Exhaled Concentration Research Articles

Application of electrical impedance spirometry to evaluate respiratory function

A practical method for studying the dynamics of respiratory function associated with the registration of the electrical impedance of conductive biological fluids exhaled by the patient is described. In the model measuring cell, the physical causes and patterns of change in air flow conductivity, saturated with an electrolytic fluid aerosol created by an ultrasonic nebulizer, have been investigated experimentally. The design of a new electrical impedance spirometer in the form of a mouthpiece with electrical sensors, filled with a porous medium impregnated with electrolyte, through which the patient breathes, is developed and tested. To register fluctuations in the magnitude of the impedance modulus, an original hardware and software complex is used made on the basis of a high-speed analog-to-digital converter. Based on electrical impedance analysis data, quantitative and qualitative assessment methods are proposed for the basic spirometric medical indicators characterizing the state and functioning of the patient’s breathing apparatus, such as respiration rate, entry and expiration rate, exhaled air volume, amount and concentration of exhaled lung fluid.

Influence of electronic cigarette vaping on the composition of indoor organic pollutants, particles, and exhaled breath of bystanders.

The changes of particles and organic pollutants in indoor atmospheres as consequence of vaping with electronic cigarettes have been analyzed. Changes in the composition of volatile organic compounds (VOCs) in exhaled breath of non-smoking volunteers present in the vaping environments have also been studied. The exposure experiments involved non-vaping (n = 5) and vaping (n = 5) volunteers staying 12h together in a room (54m2) without external ventilation. The same experiment was repeated without vaping for comparison. Changes in the distributions of particles in the 8-400nm range were observed, involving losses of nucleation-mode particles (below 20nm) and increases of coagulation processes leading to larger size particles. In quantitative terms, vaping involved doubling the indoor concentrations of particles smaller than 10μm, 5μm, and 1μm observed during no vaping. The increase of particle mass concentrations was probably produced from bulk ingredients of the e-liquid exhaled by the e-cigarette users. Black carbon concentrations in the indoor and outdoor air were similar in the presence and absence of electronic cigarette emissions. Changes in the qualitative composition of PAHs were observed when comparing vaping and non-vaping days. The nicotine concentrations were examined separately in the gas and in the particulate phases showing that most of the differences between both days were recorded in the former. The particulate phase should therefore be included in nicotine monitoring during vaping (and smoking). The concentration increases of nicotine and formaldehyde were small when compared with those described in other studies of indoor atmospheres or health regulatory thresholds. No significant changes were observed when comparing the concentrations of exhaled breath in vaping and no vaping days. Even the exhaled breath nicotine concentrations in both conditions were similar. As expected, toluene, xylenes, benzene, ethylbenzene, and naphthalene did not show increases in the vaping days since combustion was not involved.

Exploring the physiological link of breath N2O through nitrification and denitrification processes in human gastric juice

Over the past several decades, it has been generally believed that microbial nitrification and denitrification are not significant processes in the human gastrointestinal tract. Moreover, the underlying physiological link between exhaled nitrous oxide (N2O) and aerobic denitrification in the gastric environment is still largely unknown. In this report, we provide direct experimental evidence of the aerobic denitrification process in the human gastrointestinal tract by evaluating concentrations of dissolved N2O and its precursor nitrite () ion in the gastric juice along with exhaled N2O concentration using a high-precision laser spectroscopy technique. Moreover, in vitro studies of gastric fluid in patients reveal a new mechanism of nitrification of ammonium ion () followed by denitrification of leading to the formation of N2O in the gastric environment, which is eventually excreted in exhaled breath. This observation was subsequently validated under in vivo physiological conditions exploiting the urease activity of the gastric pathogen Helicobacter pylori. Consequently, our findings established a strong physiological link between exhaled N2O and bacterial infection in the stomach. This deepens our understanding of the unusual microbial denitrification in the gastric environment, providing new insight into the activities of human-associated microorganisms, which eventually affect the human physiology and health.

