Inhaled Corticosteroids
Inhaled corticosteroids (ICS) are the mainstay anti-inflammatory therapy in asthma and are used in combination with bronchodilators in COPD with eosinophilic features.
Key Facts
Beclometasone dipropionate is the reference ICS; low dose = 200-400mcg/day, medium = 400-800mcg/day, high = >800mcg/day Fluticasone propionate is approximately twice as potent as beclometasone; low dose = 100-250mcg/day ICS reduce asthma exacerbations by approximately 50% and are first-line preventer therapy (NICE NG80) Local side effects include oral candidiasis (thrush) and dysphonia — mitigated by using a spacer and mouth rinsing Systemic side effects at high doses include adrenal suppression, osteoporosis, cataracts, and growth retardation in children In COPD, ICS increase risk of pneumonia (TORCH and INSPIRE trials) — use only with eosinophilic/asthmatic features MHRA safety alert: High-dose ICS carry risk of adrenal crisis, particularly on abrupt withdrawal ICS should not be used as monotherapy — always in combination with bronchodilator in COPD
Overview
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.
Clinical Presentation
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
Differential Diagnosis
| Diagnosis | Key Features | Investigation |
|---|---|---|
| Poorly controlled asthma | Persistent symptoms despite ICS | Check adherence, technique, FeNO |
| Oral candidiasis (from ICS) | White plaques, sore mouth | Clinical examination, swab if atypical |
| Adrenal insufficiency (ICS-induced) | Fatigue, nausea, hypotension | Early morning cortisol, short Synacthen test |
| COPD with frequent exacerbations | Recurrent infections, purulent sputum | Spirometry, eosinophil count |
| Eosinophilic granulomatosis with polyangiitis | Asthma + eosinophilia + vasculitis | ANCA, tissue biopsy |
| Allergic bronchopulmonary aspergillosis | Worsening asthma, bronchiectasis, eosinophilia | Total IgE, Aspergillus-specific IgE, HRCT |
Diagnosis / Investigation
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
Management
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)
Prognosis
- 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
Other Relevant Information
ICS Potency Comparison
| ICS | Relative Potency | Key Notes |
|---|---|---|
| Beclometasone (non-extrafine) | 1.0 | Reference standard |
| Beclometasone (extrafine, e.g., Fostair) | 1.6 | Smaller particle size, better peripheral deposition |
| Budesonide | 1.0 | Used in MART regimens |
| Fluticasone propionate | 2.0 | Higher potency, more adrenal suppression risk |
| Ciclesonide | 1.6 | Pro-drug, activated in lungs |
| Mometasone furoate | 2.0 | Once-daily dosing possible |
Landmark Studies
| Trial | Finding |
|---|---|
| START trial | Early ICS in mild asthma reduces decline in lung function |
| TORCH trial | ICS/LABA in COPD: reduced exacerbations, increased pneumonia |
| NRAD (2014) | Preventable asthma deaths linked to ICS underuse |
| IMPACT trial | Triple therapy (ICS/LABA/LAMA) superior to LABA/LAMA in COPD |