Nocturnal Non-invasive Ventilation Research Articles

Outcomes of early-treated infants with spinal muscular atrophy: A multicenter, retrospective cohort study.

While prompt identification and treatment of infants with spinal muscular atrophy (SMA) can ameliorate outcomes, variability persists. This study assessed management and outcomes of early-treated infants with SMA. We analyzed retrospective data at 12 centers on infants with SMA treated at age ≤6 weeks from August 2018 to December 2023. Sixty-six patients, 35 with two SMN2 copies and 31 with ≥3 SMN2 copies, were included. Twenty-five (38%, 22 with two SMN2 copies), had SMA findings before initial treatment which was onasemnogene abeparvovec in 47 (71%) and nusinersen in 19 (29%). Thirty-two received sequential or combination treatments, including 16 adding nusinersen or risdiplam due to SMA findings following onasemnogene abeparvovec. All sat independently. Compared to children with ≥3 SMN2 copies, those with two SMN2 copies were less likely to walk (23/34 [68%] vs. 31/31 [100%], p < .001) and less likely to walk on time (9/34 [26%] vs. 29/31 [94%], p < .001); one non-ambulatory child was <18 months old and was excluded from this analysis. No patients required permanent ventilation or exclusively enteral nutrition; six required nocturnal non-invasive ventilation and four utilized supplemental enteral nutrition, all with two SMN2 copies. Early treatment of infants with SMA can improve outcomes as indicated by our cohort, all of whom sat independently and are without permanent ventilation. However, our study demonstrates ongoing disability in most children with two SMN2 copies despite early monotherapy and emphasizes the need for additional research, including earlier monotherapy, initial combination therapy, prenatal treatment, and non-SMN modifying treatments.

Effect of telemonitoring on the rate of dropout during home non-invasive ventilation: a retrospective study using a home care provider database

ObjectivesTelemonitoring (TM) of home non-invasive ventilation (NIV) has been shown to facilitate home/outpatient therapy set-up. However, the impact of long-term TM on therapy dropouts, compliance and leak control has not...

Severe Respiratory and Swallowing Disorders in Infantile-Onset Multisystem Neurologic, Endocrine, and Pancreatic Disease Type 1: Two Cases.

The objective of this study was to expand the phenotypic spectrum of infantile-onset multisystem neurologic, endocrine, and pancreatic disease type 1 (IMNEPD1) and highlight the importance of analyzing the PTRH2 gene in patients with neuropathy presenting with pancreatic lipomatosis. Two sisters, aged 73 and 71 years, respectively, presented a severe, length-dependent sensorimotor axonal neuropathy, associated with deafness and intellectual deficiency. They both needed a wheelchair from the fourth decade. They developed a severe respiratory dysfunction, requiring nocturnal noninvasive ventilation from around 50 years of age. The younger sister developed severe dysphagia complicated by aspiration pneumonia. A muscle biopsy of the younger sister was suggestive of mitochondrial myopathy. The youngest presented a complete pancreatic lipomatosis. A biallelic novel likely pathogenic variant within PTRH2, c.254A>G (p.Gln85Arg), was evidenced in both patients. IMNEPD1 is a rare autosomal recessive disorder caused by sequence variant in the PTRH2 gene and characterized by a peripheral neuropathy, cerebellar atrophy, intellectual disability, hearing loss, pancreatic insufficiency, hypothyroidism, and dysmorphic features. In addition to these classic manifestations of the disorder, severe dysphagia and respiratory insufficiency may develop over the course of the disease and should be systematically screened. PTRH2 gene should be considered in patients with pancreatic lipomatosis and neuropathy.

Real-world multidisciplinary outcomes of onasemnogene abeparvovec monotherapy in patients with spinal muscular atrophy type 1: experience of the French cohort in the first three years of treatment

