---

Bronchial Asthma - Long Answer (10 Marks)

---

Definition

1. Reversible airway obstruction (partially or fully reversible, spontaneously or with treatment)
2. Airway inflammation (involving multiple cells - mast cells, eosinophils, T-lymphocytes)
3. Airway hyperresponsiveness (AHR) - increased airway responsiveness to a variety of stimuli

---

Epidemiology

• Affects >300 million people worldwide; most common chronic disease of childhood
• Causes >15 million disability-adjusted life-years (DALYs) annually
• Prevalence is rising globally; in the United States, ~20 million adults and 6.1 million children are affected
• Higher rates in low-income, uninsured, and minority populations
• Hospitalization rates are 3.3x higher in Black patients vs. White patients (disparity condition)

---

Etiology and Risk Factors

• Most common type; IgE-mediated hypersensitivity
• Triggers: pollens, house dust mites, cockroach excreta, animal dander, mold spores
• Usually begins in childhood; family history of atopy common

• Triggered by non-immunologic stimuli
• Infections (viral URIs - commonest trigger of acute exacerbations)
• Exercise-induced bronchospasm (EIB)
• Cold air, fog, weather changes
• Drugs: NSAIDs, aspirin (Samter's triad = asthma + nasal polyposis + aspirin sensitivity), beta-blockers, ACE inhibitors
• Occupational exposures: isocyanates, flour dust, latex
• GERD, emotional stress

• Household smoke exposure
• Family history of asthma or atopy

---

Pathogenesis

Phase 1 - Sensitization

Phase 2 - Early Phase Reaction (0-60 min)

• Histamine - bronchospasm, mucosal edema
• Leukotrienes (LTC4, LTD4, LTE4) - potent bronchospasm and mucus secretion
• Prostaglandin D2 - bronchoconstriction
• Platelet-activating factor (PAF) - airway inflammation

Phase 3 - Late Phase Reaction (4-8 hours)

• Eosinophil degranulation releases major basic protein (MBP) and eosinophil cationic protein (ECP) -> epithelial damage
• Mucus hypersecretion, mucosal edema, inflammatory infiltrate
• Mediators released sustain AHR

Airway Remodeling (Chronic Disease)

• Sub-epithelial fibrosis (collagen deposition beneath basement membrane)
• Smooth muscle hypertrophy and hyperplasia
• Goblet cell metaplasia and mucus gland hypertrophy
• Angiogenesis and neural remodeling
• Results in fixed (irreversible) airflow limitation

---

Pathophysiology

• Airflow obstruction predominantly in expiration -> air trapping -> hyperinflation
• Increased airway resistance -> increased work of breathing
• V/Q mismatch -> hypoxemia initially (PaO2 falls)
• In mild-moderate attack: hypocapnia (compensatory hyperventilation)
• In severe/near-fatal attack: rising PaCO2 (normocapnia then hypercapnia) = respiratory failure - ominous sign

---

Clinical Features

• Paroxysmal wheezing (expiratory)
• Breathlessness (dyspnea)
• Chest tightness
• Cough (often nocturnal, productive of thick mucus)
• Symptoms typically worse at night/early morning and with triggers

• Tachypnea, tachycardia
• Use of accessory muscles (sternocleidomastoid, scalene)
• Hyperinflated chest, reduced air entry
• Prolonged expiration; diffuse bilateral expiratory wheeze
• Pulsus paradoxus (>10 mmHg fall in systolic BP on inspiration) in severe attack

• Silent chest (no wheeze despite severe obstruction)
• Cyanosis
• Altered consciousness/exhaustion
• Bradycardia, hypotension
• Inability to speak in full sentences

---

Classification by Severity (NAEPP / GINA Guidelines)

---

Investigations

• FEV1/FVC ratio <0.7 confirms obstruction
• FEV1 <80% predicted
• Reversibility test: ≥12% AND ≥200 mL increase in FEV1 after bronchodilator (salbutamol 400 mcg) = diagnostic of asthma

