An algorithm for discontinuing mechanical ventilation in boys with x-linked myotubular myopathy after positive response to gene therapy: the ASPIRO experience.

X-linked myotubular myopathy (XLMTM) is a rare, life-threatening congenital myopathy. Most (80%) children with XLMTM have profound muscle weakness and hypotonia at birth resulting in severe respiratory insufficiency, the inability to sit up, stand or walk, and early mortality. At birth, 85-90% of children with XLMTM require mechanical ventilation, with more than half requiring invasive ventilator support.

Cardiac atrial pathology in Duchenne muscular dystrophy.

Introduction/aims: Duchenne muscular dystrophy (DMD) is characterized by fibrofatty replacement of muscle. This has been documented in the ventricular myocardium of DMD patients, but there is limited description of atrial involvement. The purpose of this study is to examine the arrhythmia and ectopy burden in patients with DMD and non-DMD dilated cardiomyopathy (DCM) and to characterize the cardiac histopathologic changes in DMD patients across the disease spectrum.

Respiratory Insufficiency in Neuromuscular Disease (RIND): A Delphi Study to Establish Consensus Criteria to Define and Diagnose Hypoventilation in Pediatric Neuromuscular Disease.

Unlabelled: Chronic respiratory failure is a common endpoint in the loss of respiratory muscle function in patients with progressive neuromuscular disease (NMD). Identifying the onset of hypoventilation is critical to allow for the timely introduction of ventilator support and effectively manage respiratory failure [1-3]. While there are accepted criteria governing the diagnosis of hypoventilation during polysomnography (PSG) [4], there is concern that criteria are insufficient for identifying hypoventilation in the earlier stages of respiratory insufficiency related to NMD.

Assessment of the relationship between disease progression and goals of care by individuals with Duchenne muscular dystrophy and their caregivers.

Introduction/aims: Most patients with Duchenne muscular dystrophy (DMD) in the US are diagnosed at about age 5 years. Some adolescents and young adults (AYAs) with DMD are now living into their fourth decade, yet AYAs and caregivers are frequently unprepared to address changes in goals of care due to disease progression. The hypothesis-generating research question was how AYAs with DMD and their caregivers understand the relationship between physical changes and the need to change goals of care.

Sleep disordered breathing: Assessment and therapy in the age of emerging neuromuscular therapies.

The term neuromuscular disease (NMD) encompasses a large variety of disorders that result in abnormal muscle function. Although it may be conventional to relate the use of this term to the most common muscular diseases (Duchenne muscular dystrophy [DMD], spinal muscular atrophy [SMA], and amyotrophic lateral sclerosis, etc), it is important to extend the term to pathologies manifested by severe neurologic (brain and spinal cord) malformations and injuries. In many of these scenarios, there are common mechanisms that contribute to sleep disordered breathing (SDB) and respiratory insufficiency although comorbidities may be somewhat different.

Randomized trial of lung hyperinflation therapy in children with congenital muscular dystrophy.

Objective: Respiratory compromise in congenital muscular dystrophy (CMD) occurs, in part, from chest wall contractures. Passive stretch with hyperinsufflation therapy could reduce related costo-vertebral joint contractures. We sought to examine the impact of hyperinsufflation use on lung function and quality of life in children with CMD.

Recombinant human insulin-like growth factor-1 therapy for 6 months improves growth but not motor function in boys with Duchenne muscular dystrophy.

Introduction: Recombinant human insulin-like growth factor-1 (rhIGF-1) is a growth factor and has anabolic effects on muscle. We investigated whether rhIGF-1 therapy: 1) improves or preserves muscle function; and 2) improves growth in boys with Duchenne muscular dystrophy (DMD).

Methods: In this study we compared prepubescent, ambulatory, glucocorticoid-treated boys with DMD (n = 17) vs controls (glucocorticoid therapy only, n = 21) in a 6-month-long, prospective, randomized, controlled trial of subcutaneous rhIGF-1 therapy.

Clinically Asymptomatic Sleep-Disordered Breathing in Infants with Single-Ventricle Physiology.

