呼吸道生物制剂引入后哮喘急性加重的群体趋势
2026/06/30
摘要
重要性：呼吸道生物制剂已改变了哮喘的治疗方式，哮喘是一种全球约3亿人受其影响的疾病。
目的：评估哮喘急性加重的群体趋势，包括涵盖多种生物制剂获批期间的趋势。
设计与参与者：这项队列研究使用了马萨诸塞州波士顿一家大型医疗系统2006年1月至2025年5月的电子健康记录，涵盖专科过敏和肺科诊所。纳入18岁及以上经医生诊断为哮喘且在专科诊所就诊的成人。排除除慢性阻塞性肺疾病外的其他慢性肺部疾病患者。
暴露因素：鉴于2015年至2018年间6种呼吸道生物制剂中有4种获批，2015年被预先指定为暴露变化点，以评估哮喘急性加重的变化。
主要结果与测量指标：主要结果为每年每1000名哮喘患者急性加重事件的截距和斜率变化。采用中断时间序列分析方法评估急性加重的即时和持续减少情况。亚组分析按严重程度、基线嗜酸性粒细胞计数以及人口统计学或临床特征评估变化。
结果：在5269名哮喘成人（平均[标准差]年龄51.9[18.3]岁；3761名女性[71.4%]）中，2006年至2015年急性加重事件从每年每1000名患者155.4（95%置信区间，117.7至193.2）例增加。2015年后，出现即时减少（-474.1[95%置信区间，-783.2至-165.0]事件/1000患者/年），随后是持续的年度下降（-206.5[95%置信区间，-259.9至-153.0]事件/1000患者/年）。每年发生2次或更多次急性加重的患者改善更显著（即时：-808.2[95%置信区间，-1646.5至30.2]事件/1000患者/年；斜率：-374.5[95%置信区间，-519.4至-229.7]事件/1000患者/年），优于每年发生少于2次急性加重的患者。基线嗜酸性粒细胞水平≥450个/μL的患者较嗜酸性粒细胞水平<150个/μL的患者显著下降（即时：-1799.8[95%置信区间，-3555.3至-44.3]事件/1000患者/年；斜率：-443.4[95%置信区间，-746.7至-140.0]事件/1000患者/年）。各年龄、性别、体重指数、吸烟状况和保险亚组均出现减少，尽管吸烟者和城市居民仍保持较高绝对率。
结论与相关性：在这项5269名哮喘成人队列研究中，哮喘急性加重显著减少，尤其在严重或嗜酸性粒细胞型疾病患者中。重要的是，这些益处缩小了中重度哮喘患者与轻度哮喘患者之间的结局差距，并支持生物制剂的有效性，凸显其改善高危人群结局的潜力。
Population-Level Trends in Asthma Exacerbations After Introduction of Respiratory Biologics
Yung-Fang Tu, David W Stein, Ayobami Akenroye
Abstract
Importance:Respiratory biologics have transformed the treatment for asthma, a disease affecting approximately 300 million individuals globally.
Objective:To evaluate population-level trends in asthma exacerbations, including during a period encompassing approval of multiple biologics.
Design, setting, and participants:This cohort study used electronic health records from a large health care system in Boston, Massachusetts, including specialty allergy and pulmonology clinics, from January 2006 to May 2025. Adults aged 18 years or older with physician-diagnosed asthma seen in specialty clinics were included. Patients with other chronic lung diseases, except chronic obstructive pulmonary disease, were excluded.
Exposure:The year 2015 was designated a priori as the exposure change point to assess changes in asthma exacerbations, given that it marked the beginning of a period of rapid approval of respiratory biologics with 4 of the 6 respiratory biologics approved between 2015 and 2018.
Main outcomes and measures:The primary outcomes were the changes in the intercept and slope of annual exacerbations per 1000 asthma patients per year. Immediate and sustained reductions in exacerbations were evaluated using the interrupted time series analytic approach. Subgroup analyses evaluated changes by severity, baseline eosinophil count, and demographic or clinical characteristics.
