GC040 Cough And Wheezing: Asthma And Allergic Lung Diseases
Asthma and allergic lung diseases are chronic inflammatory airway disorders characterized by reversible bronchoconstriction, mucus hypersecretion, and airway hyperresponsiveness, presenting with episodic cough, wheezing, and dyspnea triggered by allergens or irritants.
Cough and Wheezing: Asthma and Allergic Lung Diseases
This GC lecture (GC 040) by Dr. James CM Ho is the foundational lecture on asthma for HKUMed in-house exams. It covers the entire clinical approach: definition → classification → epidemiology → risk factors (host + environment) → pathophysiology (mechanisms of airflow obstruction, immunology) → clinical features → differential diagnosis → diagnosis (spirometry, PEF) → assessment of severity and control → pharmacotherapy (relievers vs preventors, GINA stepwise approach) → biologics → allergen avoidance → patient education.
How this fits into exams: Asthma is a perennial favourite. It crosses internal medicine, paediatrics, pharmacology, and immunology. Past papers repeatedly test: the definition of variable airflow limitation, the GINA stepwise approach, severity classification, the difference between severity and control, biologics and their indications, and the approach to suboptimal asthma control.
Learning Objectives (inferred from slides):
- Define asthma and understand its heterogeneity
- Classify asthma by phenotype and endotype
- Identify host and environmental risk factors
- Explain mechanisms of airflow obstruction
- Describe clinical features and differential diagnosis of cough/wheeze
- Diagnose asthma using spirometry, bronchodilator reversibility, and PEF variability
- Assess severity and level of control (GINA framework)
- Apply stepwise pharmacotherapy (relievers vs preventors)
- Know indications for biologics
- Counsel patients on allergen avoidance and self-management
The lecture opens by framing cough and wheezing as overlapping symptom complexes with distinct differential diagnoses. [1]
| Diseases with Airflow Obstruction | Diseases with Cough |
|---|---|
| COPD | Rhinitis, sinusitis, otitis |
| Asthma | Bronchitis (chronic or post-viral) |
| Bronchiolitis obliterans | Asthma |
| Cystic fibrosis | Bronchiectasis |
| Organic or functional laryngeal narrowing | Cystic fibrosis |
| Tracheal or major bronchial obstruction | Pneumonia |
| Diffuse pulmonary fibrosis |
Why this matters: The lecture deliberately separates "airflow obstruction" from "cough" because not all cough is obstructive and not all obstruction causes cough. Asthma sits in BOTH columns — it causes cough AND airflow obstruction. This framing is classic for MCQ stems that ask "which condition causes BOTH cough and airflow obstruction?"
Wheeze Physiology Recap
A wheeze is a continuous musical sound lasting > 250 ms, produced by oscillation of airway walls narrowed almost to closure. It is most commonly expiratory because airways naturally narrow during expiration (loss of radial traction). Inspiratory or biphasic wheezes suggest severe narrowing. Polyphonic wheeze = diffuse narrowing (asthma, COPD). Monophonic wheeze not cleared by coughing = fixed obstruction (tumour, foreign body). [2]
"Asthma is a heterogeneous disease, usually characterized by chronic airway inflammation. It is defined by the history of respiratory symptoms such as wheeze, shortness of breath, chest tightness and cough that vary over time and in intensity, together with variable expiratory airflow limitation." — GINA 2022 [1]
Key words in the definition to remember for exams:
- Heterogeneous — different phenotypes and endotypes
- Chronic airway inflammation — not just episodic bronchospasm
- Variable — symptoms fluctuate; this distinguishes asthma from COPD (which is progressive and persistent)
- Expiratory airflow limitation — obstruction is worse on expiration
Why "variable"? The airflow obstruction in asthma reverses either spontaneously or with treatment. In COPD, obstruction is largely irreversible. This is the single most important discriminator between asthma and COPD in exam MCQs.
