Search

What is the central question of this study? Increased work of breathing and the accumulation of metabolites have neural and cardiovascular consequences through a respiratory muscle-induced metaboreflex. The influence of the respiratory muscle-induced metaboreflex on splanchnic blood flow in humans remains unknown. What is the main finding and its importance? Coeliac artery blood flow decreased gradually during inspiratory resistive breathing, accompanied by a progressive increase in arterial blood pressure. It is possible that the respiratory muscle-induced metaboreflex contributes to splanchnic blood flow regulation.The purpose of this study was to clarify the effect of increasing inspiratory muscle work on coeliac artery blood flow. Eleven healthy young males completed the study. The subjects performed voluntary hyperventilation with or without inspiratory resistance (loading or non-loading trial; tidal volume of 40% of vital capacity and breathing frequency of 20 breaths/min). The loading trial was conducted with inspiratory resistance (40% of maximal inspiratory pressure) and was terminated when the subjects could no longer maintain the target tidal volume or breathing frequency. The non-loading trial was conducted without inspiratory resistance and was of the same duration as the loading trial. Arterial blood pressure was recorded using finger photoplethysmography, and coeliac artery blood flow was measured using Doppler ultrasound. Mean arterial blood pressure increased gradually during the loading trial (mean ± SD; from 89.0 ± 10.8 to 103.9 ± 17.3 mmHg) but not in the non-loading trial (from 88.7 ± 5.9 to 90.4 ± 9.9 mmHg). Coeliac artery blood flow and coeliac vascular conductance decreased gradually during the loading trial (from 601.2 ± 155.7 to 482.6 ± 149.5 mL/min and from 6.9 ± 2.2 to 4.8 ± 1.7 mL/min/mmHg, respectively) but were unchanged in the non-loading trial (from 630.7 ± 157.1 to 635.6 ± 195.7 mL/min and from 7.1 ± 1.8 to 7.2 ± 2.9 mL/min/mmHg, respectively). These results show that increasing inspiratory muscle work affects splanchnic blood flow regulation, and we suggest that this might be mediated by the inspiratory muscle-induced metaboreflex.

INTRODUCTION In mechanically ventilated patients, driving pressure (ΔP) represents the dynamic stress applied to the respiratory system and is related to ICU mortality. An evolution of the Adaptive Support Ventilation algorithm (ASV® 1.1) minimizes inspiratory pressure in addition to minimizing the work of breathing. We hypothesized that ASV 1.1 would result in lower ΔP than the ΔP measured in APV-CMV (controlled mandatory ventilation with adaptive pressure ventilation) mode with physician-tailored settings. The aim of this randomized crossover trial was therefore to compare ΔP in ASV 1.1 with ΔP in physician-tailored APV-CMV mode. METHODS Pediatric patients admitted to the PICU with heterogeneous-lung disease were enrolled if they were ventilated invasively with no detectable respiratory effort, hemodynamic instability, or significant airway leak around the endotracheal tube. We compared two 60-min periods of ventilation in APV-CMV and ASV 1.1, which were determined by randomization and separated by 30-min washout periods. Settings were adjusted to reach the same minute ventilation in both modes. ΔP was calculated as the difference between plateau pressure and total PEEP measured using end-inspiratory and end-expiratory occlusions, respectively. RESULTS There were 26 patients enrolled with a median age of 16 (9-25 [IQR]) months. The median ΔP for these patients was 10.4 (8.5-12.1 [IQR]) and 12.4 (10.5-15.3 [IQR]) cmH2O in the ASV 1.1 and APV-CMV periods, respectively (p

The precise coordination of respiratory muscles during exercise minimizes work of breathing and avoids exercise intolerance. Fibrotic interstitial lung disease (f-ILD) patients are exercise-intolerant. We assessed whether respiratory muscle incoordination and thoracoabdominal asynchrony (TAA) occur in f-ILD during exercise, and their relationship with pulmonary function and exercise performance.We compared breathing pattern, respiratory mechanics, TAA and respiratory muscle recruitment in 31 f-ILD patients and 31 healthy subjects at rest and during incremental cycle exercise. TAA was defined as phase angle (PhAng)20°.During exercise, when compared with controls, f-ILD patients presented increased and early recruitment of inspiratory rib cage muscle (p 0.05), and an increase in PhAng, indicating TAA. TAA was more frequent in f-ILD patients than in controls, both at 50% of the maximum workload (42.3% vs. 10.7%, p = 0.01) and at the peak (53.8% vs. 23%, p = 0.02). Compared with f-ILD patients without TAA, f-ILD patients with TAA had lower lung volumes (forced vital capacity, p 0.01), greater dyspnoea (Medical Research Council 2 in 64.3%, p = 0.02), worse exercise performance (lower maximal work rate % predicted, p = 0.03; lower tidal volume, p = 0.03; greater desaturation and dyspnoea, p 0.01) and presented higher oesophageal inspiratory pressures with lower gastric inspiratory pressures and higher recruitment of scalene (p 0.05).Exercise induces TAA and higher recruitment of inspiratory accessory muscle in ILD patients. TAA during exercise occurred in more severely restricted ILD patients and was associated with exertional dyspnoea, desaturation and limited exercise performance.

OBJECTIVE: To determine the effect of high‐flow nasal cannula (HFNC) oxygen therapy on cardiorespiratory variables and outcome in dogs with acute hypoxemic respiratory failure. DESIGN: Prospective, sequential clinical trial. SETTING: University veterinary teaching hospital. ANIMALS: Twenty‐two client‐owned dogs that failed to respond to traditional oxygen support. INTERVENTIONS: Initiation of HFNC therapy after traditional oxygen supplementation failed to increase Spo₂ > 96% and Pao₂ > 75 mm Hg or improve respiratory rate/effort. MEASUREMENTS AND MAIN RESULTS: Physiological variables, blood gas analyses, and dyspnea/sedation/tolerance scores were collected prior to HFNC initiation (on traditional oxygen support [time 0 or T0]), and subsequently during HFNC oxygen administration at time 30 minutes, 60 minutes, and 7 ± 1 hours. Relative to T0, use of HFNC resulted in a decreased respiratory rate at 1 hour (P = 0.022) and 7 hours (P = 0.012), a decrease in dyspnea score at all times (P < 0.01), and an increase in Spo₂ at all times (P < 0.01). There was no difference in arterial/venous Pco₂ relative to T0, although Paco₂ was correlated with flow rate. Based on respiratory assessment, 60% of dogs responded to HFNC use by 30 minutes, and 45% ultimately responded to HFNC use and survived. No clinical air‐leak syndromes were observed. CONCLUSIONS: HFNC use improved oxygenation and work of breathing relative to traditional oxygen therapies, without impairing ventilation. HFNC use appears to be a beneficial oxygen support modality to bridge the gap between standard oxygen supplementation and mechanical ventilation.

Background Brachycephalic airway syndrome can pose a risk of complicated recovery from anesthesia as a result of irritation to the excess pharyngeal andlaryngeal tissue present in affected dogs. High-flow nasal cannula (HFNC) oxygen therapy is a respiratory support modality that offers provision of continuous positive airway pressure via high gas flow rates. The HFNC system actively warms and humidifies inspired gases, which improves comfort and facilitates tolerance of the high flow rates in people and dogs. HFNC oxygen therapy was applied to brachycephalic dogs that developed increased work of breathing or hypoxemia in the recovery phase of anesthesia to determine if this device would be tolerable and effective for relief of upper respiratory difficulty. Key findings The HFNC nasal prong interface is well suited to the brachycephalic facial structure. The application of HFNC was found to reduce dyspnea scores in patients with signs of upper airway obstruction after general anesthesia. Aerophagia and changes in PCO2 were noted. Significance Application of HFNC in the recovery period may result in improved airflow during times of somnolent obstructive breathing, not unlike the use of continuous positive airway pressure therapy in sleep-disordered breathing in people.