BackgroundSpinal muscular atrophy type 1 (SMA1) is the most severe and early form of SMA, a genetic disease with motor neuron degeneration. Onasemnogene abeparvovec gene transfer therapy (GT) has changed the natural history of SMA1, but real-world data are scarce.MethodsA French national expert committee identified 95 newly diagnosed treatment-naive SMA1 patients between June 2019 and June 2022. We prospectively report on children treated with GT as the first and only therapy who had more than one-year of follow-up.ResultsForty-six SMA1 patients received GT. Twelve patients received other treatments. Patients with respiratory insufficiency were oriented toward palliative care after discussion with families. Twenty-nine of the treated patients with more than 12 months of follow-up were included in the follow-up analysis. Among them, 17 had 24 months of follow-up. The mean age at treatment was 7.5 (2.1–12.5) months. Twenty-two patients had two SMN2 copies, and seven had three copies. One infant died in the month following GT due to severe thrombotic microangiopathy, and another died due to respiratory distress. Among the 17 patients with 24 months of follow-up, 90% required spinal bracing (15/17), three patients required nocturnal noninvasive ventilation, and two needed gastrostomy. Concerning motor milestones at the 24-month follow-up, all patients held their head, 15/17 sat for 30 s unassisted, and 12/17 stood with aid. Motor scores (CHOPINTEND and HINE-2) and thoracic circumference significantly improved in all patients.ConclusionsOur study shows favorable motor outcomes and preserved respiratory and feeding functions in treatment-naive SMA1 infants treated by GT as the first and only therapy before respiratory and bulbar dysfunctions occurred. Nevertheless, almost all patients developed spinal deformities.

Deventilation syndrome in patients with chronic obstructive pulmonary disease using nocturnal non-invasive ventilation: what are the underlying mechanisms?

Introduction Patients with chronic obstructive pulmonary disease (COPD) commonly experience severe dyspnea after discontinuation of nocturnal non-invasive ventilation (NIV), known as deventilation syndrome (DVS), which negatively affects quality of life. Despite various hypotheses, the precise mechanisms of DVS remain unknown. Methods An observational pilot study was performed monitoring 16 stable COPD patients, before, during and after an afternoon nap on NIV. Seven patients experienced DVS (Borge dyspnea scale ≥ 5), while nine served as controls (Borg Dyspnea Scale ≤ 2). Hyperinflation was evaluated through inspiratory capacity (IC) measurements and end-expiratory lung impedance (EELI) via electrical impedance tomography. Respiratory muscle activity was assessed by diaphragmatic surface electromyography (sEMG). Results Post-NIV dyspnea scores were significantly higher in the DVS group (5[3-7] vs. 0[0-1.5], p&lt;0.001). IC values were lower in the DVS group compared to controls, both pre- (54[41-63] vs. 88[72-94] %pred., p=0.006) and post-NIV (45[40-59] vs. 76[65-82] %pred., p=0.005), while no intergroup difference was seen in IC changes pre- and post-NIV. EELI values after NIV indicated a tendency towards lower values in controls and higher values in DVS patients. sEMG amplitudes were higher in the DVS group within the first 5 minutes post-NIV (221[112-294] vs. 100[58-177]% of baseline, p=0.030). Conclusion This study suggests that it is unlikely that DVS originates from the inability to create diaphragmatic muscle activity after NIV. Instead, NIV-induced hyperinflation in individuals with static hyperinflation may play a significant role. Addressing hyperinflation holds promise in preventing DVS symptoms in COPD patients.

P477 How the use of nocturnal non-invasive ventilation and oxygen therapy changes in patients with cystic fibrosis using elexacaftor/tezacaftor/ivacaftor

P477 How the use of nocturnal non-invasive ventilation and oxygen therapy changes in patients with cystic fibrosis using elexacaftor/tezacaftor/ivacaftor

A comparison of two weaning strategies for non-invasive ventilation in chronic obstructive pulmonary disease patients with acute respiratory failure.

