What is the role of measuring exhaled Nitric Oxide (NO) in assessing airway inflammation?

Role of Exhaled Nitric Oxide (FeNO) in Assessing Airway Inflammation

Exhaled nitric oxide (FeNO) measurement is strongly recommended as a valuable non-invasive biomarker for diagnosing eosinophilic airway inflammation and predicting steroid responsiveness in patients with respiratory symptoms. 1

Clinical Utility of FeNO Measurement

Primary Applications

• Diagnosis of eosinophilic airway inflammation

  • FeNO serves as an indirect marker for up-regulation of airway inflammation 1
  • Provides objective evidence of inflammation when clinical assessment is uncertain 1
  • Non-invasive alternative to more invasive procedures like bronchoscopy, lavage, biopsy, or induced sputum 1

• Prediction of steroid responsiveness

  • High FeNO values strongly predict likelihood of response to corticosteroid therapy 1, 2
  • Helps avoid unnecessary "trial of steroids" or long-term corticosteroid treatment 1

• Supporting asthma diagnosis

  • Adds a new dimension to traditional clinical tools (history, physical exam, lung function tests) 1
  • Particularly useful when objective evidence is needed 1
  • At a cutoff level of 16 ppb, shows specificity of 90% and positive predictive value >90% for asthma diagnosis 3

Interpretation of FeNO Values

• Adults:

  • Low: <25 ppb (eosinophilic inflammation unlikely)
  • Intermediate: 25-50 ppb (interpret with caution)
  • High: >50 ppb (eosinophilic inflammation likely)

• Children (<12 years):

  • Low: <20 ppb
  • Intermediate: 20-35 ppb
  • Intermediate: >35 ppb 1, 2

Clinical Application and Monitoring

Monitoring Treatment Response

• Significant reduction in FeNO indicates:

  • 20% decrease for values over 50 ppb

  • 10 ppb decrease for values lower than 50 ppb 1, 2

• Persistent elevation despite therapy may indicate:

  • Poor adherence to inhaled corticosteroids
  • Incorrect inhaler technique
  • Ongoing allergen exposure 1, 2

Factors Affecting FeNO Levels

• Physiological factors:

  • Age (particularly important in children <12 years)
  • Height
  • Sex
  • Atopy status 2

• External factors:

  • Smoking (reduces FeNO levels)
  • Recent respiratory infections
  • Persistent/high allergen exposure 1, 2

Important Clinical Considerations

Strengths of FeNO Testing

• Non-invasive and easily repeatable 1
• Standardized measurement techniques available 1
• Particularly useful in patients with severe airflow obstruction where other techniques are difficult to perform 1
• Provides immediate results to guide clinical decision-making 2

Limitations and Pitfalls

• Not all asthma is associated with high FeNO:

  • Non-eosinophilic/neutrophilic asthma phenotypes may have normal FeNO 1
  • Should not be used as the sole diagnostic criterion for asthma 2

• Interpretation challenges:

  • Values between 25-50 ppb (20-35 ppb in children) require cautious interpretation 1
  • Must be interpreted within clinical context 1, 2
  • Prior steroid treatment may lead to falsely negative results 1

• Technical considerations:

  • Standardized measurement techniques are essential 1
  • Cut points rather than reference values should be used 1

Practical Algorithm for Clinical Use

1. Measure FeNO in patients with:

   • Unexplained respiratory symptoms
   • Suspected asthma requiring objective confirmation
   • Known asthma with poor control or exacerbations

2. Interpret results based on cutoff values:

   • If FeNO <25 ppb (adults) or <20 ppb (children):

     • Eosinophilic inflammation unlikely
     • Consider alternative diagnoses or non-eosinophilic asthma phenotypes
     • Less likely to respond to corticosteroids

   • If FeNO >50 ppb (adults) or >35 ppb (children):

     • Eosinophilic inflammation likely
     • High probability of steroid responsiveness
     • Consider initiating or increasing corticosteroid therapy

   • If FeNO 25-50 ppb (adults) or 20-35 ppb (children):

     • Interpret cautiously within clinical context
     • Consider other clinical factors and additional testing

3. Use FeNO for monitoring:

   • Establish baseline during clinical stability
   • Monitor treatment response
   • Guide step-up/step-down therapy decisions
   • Assess adherence to anti-inflammatory medications

FeNO measurement represents a significant advance in the non-invasive assessment of airway inflammation, providing clinically relevant information that can improve diagnosis and management of respiratory conditions, particularly asthma with an eosinophilic inflammatory component.