Jonas Herth, Felix Schmidt, Sarah Basler, Noriane A Sievi and Malcolm Kohler

Exhaled breath analysis has emerged as a non-invasive and promising method for early detection of lung cancer, offering a novel approach for diagnosis through the identification of specific biomarkers present in a patient's breath…

M. Z. Islam, S. E. Räisänen, A. Schudel, K. Wang, T. He, C. Kunz, Y. Li, X. Ma, A. M. Serviento, Z. Zeng, F. Wahl, R. Zenobi, S. Giannoukos, and M. Niu.

Previously, we used secondary electrospray ionization-mass spectrometry (SESI-MS) to investigate the diurnal patterns and signal intensities of exhaled (EX) volatile fatty acids (VFA) of dairy cows. The current study aimed to validate the potential of an exhalomics approach for evaluating rumen fermentation. The experiment was conducted in a switchback design, with 3 periods of 9 d each, including 7 d for adaptation and 2 d for sampling. Four rumen-cannulated original Swiss Brown (Braunvieh) cows were randomly assigned to 1 of 2 diet sequences (ABA or BAB): (A) low starch (LS; 6.31% starch on a dry matter basis) and (B) high starch (HS; 16.2% starch on a dry matter basis). Feeding was once per day at 0830 h. Exhalome (with the GreenFeed System), and rumen samples were collected 8 times to represent every 3 h of a day, and EX-VFA and ruminal (RM)-VFA were analyzed using SESI-MS and HPLC, respectively. Furthermore, the VFA concentration in the gas phase (HR-VFA) was predicted based on RMVFA and Henry’s Law (HR) constants….

Chen Tao, Peter Mettke, Yaru Wang, Xue Li, Ligang Hu

Highlights

• Near-surface ozone pollution has a significant impact on respiratory health.

• Lung microenvironment is involved in respiratory health effects of ozone pollution.

• Exhalation metabolomics provides a new method to explore the respiratory health effects of ozone pollution.

• Exhalation metabolomics could be a potential basis for concentration limits in ozone pollution control.

Mo Awchi, Kapil Dev Singh, Sara Bachmann Brenner, Marie-Anne Burckhardt, Melanie Hess, Jiafa Zeng, Alexandre N Datta, Urs Frey, Urs Zumsteg, Gabor Szinnai, Pablo Sinues

Purpose: This feasibility study aimed to investigate the use of exhaled breath analysis to capture and quantify relative changes of metabolites during resolution of acute diabetic ketoacidosis under insulin and rehydration therapy…

Cedric Wüthrich, Renato Zenobi, Stamatios Giannoukos

Rationale

Secondary-electrospray ionization (SESI) coupled with high-resolution mass spectrometry is a powerful tool for the discovery of biomarkers in exhaled breath. A primary electrospray consisting of aqueous formic acid (FA) is currently used to charge the volatile organic compounds in breath. To investigate whether alternate electrospray compositions could enable different metabolite coverage and sensitivities, the electrospray dopants NaI and AgNO3 were tested….

Mateusz Fido, Simone Hersberger, Andreas Güntner, Renato Zenobi, Stamatios Giannoukos

Polymeric bags are a widely applied, simple, and cost-effective method for the storage and offline analysis of gaseous samples. Various materials have been used as sampling bags, all known to contain impurities and differing in their cost, durability, and storage capabilities. Herein, we present a comparative study of several well-known bag materials...

Cedric Wüthrich, Renato Zenobi, Stamatios Giannoukos

The mass spectrometer used in this study was an Orbitrap Q-Exactive Plus (Thermo Scientific) operated with the manufacturer’s standard control software (ExactiveTune, version 2.9, Thermo Scientific) and Xcalibur (version 4.1. 31.9, Thermo Scientific). Mass calibration was done according to the instrument manual and was always more recent than seven days according to specifications…

WANG Kangyi, TAO Chen, LUO Zuo, TANG Zhifeng, BAI Te, LI Hang, HU Ligang, ZHANG Zuo, LI Xue

Breath samples can be collected from the oral and nasal cavity.However,the oral and nasal environment affect the chemical composition of breath sample. It was found that the number of unique component(m/z)detected in mouth-exhaled breath(167)was 2.2 times greater than that detected in nose-exhaled breath(76), which might result from the complex environment in oral cavity. The signal intensity of common component (163) was significantly different between mouth-exhaled breath and nose-exhaled breath. Additionally, the elemental composition analysis showed that the proportion of polar compounds detected in nose-exhaled breath was higher than that in mouth-exhaled breath. This study demonstrated that there was significant differences in the chemical composition between mouth-exhaled and nose-exhaled breath, which provided a theoretical basis for selection of exhalation mode.

Stamatios Giannoukos, Cedric Wüthrich

This review discusses the technical aspects behind SESI, the advancements, and the technical hurdles faced. Additionally, the recent advances in the applications of SESI in human and animal-centered research are presented.

Wei Liu, Li Zhou, Wenting Yuan, Ling Ruan, Xinkai Wang, Yucong Guo, Zhouqing Xie, Qifan Liu, Chen Wang

This review article summarizes the principles of different online mass spectrometry techniques and their application to indoor VOC measurements. The sources, emission characteristics, and chemical compositions of primary indoor VOCs are discussed. Recent advances in the fundamental understanding of chemical transformations and formation mechanisms related to secondary indoor VOCs are also discussed

Hui Huang, Jianming Yang, Chen Tao, Ligang Hu, Tao Huan, Wei Zhang, Keda Zhang, Xue Li

Exhaled breath is a promising specimen for in vivo drug analysis. The analysis of non-volatile drugs (NVDs) in exhaled breath is especially valuable due to the clinical prevalence of NVDs…

This review thoroughly describes the origin of NVDs in exhaled breath, and summarizes the characteristics and limitations of current analytical methods for exhaled NVDs, as well as the applications of breath analysis for NVDs, in order to provide helpful guidance for subsequent basic and translational research.

