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Introduction: Home noninvasive ventilation (NIV), targeting a reduction of carbon dioxide with a combination of sufficient inspiratory support and backup-rate improves outcomes in patients with chronic obstructive pulmonary disease. The aim of this systematic review with individual participant data (IPD) meta-analysis was to evaluate the effects of intensity of home NIV on respiratory outcomes in individuals with slowly progressive neuromuscular (NMD) or chest-wall disorders (CWD)., Methods: Controlled, non-controlled and cohort studies indexed between January-2000 and December-2020 were sought from Medline, Embase and the Cochrane Central Register. Outcomes were diurnal PaCO 2 , PaO 2 , daily NIV usage, and interface type (PROSPERO-CRD 42021245121). NIV intensity was defined according to the Z-score of the product of pressure support (or tidal volume) and backup-rate., Results: 16 eligible studies were identified; we obtained IPD for 7 studies (176 participants: 113-NMD; 63-CWD). The reduction in PaCO 2 was greater with higher baseline PaCO 2 . NIV intensity per se was not associated with improved PaCO 2 except in individuals with CWD and the most severe baseline hypercapnia. Similar results were found for PaO 2 . Daily NIV usage was associated with improvement in gas exchange but not with NIV intensity. No association between NIV intensity and interface type was found., Conclusion: Following home NIV initiation in NMD or CWD patients, no relationship was observed between NIV intensity and PaCO 2 , except in individuals with the most severe CWD. The amount of daily NIV usage, rather than intensity, is key to improving hypoventilation in this population during the first few months after introduction of therapy., (Copyright © 2023 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

In neuromuscular disorders (NMDs), nocturnal non-invasive ventilation (NIV) via a nasal mask is offered when hypercapnic respiratory failure occurs. With disease progression, nocturnal NIV needs to be extended into the daytime. Mouthpiece ventilation (MPV) is an option for daytime NIV. MPV represents a difficult task for home ventilators due to rapidly changing load conditions resulting from intermittent connections and disconnections from MPV circuit. The 252nd ENMC International Expert Workshop, held March 6th to 8th 2020 in Amsterdam, reported general guidelines for management of daytime MPV in NMDs. This report could not present all the detail regarding the technical issues important for clinical success of MPV. Based on the expert workshop discussions and the evidence from existing studies, the current narrative review aims to identify the technical issues of MPV and offers guidance via a decisional algorithm and educational figures providing relevant information that is important for successful implementation of MPV., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Breath-stacking, which consists of taking 2 or more consecutive ventilator insufflations without exhaling, is a noninvasive and inexpensive cough-assistance technique for patients with neuromuscular disease. Volumetric cough mode (VCM) is a recently introduced ventilator mode consisting of a programmable intermittent deep breath equal to a set percentage of the baseline tidal volume. Here, our objective was to compare VCM to breath-stacking during volume-control continuous mandatory ventilation in subjects on long-term noninvasive mechanical ventilation at home., Methods: We included 20 subjects with neuromuscular disease causing severe respiratory muscle dysfunction with a cough peak flow (CPF) < 270 L/min or maximum expiratory pressure < 45 cm H 2 O. Each subject tested breath-stacking and VCM in random order., Results: CPF increased with both techniques but was higher with VCM than with breath-stacking in 16 subjects. In 17 subjects, CPF was highest with the technique that produced the greatest inspiratory capacity., Conclusion: Our results indicate that both breath-stacking and VCM are useful cough-augmentation techniques. Displaying insufflated volumes on the ventilator screen is a simple and accessible method for selecting the most efficient cough-augmentation technique delivered by a home ventilator., (Copyright © 2019 by Daedalus Enterprises.)

