Breath Acetone Analysis Research Articles

A fully integrated standalone portable cavity ringdown breath acetone analyzer.

Breath analysis is a promising new technique for nonintrusive disease diagnosis and metabolic status monitoring. One challenging issue in using a breath biomarker for potential particular disease screening is to find a quantitative relationship between the concentration of the breath biomarker and clinical diagnostic parameters of the specific disease. In order to address this issue, we need a new instrument that is capable of conducting real-time, online breath analysis with high data throughput, so that a large scale of clinical test (more subjects) can be achieved in a short period of time. In this work, we report a fully integrated, standalone, portable analyzer based on the cavity ringdown spectroscopy technique for near-real time, online breath acetone measurements. The performance of the portable analyzer in measurements of breath acetone was interrogated and validated by using the certificated gas chromatography-mass spectrometry. The results show that this new analyzer is useful for reliable online (online introduction of a breath sample without pre-treatment) breath acetone analysis with high sensitivity (57 ppb) and high data throughput (one data per second). Subsequently, the validated breath analyzer was employed for acetone measurements in 119 human subjects under various situations. The instrument design, packaging, specifications, and future improvements were also described. From an optical ringdown cavity operated by the lab-set electronics reported previously to this fully integrated standalone new instrument, we have enabled a new scientific tool suited for large scales of breath acetone analysis and created an instrument platform that can even be adopted for study of other breath biomarkers by using different lasers and ringdown mirrors covering corresponding spectral fingerprints.

An acetone bio-sniffer (gas phase biosensor) enabling assessment of lipid metabolism from exhaled breath.

Several volatile organic compounds (VOCs) are released from human breath or skin. Like chemical substances in blood or urine, some of these vapors can provide valuable information regarding the state of the human body. A highly sensitive acetone biochemical gas sensor (bio-sniffer) was developed and used to measure exhaled breath acetone concentration, and assess lipid metabolism based on breath acetone analysis. A fiber-optic biochemical gas sensing system was constructed by attaching a flow-cell with nicotinamide adenine dinucleotide (NADH)-dependent secondary alcohol dehydrogenase (S-ADH) immobilized membrane onto a fiber-optic NADH measurement system. The NADH measurement system utilizes an ultraviolet-light emitting diode with peak emission of 335 nm as an excitation light source. NADH is consumed by the enzymatic reaction of S-ADH, and the consumption is proportional to the concentration of acetone vapor. Phosphate buffer which contained NADH was circulated into the flow-cell to rinse products and the excessive substrates from the optode. The change of fluorescent emitted from NADH is analyzed by the PMT. Hence, fluorescence intensity decreased as the acetone concentration increased. The relationship between fluorescence intensity and acetone concentration was identified from 20 ppb to 5300 ppb. This interval included the concentration of acetone vapor in the breath of healthy people and those suffering from disorders of carbohydrate metabolism. Finally, the acetone bio-sniffer was used to measure breath acetone during an exercise stress test on an ergometer after a period of fasting. The concentration of acetone in breath was shown to significantly increase after exercise. This biosensor allows rapid, highly sensitive and selective measurement of lipid metabolism.

Determination of breath acetone in 149 type 2 diabetic patients using a ringdown breath-acetone analyzer.

Over 90% of diabetic patients have Type 2 diabetes. Although an elevated mean breath acetone concentration has been found to exist in Type 1 diabetes (T1D), information on breath acetone in Type 2 diabetes (T2D) has yet to be obtained. In this study, we first used gas chromatography-mass spectrometry (GC-MS) to validate a ringdown breath-acetone analyzer based on the cavity-ringdown-spectroscopy technique, through comparing breath acetone concentrations in the range 0.5-2.5 ppm measured using both methods. The linear fitting of R = 0.99 suggests that the acetone concentrations obtained using both methods are consistent with a largest standard deviation of ±0.4 ppm in the lowest concentration of the range. Next, 620 breath samples from 149 T2D patients and 42 healthy subjects were collected and tested using the breath analyzer. Four breath samples were taken from each subject under each of four different conditions: fasting, 2 h post-breakfast, 2 h post-lunch, and 2 h post-dinner. Simultaneous blood glucose levels were also measured using a standard diabetic-management blood-glucose meter. For the 149 T2D subjects, their exhaled breath acetone concentrations ranged from 0.1 to 19.8 ppm; four different ranges of breath acetone concentration, 0.1-19.8, 0.1-7.1, 0.1-6.3, and 0.1-9.5 ppm, were obtained for the subjects under the four different conditions, respectively. For the 42 healthy subjects, their breath acetone concentration ranged from 0.1 to 2.6 ppm; four different ranges of breath acetone concentration, 0.3-2.6, 0.1-2.6, 0.1-1.7, and 0.3-1.6 ppm, were obtained for the four different conditions. The mean breath acetone concentration of the 149 T2D subjects was determined to be 1.5 ± 1.5 ppm, which was 1.5 times that of 1.0 ± 0.6 ppm for the 42 healthy subjects. No correlation was found between the breath acetone concentration and the blood glucose level of the T2D subjects and the healthy volunteers. This study using a relatively large number of subjects provides new data regarding breath acetone in diabetes (T1D and T2D) and suggests that an elevated mean breath acetone concentration also exists in T2D.

