Inspiratory Threshold Loading Research Articles

Influence of inspiratory threshold load on cardiovascular responses to controlled breathing at 0.1 Hz.

Slow, deep breathing is being used as a self-management intervention for various health conditions including pain and hypertension. Stimulation of the arterial baroreceptors and increased vagal modulation are among the proposed mechanisms for the therapeutic effects of slow, deep breathing. We investigated whether adding inspiratory threshold load can enhance the cardiovascular responses to controlled breathing at the frequency of 0.1Hz, a common form of slow, deep breathing. Healthy volunteers (N=29) performed controlled breathing at 0.1Hz (6 breaths/minute) without load and with inspiratory threshold loads of 5 cmH2 O and 10 cmH2 O. Respiratory airflow, heart rate, and blood pressure were continuously recorded. The amplitude of the systolic blood pressure variation during respiratory cycles increased with increasing loads. Respiratory sinus arrhythmia was higher during controlled breathing at 0.1Hz with the load of 10 cmH2 O compared to without load. Baroreflex sensitivity was not affected by loads. The effect of loads on respiratory sinus arrhythmia was mediated by increasing the amplitude of systolic blood pressure variation during respiratory cycles. These results suggest that applying small inspiratory threshold loads during controlled breathing at 0.1Hz increases cardiac vagal modulation by this breathing exercise. This effect seems to be mediated by stronger stimulation of the arterial baroreceptors because of larger systolic blood pressure swings along the respiratory cycle. The potential benefit of long-term practice of controlled breathing at 0.1Hz with inspiratory threshold loads on baroreflex function and cardiac vagal control needs to be investigated, particularly in pain and hypertension patients.

Inspiratory threshold loading reduces lipoperoxidation in obese and normal-weight subjects.

Obesity is related to increased oxidative stress. Although low-intensity physical exercise reduces oxidative stress, obese subjects may show exercise intolerance. For these subjects, inspiratory threshold loading could be an alternative tool to reduce oxidative stress. We investigated the effects of inspiratory threshold loading on biomarkers of oxidative stress in obese and normal-weight subjects. Twenty obese (31.4 ± 6 years old, 10 men and 10 women, 37.5 ± 4.7kg/m2) and 20 normal-weight (29.4 ± 8 years old, 10 men and 10 women, 23.2 ± 1.5kg/m2) subjects matched for age and gender participated in the study. Maximal inspiratory pressure (MIP) was assessed by a pressure transducer. Blood sampling was performed before and after loading and control protocols to assess thiobarbituric acid reactive substances (TBARS), protein carbonylation, and reduced glutathione. Inspiratory threshold loading was performed at 60% MIP and maintained until task failure. The 30-min control protocol was performed at 0cmH2O. Our results demonstrated that inspiratory threshold loading reduced TBARS across time in obese (6.21 ± 2.03 to 4.91 ± 2.14nmolMDA/ml) and normal-weight subjects (5.60 ± 3.58 to 4.69 ± 2.80nmolMDA/ml; p = 0.007), but no change was observed in protein carbonyls and glutathione in both groups. The control protocol showed no significant changes in TBARS and protein carbonyls. However, reduced glutathione was increased across time in both groups (obese: from 0.50 ± 0.37 to 0.56 ± 0.35μmol GSH/ml; normal-weight: from 0.61 ± 0.11 to 0.81 ± 0.23μmol GSH/ml; p = 0.002). These findings suggest that inspiratory threshold loading could be potentially used as an alternative tool to reduce oxidative stress in both normal-weight and obese individuals.