Smoking Behavior and Psychological Status Related to Successful Smoking Cessation in Heavy Smokers

Objectives ： The purpose of this study was to determine the factors affecting smoking cessation rate of heavy smokers. Methods ： Typically, 81 participants enrolled in the smoking cessation camp at Chungbuk National University Hospital from April 2016 to November 2016 were included in the present study. The psychological factors related to group classification and the factors related to the success of smoking cessation were analyzed. Results ： After 24 weeks of leaving the camp, 57 out of 81 participants successfully quit smoking and 24 failed in doing so. In the successful group, depression scale, stress scale, and various smoking-related factors exhibited intercorrelation and in the failure group, no significant correlation was observed. However, a comparison of correlation coefficients showed no significant difference. In addition, smoking cessation success rate was low when exhaled CO concentration was high at the time of admission when the smoking initiation age was juvenile, and when the smoking type was A (stimulus seeking type). Conclusion : Exhaled CO concentration at the time of admission, smoking initiation age, and smoking type A (stimulus seeking type) were associated with smoking cessation success.

In-Situ Measurement of Exhaled Formaldehyde and Acetone Kinetics As Early-Stage Non-Invasive Markers of Lung Disease Using Nanostructured Polymeric Membranes

Early stage discovery of lung cancer can significantly improve patient prognosis. Unfortunately, the impact of a well-known technique such as computed tomography screening on mortality rates is uncertain. It has been postulated that tumor growth may lead to peroxidation of cell membranes and is responsible for the observed emission of volatile organic compounds (VOC’s) such as acetone and formaldehyde. This observation has stimulated significant recent effort in the measurement of these compounds in exhaled breath. While promising approaches have been developed for analyzing average VOC concentrations in exhaled breath, an unrecognized drawback to current efforts is the presumption that gas partitioning between the blood and gas phases occurs so rapidly that the time averaged concentration of collected VOCs is representative of their saturation concentration in the lungs. In fact, when one considers the mass transport resistances encountered, VOC lung concentration is likely to be time-dependent and any sensing approach must have sufficient time resolution to capture the dynamic evolution of this concentration during a typical breath exhalation period of not more than 40 seconds in a high humidity environment. In this presentation, we describe development of an optical exhaled gas sensing approach utilizing a nanostructured polymeric membrane that meets these requirements and demonstrates the dynamic evolution of exhaled breath biomarker concentration. We show that the activity of a solid acid catalyst toward the heterogeneous condensation reactions of immobilized resorcinol reagent with gas-phase acetone and formaldehyde can be preserved even at 100% ambient relative humidity through the incorporation of organic acids such as vanillic or tiglic. The reaction produces a colored flavan and poly-condensation products that permits highly selective and sensitive correlation to acetone and formaldehyde concentrations in exhaled breath. Such behavior relies on the complex heterophase morphology of the membrane as will be described. Figure 1

Natural menstrual rhythm and oral contraception diversely affect exhaled breath compositions

Natural menstrual cycle and/or oral contraception diversely affect women metabolites. Longitudinal metabolic profiling under constant experimental conditions is thereby realistic to understand such effects. Thus, we investigated volatile organic compounds (VOCs) exhalation throughout menstrual cycles in 24 young and healthy women with- and without oral contraception. Exhaled VOCs were identified and quantified in trace concentrations via high-resolution real-time mass-spectrometry, starting from a menstruation and then repeated follow-up with six intervals including the next bleeding. Repeated measurements within biologically comparable groups were employed under optimized measurement setup. We observed pronounced and substance specific changes in exhaled VOC concentrations throughout all cycles with low intra-individual variations. Certain blood-borne volatiles changed significantly during follicular and luteal phases. Most prominent changes in endogenous VOCs were observed at the ovulation phase with respect to initial menstruation. Here, the absolute median abundances of alveolar ammonia, acetone, isoprene and dimethyl sulphide changed significantly (P-value ≤ 0.005) by 18.22↓, 13.41↓, 18.02↑ and 9.40↓%, respectively. These VOCs behaved in contrast under the presence of combined oral contraception; e.g. isoprene decreased significantly by 30.25↓%. All changes returned to initial range once the second bleeding phase was repeated. Changes in exogenous benzene, isopropanol, limonene etc. and smoking related furan, acetonitrile and orally originated hydrogen sulphide were rather nonspecific and mainly exposure dependent. Our observations could apprehend a number of known/pre-investigated metabolic effects induced by monthly endocrine regulations. Potential in vivo origins (e.g. metabolic processes) of VOCs are crucial to realize such effects. Despite ubiquitous confounders, we demonstrated the true strength of volatolomics for metabolic monitoring of menstrual cycle and contraceptives. These outcomes may warrant further studies in this direction to enhance our fundamental and clinical understanding on menstrual metabolomics and endocrinology. Counter-effects of contraception can be deployed for future noninvasive assessment of birth control pills. Our findings could be translated toward metabolomics of pregnancy, menopause and post-menopausal complications via breath analysis.

