Pediatric Asthma: Case Discussion and Key Points
Model Case Presentation
Patient Demographics
Name: Master Arjun, Age: 8 years, Gender: Male, Informant: Mother (Reliable)
Chief Complaints
- Recurrent episodes of breathlessness and wheeze – 2 years
- Nocturnal cough disturbing sleep – 6 months
- Current episode of breathlessness – 6 hours
History Summary
Master Arjun is an 8-year-old boy with a 2-year history of recurrent episodes of wheeze and breathlessness, typically triggered by upper respiratory tract infections, dust exposure, and cold weather. Episodes occur 3–4 times per month and last 2–3 days each. He also has nocturnal cough that wakes him from sleep 3–4 nights per week. During the current episode (started 6 hours ago after playing in a dusty field), he has severe breathlessness, speaking in 1–2 word sentences, and is using accessory muscles. He has already taken 4 puffs of his salbutamol inhaler at home without relief.
History of eczema since age 2. Allergic rhinitis diagnosed at age 6. Elder sister has allergic asthma. Father smokes at home. No history of foreign body aspiration, whooping cough, or cardiac disease. No tuberculosis contact. Immunizations up to date.
Examination Summary
| Parameter | Finding | Significance |
|---|---|---|
| RR | 40/min | Severe tachypnea |
| HR | 126/min | Tachycardia |
| SpO₂ | 89% (room air) | Significant hypoxia → Severe exacerbation |
| Speech | 1–2 words/breath | Severe distress |
| Temperature | 37.2°C | Afebrile |
| PEFR | 42% predicted | Severe obstruction |
General: Anxious, sitting upright, unable to lie flat. Nasal flaring. Intercostal and subcostal retractions. Supraclavicular indrawing. Accessory muscle use (sternocleidomastoid).
Chest: Barrel-shaped chest with hyperinflation. Percussion: bilateral hyperresonance. Auscultation: diffuse bilateral expiratory wheeze, prolonged expiration. Reduced air entry bilaterally.
Other: Allergic shiners (periorbital darkening), transverse nasal crease. Atopic eczema patches on cubital fossae. No cyanosis. No clubbing.
✅ Complete Diagnosis
Bronchial Asthma — Moderate Persistent (baseline) — in Severe Acute Exacerbation (triggered by allergen exposure), with Atopic Triad (Asthma + Allergic Rhinitis + Eczema).
📝 History — Exam Q&A
Asthma is a chronic inflammatory disorder of the airways characterized by variable and reversible expiratory airflow limitation, associated with airway hyperresponsiveness.
Pathophysiology triad:
- Bronchoconstriction — smooth muscle contraction triggered by allergens, exercise, cold air
- Airway wall inflammation and edema — Th2-mediated eosinophilic inflammation, mast cell activation, IgE-mediated
- Mucus hypersecretion — goblet cell hyperplasia → thick tenacious mucus plugs obstructing airway lumen
Chronic, untreated inflammation leads to airway remodeling (subepithelial fibrosis, smooth muscle hypertrophy) causing irreversible obstruction.
The classic triad: Wheeze + Breathlessness + Cough. Key features:
- Episodic wheeze — bilateral, expiratory, recurrent
- Nocturnal or early morning cough — hallmark symptom, often the sole presenting feature (cough-variant asthma)
- Breathlessness and chest tightness — worsening with activity
- Variable symptoms — better with bronchodilators, vary over time
- Trigger-precipitated — viral URTIs, dust, smoke, cold air, exercise, strong emotions, allergens
💡 Mnemonics for Triggers
ESCAPED: Exercise, Smoke/pollution, Cold air, Allergens (dust mites, pollen, pet dander), Pests (cockroach), Emotional stress, Drugs (aspirin, beta-blockers, NSAIDs)
- Circadian fall in serum cortisol and epinephrine levels at night → bronchial smooth muscle hyperresponsiveness
- Increased parasympathetic tone (vagal) at night → bronchoconstriction
- Supine position → increased airway secretions pooling, reduced functional residual capacity
- Exposure to bedroom allergens (dust mites in mattress/pillows)
- Reduced mucociliary clearance during sleep
- Circadian rise in histamine and fall in beta-2 receptor sensitivity
The Atopic Triad consists of Asthma + Allergic Rhinitis + Atopic Eczema/Dermatitis. All three are IgE-mediated (Type I hypersensitivity) disorders with a shared Th2-driven immune mechanism.