The use of cognitive mobile games to assess cognitive function of healthy subjects under various inspiratory loads

ObjectiveThe aim of this work was to determine if scoring mechanisms embedded in cognitive mobile games (CMG) designed for cognitive training are sensitive enough to detect changes in cognitive function induced by various acute respiratory loads in healthy subjects. Material and methodsThirty healthy subjects participated in this study (25 ± 4 years old, 13 women). A set of three brief CMG was used to assess cognitive function (Rush Back, Must Sort, True Color) in control situation and at four different inspiratory loads (through a mouthpiece without resistance and with 10, 50 and 70% of the maximal inspiratory pressure). ResultsStatistically significant decreases in CMG scores were observed in Rush Back (p = 0.032) and True Color (p = 0.002) when the subjects breathed through the mouthpiece without resistance compared to the control condition. A statistical difference was observed for Must Sort (p = 0.003) between baseline and 10% of Inspiratory Threshold Load (ITL). Significant differences for the three games were observed between the baseline and 50% of ITL and between baseline and 70% of ITL. ConclusionCMG designed for cognitive training are sensitive in detecting transitional changes in cognitive function induced by low, medium and high acute respiratory loads in healthy subjects. This offers interesting new possibilities for the assessment and long-term follow-up of patients suffering from chronic respiratory disease, since this type of assessment could easily be completed independently by patients in their own homes, and could be combined with rehabilitation exercises as an evaluative measure.

Noninvasive Assessment of Inspiratory Muscle Neuromechanical Coupling During Inspiratory Threshold Loading

Diaphragm neuromechanical coupling (NMC), which reflects the efficiency of conversion of neural activation to transdiaphragmatic pressure (Pdi), is increasingly recognized to be a useful clinical index of diaphragm function and respiratory mechanics in neuromuscular weakness and cardiorespiratory disease. However, the current gold standard assessment of diaphragm NMC requires invasive measurements of Pdi and crural diaphragm electromyography (oesEMGdi), which complicates the measurement of diaphragm NMC in clinical practice. This is the first study to compare invasive measurements of diaphragm NMC (iNMC) using the relationship between Pdi and oesEMGdi, with noninvasive assessment of NMC (nNMC) using surface mechanomyography (sMMGlic) and electromyography (sEMGlic) of lower chest wall inspiratory muscles. Both invasive and noninvasive measurements were recorded in twelve healthy adult subjects during an inspiratory threshold loading protocol. A linear relationship between noninvasive sMMGlic and sEMGlic measurements was found, resulting in little change in nNMC with increasing inspiratory load. By contrast, a curvilinear relationship between invasive Pdi and oesEMGdi measurements was observed, such that there was a progressive increase in iNMC with increasing inspiratory threshold load. Progressive recruitment of lower ribcage muscles, serving to enhance the mechanical advantage of the diaphragm, may explain the more linear relationship between sMMGlic and sEMGlic (both representing lower intercostal plus costal diaphragm activity) than between Pdi and crural oesEMGdi. Noninvasive indices of NMC derived from sEMGlic and sMMGlic may prove to be useful indices of lower chest wall inspiratory muscle NMC, particularly in settings that do not have access to invasive measures of diaphragm function.

Wearable Bioimpedance Measurement for Respiratory Monitoring During Inspiratory Loading

Bioimpedance is an unobtrusive noninvasive technique to measure respiration and has a linear relation with volume during normal breathing. The objective of this paper was to assess this linear relation during inspiratory loading protocol and determine the best electrode configuration for bioimpedance measurement. The inspiratory load is a way to estimate inspiratory muscle function and has been widely used in studies of respiratory mechanics. Therefore, this protocol permitted us to evaluate bioimpedance performance under breathing pattern changes. We measured four electrode configurations of bioimpedance and airflow simultaneously in ten healthy subjects using a wearable device and a standard wired laboratory acquisition system, respectively. The subjects were asked to perform an incremental inspiratory threshold loading protocol during the measurements. The load values were selected to increase progressively until the 60% of the subject's maximal inspiratory pressure. The linear relation of the signals was assessed by Pearson correlation (${r}$ ) and the waveform agreement by the mean absolute percentage error (MAPE), both computed cycle by cycle. The results showed a median greater than 0.965 in ${r}$ coefficients and lower than 11 % in the MAPE values for the entire population in all loads and configurations. Thus, a strong linear relation was found during all loaded breathing and configurations. However, one out of the four electrode configurations showed robust results in terms of agreement with volume during the highest load. In conclusion, bioimpedance measurement using a wearable device is a noninvasive and a comfortable alternative to classical methods for monitoring respiratory diseases in normal and restrictive breathing.

