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Exhaled human breath measurement method for assessing exposure to halogenated volatile organic compounds.

The organic constituents of exhaled human breath are representative of blood-borne concentrations through gas exchange in the blood/breath interface in the lungs. The presence of specific compounds can be an indicator of recent exposure or represent a biological response of the subject. For volatile organic compounds (VOCs), sampling and analysis of breath is preferred to direct measurement from blood samples because breath collection is noninvasive, potentially infectious waste is avoided, and the measurement of gas-phase analytes is much simpler in a gas matrix rather than in a complex biological tissue such as blood. To exploit these advantages, we have developed the "single breath canister" (SBC) technique, a simple direct collection method for individual alveolar breath samples, and adapted conventional gas chromatography-mass spectrometry analytical methods for trace-concentration VOC analysis. The focus of this paper is to describe briefly the techniques for making VOC measurements in breath, to present some specific applications for which these methods are relevant, and to demonstrate how to estimate exposure to example VOCs on the basis of breath elimination. We present data from three different exposure scenarios: (a) vinyl chloride and cis-1,2-dichloroethene from showering with contaminated water from a private well, (b) chloroform and bromodichloromethane from high-intensity swimming in chlorinated pool water, and (c) trichloroethene from a controlled exposure chamber experiment. In all cases, for all subjects, the experiment is the same: preexposure breath measurement, exposure to halogenated VOC, and a postexposure time-dependent series of breath measurements. Data are presented only to demonstrate the use of the method and how to interpret the analytical results.

Breath Tests↗

Increased nitric oxide in exhaled air in patients with systemic sclerosis.

OBJECTIVE: To assess the lung production of nitric oxide (NO) in patients with systemic sclerosis. METHODS: The NO concentration and its rate of production by the lungs were measured in the exhaled air in 14 patients with systemic sclerosis and in 12 healthy control subjects using the chemiluminescent method. RESULTS: The NO concentration and its rate of production were significantly increased in scleroderma patients (mean +/- SEM, 18.7 +/- 1.7 ppb and 5.8 +/- 0.5 nmol/min, respectively), as compared with control subjects (11.2 +/- 0.8 ppb and 4.3 +/- 0.4 nmol/min, p < 0.01 and p < 0.05, respectively). CONCLUSION: The pulmonary production of NO is increased in scleroderma patients, which might reflect and contribute to the inflammatory processes of the lungs in systemic sclerosis.

Adult↗

Increase in exhaled nitric oxide (eNO) after work-related isocyanate exposure.

UNLABELLED: The objective of this study was to evaluate the role of eNO changes post inhalative isocyanate challenge tests (DeltaeNO) with regard to specific asthmatic reactions and unspecific bronchial hyperresponsiveness (BHR) to predict clinical and subclinical responses of isocyanate workers. METHODS: 55 workers with isocyanate-related respiratory complaints (29 with BHR and 25 without BHR) underwent occupational-type challenge tests. We determined eNO before, during and up to 22 h after diagnostic isocyanate challenge. RESULTS: The 12 asthmatic responders (22%) in the isocyanate-challenge test showed the highest eNO changes 22 h after challenge as well as a significant association between these changes and BHR. There was a positive association between an eNO increase of > 50% and an asthmatic response when compared to nonresponders with an odds ratio of 6.1; 95% CI 1.4-26.3; P = 0.02. More than half of the employees with BHR (52%) but only 20% of those without BHR developed an eNO rise of > 50% after 22 h. Furthermore, a significant positive association was found between the combination of BHR plus eNO increase of 50% after 22 h and the maximum sRaw change (% of baseline value) during the period 0-22 h after isocyanate exposure. The combination of BHR and eNO increase of > 50% was also associated with clinical symptoms during specific challenge tests (cough, shortness of breath, and/or rhinitis). DISCUSSION AND CONCLUSIONS: An eNO increase 22 h post isocyanate challenge occurred in two-thirds of responders and in approximately half of nonresponders with BHR but only rarely in those without BHR. The combination of BHR and eNO increase in nonresponders may offer a new diagnostic tool to register subjects with an increased risk of developing occupational asthma. However, a large study group to perform follow-up investigations into this topic would be helpful to emphasize the importance of this finding.

Asthma↗

Determination of in vivo carbon monoxide production in laboratory animals via exhaled air.

INTRODUCTION: In vitro assays play an important role in the understanding of the heme oxygenase (HO)/carbon monoxide (CO) pathway. However, because physiological roles for the products of this pathway are hypothesized, it is becoming increasingly important to perform in vivo studies. Since CO production is primarily mediated by HO and is excreted mainly by the lungs, measurements of total body CO excretion (VeCO) via the breath allow continuous, noninvasive monitoring of heme degradation and CO and bilirubin production. Here, we describe a modified flow-through method for the collection and quantitation of CO from small laboratory animals. METHODS: Mice and rats were studied in gas-tight chambers supplied with a continuous flow of CO-free air. CO in the exhaust air was measured by gas chromatography with a reduction gas analyzer. After establishing baseline VeCO levels, animals were administered various xenobiotics known to alter HO activity and further monitored for changes in CO production for up to 12 h without observable distress. RESULTS: Administration of heme (substrate for HO) resulted in reproducible increases in CO production; whereas, prior administration of zinc protoporphyrin (ZnPP, HO inhibitor) or cobalt protoporphyrin (CoPP, HO inducer) resulted in respective dose-dependent decreases and increases in the heme-induced CO production. DISCUSSION: We have demonstrated that this noninvasive method of CO quantitation reliably estimates heme degradation with sensitivity to distinguish between different types of HO-manipulating xenobiotics in a dose-dependant manner in both mouse and rat models. Furthermore, VeCO measurements allow nearly real-time determinations of CO and bilirubin formation, which helps to illustrate the time course of drug action.

Animals↗