Asthma
Asthma is a chronic inflammatory airway disease characterized by reversible bronchoconstriction, bronchial hyperresponsiveness, and mucus hypersecretion leading to episodic wheezing, dyspnea, and cough.
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References
[1] Lecture slides: GC 040. Cough and wheezing_asthma and allergic lung diseases.pdf [2] Senior notes: Ryan Ho Respiratory.pdf (pp. 95–107) [3] Senior notes: Ryan Ho Critical Care.pdf (p. 13)
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. [1]
This is the GINA (Global Initiative for Asthma) definition — let's break it down from first principles:
- "Heterogeneous disease" → asthma is not one disease; it is an umbrella term for multiple phenotypes (atopic, non-atopic, eosinophilic, etc.) that share the final common pathway of variable airflow obstruction.
- "Chronic airway inflammation" → the inflammation is always there, even between attacks. This is why controller therapy (e.g., inhaled corticosteroids) is the backbone of management — you are treating the underlying inflammation, not just the symptoms.
- "Symptoms that vary over time and in intensity" → unlike COPD where symptoms are persistent and progressive, asthma symptoms wax and wane. A patient may be completely well between episodes.
- "Variable expiratory airflow limitation" → the key word is variable (and reversible). The obstruction changes — it can worsen with triggers and improve spontaneously or with bronchodilators. This is the hallmark that distinguishes asthma from fixed obstruction (e.g., COPD).
The hallmark of asthma is reversibility: FEV₁ increase ≥ 12% AND ≥ 200 mL after bronchodilator (SABA) treatment. [2][3]
Status asthmaticus = persistence of severe asthmatic airway obstruction despite appropriate acute therapy. Onset and progression may be rapid, potentially leading to asphyxiation (i.e., it can kill). [3]
Key Concept — Asthma vs COPD
Both are obstructive lung diseases, but asthma features variable and reversible airflow limitation with eosinophilic inflammation, while COPD features persistent and progressive (largely irreversible) airflow limitation with neutrophilic inflammation. However, the overlap entity "Asthma-COPD Overlap (ACO)" exists — ~20% of asthmatic patients eventually develop irreversible airflow obstruction (airway remodelling). [5]
- Global burden: ~300 million affected worldwide; ~15 million DALYs lost; ~250,000 deaths/year worldwide [2][4]
- Hong Kong prevalence: ~8.6% (with a decreasing trend) [2][4]
- Most common chronic respiratory disease overall [4]
- Age of onset: Can develop at any age, but ~75% are diagnosed before age 7 [2][3][4]
- New-onset asthma is less frequent in older adults
- Adult-onset subtypes include: occupational asthma, aspirin-sensitive asthma, eosinophilic asthma [3]
- Gender distribution [2][3][4]:
- Childhood: M > F ≈ 2:1 (boys have smaller airways relative to lung size → more symptomatic)
- Adulthood: M ≈ F (1:1)
- > 40 years: F > M (hormonal factors — oestrogen may promote airway inflammation and hyperresponsiveness; also, severe and uncontrolled asthma usually occurs in females [3])
- Ethnicity: Caucasians have higher prevalence rate than Chinese [3] — but this may partly reflect diagnostic/reporting differences and environmental exposures.
Risk Factors
Risk factors for asthma can be divided into host predisposition and environmental factors. An important clinical distinction exists between causes (factors that lead to the development of asthma) vs triggers (factors that provoke exacerbations in someone who already has asthma) — though these are often hard to distinguish. [1][2]
Host predisposition includes: Genetics, Atopy, Gender, Obesity [1]
| Factor | Detail | Mechanism |
|---|---|---|
| Genetics | Certain genes with ↑ risk: IL-3, IL-4, TNF-α, defects in genes encoding β-adrenoceptors and IFN-γ [2][3] | IL-4 drives Th2 differentiation and IgE production; defective β₂-receptors → decreased bronchodilation; defective IFN-γ → poor Th1 response → Th2 dominance |
| Atopy | ↑ asthma prevalence with ↑ serum IgE level; > 80% of asthmatics are atopic [2][3] | Predisposition to synthesize IgE to common environmental allergens → Type I hypersensitivity |
| Gender | M > F in childhood; F > M in adulthood [2][3] | Boys: smaller airways relative to lung size; Women: oestrogen may promote airway inflammation; severe/uncontrolled asthma more common in females |
| Obesity | More common and difficult to control if BMI > 30 kg/m² [2] | Poorer lung function (↓FRC from abdominal fat compressing diaphragm), more comorbidities, possible cytokine release from adipocytes (adipokines such as leptin promote inflammation) |
Environmental risk factors include allergens (indoor, outdoor, occupational), environmental tobacco smoke, outdoor air pollution, infection, and other triggers (exercise, cold air) [1][2]
| Factor | Detail | Mechanism / Pathophysiological Basis |
|---|---|---|
| Indoor aeroallergens | House dust mite (most important in HK — warm, humid climate ideal for mites), pets, cockroaches [1] | Fecal pellets contain proteases (e.g., Der p 1) that disrupt epithelial tight junctions → increased allergen penetration → IgE-mediated mast cell degranulation |
| Outdoor aeroallergens | Alternaria (a genus of Ascomycete fungi) [1] | Fungal spores are potent aeroallergens; protease activity similar to house dust mite |
| Occupational agents | Responsible for 5–15% of adult-onset asthma [1][2] | Isocyanates (paint sprays), flour dust (bakers), animal proteins (lab workers), wood dust — can act as sensitizers (→ IgE production) or irritants (→ direct airway damage) |
| Environmental tobacco smoke | Active or passive smoking [1][2] | Directly damages airway epithelium → increased permeability to allergens; promotes neutrophilic and eosinophilic inflammation; impairs mucociliary clearance |
| Outdoor air pollution | Mainly acts as a trigger rather than a cause [1][2] | Ozone, NO₂, particulate matter → oxidative stress → epithelial damage and inflammatory mediator release |
| Infection | Mainly acts as a trigger (esp. rhinovirus — most common trigger of acute exacerbation) [2][6] | Viral URTI → epithelial damage → exposure of sensory nerve endings → neurogenic inflammation; also disrupts epithelial barrier → increased allergen penetration |
| Exercise | Exercise-induced bronchoconstriction (EIB) [2] | Hyperventilation → airway cooling and drying → osmotic changes in airway surface liquid → mast cell degranulation → bronchoconstriction |
| Cold air | Another trigger [2] | Similar mechanism to exercise: airway cooling → mucosal oedema and mast cell degranulation |
| Drugs | Aspirin, beta-blockers [6] | Aspirin: inhibits COX-1 → shunts arachidonic acid metabolism towards lipoxygenase pathway → excess leukotriene production (LTC₄, LTD₄) → bronchoconstriction. Beta-blockers: block β₂-receptors on bronchial smooth muscle → unopposed cholinergic bronchoconstriction |
High Yield — Causes vs Triggers
"Causes vs Triggers?" is explicitly highlighted in the GC lecture slides [1]. Causes = factors that initiate asthma development (e.g., genetics, atopy, occupational sensitizers). Triggers = factors that provoke symptoms in an already-asthmatic patient (e.g., URTI, exercise, cold air, pollution). Some factors (e.g., allergens, tobacco smoke) can act as both.
This is a proposed explanation for why atopy and asthma are increasing in developed countries [4]:
- Observation: Childhood microbial exposure (larger family size, older siblings, day care attendance, farm animal contact, drinking unpasteurized milk, pet keeping) is associated with ↓ allergy and asthma.
- Mechanism: Reduced childhood Th1 activation (from fewer infections) → poor Th1 development → hyperactive Th2 system → overreaction to allergens (Type I hypersensitivity).
- Remember the Th1/Th2 balance: Th1 (IFN-γ, IL-12) fights intracellular pathogens; Th2 (IL-4, IL-5) drives IgE and eosinophil responses. They reciprocally inhibit each other. If Th1 is under-stimulated in childhood, Th2 dominates.
Anatomy and Relevant Functional Concepts
To understand asthma pathophysiology, you need to understand the structure you are dealing with:
- Asthma is primarily a disease of the small airways (bronchi and bronchioles, typically airways < 2 mm diameter), though larger airways are also involved.
- Layers of the airway wall (from inside out):
- Mucosa: pseudostratified ciliated columnar epithelium with goblet cells → produces mucus; cilia beat in coordinated waves to clear mucus (mucociliary escalator)
- Basement membrane: in asthma, this undergoes sub-epithelial fibrosis (thickening due to collagen deposition — a key feature of airway remodelling)
- Lamina propria: contains inflammatory cells (eosinophils, mast cells, lymphocytes in asthma)
- Smooth muscle layer: in asthma, undergoes hypertrophy and hyperplasia → exaggerated bronchoconstriction
- Submucosa: contains mucous glands (undergo hyperplasia in asthma → mucus hypersecretion)
- Adventitia: connective tissue
- Small airways lack cartilaginous support → they rely on radial traction from surrounding alveolar attachments to stay open.
- When inflammation causes mucosal oedema, smooth muscle contraction, and mucus plugging, small airways collapse easily → this is where the obstruction predominantly occurs.
- Expiratory airflow limitation: during expiration, positive intrathoracic pressure compresses airways. In asthma, the narrowed airways close prematurely → air trapping → hyperinflation.
Understanding this explains why certain drugs work:
| Nervous System | Receptor | Effect | Clinical Relevance |
|---|---|---|---|
| Parasympathetic (vagal) | Muscarinic (M₃) | Bronchoconstriction, mucus secretion | Anticholinergics (ipratropium) block this |
| Sympathetic | β₂-adrenergic | Bronchodilation, ↓ mast cell degranulation | β₂-agonists (salbutamol) stimulate this |
| Non-adrenergic non-cholinergic (NANC) | Substance P, neurokinin A (excitatory); VIP, NO (inhibitory) | Neurogenic inflammation (excitatory NANC) | Sensory nerve C-fibres exposed by epithelial damage → release substance P → bronchoconstriction, oedema |
Etiology and Pathophysiology
Immunological Basis of Atopic Asthma (Type I Hypersensitivity)
This is the most common mechanism — understanding it is essential.
- Naïve CD4⁺ T cells (Th0) are activated by interaction with antigen presented by MHC class II on antigen-presenting cells (dendritic cells in the airway epithelium).
- Further differentiation depends on the cytokine milieu:
- Th1 differentiation (facilitated by IFN-γ, IL-12) → promotes cell-mediated immunity → ↑ macrophage, neutrophil, CD8⁺ T cell activity → eliminates intracellular bacteria and viruses
- Th2 differentiation (facilitated by IL-4, IL-5) → promotes humoral immunity → ↑ IgE production, mast cell and eosinophil recruitment, growth and differentiation → eliminates extracellular pathogens (e.g., parasites)
- Reciprocal inhibition → the immune system is directed towards a particular response. In atopic asthma, there is Th2 dominance.
| Phase | Timing | Mediators | Effects |
|---|---|---|---|
| Early (Immediate) Phase | Within minutes of allergen exposure | Histamine, leukotrienes (LTC₄, LTD₄, LTE₄), prostaglandin D₂, tryptase | Bronchoconstriction (smooth muscle contraction), mucosal oedema (↑ vascular permeability), mucus secretion |
| Late Phase | 4–8 hours after exposure | Eosinophils (major basic protein, eosinophil cationic protein), Th2 cytokines (IL-4, IL-5, IL-13), neutrophils | Sustained inflammation, epithelial damage, further bronchoconstriction, airway hyperresponsiveness. This phase is responsible for the prolonged symptoms and is what ICS targets. |
Why ICS is the cornerstone of asthma therapy
Inhaled corticosteroids suppress the late-phase inflammatory response — reducing eosinophilic infiltration, cytokine production, and epithelial damage. Bronchodilators (SABA) only treat the early-phase bronchoconstriction. That's why a patient who only uses a reliever (SABA) without a controller (ICS) has poorly controlled asthma — the underlying inflammation rages on.
Pathophysiology of Asthmatic Symptoms — The Triad
The disease is characterized by acute inflammation on a background of chronic inflammation and airway remodelling [4]:
Three pathological processes narrow the airway lumen:
| Process | Mechanism | Contribution |
|---|---|---|
| Bronchospasm | Smooth muscle contraction triggered by mediators (histamine, leukotrienes, acetylcholine from vagal reflex) | Most rapidly reversible component — responds to SABA |
| Mucosal oedema | Increased vascular permeability from inflammatory mediators → plasma leaks into airway wall | Takes hours to resolve — responds to corticosteroids |
| Mucus plugging | Goblet cell hyperplasia + mucous gland hypertrophy → thick, tenacious mucus; shedded epithelial cells (Creola bodies) and inflammatory debris form mucus plugs | Most dangerous in severe/fatal asthma — can completely occlude airways |
- Eosinophils are the hallmark inflammatory cell (in Type 2/Th2-high asthma)
- Release major basic protein (MBP) and eosinophil cationic protein (ECP) → directly toxic to airway epithelium
- Mast cells reside in the airway mucosa, loaded with IgE
- Th2 lymphocytes orchestrate the response via IL-4, IL-5, IL-13
- Epithelial cells are both victims (damaged by eosinophils) and active participants (release alarmins: TSLP, IL-25, IL-33 → activate type 2 innate lymphoid cells, ILC2s)
- Occurs with chronic, poorly controlled asthma over years
- Can potentially lead to irreversible airway remodelling → progressive loss of lung function [6]
- Components:
| Remodelling Feature | What Happens | Consequence |
|---|---|---|
| Sub-epithelial fibrosis | Collagen deposition below the basement membrane (reticular basement membrane thickening) | Airway wall stiffening |
| Smooth muscle hypertrophy and hyperplasia | Smooth muscle mass increases | Exaggerated bronchoconstriction |
| Goblet cell metaplasia / mucous gland hyperplasia | More mucus-producing cells | Chronic mucus hypersecretion |
| Angiogenesis | New blood vessel formation in airway wall | ↑ oedema, ↑ inflammatory cell recruitment |
| Loss of epithelial integrity | Chronic damage and incomplete repair | ↑ permeability to allergens, ↑ sensitivity of sensory nerves |
This is why early and adequate ICS treatment is so important — it prevents or slows remodelling.
