Key Facts

Inhaled corticosteroids are synthetic glucocorticoids delivered directly to the airways, minimising systemic exposure while maximising anti-inflammatory effect at the target site.

Epidemiology

Approximately 3.5 million people in the UK use ICS regularly. Over-reliance on SABA rather than regular ICS remains a key contributor to preventable asthma deaths - the National Review of Asthma Deaths (NRAD) found that 39% of asthma deaths occurred in patients not prescribed ICS.

Aetiology

ICS act by:

• Binding intracellular glucocorticoid receptors
• Translocating to the nucleus and modifying gene transcription (transactivation and transrepression)
• Suppressing inflammatory mediator production (IL-4, IL-5, IL-13, TNF-alpha)
• Reducing eosinophilic airway inflammation
• Decreasing mucus secretion and vascular permeability

Pathophysiology

The therapeutic target is chronic airway inflammation characterised by:

• Eosinophil and mast cell infiltration
• Th2 cytokine release
• Basement membrane thickening
• Goblet cell hyperplasia
• Smooth muscle hypertrophy (airway remodelling)

ICS reduce all components except established remodelling, highlighting the importance of early initiation.

Indications

• Asthma: Any patient requiring SABA more than twice per week or with symptoms more than twice per week
• COPD: In combination with LABA ± LAMA when blood eosinophils ≥300 cells/µL or ≥100 with ≥2 exacerbations/year
• Eosinophilic bronchitis: Chronic cough with sputum eosinophilia

Side Effects to Recognise

• Local: Oral candidiasis (seen in 5-10%), dysphonia (up to 30-50% at high doses), pharyngeal irritation
• Systemic (at high doses): Adrenal suppression, reduced bone mineral density, easy bruising, posterior subcapsular cataracts, growth velocity reduction in children (approximately 0.5cm in first year)

Red Flags

• Features of adrenal insufficiency on high-dose ICS: fatigue, weight loss, hypotension
• Recurrent pneumonia in COPD patients on ICS
• Poor growth in children on ICS - plot on growth chart at every review

Bedside

• PEF diary: Assess response to ICS - improvement >20% supports asthma diagnosis
• Inhaler technique assessment: Critical at every consultation
• Adherence check: Prescription refill records, direct questioning

Bloods

• Blood eosinophil count: Guides ICS use in COPD (≥300 cells/µL favours ICS)
• Early morning cortisol: If adrenal suppression suspected (level <100nmol/L is abnormal)
• Short Synacthen test: If cortisol equivocal

Imaging

• CXR: Baseline, and if pneumonia suspected (particularly in COPD on ICS)
• DEXA scan: If prolonged high-dose ICS use (>3 months high-dose or equivalent)

Special Tests

• FeNO: To assess eosinophilic inflammation and guide ICS dose titration (target <25 ppb)
• Sputum eosinophil count: In specialist settings to guide ICS therapy
• Spirometry: Monitor FEV1 response to ICS initiation

Non-pharmacological

• Spacer device with all MDI ICS - improves lung deposition and reduces oral candidiasis
• Mouth rinsing after ICS use
• Regular inhaler technique review
• Personalised asthma action plan with ICS adjustment guidance

Pharmacological

ICS Dose Equivalence (beclometasone equivalent):

• Low dose: Beclometasone 200-400mcg/day, Budesonide 200-400mcg/day, Fluticasone 100-250mcg/day
• Medium dose: Beclometasone 400-800mcg/day, Budesonide 400-800mcg/day, Fluticasone 250-500mcg/day
• High dose: Beclometasone >800mcg/day, Fluticasone >500mcg/day

MART (Maintenance and Reliever Therapy):

• Budesonide/formoterol combination used as both preventer and reliever
• Reduces severe exacerbations compared to fixed-dose ICS/LABA + SABA reliever

Step-down:

• Reduce ICS dose by 25-50% every 3 months once well-controlled for ≥3 months
• Never stop ICS abruptly in patients on high doses - risk of adrenal crisis

Referral Criteria

• Uncontrolled symptoms despite medium-dose ICS + add-on therapy
• Suspected adrenal suppression
• Consideration of biological therapies (omalizumab, mepolizumab, benralizumab)

• ICS reduce asthma hospitalisations by 50% and mortality by approximately 20%
• NRAD found 65% of asthma deaths were in patients with mild-moderate disease - highlighting underuse of ICS
• In COPD, ICS reduce exacerbation rates by approximately 25% but increase pneumonia risk by 60-70% (TORCH trial)
• Growth suppression in children is typically 0.5cm in the first year and non-progressive
• Long-term high-dose ICS: 5-year cumulative dose associated with dose-dependent cataract risk

ICS Potency Comparison

Landmark Studies