严重哮喘的死亡率——来自NORDSTAR队列的结果
2025/11/28
摘要
背景：目前缺乏关于哮喘严重程度对死亡率影响的纵向数据。本研究旨在根据哮喘严重程度探讨全因死亡率及特定病因死亡率。
方法：本注册性队列研究基于NORdic Dataset for aSThmA Research（NORDSTAR）研究合作平台中的丹麦数据。将成年严重哮喘患者按年龄和性别与10名轻度至中度哮喘患者进行匹配，随访时间为2000年至2020年。排除入组前已诊断为慢性阻塞性肺疾病（COPD）的患者。比较严重哮喘与轻度至中度哮喘患者的全因死亡率及特定病因死亡率的绝对和相对指标。
结果：我们分别纳入了11,811名严重哮喘患者和118,810名轻度至中度哮喘患者。严重哮喘患者的全因死亡率显著高于轻度至中度哮喘患者，无论是随访20年后的累积死亡率绝对指标[34%（95%置信区间：32, 35）对比20%（19, 20），p<0.001]，还是相对指标[风险比（HR）=1.99（1.90, 2.09），p<0.001]。调整口服皮质类固醇（OCS）使用后，全因死亡率的HR减弱[HR=1.30（95% CI：1.23, 1.37），p<0.001]；调整T2炎症标志物后，HR为1.34（1.09, 1.64，p<0.001）。累积死亡率风险增加主要归因于呼吸系统疾病[12.6%（95% CI：11.7, 13.6）对比3.3%（3.2, 3.5），p<0.001]，而癌症[7.5%（95% CI：6.8, 8.3）对比5.9%（5.7, 6.2），p<0.001]和心血管疾病[4.7%（95% CI：4.1, 5.3）对比3.8%（3.6, 4.0），p<0.001]也有贡献。尽管罕见，严重哮喘患者哮喘相关死亡的相对风险增加了三倍[HR=2.95（2.08, 4.18），p<0.001]。
结论：在这一全国性队列中，与轻度至中度哮喘相比，严重哮喘与显著更高的死亡风险相关。风险增加主要由呼吸相关死亡驱动，OCS使用和T2炎症是重要的死亡风险因素。
Mortality in Severe Asthma-results from the NORDSTAR cohort
Hansen S, von Bülow A, Cooper A, et al.
Abstract
BACKGROUND:Longitudinal data addressing the impact of asthma severity on mortality are lacking. We aimed to explore all-cause and cause-specific mortality according to asthma severity.
METHODS:The present registry-based cohort study is based on Danish data from the NORdic Dataset for aSThmA Research (NORDSTAR) research collaboration platform. Adult patients with severe asthma were matched on age and sex to 10 patients with mild-to-moderate asthma and followed from 2000-2020. Patients with chronic obstructive pulmonary disease (COPD) diagnosed prior to inclusion were excluded. Absolute and relative measures of all-cause and cause-specific mortality were compared between severe and mild-to-moderate asthma.
RESULTS:We included 11 811 and 118 810 patients with severe and mild-to-moderate asthma, respectively. All-cause mortality was significantly higher in patients with severe asthma compared to patients with mild-to-moderate asthma, both in absolute measures of the cumulative mortality [34% (95% CI: 32, 35) versus 20% (19, 20), p<0.001] after 20 years of follow-up and in relative measures [hazard ratio (HR)=1.99 (1.90, 2.09), p<0.001]. The HR of all-cause mortality was attenuated after adjustment for oral corticosteroid (OCS) use [HR=1.30 (95% CI: 1.23, 1.37, p<0.001)] and T2 inflammatory markers [HR=1.34 (1.09, 1.64), p<0.001]. The increased cumulative mortality risk was mainly due to respiratory diseases [12.6% (95% CI:11.7, 13.6) versus 3.3% (3.2, 3.5), p<0.001] with cancer [7.5% (95% CI: 6.8, 8.3) versus 5.9% (5.7, 6.2), p<0.001 ] and cardiovascular diseases [4.7% (95% CI: 4.1, 5.3) versus 3.8% (3.6, 4.0), p<0.001] also contributing. Though rare, the relative risk of asthma-related deaths was three-fold in severe asthma patients [HR=2.95 (2.08, 4.18), p<0.001].
CONCLUSION:In this nationwide cohort, severe asthma was associated with a significantly higher mortality risk compared to mild-to-moderate asthma. The increased risk was primarily driven by respiratory-related deaths, with OCS use and T2 inflammation as contributing mortality risk factors.
