Dept of Respiratory Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands Dept of Pediatric Respiratory Medicine and Allergy, Emma's Children Hospital, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands Dept of Pediatric Respiratory Medicine, VU Medical Centre, VU University of Amsterdam, Amsterdam, The Netherlands
Dept of Respiratory Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Eur Respir J. 2015 Feb;45(2):440-8. doi: 10.1183/09031936.00044414. Epub 2014 Oct 16.
Preschool rhinovirus-induced wheeze is associated with an increased risk of asthma. In adult asthma, exhaled volatile organic compounds (VOC) are associated with inflammatory activity. We therefore hypothesised that acute preschool wheeze is accompanied by a differential profile of exhaled VOC, which is maintained after resolution of symptoms in those children with rhinovirus-induced wheeze. We included 178 children (mean±sd age 22±9 months) from the EUROPA cohort comparing asymptomatic and wheezing children during respiratory symptoms and after recovery. Naso- and oropharyngeal swabs were tested for rhinovirus by quantitative PCR. Breath was collected via a spacer and analysed using an electronic nose. Between-group discrimination was assessed by constructing a 1000-fold cross-validated receiver operating characteristic curve. Analyses were stratified by rhinovirus presence/absence. Wheezing children demonstrated a different VOC profile when compared with asymptomatic children (p<0.001), regardless of the presence (area under the curve (AUC) 0.77, 95% CI 0.07) or absence (AUC 0.81, 95% CI 0.05) of rhinovirus. After symptomatic recovery, discriminative accuracy was maintained in children with rhinovirus-induced wheeze (AUC 0.84, 95% CI 0.06), whereas it dropped significantly in infants with non-rhinovirus-induced wheeze (AUC 0.67, 95% CI 0.06). Exhaled molecular profiles differ between preschool children with and without acute respiratory wheeze. This appears to be sustained in children with rhinovirus-induced wheeze after resolution of symptoms. Therefore, exhaled VOC may qualify as candidate biomarkers for early signs of asthma.
学龄前儿童鼻病毒诱发的喘息与哮喘风险增加有关。在成人哮喘中，呼出的挥发性有机化合物（VOC）与炎症活动有关。因此，我们假设急性学龄前喘息伴有呼出 VOC 的差异特征，而在那些因鼻病毒诱发喘息而缓解症状的儿童中，这种特征仍然存在。我们纳入了 EUROPA 队列的 178 名儿童（平均年龄 22±9 个月），这些儿童在呼吸道症状期间和症状缓解后，分为无症状和喘息儿童。通过定量 PCR 检测鼻拭子和咽拭子中的鼻病毒。通过间隔器采集呼气并使用电子鼻进行分析。通过构建 1000 倍交叉验证的接收器操作特征曲线评估组间差异。分析按鼻病毒的存在/不存在进行分层。与无症状儿童相比，喘息儿童表现出不同的 VOC 特征（p<0.001），无论存在（曲线下面积（AUC）为 0.77，95%置信区间 0.07）还是不存在（AUC 为 0.81，95%置信区间 0.05）鼻病毒。在症状缓解后，在因鼻病毒诱发喘息的儿童中，区分准确性得以维持（AUC 为 0.84，95%置信区间 0.06），而在因非鼻病毒诱发喘息的婴儿中，区分准确性显著下降（AUC 为 0.67，95%置信区间 0.06）。患有急性呼吸道喘息和无急性呼吸道喘息的学龄前儿童呼出的分子谱存在差异。在症状缓解后，因鼻病毒诱发喘息的儿童中，这种差异似乎持续存在。因此，呼出 VOC 可能有资格成为哮喘早期迹象的候选生物标志物。
