Nutrition and Exercise Rehabilitation in Obesity hypoventilation syndrome (NERO): a pilot randomised controlled trial.

BACKGROUND: Respiratory management of obesity hypoventilation syndrome (OHS) focusses on the control of sleep-disordered breathing rather than the treatment of obesity. Currently, there are no data from randomised trials of weight loss targeted rehabilitation programmes for patients with OHS. INTERVENTION: A 3-month multimodal hybrid inpatient-outpatient motivation, exercise and nutrition rehabilitation programme, in addition to non invasive ventilation (NIV), would result in greater per cent weight loss compared with standard care. METHODS: A single-centre pilot randomised controlled trial allocated patients to either standard care or standard care plus rehabilitation. Primary outcome was per cent weight loss at 12 months with secondary exploratory outcomes of weight loss, exercise capacity and health-related quality of life (HRQOL) at the end of the rehabilitation programme to assess the intervention effect. RESULTS: Thirty-seven patients (11 male, 59.8±12.7 years) with a body mass index of 51.1±7.7 kg/m2 were randomised. At 12 months, there was no between-group difference in per cent weight loss (mean difference -5.9% (95% CI -14.4% to 2.7%; p=0.17)). At 3 months, there was a greater per cent weight loss (mean difference -5% (95% CI -8.3% to -1.4%; p=0.007)), increased exercise capacity (6 min walk test 60 m (95% CI 29.5 to 214.5) vs 20 m (95% CI 11.5 to 81.3); p=0.036) and HRQL (mean difference SF-36 general health score (10 (95% CI 5 to 21.3) vs 0 (95% CI -5 to 10); p=0.02)) in the rehabilitation group. CONCLUSION: In patients with OHS, a 3-month comprehensive rehabilitation programme, in addition to NIV, resulted in improved weight loss, exercise capacity and QOL at the end of the rehabilitation period, but these effects were not demonstrated at 12 months, in part, due to the limited retention of patients at 12 months. TRIAL REGISTRATION NUMBER: Pre-results; NCT01483716.

Electrical stimulation for the treatment of obstructive sleep apnoea: a review of the evidence.

INTRODUCTION: Obstructive sleep apnoea is an increasingly prevalent clinical condition with significant impact on individuals and public health. Continuous positive airway pressure therapy is the standard treatment, but adherence is limited and alternative treatments are needed. In this context, non-invasive and invasive methods for the electrical stimulation of upper airway dilator muscles have been demonstrated to be effective in selected patients. Areas covered: This review will cover investigations on the clinical effects, safety, and tolerability of non-invasive and invasive electrical stimulation of the upper airway for the management of obstructive sleep apnoea. Following a search of the relevant literature published on PubMed this review is focused mainly on data obtained from randomized clinical trials and clinical studies. Expert commentary: The available evidence provides a rationale to consider upper airway electrical stimulation as treatment for selected patients with obstructive sleep apnoea, who have poor adherence or experience difficulties with continuous positive airway pressure therapy. Non-invasive stimulation using transcutaneous electrodes and implantable hypoglossal nerve stimulator technologies may provide an alternative to continuous positive airway pressure for the treatment of obstructive sleep apnoea via restoration of neuromuscular tone and improved upper airway patency.

Randomised sham-controlled trial of transcutaneous electrical stimulation in obstructive sleep apnoea.

INTRODUCTION: Obstructive sleep apnoea (OSA) is characterised by a loss of neuromuscular tone of the upper airway dilator muscles while asleep. This study investigated the effectiveness of transcutaneous electrical stimulation in patients with OSA. PATIENTS AND METHODS: This was a randomised, sham-controlled crossover trial using transcutaneous electrical stimulation of the upper airway dilator muscles in patients with confirmed OSA. Patients were randomly assigned to one night of sham stimulation and one night of active treatment. The primary outcome was the 4% oxygen desaturation index, responders were defined as patients with a reduction >25% in the oxygen desaturation index when compared with sham stimulation and/or with an index <5/hour in the active treatment night. RESULTS: In 36 patients (age mean 50.8 (SD 11.2) years, male/female 30/6, body mass index median 29.6 (IQR 26.9-34.9) kg/m(2), Epworth Sleepiness Scale 10.5 (4.6) points, oxygen desaturation index median 25.7 (16.0-49.1)/hour, apnoea-hypopnoea index median 28.1 (19.0-57.0)/hour) the primary outcome measure improved when comparing sham stimulation (median 26.9 (17.5-39.5)/hour) with active treatment (median 19.5 (11.6-40.0)/hour; p=0.026), a modest reduction of the mean by 4.1 (95% CI -0.6 to 8.9)/hour. Secondary outcome parameters of patients' perception indicated that stimulation was well tolerated. Responders (47.2%) were predominantly from the mild-to-moderate OSA category. In this subgroup, the oxygen desaturation index was reduced by 10.0 (95% CI 3.9 to 16.0)/hour (p<0.001) and the apnoea-hypopnoea index was reduced by 9.1 (95% CI 2.0 to 16.2)/hour (p=0.004). CONCLUSION: Transcutaneous electrical stimulation of the pharyngeal dilators during a single night in patients with OSA improves upper airway obstruction and is well tolerated. TRIAL REGISTRATION NUMBER: NCT01661712.