3. Classification of Asthma
Atopic asthma – in individuals with a tendency to atopy or predisposition to synthesize IgE to common allergens. Usually in children and young adults with a history of infantile eczema and allergic rhinitis (early-onset). [1]
Nonatopic asthma – in those with no evidence of atopy. Usually in adults (late-onset). [1]
| Feature | Atopic (Extrinsic) | Non-atopic (Intrinsic) |
|---|---|---|
| IgE | Elevated | Normal |
| Skin prick test | Positive to common allergens | Negative |
| Onset | Childhood/young adult | Adult |
| History | Eczema, allergic rhinitis (atopic march) | Often triggered by infections, pollutants |
| Inflammation | Eosinophilic (Type 2-high) | May be eosinophilic or neutrophilic |
| Response to ICS | Usually good | Variable |
| Prognosis with biologics | Better (targetable pathways) | Limited biologic options if Type 2-low |
The Atopic March (from dermatology/allergology lectures): Eczema → Allergic rhinitis → Asthma. The skin is the first barrier in contact with the external environment, so sensitization starts there. Why eczema comes first and asthma later is not fully understood, but the concept is heavily tested. [3]
Phenotypes – characteristics or disease traits. Mechanisms – immunological pathways (endotypes): Type 2-high vs Type 2-low. [1]
Type 2-high asthma:
- Driven by Th2 cytokines (IL-4, IL-5, IL-13)
- Features: eosinophilia, elevated IgE, elevated FeNO
- Responsive to ICS and biologics (anti-IgE, anti-IL5, anti-IL4Rα)
- Includes both allergic (atopic) and eosinophilic non-allergic phenotypes
Type 2-low asthma:
- Neutrophilic or paucigranulocytic
- Less responsive to ICS
- Fewer biologic options available
- Often associated with obesity, smoking, adult-onset
Exam Pearl: Phenotype vs Endotype
Phenotype = observable trait (e.g., "eosinophilic asthma," "obesity-associated asthma"). Endotype = underlying immunological mechanism (e.g., Type 2-high). The lecture explicitly distinguishes these — examiners may test this distinction.
~300 million affected individuals globally. Global prevalence 1–18%. ~250,000 deaths from asthma. 15 million DALYs lost annually. [1]
In HK, current wheeze has decreased from 12.4% to 8.6% over 7 years (ISAAC Phase Three data). [1]
Key epidemiological points:
- Decreasing prevalence in North America and Western Europe
- Increasing asthma symptom prevalence in Africa, Latin America and parts of Asia
- Demographics: Can develop at any age, but ~75% diagnosed before age 7. M > F in childhood; F > M in adulthood (> 40y). [4][5]
5. Risk Factors
5A. Host Predisposition
Genetics, Atopy, Gender, Obesity — these are the four host factors listed on the slide. [1]
The lecture provides a specific table of candidate genes for asthma and atopy: [1]
| Chromosome | Candidate Gene | Function |
|---|---|---|
| 5q31 | IL-3, -4, -5, -9, -13 | Upregulate IgE |
| 5q32 | β2 adrenoreceptor | Bronchodilation |
| 6p | HLA complex | Antigen presentation |
| 6p21.3 | TNF-α | Inflammatory |
| 11q13 | FcεRI | Transduction signalling |
| 12q | Interferon-γ | Inhibition of Th1 |
| 12q | Nitric oxide synthase | (Airway inflammation marker) |
| 20q | ADAM33 | Metalloprotease (airway remodelling) |
Why these genes matter: They cluster around two themes — (1) IgE/Th2 skewing (IL-4, IL-5, IL-13, FcεRI) and (2) airway structural changes (ADAM33, β2-AR). Knowing the chromosome loci is low-yield for the written exam, but knowing the functions is high-yield because it links directly to pharmacotherapy targets.
Atopy = predisposition to synthesize IgE to common allergens. Increased asthma prevalence correlates with increased serum IgE level. [1]
Important nuance from allergology: High IgE ≠ allergy necessarily. Atopy means you produce more IgE, but the IgE still needs to trigger mast cell degranulation upon allergen exposure to cause clinical disease. [6]
- Children: M > F (~2:1) — boys have smaller airways relative to lung size
- Adults: equalizes, then F > M after age 40 — hormonal influences, possible airway remodelling differences
Asthma more common and difficult to control in grossly obese subjects (BMI > 30 kg/m²). Obese asthmatics have ↓lung function and ↑co-morbidities. Exact mechanisms unknown — possibly effect on lung mechanics and/or pro-inflammatory state (cytokines from adipocytes). [1]
Why obesity worsens asthma:
- Mechanical: Excess abdominal/thoracic fat reduces FRC and tidal volume, causing airways to close more easily
- Inflammatory: Adipokines (leptin, TNF-α, IL-6) from adipose tissue create a systemic pro-inflammatory milieu
- Co-morbidities: GERD, OSA — both independently worsen asthma symptoms
- Treatment resistance: Obese asthmatics often have Type 2-low phenotype, responding poorly to ICS
5B. Environmental Risk Factors
The lecture distinguishes causes (that initiate the disease) from triggers (that provoke exacerbations in someone who already has asthma). In practice, the distinction is often blurred.
Indoor aeroallergens: house dust mite, pets, cockroaches. Outdoor aeroallergens: alternaria. Occupational agents: responsible for 5–15% of adult-onset asthma. [1]
- House dust mite (Dermatophagoides) — the dominant allergen in Hong Kong and most tropical/subtropical climates. Thrives in warm, humid environments. The allergen is in the faecal pellets, not the mite itself.
- Pets — cat dander (Fel d 1) is a potent allergen; dog dander less so
- Cockroaches — significant in urban Asian households
- Alternaria — outdoor fungal spore; associated with severe/fatal asthma exacerbations
- Occupational agents — isocyanates (paint), flour dust (bakers), wood dust, latex. Ask about occupation in every asthma history!
