Bronchial Asthma: Pathophysiology, Diagnosis and GINA

Year 4 · Internal Medicine · Respiratory — Based on the Imed class presentation by Naomi Chebet, expanded with Davidson's Medicine (24th ed.) and GINA guidance. Definition Asthma is a heterogeneous disease, usually characterised by chronic airway inflammation . It is defined by a history of respiratory symptoms — wheeze, shortness of breath, chest tightness and cough — that vary over time and in intensity , together with variable expiratory airflow limitation . Three core features: Airway inflammation (eosinophils, mast cells, Th2 lymphocytes) Bronchial hyper-responsiveness to triggers Reversible airflow obstruction Causes and Risk Factors Trigger Mechanism --- --- Allergens (house dust mite, pollen, cockroach, pets, moulds) IgE-mediated type I hypersensitivity Aspirin / NSAIDs COX blocked → arachidonic acid shunted to lipoxygenase → ↑ leukotrienes → bronchoconstriction and inflammation Beta-blockers (e.g. propranolol) Block β2 receptors on bronchial smooth muscle → bronchospasm Viral URTIs (especially rhinovirus) Epithelial inflammation → ↑ hyper-responsiveness → bronchoconstriction, mucus, narrowing Cold air and exercise Airway cooling and drying → mast-cell mediator release Smoke, vaping, pollution, occupational agents Irritant / sensitiser effect Emotional stress Vagal and inflammatory pathways Host factors: atopy, family history (atopic triad — asthma, eczema, allergic rhinitis), obesity, prematurity, maternal smoking. Clinical Phenotypes Allergic — childhood onset, atopy, eosinophilic, good ICS response Non-allergic — neutrophilic, poorer ICS response Adult (late) onset — often women, may need higher ICS doses Persistent airflow limitation — long-standing disease with remodelling Asthma with obesity — prominent symptoms, little eosinophilia Aspirin-exacerbated respiratory disease (Samter's triad) — asthma + nasal polyps + aspirin sensitivity Immunological Mechanism on Allergen Exposure 1. Sensitisation: dendritic cells present allergen → Th2 differentiation. 2. Th2 cytokines: IL-4 → IgE class switching; IL-5 → eosinophils; IL-13 → goblet-cell hyperplasia, mucus, hyper-responsiveness. 3. Re-exposure: allergen cross-links IgE on mast cells. Early phase (minutes): histamine, leukotrienes, PGD2 → bronchospasm Late phase (4–8 h): eosinophil influx → sustained inflammation 4. Remodelling: sub-epithelial fibrosis, smooth-muscle hypertrophy, mucous-gland hyperplasia. Pathophysiology 1. Bronchial wall oedema and inflammation → airway narrowing → dyspnoea, hyper-resonance (air trapping), wheeze (difficulty getting air out). 2. Mucus hypersecretion — activated goblet cells secrete mucus that narrows the airway further; it irritates receptors and triggers cough. 3. Bronchoconstriction and bronchospasm — O₂ in and CO₂ out are impaired; expiration is compromised more → air trapping → alveoli balloon out → hyperinflated lungs . Complications 1. Respiratory failure Especially in status asthmaticus . Air trapping → hypoventilation → hypoxia and hypercapnia (respiratory acidosis). The patient compensates with ↑ respiratory rate and accessory-muscle use. Exam pearl: a normal or rising PaCO₂ in an acute attack is ominous — the patient is tiring. 2. Pneumothorax Hyperinflation raises the risk of apical rupture → absent breath sounds on one side, tracheal deviation, sudden hypoxaemia. 3. Pulsus paradoxus Fall of 10 mmHg in systolic BP on inspiration. Exaggerated negative intrathoracic pressure ↑ right-heart venous return → septum shifts into the LV → ↓ LV filling and stroke volume. Others Pneumomediastinum, subcutaneous emphysema, mucus plugging with lobar collapse, ABPA, steroid side-effects, death. Clinical Presentation History Wheeze, cough, chest tightness, dyspnoea, exhaustion More likely asthma if symptoms: worse at night/early morning; vary over time and intensity; triggered by viral infection, exercise, allergens, weather change, laughter or irritants Family history — atopic triad Drug history — aspirin, NSAIDs, beta-blockers Examination Signs of respiratory distress ↑ anteroposterior diameter (hyperinflation) Hyper-resonant percussion Polyphonic expiratory wheeze Silent chest — so little air entry no wheeze is heard (life-threatening) Nose — allergic rhinitis, nasal polyps Diagnostic Approach Test Finding --- --- Chest X-ray Normal or hyperinflation; excludes pneumothorax and pneumonia ECG Usually normal; sinus tachycardia in attacks ABG Low pH, ↑ pCO₂ in severe attacks Spirometry ↓ FEV₁, mildly ↓ FVC → FEV₁/FVC < 0.70 Reversibility FEV₁ ↑ 12% and 200 mL after salbutamol Methacholine challenge FEV₁ falls ≥20% Peak expiratory flow Diurnal variability 10%; serial readings FeNO Raised ( 40–50 ppb) supports eosinophilic inflammation Eosinophils, IgE, skin-prick tests Phenotyping Grading an Acute Attack Severity Features --- --- Moderate PEF 50–75% best/predicted Acute severe PEF 33–50%, RR ≥25, HR ≥110, cannot complete sentences Life-threatening PEF <33%, SpO₂ <92%, normal PaCO₂ , silent chest, cyanosis, exhaustion, a