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.
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 responsiveness, 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 narrowed intrathoracic airways. It is most commonly expiratory because intrathoracic airways narrow during expiration (loss of radial traction). A predominantly inspiratory high-pitched sound is stridor until proved otherwise and points to upper/central airway obstruction; biphasic noise suggests a fixed central lesion. Polyphonic wheeze suggests diffuse narrowing (asthma, COPD), while a persistent monophonic wheeze suggests focal obstruction (tumour, foreign body). [2][14]
"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 and expiratory airflow fluctuate; this supports asthma but is not an exclusive asthma–COPD discriminator
- Expiratory airflow limitation — obstruction is worse on expiration
Why "variable"? Symptoms and expiratory airflow fluctuate spontaneously or with treatment. However, this is a pattern, not a binary test: asthma may have normal spirometry between attacks or persistent airflow limitation after remodelling, while COPD can also show a significant bronchodilator response. Diagnose from the whole clinical pattern plus objective testing; the size of one bronchodilator response does not by itself separate asthma from COPD. [14][19]
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/sensitization | Allergen-specific IgE or skin-prick sensitization present; total IgE may be elevated | No relevant allergic sensitization demonstrated |
| Onset (typical, not absolute) | 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.
Lecture-era data (GINA 2012): ~300 million affected individuals globally; prevalence 1–18%; ~250,000 deaths; 15 million DALYs lost annually. [1]
In Hong Kong, current wheeze decreased from 12.4% to 8.6% over 7 years in the historical ISAAC Phase Three comparison shown on the slide (published 2006). This is not a current prevalence estimate. [1]
Current context (GINA 2026): asthma affects over 260 million people and causes over 450,000 deaths each year worldwide; most deaths are considered preventable. Different estimates reflect different years, definitions and data sources, so retain the older numbers only when reproducing the lecture. [14]
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]
Reading the slide 9 graph: asthma prevalence rises stepwise across serum-IgE z-score bands, from almost zero in the lowest band to about 30% in the highest band. It demonstrates a strong population-level association, not a diagnostic cut-off for an individual.
Important nuance from allergology: high total IgE alone does not prove clinical allergy. Atopy is the tendency to make allergen-specific IgE to common environmental allergens; symptoms still need to correlate with exposure, and sensitization is assessed with skin-prick or specific-IgE testing. [6]
- Children: M > F (~2:1) — boys have smaller airways relative to lung size
- Adults: the historical age–sex graph shows the curves crossing after childhood, with female prevalence higher through much of early-to-middle adulthood; the plotted male line rises again in older age. Treat the shape as descriptive lecture data, not a universal age cut-off.
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
Allergen prevalence in Hong Kong adult asthmatics (skin prick test reactivity, n = 666): [1]
| Allergen | Approximate Prevalence |
|---|---|
| D. pteronyssinus (house dust mite) | ~63% |
| Cockroach | ~41% |
| Cat dander | ~24% |
| Dog hair | ~16% |
| Penicillium | ~13% |
| Ragweed pollen | ~16% |
| Grass pollen | ~7% |
This confirms that house dust mite is by far the dominant allergen in Hong Kong, followed by cockroach — both indoor allergens consistent with the subtropical urban environment.
- 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 clearly acts as a trigger for exacerbations and is also associated with asthma development; the causal contribution varies by pollutant, life stage and exposure pattern. Particulate matter (PM2.5, PM10), ozone, NO₂, and SO₂ are key pollutants. The slide's dose-response message is that greater exposure correlates with more admissions, A&E attendances and unscheduled visits. [1]
Parental smoking and childhood asthma — reading the forest plot: most point estimates lie to the right of an odds ratio of 1, although several confidence intervals cross 1; the pooled estimate shows a modest increased risk. This is a 1997 meta-analysis, so the visual teaches the direction and consistency of association rather than a current effect-size estimate. Avoiding tobacco smoke remains a key modifiable exposure. [1]
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]
Observational exposures associated with less allergy and asthma in the lecture: large family size, older siblings, day care, farming/animal/stable exposure, reported unpasteurized farm-milk exposure, and pet keeping. [1]
Interpretation: this is an epidemiological hypothesis, not a preventive prescription. Modern explanations extend beyond a simple Th1-versus-Th2 switch and include microbial diversity, epithelial-barrier and regulatory-immune effects. The associations are confounded by the wider farm environment and do not justify deliberately exposing a child to infection or allergens.
