Sherri L. Katz

Outcome of non-invasive positive pressure ventilation in paediatric neuromuscular disease

Background: Non-invasive positive pressure ventilation (NPPV) has a beneficial effect on nocturnal hypoventilation and hospitalisation rates in adults with static or slowly progressive neuromuscular disease and respiratory failure. Its role in children affected with similar disease processes, however, remains unclear. Aims: To investigate the impact of NPPV on hospitalisations and sleep related respiratory parameters in children with neuromuscular disease. Methods: Fifteen children (mean age 11.7, range 3.4–17.8 years) diagnosed with neuromuscular disease who had been started on nocturnal NPPV and had at least one year of follow up since the initiation of such therapy were studied. Patients served as their own controls and comparison was made of the years preceding and following the initiation of NPPV. Results: Children spent 85% fewer days in hospital (mean pre-NPPV 48.0 days, mean post-NPPV 7.0 days) and 68% less days in intensive care after initiation of NPPV (mean pre-NPPV 12.0 days, mean post-NPPV 3.9 days). Sleep study parameters including number of desaturations, apnoea-hypopnoea index and transcutaneous pCO2 levels improved after initiation of NPPV. Conclusions: NPPV can decrease hospitalisations for children with neuromuscular disease and improves sleep related respiratory parameters. A prospective study is now needed to further delineate the role of NPPV in this population of children.

Inter‐ and intra‐rater reliability of neck circumference measurements in children

Increased neck circumference is a risk factor for obstructive sleep apnea in adults. With rising obesity prevalence in children, it may be an important identifier of obstructive sleep apnea in children. The reliability of measuring neck circumference in children has not been systematically evaluated.

Lung volume recruitment slows pulmonary function decline in Duchenne muscular dystrophy.

OBJECTIVE To evaluate the long-term effect on measures of forced vital capacity (FVC) before and after the introduction of regular lung volume recruitment (LVR) maneuvers (breath-stacking) in individuals with Duchenne muscular dystrophy (DMD). DESIGN Retrospective cohort study of pulmonary function data, including FVC, cough peak flow (CPF), maximum inspiratory pressure (MIP), and maximum expiratory pressure (MEP). Data were collected for 33 months prior to and 45 months after LVR introduction. SETTING Ambulatory care in a tertiary level regional rehabilitation center in Canada. PARTICIPANTS All individuals (N=22) with DMD (mean age ± SD, 19.6±2.4y), who were prescribed LVR and reported adherence with therapy. INTERVENTIONS Introduction of regular LVR (breath-stacking); 3 to 5 maximal lung inflations (maximum insufflation capacity [MIC]) using a hand-held resuscitation bag and mouthpiece, twice daily. MAIN OUTCOME MEASURES Measures included the rate of decline of FVC in percent-predicted, before and after the introduction of regular LVR. Changes in maximum pressures (MIP, MEP), MIC, and cough peak flows were also measured. RESULTS At LVR initiation, FVC was 21.8±16.9 percent-predicted, and cough peak flows were <270L/min (144.8±106.9L/min). Annual decline of FVC was 4.7 percent-predicted a year before LVR and 0.5 percent-predicted a year after LVR initiation. The difference, 4.2 percent-predicted a year (95% confidence interval, 3.5-4.9; P<.000), represents an 89% improvement in the annual rate of FVC decline. CONCLUSIONS The rate of FVC decline in DMD patients improves dramatically with initiation of regular LVR.

