What is the recommended treatment for moderate persistent asthma?

Treatment of Moderate Persistent Asthma

The preferred treatment for moderate persistent asthma in adults and children older than 5 years is the combination of low-to-medium-dose inhaled corticosteroids (ICS) with long-acting beta2-agonists (LABA). 1

First-Line Treatment Options

• For adults and children >5 years old, low-to-medium-dose ICS plus LABA is the preferred treatment, with strong evidence consistently showing improved outcomes 1
• The combination provides superior control of symptoms, improved lung function, and reduced exacerbation rates compared to other treatment options 1, 2
• Budesonide/formoterol (Symbicort) can be used as both maintenance and reliever therapy (SMART protocol) for patients ≥12 years old 2
• For children younger than 5 years, two preferred options exist:
  • Addition of LABA to low-dose ICS
  • Medium-dose ICS as monotherapy 1

Alternative Treatment Options

• Increase inhaled corticosteroids within medium-dose range (less effective than adding LABA) 1, 3
• Low-to-medium-dose ICS plus leukotriene modifier (e.g., montelukast) 1
• Low-to-medium-dose ICS plus theophylline (less preferred due to side effect profile) 1

Treatment Considerations for Patients with Frequent Exacerbations

• For patients with recurring severe exacerbations, increase ICS within medium-dose range AND add a LABA 1
• Alternative approach for these patients: increase ICS within medium-dose range and add either leukotriene modifier OR theophylline 1

Scientific Rationale for Combination Therapy

• ICS suppress chronic inflammation and reduce airway hyperresponsiveness 4
• LABA provide bronchodilation and also inhibit mast cell mediator release and plasma exudation 4
• Positive interactions exist between these drug classes:
  • Corticosteroids increase expression of beta2-receptors 4
  • Beta2-agonists may potentiate corticosteroid actions with increased nuclear localization of glucocorticoid receptors 4

Clinical Evidence Supporting Combination Therapy

• Fixed-dose combinations (e.g., fluticasone/salmeterol, budesonide/formoterol) show greater efficacy than increasing ICS dose alone 5, 6
• Combination therapy provides:
  • Improved morning peak expiratory flow 7
  • Increased percentage of symptom-free days 7
  • Increased percentage of rescue-free days 7
  • Reduced exacerbation rates 5

Important Considerations and Pitfalls

• LABA should never be used as monotherapy for asthma due to increased risk of asthma-related events including deaths 2, 8
• Always combine LABA with ICS to mitigate this risk 2, 8
• Formoterol-containing combinations are preferred for SMART protocol due to rapid onset of action 2
• For children <5 years, limited data exists on combination therapy; budesonide nebulizer solution is approved for children 1-8 years, and fluticasone DPI for children ≥4 years 1
• Salmeterol DPI is approved for children ≥4 years, while montelukast is approved for children ≥2 years 1

Step-Up Approach

• If moderate persistent asthma is not controlled with the above regimen, consider:
  • Increasing to medium-to-high-dose ICS/LABA 1, 2
  • For severe persistent asthma: high-dose ICS plus LABA, with addition of oral corticosteroids if needed 1