2017 |
Butz, Daniel E; Schoeller, Dale A; Breunig, Emily; Brassil, John; Chu, Johnny; Weidmann, Damien Exhaled 13CO2/12CO2 Delta Value as a Metabolic Marker for Metabolism in Performance Training Conference The FASEB Journal, 31 (1 Supplement:1036.18), 2017. | Links: @conference{Butz2017, title = {Exhaled 13CO2/12CO2 Delta Value as a Metabolic Marker for Metabolism in Performance Training}, author = {Daniel E Butz and Dale A Schoeller and Emily Breunig and John Brassil and Johnny Chu and Damien Weidmann}, url = {http://www.fasebj.org/content/31/1_Supplement/1036.18 http://isomark.com/athletics-study-eb2017-web/}, year = {2017}, date = {2017-04-01}, booktitle = {The FASEB Journal}, volume = {31}, number = {1 Supplement:1036.18}, keywords = {}, pubstate = {published}, tppubtype = {conference} } |
2016 |
Cook, Mark E; Butz, Daniel E; Yang, M; Sand, Jordan Host-targeted approaches to managing animal health: old problems and new tools. Journal Article Domestic Animal Endocrinology, 56 (Supp: S11-22), 2016. Abstract | Links: @article{Cook2016, title = {Host-targeted approaches to managing animal health: old problems and new tools.}, author = {Mark E Cook and Daniel E Butz and M Yang and Jordan Sand}, doi = {10.1016/j.domaniend.2016.04.001}, year = {2016}, date = {2016-07-01}, journal = {Domestic Animal Endocrinology}, volume = {56}, number = {Supp: S11-22}, abstract = {Our fellow medical and regulatory scientists question the animal producer's dependence on antibiotics and antimicrobial chemicals in the production of animal products. Retail distributors and consumers are putting even more pressure on the animal industry to find new ways to produce meat without antibiotics and chemicals. In addition, federal funding agencies are increasingly pressuring researchers to conduct science that has application. In the review that follows, we outline our approach to finding novel ways to improve animal performance and health. We use a strict set of guidelines in our applied research as follows: (1) Does the work have value to society? (2) Does our team have the skills to innovate in the field? (3) Is the product we produce commercially cost-effective? (4) Are there any reasons why the general consumer will reject the technology? (5) Is it safe for the animal, consumer, and the environment? Within this framework, we describe 4 areas of research that have produced useful products, areas that we hope other scientists will likewise explore and innovate such as (1) methods to detect infection in herds and flocks, (2) methods to control systemic and mucosal inflammation, (3) improvements to intestinal barrier function, and (4) methods to strategically potentiate immune defense. We recognize that others are working in these areas, using different strategies, but believe our examples will illustrate the vast opportunity for research and innovation in a world without antibiotics. Animal scientists have been given a new challenge that may help shape the future of both animal and human medicine.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Our fellow medical and regulatory scientists question the animal producer's dependence on antibiotics and antimicrobial chemicals in the production of animal products. Retail distributors and consumers are putting even more pressure on the animal industry to find new ways to produce meat without antibiotics and chemicals. In addition, federal funding agencies are increasingly pressuring researchers to conduct science that has application. In the review that follows, we outline our approach to finding novel ways to improve animal performance and health. We use a strict set of guidelines in our applied research as follows: (1) Does the work have value to society? (2) Does our team have the skills to innovate in the field? (3) Is the product we produce commercially cost-effective? (4) Are there any reasons why the general consumer will reject the technology? (5) Is it safe for the animal, consumer, and the environment? Within this framework, we describe 4 areas of research that have produced useful products, areas that we hope other scientists will likewise explore and innovate such as (1) methods to detect infection in herds and flocks, (2) methods to control systemic and mucosal inflammation, (3) improvements to intestinal barrier function, and (4) methods to strategically potentiate immune defense. We recognize that others are working in these areas, using different strategies, but believe our examples will illustrate the vast opportunity for research and innovation in a world without antibiotics. Animal scientists have been given a new challenge that may help shape the future of both animal and human medicine. |
Butz, Daniel E; Pillers, De-Ann Exhaled breath carbon isotopes are a marker for inflammation in neonates with a chorioamnionitis risk factor. Conference 30 (1), 2016. Abstract | Links: @conference{Butz2016, title = {Exhaled breath carbon isotopes are a marker for inflammation in neonates with a chorioamnionitis risk factor.}, author = {Daniel E Butz and De-Ann Pillers}, url = {http://www.fasebj.org/content/30/1_Supplement/925.19.short}, year = {2016}, date = {2016-04-01}, journal = {The FASEB Journal}, volume = {30}, number = {1}, pages = {Supplement 925.19}, abstract = {Chorioamnionitis is an inflammatory response of the chorioamnion (i.e. fetal membranes) related to infection. Chorioamnionitis is a leading cause of premature rupture of membranes and of premature birth. Although only 3 to 10% of neonates develop congenital sepsis from confirmed cases of chorioamnionitis, empiric antibiotic treatment is initiated as a precautionary measure in all chorioamnionitis cases. Antibiotic treatment continues for 48–72 hours while infants are evaluated and cultures grown to confirm the presence or absence of infection. During this time, the infant may be isolated from the mother while they are in the neonatal intensive care unit for antibiotic treatment. Thus up to three days of unnecessary treatment and isolation occurs in almost 97% of cases, at a significant cost to the healthcare system. Furthermore, there are untold human costs associated with separation of the neonate from their mother, including compromise of maternal-infant bonding, disruption of breastfeeding, and uncertainty and stress for the parent.