Environmental tobacco smoke. Outdoor air pollution. [1]
Air pollution: increase in health care utilization — hospital admission, A&E visits, unscheduled visits to doctors. Dose-response relationship with air pollutants. [1]
Air pollution acts primarily as a trigger (exacerbating pre-existing asthma) rather than a cause. Particulate matter (PM2.5, PM10), ozone, NO₂, and SO₂ are the key pollutants. The dose-response relationship means: the more pollution, the more exacerbations — this is important for public health exam questions.
Viral infection may trigger an acute attack in those with pre-existing asthma. Exposure to some microbes in early infancy may protect against the development of asthma in children (hygiene hypothesis). [1]
Two opposing roles of infection:
| Role | Mechanism | Clinical Relevance |
|---|---|---|
| Trigger | Viral URTI (especially rhinovirus) → epithelial damage → inflammation → bronchospasm | Most common trigger for acute exacerbation in both adults and children |
| Protective | Early microbial exposure → Th1 stimulation → counterbalances Th2 skewing → less atopy | Hygiene hypothesis |
First postulated by Strachan: "Allergic diseases are prevented by infections in early childhood, transmitted by contact with older children." [1]
Microbial exposures associated with less allergy and asthma: large family size, having older siblings, day care, farming (animal contact, stable exposure, drinking unpasteurized farm milk), animal exposure (pet keeping). [1]
Why it works (proposed mechanism): Early microbial exposure activates Th1 responses. Without this counterbalance, the immune system skews towards Th2 dominance → more IgE → more atopy. Children raised in overly hygienic environments miss out on Th1 "training."
Exercise. Cold air. [1]
- Exercise-induced bronchoconstriction (EIB): Occurs 5–15 min after vigorous exercise, especially in cold, dry air. Mechanism: rapid airway cooling and drying → osmotic changes in airway lining fluid → mast cell degranulation → bronchospasm. Distinct from simple exertional dyspnoea (which occurs during exertion and resolves within 5 min of stopping). [5]
- Cold air: Direct mucosal cooling triggers vagal reflexes and mediator release
Airway inflammation — eosinophils, lymphocytes. Mucous hypersecretion, goblet cell hyperplasia. Smooth muscle constriction and hyperplasia. [1]
Three mechanisms combine to narrow the airway lumen:
| Mechanism | What Happens | Reversible? |
|---|---|---|
| 1. Bronchospasm | Smooth muscle constriction narrows lumen acutely | Yes (with bronchodilators) |
| 2. Mucosal inflammation + oedema | Eosinophils, T-lymphocytes infiltrate; submucosal oedema | Partly (with anti-inflammatory drugs) |
| 3. Mucus plugging | Goblet cell hyperplasia → hypersecretion → intraluminal mucus plugs | Yes (slowly, with anti-inflammatory treatment) |
| 4. Airway remodelling (chronic) | Smooth muscle hyperplasia, subepithelial fibrosis, wall thickening | No — irreversible component |
Why Airflow Obstruction Is Predominantly Expiratory
During inspiration, negative intrapleural pressure + radial traction from lung parenchyma pull airways open. During expiration, positive intrapleural pressure compresses airways. In asthma, already-narrowed airways collapse more easily during expiration → air trapping → hyperinflation. This is why wheezing is predominantly expiratory and why PEF (a measure of forced expiration) is reduced. [7]
Immunology of Asthma
The lecture shows two key immunological pathways:
IgE-Mediated Pathway (Type I Hypersensitivity)
Immunology of asthma: IgE [1]
- Allergen encountered by antigen-presenting cells (dendritic cells) in airway epithelium
- Allergen presented to naïve T-cells → differentiation into Th2 cells
- Th2 cells produce IL-4 → B-cell class switching to IgE production
- IgE binds to FcεRI on mast cells (sensitization)
- On re-exposure: allergen cross-links IgE on mast cells → degranulation → release of histamine, leukotrienes, prostaglandins → immediate bronchospasm (early phase, within minutes)
- Late phase (4–8 hours): recruitment of eosinophils, T-cells → sustained inflammation
Th2-Driven Pathway (Type 2-High Asthma)
Immunology of asthma: Th2. Type 2-high asthma. [1]
Key cytokines:
- IL-4: B-cell IgE switching; promotes Th2 differentiation
- IL-5: Eosinophil recruitment, activation, and survival (target of mepolizumab)
- IL-13: Mucus hypersecretion, goblet cell metaplasia, smooth muscle hyperreactivity, subepithelial fibrosis
- IL-33, TSLP, IL-25: Epithelial alarmins that activate ILC2 (innate lymphoid cells type 2) → amplify Type 2 response even without allergen-specific IgE
This dual pathway (IgE + Th2) explains why some patients are atopic (IgE-driven) while others are non-atopic but still eosinophilic (ILC2/Th2-driven without specific IgE).