Objectives To describe the long-term effects of ivacaftor (Kalydeco®) in individuals with cystic fibrosis (CF) on body mass index (BMI), body composition (BC), pulmonary function (PF), resting energy expenditure (REE), and exercise capacity (EC) after ≥12 months of treatment. Working hypothesis BMI, lean and fat mass, PF, and EC will increase and REE will decrease after treatment. Study design Observational study. Methodology Seven individuals with CF (mean age 15.4 ± 5.8 years) heterozygous for S1251N mutation, starting with ivacaftor, were included. Paired t tests were performed to assess the effects of ivacaftor. Height and weight were used to calculate BMI and BMI Z-scores. Dual-energy X-ray absorptiometry was used to assess BC. Spirometry and body plethysmography were used to assess PF. Indirect calorimetry was used to measure REE and cardiopulmonary exercise testing (CPET) was used to measure oxygen uptake (VO2peak ), peak work rate (Wpeak ), and other CPET variables. Results After a median of 15 (interquartile range: 13-16) months of treatment, BMI increased significantly (P = .03), but not BMI Z-score (P = .23) or BC. Significant improvements were found for several PF variables, especially measures of hyperinflation (P = .02). Absolute VO2peak (P = .01), VO2peak related to body weight (P = .00), and oxygen cost of work (P = .01) decreased. Absolute Wpeak (P = .59) and Wpeak related to body weight (P = .31) remained stable. Conclusions The results showed that long-term treatment of ivacaftor is associated with improvement of BMI and PF, but not of BC and REE. Oxygen uptake reduced after treatment, which may be due to a decrease in work of breathing.

Effective specific airway resistance (sReff), its reciprocal the effective specific airway conductance (sGeff) are computed as ratios between the integral of the resistive aerodynamic work of breathing (sWOB) and the integral of the tidal flow/volume loop, the reciprocal, respectively. Unfortunately, reference equations to obtain normative values for sReff, sGeff, and sWOB are not yet available. To assess reference equations for sWOB, sReff, and sGeff during tidal breathing at resting level in healthy infants, children, and adults by a multidimensional model. Retrospectively exported data were collected from databases of five Swiss lung function centers, in which plethysmography (Jaeger Würzburg, Germany) was performed for the assessment of airway dynamics, static lung volumes, and forced breathing flow‐volume loops, in a collective of 28 healthy infants, 47 children, and 273 adults. From this cohort, reference equations were computed based on anthropometric measures, lung volumes, indices of the breathing pattern, and timing of breathing. By multi‐linear modeling reference equations of sReff, sGeff, and sWOB could be defined taking as independent parameters apart from anthropometric parameters, also parameters given by the ratio between the tidal volume and functional residual capacity (FRCpleth/V T), and the ratio between V T and inspiratory time (V T/T I). An alternative statistical approach to define reference equations of airway dynamics reveals that apart from the subject's anthropometric measurements, parameters of the magnitude of static lung volumes, the breathing pattern, and the timing of breathing are co‐variants of reference equations of airway dynamics over a large age range., By the work presented, the gap of the effectiveness regarding the embodiment of airway dynamics in the assessment of functional severity in various diseases can be bridged.

NEW FINDINGS What is the central question of this study? Recent studies have suggested potential utility of non-normalized respiratory muscle EMG as an index of neural respiratory drive (NRD). Whether NRD measured using non-normalized surface EMG of the lateral chest wall overlying the diaphragm (sEMGcw) recorded during nocturnal clinical polysomnography can differentiate children with and without obstructive sleep apnoea (OSA) is not known. What is the main finding and its importance? Non-normalized sEMGcw was increased in children with OSA and an additional group of snoring children without OSA but subjectively increased respiratory effort compared with primary snorers. The sEMGcw has potential clinical utility in evaluation of children with sleep-disordered breathing as an objective, non-invasive, non-volitional marker of NRD. ABSTRACT Our aim was to investigate whether neural respiratory drive measured by non-normalized surface EMG recorded from the chest wall overlying the diaphragm (sEMGcw) differentiates children with and without obstructive sleep apnoea (OSA). Polysomnography data of children aged 0-18 years were divided into the following three groups: (i) primary snorers (PS); (ii) snoring children without OSA but with increased work of breathing (incWOB; subjective physician report of increased respiratory effort during sleep); and (iii) children with OSA [obstructive apnoea-hypopnoea index (OAHI) >1 h-1 ]. Excerpts of sEMGcw obtained during tidal unobstructed breathing from light, deep and rapid eye movement sleep were exported for quantitative analysis. Overnight polysomnography data from 45 PS [median age 4.4 years (interquartile range 3.0-7.7 years), OAHI 0 h-1 (0.0-0.2 h-1 )], 19 children with incWOB [age 2.8 years (2.4-5.7 years), OAHI 0.1 h-1 (0.0-0.4 h-1 )] and 27 children with OSA [age 3.6 years (2.6-6.2 years), OAHI 3.7 h-1 (2.3-6.9 h-1 )] were analysed. The sEMGcw was higher in those with OSA [8.47 μV (5.98-13.07 μV); P

Nasal high flow (nHF) therapy is a commonly used method of providing non-invasive respiratory support for neonates. It has several potential mechanisms of action: continuous distending pressure, nasopharyngeal dead space washout, provision of heated and humidified gases and reduction of work of breathing. nHF is used in a number of clinical scenarios for preterm and term infants, including primary respiratory and post-extubation support. In recent years, large trials have generated evidence pertinent to these indications. Novel applications for nHF in neonates warrant further research: during endotracheal intubation, for initial delivery room stabilisation of preterm infants and in conjunction with minimally invasive surfactant therapy.

Introduction It remains unclear if naturally occurring respiratory muscle (RM) work influences leg diffusive O2 transport during exercise in heart failure patients with reduced ejection fraction (HFrEF). In this retrospective study, we hypothesized that RM unloading during submaximal exercise will lead to increases in locomotor muscle O2 diffusion capacity (DMO2) contributing to the greater leg VO2. Methods Ten HFrEF patients and 10 healthy control matched participants performed two submaximal exercise bouts (i.e., with and without RM unloading). During exercise, leg blood flow was measured via constant infusion thermodilution. Intrathoracic pressure was measured via esophageal balloon. Radial arterial and femoral venous blood gases were measured and used to calculate leg arterial and venous content (CaO2 and CvO2, respectively), VO2, O2 delivery, and DMO2. Results From CTL to RM unloading, leg VO2, O2 delivery, and DMO2 were not different in healthy participants during submaximal exercise (all, p > .15). In HFrEF, leg VO2 (CTL: 0.7 ± 0.3 vs. RM unloading: 1.0 ± 0.4 L/min, p, Respiratory muscle work negatively influences convective O2 transport in heart failure patients. The present study investigated the impact of respiratory muscle work on leg O2 diffusive capacity during submaximal exercise. We found the degree of respiratory muscle unloading in heart failure patients is related to the improvement in leg O2 diffusive capacity during submaximal exercise.

