Real-Time Breath Analysis Reveals Specific Metabolic Signatures of COPD Exacerbations.


Journal

Chest
ISSN: 1931-3543
Titre abrégé: Chest
Pays: United States
ID NLM: 0231335

Informations de publication

Date de publication:
08 2019
Historique:
received: 19 07 2018
revised: 19 11 2018
accepted: 03 12 2018
pubmed: 28 1 2019
medline: 18 4 2020
entrez: 28 1 2019
Statut: ppublish

Résumé

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.

Sections du résumé

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.

Identifiants

pubmed: 30685334
pii: S0012-3692(19)30062-5
doi: 10.1016/j.chest.2018.12.023
pii:
doi:

Substances chimiques

Biomarkers 0

Banques de données

ClinicalTrials.gov
['NCT02186639']

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

269-276

Informations de copyright

Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Auteurs

Martin Thomas Gaugg (MT)

Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.

Yvonne Nussbaumer-Ochsner (Y)

Department of Pulmonology, University Hospital Zurich, Zurich, Switzerland.

Lukas Bregy (L)

Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.

Anna Engler (A)

Department of Pulmonology, University Hospital Zurich, Zurich, Switzerland.

Nina Stebler (N)

Department of Pulmonology, University Hospital Zurich, Zurich, Switzerland.

Thomas Gaisl (T)

Department of Pulmonology, University Hospital Zurich, Zurich, Switzerland.

Tobias Bruderer (T)

Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland; Division of Respiratory Medicine, Childhood Research Center, University Children's Hospital Zurich, Zurich, Switzerland.

Nora Nowak (N)

Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.

Pablo Sinues (P)

Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland; University Children's Hospital Basel, University of Basel, Basel, Switzerland.

Renato Zenobi (R)

Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.

Malcolm Kohler (M)

Department of Pulmonology, University Hospital Zurich, Zurich, Switzerland; Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland. Electronic address: Malcolm.Kohler@usz.ch.

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Classifications MeSH