}, keywords = {}, pubstate = {published}, tppubtype = {conference} } Chorioamnionitis is an inflammatory response of the chorioamnion (i.e. fetal membranes) related to infection. Chorioamnionitis is a leading cause of premature rupture of membranes and of premature birth. Although only 3 to 10% of neonates develop congenital sepsis from confirmed cases of chorioamnionitis, empiric antibiotic treatment is initiated as a precautionary measure in all chorioamnionitis cases. Antibiotic treatment continues for 48–72 hours while infants are evaluated and cultures grown to confirm the presence or absence of infection. During this time, the infant may be isolated from the mother while they are in the neonatal intensive care unit for antibiotic treatment. Thus up to three days of unnecessary treatment and isolation occurs in almost 97% of cases, at a significant cost to the healthcare system. Furthermore, there are untold human costs associated with separation of the neonate from their mother, including compromise of maternal-infant bonding, disruption of breastfeeding, and uncertainty and stress for the parent. |
2015 |
Butz, Daniel E; Weidmann, Damien; Brownsword, Richard; Cook, Mark E; Schoeller, Dale A; Whigham, Leah D Immediate biofeedback for energy balance via expired breath δ13CO2 Conference Conf Proc IEEE Eng Med Biol Soc, Milan, Italy, 2015. Abstract | Links: @conference{Butz2015, title = {Immediate biofeedback for energy balance via expired breath δ13CO2}, author = {Daniel E Butz and Damien Weidmann and Richard Brownsword and Mark E Cook and Dale A Schoeller and Leah D Whigham}, doi = {10.1109/EMBC.2015.7320299}, year = {2015}, date = {2015-01-01}, booktitle = {Conf Proc IEEE Eng Med Biol Soc}, pages = {8205-8208}, address = {Milan, Italy}, abstract = {Expired breath δ13CO2 measured in real time serves as a useful biomarker of altered macronutrient metabolism in response to changes in energy balance. Altered breath δ13CO2 is believed to be a result of changes in macronutrient oxidation and the kinetic isotope effect where enzymatic processes discriminate against metabolites naturally enriched with 13C. Use of breath δ13CO2 as a rapid biofeedback of energy balance status will enhance an individual’s ability to modify behavior during weight loss efforts. Herein we describe a novel approach for immediate biofeedback for energy deficit using a moderate exercise challenge. Our new mid-infrared isotope ratio-meter for δ13CO2 is a step toward miniaturization of a personal device for instant biofeedback for people attempting to lose weight. }, keywords = {}, pubstate = {published}, tppubtype = {conference} } Expired breath δ13CO2 measured in real time serves as a useful biomarker of altered macronutrient metabolism in response to changes in energy balance. Altered breath δ13CO2 is believed to be a result of changes in macronutrient oxidation and the kinetic isotope effect where enzymatic processes discriminate against metabolites naturally enriched with 13C. Use of breath δ13CO2 as a rapid biofeedback of energy balance status will enhance an individual’s ability to modify behavior during weight loss efforts. Herein we describe a novel approach for immediate biofeedback for energy deficit using a moderate exercise challenge. Our new mid-infrared isotope ratio-meter for δ13CO2 is a step toward miniaturization of a personal device for instant biofeedback for people attempting to lose weight. |
2014 |
Boriosi, Juan P; Maki, Dennis G; Wald, Ellen; Butz, Daniel E Noninvasive infection detection in mechanically ventilated adults via the breath delta value Conference Poster Abstract Session: Biomarkers of Immune Responses IDWeek The Pennsylvania Convention Center: IDExpo Hall BC, 2014. Abstract | Links: @conference{Boriosi2014, title = {Noninvasive infection detection in mechanically ventilated adults via the breath delta value}, author = {Juan P Boriosi and Dennis G Maki and Ellen Wald and Daniel E Butz}, url = {https://idsa.confex.com/idsa/2014/webprogram/Paper46680.html}, year = {2014}, date = {2014-10-11}, address = {The Pennsylvania Convention Center: IDExpo Hall BC}, organization = {IDWeek}, series = {Poster Abstract Session: Biomarkers of Immune Responses}, abstract = {Background: The breath delta value (i.e. 13CO2/12CO2 or BDV) is a non-invasive marker for altered metabolism due to infection. Infection detection is achieved by monitoring stable isotopes of carbon in exhaled CO2 termed the BDV. Exhaled breath samples may be taken non-invasively from the ventilator exhaust and isotopic CO2 analyzed. Animal studies and a pilot study in the pediatric intensive care unit (ICU) indicate that the BDV may be an indicator for the onset of infection. We report here the variation in the BDV in critically ill mechanically ventilated adults with and without infection. Methods: Subjects were given the standard of care, and breath was sampled every 8 hours for 72 hours. BDV was determined using the Canary BDV monitor (Isomark, LLC, Madison, WI) currently under development and not yet cleared by the FDA. Infection was defined as either clinically diagnosed sepsis and/or pneumonia. Trends were analyzed using the mixed procedure accounting for autocorrelation of repeated measures (SAS version 9.2, SAS Inst. Cary, NC). Differences were considered significant with p<0.05. Results: Table 1 shows the demographics of the subjects. Figure 1 shows the BDV trends over time. The trends remained stable over time and did not increase or decrease significantly from the first sample. The BDV from subjects with an infection was significantly lower than subjects without infection at all time-points. The mean BDV was -21.07%o (0.19 SEM) in subjects without infection and -23.39%o (0.18 SEM) in subjects with an infection. Conclusion: The BDV is significantly lower in critically ill mechanically ventilated adults with an infection than in similar subjects without an infection. These data suggest that BDV may be a marker for infection in critically ill mechanically ventilated adults. Further testing is underway, to determine if the BDV is a useful marker for the onset of infections in the ICU.