Breath alcohol concentrations in Japanese outpatients following paclitaxel and docetaxel infusion

Patients receiving paclitaxel or docetaxel also receive a significant amount of ethanol, as both products contain ethanol as solvent. Patients in our clinics have occasionally exhibited signs of alcohol intoxication immediately after paclitaxel infusion. In 2002, the Japanese government lowered the minimum ethanol concentration for the definition of drunk driving, with the threshold breath alcohol concentration (BRAC) of 0.15 mg/l. The aim of this study was to measure BRAC in Japanese outpatients treated with paclitaxel or docetaxel and to assess intoxication according to this standard. Fifty-two Japanese patients were enrolled from October 2003 to February 2004. Patient characteristics were as follows: male/female, 13/39: median age, 71 (range: 34-78); breast/lung/ovarian cancer 24/16/12; and paclitaxel/docetaxel treatment: 36/16, respectively. The mean total doses of paclitaxel or docetaxel were 178 mg (range: 107-300) and 53 mg (30-100), respectively. Breath samples were measured three times immediately following the infusion of paclitaxel or docetaxel via ethyl alcohol detector and the mean value was recorded. BRAC was detected in 20 patients (56%) with paclitaxel and in none of the docetaxel patients. BRAC was measured again 30 min after the initial measurement in BRAC-detected cases with the patients' permission. In four of six BRAC-remeasured patients, BRAC became undetectable after 30 min. There was no correlation between the total doses of paclitaxel and BRAC or between the infusion rates of paclitaxel and BRAC. In conclusion, clinicians should recognize the potential for alcohol intoxication with paclitaxel administration. Patients should be instructed to avoid driving on the day of paclitaxel administration.     

Laboratory evaluation of two passive alcohol sensors.

Passive alcohol sensors are screening devices designed to sample nonintrusively the exhaled breath of a person to determine whether or not it contains alcohol and if so approximately how much. Two production passive alcohol sensors (NPAS passive alcohol sensor and the Life-Loc PBA 2000) were evaluated in a laboratory environment to establish appropriate threshold measurements that indicate probable alcohol impairment. The laboratory evaluation was conducted using both instrument types with 12 drinking subjects. Both sensors were able to identify alcohol in exhaled breath with sufficient accuracy to identify persons with high blood alcohol concentrations (BACs). The accuracy of both sensors was related to the distance from the subject's mouth: the further away they were from a subject's mouth the greater the chance that high BACs would not be detected. Under ideal conditions, it was estimated that the Life-Loc sensor could be expected to correctly detect 80% of drivers at 0.10% BAC (99% at 0.15% BAC) as being impaired while incorrectly identifying only about one in eight drivers with BACs of 0.02% (false positives). In comparison, the NPAS sensor could be expected to correctly detect about 75% of drivers at 0.10% BAC (97% at 0.15% BAC) while incorrectly identifying one in five drivers at 0.02% BAC.     

In vitro estimations of in vivo jet nebulizer efficiency using actual and simulated tidal breathing patterns.

In vivo aerosol delivery efficiency was estimated in vitro for two jet nebulizers using a breath monitor (Breathe!; Pari GmbH, Germany) and breath simulator (COMPAS; Pari GmbH) to reproduce subject tidal breathing patterns. The AeroEclipse (Trudell Medical International, Canada), a breath-actuated nebulizer, and the LC Star (Pari GmbH), a breath-enhanced nebulizer, were filled with levalbuterol HCl solution (Sepracor, USA) and operated with compressed O(2) at 8 lpm. Tidal breathing patterns of 20 adult subjects were digitally recorded with the Breathe! Breath Monitor. Subjects then breathed tidally from each nebulizer separately for 1 minute and to nebulizer dryness. Levalbuterol aerosol collected on filters placed between the nebulizer and mouth was chemically assayed to determine the inspired mass (IM), wasted mass (WM) and total emitted mass (TM). Measurements were repeated using the COMPAS Breath Simulator to simulate each subject's tidal breathing pattern. IM, WM, and TM measurements using actual versus simulated tidal breathing were highly comparable for each nebulizer, except the IM (p < 0.05) from LC Star measured at nebulizer dryness. Breath simulation was an inaccurate tool for estimating the time to nebulizer dryness as simulated measurements to nebulizer dryness took significantly longer than measurements preformed with actual tidal breathing (p < 0.001). While breath simulation provides an accurate in vitro tool for estimating in vivo aerosol delivery, it should not completely replace in vivo measurements until inherent limitations in simulator operation can be overcome to provide a more clinically realistic simulation.     

