Isoproterenol modulates expiratory activities in the brainstem spinal cord preparation in neonatal mice in vitro.

Motor behaviors such as breathing required temporal coordination of different muscle groups to insured efficient ventilation and provide oxygen to the body. This action is the result of interactions between neural networks located within the brainstem. Inspiration and expiration depend at least in part on interactions between two separate oscillators: inspiration is driven by a neural network located in the preBötzinger complex (PreBötC) and active expiration is driven by a network in the parafacial respiratory group (pFRG). Neurons of the pFRG are silent at rest and become active when the respiratory drive increased. This study investigated the temporal coordination between the brainstem respiratory network and the lumbar spinal network that generates spontaneous activities that is different of the induced fictive locomotion. The remaining question is how these activities coordinate early during the development. Results of this study show that brainstem networks contribute to the temporal coordination of the lumbar spontaneous activity during inspiration since lumbar motor activity occurs exclusively during the expiratory time. This study also investigated the role of the ß-noradrenergic modulation on the respiratory activities. ß-noradrenergic receptors activation increased the frequency of the double bursts and increased expiratory activity at the lumbar level. These results suggest interactions between brainstem and spinal networks and reveal a descending drive that may contribute to the coordination of the respiratory and lumbar spontaneous activities.

Instrumental Assessment of Aero-Resistive Expiratory Muscle Strength Rehabilitation Devices.

PURPOSE: Expiratory muscle strength training (EMST) is increasingly being used to treat voice, cough, and swallowing deficits in a wide range of conditions. However, a multitude of aero-resistive EMST models are commercially available, and the absence of side-by-side comparative data interferes with clinicians' ability to assess which model is best suited to a particular client's needs. The primary aim of this research was to test and compare the pressure and flow parameters of six currently available EMST models to help inform clinical decision making. METHOD: We identified and tested five devices of each of six different EMST models to generate benchmark data for minimum trigger pressures across settings. The reliability was tested within each device and between five devices of the same model across settings using coefficient of variation. RESULTS: All six models required higher pressures to initiate flow at the highest setting compared to the lowest setting, as expected. Detailed descriptive statistics for each model/setting combination include average flow-triggering pressure for each model/setting and the variability across trials within a device and across devices of the same model. From these, ranked order of the least to most stable EMST model was derived. CONCLUSIONS: Systematic testing of several commercially available expiratory resistance training devices yielded clinical benchmarks and reliability data to aid clinicians in selecting an appropriate therapy device and regimen for a client based on their available airflow and air pressure as well as reliability of the device. These findings allow clinicians to directly compare key parameters across EMST devices.

Self-powered triboelectric nanogenerator sensor for detecting humidity level and monitoring ethanol variation in a simulated exhalation environment.

Respiration stands as a vital process reflecting physiological and pathological human health status. Exhaled breath analysis offers a facile, non-invasive, swift, and cost-effective approach for diagnosing and monitoring diseases by detecting concentration changes of specific biomarkers. In this study, we employed Polyethylene oxide/copper (I) oxide composite nanofibers (PCNFs), synthesized via the electrospinning method as the sensing material to measure ethanol levels (1-200 ppm) in an exhaled breath simulator environment. The integrated contact-separation triboelectric nanogenerator was utilized to power the self-powered PCNFs exhaled breath sensor. The PCNFs-based gas sensor demonstrates promising results with values of 0.9 and 3.2 for detecting 5 ppm and 200 ppm ethanol, respectively, in the presence of interfering gas at 90% relative humidity (RH). Notably, the sensor displayed remarkable ethanol selectivity, with ratios of 10:1 to methanol and 25:1 to acetone. Response and recovery times for 200 ppm ethanol at 90 RH% were rapid, at 2.7 s and 5.8 s, respectively. The PCNFs-based exhaled breath sensor demonstrated consistent and stable performance in practical conditions, showcasing its potential for integration into wearable devices. This self-powered breath sensor enabling continuous monitoring of lung cancer symptoms and facilitating compliance checks with legal alcohol consumption limits.

Body positioning-related laryngeal narrowing pattern and expiratory mechanical constraints in advanced chronic obstructive pulmonary disease: A case report.