Patients' experiences of a new integrated breathlessness support service for patients with refractory breathlessness: Results of a postal survey.

BACKGROUND: We developed a new single point of access to integrated palliative care, respiratory medicine and physiotherapy: the breathlessness support service for patients with advanced disease and refractory breathlessness. This study aimed to describe patients' experiences of the service and identify the aspects valued. DESIGN: We attempted to survey all patients who had attended and completed the 6-week breathlessness support service intervention by sending them a postal questionnaire to self-complete covering experience, composition, effectiveness of the BSS and about participation in research. Data were analysed using descriptive statistics and thematic analysis of free text comments. RESULTS: Of the 70 postal questionnaires sent out, 25 (36%) returned. A total of 21 (84% (95% confidence interval: 69%-98%)) responding patients reported that they definitely found the breathlessness support service helpful and 13 (52% (95% confidence interval: 32%-72%)) rated the breathlessness support service as excellent. A total of 21 (84% (95% confidence interval: 69%-98%)) patients reported that the breathlessness support service helped with their management of their breathlessness along with additional symptoms and activities (e.g. mood and mobility). Four key themes were identified: (1) personalised care, (2) caring nature of the staff, (3) importance of patient education to empower patients and (4) effectiveness of context-specific breathlessness interventions. These were specific aspects that patients valued. CONCLUSION: Patients' satisfaction with the breathlessness support service was high, and identified as important to this was a combination of personalised care, nature of staff, education and empowerment, and use of specific interventions. These components would be important in any future breathlessness service.

Neuromuscular electrical stimulation to improve exercise capacity in patients with severe COPD: a randomised double-blind, placebo-controlled trial.

BACKGROUND: Skeletal muscle dysfunction and exercise intolerance are common in severe chronic obstructive pulmonary disease (COPD). We assessed the effectiveness of neuromuscular electrical stimulation (NMES) as a home-based exercise therapy. METHODS: In this double-blind, placebo-controlled trial, undertaken across three UK National Health Service sites, we randomly assigned (1:1) adults with COPD, a forced expiratory volume in 1 s (FEV1) less than 50% predicted, and incapacitating breathlessness (Medical Research Council dyspnoea scale ≥4) to receive active or placebo NMES, daily over a 6-week period. Randomisation was by an independent system using minimisation to balance age, GOLD stage, and quadriceps strength. Participants and outcome assessors were masked to group allocation. The primary endpoint was change in 6-min walk test (6MWT) distance at 6 weeks. Analysis was by intention to treat. The trial was registered as ISRCTN15985261 and is now closed. FINDINGS: Between June 29, 2012, and July 4, 2014, we enrolled 73 participants, of whom 52 participants were randomly assigned; 25 to receive active NMES and 27 to placebo NMES. Change in 6MWT distance was greater in the active NMES group (mean 29·9 [95% CI 8·9 to 51·0]) compared with in the placebo group (-5·7 [-19·9 to 8·4]; mean difference at 6 weeks 35·7 m [95% CI 10·5 to 60·9]; p=0·005). Sensitivity analyses for complete-cases and adjustment for baseline values showed similar results. 6 weeks after stopping the intervention the effect waned (7·3 m [95% CI -32·5 to 47·0]; p=0·50). The proportion of participants who had adverse events was similar between groups (five [20%] in the active NMES group and nine [33%] in the placebo group). Two participants, one from each group, reported persistent erythema, which was considered to be possibly related to NMES and the use of adhesive electrodes. INTERPRETATION: NMES improves functional exercise capacity in patients with severe COPD by enhancing quadriceps muscle mass and function. These data support the use of NMES in the management of patients unable to engage with conventional pulmonary rehabilitation. More work is needed to study how to maintain the effect. FUNDING: National Institute for Health Research.

