Chronic respiratory failure negatively affects speech function in patients with bulbar and spinal onset amyotrophic lateral sclerosis: retrospective data from a tertiary referral center.

Background: Although dysarthria and respiratory failure are widely described in literature as part of the natural history of Amyotrophic lateral sclerosis (ALS), the specific interaction between them has been little explored.Aim: To investigate the relationship between chronic respiratory failure and the speech of ALS patients.Materials and methods: In this cross-sectional retrospective study we reviewed the medical records of all patients diagnosed with ALS that were accompanied by a tertiary referral center. In order to determine the presence and degree of speech impairment, the Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-R) speech sub-scale was used. Respiratory function was assessed through spirometry and through venous blood gasometry obtained from a morning peripheral venous sample. To determine whether differences among groups classified by speech function were significant, maximum and mean spirometry values of participants were compared using multivariate analysis of variance (MANOVA) with Tukey's post hoc test.Results: Seventy-five cases were selected, of which 73.3% presented speech impairment and 70.7% respiratory impairment. Respiratory and speech functions were moderately correlated (seated FVC r = 0.64; supine FVC r = 0.60; seated FEV1 r = 0.59 and supine FEV1 r = 0.54, p < .001). Multivariable logistic regression revealed that the following variables were significantly associated with the presence of speech impairment after adjusting for other risk factors: seated FVC (odds ratio [OR] = 0.862) and seated FEV1 (OR = 1.106). The final model was 81.1% predictive of speech impairment. The presence of daytime hypercapnia was not correlated to increasing speech impairment.Conclusion: The restrictive pattern developed by ALS patients negatively influences speech function. Speech is a complex and multifactorial process, and lung volume presents a pivotal role in its function. Thus, we were able to find that lung volumes presented a significant correlation to speech function, especially in those with bulbar onset and respiratory impairment. Neurobiological and physiological aspects of this relationship should be explored in further studies with the ALS population.

Adjunctive inspiratory muscle training for patients with COVID-19 (COVIDIMT): protocol for randomised controlled double-blind trial.

INTRODUCTION: A significant number of patients with COVID-19 may experience dyspnoea, anxiety, depression, pain, fatigue and physical impairment symptoms, raising the need for a multidisciplinary rehabilitation approach, especially for those with advanced age, obesity, comorbidities and organ failure. Traditional pulmonary rehabilitation (PR), including exercise training, psychosocial counselling and education, has been employed to improve pulmonary function, exercise capacity and quality of life in patients with COVID-19. However, the effects of inspiratory muscle training (IMT) in PR programmes remain unclear. This study aimed to determine whether the addition of a supervised IMT in a PR is more effective than PR itself in improving dyspnoea, health-related quality of life and exercise capacity in symptomatic patients with post-COVID-19. METHODS AND ANALYSIS: This parallel-group, assessor-blinded randomised controlled trial, powered for superiority, aimed to assess exercise capacity as the primary outcome. A total of 138 are being recruited at two PR centres in Brazil. Following baseline testing, participants will be randomised using concealed allocation, to receive either (1) standard PR with sham IMT or (2) standard PR added to IMT. Treatment effects or differences between the outcomes (at baseline, after 8 and 16 weeks, and after 6 months) of the study groups will be analysed using an ordinary two-way analysis of variance. ETHICS AND DISSEMINATION: This trial was approved by the Brazilian National Ethics Committee and obtained approval on 7 October 2020 (document number 4324069). The findings will be disseminated through publications in peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: NCT04595097.

Bench evaluation of commercially available and newly developed interfaces for mouthpiece ventilation.