Summary Healthcare workers are at risk of infection during the severe acute respiratory syndrome coronavirus‐2 pandemic. International guidance suggests direct droplet transmission is likely and airborne transmission occurs only with aerosol‐generating procedures. Recommendations determining infection control measures to ensure healthcare worker safety follow these presumptions. Three mechanisms have been described for the production of smaller sized respiratory particles (‘aerosols’) that, if inhaled, can deposit in the distal airways. These include: laryngeal activity such as talking and coughing; high velocity gas flow; and cyclical opening and closure of terminal airways. Sneezing and coughing are effective aerosol generators, but all forms of expiration produce particles across a range of sizes. The 5‐μm diameter threshold used to differentiate droplet from airborne is an over‐simplification of multiple complex, poorly understood biological and physical variables. The evidence defining aerosol‐generating procedures comes largely from low‐quality case and cohort studies where the exact mode of transmission is unknown as aerosol production was never quantified. We propose that transmission is associated with time in proximity to severe acute respiratory syndrome coronavirus‐1 patients with respiratory symptoms, rather than the procedures per se. There is no proven relation between any aerosol‐generating procedure with airborne viral content with the exception of bronchoscopy and suctioning. The mechanism for severe acute respiratory syndrome coronavirus‐2 transmission is unknown but the evidence suggestive of airborne spread is growing. We speculate that infected patients who cough, have high work of breathing, increased closing capacity and altered respiratory tract lining fluid will be significant producers of pathogenic aerosols. We suggest several aerosol‐generating procedures may in fact result in less pathogen aerosolisation than a dyspnoeic and coughing patient. Healthcare workers should appraise the current evidence regarding transmission and apply this to the local infection prevalence. Measures to mitigate airborne transmission should be employed at times of risk. However, the mechanisms and risk factors for transmission are largely unconfirmed. Whilst awaiting robust evidence, a precautionary approach should be considered to assure healthcare worker safety.

It has been found that high-flow oxygen therapy (HFOT) can reduce mortality of patients admitted to intensive care unit (ICU) for de novo acute respiratory failure (ARF) as compared to non-invasive ventilation (NIV). HFOT might therefore be considered as a first-line strategy of oxygenation in these patients. The beneficial effects of HFOT may be explained by its good tolerance and by physiological characteristics including delivery of high FiO2 , positive end expiratory pressure (PEEP) effect and continuous dead space washout contributing to decreased work of breathing. In contrast, NIV should be used cautiously in patients with de novo ARF due to high tidal volumes promoted by pressure support and that may potentially worsen pre-existing lung injury. Although recent studies have reported no benefit and even deleterious effects of NIV in immunocompromised patients with ARF, the experts have recommended its use as a first-line strategy. In patients with acute-on-chronic respiratory failure and respiratory acidosis, it has been clearly shown that NIV is the best strategy of oxygenation. However, HFOT seems able to reverse respiratory acidosis and further studies are needed to evaluate whether HFOT could represent an alternative to standard oxygen. Although NIV is recommended to treat ARF in post-operative patients or to prevent post-extubation respiratory failure in ICU, recent large-scale randomized studies suggest that HFOT could be equivalent to NIV. While recent recommendations have been established from studies comparing NIV with standard oxygen, new studies are needed to compare NIV versus HFOT in order to better define the appropriate indications for both treatments.

Background Pulmonary function testing (PFT) is essential for the clinical assessment of respiratory problems. Respiratory inductance plethysmography (RIP) is a non-invasive method of PFT requiring minimal patient cooperation. RIP measures the volumetric change in the ribcage and abdomen, from which work of breathing (WOB) indices are derived. WOB indices include: phase angle (Ф), percent ribcage (RC%), respiratory rate (RR), and labored breathing index (LBI). Heart rate (HR) is collected separately. Aim The goal of this study was to assess the utility of a newly developed RIP system, the pneuRIP, in an outpatient clinic setting in children with neuromuscular (NM) disease. Method The pneuRIP system measures and displays the WOB indices in real-time on an iPad display. Forty-three subjects, 22 NM patients and 21 healthy children (ages: 5-18 years) were enrolled. Results Patients' means showed an increase of 119.8% for Ф, 15.7% for LBI, and 19.9% for HR compared with healthy subjects, when adjusted for age and gender. The study found significant differences between the mean values of the healthy subjects and patients in Ф (P = 0.000), LBI (P = 0.001), and HR (P = 0.001). No differences were noted for RC% and RR between groups. Data for Ф in NM patients were diffusely distributed as compared with healthy subjects based on analysis of histograms. Conclusion Non-invasive pneuRIP testing provided instantaneous PFT results. As compared to healthy subjects, NM patients showed abnormal results with increased markers of thoracoabdominal asynchrony, WOB indices, and biphasic breathing patterns likely resulting from NM weakness.

Objectives Neuroendocrine cell hyperplasia of infancy (NEHI) is a children's interstitial and diffuse lung disease of unknown etiology that presents in infancy with characteristic findings of tachypnea, retractions, crackles, and hypoxemia. At the present, the mainstay of treatment is oxygen supplementation to normalize oxygen saturations and decrease work of breathing. There are characteristic pulmonary function, radiographic, and histologic findings, but polysomnography (PSG) data has not been reported. We sought to report PSG data and implications for management and treatment of NEHI patients. Methods A retrospective chart review was performed under a Colorado Institutional Review Board approved protocol for which consent was waived. Informatics for Integrating Biology and the Bedside was used to query the electronic medical record at Children's Hospital Colorado for patients with both a diagnosis of NEHI and a PSG. PSG was performed for clinical reasons. Routine sleep quality and respiratory parameters were recorded and analyzed. Results Of our 77 patients with NEHI, 14 (19%) children underwent PSG during the study period. Eight children met criteria for OSA and three met criteria for CSA. Ten patients had low oxygen saturations during a study, six had low sleep efficiency, and three had periodic limb movement disorder. Conclusions Patients with NEHI may have sleep related breathing disorders that contribute to disrupted sleep, including obstructive and central sleep apnea, hypoxemia, decreased sleep efficiency, and increased periodic limb movement disorder. PSG should be considered as part of NEHI management, as it may lead to recognition of clinically significant sleep-disordered breathing.

Background Neonates, particularly premature babies, are often managed with endotracheal intubation and subsequent mechanical ventilation to maintain adequate pulmonary gas exchange. There is no consensus on the standard length of endotracheal tube. Although a short tube reduces resistance and respiratory dead space, it is believed to increase the risk of accidental extubation. There are not entirely coherent data regarding the effect of endotracheal tube length on work of breathing in infants. Aim The aim of this study was to evaluate the impact of neonatal endotracheal tube diameter and length on the work of breathing using an infant in vitro lung model. Method We assessed the work of breathing index and mechanical ventilation settings with various endotracheal tube diameters and lengths using the JTR100 in vitro infant lung model. The basic parameters of the model were breathing frequency of 20 per minutes, inspiratory-expiratory ratio of 1:3, and positive end-expiratory pressure of 5 cmH2 O. In addition, the diaphragm driving pressure to maintain the set tidal volume was measured as the work of breathing index. The JTR100 was connected to the Babylog 8000plus through the endotracheal tube. Finally, we monitored the peak inspiratory pressure generated during assist-control volume guarantee mode with a targeted tidal volume of 10-30 mL. Results The diaphragm driving pressure using a 2.0-mm inner diameter tube was twice as high as that using a 4.0-mm inner diameter tube. To maintain the targeted tidal volume, a shorter tube reduced both the diaphragm driving pressure and ventilator-generated peak inspiratory pressure. The difference in the generated peak inspiratory pressure between the shortest and longest tubes was 5 cmH2 O. Conclusion In our infant lung model, a shorter tube resulted in a lower work of breathing and lower ventilator-generated peak inspiratory pressure.

