小气道功能障碍影响成人哮喘临床缓解：ATLANTIS研究事后分析
2026/03/30
摘要
背景： 哮喘缓解是一个可实现的治疗目标。然而，目前哮喘缓解定义尚不统一，相关预测性生物标志物仍显不足。
方法： 本研究对ATLANTIS（NCT02123667）进行事后分析，ATLANTIS是一项多国、多中心前瞻性研究，共纳入684名成人哮喘患者。哮喘缓解根据3组成分（3C）和4组成分（4C）标准定义。3C缓解包括：（1）ACQ-6<1.5，（2）未使用维持性口服糖皮质激素，（3）无急性加重。在4C定义中，额外增加一个指标：支气管舒张前FEV1%预计值下降幅度 < 10%。采用多变量Logistic回归分析确定缓解的预测因素。基于五项临床变量（ACQ-6、FeNO、BEC和FEV1）并结合一种新型的小气道功能障碍问卷工具（SADT）进行因素分析，构建了新的低疾病活动度（LDA）评分。此外，对鼻腔转录组进行差异基因表达和通路富集分析，并在U-BIOPRED（NCT01976767）中通过痰液转录组进行验证。U-BIOPRED仅用于验证ATLANTIS中发现的哮喘缓解相关通路。
结果： 48%（3C）和45%（4C）患者实现哮喘缓解。预测因素包括男性、肺功能改善、既往急性发作较少以及更高的SADT评分（提示小气道症状较少）。LDA评分可识别较轻的疾病状态，并与缓解相关［3C OR 4.43（2.80，7.10），4C OR 3.46（2.23，5.43）］，同时与生活质量改善［OR 2.07（1.65，2.60）］及未来急性加重减少［OR 0.43（0.22，0.85）］相关。转录组分析显示，ATLANTIS和U-BIOPRED均存在白介素4/13相关信号通路上调和凝血通路的下调。
结论： 小气道功能障碍与哮喘缓解减少相关。新建的LDA工具在哮喘前瞻性风险分层方面具有临床应用价值。关键的免疫和凝血通路可能参与缓解机制，并为未来干预提供潜在靶点。
关键词：哮喘；疾病加重；因素分析；基因表达分析；诱导缓解；自发缓解。
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.
Keywords: asthma; disease exacerbation; factor analysis; gene expression analysis; remission induction; spontaneous remission.
背景： 哮喘缓解是一个可实现的治疗目标。然而，目前哮喘缓解定义尚不统一，相关预测性生物标志物仍显不足。
方法： 本研究对ATLANTIS（NCT02123667）进行事后分析，ATLANTIS是一项多国、多中心前瞻性研究，共纳入684名成人哮喘患者。哮喘缓解根据3组成分（3C）和4组成分（4C）标准定义。3C缓解包括：（1）ACQ-6<1.5，（2）未使用维持性口服糖皮质激素，（3）无急性加重。在4C定义中，额外增加一个指标：支气管舒张前FEV1%预计值下降幅度 < 10%。采用多变量Logistic回归分析确定缓解的预测因素。基于五项临床变量（ACQ-6、FeNO、BEC和FEV1）并结合一种新型的小气道功能障碍问卷工具（SADT）进行因素分析，构建了新的低疾病活动度（LDA）评分。此外，对鼻腔转录组进行差异基因表达和通路富集分析，并在U-BIOPRED（NCT01976767）中通过痰液转录组进行验证。U-BIOPRED仅用于验证ATLANTIS中发现的哮喘缓解相关通路。
结果： 48%（3C）和45%（4C）患者实现哮喘缓解。预测因素包括男性、肺功能改善、既往急性发作较少以及更高的SADT评分（提示小气道症状较少）。LDA评分可识别较轻的疾病状态，并与缓解相关［3C OR 4.43（2.80，7.10），4C OR 3.46（2.23，5.43）］，同时与生活质量改善［OR 2.07（1.65，2.60）］及未来急性加重减少［OR 0.43（0.22，0.85）］相关。转录组分析显示，ATLANTIS和U-BIOPRED均存在白介素4/13相关信号通路上调和凝血通路的下调。
结论： 小气道功能障碍与哮喘缓解减少相关。新建的LDA工具在哮喘前瞻性风险分层方面具有临床应用价值。关键的免疫和凝血通路可能参与缓解机制，并为未来干预提供潜在靶点。
关键词：哮喘；疾病加重；因素分析；基因表达分析；诱导缓解；自发缓解。
（南方医科大学南方医院 凌嘉骏 樊可可 赵海金）
（Kumar A, Chan R, Zounemat-Kermani N, Quek E, Adcock IM, Beghe B, et al. Small Airways Dysfunction and Remission in Adults With Asthma: A Longitudinal Exploratory Analysis of the AssessmenT of smalL Airways involvemeNT In aSthma (ATLANTIS) Study. Allergy 2026:10.1111/all.70264.）
（Kumar A, Chan R, Zounemat-Kermani N, Quek E, Adcock IM, Beghe B, et al. Small Airways Dysfunction and Remission in Adults With Asthma: A Longitudinal Exploratory Analysis of the AssessmenT of smalL Airways involvemeNT In aSthma (ATLANTIS) Study. Allergy 2026:10.1111/all.70264.）
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.
Keywords: asthma; disease exacerbation; factor analysis; gene expression analysis; remission induction; spontaneous remission.
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