- Individuals with no evidence of atopy (normal IgE, negative skin prick tests) [2][6]
- Usually adult-onset
- Often triggered by respiratory infections and inhaled air pollutants [2]
- Mostly eosinophilic (i.e., still responds to ICS in many cases) [6]
- Pathogenesis less well understood — may involve:
- Epithelial cell-derived alarmins (TSLP, IL-25, IL-33) activating ILC2s → eosinophilic inflammation without IgE
- Viral infection-triggered inflammation
- Autonomic nervous system dysregulation
Drug-Induced Asthma
- Also known as Samter's triad (or Widal's triad): Asthma + Nasal polyps + Aspirin sensitivity [6]
- Mechanism: Aspirin inhibits COX-1 → shunts arachidonic acid metabolism from the prostaglandin pathway towards the 5-lipoxygenase pathway → excess production of cysteinyl leukotrienes (LTC₄, LTD₄, LTE₄) → potent bronchoconstriction + mucosal oedema
- Cross-reacts with all NSAIDs that inhibit COX-1 (not specific to aspirin)
- Leukotriene receptor antagonists (LTRAs, e.g., montelukast) are particularly useful in this phenotype
- Mechanism: Non-selective beta-blockers (e.g., propranolol) block β₂-receptors on bronchial smooth muscle → removes the tonic bronchodilatory effect of circulating adrenaline → unopposed cholinergic bronchoconstriction
- Even cardioselective beta-blockers (e.g., atenolol, bisoprolol) should be used with caution in asthmatics
- Responsible for 5–15% of adult-onset asthma [1][2]
- Two types:
- Sensitizer-induced: requires a latency period (weeks to years); involves immunological sensitization (IgE-mediated or cell-mediated). Examples: isocyanates, flour dust, animal proteins, latex.
- Irritant-induced (Reactive Airways Dysfunction Syndrome, RADS): occurs after a single, high-level exposure to an irritant; no latency period.
- Key clinical clue: symptoms improve on days away from work (weekends, holidays) and worsen on return.
Classification
Asthma is a heterogeneous disease [1] — multiple phenotypes exist:
| Phenotype | Key Features |
|---|---|
| Atopic (Extrinsic) Asthma | Type I HSR (↑ serum IgE), eosinophilic (responsive to ICS), most common phenotype in children, better prognosis with newer treatment (e.g., biologics) [6] |
| Non-Atopic (Intrinsic) Asthma | Normal IgE, mostly eosinophilic, usually adult-onset [6] |
| Drug-induced Asthma | Provoked by aspirin/NSAIDs or beta-blockers [2] |
| Occupational Asthma | Provoked by occupational sensitizers or irritants [1][2] |
| Exercise-Induced Bronchoconstriction (EIB) | Bronchoconstriction triggered by exercise; may occur in isolation or as part of asthma |
| Obesity-Related Asthma | BMI > 30; more symptomatic, less eosinophilic, less responsive to ICS |
| Late-Onset Eosinophilic Asthma | Adult-onset, often non-atopic, high blood/sputum eosinophils, may require biologics (anti-IL-5) |
| Endotype | Pathway | Biomarkers | Treatment Implications |
|---|---|---|---|
| Type 2 (T2)-High | Th2 / ILC2 driven; IL-4, IL-5, IL-13 | ↑ blood eosinophils ( ≥ 150/μL), ↑ FeNO ( ≥ 20 ppb), ↑ serum IgE | Good response to ICS; candidates for biologics (omalizumab, mepolizumab, dupilumab) |
| Type 2 (T2)-Low | Neutrophilic or paucigranulocytic | Normal eosinophils, normal FeNO | Poor response to ICS; may respond to macrolides, bronchial thermoplasty |
High Yield — T2-High vs T2-Low
The T2-high/T2-low distinction is critical for selecting add-on therapies in severe asthma. T2-high patients are candidates for biologics targeting IgE (omalizumab), IL-5/IL-5R (mepolizumab/benralizumab), or IL-4Rα (dupilumab). T2-low patients have fewer targeted options and represent an area of active research.
Assessment of severity of exacerbation [3]:
| Parameter | Moderate Exacerbation | Severe Exacerbation | Life-Threatening |
|---|---|---|---|
| Clinical presentation | Appears calm; Talks in phrases; Prefers sitting to lying | Appears agitated; Talks in words; Sits hunched forward | Drowsy, confused, or silent chest |
| Pulse rate | 100–120/min | > 120/min | Bradycardia (ominous) |
| Respiratory rate | ↑ | ↑↑ > 30/min | Poor respiratory effort |
| Use of accessory muscles | No | Yes | Paradoxical thoracoabdominal movement |
| SpO₂ | 90–95% | < 90% | < 90% |
| PEF | > 50% predicted/best | ≤ 50% predicted/best | < 25% predicted/best |
| ABG | — | — | PaCO₂ normal or ↑ (exhaustion), PaO₂ < 60 mmHg |
Critical Concept — The 'Normal' PaCO₂ in Acute Asthma
In an acute asthma attack, the patient hyperventilates → PaCO₂ should be LOW (respiratory alkalosis). If PaCO₂ is normal or rising in a patient who is still wheezing and tachypnoeic, this means the patient is tiring and heading towards respiratory failure. A "normal" PaCO₂ in acute asthma is a RED FLAG — consider ICU admission and possible intubation.
- Episodes characterized by:
- Progressive ↑ in symptoms of SOB, cough, wheezing or chest tightness (AND)
- Progressive ↓ in lung function or expiratory flow (PEF or FEV₁)
Clinical Features
Characteristic respiratory symptoms: wheeze, dry cough, SOB, decreased exercise tolerance, chest tightness [6]
| Symptom | Pathophysiological Basis |
|---|---|
| Wheeze (polyphonic, expiratory > inspiratory) | Turbulent airflow through narrowed airways (bronchospasm + mucosal oedema + mucus). Polyphonic = multiple airways of different calibres narrowed simultaneously (vs monophonic in focal obstruction). Predominantly expiratory because positive intrathoracic pressure during expiration further narrows already-obstructed airways. |
| Dry cough (non-productive, or minimal clear sputum) | Stimulation of cough receptors (rapidly adapting receptors, C-fibres) in the airway epithelium by inflammatory mediators (histamine, leukotrienes, prostaglandins) and by mechanical irritation from mucosal oedema. Cough may be the sole presenting symptom ("cough-variant asthma"). |
| Shortness of breath (SOB / Dyspnoea) | Increased work of breathing due to airway narrowing → air trapping → dynamic hyperinflation (lungs over-inflated, diaphragm flattened, mechanically disadvantaged). Also, V/Q mismatch → ↓ PaO₂ → stimulation of peripheral chemoreceptors. |
| Decreased exercise tolerance | Increased airway resistance during exercise → increased work of breathing; exercise-induced bronchoconstriction (EIB) from airway cooling/drying. |
| Chest tightness | Hyperinflation stretches the chest wall → sensation of tightness. Also, bronchospasm stimulates sensory nerve endings in the airway wall. |
Key Symptom Patterns
- Diurnal pattern: worse at night or on waking [6]
- Why? Circadian variation: cortisol levels are lowest at ~4 AM → less endogenous anti-inflammatory effect; vagal tone is highest at night → more bronchoconstriction; supine position → pooling of secretions and reduced lung volumes; sleep-related reduction in minute ventilation.
- Triggers: URTI (rhinovirus), exercise, allergens (bed sheets, pets, dust/pollen), cold air, drugs (e.g., aspirin, beta-blockers), smoking [6]
- Seasonal variation: symptoms may worsen during pollen season (spring/autumn) or in cold/dry weather.
- Episodic: symptom-free intervals between attacks (unlike COPD which is persistent).
- Personal or family history of atopy: eczema, allergic rhinitis, food allergy — the "atopic march" (eczema → food allergy → allergic rhinitis → asthma, typically in childhood). [6]
Cough-Variant Asthma
Some patients present with chronic cough as the only symptom — no wheeze, no SOB. This is "cough-variant asthma." It should be suspected in patients with chronic dry cough (especially nocturnal), positive bronchoprovocation test, and response to ICS. It's a common exam question.
| Sign | Pathophysiological Basis |
|---|---|
| Expiratory polyphonic wheeze on auscultation | Multiple airways of varying calibre narrowed → turbulent flow produces musical sounds of different pitches |
| Prolonged expiratory phase | Air trapping — narrowed airways take longer to empty |
| Tachypnoea | Compensatory increase in respiratory rate to maintain minute ventilation despite reduced tidal volume (from hyperinflation) |
| Tachycardia | Sympathetic activation from hypoxia, increased work of breathing, and anxiety; also, β₂-agonist use causes reflex tachycardia |
| Use of accessory muscles (sternocleidomastoid, scalenes, intercostals) | In severe obstruction, the diaphragm is flattened by hyperinflation and mechanically disadvantaged → accessory muscles recruited to generate sufficient negative intrathoracic pressure for inspiration |
| Intercostal/subcostal/suprasternal recession | Exaggerated negative intrathoracic pressure during inspiration in severe obstruction → chest wall is pulled inward |
| Hyperinflated (barrel) chest | Chronic air trapping → ↑ residual volume → increased AP diameter of chest (more common in chronic severe asthma or COPD) |
| Hyperresonant percussion | Air trapping → hyperinflated lungs transmit percussion force more efficiently |
| Reduced breath sounds | Severely narrowed airways → reduced airflow → quieter breath sounds. A "silent chest" is ominous — it means airflow is so severely reduced that no wheeze can be generated. |
| Pulsus paradoxus ( > 10 mmHg drop in systolic BP during inspiration) | Exaggerated negative intrathoracic pressure during inspiration → ↑ venous return to right heart → RV distension → interventricular septum bows into LV → ↓ LV filling → ↓ stroke volume → ↓ systolic BP during inspiration. Significant in severe asthma. |
| Central cyanosis (late sign) | Severe V/Q mismatch and shunt → ↓ PaO₂ → ↑ deoxyhaemoglobin > 5 g/dL in arterial blood |
| Tripod position / sitting hunched forward | Optimizes accessory muscle mechanics; patient instinctively positions to maximise diaphragmatic and accessory muscle efficiency |
Signs of Atopy (look for these in a clinical exam)
- Allergic shiners: dark discolouration under the eyes (venous congestion from chronic nasal congestion)
- Dennie-Morgan lines: extra skin folds below the lower eyelids (associated with atopy)
- Nasal crease: transverse crease across the nose from habitual rubbing ("allergic salute")
- Nasal polyps: especially in adults with aspirin-sensitive asthma (Samter's triad)
- Eczematous skin changes: flexural lichenification (if concomitant atopic dermatitis) [7]
Silent Chest — Exam Must-Know
A "silent chest" in acute asthma is a life-threatening sign. It does NOT mean the patient is getting better — it means airflow is so severely reduced that there is insufficient air movement to generate wheeze. This patient needs immediate ICU escalation, IV magnesium sulphate, and consideration for intubation.
- Chronic sinusitis (Samter's triad) — asthma + nasal polyps + aspirin sensitivity
- Obstructive sleep apnoea (OSA) — upper airway inflammation; obesity link
- Obesity — both a risk factor and comorbidity
- GERD — reflux of gastric acid can trigger vagal-mediated bronchoconstriction; also, microaspiration of acid damages airway epithelium
- Allergic rhinitis — "one airway, one disease" concept; treating allergic rhinitis improves asthma control
- Anxiety and depression — common in chronic disease; can worsen symptom perception and adherence
- House dust mite is the most important allergen in Hong Kong due to the warm, humid subtropical climate — ideal for mite proliferation.
- Cockroach allergens are significant in Hong Kong's dense urban housing.
- Outdoor air pollution (high levels of NO₂, PM₂.₅ from traffic and cross-border pollution) acts as a major trigger.
- Occupational asthma: relevant occupations in HK include textile workers, bakers, healthcare workers (latex), electronics manufacturing workers.
- Chinese herbal medicine: some patients self-medicate with Chinese herbal preparations that may contain corticosteroids or unknown compounds — important to ask about in the history.
- Prevalence: ~8.6% (declining trend), but asthma remains the most common chronic respiratory disease.
High Yield Summary
Definition: Asthma = heterogeneous disease, chronic airway inflammation, variable and reversible expiratory airflow limitation (GINA).
Epidemiology: 300M worldwide, 8.6% HK, 75% diagnosed < 7yo, M > F in children, F > M in adults.
Risk Factors: Host (genetics, atopy, gender, obesity) + Environmental (allergens [indoor: HDM, pets, cockroaches; outdoor: Alternaria; occupational 5-15%], tobacco, air pollution, infection, exercise, cold air, drugs [aspirin, beta-blockers]).
