Description
- Chronic airway inflammation + variable expiratory airflow limitation + airway hyper-responsiveness
- Variability is the defining feature - in time, in trigger, in severity
Phenotypes - drive treatment choice
| Features | Marker | |
|---|---|---|
| Allergic (T2-high) | Childhood onset, atopy, eczema/rhinitis, FHx | Eos, IgE, FeNO |
| Late-onset eosinophilic (T2-high) | Adult, non-atopic, nasal polyps, steroid-dependent | High eos, often AERD |
| Non-T2 / neutrophilic | Adult, obese, smoker, poor steroid response | Low eos, low FeNO |
| Obesity-related | Prominent symptoms, little eosinophilic inflammation | - |
| With fixed obstruction | Long-standing, remodelled | Overlaps COPD |
Definitions that matter
- Difficult-to-treat - uncontrolled despite medium/high ICS-LABA
- Most is adherence, inhaler technique, comorbidity or wrong diagnosis
- Severe asthma - remains uncontrolled after those are corrected, or worsens when treatment is stepped down
- ~3-10% of asthma; the biologics population
Special syndromes
- AERD / Samter triad - nasal polyps + asthma + aspirin/NSAID sensitivity
- COX-1 inhibition -> shunt to cysteinyl leukotrienes
- Alcohol (red wine, beer) is a common trigger
- Responds to LTRA, aspirin desensitisation, dupilumab
- ABPA - Aspergillus hypersensitivity in asthma or CF -> bronchiectasis
- Occupational asthma - better on holidays/weekends; isocyanates, flour, latex, epoxy
- Potentially curable if removed early; permanent if exposure continues
- Exercise-induced bronchoconstriction - usually a marker of uncontrolled asthma
Epidemiology
- ~11% of Australians (~2.8 million) - one of the highest rates in the world
- Aboriginal and Torres Strait Islander peoples ~2x prevalence and hospitalisation
- Childhood M>F; adulthood F>M (and adult-onset asthma is more often severe)
- ~400 asthma deaths/yr in Australia; most in people with mild-to-moderate disease and are preventable
- Over-reliance on SABA (>=3 canisters/yr) is the clearest death risk marker
Aetiopathogenesis
Risk factors
- Atopy - the strongest; eczema -> rhinitis -> asthma ("atopic march")
- Family history, filaggrin loss-of-function, 17q21 variants
- Prematurity, low birth weight, bronchiolitis (RSV/rhinovirus)
- Maternal smoking, air pollution, obesity
- Hygiene hypothesis - farm exposure, early microbial diversity are protective
Triggers
- Allergen (house dust mite dominant in Australia), viral URTI (the commonest exacerbation trigger), exercise, cold air, smoke, thunderstorm asthma (rye grass + spring storms - a distinctly Australian mass-casualty phenomenon)
- Drugs: NSAIDs, aspirin, non-selective beta blockers
- Occupational sensitisers, GORD, stress, menses
Mechanism - T2-high
- Allergen -> dendritic cell -> Th2 + ILC2
- Epithelial alarmins TSLP, IL-25, IL-33 drive both (the tezepelumab target - upstream of the T2/non-T2 split)
- IL-4/IL-13 -> B-cell class switch -> IgE -> mast cell sensitisation
- IL-13 also -> goblet cell metaplasia, inc FeNO, smooth muscle hyper-responsiveness
- IL-5 -> eosinophil maturation, recruitment, survival
- Mast cell degranulation -> histamine, leukotrienes, prostaglandins -> bronchoconstriction, oedema
- Remodelling - subepithelial (reticular basement membrane) fibrosis, smooth muscle hypertrophy, angiogenesis, mucus gland hyperplasia
- -> fixed obstruction; occurs early, before severe disease
Mechanism - non-T2
- Neutrophilic, IL-17/Th17 driven, or paucigranulocytic
- Corticosteroid-insensitive - this is why some "severe asthma" does not respond to steroids or to T2 biologics
Diagnosis5 exam ›
Two components required: symptom pattern + objective demonstration of variable airflow limitation.