Significance:
- Presence of one atopic condition increases likelihood of others
- Strong family history of atopy increases risk of asthma
- Concept of "Atopic March" — eczema in infancy → allergic rhinitis → asthma as child grows
- Untreated allergic rhinitis worsens asthma control ("united airway disease")
Asthma severity is classified at initial assessment before treatment. Based on: daytime symptoms, nighttime symptoms, SABA use, activity limitation, and lung function (FEV₁/PEFR).
| Feature | Intermittent | Mild Persistent | Moderate Persistent | Severe Persistent |
|---|---|---|---|---|
| Daytime symptoms | ≤2 days/week | >2 days/week but not daily | Daily | Throughout the day |
| Nighttime symptoms | ≤2/month | 3–4/month | >1/week | Often 7 nights/week |
| SABA use | ≤2 days/week | >2 days/week | Daily | Several times/day |
| Activity limitation | None | Minor | Some | Extreme |
| FEV₁ / PEFR | >80% | >80% | 60–80% | <60% |
| Step to start | Step 1 | Step 2 | Step 3 | Step 4–5 |
💡 Key Principle
Severity guides initiating treatment. Thereafter, use asthma control (well-controlled / partially controlled / uncontrolled) to adjust step therapy.
| Question | Rules Out |
|---|---|
| No sudden choking episode (onset while eating/playing) | Foreign body aspiration |
| No paroxysmal whooping cough with vomiting | Pertussis |
| No failure to thrive + steatorrhea | Cystic fibrosis |
| No stridor (noisy breathing) | Laryngotracheomalacia, croup |
| No TB contact / no evening fever | Endobronchial TB |
| No symptoms since birth | Congenital lung/cardiac anomaly |
| No feeding difficulty / no CHD signs | Cardiac cause of wheeze |
| No steroid use (immune status) | Allergic bronchopulmonary aspergillosis (ABPA) |
EIB is transient bronchoconstriction occurring 5–15 minutes after vigorous exercise and resolves spontaneously in 30–60 minutes. Mechanism: rapid breathing during exercise causes airway cooling and drying → osmotic change → mast cell degranulation → bronchoconstriction.
Clinical features: Cough, wheeze, and chest tightness after running/sports, not during exercise.
Diagnosis: Fall in FEV₁ ≥10% after standard exercise challenge test.
Management: Pre-exercise SABA (salbutamol 2 puffs) 15–20 min before exercise. ICS as controller if frequent.
A form of asthma where chronic cough is the only/predominant symptom, without typical wheeze or breathlessness. Common in children; often misdiagnosed as recurrent bronchitis.
Features: Nocturnal or early morning cough, worse with cold air/exercise, no apparent chest signs on examination.
Diagnosis:
- Spirometry: may show airflow obstruction
- Methacholine challenge test: positive (bronchial hyperresponsiveness)
- Therapeutic trial: >2-week trial of ICS + SABA → improvement confirms diagnosis
- FeNO elevated (type 2 inflammation)
- One asthmatic parent: 25–30% risk in child
- Both asthmatic parents: 50–75% risk
- Asthma is a polygenic disease; key susceptibility genes include ADAM33, PHF11, DPP10 on chromosomes 5q, 6p, 11q, 12q
- Environmental factors (allergen exposure, infections, smoking) significantly modify genetic risk
The hygiene hypothesis proposes that reduced early childhood exposure to infections and microbes shifts the immune system from a Th1-dominant (anti-microbial) to a Th2-dominant (atopic/allergic) response, increasing the risk of allergic diseases including asthma.
Evidence: Children raised on farms, with siblings, in daycare centers, or in developing countries have lower rates of asthma. The "Old Friends" hypothesis extends this to include helminths and saprophytic environmental organisms that once regulated immune tolerance.
🩺 Examination — Exam Q&A
General: Anxious, agitated, tripod position (sitting forward on hands), unable to lie flat. Nasal flaring, cyanosis in severe cases.