Pathophysiology: Th2-dominant immune response → IgE → mast cell sensitization → early phase (histamine, leukotrienes → bronchospasm) + late phase (eosinophils → chronic inflammation → airway remodelling). Three components of airway narrowing: bronchospasm + mucosal oedema + mucus plugging.
Classification: Atopic (↑IgE, eosinophilic, children) vs Non-atopic (normal IgE, adult-onset) vs Drug-induced vs Occupational. T2-high vs T2-low endotype. Exacerbation severity: moderate → severe → life-threatening (silent chest, normal/rising PaCO₂ = RED FLAGS).
Clinical Features: Wheeze + dry cough + SOB + chest tightness, worse at night, triggered by URTI/exercise/allergens/cold/drugs. Signs: polyphonic expiratory wheeze, prolonged expiration, tachypnoea, accessory muscle use, hyperinflation. Silent chest = life-threatening.
Comorbidities: Allergic rhinitis, chronic sinusitis (Samter's triad), GERD, obesity, OSA.
Active Recall - Asthma (Definition, Epidemiology, Risk Factors, Pathophysiology, Classification, Clinical Features)
[1] Lecture slides: GC 040. Cough and wheezing_asthma and allergic lung diseases.pdf (pp. 3, 7, 12, 14) [2] Senior notes: Ryan Ho Respiratory.pdf (pp. 95) [3] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (pp. 187, 189) [4] Senior notes: Adrian Lui Pediatrics Notes.pdf (pp. 168–169) [5] Senior notes: Ryan Ho Respiratory.pdf (p. 107 — Asthma-COPD overlap) [6] Senior notes: Maksim Medicine Notes.pdf (p. 295) [7] Senior notes: Ryan Ho Rheumatology.pdf (p. 113 — Atopic Dermatitis)
Differential Diagnosis of Asthma
Asthma is a clinical diagnosis — there is no single gold-standard test. This means you must always consider what else could be causing the patient's wheeze, cough, and dyspnoea. The key question is: "Is this really asthma, or is something else mimicking it?"
The approach to the DDx depends on the presenting symptom pattern:
- Generalized wheeze → conditions affecting multiple airways diffusely
- Localized wheeze → focal airway obstruction (think tumour or foreign body)
- Chronic cough (with or without wheeze) → broader DDx including upper airway, GI, and cardiac causes
- Dyspnoea with airflow obstruction → other obstructive lung diseases
The GC lecture slides categorize the differential diagnosis of cough and wheeze as follows: [1]
Generalized wheeze:
- Chronic obstructive lung disease
- Bronchiectasis
- Bronchiolitis obliterans
- Viral bronchiolitis (children)
Localized wheeze:
- Tumour
- Foreign body
This is the highest-yield framework for the in-house exam. Let's now expand each DDx with differentiating features and explain why each can mimic asthma.
Detailed DDx Table — Conditions Mimicking Asthma
| Differential | Why It Mimics Asthma | Key Differentiating Features | Pathophysiological Basis for Differentiation |
|---|---|---|---|
| COPD | Also presents with chronic dyspnoea, cough, and airflow obstruction [2][3] | Usually a chronic smoker ( > 20 pack-years) with persistent SOB without much diurnal variation; incompletely reversible on spirometry (post-BD FEV₁/FVC remains < 0.7); often co-exists with asthma as asthma-COPD overlap (ACO) [2] | COPD has fixed structural damage (emphysema + small airway fibrosis) → obstruction is persistent and progressive, unlike asthma's variable, reversible obstruction. Neutrophilic inflammation predominates (vs eosinophilic in asthma). |
| Bronchiectasis | Also associated with chronic dyspnoea, cough, and airflow obstruction; recurrent infections [2][4] | Usually presents with prominent cough with mucopurulent sputum production ± haemoptysis; finger clubbing (absent in uncomplicated asthma); diagnosed by CXR/HRCT demonstrating airway dilatation ("tram-line" appearance) [2][4]; often non-smokers with symptoms dating back to childhood [3] | Bronchiectasis involves permanent, irreversible dilatation of bronchi from transmural inflammation and wall destruction → chronic sputum production and recurrent infections. Asthma has narrowed (not dilated) airways. |
| Bronchiolitis obliterans | Presents with dyspnoea and obstructive pattern on spirometry [3][5] | Inflammation of small airways (bronchioles) leading to obstruction; associated with small airway injury due to post-viral infection, autoimmune diseases, lung or haematopoietic transplantation, and inhalational agents; irreversible with inhaled bronchodilators [3][5] | Submucosal and peribronchiolar fibrosis leads to fixed narrowing of bronchiolar lumen → no reversibility (unlike asthma). The obstruction is structural, not due to bronchospasm or mucosal oedema. |
| Viral bronchiolitis (children) | Wheezing and respiratory distress in young children, may look exactly like asthma in the acute setting [1][5] | Typically < 2 years old (especially < 1 year); first episode of wheezing (asthma is recurrent by definition); caused by RSV (most common) or other respiratory viruses; preceded by coryzal prodrome; fine inspiratory crackles often more prominent than wheeze | Viral infection causes direct epithelial necrosis and oedema in the smallest airways (bronchioles) → obstruction. In asthma, the mechanism is Th2-mediated inflammation with bronchospasm. Bronchiolitis is a single-episode disease; recurrent wheezing episodes suggest asthma. |
| Differential | Why It Mimics Asthma | Key Differentiating Features | Pathophysiological Basis for Differentiation |
|---|---|---|---|
| Tumour (central airway obstruction) | Can cause dyspnoea and wheezing [1][2][4] | Monophonic wheeze (single pitch from single-point obstruction) vs asthma's polyphonic wheeze; exertional dyspnoea; spirometry shows obstructive pattern but flow-volume loop is characteristic for upper airway obstruction (expiratory plateau) [4]; may have haemoptysis, weight loss, hoarseness (recurrent laryngeal nerve involvement) | A tumour (luminal or extraluminal) causes fixed, focal airway narrowing → monophonic wheeze that doesn't change with bronchodilators. Asthma causes diffuse, variable narrowing of multiple airways → polyphonic wheeze that responds to SABA. |
| Foreign body aspiration | Acute onset of wheeze and cough, especially in children [5] | Localized unilateral wheeze instead of generalized wheeze; expiratory CXR should be taken when foreign body aspiration is suspected since the unilateral hyperinflation may be more apparent on the expiratory film [5]; sudden onset; history of choking episode; may present with recurrent pneumonia in the same lobe | Foreign body lodges in one bronchus → ball-valve mechanism: air enters past the FB on inspiration but gets trapped on expiration → unilateral hyperinflation and localized wheeze. Asthma is bilateral and diffuse. |
Monophonic vs Polyphonic Wheeze — Exam Must-Know
Polyphonic wheeze (multiple pitches) = multiple airways of different sizes narrowed simultaneously → think diffuse disease (asthma, COPD). Monophonic wheeze (single pitch, fixed) = single-point obstruction → think focal lesion (tumour, foreign body). This distinction is a classic exam question.
These are conditions that may present with similar symptoms (cough, dyspnoea, wheeze) but have different underlying mechanisms:
| Differential | Why It Mimics Asthma | Key Differentiating Features |
|---|---|---|
| Acute bronchiolitis [5] | Wheeze and dyspnoea in infants/toddlers | Age < 2 years, first episode, RSV, coryzal prodrome, fine crackles |
| Pneumonia [5] | Cough, dyspnoea, wheeze possible | Fever, productive cough with purulent sputum, focal crackles/bronchial breathing on auscultation, CXR consolidation |
| GERD [5][6] | Chronic cough ± wheeze, worse at night (supine position) | Heartburn, acid brash, post-prandial symptoms; mechanism: micro-aspiration of gastric acid → airway irritation + vagal-mediated reflex bronchoconstriction; may co-exist with asthma (comorbidity) |
| Bronchopulmonary dysplasia (BPD) [5] | Chronic respiratory symptoms with wheeze in infants | History of prematurity (typically < 28 weeks gestation, required prolonged supplemental O₂/ventilation); CXR shows characteristic changes |
| Primary ciliary dyskinesia (PCD) [5] | Chronic cough, wheeze, recurrent infections | Recurrent infections (sinopulmonary); situs inversus in ~50% (Kartagener's syndrome); diagnosis by nasal NO measurement + electron microscopy of cilia |
| Cystic fibrosis (CF) [5] | Chronic cough, wheeze, recurrent respiratory infections | Ethnicity (rare in Chinese/Asian populations — autosomal recessive, CFTR mutation common in Caucasians); presence of GI symptoms (pancreatic insufficiency → steatorrhoea, failure to thrive); diagnosis by sweat chloride test |
| Congestive heart failure (CHF) | "Cardiac asthma" — wheeze from pulmonary oedema | Orthopnoea, PND, bilateral basal crackles, S3 gallop, peripheral oedema, raised JVP; CXR: cardiomegaly, upper lobe diversion, Kerley B lines; BNP elevated. Wheeze is caused by peribronchial oedema compressing small airways. |
| Post-nasal drip / Upper airway cough syndrome | Chronic cough, throat clearing | Sensation of nasal dripping, frequent throat clearing, cobblestone appearance of posterior pharynx; responds to intranasal corticosteroids/antihistamines |
| ACEI-induced cough | Chronic dry cough | Onset 1–2 weeks after starting ACEI; mechanism: ACE inhibition → ↓ bradykinin breakdown → bradykinin accumulates in airways → stimulates cough receptors; resolves on drug cessation (switch to ARB) |
| Vocal cord dysfunction (VCD) / Inducible laryngeal obstruction | Episodic dyspnoea, wheeze (often inspiratory), stridor | Does NOT respond to bronchodilators; flow-volume loop shows inspiratory flattening (variable extrathoracic obstruction); often triggered by stress/exercise; diagnosed by direct laryngoscopy during symptoms showing paradoxical vocal cord adduction |
| Psychogenic dyspnoea / Hyperventilation syndrome | Episodic dyspnoea at rest | Features: subjective "inability to take a deep breath," frequent sighing, digital/perioral paraesthesiae, light-headedness, central chest discomfort; occurs at rest, rarely disturbs sleep (unlike asthma which is characteristically worse at night) [7] |
High Yield — 'Cardiac Asthma'
"Cardiac asthma" is NOT asthma — it is wheeze caused by left heart failure. Pulmonary oedema causes peribronchial cuff oedema that compresses small airways from the outside → airflow obstruction and wheeze. The clue is the presence of cardiac signs (orthopnoea, PND, S3, raised JVP, ankle oedema) and CXR showing cardiomegaly/pulmonary congestion. Treating with bronchodilators alone won't help — the patient needs diuretics and heart failure management.
The following diagram shows the clinical reasoning pathway when a patient presents with wheeze and/or chronic cough. This is how you systematically work through the DDx:
This is one of the most commonly tested DDx comparisons. The table below synthesizes the key distinguishing features:
| Feature | Asthma | COPD |
|---|---|---|
| Age of onset | Usually childhood (75% < 7y) | Usually > 40 years |
| Smoking history | Usually non-smoker (or smoking is a trigger, not a cause) | Usually smoker ( > 20 pack-years) |
| Symptoms | Episodic, variable, with symptom-free intervals | Persistent, progressive, chronic |
| Diurnal variation | Worse at night or early morning [8] | Little diurnal variation |
| Atopy | Common (> 80% atopic) | Not typically associated |
| Reversibility | FEV₁ ↑ ≥ 12% AND ≥ 200 mL post-BD | Incomplete reversibility (post-BD FEV₁/FVC remains < 0.7) |
| Inflammation | Eosinophilic, Th2-driven | Neutrophilic, CD8⁺ T cell-driven |
| Airway remodelling | Sub-epithelial fibrosis, smooth muscle hypertrophy | Emphysema, small airway fibrosis, mucus gland hyperplasia |
| DLCO | Normal or increased | Decreased (emphysema → loss of alveolar surface area) |
| Response to ICS | Excellent | Limited (mainly reduces exacerbations in eosinophilic COPD) |
| Prognosis | Generally good if well-controlled | Progressive decline in lung function |
Asthma-COPD Overlap (ACO)
~20% of asthma patients eventually develop irreversible airflow obstruction resembling COPD — this is "asthma-COPD overlap." These patients have features of BOTH: variable symptoms with some reversibility (asthma-like) PLUS persistent airflow limitation (COPD-like). They often require treatment with BOTH ICS (for the asthma component) AND long-acting bronchodilators (for the COPD component). [2]
In children, the DDx is somewhat different from adults. The senior notes explicitly list:
- Acute bronchiolitis — age < 2y, first episode, RSV
- Pneumonia — fever, productive cough, consolidation
- Foreign body aspiration ± aspiration pneumonia — localized unilateral wheeze, expiratory CXR for unilateral hyperinflation
- Bronchiectasis — recurrent infections
- GERD — chronic cough, vomiting, failure to thrive
- Bronchopulmonary dysplasia (BPD) — history of prematurity
- Primary ciliary dyskinesia — recurrent infections, situs inversus
- Cystic fibrosis — ethnicity (Caucasian) and presence of GI symptoms (steatorrhoea)
Red Flags That This Is NOT Asthma in a Child
Always consider alternative diagnoses if a wheezy child has:
- Failure to thrive / poor weight gain → CF, immunodeficiency, GERD
- Recurrent pneumonia in the same lobe → foreign body, congenital anomaly
- Symptoms from birth or neonatal period → congenital airway anomaly, BPD
- Productive purulent sputum / haemoptysis → bronchiectasis, CF, TB
- Finger clubbing → bronchiectasis, CF, lung abscess (NOT a feature of asthma)
- Situs inversus → primary ciliary dyskinesia (Kartagener's)
When you suspect asthma, ask yourself these questions to rule out mimics:
- Is it truly episodic and variable? → If persistent and progressive → think COPD
- Does it respond to bronchodilators? → If no response → think bronchiolitis obliterans, VCD, tumour
- Is the wheeze generalized or localized? → If localized → think FB or tumour
- Is there significant sputum production? → If purulent/copious → think bronchiectasis, CF
- Are there cardiac signs? → If orthopnoea, PND, S3 → think "cardiac asthma" (CHF)
- Is there a medication history? → ACEI? Beta-blocker? Aspirin?