Aim The aim of this study was to highlight the incidence of unplanned extubation (UE) and identify associated factors in our neonatal population. Methods This study was a prospective audit. Results A specifically designed audit tool was used to capture UE events; 182 neonates required mechanical ventilation for 863 days. There were 41 episodes of UE. The UE rate was 4.75 per 100 days of ventilation. At the time of UE, median gestational age of patients was 27.3 weeks (23.4-37.6), with a corrected age median of 29.2 weeks (23.4-37.6). Re-intubation was required in two thirds of the patients for increasing apnoea and increased work of breathing. Endotracheal tubes are secured in a standardised way either using Neobar or brown tape. UE events occurred with both methods. The two most common factors associated with UE included active handling of the baby and the time of day (0700-1000 h). Conclusions This audit has provided our neonatal intensive care unit with a benchmark for improvement. It has also created staff awareness of the risk of UE and promoted staff engagement to reduce UE. A bundle approach to reduce UE has been introduced. Future audits are planned to monitor the impact of these initiatives.

The lung permits gaseous exchange between the body and atmosphere. The principal interchange site is the alveolar space, which is bathed in a lipid-protein blend called pulmonary surfactant. This material minimises the surface tension and maintains airway patency. Pulmonary surfactant is the initial contacting site for orally inhaled products and environmental toxins. Langmuir monolayer technology can be applied to model the alveolar space. A recent development in this field is the lung biosimulator. The aim of this study was to investigate the influence of cannabis smoke on the activity of the lung surfactant replacement product, Curosurf®. Here, the lung biosimulator facilitated controlled operating conditions of 37C, elevated humidity and accepted fluid hydrodynamics. Initially, 50mg cannabis material was pyrolysed and the smoke collected. For complete pyrolysis, a regimen involving 4 puffs, 50ml volume, 3 second puff duration and a 30-second interval was applied. Quantification for cannabis smoke was conducted via gas chromatography – mass spectroscopy, with a mean concentration of 1% 9 tetrahydrocannabinol (THC) determined. Cannabis smoke aliquots were transferred to the lung biosimulator and 10 minutes allowed for interaction. Expansion – contraction cycles were then initiated to mimic tidal breathing. Baseline data confirmed that Curosurf® works effectively, under physiologically relevant conditions. High surface pressures (e.g. 70mN/m) were attained on full compression. Exposure to cannabis smoke from two independent batches increased the compressibility term and reduced the Langmuir isocycle maximum surface pressure by approximately 20%; interbatch variation was detected. Cannabis smoke impaired the ability of Curosurf® to lower the surface tension term. This was ascribed to the penetration of the planar, hydrophobic drug into the two-dimensional film and destructive interaction with polar functionalities. The net effect would be increased work of breathing for the individual.

New Findings What is the central question of this study? Does manipulation of the work of breathing during high-intensity exercise alter respiratory and locomotor muscle blood flow? What is the main finding and its importance? We found that when the work of breathing was reduced during exercise, respiratory muscle blood flow decreased, while locomotor muscle blood flow increased. Conversely, when the work of breathing was increased, respiratory muscle blood flow increased, while locomotor muscle blood flow decreased. Our findings support the theory of a competitive relationship between locomotor and respiratory muscles during intense exercise. Manipulation of the work of breathing (WOB) during near-maximal exercise influences leg blood flow, but the effects on respiratory muscle blood flow are equivocal. We sought to assess leg and respiratory muscle blood flow simultaneously during intense exercise while manipulating WOB. Our hypotheses were as follows: (i) increasing the WOB would increase respiratory muscle blood flow and decrease leg blood flow; and (ii) decreasing the WOB would decrease respiratory muscle blood flow and increase leg blood flow. Eight healthy subjects (n = 5 men, n = 3 women) performed a maximal cycle test (day 1) and a series of constant-load exercise trials at 90% of peak work rate (day 2). On day 2, WOB was assessed with oesophageal balloon catheters and was increased (via resistors), decreased (via proportional assist ventilation) or unchanged (control) during the trials. Blood flow was assessed using near-infrared spectroscopy optodes placed over quadriceps and the sternocleidomastoid muscles, coupled with a venous Indocyanine Green dye injection. Changes in WOB were significantly and positively related to changes in respiratory muscle blood flow (r = 0.73), whereby increasing the WOB increased blood flow. Conversely, changes in WOB were significantly and inversely related to changes in locomotor blood flow (r = 0.57), whereby decreasing the WOB increased locomotor blood flow. Oxygen uptake was not different during the control and resistor trials (3.8 ± 0.9 versus 3.7 ± 0.8 l min−1, P > 0.05), but was lower on the proportional assist ventilator trial (3.4 ± 0.7 l min−1, P

This study was supported by the Natural Science and Engineering Research Council of Canada (NSERC). PBD, YMS and CMP were supported by a graduate scholarship from NSERC. PBD was also supported by the Canadian Thoracic Society.

Pulmonary surfactant is an endogenous material that lines and stabilises the alveolar air-liquid interface. Respiratory mechanics can be compromised by exposure to environmental toxins such as cigarette vapour, which contains nicotine. This study aims to determine the influence of nicotine on the activity of simulated lung surfactant at pH 7 and pH 9. In all cases, the addition of nicotine to the test zone caused deviation in surfactant film performance. Importantly, the maximum surface pressure was reduced for each system. Computational modelling was applied to assess key interactions between each species, with the Gaussian 09 software platform used to calculate electrostatic potential surfaces. Modelling data confirmed either nicotine penetration into the two-dimensional structure or interfacial / electrostatic interactions across the underside. The results obtained from this study suggest that nicotine can impair the ability of pulmonary surfactant to reduce the surface tension term, which can increase the work of breathing. When extrapolated to gross lung function alveolar collapse and respiratory disease (e.g. chronic airway obstruction) may result. The delivery of nicotine to the (deep) lung can cause a deterioration in lung function and lead to reduced quality of life.

Seizure spread into autonomic and respiratory brainstem regions is thought to play an important role in sudden unexpected death in epilepsy (SUDEP). As the clinical dataset of cases of definite SUDEP available for study grows, evidence points to a sequence of events that includes postictal apnea, bradycardia, and asystole as critical events that can lead to death. One possible link between the precipitating seizure and the critical postictal sequence is seizure-driven laryngospasm sufficient to completely obstruct the airway for an extended period, but ictal laryngospasm is difficult to fully assess. Herein, we demonstrate in a rat model how the electrical artifacts of attempts to inspire during airway obstruction and features of the cardiac rhythm establish this link between ictal and postictal activity and can be used as practical biomarkers of obstructive apnea due to laryngospasm or other causes of airway obstruction.