We previously reported that laryngeal widening led to improved exercise tolerance in COPD. However, it is not clear whether laryngeal narrowing occurs as a compensatory response to tracheal movement or is affected by posture. Here, we report the case of an advanced COPD patient whose more prolonged expiration in a head-forward leaning position compared with that in a neck-extended position occurred with an excessive duration of severe laryngeal narrowing without tracheal obstruction, which led to exercise intolerance with expiratory mechanical constraints. This case provided useful insights into the regulation of the upper airway with body positioning for improving exercise tolerance.

Effects of the intermittent intrapulmonary deflation technique on expiratory flow limitation: an in vitro study.

INTRODUCTION: The intermittent intrapulmonary deflation (IID) technique is a recent airway clearance technique that intends to delay the onset of expiratory flow limitation (EFL) during exhalation. We showed in a previous study that IID increased the expiratory volume of COPD patients compared to quiet breathing and positive expiratory pressure (PEP) therapy. We hypothesized that it was due to the attenuation of the EFL. OBJECTIVES: To verify the physiologic effects of IID and PEP techniques on EFL with a mechanical lung model. METHODS: A mechanical lung model was created to assess the effects of IID and PEP techniques. The thorax was simulated by a plexiglas box in which an adult test lung was connected. A calibration syringe simulated the inspiratory phase. Later, with activation of the IID, the expiratory phase was driven by the deflation generated by the device. With PEP, the expiration occurred maintaining an expiratory pressure between 5 and 10 cmH2O. A pneumotachograph and a pressure transducer were placed in series for flow, volumes and pressure measurements. RESULTS: The model reproduced physiological characteristics of EFL. However, the deflation of the model was slowed by IID and PEP, and flow remained almost constant, so flow limitation was reduced. CONCLUSION: The IID and PEP attenuate EFL and increase exhaled volume in the in vitro model.

Effects of three physical exercise modalities on respiratory function of older adults with Parkinson's disease: A randomized clinical trial.

INTRODUCTION: Deficits in respiratory function of patients with Parkinson's disease contribute to aspiration pneumonia, one of the main causes of mortality in this population. The aim of this study was to evaluate the effects of functional training, bicycle exercise, and exergaming on respiratory function of elderly with Parkinson's disease. METHODS: A randomized clinical trial with single blinding was conducted in a public reference outpatient clinic for the elderly. The participants were randomly assigned to three groups. Group 1 was submitted to functional training (n = 18); group 2 performed bicycle exercise (n = 20), and group 3 trained with Kinect Adventures exergames (n = 20). The sessions performed lasted 8 weeks with a frequency of three 50-min sessions per week. The primary outcome was the forced expiratory volume in the first second; and the secondary outcomes were forced vital capacity, peak expiratory flow, and maximum inspiratory and expiratory pressures. RESULTS: The interventions performed did not improve the forced expiratory volume in the first second, forced vital capacity, and peak expiratory flow. However, group 2 improved (p = 0.03) maximum expiratory pressure (from 65.5cmH2O to 73.1cmH2O) (effect size 0.47), and group 3 increased (p = 0.03) maximum inspiratory pressure (from -61.3cmH2O to -71.6cmH2O) (effect size 0.53). CONCLUSIONS: No effect was found on lung volume, forced respiratory flow and capacity of the participants with Parkinson's disease submitted to three different modalities of motor training. However, bicycle exercise and exergaming have improved expiratory and inspiratory muscle strength, respectively. NCT02622737.

Exhaled breath particles as a novel tool to study lipid composition of epithelial lining fluid from the distal lung.

BACKGROUND: Surfactant phospholipid (PL) composition plays an important role in lung diseases. We compared the PL composition of non-invasively collected exhaled breath particles (PEx) with bronchoalveolar lavage (BAL) and induced sputum (ISP) at baseline and following endotoxin (LPS) challenges. METHODS: PEx and BAL were collected from ten healthy nonsmoking participants before and after segmental LPS challenge. Four weeks later, PEx and ISP were sampled in the week before and after a whole lung LPS inhalation challenge. PL composition was analysed using mass spectrometry. RESULTS: The overall PL composition of BAL, ISP and PEx was similar, with PC(32:0) and PC(34:1) representing the largest fractions in all three sample types (baseline PC(32:0) geometric mean mol%: 52.1, 56.9, and 51.7, PC(34:1) mol%: 11.7, 11.9 and 11.4, respectively). Despite this similarity, PEx PL composition was more closely related to BAL than to ISP. For most lipids comparable inter-individual differences in BAL, ISP, and PEx were found. PL composition of PEx was repeatable. The most pronounced increase following segmental LPS challenge was detected for SM(d34:1) in BAL (0.24 to 0.52 mol%) and following inhalation LPS challenge in ISP (0.45 to 0.68 mol%). An increase of SM(d34:1) following segmental LPS challenge was also detectable in PEx (0.099 to 0.103 mol%). The inhalation challenge did not change PL composition of PEx. CONCLUSION: Our data supports the peripheral origin of PEx. The lack of PL changes in PEx after inhalation challenge might to be due to the overall weaker response of inhaled LPS which primarily affects the larger airways. Compared with BAL, which always contains lining fluid from both peripheral lung and central airways, PEx analysis might add value as a selective and non-invasive method to investigate peripheral airway PL composition. TRIAL REGISTRATION: NCT03044327, first posted 07/02/2017.