Comparison of different analysis algorithms to calculate multiple-breath washout outcomes.

Lung clearance index (LCI) is the main outcome of the multiple-breath washout (MBW) test. Current recommendations for LCI acquisition are based on low-grade evidence. The aim of this study was to challenge those recommendations using alternative methods for LCI analysis.Nitrogen MBW measurements from school-aged children, 20 healthy controls, 20 with cystic fibrosis (CF) and 17 with primary ciliary dyskinesia (PCD), were analysed using 1) current algorithms (standard), 2) three alternative algorithms to detect with higher precision the end of MBW testing and 3) two alternative algorithms to determine exhaled tracer gas concentrations. LCI values, intra-test repeatability, and ability to discriminate between health and lung disease were compared between these methods.The analysis methods strongly influenced LCI (mean±sd overall differences (%) between standard and alternative analysis methods: −4.9±5.7%; range: −66–19%), but did not improve intra-test variability. Discrimination between health and disease was comparable as areas under the receiver operator curves were not greater than that from standard analysis.This study supports current recommendations for LCI calculation in children. Alternative methods influence LCI estimates and hamper comparability between MBW setups. Alternative algorithms, whenever used, should be carefully reported.

Ultrasensitive flexible self-powered ammonia sensor based on triboelectric nanogenerator at room temperature

An ultrasensitive self-powered ammonia (NH3) sensing system based on a vertical contact-separate mode triboelectric nanogenerator (TENG) has been proposed for room temperature detection of NH3 concentrations both in the ambient environment and in human exhaled gases. Owing to the special output characteristics of the TENG adjusted by the load resistance of the NH3 sensor, output voltage of the fabricated gas sensor has a proportional relationship with NH3 concentration, which is the fundamental working mechanism of the self-powered gas-sensing system. The triboelectric ammonia sensor (TEAS) based on PANI-MWCNTs composite thin film possesses a NH3-sensing response of 10% at 0.01 ppm NH3 and exhibits a great response of 255% at 100 ppm NH3. Meanwhile, the TEAS also holds fast response/recovery time (89–120 s/103–127 s for 0.6–100 ppm NH3), excellent long-term stability, satisfactory selectivity and good anti-bending ability. Furthermore, a preliminary test of human exhaled NH3 concentration has been carried out to further expand the practical application of the developed TEAS. The results not only provide an effective technique in ultrasensitive NH3 sensing but also greatly broaden the applicability of TENG in the detection of human kidney health through comparing to average NH3 concentrations within exhaled gases of healthy people.

Carbonic anhydrase is not a relevant nitrite reductase or nitrous anhydrase in the lung.

Carbonic anhydrase (CA) inhibitors such as acetazolamide inhibit hypoxic pulmonary vasoconstriction (HPV) in humans and other mammals, but the mechanism of this action remains unknown. It has been postulated that carbonic anhydrase may act as a nitrous anhydrase in vivo to generate nitric oxide (NO) from nitrite and that this formation is increased in the presence of acetazolamide. Acetazolamide reduces HPV in pigs without evidence of any NO generation, whereas nebulized sodium nitrite reduces HPV by NO formation; however; combined infusion of acetazolamide with sodium nitrite inhalation did not further increase exhaled NO concentration over inhaled nitrite alone in pigs exposed to alveolar hypoxia. We conclude that acetazolamide does not function as either a nitrous anhydrase or a nitrite reductase in the lungs of pigs, and probably other mammals, to explain its vasodilating actions in the pulmonary or systemic circulations. The carbonic anhydrase (CA) inhibitors acetazolamide and its structurally similar analogue methazolamide prevent or reduce hypoxic pulmonary vasoconstriction (HPV) in dogs and humans in vivo, by a mechanism unrelated to CA inhibition. In rodent blood and isolated blood vessels, it has been reported that inhibition of CA leads to increased generation of nitric oxide (NO) from nitrite and vascular relaxation in vitro. We tested the physiological relevance of augmented NO generation by CA from nitrite with acetazolamide in anaesthetized pigs during alveolar hypoxia in vivo. We found that acetazolamide prevents HPV in anaesthetized pigs, as in other mammalian species. A single nebulization of sodium nitrite reduces HPV, but this action wanes in the succeeding 3h of hypoxia as nitrite is metabolized and excreted. Pulmonary artery pressure reduction and NO formation as measured by exhaled gas concentration from inhaled sodium nitrite were not increased by acetazolamide during alveolar hypoxia. Thus, our data argue against a physiological role of carbonic anhydrase as a nitrous anhydrase or nitrite reductase as a mechanism for its inhibition of HPV in the lung and blood in vivo.

