How should asthma be treated across severity levels, including medication choices and management of exacerbations?

Treatment of Asthma

Asthma treatment should follow a stepwise approach based on disease severity and control status, with inhaled corticosteroids (ICS) as the cornerstone of therapy for all persistent asthma, and treatment intensity adjusted upward or downward based on whether control is achieved. 1

Initial Assessment and Classification

Before initiating therapy, classify asthma severity using two domains: 1, 2

• Impairment Domain: FEV1 measurements (≥80% = intermittent/mild; 60-80% = moderate; <60% = severe), symptom frequency, nighttime awakenings, SABA use, and activity limitation 1, 2
• Risk Domain: History of exacerbations requiring oral corticosteroids (≥2 per year indicates persistent asthma regardless of lung function) 1, 2

Critical point: Patients with ≥2 exacerbations requiring oral corticosteroids in the past year must be classified as having persistent asthma even if their FEV1 is normal. 1, 2

Stepwise Pharmacotherapy Algorithm

Step 1: Mild Intermittent Asthma

• Short-acting β-agonist (SABA) as needed only 1
• All patients at every step should have SABA available for rescue 1, 3

Step 2: Mild Persistent Asthma

• Low-dose inhaled corticosteroids (preferred) 1, 4
• Alternative options: leukotriene modifiers, theophylline, cromolyn, or nedocromil 1
• Continue SABA as needed for symptom relief 1

Step 3: Moderate Persistent Asthma

• Low-to-medium dose ICS plus long-acting β-agonist (LABA) (preferred combination) 1, 4
• Alternative: Medium-dose ICS alone 1
• Alternative: Low-to-medium dose ICS plus either leukotriene modifier or theophylline 1

Warning: Never use LABA as monotherapy—it must always be combined with ICS. 4

Step 4: Severe Persistent Asthma

• High-dose ICS plus LABA 1, 4
• Add systemic corticosteroids if needed 1
• Consider monoclonal anti-IgE (omalizumab) for allergic asthma 1, 4
• Consider long-acting muscarinic antagonists (tiotropium) 4, 5
• Consider biologic agents (mepolizumab, reslizumab, dupilumab) for severe eosinophilic asthma 6, 4, 5

Monitoring and Adjusting Therapy

At each clinical encounter, determine control status as either well controlled or not well controlled: 1

• Well controlled: Maintain current therapy or consider step-down 1
• Not well controlled: Step up therapy or change treatment approach 1

Common pitfall: Both patients and physicians systematically underestimate symptom severity—39-70% of patients with moderate symptoms incorrectly believe their asthma is well controlled. 1 Always use objective measures (spirometry, validated questionnaires) rather than relying solely on patient perception. 1

Detailed Assessment for Poor Control

When asthma is not well controlled, systematically evaluate: 1

• Adherence issues: Most common cause of treatment failure 1
• Allergen or occupational exposures: Identify and eliminate triggers 1, 2
• Medication affordability: Address cost barriers 1
• Respiratory infections: Treat appropriately 1
• Comorbidities: Manage GERD, rhinosinusitis, obesity 1
• Incorrect diagnosis: Reconsider if treatment repeatedly fails 1

Biologic Therapy Selection

For severe uncontrolled asthma despite high-dose ICS/LABA: 6, 4

• Dupilumab: For patients with baseline eosinophils ≥150 cells/mcL or FeNO ≥25 ppb; reduces exacerbations by 46-48% and improves FEV1 by 0.13-0.14 L compared to placebo 6
• Omalizumab: For IgE-mediated allergic asthma 1, 4
• Mepolizumab/Reslizumab: For severe eosinophilic asthma 4, 5

Note: Dupilumab shows minimal benefit in patients with eosinophils <150 cells/mcL AND FeNO <25 ppb. 6

Managing Acute Exacerbations

Home Management

Patients should have a written asthma action plan that includes: 1

• Increase SABA use immediately when symptoms worsen 1
• Add short course of oral corticosteroids (typically 3-5 days) for moderate-to-severe exacerbations 1, 7
• Do NOT double ICS dose—this strategy is ineffective 1
• Seek emergency care if: PEF <50% predicted, severe dyspnea, altered mental status, or poor response to SABA 1, 7

Severity Classification of Exacerbations

• Mild: PEF 70-90% predicted; manage at home 7
• Moderate: PEF 50-79% predicted; may require ED evaluation 7
• Severe: PEF <50% predicted; requires ED treatment and possible hospitalization 7
• Life-threatening: Altered mental status, inability to speak in phrases, severe respiratory distress 7

High-Risk Patients Requiring Intensive Monitoring

Never underestimate exacerbation risk—severe exacerbations can occur at any baseline severity level. 7, 8 Patients at highest risk include those with: 1, 8

• Prior intubation or ICU admission for asthma 1, 8
• ≥2 hospitalizations in past year 1, 8
• ≥3 ED visits in past year 1, 8
• Using >2 SABA canisters per month 1, 8
• Difficulty perceiving symptom severity 1, 8
• Low socioeconomic status, illicit drug use, or psychiatric disease 1, 8
• Cardiovascular disease or other chronic lung disease 1, 8

These patients require more aggressive controller therapy, frequent monitoring, and early intervention during exacerbations. 8

Special Considerations

Leukotriene modifiers (montelukast): Not for acute symptom relief; patients must continue SABA for rescue and should not abruptly substitute montelukast for corticosteroids. 3 Monitor for neuropsychiatric side effects (agitation, depression, suicidal thinking). 3

Aspirin-sensitive asthma: Continue aspirin/NSAID avoidance even while on controller therapy. 3

Step-down therapy: Once control is maintained for at least 3 months, consider reducing treatment intensity by decreasing ICS dose, reducing medication frequency, or discontinuing add-on therapies while maintaining close monitoring. 1