- Are there red flags for an alternative diagnosis? → Clubbing, haemoptysis, weight loss, failure to thrive
High Yield Summary — DDx of Asthma
GC Lecture Slide Framework (highest yield):
- Generalized wheeze DDx: COPD, bronchiectasis, bronchiolitis obliterans, viral bronchiolitis (children)
- Localized wheeze DDx: tumour, foreign body
Key differentiators:
- COPD: smoker, persistent, progressive, poor reversibility, ↓DLCO
- Bronchiectasis: purulent sputum, haemoptysis, clubbing, tram-tracks on HRCT
- Bronchiolitis obliterans: post-transplant/post-viral, irreversible obstruction
- Foreign body: unilateral wheeze, sudden onset, unilateral hyperinflation on expiratory CXR
- Tumour: monophonic wheeze, haemoptysis, weight loss, expiratory plateau on flow-volume loop
- Cardiac asthma (CHF): orthopnoea, PND, S3, cardiomegaly on CXR
- Cough-variant asthma: chronic cough as sole symptom, responds to ICS
Paediatric-specific DDx: bronchiolitis (RSV, < 2y), foreign body, BPD (prematurity), PCD (recurrent infections, situs inversus), CF (Caucasian, GI symptoms)
Active Recall - Differential Diagnosis of Asthma
References
[1] Lecture slides: GC 040. Cough and wheezing_asthma and allergic lung diseases.pdf (pp. 24, 25, 26) [2] Senior notes: Ryan Ho Respiratory.pdf (p. 98) [3] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (pp. 191, 220, 233) [4] Senior notes: Adrian Lui Pediatrics Notes.pdf (pp. 170–172) [5] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (p. 176) [6] Senior notes: Maksim Medicine Notes.pdf (pp. 280, 297, 301) [7] Senior notes: Ryan Ho Fundamentals.pdf (pp. 220, 223) [8] Lecture slides: GC 040. Cough and wheezing_asthma and allergic lung diseases.pdf (p. 24)
Diagnostic Criteria for Asthma
Before diving into specific criteria and tests, let's be clear on a crucial concept:
Asthma is a CLINICAL diagnosis from history and physical examination ± spirometry [6]
There is no single definitive test for asthma. You diagnose it by putting together a compatible history + evidence of variable expiratory airflow limitation + exclusion of alternative diagnoses. Spirometry supports the diagnosis but a normal spirometry does NOT exclude asthma (the patient may be asymptomatic between attacks).
The diagnosis of asthma requires: [1]
Step 1: Compatible History
Episodes of dyspnoea, cough and wheeze [1]:
- Episodes may be transient or prolonged [1]
- Worse at night or early hours of the morning [1]
- Some may present as persistent cough (cough-variant asthma) [1]
- Triggered by exercise, allergens, cold air, URTI, laughter
- Symptom-free intervals between episodes
- ± personal/family history of atopy (eczema, allergic rhinitis)
Step 2: Evidence of Variable Expiratory Airflow Limitation
Variable airflow obstruction demonstrated by: [1]
- 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
Step 3 (if needed): Nonspecific Airway Hyperresponsiveness
- Bronchial challenge test (not essential for diagnosis) [1]
- Used when clinical suspicion is high but spirometry is normal
GC Lecture Slide — Asthma Diagnosis (Highest Yield)
The GC lecture slide summarises the diagnosis of asthma as: (1) Compatible history, (2) Variable airflow obstruction — demonstrate presence of airflow obstruction + improvement in FEV₁ or PEF after bronchodilator + diurnal variation in PEF, (3) Nonspecific airway hyperresponsiveness by bronchial challenge test (not essential for dx) [1]. This is the exam-ready framework.
Specific Diagnostic Thresholds (GINA)
- FEV₁/FVC ratio: ≤ 0.75 in adults (≤ 75%), ≤ 0.85–0.90 in children [2][4]
- Why FEV₁/FVC? In obstruction, the airways narrow → it takes longer to expire → FEV₁ (the volume expired in the first second) drops disproportionately compared to FVC (total volume expired) → the ratio falls.
- In a normal person, ~80% of the FVC is expired in the first second. In obstruction, this fraction drops because the narrowed airways slow expiratory flow.
There are multiple ways to demonstrate variable airflow limitation. You only need ONE positive test to support the diagnosis, but the more positive tests, the more confident the diagnosis [2][4][6]:
| Test | Positive Threshold | Interpretation / Notes |
|---|---|---|
| Excessive bronchodilator reversibility (BD reversibility test) | ↑ FEV₁ ≥ 12% AND ≥ 200 mL after bronchodilator [2][4][6] | Stop SABA ≥ 6 hours (ideally ≥ 4h), BD LABA ≥ 24h, daily LABA ≥ 36h before testing [6]; administer salbutamol 4 puffs (200–400 μg), then repeat spirometry after 15 minutes [6]. The greater the reversibility, the more confident the diagnosis. |
| Daily diurnal PEF variability | > 10% [2][4][6] | Measured as daily amplitude percent mean = (daily max − daily min) / (mean of daily max and min) × 100%. Recorded with twice daily PEF over 1–2 weeks [4]. Reflects the nocturnal dip characteristic of asthma. |
| Improvement after ICS trial | Significant ↑ in FEV₁ or PEF after 4 weeks of controller (ICS or oral steroid) [4][6] | If spirometry is non-diagnostic initially, a therapeutic trial can help — if the patient improves, it supports asthma. |
| Exercise challenge | > 10% AND > 200 mL ↓ FEV₁ after 6 min exercise [4] or > 15% ↓ in PEF | Exercise-induced bronchoconstriction — hyperventilation causes airway cooling/drying → osmotic changes → mast cell mediator release → bronchospasm. |
| Between-visit variability | Variability in FEV₁ or PEF between clinic visits (outside respiratory infections) | Less reliable, but supportive if other tests are equivocal [2] |
Practical Tip — The Bronchodilator Reversibility Test
The GC interactive tutorial case illustrates this beautifully: FEV₁ 2.0 L (55% predicted), FVC 3.5 L (70% predicted), FEV₁/FVC 57%. Post-bronchodilator FEV₁ is 2.6 L (30% increase) and FVC is 4.2 L (20% increase) [8]. The FEV₁ increased by 0.6 L (30%) — well above the 12% AND 200 mL threshold → this confirms excessive bronchodilator reversibility consistent with asthma, NOT COPD (where reversibility is incomplete/minimal).
This is used when spirometry is normal at rest but clinical suspicion remains high [2][4]:
| Provocation Agent | Positive Threshold | Mechanism |
|---|---|---|
| Methacholine (most commonly used) | ≥ 20% ↓ FEV₁ at standard dose (PC₂₀ < 4 mg/mL highly suggestive, < 16 mg/mL borderline) [2][4] | Methacholine is a direct muscarinic (M₃) agonist → stimulates bronchial smooth muscle contraction. Asthmatic airways are hyperresponsive, so they constrict at much lower doses than normal airways. |
| Histamine | ≥ 20% ↓ FEV₁ at standard dose [4] | Histamine acts on H₁ receptors → bronchial smooth muscle contraction + mucosal oedema |
| Hypertonic saline / Mannitol / Hyperventilation (indirect challenges) | ≥ 15% ↓ FEV₁ [2][4] | These are indirect challenges — they cause osmotic changes in the airway surface liquid → mast cell degranulation → mediator release → bronchoconstriction. More specific for asthma (as they test the inflammatory pathway) but less sensitive. |
Direct vs Indirect Bronchoprovocation
Direct challenges (methacholine, histamine): test smooth muscle responsiveness directly. High sensitivity (good for ruling OUT asthma — a negative methacholine challenge makes asthma very unlikely), but low specificity (can be positive in COPD, allergic rhinitis, post-viral cough). Indirect challenges (mannitol, hypertonic saline, exercise): test the inflammatory pathway (mast cell degranulation). High specificity (positive result is strongly suggestive of asthma), but lower sensitivity.
Investigation Modalities — Detailed Interpretation
1. Spirometry with Bronchodilator Reversibility (The Cornerstone)
"Spirometry" = spiro (to breathe) + metry (to measure)" — literally measuring breathing.
Spirometry involves a maximal inhalation followed by a rapid and forceful complete exhalation into a spirometer [4]. At least 6 seconds of expiration is required for accuracy [10].
| Parameter | What It Measures | Normal Values |
|---|---|---|
| FEV₁ (Forced Expiratory Volume in 1 second) | Volume of air expired in the first second of a forced expiration | Compared to predicted (based on age, sex, height, ethnicity) |
| FVC (Forced Vital Capacity) | Total volume of air expired during the entire forced expiration | Compared to predicted |
| FEV₁/FVC ratio | Proportion of FVC expired in the first second | ≥ 0.75 in adults, ≥ 0.85–0.90 in children |
| PEF (Peak Expiratory Flow) | Maximum flow rate achieved during forced expiration | Compared to predicted or personal best |
| Pattern | FEV₁ | FVC | FEV₁/FVC | Examples |
|---|---|---|---|---|
| Obstructive | ↓↓ | ↓ or Normal | < 0.7 (< 70%) [6][10] | Asthma, COPD, bronchiectasis, CF, bronchiolitis obliterans |
| Restrictive | ↓ | ↓↓ | Normal or ↑ ( > 0.7) | ILD, chest wall disease, neuromuscular disease |
| Mixed | ↓↓ | ↓↓ | ↓ | Severe asthma with remodelling, combined disease |
Why is FEV₁/FVC reduced in obstruction? Because narrowed airways offer high resistance to airflow → expiration is slowed → less air exits in the first second → FEV₁ drops proportionally more than FVC → the ratio falls.
- Normal: smooth curve with rapid rise to peak flow then gradual decline
- Asthma/obstructive: "scooped out" concave appearance of the expiratory limb → signifies diffuse intrathoracic airflow obstruction [2]. The concavity occurs because as the patient expires, the smaller airways (which are more affected) close earlier, causing progressively reduced flow rates at lower lung volumes.
- Fixed upper airway obstruction (e.g., tracheal tumour): flat plateau on BOTH inspiratory and expiratory limbs
- Variable extrathoracic obstruction (e.g., vocal cord dysfunction): flattening of the inspiratory limb
- Variable intrathoracic obstruction (e.g., tracheomalacia): flattening of the expiratory limb (similar to obstructive pattern)
High Yield — Interpreting the GC Interactive Tutorial Case
FEV₁ 2.0 L (55% predicted), FVC 3.5 L (70% predicted), FEV₁/FVC 57% → this is an obstructive pattern (ratio < 70%). Post-bronchodilator FEV₁ is 2.6 L (30% increase) → absolute increase = 600 mL, percentage increase = 30% → far exceeds the 12% AND 200 mL threshold → confirms significant bronchodilator reversibility consistent with asthma [8]. In COPD, you'd expect minimal reversibility (post-BD FEV₁/FVC usually remains < 0.7).
- What it is: A simple, portable device (peak flow meter) that measures the maximum speed of expiration.
- How it's used: Patient records PEF twice daily (morning and evening) for 1–2 weeks.
- Diagnostic threshold: > 10% diurnal variability [2][4][6]
- Calculated as: daily amplitude % mean = (daily max − daily min) / mean of daily max and min × 100%
- Why diurnal variation matters: Asthma characteristically shows a morning dip (worst PEF in early morning due to circadian cortisol nadir, increased vagal tone, and supine position overnight). This variability is a hallmark of the disease.
- In acute exacerbation: PEF is used for severity assessment — compare to predicted or personal best [3][9]:
The GC Wheezing Case 1 lecture slide shows: PEF 80 L/min in a patient with marked SOB and diffuse expiratory wheeze [11] — this is critically low and indicates a severe or life-threatening exacerbation.
- Primary role: Mainly to exclude alternative diagnoses [2][4][6] — it does NOT confirm asthma.
