Physio-Metabolic Monitoring via Breath Employing Real-Time Mass Spectrometry: Importance, Challenges, Potentials, and Pitfalls

Sukul, Pritam; Trefz, Phillip

doi:10.1007/11663_2022_19

Cited by 3 publications

(2 citation statements)

References 84 publications

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“…Volatile organic compounds (VOCs) of various endogenous and/or exogenous origins and chemical classes are continuously exhaled in trace concentrations (the ppbV-pptV range) [15]. Apart from physiological [16][17][18][19][20], metabolic [21][22][23][24][25][26], and therapeutic monitoring [27,28], the real-time mass-spectrometrybased profiling of quantified differences/changes in the alveolar concentrations of breath VOCs could provide unique insights into the disease mechanisms of respiratory infections and the host response [13,29]. Recently, we have developed an advanced setup for the safe breath sampling and VOC-based monitoring of patients experiencing highly contagious respiratory infections [30] and have successfully applied it to the breath screening of hundreds of subjects at a COVID-19 test center, as well as monitoring critically ill (mechanically ventilated) patients at an intensive care unit.…”

Section: Of 16mentioning

confidence: 99%

Effects of Contagious Respiratory Pathogens on Breath Biomarkers

Kemnitz,

Fuchs,

Remy

et al. 2024

Antioxidants

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Due to their immediate exhalation after generation at the cellular/microbiome levels, exhaled volatile organic compounds (VOCs) may provide real-time information on pathophysiological mechanisms and the host response to infection. In recent years, the metabolic profiling of the most frequent respiratory infections has gained interest as it holds potential for the early, non-invasive detection of pathogens and the monitoring of disease progression and the response to therapy. Using previously unpublished data, randomly selected individuals from a COVID-19 test center were included in the study. Based on multiplex PCR results (non-SARS-CoV-2 respiratory pathogens), the breath profiles of 479 subjects with the presence or absence of flu-like symptoms were obtained using proton-transfer-reaction time-of-flight mass spectrometry. Among 223 individuals, one respiratory pathogen was detected in 171 cases, and more than one pathogen in 52 cases. A total of 256 subjects had negative PCR test results and had no symptoms. The exhaled VOC profiles were affected by the presence of Haemophilus influenzae, Streptococcus pneumoniae, and Rhinovirus. The endogenous ketone, short-chain fatty acid, organosulfur, aldehyde, and terpene concentrations changed, but only a few compounds exhibited concentration changes above inter-individual physiological variations. Based on the VOC origins, the observed concentration changes may be attributed to oxidative stress and antioxidative defense, energy metabolism, systemic microbial immune homeostasis, and inflammation. In contrast to previous studies with pre-selected patient groups, the results of this study demonstrate the broad inter-individual variations in VOC profiles in real-life screening conditions. As no unique infection markers exist, only concentration changes clearly above the mentioned variations can be regarded as indicative of infection or colonization.

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Section: Of 16mentioning

confidence: 99%

Effects of Contagious Respiratory Pathogens on Breath Biomarkers

Kemnitz,

Fuchs,

Remy

et al. 2024

Antioxidants

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“…Real-time mass-spectrometry based breathomics offers rapid and repeated non-invasive assessment and continuous monitoring of various physiological (21)(22)(23), metabolic (24)(25)(26), pathological (27)(28)(29) and therapeutic (30)(31)(32) conditions/effects via exhaled VOCs. Years of development in real-time alveolar sampling and breath-resolved analysis allowed us to see minute systemic effects beyond the normal and confounding intra-and inter-individual physio-metabolic noise (33,34). Nevertheless, well-designed prospective studies and independent validations are the prerequisites to de ne reliable breath markers and translate those into routine clinical practice for pathophysiological and therapeutic monitoring.…”

Section: Introductionmentioning

confidence: 99%

Exhaled breath metabolites reveal postmenopausal gut-bone cross-talk and non-invasive markers for osteoporosis

