Pseudomonas aeruginosa infection drives IL-5-independent hypereosinophilia in mepolizumab, benralizumab-treated asthma.

Severe eosinophilic asthma is a chronic inflammatory condition characterized by elevated eosinophil levels, often leading to frequent exacerbations. Biologic therapies targeting interleukin-5 (IL-5) or its receptor (IL-5R), such as mepolizumab and benralizumab, effectively reduce eosinophilia and asthma exacerbations by blocking this key type 2 inflammatory pathway. However, the occurrence of breakthrough eosinophilic attacks in patients on these biologics is typically considered a treatment failure, prompting investigation into alternative mechanisms that might drive eosinophilia independently of the IL-5 axis.

This report details two case studies of patients with severe asthma receiving anti-IL-5 biologics who experienced relapsing hypereosinophilia. Case 1 involved a 71-year-old woman on mepolizumab for severe eosinophilic asthma and COPD overlap. Case 2 was a 56-year-old woman with late-onset asthma receiving benralizumab. In both cases, the sudden rebound in eosinophil counts coincided with confirmed Pseudomonas aeruginosa airway infection. The primary observation was the resolution of hypereosinophilia following targeted antibiotic treatment for the bacterial infection.

In Case 1, a 71-year-old woman on mepolizumab experienced a sudden rebound in eosinophils to 1,400 cells/μL during an acute exacerbation, coinciding with Pseudomonas aeruginosa infection. This hypereosinophilia resolved after antibiotic treatment. Similarly, Case 2, a 56-year-old woman receiving benralizumab, developed marked eosinophil rebound to 1,690 cells/μL, also associated with P. aeruginosa infection. This too resolved after antipseudomonal therapy. These findings suggest that P. aeruginosa infection can drive eosinophilia through mechanisms independent of the IL-5 pathway, even when IL-5 or IL-5R are blocked by biologics. The consistent resolution of eosinophilia post-antibiotic treatment strongly supports the bacterial infection as the primary driver of the eosinophil rebound.