Non-Invasive Ventilation (NIV) is a crucial therapy for managing acute exacerbations of Chronic Obstructive Pulmonary Disease (COPD) with hypercapnic respiratory failure. Research has shown that NIV can decrease the rate of endotracheal intubation, length of hospital and Intensive Care Unit stays, and mortality. There are three main strategies for weaning patients off NIV: gradual reduction of NIV duration, gradual reduction of NIV pressure support, and immediate cessation of NIV. To compare the rate of successful withdrawal of COPD patients with acute hypercapnic respiratory failure, one group will use a stepwise reduction of duration of NIV, while the other group will use a stepwise reduction of pressure support. This study was a prospective observational study conducted at the Department of Pulmonary Medicine, Institute of Chest Diseases, Government Medical College, Kozhikode, over a period of 15months. The study population consisted of all COPD patients admitted to the Pulmonary Medicine ward or ICU with acute hypercapnic respiratory failure who were managed with non-invasive ventilation (NIV) without the need for invasive mechanical ventilation. Exclusions included patients requiring NIV for respiratory diseases other than COPD, those with significant comorbiditieslike acute left ventricular failure or fluid overload states as in chronic kidney disease, COVID-19 positive patients, patients on home NIV, patients who needed intubation early in treatment, and patients unwilling to participate in the study. The sample size was 140. Initial NIV settings and other management decisions prior to enrolment in the study were made by the treating physician according to standard protocols. Once weaning criteria were met (i.e., arterial pH > 7.35, SpO2 ≥ 90% at an FiO2 ≤ 50%, respiratory rate ≤ 25 breaths per minute, heart rate ≤ 120 beats per minute, systolic BP > 90mm Hg, and no signs of respiratory distress), patients were assigned to either group 1 or group 2 by purposive sampling. Group 1: stepwise reduction of duration of NIV use, with a reduction to 16h per day on day 1 of enrolment, 12h on day 2 (including 6-8h of nocturnal NIV), 6-8h on day 3, and NIV withdrawal on day 4. Group 2: stepwise reduction of pressure support, with pressure support reduced by 2-4cm every 4-6h until Inspiratory Positive Airway Pressure is < 8cm H2O and Expiratory Positive Airway Pressure is < 4cm H2O, followed by NIV withdrawal. The clinical outcome was classified as either improved or weaning failure. Improved was defined as an objective or subjective sense of improvement. Weaning failure was defined as the presence of any of the following: respiratory rate ≥ 25/minute or increase of ≥ 50% from baseline, heart rate ≥ 140/minute or increase of ≥ 20% from baseline, SpO2 ≤ 90% on FiO2 ≥ 50%, arterial pH ≤ 7.35, or respiratory distress. Data was collected using a pro forma that included demographic details, smoking status, GOLD COPD category, comorbidities, and vital signs. ABG parameters, NIV settings at the time of hospital admission, at the time of study enrolment, and 48h after weaning were also recorded. Independent sample t-test was used to test the statistical significance of the difference between means of variables between the two groups. Pearson Chi square test and Fisher's exact test were used to compare categorical variables between the groups. A p-value of < 0.05 was considered statistically significant. NIV was successfully withdrawn in 56/70 (80%) and 50/70 (71.4%) patients in Groups 1 and 2, respectively. This difference was not statistically significant. The length of hospital stay was longer in the stepwise reduction of duration group (Group 1), but this was not statistically significant. On comparison of two methods of NIV withdrawal, it was found that neither method is superior to the other in terms of weaning failure, intubation rates, and average length of hospital stay.

Factors Associated With Change in S3-NIV Score Over Time in People With Chronic Respiratory Failure Treated With Long-Term Home Noninvasive Ventilation

IntroductionMonitoring changes in symptoms over time during long-term nocturnal home non-invasive ventilation (NIV) using patient-reported outcome measures is crucial. This study aimed to identify factors associated with changes in the S3-NIV total score, its two domains (“respiratory symptoms” and “sleep and NIV-related side effects”) and individual item responses. MethodsWe conducted a retrospective, longitudinal data analysis of a cohort of adults with chronic respiratory failure treated with NIV. Data were obtained from a French homecare provider. Multivariate linear and multinomial ordinal mixed effect models were used to identify factors associated with changes in S3-NIV scores over time. ResultsMedian follow-up was 2 years for 2135 participants. Each participant completed a median of five S3-NIV questionnaires; totaling 11,359 analyzed questionnaires. Type of respiratory condition, sex, age and time since NIV initiation were associated with change in S3-NIV score over time. NIV adherence was not associated with total S3-NIV score but high adherence was associated with more severe respiratory symptoms and an improvement in sleep and NIV-related side effects during the follow-up. Intensity of pressure support was associated with a lower total S3-NIV score and more side effects. Face masks and supplemental oxygen were associated with a lower S3-NIV total score. ConclusionChanges in S3-NIV scores over time are associated with the individual's characteristics and NIV settings. Analysis of the two domains and individual items of the S3-NIV could increase understanding of the difficulties experienced by people on NIV.