Episodes of dyspnea, cough and wheeze. Episodes may be transient or prolonged. Worse at night or early hours of the morning. Some may present as persistent cough. [1]
Comprehensive clinical picture:
| Feature | Detail | Why It Happens |
|---|---|---|
| Wheeze | Polyphonic, expiratory, diffuse bilateral | Diffuse airway narrowing |
| Cough | Dry or minimally productive; may be sole symptom ("cough-variant asthma") | Airway inflammation irritates cough receptors |
| Dyspnoea | Episodic; with triggers | Variable airflow obstruction |
| Chest tightness | Often described as "band around chest" | Bronchospasm and hyperinflation |
| Nocturnal/early morning worsening | Classic diurnal variation | Circadian cortisol nadir + vagal tone peak + supine position → ↑bronchoconstriction |
| Trigger-related | After allergen exposure, exercise, cold air, viral URTI | Known trigger pathways |
| Signs of atopy | Eczema, allergic rhinitis | Shared Th2 pathway |
Cough-variant asthma: Some patients present with persistent cough as the only symptom — no audible wheeze. This is frequently missed. Think of it when a patient has chronic dry cough worse at night with normal CXR. Diagnosis: bronchodilator response or PEF variability. [1][5]
Generalized wheeze: COPD, bronchiectasis, bronchiolitis obliterans, viral bronchiolitis (children). Localized wheeze: tumour, foreign body. [1]
| Category | Conditions | Key Distinguishing Features |
|---|---|---|
| Generalized wheeze | Asthma | Variable, reversible, atopic history, young onset |
| COPD | Fixed obstruction, smoker, progressive, older | |
| Bronchiectasis | Chronic productive cough, purulent sputum, clubbing | |
| Bronchiolitis obliterans | Post-viral/transplant, irreversible, young adults | |
| Viral bronchiolitis (children < 2y) | RSV, seasonal, self-limiting | |
| Localized wheeze | Tumour | Fixed monophonic wheeze, smoker, haemoptysis |
| Foreign body | Sudden onset, unilateral, children | |
| Non-respiratory | Cardiac asthma (LVF) | Pulmonary oedema → bronchial mucosal congestion → wheeze; orthopnoea, PND, basal creps [8] |
Exam Trap: Cardiac Asthma
"Cardiac asthma" is wheezing caused by left heart failure, not true asthma. The mechanism is pulmonary oedema causing bronchial mucosal congestion and airway narrowing. Clues: older patient, cardiac history, orthopnoea/PND, raised JVP, bilateral basal creps, cardiomegaly on CXR. Do NOT give beta-agonists as sole treatment — treat the heart failure! [8]
Compatible history. Variable airflow obstruction: demonstrate presence of airflow obstruction, improvement in FEV1 or PEF after bronchodilator, diurnal variation in PEF or variation in PEF over a period of time. Nonspecific airway hyperresponsiveness — bronchial challenge test (not essential for diagnosis). [1]
Step-by-Step Diagnostic Approach
| Step | Method | Criteria |
|---|---|---|
| 1. Confirm obstruction | Spirometry | FEV1/FVC < 0.7 (obstructive pattern) |
| 2. Demonstrate reversibility | Post-bronchodilator spirometry | FEV1 increase ≥ 12% AND ≥ 200 mL after SABA |
| 3. PEF variability | Serial PEF measurements (BD for 2 weeks) | Diurnal PEF variability > 10% |
| 4. Bronchial challenge (if needed) | Methacholine or histamine challenge | PC20 < 8 mg/mL (positive = hyperresponsive) |
| 5. Trial of therapy | ICS for 4 weeks | Significant improvement in FEV1 or PEF supports diagnosis |
Practical notes on spirometry:
- Stop SABA ≥ 6 hours before testing; stop LABA ≥ 12 hours before
- Administer salbutamol 400 μg (4 puffs via spacer), repeat spirometry after 15 minutes
- A normal spirometry does NOT exclude asthma (the patient may be tested between episodes when airways are open)
PEF monitoring:
- Best done twice daily (morning and evening) for at least 2 weeks
- Variability = (highest PEF − lowest PEF) / mean PEF × 100
-
10% variability supports asthma
- The "morning dip" in PEF reflects nocturnal bronchoconstriction
Bronchial challenge test:
- Useful when spirometry is normal but clinical suspicion is high
- Methacholine inhalation in increasing doses; measure FEV1 after each dose
- Positive = PC20 (provocative concentration causing 20% fall in FEV1) < 8 mg/mL
- High sensitivity but lower specificity (positive in rhinitis, COPD, post-viral)
- Not essential for diagnosis — the lecture explicitly states this
10. Assessment — Severity and Control
Asthma severity is assessed retrospectively from the level of treatment required to control symptoms and exacerbations. Assess after patient has been on controller treatment for several months. Severity is not static. [1]
Mild asthma: well-controlled with Steps 1 or 2. Moderate asthma: well-controlled with Step 3. Severe asthma: requires Step 4/5 or remains uncontrolled despite this treatment. [1]
Critical Concept: Severity vs Control
Severity is NOT the same as control. Severity is a retrospective assessment of how much treatment is needed. Control is a real-time assessment of current symptoms and risk. A patient on Step 4 who is well-controlled has "severe but controlled" asthma. A patient on Step 2 with frequent symptoms has "mild but uncontrolled" asthma — likely due to poor adherence, not severity.