Validation of the Wii Balance Board to assess balance modifications induced by increased respiratory loads in healthy subjects

BackgroundThere is a link between breathing and balance and posture. When the inspiratory loads are increased by pathologies, there is a decrease of postural control. The increase of the inspiratory load on respiratory muscles is a common feature in various chronic pulmonary pathologies. Consequently, the balance of those patients is likely affected. Research questionThe aim of this study is to validate the use of the Nintendo Wii Balance Board (WBB) to assess balance modifications induced by increased respiratory loads in healthy subjects. MethodsThirty-seven healthy young participants (25 ± 4 years old, 17 women) participated in this study. Five different conditions were tested: without anything (control), throughout a mouthpiece, and throughout three inspiratory threshold loads (ITL) at 10% (low), 40% (mid) and 60% (high) of the maximal inspiratory pressure. Each trial lasted for 60 s. Nine parameters were extracted based on center of pressure displacement based on a previously-validated method. ANOVA tests were used to compare the different conditions followed by Bonferroni’s corrections. ResultsHighly statistically significant differences (all p < 0.01) and large effect sizes (all ω2 > 0.24) were obtained for all parameters between the different loads and the mouthpiece condition. There is a linear relationship between the load and balance perturbation. SignificanceIn this study, we demonstrated the validity of the WBB to detect the effect of the inspiratory load on balance in young healthy subjects. Further studies are needed to determine if such a kind of evaluation can be used in clinics with patients suffering from chronic respiratory disease.

Surface mechanomyography and electromyography provide non-invasive indices of inspiratory muscle force and activation in healthy subjects

The current gold standard assessment of human inspiratory muscle function involves using invasive measures of transdiaphragmatic pressure (Pdi) or crural diaphragm electromyography (oesEMGdi). Mechanomyography is a non-invasive measure of muscle vibration associated with muscle contraction. Surface electromyogram and mechanomyogram, recorded transcutaneously using sensors placed over the lower intercostal spaces (sEMGlic and sMMGlic respectively), have been proposed to provide non-invasive indices of inspiratory muscle activation, but have not been directly compared to gold standard Pdi and oesEMGdi measures during voluntary respiratory manoeuvres. To validate the non-invasive techniques, the relationships between Pdi and sMMGlic, and between oesEMGdi and sEMGlic were measured simultaneously in 12 healthy subjects during an incremental inspiratory threshold loading protocol. Myographic signals were analysed using fixed sample entropy (fSampEn), which is less influenced by cardiac artefacts than conventional root mean square. Strong correlations were observed between: mean Pdi and mean fSampEn |sMMGlic| (left, 0.76; right, 0.81), the time-integrals of the Pdi and fSampEn |sMMGlic| (left, 0.78; right, 0.83), and mean fSampEn oesEMGdi and mean fSampEn sEMGlic (left, 0.84; right, 0.83). These findings suggest that sMMGlic and sEMGlic could provide useful non-invasive alternatives to Pdi and oesEMGdi for the assessment of inspiratory muscle function in health and disease.

Correlation of surface respiratory electromyography with esophageal diaphragm electromyography

