CO2 Breathing Research Articles

Fitting of single-exhalation profiles using a pulmonary gas exchange model—application to carbon monoxide

Real-time breath gas analysis coupled to gas exchange modeling is emerging as promising strategy to enhance the information gained from breath tests. It is shown for exhaled breath carbon monoxide (eCO), a potential biomarker for oxidative stress and respiratory diseases, that a weighted, nonlinear least-squares fit of simulated to measured expirograms can be used to extract physiological parameters, such as airway and alveolar concentrations and diffusing capacities. Experimental CO exhalation profiles are acquired with high time-resolution and precision using mid-infrared tunable diode laser absorption spectroscopy and online breath sampling. A trumpet model with axial diffusion is employed to generate eCO profiles based on measured exhalation flow rates and volumes. The concept is demonstrated on two healthy non-smokers exhaling at a flow rate of 250 ml s−1 during normal breathing and at 120 ml s−1 after 10 s of breath-holding. The obtained gas exchange parameters of the two subjects are in a similar range, but clearly distinguishable. Over a series of twenty consecutive expirograms, the intra-individual variation in the alveolar parameters is less than 6%. After a 2 h exposure to 10 ± 2 ppm CO, end-tidal and alveolar CO concentrations are significantly increased (by factors of 2.7 and 4.9 for the two subjects) and the airway CO concentration is slightly higher, while the alveolar diffusing capacity is unchanged compared to before exposure. Using model simulations, it is found that a three-fold increase in maximum airway CO flux and a reduction in alveolar diffusing capacity by 60% lead to clearly distinguishable changes in the exhalation profile shape. This suggests that extended breath CO analysis has clinical relevance in assessing airway inflammation and chronic obstructive pulmonary disease. Moreover, the novel methodology contributes to the standardization of real-time breath gas analysis.

Indicator amino acid oxidation protein requirement estimate in endurance-trained men 24 h postexercise exceeds both the EAR and current athlete guidelines

Despite studies indicating increased protein requirements in strength-trained or endurance-trained (ET) individuals, the Institute of Medicine has concluded that "no additional dietary protein is suggested for healthy adults undertaking resistance or endurance exercise," and the controversy regarding exercise effects on protein requirements continues. The objective of this study was to determine the dietary protein requirement of healthy young ET men (≥1 yr training experience) 24 h post exercise (to minimize any acute effects of the previous training session) by measuring the oxidation of ingested l-[1-13C]phenylalanine to 13CO2 in response to graded intakes of protein (indicator amino acid oxidation technique). Eight men [maximal oxygen consumption 64.1 ml·kg-1·min-1 (SD 3.7)] were each studied 24 h postexercise repeatedly with protein intakes ranging from 0.3 to 3.5 g·kg-1·day-1. Protein was fed as an amino acid mixture based on the protein pattern in egg, except for phenylalanine and tyrosine, which were maintained at constant amounts across all protein intakes. For 2 days before the study day, all participants consumed 1.6 g protein·kg-1·day-1. The estimated average requirement (EAR) for protein was determined by applying a nonlinear mixed-effects change-point regression analysis to F13CO2 (label tracer oxidation in 13CO2 breath), which identified a breakpoint in the F13CO2 in response to the graded amounts of protein. The EAR for protein and the upper 95% confidence interval were 2.1 and 2.6 g·kg-1·day-1, respectively. These data suggest that the protein EAR for ET men 24 h postexercise exceeds the Institute of Medicine EAR and established athlete guidelines by ~3.5- and 1.3-fold, respectively.