Does respiratory muscle training improve cough flow in acute stroke? Pilot randomized controlled trial.

BACKGROUND AND PURPOSE: Cough protects the lungs from aspiration. We investigated whether respiratory muscle training may improve respiratory muscle and cough function, and potentially reduce pneumonia risk in acute stroke. METHODS: We conducted a single-blind randomized placebo-controlled trial in 82 patients with stroke (mean age, 64±14 years; 49 men) within 2 weeks of stroke onset. Participants were masked to treatment allocation and randomized to 4 weeks of daily expiratory (n=27), inspiratory (n=26), or sham training (n=25), using threshold resistance devices. Primary outcome was the change in peak expiratory cough flow of maximal voluntary cough. Intention-to-treat analyses were conducted using ANCOVA, adjusting for baseline prognostic covariates. RESULTS: There were significant improvements in the mean maximal inspiratory (14 cmH2O; P<0.0001) and expiratory (15 cmH2O; P<0.0001) mouth pressure and peak expiratory cough flow of voluntary cough (74 L/min; P=0.0002) between baseline and 28 days in all groups. Peak expiratory cough flow of capsaicin-induced reflex cough was unchanged. There were no between-group differences that could be attributed to respiratory muscle training. There were also no differences in the 90-day incidence of pneumonia between the groups (P=0.65). CONCLUSIONS: Respiratory muscle function and cough flow improve with time after acute stroke. Additional inspiratory or expiratory respiratory muscle training does not augment or expedite this improvement. CLINICAL TRIAL REGISTRATION URL: http://www.controlled-trials.com. Unique identifier: ISRCTN40298220.

An integrated palliative and respiratory care service for patients with advanced disease and refractory breathlessness: a randomised controlled trial.

BACKGROUND: Breathlessness is a common and distressing symptom, which increases in many diseases as they progress and is difficult to manage. We assessed the effectiveness of early palliative care integrated with respiratory services for patients with advanced disease and refractory breathlessness. METHODS: In this single-blind randomised trial, we enrolled consecutive adults with refractory breathlessness and advanced disease from three large teaching hospitals and via general practitioners in South London. We randomly allocated (1:1) patients to receive either a breathlessness support service or usual care. Randomisation was computer generated centrally by the independent Clinical Trials Unit in a 1:1 ratio, by minimisation to balance four potential confounders: cancer versus non-cancer, breathlessness severity, presence of an informal caregiver, and ethnicity. The breathlessness support service was a short-term, single point of access service integrating palliative care, respiratory medicine, physiotherapy, and occupational therapy. Research interviewers were masked as to which patients were in the treatment group. Our primary outcome was patient-reported breathlessness mastery, a quality of life domain in the Chronic Respiratory Disease Questionnaire, at 6 weeks. All analyses were by intention to treat. Survival was a safety endpoint. This trial is registered with ClinicalTrials.gov, number NCT01165034. FINDINGS: Between Oct 22, 2010 and Sept 28, 2012, 105 consenting patients were randomly assigned (53 to breathlessness support service and 52 to usual care). 83 of 105 (78%) patients completed the assessment at week 6. Mastery in the breathlessness support service group improved compared with the control (mean difference 0·58, 95% CI 0·01-1·15, p=0·048; effect size 0·44). Sensitivity analysis found similar results. Survival rate from randomisation to 6 months was better in the breathlessness support service group than in the control group (50 of 53 [94%] vs 39 of 52 [75%]) and in overall survival (generalised Wilcoxon 3·90, p=0·048). Survival differences were significant for patients with chronic obstructive pulmonary disease and interstitial lung disease but not cancer. INTERPRETATION: The breathlessness support service improved breathlessness mastery. Our findings provide robust evidence to support the early integration of palliative care for patients with diseases other than cancer and breathlessness as well as those with cancer. The improvement in survival requires further investigation. FUNDING: UK National Institute for Health Research (NIHR) and Cicely Saunders International.

