Setting reference values for exhaled nitric oxide: a systematic review

Abstract

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 individualspecific 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. R 2 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. Please cite this paper as: Jacinto T, Alving K, Correia R, Costa-Pereira A and Fonseca J. Setting reference values for exhaled nitric oxide: a systematic review. Clin Respir J 2013; 7: 113-120. Key words exhaled nitric oxide -reference valuessystematic reviewCorrespondence

Determinants of, and reference equation for, exhaled nitric oxide in the Chinese population

“…Reference ranges for FeNO measured in accordance with the current ATS/ERS standards have been reported previously in children [11][12][13]17]. There were studies that assessed the reference equations of FeNO in healthy adults and, among these studies [14][15][16][17][18], only one involved healthy nonsmoking adults as in our study [14].…”

“…There were studies that assessed the reference equations of FeNO in healthy adults and, among these studies [14][15][16][17][18], only one involved healthy nonsmoking adults as in our study [14]. Many studies involved subjects who were current smokers or ex-smokers, with airway diseases or respiratory tract infections [15,16,18,21,22].…”

“…Previous studies on reference values of FeNO in the general population were mainly limited to children [11][12][13]. There are limited data on the reference value of FeNO in the adult population [14][15][16][17][18], and there is very limited information on FeNO in a healthy, nonsmoking Chinese population. FeNO is a promising noninvasive marker for the assessment of airway inflammation, especially for asthma.…”

Fraction of Exhaled Nitric Oxide (FeNO) Norms in Healthy Tunisian Adults

“…Interpretation of Fe NO data relies upon comparison of measured values with predicted ones available from published norms (e.g., fixed values, reference equations or normal values tables) [1, 7, 8]. However, to the best of our knowledge, Fe NO norms are available only for some adult populations, mainly for Caucasians ones [9–24].…”

“…However, to the best of our knowledge, Fe NO norms are available only for some adult populations, mainly for Caucasians ones [9–24]. These norms can be used in clinical practice, provided that the study characteristics (population, sampling, and objective measures) are taken into consideration when such an equation is used for the interpretation of Fe NO values [1, 7]. The published norms [9–24] differ considerably in terms of individual-specific factors that have an effect on Fe NO values, and there is little standardization of the method description in the studies, both on the statistical and technical sides [7].…”