Treatment of Asthma

Overview

• Medical Physiology (Boron & Boulpaep), p. 906
• Katzung's Basic and Clinical Pharmacology, 16th Ed.

Goals of Treatment

• Control symptoms and minimize day-to-day variability
• Prevent acute exacerbations
• Maintain normal lung function
• Avoid adverse drug effects
• Reduce risk of long-term airway remodeling

Stepwise Pharmacological Approach (GINA 2025)

Track 1 (Preferred) - ICS-Formoterol as Reliever

MART = Maintenance-and-Reliever Therapy. Using ICS-formoterol as the reliever reduces exacerbation risk by ~two-thirds vs. SABA alone, and by >one-third vs. low-dose ICS + SABA. (GINA 2025 Summary Guide)

Track 2 (Alternative) - SABA as Reliever

Drug Classes

1. Inhaled Corticosteroids (ICS) - The Cornerstone

• Examples: beclomethasone, budesonide, fluticasone, ciclesonide, mometasone, triamcinolone
• Mechanism: Broad anti-inflammatory effects - inhibit lymphocyte, eosinophil, and mast cell infiltration; reduce bronchial hyperreactivity
• Do NOT directly relax smooth muscle but reduce exacerbation frequency when taken regularly
• Key adverse effects: oropharyngeal candidiasis, dysphonia (hoarseness), growth slowing in children (~1 cm/year, first year only), osteoporosis/cataracts with chronic use
• Minimize side effects: gargle water after each use, use a spacer device
• Katzung's Basic and Clinical Pharmacology, 16th Ed., p. 557

2. Short-Acting Beta-2 Agonists (SABA) - Rescue

• Examples: albuterol (salbutamol), levalbuterol
• Mechanism: Activate beta-2 receptors on bronchial smooth muscle → bronchodilation via cAMP increase
• Used as-needed for acute symptom relief; in GINA Track 1, being replaced as reliever by ICS-formoterol

3. Long-Acting Beta-2 Agonists (LABA)

• Examples: salmeterol, formoterol
• Formoterol has rapid onset AND long duration - uniquely suited for both maintenance and as-needed use (hence MART regimens)
• Never use LABA as monotherapy in asthma - always combine with ICS
• The ICS-formoterol combination lowers the risk of asthma exacerbations significantly
• Fishman's Pulmonary Diseases, block30

4. Long-Acting Muscarinic Antagonists (LAMA)

• Example: tiotropium
• Added at Step 5 for patients ≥6 years whose asthma is uncontrolled on ICS + LABA
• Improves lung function and increases time to severe exacerbation
• Lippincott Pharmacology

5. Systemic Corticosteroids

• Reserved for severe acute exacerbations or failure of inhaled therapy
• Oral prednisone 30-60 mg/day or IV methylprednisolone 0.5-1 mg/kg every 6-12 hours for urgent treatment
• Taper over 5-10 days after improvement
• Katzung's Basic and Clinical Pharmacology, 16th Ed.

6. Leukotriene Receptor Antagonists (LTRAs)

• Example: montelukast
• Useful adjunct, especially in aspirin-sensitive asthma and allergic rhinitis comorbidity

7. Theophylline (Methylxanthine)

• Phosphodiesterase inhibitor - raises cAMP → bronchodilation
• Once a mainstay, now used far less commonly due to narrow therapeutic window and drug interactions
• Medical Physiology (Boron), p. 906

8. Biologics (Step 5 - Severe Asthma)

• Anti-IgE: Omalizumab (allergic asthma, IgE-mediated)
• Anti-IL-5: Mepolizumab, reslizumab, benralizumab (eosinophilic asthma)
• Anti-IL-4/IL-13: Dupilumab
• Indicated after phenotyping confirms the appropriate endotype

Acute Severe Exacerbation Management

1. Supplemental oxygen - target SpO2 93-95% (94-98% in children)
2. Repeated SABA - salbutamol via nebulizer or MDI with spacer every 20 minutes x3
3. Systemic corticosteroids - oral prednisolone 40-50 mg or IV methylprednisolone
4. Ipratropium bromide (anticholinergic) added for severe exacerbations
5. IV magnesium sulfate - for severe/life-threatening attacks not responding to initial therapy (meta-analysis in children supports this: PMID 38395640)
6. ICU/intubation for impending respiratory failure

Special Populations

Pregnancy

• Asthma affects ~4% of pregnant women; ~1/3 experience exacerbations
• ICS are safe in pregnancy and should be continued - risk of uncontrolled asthma far outweighs medication risk
• SABA (albuterol) safe as reliever
• Moderate-severe asthma in pregnancy increases risk of preterm labor, low birth weight, preeclampsia
• Monitor PEFR regularly; FEV1 and PEFR are unchanged in normal pregnancy
• Textbook of Family Medicine, 9th Ed.

Children 6-11 years

• Similar stepwise approach; preferred reliever at Steps 3-5 is ICS-formoterol (GINA 2025)
• Low-dose ICS is the preferred Step 2 controller

Children under 5 years

• Daily low-dose ICS is the preferred long-term controller
• SABA as reliever

Non-Pharmacological Strategies

• Trigger avoidance: allergens, tobacco smoke, occupational irritants, NSAIDs (if aspirin-sensitive)
• Smoking cessation
• Physical activity and pulmonary rehabilitation
• Weight reduction (obesity worsens asthma)
• Vaccinations: influenza, pneumococcal
• Allergen immunotherapy (HDM SLIT): consider for clinically relevant sensitization with inadequate control
• Patient education: inhaler technique, written asthma action plan, peak flow monitoring

Monitoring and Step Adjustments

• Reassess at every visit: symptoms, exacerbations, side effects, lung function, inhaler technique, and adherence
• Step up if uncontrolled after checking adherence and technique
• Step down after 3 months of good control (to find the minimum effective therapy)

Recent Evidence Note

Asthma Treatment - Quick Summary (GINA 2025)

Core Principle

Two Treatment Tracks (Adults & Adolescents ≥12 yrs)

Key Drug Classes

Acute Exacerbation

1. O2 supplementation (SpO2 target 93-95%)
2. Repeated SABA nebulization every 20 min x3
3. Systemic corticosteroids (oral prednisolone 40-50 mg or IV methylprednisolone)
4. Add ipratropium for severe attacks
5. IV magnesium sulfate for life-threatening cases
6. ICU if impending respiratory failure

Non-Pharmacological

• Trigger avoidance, smoking cessation, weight loss, vaccinations, inhaler technique education, written action plan, allergen immunotherapy (HDM SLIT if indicated)