Reference values of fractional excretion of exhaled nitric oxide among non-smokers and current smokers

Background: Fractional exhaled nitric oxide (FENO) is used to assess of airway inflammation; diagnose asthma and monitor adherence to advised therapy. Reliable and accurate reference values for FENO are needed for both non-smoking and current smoking adults in the clinical setting. The present study was performed to establish reference adult FENO values among never-smokers, former smokers and current smokers. Methods: FENO was measured in 5265 subjects aged 25-75 years in a general-population study, using a chemiluminescence (Niox (TM)) analyser according to the guidelines of the American Thoracic Society and the European Respiratory Society. Atopy was based on the presence of immunoglobulin E (IgE) antibodies to common inhalant allergens (measured using Phadiatop (R) test). Spirometry without bronchodilation was performed and forced vital capacity (FVC), forced expired volume in 1 s (FEV1) and the ratio of FEV1 to FVC values were obtained. After excluding subjects with asthma, chronic bronchitis, spirometric airway obstruction and current cold, 3378 subjects remained. Equations for predictions of FENO values were modelled using nonparametric regression models. Results: FENO levels were similar in never-smokers and former smokers, and these two groups were therefore merged into a group termed "non-smokers". Reference equations, including the 5th and 95th percentiles, were generated for female and male non-smokers, based on age, height and atopy. Regression models for current smokers were unstable. Hence, the proposed reference values for current smokers are based on the univariate distribution of FENO and fixed cut-off limits. Conclusions: Reference values for FENO among respiratory healthy non-smokers should be outlined stratified for gender using individual reference values. For current smokers separate cut-off limits are proposed.