Eosinophilic Asthma

A type 2 high phenotype of asthma driven by interleukin 5, interleukin 4 and interleukin 13, with airway and blood eosinophilia (blood eosinophils of 0.3 x 10^9/L (300 per microlitre) or more, or sputum eosinophils of 3% or more).

• Accounts for about 50% of severe asthma and about 5 to 10% of all asthma; usually adult onset, with nasal polyps, aspirin sensitivity and late onset fixed airflow obstruction.
• Mechanism: epithelial alarmins (thymic stromal lymphopoietin, interleukin 33) activate type 2 innate lymphoid and T helper 2 cells; interleukin 5 recruits and prolongs eosinophil survival, causing mucus plugging, remodelling and exacerbations.
• It carries a high exacerbation rate and need for oral corticosteroids.

Recurrent wheeze, cough, chest tightness, breathlessness; frequent exacerbations needing oral corticosteroids; poor response to inhaled therapy; night symptoms.

• Chronic rhinosinusitis with nasal polyps, anosmia, aspirin or NSAID sensitivity (exacerbated respiratory disease), eczema, and atopy.
• Examination: wheeze, nasal polyps, and in severe disease hyperinflation.
• Differential diagnosis: allergic bronchopulmonary aspergillosis, eosinophilic granulomatosis with polyangiitis, chronic eosinophilic pneumonia, parasitic infection (Strongyloides, filariasis, Toxocara), drug reaction, hypereosinophilic syndrome, vocal cord dysfunction, chronic obstructive pulmonary disease.
• Complications: recurrent severe exacerbations, fixed airflow obstruction, mucus plugging and collapse, corticosteroid adverse effects (osteoporosis, diabetes, cataract, adrenal suppression), respiratory failure and death.

Spirometry: FEV1/FVC less than 0.70 (or less than the lower limit of normal), reversibility of 12% and 200 mL or more after salbutamol 400 micrograms, or peak flow variability of 10% or more; fractional exhaled nitric oxide of more than 25 parts per billion supports type 2 inflammation.

• Blood eosinophils on at least three occasions, ideally off oral corticosteroids for 2 weeks; sputum eosinophils by induced sputum.
• Total IgE and specific IgE or skin prick tests; Aspergillus fumigatus specific IgE and IgG.
• Exclusions: antineutrophil cytoplasmic antibody (anti-myeloperoxidase) and urinalysis for eosinophilic granulomatosis with polyangiitis; stool microscopy and Strongyloides serology; chest CT for bronchiectasis and mucus; full blood count with film; echocardiogram and troponin if eosinophils exceed 1.5 x 10^9/L.
• Check inhaler technique, adherence, comorbidities (rhinitis, reflux, obesity, sleep apnoea, smoking) before labelling severe disease.

Stepwise inhaled therapy:

• Mild to moderate: budesonide-formoterol 200/6 micrograms, 1 puff twice daily and 1 puff as needed (maximum 12 puffs daily).
• Moderate to severe: budesonide-formoterol 200/6 micrograms, 2 puffs twice daily, plus as needed; or fluticasone furoate/vilanterol 184/22 micrograms once daily.
• High dose with long-acting antimuscarinic: add tiotropium 5 micrograms (2 puffs) once daily by soft mist inhaler, or use triple therapy.
• Montelukast 10 mg at night (children 4 mg or 5 mg by age) especially with rhinitis or aspirin sensitivity; stop if mood change.

```{=html} <!-- --> ``` - Biologic therapy for severe asthma despite high dose inhaled therapy with 2 or more exacerbations a year or daily oral corticosteroid, after adherence and technique are corrected:

• Mepolizumab 100 mg SC every 4 weeks (blood eosinophils 0.15 x 10^9/L or more at start, or 0.3 x 10^9/L or more in the past year).
  • Benralizumab 30 mg SC every 4 weeks for 3 doses, then every 8 weeks.
  • Reslizumab 3 mg/kg IV every 4 weeks.
  • Dupilumab 400 mg SC loading then 200 mg every 2 weeks (or 600 mg loading then 300 mg every 2 weeks; use 300 mg every 2 weeks for oral steroid dependence), for eosinophils 0.15 to 1.5 x 10^9/L or FeNO of 25 parts per billion or more.
  • Tezepelumab 210 mg SC every 4 weeks; omalizumab 75 to 600 mg SC every 2 to 4 weeks by weight and IgE when allergy is present and total IgE is 30 to 1500 IU/mL.
  • Assess response at 4 months (fewer exacerbations, less oral corticosteroid, better control and lung function) and stop if no benefit.
• Exacerbation: prednisolone 40 to 50 mg daily for 5 days (children 1 mg/kg, maximum 40 mg), salbutamol 4 to 10 puffs every 20 minutes through a spacer, ipratropium 500 micrograms nebulised, oxygen, and hospital care if severe.
• Maintenance oral corticosteroid: the lowest dose possible, prednisolone 5 to 10 mg daily, with calcium 1000 mg and vitamin D 800 units daily, bone density scan and alendronate 70 mg weekly if prolonged.
• Strongyloides: ivermectin 200 micrograms/kg orally once daily for 2 days, before steroids in endemic areas.
• Treat comorbidities: nasal polyps (mometasone 2 sprays each nostril twice daily, surgery), reflux with omeprazole 20 mg daily, weight loss, avoidance of NSAIDs if aspirin sensitive.
• Special groups: children aged 6 to 11 (mepolizumab 40 mg SC every 4 weeks, dupilumab 100 mg or 200 mg every 2 weeks by weight); pregnancy (continue inhaled corticosteroids, budesonide preferred; omalizumab has reassuring data, other biologics have limited evidence; avoid montelukast only if not responding); elderly (spacer and technique, lower oral steroid dose); renal impairment (no change); immunosuppression (screen for tuberculosis and hepatitis before biologics).
• Red flags: need for intensive care, persistent eosinophils more than 1.5 x 10^9/L, neuropathy, purpuric rash or cardiac symptoms (eosinophilic granulomatosis with polyangiitis), unexplained weight loss, fixed obstruction.
• Follow-up: review every 3 months with spirometry, control score and exacerbation count; blood eosinophils each year; check steroid adverse effects; biologic review at 4 months and yearly.