ObjectivesTo assess the correlation between surface respiratory electromyography(sEMG) and esophageal diaphragm electromyography(EMGdi) at different levels of neural respiratory drive (NRD). DesignRandomised parallel design controlled trial. SettingThe First Affiliated Hospital of Guangzhou Medical University. Participants15 healthy subjects and 1 severe to very severe stable COPD patients were studied. Interventions15 healthy subjects performed incremental inspiratory threshold loading (ILT) and 15 stable COPD patients underwent noninvasive positive pressure ventilation (NPPV).The correlation between EMGdi and sEMG at different NRD levels was analyzed. EMGdi was performed with a multi-pair esophageal electrode catheter; sEMG were was performed by surface diaphragm EMG(located in right anterior axillary line and left anterior axillary line respectively expressed as sEMGdi(r) andsEMGdi(l))、surface parasternal EMG(sEMGpara),and surface sternocleidomastoid EMG(sEMGsc).Signals were normalized using the peak EMG expressed as EMG%max. Primary and secondary outcome measuresThe mean ± standard deviation resting EMGdi%max was higher in patients with COPD than in healthy subjects (57.26%±15.45% vs13.64% ±4.96%, respectively; p < 0.001).During ILT and NPPV, EMGdi was correlated with sEMGdi (r), sEMGdi (1), sEMGpara and sEMGsc (r = 0.90, 0.87, 0.90, 0.90 and r = 0.92, 0.83, 0.92 and 0.71, respectively; all P < 0.001). ConclusionA strong relationship is present between NRD measured by EMGdi%max and NRD measured by sEMG%max. sEMG%max serves as a non-invasive marker of NRD.

Assessment of Inspiratory Muscle Activation using Surface Diaphragm Mechanomyography and Crural Diaphragm Electromyography.

The relationship between surface diaphragm mechanomyography (sMMGdi), as a noninvasive measure of inspiratory muscle mechanical activation, and crural diaphragm electromyography (oesEMGdi), as the invasive gold standard measure of diaphragm electrical activation, had not previously been examined. To investigate this relationship, oesEMGdi and sMMGdi were measured simultaneously in 6 healthy subjects during an incremental inspiratory threshold loading protocol, and analyzed using fixed sample entropy (fSampEn). A positive curvilinear relationship was observed between mean fSampEn sMMGdi and oesEMGdi (r = 0.67). Accordingly, an increasing electromechanical ratio was also observed with increasing inspiratory load. These findings suggest that sMMGdi could provide useful noninvasive measures of inspiratory muscle mechanical activation.

Inspiratory Muscle Rehabilitation in Critically Ill Adults. A Systematic Review and Meta-Analysis.

Respiratory muscle weakness is common in critically ill patients; the role of targeted inspiratory muscle training (IMT) in intensive care unit rehabilitation strategies remains poorly defined. The primary objective of the present study was to describe the range and tolerability of published methods for IMT. The secondary objectives were to determine whether IMT improves respiratory muscle strength and clinical outcomes in critically ill patients. We conducted a systematic review to identify randomized and nonrandomized studies of physical rehabilitation interventions intended to strengthen the respiratory muscles in critically ill adults. We searched the MEDLINE, Embase, HealthSTAR, CINAHL, and CENTRAL databases (inception to September Week 3, 2017) and conference proceedings (2012 to 2017). Data were independently extracted by two authors and collected on a standardized report form. A total of 28 studies (N = 1,185 patients) were included. IMT was initiated during early mechanical ventilation (8 studies), after patients proved difficult to wean (14 studies), or after extubation (3 studies), and 3 other studies did not report exact timing. Threshold loading was the most common technique; 13 studies employed strength training regimens, 11 studies employed endurance training regimens, and 4 could not be classified. IMT was feasible, and there were few adverse events during IMT sessions (nine studies; median, 0%; interquartile range, 0-0%). In randomized trials (n = 20), IMT improved maximal inspiratory pressure compared with control (15 trials; mean increase, 6 cm H2O; 95% confidence interval [CI], 5-8 cm H2O; pooled relative ratio of means, 1.19; 95% CI, 1.14-1.25) and maximal expiratory pressure (4 trials; mean increase, 9 cm H2O; 95% CI, 5-14 cm H2O). IMT was associated with a shorter duration of ventilation (nine trials; mean difference, 4.1 d; 95% CI, 0.8-7.4 d) and a shorter duration of weaning (eight trials; mean difference, 2.3 d; 95% CI, 0.7-4.0 d), but confidence in these pooled estimates was low owing to methodological limitations, including substantial statistical and methodological heterogeneity. Most studies of IMT in critically ill patients have employed inspiratory threshold loading. IMT is feasible and well tolerated in critically ill patients and improves both inspiratory and expiratory muscle strength. The impact of IMT on clinical outcomes requires future confirmation.

