Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.
Department of Pulmonology, University Hospital Zurich, Zurich, Switzerland.
Chest. 2019 Aug;156(2):269-276. doi: 10.1016/j.chest.2018.12.023. Epub 2019 Jan 24.
Exacerbations of COPD are defined by acute worsening of respiratory symptoms leading to a change in therapy. Identifying altered metabolic processes in patients at risk for future exacerbations is desirable for treatment optimization, the development of new therapeutic strategies, and perhaps diagnostic value. We aimed to identify affected pathways using the profiles of volatile organic compounds in exhaled breath from patients with COPD with and without frequent exacerbations (≥ 2 exacerbations within the past 12 months).
In this matched cohort study, exhaled breath profiles from patients with COPD and frequent exacerbations ("frequent exacerbators") and without frequent exacerbations ("nonfrequent exacerbators") were analyzed during an exacerbation-free interval using real-time secondary electrospray ionization high-resolution mass spectrometry. We analyzed exhaled breath from 26 frequent exacerbators and 26 nonfrequent exacerbators that were matched in terms of age, sex, and smoking history. To obtain new pathophysiological insights, we investigated significantly altered metabolites, which can be assigned to specific pathways. Metabolites were identified by using a Wilcoxon rank-sum test.
Metabolite levels from the ω-oxidation pathway, namely ω-hydroxy, ω-oxo, and dicarboxylic acids, were consistently decreased in frequent exacerbators. Additionally, several new nitro-aromatic metabolites, which were significantly increased in frequent exacerbators, were identified.
Real-time breath analysis by secondary electrospray high-resolution mass spectrometry allows molecular profiling of exhaled breath, providing insights about ongoing biochemical processes in patients with COPD at risk for exacerbations.
ClinicalTrials.gov; No.: NCT02186639; URL: www.clinicaltrials.gov.
COPD 加重的定义是呼吸症状急性恶化导致治疗改变。识别有未来加重风险的患者中代谢过程的改变，有利于治疗优化、新治疗策略的开发，也许还有诊断价值。我们旨在通过 COPD 患者呼气中挥发性有机化合物的特征来识别受影响的途径，这些患者有或没有频繁加重（过去 12 个月内发生≥2 次加重）。
在这项匹配队列研究中，在无加重期，使用实时二次电喷雾电离高分辨率质谱分析有频繁加重史的 COPD 患者（“频繁加重者”）和无频繁加重史的患者（“非频繁加重者”）的呼气谱。我们分析了 26 名频繁加重者和 26 名非频繁加重者的呼气，这些患者在年龄、性别和吸烟史方面匹配。为了获得新的病理生理学见解，我们研究了明显改变的代谢物，这些代谢物可以归为特定的途径。使用 Wilcoxon 秩和检验鉴定代谢物。
ω-氧化途径的代谢物水平，即 ω-羟基、ω-酮和二羧酸，在频繁加重者中持续降低。此外，还鉴定了一些新的硝基芳香代谢物，这些代谢物在频繁加重者中明显增加。
通过二次电喷雾高分辨率质谱的实时呼吸分析，允许对呼气进行分子谱分析，为有加重风险的 COPD 患者提供有关正在进行的生化过程的见解。
ClinicalTrials.gov；编号：NCT02186639；网址：www.clinicaltrials.gov。
