Asthma: A Comprehensive Overview

Definition

1. Intermittent, reversible airway obstruction
2. Chronic bronchial inflammation (predominantly eosinophilic)
3. Bronchial smooth muscle hypertrophy and hyperreactivity

Pathogenesis

Types

Atopic (Classic) Mechanism

• Th2 cell activation releasing IL-4, IL-5, and IL-13
• IL-4 and IL-13 stimulate B cells to produce IgE
• IL-5 recruits and activates eosinophils
• IL-13 increases mucus production
• IgE binds to Fc receptors on submucosal mast cells, sensitizing them to allergens
• Cross-linking of IgE by allergen triggers mast cell degranulation, releasing histamine, leukotrienes, prostaglandins, and cytokines
• This produces an early-phase reaction (acute bronchoconstriction within minutes) followed by a late-phase reaction (inflammatory cell influx over hours)

Inflammatory Cell Patterns

• Eosinophilic - most common, responds best to corticosteroids
• Neutrophilic - associated with infections, severe/refractory disease
• Mixed inflammatory
• Pauci-granulocytic - least inflammatory on biopsy

Structural Changes (Airway Remodeling)

• Subepithelial fibrosis
• Smooth muscle hypertrophy/hyperplasia
• Goblet cell metaplasia with increased mucus secretion
• Angiogenesis; decreased lymphatic vessel density in fatal asthma

Genetics

Clinical Features

• Recurrent wheezing
• Dyspnea / breathlessness
• Chest tightness
• Cough (often worse at night or early morning)

• Allergens (dust mites, pollen, pet dander)
• Viral upper respiratory infections (most common trigger in children < 5 years)
• Exercise
• Cold air
• Smoke, fumes, irritants
• Aspirin/NSAIDs
• GERD
• Stress/emotional stimuli
• Occupational exposures

Diagnosis

1. Suggestive symptoms with precipitating factors
2. Objective confirmation via pulmonary function testing
3. Symptomatic improvement with appropriate asthma therapy

Spirometry

• FEV1/FVC ratio reduced (obstructive pattern)
• Bronchodilator reversibility: ≥12% and ≥200 mL improvement in FEV1 after SABA confirms reversibility
• Methacholine/bronchoprovocation challenge: PC20 used to grade airway hyperresponsiveness when baseline spirometry is normal

Classification by Severity (Adults ≥12 years)

Differential Diagnosis

Management

Step-up Pharmacotherapy (NAEPP/GINA Framework)

• Short-acting beta-2 agonist (SABA) as needed (e.g., albuterol/salbutamol)

• Low-dose inhaled corticosteroid (ICS) (e.g., beclomethasone, fluticasone, budesonide)
• Alternative: leukotriene receptor antagonist (LTRA) or cromolyn

• Low-dose ICS + long-acting beta-2 agonist (LABA) (e.g., salmeterol, formoterol)
• OR medium-dose ICS

• Medium-dose ICS + LABA

• High-dose ICS + LABA
• Consider add-on tiotropium or LTRA

• High-dose ICS + LABA + oral corticosteroid
• Consider biologic therapy (see below)

Biologics (Severe/Refractory Asthma)

• Omalizumab - anti-IgE (for allergic, high-IgE asthma)
• Mepolizumab, Reslizumab, Benralizumab - anti-IL-5/IL-5R (eosinophilic asthma)
• Dupilumab - anti-IL-4Rα (blocks IL-4 and IL-13 signaling)

Key Non-pharmacologic Measures

• Allergen/trigger avoidance - essential first step
• Rhinitis control - often required for asthma control (united airway concept)
• Patient education and written asthma action plan
• Smoking cessation

Device Considerations

• Metered-dose inhalers (MDI) with spacer are as effective as or better than nebulizers in children (Level of Evidence: A). - Textbook of Family Medicine 9e

Asthma Exacerbations

1. SABA (albuterol) - repeated doses via nebulizer or MDI + spacer
2. Systemic corticosteroids (oral prednisone or IV methylprednisolone) - reduce airway inflammation and duration of exacerbation
3. Ipratropium bromide (anticholinergic) - additive bronchodilation in severe exacerbations
4. Supplemental oxygen to maintain SpO2 ≥92%
5. Magnesium sulfate IV - for severe exacerbations not responding to initial therapy
6. Heliox - in selected cases
7. Intubation/mechanical ventilation - for respiratory failure (avoid if possible due to risks of barotrauma)

Special Populations

Asthma in Pregnancy

• Affects approximately 4% of pregnant women
• One third experience exacerbations during pregnancy
• Severe asthma is associated with preterm labor, low birth weight, perinatal death, and preeclampsia
• FEV1 is the best parameter for monitoring
• ICS are safe in pregnancy - undertreated asthma poses greater fetal risk than medications
• Progesterone-driven increase in tidal volume causes mild respiratory alkalosis (normal PaCO2 in pregnancy = 27-32 mmHg) - a "normal" PaCO2 of 40 mmHg in a pregnant asthmatic may indicate impending respiratory failure

Asthma in Children < 5 years

• Viral URI is the most common trigger
• Long-term control therapy is indicated when:
  • Symptoms require treatment >2×/week consistently
  • Severe exacerbations <6 weeks apart

  • 4 wheeze episodes/year lasting >1 day with sleep disturbance

• Positive Asthma Predictive Index: ≥3 wheezing episodes in first 3 years + 1 major risk factor (parental asthma, atopic dermatitis) OR 2 minor risk factors (wheezing apart from colds, eosinophilia >4%, food sensitization)

ATS Impairment Rating (Occupational/Disability)

• Post-bronchodilator FEV1 (scored 0-4)
• Reversibility of FEV1 or PC20 (scored 0-3)
• Minimum medication need (scored 0-4)

Key Points Summary