1. Symptom pattern
- >1 of wheeze, dyspnoea, chest tightness, cough
- Variable in time and intensity, worse at night/early morning, triggered by exercise/allergen/cold/laughter/viruses
- Isolated chronic cough, chronic sputum, exertional dyspnoea alone, or chest pain make asthma less likely
2. Objective confirmation - any one
| Test | Positive |
|---|---|
| Bronchodilator reversibility | inc FEV1 >12% AND >200 mL after salbutamol |
| Diurnal PEF variability | >10% average over 2 weeks |
| Treatment trial | inc FEV1 >12% and >200 mL after 4 weeks ICS |
| Exercise challenge | dec FEV1 >10% and >200 mL |
| Direct provocation (methacholine/histamine) | PD20 at <=8 mg/mL. Sensitive, NOT specific - a negative is the useful result |
| Indirect provocation (mannitol, hypertonic saline, exercise) | dec FEV1 >=15%. Specific, less sensitive - indicates active airway inflammation |
- *Do it before starting treatment* - once on ICS the variability disappears and the diagnosis can never be confirmed
- GINA 2026 notes BD-reversibility criteria have historically caused under-diagnosis, particularly in young males with high baseline FEV1
Adjuncts
- FeNO - supports T2 inflammation and predicts ICS response; not diagnostic alone; lowered by smoking and ICS
- Blood eosinophils, total IgE, specific IgE / skin prick
- CXR - to exclude alternatives
When it is not asthma
- Inducible laryngeal obstruction (VCD) - inspiratory stridor, throat tightness, flattened inspiratory loop, unresponsive to bronchodilator
- COPD, bronchiectasis, HF, PE, ILD, hyperventilation, tracheal stenosis
- ACE inhibitor cough, eosinophilic bronchitis (cough + sputum eos, normal spirometry and no hyper-responsiveness)
- EGPA - asthma + eosinophilia + neuropathy/rash
Assessing control (last 4 weeks)
1. Daytime symptoms >2/week
2. Any night waking
3. Reliever use >2/week (excluding pre-exercise)
4. Any activity limitation
- 0 = well controlled; 1-2 = partly; 3-4 = uncontrolled
- Control and severity are different axes - assess control on current treatment, severity by the treatment needed to achieve it
Risk factors for exacerbation, independent of control
- >=1 exacerbation in the last 12 months (the strongest)
- SABA overuse (>=3 canisters/yr), no ICS or poor adherence
- Low FEV1 (esp. <60%), high BD reversibility, high FeNO or eos on ICS
- Ever intubated/ICU, smoking, obesity, food allergy, pregnancy, psychosocial problems
Management2 exam ›
1. Confirm before escalating - the "difficult asthma" checklist
Do this at every step-up. Most uncontrolled asthma is not severe asthma.
- Inhaler technique (watch them do it), adherence (dispensing records)
- Right diagnosis? Ongoing exposure - smoking, allergen, occupation, beta blocker, NSAID
- Comorbidity: rhinosinusitis/polyps, GORD, obesity, OSA, anxiety, VCD, bronchiectasis, ABPA
2. Everyone gets ICS. Nobody gets SABA alone.
- *SABA-only treatment is obsolete - it increases exacerbation and death risk*
### Track 1 (preferred): ICS-formoterol as the reliever
| Step | Adults/adolescents |
|---|---|
| 1-2 | As-needed low-dose budesonide-formoterol (AIR) |
| 3 | Low-dose maintenance + as-needed ICS-formoterol (MART) |
| 4 | Medium-dose MART |
| 5 | Add LAMA; assess phenotype -> biologic |
- One inhaler for maintenance and relief; simpler, better adherence, fewer severe exacerbations
- Safety limit on total daily inhalations - patients must seek review if exceeded
### Track 2: SABA reliever
- Use only if Track 1 is unavailable or the patient is stable and prefers it
- Step 1: ICS taken whenever SABA is taken (or ICS-SABA combination reliever)
- Step 2: daily low-dose ICS; Step 3: low-dose ICS-LABA; Step 4: medium/high ICS-LABA; Step 5 as above
- Never a LABA without an ICS
3. Add-on before biologics
- LAMA (tiotropium) at step 5
- LTRA (montelukast) - useful in AERD, exercise-induced, allergic rhinitis
- *Boxed warning: neuropsychiatric effects - agitation, nightmares, suicidality. Counsel and review*
- Azithromycin 3x/week - persistent symptomatic asthma; check QTc, hearing, NTM sputum
- Allergen immunotherapy if HDM-driven with allergic rhinitis
4. Severe asthma - biologics (specialist, PBS criteria)
Select by phenotype and comorbidity, not by sequence.