The lecture references the GINA Box 2-2B control assessment. The four key parameters assessed over the past 4 weeks are:
| Parameter | Well Controlled | Partly Controlled | Uncontrolled |
|---|---|---|---|
| Daytime symptoms > 2x/week | None of these | 1–2 of these | 3–4 of these |
| Night waking due to asthma | None of these | 1–2 of these | 3–4 of these |
| Reliever needed > 2x/week | None of these | 1–2 of these | 3–4 of these |
| Activity limitation | None of these | 1–2 of these | 3–4 of these |
Future risk factors (assessed separately): exacerbations, fixed airflow limitation, medication side effects.
Identify triggering factors — this is listed as a key part of assessment. [1]
11. Management
Treatment objectives: Complete control — no attacks, A&E visits or hospitalization; no symptoms or fewest possible; no limitation of activity; normal or near-normal lung function; least aerosol bronchodilator use; least side effects from medications. [1]
Management: Pharmacotherapy, Prevention, Patient education. [1]
11A. Pharmacotherapy — Two Groups of Drugs
Relievers: Bronchodilators. Preventors: Anti-inflammatory drugs. [1]
| Drug Class | Examples | Key Points |
|---|---|---|
| SABA | Salbutamol (Ventolin), Terbutaline (Bricanyl) | Inhaled > oral. Use when necessary. Side effects: tremor, headache, arrhythmia. Increased mortality with frequent use alone. [1] |
| LABA | Salmeterol (Serevent), Formoterol (Oxis) | Prolonged bronchodilation ~12 hours. Regular use. In combination with low-dose ICS (< 800 μg/day) as alternative to high-dose ICS. [1] |
| Xanthines | Theophylline | Narrow therapeutic window; bronchodilation + mild anti-inflammatory |
| Anticholinergics | Ipratropium (short-acting), Tiotropium (long-acting) | Block vagal bronchoconstriction; used as add-on in severe asthma |
SABA Monotherapy = Danger
The lecture explicitly states that frequent use of SABA alone increases mortality. GINA now recommends against SABA-only treatment even in mild asthma. The preferred approach is as-needed low-dose ICS-formoterol (SMART approach) or SABA with ICS taken whenever SABA is used. This is a high-yield exam point.
Why LABA must NEVER be used alone in asthma: LABA without ICS can mask worsening inflammation while providing symptomatic relief → paradoxically increases risk of fatal exacerbations. Always combine with ICS.
| Drug Class | Examples | Key Points |
|---|---|---|
| Inhaled Corticosteroids (ICS) | Beclomethasone (Becotide, Becloforte), Budesonide (Pulmicort), Fluticasone (Flixotide) | Improves symptom control, ↓exacerbations, ↓mortality, ↓lung function decline. Oral/systemic steroids for acute episodes. [1] |
| Cromones | Nedocromil sodium, Sodium cromoglycate | Mast cell stabilizers; mild effect; largely replaced by ICS |
| Leukotriene receptor antagonists (LTRA) | Montelukast, Zafirlukast | See detailed section below [1] |
| Anti-IgE | Omalizumab | See biologics section below [1] |
| Other biologics | Anti-IL5 (mepolizumab), Anti-IL5R (benralizumab), Anti-IL4Rα (dupilumab) | See biologics section below [1] |
ICS suppress airway inflammation by:
- Inhibiting transcription of pro-inflammatory cytokines (IL-4, IL-5, IL-13)
- Reducing eosinophil survival and activation
- Decreasing mucus secretion
- Reducing vascular permeability and oedema
- Preventing airway remodelling over time
Side effects of ICS:
- Local: oral candidiasis (thrush), dysphonia — minimized by rinsing mouth after use
- Systemic (high dose): adrenal suppression, osteoporosis, growth retardation in children, cataracts
Oral, once daily. Used in patients with mild to moderate asthma. Effective in exercise-induced bronchospasm. Effective in preventing aspirin-induced asthma, angioedema etc. Have steroid-sparing effect. Unmask previously undiagnosed Churg-Strauss Syndrome (or eosinophilic granulomatosis with polyangiitis). [1]
Why LTRAs can "unmask" Churg-Strauss: When a patient with undiagnosed EGPA (eosinophilic granulomatosis with polyangiitis) is on systemic steroids for severe asthma, the steroids suppress the vasculitis. When LTRA is added and steroids are reduced (steroid-sparing effect), the underlying EGPA becomes clinically apparent. The LTRA doesn't cause Churg-Strauss — it reveals it. This is a classic exam question.