Breath Acetone Analysis of Diabetic Dogs Using a Cavity Ringdown Breath Analyzer

Some dogs develop a form of diabetes mellitus (DM) similar to that seen in children (juvenile, or Type 1 DM). It is characterized by concurrent high blood glucose (BG) and urine glucose concentrations. Elevated breath acetone concentrations have been observed in Type 1 DM in humans, though a quantitative correlation between breath acetone and BG has yet to be determined. The study of breath acetone in diabetic dogs might allow the use of breath acetone as a biomarker for diabetes in both humans and animals. We report on breath acetone analysis of 51 dogs (37 nondiabetic dogs and 14 diabetic dogs). Breath samples were collected and simultaneous BG levels (if applicable) were measured. Breath acetone tests were conducted using a real-time breath acetone analyzer that is based on the cavity ringdown spectroscopy technique. Absolute breath acetone concentrations (upper limits) were determined without the need for breath sample preconcentration and measurement calibration. For the 37 nondiabetic dogs, their exhaled breath acetone concentrations ranged from 0.16 to 2.42 parts per million (ppm). For the 14 diabetic dogs, breath acetone concentrations ranged from 0.17 to 5.80 ppm with a BG range of 30-750 mg/dL. The mean breath acetone concentration in the 14 diabetic dogs is 1.25 ppm, which is higher than that in the 37 nondiabetic dogs, i.e., 0.60 ppm. The mean breath acetone concentration in nondiabetic dogs, 0.60 ppm, is close to the mean breath acetone concentration in healthy humans. Although diabetic dogs exhibit elevated mean breath acetone concentration, as in human Type 1 DM, no correlation was found between breath acetone concentration and BG level in the diabetic dogs in this paper.

A Ringdown Breath Acetone Analyzer: Performance and Validation Using Gas Chromatography-Mass Spectrometry

Acetone in exhaled breath is a potential biomarker of diabetes mellitus (DM) and elevated breath acetone concentrations have been observed in DM patients. One of the near real-time and online breath acetone analysis techniques is cavity ringdown spectroscopy (CRDS) that has been demonstrated for breath acetone measurements in human subjects including diabetic patients in a clinic. In this work, we have constructed a ringdown breath acetone analyzer for the purpose of instrument validation. Its detection capabilities, such as limit of detection, baseline stability, detection sensitivity, and reproducibility, were investigated. For the first time, a ringdown acetone breath analyzer has been validated using gas chromatography-mass spectrometry (GC-MS), which is typically referred to as the golden standard method for trace gas analysis. The GC-MS validation challenged the analyzer’s response to various breath acetone concentrations and its quantitative measurement accuracy. Subsequently, 25 subjects including 19 healthy and 6 diabetic people were tested using the validated ringdown breath acetone analyzer. Comparison of the testing results shows that this ringdown breath acetone analyzer can be used for reliable real-time, online breath acetone analysis in a clinic.

A prototype portable breath acetone analyzer for monitoring fat loss

Acetone contained in our exhaled breath is a metabolic product of the breakdown of body fat and is expected to be a good indicator of fat-burning. Typically, gas chromatography or mass spectrometry are used to measure low-concentration compounds in breath but such large instruments are not suitable for daily use by diet-conscious people. Here, we prototype a portable breath acetone analyzer that has two types of semiconductor-based gas sensors with different sensitivity characteristics, enabling the acetone concentration to be calculated while taking into account the presence of ethanol, hydrogen, and humidity. To investigate the accuracy of our prototype and its application in diet support, experiments were conducted on healthy adult volunteers. Breath acetone concentrations obtained from our prototype and from gas chromatography showed a strong correlation throughout the experiments. Moreover, body fat in subjects with a controlled caloric intake and taking exercise decreased significantly, whereas breath acetone concentrations in those subjects increased significantly. These results prove that our prototype is practical and useful for self-monitoring of fat-burning at home or outside. Our prototype will help to prevent and alleviate obesity and diabetes.