Results:Among 5269 adults with asthma (mean [SD] age, 51.9 [18.3] years; 3761 female [71.4%]), exacerbations increased from 2006 to 2015 (155.4 [95% CI, 117.7 to 193. 2] events per 1000 patients per year). After 2015, an immediate reduction occurred (-474.1 [95% CI, -783.2 to -165.0] events per 1000 patients per year), followed by a sustained yearly decline (-206.5 [95% CI, -259.9 to -153.0] events per 1000 patients per year). Patients with 2 or more annual exacerbations showed greater improvements (immediate: -808.2 [95% CI, -1646.5 to 30.2] events per 1000 patients per year; slope: -374.5 [95% CI, -519.4 to -229.7] events per 1000 patients per year) than patients with fewer than 2 exacerbations. Those with baseline eosinophil levels of 450 cells/μL or greater exhibited significant declines (immediate: -1799.8 [95% CI, -3555.3 to -44.3] events per 1000 patients per year; slope: -443.4 [95% CI, -746.7 to -140.0] events per 1000 patients per year) compared with patients with eosinophil levels less than150 cells/μL. Reductions occurred across age, sex, body mass index, smoking, and insurance subgroups, although smokers and inner-city residents retained higher absolute rates.
Conclusions and relevance:In this cohort study of 5269 adults with asthma, there were significant reductions in asthma exacerbations, particularly among patients with severe or eosinophilic disease. Importantly, these benefits closed the outcome gap between patients with moderate to severe asthma and those with mild asthma, and support the effectiveness of biologics, highlighting their potential to improve outcomes among high-risk populations.
重要性：呼吸道生物制剂已改变了哮喘的治疗方式，哮喘是一种全球约3亿人受其影响的疾病。
目的：评估哮喘急性加重的群体趋势，包括涵盖多种生物制剂获批期间的趋势。
设计与参与者：这项队列研究使用了马萨诸塞州波士顿一家大型医疗系统2006年1月至2025年5月的电子健康记录，涵盖专科过敏和肺科诊所。纳入18岁及以上经医生诊断为哮喘且在专科诊所就诊的成人。排除除慢性阻塞性肺疾病外的其他慢性肺部疾病患者。
暴露因素：鉴于2015年至2018年间6种呼吸道生物制剂中有4种获批，2015年被预先指定为暴露变化点，以评估哮喘急性加重的变化。
主要结果与测量指标：主要结果为每年每1000名哮喘患者急性加重事件的截距和斜率变化。采用中断时间序列分析方法评估急性加重的即时和持续减少情况。亚组分析按严重程度、基线嗜酸性粒细胞计数以及人口统计学或临床特征评估变化。
结果：在5269名哮喘成人（平均[标准差]年龄51.9[18.3]岁；3761名女性[71.4%]）中，2006年至2015年急性加重事件从每年每1000名患者155.4（95%置信区间，117.7至193.2）例增加。2015年后，出现即时减少（-474.1[95%置信区间，-783.2至-165.0]事件/1000患者/年），随后是持续的年度下降（-206.5[95%置信区间，-259.9至-153.0]事件/1000患者/年）。每年发生2次或更多次急性加重的患者改善更显著（即时：-808.2[95%置信区间，-1646.5至30.2]事件/1000患者/年；斜率：-374.5[95%置信区间，-519.4至-229.7]事件/1000患者/年），优于每年发生少于2次急性加重的患者。基线嗜酸性粒细胞水平≥450个/μL的患者较嗜酸性粒细胞水平<150个/μL的患者显著下降（即时：-1799.8[95%置信区间，-3555.3至-44.3]事件/1000患者/年；斜率：-443.4[95%置信区间，-746.7至-140.0]事件/1000患者/年）。各年龄、性别、体重指数、吸烟状况和保险亚组均出现减少，尽管吸烟者和城市居民仍保持较高绝对率。
结论与相关性：在这项5269名哮喘成人队列研究中，哮喘急性加重显著减少，尤其在严重或嗜酸性粒细胞型疾病患者中。重要的是，这些益处缩小了中重度哮喘患者与轻度哮喘患者之间的结局差距，并支持生物制剂的有效性，凸显其改善高危人群结局的潜力。
（北京朝阳医院呼吸与危重症医学科 顾宪民 摘译 中日友好医院呼吸与危重症医学科 林江涛 审校）
（JAMA Netw Open. 2026 Jun 1;9(6):e2620272. doi: 10.1001/jamanetworkopen.2026.20272.）
（JAMA Netw Open. 2026 Jun 1;9(6):e2620272. doi: 10.1001/jamanetworkopen.2026.20272.）
Population-Level Trends in Asthma Exacerbations After Introduction of Respiratory Biologics
Yung-Fang Tu, David W Stein, Ayobami Akenroye
Abstract
Importance:Respiratory biologics have transformed the treatment for asthma, a disease affecting approximately 300 million individuals globally.