Objective The objective was to examine the safety and efficacy of high-flow nasal cannula (HFNC) therapy for children with bronchiolitis in a non-tertiary paediatric setting. Methods This was a single-centre retrospective study conducted over 26 months (March 2013–April 2015) on children aged 1–23 months with suspected bronchiolitis, who commenced on HFNC therapy in either the ED or the ward. Changes with respect to baseline data were analysed for effect on work of breathing (WOB), heart rate (HR) and respiratory rate (RR). Data was analysed using a linear mixed effects model and adjusted for age (≤12 months and >12 months) and location (ED vs ward). Transfer to a tertiary environment, escalation of care and adverse event rates were also recorded. Results A total of 61 children commenced on HFNC therapy, with flow rates ranging from 0.6 to 3.3L/kg/min. The proportion of patients with higher WOB scores appeared to reduce within 60 min of initiation of therapy. There was also a progressive reduction in surrogate markers of respiratory distress (HR and RR), with significant reductions evident by 60 min (P < 0.05). There were no adverse events related to HFNC therapy. The transfer rate was 13%. It was predominantly due to lack of improvement of physiological parameters post initiation of HFNC therapy. None of the transferred patients required escalation of care. Conclusion Within the limitations of this study it appears HFNC therapy may be safely commenced in both age groups in a non-tertiary ED or ward, with an appropriate level of observation and robust transfer criteria.

ObjectiveMost patients requiring intubation and mechanical ventilation are extubated successfully at the first attempt; however, a minority experience extubation failure, which is associated with increased risk of ventilator-associated pneumonia, prolonged intensive care unit (ICU) length of stay and mortality. Physiotherapists have expertise to assess cough strength, work of breathing, respiratory muscle strength, and respiratory secretion load, which are important factors in the outcome of extubation. Accurate prediction of extubation outcome could help to inform management plans pre-extubation and postextubation. The primary objective of this service evaluation was to report the accuracy of physiotherapists' prediction of extubation outcome in the adult ICU.MethodsA single-centre case note review was undertaken. All subjects who received a physiotherapy assessment of extubation suitability prior to extubation between January and March 2016 in the adult ICU of a large teaching hospital in the United Kingdom were included. Assessment, by both specialist and nonspecialist physiotherapists-which included risk stratification of extubation failure as "high," "moderate," or "low"-was undertaken prior to extubation. Logistic regression analysis was performed to determine which pre-extubation factors were predictive of extubation outcome.ResultsDuring the evaluation period, 68 subjects were extubated following a physiotherapy assessment. Physiotherapy risk stratification as "high risk" (OR 4; 95% confidence interval, CI, [1.312]; p=0.009) and "inappropriate" neurological status (OR 3.3; 95% CI [1.0410]; p=0.037) were the only pre-extubation factors significantly associated with extubation failure. Assessment by specialist physiotherapists demonstrated greater sensitivity (100% vs. 22%) but lower specificity (68% vs. 95%) to detect extubation failure compared with the assessment performed by nonspecialist physiotherapists.ConclusionPatients classified as "high risk" of extubation failure by a physiotherapist are significantly more likely to fail extubation. Specialist physiotherapists should be involved in the decision to extubate patients in the adult ICU.

Background and objective In this study, we investigate the changes in diaphragmatic kinetics, breathing pattern and work of breathing induced by 10 cmH2O of continuous positive airway pressure (CPAP). Methods We used sonography to study diaphragmatic kinetics and measured energy expenditure using indirect calorimetry in 50 healthy volunteers at 0 cmH2O positive end expiratory pressure (ZEEP) and after application of 10 cmH2O CPAP. In a subgroup of 14 subjects, the changes in thoracic and abdominal volumes and thoraco-abdominal asynchrony were recorded with inductive plethysmography, while accessory respiratory muscle activity was recorded with electromyography. Results Continuous positive airway pressure breathing induced acute lung hyperinflation of 600 mL above passive functional residual capacity. This hyperinflation induced changes in diaphragmatic kinetics and breathing pattern; diaphragmatic excursion, thickness and thickness ratio, tidal volume (Vt) and oxygen consumption (VO2) increased while respiratory rate decreased. The increase in Vt with CPAP was mainly due to rib cage contribution. Activation of the accessory inspiratory (scalene) and expiratory (transversus abdominis) muscles was recorded. The raised respiratory muscles workload induced an increase in VO2. Conclusion In healthy volunteers, CPAP therapy leads to lung overdistention and recruitment of respiratory muscles. These mechanisms operate at a high energy cost.

New Findings What is the central question of this study? Can a modern proportional assist ventilator (PAV) function to sufficiently unload the respiratory muscles during exercise? What is the main finding and its importance? A PAV can be constructed with contemporary hardware and software and be used during all exercise intensities to unload the respiratory muscles by up to 70%. Previously, PAVs have allowed researchers to address many fundamental physiological problems in clinical and healthy populations, but those versions are no longer functional or available. We describe the creation of a PAV that permits researchers to use it as an experimental tool. Manipulating the normally occurring work of breathing (WOB) during exercise can provide insights into whole-body regulatory mechanisms in clinical and healthy subjects. One method to reduce the WOB utilizes a proportional assist ventilator (PAV). Suitable commercially available units are not capable for used during heavy exercise. This investigation was undertaken in order to create a PAV and assess the degree to which the WOB could be reduced during exercise. A PAV works by creating a positive mouth pressure (Pm) during inspiration which consequently reduces the WOB. Spontaneous breathing patterns can be maintained and the amplitude of Pm is calculated using the equation of motion and predetermined proportionality constants. We generated positive Pm using a breathing apparatus consisting of rigid tubing, solenoid valves to control airflow direction and a proportional valve connected to compressed gas. Healthy male and female subjects were able to successfully use the PAV while performing cycle exercise over a range of intensities (50–100% maximum workload) for different durations (30 s to 20 min) and different protocols (constant vs. progressive workload). Inspiratory WOB was reduced up to 90%, while total WOB was be reduced 70%. The greatest reduction in WOB (50–75%) occurred during submaximal exercise, but at maximal ventilations (>180 l min−1) a 50% reduction was still possible. The calculated change in WOB and subsequent reduction in respiratory muscle oxygen consumption resulted in equivalent reductions in whole-body oxygen consumption. With adequate familiarization and practice, our PAV can consistently reduce the WOB across a range of exercise intensities. This article is protected by copyright. All rights reserved

Summary Background Early childhood wheezing substantially impacts quality of life in high-income countries, but data are sparse on early childhood wheezing in low-income countries. We estimate wheezing incidence, describe wheezing phenotypes, and explore the contribution of respiratory viral illnesses among children aged

Objectives The aim of the study was to determine if oxygen delivered through humidified high flow nasal cannulae (HHFNC) reduced the need for escalation in ventilation management and work of breathing in the ED patients presenting with acute undifferentiated shortness of breath compared with standard oxygen therapy. Methods This was an unblinded randomised control trial conducted at two hospital EDs in Sydney, Australia. Eligible patients presenting with shortness of breath were randomised to HHFNC or standard oxygen therapy. Primary outcomes were the need to escalate ventilation therapy or a reduction in respiratory rate of 20% or more within 2 h of commencement. Results One hundred patients were enrolled in the trial. The intervention group receiving HHFNC was associated with a higher proportion of patients with a reduced respiratory rate at 2 h (66.7% vs 38.5%, P = 0.005) and a lower proportion of patients requiring escalation in ventilation therapy (4.2% vs 19%, P = 0.02) compared with standard oxygen therapy. Conclusions The use of high flow nasal cannula oxygenation was associated with improved respiratory state in selected patients presenting to the ED with acute undifferentiated shortness of breath.