Tryptophan Requirement in School-Age Children Determined by the Indicator Amino Acid Oxidation Method is Similar to Current Recommendations

The requirement for dietary tryptophan in school-age children has never been empirically derived. The objective of our study was to determine the tryptophan requirement of school-age children using the indicator amino acid oxidation technique. Volunteer healthy school-age children, between 8 and 12 y, were enrolled and the oxidation of l-[13C]-phenylalanine to 13CO2 measured in response to graded intakes of dietary tryptophan. Seven children (3 boys, 4 girls) participated in the study and received randomly assigned tryptophan intakes ranging from 0.5 to 9.75 mg.kg-1.d-1 for a total of 36 studies. The diets provided energy at 1.5 times each subject's resting energy expenditure and were isocaloric. Protein was provided as an amino acid mixture on the basis of the egg protein pattern, and phenylalanine and tyrosine were maintained constant across the protein intake concentrations at 25 and 40 mg.kg-1.d-1. All subjects were adapted for 2 d before the study day to a protein intake of 1.5 g.kg-1.d-1. The mean tryptophan requirement was determined by applying a mixed-effect change-point regression analysis to F13CO2 (label tracer oxidation in 13CO2 breath) which identified a breakpoint in the F13CO2 in response to graded amounts of tryptophan. The mean [estimated average requirement (EAR)] and upper 95% CI, (approximating the RDA) of tryptophan requirements were estimated to be 4.7 and 6.1 mg.kg-1.d-1, respectively. Our results are similar to the current recommended EAR and RDA of 5 and 6 mg.kg-1.d-1 for healthy growing children based on the factorial calculation. Clinical Trials Registration No. NCT02018588.

Field-deployable measurements of free-living individuals to determine energy balance: fuel substrate usage through δ13C in breath CO2 and diet through hair δ13C and δ15N values

ABSTRACTCarbon isotopes of breath CO2 vary depending on diet and fuel substrate used. This study examined if exercise-induced δ13C-CO2 changes in substrate utilization were distinguishable from baseline δ13C-CO2 variations in a population with uncontrolled diet, and compared hair isotope values and food logs to develop an isotope model of diet. Study participants included nine women with diverse Body Mass Index (BMI), age, ancestry, exercise history, and diet. Breath samples were collected prior to and up to 12 h after a 5- or 10 K walk/run. Indirect calorimetry was measured with a smartphone-enabled mobile colorimetric device, and a field-deployable isotope analyzer measured breath δ13C-CO2 values. Diet was assessed by food logs and δ13C, δ15N of hair samples. Post-exercise δ13C-CO2 values increased by 0.54 ± 1.09‰ (1 sd, n = 9), implying enhanced carbohydrate burning, while early morning δ13C-CO2 values were lower than daily averages (p = 0.0043), indicating lipid burning during overnight fasting. Although diurnal δ13C-CO2 variation (1.90 ± 0.77‰) and participant baseline range (3.06‰) exceeded exercise-induced variation, temporal patterns distinguished exercise from dietary isotope effects. Hair δ13C and δ15N values were consistent with a new dietary isotope model. Notwithstanding the small number of participants, this study introduces a novel combination of techniques to directly monitor energy balance in free-living individuals.

Red Blood Cell Lifespan Shortening in Patients with Early-Stage Chronic Kidney Disease

Background: Although reduced red blood cell (RBC) lifespan has been reported to be a contributory factor to anemia in patients with end-stage chronic kidney disease (CKD), there are limited data regarding RBC lifespan in early-stage CKD. Serum erythropoietin (EPO) is considered a primary causative factor of renal anemia. The aims of this study were to compare the RBC lifespan, serum EPO levels, and other renal anemia indicators across CKD-stage groups of patients and to analyze the impacts of etiological factors on renal anemia. Methods: A cohort of 74 non-smoking patients with CKD were enrolled, including 15 in stage 1, 18 in stage 2, 15 in stage 3, 15 in stage 4, and 11 in stage 5. RBC lifespan was determined by CO breath tests. Potential correlations of hemoglobin (Hb) concentration with RBC lifespan, reticulocyte count (Ret), and levels of EPO, ferritin, folic acid, and vitamin B12 were analyzed. Results: CKD progression was associated with decreases in (Hb) and RBC lifespan. RBC lifespan durations in CKD stages 1–5 were 122 ± 50, 112 ± 26, 90 ± 32, 88 ± 28, and 60 ± 24 days, respectively. RBC lifespan means for the stage 3, 4 and 5 groups were significantly shorter than those for the stage 1 and 2 groups. Serum EPO did not differ significantly between the CKD stage groups. (Hb) correlated directly with RBC lifespan (r = 0.372, p = 0.002) and Ret (r = 0.308, p = 0.011), but did not correlate with serum EPO, ferritin, folic acid, or vitamin B12 levels. Conclusions: Reduced RBC lifespan in early-stage CKD, demonstrated in this study, suggests that increased RBC destruction may play a more important etiological role in renal anemia than other indicators in patients with CKD.

