Respiratory muscle activity related to flow and lung volume in preterm infants compared with term infants

Infants with chronic lung disease (CLD) have a capacity to maintain functional lung volume despite alterations to their lung mechanics. We hypothesize that they achieve this by altering breathing patterns and dynamic elevation of lung volume, leading to differences in the relationship between respiratory muscle activity, flow and lung volume. Lung function and transcutaneous electromyography of the respiratory muscles (rEMG) were measured in 20 infants with CLD and in 39 healthy age-matched controls during quiet sleep. We compared coefficient of variations (CVs) of rEMG and the temporal relationship of rEMG variables, to flow and lung volume [functional residual capacity (FRC)] between these groups. The time between the start of inspiratory muscle activity and the resulting flow (tria)--in relation to respiratory cycle time--was significantly longer in infants with CLD. Although FRC had similar associations with tria and postinspiratory activity (corrected for respiratory cycle time), the CV of the diaphragmatic rEMG was lower in CLD infants (22.6 versus 31.0%, p = 0.030). The temporal relationship of rEMG to flow and FRC and the loss of adaptive variability provide additional information on coping mechanisms in infants with CLD. This technique could be used for noninvasive bedside monitoring of CLD.

Relative impact of respiratory muscle activity on tidal flow and end expiratory volume in healthy neonates

INTRODUCTION: It has been suggested that infants dynamically regulate their tidal flow and end-expiratory volume level. The interaction between muscle activity, flow and lung volume in spontaneously sleeping neonates is poorly studied, since it requires the assessment of transcutaneous electromyography of respiratory muscles (rEMG) in matched comparison to lung function measurements. METHODS: After determining feasibility and repeatability of rEMG in 20 spontaneously sleeping healthy neonates, we measured the relative impact of intercostal and diaphragmatic EMG activity in direct comparison to the resulting tidal flow and FRC. RESULTS: We found good feasibility, repeatability and correlation of timing indices between rEMG activity and flow. The rEMG amplitude was significantly dependent on the resistive load of the face mask. Diaphragm and intercostal muscle activity commenced prior to the onset of flow and remained active during the expiratory cycle. The relative contribution of intercostal and diaphragmatic activity to flow was variable and changed dynamically. CONCLUSION: Using matched rEMG, air flow and lung volume measurements, we have found good feasibility and repeatability of intercostal and diaphragm rEMG measurements and provide the first quantitative measures of the temporal relationship between muscle activity and flow in spontaneously sleeping healthy neonates. Lung mechanical function is dynamically regulated and adapts on a breath to breath basis. So, non-invasive rEMG measurements alone or in combination with lung function might provide a more comprehensive picture of pulmonary mechanics in future studies. The data describing the timing of EMG and flow may be important for future studies of EMG triggered mechanical ventilation.

The influence of muscle strength on the gait profile score (GPS) across different patients

BACKGROUND Muscle strength greatly influences gait kinematics. The question was whether this association is similar in different diseases. METHODS Data from instrumented gait analysis of 716 patients were retrospectively assessed. The effect of muscle strength on gait deviations, namely the gait profile score (GPS) was evaluated by means of generalised least square models. This was executed for seven different patient groups. The groups were formed according to the type of disease: orthopaedic/neurologic, uni-/bilateral affection, and flaccid/spastic muscles. RESULTS Muscle strength had a negative effect on GPS values, which did not significantly differ amongst the different patient groups. However, an offset of the GPS regression line was found, which was mostly dependent on the basic disease. Surprisingly, spastic patients, who have reduced strength and additionally spasticity in clinical examination, and flaccid neurologic patients showed the same offset. Patients with additional lack of trunk control (Tetraplegia) showed the largest offset. CONCLUSION Gait kinematics grossly depend on muscle strength. This was seen in patients with very different pathologies. Nevertheless, optimal correction of biomechanics and muscle strength may still not lead to a normal gait, especially in that of neurologic patients. The basic disease itself has an additional effect on gait deviations expressed as a GPS-offset of the linear regression line.

