Treatment of Asthma

Foundation Before Any Pharmacotherapy

• Trigger identification and avoidance (allergens, occupational exposures, NSAIDs, beta-blockers, respiratory infections)
• Comorbidities: rhinitis, GERD, obesity, obstructive sleep apnea - control of rhinitis is often required to improve asthma control
• Adherence and inhaler technique - poor technique or adherence accounts for uncontrolled asthma in up to 50% of referred patients
• Patient education including a written asthma action plan based on peak expiratory flow (PEF)

Drug Classes Used in Asthma

1. Inhaled Corticosteroids (ICS) - Cornerstone of Therapy

• Beclomethasone (~20% oral bioavailability)
• Fluticasone (~1% oral bioavailability - lower systemic exposure)
• Mometasone (<1% oral bioavailability)
• Ciclesonide (activated only on lung deposition - minimal systemic effects)

2. Short-Acting Beta-2 Agonists (SABAs) - Relievers

• Albuterol (salbutamol) is the standard rapid-relief bronchodilator
• Used as-needed for acute symptom relief
• GINA now recommends ICS/formoterol as the preferred reliever over SABA monotherapy at all steps, to ensure anti-inflammatory cover with every rescue dose (the "Anti-Inflammatory Reliever" or AIR concept)

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

• Formoterol (fast onset) and salmeterol (slower onset)
• Must never be used as monotherapy in asthma - always combined with ICS
• ICS/LABA combination inhalers: budesonide/formoterol, fluticasone/salmeterol, etc.
• Formoterol's rapid onset allows it to serve as both controller and reliever ("SMART" or "MART" therapy)

4. Leukotriene Receptor Antagonists (LTRAs)

• Montelukast, zafirlukast
• Step 2 alternatives to low-dose ICS, useful in those with concomitant allergic rhinitis or exercise-induced symptoms
• Important: Montelukast carries an FDA black-box warning for neuropsychiatric events (suicidal ideation), limiting its appeal

5. Long-Acting Muscarinic Antagonists (LAMAs)

• Tiotropium - add-on therapy at steps 4-5
• Adjunctive bronchodilation when ICS/LABA is insufficient

6. Theophylline

• Phosphodiesterase inhibitor with mild anti-inflammatory properties
• Narrow therapeutic index; no longer a first-line or recommended therapy
• Sometimes used in low doses as adjunctive treatment for moderate-severe asthma difficult to control with steroids alone
• Monitor for dose-related side effects: arrhythmias, seizures, anorexia

7. Macrolides (Adjunctive)

• Azithromycin 500 mg 3 times/week - shown to reduce exacerbations in both eosinophilic and non-eosinophilic asthma
• Considered add-on at step 5 in patients with poor response to standard therapy

GINA Stepwise Treatment (Adapted)

• ICS/formoterol as the reliever at all steps (including step 1) - replaces SABA monotherapy
• "Step up" if not controlled; "step down" once controlled for 3 months
• Before stepping up: verify diagnosis, technique, adherence, and triggers

Step 5: Biologic (Targeted) Therapies

• Elevated blood eosinophils (≥150-300/μL) → anti-IL-5 agents
• Elevated IgE + positive allergen sensitization → omalizumab
• Elevated FeNO + type 2 inflammation (even without eosinophilia) → dupilumab
• No clear type-2 biomarkers with recurrent exacerbations → tezepelumab

Acute Asthma Attack Management

• Inhaled SABA (albuterol) every hour; can increase ICS dose 4-5x
• Monitor PEFR or FEV1

• Nebulized SABA every 20 minutes
• IV corticosteroids if failing to respond within 1-2 hours
• Supplemental O2 to correct hypoxemia
• Nebulized ipratropium (anticholinergic) for additional bronchodilation
• Consider IV magnesium sulfate and leukotriene modifier
• If PEFR fails to reach >60% or severe tachypnea persists beyond 4-6 hours → hospital admission

• Continuous bronchodilator nebulization
• Noninvasive positive-pressure ventilation (NIPPV) to prevent intubation
• Helium-oxygen (heliox) to reduce work of breathing
• If intubated: permissive hypercapnia strategy - low RR and low tidal volumes to minimize peak airway pressures; use NMJ blockade if needed
• Normal or rising PCO2 in a distressed asthmatic = warning sign of impending respiratory failure

Exercise-Induced Bronchoconstriction

• Pre-treatment with SABA before exercise
• Warm-up exercises and cold-weather masks help
• If regular exercise is planned, step up maintenance therapy rather than relying on pre-treatment SABAs
• LABAs alone are discouraged; ICS/LABA is preferred for regular use

High-Risk Patients (Asthma Mortality Risk)

• Prior ICU admission or intubation for asthma
• Illicit drug use
• Depression
• Low socioeconomic status, poor adherence
• Dependence on oral corticosteroids

Recent Evidence (2024-2026)

• Triple therapy vs dual inhaler therapy (2025, Ann Allergy Asthma Immunol) - updated meta-analysis confirming benefit of triple ICS/LABA/LAMA over dual therapy in moderate-severe asthma [PMID: 40516649]
• Allergen immunotherapy in children with asthma (2025, BMC Pulm Med) - systematic review/meta-analysis supporting allergen-specific immunotherapy as adjunctive therapy in allergic pediatric asthma [PMID: 40604821]
• LABAs added to ICS in preschool children (2025, Paediatr Respir Rev) - evidence supporting ICS/LABA in older preschoolers with persistent symptoms [PMID: 39510955]

• Harrison's Principles of Internal Medicine, 22E (2025, McGraw Hill) - Chapter 298: Asthma
• Murray & Nadel's Textbook of Respiratory Medicine - Specific Pharmacologic Agents, Targeted Biologic Agents
• Textbook of Family Medicine, 9E - Chapter 19/20: Asthma
• Swanson's Family Medicine Review - GINA stepwise therapy