| Biologic | Target | Best for |
|---|---|---|
| Omalizumab | IgE | Allergic, perennial sensitisation; also chronic urticaria |
| Mepolizumab / depemokimab | IL-5 | Eosinophilic; also EGPA, HES, CRSwNP (depemokimab is 6-monthly) |
| Benralizumab | IL-5Ra | Eosinophilic; near-total eos depletion |
| Dupilumab | IL-4Ra (IL-4/IL-13) | Eosinophilic + atopic dermatitis, nasal polyps, AERD. Transient eosinophilia; avoid if eos very high |
| Tezepelumab | TSLP | Works irrespective of phenotype - the option when eos and FeNO are low |
- OCS minimisation is an explicit goal - taper maintenance prednisolone once the biologic works; monitor for adrenal insufficiency and unmasked EGPA
- Bronchial thermoplasty - highly selected, non-T2, limited evidence
5. Non-pharmacological, in everyone
- Written asthma action plan - the single best-evidenced non-drug intervention
- Smoking cessation, trigger avoidance, weight loss, exercise, influenza vaccination
- Review inhaler technique at every visit; annual review minimum
6. Acute exacerbation
- Severity: talking in words + drowsy + silent chest + SpO2 <90% = life-threatening
- Salbutamol 4-12 puffs via spacer q20min x3 (spacer >= nebuliser, except in life-threatening)
- Ipratropium added in severe
- Prednisolone 37.5-50 mg daily for 5-7 days - within 1 hour; no taper if <2 weeks
- Oxygen target 93-95% (not 100%)
- IV magnesium 2 g in severe/life-threatening not responding
- IV salbutamol or aminophylline, ICU, intubation with permissive hypercapnia and long expiratory time (breath-stacking -> dynamic hyperinflation -> hypotension)
- *A rising or normalising PaCO2 in acute asthma signals exhaustion - it is a pre-arrest sign*
7. After every exacerbation
- Step up controller therapy and review within 1-2 weeks
- An exacerbation means the maintenance regimen failed, not just that the patient needed steroids
- Action plan, technique, adherence, trigger review
8. Stepping down
- Only after >=3 months of good control; reduce ICS by ~25-50% at a time
- Never withdraw ICS completely in adults
Associations
- Allergic rhinitis (~80%) and chronic rhinosinusitis with nasal polyps - treating the nose improves the chest
- Atopic dermatitis, food allergy
- AERD - polyps + aspirin sensitivity
- ABPA - Aspergillus IgE + total IgE >1000, central bronchiectasis, fleeting infiltrates
- EGPA - asthma + eosinophilia + neuropathy, sinusitis, rash
- GORD - common, often silent
- Obesity - worse control, less steroid-responsive
- OSA - independent driver of poor control
- Inducible laryngeal obstruction - coexists in up to 25% of severe asthma
- Anxiety and depression
- Bronchiectasis in long-standing severe disease
- Osteoporosis, cataract, adrenal suppression - from cumulative OCS
Natural history & complications
- Childhood asthma: remits in ~50% by adolescence; many relapse in adult life
- Adult-onset asthma: less likely to remit, more often severe and eosinophilic
- Remodelling -> fixed obstruction in a substantial minority - overlaps COPD
- Well-controlled asthma has near-normal life expectancy
What worsens the trajectory
- Smoking - accelerates decline, induces corticosteroid resistance
- Frequent exacerbations, poor adherence, ongoing allergen or occupational exposure
- Cumulative OCS: >=4 lifetime courses or >=0.5-1 g cumulative -> osteoporosis, diabetes, cataract, adrenal suppression
Death
- Preventable in most cases; risk factors are behavioural more than physiological
- SABA overuse, no ICS, no action plan, prior ICU admission, psychosocial problems, food allergy
- Most asthma deaths occur in people previously assessed as mild-moderate
Monitor
- Control (4 questions), exacerbation count, spirometry annually, inhaler technique, OCS burden, growth in children, adrenal function on high-dose ICS or maintenance OCS
7 of 7 sections written · drafted 2026-09-04