Background Asthma is a common condition that presents with varied symptomatology and exam findings. The diagnosis of asthma is made through a combination of clinical assessment and diagnostic testing. Methods A literature review was conducted through PubMed, focusing on systematic reviews and practice parameters. The highest-quality studies and those including the highest number of patients were included. References were reviewed for additional relevant articles. Results Patients with asthma present with the symptoms of cough, dyspnea, and wheezing. The physical exam can demonstrate hyperinflation, wheezing, and increased work of breathing, but most patients will present with a normal pulmonary exam because they are between episodes. The symptoms and examination of patients with asthma varies greatly from patient to patient and within the same patient over time. The diagnosis of asthma in the pediatric population may be more difficult because the classic symptoms may not be present in many of those patients. Conclusion The diagnosis of asthma is made in the setting of clinical history, physical exam, and diagnostic testing. The astute physician will rely on all 3 of these factors when making the diagnosis.

Reducing the work of breathing or eliminating exercise-induced arterial hypoxemia (EIAH) during exercise decreases the severity of quadriceps fatigue in men. Women have a greater work of breathing during exercise, dedicate a greater fraction of whole-body V̇O2 towards their respiratory muscles, and demonstrate EIAH, suggesting women may be especially susceptible to quadriceps fatigue. Healthy subjects (8M, 8F) completed three constant load exercise tests over four days. During the first (control) test, subjects exercised at ∼85% of maximum while arterial blood gases and work of breathing were assessed. Subsequent constant load exercise tests were iso-time and iso-work rate, but with EIAH prevented by inspiring hyperoxic gas or work of breathing reduced via a proportional assist ventilator (PAV). Quadriceps fatigue was assessed by measuring force in response to femoral nerve stimulation. For both sexes quadriceps force was equally reduced after the control trial (−27 ± 2% baseline) and was attenuated with hyperoxia and PAV (−18 ± 1 and −17 ± 2% baseline, P < 0.01, respectively), with no sex-difference. EIAH was similar between the sexes, and regardless of sex, subjects with the lowest oxyhaemoglobin saturation during the control test had the greatest quadriceps fatigue attenuation with hyperoxia (r2 = 0.79, P < 0.0001). For the PAV trial, despite reducing the work of breathing to a greater degree in men (men: 60 ± 5, women: 75 ± 6% control, P < 0.05), the attenuation of quadriceps fatigue was similar between the sexes (36 ± 4 vs. 37 ± 7%). Owing to a greater relative V̇O2 of the respiratory muscles in women, less of a change in work of breathing is needed to reduce quadriceps fatigue. This study was supported by the Natural Science and Engineering Research Council of Canada (NSERC). PBD, YMS and CMP were supported by a graduate scholarship from NSERC. PBD was also supported by the Canadian Thoracic Society.

The normal diaphragm has an inspiratory action on the lower ribs, but subjects with chronic obstructive pulmonary disease commonly have an inward displacement of the lateral portions of the lower rib cage during inspiration. This paradoxical displacement, conventionally called 'Hoover's sign', has traditionally been attributed to the direct action of radially oriented diaphragmatic muscle fibres. In the present study, the inspiratory intercostal muscles in all interspaces in anaesthetized dogs were severed so that the diaphragm was the only muscle active during inspiration. The displacements of the lower ribs along the craniocaudal and laterolateral axes and the changes in pleural pressure (∆Ppl) and transdiaphragmatic pressure were measured during occluded breaths and mechanical ventilation at different lung volumes between functional residual capacity (FRC) and total lung capacity. From these data, the separate effects on rib displacement of ∆Ppl and of the force exerted by the diaphragm on the ribs were determined. Isolated spontaneous diaphragm contraction at FRC displaced the lower ribs cranially and outward, but this motion was progressively reversed into a caudal and inward motion as lung volume increased. However, although the force exerted by the diaphragm on the ribs decreased with increasing volume, it continued to displace the ribs cranially and outward. These observations suggest that Hoover's sign is usually caused by the decrease in the zone of apposition and, thus, by the dominant effect of ∆Ppl on the lower ribs, rather than an inward pull from the diaphragm.

The main physiological impact of high flow nasal cannula (HFNC) therapy is presumed to be a decrease in work of breathing (WOB). To assess this, diaphragmatic electrical activity and esophageal pressure changes were measured off then on HFNC delivered at 2 L/kg/min, in 14 infants with bronchiolitis and 14 cardiac infants. Electrical activity of the diaphragm (Edi) was measured using an Edi catheter with calculations of signal peak (EdiMAX ) and amplitude (EdiAMPL ). Pressure-rate and pressure-time products (PRP, PTP) were calculated from analyses of esophageal pressure. Changes in end-expiratory lung volume were measured using respiratory inductance plethysmography (RIPEEL ). The EdiMAX and EdiAMPL were significantly higher in infants with bronchiolitis than in cardiac infants (P < 0.05). Within the bronchiolitis group, both were significantly reduced between HFNC states from 27.9 µV [20.4, 35.4] to 21.0 µV [14.8, 27.2] and from 25.1 µV [18.0, 32.2] to 19.2 µV [13.3, 25.1], respectively (mean, 95% CI, P < 0.05). A less prominent offload of the diaphragm was observed in cardiac infants (P < 0.05). WOB decreased in both groups with a significant reduction of PRP and PTP (P < 0.05). RIPEEL increased significantly in bronchiolitis only (P < 0.05). HFNC offloads the diaphragm and reduces the WOB in bronchiolitis. A similar effect was demonstrated in cardiac infants, a group without signs of airway-obstruction.

Summary Viral croup is a frequent disease in early childhood. Although it is usually self-limited, it may occasionally become life-threatening. Mild croup is characterized by the presence of stridor without intercostal retractions, whereas moderate-to-severe croup is accompanied by increased work of breathing. A single dose of orally administered dexamethasone (0.15–0.6 mg/kg) is the mainstay of treatment with addition of nebulized epinephrine only in cases of moderate-to-severe croup. Nebulized budesonide (2 mg) can be given alternatively to children who do not tolerate oral dexamethasone. Exposure to cold air or administration of cool mist are treatment interventions for viral croup that are not supported by published evidence, but breathing heliox can potentially reduce the work of breathing related to upper airway obstruction. In summary, corticosteroids may decrease the intensity of viral croup symptoms irrespective to their severity on presentation to the emergency department. Pediatr Pulmonol. 2014; 49:421–429. © 2013 Wiley Periodicals, Inc.

Summary Background High flow nasal cannula (HFNC) improves ventilation by washing out nasopharyngeal dead space while delivering oxygen. Heliox (helium–oxygen gas mixture), a low-density gas mixture, decreases resistance to airflow, reduces the work of breathing, and facilitates distribution of inspired gas. Excessive lung work and potential injury increases the workload on the immature diaphragm predisposing the muscle to fatigue, and can lead to inflammatory and oxidative stress, thereby contributing to impaired diaphragmatic function. We tested the hypothesis that HFNC with Heliox will decrease the work of breathing thereby unloading the neonatal diaphragm, and potentially reducing diaphragmatic injury. Methods Spontaneously breathing neonatal pigs were randomized to Nitrox (nitrogen–oxygen gas mixture) or Heliox, and studied over 4 hr following oleic acid injury. Gas exchange, pulmonary mechanics indices, and systemic markers of inflammation were measured serially. Diaphragm inflammation biomarkers and histology for muscle injury were assessed at termination. Results Heliox breathing animals demonstrated decreased respiratory load and work of breathing with lower pressure-rate product, lower labored breathing index, and lower levels of diaphragmatic inflammatory markers, and muscle injury score as compared to Nitrox. Conclusion These results suggest that HFNC with Heliox is a useful adjunct to attenuate diaphragmatic fatigue in the presence of lung injury by unloading the diaphragm, resulting in a more efficient breathing pattern, and decreased diaphragm injury. Pediatr Pulmonol. 2014; 49:1214–1222. © 2014 Wiley Periodicals, Inc.

