What labwork is recommended for the diagnosis of severe persistent asthma?

Laboratory Testing for Diagnosis of Severe Persistent Asthma

Spirometry with bronchodilator reversibility testing is the essential laboratory test for diagnosing severe persistent asthma, showing airflow obstruction with FEV1 <60% of predicted value and reduced FEV1/FVC ratio. 1

Core Diagnostic Tests

1. Spirometry

• Required parameters:
  • FEV1 (Forced Expiratory Volume in 1 second): <60% of predicted in severe persistent asthma 1
  • FEV1/FVC ratio: Reduced compared to normal values for age 1
  • Bronchodilator reversibility: Increase of ≥12% and 200mL in FEV1 after bronchodilator administration 1

2. Peak Expiratory Flow (PEF) Measurements

• Diurnal variation >20% over 1-2 weeks 1
• Values typically <60% of personal best in severe persistent asthma 1
• Less reliable than spirometry but useful for monitoring 1

3. Bronchial Challenge Testing

• Indicated when spirometry is normal but clinical suspicion remains high 1, 2
• Options include:
  • Methacholine challenge
  • Histamine challenge
  • Exercise challenge
  • Cold air challenge
• Positive test confirms airway hyperresponsiveness 1

Biomarkers of Inflammation

1. Fractional Exhaled Nitric Oxide (FeNO)

• Elevated in eosinophilic airway inflammation 1
• Useful for:
  • Supporting diagnosis in atopic asthma
  • Monitoring response to corticosteroid therapy
  • Assessing medication adherence 1

2. Sputum Analysis

• Eosinophil count in induced sputum
• Elevated in eosinophilic asthma phenotype 1
• Helps guide therapy, particularly for severe asthma 1

Additional Testing for Severe Asthma Phenotyping

1. Blood Tests

• Complete blood count with differential (looking for eosinophilia)
• Total IgE levels
• Allergen-specific IgE
• These tests help identify atopic phenotype and eligibility for biologic therapies 1

2. Additional Pulmonary Function Tests

• Lung volumes measurement (to rule out restrictive defects)
• Diffusing capacity (to differentiate from COPD) 1, 3
• Inspiratory flow-volume loops (to evaluate for vocal cord dysfunction) 1

Imaging Studies

• Chest X-ray: To exclude alternative diagnoses 1
• Consider CT scan of chest and sinuses in severe cases to identify complications or comorbidities 1

Diagnostic Algorithm

1. Initial assessment: Document symptoms consistent with severe persistent asthma (symptoms throughout the day, frequent nighttime awakenings, extreme activity limitation, need for rescue medication several times daily) 1

2. Confirm diagnosis with spirometry: FEV1 <60% predicted, reduced FEV1/FVC ratio, and positive bronchodilator reversibility 1

3. Document exacerbation history: ≥2 exacerbations requiring oral corticosteroids in the past year supports classification as severe persistent asthma 1

4. Phenotype the asthma: Use biomarkers (FeNO, blood eosinophils, IgE) to determine inflammatory pattern 1

5. Rule out alternative diagnoses: Use additional testing as needed to exclude conditions that mimic severe asthma 1

Common Pitfalls to Avoid

• Relying solely on symptoms: Patients often underestimate symptom severity; objective measures are essential 1

• Missing comorbidities: Conditions like GERD, vocal cord dysfunction, and allergic bronchopulmonary aspergillosis can mimic or worsen asthma 1

• Inadequate reversibility testing: A single normal spirometry does not rule out asthma; repeated testing or bronchoprovocation may be necessary 2

• Overreliance on peak flow: While useful for monitoring, PEF is less reliable than spirometry for diagnosis 1, 4

• Failure to assess small airway function: FEF25% and FEF75% may be more sensitive than FEV1 for detecting mild asthma 5

By following this comprehensive approach to laboratory testing, clinicians can accurately diagnose severe persistent asthma, determine the appropriate phenotype, and guide targeted therapy to reduce morbidity and mortality.