Online monitoring of carbon dioxide and oxygen in exhaled mouse breath via substrate-integrated hollow waveguide Fourier-transform infrared-luminescence spectroscopy

Exhaled breath offers monitoring bio markers, as well as diagnosing diseases and therapeutic interventions. In addition, vital functions may be non-invasively monitored online. Animal models are frequently used in research for determining novel therapeutic approaches and/or for investigating biological pathways. The exhaled carbon dioxide concentration, exhaled and inhaled oxygen concentration, and the subsequent respiratory quotient (RQ) offer insight into metabolic activity. One may adapt breath sampling systems and equipment designed for human applications to large animal studies. However, such adaptations are usually impossible for small animals due to their minuscule breath volume. Here, we present a system for the online monitoring of exhaled breath in a ‘mouse intensive care unit’ (MICU) based on a modified Fourier-transform infrared spectrometer equipped with a substrate-integrated hollow waveguide gas cell, and a luminescence-based oxygen flow-through sensor integrated into the respiratory equipment of the MICU. Thereby, per-minute resolution of O2 consumption and CO2 production was obtained, and the 95% confidence range of the determined RQ was ±0.04 or approximately ±5% of the nominal value. Changes in the RQ value caused by intervention in either the metabolic or respiratory system may therefore reliably be detected.

Modeling-based determination of physiological parameters of systemic VOCs by breath gas analysis, part 2

In a recent paper (Unterkofler et al 2015 J. Breath Res. 9 036002) we presented a simple two compartment model which describes the influence of inhaled concentrations on exhaled breath concentrations for volatile organic compounds (VOCs) with small Henry constants. In this paper we extend this investigation concerning the influence of inhaled concentrations on exhaled breath concentrations for VOCs with higher Henry constants. To this end we extend our model with an additional compartment which takes into account the influence of the upper airways on exhaled breath VOC concentrations.

Outdoor air pollution, exhaled 8-isoprostane and current asthma in adults: the EGEA study.

Associations between outdoor air pollution and asthma in adults are still scarce, and the underlying biological mechanisms are poorly understood. Our aim was to study the associations between 1) long-term exposure to outdoor air pollution and current asthma, 2) exhaled 8-isoprostane (8-iso; a biomarker related to oxidative stress) and current asthma, and 3) outdoor air pollution and exhaled 8-iso.Cross-sectional analyses were conducted in 608 adults (39% with current asthma) from the first follow-up of the French case-control and family study on asthma (EGEA; the Epidemiological study of the Genetic and Environmental factors of Asthma). Data on nitrogen dioxide, nitrogen oxides, particulate matter with a diameter ≤10 and ≤2.5 µm (PM10 and PM2.5), road traffic, and ozone (O3) were from ESCAPE (European Study of Cohorts for Air Pollution Effects) and IFEN (French Institute for the Environment) assessments. Models took account of city and familial dependence.The risk of current asthma increased with traffic intensity (adjusted (a)OR 1.09 (95% CI 1.00-1.18) per 5000 vehicles per day), with O3 exposure (aOR 2.04 (95% CI 1.27-3.29) per 10 µg·m-3) and with exhaled 8-iso concentration (aOR 1.50 (95% CI 1.06-2.12) per 1 pg·mL-1). Among participants without asthma, exhaled 8-iso concentration increased with PM2.5 exposure (adjusted (a)β 0.23 (95% CI 0.005-0.46) per 5 µg·m-3), and decreased with O3 and O3-summer exposures (aβ -0.20 (95% CI -0.39- -0.01) and aβ -0.52 (95% CI -0.77- -0.26) per 10 µg·m-3, respectively).Our results add new insights into a potential role of oxidative stress in the associations between outdoor air pollution and asthma in adults.

