Bronchial Asthma
Medicine · Respiratory · lean revision notes
Bronchial Asthma
Bronchial asthma is a chronic inflammatory disorder of the airways characterised by variable, reversible airflow obstruction, bronchial hyper-responsiveness, and airway remodelling. It is one of the most consistently tested topics in NEET PG Medicine — examiners love GINA staging, spirometry reversibility cut-offs, life-threatening signs, and drug mechanisms.
Definition & classification
Asthma is defined by a history of respiratory symptoms (wheeze, breathlessness, chest tightness, cough) that vary over time and in intensity, together with variable expiratory airflow limitation. The hallmark is reversibility — distinguishing it from fixed obstruction in COPD.
Phenotypes (clinically and exam-relevant):
| Phenotype | Key feature | Notes |
|---|---|---|
| Allergic (atopic / extrinsic) | Childhood onset, raised IgE, eosinophilia, family/personal atopy | Best response to ICS; Th2/eosinophilic |
| Non-allergic (intrinsic) | Adult onset, normal IgE | Often neutrophilic, less ICS responsive |
| Aspirin-exacerbated respiratory disease (AERD) | Asthma + nasal polyps + aspirin sensitivity | Samter's triad; avoid NSAIDs |
| Occupational | Symptoms relate to workplace; improve on holidays | Isocyanates (most common), flour, latex, animal dander |
| Exercise-induced bronchoconstriction | Symptoms 5–15 min after exercise | Cold dry air; pre-treat with SABA/LTRA |
| Cough-variant | Chronic cough only, no wheeze | Diagnosed by reversibility/PD20 |
High-yield: Samter's triad = asthma + nasal polyposis + aspirin (NSAID) sensitivity. Mechanism = COX-1 inhibition shunts arachidonic acid to the 5-lipoxygenase pathway → excess cysteinyl leukotrienes. Leukotriene receptor antagonists (montelukast) and 5-LOX inhibitors (zileuton) are particularly useful here.
Etiology & risk factors
- Host factors: atopy (strongest risk factor), genetic predisposition (ADAM33, ORMDL3), obesity, male sex in childhood (reverses after puberty).
- Environmental triggers: house dust mite, pollen, animal dander, cockroach antigen, moulds, tobacco smoke, air pollution, viral URTIs (rhinovirus, RSV), cold air, exercise, beta-blockers, NSAIDs, GORD, occupational sensitisers.
- Hygiene hypothesis: reduced early-life microbial exposure skews immunity toward a Th2 (allergic) phenotype.
High-yield: Non-selective beta-blockers (propranolol, timolol eye drops) and aspirin/NSAIDs can precipitate severe bronchospasm and are relatively contraindicated. Even topical timolol for glaucoma has triggered fatal attacks.
Pathophysiology
Asthma involves an interplay of inflammation, bronchoconstriction, and remodelling.
The allergic cascade (flow):
Allergen exposure → dendritic cell presentation → naive T cell → Th2 differentiation → IL-4 & IL-13 (IgE class switching by B cells) + IL-5 (eosinophil recruitment) → IgE binds mast cells → re-exposure crosslinks IgE → mast cell degranulation → release of histamine, leukotrienes (LTC4/D4/E4), prostaglandin D2, tryptase → bronchoconstriction + mucosal oedema + mucus.
- Early phase (minutes): mast-cell mediators → acute bronchospasm.
- Late phase (4–8 h): eosinophil/lymphocyte infiltration → sustained inflammation, bronchial hyper-responsiveness.
Airway remodelling (chronic, partly irreversible): subepithelial basement membrane thickening (collagen deposition), goblet cell and submucosal gland hyperplasia, airway smooth muscle hypertrophy/hyperplasia, and angiogenesis.
Classic pathology findings (often tested):
| Finding | Description |
|---|---|
| Curschmann's spirals | Whorls of shed epithelium / mucus plugs in sputum |
| Charcot–Leyden crystals | Eosinophil-derived (galectin-10), bipyramidal crystals |
| Creola bodies | Clusters of desquamated epithelial cells |
| Mucus plugging | Causes the classic widespread bronchiolar obstruction |
High-yield: A patient with asthma + peripheral eosinophilia + recurrent brown mucus plugs + fleeting pulmonary infiltrates → think allergic bronchopulmonary aspergillosis (ABPA); raised total IgE (>1000 IU/mL) and Aspergillus-specific IgE/IgG confirm it. Treat with oral corticosteroids ± itraconazole.
Clinical features
- Symptoms: episodic wheeze, breathlessness, chest tightness, and cough — classically worse at night/early morning (diurnal variation) and provoked by triggers.
- Signs in an attack: tachypnoea, prolonged expiration, polyphonic expiratory wheeze, use of accessory muscles, hyperinflated chest.
- Silent chest — ominous; indicates airflow so reduced that wheeze is no longer audible (life-threatening).
- Hyperresonant percussion, reduced breath sounds.
Diagnosis & investigations
Diagnosis is clinical + demonstration of variable airflow limitation.
Spirometry — investigation of choice:
- Obstructive pattern: FEV1/FVC < 0.70 (or below lower limit of normal).
