Expiratory flow rate, breath hold and anatomic dead space influence electronic nose ability to detect lung cancer

BACKGROUND: Electronic noses are composites of nanosensor arrays. Numerous studies showed their potential to detect lung cancer from breath samples by analysing exhaled volatile compound pattern ("breathprint"). Expiratory flow rate, breath hold and inclusion of anatomic dead space may influence the exhaled levels of some volatile compounds; however it has not been fully addressed how these factors affect electronic nose data. Therefore, the aim of the study was to investigate these effects. METHODS: 37 healthy subjects (44 +/- 14 years) and 27 patients with lung cancer (60 +/- 10 years) participated in the study. After deep inhalation through a volatile organic compound filter, subjects exhaled at two different flow rates (50 ml/sec and 75 ml/sec) into Teflon-coated bags. The effect of breath hold was analysed after 10 seconds of deep inhalation. We also studied the effect of anatomic dead space by excluding this fraction and comparing alveolar air to mixed (alveolar + anatomic dead space) air samples. Exhaled air samples were processed with Cyranose 320 electronic nose. RESULTS: Expiratory flow rate, breath hold and the inclusion of anatomic dead space significantly altered "breathprints" in healthy individuals (p 0.05). These factors also influenced the discrimination ability of the electronic nose to detect lung cancer significantly. CONCLUSIONS: We have shown that expiratory flow, breath hold and dead space influence exhaled volatile compound pattern assessed with electronic nose. These findings suggest critical methodological recommendations to standardise sample collections for electronic nose measurements

Standardised exhaled breath collection for the measurement of exhaled volatile organic compounds by proton transfer reaction mass spectrometry

BACKGROUND: Exhaled breath volatile organic compound (VOC) analysis for airway disease monitoring is promising. However, contrary to nitric oxide the method for exhaled breath collection has not yet been standardized and the effects of expiratory flow and breath-hold have not been sufficiently studied. These manoeuvres may also reveal the origin of exhaled compounds. METHODS: 15 healthy volunteers (34 +/- 7 years) participated in the study. Subjects inhaled through their nose and exhaled immediately at two different flows (5 L/min and 10 L/min) into methylated polyethylene bags. In addition, the effect of a 20 s breath-hold following inhalation to total lung capacity was studied. The samples were analyzed for ethanol and acetone levels immediately using proton-transfer-reaction mass-spectrometer (PTR-MS, Logan Research, UK). RESULTS: Ethanol levels were negatively affected by expiratory flow rate (232.70 +/- 33.50 ppb vs. 202.30 +/- 27.28 ppb at 5 L/min and 10 L/min, respectively, p < 0.05), but remained unchanged following the breath hold (242.50 +/- 34.53 vs. 237.90 +/- 35.86 ppb, without and with breath hold, respectively, p = 0.11). On the contrary, acetone levels were increased following breath hold (1.50 +/- 0.18 ppm) compared to the baseline levels (1.38 +/- 0.15 ppm), but were not affected by expiratory flow (1.40 +/- 0.14 ppm vs. 1.49 +/- 0.14 ppm, 5 L/min vs. 10 L/min, respectively, p = 0.14). The diet had no significant effects on the gasses levels which showed good inter and intra session reproducibility. CONCLUSIONS: Exhalation parameters such as expiratory flow and breath-hold may affect VOC levels significantly; therefore standardisation of exhaled VOC measurements is mandatory. Our preliminary results suggest a different origin in the respiratory tract for these two gasses

Investigations on the use of breath gas analysis with Proton Transfer Reaction Mass Spectrometry (PTR-MS) for a non-invasive method of early lung cancer detection.

The analysis of volatile organic compounds (VOCs) in exhaled air is an inexpensive and non-invasive method for early detection and diagnosis of human disease. This biophysical methodology in the context of a clinical study based on whether certain lung diseases (including cancer) can be identified early using proton-transfer mass spectrometry (PTR-MS) has been tested. For different groups, such as lung cancer patients, patients with other lung diseases and healthy controls in different environments and lifestyles (e.g. smoking) the measured exhaled VOCs found a significant effect of lung disease on the measured signals

Untersuchung einer m&ouml;glicher Strahlenwirkung auf die Zusammensetzung von Atemgas und von Emissionen aus Zellen mittels Protonen-Transfer-Reaktions Massenspektrometrie (PTR-MS).