Artificial neural network identification of exercise expiratory flow-limitation in adults.

Identification of ventilatory constraint is a key objective of clinical exercise testing. Expiratory flow-limitation (EFL) is a well-known type of ventilatory constraint. However, EFL is difficult to measure, and commercial metabolic carts do not readily identify or quantify EFL. Deep machine learning might provide a new approach for identifying EFL. The objective of this study was to determine if a convolutional neural network (CNN) could accurately identify EFL during exercise in adults in whom baseline airway function varied from normal to mildly obstructed. 2931 spontaneous exercise flow-volume loops (eFVL) were placed within the baseline maximal expiratory flow-volume curves (MEFV) from 22 adults (15 M, 7 F; age, 32 yrs) in whom lung function varied from normal to mildly obstructed. Each eFVL was coded as EFL or non-EFL, where EFL was defined by eFVLs with expired airflow meeting or exceeding the MEFV curve. A CNN with seven hidden layers and a 2-neuron softmax output layer was used to analyze the eFVLs. Three separate analyses were conducted: (1) all subjects (n = 2931 eFVLs, [GRALL]), (2) subjects with normal spirometry (n = 1921 eFVLs [GRNORM]), (3) subjects with mild airway obstruction (n = 1010 eFVLs, [GRLOW]). The final output of the CNN was the probability of EFL or non-EFL in each eFVL, which is considered EFL if the probability exceeds 0.5 or 50%. Baseline forced expiratory volume in 1 s/forced vital capacity was 0.77 (94% predicted) in GRALL, 0.83 (100% predicted) in GRNORM, and 0.69 (83% predicted) in GRLOW. CNN model accuracy was 90.6, 90.5, and 88.0% in GRALL, GRNORM and GRLOW, respectively. Negative predictive value (NPV) was higher than positive predictive value (PPV) in GRNORM (93.5 vs. 78.2% for NPV vs. PPV). In GRLOW, PPV was slightly higher than NPV (89.5 vs. 84.5% for PPV vs. NPV). A CNN performed very well at identifying eFVLs with EFL during exercise. These findings suggest that deep machine learning could become a viable tool for identifying ventilatory constraint during clinical exercise testing.

Role of the postinspiratory complex in regulating swallow-breathing coordination and other laryngeal behaviors.

Breathing needs to be tightly coordinated with upper airway behaviors, such as swallowing. Discoordination leads to aspiration pneumonia, the leading cause of death in neurodegenerative disease. Here, we study the role of the postinspiratory complex (PiCo) in coordinating breathing and swallowing. Using optogenetic approaches in freely breathing anesthetized ChATcre:Ai32, Vglut2cre:Ai32 and intersectional recombination of ChATcre:Vglut2FlpO:ChR2 mice reveals PiCo mediates airway protective behaviors. Activation of PiCo during inspiration or the beginning of postinspiration triggers swallow behavior in an all-or-nothing manner, while there is a higher probability for stimulating only laryngeal activation when activated further into expiration. Laryngeal activation is dependent on stimulation duration. Sufficient bilateral PiCo activation is necessary for preserving the physiological swallow motor sequence since activation of only a few PiCo neurons or unilateral activation leads to blurred upper airway behavioral responses. We believe PiCo acts as an interface between the swallow pattern generator and the preBötzinger complex to coordinate swallow and breathing. Investigating PiCo's role in swallow and laryngeal coordination will aid in understanding discoordination with breathing in neurological diseases.

Inspiratory-Expiratory Muscle Training Improved Respiratory Muscle Strength in Dialysis Patients: A Pilot Randomised Trial.