Effect of Hemodialysis on the Red Blood Cell Life Span in Patients with End-Stage Kidney Disease.

The aim of this study was to use a CO breath test to investigate hemodialysis effects on red blood cell lifespan in patients with chronic kidney disease. A cohort of 17 non-smoking men with end-stage kidney disease undergoing hemodialysis via a polysulfone dialysis membrane (as opposed to a traditional cellulose acetate membrane) were subjected to a repeated Levitt's CO breath test to compare red blood cell lifespan before vs. after dialysis. None of the patients showed significant fluctuations in endogenous CO concentration during the dialysis procedure. The mean red blood cell lifespan was 66.0 ± 31.0 days before dialysis and 72.0 ± 26.0 days after dialysis, with no significant difference between the assessment time points (P > 0.05). In conclusion, dialysis using a polysulfone membrane did not appear to disrupt red blood cells or reduce their lifespan in patients with end-stage kidney disease.

A reflection-mode fibre-optic sensor for breath carbon dioxide measurement in healthcare

A reflection-mode carbon dioxide (CO2) fibre optic sensor (FOS) is developed based on the colorimetric change of pH indicator dye thymol blue. The CO2 sensing film comprises thymol blue and tetramethylammonium hydroxide in the form of an ion pair doped in an organically modified silica film. A dip coating process was conducted to coat the sensing film on the tip of optical fibre with a film thickness approximately 2.7 ± 0.1 μm. The observed reflection signal at a wavelength of 608 nm exhibits a reversible change for the concentration of CO2 range from 0 to 6% with a response time of 19 s and recovery time of 170 s for 6% of CO2. An optimal concentration of thymol blue in the preparation of coating solution that provides a highest sensitivity was found to be 2.9 mg/ml. Storing the FOS in a pure nitrogen atmosphere provided a stable film with a shelf-life of over 15 days as compared to a gradual degradation in film performance and complete loss of sensitivity after 10 days with storage in ambient air. The FOS response is affected by relative humidity (RH) and a humidity filter was demonstrated to reduce humidity levels in breath from 90% to 40–50% to reduce this effect. The developed FOS was used to measure the end-tidal breath CO2 for testing its applicability in healthcare. The CO2 measurement from breath sample using our FOS shows a good agreement (percentage error~3%) with a commercial CO2 datalogger (K-33 BLG, CO2 Meter, USA). Due to the limitation of response time, at present the FOS is limited to measuring variation of the CO2 from slow breath to breath.

Title: Differentiating the effects of whey protein and guar gum preloads on postprandial glycemia in type 2 diabetes

Background and aimsWhey protein and guar gum have both been reported to reduce postprandial glycemia in health and type 2 diabetes, associated with stimulation of glucagon-like peptide-1 (GLP-1) and/or slowing of gastric emptying. Our aim was to evaluate, in type 2 diabetes, the acute effects of low dose “preloads” of whey and guar, given alone or in combination before a meal, on postprandial glycemia, insulin, GLP-1, and gastric emptying. Methods21 patients with type 2 diabetes, managed by diet or metformin alone, were each studied on 4 days. They received a preload “shake” 15min before a mashed potato meal (368.5 kcal) labeled with 13C-octanoic-acid. The preloads comprised either (i) 17 g whey (W), (ii) 5 g guar (G), (iii) 17 g whey + 5 g guar (WG) each sweetened with 60 mg sucralose, and (iv) 60 mg sucralose alone (control; C), all dissolved in 150 mL water. Venous blood was sampled frequently for measurements of glucose, insulin, and GLP-1 concentrations. Gastric half-emptying time (T50) was calculated from breath 13CO2 excretion over 240 min. ResultsPostprandial blood glucose concentrations were lower with W and WG compared to C (each P < 0.0001, treatment × time interaction), and lower after G than C only at 30min. Insulin, GLP-1, and glucagon concentrations were higher after W than WG, G, or C (P < 0.05, treatment × time interaction), without differences between the latter three. Gastric emptying was slower with W (T50: 179.6 ± 6.1 min, P < 0.05) and WG (T50: 197.6 ± 9.7 min, P < 0.0001) when compared to C (T50: 162.9 ± 6.2 min), but did not differ between G (T50: 171.3 ± 7.0) and C (P > 0.99). ConclusionBoth whey and whey/guar preloads reduced postprandial glycemia, associated with slowing of gastric emptying. Low dose guar was less effective as a preload for glucose-lowering and did not slow gastric emptying. Clinical Trial Registry number and websiteAustralian and New Zealand Clinical Trials Registry, Trial ID ACTRN12615001272583, http://www.anzctr.org.au

