基于气道炎症与生物影像学指标改善重度哮喘高临床缓解率：为期2年的前瞻性研究
2025/08/18
摘要
背景：临床缓解是重度哮喘的一个多维度治疗目标。然而，当治疗决策仅依据血嗜酸性粒细胞计数和呼出气一氧化氮(FeNO)水平进行指导时，仅约30%的患者能达到临床缓解。
目的： 评估综合性个体化治疗策略在重度哮喘患者中实现24个月临床缓解的有效性。
方法：依据临床评估、气道生理、气道炎症测定及生物影像学结果，为重度哮喘患者制定个体化综合治疗方案，包括抗炎药物、生物制剂、抗生素、免疫调节剂及支气管热成形术。临床缓解定义为：24个月内无急性发作、未使用口服糖皮质激素(OCS)、症状达到部分/良好控制，可包含或不包含肺功能标准。
结果：共纳入178例重度哮喘患者进行评估。其中，88.2%的患者接受了生物制剂单药或联合治疗方案；20.2%的患者接受了抗生素、高渗盐水和/或免疫球蛋白治疗；9%的患者在炎症控制后行支气管热成形术。随访24个月后发现，89.9%的患者无急性发作，83.1%的患者停用了OCS，78.1%的患者症状得到部分/良好控制，84.8%的患者肺功能保持稳定。基于三项主要标准（无急性发作、无OCS使用、症状部分/良好控制），66.3%的患者达到了临床缓解。若将FEV1%较基线下降幅度≤5%纳入标准，临床缓解率降至为61.6%。然而，当采用最严格标准（ACQ-5≤0.75且FEV1≥80%预计值）时，临床缓解率仅为29.1%。残留疾病活动度主要源于气道感染和气道高反应性，而非2型(T2)炎症。
结论：尽管临床缓解定义存在差异，通过多维度生物标志物整合分析及个体化病理生物学导向的管理策略，重度哮喘患者仍可实现临床缓解率显著升高。然而，反复发作的气道感染、黏液分泌亢进及气道高反应性，仍是阻碍重度哮喘完全缓解的核心瓶颈。
关键词：影像学；炎症指标检测；缓解；重度哮喘；痰液。
背景：临床缓解是重度哮喘的一个多维度治疗目标。然而，当治疗决策仅依据血嗜酸性粒细胞计数和呼出气一氧化氮(FeNO)水平进行指导时，仅约30%的患者能达到临床缓解。
目的： 评估综合性个体化治疗策略在重度哮喘患者中实现24个月临床缓解的有效性。
方法：依据临床评估、气道生理、气道炎症测定及生物影像学结果，为重度哮喘患者制定个体化综合治疗方案，包括抗炎药物、生物制剂、抗生素、免疫调节剂及支气管热成形术。临床缓解定义为：24个月内无急性发作、未使用口服糖皮质激素(OCS)、症状达到部分/良好控制，可包含或不包含肺功能标准。
结果：共纳入178例重度哮喘患者进行评估。其中，88.2%的患者接受了生物制剂单药或联合治疗方案；20.2%的患者接受了抗生素、高渗盐水和/或免疫球蛋白治疗；9%的患者在炎症控制后行支气管热成形术。随访24个月后发现，89.9%的患者无急性发作，83.1%的患者停用了OCS，78.1%的患者症状得到部分/良好控制，84.8%的患者肺功能保持稳定。基于三项主要标准（无急性发作、无OCS使用、症状部分/良好控制），66.3%的患者达到了临床缓解。若将FEV1%较基线下降幅度≤5%纳入标准，临床缓解率降至为61.6%。然而，当采用最严格标准（ACQ-5≤0.75且FEV1≥80%预计值）时，临床缓解率仅为29.1%。残留疾病活动度主要源于气道感染和气道高反应性，而非2型(T2)炎症。
结论：尽管临床缓解定义存在差异，通过多维度生物标志物整合分析及个体化病理生物学导向的管理策略，重度哮喘患者仍可实现临床缓解率显著升高。然而，反复发作的气道感染、黏液分泌亢进及气道高反应性，仍是阻碍重度哮喘完全缓解的核心瓶颈。
关键词：影像学；炎症指标检测；缓解；重度哮喘；痰液。
（南方医科大学南方医院 樊可可 朱邦 赵文驱 赵海金）
（Nolasco S, Kjarsgaard M, et, al. Clinical Remission by a Comprehensive Severe Asthma Management Strategy Guided by Airway Inflammometry and Bioimaging. Am J Respir Crit Care Med. 2025 Jun 20. doi: 10.1164/rccm.202412-2438OC. Epub ahead of print. PMID: 40540629.）
Abstract
Rationale: Clinical remission is a multicomponent treatment goal in severe asthma. However, only about 30% of patients achieve clinical remission when treatment decisions are guided using blood eosinophil and FeNO levels.