}, keywords = {}, pubstate = {published}, tppubtype = {conference} } Background: The breath delta value (i.e. 13CO2/12CO2 or BDV) is a non-invasive marker for altered metabolism due to infection. Infection detection is achieved by monitoring stable isotopes of carbon in exhaled CO2 termed the BDV. Exhaled breath samples may be taken non-invasively from the ventilator exhaust and isotopic CO2 analyzed. Animal studies and a pilot study in the pediatric intensive care unit (ICU) indicate that the BDV may be an indicator for the onset of infection. We report here the variation in the BDV in critically ill mechanically ventilated adults with and without infection. Methods: Subjects were given the standard of care, and breath was sampled every 8 hours for 72 hours. BDV was determined using the Canary BDV monitor (Isomark, LLC, Madison, WI) currently under development and not yet cleared by the FDA. Infection was defined as either clinically diagnosed sepsis and/or pneumonia. Trends were analyzed using the mixed procedure accounting for autocorrelation of repeated measures (SAS version 9.2, SAS Inst. Cary, NC). Differences were considered significant with p<0.05. Results: Table 1 shows the demographics of the subjects. Figure 1 shows the BDV trends over time. The trends remained stable over time and did not increase or decrease significantly from the first sample. The BDV from subjects with an infection was significantly lower than subjects without infection at all time-points. The mean BDV was -21.07%o (0.19 SEM) in subjects without infection and -23.39%o (0.18 SEM) in subjects with an infection. Conclusion: The BDV is significantly lower in critically ill mechanically ventilated adults with an infection than in similar subjects without an infection. These data suggest that BDV may be a marker for infection in critically ill mechanically ventilated adults. Further testing is underway, to determine if the BDV is a useful marker for the onset of infections in the ICU. |
Whigham, Leah D; Butz, Daniel E; Dashti, Hesam; Tonelli, Marco; Johnson, LuAnn K; Cook, Mark E; Porter, Warren P; Eghbalnia, Hamid R; Markley, John L; Lindheim, Steven R; Schoeller, Dale A; Abbott, David H; Assadi-Porter, Fariba M Metabolic Evidence of Diminished Lipid Oxidation in Women with Polycystic Ovary Syndrome Journal Article Current Metabolomics, 2 (4), pp. 269-278, 2014. Abstract | Links: @article{Whigham2014b, title = {Metabolic Evidence of Diminished Lipid Oxidation in Women with Polycystic Ovary Syndrome}, author = {Leah D Whigham and Daniel E Butz and Hesam Dashti and Marco Tonelli and LuAnn K Johnson and Mark E Cook and Warren P Porter and Hamid R Eghbalnia and John L Markley and Steven R Lindheim and Dale A Schoeller and David H Abbott and Fariba M Assadi-Porter}, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3994884/pdf/nihms559015.pdf }, doi = {10.2174/2213235X01666131203230512}, year = {2014}, date = {2014-04-22}, journal = {Current Metabolomics}, volume = {2}, number = {4}, pages = {269-278}, abstract = {Polycystic ovary syndrome (PCOS), a common female endocrinopathy, is a complex metabolic syndrome of enhanced weight gain. The goal of this pilot study was to evaluate metabolic differences between normal (n=10) and PCOS (n=10) women via breath carbon isotope ratio, urinary nitrogen and nuclear magnetic resonance (NMR)-determined serum metabolites. Breath carbon stable isotopes measured by cavity ring down spectroscopy (CRDS) indicated diminished (p<0.030) lipid use as a metabolic substrate during overnight fasting in PCOS compared to normal women. Accompanying urinary analyses showed a trending correlation (p<0.057) between overnight total nitrogen and circulating testosterone in PCOS women, alone. Serum analyzed by NMR spectroscopy following overnight, fast and at 2 h following an oral glucose tolerance test showed that a transient elevation in blood glucose levels decreased circulating levels of lipid, glucose and amino acid metabolic intermediates (acetone, 2-oxocaporate, 2-aminobutyrate, pyruvate, formate, and sarcosine) in PCOS women, whereas the 2 h glucose challenge led to increases in the same intermediates in normal women. These pilot data suggest that PCOS-related inflexibility in fasting-related switching between lipid and carbohydrate/protein utilization for carbon metabolism may contribute to enhanced weight gain.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Polycystic ovary syndrome (PCOS), a common female endocrinopathy, is a complex metabolic syndrome of enhanced weight gain. The goal of this pilot study was to evaluate metabolic differences between normal (n=10) and PCOS (n=10) women via breath carbon isotope ratio, urinary nitrogen and nuclear magnetic resonance (NMR)-determined serum metabolites. Breath carbon stable isotopes measured by cavity ring down spectroscopy (CRDS) indicated diminished (p<0.030) lipid use as a metabolic substrate during overnight fasting in PCOS compared to normal women. Accompanying urinary analyses showed a trending correlation (p<0.057) between overnight total nitrogen and circulating testosterone in PCOS women, alone. Serum analyzed by NMR spectroscopy following overnight, fast and at 2 h following an oral glucose tolerance test showed that a transient elevation in blood glucose levels decreased circulating levels of lipid, glucose and amino acid metabolic intermediates (acetone, 2-oxocaporate, 2-aminobutyrate, pyruvate, formate, and sarcosine) in PCOS women, whereas the 2 h glucose challenge led to increases in the same intermediates in normal women. These pilot data suggest that PCOS-related inflexibility in fasting-related switching between lipid and carbohydrate/protein utilization for carbon metabolism may contribute to enhanced weight gain. |