Attitudes about smoking cessation treatment, intention to quit, and cessation treatment utilization among young adult smokers with severe mental illnesses

SignificanceYoung adults with schizophrenia, bipolar disorder and other severe mental illnesses (SMI) have high rates of smoking, but little research has evaluated predictors of cessation activity and treatment utilization in this group. MethodsWe assessed attitudes, beliefs, social norms, perceived behavioral control, intention, quit attempts, treatment utilization, and cessation among 58 smokers with SMI, age 18–30, enrolled in a randomized pilot study comparing a brief interactive/motivational vs. a static/educational computerized intervention. Subjects were assessed at baseline, post intervention, and 3-month follow-up. ResultsOver follow-up, one-third of participants self-reported quit attempts. Baseline measures indicating lower breath CO, greater intention to quit, higher perceptions of stigma, higher perceptions of psychological benefits of smoking, and greater symptom distress were associated with quit attempts, whereas gender, diagnosis, social support, attitudes about smoking, and use of cessation treatment were not. In the multivariate analysis, lower breath CO, higher intention to quit and symptom distress were significantly related to quit attempts.Only 5% of participants utilized verified cessation treatment during follow-up. Consistent with the Theory of Planned Behavior, attitudes, social norms and perceived behavioral control regarding cessation treatments correlated significantly with intention to use treatment. Norms and beliefs about treatment were somewhat positive and some improved after intervention, with a pattern significantly favoring the interactive intervention, but intentions to use treatments remained low, consistent with low treatment utilization. ConclusionsPerceptions of traditional cessation treatments improved somewhat after brief interventions, but most young adult smokers with SMI did not use cessation treatment. Instead, interventions led to quit attempts without treatment.

The prebiotic inulin improves substrate metabolism and promotes short-chain fatty acid production in overweight to obese men

Background and AimsHuman gut microbiota play an important role in maintaining human health. Dietary fibers, i.e. prebiotics, are fermented by human gut microbiota into the short-chain fatty acids (SCFAs) acetate, propionate, and butyrate. SCFAs promote fat oxidation and improve metabolic health. Therefore, the prebiotic inulin might be an effective dietary strategy to improve human metabolism. We aimed to investigate the acute metabolic effects of ingesting inulin compared with digestible carbohydrates and to trace inulin-derived SCFAs using stable isotope tracer methodology. MethodsIn a double-blind, randomized, placebo-controlled crossover design, 14 healthy, overweight to obese men consumed a high-fat milkshake containing A) 24 g inulin of which 0.5 g was U-13C-inulin (INU) or B) 24 g maltodextrin placebo (PLA), with a wash-out period of at least five days. Fat oxidation was measured via an open-circuit ventilated hood and blood samples were collected up to 7 h after ingestion. Plasma, breath, and fecal samples were collected, and appetite and satiety scores were assessed. ResultsFat oxidation increased in the early postprandial phase (0−3 h), and both plasma glucose and insulin were lower after INU ingestion compared with PLA (all P < 0.05). Plasma free fatty acids were higher in the early, and lower in the late postprandial period after INU ingestion. Inulin was fermented into SCFAs as indicated by higher plasma acetate concentrations after INU compared with PLA (P < 0.05). In addition, we found continuous increases in plasma 13C-SCFA enrichments (P < 0.05 from t = 120 onwards) and breath 13CO2 enrichments after INU intake. There were no effects on plasma triglycerides, free glycerol, satiety hormones GLP-1 and PYY, and appetite and satiety scores. ConclusionsIngestion of the prebiotic inulin improves fat oxidation and promotes SCFA production in overweight to obese men. Overall, replacing digestible carbohydrates with the fermentable inulin may favor human substrate metabolism. Clinical Trial RegistryThe trial was registered at clinicaltrials.gov under number NCT02009670.

