Asthma

Atopic / allergic

House dust mite, pollen, animal dander, moulds, cockroach; associated eczema and rhinitis

Genetic

Polygenic; family history of atopy, filaggrin and 17q21 loci associations

Occupational

Isocyanates, flour, latex, wood dust, cleaning agents — symptoms improve away from work

Drug-induced

NSAID-exacerbated respiratory disease, beta-blockers

Environmental

Tobacco smoke, biomass fuel, air pollution, cold air, exercise, viral infections

Eosinophilic non-allergic

Adult-onset, often with nasal polyposis, steroid-responsive, biologic-eligible

• Approximately 260 million people affected worldwide with over 450,000 deaths annually — most avoidable.
• Childhood-onset disease is often atopic; adult-onset is more often eosinophilic or occupational.
• Mortality is concentrated in low- and middle-income countries where inhaled corticosteroid access is limited.

• Personal or family history of atopy
• Early-life viral bronchiolitis, prematurity, low birth weight
• Tobacco smoke exposure including in utero
• Obesity
• Occupational sensitisers
• Air pollution and indoor allergen burden
• Poor adherence, incorrect inhaler technique and over-reliance on relievers (exacerbation risk)

1. 1Allergen or irritant exposure activates epithelium releasing IL-25, IL-33 and TSLP.
2. 2Type 2 immune activation: Th2 cells and ILC2s produce IL-4, IL-5 and IL-13.
3. 3IgE class switching, mast cell sensitisation and eosinophil recruitment follow.
4. 4Mediator release causes bronchoconstriction, mucus hypersecretion and oedema.
5. 5Persistent inflammation drives airway remodelling: subepithelial fibrosis, smooth-muscle hypertrophy, goblet-cell hyperplasia.

Normal physiology → mechanism → tissue change → clinical picture

1. 1Normal physiology: airway calibre is maintained by balanced bronchial smooth-muscle tone and thin mucus layer.
2. 2Mechanism: hyperresponsive smooth muscle constricts to sub-threshold stimuli; inflammation narrows the lumen further.
3. 3Tissue change: airway wall oedema, mucus plugging, dynamic hyperinflation with air trapping.
4. 4Functional effect: reduced FEV1 and FEV1/FVC, increased work of breathing, V/Q mismatch.
5. 5Clinical manifestation: episodic wheeze, cough, chest tightness and dyspnoea with diurnal variability.

Gross (fatal asthma)

Hyperinflated lungs with tenacious mucus plugs occluding bronchi

Microscopic

Basement membrane thickening, eosinophilic infiltrate, smooth-muscle hypertrophy, goblet-cell hyperplasia

Cytology

Curschmann spirals, Charcot-Leyden crystals, Creola bodies in sputum

Physiology correlate

Reversible obstruction early, fixed component with remodelling in chronic uncontrolled disease

• Episodic wheeze, cough, chest tightness and breathlessness
• Nocturnal or early-morning worsening
• Triggered by exercise, cold air, allergens, smoke, viral infection, laughter, NSAIDs
• Symptom-free intervals between episodes

• Widespread polyphonic expiratory wheeze; may be normal between episodes
• Prolonged expiratory phase, hyperinflated chest
• Signs of atopy: eczema, allergic rhinitis, nasal polyps
• In severe exacerbation: accessory muscle use, inability to complete sentences, tachycardia, silent chest

Typical

• Variable wheeze and cough with reversible obstruction on spirometry and a good response to inhaled corticosteroid.

Atypical

• Cough-variant asthma: chronic dry cough with no wheeze
• Exercise-induced bronchoconstriction only
• Occupational asthma with a Monday-to-Friday pattern
• Older adults where asthma is mistaken for COPD or heart failure

1. 1Take a history of variable respiratory symptoms with recognisable triggers and diurnal pattern.
2. 2Document variable expiratory airflow limitation objectively before committing to long-term therapy.
3. 3Spirometry with bronchodilator reversibility: FEV1 increase ≥ 12% and ≥ 200 mL in adults.
4. 4If spirometry is normal, use peak-flow variability, exercise challenge, FeNO or bronchial provocation.
5. 5Assess phenotype and comorbidity: allergy testing, blood eosinophils, rhinitis, reflux, obesity, anxiety.
6. 6Grade control and future risk, then start at the appropriate GINA step.
7. 7Review inhaler technique and adherence at every visit before escalating therapy.

• Documented variable respiratory symptoms PLUS documented variable expiratory airflow limitation.
• Confirmatory options: bronchodilator reversibility ≥ 12% and 200 mL; average diurnal PEF variability > 10%; FEV1 rise > 12% after 4 weeks of anti-inflammatory therapy; positive bronchial challenge.
• Diagnosis is harder once controller therapy has started — document before or during a step-down under supervision.

Initial

• Spirometry with reversibility, peak expiratory flow diary, pulse oximetry.

Confirmatory / phenotyping

• FeNO, blood eosinophil count, total and specific IgE, skin-prick testing, methacholine or mannitol challenge.

Severity

• Blood gas in severe exacerbation, chest radiograph if atypical features or suspected pneumothorax/pneumonia.

Monitoring

• Serial PEF, symptom control score (ACT/ACQ), exacerbation and oral-steroid-course count, adherence data.

COPD

Rule in: > 10 pack-year smoking, persistent post-bronchodilator FEV1/FVC < 0.7, minimal variability. Rule out: marked reversibility and childhood atopy.