The Relationship Between Respiratory-Related Premotor Potentials and Small Perturbations in Ventilation.

Respiratory-related premotor potentials from averaged electroencephalography (EEG) over the motor areas indicate cortical activation in healthy participants to maintain ventilation in the face of moderate inspiratory or expiratory loads. These experimental conditions are associated with respiratory discomfort, i.e., dyspnea. Premotor potentials are also observed in resting breathing in patients with reduced automatic respiratory drive or respiratory muscle strength due to respiratory or neurological disease, presumably in an attempt to maintain ventilation. The aim of this study was to determine if small voluntary increases in ventilation or smaller load-capacity imbalances, that generate an awareness of breathing but aren’t necessarily dyspneic, give rise to respiratory premotor potentials in healthy participants. In 15 healthy subjects, EEG was recorded during voluntary large breaths (∼3× tidal volume, that were interspersed with smaller non-voluntary breaths in the same trial; in 10 subjects) and breathing with a ‘low’ inspiratory threshold load (∼7 cmH2O; in 8 subjects). Averaged EEG signals at Cz and FCz were assessed for premotor potentials prior to inspiration. Premotor potential incidence in large breaths was 40%, similar to that in the smaller non-voluntary breaths in the same trial (20%; p > 0.05) and to that in a separate trial of resting breathing (0%; p > 0.05). The incidence of premotor potentials was 25% in the low load condition, similar to that in resting breathing (0%; p > 0.05). In contrast, voluntary sniffs were always associated with a higher incidence of premotor potentials (100%; p < 0.05). We have demonstrated that in contrast to respiratory and neurological disease, there is no significant cortical contribution to increase tidal volume or to maintain the load-capacity balance with a small inspiratory threshold load in healthy participants as detected using event-related potential methodology. A lack of cortical contribution during loading was associated with low ratings of respiratory discomfort and minimal changes in ventilation. These findings advance our understanding of the neural control of breathing in health and disease and how respiratory-related EEG may be used for medical technologies such as brain-computer interfaces.

Weaning failure and respiratory muscle function: What has been done and what can be improved?

Respiratory muscle dysfunction, being a common cause of weaning failure, is strongly associated with prolonged mechanical ventilation (MV) and prolonged stay in intensive care units. Inspiratory muscle training (IMT) has been described as an important contributor to the treatment of respiratory muscle dysfunction in critically ill patients. Its effectiveness is however yet controversial. To discuss evidence for assessment of readiness and the effectiveness of interventions for liberation from MV, with special attention to the role of IMT. PubMed, LILACS, PEDro and Web of Science were searched for papers of assessment and treatment of patients who failed liberation from MV after at least one attempt published in English or Portuguese until June 2016. Weaning predictors are related to weaning success (86%-100% for sensitivity and 7%-69% for specificity) and work of breathing (73%-100% for sensitivity and 56%-100% for specificity). Spontaneous breathing trials (SBT), noninvasive MV and early mobilization have been reported to improve weaning outcomes. Two modalities of IMT were identified in five selected studies: 1) adjustment of ventilator trigger sensitivity 2) inspiratory threshold loading. Both IMT training modalities promoted significant increases in respiratory muscle strength. IMT with threshold loading showed positive effect on endurance compared to control. Methods to indentify respiratory muscle weakness in critically ill patients are feasible and described as indexes that show good accuracy. Individualized and supervised rehabilitation programs including IMT, SBT, noninvasive MV and early mobilization should be encouraged in patients with inspiratory muscle weakness.

