Eosinophilic Asthma: Causes and Treatment
Pathophysiology and Causes
Eosinophilic asthma is driven by Type 2 (Th2) immune responses that lead to eosinophilic airway inflammation, characterized by infiltration of eosinophils into the airway wall and smooth muscle, resulting in airway hyperresponsiveness, inflammation, and remodeling. 1
Key Pathogenic Mechanisms:
- Eosinophils act as central effector cells producing cytokines, chemokines, and granule proteins that perpetuate airway inflammation and contribute to disease severity 2
- IL-5 and IL-13 are critical cytokines driving eosinophil maturation, recruitment, and survival in the airways 1
- Mast cell infiltration into airway smooth muscle distinguishes eosinophilic asthma from nonasthmatic eosinophilic bronchitis, where mast cells infiltrate the epithelium instead 1
- Airway remodeling occurs through persistent eosinophilic inflammation, leading to structural changes and progressive disease 3
Triggering Factors:
- Allergen exposure (environmental or occupational sensitizers) can initiate eosinophilic inflammation 1, 4
- Late-onset disease is commonly associated with eosinophilic phenotype 5
- Atopy frequently accompanies eosinophilic asthma 5
Treatment Algorithm
First-Line Treatment: Inhaled Corticosteroids
Inhaled corticosteroids are the cornerstone of treatment for eosinophilic asthma, effectively reducing sputum eosinophils and improving symptoms. 6
- Start with high-dose inhaled corticosteroids as the primary therapy for patients with TH2-high asthma, which demonstrates upregulated IL-13 targets, increased bronchial hyperresponsiveness, and positive response to corticosteroid treatment 1
- Budesonide 400 μg twice daily has been specifically studied and normalizes cough sensitivity after 4 weeks of treatment 4, 6
- Monitor clinical response and eosinophil counts (blood or sputum) to assess treatment efficacy 6
Critical Distinction—Do Not Confuse with Eosinophilic Pneumonitis:
- Never use inhaled corticosteroids alone for eosinophilic pneumonitis—treatment failure occurs in 100% of cases, unlike eosinophilic asthma where inhaled steroids are highly effective 7, 4
Escalation for Severe or Refractory Disease
When to Add Systemic Corticosteroids:
Reserve oral corticosteroids for patients with persistently troublesome symptoms despite high-dose inhaled corticosteroids or when eosinophilic inflammation progresses despite maximal inhaled therapy. 4, 6
- Do not discontinue systemic or inhaled corticosteroids abruptly when initiating biologic therapy—taper gradually under direct physician supervision to avoid withdrawal symptoms and unmasking of previously suppressed conditions 8, 9
Biologic Therapies for Severe Eosinophilic Asthma
Anti-IL-5 Pathway Agents:
For patients with severe eosinophilic asthma uncontrolled on high-dose corticosteroids, biologic agents targeting the IL-5 pathway provide significant reduction in exacerbations and improvement in quality of life. 1, 10
Benralizumab (FASENRA):
- FDA-approved for add-on maintenance treatment of severe asthma with eosinophilic phenotype in patients ≥6 years old 8
- Dosing for adults and adolescents ≥12 years: 30 mg subcutaneously every 4 weeks for first 3 doses, then every 8 weeks 8
- Dosing for children 6-11 years: 10 mg every 4 weeks for 3 doses then every 8 weeks (if <35 kg); 30 mg with same schedule (if ≥35 kg) 8
- Mechanism: Directly depletes eosinophils through antibody-dependent cell-mediated cytotoxicity by binding IL-5 receptor alpha 11
- Advantage over other anti-IL-5 agents: Direct eosinophil depletion rather than indirect effect 11
Reslizumab (CINQAIR):
- FDA-approved for maintenance treatment of severe asthma with eosinophilic phenotype in adults ≥18 years 9
- Dosing: Intravenous infusion every 4 weeks (20-50 minutes infusion time) 9
- Reduces blood eosinophils and prevents severe asthma attacks 9
Patient Selection for Biologics:
Select patients based on accurate phenotyping—specifically those with steroid-refractory eosinophilia or frequent exacerbations despite high-dose inhaled corticosteroids. 1
- Anti-IL-5 therapy reduces exacerbations by 50% in patients with steroid-refractory eosinophilic asthma 1
- TH2-high asthma patients (with upregulated IL-13 targets and eosinophilia) respond best to targeted biologic therapy 1
Critical Clinical Pitfalls
Allergen Avoidance Takes Priority:
When a causal allergen or occupational sensitizer is identified, avoidance is the best treatment and should take priority over pharmacotherapy. 4, 6
- Always consider occupation-related causes in patients with eosinophilic asthma 4
Hypersensitivity Reactions with Biologics:
- Anaphylaxis can occur with benralizumab and reslizumab—monitor patients during and after administration 8, 9
- Discontinue immediately if hypersensitivity reaction occurs 8
Helminth Infections:
- Treat pre-existing helminth infections before initiating biologic therapy; if patients become infected during treatment and don't respond to anti-helminth treatment, discontinue biologic until infection resolves 8
Not for Acute Symptoms:
- Biologics are not for relief of acute bronchospasm or status asthmaticus—they are maintenance therapies only 8, 9
Monitoring and Long-Term Management
- Assess treatment response by monitoring sputum eosinophil counts and clinical symptoms 4
- Treatment-induced changes in cough sensitivity correlate positively with reduction in sputum eosinophil count 4
- Duration of treatment remains unclear—evidence suggests airway remodeling may necessitate long-term therapy even after symptom resolution 4
- Malignancy risk should be discussed with patients on biologic therapy 9