Diaphragm weakness in late-onset Pompe disease: A complex interplay between lower motor neuron and muscle fibre degeneration

BackgroundLate-onset Pompe disease (LOPD) patients may still need ventilation support at some point of their disease course, despite regular recombinant human alglucosidase alfa treatment. This suggest that other pathophysiological mechanisms than muscle fibre lesion can contribute to the respiratory failure process. We investigate through neurophysiology whether spinal phrenic motor neuron dysfunction could contribute to diaphragm weakness in LOPD patients. Material and methodsA group of symptomatic LOPD patients were prospectively studied in our centre from January 2022 to April 2023. We collected both demographic and clinical data, as well as neurophysiological parameters. Phrenic nerve conduction studies and needle EMG sampling of the diaphragm were perfomed. ResultsEight treated LOPD patients (3 males, 37.5%) were investigated. Three patients (37.5%) with no respiratory involvement had normal phrenic nerve motor responses [median phrenic compound muscle action potential (CMAP) amplitude of 0.49 mV; 1st-3rd interquartile range (IQR), 0.48–0.65]. Those with respiratory failure (under nocturnal non-invasive ventilation) had abnormal phrenic nerve motor responses (median phrenic CMAP amplitude of 0 mV; 1st-3rd IQR, 0–0.15), and were then investigated with EMG. Diaphragm needle EMG revealed both myopathic and neurogenic changes in 3 (60%) and myopathic potentials in 1 patient. In the last one, no motor unit potentials could be recruited. ConclusionsOur study provide new insights regarding respiratory mechanisms in LOPD, suggesting a contribution of spinal phrenic motor neuron dysfunction for diaphragm weakness. If confirmed in further studies, our results recommend the need of new drugs crossing the blood-brain barrier.

Respiratory involvement and sleep-related disorders in CMT1A: case report and review of the literature.

Sleep-disordered breathing has been reported in Charcot-Marie-Tooth disease (CMT) type 1A in association with diaphragmatic weakness and sleep apnea syndrome, mainly of the obstructive type (OSA). Improvement has been observed not only in sleep quality but also in neuropathy symptoms in CMT1A patients with OSA following the initiation of continuous positive airway pressure. We report the cases of two siblings affected by CMT1A associated with hemidiaphragm relaxatio necessitating nocturnal non-invasive ventilation (NIV). Two twins, now 42 years old, with a family history of CMT1A, received a genetic diagnosis of CMT1A at the age of 16. Over the years, they developed a slowly worsening gait disorder and a decline in fine motor hand movements, currently presenting with moderate disability (CMTES:13). At the age of 40, they both started complaining of daytime sleepiness, orthopnea, and exertional dyspnea. They received a diagnosis of relaxatio of the right hemidiaphragm associated with impairment of nocturnal ventilation and they both have benefited from nocturnal NIV. Disorders of breathing during sleep may be underestimated in CMT1A since routine investigations of sleep quality are rarely performed. Our two clinical cases and a literature review suggest the importance of inquiring about symptoms of excessive daytime sleepiness and respiratory disturbances in individuals with CMT1A, even in the absence of severe neuropathy. In the presence of compatible symptoms, a pneumological assessment, along with an overnight polysomnogram and lung function tests, should be performed. Recognizing sleep-related symptoms is essential for providing accurate treatment and improving the quality of life for patients with CMT1A.

Residual upper airway obstruction during nocturnal noninvasive ventilation despite high positive expiratory pressure. Impact of oronasal mask to nasal mask switch

BackgroundNasal mask (NM) and oronasal masks (OM) can be used to provide noninvasive ventilation (NIV). Recent studies suggested that OM is the most used interface and that there is no difference in efficacy or in tolerance between OM and NM for chronic use. However, studies focusing on video laryngoscopy underlined the impact of OM in residual upper airway obstruction (UAO) under NIV. We sought to assess the real-life practice of switching from OM to NM when UAO events persist despite high EPAP levels. MethodsIn an open-label single center prospective cohort study, data from files and full night polysomnography on NM and OM were collected for patients wearing OM and presenting an UAO index ≥15/h despite an EPAP level ≥ 10 cmH20. ResultsForty-four patients were included in the study. In 31 patients (74 %), switching to a NM reduced UAOi to ≥10/h. Interestingly, 92 % of these patients still had NM at 3 to 12 months of follow-up. Switching to a NM was also associated with a trend in paCO2 reduction and significant improvements in Epworth, sleep quality and NIV compliance. Successful interface switching was significantly associated with female gender, and a trend was observed in non-smokers. ConclusionAs for CPAP, switching to a NM improved NIV efficacy in a selected group of patients presenting residual UAO events despite high EPAP levels. Additionally, this switch has an impact on compliance and subjective sleepiness. Thus, in patients with persisting UAO on OM, switching to a NM could be a first-line intervention before considering further investigation such as polygraphy or video laryngoscopy. We also derive an algorithm for mask allocation and adaptation in acute and chronic NIV use.