Whigham, Leah D; Butz, Daniel E; Johnson, LK; Schoeller, Dale A; Abbott, David H; Porter, Warren P; Cook, Mark E Breath carbon stable isotope ratios identify changes in energy balance and substrate utilization in humans Journal Article International Journal of Obesity, 38 , pp. 1248-1250, 2014. Abstract | Links: @article{Whigham2014, title = {Breath carbon stable isotope ratios identify changes in energy balance and substrate utilization in humans}, author = {Leah D Whigham and Daniel E Butz and LK Johnson and Dale A Schoeller and David H Abbott and Warren P Porter and Mark E Cook}, url = {http://www.nature.com/ijo/journal/v38/n9/abs/ijo20147a.html}, year = {2014}, date = {2014-02-18}, journal = {International Journal of Obesity}, volume = {38}, pages = {1248-1250}, abstract = {Rapid detection of shifts in substrate utilization and energy balance would provide a compelling biofeedback tool for individuals attempting weight loss. As a proof of concept, we tested whether the natural abundance of exhaled carbon stable isotope ratios (breath δ13C) reflects shifts between negative and positive energy balance. Volunteers (n=5) consumed a 40% energy-restricted diet for 6 days followed by 50% excess on day 7. Breath was sampled immediately before and 1 h and 2 h after breakfast, lunch and dinner. Exhaled breath δ13C values were measured by cavity ring-down spectroscopy. Using repeated measures analysis of variance (ANOVA) followed by Dunnett’s contrasts, pre-breakfast breath values on days 2–6 were compared with day 1, and postprandial day 7 time points were compared with pre-breakfast day 7. Energy restriction diminished pre-breakfast breath δ13C by day 3 (P<0.05). On day 7, increased energy intake was first detected immediately before dinner (−23.8±0.6 vs −21.9±0.7‰, P=0.002 (means±s.d.)), and breath δ13C remained elevated at least 2 h post dinner. In conclusion, when shifting between negative and positive energy balance, breath δ13C showed anticipated isotopic changes. Although additional research is needed to determine specificity and repeatability, this method may provide a biomarker for marked increases in caloric intake.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Rapid detection of shifts in substrate utilization and energy balance would provide a compelling biofeedback tool for individuals attempting weight loss. As a proof of concept, we tested whether the natural abundance of exhaled carbon stable isotope ratios (breath δ13C) reflects shifts between negative and positive energy balance. Volunteers (n=5) consumed a 40% energy-restricted diet for 6 days followed by 50% excess on day 7. Breath was sampled immediately before and 1 h and 2 h after breakfast, lunch and dinner. Exhaled breath δ13C values were measured by cavity ring-down spectroscopy. Using repeated measures analysis of variance (ANOVA) followed by Dunnett’s contrasts, pre-breakfast breath values on days 2–6 were compared with day 1, and postprandial day 7 time points were compared with pre-breakfast day 7. Energy restriction diminished pre-breakfast breath δ13C by day 3 (P<0.05). On day 7, increased energy intake was first detected immediately before dinner (−23.8±0.6 vs −21.9±0.7‰, P=0.002 (means±s.d.)), and breath δ13C remained elevated at least 2 h post dinner. In conclusion, when shifting between negative and positive energy balance, breath δ13C showed anticipated isotopic changes. Although additional research is needed to determine specificity and repeatability, this method may provide a biomarker for marked increases in caloric intake. |
Butz, Daniel E; Morello, Samantha L; Sand, Jordan; Holland, Neil G; Cook, Mark E Expired breath carbon delta value is a marker for the onset of sepsis in a swine model Journal Article Journal of Analytical Atomic Spectrometry, 29 , pp. 606-613, 2014. Abstract | Links: @article{Butz2014b, title = {Expired breath carbon delta value is a marker for the onset of sepsis in a swine model}, author = {Daniel E Butz and Samantha L Morello and Jordan Sand and G Neil Holland and Mark E Cook}, url = {http://isomark.com/wp-content/uploads/2012/11/Butz-2013-Expired-breath-carbon-delta-value-is-a-marker-for-the-onset-of-sepsis-in-a-swine-model.pdf}, doi = {10.1039/c3ja50340b}, year = {2014}, date = {2014-01-01}, journal = {Journal of Analytical Atomic Spectrometry}, volume = {29}, pages = {606-613}, abstract = {Approximately 750 000 people develop sepsis each year with more than 215 000 deaths. Earlier diagnosis and treatment of sepsis are critical to improving the outcome. The exhaled breath delta value (i.e.13CO2/12CO2 ratio, or BDV) is a biomarker for the acute phase response in sepsis models. The objective of this study was to define the temporal relationship between changes in the BDV, physiological and blood markers of sepsis in a porcine cecal ligation and puncture (CLP) model of sepsis. CLP led to a significant decrease in BDV in animals with stable mean arterial pressure during the course of the study, while the BDV of control animals was similar to that in animals that rapidly progressed into