- Bronchodilator reversibility: post-bronchodilator (salbutamol) increase in FEV1 ≥ 12% AND ≥ 200 mL confirms reversibility (adults).
High-yield: The single most commonly tested cut-off: post-bronchodilator FEV1 improvement ≥12% and ≥200 mL = significant reversibility → asthma. In children, ≥12% (no absolute mL needed).
Peak expiratory flow (PEFR):
- Diurnal variability > 10% (adults; >13% children) over 1–2 weeks supports asthma.
- Useful for home monitoring; PEFR diary.
Bronchial provocation testing (when spirometry normal but suspicion high):
- Methacholine / histamine challenge — a fall in FEV1 ≥ 20% (PC20/PD20) indicates hyper-responsiveness. High negative predictive value (a negative test largely rules out asthma).
- Exercise / mannitol challenge alternatives.
Other tests:
- FeNO (fraction of exhaled nitric oxide): marker of eosinophilic (Th2) airway inflammation; ≥ 25 ppb supports the diagnosis and predicts steroid responsiveness.
- Blood eosinophils, total/specific IgE, skin-prick testing for allergens.
- CXR — usually normal (hyperinflation in acute attack); used to exclude complications/differentials.
Diagnostic flow: Symptoms suggestive of asthma → spirometry with reversibility → if positive, confirm; if normal but symptoms typical → bronchoprovocation (methacholine) or PEFR variability/FeNO → confirm.
Severity assessment of an acute attack
| Feature | Moderate | Acute severe | Life-threatening |
|---|---|---|---|
| PEFR (% predicted/best) | 50–75% | 33–50% | < 33% |
| Speech | Sentences | Can't complete sentences | Unable to speak |
| RR | < 25/min | ≥ 25/min | — |
| Pulse | < 110/min | ≥ 110/min | Bradycardia, hypotension |
| SpO2 | ≥ 92% | ≥ 92% | < 92% |
| Other | — | — | Silent chest, cyanosis, exhaustion, confusion, feeble effort, PaCO2 normal/high |
High-yield: In acute asthma, the ABG normally shows respiratory alkalosis with hypocapnia (tachypnoea blows off CO2). A rising or normal/high PaCO2 ("normalising") is an alarming sign of impending respiratory failure — the patient is tiring. This is a classic NEET PG trap. Near-fatal asthma = raised PaCO2 and/or need for mechanical ventilation.
Management — chronic asthma (GINA stepwise)
GINA now recommends all adults/adolescents receive ICS-containing therapy — SABA-only treatment is no longer preferred because of risk of severe exacerbations.
Preferred track (ICS-formoterol as reliever — "MART/AIR"):
| Step | Preferred controller + reliever |
|---|---|
| 1–2 | As-needed low-dose ICS-formoterol |
| 3 | Low-dose maintenance ICS-formoterol + as-needed ICS-formoterol |
| 4 | Medium-dose maintenance ICS-formoterol |
| 5 | High-dose ICS-formoterol; add LAMA (tiotropium); refer for phenotyping ± biologics |
Stepwise escalation principle: Low-dose ICS → add LABA → increase ICS dose / add LAMA → biologics / oral steroids. Step up if uncontrolled; step down once controlled for ~3 months.
High-yield: LABA (salmeterol/formoterol) must NEVER be used as monotherapy in asthma — it increases asthma-related deaths. Always combine with an ICS. Formoterol has a rapid onset, so it doubles as a reliever (unlike salmeterol).
Drug mechanisms (frequently asked):
| Drug | Class / mechanism | Pearl |
|---|---|---|
| Salbutamol/albuterol | Short-acting β2-agonist (SABA) → ↑cAMP → bronchodilation | Reliever; tremor, hypokalaemia, tachycardia |
| Salmeterol/formoterol | LABA | Never alone; formoterol fast-onset |
| Budesonide/fluticasone | Inhaled corticosteroid — ↓ airway inflammation | Most effective controller; oral candidiasis, dysphonia — rinse mouth |
| Ipratropium/tiotropium | SAMA/LAMA — muscarinic antagonist | Tiotropium add-on in severe asthma |
| Montelukast/zafirlukast | Leukotriene receptor (CysLT1) antagonist | Useful in AERD, exercise-induced, allergic rhinitis; neuropsychiatric warning |
| Zileuton | 5-lipoxygenase inhibitor | Hepatotoxic — monitor LFTs |
| Theophylline | PDE inhibitor + adenosine antagonist | Narrow therapeutic index; arrhythmias, seizures |
| Omalizumab | Anti-IgE monoclonal | Severe allergic asthma, raised IgE |
| Mepolizumab/reslizumab | Anti-IL-5 | Severe eosinophilic asthma |
| Benralizumab | Anti-IL-5 receptor α | Eosinophilic |
| Dupilumab | Anti-IL-4Rα (blocks IL-4 & IL-13) | Eosinophilic / Type 2 high; also for AD, polyps |
| Tezepelumab | Anti-TSLP (thymic stromal lymphopoietin) | Works across phenotypes (upstream alarmin) |
High-yield: Match the biologic — Omalizumab = anti-IgE (allergic); Mepolizumab/Reslizumab/Benralizumab = anti-IL-5 (eosinophilic); Dupilumab = anti-IL-4Rα; Tezepelumab = anti-TSLP. This mapping is a recurring NEET PG one-liner.