Ineffective efforts (IEs) are among the most common types of patient-ventilator asynchrony. The objective of this study is to validate IE detection during expiration using pressure and flow signals, with respiratory effort detection by esophageal pressure (Pes) measurement as the reference, in patients with neuromuscular diseases (NMDs). We included 10 patients diagnosed with chronic respiratory failure related to NMD. Twenty-eight 5-minute recordings of daytime ventilation were studied for IE detection. Standard formulas were used to calculate sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of IE detection using pressure and flow signals compared to Pes measurement. Mean sensitivity and specificity of flow and pressure signal-based IE detection versus Pes measurement were 97.5% ± 5.3% and 91.4% ± 13.7%, respectively. NPV was 98.1% ± 8.2% and PPV was 67.6% ± 33.8%. Spearman's rank correlation coefficient indicated a moderately significant correlation between frequencies of IEs and controlled cycles ( ρ = 0.50 and p = 0.01). Among respiratory cycles, 311 (11.2%) were false-positive IEs overall. Separating false-positive IEs according to their mechanisms, we observed premature cycling in 1.2% of cycles, delayed ventilator triggering in 0.1%, cardiac contraction in 9.2%, and upper airway instability during expiration in 0.3%. Using flow and pressure signals to detect IEs is a simple and rapid method that produces adequate data to support clinical decisions.

Few studies have assessed the impact of home ventilation in patients with myotonic dystrophy type 1 (DM1) and no specific recommendations are available. We assessed the survival associated with category of home ventilation adherence of patients with DM1 followed up at a home ventilation unit using a Cox proportional hazards model. 218 patients were included; those who refused or delayed their acceptance of non-invasive ventilation were at higher risk for severe events (invasive ventilation or death) (P=0.03). Risk of death was associated with orthopnoea (HR 2.37; 95% CI 1.17 to 4.80; P<0.02) and adherence category (100 to 90% vs >75%: HR 3.26; 95% CI 1.32 to 8.04; P<0.03). Failure to use home ventilation as prescribed may be associated with increased mortality in patients with DM1., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

New treatments are being developed for myotonic dystrophy type 1 (DM1). To evaluate their efficacy, knowledge about the natural history of respiratory dysfunction and its relationship with the genotype will be crucial. Also needed is information on factors predicting the time-course of respiratory function in DM1. Using data from 283 patients, we built a segmented linear mixed-effects regression model to assess respiratory function changes over time. Respiratory variables associated with the CTG repeat number were identified by multivariate linear regression analysis. Cox proportional-hazards regression was used to estimate hazard ratios (HRs) for starting non-invasive ventilation (NIV). Higher CTG repeat number was associated with peak cough flow impairment (p = 0.007) and with lower values for maximal inspiratory pressure (p <0.0001) and upright vital capacity. A vital capacity decline over time was associated with older age at first evaluation (p <0.0001), higher CTG repeat number (p <0.0001), and higher baseline body mass index (p = 0.0004). NIV initiation was associated with lower peak cough flow (p <0.001) after age and PaCO 2 adjustment. Earlier and closer monitoring with routine peak cough flow determination in adults with congenital DM1, combined with weight control, may diminish the risk of respiratory complications and optimise other aspects of management., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Because progressive respiratory muscle weakness leads to decreased chest-wall motion with eventual ribcage stiffening, the purpose was to compare vital capacity (VC) and contributions of chest-wall compartments before and after volume recruitment-derecruitment manoeuvres (VRDM) in Duchenne muscular dystrophy (DMD). We studied nine patients with DMD and VC lower than 30% of predicted. VRDM was performed using 15 insufflations-exsufflations of +30 to -30 cmH 2 O. VC and three-dimensional chest-wall motion were measured, as well as oxygen saturation, transcutaneous partial pressure of carbon dioxide and the rapid shallow breathing index (respiratory rate/tidal volume) before (baseline) and immediately and 1 hour after VRDM. VC increased significantly immediately after VRDM (108% ± 7% of baseline, p = 0.018) but returned to baseline within 1 hour, and the rapid shallow breathing index increased significantly. The non-dominant side systematically increased immediately after VRDM ( p = 0.0077), and in the six patients with abnormal breathing asymmetry (difference >10% of VC) at baseline, this asymmetry was corrected immediately and/or 1 hour after VRDM. VRDM improved VC and reduced chest-wall motion asymmetry, but this beneficial effect waned rapidly with respiratory muscle fatigue, suggesting that VRDM may need to be repeated during the day to produce lasting benefits.