Activation of respiratory muscles during respiratory muscle training

It is unknown which respiratory muscles are mainly activated by respiratory muscle training. This study evaluated Inspiratory Pressure Threshold Loading (IPTL), Inspiratory Flow Resistive Loading (IFRL) and Voluntary Isocapnic Hyperpnea (VIH) with regard to electromyographic (EMG) activation of the sternocleidomastoid muscle (SCM), parasternal muscles (PARA) and the diaphragm (DIA) in randomized order.Surface EMG were analyzed at the end of each training session and normalized using the peak EMG recorded during maximum inspiratory maneuvers (Sniff nasal pressure: SnPna, maximal inspiratory mouth occlusion pressure: PImax).41 healthy participants were included. Maximal activation was achieved for SCM by SnPna; the PImax activated predominantly PARA and DIA. Activations of SCM and PARA were higher in IPTL and VIH than for IFRL (p<0.05). DIA was higher applying IPTL compared to IFRL or VIH (p<0.05).IPTL, IFRL and VIH differ in activation of inspiratory respiratory muscles. Whereas all methods mainly stimulate accessory respiratory muscles, diaphragm activation was predominant in IPTL.

Experimental dyspnea as a stressor: differential cardiovegetative responses to inspiratory threshold loading in healthy men and women.

Dyspnea is associated with an emotional reaction that involves limbic activation. The inspiratory threshold load (ITL) is known to elicit a dyspneic response in healthy subjects. Laboratory-induced stress conditions have been shown to elicit sex-related differences in cardiovascular responses. The aim of this study was to evaluate how healthy men (n = 8) and women (n = 9) react and adapt to 5-min periods of ITL at three levels (low, medium, and high) in terms of heart rate (HR), temporal (RMSSD) and spectral (LF, HF, LF/HF ratio) HRV indexes, and rating of breathing discomfort. HR increased with low, medium, and high ITL in men, whereas it increased only with high ITL in women. LF/HF ratio increased at low ITL in both men and women. Modifications appear to depend essentially on increased LF in men and on reduced HF in women. In addition, HRV modifications differ between men and women, following the order of presentation of ITLs. Our results show a continuous and sustained stress in men (increased HR, LF, and LF/HF ratio across ITL presentation) and a stress adaptation in women. Subjective responses of breathing discomfort were not correlated with sympatho-vagal balance modifications for a subgroup of subjects (n = 10). Breathing against the ITL induced autonomic modifications that are different between men and women, i.e., driven by sympathetic mediated responses in men, whereas women showed a greater parasympathetic modulation of cardiovascular activity. These results highlight the role of the mechanical inspiratory load in the heart rate variability seen in chronic obstructive pulmonary disease.NEW & NOTEWORTHY Breathing against the ITL induced autonomic modifications driven by sympathetic mediated responses in men, whereas women showed a greater parasympathetic modulation of cardiovascular activity, even for low load. A stress circuit could be at the origin of autonomic modifications induced by ITL. Our results would underline the role of the mechanic inspiratory load in the abnormalities in heart rate variability seen in COPD patients.

Transdiaphragmatic pressure and neural respiratory drive measured during inspiratory muscle training in stable patients with chronic obstructive pulmonary disease.

PurposeInspiratory muscle training (IMT) is a rehabilitation therapy for stable patients with COPD. However, its therapeutic effect remains undefined due to the unclear nature of diaphragmatic mobilization during IMT. Diaphragmatic mobilization, represented by transdiaphragmatic pressure (Pdi), and neural respiratory drive, expressed as the corrected root mean square (RMS) of the diaphragmatic electromyogram (EMGdi), both provide vital information to select the proper IMT device and loads in COPD, therefore contributing to the curative effect of IMT. Pdi and RMS of EMGdi (RMSdi%) were measured and compared during inspiratory resistive training and threshold load training in stable patients with COPD.Patients and methodsPdi and neural respiratory drive were measured continuously during inspiratory resistive training and threshold load training in 12 stable patients with COPD (forced expiratory volume in 1 s ± SD was 26.1%±10.2% predicted).ResultsPdi was significantly higher during high-intensity threshold load training (91.46±17.24 cmH2O) than during inspiratory resistive training (27.24±6.13 cmH2O) in stable patients with COPD, with P<0.01 for each. Significant difference was also found in RMSdi% between high-intensity threshold load training and inspiratory resistive training (69.98%±16.78% vs 17.26%±14.65%, P<0.01).ConclusionWe concluded that threshold load training shows greater mobilization of Pdi and neural respiratory drive than inspiratory resistive training in stable patients with COPD.