End-stage kidney disease (ESKD) exposes patients to progressive physical deconditioning involving the respiratory muscles. The aim of this pilot randomized controlled trial was to determine the feasibility and effectiveness of low-intensity respiratory muscle training (RMT) learned at the hospital and performed at home. A group of ESKD patients (n = 22) were randomized into RMT or usual care (control group, CON) in a 1:1 ratio. The respiratory training was performed at home with an inspiratory-expiratory system for a total of 5 min of breathing exercises in a precise rhythm (8 breaths per minute) interspersed with 1 min of rest, two times per day on nondialysis days for a total of 4 weeks, with the air resistance progressively increasing. Outcome measures were carried out every 4 weeks for 3 consecutive months, with the training executed from the 5th to the 8th week. Primary outcomes were maximal inspiratory and expiratory pressure (MIP, MEP), while secondary outcomes were lung capacity (FEV1, FVC, MVV). Nineteen patients without baseline between-group differences completed the trial (T: n = 10; Age: 63 ± 10; Males: n = 12). Both MIP and MEP significantly improved at the end of training in the T group only, with a significant difference of MEP of 23 cmH2O in favor of the RMT group (p = 0.008). No significant variations were obtained for FVC, FEV1 or MVV in either group, but there was a greater decreasing trend over time for the CON group, particularly for FVC (t = -2.00; p = 0.046). Low-fatiguing home-based RMT, with a simple device involving both inspiratory and expiratory muscles, may significantly increase respiratory muscle strength.

Respiratory dysfunction in patients with chronic neck pain: systematic review and meta-analysis.

PURPOSE: To determine the differences in respiratory muscle strength and pulmonary function between patients with chronic neck pain (CNP) and asymptomatic individuals. METHODS: Databases were MEDLINE, CINAHL, Scopus, Web of Science and EMBASE up to the end of September 2021. Studies with cross-sectional and longitudinal design were selected, with adult patients with CNP and asymptomatic individuals with reports respiratory function. RESULTS: 11 studies met the inclusion criteria and 10 were included in the meta-analysis showing a statistically significant reduction in inspiratory/expiratory muscle strength (MIP/MEP) in the patients with CNP compared with the asymptomatic individuals (mean difference (MD) for MIP, -11.67 [-14.57 to -8.77]; MD for MEP, -11.80 [-14.99 to -8.60]) and pulmonary function: vital capacity (standardized mean difference (SMD), -0.31 [-0.56 to -0.06]); maximum voluntary ventilation (SMD, -0.36 [-0.59 to -0.14]); forced vital capacity (SMD, -0.53 [-0.99 to -0.06]); peak expiratory flow (SMD, -0.58 [-1.03 to -0.12]); and forced expiratory volume in the first second (SMD, -0.28 [-0.51 to -0.05]). CONCLUSIONS: Patients with CNP have reduced respiratory muscle strength and pulmonary function compared with asymptomatic individuals, and this difference could be clinically meaningful. However, more studies of high methodological quality and longitudinal studies are needed to strengthen the results of this meta-analysis. IMPLICATIONS FOR REHABILITATIONRespiratory dysfunction has been observed in patients with chronic neck pain.Patients with chronic neck pain present a decrease in respiratory muscle strength and pulmonary function compared with asymptomatic individuals.Respiratory pattern disorders should be considered in the clinical context of chronic neck pain.Interventions focused on respiratory muscle training could be helpful for this population.

Tracheobronchoplasty yields long-term anatomy, function, and quality of life improvement for patients with severe excessive central airway collapse.