Using empirical mode decomposition to increase the sensitivity of diode laser-based detection of 13CO2 in human exhaled breath

This paper reports on using the empirical mode decomposition of an experimental signal to improve the accuracy of 13CO2 detection in expired air through an absorption spectroscopy method that employs a frequency-tunable diode laser operating near a wavelength of 2 µm. The conducted research shows that using this method can increase the sensitivity of 13СO2 detection in human exhaled breath by two orders of magnitude.

Using the indicator amino acid oxidation technique to study threonine requirements in horses receiving a predominantly forage diet

Threonine has been reported to be the second limiting amino acid in typical equine diets, but its actual requirement has not been determined in horses. To evaluate amino acid metabolism and requirements, the indicator amino acid oxidation (IAAO) method has been successfully used in other species. The objective of this research was to estimate threonine requirements in mature horses fed timothy hay and concentrate in 4:1 ratio using the IAAO method. Six Thoroughbred mares (579.9±46.7kg) received each of 6 levels of threonine intake, 41, 51, 61, 70, 80 and 89mg/kg BW/day, in a randomly determined order. Each study period was 7-day long, and on day 6, blood samples were collected before and 90min after feeding to measure amino acid concentrations using HPLC. On day 7, horses underwent IAAO procedures, which included a 2-hr primed, constant intravenous infusion of [13 C]sodium bicarbonate to measure total CO2 production and a 4-hr primed, constant oral administration of [1-13 C]phenylalanine to estimate phenylalanine oxidation to CO2 . Blood and breath samples were collected to measure blood [13 C]phenylalanine, using GC-MS analysis and breath 13 CO2 enrichment, using an infrared isotope analyser. Increasing threonine intake levels did not affect plasma phenylalanine oxidation by the ANOVA test (p>0.05) but resulted in a linear decrease in phenylalanine oxidation (p=0.04) without a breakpoint by the orthogonal linear contrast. This study is the first attempt to evaluate threonine requirements in horses by the IAAO method; however, threonine requirements are still unknown in mature horses at this time.

13C-Labeled-Starch Breath Test in Congenital Sucrase-isomaltase Deficiency.

Human starch digestion is a multienzyme process involving 6 different enzymes: salivary and pancreatic α-amylase; sucrase and isomaltase (from sucrose-isomaltase [SI]), and maltase and glucoamylase (from maltase-glucoamylase [MGAM]). Together these enzymes cleave starch to smaller molecules ultimately resulting in the absorbable monosaccharide glucose. Approximately 80% of all mucosal maltase activity is accounted for by SI and the reminder by MGAM. Clinical studies suggest that starch may be poorly digested in those with congenital sucrase-isomaltase deficiency (CSID). Poor starch digestion occurs in individuals with CSID and can be documented using a noninvasive C-breath test (BT). C-Labled starch was used as a test BT substrate in children with CSID. Sucrase deficiency was previously documented in study subjects by both duodenal biopsy enzyme assays and C-sucrose BT. Breath CO2 was quantitated at intervals before and after serial C-substrate loads (glucose followed 75 minutes later by starch). Variations in metabolism were normalized against C-glucose BT (coefficient of glucose absorption). Control subjects consisted of healthy family members and a group of children with functional abdominal pain with biopsy-proven sucrase sufficiency. Children with CSID had a significant reduction of C-starch digestion mirroring that of their duodenal sucrase and maltase activity and C-sucrase BT. In children with CSID, starch digestion may be impaired. In children with CSID, starch digestion correlates well with measures of sucrase activity.

