成人哮喘患者的小气道功能障碍与缓解：哮喘小气道受累评估（ATLANTIS）研究的纵向探索性分析
2026/03/04
摘要
背景：哮喘缓解是一个可行的治疗目标。然而，缓解的定义各不相同，且预测性生物标志物仍未得到充分研究。
方法：我们对ATLANTIS研究（NCT02123667）进行了事后分析，这是一项多国前瞻性研究，纳入了684名成年哮喘患者。缓解根据三要素（3C）和四要素（4C）标准定义。3C缓解包括：（1）哮喘控制问卷6项（ACQ - 6）评分＜1.5；（2）无维持性口服皮质类固醇治疗；（3）无病情加重。4C定义在此基础上增加了支气管扩张剂使用前第1秒用力呼气容积占预计值百分比（FEV1%）的绝对下降＜10%。多变量逻辑回归确定了缓解的预测因素。通过对五项临床变量（ACQ - 6、呼出气一氧化氮（FeNO）、血嗜酸性粒细胞计数（BEC）和FEV1）进行因子分析，开发了一种新的低疾病活动度（LDA）评分，其中包括一种创新的小气道功能障碍问卷工具（SADT）。分析了鼻腔转录组学的差异基因表达和通路富集情况，并在U - BIOPRED研究（NCT01976767）中使用痰液转录组学进行了验证。纳入U - BIOPRED研究仅用于研究在ATLANTIS研究中确定的缓解通路的组学验证。
结果：48%（3C）和45%（4C）的患者出现缓解。预测因素包括男性、肺功能较好、既往病情加重次数较少以及SADT评分较高（小气道症状较少）。LDA评分可识别病情较轻的患者，且与缓解相关[3C的比值比（OR）为4.43（2.80，7.10），4C的OR为3.46（2.23，5.43）]，与生活质量改善相关[OR为2.07（1.65，2.60）]，且与未来病情加重次数减少相关[OR为0.43（0.22，0.85）]。转录组学分析显示，在ATLANTIS和U - BIOPRED研究中，缓解均与白细胞介素4/13信号通路的上调和凝血通路的下调有关。
解读：小气道功能障碍与哮喘缓解减少有关。一种新的LDA工具在分层预测哮喘风险方面显示出临床应用价值。关键的免疫和止血通路可能是缓解的基础，为未来的干预提供了潜在靶点。
Small Airways Dysfunction and Remission in Adults With Asthma: A Longitudinal Exploratory Analysis of the AssessmenT of smalL Airways involvemeNT In aSthma (ATLANTIS) Study
Akshi Kumar, Rory Chan, Nazanin Zounemat-Kermani, Eleanor Quek, Ian M Adcock, Bianca Beghe, Christopher Brightling, Dave Singh, Janwillem Kocks, Alberto Papi, Klaus F Rabe, Ulrica Scaffidi-Argentina, Maarten van den Berge, Monica Kraft, Salman Siddiqui
Abstract
Background: Asthma remission is a feasible treatment goal. However, remission definitions vary, and predictive biomarkers remain underexplored.
Methods: We conducted a post hoc analysis of ATLANTIS (NCT02123667), a multinational prospective study including 684 adult asthmatics. Remission was defined by 3-component (3C) and 4-component (4C) criteria. 3C remission included: (1) ACQ-6 < 1.5, (2) no maintenance oral corticosteroids, (3) no exacerbations. An absolute decline < 10% in pre-bronchodilator FEV1% predicted, was added for the 4C definition. Multivariate logistic regression identified remission predictors. A novel Low Disease Activity (LDA) score was developed using factor analysis of five clinical variables (ACQ-6, FeNO, BEC, and FEV1) including an innovative small airways dysfunction questionnaire tool (SADT). Nasal transcriptomics were analysed for differential gene expression and pathway enrichment and were replicated in U-BIOPRED (NCT01976767) using sputum transcriptomics. U-BIOPRED was included only to study omics replication of remission pathways identified in ATLANTIS.
Findings: Remission occurred in 48% (3C) and 45% (4C) of patients. Predictors included male sex, better lung function, fewer previous exacerbations, and higher SADT (fewer small airways symptoms). LDA identified milder disease and was associated with remission [OR 3C 4.43 (2.80, 7.10) and 4C 3.46 (2.23, 5.43)], improved QoL [OR 2.07 (1.65, 2.60)], and fewer future exacerbations [OR 0.43 (0.22, 0.85)]. Transcriptomic analyses revealed remission-associated upregulation of interleukin 4/13 signalling and downregulation of coagulation pathways, in both ATLANTIS and U-BIOPRED.
Interpretation: SAD was associated with reduced asthma remission. A novel LDA tool demonstrated clinical utility in stratifying prospective asthma risk. Key immunologic and haemostatic pathways may underpin remission, offering potential targets for future intervention.