Online Monitoring of Intraoperative Exhaled Propofol by Acetone-Assisted Negative Photoionization Ion Mobility Spectrometry Coupled with Time-Resolved Purge Introduction.

Online monitoring of exhaled propofol concentration is important for anesthetists to provide adequate anesthesia as propofol concentrations in plasma and breath are correlated reasonably well. Exhaled propofol could be detected by 63Ni ion mobility spectrometry in negative ion mode; however, the radioactivity of 63Ni source restricts its clinical application due to safety, environmental, and regulatory concerns. An acetone-assisted negative photoionization ion mobility spectrometer (AANP-IMS) using a side-mounted vacuum ultraviolet (VUV) lamp in the unidirectional (UD) flow mode was developed for sensitive measurement of exhaled propofol by producing a high percentage of O2-(H2O) n. An adsorption sampling and time-resolved purge introduction system was developed to eliminate the interference of residual inhaled anesthetic sevoflurane based on their different adsorptions between propofol and sevoflurane on the inwall of the fluorinated ethylene propylene (FEP) sample loop. The effects of the inner diameter and the length of the sample loop on the signal intensity of propofol and the time-resolution between propofol and sevoflurane were theoretically and experimentally investigated. A sample loop with 3 mm i.d. and 150 cm length allowed sensitive measurement of exhaled propofol with a response time of 4 s, a linear response range for propofol was achieved to be 0.2 to 14 ppbv with a limit of detection (LOD) of 60 pptv, and the quantification of propofol was not influenced by the change of the sevoflurane concentration. Finally, the performance of monitoring exhaled propofol during surgery was demonstrated on a patient undergoing laparoscopic distal pancreatectomy combined with cholecystectomy.

Exhaled air dispersion during bag-mask ventilation and sputum suctioning - Implications for infection control

Mask ventilation and coughing during oro-tracheal suctioning produce aerosols that enhance nosocomial transmission of respiratory infections. We examined the extent of exhaled air dispersion from a human-patient-simulator during mask ventilation by different groups of healthcare workers and coughing bouts. The simulator was programmed to mimic varying severity of lung injury. Exhaled airflow was marked with tiny smoke particles, and highlighted by laser light-sheet. We determined the normalized exhaled air concentration in the leakage jet plume from the light scattered by smoke particles. Smoke concentration ≥20% was considered as significant exposure. Exhaled air leaked from mask-face interface in the transverse plane was most severe (267 ± 44 mm) with Ambu silicone resuscitator performed by nurses. Dispersion was however similar among anesthesiologists/intensivists, respiratory physicians and medical students using Ambu or Laerdal silicone resuscitator, p = 0.974. The largest dispersion was 860 ± 93 mm during normal coughing effort without tracheal intubation and decreased with worsening coughing efforts. Oro-tracheal suctioning reduced dispersion significantly, p < 0.001, and was more effective when applied continuously. Skills to ensure good fit during mask ventilation are important in preventing air leakage through the mask-face interface. Continuous oro-tracheal suctioning minimized exhaled air dispersion during coughing bouts when performing aerosol-generating procedures.

Evaluation of a novel waste anaesthetic gas scavenger device for use during recovery from anaesthesia.

Volatile anaesthetic agents are a potential occupational health hazard to theatre and recovery staff. Operating theatres and anaesthetic rooms are required to be equipped with scavenging systems, but recovery units often are not. We compared exhaled, spectrophotometric sevoflurane and desflurane concentrations 15 cm from the mouth ('patient breathing zone') and 91 cm laterally to the patient ('nurse work zone') in 120 patients after tracheal extubation who were consecutively allocated to either ISO-Gard mask oxygen/scavenging or standard oxygen mask, 0 min, 10 min and 20 min after arrival in the theatre recovery unit. Median (IQR [range]) duration of anaesthesia was similar between groups (control 76 (44-119 [15-484]) min vs. study group 90 (64-130 [15-390]) min, p = 0.136). Using the ISO-Gard mask, the 20-min mean patient breathing zone and nurse work zone exhaled anaesthetic levels were ~ 90% and 78% lower than those recorded in the control group, respectively, and were within the recommended 2 ppm maximum environmental exposure limit in the patient breathing zone of 53 out of 60 (88%) and the nurse work zone of all 60 (100%) patients on first measurement in the recovery room (vs. 10 out of 60 (17%) and 40 out of 60 (67%) in the control group). Our study indicates that the ISO-Gard oxygen/scavenging mask reduces the level of exhaled sevoflurane and desflurane below recommended maximum exposure limits near > 85% of extubated patients within ~ 20 s of application in the recovery unit after surgery. We encourage the use of this mask to minimise the occupational exposure of recovery staff to exhaled volatile agents.

