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

Fractional exhaled nitric oxide (FE_NO) is used to assess of airway inflammation; diagnose asthma and monitor adherence to advised therapy. Reliable and accurate reference values for FE_NO are needed for both non-smoking and current smoking adults in the clinical setting. The present study was performed to establish reference adult FE_NO values among never-smokers, former smokers and current smokers.

FE_NO was measured in 5265 subjects aged 25-75 years in a general-population study, using a chemiluminescence (Niox ™) 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® 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 FE_NO values were modelled using nonparametric regression models.

FE_NO 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 FE_NO and fixed cut-off limits.

Reference values for FE_NO among respiratory healthy non-smokers should be outlined stratified for gender using individual reference values. For current smokers separate cut-off limits are proposed.