Asthma

Asthma is a chronic inflammatory disorder of the airways characterized by variable and recurring symptoms, airflow obstruction, bronchial hyperresponsiveness, and underlying inflammation. It affects both children and adults, with varying severity, ranging from mild intermittent symptoms to life-threatening exacerbations. The condition significantly impacts quality of life and can be controlled with appropriate management strategies.

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Pathophysiology

Asthma involves a complex interplay of genetic, immunologic, and environmental factors. The primary mechanisms include:

• Airway inflammation: Involves eosinophils, mast cells, T-helper type 2 lymphocytes, neutrophils (in severe asthma), and release of inflammatory mediators such as histamine, leukotrienes, and cytokines.

• Airway hyperresponsiveness: Bronchial smooth muscle contracts excessively in response to triggers (e.g., allergens, cold air, exercise, pollutants).

• Airway remodeling: Chronic inflammation can lead to structural changes, such as subepithelial fibrosis, smooth muscle hypertrophy, and mucus gland hyperplasia, contributing to persistent airflow limitation.

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Causes and Risk Factors

• Genetic predisposition: Family history of asthma, atopy, or allergic diseases.

• Environmental factors: Allergens (dust mites, pollen, animal dander, mold), occupational exposures, smoking, and air pollution.

• Infections: Viral respiratory infections in early childhood can contribute to airway sensitivity.

• Lifestyle and diet: Obesity and low vitamin D levels are associated with increased risk.

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Clinical Features

Asthma is typically characterized by episodic symptoms that vary in frequency and severity.

• Common symptoms:

  • Wheezing (whistling sound on exhalation)

  • Shortness of breath

  • Cough (often worse at night or early morning)

  • Chest tightness

• Triggers: Exercise, allergens, smoke, weather changes, respiratory infections, strong emotions, and certain medications (e.g., NSAIDs, β-blockers).

• Symptom patterns:

  • Worse at night or early morning

  • Episodic and reversible with treatment

  • Associated with identifiable triggers

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Diagnosis

Diagnosis is based on a combination of clinical history, physical examination, and objective testing:

• Spirometry: Demonstrates variable airflow limitation, reversible with bronchodilator (≥12% and ≥200 mL increase in FEV1 after inhaled salbutamol).

• Peak expiratory flow (PEF): Diurnal variability supports diagnosis.

• Bronchoprovocation testing: For patients with normal spirometry but suggestive symptoms.

• Allergy testing: Identifies atopic triggers.

• Differential diagnoses: COPD, vocal cord dysfunction, heart failure, GERD, and anxiety disorders.

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Classification (Severity and Control)

Asthma can be classified based on symptom frequency, night-time awakenings, need for reliever medication, and lung function:

1. Intermittent: Symptoms <2 days/week, normal FEV1 between episodes.

2. Mild persistent: Symptoms >2 days/week but not daily, minor activity limitation.

3. Moderate persistent: Daily symptoms, frequent exacerbations, FEV1 60–80% predicted.

4. Severe persistent: Symptoms throughout the day, frequent night symptoms, FEV1 <60%.

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Management

Asthma management focuses on controlling symptoms, preventing exacerbations, maintaining normal activity levels, and minimizing medication side effects. Treatment follows a stepwise approach, adjusting therapy based on control.

General Measures

• Education: Self-monitoring, inhaler technique, adherence to treatment.

• Trigger avoidance: Allergen avoidance, smoking cessation, occupational modifications.

• Vaccinations: Annual influenza and pneumococcal vaccines.

Pharmacological Treatment

1. Reliever (Rescue) Medications

   • Short-acting β2-agonists (SABA):

     • Salbutamol (albuterol): 100–200 mcg inhaled as needed (maximum 200 mcg every 4–6 hours).

     • Terbutaline: 0.25–0.5 mg inhaled as needed.

   • Used for acute symptom relief.

2. Controller (Preventive) Medications

   • Inhaled corticosteroids (ICS) – cornerstone of therapy:

     • Beclometasone dipropionate: 200–400 mcg twice daily (mild to moderate asthma).

     • Budesonide: 200–400 mcg twice daily.

     • Fluticasone propionate: 100–250 mcg twice daily.

   • Reduce airway inflammation and exacerbations.

   • Long-acting β2-agonists (LABA) – always used in combination with ICS:

     • Formoterol: 12 mcg twice daily.

     • Salmeterol: 50 mcg twice daily.

   • Leukotriene receptor antagonists (LTRA):

     • Montelukast: 10 mg orally once daily (adults); 4–5 mg for children.

     • Useful in exercise-induced asthma or aspirin-sensitive asthma.

   • Theophylline (methylxanthine):

     • Extended-release tablets, dose adjusted by serum levels (5–15 mcg/mL therapeutic range).

     • Less preferred due to side effects (nausea, arrhythmia, seizures).

   • Anti-IgE therapy (biologics for severe allergic asthma):

     • Omalizumab: Subcutaneous injection every 2–4 weeks, dose based on IgE levels and body weight.

   • Anti-IL-5 therapy (for severe eosinophilic asthma):

     • Mepolizumab: 100 mg SC every 4 weeks.

     • Benralizumab: 30 mg SC every 4 weeks for 3 doses, then every 8 weeks.

     • Reslizumab: 3 mg/kg IV every 4 weeks.

   • Anti-IL-4/IL-13 therapy:

     • Dupilumab: Initial 400–600 mg SC, followed by 200–300 mg every 2 weeks.

3. Oral Corticosteroids (for acute exacerbations or severe asthma)

   • Prednisolone: 30–50 mg orally once daily for 5–7 days (adults).

   • Methylprednisolone: IV in severe attacks if oral not feasible.

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Acute Severe Asthma (Status Asthmaticus)

This is a life-threatening emergency requiring immediate intervention:

• High-dose oxygen to maintain SpO2 >94%.

• Frequent or continuous nebulized SABA (salbutamol 2.5–5 mg every 20 minutes for first hour, then 2.5–10 mg every 1–4 hours).

• Ipratropium bromide (anticholinergic): 0.5 mg nebulized every 20 minutes for first 3 doses, then every 4–6 hours.

• Systemic corticosteroids (prednisolone or IV methylprednisolone).

• Consider IV magnesium sulfate (2 g over 20 minutes) if poor response.

• Hospital admission if severe or not improving.

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Complications

• Recurrent hospital admissions and life-threatening exacerbations.

• Chronic airflow limitation (overlap with COPD).

• Side effects of long-term corticosteroid use (osteoporosis, adrenal suppression, growth retardation in children, cataracts).

• Reduced quality of life and increased healthcare utilization.

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Prognosis

With appropriate management, most patients achieve good control, minimizing exacerbations and maintaining normal daily activity. Severe asthma may require advanced biologic therapies. Poorly controlled asthma increases the risk of mortality.