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.

INCEPTUS Natural History, Run-in Study for Gene Replacement Clinical Trial in X-Linked Myotubular Myopathy.

Background: X-linked myotubular myopathy (XLMTM) is a life-threatening congenital myopathy that, in most cases, is characterized by profound muscle weakness, respiratory failure, need for mechanical ventilation and gastrostomy feeding, and early death.

Objective: We aimed to characterize the neuromuscular, respiratory, and extramuscular burden of XLMTM in a prospective, longitudinal study.

Methods: Thirty-four participants < 4 years old with XLMTM and receiving ventilator support enrolled in INCEPTUS, a prospective, multicenter, non-interventional study.

Participant retention in follow-up studies of prematurely born children.

Background: Follow-up studies of infants born prematurely are essential to understand the long-term consequences of preterm birth and the efficacy of interventions delivered in the neonatal period. Retention of participants for follow-up studies, however, is challenging, with attrition rates of up to 70%. Our aim was to examine retention rates in two follow-up studies of prematurely born children and identify participant or study characteristics that were associated with higher attrition, and to discuss retention strategies with regard to the literature.

Parental views on attending neonatal intensive care ward rounds.

Objectives: To ascertain parental views regarding taking part in neonatal unit ward rounds.

Design: A service evaluation project.

Setting: Tertiary neonatal intensive care unit.

The influence of affective state on respiratory muscle activity.

Measures of neural respiratory drive through the use of electromyography of the parasternal intercostal muscles (EMGpara) are accurate markers of respiratory load and are reflective of pulmonary function. A previous observation of a significant reduction in EMGpara from a first to second measurement occasion was attributed to participants' acclimatization to the laboratory environment and a reduction in anxiety. This study therefore aimed to investigate whether manipulation of participants' affective state would influence EMGpara and related variables.

The influence of posture on parasternal intercostal muscle activity in healthy young adults.

Objective: Parasternal intercostal muscle electromyography (EMGpara) has been used as an index of respiratory load in health and disease. While reference values are available, such data have been obtained with subjects in the seated position only. The objective of the current study was to determine the influence of posture on measurements of EMGpara.

Predicting healthcare outcomes in prematurely born infants using cluster analysis.

Aims: Prematurely born infants are at high risk of respiratory morbidity following neonatal unit discharge, though prediction of outcomes is challenging. We have tested the hypothesis that cluster analysis would identify discrete groups of prematurely born infants with differing respiratory outcomes during infancy.

Methods: A total of 168 infants (median (IQR) gestational age 33 (31-34) weeks) were recruited in the neonatal period from consecutive births in a tertiary neonatal unit.

Respiratory viral infections in infancy and school age respiratory outcomes and healthcare costs.

Objectives: To determine the impact of viral lower respiratory tract infections (LRTIs) in infancy including rhinovirus (RV) and infancy respiratory syncytial virus (RSV), on school age pulmonary function and healthcare utilization in prematurely born children.

Working Hypothesis: School age respiratory outcomes would be worse and healthcare utilization greater in children who had viral LRTIs in infancy.

Study Design: Prospective study.

The influence of dilution on the offline measurement of exhaled nitric oxide.

Objective: Measurement of fractional exhaled nitric oxide (FeNO) is used to determine the presence and severity of eosinophilic airway inflammation in asthma and other wheezing illnesses. The gold standard of online measurement during a single prolonged exhalation is not suitable for use in young children. The international guidelines for offline measurements recommend collection of exhaled gas in an appropriate reservoir for later analysis in young children.

Nonvolitional assessment of tibialis anterior force and architecture during critical illness.

Introduction: Contemporaneous measures of muscle architecture and force have not previously been conducted during critical illness to examine their relationship with intensive care unit (ICU)-acquired weakness.

Methods: Ankle dorsiflexor muscle force (ADMF) with high-frequency electrical peroneal nerve stimulation and skeletal muscle architecture via ultrasound were measured in 21 adult, critically ill patients, 16 at ICU admission.

Results: Thirteen patients were measured on 2 occasions.

Respiratory load perception in overweight and asthmatic children.

Overweight asthmatic children report greater symptoms than normal weight asthmatics, despite comparable airflow obstruction. This has been widely assumed to be due to heightened perception of respiratory effort. Three groups of children (healthy weight controls, healthy weight asthmatics, overweight asthmatics) rated perceived respiratory effort throughout an inspiratory resistive loading protocol.

Parasternal intercostal muscle activity during methacholine-induced bronchoconstriction.

What is the central question of this study? The parasternal intercostal electromyogram (EMGpara) is known to provide an accurate, non-invasive index of respiratory load-capacity balance. Although relationships between EMGpara and both airflow obstruction and hyperinflation have been shown, the independent contribution of each factor has not been examined. What is the main finding and its importance? Reductions in airway calibre and inspiratory capacity along with increases in EMGpara were induced via methacholine challenge.

Physiological markers of exercise capacity and lung disease severity in cystic fibrosis.

Background And Objective: Peak aerobic capacity (VO peak) is an important outcome measure in cystic fibrosis (CF), but measurement is not widely available and can be influenced by patient motivation, pain and fatigue. Alternative markers of disease severity would be helpful. Neural respiratory drive, measured using parasternal intercostal muscle electromyography (EMGpara), reflects the load to capacity balance of the respiratory system and provides a composite measure of pulmonary function impairment in CF.

Parasternal intercostal electromyography: a novel tool to assess respiratory load in children.

Background: Parasternal intercostal muscle electromyography (EMGpara) represents a novel tool to assess respiratory load when volitional techniques are not possible. This study examined the application of EMGpara in healthy, wheezy, and critically ill children.

Methods: Surface EMGpara was measured during tidal breathing in 92 healthy children, 20 wheezy preschool children (with measurements repeated following bronchodilator), and 25 mechanically ventilated children during supported ventilation and on continuous positive airways pressure.

Accuracy of portable devices in measuring peak cough flow.

Peak cough flow (PCF) measurements can be used as indicators of cough effectiveness. Portable peak flow meters and spirometers have been used to measure PCF, but little is known about their accuracy compared to pneumotachograph systems. The aim of this study was to compare the accuracy of four portable devices (Mini-Wright and Assess peak flow meters, SpiroUSB and Microlab spirometers) in measuring PCF with a calibrated laboratory based pneumotachograph system.

Neural respiratory drive measured during inspiratory threshold loading and acute hypercapnia in healthy individuals.

Understanding the effects of respiratory load on neural respiratory drive and respiratory pattern are key to understanding the regulation of load compensation in respiratory disease. The aim of the study was to examine and compare the recruitment pattern of the diaphragm and parasternal intercostal muscles when the respiratory system was loaded using two methods. Twelve subjects performed incremental inspiratory threshold loading up to 50% of their maximal inspiratory pressure, and 10 subjects underwent incremental, steady-state hypercapnia to a maximal inspired CO2 of 5%.