Heart failure

Rule in: orthopnoea, oedema, raised BNP, cardiomegaly. Rule out: symptom relief with bronchodilator and normal BNP.

Inducible laryngeal obstruction

Rule in: inspiratory stridor, throat tightness, flattened inspiratory loop. Rule out: expiratory wheeze with ICS response.

Bronchiectasis

Rule in: chronic copious purulent sputum, CT tram-track sign. Rule out: dry episodic symptoms.

Foreign body / tracheomalacia (children)

Rule in: sudden onset, unilateral wheeze, focal findings. Rule out: bilateral variable wheeze responding to ICS.

ABPA / eosinophilic disease

Rule in: very high IgE, Aspergillus sensitisation, central bronchiectasis. Rule out: normal eosinophils and IgE.

GINA symptom control (past 4 weeks)

Well controlled

None of: daytime symptoms > 2×/week, night waking, reliever > 2×/week, activity limitation

Partly controlled

1-2 of the above features in 4 weeks

Uncontrolled

3-4 of the above features

Severity

Assessed retrospectively by the treatment step needed to maintain control

• Acute exacerbation grading: mild-moderate (PEF > 50%), severe (PEF 33-50%, RR ≥ 25, HR ≥ 110, cannot complete sentence), life-threatening (PEF < 33%, silent chest, altered consciousness, normal/raised PaCO2).

Acute exacerbation

• Oxygen to target SpO2 93-95% (94-98% in children)
• Repeated inhaled SABA via spacer or nebuliser; add ipratropium in severe attacks
• Systemic corticosteroid (prednisolone 40-50 mg orally, 5-7 days) early
• IV magnesium sulfate in severe or poorly responsive cases
• Escalate to critical care for exhaustion, rising CO2 or reduced consciousness

Long-term control

• Track 1 (preferred): as-needed low-dose ICS-formoterol at steps 1-2; maintenance-and-reliever ICS-formoterol at steps 3-5.
• Track 2: daily ICS with as-needed SABA where ICS-formoterol is unavailable.
• Step up by adding LAMA before considering biologics; check technique and adherence first.

Severe / refractory

• Anti-IgE, anti-IL-5/5R or anti-IL-4R biologics for severe eosinophilic or allergic phenotypes after specialist assessment.
• Bronchial thermoplasty in highly selected refractory cases.

Supportive

• Trigger avoidance, smoking cessation, weight loss, vaccination, treat rhinitis and reflux, written asthma action plan, breathing retraining.

Monitoring

• Review 1-3 months after starting therapy then every 3-12 months; review 1 week after an exacerbation; consider step-down after 3 months of good control.

Linked drug entities

• budesonide-formoterol — the anti-inflammatory reliever and maintenance backbone
• salbutamol — rescue bronchodilation; escalating use signals poor control
• prednisolone — exacerbation therapy; count courses as a risk marker
• montelukast — add-on option; counsel on neuropsychiatric adverse effects

Acute

• Life-threatening exacerbation, respiratory failure, pneumothorax, pneumomediastinum, mucus plugging with atelectasis.

Chronic

• Airway remodelling with fixed obstruction, growth suppression with high-dose ICS in children, oral candidiasis and dysphonia.

Treatment-related

• Cumulative oral corticosteroid harm: osteoporosis, diabetes, adrenal suppression, cataract, obesity — a key reason to escalate inhaled/biologic therapy instead.

• Most patients achieve good control with correct inhaled therapy and technique.
• Childhood asthma often improves in adolescence but may relapse in adulthood.
• Frequent exacerbations, ongoing smoking and poor adherence predict fixed airflow limitation.
• Asthma deaths cluster in patients with recent oral steroid courses, high SABA use and no controller prescription.

• Avoid tobacco smoke exposure including in pregnancy
• Reduce identified allergen and occupational exposure
• Annual influenza vaccination; pneumococcal per local policy
• Written personalised action plan for every patient
• Address adherence, technique and reliever overuse at every review

• Review 1-3 months after initiation, then 3-12 monthly
• Post-exacerbation review within 1 week — 40% of severe attacks recur without it
• Annual spirometry and control-score assessment
• Recheck technique with the actual device the patient uses

Pregnancy

Continue ICS — uncontrolled asthma is more dangerous than inhaled therapy; monitor control monthly

Lactation

Inhaled therapy and prednisolone compatible with breastfeeding

Children

Device by age (spacer with mask under 4 y); monitor growth; diagnose cautiously under 5 y

Elderly

Consider comorbid COPD and heart failure; simplify devices; watch anticholinergic and steroid burden

Athletes

Pre-exercise ICS-formoterol; document diagnosis for anti-doping compliance

Obesity

Weight loss improves control; symptoms may be non-eosinophilic and less steroid-responsive

• GINA Global Strategy for Asthma Management and Prevention (2025)
• GOLD 2025 where asthma-COPD overlap is suspected

• Anti-inflammatory reliever strategy reduces severe exacerbations compared with SABA reliever in landmark trials.
• Biologics markedly reduce exacerbations and oral steroid burden in severe type 2 asthma.
• Digital adherence monitoring shows most 'refractory' asthma is under-treated or poorly inhaled asthma.

• GINA 2025 report (guideline, global).
• DrZep editorial summary, demo dataset v0.1.