A real-time method to evaluate the nasal deposition and clearance of acetone in the human volunteer

Nasal dosimetry models have become increasingly quantitative as insights into tissue deposition/clearance and computational fluid dynamics have become available. Validation of these models requires sufficient experimental data. However, investigations into respiratory deposition, particularly in human volunteers, have been historically limited due to methodological limitations. To overcome this, a method for evaluating the nasal wash-in, wash-out phenomena of a highly water-soluble compound in human volunteers was developed and characterized. This methodology was assessed using controlled human inhalation exposures to uniformly labeled [(13)C]acetone at approximately 1 ppm concentration for 30 min under different breathing maneuvers (inhale nose/exhale nose; inhale nose/exhale mouth; inhale mouth/exhale nose). A small-diameter air-sampling probe inserted in the nasopharyngeal cavity of the volunteer was connected directly to an ion-trap mass spectrometer capable of sampling every 0.8 s. A second ion-trap mass spectrometer simultaneously sampled from the volunteer's exhaled breath stream via a breath-inlet device interface. Together, the two mass spectrometers provided real-time appraisal of the [(13)C]acetone concentrations in the nasopharyngeal region and in the exhaled breath stream before, during, and after the different breathing maneuvers. The breathing cycle (depth and frequency) and heart rate were concurrently monitored throughout the exposure using a heart-rate monitor and a human plethysmograph to differentiate inhalation and exhalation. Graphical overlay of the plethysmography results with the mass spectrometer measurements show clear quantifiable differences in [(13)C]acetone levels at the nasal probe as a function of breathing maneuvers. Breath-by-breath analyses of [(13)C]acetone concentrations indicate that between 40 and 75% of the compound is absorbed upon inhalation and nearly all of that absorbed is released back into the breath stream during exhalation.     

A Real-Time Method to Evaluate the Nasal Deposition and Clearance of Acetone in the Human Volunteer

Nasal dosimetry models have become increasingly quantitative as insights into tissue deposition/clearance and computational fluid dynamics have become available. Validation of these models requires sufficient experimental data. However, investigations into respiratory deposition, particularly in human volunteers, have been historically limited due to methodological limitations. To overcome this, a method for evaluating the nasal wash-in, wash-out phenomena of a highly water-soluble compound in human volunteers was developed and characterized. This methodology was assessed using controlled human inhalation exposures to uniformly labeled [13 C]acetone at approximately 1 ppm concentration for 30 min under different breathing maneuvers (inhale nose/exhale nose; inhale nose/exhale mouth; inhale mouth/exhale nose). A small-diameter air-sampling probe inserted in the nasopharyngeal cavity of the volunteer was connected directly to an ion-trap mass spectrometer capable of sampling every 0.8 s. A second ion-trap mass spectrometer simultaneously sampled from the volunteer's exhaled breath stream via a breath-inlet device interface. Together, the two mass spectrometers provided real-time appraisal of the [13 C]acetone concentrations in the nasopharyngeal region and in the exhaled breath stream before, during, and after the different breathing maneuvers. The breathing cycle (depth and frequency) and heart rate were concurrently monitored throughout the exposure using a heart-rate monitor and a human plethysmograph to differentiate inhalation and exhalation. Graphical overlay of the plethysmography results with the mass spectrometer measurements show clear quantifiable differences in [13 C]acetone levels at the nasal probe as a function of breathing maneuvers. Breath-by-breath analyses of [13 C]acetone concentrations indicate that between 40 and 75% of the compound is absorbed upon inhalation and nearly all of that absorbed is released back into the breath stream during exhalation.     

Do breath tests really underestimate blood alcohol concentration?