Raw Milk Is Not an Asthma-Prevention Strategy
The slide's unpasteurized-milk item is an observed association, not advice. CDC warns that raw milk can carry serious food-borne pathogens and recommends choosing pasteurized milk; possible allergy associations do not outweigh that infection risk. [18]
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 | Often incompletely reversible |
Reading the slide 21 histology panels:
- The low-power airway is nearly occluded by a dense mucus plug amid an inflamed, thickened wall.
- The transverse bronchial section has a small, irregular/stellate lumen with prominent mucosal folds and a thick smooth-muscle layer.
- The high-power epithelial panel highlights goblet-cell/mucous change and inflammatory wall thickening.
Together, the pictures explain why a bronchodilator treats only one part of acute obstruction: airway-wall inflammation and mucus plugging also need ICS-containing anti-inflammatory treatment.
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
- Epithelial cells are activated via TLR4 and PAR2 receptors → NF-κB activation → release of alarmins (TSLP, IL-33, IL-1)
- 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
Additional mediators from mast cells/basophils (from slide diagram): chymase, tryptase, MCPs, proteoglycans, PGD₂, histamine, serotonin, and cytokines. Vascular effects include plasma extravasation and vasodilation (early allergic reaction) followed by vessel wall priming (late allergic reaction). [1]
Viral exacerbation pathway: Plasmacytoid dendritic cells (pDCs) in asthmatic airways produce crippled type I interferon (IFN) responses, impairing antiviral defence and predisposing to viral exacerbations. [1]
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
Detailed Th2/ILC2 pathway (from slide 23): [1]
- TH2/ILC2 cells are Gata3⁺ and express IL-33R, TSLPR, and CRTH2 receptors
- IL-5 → eosinophil recruitment and release of EPO (eosinophil peroxidase), ECP (eosinophil cationic protein), EDN (eosinophil-derived neurotoxin) → tissue eosinophilia and airway remodelling
- IL-13 → goblet cell metaplasia, chemokine production, iNOS upregulation, and bronchial hyperreactivity
- IL-4 + IL-13 → vessel wall priming via endothelial adhesion molecules (ICAM-1, VCAM-1) facilitating leukocyte transmigration
- Histological hallmark: Charcot-Leyden crystals (from eosinophil breakdown) visible in airway tissue
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. Document expiratory obstruction | Spirometry | Reduced FEV1/FVC compared with the age-adjusted lower limit of normal (or the patient's baseline); a fixed 0.70 ratio is a COPD criterion and can misclassify younger or older patients [14] |
| 2. Demonstrate bronchodilator responsiveness | Post-bronchodilator spirometry | Adults: FEV1 or FVC increase ≥12% AND ≥200 mL; children: FEV1 increase ≥12% of predicted [14] |
| 3. PEF variability | Twice-daily PEF for 1–2 weeks | Average daily diurnal variability: adults > 10%, children > 13% [14] |
| 4. Bronchial provocation (if needed) | Methacholine, exercise or another standardized challenge | Methacholine: fall in FEV1 ≥20%; use protocol-specific thresholds [14] |
| 5. Response to ICS-containing therapy | Repeat lung function after 4 weeks | Adults: FEV1 increase ≥12% and ≥200 mL (or PEF ≥20%); interpret with the clinical picture [14] |
Practical notes on spirometry:
- If safe, withhold SABA for ≥4 hours and long-acting bronchodilators for 24–48 hours (molecule-dependent) to make a positive response more likely [14]
- Administer salbutamol 200–400 μg via spacer and repeat spirometry after 10–15 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
- At each session make three attempts and record the highest; use the same meter, because meters are not interchangeable
- For each day: variability = (day's highest − day's lowest) / mean of that day's highest and lowest × 100; average the daily values over 1–2 weeks
- The "morning dip" in PEF reflects nocturnal bronchoconstriction