septic shock. The BDV indicated the onset of sepsis with a mean time of 3.54 hours (SEM 0.96) while physiological parameters detected the onset of sepsis in 11.11 hours (SEM 0.94) (p < 0.001). Biologic protein markers of inflammation (cytokines, including interleukin (IL)-1β, IL-4, IL-12, granulocyte/macrophage colony stimulating factor, interferon-gamma, and transforming growth factor-beta) did not change significantly during the experiment. Tumor necrosis factor-alpha was present at the baseline, at 2 hours in the control and CLP group with falling blood pressure, and at 8 hours in the control group. IL-6 was present at the baseline in all groups and spiked in the CLP animals with stable mean arterial pressure by 15 hours. The C-reactive protein was elevated in CLP and control animals by 8 hours (p < 0.05). Procalcitonin was present pre-surgery and increased above the baseline by 8 in CLP animals. These data show that the breath delta value is a leading indicator of sepsis in a porcine CLP model when compared to other physiological parameters.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Approximately 750 000 people develop sepsis each year with more than 215 000 deaths. Earlier diagnosis and treatment of sepsis are critical to improving the outcome. The exhaled breath delta value (i.e.13CO2/12CO2 ratio, or BDV) is a biomarker for the acute phase response in sepsis models. The objective of this study was to define the temporal relationship between changes in the BDV, physiological and blood markers of sepsis in a porcine cecal ligation and puncture (CLP) model of sepsis. CLP led to a significant decrease in BDV in animals with stable mean arterial pressure during the course of the study, while the BDV of control animals was similar to that in animals that rapidly progressed into septic shock. The BDV indicated the onset of sepsis with a mean time of 3.54 hours (SEM 0.96) while physiological parameters detected the onset of sepsis in 11.11 hours (SEM 0.94) (p < 0.001). Biologic protein markers of inflammation (cytokines, including interleukin (IL)-1β, IL-4, IL-12, granulocyte/macrophage colony stimulating factor, interferon-gamma, and transforming growth factor-beta) did not change significantly during the experiment. Tumor necrosis factor-alpha was present at the baseline, at 2 hours in the control and CLP group with falling blood pressure, and at 8 hours in the control group. IL-6 was present at the baseline in all groups and spiked in the CLP animals with stable mean arterial pressure by 15 hours. The C-reactive protein was elevated in CLP and control animals by 8 hours (p < 0.05). Procalcitonin was present pre-surgery and increased above the baseline by 8 in CLP animals. These data show that the breath delta value is a leading indicator of sepsis in a porcine CLP model when compared to other physiological parameters. |
Boriosi, Juan P; Maki, Dennis G; Yngsdal-Krenz, Rhonda A; Wald, Ellen R; Porter, Warren P; Cook, Mark E; Butz, Daniel E Changes in breath carbon isotope composition as a potential biomarker of inflammatory acute phase response in mechanically ventilated pediatric patients Journal Article Journal of Analytical Atomic Spectrometry, 29 , pp. 599-605, 2014. Abstract | Links: @article{Boriosi2014, title = {Changes in breath carbon isotope composition as a potential biomarker of inflammatory acute phase response in mechanically ventilated pediatric patients}, author = {Juan P Boriosi and Dennis G Maki and Rhonda A Yngsdal-Krenz and Ellen R Wald and Warren P Porter and Mark E Cook and Daniel E Butz}, url = {http://isomark.com/wp-content/uploads/2014/01/Pediatrics-CO2-Study-Article-final.pdf}, doi = {10.1039/c3ja50331c}, year = {2014}, date = {2014-01-01}, journal = {Journal of Analytical Atomic Spectrometry}, volume = {29}, pages = {599-605}, abstract = {Sepsis is a leading cause of mortality in intensive care units. Animal studies have shown exhaled breath carbon isotope delta values (BDVs, i.e., 13CO2/12CO2 delta value) to be a marker for the inflammatory acute phase response (APR). The purpose of this study was to determine the baseline variability of BDVs in mechanically ventilated pediatric patients with and without systemic inflammatory response syndrome (SIRS) and to correlate the BDV with clinical course over time. The study was an observational pilot study in a pediatric intensive care unit at an urban, tertiary care children's hospital. Seventeen mechanically ventilated pediatric patients underwent measurement of exhaled BDVs every 8 hours for 72 hours. The BDV was not statistically different between SIRS, No-SIRS and SIRS with shock. The mean BDV was significantly lower in subjects with active sepsis or trauma/post-op status compared to subjects with No-Infection/Trauma/Surgery (No-ITS) or septic shock. Trend analysis over time revealed that the No-ITS and ITS in recovery groups had positive slopes. Subjects who developed infections during the study and subjects who underwent shock had a negative trend over time. These results indicate that the BDV does not correlate well with the SIRS status. However, when patients are classified based on their inflammatory APR the BDV correlates with the severity of systemic inflammation. When monitored over time, changes in the BDV may correlate with changes in physiology related to fractionation during the APR to infection, trauma or due to altered macronutrient oxidation during episodes of septic shock.