A pilot study of respiratory muscle training to improve cough effectiveness and reduce the incidence of pneumonia in acute stroke: study protocol for a randomized controlled trial.

BACKGROUND: After stroke, pneumonia is a relevant medical complication that can be precipitated by aspiration of saliva, liquids, or solid food. Swallowing difficulty and aspiration occur in a significant proportion of stroke survivors. Cough, an important mechanism protecting the lungs from inhaled materials, can be impaired in stroke survivors, and the likely cause for this impairment is central weakness of the respiratory musculature. Thus, respiratory muscle training in acute stroke may be useful in the recovery of respiratory muscle and cough function, and may thereby reduce the risk of pneumonia. The present study is a pilot study, aimed at investigating the validity and feasibility of this approach by exploring effect size, safety, and patient acceptability of the intervention. METHODS/DESIGN: Adults with moderate to severe stroke impairment (National Institutes of Health Stroke Scale (NIHSS) score 5 to 25 at the time of admission) are recruited within 2 weeks of stroke onset. Participants must be able to perform voluntary respiratory maneuvers. Excluded are patients with increased intracranial pressure, uncontrolled hypertension, neuromuscular conditions other than stroke, medical history of asthma or chronic obstructive pulmonary disease, and recent cardiac events. Participants are randomized to receive inspiratory, expiratory, or sham respiratory training over a 4-week period, by using commercially available threshold resistance devices. Participants and caregivers, but not study investigators, are blind to treatment allocation. All participants receive medical care and stroke rehabilitation according to the usual standard of care. The following assessments are conducted at baseline, 4 weeks, and 12 weeks: Voluntary and reflex cough flow measurements, forced spirometry, respiratory muscle strength tests, incidence of pneumonia, assessments of safety parameters, and self-reported activity of daily living. The primary outcome is peak expiratory cough flow of voluntary cough, a parameter indicating the effectiveness of cough. Secondary outcomes are incidence of pneumonia, peak expiratory cough flow of reflex cough, and maximum inspiratory and expiratory mouth pressures. DISCUSSION: Various novel pharmacologic and nonpharmacologic approaches for preventing stroke-associated pneumonia are currently being researched. This study investigates a novel strategy based on an exercise intervention for cough rehabilitation. TRIAL REGISTRATION: Current Controlled Trials ISRCTN40298220.

Respiratory muscle strength and training in stroke and neurology: a systematic review.

We undertook two systematic reviews to determine the levels of respiratory muscle weakness and effects of respiratory muscle training in stroke patients. Two systematic reviews were conducted in June 2011 using a number of electronic databases. Review 1 compared respiratory muscle strength in stroke and healthy controls. Review 2 was expanded to include randomized controlled trials assessing the effects of respiratory muscle training on stroke and other neurological conditions. The primary outcomes of interest were maximum inspiratory and expiratory mouth pressure (maximum inspiratory pressure and maximum expiratory pressure, respectively). Meta-analysis of four studies revealed that the maximum inspiratory pressure and maximum expiratory pressure were significantly lower (P < 0·00001) in stroke patients compared with healthy individuals (weighted mean difference -41·39 and -54·62 cmH(2) O, respectively). Nine randomized controlled trials indicate a significantly (P = 0·0009) greater effect of respiratory muscle training on maximum inspiratory pressure in neurological patients compared with control subjects (weighted mean difference 6·94 cmH(2) O) while no effect on maximum expiratory pressure. Respiratory muscle strength appears to be impaired after stroke, possibly contributing to increased incidence of chest infection. Respiratory muscle training can improve inspiratory but not expiratory muscle strength in neurological conditions, although the paucity of studies in the area and considerable variability between them is a limiting factor. Respiratory muscle training may improve respiratory muscle function in neurological conditions, but its clinical benefit remains unknown.

High pressure versus high intensity noninvasive ventilation in stable hypercapnic chronic obstructive pulmonary disease: a randomized crossover trial.

