Analysis of volatile organic compounds (VOCs) in breath holds great promise for noninvasive diagnostic applications. However, concentrations of VOCs in breath may change quickly, and actual and previous uptakes of exogenous substances, especially in the clinical environment, represent crucial issues. We therefore adapted proton-transfer-reaction-time-of-flight-mass spectrometry for real time breath analysis in the clinical environment. For reasons of medical safety, a 6 m long heated silcosteel transfer line connected to a sterile mouth piece was used for breath sampling from spontaneously breathing volunteers and mechanically ventilated patients. A time resolution of 200 ms was applied. Breath from mechanically ventilated patients was analyzed immediately after cardiac surgery. Breath from 32 members of staff was analyzed in the post anesthetic care unit (PACU). In parallel, room air was measured continuously over 7 days. Detection limits for breath-resolved real time measurements were in the high pptV/low ppbV range. Assignment of signals to alveolar or inspiratory phases was done automatically by a matlab-based algorithm. Quickly and abruptly occurring changes of patients' clinical status could be monitored in terms of breath-to-breath variations of VOC (e.g. isoprene) concentrations. In the PACU, room air concentrations mirrored occupancy. Exhaled concentrations of sevoflurane strongly depended on background concentrations in all participants. In combination with an optimized inlet system, the high time and mass resolution of PTR-ToF-MS provides optimal conditions to trace quick changes of breath VOC profiles and to assess effects from the clinical environment.

Concentrations of exhaled volatile organic compounds (VOCs) may depend not only on biochemical or pathologic processes but also on physiological parameters. As breath sampling may be done in different body positions, effects of the sampling position on exhaled VOC concentrations were investigated by means of real-time mass spectrometry. Breaths from 15 healthy volunteers were analyzed in real-time by PTR-ToF-MS-8000 during paced breathing (12/min) in a continuous side-stream mode. We applied two series of body positions (setup 1: sitting, standing, supine, and sitting; setup 2: supine, left lateral, right lateral, prone, and supine). Each position was held for 2 min. Breath VOCs were quantified in inspired and alveolar air by means of a custom-made algorithm. Parallel monitoring of hemodynamics and capnometry was performed noninvasively. In setup 1, when compared to the initial sitting position, normalized mean concentrations of isoprene, furan, and acetonitrile decreased by 24%, 26%, and 9%, respectively, during standing and increased by 63%, 36%, and 10% during lying mirroring time profiles of stroke volume and pET-CO2. In contrast, acetone and H2S concentrations remained almost constant. In setup 2, when compared to the initial supine position, mean alveolar concentrations of isoprene and furan increased significantly up to 29% and 16%, respectively, when position was changed from lying on the right side to the prone position. As cardiac output and stroke volume decreased at that time, the reasons for the observed concentrations changes have to be linked to the ventilation/perfusion ratio or compartmental distribution rather than to perfusion alone. During final postures, all VOC concentrations, hemodynamics, and pET-CO2 returned to baseline. Exhaled blood-borne VOC profiles changed due to body postures. Changes depended on cardiac stroke volume, origin, compartmental distribution and physico-chemical properties of the substances. Patients' positions and cardiac output have to be controlled when concentrations of breath VOCs are to be interpreted in terms of biomarkers.

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BackgroundWhile assumed to protect against coronavirus transmission, face-masks may have effects on respiratory-haemodynamic parameters. Within this pilot study, we investigated immediate and progressive effects of FFP2 and surgical masks on exhaled breath constituents and physiological attributes in 30 adults at rest.MethodsWe continuously monitored exhaled breath profiles within mask space in older (age: 60–80 years) and young to mid-aged (age: 20–60 years) adults over the period of 15 and 30 min, respectively by high-resolution real-time mass-spectrometry (PTR-ToF-MS). Peripheral oxygen saturation, respiratory- and haemodynamic parameters were measured (non-invasively) simultaneously.ResultsProfound, consistent and significant (p-value≤0.001) changes in SpO2 (Adults>60_FFP2-15 min: 5.8±1.3%↓, Adults>60_surgical-15 min: 3.6±0.9%↓, Adults<60_FFP2-30 min: 1.9±1.0%↓, Adults<60_surgical-30 min: 0.9±0.6%↓) and pET-CO2 (Adults>60_FFP2-15 min: 19.1±8.0%↑, Adults>60_surgical-15 min: 11.6±7.6%↑, Adults<60_FFP2- 30 min: 12.1±4.5%↑, Adults<60_surgical- 30 min: 9.3±4.1%↑) indicate ascending deoxygenation and hypercarbia. Secondary changes (p-value≤0.005) to hemodynamic parameters (e.g. MAP: Adults>60_FFP2-15 min: 9.8±10.4%↑) were found. Exhalation of blood-borne volatile metabolites e.g. aldehydes, hemiterpene, organosulfur, short-chain fatty acids, alcohols, ketone, aromatics, nitrile and monoterpene mirrored behaviour of cardiac output, MAP, SpO2, respiratory rate and pET-CO2. Exhaled humidity (e.g. Adults>60_FFP2-15 min: 7.1±5.8%↑) and exhaled oxygen (e.g. Adults>60_FFP2-15 min: 6.1±10.0%↓) changed significantly (p-value≤0.005) over time.ConclusionsBreathomics allows unique physio-metabolic insights into immediate and transient effects of face-mask wearing. Physiological parameters and breath profiles of endogenous and/or exogenous volatile metabolites indicated putative cross-talk between transient hypoxemia, oxidative stress, hypercarbia, vasoconstriction, altered systemic microbial activity, energy homeostasis, compartmental storage and washout. FFP2 masks affected more pronouncedly than surgical masks. Older adults were more vulnerable to FFP2 mask induced hypercarbia, arterial oxygen decline, blood pressure fluctuations and concomitant physiological and metabolic effects.

Breath volatile organic compound (VOC) analysis can open a non-invasive window onto pathological and metabolic processes in the body. Decades of clinical breath-gas analysis have revealed that changes in exhaled VOC concentrations are important rather than disease specific biomarkers. As physiological parameters, such as respiratory rate or cardiac output, have profound effects on exhaled VOCs, here we investigated VOC exhalation under respiratory manoeuvres. Breath VOCs were monitored by means of real-time mass-spectrometry during conventional FEV manoeuvres in 50 healthy humans. Simultaneously, we measured respiratory and hemodynamic parameters noninvasively. Tidal volume and minute ventilation increased by 292 and 171% during the manoeuvre. FEV manoeuvre induced substance specific changes in VOC concentrations. pET-CO2 and alveolar isoprene increased by 6 and 21% during maximum exhalation. Then they decreased by 18 and 37% at forced expiration mirroring cardiac output. Acetone concentrations rose by 4.5% despite increasing minute ventilation. Blood-borne furan and dimethyl-sulphide mimicked isoprene profile. Exogenous acetonitrile, sulphides, and most aliphatic and aromatic VOCs changed minimally. Reliable breath tests must avoid forced breathing. As isoprene exhalations mirrored FEV performances, endogenous VOCs might assure quality of lung function tests. Analysis of exhaled VOC concentrations can provide additional information on physiology of respiration and gas exchange.