Respiratory signs:
- Tachypnea, tachycardia
- Intercostal, subcostal, supraclavicular retractions (indrawing)
- Accessory muscle use (sternocleidomastoid)
- Hyperinflated chest (barrel-shaped) — increased A-P diameter
- Percussion: bilateral hyperresonance
- Auscultation: diffuse bilateral expiratory wheeze, prolonged expiratory phase, reduced air entry
🚨 Silent Chest — Danger Sign
A "silent chest" (no wheeze audible) in a severely dyspneic child with accessory muscle use indicates near-total airway obstruction with minimal airflow — life-threatening emergency. Do NOT interpret as improvement.
| Feature | Mild | Moderate | Severe | Life-Threatening |
|---|---|---|---|---|
| Breathlessness | Walking, can lie flat | Talking, prefers sitting | At rest, hunched forward | Exhausted |
| Speech | Sentences | Phrases | Words | Unable to speak |
| Alertness | Normal | Agitated | Agitated | Drowsy / confused |
| RR (child) | Normal–mild increase | Increased | Often >30/min | — |
| Accessory muscles | Absent/mild | Present | Marked | Paradoxical breathing |
| Wheeze | Moderate | Loud | Loud | Silent chest |
| SpO₂ (room air) | ≥95% | 91–94% | <91% | <88% |
| PEFR (% predicted) | >80% | 50–80% | <50% | <33% |
| PaCO₂ | Normal | Normal / low | Low / normal | Elevated (respiratory failure) |
- Allergic shiners — periorbital darkening (venous stasis from nasal congestion)
- Dennie-Morgan lines — double infraorbital skin folds below the lower eyelid
- Transverse nasal crease — horizontal crease on nose bridge from repeated "allergic salute" (wiping nose upward)
- Allergic salute — rubbing nose upward with palm
- Nasal mucosa — pale, bluish, boggy (allergic rhinitis)
- Eczema — flexural surfaces (antecubital, popliteal fossae), dry scaly plaques
- Pale conjunctivae, cobblestoning of posterior pharynx
Pulsus paradoxus is an exaggerated fall in systolic blood pressure (>10 mmHg) during inspiration. Normally there is a slight drop (≤10 mmHg) during inspiration.
Mechanism in asthma: Severe airway obstruction → markedly increased negative intrapleural pressure during inspiration → increased right ventricular venous return → ventricular interdependence → decreased LV filling → reduced pulse pressure.
Significance:
- >10 mmHg: moderate-severe exacerbation
- >20 mmHg: severe exacerbation
- Disappears with fatigue/respiratory failure (false reassurance)
Signs of impending respiratory failure (DANGER signs):
- Decreasing level of consciousness, confusion, drowsiness
- Silent chest
- Paradoxical chest movement (thoracoabdominal dissociation)
- Cyanosis despite O₂ therapy
- Bradycardia (pre-arrest)
- SpO₂ <88% despite high-flow O₂
- Rising PaCO₂ (hypercapnia) — a normal or elevated PaCO₂ in a wheezing child is alarming (they should be hyperventilating)
Indications for intubation: Respiratory arrest or imminent arrest, GCS falling, SpO₂ unresponsive to maximal therapy, progressive hypercapnia. Use ketamine for induction (bronchodilator properties).
Peak Expiratory Flow Rate (PEFR): Best of 3 forced exhalations measured with a peak flow meter. Results expressed as % predicted (based on height, age, sex) or % personal best.
Interpretation: Green zone (>80%) = well-controlled; Yellow zone (50–80%) = caution; Red zone (<50%) = emergency.
Limitations in children:
- Requires patient cooperation and effort — unreliable in children <5 years
- Effort-dependent — an exhausted/severely ill child underestimates severity
- Different meters give different readings — always use same meter
- PEFR may be falsely normal early in an attack (large airway measure, not small)
🔬 Investigations — Exam Q&A
Spirometry with bronchodilator reversibility testing is the gold standard for children ≥5 years.
