K.Dev Singh, G. Tancev, F. Decrue, J. Usemann, R. Appenzeller, P.Barreiro, G. Jaumà, M. Macia Santiago, G. Vidal de Miguel, U.Frey, P. Sinues

Despite the attractiveness of breath analysis as a non-invasive means to retrieve relevant metabolic information, its introduction into routine clinical practice remains a challenge.

Martin Thomas Gaugg, Anna Engler, Lukas Bregy, Yvonne Nussbaumer-Ochsner, Lara Eiffert, Tobias Bruderer, Renato Zenobi, Pablo ML Sinues and Malcolm Kohler.

BackgroundCollagen-related amino acids are significantly increased in exhaled breath of idiopathic pulmonary fibrosis (IPF) patients compared with healthy controls. The detection of these amino acids using real-time breath analysis results in a good discrimination between the groups, indicating the possibility for a rapid, non-invasive screening for IPF.

Lukas Bregy, Constanze Hirsigerb, Stefanie Gartenmann, Tobias Bruderer, Renato Zenobi, Patrick R.Schmidlinb

It has been shown that bacteria in periodontally diseased patients can be recognized by the detection of volatile metabolites in the headspace of saliva by real-time ambient mass spectrometry. The aim of this study was to use this detection method to analyze the oral metabolome in diseased periodontitis patients before and after therapy to monitor disease evolution and healing events.

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.

BackgroundExacerbations of chronic obstructive pulmonary disease (COPD) are defined by acute worsening of respiratory symptoms leading to a change in therapy.

Haorong Li, Mengyang Xu, and Jiangjiang Zhu

This study aimed to sensitively detect volatile metabolites from the headspace of in vitro gut microbial culture in a human colonic model (HCM). Two SESI-tandem mass spectrometry panels with a comparable number of targeted metabolites/features were established.

Haorong Li and Jiangjiang Zhu

SESIMS/MS was applied to examine the VOC metabolome of a pair of isogenic methicillin-susceptible and resistant Staphylococcus aureus (MSSA and MRSA) strains. Our results indicated that MSSA and MRSA strains can be clearly differentiated Furthermore, we studied the stress response of MSSA and MRSA to antibiotics treatment.

Katharina Heschl, Naemi Haas-Baumann, Ronja Weber, Astghik Baghdasaryan, Srdjan J. Micic, Florian Singer, Renato Zenobi, Tobias Bruderer, Alexander Möller

We present data of 41 children, 4-16yrs (23 CF and 17 healthy controls) from an ongoing cross-sectional study. Children were breathing via a mouthpiece into a heated sampling tube connected to the SESI-HRMS-analyser. Carefully pre-processed MS data was used for biomarker detection and classification. Mann-Whitney U tests together with FDR adjusted p-values were applied to isolate mass-to-charge ratios (m/z: representing potential biomarkers) Subsequent variable reduction through principal component analysis was used to perform binary logistic regression.
CF and HC had comparable BMI (17.7±3.0 vs 16.9±2.3; p=0.17) and FEV1 (z-scores -0.45±1.18 vs -0.27±1.13; p=0.37). 4 children were P.aeruginosa positive. We were able to isolate 43 m/z peaks with elevated intensity signals in CF vs HC below an FDR control level of q = 0.15. Classification applied to first principal components resulted in significant outcomes (CF vs. HC) with an average accuracy of 81.3% and a Cohen’s Kappa value of 0.61.
We could annotate the detected m/z peaks with molecular formula and identify different sets of related molecules. Structure elucidation is ongoing based on comparison of fragment spectra with reference chemicals for unequivocal confirmation of the involved molecular markers.
Non-invasive breath analysis with SESI-HRMS identifies CF specific compounds in children. This will allow further phenotyping of CF lung disease with the potential for early detection of airway infection.

Astghik Baghdasaryan, Tobias Bruderer, Simona Mueller, Ronja Weber, Naemi Haas-Baumann, Srdjan J. Micic, Christoph Berger, Renato Zenobi, Alexander Möller

Microbial infection entails recruitment of inflammatory cells and release of proteases and contributes to morbidity in CF. The non-invasive early detection of airway colonization and infection would be a great step forward in the management of children with CF. The Zurich Exhalomics program aims to describe disease state specific breath-prints to assess airway inflammation and infection in children with CF.
We used headspace secondary electrospray Ionisation high-resolution mass spectrometry (SESI-HRMS) to analyze three biological replicates in randomized order for strain specific volatile metabolites of the following CF pathogens: S. aureus, S. maltophilia, H. influenzae, S. pneumoniae, E. coli, B. cepacia, P. aeruginosa and growth medium.
We found good repeatability between measurements and minimal variation between biological replicates. We performed ANOVA on 130 m/z features with intensities over 1000 cps. 61 showed significant difference in signal intensity between strains (under the FDR adjusted significance level of 5%). This resulted in unique sets of 4-12 volatile markers for P. aeruginosa, H. influenzae, S. pneumoniae, S. aureus and E. coli. Several markers for P. aeruginoas, B. cepacia and S. maltophilia were closely related. Compound identification has started by comparison of headspace fragment spectra for cultures with proposed reference compounds. So far, we could identify molecules from the following compound classes: heterocyclic organic compounds, aromatic aldehydes and aromatic heterocyclic organic compounds.
We report unique sets of volatile markers for CF relevant bacteria detected with SESI-HRMS.

aorong Li, Jiangjiang Zhu, Jane E. Hill

Spurred by recent events, there is an ever-growing interest in the detection of volatile metabolites through human breath. Breath analysis, which is entirely noninvasive, can be applied to clinical diagnosis and therapeutic monitoring, where frequent sampling is required.

