T2 High Asthma Workup
The workup for T2-high asthma centers on measuring blood eosinophils and FeNO (fractional exhaled nitric oxide), supplemented by total IgE and allergen-specific testing, to confirm type 2 inflammation and guide biologic therapy selection.
Core Biomarker Assessment
The essential workup includes:
Blood Eosinophils
- Primary threshold: ≥150 cells/μL indicates eosinophilic asthma 1
- Higher threshold: ≥300 cells/μL (≥0.30×10⁹/L) strongly supports T2-high classification 2
- This is the most accessible and widely used T2 biomarker
FeNO Testing
Age-specific cutoffs for T2 inflammation 3:
- Adults and children >12 years: >50 ppb indicates high T2 inflammation
- Children 5-12 years: >35 ppb indicates high T2 inflammation
- Intermediate range (25-50 ppb in adults, 20-35 ppb in children 5-12): interpret with caution in clinical context
- Low values (<25 ppb adults, <20 ppb children): inconsistent with T2 inflammation
Critical considerations for FeNO interpretation 3:
- Must account for atopy and allergic rhinitis (both elevate FeNO independent of asthma)
- Smoking and corticosteroid use lower FeNO levels
- Should be performed in corticosteroid-naïve patients when possible for diagnostic accuracy
- Cannot be used alone—requires integration with clinical assessment
Allergy Testing
- Total serum IgE: part of T2 phenotyping 1
- Allergen-specific IgE or skin prick testing: identifies allergic sensitization 3
- Positive testing (specific IgE ≥0.3 ISU or positive SPT) supports T2-high classification 2
Pulmonary Function Testing
Spirometry with bronchodilator response 3:
- Confirms asthma diagnosis
- Assesses reversibility (greater in T2-high patients) 2
- Establishes baseline lung function
- Required before considering biologic therapy
Clinical Phenotyping
Document these T2-high associated features 4, 2:
- Age of onset: adult-onset more common in eosinophilic asthma
- Exacerbation history: T2-high patients have increased exacerbation rates
- Comorbidities: chronic rhinosinusitis with nasal polyps (CRSwNP), atopic dermatitis, allergic rhinitis
- Corticosteroid response: T2-high inflammation typically responds to ICS 3
Important Caveats
Stability Over Time
T2 biomarkers show reasonable stability but can shift 2:
- 68-76% of patients remain in their initial T2 category over 12 years
- Transitions from low to high T2 associate with higher BMI
- Transitions from high to low T2 associate with older age, more comorbidities
- Implication: Reassess biomarkers if clinical response to T2-targeted therapy is inadequate
When FeNO Testing Is Most Useful
FeNO has supportive, not definitive diagnostic role 3:
- Best used when asthma diagnosis is uncertain (age ≥5 years)
- Helpful when spirometry cannot be performed accurately
- Do not use in children <4 years (insufficient diagnostic data)
- Increases asthma likelihood 2.8-7.0 times when high
- Never withhold ICS based solely on low FeNO
Biomarker-Guided Biologic Selection
Once T2-high status is confirmed, specific biomarker patterns guide therapy 5:
- High eosinophils + high FeNO: consider anti-IL-5/5R (mepolizumab, benralizumab, reslizumab) or anti-IL-4Rα (dupilumab)
- High IgE + allergic sensitization: consider anti-IgE (omalizumab)
- CRSwNP comorbidity: dupilumab or omalizumab (treat both conditions)
- Low/variable biomarkers but severe disease: consider anti-TSLP (tezepelumab) for broader T2 and non-T2 coverage
Practical Algorithm
- Measure blood eosinophils (≥150 cells/μL suggests T2-high; ≥300 cells/μL strongly supports)
- Perform FeNO testing in corticosteroid-naïve patients when feasible (use age-specific cutoffs)
- Obtain allergy testing (total IgE and specific IgE or SPT)
- Complete spirometry with bronchodilator response
- Assess for T2-associated comorbidities (CRSwNP, atopic dermatitis, allergic rhinitis)
- Classify as T2-high if ≥1 of: blood eosinophils ≥300 cells/μL, FeNO >50 ppb (>35 ppb in children 5-12), or positive allergen sensitization 2
This biomarker-driven approach enables precision phenotyping for targeted biologic therapy, which significantly reduces exacerbations in T2-high asthma 4, 6.