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder associated with respiratory muscle weakness and respiratory failure. Non-invasive ventilation alleviates respiratory symptoms and prolongs life, but is a palliative intervention. Slowing the deterioration of diaphragm function before respiratory failure would be desirable. We aimed to assess whether early diaphragm pacing could slow down diaphragm deterioration and would therefore delay the need for non-invasive ventilation., Methods: We did a multicentre, randomised, controlled, triple-blind trial in patients with probable or definite ALS in 12 ALS centres in France. The main inclusion criterion was moderate respiratory involvement (forced vital capacity 60-80% predicted). Other key eligibility criteria were age older than 18 years and bilateral responses of the diaphragm to diagnostic phrenic stimulation. All patients were operated laparoscopically and received phrenic stimulators. Clinicians randomly assigned patients (1:1) to receive either active or sham stimulation with a central web-based randomisation system (computer-generated list). Investigators, patients, and an external outcome allocation committee were masked to treatment. The primary outcome was non-invasive ventilation-free survival, analysed in the intention-to-treat population. Safety outcomes were also assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01583088., Findings: Between Sept 27, 2012, and July 8, 2015, 74 participants were randomly assigned to receive either active (n=37) or sham (n=37) stimulation. On July 16, 2015, an unplanned masked analysis was done after another trial showed excess mortality with diaphragm pacing in patients with hypoventilation (DiPALS, ISRCTN 53817913). In view of this finding, we analysed mortality in our study and found excess mortality (death from any cause) in our active stimulation group. We therefore terminated the study on July, 16, 2015. Median non-invasive ventilation-free survival was 6·0 months (95% CI 3·6-8·7) in the active stimulation group versus 8·8 months (4·2-not reached) in the control (sham stimulation) group (hazard ratio 1·96 [95% CI 1·08-3·56], p=0·02). Serious adverse events (mainly capnothorax or pneumothorax, acute respiratory failure, venous thromboembolism, and gastrostomy) were frequent (24 [65%] patients in the active stimulation group vs 22 [59%] patients in the control group). No treatment-related death was reported., Interpretation: Early diaphragm pacing in patients with ALS and incipient respiratory involvement did not delay non-invasive ventilation and was associated with decreased survival. Diaphragm pacing is not indicated at the early stage of the ALS-related respiratory involvement., Funding: Hospital Program for Clinical Research, French Ministry of Health; French Patients' Association for ALS Research (Association pour la Recherche sur la Sclérose Latérale Amyotrophique); and Thierry de Latran Foundation., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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 H 2 O), and maximum expiratory pressure (from 2.00 to 1.00 cm H 2 O). 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., (Copyright © 2016 by Daedalus Enterprises.)

Pompe disease is an autosomal-recessive lysosomal storage disorder characterized by progressive myopathy with proximal muscle weakness, respiratory muscle dysfunction, and cardiomyopathy (in infants only). In patients with juvenile or adult disease onset, respiratory muscle weakness may decline more rapidly than overall neurological disability. Sleep-disordered breathing, daytime hypercapnia, and the need for nocturnal ventilation eventually evolve in most patients. Additionally, respiratory muscle weakness leads to decreased cough and impaired airway clearance, increasing the risk of acute respiratory illness. Progressive respiratory muscle weakness is a major cause of morbidity and mortality in late-onset Pompe disease even if enzyme replacement therapy has been established. Practical knowledge of how to detect, monitor and manage respiratory muscle involvement is crucial for optimal patient care. A multidisciplinary approach combining the expertise of neurologists, pulmonologists, and intensive care specialists is needed. Based on the authors' own experience in over 200 patients, this article conveys expert recommendations for the diagnosis and management of respiratory muscle weakness and its sequelae in late-onset Pompe disease., Competing Interests: Conflicts of InterestMatthias Boentert has received speaker honoraria from Genzyme GmbH, Neu-Isenburg, Germany, and Genzyme Corporation, a Sanofi Company. Hélène Prigent received speaker honoraria and travel grants from Genzyme Corporation. Harrison N. Jones has received research support and speaker honoraria from Genzyme Corporation. Katalin Várdi, Marco Confalonieri, Uwe Mellies, Anita K. Simonds, Stephan Wenninger, and Emilia Barrot Cortés declare no conflict of interest.

