Techniques and issues in breath and clinical sample headspace analysis for disease diagnosis

Analysis of volatile organic compounds (VOCs) from breath or clinical samples for disease diagnosis is an attractive proposition because it is noninvasive and rapid. There are numerous studies showing its potential, yet there are barriers to its development. Sampling and sample handling is difficult, and when coupled with a variety of analytical instrumentation, the same samples can give different results. Background air and the environment a person has been exposed to can greatly affect the VOCs emitted by the body; however, this is not an easy problem to solve. This review investigates the use of VOCs in disease diagnosis, the analytical techniques employed and the problems associated with sample handling and standardization. It then suggests the barriers to future development

Bronchoalveolar lavage, sputum and exhaled clinically relevant inflammatory markers: values in healthy adults.

11noBronchoalveolar lavage (BAL), induced sputum and exhaled breath markers (exhaled nitric oxide and exhaled breath condensate) can each provide biological insights into the pathogenesis of respiratory disorders. Some of their biomarkers are also employed in the clinical management of patients with various respiratory diseases. In the clinical context, however, defining normal values and cut-off points is crucial. The aim of the present review is to investigate to what extent the issue of defining normal values in healthy adults has been pursued for the biomarkers with clinical value. The current authors reviewed data from literature that specifically addressed the issue of normal values from healthy adults for the four methodologies. Most studies have been performed for BAL (n = 9), sputum (n = 3) and nitric oxide (n = 3). There are no published studies for breath condensate, none of whose markers yet has clinical value. In healthy adult nonsmokers the cut-off points (mean+2sd) for biomarkers with clinical value were as follows. BAL: 16.7% lymphocytes, 2.3% neutrophils and 1.9% eosinophils; sputum: 7.7 x 10(6).mL(-1) total cell count and 2.2% eosinophils; nitric oxide: 20.2 ppb. The methodologies differ concerning the quantity and characteristics of available reference data. Studies focusing on obtaining reference values from healthy individuals are still required, more evidently for the new, noninvasive methodologies.nonemixedBALBI B; PIGNATTI P; CORRADI M; BAIARDI P; BIANCHI L; BRUNETTI G; RADAELI A; MOSCATO G; MUTTI A; SPANEVELLO A; MALERBA MBalbi, B; Pignatti, P; Corradi, M; Baiardi, P; Bianchi, L; Brunetti, G; Radaeli, A; Moscato, G; Mutti, A; Spanevello, Antonio; Malerba, M

Standardizing the Collection and Measurement of Glucose in Exhaled Breath and Its Relationship to Blood Glucose Concentrations

Blood glucose level control (glycemic control) is crucial in diabetes. Limitations in current commercially available monitoring devices include causing patient pain leading to poor blood glucose level management. The development of a non-invasive measurement system may lead to improved patient glycemic control, reducing unwanted side-effects and complications of poor blood glucose level maintenance. This work explores the use of glucose within exhaled breath in attempt to establish an indirect method of blood glucose level measurement. Specifically, exhaled breath condensate (EBC) is examined. A breath condensing unit was designed to measure the temperature of the system, flow rate, volume of expired air, ambient humidity, and remove exhaled dead volume before condensing breath. A fluorometric assay was used to analyze and measure the glucose concentrations in the EBC samples. The results directly relate to the feasibility of developing a noninvasive EBC-based glucose measuring device. A nebulizer study was performed to verify that the amount of glucose present in the condensate was predictable, given a known concentration of aerosolized glucose. The nebulizer study revealed that some glucose interferent is present in the ambient air. Further exploration allowed for a humidity based model to be developed that can accurately and consistently predict the concentration of the condensate. An IRB approved study, using a total of five human subjects, was employed to quantitatively evaluate the change in both blood and EBC glucose levels associated with the intake of either food or water. The human subject study results indicate that, with the use of the humidity based model derived from the nebulizer study, it is possible to predict blood glucose levels from EBC glucose levels. These results provide motivation for the further exploration of an EBC-based non-invasive blood monitoring device

A microreactor approach for chemoselective capture and analysis of carbonyl compounds in air and exhaled breath.

