基于可治疗特征的哮喘管理：一项可行性研究
2025/08/18
摘要
背景与目的：基于“可治疗特征”的个体化医学管理策略已被证实可改善重度哮喘患者的临床结局。本研究旨在评估一项以标准化“可治疗特征”指导的哮喘管理方案，在非重度哮喘门诊患者中开展随机对照试验（RCT）的可行性。
方法：本研究为期10周的单臂队列研究。受试者为经医生确诊的哮喘患者，入组条件包括ACQ-5评分>1，且过去一年内至少出现过一次急性加重。干预措施为依据标准化算法，基于生物标志物对2型炎症与气流受限等特征进行靶向治疗。研究可行性评估指标包括：招募率、干预方案的接受度、参与未来RCT的意愿、10周后仍需“扩展”特征评估的患者比例，以及特征患病率估算。
结果：因COVID-19疫情影响，研究在14个月后停止招募，共纳入29名参与者（目标为50人），招募率为29/118（25%，95% CI：17%-33%）。24/26（92%）的受试者认为干预方案可接受，并愿意参与后续研究。干预10周后，65%的患者哮喘仍未良好控制（ACQ-5 >1），需进一步进行“扩展”特征评估。平均每位患者具有13项特征中的4.8项（标准差为2.3）。
研究期间，ACQ-5评分平均改善1.0分（95% CI：0.3～1.8）；使用支气管扩张剂后的气流受限比例从59%降至35%。研究期间有41%的患者（12/29）在某一阶段持续使用口服糖皮质激素。
结论：标准化的“可治疗特征”管理策略在患者中具有良好接受度，并带来了显著的临床改善，开展完整RCT是可行的。然而，仅针对2型炎症和气流受限的靶向治疗，在大多数患者中尚不足以实现理想的哮喘控制，即便是使用了较高剂量的系统性糖皮质激素。
关键词：哮喘；临床试验；炎症测量；表型；可治疗特征
Background and Objectives：Treatable trait-based personalised medicine improves outcomes in severe asthma clinics. We assessed the feasibility of a randomised controlled trial (RCT) of protocolised treatable trait-guided asthma management in patients not under a severe asthma clinic.
Methods：Ten week single-group cohort study. Participants had a doctor's diagnosis of asthma, Asthma Control Questionnaire-5 (ACQ-5) score > 1, and ≥ 1 exacerbation in the last year. Intervention: biomarker-guided asthma medication according to a protocolised algorithm, targeting traits of type-2 inflammation and airflow obstruction. Feasibility outcomes: recruitment rates, acceptability of intervention, willingness to enrol in an RCT, need for ‘extended’ trait assessment after 10 weeks, and estimation of trait prevalence.
Results：Recruitment ceased with 29/50 participants after 14 months due to difficulties associated with COVID-19. Recruitment rate: 29/118 (25%) of those invited to participate (95% CI 17 to 33). 24/26 (92%) participants found the intervention acceptable and were willing to participate in a future study. After 10 weeks, 65% remained not well controlled (ACQ-5 > 1) and would have required the ‘extended’ assessment. Participants had a mean (SD) 4.8 (2.3) of 13 traits assessed.
ACQ-5 improved during the study by −1.0 (0.3 to 1.8) units, and post-bronchodilator airflow limitation reduced from 59% of participants to 35%. 12/29 (41%) participants received continuous oral corticosteroids at some point during the study.
Conclusion：Protocolised treatable trait management was acceptable to participants, associated with significant clinical benefit, and a full RCT appears feasible. Targeting type-2 inflammation and airflow obstruction was insufficient to control asthma in the majority of patients, despite marked systemic corticosteroid exposure.
