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Background <p>Biologic 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.</p> Objectives <p>To 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.</p> Methods <p>We 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.</p> Results <p>Median 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 (%FEV<sub>1</sub>) 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.</p> Conclusions <p>In 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. </p>

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Systemic–airway eosinophil discordance and sputum mediator profiling in severe asthma treated with biologics: a retrospective cohort study

  • 期刊论文

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  • 发表日期：

    2026年4月13日

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  • Moe Tanaka,
  • Toshiyuki Koya,
  • Wakana Uji,
  • Hiroki Koda,
  • Masahiro Endo,
  • Kyoichiro Oshima,
  • Haruka Sofuku,
  • Takahiro Matsuda,
  • Shun Naramoto,
  • Hiroshi Ueno,
  • Ami Aoki,
  • Kenjiro Shima,
  • Yosuke Kimura,
  • Toshiaki Kikuchi

摘要

Background

Biologic 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.

Objectives

To 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.

Methods

We 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.

Results

Median 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.

Conclusions

In 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.