Aspirin-exacerbated respiratory disease (AERD) / Samter's Triad:
- Asthma + chronic rhinosinusitis with nasal polyps + aspirin/NSAID sensitivity
- Mechanism: COX-1 inhibition → shunting of arachidonic acid into leukotriene pathway → ↑LTC4/LTD4 → severe bronchospasm
- LTRAs are particularly effective because they block the downstream leukotriene-mediated bronchospasm
Omalizumab (anti-IgE Ab): Indicated in moderate or severe asthma with suboptimal control despite maximal ICS/LABA ± LTRA or theophylline, or steroid-dependent asthma. Only for atopic asthma (with elevated IgE and positive skin prick test). Side effects: anaphylaxis. [1]
Anti-IL-5: mepolizumab — targeting eosinophilic asthma. Anti-IL-5R: benralizumab — targeting eosinophilic asthma. Anti-IL-4Rα (inhibiting IL-4 and IL-13 pathways): dupilumab — targeting eosinophilic asthma with raised FeNO. Biomarker-selected biologics. [1]
| Biologic | Target | Indication (Biomarker) | Key Point |
|---|---|---|---|
| Omalizumab | IgE | Elevated total IgE + positive skin prick test | Only for atopic asthma. Risk of anaphylaxis. |
| Mepolizumab | IL-5 | Blood eosinophils ≥ 300/μL | Reduces eosinophil-driven exacerbations |
| Benralizumab | IL-5 receptor | Blood eosinophils ≥ 300/μL | Depletes eosinophils via ADCC |
| Dupilumab | IL-4Rα (blocks IL-4 + IL-13) | Eosinophils ≥ 150/μL OR FeNO ≥ 25 ppb | Broadest eligibility; also used in eczema |
Biomarker-Selected Biologics — High Yield for 2025 SAQ
The 2025 SAQ (Q9) asks for: (a) reasons for suboptimal control, (b) two blood tests that may help select specific treatments — the answer is blood eosinophil count and serum IgE (± allergen-specific IgE), and (c) two cytokines that can be therapeutically targeted — answer: IL-5, IgE, IL-4, IL-13 (any two). [9]
The lecture references GINA 2023 stepwise treatment. [1]
| Step | Controller | Reliever | Severity Category |
|---|---|---|---|
| Step 1 | As-needed low-dose ICS-formoterol | As-needed low-dose ICS-formoterol | Mild |
| Step 2 | Low-dose ICS daily OR as-needed low-dose ICS-formoterol | As-needed SABA (with ICS) or ICS-formoterol | Mild |
| Step 3 | Low-dose ICS/LABA maintenance | As-needed ICS-formoterol | Moderate |
| Step 4 | Medium-dose ICS/LABA | As-needed ICS-formoterol | Severe |
| Step 5 | High-dose ICS/LABA + add-on (LTRA, theophylline, tiotropium) + phenotyping for biologics + low-dose OCS | As-needed ICS-formoterol | Severe |
Key principles:
- Step up if uncontrolled after checking adherence and technique
- Step down if well-controlled for ≥ 3 months (to find minimum effective dose)
- Before stepping up, always check: inhaler technique, adherence, trigger avoidance, comorbidities (rhinitis, GERD, obesity)
From senior notes and GINA: [5][10]
| Feature | Moderate | Severe | Life-Threatening |
|---|---|---|---|
| Speech | Talks in phrases | Talks in words | Cannot speak |
| Posture | Prefers sitting | Sits hunched forward | Drowsy, confused |
| HR | 100–120 | > 120 | Bradycardia |
| RR | Increased | > 30 | Paradoxical chest movement |
| Accessory muscles | No | Yes | Exhaustion |
| SpO₂ | 90–95% | < 90% | < 90% |
| PEF | > 50% predicted | ≤ 50% predicted | < 33% or unmeasurable |
| Wheeze | Moderate | Loud | Silent chest |
Silent Chest = Life-Threatening
A silent chest in a wheezing patient means airflow is so severely reduced that no wheeze can be generated. This is a pre-arrest sign. Do NOT be reassured by absence of wheeze in a severely dyspnoeic patient!