Magnesium in cystic fibrosis - Systematic review of the literature

BACKGROUND The metabolism of sodium, potassium, and chloride and the acid-base balance are sometimes altered in cystic fibrosis. Textbooks and reviews only marginally address the homeostasis of magnesium in cystic fibrosis. METHODS We performed a search of the Medical Subject Headings terms (cystic fibrosis OR mucoviscidosis) AND (magnesium OR hypomagnes[a]emia) in the US National Library of Medicine and Excerpta Medica databases. RESULTS We identified 25 reports dealing with magnesium and cystic fibrosis. The results of the review may be summarized as follows. First, hypomagnesemia affects more than half of the cystic fibrosis patients with advanced disease; second, magnesemia, which is normally age-independent, relevantly decreases with age in cystic fibrosis; third, aminoglycoside antimicrobials frequently induce both acute and chronic renal magnesium-wasting; fourth, sweat magnesium concentration was normal in cystic fibrosis patients; fifth, limited data suggest the existence of an impaired intestinal magnesium balance. Finally, stimulating observations suggest that magnesium supplements might achieve an improvement in respiratory muscle strength and mucolytic activity of both recombinant and endogenous deoxyribonuclease. CONCLUSIONS The first comprehensive review of the literature confirms that, despite being one of the most prevalent minerals in the body, the importance of magnesium in cystic fibrosis is largely overlooked. In these patients, hypomagnesemia should be sought once a year. Furthermore, the potential of supplementation with this cation deserves more attention.

Nerve excitability changes in critical illness polyneuropathy

Patients in intensive care units frequently suffer muscle weakness and atrophy due to critical illness polyneuropathy (CIP), an axonal neuropathy associated with systemic inflammatory response syndrome and multiple organ failure. CIP is a frequent and serious complication of intensive care that delays weaning from mechanical ventilation and increases mortality. The pathogenesis of CIP is not well understood and no specific therapy is available. The aim of this project was to use nerve excitability testing to investigate the changes in axonal membrane properties occurring in CIP. Ten patients (aged 37-76 years; 7 males, 3 females) were studied with electrophysiologically proven CIP. The median nerve was stimulated at the wrist and compound action potentials were recorded from abductor pollicis brevis muscle. Strength-duration time constant, threshold electrotonus, current-threshold relationship and recovery cycle (refractoriness, superexcitability and late subexcitability) were recorded using a recently described protocol. In eight patients a follow-up investigation was performed. All patients underwent clinical examination and laboratory investigations. Compared with age-matched normal controls (20 subjects; aged 38-79 years; 7 males, 13 females), CIP patients exhibited reduced superexcitability at 7 ms, from -22.3 +/- 1.6% to -7.6 +/- 3.1% (mean +/- SE, P approximately 0.0001) and increased accommodation to depolarizing (P < 0.01) and hyperpolarizing currents (P < 0.01), indicating membrane depolarization. Superexcitability was reduced both in patients with renal failure and without renal failure. In the former, superexcitability correlated with serum potassium (R = 0.88), and late subexcitability was also reduced (as also occurs owing to hyperkalaemia in patients with chronic renal failure). In patients without renal failure, late subexcitability was normal, and the signs of membrane depolarization correlated with raised serum bicarbonate and base excess, indicating compensated respiratory acidosis. It is inferred that motor axons in these CIP patients are depolarized, in part because of raised extracellular potassium, and in part because of hypoperfusion. The chronic membrane depolarization may contribute to the development of neuropathy.