A Non-invasive Monitoring of Propofol Concentration in Blood by a Virtual Surface Acoustic Wave Sensor Array.

Propofol (2,6-diisopropylphenol) is widely used in total intravenous anesthesia. An unknown drug concentration in blood always leads to some side effects in patients with propofol injection. However, the drug concentration in the blood is hard to be continuously measured since invasive sampling causes a loss of blood at each measurement. Here, we introduced a virtual surface acoustic wave sensor array (VSAWSA) to non-invasively detect the propofol concentration in blood through exhaled gases. Calibration was conducted by a parallel test using gas chromatography and mass spectrometry (GC-MS) with solid-phase micro-extraction (SPME) for preconcentration. The limit of detection of VSAWSA reached 0.15 nmol/L for propofol. Six cases of clinical trials was conducted to compare the exhaled propofol concentrations to the plasma concentrations controlled by target-controlled infusion (TCI). The calibration by GC-MS ensured the feasibility, reliability, and accuracy of the VSAWSA (R = 0.9904, p <0.001). The clinical monitoring data by VSAWSA showed an excellent consistency with TCI.

A Novel Device for Monitoring Respiratory Rate as an Alternative to Capnography During Endoscopy: Linshom Thermodynamic Sensor

Introduction: Monitoring ventilation accurately is a technically challenging, yet indispensable aspect of patient care in the intra- and post-procedural settings. The current gold standard of method of measuring ventilation is by measuring exhaled carbon dioxide concentration. A prototypical inexpensive device known as the Linshom has been recently designed to non-invasively, and portably measure respiratory rate by using the temperature of exhaled breath. We aim to show that the breath detection capabilities of the temperature sensor are at least equivalent to those of the CO2 sensor. Methods: In this prospective study, participants were enrolled in our endoscopy unit and individually fitted with a face mask which was attached to both sensors: the temperature sensor (Linshom) and the CO2 tubing (Capnography) connected to the monitor which were connected to a laptop computer. For each patient, we report the mean RR for each device and also report the mean difference between the 2 devices and corresponding 95% confidence interval. In addition, Pearson's correlation coefficient was calculated to describe the correlation between Capnostream RR and Linshom BPM. Bland-Altman graphs were plotted to illustrate how the difference in respiratory rate varies based on the magnitude of the respiratory rate. All analyses were performed using SAS. Results: We enrolled 12 patients in the study of who were undergoing endoscopic procedures at our institution. Eight patients underwent colonoscopies and four patients underwent upper endoscopies (1 of the patients underwent both). 4 patients were excluded due to inadequate data, patient cooperation, capnostream failure, etc. The combined study time of the 8 used data sets was 190 minutes resulting in approximately 3000 breaths (assuming on average16 BPM). Overall, we found that Linshom RR highly correlated to Capnostream RR (p < 0.001); the average Capnostream RR increases by 0.66 breaths for every 1 additional breath measured by the Linshom device. In addition, apnea rates were 7.4% for the Capnostream and 6.4% for the Linshom, this corresponds to an average 1% difference in reporting between the two devices (95% CI: 0.92, 1.1). Conclusion: Linshom device correlated with the gold standard Capnostream with respect to respiratory rate detection and also detection of apnea events. Linshom device could be used as an alternative to capnography for measuring respiration in endoscopy. Further studies are needed to validate our findings.Figure: BPM of Linshom in red and the Capnostream in blue for subject #4.Figure: Bland-Altman graph for subject #4.Figure: Comparison of Measured RR between Capnostream and Linshom Devices.

Radon in the Exhaled Air of Patients in Radon Therapy.