Isotope-specific breath analysis to track the end-stage renal disease during hemodialysis

The underlying mechanisms towards the progression of end-stage renal disease (ESRD) in chronic kidney disease (CKD) are poorly understood and it still remains a major clinical stumbling block for early detection of CKD. Most patients with CKD pass through ESRD with the necessity of frequent hemodialysis (HD) treatment. At present, plasma urea and creatinine levels are examined in most CKD patients to monitor their health status after dialysis. But it is impossible to get immediate feedback on the patients’ health as the conventional tests involve the collection of blood samples, laboratory processing for a prolonged period of time and, finally, analysis of those samples. However, the test results are very important in deciding the treatment plan for those ESRD patients. Here, we show that the enzymatic activity of carbonic anhydrase in erythrocytes is distinctly altered in ESRD subjects under HD. This, in turn, leads to the isotopic enrichments of oxygen-18 (18O) and carbon-13 (13C) of CO2 during respiration in HD treatment. High-resolution cavity-enhanced absorption spectroscopic measurements show that 18O and 13C-isotopic fractionations of breath CO2 are correlated with Kt/V values, suggesting a novel unifying strategy for ESRD patients that can be used as an isotope-specific methodology for non-invasive assessment of dialysis adequacy and hence 12C18O16O and 13C16O16O could be used as novel markers for tracking the physiological parameters of ESRD individuals. Our findings suggest that the monitoring of 18O and 13C isotopes of breath CO2 may facilitate the proper management of advanced CKD patients. The primary advantage of this isotopic breath test is that it may reduce the valuable time lag between the completion of dialysis and obtaining the clinical report on the status of patients’ health.

Thermoelectric Array Sensors with Selective Combustion Catalysts for Breath Gas Monitoring.

Inflammable breath gases such as H2 and CH4 are used as bio markers for monitoring the condition of the colon. However, their typical concentrations of below 100 ppm pose sensitivity and selectivity challenges to current gas sensing systems without the use of chromatography. We fabricated a compact, gas-selective thermoelectric array sensor (TAS) that uses micro-machined sensor devices with three different combustion catalysts to detect gases such as H2, CO, and CH4 in breath. Using Pt/Pt-W thin-film micro-heater meanders, Pd/Al2O3, Pt,Pd,Au/Co3O4, and Pt/Al2O3 catalysts were heated to 320, 200, and 125 °C, respectively, and the gas sensing performances of the TAS for each gas and for a model breath gas mixture of 100 ppm H2, 25 ppm CO, 50 ppm CH4, and 199 ppm CO2 in air were investigated. Owing to its high catalyst temperature, the Pd/Al2O3 catalyst burned all three gases, while the Pt,Pd,Au/Co3O4 burned CO and H2 and the Pt/Al2O3 burned H2 selectively. To calibrate the gas concentration of the mixture gas without the use of a gas separation tool, linear discriminant analysis was applied to measure the sensing performance of TAS. To enhance the gas selectivity against H2, a double catalyst structure was integrated into the TAS sensor.

Non-invasive diagnosis of type 2 diabetes in Helicobacter pylori infected patients using isotope-specific infrared absorption measurements

ABSTRACTHelicobacter pylori causes several gastrointestinal diseases and may also contribute to the development of type 2 diabetes (T2D). Several studies suggest that there might be a potential link between H. pylori infection and T2D, but it still remains the subject of debate. Here, we first report the cumulative effect of H. pylori infection and T2D by exploiting the excretion kinetics of 13C/12C and 18O/16O isotope ratios of exhaled breath CO2 in response to an oral dose of 13C-enriched glucose in individuals with T2D and non-diabetic controls (NDC) harbouring the H. pylori infection. Using a high-resolution integrated cavity output spectroscopy (ICOS) technique in the infrared region, we observed that the isotopic fractionations of 13C and 18O in breath CO2 are distinctly altered in H. pylori infected T2D patients as well as in H. pylori infected NDC. Several optimal diagnostic cut-off points of 13C and 18O isotopes of breath CO2 were also determined which exhibited the diagnostic sensitivity and specificity of ∼97 % and thus suggesting that breath 13C and 18O isotopes might be considered as potential biomarkers for the non-invasive assessment of the gastric pathogen prior to the onset of T2D. This may open a new diagnostic strategy for treating these common diseases in an alternative way.