Reduced Phrenic Motoneuron Recruitment during Sustained Inspiratory Threshold Loading Compared to Single-Breath Loading: A Twitch Interpolation Study

In humans, inspiratory constraints engage cortical networks involving the supplementary motor area. Functional magnetic resonance imaging (fMRI) shows that the spread and intensity of the corresponding respiratory-related cortical activation dramatically decrease when a discrete load becomes sustained. This has been interpreted as reflecting motor cortical reorganization and automatisation, but could proceed from sensory and/or affective habituation. To corroborate the existence of motor reorganization between single-breath and sustained inspiratory loading (namely changes in motor neurones recruitment), we conducted a diaphragm twitch interpolation study based on the hypothesis that motor reorganization should result in changes in the twitch interpolation slope. Fourteen healthy subjects (age: 21–40 years) were studied. Bilateral phrenic stimulation was delivered at rest, upon prepared and targeted voluntary inspiratory efforts (“vol”), upon unprepared inspiratory efforts against a single-breath inspiratory threshold load (“single-breath”), and upon sustained inspiratory efforts against the same type of load (“continuous”). The slope of the relationship between diaphragm twitch transdiaphragmatic pressure and the underlying transdiaphragmatic pressure was −1.1 ± 0.2 during “vol,” −1.5 ± 0.7 during “single-breath,” and −0.6 ± 0.4 during “continuous” (all slopes expressed in percent of baseline.percent of baseline−1) all comparisons significant at the 5% level. The contribution of the diaphragm to inspiration, as assessed by the gastric pressure to transdiaphragmatic pressure ratio, was 31 ± 17% during “vol,” 22 ± 16% during “single-breath” (p = 0.13), and 19 ± 9% during “continuous” (p = 0.0015 vs. “vol”). This study shows that the relationship between the amplitude of the transdiaphragmatic pressure produced by a diaphragm twitch and its counterpart produced by the underlying diaphragm contraction is not unequivocal. If twitch interpolation is interpreted as reflecting motoneuron recruitment, this study supports motor reorganization compatible with “diaphragm sparing” when an inspiratory threshold load becomes sustained.

Relieving dyspnoea by non-invasive ventilation decreases pain thresholds in amyotrophic lateral sclerosis

BackgroundDyspnoea is a threatening sensation of respiratory discomfort that presents many similarities with pain. Experimental dyspnoea in healthy subjects induces analgesia. This ‘dyspnoea-pain counter-irritation’ could, in reverse, imply that relieving...

Inspiratory muscle conditioning exercise and diaphragm gene therapy in Pompe disease: Clinical evidence of respiratory plasticity

Pompe disease is an inherited disorder due to a mutation in the gene that encodes acid α-glucosidase (GAA). Children with infantile-onset Pompe disease develop progressive hypotonic weakness and cardiopulmonary insufficiency that may eventually require mechanical ventilation (MV). Our team conducted a first in human trial of diaphragmatic gene therapy (AAV1-CMV-GAA) to treat respiratory neural dysfunction in infantile-onset Pompe. Subjects (aged 2–15years, full-time MV: n=5, partial/no MV: n=4) underwent a period of preoperative inspiratory muscle conditioning exercise. The change in respiratory function after exercise alone was compared to the change in function after intramuscular delivery of AAV1-CMV-GAA to the diaphragm with continued exercise. Since AAV-mediated gene therapy can reach phrenic motoneurons via retrograde transduction, we hypothesized that AAV1-CMV-GAA would improve dynamic respiratory motor function to a greater degree than exercise alone. Dependent measures were maximal inspiratory pressure (MIP), respiratory responses to inspiratory threshold loads (load compensation: LC), and physical evidence of diaphragm activity (descent on MRI, EMG activity). Exercise alone did not change function. After AAV1-CMV-GAA, MIP was unchanged. Flow and volume LC responses increased after dosing (p<0.05 to p<0.005), but only in the subjects with partial/no MV use. Changes in LC tended to occur on or after 180days. At Day 180, the four subjects with MRI evidence of diaphragm descent had greater maximal voluntary ventilation (p<0.05) and tended to be younger, stronger, and use fewer hours of daily MV. In conclusion, combined AAV1-CMV-GAA and exercise training conferred benefits to dynamic motor function of the diaphragm. Children with a higher baseline neuromuscular function may have greater potential for functional gains.