In the Gastein valley, numerous facilities use radon for the treatment of various diseases either by exposure to radon in air or in radon rich thermal water. In this study, six test persons were exposed to radon thermal water in a bathtub and the time-dependent radon activity concentration in the exhaled air was recorded. At temperatures between 38°C and 40°C, the radon activity concentration in the water was about 900 kBq/m3 in a total volume of 600 l, where the patients were exposed for 20 min, while continuously sampling the exhaled air during the bathing and 20 min thereafter. After entering the bath, the exhaled radon activity concentration rapidly increased, reaching some kind of saturation after 20 min exposure. The radon activity concentration in the exhaled air was about 8000 Bq/m3 at the maximum, with higher concentrations for male test persons. The total radon transfer from water to the exhaled air was between 480 and 1000 Bq, which is equivalent to 0.08% and 0.2% of the radon in the water.

Volatile organic compounds in exhaled breath are independent of systemic inflammatory syndrome caused by intravenous lipopolysaccharide infusion in humans: results from an experiment in healthy volunteers

Systemic inflammatory response syndrome (SIRS) is observed during critical illness in most patients. It is defined by a clinical definition. The composition of volatile organic compounds (VOCs) in exhaled breath may change during SIRS and may thus serve as a diagnostic tool. We investigated whether exhaled breath VOCs can serve as biomarker for SIRS in a human model of endotoxemia. Eighteen healthy volunteers received 2 ng Eschericia coli lipopolysaccharide (LPS) kg−1 body weight intravenously. Venous blood and exhaled breath were collected before infusion of LPS and every 2 h thereafter, up to 8 h after infusion. The interleukin (IL)-6 concentration was measured in plasma. VOCs in the exhaled breath were measured by gas chromatography and mass spectrometry. A mixed effects model was fitted to examine the relation between the measured compounds in exhaled breath and time after LPS infusion or IL-6 levels in plasma. Partially-least squares discriminant analysis (PLS-DA) was used to investigate whether we could discriminate between samples collected before and after LPS infusion. The exhaled concentrations of 3-methyl-pentane, 4-methyl-pentanol, 1-hexanol, 2,4-dimethyl-heptane, decane and one unknown compound changed after LPS infusion. However, the false-discovery rate was 43% for the total set of 52 compounds that were present in all samples. Of these VOCs only the unknown compound was associated with systemic levels of IL-6. The PLS-DA algorithm resulted in a moderate discriminatory accuracy. SIRS induced by endotoxemia in human volunteers resulted in minor changes in exhaled VOCs. We therefore conclude that LPS infusion in healthy volunteers does not induce metabolic effects that can be detected through VOC analysis of the exhaled breath. This trial is registered at the Dutch Trial Register: NTR4455.

Oral or nasal breathing? Real-time effects of switching sampling route onto exhaled VOC concentrations

There is a need for standardisation in sampling and analysis of breath volatile organic compounds (VOCs) in order to minimise ubiquitous confounding effects. Physiological factors may mask concentration changes induced by pathophysiological effects. In humans, unconscious switching of oral and nasal breathing can occur during breath sampling, which may affect VOC patterns. Here, we investigated exhaled VOC concentrations in real-time while switching breathing routes. Breath from 15 healthy volunteers was analysed continuously by proton transfer reaction time-of-flight mass spectrometry during paced breathing (12 breaths min−1). Every two minutes breathing routes were switched (Setup-1: Oral → Nasal → Oral → Nasal; Setup-2: OralinNasalout → NasalinOralout → OralinNasalout → NasalinOralout). VOCs in inspiratory and alveolar air and respiratory and hemodynamic parameters were monitored quantitatively in parallel. Changing of the breathing routes and patterns immediately affected exhaled VOC concentrations. These changes were reproducible in both setups. In setup-1 cardiac output and acetone concentrations remained constant, while partial pressure of end-tidal CO2 (pET-CO2), isoprene and furan concentrations inversely mirrored tidal-volume and minute-ventilation. H2S (hydrogen-sulphide), C4H8S (allyl-methyl-sulphide), C3H8O (isopropanol) and C3H6O2 increased during oral exhalation. C4H10S increased during nasal exhalations. CH2O2 steadily decreased during the whole measurement. In setup-2 pET-CO2, C2H6S (dimethyl-sulphide), isopropanol, limonene and benzene concentrations decreased whereas, minute-ventilation, H2S and acetonitrile increased. Isoprene and furan remained unchanged. Breathing route and patterns induced VOC concentration changes depended on respiratory parameters, oral and nasal cavity exposure and physico-chemical characters of the compounds. Before using breath VOC concentrations as biomarkers it is essential that the breathing modality is defined and strictly monitored during sampling.