What are the treatment approaches for different inflammatory endotypes in asthma?

Treatment Approaches for Different Inflammatory Endotypes in Asthma

Treatment approaches for asthma should be tailored to the specific inflammatory endotype, with T2-high asthma requiring different therapies than T2-low asthma to effectively reduce morbidity and mortality. 1

Understanding Asthma Endotypes

Asthma is now recognized as a heterogeneous disease with distinct inflammatory pathways (endotypes) rather than a single entity. The major endotypes include:

T2-High Asthma

• Characterized by eosinophilic airway inflammation and allergic sensitization 1
• Primarily driven by IgE and type 2 cytokines (IL-4, IL-5, and IL-13) 1
• More commonly detected in asthmatic children 1
• Identifiable by elevated blood eosinophils and/or high FeNO (fractional exhaled nitric oxide) 1

T2-Low Asthma

• Featured by either neutrophilic or paucigranulocytic airway inflammation 1
• Sustained by IL-8, IL-17, IL-22 and other T-cell-related cytokines 1
• More common in adults with asthma 1
• Characterized by absence of high blood eosinophils and high FeNO 1

Treatment Approaches by Endotype

T2-High (Eosinophilic) Asthma Treatment

1. First-line therapy:

   • Inhaled corticosteroids (ICS) as the cornerstone of treatment 1
   • Patients with this endotype typically show good response to corticosteroids 1

2. For moderate persistent disease:

   • Low-dose inhaled corticosteroids plus long-acting β2-adrenergic agonists (LABA) such as salmeterol 1, 2
   • Alternative: Medium-dose inhaled corticosteroids 1

3. For severe persistent disease:

   • High-dose inhaled corticosteroids and long-acting β2-adrenergic agonists 1
   • Oral corticosteroids may be needed in some cases 1

4. Biological therapies for severe T2-high asthma:

   • Anti-IgE therapy for allergic asthma 1
   • Anti-IL5/IL5R therapies for eosinophilic asthma 1
   • Anti-IL4R (dupilumab) for type 2 asthma - inhibits both IL-4 and IL-13 signaling 1, 3
   • Anti-TSLP therapy for type 2 asthma 1

T2-Low (Neutrophilic) Asthma Treatment

1. Standard therapy:

   • Often shows poor response to conventional corticosteroid treatment, even in mild asthma 1
   • May require alternative anti-inflammatory approaches 1

2. Potential targeted therapies:

   • Anti-TSLP therapy may be beneficial after ruling out other chronic obstructive airway diseases 1
   • Antibiotics may be effective in some cases of neutrophilic inflammation 1
   • Emerging therapies targeting pathways that lead to neutrophil recruitment (TNF, IL-1, IL-6, IL-8, IL-23, and IL-17) 1

3. For refractory cases:

   • Consider pharmacologic trials with nonspecific antiinflammatory agents 1
   • Customized therapy based on pathologic features 1

Monitoring and Assessment

• Use biomarkers to guide therapy and monitor response 1:

  • Blood eosinophil counts
  • Sputum eosinophil/neutrophil counts
  • FeNO (fractional exhaled nitric oxide)
  • IgE levels

• Regular assessment of:

  • Symptom control 1
  • Lung function 1
  • Exacerbation frequency 1

Special Considerations

• Pediatric patients: T2-high endotype is more common, with eosinophilic inflammation predominating 1
• Adult patients: Higher likelihood of T2-low endotype with neutrophilic inflammation 1
• Refractory asthma: May have distinct pathologic processes requiring specialized approaches 1
• Comorbidities: Address allergic comorbidities (e.g., eczema, allergic rhinitis) that can influence asthma control 1

Common Pitfalls to Avoid

• Failure to identify the endotype: Not all asthma responds to the same treatment; endotyping is crucial for appropriate therapy selection 1
• Overreliance on symptoms alone: Objective measures of inflammation should guide therapy 1
• Inadequate dosing: Insufficient anti-inflammatory treatment can lead to poor control and increased exacerbations 1
• Not addressing environmental triggers: Environmental control remains an essential component of management 1
• Neglecting patient education: Patients must understand their specific asthma type and treatment approach 1

By tailoring treatment to the specific inflammatory endotype, clinicians can improve asthma control, reduce exacerbations, and decrease the morbidity and mortality associated with this heterogeneous disease.