- Findings in asthma:
- Findings that EXCLUDE asthma and suggest alternatives: pneumothorax, consolidation (pneumonia), cardiomegaly + pulmonary congestion (CHF), lung mass, pleural effusion, tram-track opacities (bronchiectasis)
The GC Wheezing Case 1 slide requests: "CXR — Any other Ix in this case?" [11] — reinforcing that CXR is part of the initial workup to rule out alternative diagnoses.
| Test | What It Shows | Interpretation |
|---|---|---|
| CBC with differential count | Eosinophil count [6] | Eosinophilia (> 0.5 × 10⁹/L) supports Type 2/atopic inflammation. The GC interactive tutorial case shows eosinophil 1.5 × 10⁹/L (normal < 0.5 × 10⁹/L) [8] — markedly elevated, supporting atopic asthma. |
| ESR/CRP | Inflammatory markers [6] | To rule out infection (pneumonia, TB) as alternative diagnosis or trigger for exacerbation. Not specific for asthma. |
| ABG (Arterial Blood Gas) | PaO₂, PaCO₂, pH | ABG if SpO₂ < 92% or life-threatening features [9]. In acute asthma: early = respiratory alkalosis (hyperventilation → ↓ PaCO₂); late/life-threatening = normal or ↑ PaCO₂ (fatigue → impending respiratory failure). This was discussed in detail in the prior section. |
These investigations are used for phenotyping — particularly to determine if the patient has T2-high inflammation, which guides selection of biologic therapies in severe asthma [6]:
| Test | Threshold | What It Indicates | Mechanism / Why It Matters |
|---|---|---|---|
| Skin prick test | Wheal ≥ 3 mm | Identifies specific allergen sensitization (IgE-mediated) | A small amount of allergen is introduced into the skin → if the patient has specific IgE on cutaneous mast cells → mast cell degranulation → wheal and flare reaction. The GC interactive tutorial case: skin prick test positive for house dust mite and cat fur [8] — confirms atopic sensitization. |
| Total serum IgE | Elevated (varies by lab) | Supports atopic status | High IgE indicates Th2-driven IgE overproduction. Very high IgE (> 1000 IU/mL) raises concern for ABPA [5]. |
| Allergen-specific IgE (ELISA/ImmunoCAP) | Positive | Identifies specific allergens | More specific than skin prick test; can be done even if patient is on antihistamines (which suppress skin prick test). |
| Blood eosinophils | ≥ 150 cells/μL (mild), ≥ 300 cells/μL (moderate-high T2) | T2 inflammation biomarker | Eosinophils are the hallmark cell of T2-high asthma. Counts ≥ 300/μL support anti-IL5 biologic eligibility. |
| FeNO (Fractional Exhaled Nitric Oxide) | > 50 ppb associated with good short-term response to ICS [2] | Marker of eosinophilic airway inflammation | Airway epithelial cells express inducible NO synthase (iNOS) in response to IL-13 → produces NO → exhaled and measured. High FeNO predicts good ICS response; useful for monitoring adherence (falls with adequate ICS use). |
| Sputum eosinophils | > 2% [2] | Direct measure of airway eosinophilia | Gold standard for airway inflammation phenotyping but not available in HA (Hospital Authority) [6]. Requires induced sputum collection. |
When to Order Phenotyping Investigations
You don't need phenotyping for every asthma patient. These are primarily indicated for: (1) Patients not responding to standard ICS therapy (to determine if they are T2-high or T2-low), (2) Severe asthma patients being considered for biologic add-on therapy (anti-IgE, anti-IL5, anti-IL4Rα), (3) Initial assessment to confirm atopic status and identify specific triggers for allergen avoidance.
-
Pulse oximetry (SpO₂): SpO₂ 90% is the critical threshold (sigmoid oxyhaemoglobin dissociation curve — below 90%, PaO₂ drops precipitously) [10]
- MOA: estimates arterial saturation by absorption of infrared lights (2 wavelengths) according to Beer-Lambert law [10]
- Pitfalls: Errors from dark skin, nail varnish, poor peripheral perfusion, abnormal Hb (COHb → falsely high, metHb → falsely high or low) [10]
- Normal oxygenation (SaO₂) ≠ normal ventilation [10] — a patient can have SpO₂ 95% but a rising PaCO₂ (Type 2 respiratory failure). You MUST check ABG if concerned.
-
ABG: Reserved for SpO₂ < 92% or life-threatening features [9]
| ABG Parameter | Expected in Acute Asthma | Red Flag |
|---|---|---|
| PaO₂ | ↓ (V/Q mismatch) | < 60 mmHg (8 kPa) |
| PaCO₂ | ↓ early (hyperventilation) | Normal or ↑ = patient fatiguing → impending respiratory failure |
| pH | ↑ early (respiratory alkalosis) | ↓ (respiratory acidosis) = respiratory failure |
| HCO₃⁻ | Normal acutely | May be elevated if chronic CO₂ retention |
| Investigation | When to Order | Key Findings |
|---|---|---|
| HRCT thorax | Suspect bronchiectasis, ILD, or other structural abnormality not seen on CXR | Bronchiectasis: signet ring sign, tram-tracks. ILD: ground glass, honeycombing. Normal in uncomplicated asthma. |
| ECG | Acute severe asthma (to exclude cardiac cause of dyspnoea) | May show sinus tachycardia, right heart strain (P pulmonale, RBBB) if severe. Rule out arrhythmia or ACS as cause of dyspnoea. |
| DLCO (Diffusion capacity for CO) | To differentiate asthma from COPD/emphysema | Normal in asthma (alveolar-capillary membrane intact); ↓ in emphysema (loss of alveolar surface area) [10][12]. This is a classic differentiator. |
| Investigation | Role in Asthma | Key Findings/Thresholds |
|---|---|---|
| Spirometry + BD reversibility | Confirm obstruction + variability | FEV₁/FVC < 0.75; FEV₁ ↑ ≥ 12% AND ≥ 200 mL post-BD |
| PEF monitoring | Demonstrate diurnal variability | > 10% diurnal variability over 1–2 weeks |
| Bronchoprovocation | Confirm hyperresponsiveness when spirometry is normal | ≥ 20% ↓ FEV₁ post-methacholine; ≥ 15% post-indirect challenge |
| CXR | Exclude alternative DDx | Usually normal; may show hyperinflation ± lobar collapse |
| CBC D/C | Eosinophilia | Eosinophils > 0.5 × 10⁹/L supports T2 inflammation |
| FeNO | Airway eosinophilic inflammation | > 50 ppb → good ICS response; useful for adherence monitoring |
| Skin prick test / specific IgE | Identify allergen sensitization | Positive = atopic; guides allergen avoidance |
| Total IgE | Atopic status; screen for ABPA | Markedly elevated (> 1000 IU/mL) → consider ABPA |
| Sputum eosinophils | Direct airway inflammation assessment | > 2% = eosinophilic inflammation (not available in HA) |
| ABG | Severity assessment in acute exacerbation | Normal/↑ PaCO₂ = RED FLAG (fatigue → respiratory failure) |
| DLCO | Differentiate from emphysema | Normal in asthma; ↓ in emphysema |
Once asthma is diagnosed, ongoing assessment of asthma control guides treatment stepping [3][6]:
Assessment of asthma control (ACT) — Symptom control over past 4 weeks (mnemonic: 日夜藥動): [3]
| Parameter | Well Controlled | Partly Controlled (1–2 positive) | Poorly Controlled (3–4 positive) |
|---|---|---|---|
| Daytime asthma symptoms > 2×/week | No | ||
| Night waking due to asthma | No | ||
| Reliever use > 2×/week | No | ||
| Activity limitation due to asthma | No |
High Yield — GINA Asthma Control Assessment
The 4 control questions (日夜藥動 = Day-Night-Medication-Activity): (1) Daytime symptoms > 2×/week, (2) Night waking, (3) Reliever use > 2×/week, (4) Activity limitation. None positive = well controlled; 1–2 = partly controlled; 3–4 = poorly controlled [3][6]. This determines whether to step up or step down treatment. Must also review compliance and inhaler technique, correct modifiable risk factors, and treat comorbidities (e.g., allergic rhinitis) before stepping up [3].
The GC Wheezing Case 1 physical findings: Marked SOB, audible wheeze, using accessory muscles of respiration, on 24% oxygen, respiratory rate 32/min, pulse rate 102/min, BP 137/80, chest — diffuse expiratory wheeze, occasional crackles [11]. SpO₂ 96% on 24% oxygen, PEF 80 L/min [11].
How to interpret this clinically:
- RR 32 ( > 30) + accessory muscle use + tachycardia 102 → at least severe exacerbation
- PEF 80 L/min — must compare to predicted or personal best. If predicted PEF ~400 L/min, then 80/400 = 20% → PEF < 33% predicted → life-threatening [3]
- SpO₂ 96% on supplemental O₂ — this may mask severity; ABG should be obtained
- Occasional crackles — may indicate mucus plugging or secondary infection
High Yield Summary — Diagnosis of Asthma
Diagnosis = Compatible History + Variable Expiratory Airflow Limitation:
- Compatible history: episodic wheeze, cough, SOB, chest tightness; worse at night; triggered by exercise/allergens/URTI/cold; ± atopy
- Confirm airflow obstruction: FEV₁/FVC ≤ 0.75 (adults)
- Confirm variability (any ONE of):
- BD reversibility: FEV₁ ↑ ≥ 12% AND ≥ 200 mL post-salbutamol
- PEF diurnal variability > 10% over 1–2 weeks
- Improvement after 4-week ICS trial
- Exercise challenge: > 10% AND > 200 mL ↓ FEV₁
- If spirometry normal: bronchoprovocation test (≥ 20% ↓ FEV₁ post-methacholine)
- Exclude alternatives: CXR, consider other DDx
Key investigations: Spirometry + BD reversibility (cornerstone), PEF monitoring, CXR (exclude DDx), CBC D/C (eosinophils), FeNO, skin prick test/IgE, ABG (if severe/life-threatening)
DLCO is normal in asthma (vs ↓ in emphysema) — classic differentiator
Flow-volume loop: "scooped out" concave expiratory limb = diffuse intrathoracic obstruction
Active Recall - Diagnostic Criteria, Algorithm and Investigations for Asthma
[1] Lecture slides: GC 040. Cough and wheezing_asthma and allergic lung diseases.pdf (pp. 24, 25, 26) [2] Senior notes: Ryan Ho Respiratory.pdf (p. 98) [3] Senior notes: Maksim Medicine Notes.pdf (pp. 297, 299) [4] Senior notes: Adrian Lui Pediatrics Notes.pdf (pp. 171–172) [5] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (pp. 188, 220) [6] Senior notes: Maksim Medicine Notes.pdf (p. 297) [7] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (pp. 173, 176, 180) [8] Lecture slides: GC_Interactive tutorial (Resp-Asthma case) student copy.pdf (pp. 1, 3) [9] Senior notes: Ryan Ho Critical Care.pdf (p. 13) [10] Senior notes: Maksim Medicine Notes.pdf (pp. 280, 282) [11] Lecture slides: Respiratory- Patients with Wheezing-case 1.pdf (pp. 6, 8) [12] Senior notes: Ryan Ho Fundamentals.pdf (p. 224)
Management of Asthma — Overview
The GC lecture slide identifies three pillars of asthma management: [1]
1. Pharmacotherapy 2. Prevention 3. Patient education
This is the exam-ready framework. Every management plan must address all three — pharmacotherapy alone without trigger avoidance and patient education will fail.
Before any drug is prescribed, the following principles must be understood [2][4][13]:
- Control-based management = continuous adjustment of treatment based on ongoing assessment of asthma control (the "assess–adjust–review" cycle) [3]
- Start at the appropriate step: treatment-naïve patients should start at Step 2 (or Step 3 if severe symptoms) [5][14]
- Step up if control is not achieved — but always assess inhaler technique and adherence before stepping up! [4]
- Step down if control has been sustained for > 3 months + low risk of exacerbation [5][14]
- Review treatment every 3–6 months, aiming for the lowest treatment step that controls both symptoms and exacerbations [5]
- Severity classification is retrospective — assessed from the level of treatment required to achieve control after a few months on controller therapy [2][4]:
- Mild asthma: well-controlled with Steps 1 or 2
- Moderate asthma: well-controlled with Step 3 (or 4)
- Severe asthma: well- or poorly controlled with Steps 4 or 5
The Golden Rule Before Stepping Up
Before stepping up treatment, ALWAYS: (1) Check inhaler technique — the most common cause of "uncontrolled asthma" is poor technique; (2) Assess adherence — patients often stop controllers when feeling well; (3) Correct modifiable risk factors — remove triggers, stop smoking; (4) Treat comorbidities — allergic rhinitis, GERD, obesity, OSA; (5) Reconsider the diagnosis — especially if variable airflow limitation has never been demonstrated [3][4].