Rosa A Sola-Martínez, Jiafa Zeng, Mo Awchi, Amanda Gisler, Kim Arnold, Kapil Dev Singh, Urs Frey, Manuel Cánovas Díaz, Teresa de Diego Puente, Pablo Sinues

Secondary electrospray ionization-high resolution mass spectrometry (SESI-HRMS) is an established technique in the field of breath analysis characterized by its short analysis time, as well as high levels of sensitivity and selectivity. Traditionally, SESI-HRMS has been used for real-time breath analysis, which requires subjects to be at the location of the analytical platform. Therefore, it limits the possibilities for an introduction of this methodology in day-to-day clinical practice. However, recent methodological developments have shown feasibility on the remote sampling of exhaled breath in Nalophan® bags prior to measurement using SESI-HRMS…

Fouad Choueiry, Rui Xu, Kelly Meyrath, Jiangjiang Zhu.

Secondary electrospray ionization high-resolution mass spectrometry (SESI-HRMS) is an innovative analytical technique for the rapid and non-invasive analysis of volatile organic compounds (VOCs). However, compound annotation and ion suppression in the SESI source has hindered feature detection, stability and reproducibility of SESI-HRMS in untargeted volatilomics.

Fouad Choueiry, Andrew Gold, Rui Xu, Shiqi Zhang and Jiangjiang Zhu.

The symbiotic relationship between the gut microbial population is capable of regulating numerous aspects of host physiology, including metabolism. Bacteria can modulate the metabolic processes of the host by feeding on nutritional components within the lumen and releasing bioactive components into circulation. Endogenous volatile organic compound (VOC) synthesis is dependent on the availability of precursors found in mammalian metabolism

Cedric Wüthrich, Stamatios Giannoukos, Renato Zenobi

Ion suppression is a known matrix effect in electrospray ionization (ESI), ambient pressure chemical ionization (APCI), and desorption electrospray ionization (DESI), but its characterization in secondary electrospray ionization (SESI) is lacking. A thorough understanding of this effect is crucial for quantitative applications of SESI, such as breath analysis. In this study, gas standards were generated by using an evaporation-based system to assess the susceptibility and suppression potential of acetone, deuterated acetone, deuterated acetic acid, and pyridine. Gas-phase effects were found to dominate ion suppression, with pyridine exhibiting the most significant suppressive effect, which is potentially linked to its gas-phase basicity. The impact of increased acetone levels on the volatiles from exhaled breath condensate was also examined…

Mo Awchi, Kapil Dev Singh, Patricia E Dill, Urs Frey, Alexandre N Datta, and Pablo Sinues.

Therapeutic drug monitoring (TDM) of medications with a narrow therapeutic window is a common clinical practice to minimize toxic effects and maximize clinical outcomes. Routine analyses rely on the quantification of systemic blood concentrations of drugs. Alternative matrices such as exhaled breath are appealing because of their inherent non-invasive nature. This is especially the case for pediatric patients. We have recently

H. G. Mengers

Decoding the Yeast Volatilome: From CO₂ Conversion to Real-Time SESI Profiling
This thesis explores the diverse and underexplored volatilome of Saccharomyces cerevisiae, combining metabolic engineering with advanced gas-phase analysis. Highlights include CO₂-to-formate conversion during fermentation using a Ru-catalyst system (yielding 26% conversion), and bio-based production of volatile acetaldehyde via ADH-deleted yeast strains at industrially relevant rates (100 mg/g/h). Volatile stripping and capture were achieved using custom in situ water traps. Crucially, SESI-Orbitrap MS was established as a sensitive, real-time tool to detect volatiles, including heat-labile allicin from garlic and >200 fermentation-derived compounds at 0.4 Hz resolution. This work showcases SESI’s potential in online bioprocess monitoring, from early detection of volatile metabolites to mapping dynamic metabolic shifts such as ethyl ester formation during carbon source transitions.

Bettina Streckenbach

Metabolomics, or the comprehensive study of metabolites and involved processes, provides insights into the current physiological state of humans. In the clinical setting, the detection and quantification of specific metabolites has proven to be invaluable in diagnostic testing. Herein, body samples that are non-invasively accessible are of particular interest…

M.Z. Islam, S. Giannoukos, Räisänen, K. Wang, X. Ma, F. Wahl, R. Zenobi, M. Niu.

To date, the commonly used methods to assess rumen fermentation are invasive. Exhaled breath contains hundreds of volatile organic compounds (VOC) that can reflect animal physiological processes. In the present study, for the first time, we aimed to use a non-invasive metabolomics approach based on high-resolution mass spectrometry to identify rumen fermentation parameters in dairy cows

Ronja Weber, Bettina Streckenbach, Lara Welti, Demet Inci, Malcolm Kohler, Nathan Perkins, Renato Zenobi, Srdjan Micic , and Alexander Moeller.

There is a need to improve the diagnosis and management of pediatric asthma. Breath analysis aims to address this by non-invasively assessing altered metabolism and disease-associated processes.