Leptin Stabilizes Breathing but does not affect CO2 Chemosensitivity in Newborn Rat Pups

Premature infants have periodic breathing (PB) and chronic intermittent hypoxia (CIH) that increases during the 2nd week of life. Leptin (LEP) is a hormone produced by adipocytes and increases central CO2 chemoreceptors sensitivity. LEP is also produced by the placenta, and in newborn infants LEP levels are highest at birth and then rapidly fall. We hypothesis that the fall in LEP after birth is associated with the increase frequency of PB and apnea leading to CIH during the 2nd week of life in premature infants.ObjectiveTo determine the effect of exogenous LEP on breathing stability and CO2 sensitivity during the first week of postnatal life, using whole body flow‐through plethysmograph in freely behaving newborn rats.MethodsSprague Dawley (SD) rat pups remained with the nursing dam until the time of the experiment. On postnatal day (PD) 7, rat pups were injected intraperitoneally with either vehicle (saline/n=5), LEP6 (6 μg/gr/n=4) and LEP9 (9 μg/gr/n=5). After injection the pup was returned to nursing dam and litter mates for 30 mins followed by 30 mins in the plethysmograph prior to recording. Respiratory tracings were captured using PowerLab 8 data acquisition system (ADInstruments) and analyzed using LabChart. Ventilatory parameters; frequency, VT and Ve were compared during 21% O2, 40% O2/0% CO2, 40%O2/5%CO2 and return to 40%O2/0%CO2, and the coefficient of variation (CV) for Ve was calculated for each condition in the 3 treatment groups (SAL, LEP6, LEP9).ResultsSimilar to Stunden et al. in rat pups at PD 7–8 (Stunden et al,, Respir Physiol, 2001), frequency, VT and Ve did not significantly changed in response to hypercapnia (P=0.511), and LEP6 or LEP9 did not alter this response. However, LEP exposure did stabilize breathing with a reduction in the CV during 21%O2, 40%O2/0%CO2 and 40%O2/5%CO2 (Figure 1).ConclusionOur preliminary findings are consistent with that of Stunden et al, who reported no change in Ve in response to hypercapnia at PD 6–8 in SD rats. At this age, the hypothalamus is insensitive to the effect of leptin on feeding and metabolism (MacKay H et al., Mol Metab. 2014). Here we show that leptin does not induce nor augment CO2 chemosensitivity in newborn rats at PD7, but does at PD 18 (Gauda et al, unpublished data), and adults (Isono S et al., Anesthesiology, 2009). However our data does show that leptin stabilizes breathing during the first week of life in newborn rat pups. We speculate that unstable breathing that occurs in premature infants may be associated with the precipitous fall in leptin levels after birth.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Does Behavioral Inhibition Affect the Breathing Response to Elevated CO2? Implications for a Respiratory Stress Response.