Non-Pharmacological Management
- Stop smoking — active and passive exposure
- Weight loss if obese (BMI > 30) — improves lung function and reduces inflammation
- Self-monitoring: PEF monitoring, recognizing early signs of exacerbation
- Action plan: written plan for what to do when symptoms worsen (when to increase reliever, when to start oral steroids, when to seek emergency care)
- Inhaler technique: must be demonstrated, checked, and re-checked at every visit
Measures to ↓ house dust mites: [2]
- Encasement of mattresses, pillows and duvets with vinyl covers
- Wash all bedding with hot water > 55°C regularly every ≤ 2 weeks
- Remove carpets and stuffed toys
Additional measures:
- Avoid/control triggers: change bed sheets and wash ≥ 60°C, regular vacuuming of floors [3]
- Remove or reduce pet exposure (if sensitised)
- Avoid NSAIDs/aspirin if aspirin-sensitive asthma
- Avoid beta-blockers (including eye drops for glaucoma)
- Regular physical activity (with appropriate pre-exercise reliever if needed) [3]
- Seasonal influenza vaccination [3]
- Treat comorbidities: allergic rhinitis ("one airway, one disease"), GERD, OSA, obesity [2]
Pharmacotherapy — The GINA Stepwise Approach
The GC lecture slide references: GINA (Global Initiative for Asthma) as the primary guideline [1]
| Category | Purpose | Examples |
|---|---|---|
| Reliever | Rapid relief of acute symptoms; prevents exercise-induced bronchoconstriction | SABA (salbutamol), low-dose ICS/formoterol |
| Controller (Preventer) | Reduces chronic airway inflammation; prevents exacerbations; should be initiated ASAP after diagnosis [2] | ICS, ICS/LABA, LTRA, LAMA, theophylline |
| Add-on therapy | For severe asthma refractory to standard controllers | Biologics (anti-IgE, anti-IL5, anti-IL4Rα, anti-TSLP), bronchial thermoplasty, low-dose oral steroids |
The GINA 2024/2025 Stepwise Approach — Two Tracks
GINA now recommends two tracks — the preferred track uses low-dose ICS/formoterol as both reliever and controller (the SMART approach), and an alternative track uses SABA as reliever [2][3][5]:
| Step | Reliever | Preferred Controller | When to Use |
|---|---|---|---|
| Step 1 | As-needed low-dose ICS/formoterol | None (reliever only) | Intermittent asthma without RFs for exacerbation; symptoms < 2×/month |
| Step 2 | As-needed low-dose ICS/formoterol | None (reliever only — the ICS component of the reliever provides anti-inflammatory coverage) | Mild asthma; symptoms ≥ 2×/month but not daily |
| Step 3 | As-needed low-dose ICS/formoterol | Regular low-dose ICS/formoterol (SMART) | Moderate asthma; symptoms most days or night waking ≥ 1×/week |
| Step 4 | As-needed low-dose ICS/formoterol | Regular medium-dose ICS/formoterol (SMART) | Moderate asthma with poor lung function despite Step 3 |
| Step 5 | As-needed low-dose ICS/formoterol | High-dose ICS/LABA + specialist referral for add-on therapy | Severe asthma |
| Step | Reliever | Preferred Controller | Alternatives |
|---|---|---|---|
| Step 1 | As-needed SABA | Low-dose ICS taken whenever SABA is used (PARTICS approach) | — |
| Step 2 | As-needed SABA | Regular low-dose ICS | LTRA (less effective than ICS) [2] |
| Step 3 | As-needed SABA | Regular low-dose ICS + LABA | Medium-dose ICS; Low-dose ICS + LAMA; Low-dose ICS + LTRA; Low-dose ICS + theophylline [5] |
| Step 4 | As-needed SABA | Medium/high-dose ICS + LABA | Medium/high-dose ICS + LAMA/LTRA/theophylline [5] |
| Step 5 | As-needed SABA | Refer for add-on treatment: Tiotropium (LAMA), Anti-IgE, Anti-IL5, low-dose oral steroid, bronchial thermoplasty [5] | — |
Why ICS/Formoterol as Reliever? — The SMART Rationale
Rationale of using Vannair (budesonide-formoterol) as first-line reliever: [3]
- Early use of anti-inflammatory drug: reduces risk of asthma exacerbations compared to SABA reliever — every time the patient uses their reliever, they also get a dose of ICS, treating the underlying inflammation
- Formoterol as LABA with fast onset (cf. salmeterol) — formoterol has onset of action within 1–3 minutes (comparable to SABA), unlike salmeterol which takes 15–20 minutes
- As-needed SABA alone is now considered inferior and potentially dangerous — can ↑ risk of severe exacerbation and asthma mortality because it treats bronchospasm without addressing the underlying inflammation [2]
- Max daily dose = 54 mcg formoterol = 18 puffs Vannair or Symbicort (160/4.5) [2]
Critical Safety Warning — SABA Monotherapy
As-needed SABA alone (without any ICS) is NO LONGER recommended as sole treatment even for mild intermittent asthma (GINA 2019 onwards). Patients with intermittent asthma can have severe or even fatal exacerbations. Using SABA alone leaves the airway inflammation untreated. The paradigm shift is: every asthma patient should receive ICS — either as regular controller or taken whenever reliever is used [2].
Individual Drug Classes — Detailed Pharmacology
A. Relievers (Bronchodilators)
- Examples: Salbutamol (= albuterol, brand: Ventolin), terbutaline
- Name breakdown: "β₂" = beta-2 adrenergic receptor; "agonist" = stimulates the receptor
- Mechanism: Binds β₂-adrenergic receptors on bronchial smooth muscle → activates Gs protein → ↑ adenylyl cyclase → ↑ cAMP → activates protein kinase A (PKA) → phosphorylation of myosin light chain kinase (MLCK) → inhibition of MLCK → smooth muscle relaxation → bronchodilation [2]. Also stabilizes mast cells (↓ degranulation) and ↑ mucociliary clearance.
- Onset: 1–5 minutes (rapid)
- Duration: 4–6 hours (short-acting)
- Route: Inhaled (MDI with spacer, or nebulizer); IV/SC rarely used
- Side effects: Tremor (β₂ stimulation in skeletal muscle), tachycardia (β₁ cross-stimulation + reflex from peripheral vasodilation), hypokalaemia (β₂ stimulation drives K⁺ into cells), headache
- Caution: SABA overuse ( > 3 canisters/year) is a risk factor for severe exacerbation and death
- Key difference from salmeterol: Formoterol has fast onset (1–3 min, comparable to SABA) AND long duration (12 hours), making it suitable as both reliever and controller. Salmeterol has slow onset (15–20 min) and is NOT suitable as a reliever [3].
- Always combined with ICS when used in asthma (never as monotherapy — LABA monotherapy increases mortality)
B. Controllers
- Examples: Beclomethasone (Becloforte 250 μg, Beclotide 50 μg), Budesonide (Pulmicort), Fluticasone (Flixotide) [2][3]
- Colour coding: ICS inhalers are typically brown/red [3]
- Mechanism: Binds intracellular glucocorticoid receptors → translocates to nucleus → alters gene transcription → ↓ production of pro-inflammatory cytokines (IL-4, IL-5, IL-13), ↓ eosinophil recruitment and survival, ↓ mast cell activation, ↓ mucus secretion, ↓ vascular permeability, ↑ β₂-receptor expression (prevents tachyphylaxis to SABA)
- Clinical effect: ↑ symptom control, ↓ exacerbation, ↓ mortality, ↓ lung function decline [2]
- Side effects [2][3]:
- Local: Oral candidiasis (5–10%) — due to local immunosuppression allowing Candida overgrowth; hoarseness of voice (HOV) — due to steroid myopathy of vocal cords; contact hypersensitivity
- Systemic (mainly at high doses): adrenal suppression, skin thinning/bruising, cataracts, glaucoma, osteoporosis, growth retardation in children (usually < 1 cm in first year, not progressive)
| Dose Level | Beclomethasone | Budesonide | Fluticasone |
|---|---|---|---|
| Low | 200–500 μg/day | 200–400 μg/day | 100–250 μg/day |
| Medium | 500–1000 μg/day | 400–800 μg/day | 250–500 μg/day |
| High | > 1000 μg/day | > 800 μg/day | > 500 μg/day |
- Examples: Salmeterol (Serevent), Formoterol (Oxis) [3]
- Mechanism: Same as SABA but with longer lipophilic side chain → retained in cell membrane → prolonged receptor stimulation → duration 12 hours
- Key rule: NEVER use LABA as monotherapy in asthma — must always be combined with ICS. LABA monotherapy is associated with increased severe exacerbations and death (masks worsening inflammation without treating it)
- Side effects: Tachycardia, headache, cramps [3]
- Examples: Montelukast (Singulair), zafirlukast [2][3]
- Name breakdown: "leuko" = white (leukocyte), "triene" = three double bonds (chemical structure); "antagonist" = blocks the receptor
- Mechanism: Blocks cysteinyl leukotriene receptor 1 (CysLT₁) → prevents the bronchoconstrictor and pro-inflammatory effects of leukotrienes (LTC₄, LTD₄, LTE₄)
- Route: Oral, once daily — convenient, good compliance
- Use: As steroid-sparing therapy in mild/moderate asthma; especially effective in exercise-induced and aspirin-induced asthma [2] (because aspirin-sensitive asthma is driven by excess leukotriene production from COX-1 inhibition shunting arachidonic acid to lipoxygenase pathway → blocking the leukotriene receptor addresses this directly)
- Side effects: Neuropsychiatric side effects, e.g., agitation, anxiety, psychosis, suicidal ideation [3] — FDA black box warning; must counsel patients and parents
- Note: Can unmask previously undiagnosed Churg-Strauss syndrome (EGPA) [2] — thought to occur because reducing oral steroid dose (as LTRA allows steroid-sparing) unmasks the underlying vasculitis
- Example: Tiotropium (Spiriva)
- Mechanism: Blocks muscarinic M₃ receptors on bronchial smooth muscle → prevents acetylcholine-mediated bronchoconstriction; also reduces mucus secretion
- Use: Add-on therapy at Step 4–5 for patients uncontrolled on medium/high-dose ICS/LABA [3][5]
- Not used in children < 6 years [4]
- Side effects: Dry mouth, urinary retention (anticholinergic effects)
- Mechanism: Phosphodiesterase (PDE) inhibitor → prevents breakdown of cAMP → bronchodilation + mild anti-inflammatory effect; also antagonizes adenosine receptors
- Route: Oral (sustained release) for chronic management; IV aminophylline for acute exacerbation
- Problem: Narrow therapeutic index — plasma levels must be monitored (therapeutic: 10–20 mg/L; toxic: > 20 mg/L)
- Toxicity: Nausea, vomiting, headache, insomnia, arrhythmias (SVT/VT), hypotension, seizures [2]
- Drug interactions: Metabolism by CYP1A2 — increased by smoking (need higher dose in smokers); decreased by erythromycin, ciprofloxacin, cimetidine (risk of toxicity)
- Use: Alternative add-on at Steps 3–4; not used in children < 12 years [4]; generally falling out of favour due to safety concerns
- Examples: Prednisolone (oral), Hydrocortisone (IV) [3]
- Use:
- Mechanism: Same as ICS but systemic → more potent anti-inflammatory effect but with systemic side effects
- Side effects of long-term use: Cushing's syndrome, osteoporosis, diabetes, hypertension, cataracts, adrenal suppression, growth retardation in children, skin thinning, immunosuppression, peptic ulcer disease
C. Add-On Therapies for Severe Asthma (Step 5)
These are reserved for patients with severe asthma uncontrolled despite optimized Step 4 therapy and require specialist referral [3][4][5]:
| Biologic | Target | Mechanism | Indication | Administration |
|---|---|---|---|---|
| Omalizumab (anti-IgE) | IgE | Binds free IgE → prevents binding to FcεRI on mast cells → ↓ mast cell degranulation | Moderate/severe allergic asthma with documented ↑ IgE and +ve skin prick test; age ≥ 6 years [2][4] | SC injection Q2–4 weeks |
| Mepolizumab (anti-IL-5) | IL-5 | Blocks IL-5 → ↓ eosinophil maturation, recruitment, and survival | Severe eosinophilic asthma with blood eosinophils > 300/μL; age ≥ 12 years [3][4] | SC injection Q4 weeks |
| Reslizumab (anti-IL-5) | IL-5 | Same as mepolizumab | Severe eosinophilic asthma; age ≥ 18 years [4] | IV infusion Q4 weeks |
| Benralizumab (anti-IL-5Rα) | IL-5 receptor α | Binds IL-5Rα on eosinophils → direct eosinophil apoptosis via ADCC (antibody-dependent cellular cytotoxicity) | Severe eosinophilic asthma; age ≥ 12 years [4] | SC injection Q4–8 weeks |
| Dupilumab (anti-IL-4Rα) | IL-4 receptor α subunit | Blocks both IL-4 and IL-13 signalling → ↓ IgE production, ↓ eosinophilic inflammation, ↓ mucus | Severe T2-high asthma (elevated eosinophils or FeNO) or oral steroid-dependent; age ≥ 6 years | SC injection Q2 weeks |
| Tezepelumab (anti-TSLP) | TSLP (thymic stromal lymphopoietin) | Blocks the upstream epithelial alarmin TSLP → ↓ type 2 inflammation at its source | Severe asthma irrespective of phenotype (including T2-low); age ≥ 12 years [3] | SC injection Q4 weeks |
Phenotype-Guided Biologic Selection
Phenotype-guided add-on treatment: severe allergic → anti-IgE (omalizumab); aspirin-exacerbated → LTRA (montelukast); eosinophilic asthma → anti-IL5 (mepolizumab/benralizumab) [4]. This is why phenotyping investigations (FeNO, blood eosinophils, IgE, skin prick test) are essential before starting biologics.