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Sepsis is a leading cause of mortality in intensive care units. Animal studies have shown exhaled breath carbon isotope delta values (BDVs, i.e., 13CO2/12CO2 delta value) to be a marker for the inflammatory acute phase response (APR). The purpose of this study was to determine the baseline variability of BDVs in mechanically ventilated pediatric patients with and without systemic inflammatory response syndrome (SIRS) and to correlate the BDV with clinical course over time. The study was an observational pilot study in a pediatric intensive care unit at an urban, tertiary care children's hospital. Seventeen mechanically ventilated pediatric patients underwent measurement of exhaled BDVs every 8 hours for 72 hours. The BDV was not statistically different between SIRS, No-SIRS and SIRS with shock. The mean BDV was significantly lower in subjects with active sepsis or trauma/post-op status compared to subjects with No-Infection/Trauma/Surgery (No-ITS) or septic shock. Trend analysis over time revealed that the No-ITS and ITS in recovery groups had positive slopes. Subjects who developed infections during the study and subjects who underwent shock had a negative trend over time. These results indicate that the BDV does not correlate well with the SIRS status. However, when patients are classified based on their inflammatory APR the BDV correlates with the severity of systemic inflammation. When monitored over time, changes in the BDV may correlate with changes in physiology related to fractionation during the APR to infection, trauma or due to altered macronutrient oxidation during episodes of septic shock. |
Butz, Daniel E; Casperson, Shanon L; Whigham, Leah D The emerging role of carbon isotope ratio determination in health research and medical diagnostics Journal Article Journal of Analytical Atomic Spectrometry, 29 , pp. 594-598, 2014. Abstract | Links: @article{Butz2014c, title = {The emerging role of carbon isotope ratio determination in health research and medical diagnostics}, author = {Daniel E Butz and Shanon L Casperson and Leah D Whigham}, url = {http://isomark.com/wp-content/uploads/2013/12/The-emerging-role-of-carbon-isotope-ratio.pdf}, doi = {10.1039/C3JA50327E}, year = {2014}, date = {2014-01-01}, journal = {Journal of Analytical Atomic Spectrometry}, volume = {29}, pages = {594-598}, abstract = {Variations in the isotopic signature of carbon in biological samples (e.g. breath, blood and tissues) can be used to monitor shifts in whole body metabolism. As a conservative recorder of our diet, changes in the isotopic signature of carbon in biological samples provide an objective means to distinguish dietary patterns and the relationship with diseases. In addition, metabolic discrimination of carbon within the body can be informative regarding changes in the body's metabolic fuel usage during situations where shifts in the macronutrient oxidation ratio are expected. Therefore, changes in the isotopic signature over time have proven to be a tremendously powerful and sensitive means of detecting and measuring changes in steady-state systems. As such, this review focuses on how a naturally occurring ratio of stable isotopes of carbon (13C/12C) can be used as a biomarker for nutritional and metabolic status, altered macronutrient metabolism, and health and disease.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Variations in the isotopic signature of carbon in biological samples (e.g. breath, blood and tissues) can be used to monitor shifts in whole body metabolism. As a conservative recorder of our diet, changes in the isotopic signature of carbon in biological samples provide an objective means to distinguish dietary patterns and the relationship with diseases. In addition, metabolic discrimination of carbon within the body can be informative regarding changes in the body's metabolic fuel usage during situations where shifts in the macronutrient oxidation ratio are expected. Therefore, changes in the isotopic signature over time have proven to be a tremendously powerful and sensitive means of detecting and measuring changes in steady-state systems. As such, this review focuses on how a naturally occurring ratio of stable isotopes of carbon (13C/12C) can be used as a biomarker for nutritional and metabolic status, altered macronutrient metabolism, and health and disease. |
2013 |
Butz, Daniel E; Morello, Samantha L; Sand, Jordan; Boriosi, Juan P; Holland, Neil G; Cook, Mark E Continuous exhaled breath carbon isotope analysis for early detection of sepsis Conference 27 (1), 2013. Abstract | Links: @conference{Butz2013bb, title = {Continuous exhaled breath carbon isotope analysis for early detection of sepsis}, author = {Daniel E Butz and Samantha L Morello and Jordan Sand and Juan P Boriosi and G Neil Holland and Mark E Cook}, url = {http://www.fasebj.org/content/27/1_Supplement/868.5.short}, year = {2013}, date = {2013-04-01}, journal = {The FASEB Journal}, volume = {27}, number = {1}, pages = {Supplement 868.5}, abstract = {Approximately 750,000 people develop sepsis each year with more than 215,000 deaths. Earlier diagnosis and treatment of sepsis is critical to improving outcome. The exhaled breath delta value (i.e. 13CO2/12CO2 ratio) is a biomarker for the acute phase response (APR) to endotoxin. The objective of this study was to demonstrate that the breath delta value is a leading marker for the onset of infection in a porcine sepsis model. Sepsis was induced by cecal ligation and puncture. Briefly, pigs were anesthetized and positive pressure ventilation was established. The animal was instrumented for invasive blood pressure monitoring, cardiac output measurements, and blood sampling. Heart rate, respiratory rate, arterial blood pressure, central venous pressure, blood oxygen saturation, temperature, blood glucose, end tidal CO2, and breath delta value were monitored once every 15 minutes. Sepsis caused an increase in body temperature between 6 and 15 hours after onset. Other physiological parameters did not change from baseline until vascular hypotension was observed and cardiac parameters deteriorated. The breath delta value decreased from baseline 6 to 10 hours after onset and preceded changes in body temperature, cardiac and vascular parameters by a minimum of 4 hours. These data show that the breath delta value is a leading indicator of infection in peritoneal sepsis when compared to other physiological parameters. Research supported by a Wisconsin Innovation and Economic Development Research Grant.