We investigated whether heat‐induced hyperventilation can be voluntarily prevented, and, if so, how this modulates respiratory mechanics and cerebral blood flow in resting heated humans. In two separate trials, 10 healthy men were passively heated using lower body hot‐water immersion and a water‐perfused garment covering their upper body (both 41°C) until esophageal temperature (T es) reached 39°C or volitional termination. In each trial, participants breathed normally (normal‐breathing) or voluntarily controlled minute ventilation (V E) at a level equivalent to that observed after 5 min of heating (controlled‐breathing). Respiratory gases, middle cerebral artery blood velocity (MCAV), work of breathing, and end‐expiratory and inspiratory lung volumes were measured. During normal‐breathing, V E increased as T es rose above 38.0 ± 0.3°C, whereas controlled‐breathing diminished the increase in V E (V E at T es = 38.6°C: 25.6 ± 5.9 and 11.9 ± 1.3 L min−1 during normal‐ and controlled‐breathing, respectively, P

In patients with highly contagious diseases that are spread by respiratory droplets or air-borne particles, the use of high-flow oxygen may carry a significant risk of nosocomial transmission. We tested a new oxygen delivery device designed to address these problems by simulating 108 patients with sepsis and respiratory failure. The device being tested consisted of an airtight mask, a bacterial and viral filter, a T-shaped reservoir (50 and 100 ml) and oxygen delivery tubing connected directly to the mask. When tested with a 50-ml reservoir, a high fractional oxygen concentration was achieved: mean (SD) 0.83 (0.11) at a flow of 15 l.min(-1) oxygen. The 50-ml reservoir, when compared with the 100-ml reservoir, was associated with reduced carbon dioxide rebreathing (mean (SD) inspired fractional carbon dioxide concentration 2.5 (1.0) vs 3.0 (1.1), respectively, p = 0.009) and reduced inspiratory resistive work of breathing (mean (SD) 1.0 (0.6) J.l(-1) vs 1.2 (0.5) J.l(-1), respectively, p = 0.028). However, rebreathing and work of breathing were relatively high if a high respiratory rate was simulated. We conclude that the novel oxygen device we describe, equipped with the 50-ml T-shaped reservoir, is suitable for potentially infectious patients with type-1 respiratory failure but without marked tachypnoea.

The purpose of this study was to characterize exercise-induced arterial hypoxaemia (EIAH), pulmonary gas exchange and respiratory mechanics during exercise, in young healthy women. We defined EIAH as a >10 mmHg decrease in arterial oxygen tension ( ) during exercise compared to rest. We used a heliox inspirate to test the hypothesis that mechanical constraints contribute to EIAH. Subjects with a spectrum of aerobic capacities (n = 30; maximal oxygen consumption ( ) = 49 ± 1, range 28-62 ml kg(-1) min(-1)) completed a stepwise treadmill test and a subset (n = 18 with EIAH) completed a constant load test (~85% ) with heliox gas. Throughout exercise arterial blood gases, oxyhaemoglobin saturation ( ), the work of breathing (WOB) and expiratory flow limitation (EFL) were assessed. Twenty of the 30 women developed EIAH with a nadir and ranging from 58 to 88 mmHg and 87 to 96%, respectively. At maximal exercise, was inversely related to (r = -0.57, P < 0.05) with notable exceptions where some subjects with low aerobic fitness levels demonstrated EIAH. Subjects with EIAH had a greater (51 ± 1 vs. 43 ± 2 ml kg(-1) min(-1)), lower end-exercise (93.2 ± 0.5 vs. 96.1 ± 0.3%) and a greater maximal energetic WOB (324 ± 19 vs. 247 ± 23 J min(-1)), but had similar resting pulmonary function compared to those without EIAH. Most subjects developed EIAH at submaximal exercise intensities, with distinct patterns of hypoxaemia. In some subjects with varying aerobic fitness levels, mechanical ventilatory constraints (i.e. EFL) were the primary mechanism associated with the hypoxaemia during the maximal test. Mechanical ventilatory constraints also prevented adequate compensatory alveolar hyperventilation in most EIAH subjects. Minimizing mechanical ventilatory constraints with heliox inspiration partially reversed EIAH in subjects who developed EFL. In conclusion, healthy women of all aerobic fitness levels can develop EIAH and begin to do so at submaximal intensities. Mechanical ventilatory constraints are a primary mechanism for EIAH in some healthy women and prevent reversal of hypoxaemia in women for whom it is not the primary mechanism.

Summary Background Conventional endotracheal pediatric tubes offer high resistance due to their small diameters and relatively high flow during ventilation. Any increase of the diameter of the tube lumen decreases the airway resistance and subsequently, the work of breathing (WOB). We compared ventilation mechanics using a new, cone-shaped endotracheal tube of our design to the Cole and standard tubes. Methods The study has been divided into three parts: (i) preliminary laboratory tests, (ii) in vitro study with infant lung model, and (iii) clinical study in infants. Flow resistance and WOB were compared, using standard, Cole (in experimental phase only) and cone tubes. Results We proved that inspiratory (Ri) and expiratory (Re) resistance, and WOB, were significantly lower in patients ventilated via a cone tube. Mean Ri decreased by 37%, compared with the baseline values, Re – by 35%, and total WOB – by 12%. Conclusion The cone tube offers lower resistance to gas flow than the standard, used nowadays in clinical practice. It can be especially beneficial to spontaneously breathing patients reducing WOB and improving gas exchange.

A 4-year-old girl with bilateral vocal fold palsy was successfully decannulated from tracheotomy after seven laryngeal procedures. But an important stridor and dyspnea recurred 13 months after decannulation. Nocturnal gas exchange was normal but her daytime work of breathing was increased by fourfold, without any beneficial effect of nasal noninvasive continuous positive airway pressure ventilation (CPAP), reflecting a severe fixed airway obstruction. Endoscopic examination confirmed the work of breathing findings showing glottic and supraglottic stenosis. This upper airway obstruction was successfully treated with a recannulation. In conclusion, the major message of this case report is that measurement of the work of breathing was able to document the "fixed" nature of the airway obstruction, by showing no improvement even with highest tolerated levels of nasal CPAP. As such, the work of breathing may be proposed as a screening tool to quantify and assess the reversibility of severe upper airway obstruction in children.