OBJECTIVES: This study examines the long-term anatomic and clinical effects of tracheobronchoplasty in severe excessive central airway collapse. METHODS: Included patients underwent tracheobronchoplasty for excessive central airway collapse (2002-2016). The cross-sectional area of main airways on dynamic airway computed tomography was measured before and after tracheobronchoplasty. Expiratory collapse was calculated as the difference between inspiratory and expiratory cross-sectional area divided by inspiratory cross-sectional area ×100. The primary outcome was improvement in the percentage of expiratory collapse in years 1, 2, and 5 post-tracheobronchoplasty. Secondary outcomes included mean response profile for the 6-minute walk test, Cough-Specific Quality of Life Questionnaire, Karnofsky Performance Status score, and St George Respiratory Questionnaire. Repeated-measures analysis of variance was used for statistical analyses. RESULTS: The cohort included 61 patients with complete radiological follow-up at years 1, 2, and 5 post-tracheobronchoplasty. A significant linear decrease in the percentage of expiratory collapsibility of the central airways after tracheobronchoplasty was present. Anatomic repair durability was preserved 5 years after tracheobronchoplasty, with decrease in percentage of expiratory airway collapse up to 40% and 30% at years 1 and 2, respectively. The St George Respiratory Questionnaire (74.7 vs 41.8%, P < .001) and Cough-Specific Quality of Life Questionnaire (78 vs 47, P < .001) demonstrated significant improvement at year 5 compared with baseline. Similar results were observed in the 6-minute walk test (1079 vs 1268 ft, P < .001) and Karnofsky score (57 vs 82, P < .001). CONCLUSIONS: Tracheobronchoplasty has durable effects on airway anatomy, functional status, and quality of life in carefully selected patients with severe excessive central airway collapse.

Numerical study on the distribution of nitric oxide concentration in the nasal cavity of healthy people during breathing.

BACKGROUND: In the nasal cavity, nitric oxide (NO) is involved in many physiological functions, including antibacterial and antiviral activity, promotion of nasal mucociliary clearance, and regulation of blood vessel expansion in the nasal mucosa. We investigated the distribution of NO concentration in the nasal cavity of healthy individuals during breathing. METHODS: A three-dimensional numerical model of the nasal airway, including the bilateral maxillary sinuses, was created to simulate NO distribution in the nasal cavity during normal breathing. The effect of different nasal airflow velocities and NO concentrations in the maxillary sinus on NO distribution in the nasal cavity was evaluated. The NO concentration in the nasal exhalation of 50 healthy people in Dalian was measured using an NO analyzer, and the growth rate of the NO concentration in the nasal cavity was measured under breath-holding conditions. RESULTS: The distribution of NO concentration in the nasal cavity of healthy people during breathing was obtained from numerical simulation results. Lower the airflow rate, higher was the NO concentration and greater was the diffusion range in the nasal cavity. The NO concentration in the nasal cavity increased with an increase in its concentration in the maxillary sinus, indicating a linear relationship. The NO concentration in the nasal exhalation of healthy people in Dalian and the growth rate of the NO concentration in the nasal cavity under breath-holding conditions were obtained through experiments. The numerical results correspond with the experimental results. CONCLUSIONS: The NO entered the nasal cavity mainly by diffusion and followed the convection flow of the respiratory air in the nasal cavity. NO concentration in the nasal cavity was related to the respiratory airflow velocity and NO concentration in the maxillary sinus. During inspiration, NO was present only in the nasal airway posterior to the maxillary sinus ostium, whereas during exhalation, the exhaled NO diffusely distributed throughout the nasal cavity.

The advantages of standardizing exhaled breath-alcohol concentration to a reference respiratory gas-water vapor.

Measuring the concentration of alcohol (ethanol) in exhaled breath (BrAC) provides a rapid and non-invasive way to determine the co-existing concentration in arterial blood (A-BAC). The results of breath-alcohol testing are used worldwide as evidence of excessive drinking, such as when traffic offenders are prosecuted. Two types of breath-alcohol analyzer are in common use; hand-held instruments used as preliminary screening tests of sobriety and more sophisticated evidential instruments, the results of which are accepted as evidence for prosecution of drunken drivers. Most evidential breath-alcohol analyzers are designed to capture the last portion of a prolonged exhalation, which is thought to reflect the alcohol concentration in substantially alveolar air. The basic premise of breath-alcohol analysis is that there is a physiological relationship between A-BAC and BrAC and close agreement between the two analytical methods. This article reviews the principles and practice of breath-alcohol analysis and introduces the concept of standardizing the results to a secondary physiological gas (water vapor), which therefore serves as an internal standard. The measured BrAC is thus adjusted to an alveolar air water content of 43.95 mg l-1at 37 °C. This has several advantages, and means that a sample of breath can be captured without the person having to blow directly into the instrument. Adjusting the breath-alcohol concentration to water vapor concentration also compensates for variations in temperature of the expired air. The contact-free method of sampling breath means that a mouthpiece is unnecessary and the test subject does not need to make a continuous end exhalation.

A glimpse in post-COVID pathophysiology: the role of exhaled breath condensate pH as an early marker of residual alveolar inflammation.