}, keywords = {}, pubstate = {published}, tppubtype = {conference} } Approximately 750,000 people develop sepsis each year with more than 215,000 deaths. Earlier diagnosis and treatment of sepsis is critical to improving outcome. The exhaled breath delta value (i.e. 13CO2/12CO2 ratio) is a biomarker for the acute phase response (APR) to endotoxin. The objective of this study was to demonstrate that the breath delta value is a leading marker for the onset of infection in a porcine sepsis model. Sepsis was induced by cecal ligation and puncture. Briefly, pigs were anesthetized and positive pressure ventilation was established. The animal was instrumented for invasive blood pressure monitoring, cardiac output measurements, and blood sampling. Heart rate, respiratory rate, arterial blood pressure, central venous pressure, blood oxygen saturation, temperature, blood glucose, end tidal CO2, and breath delta value were monitored once every 15 minutes. Sepsis caused an increase in body temperature between 6 and 15 hours after onset. Other physiological parameters did not change from baseline until vascular hypotension was observed and cardiac parameters deteriorated. The breath delta value decreased from baseline 6 to 10 hours after onset and preceded changes in body temperature, cardiac and vascular parameters by a minimum of 4 hours. These data show that the breath delta value is a leading indicator of infection in peritoneal sepsis when compared to other physiological parameters. Research supported by a Wisconsin Innovation and Economic Development Research Grant. |
2010 |
Butz, Daniel E; Cook, Mark E; Porter, Warren P; Assadi-Porter, Fariba M Early detection of the acute phase response in sepsis by identification of small molecule metabolites in breath and biofluids. Conference The FASEB Journal, 24 (1_MeetingAbstracts: 752.754), 2010. Abstract | Links: @conference{Butz2010b, title = {Early detection of the acute phase response in sepsis by identification of small molecule metabolites in breath and biofluids.}, author = {Daniel E Butz and Mark E Cook and Warren P Porter and Fariba M Assadi-Porter}, url = {http://www.fasebj.org/content/24/1_Supplement/752.4}, year = {2010}, date = {2010-04-01}, booktitle = {The FASEB Journal}, volume = {24}, number = {1_MeetingAbstracts: 752.754}, abstract = {The systemic inflammatory response associated with sepsis and septic shock causes significant morbidity and mortality in the critically ill, and early detection is critical to desirable outcomes. Septic shock is currently diagnosed using criteria such as body temperature and hypotension. This study assessed the acute phase response to an infectious insult using breath 13CO2/12CO2 ratios (delta value) combined with metabolomic biomarker fingerprinting in serum. Breath delta values drop 2–4 hours after endotoxin injection, whereas there is no breath response to dexamethasone or saline injected controls. In rat fecal peritonitis, the breath carbon delta value drops about 6 hours after injection while hypotension does not occur until 14 to 18 hours. Fingerprinting of small molecules in plasma by NMR spectroscopy indicates that concentrations of lactic acid, glucose, 2-hydroxy-butyrate, 3-hydroxy-butyrate, citrate, acetate, and ketogenic amino acids are increased. Similar metabolite profiles are exaggerated in plasma from ICU patients diagnosed with septic shock. These data indicate that metabolic perturbations are evident at a very early stage of the acute phase response, and in the peritonitis model up to 12 hours prior to onset of septic shock. These technologies can provide an early warning for sepsis and may be used as a powerful diagnostic tool. Supported by WARF and the Wisconsin Institute for Discovery.}, keywords = {}, pubstate = {published}, tppubtype = {conference} } The systemic inflammatory response associated with sepsis and septic shock causes significant morbidity and mortality in the critically ill, and early detection is critical to desirable outcomes. Septic shock is currently diagnosed using criteria such as body temperature and hypotension. This study assessed the acute phase response to an infectious insult using breath 13CO2/12CO2 ratios (delta value) combined with metabolomic biomarker fingerprinting in serum. Breath delta values drop 2–4 hours after endotoxin injection, whereas there is no breath response to dexamethasone or saline injected controls. In rat fecal peritonitis, the breath carbon delta value drops about 6 hours after injection while hypotension does not occur until 14 to 18 hours. Fingerprinting of small molecules in plasma by NMR spectroscopy indicates that concentrations of lactic acid, glucose, 2-hydroxy-butyrate, 3-hydroxy-butyrate, citrate, acetate, and ketogenic amino acids are increased. Similar metabolite profiles are exaggerated in plasma from ICU patients diagnosed with septic shock. These data indicate that metabolic perturbations are evident at a very early stage of the acute phase response, and in the peritonitis model up to 12 hours prior to onset of septic shock. These technologies can provide an early warning for sepsis and may be used as a powerful diagnostic tool. Supported by WARF and the Wisconsin Institute for Discovery. |