Findings in asthma:
- Obstructive pattern: reduced FEV₁, normal/increased FVC, reduced FEV₁/FVC ratio (below lower limit of normal)
- Significant reversibility: ≥12% increase in FEV₁ AND ≥200 mL absolute increase after salbutamol (in children: ≥12% increase from baseline)
- Flow-volume loop: concave expiratory limb (small airway obstruction), "scooped out" appearance
💡 Important Note (GINA 2024)
FEV₁/FVC should be compared to the Lower Limit of Normal (LLN), not a fixed cutoff, especially in children. A normal spirometry does not exclude asthma — intermittent obstruction may be absent between attacks.
In acute exacerbation:
- Bilateral hyperinflation (most common) — flattening of diaphragms, increased AP diameter, hyperlucent lung fields
- Peribronchial thickening ("tram-track" or "ring shadows") — bronchial wall edema
- CXR may be normal in mild exacerbation
CXR is NOT routinely needed in asthma. Indications: first episode of severe wheeze, suspected pneumothorax, suspected foreign body, no response to treatment, signs of pneumonia.
Complications visible on CXR:
- Pneumothorax / pneumomediastinum (rare, severe asthma)
- Segmental/lobar collapse (mucus plugging)
- Consolidation (concomitant pneumonia)
| Test | Finding in Asthma | Significance |
|---|---|---|
| Total Eosinophil Count (TEC) | Often elevated (>400/μL) | Supports atopic/eosinophilic asthma phenotype; >400 suggests response to biologics |
| Total IgE (serum) | Often elevated | Atopic disease; guides anti-IgE therapy (Omalizumab) |
| Specific IgE / RAST | Positive to specific allergen | Identifies triggering allergens for avoidance/immunotherapy |
| Skin Prick Test | Positive wheal-and-flare | Gold standard for allergen sensitization testing |
| ABG (acute severe) | Initially: respiratory alkalosis (low PaCO₂); Late: respiratory acidosis (rising PaCO₂) | Rising CO₂ = impending respiratory failure |
| CBC | Eosinophilia; leukocytosis if superadded infection | — |
Fractional exhaled Nitric Oxide (FeNO) is a non-invasive biomarker of eosinophilic airway inflammation. Nitric oxide is produced by eosinophils and airway epithelium under IL-13 stimulation.
Normal values: <25 ppb (adults and children >12 years); <20 ppb (children <12 years)
Interpretation:
- <25 ppb: Low — eosinophilic inflammation unlikely; asthma diagnosis less likely
- 25–50 ppb: Intermediate — consider clinical context
- >50 ppb: High — eosinophilic inflammation; supports asthma diagnosis; predicts steroid responsiveness and exacerbation risk
Clinical uses: Aids diagnosis in uncertain cases; guides ICS dose adjustment; identifies steroid-responsive phenotype; assesses adherence to ICS (FeNO rises if ICS stopped); helps in biologic therapy decision-making.
A bronchial provocation test that measures airway hyperresponsiveness. Methacholine (a cholinergic agonist) is inhaled in increasing concentrations; FEV₁ is measured after each dose.
Positive: ≥20% fall in FEV₁ at a concentration ≤16 mg/mL (PC₂₀ ≤16 mg/mL) — indicates airway hyperresponsiveness.
Indications:
- Suspected asthma with normal spirometry
- Cough-variant asthma
- Occupational asthma evaluation
- Assessment of severity of airway hyperresponsiveness
Contraindications: FEV₁ <60% predicted, recent myocardial infarction, uncontrolled hypertension, pregnancy.
ABG progression in asthma:
- Mild–moderate: Respiratory alkalosis — patient hyperventilating to compensate → low PaCO₂, normal–low PaO₂, pH elevated
- Severe: PaCO₂ starts rising toward normal — "normocapnia in a breathless wheezing child is alarming"
- Critical/Pre-arrest: Respiratory acidosis — CO₂ rises above normal, PaO₂ falls, pH <7.35 — indicates respiratory muscle fatigue and near-respiratory failure
A normal PaCO₂ (35–45 mmHg) in a child who should be hyperventilating indicates that they can no longer compensate → impending respiratory failure → requires urgent escalation of management (ICU, possible intubation).
