3739 references, 15 studies were included. Four studies included children and adolescents. In nine studies, samples were selected from the general population. Most studies reported objective measures for atopy (nine studies), but not for smoking status (one). Significant determinants of FeNO values reported were age and height (seven studies), atopy (six), smoking (four), weight (four), sex (three) and race (three). Additional factors were included in eight studies. R2 was reported in only five studies. The logarithmic transformation of FeNO was inadequately described in seven studies.

Conclusion: There are several equations for FeNO reference values that may be used in clinical practice, although the factors they include and the statistical methods they use vary considerably. We recommend the development of standard methods for the evaluation of normal FeNO data and that reference equations should be formulated based on a predetermined physiological model.