Background: Respiratory involvement in neuromuscular disorders may contribute to impaired breathing-swallowing interactions, swallowing disorders and malnutrition. We investigated whether the use of non-invasive ventilation (NIV) controlled by the patient could improve swallowing performances in a population of neuromuscular patients requiring daytime NIV., Methods: Ten neuromuscular patients with severe respiratory failure requiring extensive NIV use were studied while swallowing without and with NIV (while ventilated with a modified ventilator allowing the patient to withhold ventilation as desired). Breathing-swallowing interactions were investigated by chin electromyography, cervical piezoelectric sensor, nasal flow recording and inductive plethysmography. Two water-bolus sizes (5 and 10ml) and a textured yogurt bolus were tested in a random order., Results: NIV use significantly improved swallowing fragmentation (defined as the number of respiratory interruption of the swallowing of a single bolus) (p = 0.003) and breathing-swallowing synchronization (with a significant increase of swallows followed by an expiration) (p <0.0001). Patient exhibited piecemeal swallowing which was not influenced by NIV use (p = 0.07). NIV use also significantly reduced dyspnea during swallowing (p = 0.04) while preserving swallowing comfort, regardless of bolus type., Conclusion: The use of patient controlled NIV improves swallowing parameters in patients with severe neuromuscular respiratory failure requiring daytime NIV, without impairing swallowing comfort., Trial Registration: ClinicalTrials.gov NCT01519388.

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., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Mechanical insufflation-exsufflation (MI-E), more commonly known as 'cough assist therapy', is a method which produces inspiratory and expiratory assistance to improve cough performances. However, other alternatives or combinations are possible., Objective: The objective was to compare the effects of mechanical insufflation combined with manually assisted coughing (MAC), insufflation-exsufflation alone and insufflation-exsufflation combined with MAC in neuromuscular patients requiring cough assistance., Methods: Eighteen neuromuscular patients with severe respiratory muscle dysfunction and peak cough flow (PCF) lower than 3 liters/s or maximal expiratory pressure (MEP) lower than +45 cm H2O were studied. Patients were studied under three cough-assisted conditions, which were used in random order: insufflation by intermittent positive-pressure breathing (IPPB) combined with MAC, MI-E and MI-E + MAC., Results: Overall, PCF was higher with IPPB + MAC than with MI-E + MAC or MI-E alone. Among the 12 patients who had higher PCF values with IPPB + MAC than with the two other techniques, 9 exhibited mask pressure swings during MI-E exsufflation, with a transient positive-pressure value due to the expiratory flow produced by the combined patient cough effort and MAC. Each of these 9 patients had higher PCF values (>5 liters/s) than did the other 9 patients when using IPPB + MAC., Conclusion: Our results indicate that adding the MI-E device to MAC is unhelpful in patients whose PCF with an insufflation technique and MAC exceeds 5 liters/s. This is because the expiratory flow produced by the patient's effort and MAC transitorily exceeds the vacuum capacity of the MI-E device, which therefore becomes a transient load against the PCF.

Objective: To determine whether optoelectronic plethysmography accurately evaluated vital capacity (VC) in patients with respiratory muscle dysfunction of variable severity, including those with paradoxical abdominal movements., Methods: In 20 subjects, VC was measured in the supine position using both spirometry and optoelectronic plethysmography (6 optoelectronic cameras and 52 reflective markers on the anterior chest wall)., Results: Spirometry VC (VC-Spiro) correlated positively with optoelectronic VC (VC-Opto) (r(2) = 0.99, P < .001), and the regression line was very close to the identity line (VC-Opto [mL] = -1.202 + 1.007 × VC-Spiro [mL]). A Bland-Altman plot showed that the mean difference was -20 mL (95% CI -63 mL to 24 mL) and the limits of agreement were 163 mL (95% CI 106 mL to 231 mL) and -203 mL (95% CI -271 mL to -146 mL). The difference between the 2 values expressed as the percentage of the mean value was < 15% in all 20 subjects, < 10% in 17 (85%) subjects, and < 5% in 11 (55%) subjects. The difference, expressed as the percentage of the mean value, was unrelated to the contribution of abdominal motion to VC (r = 0.02 and P = .94), but was significantly related to body mass index (r = 0.53, P = .02)., Conclusions: Optoelectronic plethysmography is accurate and suitable for VC measurement in patients with various degrees of respiratory failure, including those with paradoxical abdominal movements. This noninvasive method may be an attractive alternative for accurately measuring VC in the event of air leakage (through the mouth or tracheostomy) or when patients are unable to breathe with the dead space added by the spirometer.

