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. Objective 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 to 52 parts per billion (ppb) in the entire sample (N=943), and from 26 to 37 ppb among individuals 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 and in asthma and COPD clinics.

LL reports personal fees from ALK, AstraZeneca, Berlin Chemie, Boehringer-Ingelheim, Chiesi, GSK, Novartis, Orion Pharma and Sanofi outside the current work. SSOE reports conference-attendance related costs from Thermo Fisher Scientific outside the current work. TP reports fees for lectures and/or consulting from AstraZeneca, Chiesi, GSK, Novartis and Sanofi outside the current work. HB reports personal fees for lectures form AstraZeneca, Boehringer Ingelheim and GSK outside the current work. NIB reports personal fees for lectures and consulting from DBV Technologies and AstraZeneca outside the current work. HK reports fees for lectures and/or consulting from AstraZeneca, Boehringer-Ingelheim, Chiesi, Covis Pharma, GSK, MedScape, MSD, Novartis, Orion Pharma and Sanofi outside the current work. The rest of the authors have no conflict of interest to declare.

The study was funded by the VBG Group Herman Krefting Foundation for Asthma and Allergy Research (Trollhattan, Sweden), Swedish Research Council, the Swedish Heart-Lung Foundation (Stockholm, Sweden), the Swedish Asthma and Allergy Foundation (Stockholm, Sweden), Tampere Tuberculosis Foundation (Tampere, Finland), and ALF agreement (grant from the Swedish state under the agreement between the Swedish Government and the county councils, Sweden).

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All participants signed informed consent, and the study was approved by the regional ethics board in Gothenburg, Sweden which as a part of the national Swedish Ethical Review Authority that examines applications for ethics review of research involving humans and human biological material. More info can be found in: https://etikprovningsmyndigheten.se/en/

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All data produced in the present study are available upon reasonable request to the authors