Key Facts

Asthma is a chronic inflammatory disease of the airways characterised by reversible airflow limitation, bronchial hyperresponsiveness, and mucus hypersecretion. It is the commonest chronic respiratory disease in the UK.

Epidemiology

• Prevalence: ~5.4 million people in the UK (~8% of adults, ~10% of children)
• UK has among the highest asthma prevalence and mortality rates in Europe
• ~1,400 deaths per year in the UK from asthma
• More common in boys in childhood; equal sex distribution in adults
• Higher prevalence in urban areas and lower socioeconomic groups

Aetiology

Atopic (extrinsic) asthma (most common):

• IgE-mediated hypersensitivity to environmental allergens (house dust mite, pollen, animal dander, moulds)
• Strong association with atopic triad (asthma, eczema, allergic rhinitis)

Non-atopic (intrinsic) asthma:

• Triggers: exercise, cold air, infections, occupational agents, drugs (NSAIDs, beta-blockers), GORD

Risk factors: family history of atopy, maternal smoking, low birth weight, viral bronchiolitis in infancy, air pollution

Pathophysiology

• Early response (minutes): IgE-mediated mast cell degranulation releasing histamine, leukotrienes, prostaglandins → bronchoconstriction
• Late response (4-8 hours): eosinophilic inflammation, Th2 cytokine release (IL-4, IL-5, IL-13), airway oedema
• Chronic changes: airway remodelling — subepithelial fibrosis, smooth muscle hypertrophy, goblet cell hyperplasia, basement membrane thickening
• Bronchial hyperresponsiveness to non-specific stimuli persists between attacks

Typical Presentation

• Episodic wheeze, breathlessness, chest tightness, and cough
• Symptoms worse at night and early morning
• Triggered by allergens, exercise, cold air, viral infections
• Diurnal variation in symptoms and peak flow
• Good response to bronchodilators
• History of atopy (eczema, hayfever, food allergies) or family history

Clinical Signs

• Bilateral polyphonic expiratory wheeze
• Prolonged expiratory phase
• Hyperinflated chest
• May be completely normal between exacerbations

Phenotypes

• Allergic eosinophilic: atopic, elevated IgE, responds to ICS
• Non-allergic eosinophilic: adult-onset, responds to anti-IL-5
• Obesity-related: female predominance, poor response to standard therapy
• Exercise-induced: symptoms predominantly with exertion

Red Flags

• Worsening symptoms despite treatment escalation
• Frequent exacerbations (≥3/year) or hospital admissions
• Near-fatal asthma (previous ICU admission/ventilation)
• Poor peak flow variability (<20% diurnal variation) despite symptoms — consider alternative diagnosis
• Fixed airflow obstruction — consider COPD overlap

Bedside

• Peak expiratory flow (PEF): diurnal variability >20% supports diagnosis; serial monitoring
• FeNO (fractional exhaled nitric oxide): ≥40 ppb in adults supports eosinophilic airway inflammation (NICE NG80)
• Pulse oximetry: SpO₂ assessment during exacerbations

Bloods

• FBC: eosinophilia (supports atopic/eosinophilic phenotype)
• Total IgE: elevated in allergic asthma
• Specific IgE/skin prick testing: identify allergen triggers
• Aspergillus-specific IgE: if ABPA suspected

Imaging

• Chest X-ray: usually normal; exclude pneumothorax, infection, or alternative diagnosis in acute presentations
• HRCT: if bronchiectasis, ILD, or ABPA suspected

Special Tests

• Spirometry with reversibility: FEV₁/FVC <0.7 with ≥12% AND ≥200mL improvement post-bronchodilator
• Bronchial provocation testing: methacholine or histamine challenge (positive if PC₂₀ <8 mg/mL) — high sensitivity
• Peak flow diary: 2-4 weeks of BD recordings to assess variability
• Sputum eosinophil count: ≥3% supports eosinophilic phenotype

Non-pharmacological

• Personalised asthma action plan for all patients
• Allergen avoidance where triggers identified
• Smoking cessation
• Weight management if obese
• Annual influenza and pneumococcal vaccination
• Occupational exposure assessment and avoidance

Pharmacological

BTS/SIGN stepwise approach (adults):

Step 1: SABA as required (salbutamol 100-200mcg PRN via MDI + spacer)

Step 2: Add low-dose ICS (beclometasone 200-400mcg/day or budesonide 200-400mcg/day)

Step 3: Add LABA (salmeterol 50mcg BD or formoterol 6-12mcg BD) — if no response, stop LABA and increase ICS to medium dose, or trial LTRA (montelukast 10mg ON)

Step 4: Medium-dose ICS + LABA ± LTRA; consider MART regimen (budesonide/formoterol as maintenance and reliever)

Step 5: High-dose ICS + LABA ± LTRA ± theophylline (plasma level 10-20 mg/L); refer to specialist

Specialist add-ons (severe asthma):

• Omalizumab (anti-IgE): severe allergic asthma, high IgE (NICE TA278)
• Mepolizumab (anti-IL-5): severe eosinophilic asthma (NICE TA431)
• Benralizumab (anti-IL-5R): severe eosinophilic asthma (NICE TA565)
• Dupilumab (anti-IL-4Rα): severe type 2 asthma (NICE TA751)
• Low-dose oral prednisolone as last resort

ICS dose equivalents (beclometasone):

• Low: 200-400 mcg/day
• Medium: 400-800 mcg/day
• High: >800 mcg/day

Surgical/Interventional

• Bronchial thermoplasty: radiofrequency ablation of airway smooth muscle for severe refractory asthma (NICE IPG635); limited evidence, specialist centres only

Referral Criteria

• Specialist referral if uncontrolled on step 3-4 therapy
• Severe asthma clinic for biologic therapy assessment
• Occupational asthma: refer to occupational lung disease specialist
• Life-threatening or near-fatal asthma: specialist follow-up within 2 working days

• Most patients achieve good control with appropriate therapy
• ~1,400 deaths/year in the UK — majority preventable
• National Review of Asthma Deaths (NRAD): 45% had severe asthma, 57% not under specialist care, 47% died without seeking medical help
• Children: ~50% become asymptomatic by adulthood; higher remission if mild intermittent pattern
• Risk factors for fatal asthma: previous ICU admission, frequent OCS use, poor adherence, psychosocial factors, three or more drug classes
• Chronic poorly controlled asthma leads to irreversible airway remodelling

Asthma Severity Classification

BTS/SIGN Treatment Steps Summary

Key Biologic Therapies