Background: The objective is to determine whether maximal inspiratory pressure (P(imax)) measurement is more sensitive than vital capacity (VC) measurement to detect acute respiratory muscle failure considering a theoretical curvilinear relationship between volume and pressure., Methods: Review of VC and P(imax) of all patients hospitalized in ICU for Guillain-Barré syndrome (GBS) and myasthenia gravis (MG) exacerbation., Results: 84 consecutive caucasian patients between 19- and 70-years-old hospitalized in intensive care unit from April 2008 to December 2010, for MG exacerbation (44 patients) and GBS (40 patients). The regression curve between VC and P(imax) was linear rather than exponential (r = 0.599, P > 0.0001). The contingency table demonstrated agreement between VC and P(imax) (χ(2)= 26.7, P = 0.0001), with similar number of patients having abnormal P(imax) associated to normal VC and normal P(imax) associated to abnormal VC (9 (10.7%) vs. 8 (9.5%) respectively). Six of the patients developed an important decrease of VC from normal value to less than 60% of the predicted value and did not present evident curvilinear relationship between VC and P(imax) during this follow-up., Conclusions: Because the regression between VC and P(imax) was linear rather than curvilinear, P(imax) was not more sensitive than VC for early detection of respiratory muscle failure in patients hospitalized in ICU for GBS and MG exacerbation. Therefore, VC remains well suited to assess acute respiratory muscle failure and P(imax) gives poor additional information.

Pompe disease is a rare metabolic myopathy caused by lysosomal α-glucosidase deficiency. Pompe disease ranges from a rapidly progressive course when symptoms present in infancy to a more slowly progressive rate when symptoms present in childhood or adulthood. This open-label prospective exploratory study investigated the effect of 12 months of recombinant enzyme replacement therapy in 5 adult patients who had already advanced to a very severe stage of Pompe disease. Muscular and respiratory function, quantitative muscle testing and spirometry were assessed. Four patients were tracheostomized. Respiratory parameters did not deteriorate. A moderate improvement in sitting/supine slow vital capacity in 2 patients (from 7% to 11% and 28% to 32% of predicted) and reductions of ventilation support in 2 patients was observed. Three patients, wheelchair bound at baseline, improved sitting and proximal motor function; 2 patients improved in their ability to stand and transfer. The treatment was well tolerated. Alglucosidase alfa may stabilize or even slightly improve muscle strength and respiratory function among patients with severe Pompe disease., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Purpose: Many patients with respiratory failure related to neuromuscular disease receive chronic invasive ventilation through a tracheostomy. Improving quality of life, of which speech is an important component, is a major goal in these patients. We compared the effects on breathing and speech of low-level positive end-expiratory pressure (PEEP, 5 cmH(2)O) and of a Passy-Muir speaking valve (PMV) during assist-control ventilation., Methods: We studied ten patients with neuromuscular disorders, between December 2008 and April 2009. Flow was measured using a pneumotachograph. Microphone speech recordings were subjected to both quantitative measurements and qualitative assessments; the latter consisted of both an intelligibility score (using a French adaptation of the Frenchay Dysarthria Assessment) and a perceptual score determined by two speech therapists., Results: Text reading time, perceptive score, intelligibility score, speech comfort, and respiratory comfort were similar with PEEP and PMV. During speech with 5 cmH(2)O PEEP, six of the ten patients had no return of expiratory gas to the expiratory line and, therefore, had the entire insufflated volume available for speech, a condition met during PMV use in all patients. During speech, the respiratory rate increased by at least 3 cycles/min above the backup rate in seven patients with PEEP and in none of the patients with PMV., Conclusions: Low-level PEEP is as effective as PMV in ensuring good speech quality, which might be explained by sealed expiratory line with low-level PEEP and/or respiratory rate increase during speech with PEEP observed in most of the patients.