INTRODUCTION: Mouthpiece ventilation represents a valuable treatment for patients needing daytime non-invasive ventilation. This modality is however underused, in part because of limitations in the available equipment. OBJECTIVE: To develop a new flexible and moldable mouthpiece, aiming to address some of the issues of the currently available interfaces. METHODS: We compared two commercially available and the newly developed mouthpieces in a bench test using four life-support home ventilators and three settings per ventilator. RESULTS: The three interfaces showed marked differences in their resistive characteristics. In the volume-controlled setting (VC-CMV) with 500 mL tidal volume (VT ), the delivered VT , ranged between 459 ± 7 mL (-8%) and 501 ± 4 mL (+0.2%), according to the used ventilator. In the VC-CMV setting with VT 1000 mL, one of the ventilators did not assure the set VT with the new mouthpiece, because of the high-pressure limitation. In the pressure-controlled setting (PC-CMV at 20 cmH2 O), the effective pressure differed between the tested interfaces according to their resistance, resulting in a decrease in the delivered VT . CONCLUSIONS: They found measurable differences in the ventilation's performances comparing the interfaces for mouthpiece ventilation, which seem to have a minor clinical relevance in the most settings, but should be systematically checked. They validated in-vitro the newly developed mouthpiece with respect to the ventilation performances; a clinical study is needed to investigate the potential advantages we expect from the new mouthpiece.

Assisted vital capacity to assess recruitment level in neuromuscular diseases.

Respiratory muscle weakness and chest wall abnormalities in neuromuscular diseases (NMD) may lead to decreased pulmonary volumes. We assessed the reversibility of vital capacity (VC) reduction with mechanical In-Exsufflation (MI-E). We evaluated the effects of positive inspiratory and negative expiratory pressures on spirometric variables under passive (without patients' participation) and active (with active participation) application in 47 NMD patients. VC, inspiratory capacity (IC), expiratory reserve volume (ERV) were measured during maneuvers without and with MI-E assistance, delivering inspiratory assistance (+40cmH2O), expiratory assistance (-40cmH2O) and both (±40cmH2O). Passive and active assistance improved significantly VC and IC compared to baseline (P<0.0001 for both). ERV improved only with active assistance which normalized VC in 10, IC in 18 and ERV in 6 patients, mainly in patients with late-onset NMD. MI-E assistance produced greater increases in IC than in ERV, resulting in a VC increase enhanced by patients' active participation. This type of evaluation may help to evaluate the potential reversibility of restrictive ventilatory pattern in NMDs.

Twitch mouth pressure for detecting respiratory muscle weakness in suspicion of neuromuscular disorder.

Twitch mouth pressure using magnetic stimulation of the phrenic nerves and an automated inspiratory trigger is a noninvasive, non-volitional assessment of diaphragmatic strength. Our aims were to validate this method in patients with suspected neuromuscular disease, to determine the best inspiratory-trigger pressure threshold, and to evaluate whether twitch mouth pressure decreased the overdiagnosis of muscle weakness frequently observed with noninvasive volitional tests. Maximal inspiratory pressure, sniff nasal pressure, and twitch mouth pressure were measured in 112 patients with restrictive disease and suspected neuromuscular disorder. Esophageal and transdiaphragmatic pressures were measured in 64 of these patients to confirm or infirm inspiratory muscle weakness. Magnetic stimulation was triggered by inspiratory pressures of -1 and -5 cmH2O. The -5 cmH2O trigger produced the best correlation between twitch mouth pressure and twitch esophageal pressure (R2 = 0.86; P <0.0001). The best association of noninvasive tests to predict inspiratory muscle weakness was sniff nasal pressure and twitch mouth pressure. Below-normal maximal inspiratory pressure and sniff nasal pressure values suggesting inspiratory muscle weakness were found in 63/112 patients. Only 52 of these 63 patients also had abnormal twitch mouth pressure. In conclusion twitch mouth pressure measurement is a simple, noninvasive, nonvolitional technique which may help to select patients with suspected neuromuscular disorder for invasive inspiratory-muscle investigation.

Impact of Noninvasive Ventilation on Lung Volumes and Maximum Respiratory Pressures in Duchenne Muscular Dystrophy.