Butz, Daniel E; Cook, Mark E; Eghbalnia, Hamid R; Assadi-Porter, Fariba M; Porter, Warren P Changes in the natural abundance of 13CO2/12CO2 in breath due to lipopolysacchride-induced acute phase response Journal Article Rapid Communications in Mass Spectrometry, 23 (23), pp. 3729-3735, 2010. Abstract | Links: @article{Butz2010, title = {Changes in the natural abundance of 13CO2/12CO2 in breath due to lipopolysacchride-induced acute phase response}, author = {Daniel E Butz and Mark E Cook and Hamid R Eghbalnia and Fariba M Assadi-Porter and Warren P Porter}, doi = {10.1002/rcm.4310}, year = {2010}, date = {2010-01-01}, journal = {Rapid Communications in Mass Spectrometry}, volume = {23}, number = {23}, pages = {3729-3735}, abstract = {The natural abundance of carbon-13 in blood proteins increases during the cachectic state and may be a biomarker for disease status. We hypothesized a corresponding drop in the relative abundance of 13C in breath CO2. Using the lipopolysacchride (LPS)-induced endotoxemia model of the acute cachectic state, we demonstrated that the acute phase response causes shifts in the stable isotopes of carbon in exhaled CO2 (13CO2/12CO2 delta value) shortly after administration of LPS while glucocorticoid treatment does not. Mice were injected with LPS and stable isotopes of blood amino acids and carbon in exhaled CO2 were monitored. An increase in the relative isotopic mass of serum alanine, proline and threonine was observed at 3 h after LPS injection. Breath delta values began dropping immediately after administration of LPS, and were 4–5 delta values lower than those of the control animals by 2.5 h after injection. A corresponding drop in delta value was not observed with dexamethasone treatment. Thus protein synthesis during the acute phase response probably caused the fractionation of stable isotopes observed in the plasma amino acids and in exhaled breath 13CO2 delta values. The exhaled breath 13CO2 delta value may be a valuable real-time biomarker of cachexia associated with an acute phase response due to endotoxemia. Copyright © 2009 John Wiley & Sons, Ltd.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The natural abundance of carbon-13 in blood proteins increases during the cachectic state and may be a biomarker for disease status. We hypothesized a corresponding drop in the relative abundance of 13C in breath CO2. Using the lipopolysacchride (LPS)-induced endotoxemia model of the acute cachectic state, we demonstrated that the acute phase response causes shifts in the stable isotopes of carbon in exhaled CO2 (13CO2/12CO2 delta value) shortly after administration of LPS while glucocorticoid treatment does not. Mice were injected with LPS and stable isotopes of blood amino acids and carbon in exhaled CO2 were monitored. An increase in the relative isotopic mass of serum alanine, proline and threonine was observed at 3 h after LPS injection. Breath delta values began dropping immediately after administration of LPS, and were 4–5 delta values lower than those of the control animals by 2.5 h after injection. A corresponding drop in delta value was not observed with dexamethasone treatment. Thus protein synthesis during the acute phase response probably caused the fractionation of stable isotopes observed in the plasma amino acids and in exhaled breath 13CO2 delta values. The exhaled breath 13CO2 delta value may be a valuable real-time biomarker of cachexia associated with an acute phase response due to endotoxemia. Copyright © 2009 John Wiley & Sons, Ltd. |
2017 |
Exhaled 13CO2/12CO2 Delta Value as a Metabolic Marker for Metabolism in Performance Training Conference The FASEB Journal, 31 (1 Supplement:1036.18), 2017. | Links: |
2016 |
Host-targeted approaches to managing animal health: old problems and new tools. Journal Article Domestic Animal Endocrinology, 56 (Supp: S11-22), 2016. Abstract | Links: |
Exhaled breath carbon isotopes are a marker for inflammation in neonates with a chorioamnionitis risk factor. Conference 30 (1), 2016. Abstract | Links: |
2015 |
Immediate biofeedback for energy balance via expired breath δ13CO2 Conference Conf Proc IEEE Eng Med Biol Soc, Milan, Italy, 2015. Abstract | Links: |
2014 |
Noninvasive infection detection in mechanically ventilated adults via the breath delta value Conference Poster Abstract Session: Biomarkers of Immune Responses IDWeek The Pennsylvania Convention Center: IDExpo Hall BC, 2014. Abstract | Links: |
Metabolic Evidence of Diminished Lipid Oxidation in Women with Polycystic Ovary Syndrome Journal Article Current Metabolomics, 2 (4), pp. 269-278, 2014. Abstract | Links: |
Breath carbon stable isotope ratios identify changes in energy balance and substrate utilization in humans Journal Article International Journal of Obesity, 38 , pp. 1248-1250, 2014. Abstract | Links: |
Expired breath carbon delta value is a marker for the onset of sepsis in a swine model Journal Article Journal of Analytical Atomic Spectrometry, 29 , pp. 606-613, 2014. Abstract | Links: |
Changes in breath carbon isotope composition as a potential biomarker of inflammatory acute phase response in mechanically ventilated pediatric patients Journal Article Journal of Analytical Atomic Spectrometry, 29 , pp. 599-605, 2014. Abstract | Links: |
The emerging role of carbon isotope ratio determination in health research and medical diagnostics Journal Article Journal of Analytical Atomic Spectrometry, 29 , pp. 594-598, 2014. Abstract | Links: |
2013 |
Continuous exhaled breath carbon isotope analysis for early detection of sepsis Conference 27 (1), 2013. Abstract | Links: |
2010 |
Early detection of the acute phase response in sepsis by identification of small molecule metabolites in breath and biofluids. Conference The FASEB Journal, 24 (1_MeetingAbstracts: 752.754), 2010. Abstract | Links: |
Changes in the natural abundance of 13CO2/12CO2 in breath due to lipopolysacchride-induced acute phase response Journal Article Rapid Communications in Mass Spectrometry, 23 (23), pp. 3729-3735, 2010. Abstract | Links: |
