Abstract Rationale Asthma exacerbations are often managed generically based on symptoms, leading to frequent use of oral corticosteroids (OCS) and antibiotics, both linked to adverse effects. Our center is conducting a prospective interventional study evaluating whether objective assessment during exacerbations can reduce inappropriate treatment. Sputum is induced within safe boundaries in all assessed patients. Evidence increasingly supports that exacerbations display distinct inflammatory phenotypes, with improved outcomes when therapy is phenotype-driven. This sub-study analyzed sputum endotypes and their correlation with three common inflammatory markers (sputum and blood eosinophils, neutrophils, and FeNO) and therapy. We hypothesized that incorporating sputum analysis better identifies exacerbation endotypes and enables more personalized therapy than blood biomarkers or FeNO alone. Methods The exacerbation clinic has assessed 232 exacerbations using a standardized protocol in its first 18 months of existence at the Institut Universitaire de Cardiologie et de Pneumologie de Québec-Université Laval. Beyond FeNO and complete blood count, sputum was induced and processed for cell differential count and collection of supernatants. IL-1β, IL-4, IL-5, IL-6, IL-13, IL-33, CCL-17, Eotaxin-3, TNF-α, and TSLP were quantified for each sample using the automated ELLA ELISA system. Statistical analysis was performed across predefined groups 1) sputum inflammation (eosinophilic: ≥2% eosinophils; neutrophilic: ≥64% neutrophils; mixed: ≥2% eosinophils and ≥64% neutrophils; paucigranulocytic: 2% eosinophils and 64% neutrophils), 2) FeNO (≥25 vs 25), 3) blood inflammation (eosinophils ≥300 cells/uL vs eosinophils 300 cells/uL, neutrophils ≥4,000 cells/UL vs eosinophils 4,000 cells/uL), and 4) according to prescribed treatment (OCS and antibiotics). Results A total of 174 sputum samples were analyzed. Significant variations in both T2 and non-T2 cytokines were observed across sputum inflammatory phenotypes (Table 1). In contrast, cytokine levels did not differ when exacerbations were stratified by blood eosinophils, blood neutrophils, or FeNO. Exacerbations successfully treated with antibiotics showed higher sputum IL-1β, IL-6, TNF-α, and neutrophil counts (P 0.05). The strongest correlation was between blood neutrophils and antibiotic therapy (r = 0.46, P 0.0001). No biomarker differences were associated with OCS prescription. Conclusions These results demonstrate that sputum induction during severe asthma exacerbations is safe and feasible. It provides superior detection of the underlying inflammatory endotypes compared with other biomarkers for both eosinophilic and neutrophilic exacerbations. Sputum findings and blood neutrophil counts correlate well with physicians’ clinical assessments, supporting appropriate antibiotic use. However, this alignment is not observed for oral corticosteroid prescriptions, highlighting the need for better guidance and biomarker integration to optimize OCS use during exacerbations. This abstract is funded by: Fondation IUCPQ and AstraZeneca
Boulay et al. (Fri,) studied this question.