Predictive value of blood eosinophils and exhaled nitric oxide in adults with mild asthma: a prespecified subgroup analysis of an open-label, parallel-group, randomised controlled trial

Pavord, Ian D; Holliday, Mark; Reddel, Helen K; Braithwaite, Irene; Ebmeier, Stefan; Hancox, Robert J; Harrison, Tim; Houghton, Claire; Oldfield, Karen; Papi, Alberto; Williams, Mathew; Weatherall, Mark; Beasley, Richard; Corin, Andrew; Helm, Colin; Poudel, Bhuwan; Sheahan, Davitt; Sheahan, Pamela; Bennett, Miriam; Chang, Caterina; Ellis, Hollie; Hancox, Bob; Hopping, Sandra; Tuffery, Christine; Ramsahai, James Michael; Simpson, Jodie; Wark, Peter; Aliani, Maria; Genco, Maddalena; Capozzolo, Alberto; Carone, Mauro; Maini, Elisa; Mancin, Jenny; Meriggi, Antonio; Perfetti, Luca; Cherubino, Francesca; Spanevello, Antonio; Visca, Dina; Zampogna, Elisabetta; Baggott, Christina; Beasley, Richard; Braithwaite, Irene; Eathorne, Allie; Ebmeier, Stefan; Fingleton, James; Hardy, Jo; Holliday, Mark; Houghton, Claire; Oldfield, Karen; Pilcher, Janine; Sabbagh, Donah; Semprini, Alex; Williams, Mathew; Harrison, Tim; Shaw, Karen; Mackisack, Summer; Montgomery, Barney; Autridge, Karen; Joseph, Joanna;...

Abstract

Background
Whether blood eosinophil counts and exhaled nitric oxide (FeNO) are associated with important outcomes in mild asthma is unclear. In this prespecified subgroup analysis of a previously published open-label clinical trial, we aimed to assess associations between blood eosinophil counts and FeNO with outcomes and response to asthma treatment.

Methods
In the previously reported 52-week, open-label, randomised controlled trial, people with mild asthma receiving only β agonist reliever inhalers were enrolled at one of 16 clinical trials units in New Zealand, the UK, Italy, or Australia. Eligible participants were randomly assigned (1:1:1, stratified by country), to receive inhalers to take as-needed salbutamol (two inhalations of 100 μg in a pressurised metered dose inhaler), maintenance budesonide (200 μg twice per day by inhaler) plus as-needed salbutamol (two inhalations of 100 μg), or as-needed budesonide–formoterol (one inhalation of 200 μg budesonide and 6μg formoterol by inhaler). The primary outcome was the annual rates of asthma exacerbations per patient, and in this prespecified subgroup analysis, we assessed whether annual exacerbation rates in each treatment group were significantly different depending on levels of blood eosinophil count, FeNO, or a composite score of both. Analyses were done for patients with available biomarker measurements The study was registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12615000999538.

Findings
675 participants were enrolled between March 17, 2016, and Aug 29, 2017, of whom 656 had results for blood eosinophil analysis and 668 had results for FeNO. Of the patients who received as-needed salbutamol, the proportion of patients having a severe exacerbation increased progressively with increasing blood eosinophil count (two [4%] of 49 participants with

Citation

Pavord, I. D., Holliday, M., Reddel, H. K., Braithwaite, I., Ebmeier, S., Hancox, R. J., …Toelle, B. (2020). Predictive value of blood eosinophils and exhaled nitric oxide in adults with mild asthma: a prespecified subgroup analysis of an open-label, parallel-group, randomised controlled trial. Lancet Respiratory Medicine, 8(7), 671-680. https://doi.org/10.1016/s2213-2600%2820%2930053-9

• Journal Article Type: Article
• Acceptance Date: Nov 1, 2019
• Online Publication Date: Mar 11, 2020
• Publication Date: Jul 1, 2020
• Deposit Date: Jan 18, 2021
• Publicly Available Date: Jan 19, 2021
• Journal: The Lancet Respiratory Medicine
• Print ISSN: 2213-2600
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 8
• Issue: 7
• Pages: 671-680
• DOI: https://doi.org/10.1016/s2213-2600%2820%2930053-9
• Keywords: Pulmonary and Respiratory Medicine
• Public URL: https://nottingham-repository.worktribe.com/output/5152453
• Publisher URL: https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30053-9/fulltext
• Additional Information: Authors on behalf of the Novel START Study Team.