Normal FeNO Values in Healthy Adults
In healthy adults, normal FeNO values are less than 25 ppb when excluding outliers and atopic individuals, though the upper limit extends to less than 35 ppb in the general healthy population. 1
Reference Values Based on Population Studies
The American Thoracic Society guidelines establish that normal FeNO ranges depend significantly on whether you account for atopy and other confounding factors 1:
- General healthy adults: Upper limit of normal is <35 ppb 1
- When outliers are removed: Upper limit reduces to <25 ppb 1
- When both outliers and atopic individuals are excluded: Upper limit further reduces to <20 ppb 1
Large population studies demonstrate considerable variability, with the 95th percentile ranging from 24-54 ppb depending on age, height, sex, and atopic status 2. A recent representative Swedish population study found the 95th percentile ranged from 26-37 ppb in those without clinical allergy, asthma, or COPD 3.
Key Factors Affecting Normal Values
Sex differences: Males typically have FeNO values 20-30% higher than females 1
Atopy status: Atopic individuals have substantially higher values 1:
- Non-atopic males (nonsmokers): 9.5-47.4 ppb 1
- Atopic males (nonsmokers): 11.2-56.5 ppb 1
- Non-atopic females (nonsmokers): 7.5-37.4 ppb 1
- Atopic females (nonsmokers): 8.8-44.6 ppb 1
Smoking: Current smokers have significantly lower values, with reductions of approximately 20-40% compared to nonsmokers 1
Age and height: Both influence FeNO values, particularly in children under 12 years, though the effect is less consistent in adults 1, 2
Clinical Interpretation Framework
The ATS recommends using clinically relevant cut-points rather than population reference values because of substantial overlap between healthy individuals and those with stable asthma 1:
- Low FeNO (<25 ppb in adults): Eosinophilic inflammation unlikely 1, 4
- Intermediate FeNO (25-50 ppb): Requires careful clinical interpretation 4
- High FeNO (>50 ppb): Eosinophilic inflammation likely present 1, 4
Important Clinical Caveats
The distribution of FeNO in unselected populations is right-skewed, with median values around 16 ppb but a wide range (2.4-199 ppb) 4. Even in patients with stable, well-controlled asthma, FeNO values range from 22-44 ppb, which overlaps considerably with healthy populations 1. This overlap means that population reference values have limited utility in clinical practice compared to using established cut-points for specific clinical decisions 1.
Multiple confounding factors (genetics, atopy, smoking, height, age, sex) account for only 9-11% of FeNO variation, making it more practical to interpret values based on clinical context rather than strict reference ranges 2. The Japanese Respiratory Society uses 37 ppb as the upper normal limit for healthy Japanese adults, with values ≥35 ppb suggesting inflammatory conditions 5.