Objective:To evaluate population-level trends in asthma exacerbations, including during a period encompassing approval of multiple biologics.
Design, setting, and participants:This cohort study used electronic health records from a large health care system in Boston, Massachusetts, including specialty allergy and pulmonology clinics, from January 2006 to May 2025. Adults aged 18 years or older with physician-diagnosed asthma seen in specialty clinics were included. Patients with other chronic lung diseases, except chronic obstructive pulmonary disease, were excluded.
Exposure:The year 2015 was designated a priori as the exposure change point to assess changes in asthma exacerbations, given that it marked the beginning of a period of rapid approval of respiratory biologics with 4 of the 6 respiratory biologics approved between 2015 and 2018.
Main outcomes and measures:The primary outcomes were the changes in the intercept and slope of annual exacerbations per 1000 asthma patients per year. Immediate and sustained reductions in exacerbations were evaluated using the interrupted time series analytic approach. Subgroup analyses evaluated changes by severity, baseline eosinophil count, and demographic or clinical characteristics.
Results:Among 5269 adults with asthma (mean [SD] age, 51.9 [18.3] years; 3761 female [71.4%]), exacerbations increased from 2006 to 2015 (155.4 [95% CI, 117.7 to 193. 2] events per 1000 patients per year). After 2015, an immediate reduction occurred (-474.1 [95% CI, -783.2 to -165.0] events per 1000 patients per year), followed by a sustained yearly decline (-206.5 [95% CI, -259.9 to -153.0] events per 1000 patients per year). Patients with 2 or more annual exacerbations showed greater improvements (immediate: -808.2 [95% CI, -1646.5 to 30.2] events per 1000 patients per year; slope: -374.5 [95% CI, -519.4 to -229.7] events per 1000 patients per year) than patients with fewer than 2 exacerbations. Those with baseline eosinophil levels of 450 cells/μL or greater exhibited significant declines (immediate: -1799.8 [95% CI, -3555.3 to -44.3] events per 1000 patients per year; slope: -443.4 [95% CI, -746.7 to -140.0] events per 1000 patients per year) compared with patients with eosinophil levels less than150 cells/μL. Reductions occurred across age, sex, body mass index, smoking, and insurance subgroups, although smokers and inner-city residents retained higher absolute rates.
Conclusions and relevance:In this cohort study of 5269 adults with asthma, there were significant reductions in asthma exacerbations, particularly among patients with severe or eosinophilic disease. Importantly, these benefits closed the outcome gap between patients with moderate to severe asthma and those with mild asthma, and support the effectiveness of biologics, highlighting their potential to improve outcomes among high-risk populations.
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Tezepelumab治疗重度哮喘的一年期临床缓解：TERESA单臂前瞻性研究