Recruitment and Deoxygenation of Selected Respiratory and Skeletal Muscles During Incremental Loading in Stable COPD Patients.

To evaluate changes in oxygenated (O2Hb), deoxygenated (HHb), and total hemoglobin (tHb) of the sternocleidomastoid (SCM), parasternal (PS), biceps (BC), and tibialis anterior (TA) using near-infrared spectroscopy during incremental loading of the inspiratory muscles and the elbow flexors in people with stable chronic obstructive pulmonary disease. Fifteen participants with obstructive pulmonary disease were recruited in a repeated-measures crossover design. Near-infrared spectroscopy optodes were applied over the SCM, PS, BC, and TA to measure O2Hb, HHb, and tHb. Participants were randomly assigned to perform incremental inspiratory threshold loading or elbow flexor loading that imposed higher loads every 2 minutes until task failure. At least 1 week later, participants performed the other test. Arterial oxygen saturation (SpO2) was monitored continuously. O2Hb of the main agonist muscles, SCM and BC, decreased compared with the other muscles during inspiratory threshold loading and elbow flexor loading, respectively. SCM O2Hb and BC O2Hb decreased at higher loads compared with baseline. SCM tHb and HHb increased, whereas TA tHb decreased during inspiratory threshold loading. tHb did not change among any muscles during elbow flexor loading. SpO2 did not change from baseline to task failure. Our data suggest that the SCM was recruited progressively during incremental inspiratory threshold loading; however, O2Hb was not maintained in this muscle. Similarly, O2Hb was not maintained in the biceps during elbow flexor loading. This regional deoxygenation in SCM and BC during incremental loading protocols was not reflected by a decrease in SpO2.

Nefopam, a non-opioid analgesic, does not alleviate experimental work/effort dyspnoea in healthy humans: A randomised controlled trial

BackgroundDyspnoea is a distressing and debilitating symptom with a major impact on quality of life. Alleviation of dyspnoea therefore constitutes a major clinical challenge. When causative physiological disorders cannot be corrected (“persistent dyspnoea”), nonspecific treatment must be considered. Morphine alleviates dyspnoea but has numerous side-effects including ventilatory depression, which justifies looking for alternatives. Certain forms of dyspnoea involve C-fibres, and can be attenuated by C-fibres blockade. We hypothesised that nefopam, a non-sedative benzoxazocine analgesic known to block the transient receptor potential vanilloid subtype 1 abundantly present on C-fibres, would attenuate dyspnoea. MethodsWe conducted a randomised, double-blind, placebo-controlled crossover study of nefopam in healthy subjects submitted to experimental work/effort dyspnoea by inspiratory threshold loading (15 healthy male volunteers; age 23–41). We studied a perceptual outcome (dyspnoea visual analogue scale —D-VAS—) and a neurophysiological outcome (effect of nefopam on dyspnoea-pain counter-irritation as assessed by laser-evoked potentials; an effect of nefopam on dyspnoea was hypothetised to reduce the ability of dyspnoea to inhibit pain). Somaesthetic evoked potentials (SEPs) were studied as a control. ResultsA statistically significant decrease in LEP amplitude was observed in response to loading with nefopam (F = 19.1; p < 0.001) and placebo (F = 5.73 and p < 0.001), with no significant difference between nefopam and placebo and no change in SEP characteristics. ConclusionsIn this study, nefopam did not exhibit any effects on dyspnoea.