Real-time breath analysis reveals specific metabolic signatures of COPD exacerbations

Real-time breath analysis reveals specific metabolic signatures of COPD exacerbations

Martin Thomas Gaugg, Yvonne Nussbaumer-Ochsner, Lukas Bregy, Anna Engler, Nina Stebler, Thomas Gaisl, Tobias Bruderer, Nora Nowak, Pablo ML Sinues, Renato Zenobi and Malcolm Kohler.


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Background: Exacerbations of chronic obstructive pulmonary disease (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 might also be of diagnostic value. We aimed to identify affected pathways using the profiles of volatile organic compounds in exhaled breath from COPD patients with and without frequent exacerbations (>2 exacerbations within the last 12 months).

Methods: In this matched cohort study, exhaled breath profiles from COPD patients with frequent exacerbations (‘frequent exacerbators’) and without frequent exacerbations (‘non-frequent 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 non-frequent exacerbators, 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.

Results: 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.

Conclusions: Real-time breath analysis by secondary electrospray-high resolution mass spectrometry allows molecular profiling of exhaled breath, providing insights about on-going biochemical processes in COPD patients at risk for exacerbations.

Trial registry:; No.: NCT02186639; URL:

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