- Bronchoscopic radiofrequency energy to shrink airway smooth muscle [3]
- Mainly for non-eosinophilic asthma [3]
- Reduces smooth muscle mass → less capacity for bronchoconstriction
- Reserved for highly selected patients with severe refractory asthma
- Complications: short-term worsening of asthma, haemoptysis, atelectasis
- Consider in those with concomitant allergic rhinitis (AR) [3]
- Involves repeated sublingual exposure to allergen extracts → induces immune tolerance (shift from Th2 to Th1/Treg responses)
- Available for house dust mite, grass pollen
Management of Acute Exacerbation of Asthma
Acute/subacute worsening in symptoms and lung function from patient's usual status [3]
- Viral respiratory infection (most common — rhinovirus)
- Allergen exposure, food allergy
- Outdoor air pollution, seasonal changes
- Poor adherence with controller medication
| Mild-Moderate | Severe (Refer ICU) | Life-Threatening (Immediate ICU) | |
|---|---|---|---|
| Clinical | Talks in phrases; prefers sitting; calm; ↑ RR; no accessory muscle use [2][3] | Talks in words; sits hunched; agitated; RR > 30; accessory muscle use [2][3] | Cannot speak; confused/drowsy; silent chest; fatigued — no accessory muscle use [3] |
| Findings | HR 100–120; SpO₂ 90–95% on RA; PEF > 50%; PaCO₂ normal/low [3] | HR > 120; SpO₂ < 90% on RA; PEF ≤ 50%; PaCO₂ normal/low [3] | HR > 160 or bradycardia; SpO₂ < 90% on O₂ 15L; PEF < 33%; PaCO₂ increased [3] |
| O₂ | Nasal cannulae/mask, aim SpO₂ 93–95% [2][3] | Same [3] | High-flow O₂ 15L via reservoir mask [9] |
| SABA | Salbutamol 4 puffs Q4H + PRN with spacer (titrate up if needed) [3] | Same + more frequent dosing; consider nebuliser | Continuous nebulised salbutamol 5 mg [9] |
| SAMA | Optional | Ipratropium bromide 4 puffs with spacer [3] | Nebulised ipratropium 0.5 mg [9] |
| Steroids | Prednisolone PO 1 mg/kg [3] | IV steroids (hydrocortisone 100 mg Q8H) [3] | IV hydrocortisone 100 mg [9] |
| MgSO₄ | — | IV MgSO₄ 2g over 20 min [3] | IV MgSO₄ 2g over 20 min [9] |
| Other | — | Consider IV aminophylline if refractory [4] | Mechanical ventilation if respiratory failure |
Key Drug Details in Acute Exacerbation
- Indicated for patients who have a life-threatening exacerbation or whose exacerbation remains severe (PEF < 40% of baseline) after therapy [5][14]
- Mechanism: bronchodilation by inhibition of Ca²⁺ influx into airway smooth muscle cells [5][14] — without Ca²⁺ entry, the contractile apparatus cannot activate, so smooth muscle relaxes
- Dose: 1.2–2g IV over 20 minutes [2]
- Caution: hypotension, CKD (↑ risk of hypermagnesaemia → paralysis) [2]
- Name breakdown: ipratropium = a quaternary ammonium compound (poorly absorbed → acts locally); "bromide" = the salt form
- Mechanism: Blocks muscarinic M₃ receptors → inhibits vagal-mediated bronchoconstriction + reduces mucus secretion
- Associated with ↓ hospitalisation and ↑ PEF/FEV₁ improvement compared to SABA alone in moderate-severe attack, but associated with ↑ risk of adverse effects (tremor, palpitation, agitation) [2]
- Avoid antibiotics (unless strong evidence of bacterial infection)
- Avoid aminophylline/theophylline (narrow therapeutic profile with poor efficacy — reserve only if truly refractory)
- Avoid sedatives/cough suppressants (suppress respiratory drive → catastrophic in respiratory failure)
- Avoid mucolytics (can worsen bronchospasm)
Reassessment required in ALL patients after 1 hour of initial treatment:
- Assess clinical status + response to treatment
- Lung function measurement (PEF or FEV₁)
- If satisfactory: controlled O₂ weaning, continue steroids 5–7 days, continue SABA
- If unsatisfactory: escalate (↑ SABA dose, add SAMA, consider MgSO₄, ICU referral)
Consider discharge when:
Discharge actions:
- Prednisolone tablets for 5–7 days [3]
- Identify and avoid triggering factors [5]
- Early OPD follow-up and review long-term treatment plan and inhaler technique [5]
- Mild/moderate: F/U in 3–4 months
- Severe: ward F/U in 1 week → asthma clinic in 1 month [4]
Hospital admission is a window of opportunity to review:
Inhaler technique, Compliance, Environment [4]. Every admission is a chance to identify and correct the factors that led to the exacerbation. Don't just treat the acute attack and send the patient home — address the root cause.
| Route | Advantages | Disadvantages | Best Used When |
|---|---|---|---|
| Nebuliser | No hand-mouth coordination needed; can deliver large doses → treatment of choice in status asthmaticus [4] | Inconvenient (requires electricity); may transmit infection; ↑ systemic S/E due to ↑ dose [4] | Acute severe exacerbation, young children, elderly |
| MDI (Metered-Dose Inhaler) | Portable, compact | Requires hand-mouth coordination (press and breathe simultaneously); significant oropharyngeal deposition → local S/E | Stable asthma; improved with spacer |
| MDI + Spacer | ↓ oropharyngeal deposition → ↓ oral candidiasis; ↓ need for coordination; as effective as nebuliser for acute management [2] | Bulky | Preferred in most situations; both acute and chronic |
| DPI (Dry Powder Inhaler) | Breath-actuated → no coordination needed; no propellant | Requires adequate inspiratory flow rate; may not be suitable for young children or severe exacerbation | Stable asthma with adequate inspiratory effort |
The SMART Approach Explained
SMART = Single Maintenance And Reliever Treatment. The same ICS/formoterol inhaler (e.g., Symbicort or Vannair) is used for both daily maintenance AND as-needed relief. When symptoms worsen, the patient takes extra puffs of the same inhaler → this automatically increases both the bronchodilator (formoterol) AND anti-inflammatory (ICS) dose. This approach has been shown to ↓ exacerbations with similar asthma control at relatively lower total ICS dose compared to SABA-only reliever [2]. Recommended for children ≥ 12 years at Steps 3–5 in GINA [4].
High Yield Summary — Management of Asthma
Three pillars: Pharmacotherapy + Prevention + Patient education
Stepwise approach (GINA): Step 1–2 (mild) → Step 3–4 (moderate) → Step 5 (severe, specialist referral)
Preferred reliever: Low-dose ICS/formoterol (NOT SABA alone — paradigm shift since GINA 2019)
Cornerstone controller: ICS — mainstay of asthma treatment; takes 2–4 weeks for full effect; local S/E: oral candidiasis (rinse mouth + spacer), hoarseness
LABA: Always combined with ICS (never monotherapy); formoterol = fast onset (can be reliever), salmeterol = slow onset (controller only)
Add-ons for severe asthma: LAMA (tiotropium), LTRA (montelukast — especially aspirin/exercise-induced), biologics (omalizumab/anti-IgE, mepolizumab/anti-IL5, dupilumab/anti-IL4Rα, tezepelumab/anti-TSLP), bronchial thermoplasty
Acute exacerbation: O₂ (aim SpO₂ 93–95%) + SABA (salbutamol) + systemic steroids ± ipratropium ± IV MgSO₄ (if severe/life-threatening). Reassess at 1 hour. Avoid: antibiotics (unless infection), sedatives, aminophylline.
ICU referral: Life-threatening features (silent chest, confusion, drowsiness, PEF < 33%, ↑ PaCO₂)
Discharge: PEF > 60% + prednisolone 5–7 days + trigger avoidance + inhaler technique review + early OPD F/U
Before stepping up: ALWAYS check inhaler technique → adherence → trigger avoidance → treat comorbidities → reconsider diagnosis
Active Recall - Management of Asthma
[1] Lecture slides: GC 040. Cough and wheezing_asthma and allergic lung diseases.pdf (pp. 33, 43) [2] Senior notes: Ryan Ho Respiratory.pdf (pp. 99, 101–102, 106–107) [3] Senior notes: Maksim Medicine Notes.pdf (pp. 296–299) [4] Senior notes: Adrian Lui Pediatrics Notes.pdf (pp. 172–174, 179) [5] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (pp. 202, 211) [9] Senior notes: Ryan Ho Critical Care.pdf (p. 13) [13] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (pp. 187, 196) [14] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p. 211) [15] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p. 107)
Complications of Asthma
Asthma complications can be divided into:
- Complications of acute severe exacerbations (immediate, life-threatening)
- Complications of chronic poorly controlled asthma (long-term structural and functional)
- Complications of asthma treatment (iatrogenic)
Understanding why each complication occurs requires linking it back to the underlying pathophysiology — airway narrowing, air trapping, chronic inflammation, and the drugs used to treat them.
A. Complications Following Severe Asthmatic Attack [5][14]
These are the acute, potentially fatal complications that arise during or immediately after a severe exacerbation.
- Excessive air trapping → leakage from weak spots of the pleura [5][14]
- First-principles explanation: During a severe asthma attack, the narrowed airways create a ball-valve mechanism — air can enter the alveoli on inspiration (when negative intrathoracic pressure pulls airways open) but cannot escape on expiration (when positive pressure compresses already-narrowed airways) → progressive air trapping → hyperinflation → alveolar overdistension → rupture of overdistended alveoli (especially marginal alveoli near the visceral pleura or perivascular spaces)
- If air tracks into the pleural space → pneumothorax
- If air tracks along the perivascular sheaths centrally into the mediastinum → pneumomediastinum (air may then extend into the subcutaneous tissues → subcutaneous emphysema, felt as crepitus over the neck and chest wall)
- Clinical clue: Sudden deterioration during an acute exacerbation — patient becomes acutely more breathless, develops pleuritic chest pain, hypotension, tracheal deviation (if tension pneumothorax)
- Key point: Always suspect (tension) pneumothorax if sudden deterioration in haemodynamics during an acute asthma exacerbation [3]
Tension Pneumothorax in Acute Asthma
This is a clinical diagnosis that requires immediate needle decompression before CXR confirmation. The high intrathoracic pressures generated by air trapping in asthma make tension pneumothorax particularly dangerous — the mediastinum shifts, compresses the contralateral lung AND kinks the great vessels → obstructive shock. Do not wait for imaging if clinical signs (hypotension, tracheal deviation, absent breath sounds on one side, distended neck veins) are present.
- Ventilatory failure (Type II respiratory failure) [5][14]
- Why Type II and not Type I?
- Early in an asthma attack: V/Q mismatch → hypoxia with hypocapnia (hyperventilation compensates) = Type I respiratory failure
- Late / severe: respiratory muscle fatigue from prolonged increased work of breathing → the patient can no longer maintain compensatory hyperventilation → CO₂ retention (rising PaCO₂) = Type II respiratory failure (hypoxia + hypercapnia)
- The transition from Type I to Type II is the most dangerous phase — it signals impending cardiorespiratory arrest
- Clinical correlate: A "normal" PaCO₂ in a severely symptomatic asthmatic is a red flag (as discussed in prior sections) — it means the patient is transitioning from compensated to decompensated respiratory failure
- Predisposed by mucus accumulation and stasis airflow [5][14]
- Example: Pneumonia [5][14]
- Why? During severe asthma:
- Mucus plugging creates stagnant pools of mucus in occluded airways → ideal culture medium for bacteria
- Impaired mucociliary clearance — the normal mucociliary escalator is disrupted by epithelial damage from eosinophilic inflammation + mucus overproduction overwhelming clearance capacity
- ICS use → local immunosuppression in the airways → may slightly increase risk of lower respiratory tract infections (particularly with high-dose ICS)
- Systemic corticosteroids → generalised immunosuppression if used long-term
- Common organisms: Streptococcus pneumoniae, Haemophilus influenzae, viruses (rhinovirus triggering the original exacerbation may pave the way for secondary bacterial infection)
- The most feared complication — status asthmaticus (persistence of severe airway obstruction despite appropriate therapy) can lead to asphyxiation and death
- Mechanism: progressive air trapping → exhaustion of respiratory muscles → Type II respiratory failure → respiratory acidosis → cardiac arrhythmia → cardiorespiratory arrest
- Risk factors for fatal asthma: previous near-fatal attack (requiring intubation), hospitalisation in previous year, overuse of SABA (> 3 canisters/year), poor adherence to ICS, psychosocial factors (poor perception of dyspnoea, psychiatric comorbidity, non-compliance)
- Thick, tenacious mucus completely occludes a bronchus → air distal to the plug is absorbed → that lobe or segment collapses (atelectasis)
- Visible on CXR as lobar collapse ± volume loss on the affected side
- This was noted in the diagnosis section: CXR may show hyperinflation ± lobar collapse (secondary to mucus obstruction) [2]
| Complication | Mechanism |
|---|---|
| Hypokalaemia | β₂-agonists (salbutamol) drive K⁺ intracellularly via Na⁺/K⁺-ATPase activation; systemic steroids also promote renal K⁺ loss. Hypokalaemia → risk of cardiac arrhythmias |
| Lactic acidosis | Excessive β₂-agonist use → increased glycogenolysis and glycolysis → lactate production; also, severe respiratory distress → anaerobic metabolism in fatiguing respiratory muscles |
| Dehydration | Hyperventilation → increased insensible water loss; reduced oral intake during severe dyspnoea; mucus hypersecretion |
B. Complications of Chronic Poorly Controlled Asthma
These develop over years of inadequately treated inflammation.