Muscle transcriptome adaptations with mild eccentric ergometer exercise

The muscle has a wide range of possibilities to adapt its phenotype. Repetitive submaximal concentric exercise (i.e., shortening contractions) mainly leads to adaptations of muscle oxidative metabolism and endurance while eccentric exercise (i.e., lengthening contractions) results in muscle growth and gain of muscle strength. Modified gene expression is believed to mediate these exercise-specific muscle adjustments. In the present study, early alterations of the gene expression signature were monitored by a muscle-specific microarray. Transcript profiling was performed on muscle biopsies of vastus lateralis obtained from six male subjects before and in a 24-h time course after a single bout of mild eccentric ergometer exercise. The eccentric exercise consisted of 15 min of eccentric cycling at 50% of the individual maximal concentric power output leading to muscle soreness (5.9 on a 0-10 visual analogue scale) and limited muscle damage (1.7-fold elevated creatine kinase activity). Muscle impairment was highlighted by a transient reduction in jumping height after the eccentric exercise. On the gene expression level, we observed a general early downregulation of detected transcripts, followed by a slow recovery close to the control values within the first 24 h post exercise. Only very few regulatory factors were increased. This expression signature is different from the signature of a previously published metabolic response after an intensive endurance-type concentric exercise as well as after maximal eccentric exercise. This is the first description of the time course of changes in gene expression as a consequence of a mild eccentric stimulus.

Relationships between structural and functional measures of nutritional status in a normally nourished population

Both anthropometric and functional measurements have been used in nutritional assessment and monitoring. Hand dynamometry is a predictor of surgical outcome and peak expiratory flow rate has been used as an index of respiratory muscle function. This study aims to measure in normal subjects the relationship between anthropometric measurements, voluntary muscle strength by hand grip dynamometry and respiratory muscle function by peak expiratory flow rate.

Combined aerobic/inspiratory muscle training vs. aerobic training in patients with chronic heart failure: The Vent-HeFT trial: a European prospective multicentre randomized trial

AIMS Vent-HeFT is a multicentre randomized trial designed to investigate the potential additive benefits of inspiratory muscle training (IMT) on aerobic training (AT) in patients with chronic heart failure (CHF). METHODS AND RESULTS Forty-three CHF patients with a mean age of 58 ± 12 years, peak oxygen consumption (peak VO2 ) 17.9 ± 5 mL/kg/min, and LVEF 29.5 ± 5% were randomized to an AT/IMT group (n = 21) or to an AT/SHAM group (n = 22) in a 12-week exercise programme. AT involved 45 min of ergometer training at 70-80% of maximum heart rate, three times a week for both groups. In the AT/IMT group, IMT was performed at 60% of sustained maximal inspiratory pressure (SPImax ) while in the AT/SHAM group it was performed at 10% of SPImax , using a computer biofeedback trainer for 30 min, three times a week. At baseline and at 3 months, patients were evaluated for exercise capacity, lung function, inspiratory muscle strength (PImax ) and work capacity (SPImax ), quality of life (QoL), LVEF and LV diameter, dyspnoea, C-reactive protein (CRP), and NT-proBNP. IMT resulted in a significantly higher benefit in SPImax (P = 0.02), QoL (P = 0.002), dyspnoea (P = 0.004), CRP (P = 0.03), and NT-proBNP (P = 0.004). In both AT/IMT and AT/SHAM groups PImax (P < 0.001, P = 0.02), peak VO2 (P = 0.008, P = 0.04), and LVEF (P = 0.005, P = 0.002) improved significantly; however, without an additional benefit for either of the groups. CONCLUSION This randomized multicentre study demonstrates that IMT combined with aerobic training provides additional benefits in functional and serum biomarkers in patients with moderate CHF. These findings advocate for application of IMT in cardiac rehabilitation programmes.

Sporadic late-onset nemaline myopathy with MGUS: long-term follow-up after melphalan and SCT.