💊 Management — Exam Q&A
ABCDE approach + concurrent asthma treatment:
- Oxygen — High-flow O₂ via face mask, target SpO₂ 94–98%
- Short-acting β₂-agonist (SABA) — First-line bronchodilator
- Salbutamol nebulization: 0.15 mg/kg (min 2.5 mg, max 5 mg) every 20 minutes for 3 doses in first hour
- In mild-moderate: MDI + spacer equally effective (4–8 puffs salbutamol)
- In severe: continuous nebulization preferred
- Ipratropium bromide (Anticholinergic) — Add to nebulization in moderate-severe: 250 mcg (<20 kg) or 500 mcg (≥20 kg) every 20 min × 3 doses; reduces hospitalization
- Systemic Corticosteroids
- Oral prednisolone: 1–2 mg/kg/day (max 40 mg) for 3–5 days
- IV methylprednisolone: if vomiting/cannot take orally — 1–2 mg/kg/dose 6-hourly
- Start within the first hour — reduces hospitalization rate
- IV/IM Magnesium Sulphate — In severe exacerbations not responding to above: 25–75 mg/kg (max 2.5 g) IV over 20 minutes. Causes smooth muscle relaxation (bronchodilator)
- IV access, monitoring, pulse oximetry, reassess every 20 min
🚨 Do NOT give:
Sedatives (respiratory depressants), antihistamines (dry secretions), adrenaline (subcutaneous, unless anaphylaxis), antibiotics (unless infection confirmed), IV aminophylline (first-line — narrow therapeutic window, toxicity).
| Step | Preferred Controller | Preferred Reliever |
|---|---|---|
| Step 1 (Intermittent) | None (or ICS when SABA taken — Track 2 option) | SABA as-needed |
| Step 2 (Mild Persistent) | Low-dose ICS daily | SABA as-needed |
| Step 3 (Moderate Persistent) | Low-dose ICS + LABA; OR medium-dose ICS | SABA as-needed |
| Step 4 (Severe Persistent) | Medium-high dose ICS + LABA; ± LAMA (tiotropium ≥6 years) | SABA as-needed |
| Step 5 (Refractory) | Refer specialist. Add-on biologic (Omalizumab, Mepolizumab, Dupilumab) | SABA as-needed |
💡 Step Up / Step Down
Step up if uncontrolled after 2–3 months at current step. Step down (reduce by one step) if well-controlled for ≥3 months — use minimum effective therapy. Always recheck inhaler technique and adherence before stepping up.
| Step | Controller | Reliever |
|---|---|---|
| Step 1 | None (or ICS at onset of viral URTI if recurrent wheezer) | SABA as-needed |
| Step 2 | Low-dose ICS daily | SABA as-needed |
| Step 3 | Double low-dose ICS; OR low-dose ICS + LTRA (montelukast) | SABA as-needed |
| Step 4 | Refer specialist; continue double dose ICS; reassess diagnosis | SABA as-needed |
Delivery devices: Pressurized MDI + valved spacer + face mask (≤3 years), MDI + valved spacer + mouthpiece (3–5 years), nebulizer as alternative only.
GINA 2025 diagnosis criteria (≤5 years): All three required: (1) Recurrent acute wheezing episodes; (2) No alternative cause for symptoms; (3) Timely clinical response to asthma medications.
Common ICS in children:
- Budesonide (Pulmicort) — available as MDI, DPI, nebulizer
- Fluticasone propionate (Flixotide) — MDI, DPI
- Beclomethasone dipropionate — MDI
- Mometasone furoate — DPI (≥4 years)
Correct MDI + Spacer Technique:
- Shake inhaler, remove cap, insert into spacer
- Exhale gently away from device
- Place mouthpiece (or mask) to mouth, ensure airtight seal
- Press canister once — inhale slowly and deeply over 5–10 seconds
- Hold breath 5–10 seconds, exhale slowly
- Wait 30–60 seconds before second puff
- Rinse mouth with water after ICS to prevent oral candidiasis
ICS side effects: Local — oral candidiasis, dysphonia. Systemic (high-dose) — growth suppression (mild, reversible), adrenal suppression, osteoporosis.
