What is the recommended approach for phenotyping asthma to guide personalized treatment plans?

Phenotyping Asthma for Personalized Treatment Plans

The recommended approach for phenotyping asthma should include assessment of clinical characteristics, biomarkers of airway inflammation, identification of triggers, and evaluation of comorbidities to guide targeted therapy selection. 1

Core Components of Asthma Phenotyping

1. Clinical Assessment

• Assess asthma severity using symptoms, exacerbation history, and lung function 2
• Evaluate level of asthma control using:
  • Frequency of daytime symptoms (>2 days/week indicates poor control)
  • Nighttime awakenings
  • Need for rescue medication (>2 days/week indicates poor control)
  • Activity limitations
  • Exacerbation history 2, 1

2. Inflammatory Biomarkers

• Measure blood eosinophil counts (≥150-300 cells/mcL suggests T2-high inflammation) 3
• Consider sputum eosinophil count (≥3% indicates eosinophilic phenotype) 2
• Measure fractional exhaled nitric oxide (FeNO) (≥50 ppb suggests T2-high inflammation) 2
• Use these biomarkers to categorize into inflammatory phenotypes:
  • T2-high (eosinophilic/allergic)
  • T2-low (neutrophilic/non-eosinophilic) 4

3. Trigger Identification

• Conduct allergen testing to identify specific allergic triggers 1, 5
• Assess occupational exposures that may contribute to symptoms 2
• Evaluate for viral-triggered exacerbations 5
• Document exercise-induced symptoms 2

4. Comorbidity Assessment

• Evaluate for conditions that may worsen asthma control:
  • Chronic rhinosinusitis and nasal polyps
  • Gastroesophageal reflux disease (GERD)
  • Obesity
  • Obstructive sleep apnea
  • Psychological factors (stress, depression) 2, 6

Phenotype-Directed Treatment Approach

Allergic/Eosinophilic Asthma

• Characterized by: elevated blood eosinophils, positive allergen testing, elevated IgE
• Treatment considerations:
  • Inhaled corticosteroids (ICS) as foundation therapy 1
  • Consider anti-IgE therapy (omalizumab) for allergic phenotype 1
  • Consider anti-IL5/anti-IL5R therapies (e.g., mepolizumab) for eosinophilic phenotype 3
  • Allergen avoidance strategies 5

Exercise-Induced Asthma

• Characterized by: symptoms primarily with physical activity
• Treatment considerations:
  • Pre-treatment with short-acting beta-agonists before exercise
  • Consider leukotriene modifiers 1
  • Regular ICS therapy for underlying inflammation 2

Neutrophilic/Non-Eosinophilic Asthma

• Characterized by: normal eosinophil counts, neutrophilic inflammation
• Treatment considerations:
  • May be less responsive to corticosteroids
  • Consider macrolide antibiotics for persistent symptoms
  • Ensure adequate ICS/LABA therapy 4

Aspirin-Exacerbated Respiratory Disease (AERD)

• Characterized by: asthma, nasal polyps, and sensitivity to aspirin/NSAIDs
• Treatment considerations:
  • Avoid aspirin/NSAIDs
  • Higher doses of ICS often required
  • Consider leukotriene modifiers
  • Aspirin desensitization in selected cases 4

Implementation Algorithm

1. Initial Assessment:

   • Confirm asthma diagnosis
   • Determine asthma severity (intermittent, mild, moderate, or severe persistent) 2
   • Assess current level of control (well-controlled or not well-controlled) 2

2. Phenotyping Workup:

   • Complete blood count with differential (focus on eosinophil count)
   • Specific IgE testing or skin prick testing for common allergens
   • FeNO measurement
   • Consider sputum induction for cell differential
   • Evaluate for comorbidities 6

3. Treatment Selection Based on Phenotype:

   • Step 1-2 (Mild): Start with low-dose ICS for all phenotypes 2
   • Step 3-4 (Moderate):
     • For eosinophilic/allergic: Medium-dose ICS/LABA 7
     • For non-eosinophilic: Consider alternative controllers (leukotriene modifiers) 2
   • Step 5-6 (Severe):
     • For eosinophilic/allergic with elevated IgE: Consider omalizumab
     • For eosinophilic with normal IgE: Consider anti-IL5 therapy (mepolizumab) 3
     • For non-eosinophilic: High-dose ICS/LABA plus consider LAMA 1

4. Monitoring and Adjustment:

   • Reassess control every 2-6 weeks initially, then every 1-6 months 2
   • Adjust therapy based on control (step up if not controlled, consider step down if well-controlled for ≥3 months) 2
   • Re-evaluate phenotype if response to therapy is inadequate 2

Common Pitfalls to Avoid

1. Relying solely on symptoms without objective measures

   • Always incorporate lung function and biomarkers in phenotyping decisions 2

2. Failure to address comorbidities

   • Untreated comorbidities can mimic poor asthma control and lead to inappropriate escalation of therapy 2

3. Not considering adherence and inhaler technique

   • Poor adherence or technique may be mistaken for severe/refractory asthma 2

4. Overlooking environmental and occupational triggers

   • Persistent exposure to triggers can limit effectiveness of any phenotype-directed therapy 2

5. Static approach to phenotyping

   • Asthma phenotypes may evolve over time; periodic reassessment is essential 2

By systematically phenotyping patients with asthma using this approach, clinicians can develop more effective personalized treatment plans that target the underlying disease mechanisms, leading to improved asthma control and quality of life.