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

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. The purpose of this project was to identify more sensitive criteria for identifying hypoventilation. METHODS: Fifteen pediatric pulmonologists with broad experience in managing patients with NMD, 10 of whom were board certified in and practice sleep medicine, were assembled and performed a review of the pertinent literature and a two-round Delphi process with 6 domains (Table 1). RESULTS: Within the 6 domains there were three pertinent items per domain (Table 2). There was clear agreement on findings on history (morning headaches) and pulmonary function testing (FVC < 50% or awake TcCO2 > 45 mmHg) indicating a high concern for nocturnal hypoventilation. There was close agreement on the definitions for nocturnal hypercapnia and hypoxemia. PSG criteria were identified that indicate a patient is likely in the transitional phase from adequate ventilation to hypoventilation. DISCUSSION: We identified a set of clinical criteria that may allow for more sensitive diagnosis of hypoventilation in NMD and earlier initiation of non-invasive ventilation leading to a reduction in the respiratory morbidity in progressive NMD. These criteria need to be further and more broadly validated prospectively to confirm their utility.

Airway clearance in patients with neuromuscular disease.

Airway clearance is a critical component of both maintenance of respiratory health and management of acute respiratory illnesses. The process of effective airway clearance begins with the recognition of secretions in the airway and culminates in expectoration or swallowing. There are multiple points on this continuum at which neuromuscular disease causes impaired airway clearance. This can result in an otherwise mild upper respiratory illness progressing unabated from an easily managed condition to a severe, life-threatening lower respiratory illness requiring intensive therapy for patient recovery. Even during periods of relative health, airway protective mechanisms can be compromised, and patients may have difficulty managing average quantities of secretions. This review summarizes airway clearance physiology and pathophysiology, mechanical and pharmacologic treatment modalities, and provides a practical approach for managing secretions in patients with neuromuscular disease. Neuromuscular disease is an umbrella term used to describe disorders that involve dysfunction of peripheral nerves, the neuromuscular junction, or skeletal muscle. Although this paper specifically reviews airway clearance pertaining to those with neuromuscular diseases (e.g., muscular dystrophy, spinal muscular atrophy, myasthenia gravis), most of its content is relevant to the management of patients with central nervous system disorders such as chronic static encephalopathy caused by trauma, metabolic or genetic abnormalities, congenital infection, or neonatal hypoxic-ischemic injury.

Thoracic insufficiency syndrome: Approaches to assessment and management.

Thoracic insufficiency syndrome (TIS) was described in 2003 as the inability of the thorax to support normal respiration or lung growth. TIS includes a broad and disparate group of typically degenerative thoracospinal conditions. Although TIS arises due to a heterogeneous group of disorders and thus its incidence is not well quantified, general approaches to management and treatment exist. Evolving imaging techniques and measurements of health-related quality of life augment tests of pulmonary function to quantify disease burden, longitudinally and pre- and post-intervention. Intervention is primarily via growth-sparing surgery, for which several device options exist, to preserve vertical growth prior to a definitive spinal fusion at skeletal maturity.

Clinical pulmonary function testing in Duchenne muscular dystrophy.

In Duchenne muscular dystrophy there is a well-established progressive loss of upper and lower extremity muscle function that is evident from the earliest stages of decline and through permanent loss of function. There is not the same visible evidence of decline in respiratory muscle function decline toward respiratory failure; therefore, comprehensive pulmonary function testing provides a critical component of a comprehensive longitudinal respiratory assessment. There are multiple ways of assessing separate inspiratory and expiratory muscle function and also a summative output of each to provide broad information to help identify disease status and guide intervention as appropriate.

Maximal Respiratory Muscle Strength and Vital Capacity in Children With Early Onset Scoliosis.

STUDY DESIGN: Descriptive cross-sectional study. OBJECTIVE: To measure respiratory muscle function in children with early onset scoliosis (EOS), determine the frequency of respiratory muscle weakness, and correlate these measures with vital capacity, body mass index, and Cobb angle. SUMMARY OF BACKGROUND DATA: Progressive restrictive respiratory disease is common among children with moderate to severe EOS. Reduced respiratory muscle strength is associated with the loss of lung function in adolescents and adults with scoliosis. We hypothesized that reduced inspiratory and expiratory respiratory muscle strength also occur in children with EOS and correlate with reduced vital capacity, poor nutritional status, and severity of the spine deformity. METHODS: We measured maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP), forced vital capacity (FVC), body mass index IBMI), and Cobb angle in 49 children with EOS but with no diagnosis of underlying muscle weakness. We measured these indices in 12 children serially over 18 months to see if abnormal respiratory muscle function was sustained. RESULTS: FVC averaged 51% (SD 21) of predicted norms with 26 subjects having an FVC <50% predicted. The mean MIP was 57% (SD 25) and the mean MEP was 53% (SD 23) of predicted norms. Thirteen (27%) of the group had MIP values >2SD below the age and sex-based norms. BMI ranged between 1% and 99% of age-based norms. Cobb angle averaged 59° (SD27). MIP% and MEP% significantly correlated with FVC% (r =0.37, P = 0.01 and r = 0.52, P < 0.001 respectively)) but not with BMI or Cobb angle. Reduced MIP% and MEP% were sustained over 7 to 41 months. CONCLUSION: Respiratory muscle weakness is common and persistent in children with EOS and correlates with reductions in vital capacity. Mechanisms for abnormal respiratory function are unclear but must be determined to develop surgical treatment strategies that preserve respiratory muscle function in children with EOS throughout childhood. LEVEL OF EVIDENCE: 2.