High-intensity non-invasive ventilation during exercise-training versus without in people with very severe COPD and chronic hypercapnic respiratory failure: a randomised controlled trial

BackgroundPeople with very severe chronic obstructive pulmonary disease (COPD) using nocturnal non-invasive ventilation (NIV) for chronic hypercapnic respiratory failure (CHRF) experience reduced exercise capacity and severe dyspnoea during exercise training...

Sleep disordered breathing in infants identified through newborn screening with spinal muscular atrophy

BackgroundSpinal muscular atrophy (SMA) is a genetic disorder that may result in neuromuscular weakness and respiratory insufficiency. Gene replacement therapy has changed the trajectory of this condition, but long-term outcomes related to sleep disordered breathing are not known. MethodsThis was a retrospective review of infants with SMA identified via newborn screening who subsequently received onasemnogene abeparvovec at the Hospital for Sick Children (Ontario, Canada). Polysomnograms were conducted at the time of confirmed diagnosis as well as regularly thereafter. ResultsEleven children (4 female) were identified via newborn screen (7 with 2 copies of the SMN2 gene and 4 with 3 copies of the SMN2 gene) and received onasemnogene abeparvovec at a median age of 3.6 weeks. All eleven infants met criteria for sleep disordered breathing based on their first completed polysomnograms but improved over time. Three infants required respiratory technology, including a premature infant who was prescribed nocturnal supplemental oxygen therapy for central sleep apnea and two symptomatic infants with neuromuscular weakness who required nocturnal noninvasive ventilation. We did not find a correlation between motor scores and polysomnogram parameters. ConclusionChildren treated with onasemnogene abeparvovec have reduced sleep disordered breathing over time. Polysomnograms revealed abnormal parameters in all children, but the clinical significance of these findings was unclear for children who were asymptomatic for sleep disordered breathing or neuromuscular weakness. These results highlight the need to evaluate both motor scores and respiratory symptoms to ensure a holistic evaluation of clinical status.

The Safety of a High-Flow Nasal Cannula in Neuromuscular Disease Patients with Acute Respiratory Failure: A Retrospective Case-Series Study.

(1) Background: Although Non-Invasive Ventilation (NIV) is effective in preventing mortality and endotracheal intubation in patients with Acute Respiratory Failure (ARF) linked to a neuromuscular disorder, its efficacy can be affected by patient intolerance. A High-Flow Nasal Cannula (HFNC) appears to have a significant advantage over NIV as far as patient tolerance is concerned. The aim of the study was to investigate HFNC's safety profile in a group of consecutive Neuromuscular Disease (NMD) patients intolerant to NIV who were admitted to an Intermediate Respiratory Care Unit (IRCU) for ARF. (2) Methods: The clinical course of nine NMD patients intolerant to NIV and switched to HFNC was reported. HFNC was provided during daytime hours and NIV during the night-time to the NIV-intolerant patients. HFNC was utilized 24 h a day in those patients who were intolerant of even nocturnal NIV. (3) Results: HFNC was simple to use and it was well tolerated by all of the patients. Three out of nine patients experienced treatment failure, consisting of the need for ETI and/or death during their IRCU stay. The remaining 6 had a favorable outcome. Treatment failure was linked to the utilization of HFNC 24 h a day. (4) Conclusion: HFNC during the daytime hours, together with nocturnal NIV, seems to be a safe therapeutic approach for NMD patients with ARF. A round-the-clock use of HFNC tends to be linked to a high likelihood of failure.

0490 Under-Recognition and Undertreatment of Obesity Hypoventilation Syndrome (OHS) After Hospital Discharge: A Persistent Challenge

