Bronchial Asthma

Definition

1. Reversible airway obstruction
2. Airway inflammation (involving multiple cell types)
3. Increased airway hyperresponsiveness to a variety of stimuli

Pathophysiology

• Bronchoconstriction - smooth muscle contraction
• Airway wall inflammation - mucosal edema from inflammatory cell infiltration
• Excessive mucus secretion - plugging the lumen

Inflammatory Cascade

• Allergens/triggers activate mast cells via IgE cross-linking -> release of histamine, leukotrienes, prostaglandins
• Eosinophils are recruited by IL-5 and contribute to epithelial damage
• T-lymphocytes (Th2 cells) drive the cytokine milieu (IL-4, IL-5, IL-13) sustaining eosinophilic inflammation
• Cysteinyl leukotrienes (LTC4, LTD4, LTE4) cause sustained bronchoconstriction, edema, and eosinophil migration
• Autopsies in fatal asthma show lungs with luminal plugs of inflammatory cells, desquamated epithelium, and mucus - ROSEN's Emergency Medicine, p. 928

Triggers / Precipitating Factors

Diagnosis

1. Suggestive symptoms with precipitating factors
2. Confirmatory testing (spirometry, bronchodilator reversibility, methacholine challenge)
3. Symptomatic improvement with appropriate asthma therapy

• Textbook of Family Medicine 9e, p. 463

Classification of Severity (NHLBI / GINA)

Pharmacological Treatment (GINA 2024 Stepwise Approach)

Step-Based Treatment (adults ≥12 years)

Drug Classes

1. Inhaled Corticosteroids (ICS) - Foundation of Controller Therapy

• Mechanism: Inhibit phospholipase A2 -> reduce arachidonic acid release -> decrease leukotriene synthesis; decrease eosinophils, macrophages, T-lymphocytes; reverse mucosal edema; reduce airway hyperresponsiveness
• Examples: Budesonide, fluticasone, beclomethasone, mometasone
• Adverse effects: Oropharyngeal candidiasis, hoarseness; rinse mouth after use
• Oral/IV corticosteroids (methylprednisolone, prednisone) reserved for severe exacerbations - no taper needed for short courses

2. Short-Acting β2 Agonists (SABA)

• Mechanism: Direct relaxation of airway smooth muscle; rapid onset 5-15 min; duration 3-6 h
• Examples: Albuterol (salbutamol), levalbuterol
• Role: Rescue/reliever therapy; prevention of exercise-induced bronchospasm
• Adverse effects: Tachycardia, tremor, hypokalemia, hypomagnesemia, hyperglycemia
• SABA monotherapy for persistent asthma is not recommended

3. Long-Acting β2 Agonists (LABA)

• Examples: Salmeterol (onset slow), formoterol (rapid onset)
• Duration ≥12 hours; formoterol can serve as both controller and reliever
• LABA monotherapy is contraindicated in asthma - must always be combined with ICS
• LABA monotherapy carries risk of severe/fatal exacerbations

4. Leukotriene Receptor Antagonists (LTRA)

• Examples: Montelukast, zafirlukast - block CysLT1 receptors
• Zileuton - inhibits 5-lipoxygenase (upstream in pathway)
• Role: Add-on controller therapy; particularly useful in aspirin-sensitive asthma and allergic rhinitis coexistence

5. Anticholinergics

• Ipratropium (short-acting): Blocks vagally mediated bronchoconstriction; slower onset than SABA; useful as add-on in acute exacerbations in ED; not routine monotherapy
• Tiotropium (long-acting): Add-on therapy for severe asthma with history of exacerbations

6. Theophylline

• Methylxanthine bronchodilator; narrow therapeutic index; largely replaced by β2 agonists and ICS
• Risk of seizures and fatal arrhythmias with overdose; requires serum level monitoring
• CYP1A2 substrate - many drug interactions

7. Monoclonal Antibodies (Biologics) - for Severe Persistent Asthma

Acute Exacerbations / Status Asthmaticus

Features of Severe Exacerbation

• PEFR or FEV1 <40% predicted
• PaCO2 rising (initially hypocapnia, then normocapnia/hypercapnia = sign of fatigue)
• Accessory muscle use, inability to speak in full sentences, cyanosis
• Pulsus paradoxus >10 mmHg

ED Management (stepwise)

1. Initial assessment: Severity classification by PEFR, SpO2, respiratory effort
2. Mild: SABA q20 min x 3 in first hour (albuterol 0.15 mg/kg nebulized, max 5 mg)
3. Moderate-Severe:
   • Inhaled SABA (continuous or frequent) + ipratropium bromide
   • Systemic corticosteroids early (oral prednisolone or IV methylprednisolone)
   • Supplemental O2 to maintain SpO2 ≥92-94%
4. Refractory / Near-fatal:
   • IV magnesium sulfate (2g IV over 20 min - evidence-based benefit in severe ED asthma)
   • Heliox (helium-oxygen mixture) to reduce airway resistance
   • Consider IV epinephrine or terbutaline
   • Non-invasive or invasive ventilation (last resort; ventilating asthma carries high risk due to dynamic hyperinflation)

Asthma in Special Populations

Pregnancy

• ~4% of pregnant women have asthma; 1/3 will have exacerbations during pregnancy
• Moderate-severe asthma increases risk: preterm labor, LBW, perinatal death, preeclampsia
• FEV1 and PEFR are unchanged in normal pregnancy (unlike tidal volume, which increases)
• Key: undertreated asthma poses more risk to mother and fetus than asthma medications
• ICS are safe in pregnancy - Textbook of Family Medicine 9e, p. 489

Non-pharmacological / Adjunct Management

• Identify and avoid triggers (allergens, occupational agents, NSAIDs if aspirin-sensitive)
• Written asthma action plan for patients
• Control comorbid allergic rhinitis (upper-lower airway connection)
• Allergen immunotherapy for select patients with clear allergen sensitization
• Patient and family education on inhaler technique, spacer use, trigger avoidance
• Bronchial thermoplasty - bronchoscopic procedure for severe refractory asthma; reduces smooth muscle mass in airways (Murray & Nadel's Textbook of Respiratory Medicine)

Monitoring / Impairment Rating

• A. Post-bronchodilator FEV1 (0-4 points)
• B. Reversibility or degree of airway hyperresponsiveness (PC20) (0-3 points)
• C. Minimum medication requirement (0-4 points)
• Total score maps to Impairment Classes 0-V

Recent Evidence Update (2025)

• Lippincott Illustrated Reviews: Pharmacology (ICS, beta-agonists, biologics, drug mechanisms)
• Textbook of Family Medicine 9e (definition, diagnosis, classification, management steps)
• ROSEN's Emergency Medicine (acute exacerbation management, anatomy, epidemiology)
• Murray & Nadel's Textbook of Respiratory Medicine (impairment rating, thermoplasty)
• Fishman's Pulmonary Diseases and Disorders (allergic bronchial asthma, ABPA)