BACKGROUND: High-intensity (high-pressure and high backup rate) noninvasive ventilation has recently been advocated for the management of stable hypercapnic chronic obstructive pulmonary disease (COPD). However, the relative contributions of high inspiratory pressure and high backup rate to ventilator adherence and physiological outcome have not been investigated. METHODS: Patients with stable hypercapnic COPD (daytime PaCO(2) > 6 kPa) and nocturnal hypoventilation were enrolled. Patients were randomly allocated to high-pressure and high backup rate (high-intensity) and high-pressure and low backup rate (high-pressure) for a 6-week period. At the end of the first treatment period, patients were switched to the alternative treatment. The primary outcome measure was mean nightly ventilator usage. RESULTS: Twelve patients were recruited, with seven completing the 12-week trial protocol. The mean patient age was 71 ± 8 years, with a forced expiratory volume in one second (FEV(1))/forced vital capacity (FVC) of 50% ± 13% and FEV(1) of 32% ± 12%. The baseline PaCO(2) and PaO(2) were 8.6 ± 1.7 kPa and 7.3 ± 1.4 kPa, respectively. There was no significant difference demonstrated in mean nightly ventilator usage between the high-intensity and high-pressure groups (difference of 4 minutes; 95% confidence interval -45 to 53; P = 0.9). Furthermore, there were no differences in any of the secondary endpoints, with the exception of the respiratory domain of the Severe Respiratory Insufficiency questionnaire, which was lower in the high-intensity arm than in the high-pressure arm (57 ± 11 versus 69 ± 16; P < 0.05). CONCLUSION: There was no additional benefit, in terms of night-time ventilator adherence or any of the other measured parameters, demonstrated by addition of a high backup rate to high-pressure noninvasive ventilation. These data suggest that it is the high-pressure component of the high-intensity noninvasive ventilation approach that plays the important therapeutic role in the management of hypercapnic respiratory failure in COPD patients.

Development, effectiveness and cost-effectiveness of a new out-patient Breathlessness Support Service: study protocol of a phase III fast-track randomised controlled trial.

BACKGROUND: Breathlessness is a common and distressing symptom affecting many patients with advanced disease both from malignant and non-malignant origin. A combination of pharmacological and non-pharmacological measures is necessary to treat this symptom successfully. Breathlessness services in various compositions aim to provide comprehensive care for patients and their carers by a multiprofessional team but their effectiveness and cost-effectiveness have not yet been proven. The Breathlessness Support Service (BSS) is a newly created multiprofessional and interdisciplinary outpatient service at a large university hospital in South East London. The aim of this study is to develop and evaluate the effectiveness and cost effectiveness of this multidisciplinary out-patient BSS for the palliation of breathlessness, in advanced malignant and non-malignant disease. METHODS: The BSS was modelled based on the results of qualitative and quantitative studies, and systematic literature reviews. A randomised controlled fast track trial (RCT) comprising two groups: 1) intervention (immediate access to BSS in addition to standard care); 2) control group (standard best practice and access to BSS after a waiting time of six weeks). Patients are included if suffering from breathlessness on exertion or at rest due to advanced disease such as cancer, chronic obstructive pulmonary disease (COPD), chronic heart failure (CHF), interstitial lung disease (ILD) or motor neurone disease (MND) that is refractory to maximal optimised medical management. Both quantitative and qualitative outcomes are assessed in face to-face interviews at baseline, after 6 and 12 weeks. The primary outcome is patients' improvement of mastery of breathlessness after six weeks assessed on the Chronic Respiratory Disease Questionnaire (CRQ). Secondary outcomes for patients include breathlessness severity, symptom burden, palliative care needs, service use, and respiratory measures (spirometry). For analyses, the primary outcome, mastery of breathlessness after six weeks, will be analysed using ANCOVA. Selection of covariates will depend on baseline differences between the groups. Analyses of secondary outcomes will include patients' symptom burden other than breathlessness, physiological measures (lung function, six minute walk distance), and caregiver burden. DISCUSSION: Breathlessness services aim to meet the needs of patients suffering from this complex and burdensome symptom and their carers. The newly created BSS is different to other current services as it is run in close collaboration of palliative medicine and respiratory medicine to optimise medical care of patients. It also involves professionals from various medical, nursing, physiotherapy, occupational therapy and social work background. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01165034).

