How FeNO Testing Guides Asthma Treatment
FeNO testing should be used to identify eosinophilic airway inflammation and predict inhaled corticosteroid (ICS) responsiveness, with specific cutoff values determining treatment decisions: values <25 ppb (20 ppb in children) indicate ICS are unlikely to help, values >50 ppb (>35 ppb in children) strongly support ICS initiation or dose escalation, and intermediate values (25-50 ppb in adults, 20-35 ppb in children) require careful monitoring and clinical judgment. 1
Diagnostic Applications: Initial Treatment Decisions
Low FeNO (<25 ppb in adults, <20 ppb in children)
- Eosinophilic inflammation is unlikely and patients will probably not benefit from ICS therapy 1
- Consider alternative diagnoses including vocal cord dysfunction, anxiety-hyperventilation, bronchiectasis, cardiac disease, rhinosinusitis, or gastroesophageal reflux disease 1
- In symptomatic patients, pursue strategies other than ICS treatment 1
High FeNO (>50 ppb in adults, >35 ppb in children)
- Eosinophilic airway inflammation is present and patients are likely to benefit from ICS treatment 1
- A cutoff ≥30 ppb demonstrates 88% sensitivity and 91% specificity for identifying steroid-responsive patients 1
- FeNO predicts steroid responsiveness more consistently than spirometry, bronchodilator response, peak flow variation, or methacholine challenge 1
- The optimal cutpoint of 47 ppb shows an 89% negative predictive value for ICS response 1
Intermediate FeNO (25-50 ppb in adults, 20-35 ppb in children)
- Exercise caution and monitor FeNO changes over time 1
- Both intermediate and high FeNO levels predict significant improvement in asthma control after starting ICS, challenging older guidelines that only emphasized high values 2
- In one study, 78% of patients with intermediate FeNO achieved clinically meaningful improvement (ACQ score ≥1) compared to only 43% with low FeNO 2
Monitoring Established Asthma
In Symptomatic Patients with Diagnosed Asthma
High FeNO indicates:
- Poor adherence to ICS therapy 1
- Inadequate ICS dosing requiring escalation 1
- Poor inhaler technique or proximal drug deposition 1
- Persistent high allergen exposure 1
- Risk for upcoming exacerbation even if currently asymptomatic 1
Low FeNO suggests:
- Non-eosinophilic asthma (likely steroid-unresponsive) 1
- Alternative or additional diagnoses should be considered 1
- Increasing ICS dose will not help—pursue other strategies 1
In Asymptomatic Patients with Controlled Asthma
Low FeNO (<25 ppb):
- ICS dose can be safely reduced or potentially withdrawn 1
- In children with stable asthma, withdrawal of ICS when FeNO remained consistently low (optimum cutpoint 22 ppb measured 2-4 weeks after withdrawal) did not result in symptom relapse 1
- Implies adequate dosing and good adherence 1
High FeNO (>50 ppb):
- Do not reduce ICS dose—withdrawal is likely followed by relapse 1
- May indicate poor adherence or inhaler technique despite lack of symptoms 1
- Some patients remain asymptomatic but high FeNO represents risk factor for exacerbation 1
Defining Clinically Significant Changes
A change of at least 20% is required to indicate a significant rise or fall in FeNO (or >10 ppb for values <50 ppb) 1
- The within-subject coefficient of variation is approximately 20% in asthma patients 1
- Transition from good control to poor control typically shows FeNO rise ≥40% 1
- During acute asthma, FeNO levels are approximately 50% higher than during stability 1
- Acute rises (12-24 hours) after allergen exposure or infection can reach up to 150 ppb 1
Important Caveats and Limitations
When FeNO-Guided Dosing Is NOT Recommended
Randomized trials using regular FeNO measurements as the sole basis for adjusting ICS doses have failed to show important benefits over conventional management 1. However, these studies had significant methodological flaws including inappropriate dose-response relationships, adherence issues, and poorly selected cutpoints 1.
More Recent Evidence
Despite earlier negative trials, a 2021 American Thoracic Society guideline made a conditional recommendation for FeNO-based care, suggesting FeNO should be used in addition to usual care in patients with asthma in whom treatment is being considered 3. This represents evolving consensus that FeNO provides value when properly integrated into clinical decision-making.
FeNO as Adjunct, Not Standalone Test
FeNO interpretation must always be combined with history, physical examination, and lung function assessment—it is not a standalone diagnostic or monitoring tool 1. As a predictor of asthma control, FeNO performs no better than conventional lung function tests 1.
Dose-Response Relationship
There is a significant dose-response of FeNO to ICS in patients with elevated FeNO phenotype, with exponential decay patterns showing half-lives of 55-69 hours depending on ICS dose 4. This supports using FeNO to assess adequacy of ICS dosing in the elevated FeNO phenotype 4.
Practical Application
FeNO >30 ppb is associated with uncontrolled asthma (area under ROC curve 0.78) and discriminates between uncontrolled versus controlled/partially controlled disease 5. This cutpoint provides a practical threshold for clinical decision-making in real-world practice 5.