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.

Chest wall hypoplasia--principles and treatment.

The chest is a dynamic structure. For normal movement it relies on a coordinated movement of the multiple bones, joints and muscles of the respiratory system. While muscle weakness can have clear impact on respiration by decreasing respiratory motion, so can conditions that cause chest wall hypoplasia and produce an immobile chest wall. These conditions, such as Jarcho-Levin and Jeune syndrome, present significantly different challenges than those faced with early onset scoliosis in which chest wall mechanics and thoracic volume may be much closer to normal. Because of this difference more aggressive approaches to clinical and surgical management are necessary.

Scoliosis and the impact in neuromuscular disease.

Scoliosis can alter respiratory mechanics by changing the orientation of the muscles and joints of the respiratory system and in severe forms can put a patient at risk of severe respiratory morbidity or respiratory failure. However, perhaps the most important factor in determining the pulmonary morbidity in scoliosis is the balance between the "load" or altered respiratory mechanics and the "pump" or the respiratory muscle strength. Therefore, scoliosis in patients with neuromuscular disease will both lead to increased "load" and a weakened "pump", an exceptionally unfortunate combination. While progressive neuromuscular disease by its nature does not respond favorably to attempts to improve respiratory muscle strength, the natural approach of early proactive management of the "load" and in the case of scoliosis a variety of different strategies have been tried with variable short term and long term results. Figuring this out requires both an understanding of the underlying pathophysiology of a particular neuromuscular condition and the available options for and timing of surgical intervention.

Pulmonary Function Testing in Children with Restrictive Chest Wall Disorders.

Disorders of the chest wall, spine, and respiratory muscles lead to lung function abnormalities consistent with restrictive lung disease. Common disorders of the thorax include diseases with respiratory muscle weakness, growth abnormalities of the thorax and spine, such as scoliosis. Spirometry alone is not sufficient to diagnose these abnormalities but may be useful to serially monitor changes over time or in response to treatments. In contrast, obesity does not produce restrictive respiratory disease in most children and produces obstructive lung disease more often. Test of respiratory muscle function, breathing during sleep, and during exercise have led to additional insights about the pathophysiology of these conditions that may provide new avenues for future therapies.

Management of thoracic insufficiency syndrome.

PURPOSE OF THE REVIEW: Thoracic insufficiency syndrome (TIS) was first characterized by Campbell and Smith in 2003, as the inability of the thorax to support normal respiration and growth. The range of thoracospinal disorders within TIS is broad and some have poor prognosis, but all have been challenging to treat effectively. This review will describe the common approaches and report on the published outcomes of each approach. RECENT FINDINGS: Over the last 15 years progress has been made in refining the approach to treating TIS, and more recently functional outcomes have been published for some of the techniques used. A number of recent reports have demonstrated spinal growth that meets normal rates after insertion of expandable devices to support the spine and preserve growth. However, in the short term pulmonary function outcomes indicate stabilization of lung function as opposed to regaining function, though there is a paucity of published data. SUMMARY: There are a number of effective surgical interventions for treating the underlying thoracospinal disorders in TIS; however, though the short-term effect on pulmonary function indicates stabilization the longitudinal effect still needs to be elucidated.

Early changes in pulmonary function after vertical expandable prosthetic titanium rib insertion in children with thoracic insufficiency syndrome.

BACKGROUND: The vertical expandable prosthetic titanium rib (VEPTR) has been inserted in children with thoracic insufficiency syndrome for the last decade to expand and support the chest and allow for further lung growth. There are minimal published data evaluating the postoperative change in lung function after VEPTR insertion. We hypothesize that there will be a significant increase in lung function after VEPTR insertion, and the earlier the insertion, the greater the improvement. METHODS: The Chest Wall Disorders Study Group Database, containing data before and after VEPTR insertion from 7 different centers, was queried for spirometry and lung volume measurements, and the data were analyzed to assess the short-term effect on lung function of VEPTR placement. RESULTS: There was a statistically significant decrease in forced vital capacity, forced expiratory volume in 1 second as a percent of predicted, an increase in residual volume (RV) that did not reach statistical significance, and there was no change in total lung capacity at the first postoperative visit (7.7 +/- 4.8 months). There was a significant decrease in Cobb angle. There was no correlation between absolute change in any pulmonary function and Cobb angle age at the time of surgery. CONCLUSIONS: Although there is a clinically and radiographically apparent expansion of the thorax after VEPTR insertion, there is no similar improvement in lung volume, and instead there is a decrease in forced vital capacity and increase in residual volume, the explanation for which requires further study. This lack of change in pulmonary function after VEPTR insertion suggests that the benefit of VEPTR insertion may lie more in stabilizing the thorax and improving respiratory mechanics measured in other ways.

Pediatric palliative, end-of-life, and bereavement care.

The pediatric hospitalist plays an integral role in providing palliative, end-of-life, and bereavement care for children and families. This article focuses on a multifaceted approach to this domain of care in which the physician is a key member of an interdisciplinary team. We believe that we can improve quality of life and relieve suffering only by paying attention to the medical, emotional, spiritual, and practical needs and goals of dying children and their loved ones.