It has been reported that in the fully postabsorptive state, breath test results underestimate actual blood alcohol concentration (BAC) in 86% of the population. Reanalysis of the data on which this conclusion was based indicates 77% of these subjects were actually underestimated, and 23% were overestimated. Further refinements indicate 68% had their actual BAC underestimated, 16% were acceptably close to the actual BAC, and 16% were overestimated. Perhaps more importantly, comparison of this data with other results indicates fully postabsorptive status may not occur until more than three hours after drinking. Consequently, breath test results may tend to overestimate actual BAC for significant amounts of time after the peak BAC has been reached.     

The consequences of providing drinkers with blood alcohol concentration information on assessments of alcohol impairment and drunk-driving risk.

OBJECTIVE: We examined the effect of providing drinkers with blood alcohol concentration (BAC) information on subjective assessments of alcohol impairment and drunk-driving risk. METHOD: We sampled 959 drinking participants from a natural drinking environment and asked them to self-administer a personal saliva-based alcohol test. Participants then were asked to rate their alcohol impairment and to indicate whether they could drive legally under one of four BAC feedback conditions (assigned at random): (1) control condition (no BAC feedback provided before the ratings); (2) categorical BAC information (low, high, and highest risk) from the saliva test; (3) categorical BAC information corroborated by a calibrated police breath alcohol analyzer; and (4) precise (three-digit) BAC information from the breath alcohol analyzer. RESULTS: Both control participants and participants who received precise BAC feedback gave subjective impairment ratings that correlated with actual BACs. For participants who received categorical BAC information from the saliva test, subjective impairment did not correlate with the actual BAC. Providing drinkers with BAC information, however, did help them predict more accurately if their BAC was higher than the legal BAC driving limit. CONCLUSIONS: Although BAC information can influence drinkers' assessments of alcohol impairment and drunk-driving risk, there is no strong evidence that personal saliva-based alcohol tests are particularly useful.     

The size distribution of droplets in the exhaled breath of healthy human subjects.

Droplets carried in exhaled breath may carry microorganisms capable of transmitting disease over both short and long distances. The size distribution of such droplets will influence the type of organisms that may be carried as well as strategies for controlling airborne infection. The aim of this study was to characterize the size distribution of droplets exhaled by healthy individuals. Exhaled droplets from human subjects performing four respiratory actions (mouth breathing, nose breathing, coughing, talking) were measured by both an optical particle counter (OPC) and an analytical transmission electron microscope (AEM). The OPC indicated a preponderance of particles less than 1 mu, although larger particles were also found. Measurements with the AEM confirmed the existence of larger sized droplets in the exhaled breath. In general, coughing produced the largest droplet concentrations and nose breathing the least, although considerable intersubject variability was observed.     

A simple approach to validation of directed-flow nose-only inhalation chambers

Directed-flow nose-only exposure systems are designed and operated so that the genuine test atmosphere is dynamically delivered to each exposure port and exhaled air from exposed animals is immediately exhausted without the possibility of other animals rebreathing this atmosphere. This technique is particularly useful for preventing uncontrolled changes of exposure atmospheres, stimulating breathing activity due to the rebreathing of exhaled carbon dioxide, and the conserving a test material that is available only in limited quantities. The intricate relationship of the delivered flow of air at each exposure port relative to the respiratory minute volume of the exposed animal appears to be critical for the state-of-the-art performance of directed-flow nose-only exposure systems. This analysis revealed that the determination of carbon dioxide concentrations at different inhalation chamber locations, including exposure ports, is a simple and cost-effective procedure to evaluate whether the rebreathing of atmospheres can be excluded. It has been shown that directed-flow systems need to be operated at an exposure air flow rate greater than 2.5 times the respiratory minute volume of the exposed animal or optimally approximately 0.75 l min(-1) per rat exposure port ( approximately 3.75 times the minute volume of young adult rats) to prevent higher CO(2)-concentrations occurring.     

