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识别哮喘重度恶化风险患者:多变量预测模型的建立和外部验证。

Identifying patients at risk for severe exacerbations of asthma: development and external validation of a multivariable prediction model.

机构信息

Department of General Practice, Academic Medical Center-University of Amsterdam (AMC), Amsterdam, The Netherlands.

LUMC Quality of Care Institute, Leiden University Medical Center (LUMC), Leiden, The Netherlands Department of Public Health and Primary Care, Leiden University Medical Center (LUMC), Leiden, The Netherlands.

出版信息

Thorax. 2016 Sep;71(9):838-46. doi: 10.1136/thoraxjnl-2015-208138. Epub 2016 Apr 4.

Abstract

BACKGROUND

Preventing exacerbations of asthma is a major goal in current guidelines. We aimed to develop a prediction model enabling practitioners to identify patients at risk of severe exacerbations who could potentially benefit from a change in management.

METHODS

We used data from a 12-month primary care pragmatic trial; candidate predictors were identified from GINA 2014 and selected with a multivariable bootstrapping procedure. Three models were constructed, based on: (1) history, (2) history+spirometry and (3) history+spirometry+FeNO. Final models were corrected for overoptimism by shrinking the regression coefficients; predictive performance was assessed by the area under the receiver operating characteristic curve (AUROC) and Hosmer-Lemeshow test. Models were externally validated in a data set including patients with severe asthma (Unbiased BIOmarkers in PREDiction of respiratory disease outcomes).

RESULTS

80/611 (13.1%) participants experienced ≥1 severe exacerbation. Five predictors (Asthma Control Questionnaire score, current smoking, chronic sinusitis, previous hospital admission for asthma and ≥1 severe exacerbation in the previous year) were retained in the history model (AUROC 0.77 (95% CI 0.75 to 0.80); Hosmer-Lemeshow p value 0.35). Adding spirometry and FeNO subsequently improved discrimination slightly (AUROC 0.79 (95% CI 0.77 to 0.81) and 0.80 (95% CI 0.78 to 0.81), respectively). External validation yielded AUROCs of 0.69 (95% CI 0.63 to 0.75; 0.63 to 0.75 and 0.63 to 0.75) for the three models, respectively; calibration was best for the spirometry ­model.

CONCLUSIONS

A simple history-based model extended with spirometry identifies patients who are prone to asthma exacerbations. The additional value of FeNO is modest. These models merit an implementation study in clinical practice to assess their utility.

TRIAL REGISTRATION NUMBER

NTR 1756.

摘要

背景

预防哮喘加重是当前指南的主要目标。我们旨在开发一种预测模型,使从业者能够识别出有发生严重加重风险的患者,这些患者可能需要改变治疗方案。

方法

我们使用了为期 12 个月的初级保健实用试验的数据;候选预测因子是从 GINA 2014 中确定的,并通过多变量引导程序进行了选择。基于以下三个模型构建了三种模型:(1)病史,(2)病史+肺功能,(3)病史+肺功能+FeNO。通过缩小回归系数来校正模型的过度拟合;通过接受者操作特征曲线(AUROC)和 Hosmer-Lemeshow 检验来评估预测性能。在包括严重哮喘患者的数据集中对模型进行了外部验证(Unbiased BIOmarkers in PREDiction of respiratory disease outcomes)。

结果

80/611(13.1%)名参与者经历了≥1 次严重加重。保留在病史模型中的 5 个预测因子(哮喘控制问卷评分、当前吸烟、慢性鼻窦炎、既往因哮喘住院和前一年≥1 次严重加重)(AUROC 0.77(95%CI 0.75 至 0.80);Hosmer-Lemeshow p 值为 0.35)。随后增加肺功能和 FeNO 可略微提高鉴别力(AUROC 0.79(95%CI 0.77 至 0.81)和 0.80(95%CI 0.78 至 0.81))。三个模型在外部验证中的 AUROCs 分别为 0.69(95%CI 0.63 至 0.75;0.63 至 0.75 和 0.63 至 0.75);肺功能模型的校准效果最好。

结论

简单的基于病史的模型扩展为肺功能可识别容易发生哮喘加重的患者。FeNO 的附加价值不大。这些模型值得在临床实践中进行实施研究,以评估其效用。

临床试验注册号

NTR 1756。

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