Mechanism: Magnesium inhibits smooth muscle contraction (antagonizes calcium-dependent bronchoconstriction) and inhibits acetylcholine release from nerve terminals → bronchodilation.
Dose: IV Magnesium Sulphate 25–75 mg/kg (max 2.5 g in children, 2 g in adults) over 20 minutes — single dose only.
Indications: Severe exacerbation not responding to first-line therapy (SABA + ipratropium + steroids). Reduces hospitalization rates significantly in children.
Side effects: Flushing, hypotension, bradycardia, nausea. Monitor for toxicity: loss of deep tendon reflexes (serum Mg >5 mEq/L), respiratory depression (>7 mEq/L).
A written, individualized plan developed with the patient/caregiver that provides specific instructions for managing asthma daily and during exacerbations. Uses a traffic light system:
- Green Zone (PEFR >80%): Well-controlled — continue daily controller medications as prescribed
- Yellow Zone (PEFR 50–80%): Caution — increase SABA frequency, consider short course OCS, contact doctor if no improvement in 24 hours
- Red Zone (PEFR <50%): Emergency — immediate SABA, go to emergency department, give OCS
Importance: Reduces asthma exacerbations, emergency visits, hospitalizations. Empowers patients for self-management. GINA recommends every asthma patient have a written action plan.
- Moderate-severe exacerbation not responding to initial 3 rounds of SABA nebulization in emergency
- SpO₂ <92% on room air after treatment
- Silent chest, cyanosis, altered consciousness
- Child <2 years (higher risk of rapid deterioration)
- Risk factors for fatal asthma (prior ICU admission, recent OCS use, psychiatric/psychosocial issues)
- Inadequate home environment or poor caregiver understanding
- PEFR <50% after 1 hour of treatment
Indications for PICU: Impending respiratory failure, requiring IV magnesium/aminophylline, SpO₂ <88% despite max therapy, rising PaCO₂, need for NIV or intubation.
Status Asthmaticus: A severe acute asthma exacerbation that does not respond to initial treatment with standard bronchodilators and steroids, typically lasting >1 hour of maximal treatment.
Management escalation:
- Continue: Continuous SABA nebulization, high-flow O₂, IV/PO corticosteroids
- IV Magnesium Sulphate: 25–75 mg/kg IV over 20 min if not already given
- IV Aminophylline: Loading dose 5 mg/kg over 20–30 min (if not on theophylline) then maintenance infusion — only if above measures fail; monitor ECG, levels
- IV/SC Terbutaline: 0.01 mg/kg SC/slow IV for children not responding to nebulized SABA
- Heliox: Helium-oxygen mixture (70:30) — reduces turbulent airflow in obstructed airways, enhances bronchodilator delivery; used when O₂ requirements permit
- Non-Invasive Ventilation (NIV/BiPAP): May help avoid intubation in select patients
- Intubation and Mechanical Ventilation: Last resort — use ketamine induction; controlled hypoventilation strategy (permissive hypercapnia) to avoid air trapping
- Allergen avoidance: Impermeable dust-mite mattress covers, regular washing of bedding in hot water (>60°C), minimizing soft toys/carpets in bedroom
- Smoking cessation: No smoking indoors — passive smoke is a major trigger; parents must be counselled strongly
- Pet dander: Remove pets from home, or at least from bedroom (if sensitized)
- Air pollution: Avoid outdoor play on high pollution days, air purifiers indoors
- Exercise: Encourage physical activity with pre-medication if EIB; swimming preferred (humid air)
- Treat comorbidities: Allergic rhinitis (intranasal steroids), GERD (PPIs), obesity (weight loss)
- Influenza vaccination: Annual flu vaccine recommended for all children with persistent asthma
- Breathing exercises: Buteyko technique, diaphragmatic breathing — adjunct benefit
- Previous near-fatal episode requiring ICU / intubation
- Hospitalization or emergency visit for asthma in past year
- Currently using or recently stopped oral corticosteroids
- Not currently using ICS (non-adherent)
- SABA overuse (using >1 canister/month)
- Sensitivity to Alternaria (mould)
- Psychiatric illness or psychosocial problems
- Low socioeconomic status, poor access to healthcare
- Food allergy (especially peanut) with asthma — synergistic risk of fatal anaphylaxis
🔭 Recent Advances — Exam Q&A
Biologic therapies are monoclonal antibodies targeting specific inflammatory pathways in severe refractory asthma (GINA Step 5). Used when high-dose ICS-LABA fails to control asthma.
