Martin Thomas Gaugg1, Yvonne Nussbaumer-Ochsner2, Lukas Bregy1, Anna Engler2, Nina Stebler2, Thomas Gaisl2, Tobias Bruderer3, Nora Nowak1, Pablo Sinues4, Renato Zenobi1, Malcolm Kohler5. 1. Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland. 2. Department of Pulmonology, University Hospital Zurich, Zurich, Switzerland. 3. Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland; Division of Respiratory Medicine, Childhood Research Center, University Children's Hospital Zurich, Zurich, Switzerland. 4. Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland; University Children's Hospital Basel, University of Basel, Basel, Switzerland. 5. Department of Pulmonology, University Hospital Zurich, Zurich, Switzerland; Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland. Electronic address: Malcolm.Kohler@usz.ch.
Abstract
BACKGROUND: 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). METHODS: 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. 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 ongoing biochemical processes in patients with COPD at risk for exacerbations. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02186639; URL: www.clinicaltrials.gov.
BACKGROUND: 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). METHODS: 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. 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 ongoing biochemical processes in patients with COPD at risk for exacerbations. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02186639; URL: www.clinicaltrials.gov.
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