From the Guidelines
FeNO is an indirect measurement of airway inflammation and eosinophilia, serving as a biomarker for eosinophilic inflammation in the airways, particularly in conditions like asthma. It measures the concentration of nitric oxide in exhaled breath, which correlates with eosinophilic inflammation, but does not directly count or visualize eosinophils themselves. Instead, FeNO reflects the activity of inducible nitric oxide synthase (iNOS), an enzyme that becomes upregulated in airway epithelial cells during type 2 inflammation, which is often associated with eosinophilic activity 1.
Key Points to Consider
- FeNO levels can be influenced by various factors, including age, height, ethnicity, smoking, diet, exercise, and environmental exposures such as pollen 1.
- Atopy is associated with elevated FeNO, independent of asthma, and asthma treatments like inhaled corticosteroids (ICS) and leukotriene receptor antagonists (LTRA) can reduce FeNO by 25-50% 1.
- The relationship between FeNO levels and airway eosinophilia is independent of the diagnosis of asthma, as reported in patients with chronic obstructive pulmonary disease (COPD) and eosinophilic bronchitis 1.
- A low FeNO is of value in determining the absence of eosinophilic airway inflammation and, by inference, the likely absence of steroid-responsive airway inflammation 1.
Clinical Implications
- FeNO is a useful clinical tool for assessing airway inflammation non-invasively, helping to guide treatment decisions in asthma management, particularly regarding corticosteroid responsiveness.
- Clinicians should interpret FeNO results within the clinical context of each patient, considering factors that may influence measurement and the potential for variability in results.
- The most recent and highest quality study 1 supports the use of FeNO as an indirect indicator of eosinophilic inflammation, highlighting its potential as a valuable tool in clinical practice.
From the Research
Fractional Exhaled Nitric Oxide (FeNO) as a Marker of Inflammation and Eosinophilia
- FeNO is a noninvasive marker of eosinophilic airway inflammation, as indicated by studies 2, 3, 4, 5, 6
- It is primarily related to eosinophilic inflammation, suggesting its potential as a direct measurement of eosinophilia 2
- FeNO levels have been associated with the presence and type of underlying cellular inflammation in patients with severe refractory asthma 2
- A cutoff value of FeNO > 19 parts per billion was associated with a sensitivity of 0.78 and a specificity of 0.73 for sputum eosinophilia, indicating its potential as a direct measurement of eosinophilia 2
- However, FeNO levels were reduced in patients with predominant neutrophilia, regardless of the concomitant presence of eosinophilia, suggesting that it may not be a direct measurement of inflammation in all cases 2
FeNO as an Indirect Measurement of Inflammation and Eosinophilia
- FeNO has been shown to be a marker of eosinophilic airway inflammation in patients with mild-moderate steroid-naive asthma and concomitant allergic rhinitis 3
- A blood eosinophil level of ≥150 cells/µL may be a simple marker of eosinophilic airway inflammation in patients with asthma, but its low specificity requires repeated measurements and use in combination with other biomarkers 3
- FeNO has been used to guide primary care asthma management, including identifying steroid-responsive disease and guiding on-going asthma management 5
- FeNO measurement has been recommended in predicting asthma severity and Inhaled Corticosteroid (ICS) response, but further research is required to understand its clinical utility and agreement with current recommendations in specific populations 6
Clinical Utility of FeNO
- FeNO has been shown to be a useful tool in monitoring ongoing airway inflammation and understanding treatment response rate 6
- Simple algorithms to guide clinicians in the practical use of FeNO could improve diagnostic accuracy and better tailored asthma regimens 5
- FeNO has been associated with a more severe phenotype and has become a consolidated biomarker of type-2 inflammation 4
- FeNO has demonstrated to be a noninvasive and very reproducible test, encompassing many applications in the field of asthma management 4