Derivation of a prototype asthma attack risk scale centred on blood eosinophils and exhaled nitric oxide

Abstract

Reduction of the risk of asthma attacks is a major goal of current asthma management. We propose to derive a risk scale predicting asthma attacks based on the blood eosinophil count and exhaled nitric oxide (FeNO). Biomarker-stratified trial-level attack rates were extracted and pooled from the control arms of the Novel START, CAPTAIN, QUEST, Benralizumab Phase 2b, PATHWAY, STRATOS 1-2 and DREAM trials (n=3051). These were used to derive rate ratios and the predicted asthma attack rate for different patient groups. The resultant prototype risk scale shows potential to predict asthma attacks, which may be prevented by anti-inflammatory treatment.

Keywords: allergic lung disease; asthma; asthma epidemiology; clinical epidemiology; eosinophil biology; exhaled airway markers; pulmonary eosinophilia; respiratory measurement.

Conflict of interest statement

Competing interests: SC: has received a non-restricted research grant from Sanofi Genzyme for investigator-initiated type 2 innovation research and speaker honoraria from Sanofi/Regeneron, AstraZeneca and GlaxoSmithKline (GSK), all outside the submitted work. AL is an employee of Sanofi Norway. MJ has received grants from the University of Oxford and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). SR reports non-financial support from AstraZeneca and other sources of revenue from Australian Government Research Training Program and the NIHR Oxford BRC. JM has received grants from the NIHR Oxford BRC. TH has received grants from Pfizer, the University of Oxford, the Wellcome Trust, the Guardians of the Beit Fellowship and the NIHR Oxford BRC outside the submitted work. He has received personal fees from AstraZeneca, Teva and PeerVoice outside the submitted work. In the last 5 years, IP has received speaker’s honoraria for speaking at sponsored meetings from AstraZeneca, Boehringer Ingelheim, Aerocrine AB, Almirall, Novartis, Teva, Chiesi, Sanofi/Regeneron, Menarini and GSK and payments for organising educational events from AstraZeneca, GSK, Sanofi/Regeneron and Teva. He has received honoraria for attending advisory panels with Genentech, Sanofi/Regeneron, AstraZeneca, Boehringer Ingelheim, GSK, Novartis, Teva, Merck, Circassia, Chiesi and Knopp and payments to support FDA approval meetings from GSK. He has received sponsorship to attend international scientific meetings from Boehringer Ingelheim, GSK, AstraZeneca, Teva and Chiesi. He has received a grant from Chiesi to support a phase 2 clinical trial in Oxford. He is a copatent holder of the rights to the Leicester Cough Questionnaire and has received payments for its use in clinical trials from Merck, Bayer and Insmed. In 2014–2015, he was an expert witness for a patent dispute involving AstraZeneca and Teva.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.

Figures

Figure 1

Prototype asthma attack risk scale. Numbers in each cell are predicted annual asthma attack rates for patients over the age of 12 if treatment is not changed. An asthma attack is an episode of acute asthma requiring treatment with systemic steroids ≥3 days and/or hospitalisation. The blood eosinophil count is contemporaneous or the highest result in the last 12 months; fractional exhaled nitric oxide level is contemporaneous. *Risk factors are defined by the Global Initiative for Asthma (GINA) guidelines: poor symptom control (Asthma Control Questionnaire score ≥1.5), low lung function (forced expiratory volume in 1 second 200 dose of salbutamol cannister/month), intubation or intensive care unit admission for asthma previously, comorbidities (one of chronic rhinosinusitis, obesity and psychiatric disease) and environmental exposures (one of smoking, allergen and pollution).