Objectives: To assess clinically asymptomatic infants with single-ventricle physiology (SVP) for sleep-disordered breathing (SDB) in the supine and car seat positions using polysomnography. Polysomnography results also were compared with results of a standard Car Seat Challenge to measure the dependability of the standard Car Seat Challenge.

Study Design: This was an observational study of 15 infants with SVP.

Understanding adherence to noninvasive ventilation in youth with Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is an X-linked, progressive neuromuscular disorder that results in chronic respiratory insufficiency and subsequently failure requiring noninvasive ventilation (NIV). Adherence to NIV in neuromuscular disorders and related barriers are poorly described. The aim of the current study was to assess NIV adherence, adherence barriers, and identify psychosocial predictors of adherence in young boys with early DMD-related sleep disordered breathing and recommended nocturnal NIV.

Comparison of Pulmonary Function Decline in Steroid-Treated and Steroid-Naïve Patients with Duchenne Muscular Dystrophy.

Objective: To describe and compare the lung function decline in patients with Duchenne muscular dystrophy on glucocorticoid therapy in contrast with glucocorticoid-naïve patients, and to define the deciles of pulmonary decline in glucocorticoid-treated patients.

Study Design: This retrospective study examined lung function of patients with Duchenne muscular dystrophy over 6 years of age followed between 2001 and 2015 at 2 centers-glucocorticoid-treated patients in Cincinnati, Ohio, and glucocorticoid-naïve patients in Paris, France. Forced vital capacity (FVC, FVC%), forced expiratory volume in 1 second, maximal inspiratory pressure, maximal expiratory pressure, and peak expiratory flow data were analyzed.

Respiratory Management of the Patient With Duchenne Muscular Dystrophy.

In 2010, Care Considerations for Duchenne Muscular Dystrophy, sponsored by the Centers for Disease Control and Prevention, was published in , and in 2018, these guidelines were updated. Since the publication of the first set of guidelines, survival of individuals with Duchenne muscular dystrophy has increased. With contemporary medical management, survival often extends into the fourth decade of life and beyond.

Sleep disordered breathing in Duchenne muscular dystrophy.

Symptoms of sleep disordered breathing (SDB) in younger boys with DMD are often poorly perceived and/or articulated by the patients or their families. As a result it is the watchful eye of the care-provider that determines the need for early polysomnographic (PSG) assessments. The use of polysomnography without capnometry should be considered completely inadequate when it comes to diagnosis and management of SDB in these patients.

Pulmonary Endpoints in Duchenne Muscular Dystrophy. A Workshop Summary.

Development of novel therapeutics for treatment of Duchenne muscular dystrophy (DMD) has led to clinical trials that include pulmonary endpoints that allow assessment of respiratory muscle status, especially in nonambulatory subjects. Parent Project Muscular Dystrophy (PPMD) convened a workshop in Bethesda, Maryland, on April 14 and 15, 2016, to summarize published respiratory data in DMD and give guidance to clinical researchers assessing the effect of interventions on pulmonary outcomes in DMD.

Variable phenotype in a novel mutation in PHOX2B.

We evaluated a family with three siblings, two of whom ages 2 years and 19 months, had long segment colonic agangliosis and anisocoria. The mother also had anisocoria. All three affected family members were mildly dysmorphic with a flat facial profile, square appearance to the face, depressed nasal bridge, and anteverted nares.

Comparison of sitting and supine forced vital capacity in collagen VI-related dystrophy and laminin α2-related dystrophy.

Background: Progressive, restrictive, respiratory insufficiency is the major cause of morbidity and mortality in Congenital Muscular Dystrophy (CMD). Nocturnal hypoventilation precedes daytime alveolar hypoventilation, and if untreated, may lead to respiratory failure and cor pulmonale. CMD consensus care guidelines recommend screening for respiratory insufficiency by conventional and dynamic (sitting to supine) pulmonary function testing (PFT) and evaluating for sleep disordered breathing if there is more than 20% relative reduction from sitting to supine FVC(L) (ΔFVC).

Long-Term Outcome of Interdisciplinary Management of Patients with Duchenne Muscular Dystrophy Receiving Daily Glucocorticoid Treatment.