背景：哮喘缓解是一个可行的治疗目标。然而，缓解的定义各不相同，且预测性生物标志物仍未得到充分研究。
方法：我们对ATLANTIS研究（NCT02123667）进行了事后分析，这是一项多国前瞻性研究，纳入了684名成年哮喘患者。缓解根据三要素（3C）和四要素（4C）标准定义。3C缓解包括：（1）哮喘控制问卷6项（ACQ - 6）评分＜1.5；（2）无维持性口服皮质类固醇治疗；（3）无病情加重。4C定义在此基础上增加了支气管扩张剂使用前第1秒用力呼气容积占预计值百分比（FEV1%）的绝对下降＜10%。多变量逻辑回归确定了缓解的预测因素。通过对五项临床变量（ACQ - 6、呼出气一氧化氮（FeNO）、血嗜酸性粒细胞计数（BEC）和FEV1）进行因子分析，开发了一种新的低疾病活动度（LDA）评分，其中包括一种创新的小气道功能障碍问卷工具（SADT）。分析了鼻腔转录组学的差异基因表达和通路富集情况，并在U - BIOPRED研究（NCT01976767）中使用痰液转录组学进行了验证。纳入U - BIOPRED研究仅用于研究在ATLANTIS研究中确定的缓解通路的组学验证。
结果：48%（3C）和45%（4C）的患者出现缓解。预测因素包括男性、肺功能较好、既往病情加重次数较少以及SADT评分较高（小气道症状较少）。LDA评分可识别病情较轻的患者，且与缓解相关[3C的比值比（OR）为4.43（2.80，7.10），4C的OR为3.46（2.23，5.43）]，与生活质量改善相关[OR为2.07（1.65，2.60）]，且与未来病情加重次数减少相关[OR为0.43（0.22，0.85）]。转录组学分析显示，在ATLANTIS和U - BIOPRED研究中，缓解均与白细胞介素4/13信号通路的上调和凝血通路的下调有关。
解读：小气道功能障碍与哮喘缓解减少有关。一种新的LDA工具在分层预测哮喘风险方面显示出临床应用价值。关键的免疫和止血通路可能是缓解的基础，为未来的干预提供了潜在靶点。
（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）
（Allergy. 2026 Feb 18. doi: 10.1111/all.70264.）
（Allergy. 2026 Feb 18. doi: 10.1111/all.70264.）
Small Airways Dysfunction and Remission in Adults With Asthma: A Longitudinal Exploratory Analysis of the AssessmenT of smalL Airways involvemeNT In aSthma (ATLANTIS) Study
Akshi Kumar, Rory Chan, Nazanin Zounemat-Kermani, Eleanor Quek, Ian M Adcock, Bianca Beghe, Christopher Brightling, Dave Singh, Janwillem Kocks, Alberto Papi, Klaus F Rabe, Ulrica Scaffidi-Argentina, Maarten van den Berge, Monica Kraft, Salman Siddiqui
Abstract
Background: Asthma remission is a feasible treatment goal. However, remission definitions vary, and predictive biomarkers remain underexplored.
Methods: We conducted a post hoc analysis of ATLANTIS (NCT02123667), a multinational prospective study including 684 adult asthmatics. Remission was defined by 3-component (3C) and 4-component (4C) criteria. 3C remission included: (1) ACQ-6 < 1.5, (2) no maintenance oral corticosteroids, (3) no exacerbations. An absolute decline < 10% in pre-bronchodilator FEV1% predicted, was added for the 4C definition. Multivariate logistic regression identified remission predictors. A novel Low Disease Activity (LDA) score was developed using factor analysis of five clinical variables (ACQ-6, FeNO, BEC, and FEV1) including an innovative small airways dysfunction questionnaire tool (SADT). Nasal transcriptomics were analysed for differential gene expression and pathway enrichment and were replicated in U-BIOPRED (NCT01976767) using sputum transcriptomics. U-BIOPRED was included only to study omics replication of remission pathways identified in ATLANTIS.
Findings: Remission occurred in 48% (3C) and 45% (4C) of patients. Predictors included male sex, better lung function, fewer previous exacerbations, and higher SADT (fewer small airways symptoms). LDA identified milder disease and was associated with remission [OR 3C 4.43 (2.80, 7.10) and 4C 3.46 (2.23, 5.43)], improved QoL [OR 2.07 (1.65, 2.60)], and fewer future exacerbations [OR 0.43 (0.22, 0.85)]. Transcriptomic analyses revealed remission-associated upregulation of interleukin 4/13 signalling and downregulation of coagulation pathways, in both ATLANTIS and U-BIOPRED.
Interpretation: SAD was associated with reduced asthma remission. A novel LDA tool demonstrated clinical utility in stratifying prospective asthma risk. Key immunologic and haemostatic pathways may underpin remission, offering potential targets for future intervention.
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Tezepelumab 治疗依赖性口服皮质类固醇的成人重症、未控制哮喘患者的口服皮质类固醇减量与停用（WAYFINDER
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