Sukul,

Fischer,

Broderius

et al. 2024

Preprint

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Menopause driven decline in estrogen exposes women to risk of osteoporosis. Detection of early onset and silent progression are keys to prevent fractures and associated burdens. In a discovery cohort of 120 postmenopausal women (aged: 49 – 90 years), we combined repeated quantitative pulse-echo ultrasonography of bone, assessment of grip strength and serum bone markers with mass-spectrometric analysis of exhaled metabolites to find breath volatile markers and quantitative cutoff levels for osteoporosis. Obtained markers and cutoffs were validated in an independent cohort of 49 age-matched women with 6 months apart seasonal follow-ups. Within the discovery cohort median concentrations (ppbV) of exhaled end-tidal dimethyl sulfide (DMS), allyl-methyl sulfide, butanethiol and butyric acid increased significantly (p≤0.005) by 45.24%, 42.83%, 38.29% and 33.66% in subjects (n=27) with bone density at high-risk of osteoporosis and fracture, when compared to subjects (n=62) with normal bone mineral density (BMD). Increased age and decreased grip strength were concomitant. All these changes were reproduced within the independent validation cohort including seasonal follow-ups. Exhaled metabolite expressions remained age independent in either cohort. Serum bone markers showed random expressions without any reproducibility. DMS exhalations even differed between patients with recent (<1 year), old and without fractures. Metabolite exhalations and BMDs were down-regulated during winter mirroring the regional climate change. ROC analysis in the discovery cohort yielded high classification accuracy (AUC=0.86) of DMS with a cutoff at 15.88 ppbV for osteoporosis, which predicted subjects at high-risk within the independent validation cohort with high (>91%) sensitivity and specificity during both follow-ups. Non-invasive analysis of exhaled DMS allowed more reliable classification of osteoporosis risk than conventional serum bone markers. We identified associations of exhaled organosulfur and short-chain fatty acid markers to bone metabolism in postmenopausal osteoporosis via a gut-bone axis.

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Effects of contagious respiratory infections on breath biomarkers

Kemnitz

Fuchs

Remy

et al. 2023

Preprint

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Background Due to their immediate exhalation after generation at the cellular/microbiome levels, exhaled volatile organic compounds (VOCs) may provide real-time information on pathophysiological mechanisms and host response to infections. In recent years, metabolic profiling of most frequent respiratory infection gained interest as it holds potential for early non-invasive detection of pathogens and monitoring of disease progression and response to therapy. Methods In contrast to previous studies with pre-selected patient groups, we conducted a real-time mass-spectrometry based breath profiling in hundreds of consecutive subjects under an actual respiratory infection screening scenario. Recruited subjects were grouped for further comparisons, based on multiplex-PCR confirmed infection (infected by common respiratory pathogen(s) and healthy) and presence or absence of flu like symptoms. Results Amongst recruitments, we obtained 256 healthy cases and 223 infected/coinfected (171 mono-infections, 52 coinfections) with Haemophilus influenza, Streptococcus pneumoniae and Rhinovirus. We observed multiple effects of these mono-infections and co-infections onto the exhaled VOC profiles and variations, especially on endogenous ketone, short-chain fatty acid, organosulfur, aldehyde and terpene concentrations. Based on VOCs origins, we encountered changes in patient’s energy metabolism, systemic microbial immune homeostasis, inflammation, oxidative stress and antioxidative defense. Presence of bacterial pathogens depicted more complex metabolic effects and cross-talk – most likely due to their own metabolism. Conclusion Alike our recent reports on COVID-19 and in line with other recent multi-omics and clinical microbiological reports, these results offered unique insight into common respiratory infections, pathogenesis, ‘host-microbiome-pathogen’ interactions. Breathomics depicted the non-invasive potential for ‘monitoring’ respiratory mono-infections and coinfections.

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Physio-Metabolic Monitoring via Breath Employing Real-Time Mass Spectrometry: Importance, Challenges, Potentials, and Pitfalls

Cited by 3 publications

References 84 publications

Effects of Contagious Respiratory Pathogens on Breath Biomarkers

Effects of Contagious Respiratory Pathogens on Breath Biomarkers

Exhaled breath metabolites reveal postmenopausal gut-bone cross-talk and non-invasive markers for osteoporosis

Effects of contagious respiratory infections on breath biomarkers

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