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

Background: Fractional exhaled nitric oxide (FE_NO) is used to differentiate asthma inflammatory phenotypes and guide its management. However, data on FE_NO reference values in a representative adult population is limited. We aim to derive reference values and determinants of FE_NO 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 FE_NO 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. FE_NO levels were analysed in relation to the presence or absence of clinical allergy, asthma, and other factors. Results: The 95^th percentile of FE_NO 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 FE_NO levels, meanwhile, age, asthma, clinical allergy, and reversibility-related variables were significant determinants of FE_NO levels. Conclusion: The 95^th percentile (upper normal limit) for FE_NO 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 FE_NO in the general population.