Reference Values and Determinants of Fractional Exhaled Nitric Oxide in a Representative Adult Population in Western Sweden

Abstract

Background: Fractional exhaled nitric oxide (FENO) is used to differentiate asthma inflammatory phenotypes and guide its management. However, data on FENO reference values in a representative adult population is limited. We aim to derive reference values and determinants of FENO in a representative adult population. Methods: The West Sweden Asthma Study is a clinical-epidemiological population-representative study of randomly selected adults in Western Sweden. From this cohort, 943 subjects participated in comprehensive clinical investigations, including skin prick testing (SPT), specific immunoglobulin E (sIgE) analysis, and FENO measurement. Clinical allergy was defined as co-occurrence of atopy (positivity to SPT or sIgE) and self-reported allergic symptoms to the same allergen family. FENO levels were analysed in relation to the presence or absence of clinical allergy, asthma, and other factors. Results: The 95th percentile of FENO ranged from 34 parts per billion (ppb) in those between 30 and 40 years old to 52 ppb in those ≤ 30 years old in the entire sample (N = 943), and from 26 to 37 ppb in those without clinical allergy, asthma, or chronic obstructive pulmonary disease (COPD) (n = 587), depending on age. Sex, smoking, clinical allergy, atopy, asthma, and hypertension influenced FENO levels, meanwhile, age, asthma, clinical allergy, and reversibility-related variables were significant determinants of FENO levels. Conclusion: The 95th percentile (upper normal limit) for FENO ranges from 34 to 52 ppb overall, and from 26 to 37 ppb in those without clinical allergy, asthma, or COPD, depending on age. These findings provide a guide for interpreting FENO in the general population.