BACKGROUND: Duchenne muscular dystrophy (DMD) is a sex-linked genetic disorder in which progressive impairment of skeletal muscle function eventually leads to severe respiratory failure requiring continuous noninvasive ventilation (NIV) at home. A current focus of debate is whether NIV may slow the decline in respiratory function or, on the contrary, worsen respiratory function when started early. Our objective here was to describe the effects of NIV on vital capacity (VC) and maximum respiratory pressures in DMD. METHODS: We analyzed retrospective data from 71 subjects with DMD, including VC, maximum static respiratory pressures, and sniff nasal inspiratory pressure before and after NIV initiation. The declines in these variables from the highest value to the most recent value were computed. RESULTS: Although respiratory function continued to deteriorate over time, NIV introduction was followed by significant slowing in the annual rates of decline in VC (from 4.28 to 1.36 percent predicted), maximum inspiratory pressure (from 2.77 to 1.48 cm H2O), and maximum expiratory pressure (from 2.00 to 1.00 cm H2O). NIV had no effect on sniff nasal inspiratory pressure. CONCLUSIONS: Introducing NIV in subjects with DMD was followed by slowing of the declines in VC and in maximum static inspiratory and expiratory pressures.

Factors influencing compliance with non-invasive ventilation at long-term in patients with myotonic dystrophy type 1: A prospective cohort.

This study evaluated compliance with non-invasive ventilation in patients with myotonic dystrophy type 1 and identified predictors of cessation at 5 years in a cohort of patients followed in a specialist center for Neuromuscular Diseases in France. Mechanical ventilation in these patients poses a very strong challenge to caregivers. Factors predicting relative compliance were identified using multivariate linear regressions. Cox proportional-hazards regression was used to estimate hazard ratios associated with risk of cessation. One hundred and twenty-eight patients were included. Compliance during the first year was higher when symptoms of respiratory failure were initially present (+25%, p < 0.003) and lower in the case of acute respiratory failure (-29%, p < 0.003). Long-term compliance was associated with symptoms of respiratory failure (+52%, p < 0.0001) and nocturnal arterial oxygen desaturation (+23%, p < 0.007). Cessation was more frequent in the cases of excessive leaks (HR = 7.81, IC [1.47-41.88], p < 0.01), ventilator dysfunction requiring emergency technical intervention (HR = 12.58, IC [1.22-129.69], p < 0.03) or high body mass index (p < 0.02). Cessation was less frequent for patients with a professional occupation or undergoing professional training (HR = 0.11, IC [0.02-0.77], p < 0.02). Compliance with non-invasive ventilation is poor in patients with no subjective symptoms of respiratory failure. It may be improved with appropriate education and follow-up.

Impact of invasive ventilation on survival when non-invasive ventilation is ineffective in patients with Duchenne muscular dystrophy: A prospective cohort.

BACKGROUND: Many patients with DMD undergo tracheostomy. Tracheostomy is associated with certain complications, however its effect on prognosis is not known. METHODS: The relationship between type of mechanical ventilation and survival at 12 years was evaluated in a prospective cohort of patients with Duchenne muscular dystrophy followed in a French reference center for Neuromuscular Diseases. Cox proportional-hazards regressions were used to estimate the hazard ratios associated with risk of switching from non-invasive to invasive ventilation, and with risk of death. RESULTS: One hundred and fifty patients were included. Initial use of invasive ventilation was associated with an episode of acute respiratory failure (p < 0.0001) and with a severe clinical status (p < 0.05). Risk of death was associated with swallowing disorders (2.51, IC [1.12-5.66], p < 0.03) and cardiac failure (p < 0.05) but not with type of mechanical ventilation. CONCLUSION: Switching to invasive ventilation is appropriate when non-invasive ventilation is ineffective.

Accuracy of tidal volume delivered by home mechanical ventilation during mouthpiece ventilation: A bench evaluation.

