Changing minds: Understanding the use of oral steroids in acute asthma

Thesis

Asthma is a heterogenous disease with a substantial global burden. Asthma attacks are treated based on symptoms alone with oral steroids despite some attacks displaying little evidence of type-2 inflammation. Type-2 low inflammatory attacks may experience more dose-dependent harm from steroids than clinical benefits. A personalised medicine approach to treating asthma attacks using biomarkers may improve patient clinical outcomes and minimise side effects. FeNO and blood eosinophils are the two key biomarkers that measure type-2 inflammation. The goal of my DPhil was to provide supportive evidence for a biomarker-directed, placebo-controlled trial of oral steroid treatment for asthma attacks.

A systematic review identified that trials of asthma attack treatment have been set almost entirely in urgent care, focussing on short-term, physiological outcome measures.

A discrete choice experiment identified that patients and healthcare professionals will trade-off treatment benefits to avoid the side-effects associated with OCS. While symptom recovery was the most important clinical outcome to HCPs and patients, HCPs preferred avoiding further healthcare utilisation more than patients.

Proteomic analysis of sputum and blood samples identified that prednisolone still had broad anti-inflammatory airway effects on top of anti-IL5 monoclonal antibody therapy. However, these effects were heterogeneous and not present in some participants.

A prospective observational study of adults on anti-IL5/5Rα therapy identified that FeNO-high attacks were associated with larger clinical improvements and airway anti-inflammatory effects after 7 days prednisolone treatment compared to FeNO-low attacks.

In conclusion, after systemic blood eosinophil suppression there is heterogeneity in steroid-responsiveness amongst the asthma population, which can be discriminated by FeNO testing at attack. There is clinical equipoise in using oral steroids treatment for type-2 low asthma attacks. Given the willingness of patients and healthcare professionals to trade-off clinical benefits to avoid oral steroid risks, my thesis supports pursuing a biomarker-directed approach to treating asthma attacks.

Authors: Howell, I

• DOI: 10.5287/ora-5r78yro7k
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: asthma; oral steroids; asthma attacks; asthma exacerbations
• Subjects: Steroids; Asthma; Asthma--Treatment