Guillain-Barré Syndrome is the leading cause of nontraumatic acute paralysis in industrialized countries. About 30% of patients have respiratory failure requiring intensive care unit (ICU) admission and invasive mechanical ventilation. Progressive weakness of both the inspiratory and the expiratory muscles is the mechanism leading to respiratory failure. Aspiration pneumonia and atelectasis are common consequences of the bulbar muscle weakness and ineffective cough. The classical signs of respiratory distress occur too late to serve as guidelines for management, and measurements of vital capacity and static respiratory pressures are useful to determine the best times for starting and stopping mechanical ventilation. Several factors present at admission and during the ICU stay are known to predict a need for invasive mechanical ventilation. They include rapidly progressive motor weakness, involvement of both the peripheral limb and the axial muscles, ineffective cough, bulbar muscle weakness, and a rapid decrease in vital capacity. Specific treatments (plasma exchange and intravenous immunoglobulins) have decreased both the number of patients requiring ventilation and the duration of ventilation. The need for mechanical ventilation is associated with residual functional impairments, although all patients eventually recover normal respiratory muscle function.

Many patients with respiratory failure related to neuromuscular disease receive chronic invasive ventilation through a tracheostomy. Improving quality of life, of which speech is an important component, is a major goal in these patients. We compared the effects on breathing and speech production of assist-control ventilation (ACV) and bilevel positive-pressure ventilation (BPPV) in nine patients with neuromuscular disease. Ventilator-delivered flow was measured using a pneumotachograph, and respiratory rate, inspiratory time, and ventilator-delivered volume were measured on this flow signal. Gas exchange was assessed using oxygen saturation and end-tidal carbon dioxide measurement. Microphone speech recordings were subjected to quantitative analysis. At rest, ventilatory parameters were similar with both modes. Speech induced an increase in inspiratory time during BPPV, with a greater increase in the volume released by the ventilator during speech as compared with ACV (172 +/- 194 versus 26 +/- 31 ml). Consequently, speech duration was longer during inspiration with BPPV. Moreover, BPPV allowed speech production to extend into expiration, and three patients could speak continuously during several respiratory cycles while receiving BPPV. Blood gas exchange was not modified by speech with BPPV or ACV. This study shows that BPPV provides better speech duration than ACV with no detectable short-term deleterious effects.

Background The efficacy of enzyme replacement therapy (ERT) in patients at an advanced stage of Pompe disease has only been addressed in a few studies. Our objective was to assess the long term effects of ERT in a cohort of patients with severe Pompe disease. Methods We identified patients from the French Pompe Registry with severe respiratory failure and permanent wheelchair use (assisted walk for a few meters was allowed) when starting ERT. Patients' medical records were collected and reviewed and respiratory and motor functions, before ERT initiation and upon last evaluation were compared. Results Twelve patients (7 males) were identified. Median age at symptom onset was 24 years [IQR = 15.5; 36.0]. At baseline ventilation was invasive in 11 patients and noninvasive in one, with a median ventilation time of 24 h [IQR = 21.88; 24.00] (min 20; max 24). ERT was initiated at a median age of 52.5 years [IQR = 35.75; 66.50]. Median treatment duration was 55 months [IQR = 39.5; 81.0]. During observational period no adverse reaction to ERT was recorded, five patients (41.67%) died, three decreased their ventilation time by 30, 60 and 90 min and two increased their assisted walking distance, by 80 and 20 m. Conclusion Some patients at a very advanced stage of Pompe disease may show a mild benefit from ERT, in terms of increased time of autonomous ventilation and of enlarged distance in assisted walk. ERT can be initiated in these patients in order to retain their current level of independence and ability to perform daily life activities. [ABSTRACT FROM AUTHOR]