学龄前呼出生物标志物和基因表达可提高 6 岁时哮喘预测的准确性。

Exhaled biomarkers and gene expression at preschool age improve asthma prediction at 6 years of age.

机构信息

1 Department of Pediatric Pulmonology and.

出版信息

Am J Respir Crit Care Med. 2015 Jan 15;191(2):201-7. doi: 10.1164/rccm.201408-1537OC.

DOI:10.1164/rccm.201408-1537OC

PMID:25474185

Abstract

RATIONALE

A reliable asthma diagnosis is difficult in wheezing preschool children.

OBJECTIVES

To assess whether exhaled biomarkers, expression of inflammation genes, and early lung function measurements can improve a reliable asthma prediction in preschool wheezing children.

METHODS

Two hundred two preschool recurrent wheezers (aged 2-4 yr) were prospectively followed up until 6 years of age. At 6 years of age, a diagnosis (asthma or transient wheeze) was based on symptoms, lung function, and asthma medication use. The added predictive value (area under the receiver operating characteristic curve [AUC]) of biomarkers to clinical information (assessed with the Asthma Predictive Index [API]) assessed at preschool age in diagnosing asthma at 6 years of age was determined with a validation set. Biomarkers in exhaled breath condensate, exhaled volatile organic compounds (VOCs), gene expression, and airway resistance were measured.

MEASUREMENTS AND MAIN RESULTS

At 6 years of age, 198 children were diagnosed (76 with asthma, 122 with transient wheeze). Information on exhaled VOCs significantly improved asthma prediction (AUC, 89% [increase of 28%]; positive predictive value [PPV]/negative predictive value [NPV], 82/83%), which persisted in the validation set. Information on gene expression of toll-like receptor 4, catalase, and tumor necrosis factor-α significantly improved asthma prediction (AUC, 75% [increase of 17%]; PPV/NPV, 76/73%). This could not be confirmed after validation. Biomarkers in exhaled breath condensate and airway resistance (pre- and post- bronchodilator) did not improve an asthma prediction. The combined model with VOCs, gene expression, and API had an AUC of 95% (PPV/NPV, 90/89%).

CONCLUSIONS

Adding information on exhaled VOCs and possibly expression of inflammation genes to the API significantly improves an accurate asthma diagnosis in preschool children. Clinical trial registered with www.clinicaltrial.gov (NCT 00422747).

摘要

原理

在有喘息的学龄前儿童中，可靠的哮喘诊断较为困难。

目的

评估呼出气生物标志物、炎症基因表达和早期肺功能测量是否能提高学龄前喘息儿童可靠的哮喘预测。

方法

前瞻性随访 202 例学龄前反复喘息患儿（年龄 2-4 岁），直至 6 岁。6 岁时，根据症状、肺功能和哮喘药物使用情况进行诊断（哮喘或一过性喘息）。使用验证集确定生物标志物在学龄前评估的临床信息（使用哮喘预测指数[API]评估）对 6 岁时哮喘诊断的附加预测价值（受试者工作特征曲线下面积[AUC]）。测量呼出气冷凝物、呼出气挥发性有机化合物（VOC）、基因表达和气道阻力的生物标志物。

测量和主要结果

6 岁时，198 例患儿被诊断为（哮喘 76 例，一过性喘息 122 例）。呼出气 VOC 信息显著改善哮喘预测（AUC，89%[增加 28%]；阳性预测值[PPV]/阴性预测值[NPV]，82/83%），且在验证集中仍存在。Toll 样受体 4、过氧化氢酶和肿瘤坏死因子-α基因表达信息显著改善哮喘预测（AUC，75%[增加 17%]；PPV/NPV，76/73%）。验证后无法确认这一点。呼出气冷凝物和气道阻力（支气管扩张剂前后）的生物标志物不能改善哮喘预测。结合 API 联合使用 VOC、基因表达的模型 AUC 为 95%（PPV/NPV，90/89%）。