Expresión y localización del factor de transcripción Yin Yang 1 en el músculo cuádriceps en la enfermedad pulmonar obstructiva crónica / Yin Yang 1 expression and localisation in quadriceps muscle in COPD

Introducción: El Ying Yang 1 (YY1) es un factor de transcripción represor que inhibe la expresión génicamuscular y la miogénesis. Este factor no se ha investigado previamente este factor no se ha investigado enel músculo esquelético de pacientes con enfermedad pulmonar obstructiva crónica (EPOC). Los objetivosdel presente estudio fueron investigar la expresión de YY1 y su localización en el músculo cuádricepsde pacientes con EPOC, comparado con individuos control sanos, emparejados por edad, y examinar larelación entre la expresión y localización de YY1 en las áreas transversales (AT) de las fibras muscularesdel cuádriceps en pacientes con EPOC.Pacientes y métodos: Se sometió a 15 pacientes con EPOC y a 8 individuos de control, emparejados poredad, a valoraciones de la función pulmonar y del cuádriceps y a una biopsia percutánea de este músculo.Mediante inmunofluorescencia se determinó el AT de las fibras musculares del cuádriceps las proporcionesde fibras y localización de YY1. YY1 se inmunoprecipitó a partir del músculo y sus niveles se evaluaronmediante inmunotransferencia.Resultados: Los niveles de YY1 se correlacionaron inversamente con el AT de las fibras de tipo IIx y de tipo Ien pacientes e individuos de control, aunque los niveles de YY1 no fueron significativamente diferentesentre ambos grupos. En los pacientes, pero no en los individuos control, se demostró la localizaciónnuclear de YY1.Conclusión: La expresión de YY1 se asocia a un AT más pequeña de las fibras del cuádriceps en pacientescon EPOC, en cuyo músculo también se observa una localización nuclear del factor, a diferencia de losindividuos control. La regulación de YY1 parece alterada en la EPOC y podría estar implicada en la atrofiamuscular relacionada con la enfermedad(AU)

Introduction: Yin Yang 1 (YY1) is a transcriptional repressor that inhibits muscle gene expression andmyogenesis. YY1 has not previously been investigated in the skeletal muscle of patients with COPD.The aims of this study were to investigate YY1 expression and localisation in the quadriceps muscle ofCOPD patients compared to healthy age-matched controls, and examine the relationship between YY1expression and localisation and quadriceps muscle fibre cross-sectional area (CSA) in COPD patients.Patients and methods: 15 COPD patients and 8 age-matched controls underwent lung and quadriceps function assessments and a percutaneous quadriceps biopsy. Quadriceps muscle fibre CSA and fibre proportions and YY1 localisation were determined by immunofluorescence. YY1 was immunoprecipitated from muscle and YY1 levels assessed by western blotting.

Yin Yang 1 expression and localisation in quadriceps muscle in COPD.

INTRODUCTION: Yin Yang 1 (YY1) is a transcriptional repressor that inhibits muscle gene expression and myogenesis. YY1 has not previously been investigated in the skeletal muscle of patients with COPD. The aims of this study were to investigate YY1 expression and localisation in the quadriceps muscle of COPD patients compared to healthy age-matched controls, and examine the relationship between YY1 expression and localisation and quadriceps muscle fibre cross-sectional area (CSA) in COPD patients. PATIENTS AND METHODS: 15 COPD patients and 8 age-matched controls underwent lung and quadriceps function assessments and a percutaneous quadriceps biopsy. Quadriceps muscle fibre CSA and fibre proportions and YY1 localisation were determined by immunofluorescence. YY1 was immunoprecipitated from muscle and YY1 levels assessed by western blotting. RESULTS: YY1 levels were inversely correlated with type IIx and type I fibre CSA in patients and controls, though YY1 levels were not significantly different between the groups. Nuclear localisation of YY1 was demonstrated in the patients but not in controls. CONCLUSION: YY1 expression is associated with smaller quadriceps fibre CSA in COPD and nuclear localisation of YY1 was found in muscle of patients but not controls. Regulation of YY1 appears altered in COPD and may be implicated in COPD-related muscle atrophy.

Continuous transcutaneous submental electrical stimulation in obstructive sleep apnea: a feasibility study.