Ana María Casas-Ferreira, Miguel del Nogal-S
anchez*, Jos
e Luis P
erez-Pav
on, Bernardo Moreno-Cordero

In this review, an assessment of non-separative methods based on mass spectrometry used to analyse volatile organic compounds in the field of bioanalysis is performed. The use of non-separative methods based on mass spectrometry has been established as an attractive option for analysing compounds.

A.Tejero Rioseras, K.D. Singh, N. Nowak, M. T. Gaugg, T. Bruderer, R. Zenobi, P. M-L Sinues

The tricarboxylic acid (TCA) cycle is one of the most important metabolic pathway for cellular respiration in aerobic organisms. It provides and collects intermediates for many other interconnecting pathways and acts as a hub connecting metabolism of carbohydrates, fatty acids, and amino acids.

T. Gaisl, L. Bregy, N. Stebler, M. T. Gaugg, T. Bruderer, D. García-Gómez, A, Moeller, F. Singer, E. I. Schwarz, C. Benden, P. M-L Sinues, R. Zenobi, M. Kohler

We aimed at defining profiles of volatile organic compounds in exhaled breath from patients with cystic fibrosis (CF) using a novel real-time mass spectrometry technique. In this prospective matched case-control study, 30 patients with CF, and 30 healthy control 4 subjects were matched one-to-one according to age, gender, and smoking state.

Xue Li, Dan D. Huang, Rui Du, Zhi J. Zhang, Chak K. Chan, Zheng X. Huang, Zhen Zhou

Exhaled volatile organic compounds (VOCs) have aroused considerable interest, since they can serve as biomarkers for disease diagnosis and environmental exposure in a non-invasive manner. In this work, we present a protocol to characterize the exhaled VOCs in real time by using secondary nanoelectrospray ionization coupled to high resolution mass spectrometry (Sec-nanoESI-HRMS).

K. D. Singh, G. Vidal-de-Miguel, M. T.s Gaugg, A. J. Ibañez, R. Zenobi, M. Kohler, U. Frey and P. M-L Sinues

While there has been progress in making use of breath tests to guide clinical decision making, the full potential of exhaled breath analysis still remains to be exploited. Here we summarize some of the reasons why this is the case, what we have done so far to overcome some of the existing obstacles, and our vision of how we think breath analysis will play a more prominent role …

L. Bregy, Y Nussbaumer-Ochsnerb, P. M-L Sinues, D. García-Gómez, Y. Suter, T. Gaisl, N. Stebler, M. T. Gaugg, M. Kohler, R. Zenobi

New mass spectrometry (MS) techniques analysing exhaled breath have the potential to better define airway diseases. Here, we present our work to profile the volatile organic compounds (VOCs) in exhaled breath from patients with chronic obstructive pulmonary disease (COPD), using real-time MS, and relate this disease-specific breath profile to functional disease markers …

L. Bregy, D. García-Gómez, M. Kohler, Y Nussbaumer-Ochsnerb, P. M-L Sinues, Y. Suter, R. Zenobi, J. Schmitz

The present invention provides a method for determining whether a patient suffers from COPD, said method comprising the step of: a. providing at a sample comprising, or consisting of, exhaled breath of said patient to an ionization chamber of a mass spectrometer; b. simultaneously determining the presence, absence or relative concentration of at least two metabolites in said sample using …

M. Mansurova; Birgitta E. Ebert; Lars M. Blank & Alfredo J. Ibáñez

Here, we introduce the reader to these diverse applications associated with the monitoring and analysis of VOC emissions. We also present our vision of real-time VOC analysis enabled by newly developed analytical techniques, which will further broaden the use of VOCs in even wider applications.

A. Tejero-Rioseras, D. Garcia-Gomez, B. E. Ebert, L. M. Blank, A. J. Ibanez and P. M-L Sinues

While yeast is one of the most studied organisms, its intricate biology remains to be fully mapped and understood. This is especially the case when it comes to capture rapid, in vivo fluctuations of metabolite levels. According to the authors, the results suggest that a large number of metabolites produced by yeast from glucose neither are reported in the literature nor are their biochemical origins deciphered.

M. T. Gaugg, A. Engler, Y. Nussbaumer-Ochsner, L. Bregy, A. S Stöberl, T. Gaisl, T. Bruderer, R. Zenobi, M. Kohler and P. M-L Sinues

The authors explore whether real-time breath research & analysis by SESI-HRMS is suitable to monitor changes at the metabolic level due to inhaling bronchodilator medication. The experimental results strengthen the notion that certain biochemical processes can be monitored.

M. T. Gaugg, T. Bruderer, N. Nowak, L. Eiffert, P. M-L Sinues, M. Kohler, R. Zenobi

Omega-oxidation is a fatty acid degradation pathway that can occur alternatively to the dominant b-oxidation. The dysregulation of fatty acid oxidation has been related with a variety of diseases, termed fatty acid oxidation disorders. This work shows evidence for real-time detection in exhaled breath of the complete series of saturated linear w-hydroxyalkanoic acids, w-oxoalkanoic acids and alkanedioic acids with carbon chain lengths of 5-15.