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.

Yue Zhao, Jeremy K. Chan, Felipe D. Lopez-Hilfiker, Megan A. McKeown, Emma L. D'Ambro, Jay G. Slowik, Jeffrey A. Riffell, and Joel A. Thornton

We present an electrospray ion source coupled to an orthogonal continuous-flow atmospheric pressure chemical ionization region…

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.

I. A. Ratiu, T. Ligor, Victor B.-Bintintan, B. Buszewski

Bacteria are the main cause of many human diseases. Typical bacterial identification methods, for example culture-based, serological and genetic methods, are time-consuming, delaying the potential for an early and accurate diagnosis and the appropriate subsequent treatment.

A. T. Rioseras, M. T. Gaugg and P. M-L Sinues

Our main goal was to gain further insights into the mechanism by which gas-phase analytes are ionized by interaction with plumes of electrospray solvents. We exposed target vapors to electrosprays of either water or deuterated water and mass analyzed them …

Ta-Hsuan Ong*, Ted Mendum, Geoff Geurtsen, Jude Kelley, Alla Ostrinskaya, Roderick Kunz

Canines remain the gold standard for explosives detection in many situations, and there is an ongoing desire for them to perform at the highest level. This goal requires canine training to be approached similarly to scientific sensor design. A sensitive, real-time (∼1 s) vapor analysis mass spectrometer was developed to provide tools, techniques, and knowledge to better understand, train, and utilize canines.

P. M-L Sinues, Y. Nussbaumer Ochsner, M.T. Gaugg, L. Bregy, A. Engler, R. Zenobi, M. Kohler.

Idiopathic pulmonary fibrosis (IPF) is recognized as a distinct clinical disorder, however, the diagnosis method remains elusive. Metabolic profiling of biopsied tissue specimens has shown promise to gain insights into IPF pathogenesis. In view of this, the authors hypothesized that the analysis of exhaled metabolites may also provide further insights.

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

Recently we found markers in exhaled breath discriminating patients with chronic obstructive pulmonary disease (COPD) from healthy controls using real-time mass spectrometry. The aim of this study was to validate the previously found disease specific metabolic profile of COPD in an independent cohort of patients suffering from chronic obstructive lung disease …

T. Bruderer, A. Baghdasaryan, J. Wyler, M. Kohler, R. Zenobi, A. Möller

Early and often subclinical pulmonary infection and pronounced neutrophilic inflammation are major contributors to CF-related morbidity. There is a causal relationship between high airway neutrophil elastase activity and the development of bronchiectasis. Early detection of disease and disease-associated .