ArticleBMC pulmonary medicine2026
Systemic-airway eosinophil discordance and sputum mediator profiling in severe asthma treated with biologics: a retrospective cohort study.
Article in BMC pulmonary medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundBiologic therapies have expanded treatment options for severe asthma; however, systemic biomarkers do not always reflect airway inflammation. Induced sputum may provide complementary information for inflammatory phenotyping and for exploring predictors of treatment response.
objectivesTo characterize sputum inflammatory profiles in severe asthma using a three-group stratification by peripheral blood eosinophils (PBE) and sputum eosinophils, and to explore whether sputum soluble mediators relate to clinical remission after anti–IL-4Rα therapy.
methodsWe retrospectively analyzed 67 adult asthma patients with paired blood and induced sputum assessments. Patients were stratified using commonly applied thresholds for type 2–related systemic eosinophilia and eosinophilic airway inflammation (PBE ≥ 300/µL and sputum eosinophils ≥ 3%). Among biologic-treated patients, we compared baseline characteristics between anti–IL-5/IL-5R and anti–IL-4Rα users and explored predictors of 12-month clinical remission in the anti–IL-4Rα cohort.
resultsMedian sputum eosinophil and neutrophil percentage were 11.8% and 53.5%, respectively. Eosinophil cationic protein (ECP) correlated positively with PBE, FeNO, IgE, and sputum eosinophils and inversely with percent of predicted forced expiratory volume in one second (%FEV1) and sputum neutrophils, whereas human chitinase-3-like-1 (YKL-40) and IL-6 correlated positively with sputum neutrophils and inversely with T2 indices. The optimal PBE threshold for sputum eosinophils ≥ 3% was 266/µL (sensitivity 84.8%, specificity 93.8%). Among biologic users, anti-IL-5/5R recipients had higher sputum eosinophils than anti-IL-4Rα recipients at baseline. Notably, within the anti-IL-4Rα subgroup, baseline sputum IL-6 was higher in those who achieved clinical remission at 12 months, while FeNO tended to be higher.
conclusionsIn this exploratory cohort, sputum-based phenotyping uncovered systemic–airway discordance and identified an unexpected yet potentially actionable signal: higher baseline sputum IL-6 was associated with 12-month clinical remission under anti–IL-4Rα. If externally validated, IL-6—alongside FeNO and sputum cell counts—may help inform biologic selection to achieve 12-month clinical remission in severe asthma.
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