What is the treatment for refractory moderate persistent asthma?

Treatment for Refractory Moderate Persistent Asthma

The cornerstone of treatment for refractory moderate persistent asthma is high-dose inhaled corticosteroids (ICS) combined with a long-acting beta-agonist (LABA), with additional controller medications added in a stepwise fashion if symptoms remain uncontrolled. 1, 2

Definition and Characteristics of Refractory Asthma

Refractory asthma is characterized by:

• Persistent symptoms despite high-dose ICS therapy
• Requirement for additional controller medications
• Persistent airflow obstruction (FEV1 < 80% predicted)
• Frequent exacerbations requiring oral corticosteroid "bursts"
• Prompt deterioration with reduction in corticosteroid dose 1

Treatment Algorithm

Step 1: Optimize Current Therapy

• Ensure proper inhaler technique and medication adherence
• Identify and address potential triggers (allergens, occupational sensitizers, irritants)
• Assess for comorbidities that may worsen asthma control (GERD, rhinosinusitis) 2

Step 2: High-Dose ICS + LABA Combination

• Use high-dose ICS plus LABA as foundation therapy:
  • Fluticasone propionate > 880 mcg/day (or equivalent)
  • Combined with a long-acting beta-agonist 1, 2
• Combination therapy provides greater asthma control than increasing ICS dose alone 3

Step 3: Add Additional Controller Medications

If symptoms remain uncontrolled, add one or more of the following:

1. Leukotriene modifier

   • Add to high-dose ICS/LABA therapy 1, 2
   • Particularly beneficial for patients with aspirin sensitivity or allergic rhinitis

2. Theophylline

   • Can be added as a third controller medication
   • Requires monitoring of serum levels due to narrow therapeutic window 1, 2

3. Oral corticosteroids

   • For patients who fail to respond to the above combinations
   • Prednisone 1-2 mg/kg/day (or equivalent)
   • Make repeated attempts to reduce systemic corticosteroids while maintaining control 1, 2

Step 4: Biologic Therapies

For appropriate candidates with persistent symptoms despite the above treatments:

• Omalizumab (anti-IgE therapy)
  • For patients with allergic asthma and elevated IgE levels
  • Must be administered in a healthcare setting equipped to manage anaphylaxis
  • Monitor patients closely for signs of anaphylaxis, which can occur up to 4 days after administration 4

Important Clinical Considerations

Medication Adherence

• Poor adherence to therapy, particularly inhaled corticosteroids, is a common reason for poor response 5
• Implement adherence strategies such as:
  • Linking inhaler use to daily activities
  • Setting phone reminders
  • Keeping inhalers in visible locations 2

Corticosteroid Reduction

• Do not discontinue systemic or inhaled corticosteroids abruptly
• Decrease corticosteroids gradually under direct physician supervision 4
• Make repeated attempts to reduce systemic corticosteroids while maintaining control with high-dose inhaled corticosteroids 1

Monitoring for Side Effects

• Monitor for potential steroid side effects:
  • Delayed growth (in children)
  • Increased blood pressure
  • Osteoporosis
  • Adrenal suppression
  • Cataracts 2
• Oral candidiasis can be prevented by rinsing the mouth after ICS use 2

Specialist Referral

• Refer to an asthma specialist if:
  • Symptoms remain uncontrolled despite Step 3 therapy
  • Patient has had ≥2 exacerbations requiring oral corticosteroids in the past year
  • Patient requires Step 4 care or higher
  • Additional testing is needed to identify triggers or comorbidities 2

Pitfalls and Caveats

1. Never use LABAs alone for asthma management due to increased risk of asthma-related death 2, 4

2. Do not use biologic therapies for acute exacerbations - they are not indicated for emergency treatment of allergic reactions or acute bronchospasm 4

3. Carefully assess for alternative diagnoses before labeling asthma as "refractory":

   • COPD
   • Vocal cord dysfunction
   • Other systemic diseases 5

4. Evaluate for pharmacokinetic issues in patients who fail to respond to corticosteroids:

   • Incomplete absorption
   • Failure to convert inactive to active form
   • Rapid elimination 1

By following this structured approach to refractory moderate persistent asthma, clinicians can optimize therapy and improve outcomes for these challenging patients.