Sievi Noriane A, Schmidt Felix, Fricke Kai, Baur Diego M, Basler Sarah, Herth Jonas, Kohler Malcolm
Department of Pulmonology, University Hospital Zurich, Raemistrasse 100, Zurich, 8091, Switzerland.
University of Zurich, Zurich, Switzerland.
Respir Res. 2025 Sep 26;26(1):273. doi: 10.1186/s12931-025-03352-0.
Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder characterized by persistent airflow limitation and acute exacerbations (AECOPD), which accelerate disease progression. Although triple inhaled therapy is recommended for patients with severe COPD and frequent AECOPD, some patients continue to experience exacerbations. The mechanisms behind this remain unclear. Exhaled breath analysis has the potential to unravel molecular changes during AECOPD, thereby adding to the understanding of molecular drivers for AECOPD. This study aimed to investigate metabolic changes in exhaled breath during AECOPD compared to stable state.
In COPD patients treated with triple inhaled therapy we conducted real time breath analysis during AECOPD and subsequent stable state. Molecular breath patterns were compared between AECOPD and stable state by pathway enrichment analysis. Minimum description length model was used to build a feature based prediction model differentiating AECOPD from stable state.
28 patients (61% male) with a mean (SD) age of 65 (10.2) years with severe AECOPD were included. Metabolic alterations were predominantly detected in aminosugar, linoleate, and butanoate pathways. AECOPD could be discriminated from stable state with high power (AUC = 0.84), and balanced good sensitivity and specificity (86% each).
Metabolic analysis of AECOPD revealed disturbances in aminosugar metabolism as a potential driver mechanism and thus may be a therapeutic target for patients with exacerbations despite triple inhaled therapy. Moreover, real-time breath analysis could enable rapid detection of AECOPD, improving diagnostic accuracy and treatment efficiency.
ClinicalTrials.gov (NCT04638920), registered on 20.11.2020.
慢性阻塞性肺疾病（COPD）是一种进行性呼吸系统疾病，其特征为持续气流受限和急性加重（AECOPD），后者会加速疾病进展。尽管对于重度COPD和频繁发生AECOPD的患者推荐三联吸入疗法，但仍有一些患者会继续出现病情加重。其背后的机制尚不清楚。呼出气分析有潜力揭示AECOPD期间的分子变化，从而增进对AECOPD分子驱动因素的理解。本研究旨在调查与稳定期相比，AECOPD期间呼出气中的代谢变化。
在接受三联吸入疗法的COPD患者中，我们在AECOPD期间及随后的稳定期进行了实时呼气分析。通过通路富集分析比较AECOPD和稳定期之间的分子呼气模式。使用最小描述长度模型构建基于特征的预测模型，以区分AECOPD和稳定期。
纳入了28例重度AECOPD患者（61%为男性），平均（标准差）年龄为65（10.2）岁。代谢改变主要在氨基糖、亚油酸酯和丁酸途径中被检测到。AECOPD与稳定期能够以高功效被区分开（AUC = 0.84），且具有良好的平衡敏感性和特异性（均为86%）。
AECOPD的代谢分析揭示了氨基糖代谢紊乱是一种潜在的驱动机制，因此对于尽管接受了三联吸入疗法仍出现病情加重的患者而言患者而言，这可能是一个治疗靶点。此外，实时呼气分析能够实现对AECOPD的快速检测，提高诊断准确性和治疗效率。
ClinicalTrials.gov（NCT04638920），于2020年11月20日注册。
