Longer Asthma Duration Is Associated With Elevated Non-T2 Sputum Biomarkers and Reduced T2 Inflammation in Severe Asthma

IF 11.3 1区医学 Q1 ALLERGY

Allergy Pub Date : 2026-09-11 Epub Date: 2026-07-09 DOI:10.1111/all.70436

Freda Yang, Sujin Seo, Takehiro Hasegawa, Chloe I. Bloom, Nazanin Zounemat-Kermani, Pankaj K. Bhavsar, Katie Raby, Ian M. Adcock, Sungho Won, Tae-Bum Kim, Kian Fan Chung, the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) Consortium

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引用次数: 0

Abstract

Background

Longer asthma duration predicts non-remission in Type-2 (T2) biologic-treated severe asthma, but underlying mechanisms remain unclear. We investigated associations between asthma duration and inflammatory biomarkers that may explain differential biologic response.

Methods

We analysed cross-sectional data from adults with severe asthma in U-BIOPRED. Asthma duration was defined as years from diagnosis to study entry. T2 and non-T2 biomarkers were measured in blood and sputum. Identical assays were performed in PRISM, a validation cohort of biologic-initiators. Multivariable regression models adjusted for age, sex, ethnicity, BMI, smoking and oral corticosteroid dose. Associations between duration-related biomarkers and 12-month biologic remission were explored in PRISM.

Results

In U-BIOPRED (n = 411), median asthma duration was 23 years (IQR 12–38). Longer duration was associated with higher non-T2 biomarkers including sputum CXCL9 (β = 0.024, 95% CI 0.011–0.038), sputum IL-6 (β = 0.024, 95% CI 0.011–0.037) and sputum neutrophils (β = 0.009, 95% CI 0.001–0.017), but lower T2 biomarkers including plasma periostin (β = −0.006, 95% CI −0.009 to −0.003), eosinophils (blood: β = −0.002, 95% CI −0.003 to −0.001; sputum: β = −0.023, 95% CI −0.035 to −0.011), sputum EDN (β = −0.032, 95% CI −0.049 to −0.014) and FeNO (β = −0.006, 95% CI −0.010 to −0.001). PRISM (n = 474) confirmed these associations. Higher sputum CXCL9 was associated with reduced remission in anti-IL-4Rα-treated patients with asthma duration ≥ 20 years (β = −1.73, 95% CI −3.180 to −0.276).

Conclusion

Longer asthma duration was associated with elevated airway non-T2 inflammation and reduced systemic and airway T2 inflammation. This highlights the importance of airway biomarker sampling and suggests combined T2 and non-T2 therapeutic strategies may be needed to achieve remission in long-standing asthma.

Trial Registration

ClinicalTrials.gov identifier: NCT05164939

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哮喘持续时间延长与重度哮喘患者非T2痰生物标志物升高和T2炎症降低相关

背景：较长的哮喘持续时间预示着2型（T2）生物治疗的严重哮喘无法缓解，但潜在的机制尚不清楚。我们研究了哮喘持续时间和炎症生物标志物之间的关系，这些生物标志物可能解释了不同的生物反应。方法：我们分析了U-BIOPRED中患有严重哮喘的成人的横断面数据。哮喘持续时间定义为从诊断到进入研究的年数。检测血液和痰中T2和非T2生物标志物。在PRISM中进行了相同的测定，这是一个生物引发剂的验证队列。多变量回归模型调整了年龄、性别、种族、BMI、吸烟和口服皮质类固醇剂量。在PRISM中探讨病程相关生物标志物与12个月生物缓解之间的关系。结果在U-BIOPRED中（n = 411），中位哮喘持续时间为23年（IQR 12-38）。较长的治疗时间与较高的非T2生物标志物相关，包括痰CXCL9 （β = 0.024, 95% CI 0.011-0.038）、痰IL-6 （β = 0.024, 95% CI 0.011-0.037）和痰中性粒细胞（β = 0.009, 95% CI 0.001-0.017），但较低的T2生物标志物包括血浆骨膜蛋白（β = -0.006, 95% CI -0.009至-0.003）、嗜酸性粒细胞(血液：β = -0.002, 95% CI -0.003至-0.001；痰:β= -0.023,95%可信区间-0.035到-0.011),痰版(β= -0.032,95%可信区间-0.049到-0.014)和FeNO(β= -0.006,95%可信区间-0.010到-0.001)。PRISM （n = 474）证实了这些关联。在抗il - 4r α治疗的哮喘病程≥20年的患者中，高痰CXCL9与缓解降低相关（β = -1.73, 95% CI -3.180 ~ -0.276）。结论哮喘持续时间延长与气道非T2炎症升高、全身和气道T2炎症降低相关。这突出了气道生物标志物采样的重要性，并表明可能需要联合T2和非T2治疗策略来实现长期哮喘的缓解。临床试验注册号：NCT05164939。

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来源期刊

Allergy 医学-过敏

CiteScore

26.10

自引率

9.70%

发文量

393

审稿时长

2 months

期刊介绍： Allergy is an international and multidisciplinary journal that aims to advance, impact, and communicate all aspects of the discipline of Allergy/Immunology. It publishes original articles, reviews, position papers, guidelines, editorials, news and commentaries, letters to the editors, and correspondences. The journal accepts articles based on their scientific merit and quality. Allergy seeks to maintain contact between basic and clinical Allergy/Immunology and encourages contributions from contributors and readers from all countries. In addition to its publication, Allergy also provides abstracting and indexing information. Some of the databases that include Allergy abstracts are Abstracts on Hygiene & Communicable Disease, Academic Search Alumni Edition, AgBiotech News & Information, AGRICOLA Database, Biological Abstracts, PubMed Dietary Supplement Subset, and Global Health, among others.