BACKGROUND: Residual alveolar inflammation seems to be paramount in post-COVID pathophysiology. Currently, we still lack a reliable marker to detect and track alveolar phlogosis in these patients. Exhaled Breath Condensate (EBC) pH has robust evidences highlighting its correlation with lung phlogosis in various diseases. We aim to define the reliability of alveolar and bronchial EBC pH in the assessment and in the follow up of post-COVID-related inflammation. RESEARCH DESIGN AND METHODS: We enrolled 10 patients previously hospitalized due to COVID-19 pneumonia. We performed a complete follow-up after 3 months and 6 months from discharge. Each visit included routine blood tests, arterial blood gas analysis, 6-minute walking test, spirometry, diffusing capacity and body plethysmography. Finally, bronchial and alveolar EBC were collected at the end of each visit. RESULTS: Alveolar EBC pH was significantly lower than bronchial EBC pH at T1, alveolar EBC pH tended to be more acid after 3 months from hospital discharge compared to the same sample 6 months later. Serum inflammatory biomarkers showed no significant differences from T1 to T2. Alveolar EBC pH was positively correlated with neutrophil-lymphocyte ratio. CONCLUSIONS: Collecting EBC pH could help to understand pathophysiologic mechanism as well as monitoring alveolar inflammation in the post-COVID syndrome.

Automated ultrasound measurements of lateral abdominal muscles under controlled breathing phases.

BACKGROUND AND OBJECTIVES: A breathing phase during ultrasound measurements of the lateral abdominal muscles (LAMs) are usually indirectly controlled by visual inspection of the position of the transversus abdominis (TrA) muscle. This is due to the lack of devices to directly control airflow that are connected to the ultrasound in order to automatically and simultaneously freeze ultrasound images at the programmed breathing phase. Such indirect control may be related with potential measurement error because LAMs are respiratory muscles. Thus, the aim of this study was to present a newly developed and automatic measurement procedure to directly control airflow and at the same time automatically collect ultrasound images at the programed breathing phase. Additionally, it was decided to compare LAMs measurements obtained manually by the examiner and with an external device controlling the peak phase of tidal inspiration and expiration and compare the elasticity and thickness measurements between tidal inspiration and expiration in young participants. METHODS: The study was carried out on 10 healthy youth. The thickness and shear modulus were measured by an Aixplorer ultrasound scanner. The measurements were obtained manually by the examiner and with a newly developed external device controlling the peak phases of tidal inspiration and expiration. RESULTS: A significant difference in external/internal oblique thickness between the expiration and inspiration phases depended on the measurement procedure. The TrA thickness was similar during inspiration and expiration. During inspiration, the TrA shear modulus was higher than during expiration, and the TrA shear modulus depended on the measurement procedure. CONCLUSION: Although the raw LAMs thickness and external/internal oblique thickness/shear modulus data were similar, the measurement procedure may affect the interpretation of the results. The TrA shear modulus is the most vulnerable to errors related to the measurement procedure. Construction of this study device controlling airflow and automatically collecting ultrasound images at the selected breathing phase seems to be promising in future studies considering measurements of respiratory muscles in a strictly defined breathing phase.

Peripheral chemoreflex activation induces expiratory but not inspiratory excitation of C1 pre-sympathetic neurones of rats.

AIMS: Stimulation of peripheral chemoreceptors, as during hypoxia, increases breathing and respiratory-related sympathetic bursting. Activation of catecholaminergic C1 neurones induces sympathoexcitation, while its ablation reduces the chemoreflex sympathoexcitatory response. However, no study has determined the respiratory phase(s) in which the pre-sympathetic C1 neurones are recruited by peripheral chemoreceptor and whether C1 neurone activation affects all phases of respiratory modulation of sympathetic activity. We addressed these unknowns by testing the hypothesis that peripheral chemoreceptor activation excites pre-sympathetic C1 neurones during inspiration and expiration. METHODS: Using the in situ preparation of rat, we made intracellular recordings from baroreceptive pre-sympathetic C1 neurones during peripheral chemoreflex stimulation. We optogenetically activated C1 neurones selectively and compared any respiratory-phase-related increases in sympathetic activity with that which occurs following stimulation of the peripheral chemoreflex. RESULTS: Activation of peripheral chemoreceptors using cytotoxic hypoxia (potassium cyanide) increased the firing frequency of C1 neurones and both the frequency and amplitude of their excitatory post-synaptic currents during the phase of expiration only. In contrast, optogenetic stimulation of C1 neurones activates inspiratory neurones, which secondarily inhibit expiratory neurones, but produced comparable increases in sympathetic activity across all phases of respiration. CONCLUSION: Our data reveal that the peripheral chemoreceptor-mediated expiratory-related sympathoexcitation is mediated through excitation of expiratory neurones antecedent to C1 pre-sympathetic neurones; these may be found in the Kölliker-Fuse nucleus. Despite peripheral chemoreceptor excitation of inspiratory neurones, these do not trigger C1 neurone-mediated increases in sympathetic activity. These studies provide compelling novel insights into the functional organization of respiratory-sympathetic neural networks.