Objectives: To assess the effectiveness of a comprehensive, individualized treatment strategy in achieving clinical remission over 24 months in patients with severe asthma.
Methods: Treatment strategies-including anti-inflammatory therapies, biologics, antibiotics, immunomodulators, and bronchial thermoplasty-were guided by clinical assessment, airway physiology, airway inflammometry, and bioimaging. Clinical remission was defined as no exacerbations for 24 months, no oral corticosteroid (OCS) use, and partly/well-controlled symptoms, with or without lung function criteria.
Measurements and Main Results: One-hundred seventy-eight patients with severe asthma were evaluated. Of these, 88.2% were treated with biologics alone or in combination with other strategies; 20.2% were treated with antibiotics, hypertonic saline, and/or immunoglobulins; and 9% underwent bronchial thermoplasty after controlling the inflammatory component. After 24 months, 89.9% of patients were exacerbation-free, 83.1% were OCS-free, 78.1% had partly/well-controlled symptoms, and 84.8% had preserved lung function. Clinical remission was achieved in 66.3% of patients based on the three primary criteria and in 61.6% when including FEV1% decline ≤5% from baseline. However, when the most stringent criteria were applied (ACQ-5 ≤0.75 and FEV1 ≥80%), the clinical remission rate was 29.1%. Residual disease activity was driven primarily by airway infections and airway hyperresponsiveness rather than T2 inflammation.
Conclusions: By using a comprehensive set of biomarkers and employing a management strategy tailored to individual pathobiology, a high proportion of patients with severe asthma can achieve clinical remission, depending on the definitions used. Nonetheless, recurrent airway infections, mucus, and airway hyperresponsiveness remain key unmet needs in severe asthma.
Keywords: imaging; inflammometry; remission; severe asthma; sputum.
Rationale: Clinical remission is a multicomponent treatment goal in severe asthma. However, only about 30% of patients achieve clinical remission when treatment decisions are guided using blood eosinophil and FeNO levels.
Objectives: To assess the effectiveness of a comprehensive, individualized treatment strategy in achieving clinical remission over 24 months in patients with severe asthma.
Methods: Treatment strategies-including anti-inflammatory therapies, biologics, antibiotics, immunomodulators, and bronchial thermoplasty-were guided by clinical assessment, airway physiology, airway inflammometry, and bioimaging. Clinical remission was defined as no exacerbations for 24 months, no oral corticosteroid (OCS) use, and partly/well-controlled symptoms, with or without lung function criteria.
Measurements and Main Results: One-hundred seventy-eight patients with severe asthma were evaluated. Of these, 88.2% were treated with biologics alone or in combination with other strategies; 20.2% were treated with antibiotics, hypertonic saline, and/or immunoglobulins; and 9% underwent bronchial thermoplasty after controlling the inflammatory component. After 24 months, 89.9% of patients were exacerbation-free, 83.1% were OCS-free, 78.1% had partly/well-controlled symptoms, and 84.8% had preserved lung function. Clinical remission was achieved in 66.3% of patients based on the three primary criteria and in 61.6% when including FEV1% decline ≤5% from baseline. However, when the most stringent criteria were applied (ACQ-5 ≤0.75 and FEV1 ≥80%), the clinical remission rate was 29.1%. Residual disease activity was driven primarily by airway infections and airway hyperresponsiveness rather than T2 inflammation.
Conclusions: By using a comprehensive set of biomarkers and employing a management strategy tailored to individual pathobiology, a high proportion of patients with severe asthma can achieve clinical remission, depending on the definitions used. Nonetheless, recurrent airway infections, mucus, and airway hyperresponsiveness remain key unmet needs in severe asthma.
Keywords: imaging; inflammometry; remission; severe asthma; sputum.
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