Abstract Introduction Hospitalization for acute-on-chronic hypercapnic respiratory failure (ACHRF) in OHS is associated with increased short-term mortality. The 2019 American Thoracic Society’s guidelines recommend that hospitalized OHS patients be discharged on nocturnal noninvasive ventilation (NIV). However, this was graded as a weak recommendation given that the data was retrospective and derived from European/Australian studies limiting generalizability to other healthcare systems. We aimed to assess post-discharge therapeutic plans for hospitalized patients with ACHRF and suspected OHS in an urban, tertiary care center in Chicago serving a large minority population. Methods We retrospectively queried the electronic health record of University of Chicago from 2008 to 2020 for hospitalized adults with BMI ≥35 kg/m2 admitted from the emergency department, requiring NIV/mechanical ventilation with evidence of respiratory acidosis on first blood gas (pH &amp;lt; 7.35 with PaCO2 ≥ 45 mmHg or PvCO2 ≥ 50mmHg). Subjects were excluded for obstruction on spirometry, greater than 20-pack year smoking history, CT evidence of parenchymal lung disease, acute neurologic process, significant left-sided heart failure and neuromuscular disease. Results Of the 797 obese patients requiring NIV/mechanical ventilation, we excluded 672 for lack of acute hypercapnia or low suspicion for OHS. The remaining 125 patients were predominantly Black (n = 116, 93%) and female (n = 94, 75%), mean age of 53±13.9 years, mean BMI of 50.8±12.8 kg/m2, mean first pH of 7.22±0.097, PaCO2 79.9±24.5 mmHg (n = 31) and PvCO2 74.7± 20.2mmHg (n = 94). On admission, 84 patients (67%) did not carry a diagnosis of OHS and 66 patients (53%) were PAP-naïve. 54% were discharged on PAP (43% CPAP, 43% Bilevel, and 14% other). Patients discharged on PAP were more obese (p = 0.001) and more hypercapnic (p = 0.002). Post-discharge polysomnography/sleep clinic referral was planned for 40% of patients. The 1-year mortality rate was 8% with no association recognized between 1-year mortality and PAP on discharge. Conclusion In our cohort, the proportion of patients discharged on nocturnal NIV was low. In contrast to the guideline recommendation, we did not find an association between being discharged on PAP therapy and mortality. Larger studies in more diverse populations are needed. Support (if any)

Homozygous splice variant (c.1741-6G>A) of the COL6A1 gene in three patients with Ullrich congenital muscular dystrophy

The three major collagen VI genes: COL6A1, COL6A2, and COL6A3 encode microfibrillar components of extracellular matrices in multiple tissues including muscles and tendons. Pathogenic variants in the collagen VI genes cause collagen VI-related dystrophies representing a continuum of conditions from Bethlem myopathy at the milder end to Ullrich congenital muscular dystrophy at the more severe end. Here we describe a pathogenic variant in the COL6A1 gene (NM_001848.3; c.1741-6G>A) found in homozygosity in three patients with Ullrich congenital muscular dystrophy. The patients suffered from severe muscle impairment characterised by proximal weakness, distal hyperlaxity, joint contractures, wheelchair-dependency, and use of nocturnal non-invasive ventilation. The pathogenicity was verified by RNA analyses showing that the variant induced aberrant splicing leading to a frameshift and loss of function. The analyses were in line with immunocytochemistry studies of patient-derived skin fibroblasts and muscle tissue demonstrating impaired secretion of collagen VI into the extracellular matrix. Thereby, we add the variant c.1741-6G>A to the list of pathogenic, recessive, splice variants in COL6A1 causing Ullrich congenital muscular dystrophy. The variant is listed in ClinVar as of “uncertain significance” and “likely benign” and may presumably have been overlooked in other patients.

Impact of loss of ambulation on right ventricular size in patients with neuromuscular disorders