PTR-MS gestattet die Online-Analyse von volatilen organischen Komponenten (VOC) in der Luft mit hoher Empfindlichkeit und ohne Probenvorbereitung. Damit wurden m&ouml;gliche Strahleneffekte auf (i) den Metabolismus von Zellen und (ii) das menschliche Atemgas untersucht. Bei den in-vitro Versuchen mit Zellen wurden VOCs im Gasraum &uuml;ber retinalen Ephithelzellen analysiert. Mehrere f&uuml;r die Zellkultur charakteristische VOCs konnten nachgewiesen werden. Nach einer Strahlendosis von bis zu 10 Gy konnten bisher keine signifikanten Konzentrations&auml;nderung festgestellt werden. Au&szlig;erdem wurden Atemgasproben von 20 Krebspatienten analysiert die in Verlaufe einer Strahlentherapie einer Dosis von bis zu 12 Gy ausgesetzt waren. Zwar zeigten die Proben vor und nach der Strahlentherapie teilweise deutliche Unterschiede, aber ganz &auml;hnliche Unterschiede traten auch bei nicht bestrahlten Kontrollpersonen auf. Untersuchungen, ob und wie diese Ver&auml;nderungen reduziert werden k&ouml;nnen, um den strahleninduzierten Metabolismus zu detektieren, werden diskutiert

Influences of mixed expiratory sampling parameters on exhaled volatile organic compound concentrations.

Breath gas analysis is a promising technology for medical applications. By identifying disease-specific biomarkers in the breath of patients, a non-invasive and easy method for early diagnosis or therapy monitoring can be developed. In order to achieve this goal, one essential prerequisite is the reproducibility of the method applied, i.e. the quantification of exhaled volatile organic compounds (VOCs). The variability of breath gas VOC measurements can be affected by many factors. In this respect, sampling-specific parameters like flow rate and volume of exhalation, exhalation with or without breath holding, exhalation in single or multiple breathing and volume of air inhaled before breath gas exhalation can play a vital role. These factors affecting the measurements must be controlled by optimizing the sampling procedure. For such an optimization, it is important to know how exactly the different parameters affect the exhaled VOC concentrations. Therefore, a study has been undertaken in order to identify some effects of different breath sampling-specific parameters on the exhaled VOC profile using the mixed expired breath sampling technique. It was found that parameters such as filling the sampling bag with high or low flow rate of exhalation, with multiple or single exhalations, in different volumes of exhalation, with breath holding and under different surrounding air conditions significantly affect the concentrations of the exhaled VOCs. Therefore, the specific results of this work should be taken into account before planning new breath gas studies or developing new breath gas collection systems in order to minimize the number of artefacts affecting the concentration of exhaled VOCs

Investigations on the variability of breath gas sampling using PTR-MS.

Breath gas analysis is a promising technology in the frame of medical diagnostics. By identifying disease-specific biomarkers in the breath of patients, a non-invasive and easy method for early diagnosis or therapy monitoring might be developed. However, to verify this potential and develop diagnostic tools based on breath gas analysis one essential prerequisite is a low variability in measurement of exhaled volatile organic compounds. Therefore, a study has been undertaken in order to identify possible artefacts within the application of a breath gas test in practice, for which the breath gas is analysed by proton transfer reaction-mass spectrometry (PTR-MS). After validating the low instrumental variability by repeatedly measuring standard gas, the variability of breath gas sampling has been evaluated. The latter has been carried out by measuring single breath gas samples (mixed expiratory breath) collected over different periods of time such as 1 min (10 volunteers, 4 breath gas samples each), 1 h (10 volunteers, 11 breath gas samples each) and several days (11 volunteers, 10 breath gas samples each). The breath gas samples were collected in Teflon bags and consecutively measured with PTR-MS. It was found that those samples collected within 1 min and 1 h show a low variability. This was, however, not the case for samples being collected over longer periods of time (15&ndash;70 days). Under these circumstances, many volatile organic compounds (VOCs) showed significant day-to-day variation in concentration, although the breath collection had been performed under the same conditions (similar sampling time, sampling technique, sample storage time, measurement conditions, etc). This large variation might be assigned to the influence of room air VOCs, which have been investigated in this work, or with other parameters which will be discussed. It was also found that the variability in the measurement of exhaled concentrations of methanol, acetone and isoprene within different individuals (inter individual variability) is much higher than differences in the same volunteer (intra individual variability) measured over a longer time interval