- Oxygen — target SpO₂ 93–95% (adults), 94–98% (children)
- Inhaled SABA — salbutamol via nebulizer (2.5–5 mg) or MDI + spacer (4–8 puffs), repeat every 20 min × 3
- Ipratropium bromide — add for severe exacerbation (0.5 mg nebulized)
- Systemic corticosteroids — prednisolone 40–50 mg PO or hydrocortisone 100 mg IV; give within first hour
- Magnesium sulphate IV — 2 g over 20 min for life-threatening exacerbation not responding to initial treatment
- Consider: IV aminophylline, IV salbutamol in ICU setting
- Reassess — if deteriorating despite above → ICU, consider intubation
12. Prevention and Patient Education
Encasement of mattresses, pillows and duvets with vinyl covers. Hot water wash of all bedding regularly < 2 weeks. Remove carpets. No stuffed toys. [1]
Why each measure works:
- Vinyl covers: Physical barrier preventing mite allergens from reaching the patient
- Hot water wash (≥ 60°C): Kills mites (lower temperatures don't)
- Remove carpets: Carpets harbor mites; hard floors are easier to clean
- No stuffed toys: Major mite reservoir in children's bedrooms
What is asthma. What are the triggers and how to avoid them. How the drugs work. How to use inhalers properly. Why is it necessary to use IS (inhaled steroids) regularly. What to do during an acute attack. When to contact a doctor or go to A&E. [1]
Inhaler technique is critical. Studies consistently show that most patients use inhalers incorrectly, leading to poor drug delivery and apparent treatment failure. Always check technique before stepping up treatment.
Written asthma action plan: Should include:
- Daily maintenance therapy
- How to recognize worsening (symptoms, PEF thresholds)
- What to do when worsening (step-up instructions)
- When to seek emergency care
Based on the 2025 SAQ Q9 and lecture content [1][9]:
- Poor inhaler technique — the #1 reason
- Poor adherence to regular ICS (patients stop when feeling well)
- Ongoing trigger exposure (allergens, smoking, occupational)
- Incorrect diagnosis (not actually asthma)
- Untreated comorbidities (allergic rhinitis, GERD, OSA, nasal polyps)
- Subtherapeutic drug dose
| Feature | Asthma | COPD |
|---|---|---|
| Age of onset | Usually < 40 | Usually > 40 |
| Smoking history | Not required | Almost always |
| Symptoms | Episodic, variable | Persistent, progressive |
| Airflow obstruction | Reversible | Largely irreversible |
| Diurnal variation | Prominent (worse at night) | Less prominent |
| Sputum | Scant, mucoid | Chronic, often purulent |
| Eosinophilia | Common | Less common (unless overlap) |
| Family history | Atopy | COPD, α1-antitrypsin deficiency |
| FEV1 reversibility | ≥ 12% + 200 mL | < 12% |
| Response to ICS | Good | Limited (unless overlap) |
Asthma-COPD Overlap (ACO): Some patients have features of both. Typically older asthmatic smokers or COPD patients with significant eosinophilia/reversibility. Manage with ICS/LABA (do not withhold ICS as you might in pure COPD).
From 2024 MCQ paper [11]:
| Finding | Most Likely Diagnosis |
|---|---|
| Wheezing during inspiration | Retrosternal goitre (extrathoracic obstruction → inspiratory stridor/wheeze) |
| Stony dull percussion note | Malignant pleural effusion |
| Bilateral fine basal crackles, JVP not raised | Idiopathic pulmonary fibrosis |
| Bronchial breath sound + increased vocal resonance | Pneumococcal pneumonia |
Trap: Inspiratory wheeze ≠ asthma. Think of extrathoracic obstruction (goitre, tumour, laryngeal narrowing).
16. Specific Past Paper Question Analysis
A 40-year-old lady had asthma on inhaled beclomethasone 250 mcg twice daily for the past 1 year. Which of the following would warrant increased dose of beclomethasone? A. Daytime symptoms once per week B. Nocturnal wheeze twice per month C. Raised fractional exhaled nitric oxide D. Raised serum IgE
Answer: C. Raised FeNO indicates ongoing Type 2 airway inflammation despite current ICS dose → warrants dose increase. Options A and B describe well-controlled asthma by GINA criteria. Raised IgE alone does not indicate poor control — it indicates atopic status (useful for biologic selection, not ICS dose).
45-year-old man, non-smoker, insidious onset of exertional dyspnoea, cough with mucoid sputum, works in brewery factory for 3 years.
Answer: B. Hypersensitivity pneumonitis. Brewery → organic antigens (barley dust, mold). Insidious onset over years = chronic HP. Chemical pneumonitis is acute. This is an allergic lung disease question adjacent to the asthma lecture.
32-year-old woman, allergic rhinitis since childhood, cough/chest tightness/wheeze × 1 year, on beclomethasone 100 mcg BD × 3 months, nocturnal awakenings 2×/week, daytime symptoms every morning, exercise limitation.