Detection of volatile organic compounds (VOCs) at trace level (parts per billion volume (ppbv) to parts per trillion (pptv)) has become an important research area because of demanding applications in homeland security, environmental monitoring, and noninvasive diagnosis of diseases. The analysis of trace VOCs challenges existing analytical instruments because their concentrations are beyond current instrument limits of detection. In this dissertation, we have investigated an innovative microreactor that is suitable for quantitative analysis of volatile carbonyl compounds in ambient air as well as in human exhaled breath. The approach is based on microreactor chips fabricated from four inch silicon wafers. The chips have thousands of micropillars in the microfluidic channels for uniformly distributing gaseous samples flowing through the microreactors. The surfaces of the micropillars are functionalized with a quaternary ammonium aminooxy salt 2-(aminooxy)-N,N,N-trimethylethanammonium (ATM) iodide for trapping trace ketones and aldehydes by means of oximation reactions. ATM adducts and unreacted ATM are eluted from the microreactor with less than 40µL of methanol and directly analyzed by nanoelectrospray Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS). Capture efficiencies of above 98% have been achieved for ketones and aldehydes. Carbonyl compounds at levels of 1 ppbv have been detected using the microreactor for capture. Ambient air samples from indoor and outdoor areas were collected using Tedlar bags, and analyzed using the microreactor and FTICR-MS. The analysis of air samples provides the reference for analysis of exhaled breath samples. Finally, exhaled breath samples from patients with untreated lung cancer (LC) patients, patients with benign pulmonary nodules and healthy volunteers (smokers and non-smokers) were collected and analyzed using the same method. The FTICR-MS spectra showed that the exhaled breath samples from LC patients have a unique pattern of VOCs, in comparison with healthy controls and patients with benign pulmonary nodules. 2-Butanone, hydroxy-acetaldehyde, 3-hydroxy-2-butanone, and 4-hydroxy-hexenal (4-HHE) were found to have significant higher concentrations for LC patients. A simple diagnosis method based on four elevated VOCs could easily discriminate lung cancer patients from healthy controls and patients with pulmonary nodules with 90.6% diagnosis sensitivity and 81.3% specificity

Dissociated Oxygen Consumption and Carbon Dioxide Production in the Post-Cardiac Arrest Rat: A Novel Metabolic Phenotype.

BACKGROUND: The concept that resuscitation from cardiac arrest (CA) results in a metabolic injury is broadly accepted, yet patients never receive this diagnosis. We sought to find evidence of metabolic injuries after CA by measuring O METHODS AND RESULTS: Rats were anesthetized and randomized into 3 groups: resuscitation from 10-minute asphyxia with inhaled 100% O CONCLUSIONS: CA altered cellular metabolism resulting in increased V

New diagnostic approaches to monitor irrigating fluid absorption

New diagnostic approaches to monitor irrigating fluid absorption Rinsing the endoscopic operating field with an irrigating solution entails the risk of absorption of the fluid. The physiological consequences of such absorption are explored and two new methods for monitoring the amount of absorption are proposed. Methods: Paper 1: 25 anesthetized pigs were randomized to control or continuous infusion of 100 ml/kg over 90 min of either glycine 1.5%, mannitol 3% or mannitol 5%. Several invasive measurements and calculations were performed to describe the pathophysiological processes. Paper 2: Exhaled air nitrous oxide (N2O) concentrations were measured in 12 volunteers receiving intravenous infusions, containing dissolved nitrous oxide and simulating fluid absorption. Paper 3: Comparison of N2O and ethanol for detecting absorption in 86 patients, at 2 centres, undergoing transurethral resection of the prostate (TURP) in spinal anesthesia. Paper 4: A 3-part evaluation of glucose as a tracer in fluid absorption detection. Part 1 was a clinical study in 250 patients undergoing TURP with and without a glucose-containing irrigant. Part 2 investigated the glucose kinetics in 10 volunteers receiving 20 ml/kg of acetated Ringer's solution with 1% glucose over 30 min. In part 3, data was used for computer simulations of various absorption patterns. Results: (Paper 1): Infusions rendered a hypokinetic hypotensive state. Intracellular volume expansion, intracranial pressure elevation and myocardial damage were greater for glycine 1.5%. (Paper 2): N2O is a useful tracer for noninvasive fluid absorption monitoring. It identifies the pattern and the volume of absorption with a 95% predicition interval of ± 200 ml. (Paper 3): The N2O method is feasible in a clinical setting. Agreement with the ethanol method was volume dependent and about twice that of N2O versus known volume. (Paper 4): Sodium and glucose showed a strong inverse linear relation for all patients including diabetics. The glucose levels almost doubled after the experimental infusions, which volume diluted the plasma by 17.7%. Simulations showed that the infused volume correlated with the rise in glucose where an increase by more than 1.4 mmol/L could detect absorption with 95% confidence. Conclusion: The pathophysiological process and treatment rationale of massive nonelectrolytic irrigating fluid absorption was outlined. The N2O method allows noninvasive online monitoring of irrigating fluid absorption with better resolution and similar or better prediction of absorbed volume compared to the ethanol method. Glucose can be used as a tracer for retrospective evaluation of irrigating fluid absorption

Simulating Gas Exchange in the Human Lung and Body

We have implemented a real-time simulator of gas exchange in the human body and lung. The system realistically mimics respiratory gas uptake and production as a function of pulmonary, cardiovascular, and metabolic parameters. The implementation consists of hardware and software to control the flow of gases entering and leaving a ventilated test lung. Such a device could serve as a bench-top resource for testing newly developed anesthesia, hemo-dynamic, and patient monitors. Preliminary tests have been performed for validation of a non-invasive cardiac monitor. The results, while promising, expose the need for more sophisticated models of the human respiratory and circulatory physiology