Inflammation, oxidative stress and systemic effects in mild chronic obstructive pulmonary disease

Chronic obstructive pulmonary diseases (COPD) is a pulmonary disease characterized by systemic abnormalities. The aim of this study is to investigate inflammation and systemic effects in mild COPD. Twenty-seven mild stable smoking related COPD patients and 15 age-matched healthy subjects were enrolled in the study. IL-6, TNF-alpha and IL-4 in plasma, sputum and exhaled breath condensate were measured. We also measured exhaled nitric oxide (NO) and pH in sputum and in breath condensate. Moreover, fat-free mass, body mass index (BMI), respiratory muscle strength, plasma oxidative stress and C-reactive protein (CRP) were measured. Higher concentrations were found of CRP, of diacron reactive oxygen metabolites (DROMs) and of IL-6, TNF-alpha and IL-4 either in plasma or in supernatant of induced sputum or in exhaled breath condensate of COPD subjects compared to healthy controls. Furthermore, higher concentrations were observed of exhaled NO and lower exhaled pH in breath condensate of COPD when compared with healthy subjects. In the group of COPD patients, the subjects with airway reversibility showed an increase of sputum eosinophils and exhaled NO, whereas the subjects without airway obstruction reversibility showed an increase in sputum neutrophils, TNF-alpha and IL-6. We also found a trend towards a decrease in fat-free mass and respiratory muscle strength in COPD compared to healthy subjects and a negative correlation between these systemic indices (fat-free mass, maximal inspiratory pressure, maximal expiratory pressure) and TNF-alpha concentrations in the blood, sputum and breath condensate. We conclude that mild COPD subjects present an increase in inflammatory markers in blood and in airways of similar pattern and furthermore, the neutrophilic pattern of airway inflammation observed in the group of COPD subjects without an airway obstruction reversibility makes it more likely that systemic features are present.     

A device for sampling of human alveolar breath for the measurement of expired volatile organic compounds

This report describes the development of a portable spirometer capable of collecting primarily alveolar breath into 1.8-L canisters for subsequent gas chromatographic/mass spectrometric (GC/MS) analysis. Based on CO2 measurements, greater than 97% of the breath collected is alveolar in origin. Sample collection takes place in approximately two minutes. Clean air for inhalation is provided by two organic vapor respirator cartridges. Studies of the breakthrough volume of test compounds at both the 5- and 50-micrograms/m3 levels indicate that each cartridge filter can be used to sample over 300 L of air and that this volume is not altered by intermittent use and storage of the filter for up to five days. In experiments designed to mimic human breathing, recoveries of test compounds through the device at the 5-mu/m3 level ranged from 87 to 112%. Essentially no volatile organic compound (VOC) memory (i.e., adsorption carryover by the device) was measured at the 50-micrograms/m3 level. The data suggest that the device can be used successfully for organic compounds with volatilities greater than that of p-dichlorobenzene.     

FT-IR breath test in the diagnosis and control of treatment of methanol intoxications

A portable Fourier transform infrared (FT-IR) multicomponent point-of-care analyzer was tested for the diagnosis of methanol intoxications. Breath analysis with FT-IR was fast and easy, and no sample preparation was needed. The analyzer was adequately sensitive and accurate in detecting and quantitating clinically relevant amounts of ethanol and methanol in the breath of seriously ill patients. FT-IR spectrometry was also suitable for nearly on-line monitoring of the exhaled ethanol and methanol during hemodialysis. The breath analysis results correlated well with blood samples. The FT-IR method used also has a traceable calibration to physical properties of the analyte, and the measured spectra can be saved for later analysis.     

Autonomic responses to breath holding and its variations following pranayama

Autonomic responses to breath holding were studied in twenty healthy young men. Breath was held at different phases of respiration and parameters recorded were Breath holding time, heart rate systolic and diastolic blood pressure and galvanic skin resistance (GSR). After taking initial recordings all the subjects practised Nadi-Shodhana Pranayama for a period of 4 weeks. At the end of 4 weeks same parameters were again recorded and the results compared. Baseline heart rate and blood pressure (systolic and diastolic) showed a rendency to decrease and both these autonomic parameters were significantly decreased at breaking point after pranayamic breathing. Although the GSR was recorded in all subjects the observations made were not conclusive. Thus pranayama breathing exercises appear to alter autonomic responses to breath holding probably by increasing vagal tone and decreasing sympathetic discharges.     

