TOPLINE:

Asthma exacerbations during therapy with benralizumab — an interleukin-5 receptor alpha antagonist — did not involve eosinophilic inflammation; instead, airway neutrophilia, elevated levels of neutrophil activation markers, detectable respiratory viruses, and shifts in the sputum microbiome indicated that infection was the dominant cause of asthma exacerbations.

METHODOLOGY:

• Researchers conducted a phase 4 prospective cohort study across 15 centers to characterize the inflammatory and physiologic features of exacerbations during treatment with benralizumab in patients with severe eosinophilic asthma.
• They assessed 156 patients (mean age, 54.2 years; 57.7% women) treated with benralizumab; patients received 30 mg of benralizumab via subcutaneous injection every 4 weeks for the first three doses and subsequently every 8 weeks, with follow-up for 12-18 months.
• Exacerbation events were assessed before initiating oral corticosteroids or antibiotics, with evaluations involving fractional exhaled nitric oxide measurement, spirometry, and blood tests that measured full blood count and C-reactive protein (CRP) levels.
• Sputum was collected for microbiome analysis, viral detection, and assessment of neutrophil activity (based on the concentrations of neutrophil elastase-conjugated DNA and azurocidin-1).
• Changes in all measured parameters from baseline to exacerbation were analyzed.

TAKEAWAY:

• Overall, 58.3% of patients experienced an exacerbation, accounting for 272 events during the study. At exacerbation, the median blood eosinophil count was 0 cells/µL, and the median percentage of eosinophils in sputum was 0%, indicating that eosinophils were fully suppressed during benralizumab therapy.
• A sputum neutrophil percentage ≥ 60% was observed in 55.1% of samples collected during exacerbations. Median levels of CRP and levels of both neutrophil elastase-conjugated DNA and azurocidin-1 increased significantly from baseline (P < .05 for all).
• Samples collected during exacerbations showed a higher abundance of Moraxella than those collected at baseline, with reduced diversity, and a significant difference in microbial composition between stable and exacerbation samples (P < .05 for all).
• Influenza A, metapneumovirus, and rhinovirus were the most frequently detected viruses; new acquisitions of Moraxella catarrhalis, Haemophilus influenzae, and Streptococcus pneumoniae were observed during exacerbations. 

IN PRACTICE:

“Asthma exacerbations during treatment with benralizumab are not precipitated by eosinophilic inflammation. Prevalence of airway neutrophilia increased neutrophil activation markers, detectable viral pathogens, and alteration of sputum microbiome composition (eg, reduced alpha-diversity and acquisition of new pathogens) suggest that infection is the most prominent cause,” the authors wrote.

SOURCE:

This study was led by Jennifer Logan, MRCP, Gartnavel General Hospital, Glasgow, Scotland. It was published online on May 29, 2026, in The Lancet Respiratory Medicine.

LIMITATIONS:

More than half of exacerbation events were not assessed onsite before treatment began. Sputum samples were unavailable for a substantial proportion of assessed exacerbations. Hospital admissions were more frequent among missed exacerbations than assessed ones, and the inflammatory mechanisms underlying these potentially more severe, missed events could not be characterized. 

DISCLOSURES:

This study was funded by AstraZeneca. Several authors disclosed receiving speaker fees, consulting fees, research grants to their institutions, lecture fees, support for attending meetings, or participation on advisory boards from multiple organizations, including AstraZeneca and Medscape.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.