Off-line breath acetone analysis in critical illness

Analysis of breath acetone could be useful in the Intensive Care Unit (ICU) setting to monitor evidence of starvation and metabolic stress. The aims of this study were to examine the relationship between acetone concentrations in breath and blood in critical illness, to explore any changes in breath acetone concentration over time and correlate these with clinical features. Consecutive patients, ventilated on controlled modes in a mixed ICU, with stress hyperglycaemia requiring insulin therapy and/or new pulmonary infiltrates on chest radiograph were recruited. Once daily, triplicate end-tidal breath samples were collected and analysed off-line by selected ion flow tube mass spectrometry (SIFT-MS). Thirty-two patients were recruited (20 males), median age 61.5 years (range 26–85 years). The median breath acetone concentration of all samples was 853 ppb (range 162–11 375 ppb) collected over a median of 3 days (range 1–8). There was a trend towards a reduction in breath acetone concentration over time. Relationships were seen between breath acetone and arterial acetone (rs = 0.64, p < 0.0001) and arterial beta-hydroxybutyrate (rs = 0.52, p < 0.0001) concentrations. Changes in breath acetone concentration over time corresponded to changes in arterial acetone concentration. Some patients remained ketotic despite insulin therapy and normal arterial glucose concentrations. This is the first study to look at breath acetone concentration in ICU patients for up to 8 days. Breath acetone concentration may be used as a surrogate for arterial acetone concentration, which may in future have a role in the modulation of insulin and feeding in critical illness.

Toward portable breath acetone analysis for diabetes detection

Diabetes is a lifelong condition that may cause death and seriously affects the quality of life of a rapidly growing number of individuals. Acetone is a selective breath marker for diabetes that may contribute to the monitoring of related metabolic disorder and thus simplify the management of this illness. Here, the overall performance of Si-doped WO3 nanoparticles, made by flame spray pyrolysis, as portable acetone detectors is critically reviewed focusing on the requirements for medical diagnostics. The effect of flow rate, chamber volume and acetone dissociation within the measuring chamber is discussed with respect to the calibration of the sensor response. The challenges for the fabrication of portable breath acetone sensors based on chemo-resistive detectors are underlined indicating possible solutions and novel research directions.

A Study on Breath Acetone in Diabetic Patients Using a Cavity Ringdown Breath Analyzer: Exploring Correlations of Breath Acetone With Blood Glucose and Glycohemoglobin A1C

Acetone is qualitatively known as a biomarker of diabetes; however, the quantitative information on acetone concentration in diabetic breath is incomplete, and the knowledge of correlations of breath acetone with diabetic diagnostic parameters, namely, blood glucose (BG) and glycohemoglobin A1C (A1C), are unknown. We utilized a pilot-scale breath acetone analyzer based on the cavity ringdown spectroscopy (CRDS) technique to conduct breath tests with 34 Type 1 diabetic (T1D), ten Type 2 diabetic (T2D) patients, and 15 apparently healthy individuals. Relations between breath acetone and BG, A1C, and several other bio indices, such as the type of diabetes, onset-time, gender, age, and weight were investigated. Our observations show that a linear correlation between the mean group acetone and the mean group BG level does exist (R = 0.98, P < 0.02) when all the T1D subjects tested are grouped by different BG levels, 40-100, 101-150, 151-200, and 201-419 mg/dL. Similarly, among the T1D subjects studied, when their A1C's are grouped by < 7, 7-9.9, and 10-13, a linear correlation between the mean group A1C and the mean group acetone concentration is observed (R = 0.98, P < 0.02). No strong correlations are observed when the BG and A1C numbers are not grouped. The mean breath acetone concentration in the T1D subjects studied in this work is determined to be 2.19 ppmv (parts per million by volume), which is higher than the mean breath acetone concentration, 0.48 ppmv, in the 15 healthy people tested.