BACKGROUND: The therapeutic value of transcutaneous electrical stimulation of the genioglossus muscle in patients with obstructive sleep apnea (OSA) to reduce sleep-disordered breathing is unclear. METHODS: Contraction of the genioglossus muscles during transcutaneous stimulation was investigated using ultrasonography in 11 healthy subjects (seven men, mean [SD] age 30 [6] years; BMI, 24.2 [3.5] kg/m(2)). Esophageal and gastric pressures were measured with balloon catheters, and transesophageal diaphragm electromyogram (EMGdi) was recorded during polysomnography in 11 patients with OSA (eight men, aged 51 [16] years; BMI, 42.0 [9.7] kg/m(2)) while transcutaneous electrical stimulation of the genioglossus was applied in non-rapid eye movement sleep (stage N2). RESULTS: Ultrasonography measurements showed a significant increase in tongue diameter during stimulation (sagittal: 10.0% [2.8%]; coronal: 9.4 % [3.7%]). The measurements were reproducible and repeatable. In patients with OSA, snoring decreased during stimulation (P < .001) and oxygenation improved (P = .001); the respiratory disturbance index (RDI) fell from 28.1 (26.3) to 10.2 (10.2) events per hour during stimulation (P = .002), returning to 26.6 (26.0) events per hour after stimulation was stopped. Transdiaphragmatic pressure swing decreased from 24.1 (13.5) cm H(2)O to 19.7 (7.1) cm H(2)O (P = .022), increasing to 24.2 (10.8) cm H(2)O afterward, and EMGdi fell from 23.8% max (12.6% max) to 15.7% max (6.4% max) (P < .001), rising to 22.6% max (10.4% max) post stimulation. CONCLUSIONS: Continuous transcutaneous electrical stimulation of the genioglossus contracts the genioglossus muscle and reduces ventilatory load and neural respiratory drive in patients with OSA.

Exercise and muscle dysfunction in COPD: implications for pulmonary rehabilitation.

Skeletal muscle dysfunction in COPD (chronic obstructive pulmonary disease) patients, particularly of the quadriceps, is of clinical interest because it not only influences the symptoms that limit exercise, but may also contribute directly to poor exercise performance and health status, increased healthcare utilization, and mortality. Furthermore, unlike the largely irreversible impairment of the COPD lung, skeletal muscles represent a potential site to improve patients' level of function and quality of life. However, despite expanding knowledge of potential contributing factors and greater understanding of molecular mechanisms of muscle wasting, only one intervention has been shown to be effective in reversing COPD muscle dysfunction, namely exercise training. Pulmonary rehabilitation, an intervention based on individually tailored exercise training, has emerged as arguably the most effective non-pharmacological intervention in improving exercise capacity and health status in COPD patients. The present review describes the effects of chronic exercise training on skeletal muscles and, in particular, focuses on the known effects of pulmonary rehabilitation on the quadriceps muscle in COPD. We also describe the current methods to augment the effects of pulmonary rehabilitation and speculate how greater knowledge of the molecular pathways of skeletal muscle wasting may aid the development of novel pharmaceutical agents.

Motor control of the costal and crural diaphragm--insights from transcranial magnetic stimulation in man.

The costal and crural parts of the diaphragm differ in their embryological development and physiological function. It is not known if this is reflected in differences in their motor cortical representation. We compared the response of the costal and crural diaphragms using varying intensities of transcranial magnetic stimulation of the motor cortex at rest and during submaximal and maximal inspiratory efforts. The costal and crural motor evoked potential recruitment curves during submaximal inspiratory efforts were similar. The response to stimulation before, during and at 10 and 30 min after 44 consecutive maximal inspiratory efforts was also the same. Using paired stimulations to investigate intra-cortical facilitatory and inhibitory circuits we found no difference between the costal and crural response with varying interstimulus intervals, or when conditioning and test stimulus intensity were varied. We conclude that supraspinal control of the costal and crural diaphragm is identical during inspiratory tasks.

The effect of treatment on diaphragm contractility in obstructive sleep apnea syndrome.

In untreated obstructive sleep apnea syndrome (OSAS) inspiratory efforts are made against an occluded airway and diaphragm fatigue might therefore complicate OSAS. To test this hypothesis we measured twitch transdiaphragmatic pressure (Tw Pdi) in response to bilateral cervical magnetic stimulation of the phrenic nerve roots in nine patients with OSAS before and one month after successful therapy with nasal continuous positive airways pressure (nCPAP). The mean Tw Pdi before therapy was 23.2cm H2O and after therapy was 22.8cm H2O (P = 0.59); the mean change after initiation of nCPAP was 0.4cm H2O with 95% confidence intervals of -1.3cm H2O and +2.1 cm H2O. We conclude that low frequency diaphragm fatigue does not complicate untreated OSAS.