生物缓解作为重度哮喘治疗靶点的观察性分析：英国重症哮喘登记研究
2025/10/11
摘要
背景：重度哮喘生物治疗的目的是抑制T2炎症通路。
目的：我们假设通过生物治疗（FeNO<20ppb和血液嗜酸性粒细胞计数（BEC）<0.15x109，“生物缓解”）完全抑制IL-5和IL4/IL13途径的患者比T2生物学不完全抑制的患者有更好的结果。
方法：回顾性分析英国重症哮喘登记研究（UKSAR）中严格符合国家生物制剂准入标准的重症哮喘患者。在生物缓解（BR）和非BR之间比较了生物学前和年度回顾的特征。
结果：在778例患者中，148例（19%）患有BR，630例（81%）患有非BR。BR在减少恶化，口服类固醇暴露，肺功能改善，症状改善或T2生物标志物减少方面没有带来额外的益处。在开始使用生物制剂之前，BR队列的T2值较低。疾病持续时间长（adjOR 1.96，95%CI 1.17-3.28），大环内酯类药物治疗（adjOR 2.08，95%CI 1.17-3.71）和吸烟史（adjOR 1.63，95%CI 1.11-2.39）是BR的阳性预测因子，而高T2生物标志物预测非BR。然而，BEC和FeNO均与肺功能呈负相关。
结论：与未达到BR的患者相比，达到BR的患者没有更好的结果。BR表示T2疾病负担较低的患者队列和驱动疾病严重程度的其他因素。然而，抑制T2生物学对于肺功能获得很重要。需要对高T2复合患者完全抑制IL5和IL4/13途径的治疗策略进行前瞻性评估。
Observational analysis of biological remission as a treatment target for severe asthma: UK severe asthma registry
McDowell P Jane, Redmond Charlene, Busby John, Patel Pujan, Jackson David J, Pfeffer Paul E, Mansur Adel H, Patel Mitesh, Brown Thomas, Burhan Hassan, Chaudhuri Rekha, Rupani Hitasha, Heaney Liam G
Abstract
Background: The aim of biologic therapies in severe asthma is inhibition of T2 inflammatory pathways.
Objective: We hypothesized that patients who achieve complete suppression of IL-5 & IL4/IL13 pathways with biologic therapy (FeNO <20ppb & blood eosinophil count (BEC) <0.15x10ˆ9, 'biological remission') would have better outcomes than patients with incomplete suppression of T2 biology.
Methods: Retrospective analysis of severe asthma patients in the United Kingdom Severe Asthma Registry (UKSAR) who met strict national access criteria for biologics. Characteristics pre-biologic & at annual review were compared across biological remission (BR) & non-BR.
Results: Of 778 patients, 148 (19%) had BR and 630 (81%) non-BR. BR did not confer additional benefit in exacerbation reduction, oral steroid exposure, lung function improvement, symptom improvement or T2-biomarker reduction. The BR cohort were less T2-high prior to commencing biologics. Long disease duration (adjOR 1.96, 95% CI 1.17 to 3.28), macrolide therapy (adjOR 2.08, 95% CI 1.17 to 3.71), & smoking history (adjOR 1.63, 95% CI 1.11 to 2.39) were positive predictors of BR, while higher-T2 biomarkers predicted non-BR. However, BEC & FeNO both had a negative correlation with lung function.
Conclusion: Patients who achieve BR do not have superior outcomes compared to those who do not achieve BR. BR denotes a cohort of patients with a lower burden of T2 disease & additional factors driving disease severity. However, suppression of T2 biology is important for lung function gain. Prospective evaluation of treatment strategies that completely supress IL5 & IL4/13 pathways in T2-composite high patients is needed.
背景：重度哮喘生物治疗的目的是抑制T2炎症通路。
目的：我们假设通过生物治疗（FeNO<20ppb和血液嗜酸性粒细胞计数（BEC）<0.15x109，“生物缓解”）完全抑制IL-5和IL4/IL13途径的患者比T2生物学不完全抑制的患者有更好的结果。
方法：回顾性分析英国重症哮喘登记研究（UKSAR）中严格符合国家生物制剂准入标准的重症哮喘患者。在生物缓解（BR）和非BR之间比较了生物学前和年度回顾的特征。
结果：在778例患者中，148例（19%）患有BR，630例（81%）患有非BR。BR在减少恶化，口服类固醇暴露，肺功能改善，症状改善或T2生物标志物减少方面没有带来额外的益处。在开始使用生物制剂之前，BR队列的T2值较低。疾病持续时间长（adjOR 1.96，95%CI 1.17-3.28），大环内酯类药物治疗（adjOR 2.08，95%CI 1.17-3.71）和吸烟史（adjOR 1.63，95%CI 1.11-2.39）是BR的阳性预测因子，而高T2生物标志物预测非BR。然而，BEC和FeNO均与肺功能呈负相关。
结论：与未达到BR的患者相比，达到BR的患者没有更好的结果。BR表示T2疾病负担较低的患者队列和驱动疾病严重程度的其他因素。然而，抑制T2生物学对于肺功能获得很重要。需要对高T2复合患者完全抑制IL5和IL4/13途径的治疗策略进行前瞻性评估。
（中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校）
（J Allergy Clin Immunol Pract. 2025 Sep 5:S2213-2198(25)00828-1. doi: 10.1016/j.jaip.2025.08.027.）
Observational analysis of biological remission as a treatment target for severe asthma: UK severe asthma registry
McDowell P Jane, Redmond Charlene, Busby John, Patel Pujan, Jackson David J, Pfeffer Paul E, Mansur Adel H, Patel Mitesh, Brown Thomas, Burhan Hassan, Chaudhuri Rekha, Rupani Hitasha, Heaney Liam G
Abstract
Background: The aim of biologic therapies in severe asthma is inhibition of T2 inflammatory pathways.
Objective: We hypothesized that patients who achieve complete suppression of IL-5 & IL4/IL13 pathways with biologic therapy (FeNO <20ppb & blood eosinophil count (BEC) <0.15x10ˆ9, 'biological remission') would have better outcomes than patients with incomplete suppression of T2 biology.
Methods: Retrospective analysis of severe asthma patients in the United Kingdom Severe Asthma Registry (UKSAR) who met strict national access criteria for biologics. Characteristics pre-biologic & at annual review were compared across biological remission (BR) & non-BR.
Results: Of 778 patients, 148 (19%) had BR and 630 (81%) non-BR. BR did not confer additional benefit in exacerbation reduction, oral steroid exposure, lung function improvement, symptom improvement or T2-biomarker reduction. The BR cohort were less T2-high prior to commencing biologics. Long disease duration (adjOR 1.96, 95% CI 1.17 to 3.28), macrolide therapy (adjOR 2.08, 95% CI 1.17 to 3.71), & smoking history (adjOR 1.63, 95% CI 1.11 to 2.39) were positive predictors of BR, while higher-T2 biomarkers predicted non-BR. However, BEC & FeNO both had a negative correlation with lung function.
Conclusion: Patients who achieve BR do not have superior outcomes compared to those who do not achieve BR. BR denotes a cohort of patients with a lower burden of T2 disease & additional factors driving disease severity. However, suppression of T2 biology is important for lung function gain. Prospective evaluation of treatment strategies that completely supress IL5 & IL4/13 pathways in T2-composite high patients is needed.
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基于气道炎症测量学与生物成像指导的重度哮喘综合管理策略实现临床缓解的研究
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用于哮喘治疗的孢子启发式吸入给药系统