Nocturnal hypoventilation: predictors and outcomes in childhood progressive neuromuscular disease

Objectives To determine: (a) prevalence of clinically unsuspected nocturnal hypoventilation (NH) in a clinic population of children with progressive neuromuscular disease; (b) whether NH can be predicted from clinical/laboratory parameters; and (c) change over 1 year in pulmonary function decline, quality of life and attention in children with NH treated with non-invasive positive pressure ventilation (NPPV) compared with children without NH. Design Prospective cohort study. Setting Two tertiary-care paediatric neuromuscular clinics. Patients 46 children (6–17 years) with progressive neuromuscular disease without neurocognitive impairment or dystrophinopathy. Interventions Polysomnography, pulmonary function, manual muscle strength, quality of life (CHQ-PF50) and Conners questionnaires. Outcome measures (a) Prevalence of NH; (b) predictive value of surrogate clinical measures for NH; and (c) differences in change over 1 year in pulmonary function, muscle strength, quality of life and attention between children with and without NH. Results Prevalence of NH was 14.8%, 95% CI 8.0% to 25.7%. Maximal sensitivity and specificity for NH were achieved with thresholds of forced vital capacity <70% and forced expiratory volume in 1 s <65% predicted (sensitivities: 71.4, 71.4; specificities: 64.1, 79.5). Scoliosis also predicted NH (sensitivity 88.9; specificity 80.4). Over 1 year, those with NH had a greater increase in residual volume/total lung capacity (0.075 (−0.003 to 0.168) vs −0.03 (−0.065 to 0.028)), decline in muscle strength (−0.67 (−0.90 to 0.10) vs 0.53 (−0.05 to 0.90)) and worsened perception of health status. Conclusions 15% of subjects had clinically unsuspected NH, predicted by moderate pulmonary function test impairment and scoliosis. Over 1 year those with NH had increased gas trapping, decline of muscle strength and worse perception of health status, despite NPPV.

Home Mechanical Ventilation in Canada: A National Survey

BACKGROUND: No comprehensive Canadian national data describe the prevalence of and service provision for ventilator-assisted individuals living at home, data critical to health-care system planning for appropriate resourcing. Our objective was to generate national data profiling service providers, users, types of services, criteria for initiation and monitoring, ventilator servicing arrangements, education, and barriers to home transition. METHODS: Eligible providers delivering services to ventilator-assisted individuals (adult and pediatric) living at home were identified by our national provider inventory and referrals from other providers. The survey was administered via a web link from August 2012 to April 2013. RESULTS: The survey response rate was 152/171 (89%). We identified 4,334 ventilator-assisted individuals: an estimated prevalence of 12.9/100,000 population, with 73% receiving noninvasive ventilation (NIV) and 18% receiving intermittent mandatory ventilation (9% not reported). Services were delivered by 39 institutional providers and 113 community providers. We identified variation in initiation criteria for NIV, with polysomnography demonstrating nocturnal hypoventilation (57%), daytime hypercapnia (38%), and nocturnal hypercapnia (32%) as the most common criteria. Various models of ventilator servicing were reported. Most providers (64%) stated that caregiver competency was a prerequisite for home discharge; however, repeated competency assessment and retraining were offered by only 45%. Important barriers to home transition were: insufficient funding for paid caregivers, equipment, and supplies; a shortage of paid caregivers; and negotiating public funding arrangements. CONCLUSIONS: Ventilatory support in the community appears well-established, with most individuals managed with NIV. Although caregiver competency is a prerequisite to discharge, ongoing assessment and retraining were infrequent. Funding and caregiver availability were important barriers to home transition.

Respiratory management strategies for Duchenne muscular dystrophy: practice variation amongst canadian sub-specialists†

Respiratory management of Duchenne muscular dystrophy (DMD) is not well studied and may vary across centers and practitioners. Our objective was to describe and compare the respiratory management practices of Canadian Pediatric Respirologists and Neuromuscular specialists for children with DMD.

Neck circumference percentile: A screening tool for pediatric obstructive sleep apnea

Large neck circumference (NC) is associated with obstructive sleep apnea (OSA) in adults, especially males. Since NC changes with age and sex, a lack of reference ranges makes neck size difficult to assess as a screening tool in children.

Preterm birth: risk factor for early-onset chronic diseases.