The use of low-resolution FT-IR spectrometry for the analysis of alcohols in breath

Fast and reliable diagnostic methods are needed for detection or exclusion of industrial solvents as a cause of intoxication. Analyzing human breath reveals the presence of any volatile substance. A portable Fourier transform infrared (FT-IR) multicomponent point-of-care analyzer was developed for exhaled breath. The analyzer proved to be accurate and precise in laboratory tests for simultaneous measurement of methanol and ethanol in water. Ethanol, in addition to normal contents of breath, was simultaneously analyzed in human experiments, and the results correlated well with blood samples. FT-IR method has a traceable calibration to physical properties of the analyte. The measured spectra can also be saved and analyzed later. Breath analysis with FT-IR is fast and easy, and no preparation of the sample is needed.     

The uptake and elimination of 1,1,1-trichloroethane during and following inhalation exposures in rats

The pharmacokinetics of 1,1,1-trichloroethane (TRI) was studied in male Sprague-Dawley rats in order to characterize and quantify TRI uptake and elimination oby direct measurements of the inhaled and exhaled compound. Fifty or 500 ppm TRI was inhaled for 2 hr through a one-way breathing valve by unanesthetized rats of 325-375 g. Repetitive samples of the separate inhaled and exhaled breath streams, as well as arterial blood, were collected concurrently both during and following TRI inhalation and analyzed for TRI by gas chromatography. Respiratory rates and volumes were continuously monitored during and following exposure and were used in conjunction with the pharmacokinetic data to characterize profiles of uptake and elimination. TRI was very rapidly absorbed from the lung, in that substantial levels were present in arterial blood at the first sampling time (i.e., 2 min). Blood and exhaled breath concentrations of TRI increased rapidly after the initiation of exposure, approaching but not reaching steady state during the 2-hr exposures. The blood and exhaled breath concentrations were directly proportional to the exposure concentration during the exposures. Percentage uptake of TRI decreased 30-35% during the first hour of inhalation, diminishing to approximately 45-50% by the end of the exposure. Total cumulative uptake in the 50 and 500 ppm groups over the 2-hr inhalation exposures was determined to be 6 and 48 mg/kg body wt, respectively. By the end of the exposure period, 2.1 and 20.8 mg, respectively, of inhaled TRI was eliminated from rats inhaling 50 and 500 ppm TRI. A physiological pharmacokinetic model for TRI inhalation was utilized to predict blood and exhaled breath concentrations for comparison with observed experimental values. Overall, values predicted by the physiological pharmacokinetic model for TRI levels in the blood and exhaled breath were in close agreement with measured values both during and following TRI inhalation.     

The pharmacodynamics of ethanol: effects on performance and judgment

The objective and subjective effects produced by increasing and decreasing ethanol concentrations were studied in healthy volunteers on three separate occasions. A randomized, double-blind, placebo-controlled, four-way crossover study was used to determine whether there is any disparity between the time course of blood ethanol concentration and its effects on either objective test performance or self rated impairment. On each study day the subjects received one of four treatments consisting of either placebo or sufficient alcohol to achieve peak estimated blood alcohol concentration (Est.BAC) of 0.07 gm/dL, 0.1 gm/dL or 0.14 gm/dL. Est.BAC determined from breath alcohol concentrations were measured 20 minutes after each "dose" until peak Est.BAC was achieved, then 1, 2, 3.5, and 4.5 hours after peak Est.BAC. Digit symbol substitution (DSS), simulated driving reaction time (SDRT), choice reaction time (CRT) and self assessment of impairment (SRI) were measured simultaneously with Est.BAC. Changes in objective performance test scores were well correlated with Est.BAC (r2 = 0.60 P less than .01). Maximum impairment in test performance occurred at the same time as peak Est.BAC. Threshold Est.BAC needed to produce changes in objective test scores greater than placebo were 0.06 +/- 0.01 for DSS, 0.04 +/- 0.01 for SDRT, and 0.04 +/- 0.02 for CRT. There was no evidence of between dose or within dose tolerance to the effects produced by various Est.BAC on any of these performance tests. Subjects' self rated degrees of impairment at various Est.BAC were influenced by whether alcohol concentrations were rising or falling. Subjective impairment ratings were greater while alcohol concentrations were increasing compared to the same Est.BAC occurring during falling alcohol concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Self-estimates of blood alcohol concentration in drinking-driving context

A total of 72 social drinkers between the ages of 20 and 57 years participated in an ad lib social drinking session. At various intervals throughout the session participants provided estimates of their blood alcohol concentration (BAC) along with breath samples for objective determination of their BAC. Participants were classified into three groups, based on the pattern of their BAC estimation errors-Underestimators, Overestimators, or Mixed Pattern estimators. Underestimators consumed more alcohol and attained higher BACs during the drinking session than the other two groups. Underestimators also rated their level of intoxication significantly lower than other groups and were most likely to judge themselves fit to drive when their actual BAC was in excess of the statutory limit.     