PEF diary pattern — reading slides 27–29: slide 27 shows several mechanical peak-flow-meter designs; whichever design is used, follow the same technique and continue with the same meter. In slide 28, the paired AM/PM trace develops a marked trough (about 400 to 175 L/min) while the reliever-dose row rises from 0 to about 4 doses/day—symptoms, medication use and objective airflow worsen together. In slide 29, a labelled trial of prednisolone 30 mg daily is followed by a progressive rise from roughly 150 to 400 L/min over 1–2 weeks. This is a teaching example of treatment responsiveness, not a self-start steroid instruction. [1]
Bronchial challenge test:
- Useful when spirometry is normal but clinical suspicion is high
- Methacholine inhalation in increasing doses; measure FEV1 after each dose
- A ≥20% fall in FEV1 with a standardized methacholine protocol is consistent with airway hyperresponsiveness; the reported PC20 depends on the protocol
- 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 |
| SABA 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.
Current-use qualifier: the reliever-frequency item applies to people using a SABA reliever and excludes doses taken before exercise; it is not scored this way for an ICS-formoterol reliever. Symptom control and future risk must be assessed separately—a patient can report few symptoms yet remain at high risk because of a previous severe attack, low FEV1, SABA overuse, inadequate ICS or incorrect technique. [14]
GINA risk factor assessment protocol: Measure FEV₁ at the start of treatment, after 3–6 months of controller treatment (to record the patient's personal best), and then periodically for ongoing risk assessment. [1]
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]
The lecture's slides 34–37 use the older split of “bronchodilator relievers” versus “anti-inflammatory preventors” and place LABA, xanthines and anticholinergics together under relievers. Do not carry that classification into current prescribing.
| Current role | Examples | Key Points |
|---|---|---|
| Preferred anti-inflammatory reliever (Track 1) | Low-dose ICS-formoterol | In Steps 1–2 this is AIR-only; in Steps 3–5 it is also the reliever within MART. Only formoterol-containing ICS/LABA combinations have the rapid onset and evidence for this use. [14] |
| Alternative anti-inflammatory reliever (Track 2) | Low-dose ICS-SABA | Preferred Track 2 reliever in GINA 2026 where available; if unavailable, take low-dose ICS immediately after SABA at Step 1, or use SABA with regular maintenance ICS-containing therapy at Steps 2–5. [14] |
| SABA | Salbutamol, terbutaline | Rapid bronchodilation but no anti-inflammatory treatment. SABA-only asthma treatment is not recommended; oral SABA is not recommended because it is less effective and causes more adverse effects. [14] |
| LABA maintenance partner | Formoterol, salmeterol | Never use LABA without ICS in asthma. Salmeterol is not a reliever; formoterol is a reliever only when delivered in an evidence-based ICS-formoterol regimen. |
| Other add-ons | Ipratropium, tiotropium, theophylline | Ipratropium is an acute severe-exacerbation add-on; tiotropium is a maintenance LAMA add-on. Theophylline has low efficacy and a narrow therapeutic window and is not a routine reliever. [14] |
AIR, MART and the LABA Safety Rule
Every adult, adolescent and child aged 6–11 years with asthma should receive ICS-containing treatment. AIR-only means as-needed ICS-formoterol without daily maintenance treatment (Steps 1–2). MART means the same ICS-formoterol inhaler is used for both daily maintenance and symptom relief (Steps 3–5). “SMART” is an older synonym for MART. LABA monotherapy remains unsafe; do not assume every ICS/LABA inhaler can be used as a reliever. [14]
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]
Current correction: LTRAs are alternative/add-on controllers and are generally less effective than low-dose ICS for preventing exacerbations; they are not acute relievers. Montelukast carries an FDA boxed warning for serious neuropsychiatric events, so counsel about mood/behaviour change and weigh benefits against risks. [14][17]
Why LTRAs may appear to "unmask" EGPA: reports often followed steroid reduction in people whose previously suppressed eosinophilic vasculitis then became apparent. This explains a temporal association but should not be converted into the categorical claim that an LTRA can never contribute; new eosinophilia, neuropathy, rash, sinus disease or systemic features require evaluation.