| Drug | Target | Age | Indication |
|---|---|---|---|
| Omalizumab (Xolair) | Anti-IgE | ≥6 years | Moderate-severe allergic asthma with elevated IgE |
| Mepolizumab (Nucala) | Anti-IL-5 | ≥6 years | Severe eosinophilic asthma (blood eosinophils ≥150/μL or FeNO ≥25 ppb) |
| Benralizumab (Fasenra) | Anti-IL-5Rα | ≥12 years | Severe eosinophilic asthma |
| Dupilumab (Dupixent) | Anti-IL-4Rα (blocks IL-4 & IL-13) | ≥6 years | Moderate-severe type 2 asthma; also treats eczema |
| Tezepelumab (Tezspire) | Anti-TSLP | ≥12 years | Severe uncontrolled asthma; works in eosinophilic and non-eosinophilic phenotypes |
💡 Tezepelumab
Targets Thymic Stromal Lymphopoietin (TSLP) — an "upstream" cytokine released by airway epithelium in response to allergens, viruses, pollutants. Unlike other biologics, it benefits both type 2 and non-type 2 asthma phenotypes.
AIT involves administering gradually increasing doses of specific allergens to induce immunological tolerance — shifts the immune response from Th2 to a tolerant state (regulatory T cells, IgG4 blocking antibodies).
Types:
- Subcutaneous Immunotherapy (SCIT): Injections, weekly build-up then monthly maintenance — 3 to 5 years
- Sublingual Immunotherapy (SLIT): Daily drops or tablets under tongue — better safety profile, preferred in children
Indications in asthma (GINA 2024): Mild-moderate allergic asthma with FEV₁ ≥70% (must be controlled before starting), demonstrated allergen sensitization (house dust mite, grass pollen), symptoms not adequately controlled by pharmacotherapy, or to modify disease course and prevent new sensitivities.
Evidence: SLIT with house dust mite tablets reduces exacerbations in allergic asthma and may allow ICS dose reduction.
GINA 2024 offers two parallel treatment tracks for adults and adolescents ≥12 years based on reliever type:
- Track 1 (ICS-formoterol MART): Preferred. ICS-formoterol used as both maintenance AND reliever therapy (MART — Maintenance And Reliever Therapy). Ensures patients always receive ICS alongside reliever → reduces exacerbations. Reliever: as-needed low-dose ICS-formoterol.
- Track 2 (SABA as reliever): Alternative. Daily ICS controller + SABA as-needed reliever. Less preferred due to risk of SABA overuse and inflammation without anti-inflammatory cover.
For children 6–11 years: MART is being evaluated; currently SABA as preferred reliever with ICS controller, but ICS-formoterol MART can be used at higher steps.
GINA 2024 introduced clinical remission as a new treatment goal: no symptoms, no exacerbations, no reliever use, and stable normal lung function on minimal therapy — sustained for ≥12 months.
In children: A proportion of children with early-onset asthma (wheezy infant phenotype) naturally "outgrow" asthma by adolescence. True remission is more achievable in children than adults.
Predictors of persistence into adulthood: Persistent allergic sensitization, severe baseline asthma, female sex, ongoing allergen exposure, and smoking.
Biologic therapies (especially Dupilumab, Mepolizumab) have been shown to achieve sustained remission in some patients with severe eosinophilic asthma even after stopping treatment.