Expiratory Muscle Relaxation-Induced Ventilator Triggering: A Novel Patient-Ventilator Dyssynchrony.

In critically ill patients receiving mechanical ventilation, expiratory muscles are recruited with high respiratory loading and/or low inspiratory muscle capacity. In this case report, we describe a previously unrecognized patient-ventilator dyssynchrony characterized by ventilator triggering by expiratory muscle relaxation, an observation that we termed expiratory muscle relaxation-induced ventilator triggering (ERIT). ERIT can be recognized with in-depth respiratory muscle monitoring as (1) an increase in gastric pressure (Pga) during expiration, resulting from expiratory muscle recruitment; (2) a drop in Pga (and hence, esophageal pressure) at the time of ventilator triggering; and (3) diaphragm electrical activity onset occurring after ventilator triggering. Future studies should focus on the incidence of ERIT and the impact in the patient receiving mechanical ventilation.

Application of a Novel Collection of Exhaled Breath Condensate to Exercise Settings.

The collection of exhaled breath condensate (EBC) is a non-invasive method for obtaining biosamples from the lower respiratory tract, an approach amenable to exercise, environmental, and work physiology applications. The purpose of this study was to develop a cost-effective, reproducible methodology for obtaining larger volume EBC samples. Participants (male: n = 10; female: n = 6; 26 ± 8 yrs.) completed a 10 min EBC collection using a novel device (N-EBC). After initial collection, a 45 min bout of cycling at 75% HRmax was performed, followed by another N-EBC collection. In a subset of individuals (n = 5), EBC was obtained using both the novel technique and a commercially available EBC collection device (R-EBC) in a randomized fashion. N-EBC volume-pre- and post-exercise (2.3 ± 0.8 and 2.6 ± 0.9 mL, respectively)-and pH (7.4 ± 0.5 and 7.4 ± 0.5, respectively) were not significantly different. When normalized for participant body height, device comparisons indicated N-EBC volumes were larger than R-EBC at pre-exercise (+12%) and post-exercise (+48%). Following moderate-intensity exercise, no changes in the pre- and post-trial values of Pentraxin 3 (0.25 ± 0.04 and 0.26 ± 0.06 pg/mL, respectively) and 8-Isoprostrane (0.43 ± 0.33 and 0.36 ± 0.24 pg/mL, respectively) concentrations were observed. In a cost-efficient fashion, the N-EBC method produced larger sample volumes, both pre- and post-exercise, facilitating more biomarker tests to be performed.

A pilot study for the prediction of liver function related scores using breath biomarkers and machine learning.

Volatile organic compounds (VOCs) present in exhaled breath can help in analysing biochemical processes in the human body. Liver diseases can be traced using VOCs as biomarkers for physiological and pathophysiological conditions. In this work, we propose non-invasive and quick breath monitoring approach for early detection and progress monitoring of liver diseases using Isoprene, Limonene, and Dimethyl sulphide (DMS) as potential biomarkers. A pilot study is performed to design a dataset that includes the biomarkers concentration analysed from the breath sample before and after study subjects performed an exercise. A machine learning approach is applied for the prediction of scores for liver function diagnosis. Four regression methods are performed to predict the clinical scores using breath biomarkers data as features set by the machine learning techniques. A significant difference was observed for isoprene concentration (p < 0.01) and for DMS concentration (p < 0.0001) between liver patients and healthy subject's breath sample. The R-square value between actual clinical score and predicted clinical score is found to be 0.78, 0.82, and 0.85 for CTP score, APRI score, and MELD score, respectively. Our results have shown a promising result with significant different breath profiles between liver patients and healthy volunteers. The use of machine learning for the prediction of scores is found very promising for use of breath biomarkers for liver function diagnosis.