Brain-derived neurotrophic factor enhances histamine-induced airway responses and changes levels of exhaled nitric oxide in guinea pigs in vivo

The neurotrophin brain-derived neurotrophic factor (BDNF) occurs in elevated levels during airway inflammation, including asthma and hypoxic lung injury, and has been suggested to be associated with airway hyperresponsiveness in these conditions. The aim of the present study was to examine whether airway responses to histamine challenge and levels of exhaled nitric oxide (NO) in vivo might be altered upon BDNF treatment. Pulmonary resistance, lung compliance, insufflation pressure, and levels of exhaled NO were measured in anaesthetized guinea pigs exposed to BDNF prior to challenge with histamine and with intact or inhibited endogenous NO production. BDNF pretreatment significantly enhanced histamine-evoked increase in pulmonary resistance and insufflation pressure, as well as the decrease in lung compliance. BDNF markedly accentuated the reduction in exhaled NO following histamine challenge. In animals with inhibited endogenous NO production BDNF induced a significantly earlier histamine-evoked increase in airway responses. The present data show that BDNF can induce an augmentation of histamine-evoked airway responses and reduce levels of NO in exhaled air in vivo. Endogenous NO seems to exert a braking action on BDNF-induced enhancement of airway responses and a reduced ability to release NO may be one mechanism for increased airway response during elevated BDNF levels. Taken together this indicates that BDNF may be of importance for airway hyperresponsiveness in vivo. The interaction between BDNF and airway NO formation, and its relation to airway responses, merit further investigation.     

Demonstration that methadone is being present in the exhaled breath aerosol fraction

Methadone has previously been found present in exhaled breath of methadone treated patients. This study aimed at studying if methadone is present in the aerosol fraction of exhaled breath and used different filter sampling techniques for that. Patients receiving methadone maintenance treatment were recruited for the study. Methadone was extracted from filters collecting methadone from exhaled breath using 2-propanol, methanol and ethyl acetate and measured using liquid-chromatography-tandem mass-spectrometry. The limit of quantification was 5 pg/sample and the intra-day imprecision and accuracy within 15%. The recovery of extracting methadone from filters was >90%. Two types of micro-particle filters were used in this study and were compared with the C18 silica filter (Empore) used before. The Glass fiber filter collected methadone from exhaled breath of methadone patients. The amount collected significantly exceeded the amount using the C18 Empore filter (3.6-14-fold), but the variability of amount trapped was large. The second filter type was a polymer filter. Also this filter was able to trap methadone from exhaled breath of methadone patients. The amount and variability was similar to the C18 Empore filter but smaller than the Glass fiber filter. The mean rate of methadone excretion measured with the best polymer filter was 92 pg/min with a range between 20 and 287 (n = 5). The polymer filter has the practical advantage of having a low flow resistance making it possible to sample without pumping assistance. The polymer filter was found to collect >90% of the exhaled methadone. The conclusion of this study was that methadone in exhaled breath is carried in the aerosol fraction known to be formed in the lung as a result of normal breathing.     

Alcohol absorption, gastric emptying and a breathalyser.

1 The value of a portable breathlyser (Alcometer AE-M2) in the assessment of gastric emptying after alcohol ingestion was investigated by comparing breath and venous blood alcohol concentrations with simultaneous scintigraphic measurements of gastric emptying rate. 2 Alcohol absorption, as determined by the area under the venous blood alcohol concentration-time curve during the first 30 min, correlated with gastric emptying during the same period, implying dependence of the rate of alcohol absorption on gastric emptying rate. 3 There was no correlation between breath and venous alcohol concentrations during the first 15 min after alcohol ingestion, but a significant correlation was observed thereafter. 4 Breath alcohol measurements may be sufficient to detect gross alterations in gastric emptying but measurements of venous blood alcohol are likely to be more reliable.