Breathborne biomarkers carry information on the state of human health, and their role in aiding clinical diagnosis or in therapeutic monitoring has become increasingly important as advances in the field are made. Breathborne Biomarkers and the Human Volatilome, Second Edition, provides a comprehensive update and reworking of the 2013 book Volatile Biomarkers, by Anton Amann and David Smith. The new editing team has expanded this edition beyond volatile organic compounds to cover the broad field of breath analysis, including the many exciting developments that have occurred since the first edition was published. This thoroughly revised volume includes the latest discoveries and applications in breath research from the world's foremost scientists, and offers insights into related future developments. It is an ideal resource for researchers, scientists, and clinicians with an interest in breath analysis.

Majda Mekic, Jiafa Zeng, Bin Jiang, Xue Li, Yannis G. Lazarou, Marcello Brigante, Hartmut Herrmann, Sasho Gligorovski

When aqueous solutions containing a mixture of fluorene (FL) and DMSO are irradiated with actinic radiation, a large suite of unsaturated high molecular weight compounds appear in the aqueous phase; a broad variety of saturated and unsaturated oxygenated multifunctional compounds are also observed in the gas phase, most of which are more toxic than FL

Jiafa Zeng, Zhujun Yu, Majda Mekic, Jiangping Liu, Sheng Li, Gwendal Loisel, Wei Gao, Adrien Gandolfo, Zhen Zhou, Xinming Wang, Hartmut Herrmann, Sasho Gligorovski, and Xue Li.

Cooking emissions represent a major source of air pollution in the indoor environment and exhibit adverse health effects caused by particulate matter together with volatile organic compounds (VOCs).

Stamatios Giannoukos, Chuan Ping Lee, Mohamed Tarik, Christian Ludwig, Serge Biollaz, Houssni Lamkaddam, Urs Baltensperger, Andre Stephan Henry Prevot, and Jay Slowik

Metal emissions are of major environmental and practical concern because of their highly toxic effects on human health and ecosystems. Current technologies available in the market for their detection are typically limited by a time resolution of 1 h or longer (e.g., via semicontinuous X-ray fluorescence measurements) or are nonquantitative (e.g., laser ablation mass spectrometry). In this work, we report the development of a novel technique for the real-time detection and monitoring of metal particles in situ using an extractive electrospray ionization (EESI) source coupled to a high-resolution time-of-flight mass spectrometer (TOF-MS)…

Tobias Bruderer; Thomas Gaisl; Martin T. Gaugg; Nora Nowak; Bettina Streckenbach; Simona Müller; Alexander Moeller; Malcolm Kohler; Renato Zenobi*

On-line analysis of exhaled breath offers insight into a person’s metabolism without the need for sample preparation or sample collection. Due to its noninvasive nature and the possibility to sample continuously, the analysis of breath has great clinical potential

Martin Thomas Gaugg

Respiratory diseases are among the leading causes of death worldwide and pose a great financial burden on the health care system. During the last decades the medical community has started to recognize that a patient’s individual set of genes, along with environmental factors, are immensely important for the diagnosis and treatment of diseases. This has led to a strong drive towards further developments in personalized and evidencebased medicine. Understanding the underlying metabolic fundamentals of diseases is crucial to provide the appropriate patient care.One of the fastest methods to obtain new insights in this regard is to analyze metabolites in exhaled breath, which offers a non-invasive window into human metabolism, and which can be monitored in real time.

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.

Xue Li, Dandan Huang, Jiafa Zeng, Chak Keung Chan, Zhen Zhou

the complicated chemical composition and large raw datasets involved in breath analysis have hindered the discovery of sources contributing to the exhaled VOCs. The positive matrix factorization (PMF) receptor model has been…

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).