Neuromuscular disorders (NMD) are a group of hereditary and acquired neurological diseases with skeletal disability. Patients may be wheelchair bound, depending of clinical severity and mechanical ventilation support is needed in patients with significant respiratory insufficiency. Right ventricular (RV) dimensions may be affected by intrathoracic pressures and venous return, this last one depending on peripheral skeletal function. We aimed to assess the impact of loss of ambulation on right ventricular size in patients with neuromuscular disorders, using the RV end diastolic area (RVEDA). We reviewed from our database patients with neuromuscular disorders who underwent transthoracic echocardiography. We systematically assessed right ventricular size, skeletal muscle function and pulmonary function. We included 320 patients (female gender: 32%) with neuromuscular disorders (including 40% myotonic dystrophy type I, 20% Duchenne muscular dystrophy, 10% Becker muscular dystrophy). Median age was 37 years [28–48], median body mass index (BMI) at 22.6 kg/m2 [19.4–26], median forced pulmonary vital capacity (FVC) at 75% of predicted value [45–96.5], 28% of patients were wheelchair bound and 35% of patients were on nocturnal noninvasive ventilation (NIV). Median left ventricular ejection fraction (LVEF) was 60% [55–66], median RVEDA was 17 cm2 [13–20] and median right ventricular peak systolic tissue Doppler velocity (Sm RV) was 13 cm/s [11–15]. The RVEDA was reduced in patients with beta-blocker (BB) use (14 cm2 vs. 17 cm2, P < 0.001), ACE inhibitor use (14 cm2 vs. 17.8 cm2, P < 0.001), NIV use (14 cm2 vs. 18 cm2, P < 0.001), wheelchair use (12.5cm2 vs. 18.6 cm2, P < 0.001). The RVEDA was associated with age (r = 0.1, p 0.04), BMI (r = 0.27, P < 0.001), Walton score (r = −0.53, P < 0.001), FVC (r = 0.5, P < 0.001), minimal vena cava diameter (r = −0.3, P < 0.001), left atrial diameter (r = 0.3, P < 0.001), right ventricular end diastolic volume (r = 0.97, P < 0.001), left ventricular end diastolic volume (r = 0.37, P < 0.001) and systolic arterial pulmonary pressure (r = 0.15, P 0.025). Using multivariate analysis, at the risk of 5%, by adjusting for age, BB, ACE inhibitor, LVEF, NIV and history of pacemaker, wheelchair use remained significantly associated with RVEDA (P < 0.001). In patients with NMD, the loss of ambulation is associated with a reduction of the right ventricular size, irrespective of age, betablockers, ACE inhibitor, LVEF and ventilation

Getting It Right in Obstructive Lung Disease.

Chronic hypercapnic respiratory failure in obstructive lung diseases may benefit from nocturnal Home non-invasive ventilation (HNIV). It has been shown that in patients with persistence of hypercapnia after an acute episode of chronic obstructive pulmonary disease (COPD) exacerbation requiring mechanical ventilation, HNIV may improve the risk for new admission and survival. The ability to reach these aims depends on the correct timing of enrolling patients, as well as a correct definition of ventilatory needing and setting of the ventilator. This review tries to define a possible home treatment path of hypercapnic respiratory failure in COPD by analyzing the main studies published in recent years.

Hereditary myopathy with early respiratory failure: case report

BackgroundHereditary myopathy with early respiratory failure (HMERF) is a rare myopathy that affects respiratory muscles in the early course of the disease leading to respiratory insufficiency. It is caused by mutation in titin (TTN) gene.Case reportAt the age of 29, our female patient presented with a slowly progressive proximal lower limb and axial muscle weakness and respiratory issues. Her late mother had similar problems, she died at a young age and was never properly diagnosed. Patient’s creatine kinase level was elevated up to three times above the upper limit of normal. Whole exome sequencing showed a pathogenic variant c.95372G>A in the TTN gene leading to the final diagnosis of HMERF. Cardiac examination was normal. Patient started to use a non-invasive nocturnal ventilation at age of 35.ConclusionsOur case is the first described case of HMERF in Serbian population. Multidisciplinary neurological and pulmonary approach is of great importance in HMERF and similar diseases. This case highlights the importance of considering early neuromuscular respiratory insufficiency as a distinctive syndrome leading to a challenging and broad differential diagnosis.

Inherited myopathies in patients from Sub-Saharan Africa: Results from a retrospective cohort

The clinical epidemiology of inherited myopathies in sub-Saharan Africa (SSA) is unknown but likely underdiagnosed due to problems of scientific research and social issues. We report a case series of patients born in SSA, evacuated to Portugal through an international health protocol and seen at a single neuromuscular disorders centre, between January/2004 and August/2021. We identified 9 patients (5 males), 35.6 ± 19.3 years-old (10–64), from Cape Verde (n = 4), Angola (n = 2), Sao Tome and Principe (n = 2) and Guinea-Bissau (n = 1), with a delay in diagnosis of 19.7 ± 14.3 years. Seven patients (77.8 %) had positive family history. Most patients had significant morbidity, requiring wheelchair (55.6 %), and nocturnal non-invasive ventilation (55.6 %). The diagnosis included Bethlem myopathy (n = 2), Duchenne muscular dystrophy (n = 2), Emery-Dreifuss muscular dystrophy (n = 1), LGMDR1 (n = 2), LGMDR2 (n = 1), and type-1 myotonic dystrophy (n = 1). Genetic testing was remarkable for 3 mutations previously not described. Despite the small sample, the spectrum of hereditary myopathies in our cohort is like western studies. Further studies are needed to better understand the epidemiology of muscle diseases in SSA.