A proof-of-concept scale to predict asthma attacks: the OxfoRd Asthma attaCk risk ScaLE (ORACLE)

Abstract

Reduction of the risk of asthma attacks is a major goal of current Global Initiative for Asthma (GINA) guidelines. OBJECTIVE: To develop a risk scale to predict asthma attacks based on the blood eosinophil count and exhaled nitric oxide. METHODS: Trial-level data were extracted from the Novel START, CAPTAIN, LIBERTY ASTHMA QUEST and DREAM trials. Attack rates for control or placebo-treated patients (n=1989) were stratified by blood eosinophils and exhaled nitric oxide in a 3×3 grid using cut-offs 0.15-0.30×10 9 cells/L and 25-50 ppb. Rate ratios and relative risks were used to derive biomarker-stratified multipliers for GINA treatment step attack rates derived from 222,817 patients. Other parameters included were a recent asthma attack history (≤1 year), ≥2 concurrent clinical risk factors*, and GINA treatment step. We compared predicted versus observed biomarker-stratified asthma attack rates in placebo-treated groups reported in 17 independent clinical trials. RESULTS: Biomarker-stratified asthma attack rates were multiplied by 0.64 in the lowest type 2 biomarker combination group and 1.96 in the highest. A previous asthma attack and/or having concurrent risk factors independently increased rates 2.8and/or 1.4-fold, respectively. Predicted annual attack rates ranged from 0.06 in the lowest biomarker step 1&2 patients to 2.4 in the highest biomarker step 5 patients. The resultant scale is shown in Figure 1. There was close agreement between observed and predicted asthma attack rates (intraclass correlation coefficient 0.80; 95% CI 0.56-0.90). CONCLUSION: Our prototype scale based on biomarkers of type 2 airway inflammation proves feasibility and shows potential to predict asthma attacks which can be prevented by anti-inflammatory treatment. FIGURE 1. Prototype Oxford Asthma Attack Risk ScaLE (ORACLE). Numbers in each cell are predicted annual asthma attack rates for patients over the age of 12. An asthma attack is an episode of acute asthma requiring treatment with systemic steroids ≥ 3 days. Blood eosinophil count is contemporaneous or the highest result in last 12 months; fractional exhaled nitric oxide level is contemporaneous. *Risk factors are GINA-defined: poor symptom control, low lung function, adherence issues, reliever overuse, intubation or intensive care unit admission for asthma previously, comorbidities (chronic rhinosinusitis, obesity, psychiatric disease), environmental exposures (smoking, allergen, pollution).