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
- An LTRA can attenuate leukotriene-mediated respiratory symptoms in AERD, but it does not make aspirin/NSAID exposure safe and does not prevent aspirin-related angioedema or anaphylaxis. Avoid the culprit COX-1 inhibitor unless a specialist has performed/maintains aspirin desensitization.
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 | Severe-asthma phenotype / selection clue | Key Point |
|---|---|---|---|
| Omalizumab | IgE | Severe allergic asthma with sensitization and total IgE/body weight within the local dosing range | Anaphylaxis is uncommon but important; response is not predicted by total IgE level alone |
| Mepolizumab | IL-5 | Severe eosinophilic asthma | Higher blood eosinophils and prior exacerbations predict greater benefit |
| Benralizumab | IL-5 receptor | Severe eosinophilic asthma | Depletes eosinophils via antibody-dependent cell-mediated cytotoxicity |
| Dupilumab | IL-4Rα (blocks IL-4 + IL-13) | Severe Type 2/eosinophilic asthma, elevated FeNO or maintenance-OCS dependence | Also treats selected comorbid Type 2 disease |
| Tezepelumab | TSLP | Severe asthma, including patients without a mandatory single Type 2 biomarker | Higher eosinophils/FeNO still tend to predict greater response |
Do not memorize the former table's 150/300 cells/μL and FeNO 25 ppb as universal indication cut-offs. They are commonly used trial, response-prediction or payer thresholds, but licensed ages, biomarker requirements and funding rules vary by product and jurisdiction. GINA 2026 recommends checking local eligibility, then reviewing response after a therapeutic trial. [15]
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 — blood eosinophil count and serum IgE (± allergen-specific IgE), and (c) two cytokines that can be therapeutically targeted — IL-5, IL-4 or IL-13 (any two). IgE is a therapeutic target but is an immunoglobulin, not a cytokine. [9]
The slide reproduces the GINA 2023 adult/adolescent treatment figure. Preserve it as lecture-era examinable material, but use the current GINA 2026 distinctions below for clinical practice. [1][14]
| Step | Track 1 — preferred | Track 2 — alternative if Track 1 is not possible |
|---|---|---|
| Steps 1–2 | As-needed low-dose ICS-formoterol (AIR-only) | Step 1: as-needed low-dose ICS-SABA, or low-dose ICS immediately after SABA if the combination is unavailable. Step 2: daily low-dose ICS plus ICS-SABA/SABA reliever |
| Step 3 | Low-dose maintenance ICS-formoterol MART | Low-dose maintenance ICS/LABA plus ICS-SABA/SABA reliever |
| Step 4 | Medium-dose maintenance ICS-formoterol MART | Medium/high-dose maintenance ICS/LABA plus ICS-SABA/SABA reliever |
| Step 5 | Continue ICS-formoterol, refer for phenotype assessment and add-on therapy | Continue ICS/LABA, refer for phenotype assessment and add-on therapy; biologics/LAMA according to phenotype and eligibility |
Long-term maintenance oral corticosteroid is a last resort because even low cumulative exposure causes substantial harm; optimize inhaled treatment and consider biologics first. [14][15]
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)
GINA 2023 management cycle: The framework follows an Assess → Adjust → Review cycle: [1]
- Assess: Confirm diagnosis, evaluate symptom control and modifiable risk factors, comorbidities, inhaler technique, adherence, and patient preferences
- Adjust: Treat modifiable risk factors and comorbidities, apply non-pharmacological strategies, adjust medications (step up/down/between tracks), provide education and skills training
- Review: Monitor symptoms, exacerbations, side effects, lung function, comorbidities, and patient satisfaction
Current dual-track terminology: [14]
- Track 1 (preferred): as-needed low-dose ICS-formoterol is the reliever at every step; AIR-only at Steps 1–2 and MART at Steps 3–5.