Management — acute exacerbation / status asthmaticus
Status asthmaticus = a severe acute attack not responding to standard bronchodilators, risking respiratory failure.
Emergency approach (flow):
- Oxygen → target SpO2 93–95% (88–92% if risk of CO2 retention).
- Nebulised SABA (salbutamol) ± ipratropium (back-to-back/continuous in severe).
- Systemic corticosteroids early — oral prednisolone 40–50 mg or IV hydrocortisone (give within the first hour).
- IV magnesium sulphate (1.5–2 g over 20 min) for life-threatening/poor-responding attacks → smooth-muscle relaxation.
- Reassess; consider IV salbutamol/aminophylline in refractory cases.
- ICU + ventilation if exhaustion, rising PaCO2, silent chest, altered consciousness.
High-yield: IV magnesium sulphate is the classic add-on in severe/life-threatening acute asthma not responding to initial nebulisation. Steroids should be given early — they take ~4–6 h to act, so do not delay.
High-yield: Mechanical ventilation in asthma uses permissive hypercapnia with low tidal volumes and prolonged expiratory time to avoid dynamic hyperinflation / auto-PEEP and barotrauma.
Complications
- Acute: status asthmaticus, respiratory failure, pneumothorax / pneumomediastinum, atelectasis from mucus plugging.
- Chronic: airway remodelling → fixed airflow obstruction, recurrent exacerbations.
- Treatment-related: oral candidiasis, dysphonia, osteoporosis/adrenal suppression (chronic systemic steroids), growth retardation (high-dose ICS in children), theophylline toxicity.
- ABPA, allergic rhinitis, and chronic rhinosinusitis as associated conditions.
Key differentials
| Differential | Distinguishing clue |
|---|---|
| COPD | Older smoker, irreversible/partially reversible obstruction, less diurnal variation |
| Vocal cord dysfunction | Inspiratory stridor, normal SpO2, flattened inspiratory loop on flow-volume; non-responsive to bronchodilators |
| Cardiac failure ("cardiac asthma") | Orthopnoea, PND, basal crepitations, raised JVP, S3 |
| Bronchiectasis | Copious purulent sputum, clubbing, fixed crackles |
| Foreign body / tumour | Localised monophonic wheeze, fixed |
| ABPA / eosinophilic granulomatosis (Churg–Strauss) | Asthma + eosinophilia + multisystem involvement (EGPA: vasculitis, neuropathy, p-ANCA) |
High-yield: Asthma + eosinophilia + mononeuritis multiplex + p-ANCA (MPO) → Eosinophilic Granulomatosis with Polyangiitis (Churg–Strauss). Montelukast withdrawal of steroids has been associated with unmasking it.
Recently asked / exam angle
- Reversibility cut-off: post-bronchodilator FEV1 rise ≥12% and ≥200 mL — repeatedly asked.
- Methacholine challenge has high negative predictive value (rules out asthma).
- Normalising/rising PaCO2 in acute asthma = impending respiratory failure (NOT reassuring).
- Biologic–target matching (omalizumab→IgE, mepolizumab→IL-5, dupilumab→IL-4Rα, tezepelumab→TSLP).
- Samter's triad and the leukotriene mechanism behind aspirin sensitivity.
- Occupational asthma: isocyanates (spray painting, polyurethane) are the commonest cause; symptoms improve on weekends/holidays — diagnosed with serial PEFR at and away from work.
- LABA monotherapy is contraindicated; formoterol can be a reliever (MART regimen).
- Charcot–Leyden crystals (galectin-10), Curschmann's spirals in sputum.
- IV magnesium sulphate for life-threatening attack.
- GINA shift away from SABA-only treatment toward ICS-formoterol reliever.
Rapid revision
- Asthma = reversible, variable airflow obstruction with bronchial hyper-responsiveness.
- Reversibility = FEV1 ↑ ≥12% AND ≥200 mL post-bronchodilator.
- PEFR diurnal variability > 10% supports asthma; useful for home monitoring.
- Methacholine challenge → ≥20% fall in FEV1 (PC20); high NPV.
- Samter's triad = asthma + nasal polyps + aspirin sensitivity (excess leukotrienes).
- Silent chest, cyanosis, exhaustion, normal/high PaCO2 = life-threatening asthma.
- Acute ABG starts as respiratory alkalosis; rising CO2 = danger.
- LABA never as monotherapy; combine with ICS; formoterol can act as reliever.
- IV MgSO4 for severe/life-threatening attacks; give steroids early.
- Omalizumab (anti-IgE), mepolizumab/benralizumab (anti-IL-5), dupilumab (anti-IL-4Rα), tezepelumab (anti-TSLP).
- Isocyanates = commonest occupational asthma trigger; improves away from work.
- Sputum: Curschmann's spirals, Charcot–Leyden crystals, Creola bodies; remodelling = basement membrane thickening.