Ian D Pavord, Mark Holliday, Helen K Reddel, Irene Braithwaite, Stefan Ebmeier, Robert J Hancox, Tim Harrison, Claire Houghton, Karen Oldfield, Alberto Papi, Mathew Williams, Mark Weatherall, Richard Beasley, Andrew Corin, Colin Helm, Bhuwan Poudel, Davitt Sheahan, Pamela Sheahan, Miriam Bennett, Caterina Chang, Hollie Ellis, Bob Hancox, Sandra Hopping, Christine Tuffery, James Michael Ramsahai, Jodie Simpson, Peter Wark, Maria Aliani, Maddalena Genco, Alberto Capozzolo, Mauro Carone, Elisa Maini, Jenny Mancin, Antonio Meriggi, Luca Perfetti, Francesca Cherubino, Antonio Spanevello, Dina Visca, Elisabetta Zampogna, Christina Baggott, Allie Eathorne, James Fingleton, Jo Hardy, Janine Pilcher, Donah Sabbagh, Alex Semprini, Karen Shaw, Summer Mackisack, Barney Montgomery, Karen Autridge, Joanna Joseph, Stella Moon, Dean Quinn, Dean Millar-Coote, Jim Reid, Federico Bellini, Martina Marchi, Luca Morandi, Marianna Padovani, Daniela Scalet, Katie Borg, Clare Connolly, Anna Gittins, Gareth Hynes, Helen Jeffers, Ian Pavord, Rahul Shrimanker, Gloria Foxley, Elyse Guevara-Rattray, Stephen Milne, Helen Reddel, and Brett Toelle
Summary 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 Interpretation In patients with mild asthma, the effects of as-needed budesonide–formoterol on exacerbations are independent of biomarker profile, whereas the benefits of maintenance inhaled budesonide are greater in patients with high blood eosinophil counts than in patients with low counts. Funding AstraZeneca, Health Research Council of New Zealand.