OBJECTIVE Sporadic late-onset nemaline myopathy (SLONM) is a rare, late-onset myopathy that progresses subacutely. If associated with a monoclonal gammopathy of unknown significance (MGUS), the outcome is unfavorable: the majority of these patients die within 1 to 5 years of respiratory failure. This study aims to qualitatively assess the long-term treatment effect of high-dose melphalan (HDM) followed by autologous stem cell transplantation (SCT) in a series of 8 patients with SLONM-MGUS. METHODS We performed a retrospective case series study (n = 8) on the long-term (1-8 years) treatment effect of HDM followed by autologous SCT (HDM-SCT) on survival, muscle strength, and functional capacities. RESULTS Seven patients showed a lasting moderate-good clinical response, 2 of them after the second HDM-SCT. All of them had a complete, a very good partial, or a partial hematologic response. One patient showed no clinical or hematologic response and died. CONCLUSIONS This case series shows the positive effect of HDM-SCT in this rare disorder. Factors that may portend an unfavorable outcome are a long disease course before the hematologic treatment and a poor hematologic response. Age at onset, level and type of M protein (κ vs λ), and severity of muscle weakness were not associated with a specific outcome. CLASSIFICATION OF EVIDENCE This study provides Class IV evidence that for patients with SLONM-MGUS, HDM-SCT increases the probability of survival and functional improvement.

Cessation and resuming of alglucosidase alfa in Pompe disease: a retrospective analysis.

Enzyme replacement therapy (ERT) with recombinant human alglucosidase alfa (rhGAA) in late-onset Pompe disease is moderately effective. Little is known about the clinical course after treatment termination and the resumption of ERT. In Switzerland, rhGAA therapy for Pompe disease was temporarily withdrawn after the federal court judged that the treatment costs were greatly out of proportion compared to the benefits. Re-treatment was initiated after the therapy was finally licensed. We retrospectively analysed seven Pompe patients, who underwent cessation and resumption of ERT (median age 43 years). The delay from first symptoms to final diagnosis ranged from 4 to 20 years. The demographics, clinical characteristics, assessments with the 6-min walking test (6-MWT), the predicted forced vital capacity (FVC) and muscle strength were analysed. Before initiation of ERT, all patients suffered from proximal muscle weakness of the lower limbs; one was wheelchair-bound and two patients received night-time non-invasive ventilation. Initial treatment stabilised respiratory function in most patients and improved their walking performance. After treatment cessation, upright FVC declined in most and the 6-MWT declined in all patients. Two patients needed additional non-invasive ventilatory support. Twelve months after resuming ERT, the respiratory and walking capacity improved again in most patients. However, aside for one patient, none of the patients reached the same level of respiratory function or distance walked in 6 min, as at the time of ERT withdrawal. We conclude that cessation of ERT in Pompe disease causes a decline in clinical function and should be avoided. Resuming treatment only partially recovers respiratory function and walking capacity.

Involuntary reflexive pelvic floor muscle training in addition to standard training versus standard training alone for women with stress urinary incontinence: study protocol for a randomized controlled trial

BACKGROUND Pelvic floor muscle training is effective and recommended as first-line therapy for female patients with stress urinary incontinence. However, standard pelvic floor physiotherapy concentrates on voluntary contractions even though the situations provoking stress urinary incontinence (for example, sneezing, coughing, running) require involuntary fast reflexive pelvic floor muscle contractions. Training procedures for involuntary reflexive muscle contractions are widely implemented in rehabilitation and sports but not yet in pelvic floor rehabilitation. Therefore, the research group developed a training protocol including standard physiotherapy and in addition focused on involuntary reflexive pelvic floor muscle contractions. METHODS/DESIGN The aim of the planned study is to compare this newly developed physiotherapy program (experimental group) and the standard physiotherapy program (control group) regarding their effect on stress urinary incontinence. The working hypothesis is that the experimental group focusing on involuntary reflexive muscle contractions will have a higher improvement of continence measured by the International Consultation on Incontinence Modular Questionnaire Urinary Incontinence (short form), and - regarding secondary and tertiary outcomes - higher pelvic floor muscle activity during stress urinary incontinence provoking activities, better pad-test results, higher quality of life scores (International Consultation on Incontinence Modular Questionnaire) and higher intravaginal muscle strength (digitally tested) from before to after the intervention phase. This study is designed as a prospective, triple-blinded (participant, investigator, outcome assessor), randomized controlled trial with two physiotherapy intervention groups with a 6-month follow-up including 48 stress urinary incontinent women per group. For both groups the intervention will last 16 weeks and will include 9 personal physiotherapy consultations and 78 short home training sessions (weeks 1-5 3x/week, 3x/day; weeks 6-16 3x/week, 1x/day). Thereafter both groups will continue with home training sessions (3x/week, 1x/day) until the 6-month follow-up. To compare the primary outcome, International Consultation on Incontinence Modular Questionnaire (short form) between and within the two groups at ten time points (before intervention, physiotherapy sessions 2-9, after intervention) ANOVA models for longitudinal data will be applied. DISCUSSION This study closes a gap, as involuntary reflexive pelvic floor muscle training has not yet been included in stress urinary incontinence physiotherapy, and if shown successful could be implemented in clinical practice immediately. TRIAL REGISTRATION NCT02318251 ; 4 December 2014 First patient randomized: 11 March 2015.