Objective: To evaluate clinical outcomes and steroid side effects in a cohort of patients with Duchenne muscular dystrophy (DMD) treated with long-term daily glucocorticoid therapy. Although daily glucocorticoid therapy has been shown to extend ambulatory function in DMD, less frequent dosing is often used because of side effect concerns.

Study Design: Retrospective study of 97 patients with DMD aged 10 to <16 years treated with daily glucocorticoid (89% on deflazacort) for a mean of 8.

Adherence and barriers to hyperinsufflation in children with congenital muscular dystrophy.

Background: Congenital muscular dystrophy (CMD) is a rare, inherited neuromuscular disease characterized by progressive muscle weakness, thoracic insufficiency, and ultimately respiratory failure. Adherence to respiratory therapies in children with neuromuscular disorders is unknown. This study examined the multimodal assessment of adherence and barriers to 15 min, twice daily hyperinsufflation in children with CMD.

The Performance of the Upper Limb scores correlate with pulmonary function test measures and Egen Klassifikation scores in Duchenne muscular dystrophy.

The Performance of the Upper Limb scale was developed as an outcome measure specifically for ambulant and non-ambulant patients with Duchenne muscular dystrophy and is implemented in clinical trials needing longitudinal data. The aim of this study is to determine whether this novel tool correlates with functional ability using pulmonary function test, cardiac function test and Egen Klassifikation scale scores as clinical measures. In this cross-sectional study, 43 non-ambulatory Duchenne males from ages 10 to 30 years and on long-term glucocorticoid treatment were enrolled.

Implementation of Postoperative Respiratory Care for Pediatric Orthopedic Patients.

Background And Objectives: At our institution, one-fifth of pediatric patients undergoing hip and spine surgery require prolonged oxygen supplementation, most likely due to postoperative atelectasis. Using quality improvement methodology, we aimed to implement an innovative postoperative respiratory care algorithm for hip and spine surgery patients, with a global aim of improving respiratory outcomes.

Methods: A multidisciplinary team developed a care algorithm that relied on an activated respiratory therapist (RT) and engagement of patients and families.

Sleep disordered breathing in young boys with Duchenne muscular dystrophy.

Objectives: To describe sleep-disordered breathing (SDB) in young boys with Duchenne muscular dystrophy (DMD) and its relationship with pulmonary function tests (PFTs).

Study Design: This retrospective study examined diagnostic polysomnogram and PFT data of boys younger than 18 years with DMD and treated with steroids. Spirometry, respiratory muscle strength, body mass index (BMI), sleep architecture variables, and indices of SDB were analyzed.

Implantation of the HeartMate II and HeartWare left ventricular assist devices in patients with duchenne muscular dystrophy: lessons learned from the first applications.

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder affecting 1 in 3,500 males, characterized by progressive skeletal muscle weakness and death secondary to cardiac or respiratory failure in the 2nd or 3rd decade. Being a progressive disease, patients are rarely candidates for cardiac transplantation and death from dilated cardiomyopathy (DCM) is common. Implantation of left ventricular assist device (LVAD) offers the potential to alter clinical trajectory by alleviating heart failure symptoms.

Growth hormone treatment in boys with Duchenne muscular dystrophy and glucocorticoid-induced growth failure.

This study evaluated efficacy and safety of growth hormone treatment in Duchenne muscular dystrophy boys with glucocorticoid-induced growth failure. We reviewed 39 consecutive boys (average age 11.5 years; 32 ambulatory) treated with growth hormone for 1 year during a four-year period.

Influence of gender on pharyngeal airway length in obese adolescents.

Objectives: Although pharyngeal airway length has been implicated in an increased male predisposition for obstructive sleep apnea (OSA) in adults, data in obese children and adolescents are lacking. Our objective was to determine the influence of gender on pharyngeal airway length in obese adolescents, and to apply computational simulations to better understand the effect of pharyngeal airway length on the airway's predisposition to collapse in this select group.

Methods: Obese subjects without OSA were recruited from our Sleep Center.