- Track 2 (alternative): GINA 2026 prefers an ICS-SABA anti-inflammatory reliever where available. SABA is the fallback, coupled with ICS immediately afterward at Step 1 or regular maintenance ICS-containing treatment at Steps 2–5. Before choosing a SABA-reliever regimen, assess whether daily ICS adherence is likely.
Additional options printed below the lecture's GINA 2023 figure (limited indications or less evidence; verify against current/local guidance): [1]
- Step 2: Low-dose ICS whenever SABA taken, daily LTRA, or HDM sublingual immunotherapy (SLIT)
- Step 3: Medium-dose ICS, add LTRA, or add HDM SLIT
- Step 4: Add LAMA, LTRA, HDM SLIT, or switch to high-dose ICS
- Step 5: Add azithromycin (adults), LTRA, or anti-TSLP biologic; low-dose OCS only as last resort
Note on anti-TSLP: The GINA 2023 slide includes anti-TSLP (tezepelumab) alongside anti-IgE, anti-IL5/5R, and anti-IL4Rα as a Step 5 biologic option. [1]
The following lecture/senior-note categories are useful for rapid pattern recognition, but thresholds vary among protocols. Assess the whole patient, classify by the worst feature, start treatment while assessing, and repeat clinical status, SpO2 and lung function. Drowsiness/confusion, exhaustion, a silent chest or worsening hypoxemia requires immediate senior/ICU involvement. [5][10][14]
| 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!
- Controlled oxygen — titrate to SpO₂ 93–95% in adults/adolescents and at least 94% in children 6–11 years; do not default to unmonitored high-concentration oxygen. [14]
- Rapid inhaled bronchodilator — repeated salbutamol by pMDI + spacer is efficient for most exacerbations; use oxygen-driven nebulization for severe/near-fatal disease or when the patient cannot use a spacer effectively.
- Ipratropium bromide — add to SABA for severe exacerbations in acute care.
- Systemic corticosteroid early — give within the first hour when indicated. Oral prednisolone is as effective as IV corticosteroid and is preferred unless the patient cannot swallow, is vomiting, or requires ventilatory support. [14]
- IV magnesium sulfate selectively — not routine; consider a single 2 g infusion over 20 minutes after poor response to initial treatment with persistent hypoxemia/very low lung function. [14]
- Do not use routine IV aminophylline/theophylline — poor efficacy and potentially severe or fatal adverse effects. Routine IV beta2-agonist is also unsupported for most severe attacks. [14]
- Reassess and escalate — worsening despite intensive inhaled bronchodilator and corticosteroid treatment, altered consciousness, exhaustion or a silent chest warrants ICU transfer and preparation for ventilatory support. After recovery, prescribe ongoing ICS-containing treatment, an action plan and early follow-up. [14]
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]
This slide is a historical blanket checklist, not a current one-size-fits-all prescription. First establish both clinically relevant sensitization and ongoing exposure. NHLBI recommends a tailored multicomponent mitigation plan in that setting; allergen-impermeable pillow/mattress covers should not be used as the sole intervention, and routine mitigation is not recommended when there is no relevant sensitization/exposure. Practical components may include impermeable covers, regular laundering, humidity control and HEPA-filter vacuuming, selected according to the home and patient. [16]
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.