Given that aerobic metabolism is the predominant energy pathway for most sports, the respiratory system can be a rate-limiting factor in the exercise capacity of fit and healthy horses. Consequently, respiratory diseases, even in mild forms, are potentially deleterious to any athletic performance. The functional impairment associated with a respiratory condition depends on the degree of severity of the disease and the equestrian discipline involved. Respiratory abnormalities generally result in an increase in respiratory impedance and work of breathing and a reduced level of ventilation that can be detected objectively by deterioration in breathing mechanics and arterial blood gas tensions and/or lactataemia. The overall prevalence of airway diseases is comparatively high in equine athletes and may affect the upper airways, lower airways or both. Diseases of the airways have been associated with a wide variety of anatomical and/or inflammatory conditions. In some instances, the diagnosis is challenging because conditions can be subclinical in horses at rest and become clinically relevant only during exercise. In such cases, an exercise test may be warranted in the evaluation of the patient. The design of the exercise test is critical to inducing the clinical signs of the problem and establishing an accurate diagnosis. Additional diagnostic techniques, such as airway sampling, can be valuable in the diagnosis of subclinical lower airway problems that have the capacity to impair performance. As all these techniques become more widely used in practice, they should inevitably enhance veterinarians' diagnostic capabilities and improve their assessment of treatment effectiveness and the long-term management of equine athletes.

Horses are elite athletes when compared with other mammalian species. In the latter, performance is limited by cardiovascular or musculoskeletal performance whereas in athletic horses it is the respiratory system that appears to be rate limiting and virtually all horses exercising at high intensities become hypoxaemic and hypercapnoeic. This is due to both diffusion limitation and a level of ventilation inadequate for the metabolic level that enables horses to exercise at these intensities. In conjunction with these blood gas changes, total pulmonary resistance increases and the work of breathing rises exponentially and airflow eventually plateaus despite increases in inspiratory and expiratory intrapleural pressures. Horses breathe at comparatively high frequencies when galloping due to the tight 1:1 coupling of strides to breathing. Whether this effects gas exchange and, if so, to what extent, has not been fully elucidated.

ACADEMIC EMERGENCY MEDICINE 2012; 19: 421–429 © 2012 by the Society for Academic Emergency Medicine Abstract Objectives: This study assessed the feasibility of an investigational vagus nerve stimulation (VNS) device for treating acute asthma exacerbations in patients not responding to at least 1 hour of initial standard care therapy. Methods: This was a prospective, nonrandomized study of patients treated in the ED for moderate to severe acute asthma (forced expiratory volume in 1 second [FEV1] 25% to 70% of predicted). Treatment entailed percutaneous placement of an electrode near the right carotid sheath and 60 minutes of VNS and continued standard care. VNS voltage was adjusted to perceived improvement, muscle twitching, or adverse events (AEs). All AEs, vital signs, FEV1, perceived work of breathing (WOB), and final disposition were recorded. Results: Twenty-five subjects were enrolled. There were no serious AEs and no significant changes in vital signs. No subject required terminating VNS. One patient had minor bleeding from the procedure, and one had a hematoma and withdrew prior to VNS. AEs related to VNS were temporary and included cough (1 of 24), swallowing difficulty (2 of 24), voice change (2 of 24), and muscle twitching (14 of 24). These resolved when VNS ended. The FEV1 improved at 15 minutes (median = 15.8%, 95% confidence interval [CI] = 9.3% to 22.4%), 30 minutes (median = 21.3%, 95% CI = 8.1% to 36.5%), and 60 minutes (median = 27.5%, 95% CI = 11.3% to 43.5%). WOB improved at 15 minutes (median = 53.9%, 95% CI = 33.7% to 73.9%), 30 minutes (median = 69.1%, 95% CI = 56.4% to 81.8%), and 60 minutes (median = 81.0%, 95% CI = 68.5% to 93.5%). Conclusions: Percutaneous VNS did not result in serious AEs and was associated with improvements in FEV1 and perceived dyspnea. Percutaneous VNS appears to be feasible for use in the treatment of moderate to severe acute asthma in patients unresponsive to initial standard care treatment.

Obesity, particularly severe central obesity, affects respiratory physiology both at rest and during exercise. Reductions in expiratory reserve volume, functional residual capacity, respiratory system compliance and impaired respiratory system mechanics produce a restrictive ventilatory defect. Low functional residual capacity and reductions in expiratory reserve volume increase the risk of expiratory flow limitation and airway closure during quiet breathing. Consequently, obesity may cause expiratory flow limitation and the development of intrinsic positive end expiratory pressure, especially in the supine position. This increases the work of breathing by imposing a threshold load on the respiratory muscles leading to dyspnoea. Marked reductions in expiratory reserve volume may lead to ventilation distribution abnormalities, with closure of airways in the dependent zones of the lungs, inducing ventilation perfusion mismatch and gas exchange abnormalities. Obesity may also impair upper airway mechanical function and neuromuscular strength, and increase oxygen consumption, which in turn, increase the work of breathing and impair ventilatory drive. The combination of ventilatory impairment, excess CO2 production and reduced ventilatory drive predisposes obese individuals to obesity hypoventilation syndrome.

Central chemoreception traditionally refers to a change in ventilation attributable to changes in CO2/H(+) detected within the brain. Interest in central chemoreception has grown substantially since the previous Handbook of Physiology published in 1986. Initially, central chemoreception was localized to areas on the ventral medullary surface, a hypothesis complemented by the recent identification of neurons with specific phenotypes near one of these areas as putative chemoreceptor cells. However, there is substantial evidence that many sites participate in central chemoreception some located at a distance from the ventral medulla. Functionally, central chemoreception, via the sensing of brain interstitial fluid H(+), serves to detect and integrate information on (i) alveolar ventilation (arterial PCO2), (ii) brain blood flow and metabolism, and (iii) acid-base balance, and, in response, can affect breathing, airway resistance, blood pressure (sympathetic tone), and arousal. In addition, central chemoreception provides a tonic "drive" (source of excitation) at the normal, baseline PCO2 level that maintains a degree of functional connectivity among brainstem respiratory neurons necessary to produce eupneic breathing. Central chemoreception responds to small variations in PCO2 to regulate normal gas exchange and to large changes in PCO2 to minimize acid-base changes. Central chemoreceptor sites vary in function with sex and with development. From an evolutionary perspective, central chemoreception grew out of the demands posed by air versus water breathing, homeothermy, sleep, optimization of the work of breathing with the "ideal" arterial PCO2, and the maintenance of the appropriate pH at 37°C for optimal protein structure and function.

Aim: The aim of this study was to investigate the effect of different pattern of spontaneous breathing on the respiratory mechanics and on the integrity of the pulmonary extracellular matrix. Methods: Experiments were performed on adult healthy rats in which different spontaneously breathing pattern was elicited through administration of two commonly used anaesthetic mixtures: pentobarbital/urethane (P/U) and ketamine/medetomidine (K/M). The animals (five per group) were randomized and left to spontaneously breath for 10 min (P/U-sham; K/M-sham) or for 4 h (P/U-4 h; K/M-4 h), targeting the anaesthesia level to obtain a tidal volume of about 8 mL kg−1 body wt. At the end of the experiment, lung matrix integrity was assessed through determination of the glycosaminoglycans (GAGs) content in the lung parenchyma. Results: Compared with K/M, anaesthesia with P/U cocktail induced: (1) a higher respiratory rate and minute ventilation attained with lower PaCO2; (2) a higher pressure-time-product and work of breathing per minute; (3) a lower static lung compliance; (4) an increased activation of lung tissue metalloproteases; and (5) greater extraction of pulmonary interstitial GAGs. Conclusions: This study suggests that the breathing pattern induced by the different anaesthetic regimen may damage the pulmonary interstitium even during spontaneous breathing at physiological tidal volumes.