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
2025/10/11
摘要
背景：临床缓解是重度哮喘的多维度治疗目标。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浓度时，仅约30%患者能达到临床缓解。本研究旨在评估为期24个月的个体化综合治疗策略对重度哮喘患者实现临床缓解的有效性。
方法：治疗策略（包括抗炎疗法、生物制剂、抗生素、免疫调节剂和支气管热成形术）均通过临床评估、气道生理学、气道炎症测量学和生物成像技术进行指导。临床缓解定义为：24个月内无急性发作、未使用口服皮质类固醇、症状达到部分/完全控制（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。其中88.2%接受生物制剂单药或联合治疗；20.2%接受抗生素、高渗盐水和/或免疫球蛋白治疗；9%在控制炎症后接受支气管热成形术。24个月后，89.9%患者无急性发作，83.1%停用口服皮质类固醇，78.1%实现症状部分/完全控制，85.4%保持肺功能稳定。基于三项主要标准，66.3%患者达到临床缓解；若加入FEV1%较基线下降≤5%的标准，缓解率为61.6%。但当采用最严格标准（哮喘控制问卷分值≤0.75且FEV1≥80%）时，临床缓解率为29.1%。残留疾病活动主要源于气道感染和气道高反应性，而非2型炎症。
结论：通过采用综合生物标志物组和个体化病理生物学管理策略，可根据不同定义使大部分重度哮喘患者获得临床缓解。然而，反复气道感染、黏液分泌过多和气道高反应性仍是当前未满足的治疗需求。
Clinical Remission by a Comprehensive Severe Asthma Management Strategy Guided by Airway Inflammometry and Bioimaging
Nolasco S, Kjarsgaard M, Lauks S, Treleaven O, Ho T, Huang C, Radford K, Swindall T, Venegas Garrido C, Bhalla A, Thawanaphong S, Friedlander Y, Dyment L, Surette M, Trus M, Sehmi R, Haider E, Khalidi N, Sommer DD, Waserman S, Mukherjee M, Svenningsen S, Cox G, Nair P.
Abstract
BACKGROUND:
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 counts and fractional exhaled nitric oxide concentrations. 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 antiinflammatory 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 use, and partly/well-controlled symptoms, with or without lung function criteria.
RESULTS:
A total of 178 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 oral corticosteroid-free, 78.1% had partly/well-controlled symptoms, and 85.4% 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 (five-point Asthma Control Questionnaire ⩽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 type 2 inflammation.
CONCLUSION:
By using a comprehensive set of biomarkers and 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.
背景：临床缓解是重度哮喘的多维度治疗目标。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浓度时，仅约30%患者能达到临床缓解。本研究旨在评估为期24个月的个体化综合治疗策略对重度哮喘患者实现临床缓解的有效性。
方法：治疗策略（包括抗炎疗法、生物制剂、抗生素、免疫调节剂和支气管热成形术）均通过临床评估、气道生理学、气道炎症测量学和生物成像技术进行指导。临床缓解定义为：24个月内无急性发作、未使用口服皮质类固醇、症状达到部分/完全控制（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。其中88.2%接受生物制剂单药或联合治疗；20.2%接受抗生素、高渗盐水和/或免疫球蛋白治疗；9%在控制炎症后接受支气管热成形术。24个月后，89.9%患者无急性发作，83.1%停用口服皮质类固醇，78.1%实现症状部分/完全控制，85.4%保持肺功能稳定。基于三项主要标准，66.3%患者达到临床缓解；若加入FEV1%较基线下降≤5%的标准，缓解率为61.6%。但当采用最严格标准（哮喘控制问卷分值≤0.75且FEV1≥80%）时，临床缓解率为29.1%。残留疾病活动主要源于气道感染和气道高反应性，而非2型炎症。
结论：通过采用综合生物标志物组和个体化病理生物学管理策略，可根据不同定义使大部分重度哮喘患者获得临床缓解。然而，反复气道感染、黏液分泌过多和气道高反应性仍是当前未满足的治疗需求。
（中日友好医院呼吸与危重症医学科 沈焜路 摘译 林江涛 审校）
（Am J Respir Crit Care Med. 2025 Sep; DOI: 10.1164/rccm.202412-2438OC）
Clinical Remission by a Comprehensive Severe Asthma Management Strategy Guided by Airway Inflammometry and Bioimaging
Nolasco S, Kjarsgaard M, Lauks S, Treleaven O, Ho T, Huang C, Radford K, Swindall T, Venegas Garrido C, Bhalla A, Thawanaphong S, Friedlander Y, Dyment L, Surette M, Trus M, Sehmi R, Haider E, Khalidi N, Sommer DD, Waserman S, Mukherjee M, Svenningsen S, Cox G, Nair P.
Abstract
BACKGROUND:
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 counts and fractional exhaled nitric oxide concentrations. 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 antiinflammatory 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 use, and partly/well-controlled symptoms, with or without lung function criteria.
RESULTS:
A total of 178 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 oral corticosteroid-free, 78.1% had partly/well-controlled symptoms, and 85.4% 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 (five-point Asthma Control Questionnaire ⩽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 type 2 inflammation.
CONCLUSION:
By using a comprehensive set of biomarkers and 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.
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