• Portable, inexpensive monitoring tool
• Diurnal variation >20% is diagnostic
• Used for monitoring and action plans

• Methacholine or histamine challenge
• PC20 (concentration causing 20% fall in FEV1) <8 mg/mL = AHR
• Used when spirometry is normal but asthma suspected

• Usually normal between attacks
• During attack: hyperinflation (flattened diaphragm, increased AP diameter, increased intercostal spaces)
• Excludes: pneumothorax, consolidation, foreign body

• CBC: eosinophilia (>400/mm3) suggests atopic disease
• Total serum IgE - elevated in atopic asthma
• Arterial Blood Gas (ABG) in acute severe attack:
  • Mild/moderate: hypoxemia + hypocapnia (respiratory alkalosis)
  • Severe/near-fatal: normocapnia or hypercapnia + acidosis

• Identify specific allergens causing IgE-mediated sensitization

• 25 ppb indicates eosinophilic airway inflammation

• Guides ICS therapy

---

Treatment

Step-Up Pharmacotherapy (NAEPP Stepwise Approach)

• SABA (Short-Acting Beta-2 Agonist) PRN only: Salbutamol (albuterol) 100-200 mcg inhaled

• Daily Inhaled Corticosteroid (ICS) (first-line controller): Beclomethasone, Budesonide, Fluticasone (low dose)
• Alternative: Leukotriene Receptor Antagonist (LTRA) - Montelukast

• Low-dose ICS + LABA (Long-Acting Beta-2 Agonist): Salmeterol or Formoterol
• Or medium-dose ICS alone

• Medium-to-high dose ICS + LABA
• Add LTRA or theophylline if needed

• High-dose ICS + LABA + oral corticosteroids
• Consider anti-IgE therapy: Omalizumab (monoclonal antibody) for severe allergic asthma
• Consider bronchial thermoplasty

Drug Classes:

---

Management of Acute Severe Asthma (Status Asthmaticus)

1. Oxygen: High-flow via face mask to maintain SpO2 >94%
2. Nebulized SABA: Salbutamol 5 mg via oxygen-driven nebulizer every 20 min x 3 (or continuous)
3. Nebulized Ipratropium: 0.5 mg with salbutamol (additive bronchodilation)
4. Systemic corticosteroids: Oral prednisolone 40-50 mg OR IV hydrocortisone 200 mg
5. IV Magnesium sulfate: 2 g IV over 20 min (bronchodilator; for severe attacks not responding to initial therapy)
6. IV Aminophylline: Loading dose 5 mg/kg (if not on theophylline) then infusion
7. Heliox (helium-oxygen mixture): Reduces airway resistance in very severe cases
8. Mechanical ventilation (ICU): For respiratory failure (rising CO2, exhaustion, altered consciousness)

---

Non-Pharmacological Management

• Trigger avoidance: House dust mite control (mattress covers), HEPA filters, avoiding known allergens
• Smoking cessation: Most important environmental intervention
• Patient education: Inhaler technique, action plans, PEFR self-monitoring
• Allergen immunotherapy (AIT): Subcutaneous or sublingual; for allergic asthma unresponsive to standard therapy
• Breathing exercises: Buteyko technique, yoga
• Weight loss: Obesity worsens asthma
• Control of GERD and rhinitis: Both worsen asthma control

---

Differential Diagnosis

---

Complications

• Acute: Status asthmaticus, pneumothorax, respiratory failure, death
• Chronic: Fixed airflow limitation (remodeling), cor pulmonale, growth retardation (children), side effects of long-term corticosteroids (osteoporosis, cataracts, adrenal suppression)
• Aspergilloma/ABPA: Allergic bronchopulmonary aspergillosis - complication of severe asthma

---

Prognosis

• Most patients achieve good control with appropriate therapy
• About 50% of children with mild asthma go into remission by adulthood
• Severe persistent asthma with fixed obstruction carries significant morbidity
• Risk factors for death: previous near-fatal attack, poor adherence, over-reliance on SABAs, underuse of ICS, low socioeconomic status, psychiatric comorbidity

---

Summary Table

---