背景：目前缺乏关于哮喘严重程度对死亡率影响的纵向数据。本研究旨在根据哮喘严重程度探讨全因死亡率及特定病因死亡率。
方法：本注册性队列研究基于NORdic Dataset for aSThmA Research（NORDSTAR）研究合作平台中的丹麦数据。将成年严重哮喘患者按年龄和性别与10名轻度至中度哮喘患者进行匹配，随访时间为2000年至2020年。排除入组前已诊断为慢性阻塞性肺疾病（COPD）的患者。比较严重哮喘与轻度至中度哮喘患者的全因死亡率及特定病因死亡率的绝对和相对指标。
结果：我们分别纳入了11,811名严重哮喘患者和118,810名轻度至中度哮喘患者。严重哮喘患者的全因死亡率显著高于轻度至中度哮喘患者，无论是随访20年后的累积死亡率绝对指标[34%（95%置信区间：32, 35）对比20%（19, 20），p<0.001]，还是相对指标[风险比（HR）=1.99（1.90, 2.09），p<0.001]。调整口服皮质类固醇（OCS）使用后，全因死亡率的HR减弱[HR=1.30（95% CI：1.23, 1.37），p<0.001]；调整T2炎症标志物后，HR为1.34（1.09, 1.64，p<0.001）。累积死亡率风险增加主要归因于呼吸系统疾病[12.6%（95% CI：11.7, 13.6）对比3.3%（3.2, 3.5），p<0.001]，而癌症[7.5%（95% CI：6.8, 8.3）对比5.9%（5.7, 6.2），p<0.001]和心血管疾病[4.7%（95% CI：4.1, 5.3）对比3.8%（3.6, 4.0），p<0.001]也有贡献。尽管罕见，严重哮喘患者哮喘相关死亡的相对风险增加了三倍[HR=2.95（2.08, 4.18），p<0.001]。
结论：在这一全国性队列中，与轻度至中度哮喘相比，严重哮喘与显著更高的死亡风险相关。风险增加主要由呼吸相关死亡驱动，OCS使用和T2炎症是重要的死亡风险因素。
（中日友好医院呼吸与危重症医学科 李春晓 摘译 林江涛 审校）
（Eur Respir J. 2025 Nov 6:2501289.DOI: 10.1183/13993003.01289-2025.）
Mortality in Severe Asthma-results from the NORDSTAR cohort
Hansen S, von Bülow A, Cooper A, et al.
Abstract
BACKGROUND:Longitudinal data addressing the impact of asthma severity on mortality are lacking. We aimed to explore all-cause and cause-specific mortality according to asthma severity.
METHODS:The present registry-based cohort study is based on Danish data from the NORdic Dataset for aSThmA Research (NORDSTAR) research collaboration platform. Adult patients with severe asthma were matched on age and sex to 10 patients with mild-to-moderate asthma and followed from 2000-2020. Patients with chronic obstructive pulmonary disease (COPD) diagnosed prior to inclusion were excluded. Absolute and relative measures of all-cause and cause-specific mortality were compared between severe and mild-to-moderate asthma.
RESULTS:We included 11 811 and 118 810 patients with severe and mild-to-moderate asthma, respectively. All-cause mortality was significantly higher in patients with severe asthma compared to patients with mild-to-moderate asthma, both in absolute measures of the cumulative mortality [34% (95% CI: 32, 35) versus 20% (19, 20), p<0.001] after 20 years of follow-up and in relative measures [hazard ratio (HR)=1.99 (1.90, 2.09), p<0.001]. The HR of all-cause mortality was attenuated after adjustment for oral corticosteroid (OCS) use [HR=1.30 (95% CI: 1.23, 1.37, p<0.001)] and T2 inflammatory markers [HR=1.34 (1.09, 1.64), p<0.001]. The increased cumulative mortality risk was mainly due to respiratory diseases [12.6% (95% CI:11.7, 13.6) versus 3.3% (3.2, 3.5), p<0.001] with cancer [7.5% (95% CI: 6.8, 8.3) versus 5.9% (5.7, 6.2), p<0.001 ] and cardiovascular diseases [4.7% (95% CI: 4.1, 5.3) versus 3.8% (3.6, 4.0), p<0.001] also contributing. Though rare, the relative risk of asthma-related deaths was three-fold in severe asthma patients [HR=2.95 (2.08, 4.18), p<0.001].
CONCLUSION:In this nationwide cohort, severe asthma was associated with a significantly higher mortality risk compared to mild-to-moderate asthma. The increased risk was primarily driven by respiratory-related deaths, with OCS use and T2 inflammation as contributing mortality risk factors.
上一篇：
肥胖成年哮喘患者减重对哮喘的影响 —— 一项系统综述与荟萃分析
下一篇：
美国空气污染混合物年度暴露与哮喘住院率的关联性
