Symptom burden to characterise, predict, and prevent asthma attacks: a patient-level meta-analysis of randomised trials and translational prospective studies.

We evaluated the extent to which symptom burden measured by the 5-item Asthma Control Questionnaire (ACQ-5) predicts future severe asthma attacks and response to anti-inflammatory therapy.

我们评估了通过5项哮喘控制问卷（ACQ-5）测量的症状负担在预测未来严重哮喘发作和对炎症治疗反应方面的程度。

Methods

We conducted an individual participant data meta-analysisof selected randomised controlled trials and translational observational cohort studies of asthma of varying severity.

我们对不同严重程度的哮喘进行了随机对照试验和转化观察队列研究的个体参与者数据荟萃分析。

Primary analyses used the ORACLE2 patient-level meta-analysis(n=6513) of control-group participants from 22 randomised controlled trials.

主要分析使用了ORACLE2患者级荟萃分析（n=6513），该分析包括来自22个随机对照试验的对照组参与者。

Additional datasets from studies assessing type 2 targeting anti-inflammatory therapies were included on the basis of availability of data, to provide insight into the association between ACQ-5 and sputum cell counts or mediator data.

基于数据的可用性，包括了评估2型靶向抗炎疗法的研究数据集，以提供ACQ-5与痰细胞计数或介质数据之间关联的洞察。

Additional datasets were the DREAM intravenous mepolizumab group (n=461); a cross-sectional severe asthma cohort (SA-OT, n=74); and two acute asthma cohorts (PRISMA, biologic-naive, n=53; BOOST, anti-interleukin-5-treated, n=60).

额外的数据集包括DREAM静脉注射美泊利单抗组（n=461）；一个横断面严重哮喘队列（SA-OT，n=74）；以及两个急性哮喘队列（PRISMA，生物制剂未经治疗，n=53；BOOST，抗白细胞介素-5治疗，n=60）。

Associations between baseline ACQ-5 scores and clinical, physiological, and inflammatory profiles, asthma attack risk, and anti-inflammatory treatment responses were examined.

检查了基线ACQ-5评分与临床、生理和炎症特征、哮喘发作风险以及抗炎治疗反应之间的关联。

Results

Across five datasets encompassing 7161 distinct participants, asthma severity, lung function, inflammatory profiles, comorbidities, and ACQ-5 results varied widely.

在包含7161名不同参与者的五个数据集中，哮喘严重程度、肺功能、炎症特征、合并症和ACQ-5结果差异很大。

The proportion of patients with high symptom burden (ACQ-5 score >1·5) ranged from 39% to 100%.

症状负担高的患者比例（ACQ-5评分>1·5）范围从39%到100%。

Baseline ACQ-5 showed no consistent cross-sectional association with other clinical, physiological, or inflammatory asthma features.

基线ACQ-5与临床、生理或炎症性哮喘特征之间没有一致的横断面关联。

Each 0·5-point increase in baseline ACQ-5 score was associated with a modest increase in future asthma attack risk (adjusted rate ratio [aRR] 1·09 [95% CI 1·06-1·12]; Δ R2=0·02 vs multivariable prediction model without ACQ-5).

基线ACQ-5评分每增加0·5分，未来哮喘发作风险适度增加（调整后率比[aRR] 1·09 [95% CI 1·06-1·12]；Δ R2=0·02与不包含ACQ-5的多变量预测模型相比）。

Baseline ACQ-5 score did not alter relative and absolute attack risk reduction from intravenous mepolizumab in DREAM.

基线ACQ-5评分并未改变静脉注射美泊利单抗在DREAM中的相对和绝对发作风险降低。

By contrast, patients with high blood eosinophil counts and high fractional exhaled nitric oxide (FeNO) had the highest relative and absolute risk reduction (2·81 vs 1·17 attacks; aRR 0·38 [95% CI 0·25-0·57]).

相比之下，高血嗜酸性粒细胞计数和高呼出气一氧化氮分数（FeNO）的患者具有最高的相对和绝对风险降低（2·81比1·17次发作；aRR 0·38 [95% CI 0·25-0·57]）。

In the PRISMA and BOOST datasets, ACQ-5 was not associated with post-corticosteroid lung function change.

在PRISMA和BOOST数据集中，ACQ-5与皮质类固醇后肺功能变化无关。

Across studies, relative and absolute treatment effects showed consistent associations with blood eosinophil counts and FeNO.

在研究中，相对和绝对治疗效果与血嗜酸性粒细胞计数和FeNO显示出一致的关联。

interpretation

In a large, individual patient-level meta-analysisof randomised controlled trials and translational prospective observational cohort studies, we observed little alignment of symptom burden with other clinical, physiological, or biological features of asthma and modest prognostic value for severe attacks.

在一项大型的个体患者水平的随机对照试验和转化性前瞻性观察队列研究的荟萃分析中，我们观察到症状负担与其他临床、生理或生物特征的哮喘对齐性很小，对严重发作的预后价值适度。

Conversely, type 2 biomarkers more reliably identified patients at high risk and those likely to respond to treatment.

相反地，2型生物标志物更能可靠地识别出高风险患者以及那些可能对治疗有反应的患者。

Symptoms might require contextual interpretation to guide anti-inflammatory escalation in asthma.

症状可能需要根据上下文进行解释，以指导哮喘的抗炎治疗升级。

funding

National Institute for Health and Care Research, Association Pulmonaire du Québec, Fonds de Recherche du Québec-Santé, and The Academy of Medical Sciences.

国家卫生与护理研究学院、魁北克省肺部协会、魁北克省健康研究基金会和医学科学院。