Inflammatory Epithelial and Macrophage Pathways Underlie Residual Asthma Exacerbations in Urban Children Treated with Mepolizumab

While biologic therapies targeting type 2 (T2) inflammation reduce acute exacerbation rates in children with asthma and T2 inflammation, exacerbations still occur, and the underlying molecular mechanisms are poorly defined. We aimed to identify multiple distinct molecular mechanisms implicated in asthma exacerbations by characterizing respiratory illnesses among urban children with eosinophilic asthma enrolled in a clinical trial comparing treatment with mepolizumab versus placebo The MUPPITS-2 study was a randomized, double-blind, placebo-controlled, parallel- group trial of children with exacerbation-prone asthma in low-income urban centers conducted from Nov 7, 2017 to April 20, 2021, and has been previously described1. MUPPITS-2 stands for “Mechanisms Underlying Asthma Exacerbations Prevented and Persistent with Immune-Based Therapy: a Systems Approach Phase 2” (ClinicalTrials.gov number, NCT03292588). Participants were recruited across urban sites in 9 U.S. cities. An individual was eligible for enrollment if he or she: was 6-17 years of age; was diagnosed with asthma by a clinician greater than 1 year prior to recruitment; had at least 2 asthma exacerbations in the prior year (defined as a requirement for SCS and/or hospitalization); was treated at study entry with at least fluticasone propionate 250 mcg 1 puff twice daily or its equivalent for those aged 6 to 11 years, or with at least fluticasone/salmeterol 250/50 mcg 1 puff twice daily or its equivalent for those aged 12-17 years; had peripheral blood eosinophils ≥ 150 per mm3; and lived in a census tract with a density of ≥1000 families per square mile and at least 10% of families with income below the poverty level.