What are fraction of exhaled nitric oxide (FeNO) and pulmonary function tests (PFTs) in terms of asthma diagnosis?

FeNO and PFTs in Asthma Diagnosis

Fractional exhaled nitric oxide (FeNO) and pulmonary function tests (PFTs) are complementary diagnostic tools for asthma, with FeNO specifically identifying T-helper 2 cell-type airway inflammation and PFTs demonstrating airflow obstruction and reversibility.

Understanding FeNO in Asthma Diagnosis

What is FeNO?

• FeNO measures the concentration of nitric oxide in exhaled breath, expressed in parts per billion (ppb)
• Standard measurement is performed at an exhalation flow rate of 50 mL/s (FENO50) 1
• Elevated levels indicate eosinophilic airway inflammation, commonly seen in asthma 1, 2

FeNO Interpretation Guidelines

According to the American Thoracic Society (ATS) guidelines, the following cut-off values apply 2:

For adults:

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

For children:

• Low: <20 ppb
• Intermediate: 20-35 ppb
• High: >35 ppb

Clinical Utility of FeNO

• Diagnostic aid: Helps identify eosinophilic/T-helper 2 cell-type inflammation 1
• Treatment guidance: Predicts likelihood of response to inhaled corticosteroids 2
• Monitoring tool: Useful for assessing treatment adherence and adequacy 2
• Risk assessment: High levels associated with increased exacerbation risk 2, 3

Limitations of FeNO

• Not sufficient alone for asthma diagnosis 1, 2
• May be elevated in healthy subjects and normal in some asthma patients 1
• Affected by multiple factors including smoking, atopy, and recent allergen exposure 2
• Not included in WHO recommendations for asthma diagnosis/monitoring due to limited specificity and sensitivity 1

Understanding PFTs in Asthma Diagnosis

Key PFT Components for Asthma

• Spirometry: Measures airflow and lung volumes
  • FEV1 (forced expiratory volume in 1 second)
  • FVC (forced vital capacity)
  • FEV1/FVC ratio (reduced in obstructive diseases like asthma)
• Bronchodilator reversibility testing: Improvement in FEV1 ≥12% and ≥200mL after bronchodilator administration supports asthma diagnosis
• Peak flow monitoring: Can demonstrate variability characteristic of asthma

Clinical Utility of PFTs

• Demonstrates airflow obstruction
• Shows reversibility of obstruction (hallmark of asthma)
• Provides objective measurement of lung function
• Helps monitor disease progression and treatment response

Limitations of PFTs

• May be normal between exacerbations 1
• Requires patient cooperation and proper technique
• May need to be repeated multiple times to demonstrate reversible airflow obstruction 1

Combining FeNO and PFTs in Clinical Practice

Diagnostic Algorithm

1. Initial assessment with PFTs:

   • Spirometry to identify airflow obstruction
   • Bronchodilator reversibility testing

2. Add FeNO when:

   • Diagnosis remains uncertain after history, physical examination, and spirometry
   • Spirometry cannot be performed accurately
   • Patient is ≥5 years old 2
   • Need to identify asthma phenotype (particularly T2-high/eosinophilic asthma)

3. Interpret results together:

   • Normal PFTs with elevated FeNO: May indicate early/mild asthma or well-controlled asthma with underlying inflammation
   • Abnormal PFTs with normal FeNO: Consider non-eosinophilic asthma phenotypes
   • Both abnormal: Strong evidence for asthma with active inflammation

Common Pitfalls to Avoid

• Overreliance on absolute FeNO values: Changes from baseline may be more meaningful than absolute values 2
• Ignoring confounding factors: Atopy, smoking, and medications affect FeNO levels 2
• Using FeNO in very young children: Not validated in children <4 years 2
• Assuming normal spirometry excludes asthma: Patients may have normal PFTs when asymptomatic 1
• Failure to establish baseline values: Important for monitoring treatment response 2

Monitoring and Treatment Guidance

Using FeNO for Monitoring

• Establish baseline FeNO before starting anti-inflammatory treatment
• Repeat measurement after 4-8 weeks of treatment
• Consider changes in FeNO rather than absolute values alone 2
• Persistently high FeNO despite prescribed inhaled corticosteroids may indicate poor adherence or incorrect inhaler technique 2

Using PFTs for Monitoring

• Regular spirometry to assess lung function stability
• Peak flow monitoring between visits to detect variability
• Assess response to therapy and need for treatment adjustments

By combining these complementary tools, clinicians can improve diagnostic accuracy, guide appropriate treatment selection, monitor treatment response, and identify patients at risk for poor outcomes.