(a) Three common reasons for suboptimal control:
- Poor inhaler technique
- Poor adherence
- Ongoing allergen exposure / untreated comorbidity (allergic rhinitis)
(b) Two blood tests for selecting specific treatments:
- Blood eosinophil count
- Serum IgE (total ± allergen-specific)
(c) Two cytokines that can be therapeutically targeted:
- IL-5 (mepolizumab/benralizumab)
- IL-4/IL-13 (dupilumab) — or IgE (omalizumab)
(d) Three possible modifications of drug treatment:
- Step up to low-dose ICS/LABA combination (e.g., budesonide-formoterol)
- Add LTRA (montelukast)
- Increase ICS dose (Also acceptable: switch to MART regimen with ICS-formoterol; treat comorbid allergic rhinitis with intranasal steroids)
Likely Exam Questions
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A 25-year-old man with childhood eczema presents with episodic wheeze. Spirometry shows FEV1/FVC 65%, post-bronchodilator FEV1 increases by 15% and 250 mL. What is the most likely diagnosis? → Asthma (reversible obstruction + atopic history)
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Which of the following differentiates asthma from COPD? → Significant bronchodilator reversibility (≥ 12% AND ≥ 200 mL)
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A patient on montelukast for asthma develops purpuric rash, peripheral neuropathy, and eosinophilia. What is the most likely diagnosis? → EGPA (Churg-Strauss syndrome) unmasked by LTRA's steroid-sparing effect
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Which biologic requires positive skin prick test and elevated IgE for indication? → Omalizumab (anti-IgE)
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List the mechanisms of airflow obstruction in asthma (4 marks). → (1) Smooth muscle constriction/bronchospasm, (2) Mucosal inflammation and oedema, (3) Mucus hypersecretion/goblet cell hyperplasia, (4) Airway remodelling (smooth muscle hyperplasia, subepithelial fibrosis)
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State the GINA criteria for well-controlled asthma (4 marks). → In past 4 weeks: (1) Daytime symptoms ≤ 2×/week, (2) No night waking, (3) Reliever needed ≤ 2×/week, (4) No activity limitation
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A patient with poorly controlled asthma has blood eosinophils 500/μL. Name two appropriate biologics. → Mepolizumab (anti-IL5), Benralizumab (anti-IL5R) [also dupilumab if FeNO elevated]
High Yield Summary
Asthma = heterogeneous chronic airway inflammation with variable expiratory airflow limitation (GINA 2022). Classified as atopic (IgE-driven, early-onset) vs non-atopic (late-onset) and Type 2-high vs Type 2-low endotypes. Host risk factors: genetics, atopy, gender, obesity. Environmental factors: allergens (house dust mite most important in HK), tobacco smoke, air pollution, viral infections, exercise, cold air. The Hygiene Hypothesis explains why reduced microbial exposure increases atopy. Mechanisms of obstruction: bronchospasm + mucosal inflammation + mucus plugging ± remodelling. Diagnosis requires compatible history + variable airflow obstruction (bronchodilator reversibility ≥ 12% + 200 mL, PEF variability > 10%). Severity assessed retrospectively by treatment step needed (NOT by symptoms alone). Treatment: Relievers (SABA, LABA) + Preventors (ICS cornerstone, LTRA, biologics). SABA alone increases mortality. GINA Steps 1–5 with step-up/step-down. Biologics (omalizumab, mepolizumab, benralizumab, dupilumab) selected by biomarkers (IgE, eosinophils, FeNO). LTRA useful for exercise-induced asthma and aspirin-exacerbated respiratory disease; can unmask EGPA. Always check inhaler technique and adherence before stepping up. Patient education: triggers, inhaler use, action plan, when to seek emergency care.
Active Recall - Lecture Notes
[1] Lecture slides: GC 040. Cough and wheezing_asthma and allergic lung diseases.pdf (all pages) [2] Senior notes: Ryan Ho Fundamentals.pdf (p.55 - Adventitious Sounds) [3] Senior notes: Block A - I have an itchy rash (eczema, urticaria, tinea infection and psoriasis).pdf (p.22 - Atopic March) [4] Senior notes: Adrian Lui Pediatrics Notes.pdf (p.168 - Asthma) [5] Senior notes: Ryan Ho Respiratory.pdf (p.95-97 - Asthma) [6] Senior notes: Block A - Fundamentals of Allergology.pdf (p.3 - Atopy and IgE) [7] Senior notes: Adrian Lui Pediatrics Notes.pdf (p.155 - Pathophysiology of stridor/wheeze) [8] Senior notes: Ryan Ho Cardiology.pdf (p.60 - Cardiac asthma) [9] Past papers: 2025 Fourth Summative SAQ.pdf (Q9) [10] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p.187 - Asthma exacerbation severity) [11] Past papers: 2024 Fourth Summative MCQ.pdf (Q35, Q36, EMQ Q1-4)
GC039 Confused And Dehydrated: Hypercalcaemia; Hypocalcaemia
Hypercalcaemia and hypocalcaemia are disorders of calcium homeostasis that can present with confusion, dehydration, neuromuscular irritability, or cardiac dysrhythmias depending on whether serum calcium is pathologically elevated or reduced.
GC041 Cough In A Chronic Smoker: COPD; Smoking Cessation
Chronic obstructive pulmonary disease (COPD) is a progressive, largely irreversible airflow limitation caused by chronic inflammatory response to inhaled irritants—predominantly tobacco smoke—necessitating smoking cessation as the single most effective intervention to slow disease progression.