Reading the slide 48 device montage: the many shapes are not interchangeable packaging; they represent pMDIs, breath-actuated/dry-powder devices and large-volume spacers with different preparation, inspiratory-flow and coordination requirements.
| Device lesson | Practical teaching point |
|---|---|
| Pressurized MDI | Slow deep inhalation coordinated with actuation; use a spacer for ICS-containing medication when appropriate |
| Dry-powder/breath-actuated device | Usually needs a forceful, deep inhalation; do not exhale into the device |
| Spacer/holding chamber | Reduces coordination demands and oropharyngeal deposition; one actuation at a time, then inhale promptly |
| Any device | Demonstrate, then ask the patient to teach back; recheck at every review and after any device switch. Rinse and spit after ICS |
A nebulizer is a delivery system, not an intrinsically “stronger” drug. Choose a device the patient can operate correctly, can afford and will use. [14]
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 | Often childhood/young adulthood, but any age | Usually later adulthood |
| Exposure history | Not required; atopy/family history may support | Tobacco, biomass, occupational or other noxious exposure is common—not “almost always smoking” |
| Symptoms | Episodic, variable | Persistent, progressive |
| Airflow obstruction | Variable; may be normal between attacks or become persistent | Persistent post-bronchodilator obstruction, but day-to-day symptoms and bronchodilator response can still vary |
| Diurnal variation | Prominent (worse at night) | Less prominent |
| Sputum | Scant, mucoid | Chronic, often purulent |
| Eosinophilia | Common in Type 2 asthma, absent in Type 2-low disease | Can be present and may guide ICS use |
| Family history | Atopy | COPD, α1-antitrypsin deficiency |
| Bronchodilator response | Supports variable airflow when present, but may be absent on one test | Can also be significant; does not distinguish COPD from asthma [19] |
| ICS role | Essential ICS-containing treatment | Used for selected exacerbation-prone/eosinophilic COPD; if asthma coexists, an ICS-containing regimen is essential |
Coexisting asthma and COPD features: there is no single agreed “ACO syndrome” or diagnostic reversibility threshold. Document each diagnosis from its own clinical and spirometric evidence. If asthma is present or strongly suspected, avoid LABA monotherapy and ensure treatment includes ICS; then individualize additional long-acting bronchodilator therapy. [14][19]
High Yield Summary
- Asthma
- = heterogeneous chronic airway inflammation with variable expiratory airflow limitation. Classified by phenotype (e.g. allergic, eosinophilic, obesity-associated) and endotype (Type 2-high vs Type 2-low). Host/environmental factors include genetics, atopy, obesity, allergens, smoke, pollution, viral infection, exercise and cold air. Obstruction reflects bronchospasm + wall inflammation/oedema + mucus plugging ± remodelling. Diagnosis requires a compatible variable history plus objective excessive airflow variability; in adults, a bronchodilator rise in FEV1 or FVC ≥12% and ≥200 mL supports asthma, and average twice-daily PEF variability > 10% is another option. Severity is assessed retrospectively by treatment needed, not current symptoms alone. Current treatment is ICS-containing at every step: Track 1 uses low-dose ICS-formoterol as the reliever (AIR-only at Steps 1–2; MART at Steps 3–5), while Track 2 uses ICS-SABA where available or SABA only within an ICS-containing strategy. LABA is never used alone. Biologics are phenotype-selected, but exact biomarker eligibility is local. Always check diagnosis, technique, adherence, exposures and comorbidities before stepping up. [14][15]
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) [14] Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention, 2026 [15] GINA. Difficult-to-Treat & Severe Asthma in Adolescent and Adult Patients: Diagnosis and Management, 2026 [16] NHLBI/NAEPP. 2020 Focused Updates to the Asthma Management Guidelines — FAQs (indoor allergen reduction) [17] US FDA. Boxed warning for serious neuropsychiatric events with montelukast [18] US CDC. Raw Milk — Food Safety [19] Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for Prevention, Diagnosis and Management of COPD, 2026
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.