Key words：asthma; clinical trial; inflammometry; phenotypes; treatable trait
背景与目的：基于“可治疗特征”的个体化医学管理策略已被证实可改善重度哮喘患者的临床结局。本研究旨在评估一项以标准化“可治疗特征”指导的哮喘管理方案，在非重度哮喘门诊患者中开展随机对照试验（RCT）的可行性。
方法：本研究为期10周的单臂队列研究。受试者为经医生确诊的哮喘患者，入组条件包括ACQ-5评分>1，且过去一年内至少出现过一次急性加重。干预措施为依据标准化算法，基于生物标志物对2型炎症与气流受限等特征进行靶向治疗。研究可行性评估指标包括：招募率、干预方案的接受度、参与未来RCT的意愿、10周后仍需“扩展”特征评估的患者比例，以及特征患病率估算。
结果：因COVID-19疫情影响，研究在14个月后停止招募，共纳入29名参与者（目标为50人），招募率为29/118（25%，95% CI：17%-33%）。24/26（92%）的受试者认为干预方案可接受，并愿意参与后续研究。干预10周后，65%的患者哮喘仍未良好控制（ACQ-5 >1），需进一步进行“扩展”特征评估。平均每位患者具有13项特征中的4.8项（标准差为2.3）。
研究期间，ACQ-5评分平均改善1.0分（95% CI：0.3～1.8）；使用支气管扩张剂后的气流受限比例从59%降至35%。研究期间有41%的患者（12/29）在某一阶段持续使用口服糖皮质激素。
结论：标准化的“可治疗特征”管理策略在患者中具有良好接受度，并带来了显著的临床改善，开展完整RCT是可行的。然而，仅针对2型炎症和气流受限的靶向治疗，在大多数患者中尚不足以实现理想的哮喘控制，即便是使用了较高剂量的系统性糖皮质激素。
关键词：哮喘；临床试验；炎症测量；表型；可治疗特征
（南方医科大学南方医院 黄海伦 龚钊乾 赵文驱 赵海金）
（Fingleton J, McLachlan R, Sparks J, et al. Treatable trait guided asthma management: a feasibility study[J]. Respirology, 2025: resp.70016. DOI: 10.1111/resp.70016.）
AbstractBackground and Objectives：Treatable trait-based personalised medicine improves outcomes in severe asthma clinics. We assessed the feasibility of a randomised controlled trial (RCT) of protocolised treatable trait-guided asthma management in patients not under a severe asthma clinic.
Methods：Ten week single-group cohort study. Participants had a doctor's diagnosis of asthma, Asthma Control Questionnaire-5 (ACQ-5) score > 1, and ≥ 1 exacerbation in the last year. Intervention: biomarker-guided asthma medication according to a protocolised algorithm, targeting traits of type-2 inflammation and airflow obstruction. Feasibility outcomes: recruitment rates, acceptability of intervention, willingness to enrol in an RCT, need for ‘extended’ trait assessment after 10 weeks, and estimation of trait prevalence.
Results：Recruitment ceased with 29/50 participants after 14 months due to difficulties associated with COVID-19. Recruitment rate: 29/118 (25%) of those invited to participate (95% CI 17 to 33). 24/26 (92%) participants found the intervention acceptable and were willing to participate in a future study. After 10 weeks, 65% remained not well controlled (ACQ-5 > 1) and would have required the ‘extended’ assessment. Participants had a mean (SD) 4.8 (2.3) of 13 traits assessed.
ACQ-5 improved during the study by −1.0 (0.3 to 1.8) units, and post-bronchodilator airflow limitation reduced from 59% of participants to 35%. 12/29 (41%) participants received continuous oral corticosteroids at some point during the study.
Conclusion：Protocolised treatable trait management was acceptable to participants, associated with significant clinical benefit, and a full RCT appears feasible. Targeting type-2 inflammation and airflow obstruction was insufficient to control asthma in the majority of patients, despite marked systemic corticosteroid exposure.
Key words：asthma; clinical trial; inflammometry; phenotypes; treatable trait
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吸入性糖皮质激素给药时间对哮喘治疗效果的影响： 一项随机三交叉试验
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小气道功能障碍介导FeNO与哮喘控制之间的关系