Preterm births (< 37 weeks’ gestation) are increasing worldwide and account for 8% of Canadian births.[1][1] With advances in perinatal care over the last 20–30 years, more than 90% of preterm infants survive and enter adulthood.[2][2] The “Barker hypothesis” of fetal origins of adult

Severe Neonatal Presentation of Mitochondrial Citrate Carrier (SLC25A1) Deficiency

Mutations of the mitochondrial citrate carrier (CIC) SLC25A1 cause combined D-2- and L-2-hydroxyglutaric aciduria (DL-2HGA; OMIM #615182), a neurometabolic disorder characterized by developmental delay, hypotonia, and seizures. Here, we describe the female child of consanguineous parents who presented neonatally with lactic acidosis, periventricular frontal lobe cysts, facial dysmorphism, recurrent apneic episodes, and deficient complex IV (cytochrome c oxidase) activity in skeletal muscle. Exome sequencing revealed a homozygous SLC25A1 missense mutation [NM_005984.4: c.593G>A; p.(Arg198His)] of a ubiquitously conserved arginine residue putatively situated within the substrate-binding site I of CIC. Retrospective review of the patients organic acids confirmed the D- and L-2-hydroxyglutaric aciduria typical of DL-2HGA to be present, although this was not appreciated on initial presentation. Cultured patient skin fibroblasts showed reduced survival in culture, diminished mitochondrial spare respiratory capacity, increased glycolytic flux, and normal mitochondrial bulk, inner membrane potential, and network morphology. Neither cell survival nor cellular respiratory parameters were improved by citrate supplementation, although oral citrate supplementation did coincide with amelioration of lactic acidosis and apneic attacks in the patient. This is the fifth clinical report of CIC deficiency to date. The clinical features in our patient suggest that this disorder, which can potentially be recognized either by molecular means or based on its characteristic organic aciduria, should be considered in the differential diagnosis of pyruvate dehydrogenase deficiency and respiratory chain disorders. One-Sentence Summary A novel homozygous missense substitution in SLC25A1 was identified in a neonate presenting with lactic acidosis, intracerebral cysts, and an apparent mitochondrial complex IV defect in muscle.

Long-Term Effects of Lung Volume Recruitment on Maximal Inspiratory Capacity and Vital Capacity in Duchenne Muscular Dystrophy

RATIONALE Lung volume recruitment therapy slows rate of decline of lung function in neuromuscular disease, possibly due to enhanced airway clearance, reduced atelectasis, or prevention of chest wall contractures. OBJECTIVES To determine if lung volume recruitment maintains maximal insufflation capacity (MIC), despite decline in VC. METHODS This was a retrospective cohort study (1991-2008) of individuals with Duchenne muscular dystrophy at pediatric and adult tertiary centers. Lung volume recruitment was prescribed twice daily, according to protocol. Changes over time in MIC, VC percentage predicted, the difference between MIC and VC, maximum inspiratory and expiratory pressures, and assisted and unassisted peak cough flow (PCF) were assessed using linear mixed effects models. MEASUREMENTS AND MAIN RESULTS Sixteen individuals, 8.6 to 33.0 years old at initiation of lung volume recruitment, with median VC percentage predicted of 13.5 (interquartile range, 8.0-20.3), were followed over a median of 6.1 years (range, 1.7-16.1 yr). MIC-VC differences were stable (change, 0.02 L/yr; P = 0.06). Post-lung volume recruitment, compared with pretreatment, rate of decline in VC decreased from 4.5% predicted/yr to 0.5% predicted/yr (P < 0.001). Maximal inspiratory and expiratory pressures were unchanged (P = 0.08, 0.59 respectively). Assisted-spontaneous PCF difference was maintained (slope, -1.59 L/min/yr, P = 0.35). CONCLUSIONS With lung volume recruitment therapy, MIC-VC differences were stable over time, indicating that respiratory system compliance remains stable, despite a loss in VC, in individuals with Duchenne muscular dystrophy. Decline in VC was significantly attenuated, and assisted PCF was maintained in a clinically effective range.