- Can potentially lead to irreversible airway remodelling → progressive loss of lung function [3]
- Components (as detailed in the pathophysiology section):
- Sub-epithelial fibrosis (collagen deposition below basement membrane)
- Smooth muscle hypertrophy and hyperplasia
- Goblet cell metaplasia and mucous gland hyperplasia
- Angiogenesis
- Clinical consequence: Over time, asthma starts to behave like COPD — the airflow obstruction becomes fixed and no longer fully reversible with bronchodilators. This is the basis of Asthma-COPD Overlap (ACO) [2]
- Prevention: Early and adequate ICS therapy is the best strategy to prevent or slow remodelling
- Long-standing poorly controlled asthma with extensive remodelling → permanent reduction in lung function → chronic hypoxaemia ± hypercapnia
- Eventually may require supplemental oxygen (though this is far more common in COPD)
- Chronic airway inflammation and recurrent infections → transmural damage to bronchial walls → irreversible bronchial dilatation
- Seen on HRCT as tram-track opacities and signet ring sign
- Creates a vicious cycle: bronchiectasis → mucus stasis → infection → more inflammation → more bronchiectasis
- A specific complication in atopic asthmatics who become sensitized to Aspergillus fumigatus
- Results in a severe inflammatory reaction with mucoid impaction, eosinophilic infiltration, and proximal bronchiectasis
- Diagnosed by: total IgE typically > 1000 IU/mL, positive Aspergillus skin test or specific IgE, blood eosinophilia, radiographic opacities [5]
- Treatment: systemic corticosteroids ± itraconazole [5]
- Poorly controlled asthma itself can impair growth (chronic systemic inflammation, increased metabolic demands, recurrent exacerbations with oral steroid courses)
- Additionally, chronic hypoxia may impair growth hormone secretion and cellular growth
| Drug | Complications | Mechanism |
|---|---|---|
| ICS (inhaled corticosteroids) | Oral candidiasis (5–10%), hoarseness (dysphonia), contact dermatitis; at high doses: adrenal suppression, cataracts, glaucoma, osteoporosis, skin thinning, growth retardation in children (< 1 cm in first year) | Local: fungal overgrowth from immunosuppression; dysphonia from steroid myopathy of vocal cords. Systemic: HPA axis suppression at high doses |
| SABA (salbutamol) | Tremor, tachycardia, hypokalaemia, headache, palpitations; tolerance/tachyphylaxis with overuse | β₂-receptor stimulation in skeletal muscle (tremor), heart (tachycardia), and cellular K⁺ uptake; chronic use downregulates β₂-receptors |
| LABA | Same as SABA; LABA monotherapy increases risk of severe exacerbation and death | Masks worsening inflammation without treating it |
| Systemic corticosteroids (long-term) | Cushing's syndrome, osteoporosis, DM, HTN, cataracts, adrenal suppression, peptic ulcers, immunosuppression, growth retardation, skin atrophy, mood disturbance | Widespread glucocorticoid and mineralocorticoid effects |
| LTRA (montelukast) | Neuropsychiatric S/E: agitation, anxiety, sleep disturbance, psychosis, suicidal ideation (FDA black box warning) | Mechanism not fully elucidated — may relate to leukotriene effects on CNS; can also unmask Churg-Strauss syndrome (EGPA) |
| Theophylline | Nausea, vomiting, insomnia, arrhythmias (SVT/VT), seizures | Narrow therapeutic index; PDE inhibition and adenosine antagonism at toxic levels |
| Omalizumab (anti-IgE) | Anaphylaxis (rare), injection site reactions | Immune complex-mediated hypersensitivity |
- Anxiety and depression: Common in chronic disease; can worsen symptom perception, reduce adherence to treatment, and increase healthcare utilisation
- Reduced quality of life: Sleep disruption (nocturnal symptoms), activity limitation, school/work absenteeism
- Social isolation: Avoidance of exercise, outdoor activities, social settings due to fear of exacerbation
Understanding prognosis helps frame the importance of good control:
| Phenotype | Prognosis |
|---|---|
| Extrinsic (atopic) asthma | May subside in adolescence if well-controlled; no long-term complications if well-controlled [5][14] |
| Intrinsic (non-atopic) asthma | Condition may not subside with age; does not show dramatic improvements [5][14] |
- Children with mild intermittent asthma have an excellent prognosis — many "outgrow" their asthma by adolescence (though airway hyperresponsiveness may persist and asthma may recur later in life)
- Risk factors for persistent asthma into adulthood: severe childhood asthma, atopy, female sex, early-onset disease, reduced lung function in childhood
- Asthma mortality has been declining with better guideline-based treatment and wider ICS use, but deaths still occur (usually from preventable causes: poor adherence, over-reliance on SABA, delayed presentation)
An important longitudinal complication/association of atopy (the broader condition of which asthma is a component):
- Atopic march: atopic dermatitis/food allergy (0–3 years) → asthma (4–9 years) → rhinoconjunctivitis (10+ years) [16]
- Early-onset atopic dermatitis is associated with ↑ risk of progression into other forms of atopic conditions [16]
- This means that eczema in infancy may predict future asthma — an important point for anticipatory guidance and early intervention
High Yield Summary — Complications of Asthma
Acute complications of severe exacerbation:
- Pneumothorax/pneumomediastinum — excessive air trapping → alveolar rupture
- Respiratory failure — Type II (hypoxia + hypercapnia from respiratory muscle fatigue)
- Pulmonary infections (pneumonia) — mucus stasis + impaired mucociliary clearance
- Mucus plugging → atelectasis (lobar collapse)
- Cardiorespiratory arrest and death (status asthmaticus)
- Metabolic: hypokalaemia (β₂-agonists), lactic acidosis, dehydration
Chronic complications:
- Airway remodelling → irreversible airflow obstruction (→ Asthma-COPD Overlap)
- Secondary bronchiectasis
- ABPA (allergic bronchopulmonary aspergillosis)
- Chronic respiratory failure
- Growth retardation in children
Treatment complications:
- ICS: oral candidiasis, hoarseness; high doses → systemic steroid effects
- SABA overuse: tachyphylaxis, hypokalaemia, increased mortality if used alone
- LTRA: neuropsychiatric S/E (FDA black box), unmasking Churg-Strauss
- Long-term oral steroids: Cushing's, osteoporosis, DM, cataracts, immunosuppression
Prognosis:
- Extrinsic asthma: may subside in adolescence if well-controlled
- Intrinsic asthma: tends to persist, less dramatic improvement
Active Recall - Complications of Asthma
References
[2] Senior notes: Ryan Ho Respiratory.pdf (pp. 98, 107, 109) [3] Senior notes: Maksim Medicine Notes.pdf (pp. 297, 299) [4] Senior notes: Adrian Lui Pediatrics Notes.pdf (pp. 170, 173) [5] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (pp. 188, 213) [9] Senior notes: Ryan Ho Critical Care.pdf (p. 13) [14] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (p. 198) [16] Senior notes: Ryan Ho Rheumatology.pdf (p. 114)
High Yield Summary
Definition: Asthma = heterogeneous disease, chronic airway inflammation, variable and reversible expiratory airflow limitation (GINA).
Epidemiology: 300M worldwide, 8.6% HK, 75% diagnosed < 7yo, M > F in children, F > M in adults.
Risk Factors: Host (genetics, atopy, gender, obesity) + Environmental (allergens [indoor: HDM, pets, cockroaches; outdoor: Alternaria; occupational 5-15%], tobacco, air pollution, infection, exercise, cold air, drugs [aspirin, beta-blockers]).
Pathophysiology: Th2-dominant immune response → IgE → mast cell sensitization → early phase (histamine, leukotrienes → bronchospasm) + late phase (eosinophils → chronic inflammation → airway remodelling). Three components of airway narrowing: bronchospasm + mucosal oedema + mucus plugging.
Classification: Atopic (↑IgE, eosinophilic, children) vs Non-atopic (normal IgE, adult-onset) vs Drug-induced vs Occupational. T2-high vs T2-low endotype. Exacerbation severity: moderate → severe → life-threatening (silent chest, normal/rising PaCO₂ = RED FLAGS).
Clinical Features: Wheeze + dry cough + SOB + chest tightness, worse at night, triggered by URTI/exercise/allergens/cold/drugs. Signs: polyphonic expiratory wheeze, prolonged expiration, tachypnoea, accessory muscle use, hyperinflation. Silent chest = life-threatening.
Comorbidities: Allergic rhinitis, chronic sinusitis (Samter's triad), GERD, obesity, OSA.
High Yield Summary — DDx of Asthma
GC Lecture Slide Framework (highest yield):
- Generalized wheeze DDx: COPD, bronchiectasis, bronchiolitis obliterans, viral bronchiolitis (children)
- Localized wheeze DDx: tumour, foreign body
Key differentiators:
- COPD: smoker, persistent, progressive, poor reversibility, ↓DLCO
- Bronchiectasis: purulent sputum, haemoptysis, clubbing, tram-tracks on HRCT
- Bronchiolitis obliterans: post-transplant/post-viral, irreversible obstruction
- Foreign body: unilateral wheeze, sudden onset, unilateral hyperinflation on expiratory CXR
- Tumour: monophonic wheeze, haemoptysis, weight loss, expiratory plateau on flow-volume loop
- Cardiac asthma (CHF): orthopnoea, PND, S3, cardiomegaly on CXR
- Cough-variant asthma: chronic cough as sole symptom, responds to ICS
Paediatric-specific DDx: bronchiolitis (RSV, < 2y), foreign body, BPD (prematurity), PCD (recurrent infections, situs inversus), CF (Caucasian, GI symptoms)
High Yield Summary — Diagnosis of Asthma
Diagnosis = Compatible History + Variable Expiratory Airflow Limitation:
- Compatible history: episodic wheeze, cough, SOB, chest tightness; worse at night; triggered by exercise/allergens/URTI/cold; ± atopy
- Confirm airflow obstruction: FEV₁/FVC ≤ 0.75 (adults)
- Confirm variability (any ONE of):
- BD reversibility: FEV₁ ↑ ≥ 12% AND ≥ 200 mL post-salbutamol
- PEF diurnal variability > 10% over 1–2 weeks
- Improvement after 4-week ICS trial
- Exercise challenge: > 10% AND > 200 mL ↓ FEV₁
- If spirometry normal: bronchoprovocation test (≥ 20% ↓ FEV₁ post-methacholine)
- Exclude alternatives: CXR, consider other DDx
Key investigations: Spirometry + BD reversibility (cornerstone), PEF monitoring, CXR (exclude DDx), CBC D/C (eosinophils), FeNO, skin prick test/IgE, ABG (if severe/life-threatening)
DLCO is normal in asthma (vs ↓ in emphysema) — classic differentiator
Flow-volume loop: "scooped out" concave expiratory limb = diffuse intrathoracic obstruction
High Yield Summary — Management of Asthma
Three pillars: Pharmacotherapy + Prevention + Patient education
Stepwise approach (GINA): Step 1–2 (mild) → Step 3–4 (moderate) → Step 5 (severe, specialist referral)
Preferred reliever: Low-dose ICS/formoterol (NOT SABA alone — paradigm shift since GINA 2019)
Cornerstone controller: ICS — mainstay of asthma treatment; takes 2–4 weeks for full effect; local S/E: oral candidiasis (rinse mouth + spacer), hoarseness
LABA: Always combined with ICS (never monotherapy); formoterol = fast onset (can be reliever), salmeterol = slow onset (controller only)
Add-ons for severe asthma: LAMA (tiotropium), LTRA (montelukast — especially aspirin/exercise-induced), biologics (omalizumab/anti-IgE, mepolizumab/anti-IL5, dupilumab/anti-IL4Rα, tezepelumab/anti-TSLP), bronchial thermoplasty
Acute exacerbation: O₂ (aim SpO₂ 93–95%) + SABA (salbutamol) + systemic steroids ± ipratropium ± IV MgSO₄ (if severe/life-threatening). Reassess at 1 hour. Avoid: antibiotics (unless infection), sedatives, aminophylline.
ICU referral: Life-threatening features (silent chest, confusion, drowsiness, PEF < 33%, ↑ PaCO₂)
Discharge: PEF > 60% + prednisolone 5–7 days + trigger avoidance + inhaler technique review + early OPD F/U
Before stepping up: ALWAYS check inhaler technique → adherence → trigger avoidance → treat comorbidities → reconsider diagnosis
High Yield Summary — Complications of Asthma
Acute complications of severe exacerbation:
- Pneumothorax/pneumomediastinum — excessive air trapping → alveolar rupture
- Respiratory failure — Type II (hypoxia + hypercapnia from respiratory muscle fatigue)
- Pulmonary infections (pneumonia) — mucus stasis + impaired mucociliary clearance
- Mucus plugging → atelectasis (lobar collapse)
- Cardiorespiratory arrest and death (status asthmaticus)
- Metabolic: hypokalaemia (β₂-agonists), lactic acidosis, dehydration
Chronic complications:
- Airway remodelling → irreversible airflow obstruction (→ Asthma-COPD Overlap)
- Secondary bronchiectasis
- ABPA (allergic bronchopulmonary aspergillosis)
- Chronic respiratory failure
- Growth retardation in children
Treatment complications:
- ICS: oral candidiasis, hoarseness; high doses → systemic steroid effects
- SABA overuse: tachyphylaxis, hypokalaemia, increased mortality if used alone
- LTRA: neuropsychiatric S/E (FDA black box), unmasking Churg-Strauss
- Long-term oral steroids: Cushing's, osteoporosis, DM, cataracts, immunosuppression
Prognosis:
- Extrinsic asthma: may subside in adolescence if well-controlled
- Intrinsic asthma: tends to persist, less dramatic improvement
Heart Failure
Heart failure is a clinical syndrome caused by a structural or functional cardiac abnormality, producing symptoms and signs through elevated intracardiac pressures and/or inadequate cardiac output.
COPD
Chronic obstructive pulmonary disease is a progressive inflammatory lung disorder characterized by persistent, largely irreversible airflow limitation due to chronic bronchitis and/or emphysema, most commonly caused by smoking.