哮喘联盟

   摘要
   背景：对学龄前喘息儿童进行可靠的哮喘诊断非常困难。
   目的：旨在评估呼出气生物标记物、炎症基因表达和早期肺功能检测是否能提高学龄前喘息儿童哮喘预测的可靠性。
   方法：对202例学龄前反复发作喘息儿童（2～4岁）进行前瞻性随访，直至6岁。6岁时，基于症状、肺功能和哮喘药物的使用做出诊断（哮喘或短暂的喘息）。对6岁儿童进行哮喘诊断时，将针对学龄前评估的临床信息（评估哮喘预测指数(API)）的生物标记物的增加预测值（受试者测得的特征曲线下面积(AUC)）作为验证集。检测呼出气冷凝液中的生物标记物、呼出气挥发性有机化合物（VOCs）、基因表达和气道阻力。
   结果：在6岁龄时，对198例儿童进行诊断（76例患有哮喘，122例为短暂性喘息）。呼出气VOCs检测显著提高哮喘的预测（AUC，89%[增加28%]）；阳性预测值[PPV]/阴性预测值[NPV]为82/83%，并在验证集中得到验证。Toll样受体4、过氧化氢酶和肿瘤坏死因子的表达检测显著提高哮喘的预测（AUC，75%[增加17%]）；PPV/NPV为76/73%，但并没有得到验证。呼出气冷凝液中的生物标记物和气道阻力（使用支气管扩张剂之前和之后）不能改善哮喘的预测。结合VOCs、基因表达和API的模型总AUC为95% (PPV/NPV, 90/89%)。
   结论：在API的基础上，添加呼出气VOCs和可能的炎症基因表达的信息，能显著提高对学龄前儿童急性哮喘的诊断。
 

（杨冬 审校）
Am J Respir Crit CareMed. 2015Jan15;191(2):201-7.doi:10.1164/rccm.201408-1537OC.
 

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

Klaassen EM1, van de Kant KD, Jöbsis Q, van Schayck OC, Smolinska A, Dallinga JW, van Schooten FJ, den Hartog GJ, de Jongste JC, Rijkers GT, Dompeling E.

Author information
 

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).

Am J Respir Crit CareMed. 2015Jan15;191(2):201-7.doi:10.1164/rccm.201408-1537OC.