An acetone breath analyzer using cavity ringdown spectroscopy: an initial test with human subjects under various situations

We have developed a portable breath acetone analyzer using cavity ringdown spectroscopy (CRDS). The instrument was initially tested by measuring the absorbance of breath gases at a single wavelength (266 nm) from 32 human subjects under various conditions. A background subtraction method, implemented to obtain absorbance differences, from which an upper limit of breath acetone concentration was obtained, is described. The upper limits of breath acetone concentration in the four Type 1 diabetes (T1D) subjects, tested after a 14 h overnight fast, range from 0.80 to 3.97 parts per million by volume (ppmv), higher than the mean acetone concentration (0.49 ppmv) in non-diabetic healthy breath reported in the literature. The preliminary results show that the instrument can tell distinctive differences between the breath from individuals who are healthy and those with T1D. On-line monitoring of breath gases in healthy people post-exercise, post-meals and post-alcohol-consumption was also conducted. This exploratory study demonstrates the first CRDS-based acetone breath analyzer and its potential application for point-of-care, non-invasive, diabetic monitoring.

Epilepsy and the ketogenic diet: assessment of ketosis in children using breath acetone.

High-fat ketogenic diets increase ketones (acetoacetate, beta-hydroxybutyrate, and acetone) and are used to treat refractory seizures. Although ketosis is an integral aspect of these therapeutic regimens, the direct importance of ketosis to seizure control needs further investigation. An examination of this relationship requires a reliable, minimally invasive measure of ketosis that can be performed frequently. In the present study, we examined the use of breath acetone as a measure of ketosis in children with refractory seizures on a classic ketogenic diet. Results were compared with breath acetone levels in epilepsy and healthy controls. Children on the ketogenic diet had significantly higher fasting breath acetone compared with epilepsy or healthy controls (2530 +/- 600 nmol/L versus 19 +/- 9 nmol/L and 21 +/- 4 nmol/L, respectively; p < 0.05). One hour after consumption of a ketogenic breakfast meal, breath acetone increased significantly in epilepsy and healthy controls (p < 0.05), but not in children on a ketogenic diet. Children who were on the ketogenic diet for longer periods of time had a significantly lower fasting breath acetone (R(2) = 0.55, p = 0.014). In one child on the ketogenic diet, breath acetone was determined hourly over a 9-h period, both by gas chromatography and by a prototype hand-held breath acetone analyzer. Preliminary results using this hand-held breath acetone analyzer are encouraging. Breath acetone may be a useful tool in examining the relationship between ketosis and seizure control and enhancing our understanding of the mechanism of the ketogenic diet.

Epilepsy and the Ketogenic Diet: Assessment of Ketosis in Children Using Breath Acetone

High-fat ketogenic diets increase ketones (acetoacetate, β-hydroxybutyrate, and acetone) and are used to treat refractory seizures. Although ketosis is an integral aspect of these therapeutic regimens, the direct importance of ketosis to seizure control needs further investigation. An examination of this relationship requires a reliable, minimally invasive measure of ketosis that can be performed frequently. In the present study, we examined the use of breath acetone as a measure of ketosis in children with refractory seizures on a classic ketogenic diet. Results were compared with breath acetone levels in epilepsy and healthy controls. Children on the ketogenic diet had significantly higher fasting breath acetone compared with epilepsy or healthy controls (2530 ± 600 nmol/L versus 19 ± 9 nmol/L and 21 ± 4 nmol/L, respectively;p < 0.05). One hour after consumption of a ketogenic breakfast meal, breath acetone increased significantly in epilepsy and healthy controls (p < 0.05), but not in children on a ketogenic diet. Children who were on the ketogenic diet for longer periods of time had a significantly lower fasting breath acetone (R2 = 0.55, p = 0.014). In one child on the ketogenic diet, breath acetone was determined hourly over a 9-h period, both by gas chromatography and by a prototype hand-held breath acetone analyzer. Preliminary results using this hand-held breath acetone analyzer are encouraging. Breath acetone may be a useful tool in examining the relationship between ketosis and seizure control and enhancing our understanding of the mechanism of the ketogenic diet.

Breath acetone analyzer: diagnostic tool to monitor dietary fat loss

Acetone, a metabolite of fat catabolism, is produced in excessive amounts in subjects on restricted-calorie weight-loss programs. Breath acetone measurements are useful as a motivational tool during dieting and for monitoring the effectiveness of weight-loss programs. We have developed a simple, easy-to-read method that quantifies the amount of acetone in a defined volume of exhaled breath after trapping the sample in a gas-analyzer column. The concentration of acetone, as measured by the length of a blue color zone in the analyzer column, correlates with results obtained by gas chromatography. Using the breath acetone analyzer to quantify breath acetone concentrations of dieting subjects, we established a correlation between breath acetone concentration and rate of fat loss (slope 52.2 nmol/L per gram per day, intercept 15.3 nmol/L, n = 78, r = 0.81). We also discussed the possibility of using breath acetone in diabetes management.