The aim of our study was to evaluate efficacy and reliability of currently available ventilators for mouthpiece ventilation (MPV). Five life-support home ventilators were assessed in a bench test using different settings simulating the specificities of MPV, such as intermittent circuit disconnection and presence of continuous leaks. The intermittent disconnection of the circuit caused relevant swings in the delivered tidal volume ( VT), showing a VT overshoot during the disconnection periods and a VT decrease when the interface was reconnected to the test lung. The five ventilators showed substantial differences in the number of respiratory cycles necessary to reach a stable VT in the volume-controlled setting, ranging from 1.3 ± 0.6 to 7.3 ± 1.2 cycles. These differences were less accentuated in the volume-assisted setting (MPV-dedicated mode, when available). Our data show large differences in the capacity of the different ventilators to deal with the rapidly changing respiratory load features that characterize MPV, which can be further accentuated according to the used ventilator setting. The dedicated MPV modes allow improvement in the performance of ventilators only in some defined situations. This has practical consequences for the choice of the ventilator to be used for MPV in a specific patient.

Respiratory muscle dysfunction in facioscapulohumeral muscular dystrophy.

Respiratory insufficiency in facioscapulohumeral muscular dystrophy has rarely been studied. We compared two age- and sex-matched groups of 29 patients, with and without respiratory dysfunction. Tests in the 29 patients with respiratory dysfunction suggested predominant expiratory muscle dysfunction, leading to ineffective cough in 17 patients. Supine and upright vital capacities were not different (P = 0.76), suggesting absence of diaphragmatic dysfunction. By stepwise regression, only expiratory reserve volume correlated with the Walton and Gardner-Medwin score (R(2) = 0.503; P = 0.001). Compared to controls, patients with respiratory dysfunction had higher values for the Walton and Gardner-Medwin score (6.1 ± 1.9 vs. 3.2 ± 1.2; P <0.0001) and body mass index (26.9 ± 6.0 vs. 22.9 ± 4.0 kg/m(2); P = 0.003) and a smaller number of D4Z4 allele repeats (4.8 ± 1.6 vs. 5.7 ± 1.8; P = 0.05). Mechanical ventilation was required eventually in 20 patients, including 14 who were wheelchair bound. Three patients had acute respiratory failure requiring mechanical ventilation; 16 patients had poor airway clearance, including 10 with sleep apnea syndrome, responsible in 7 for chronic hypercapnia. Two patients presented isolated severe sleep apnea syndrome. Respiratory dysfunction in facioscapulohumeral muscular dystrophy is predominantly related to expiratory muscle weakness. Respiratory function and cough effectiveness should especially be monitored in patients with severe motor impairment and high body mass index.

Correlation of levels of obstruction in COPD with lactate and six-minute walk test.

UNLABELLED: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbid-mortality world wide, leading not only to pulmonary damage but also to multisystemic impairment, with repercussions on skeletal muscles and the ability to undertake effort, as measured in the six-minute walk test (6-MWT). AIMS: To correlate the level of obstruction in COPD with lactate concentration and heart rate (HR) at rest, and distance walked. To correlate distance walked with blood gas analysis and correlate desaturation in 6-MWT with post 6-MWT lactate concentration and heart rate. METHODS: COPD patients underwent spirometry, blood gas analysis and 6-MWT to evaluate distance walked, heart rate, capillary lactate (CL) concentration pre- and post 6-MWT, and desaturation with 6-MWT. RESULTS: 91 patients with all levels of obstruction were evaluated. HR and CL increased significantly post 6-MWT. The decrease in peripheral saturation of haemoglobin to oxygen observed with 6-MWT was also significant. The distance walked was shorter the greater the obstruction. The correlation analysis was significantly positive between FEV1 and distance walked, negative between FEV(1) and HR at rest and negative between distance walked and PaCO(2), and not significant for the other variables. CONCLUSIONS: Increased obstruction in COPD and higher PaCO(2) values contribute to a reduction in distance walked in 6-MWT. The level of obstruction in COPD leads to a haemodynamic impairment with increased HR at rest of these patients.