Asthma phenotypes describe the observable characteristics; endotypes describe the underlying biological mechanism.
| Phenotype | Features | Biologic Target |
|---|---|---|
| Allergic (Type 2 high) | Childhood onset, atopy, eosinophilia, high IgE, FeNO elevated | Omalizumab, Dupilumab |
| Eosinophilic (Late-onset) | Adult-onset, blood eosinophilia, severe, frequent exacerbations | Mepolizumab, Benralizumab |
| Exercise-induced | Symptoms only after exercise | SABA pre-exercise |
| Aspirin-exacerbated | Nasal polyps + chronic sinusitis + aspirin sensitivity (Samter's Triad) | Dupilumab; aspirin desensitization |
| Obesity-associated | Non-eosinophilic, steroid-resistant, metabolic | Weight loss; limited biologic data |
| Viral-triggered (recurrent wheeze in children) | Episodic wheeze with viral URTI, asymptomatic between episodes | Intermittent ICS at onset of URTI |
- Smart inhalers: Electronic sensors attached to MDI/DPI that record time, date, and number of inhalations → transmitted to smartphone/cloud → tracks adherence and technique objectively
- Electronic monitoring devices (EMDs): Help identify SABA overuse (a marker of poor control and exacerbation risk)
- AI-based platforms: Predict exacerbation risk from usage patterns, environmental data, and symptom reports → alert patients/clinicians proactively
- Telemedicine: Remote monitoring of asthma control, virtual consultations — particularly valuable for follow-up in children
- GINA 2024 highlights the growing role of digital tools to improve adherence and self-management outcomes
⚡ Key Points — Quick Revision
One-Liners for Exam
- Definition: Chronic inflammatory airway disorder → variable, reversible expiratory airflow limitation + hyperresponsiveness
- Pathophysiology triad: Bronchoconstriction + Airway inflammation + Mucus hypersecretion
- Classic symptoms: Wheeze + Breathlessness + Nocturnal cough (variable, episodic)
- Atopic Triad: Asthma + Allergic Rhinitis + Atopic Eczema
- Gold standard Dx: Spirometry with bronchodilator reversibility (FEV₁ ≥12% increase after salbutamol)
- FeNO >50 ppb: Eosinophilic inflammation; steroid-responsive; guides biologic therapy
- PEFR zones: Green >80% / Yellow 50–80% / Red <50%
- Silent chest: Life-threatening — near-total obstruction, not improvement
- Normal PaCO₂ in severe asthma: Warning — impending respiratory failure
- First-line acute Rx: O₂ + SABA nebulization (0.15 mg/kg salbutamol) + Ipratropium + Steroids
- MgSO₄ dose: 25–75 mg/kg IV over 20 min (max 2.5 g) — for severe, non-responding exacerbation
- Stepwise Rx: Step 1 = SABA only → Step 2 = Low-dose ICS → Step 3 = ICS+LABA → Step 4 = High ICS+LABA±LAMA → Step 5 = Biologics
- Inhaler of choice ≤5 years: pMDI + Valved Spacer + Face mask
- ICS side effect: Rinse mouth after to prevent oral candidiasis
- Omalizumab: Anti-IgE; ≥6 years; allergic asthma with elevated serum IgE
- Mepolizumab: Anti-IL-5; ≥6 years; eosinophilic asthma
- Dupilumab: Anti-IL-4Rα; ≥6 years; type 2 inflammation; treats both asthma and eczema
- Tezepelumab: Anti-TSLP; ≥12 years; works across all asthma phenotypes
- GINA 2025 Dx ≤5 years: All 3 required — recurrent wheeze + no alternative cause + response to asthma treatment
- Ketamine: Preferred induction agent for intubation in status asthmaticus (bronchodilator)
- Nocturnal asthma mechanism: Low cortisol + high parasympathetic tone + circadian histamine rise + dust mite exposure
🚨 High-Yield Differentials — "Not All That Wheezes is Asthma"
- Foreign body aspiration — sudden onset, unilateral wheeze, history of choking
- Bronchiolitis — age <2 years, viral, first episode, bilateral fine crepitations
- Cystic fibrosis — recurrent wheeze + FTT + steatorrhea; sweat chloride >60 mEq/L
- Tracheomalacia / Laryngomalacia — stridor since birth, positional change
- GERD — postprandial wheeze, reflux symptoms
- Endobronchial TB — TB contact, evening fever, hilar adenopathy on CXR
- ABPA — uncontrolled asthma + central bronchiectasis + elevated IgE + Aspergillus sensitization
- Vocal cord dysfunction (VCD) — inspiratory stridor, normal spirometry between attacks, psychiatric comorbidity