Inhaled Corticosteroids and Combination Controller Therapy
Inflammation phenotypes, ICS pharmacology, adverse effects, and combination strategies
Airway Inflammation Phenotypes
Asthma — T2-High
Eosinophilic Inflammation
- IL-5 → eosinophil recruitment & survival
- IL-4 / IL-13 → IgE, goblet cell hyperplasia
- Mast cell degranulation → acute bronchospasm
- Highly glucocorticoid-sensitive
COPD — T2-Low
Neutrophilic Inflammation
- IL-8, LTB4 → neutrophil recruitment
- Macrophage proteases → emphysema
- CD8+ T cells dominant
- Glucocorticoid-resistant (except eos ≥300)
ICS Adverse Effects
|
Local |
Systemic (high dose) |
| Effect | Oral candidiasis, dysphonia | HPA suppression, bone loss, growth (children) |
| Mechanism | Oropharyngeal deposition → immune suppression / laryngeal myopathy | Systemic absorption → transactivation |
| Prevention | Mouth rinse after dose; spacer use | Lowest effective dose; Ca + vit D |
| Pneumonia | — | Fluticasone propionate in COPD (TORCH trial) |
ICS/LABA Combinations and SMART Therapy
ICS/LABA
Fluticasone / Salmeterol
- Twice-daily; DPI or pMDI
- Asthma and COPD
- Pneumonia signal in COPD
- Salmeterol: no rescue use
SMART Therapy
Budesonide / Formoterol
- Same inhaler = maintenance + rescue
- Formoterol onset 1–3 min → rescue capable
- Each rescue dose delivers ICS
- SYGMA trials: fewer exacerbations vs SABA
Once-Daily
Fluticasone Furoate / Vilanterol
- Highest GR affinity ICS available
- Once-daily (Breo Ellipta)
- Asthma and COPD
- Used in Trelegy triple therapy
Eosinophil-Guided ICS in COPD
≥300 cells/µL: add ICS — clear exacerbation benefit |
100–299: consider ICS individually |
<100: avoid ICS — pneumonia risk exceeds benefit