Behavioral inhibition (BI) is a temperament characteristic in which an individual tends to avoid unfamiliar situations or environments. Individuals with high BI are more vulnerable to developing an anxiety disorder, such as Post‐Traumatic Stress Disorder (PTSD), when placed under stressful conditions (Gladstone and Parker, 2005). Behaviorally inhibited organisms learn faster and are slower to extinguish the response to a stimulus (Sheynin et al., 2013; Servatius et al.,, 2008). Our lab over the past several years has been investigating the relationship between a respiratory stress response to CO2 and BI. In this study, participants played a computer game used previously by Sheynin et al., 2013, to evaluate avoidance acquisition and extinction. BI and non‐BI individuals were separated based on Adult Measure of Behavioral Inhibition (AMBI) and Retrospective Measure of Behavioral Inhibition (RMBI). Gas volumes of 4.5% and 7.0% CO2 were applied as different doses of a respiratory stimulant to further the understanding of any physiological differences in breathing between those with BI compared to those without. We hypothesize that individuals with high BI exhibit differences in all parameters of breathing compared to non‐BI individuals during both levels of CO2, and therefore predict that individuals with high BI respond more robustly to CO2. The 4.5% and 7.0% CO2 were obtained by mixing room air with pure CO2 in a Tissot Spirometer and validated using an Oxygraph O2 and CO2 analyzer. The mixed gas was then delivered from a 100 liter gas bag attached to a breathing tube attached to a Hans Rudolph two‐way non‐rebreathing valve. The subjects placed a two‐way valve attached to a mouthpiece into their mouths and then had a nose clip placed over their noses to create a tight seal between the breathing gas bags and themselves. Respiratory data were collected using a BioPac computer data collection system. Our sample sizes are for 4.5% CO2 – Air BI (n=8) and for non‐BI (n=7), and for 7.0% CO2 – Air BI (n=5) and for non‐BI (n=7). When the data were analyzed there were no apparent differences for VT, VI, Fbr between BI and non‐BI individuals exposed to 7.0% CO2, however, in the 4.5% CO2 breathing parameters there was a marked increased both in absolute value and in percent change for Fbr for BI individuals when compared to non‐BI individuals. Given the small sample sizes of the groups, we conclude that increasing the sample sizes is necessary before any more substantive conclusions can be drawn. In addition, our future studies will include measurements of heart rate, blood pressure, salivary cortisol and salivary amylase.Support or Funding InformationNASA Training Grant #NNX15Aj12H, Wisconsin Space Grant Consortium Infrastructure Grant, RIP‐17 #30116‐03This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Pilot Randomized Trial of an Automated Smoking Cessation Intervention via Mobile Phone Text Messages as an Adjunct to Varenicline in Primary Care

Objective: Varenicline is a safe and effective aid to smoking cessation but most trials have involved frequent visits or intensive behavioral support unlike that typically provided in primary care. The current study examined if motivational text messages, sent via cellphone, would increase quit rates in smokers being treated with varenicline and 3 brief sessions in a family practice setting. Methods: This study was a randomized controlled, parallel-group smoking cessation trial. Intervention group participants (n = 74) received daily motivational text messages, additional texted tips in response to keywords, and weekly study questions while control group participants (n = 76) received only weekly study questions. Both groups received individualized counseling. Self-reported non-smoking and exhaled breath CO <10ppm were used to validate smoking abstinence at 3 weeks and 12 weeks. Results: Overall, 30.7% (46/150) of participants were abstinent at the 12 week follow-up and the abstinence rate did not differ between groups (INT 31.1% v. CON 30.3%, p = .91). The only predictor of abstinence at 12 weeks was use of varenicline during a previous quit attempt (p = .01). Intervention group participants were more likely to rate the text messaging program as good or excellent (p < .01), to recommend a similar program to family or friends (p < .01), and to complete positive smoking cessation activities (p = .04), when compared with the control group. Conclusion: Although there were no differences in quit rates between the intervention and control group, intervention group participants rated the text messaging system more favorably, were more likely to recommend the program to others, and were more likely to complete positive smoking cessation activities.

A broadband Tm/Ho-doped fiber laser tunable from 1.8 to 2.09 µm for intracavity absorption spectroscopy

A broadband tunable Tm/Ho-doped fiber laser is developed for sensitive in situ measurements of intracavity absorption spectra in the spectral range of 4780–5560 cm−1. This spectral range includes an atmospheric transmission window enabling sensitive measurements of various species. The spectral bandwidth of laser emission varies from 20 to 60 cm−1 and is well suitable for multicomponent spectroscopy. The sensitivity achieved in cw operation corresponds to an effective absorption path length of Leff = 20 km, with a spectral noise of less than 1%. The spectroscopic system is applied for measurements of absorption spectra of H2O, NH3 and for simultaneous in situ detection of three isotopes of CO2 in human breath, which is important for medical diagnostics procedures.