Is measuring fractional exhaled nitric oxide (FeNO) effective for diagnosing and monitoring bronchial asthma?

Effectiveness of Fractional Exhaled Nitric Oxide (FeNO) for Diagnosing and Monitoring Bronchial Asthma

FeNO measurement is a valuable adjunct tool for diagnosing asthma in uncertain cases and monitoring airway inflammation, but should not be used as the sole diagnostic criterion due to its moderate specificity and variable sensitivity in different asthma phenotypes. 1

Diagnostic Utility of FeNO

Evidence for Diagnosis

FeNO serves as a biomarker of type 2 (T2) bronchial or eosinophilic inflammation in asthma patients. The American Thoracic Society (ATS) guidelines provide specific cut-off values:

• Low FeNO (<25 ppb in adults; <20 ppb in children): Eosinophilic airway inflammation is unlikely 1
• High FeNO (>50 ppb in adults; >35 ppb in children): Suggests eosinophilic inflammation, likely to respond to inhaled corticosteroids 1
• Intermediate values (25-50 ppb in adults; 20-35 ppb in children): Require interpretation in clinical context 1

Diagnostic Algorithm

1. Consider FeNO testing when:

   • Diagnosis of asthma is uncertain after history, physical examination, and spirometry
   • Spirometry cannot be performed accurately
   • Patient is ≥5 years old (not recommended for children <4 years) 1

2. Interpret results in context of:

   • Atopy status (atopic individuals have higher baseline FeNO)
   • Smoking status (reduces FeNO)
   • Recent allergen exposure
   • Medication use (especially corticosteroids)

3. High FeNO suggests:

   • Atopic asthma
   • Eosinophilic bronchitis
   • Likely responsiveness to inhaled corticosteroids 1

Diagnostic Limitations

• Not all asthma patients have elevated FeNO (especially non-allergic asthma) 2
• Some non-asthmatic conditions can elevate FeNO
• Sensitivity varies between allergic (higher FeNO) and non-allergic asthma (31% of non-allergic asthmatics have FeNO <20 ppb) 2

Monitoring Utility of FeNO

Evidence for Monitoring

The ATS recommends FeNO for monitoring airway inflammation in asthma patients, though the quality of evidence is rated as low 1. FeNO monitoring can help:

1. Assess treatment response: FeNO typically decreases with effective corticosteroid treatment 1
2. Detect non-adherence: Persistently high FeNO despite prescribed inhaled corticosteroids may indicate poor adherence or incorrect inhaler technique 1
3. Guide medication adjustments:
   • Low FeNO in asymptomatic patients suggests adequate anti-inflammatory therapy
   • High FeNO in asymptomatic patients may indicate risk for future exacerbation 1

Monitoring Algorithm

1. Establish baseline FeNO before starting anti-inflammatory treatment
2. Repeat measurement after 4-8 weeks of treatment
3. Consider the change in FeNO rather than absolute value alone 1
4. In patients with stable asthma on treatment:
   • Low FeNO: Consider step-down of inhaled corticosteroid (repeat FeNO in 4 weeks) 1
   • High FeNO despite treatment: Consider poor adherence, incorrect technique, or need for dose increase 1

Monitoring Limitations

• The definition of a clinically significant change in FeNO remains to be established 1
• FeNO-based treatment has shown inconsistent results in improving outcomes 3
• The 2020 NAEPP guidelines note that FeNO should not be the sole measure for asthma management 1

Clinical Pearls and Pitfalls

Important Considerations

• FeNO is affected by multiple factors including:
  • Age, height, sex (reference ranges vary)
  • Atopy (increases FeNO)
  • Smoking (decreases FeNO)
  • Diet (nitrate-rich foods increase FeNO)
  • Recent spirometry (decreases FeNO) 3

Common Pitfalls

1. Overreliance on absolute values: The change in FeNO with treatment may be more informative than absolute values 1
2. Ignoring clinical context: FeNO should be interpreted alongside symptoms, lung function, and medical history
3. Not accounting for confounders: Failing to consider factors that affect FeNO levels
4. Using in very young children: Not recommended in children under 4 years 1

Recent Evidence

A 2021 ATS Clinical Practice Guideline made a conditional recommendation for FeNO-based care, suggesting that FeNO measurement is beneficial and should be used in addition to usual care when treatment decisions are being considered 4. This recommendation acknowledges the overall low quality of evidence but recognizes the potential benefits in clinical practice.

FeNO measurement provides valuable information about airway inflammation that complements traditional assessment methods, but should always be interpreted as part of a comprehensive evaluation rather than in isolation.