Pathophysiology of Bronchial Asthma
Bronchial asthma is a chronic inflammatory disease of the airways characterized by airway hyperresponsiveness, intermittent airflow obstruction, and bronchial inflammation. The pathophysiological mechanisms involve:
- Airway Inflammation: Chronic inflammation is central to asthma and involves various immune cells such as mast cells, eosinophils, T lymphocytes (especially Th2 cells), macrophages, neutrophils, and epithelial cells. These cells release cytokines like interleukin (IL)-4, IL-5, and IL-13 that promote allergic inflammation. This leads to:
- Mucosal edema.
- Increased mucus production.
- Epithelial damage.
- Airway Hyperresponsiveness: The inflamed airways become overly sensitive to various stimuli (triggers). This exaggerated response results in bronchoconstriction due to smooth muscle contraction.
- Airflow Obstruction: Airflow limitation occurs due to:
- Acute bronchoconstriction caused by smooth muscle contraction.
- Airway edema from increased vascular permeability.
- Mucus plugging from excessive secretion.
- Structural changes (airway remodeling) such as smooth muscle hypertrophy and subepithelial fibrosis in chronic cases.
- Ventilation-Perfusion Mismatch: Due to uneven airflow distribution, hypoxemia can occur during an asthma attack. Severe cases may lead to hypercapnia and respiratory acidosis if ventilation fails.
The severity of these processes varies among individuals and determines the clinical presentation.
Etiology of Bronchial Asthma
Asthma has a multifactorial etiology involving genetic predisposition and environmental factors:
- Genetic Factors:
- Family history of asthma or atopy increases susceptibility.
- Polymorphisms in genes related to immune responses (e.g., IL-4 receptor gene) are implicated.
- Environmental Factors:
- Allergens: House dust mites, animal dander, cockroach allergens, molds, and pollens.
- Viral infections: Respiratory syncytial virus (RSV) or rhinovirus can trigger asthma exacerbations.
- Occupational exposures: Chemicals like diisocyanates or irritants in workplaces can induce occupational asthma.
- Other Contributing Factors:
- Tobacco smoke exposure (active or passive).
- Air pollution (e.g., particulate matter or ozone).
- Obesity increases systemic inflammation that worsens asthma symptoms.
- Gastroesophageal reflux disease (GERD) can exacerbate symptoms through vagal reflexes.
Clinical Presentations
Asthma presents with episodic symptoms that vary in frequency and severity:
- Common Symptoms:
- Wheezing: A high-pitched whistling sound during expiration due to narrowed airways.
- Coughing: Often worse at night or early morning; may be dry or productive with mucus.
- Shortness of breath (dyspnea): Difficulty breathing during exertion or rest.
- Chest tightness/pain.
- Triggers for Asthma Attacks: Asthma attacks are often provoked by specific triggers such as:
- Allergens (dust mites, pollen).
- Respiratory infections (viral colds).
- Physical activity/exercise-induced bronchoconstriction.
- Cold air exposure.
- Irritants like smoke or strong odors.
- Emotional stress or anxiety.
Aims of Therapy for Bronchial Asthma
The primary goals of asthma therapy are:
- Achieve and maintain control over symptoms to improve quality of life.
- Prevent acute exacerbations (“asthma attacks”).
- Minimize the need for rescue medications like short-acting beta agonists (SABAs).
- Preserve normal lung function and prevent long-term airway remodeling.
- Reduce hospitalizations due to severe exacerbations.
Drugs Used in the Treatment of Bronchial Asthma
1. Beta Agonists
- Examples: Albuterol (short-acting), Salmeterol/Formoterol (long-acting).
- Mechanism of Action: Stimulate β2-adrenergic receptors on airway smooth muscles → relaxation → bronchodilation.
- Administration: Inhalation via metered-dose inhalers or nebulizers; oral forms available but less common due to systemic side effects.
- Pharmacokinetics: Short-acting agents act within minutes; duration ~4–6 hours; long-acting agents last ~12 hours or more.
- Side Effects: Tremors, tachycardia, palpitations.
2. Corticosteroids
- Examples: Budesonide/Fluticasone (inhaled), Prednisone/Prednisolone (oral/systemic).
- Mechanism of Action: Suppress airway inflammation by inhibiting cytokine production; reduce airway hyperresponsiveness over time.
- Administration: Inhalation for maintenance therapy; oral/systemic for severe exacerbations only short-term use recommended due to side effects.
- Pharmacokinetics: Inhaled corticosteroids have localized action with minimal systemic absorption; systemic corticosteroids have widespread effects but higher risk of adverse effects with prolonged use.
- Side Effects: Oral thrush with inhaled forms; weight gain, osteoporosis with systemic use.
3. Anticholinergic Agents
- Examples: Ipratropium bromide (short-acting), Tiotropium bromide (long-acting).
- Mechanism of Action: Block muscarinic receptors → inhibit parasympathetic-mediated bronchoconstriction → bronchodilation.
- Administration: Inhalation via nebulizers/inhalers.
- Side Effects: Dry mouth, urinary retention.
4. Theophylline
- Mechanism of Action: Non-selective phosphodiesterase inhibitor → increases cyclic AMP levels → bronchodilation + anti-inflammatory effects on airways.
- Administration: Oral tablets/capsules; intravenous formulations for acute settings.
- Pharmacokinetics & Side Effects: Narrow therapeutic index requiring blood level monitoring; side effects include nausea/vomiting, arrhythmias.
5. Mast Cell Stabilizers
- Examples: Cromolyn sodium/Nedocromil sodium.
- Mechanism of Action: Prevent degranulation of mast cells → reduce histamine release → prevent allergic reactions leading to bronchospasm.
- Administration: Inhalation via nebulizer/inhaler before exposure to triggers/exercise-induced asthma prevention only.
6. Anti-Leukotrienes
- Examples: Montelukast/Zafirlukast/Zileuton, Montelukast blocks leukotriene receptors while Zileuton inhibits leukotriene synthesis.
