质子转移反应质谱法分析小儿过敏性哮喘的呼吸特征
Breath profiles in paediatric allergic asthma by proton transfer reaction mass spectrometry.
作者信息
Houssni Lamkaddam, Srdjan Micic, Tobias Bruderer, Yvette Baumann, Fabio Di Francesco, Patricia Koch, Tommaso Lomonaco, André Prévôt, Tiwari Prince, Serena Reale, Matyas Ripszam, Ronja Weber, El Haddad Imad, Moeller Alexander
机构信息
Laboratory of Atmospheric Chemistry, Paul Scherrer Institut PSI, Villigen, Aargau, Switzerland.
Department of Respiratory Medicine, University Children's Hospital Zürich, Zurich, Switzerland.
出版信息
BMJ Open Respir Res. 2025 Jun 27;12(1):e003223. doi: 10.1136/bmjresp-2025-003223.
INTRODUCTION
Enhancing paediatric asthma diagnosis is crucial. Molecular analysis of exhaled breath is a rapidly evolving field aimed at harnessing established and innovative technologies for clinical applications. This study evaluates the feasibility of using online proton-transfer-reaction mass spectrometry (PTR-MS) to identify distinctive breath signatures in children with allergic asthma.
METHODS
Exhaled breath samples of 81 children (41 with allergic asthma and 40 healthy controls) were analysed using the Vocus CI-TOF mass spectrometer (Tofwerk AG, Switzerland), with mass spectra acquired in HO and NH ionisation modes. Significant mass-to-charge (m/z) features were extracted using the Wilcoxon rank-sum test. Molecular identification was conducted using two-dimensional gas chromatography time-of-flight mass spectrometry (GCxGC-Q-TOF).
RESULTS
Statistical analysis revealed 89 significant m/z features associated with paediatric allergic asthma, 66 in HO mode and 23 in NH mode. Supervised machine learning achieved an average accuracy of 74.7% in distinguishing between the groups. GCxGC-QTOF analysis identified a subset of significant features, including four previously reported asthma predictors in breath analysis studies. 16 novel asthma predictor candidates were additionally detected, including 7 likely endogenous, 4 unknowns and 3 exogenous. The main group of breath metabolites was structurally related fatty acids, methyl esters and aldehydes, including four known biomarkers of lipid peroxidation.
CONCLUSION
Our findings demonstrate the suitability of PTR-MS for real-time breath analysis in paediatric populations. Moreover, the identification of distinct breath signatures exclusive to allergic asthma in children suggests the potential of leveraging such technology for non-invasive diagnostic applications.
引言
加强儿童哮喘诊断至关重要。呼出气的分子分析是一个快速发展的领域,旨在利用成熟和创新技术用于临床应用。本研究评估了使用在线质子转移反应质谱(PTR-MS)识别过敏性哮喘儿童独特呼吸特征的可行性。
方法
使用Vocus CI-TOF质谱仪(瑞士Tofwerk AG公司)对81名儿童(41名过敏性哮喘患儿和40名健康对照)的呼出气样本进行分析,在HO和NH离子化模式下采集质谱图。使用Wilcoxon秩和检验提取显著的质荷比(m/z)特征。使用二维气相色谱飞行时间质谱(GCxGC-Q-TOF)进行分子鉴定。
结果
统计分析显示与儿童过敏性哮喘相关的89个显著m/z特征,HO模式下有66个,NH模式下有23个。监督式机器学习在区分两组时的平均准确率达到74.7%。GCxGC-QTOF分析确定了一组显著特征,包括呼吸分析研究中先前报道的四个哮喘预测指标。另外还检测到16个新的哮喘预测指标候选物,包括7个可能的内源性、4个未知和3个外源性。呼出气代谢物的主要类别是结构相关的脂肪酸、甲酯和醛,包括四个已知的脂质过氧化生物标志物。
结论
我们的研究结果表明PTR-MS适用于儿科人群的实时呼吸分析。此外,在儿童中识别出过敏性哮喘特有的独特呼吸特征表明利用此类技术进行非侵入性诊断应用的潜力。