What are the treatment options and medications used for asthma management?

Asthma Treatment and Medications

Inhaled corticosteroids (ICS) are the preferred first-line controller medication for all patients with persistent asthma, as they are the most consistently effective treatment for reducing symptoms, improving lung function, and preventing exacerbations. 1, 2, 3, 4

Stepwise Treatment Algorithm

The treatment approach follows a stepwise escalation based on symptom control and exacerbation risk, with the ability to step down after prolonged control 1:

Step 1: Intermittent Asthma

• As-needed short-acting beta-agonists (SABA) such as albuterol for symptom relief 1, 3
• No daily controller medication required 1, 3
• Alternative emerging approach: Low-dose ICS taken whenever SABA is used (off-label) 1

Step 2: Mild Persistent Asthma

• Daily low-dose inhaled corticosteroid is the preferred controller treatment 1, 2, 3
• Alternative options (second-line, less effective):
  • Leukotriene receptor antagonists (LTRAs): montelukast or zafirlukast 1, 5, 2
  • Cromolyn sodium or nedocromil (mast cell stabilizers) 1
  • Theophylline (sustained-release formulation) 1, 2

Step 3: Moderate Persistent Asthma

• Low-dose ICS plus long-acting beta-agonist (LABA) is the preferred combination for patients ≥12 years 1, 2, 3
• Alternative: Medium-dose ICS alone 1, 2
• Emerging option: As-needed low-dose ICS-formoterol (budesonide-formoterol) for both maintenance and reliever therapy 1
• Critical warning: Never use LABA as monotherapy—it significantly increases mortality risk and must always be combined with ICS 1, 2, 6

Step 4: Moderate-to-Severe Persistent Asthma

• Medium-dose ICS-LABA combination 1, 2
• Add-on options:
  • Long-acting muscarinic antagonist (LAMA): tiotropium 1, 7
  • Leukotriene receptor antagonist (LTRA) added to ICS-LABA, particularly effective for allergic asthma during allergy season 5

Step 5-6: Severe Persistent Asthma

• High-dose ICS-LABA combination 1, 3
• Biologic therapies for severe asthma with type-2 inflammation 1, 8:
  • Omalizumab (anti-IgE): For allergic asthma with elevated IgE and sensitivity to perennial allergens in patients ≥12 years 1, 8
  • Mepolizumab, reslizumab, benralizumab (anti-IL5/IL5R): For eosinophilic asthma 1, 8
  • Dupilumab (anti-IL4R): For type-2 inflammation 1, 8
• Low-dose oral corticosteroids may be necessary but should be minimized due to significant systemic side effects 1

Complete Medication Classes

Controller Medications (Daily Use)

Inhaled Corticosteroids (ICS):

• Most effective single long-term control medication 1, 2, 4
• Reduce airway hyperresponsiveness, inhibit inflammatory cell migration, and block late-phase allergic reactions 1
• Dose-response curve is relatively flat beyond moderate doses—high doses provide minimal additional benefit with substantially increased side effects 5, 4
• Common side effects: Oral candidiasis (rinse mouth after use), dysphonia, throat irritation 1, 6
• Long-term concerns: Bone mineral density reduction, growth suppression in children, cataracts, glaucoma 6

Long-Acting Beta-Agonists (LABA):

• Salmeterol and formoterol provide 12-hour bronchodilation 6
• Must always be combined with ICS—monotherapy increases asthma-related deaths 1, 2, 6
• More effective when added to low-dose ICS than increasing ICS dose alone 2, 4

Leukotriene Modifiers:

• LTRAs: Montelukast, zafirlukast 1, 5
• 5-lipoxygenase inhibitor: Zileuton 1, 2
• Particularly effective for allergic asthma and exercise-induced bronchoconstriction 5
• Alternative to ICS for patients who cannot tolerate steroids 1, 3

Long-Acting Muscarinic Antagonists (LAMA):

• Tiotropium added to ICS-LABA for Step 4-5 treatment 1, 7
• Beneficial for patients with persistent symptoms despite ICS-LABA 7

Mast Cell Stabilizers:

• Cromolyn sodium and nedocromil 1
• Less effective than ICS; used as alternative for mild persistent asthma 1
• Can be used preventively before exercise or allergen exposure 1

Methylxanthines:

• Theophylline (sustained-release) 1, 2
• Narrow therapeutic window requiring monitoring 1
• Alternative add-on therapy when other options are not suitable 4

Biologic Therapies:

• Omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab 1, 8
• Reserved for severe asthma inadequately controlled on high-dose ICS-LABA 8
• Require phenotypic assessment and biomarker testing 1, 8

Reliever Medications (As-Needed Use)

Short-Acting Beta-Agonists (SABA):

• Albuterol (salbutamol), levalbuterol 1
• Primary treatment for acute symptom relief 1
• Critical monitoring: Use more than twice weekly indicates inadequate control and need for controller therapy intensification 5, 2, 3

Short-Acting Anticholinergics:

• Ipratropium bromide 1
• Added to SABA for severe acute exacerbations 1

ICS-Formoterol (As-Needed):

• Low-dose budesonide-formoterol or beclomethasone-formoterol used as both maintenance and reliever therapy (SMART strategy) 1, 7
• Reduces exacerbation risk compared to SABA alone 7

Acute Exacerbation Management

Immediate treatment for severe exacerbations 1:

• High-dose nebulized SABA (albuterol 5 mg or terbutaline 10 mg) 1
• Systemic corticosteroids: prednisolone 30-60 mg orally or hydrocortisone 200 mg IV 1, 3
• Oxygen to maintain saturation >90% 1

Life-threatening features (PEF <33% predicted, silent chest, altered consciousness) 1:

• Add nebulized ipratropium 0.5 mg to SABA 1
• IV aminophylline 250 mg over 20 minutes or IV salbutamol/terbutaline 250 mcg over 10 minutes 1
• Immediate hospital admission 1

Critical Monitoring Parameters

Indicators of inadequate control requiring treatment intensification 5, 2, 3:

• SABA use more than twice weekly 5, 2
• Nighttime awakenings more than twice monthly 3
• Asthma Control Test score <20 5
• Any limitation of normal activities 1
• Peak expiratory flow <80% of personal best 1

Common Pitfalls to Avoid

• Never delay ICS initiation in persistent asthma—early intervention improves outcomes 2
• Never use LABA without ICS—this combination error increases mortality 1, 2, 6
• Do not confuse intermittent with persistent asthma—patients using SABA more than twice weekly need controller therapy 2
• Verify inhaler technique before escalating therapy—poor technique is a common cause of apparent treatment failure 5
• Assess medication adherence—non-adherence often masquerades as treatment resistance 5
• Address comorbidities: GERD, rhinitis, sinusitis, obesity, and obstructive sleep apnea all worsen asthma control 1, 3

Special Considerations

Allergen immunotherapy (allergy shots):

• Effective for allergic asthma with documented sensitization 1, 3, 8
• Decreases symptoms and medication requirements 8
• Consider for patients with allergic rhinitis and controlled asthma 2, 3

Pregnancy and pediatrics:

• ICS remain the preferred controller medication 1
• Growth monitoring essential in children on long-term ICS 6

COPD overlap:

• ICS-LABA combinations approved for both asthma and COPD 6
• Increased pneumonia risk in COPD patients on ICS 6