Dysfunction of respiratory muscles in critically ill patients on the intensive care unit.

Muscular weakness and muscle wasting may often be observed in critically ill patients on intensive care units (ICUs) and may present as failure to wean from mechanical ventilation. Importantly, mounting data demonstrate that mechanical ventilation itself may induce progressive dysfunction of the main respiratory muscle, i.e. the diaphragm. The respective condition was termed 'ventilator-induced diaphragmatic dysfunction' (VIDD) and should be distinguished from peripheral muscular weakness as observed in 'ICU-acquired weakness (ICU-AW)'. Interestingly, VIDD and ICU-AW may often be observed in critically ill patients with, e.g. severe sepsis or septic shock, and recent data demonstrate that the pathophysiology of these conditions may overlap. VIDD may mainly be characterized on a histopathological level as disuse muscular atrophy, and data demonstrate increased proteolysis and decreased protein synthesis as important underlying pathomechanisms. However, atrophy alone does not explain the observed loss of muscular force. When, e.g. isolated muscle strips are examined and force is normalized for cross-sectional fibre area, the loss is disproportionally larger than would be expected by atrophy alone. Nevertheless, although the exact molecular pathways for the induction of proteolytic systems remain incompletely understood, data now suggest that VIDD may also be triggered by mechanisms including decreased diaphragmatic blood flow or increased oxidative stress. Here we provide a concise review on the available literature on respiratory muscle weakness and VIDD in the critically ill. Potential underlying pathomechanisms will be discussed before the background of current diagnostic options. Furthermore, we will elucidate and speculate on potential novel future therapeutic avenues.

Effects of eccentric cycle ergometry in alpine skiers

Eccentric cycling, where the goal is to resist the pedals, which are driven by a motor, increases muscle strength and size in untrained subjects. We hypothesized that it could also be beneficial for athletes, particularly in alpine skiing, which involves predominantly eccentric contractions at longer muscle lengths. We investigated the effects of replacing part of regular weight training with eccentric cycling in junior male alpine skiers using a matched-pair design. Control subjects ( N=7) executed 1-h weight sessions 3 times per week, which included 4-5 sets of 4 leg exercises. The eccentric group ( N=8) performed only 3 sets, followed by continuous sessions on the eccentric ergometer for the remaining 20 min. After 6 weeks, lean thigh mass increased significantly only in the eccentric group. There was a groupxtime effect on squat-jump height favouring the eccentric group, which also experienced a 6.5% improvement in countermovement-jump height. The ability to finely modulate muscle force during variable eccentric cycling improved 50% (p=0.004) only in the eccentric group. Although eccentric cycling did not significantly enhance isometric leg strength, we believe it is beneficial for alpine skiers because it provides an efficient means for hypertrophy while closely mimicking the type of muscle actions encountered while skiing.

Physiologic response to changing positive end-expiratory pressure during neurally adjusted ventilatory assist in sedated, critically ill adults

Neurally adjusted ventilatory assist (NAVA) delivers airway pressure (Paw) in proportion to neural inspiratory drive as reflected by electrical activity of the diaphragm (EAdi). Changing positive end-expiratory pressure (PEEP) impacts respiratory muscle load and function and, hence, EAdi. We aimed to evaluate how PEEP affects the breathing pattern and neuroventilatory efficiency during NAVA.