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. Disease-related adverse events, respiratory and motor function, feeding, secretions, and quality of life were assessed. RESULTS: During median (range) follow-up of 13.0 (0.5, 32.9) months, there were 3 deaths (aspiration pneumonia; cardiopulmonary failure; hepatic hemorrhage with peliosis) and 61 serious disease-related events in 20 (59%) participants, mostly respiratory (52 events, 18 participants). Most participants (80%) required permanent invasive ventilation (>16 hours/day); 20% required non-invasive support (6-16 hours/day). Median age at tracheostomy was 3.5 months (95% CI: 2.5, 9.0). Thirty-three participants (97%) required gastrostomy. Thirty-one (91%) participants had histories of hepatic disease and/or prospectively experienced related adverse events or laboratory or imaging abnormalities. CHOP INTEND scores ranged from 19-52 (mean: 35.1). Seven participants (21%) could sit unsupported for≥30 seconds (one later lost this ability); none could pull to stand or walk with or without support. These parameters remained static over time across the INCEPTUS cohort. CONCLUSIONS: INCEPTUS confirmed high medical impact, static respiratory, motor and feeding difficulties, and early death in boys with XLMTM. Hepatobiliary disease was identified as an under-recognized comorbidity. There are currently no approved disease-modifying treatments.

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. METHODS: Data from children recruited at birth to one of two studies of prematurely born infants were assessed. The two studies were the United Kingdom Oscillation Study (UKOS, a randomised study comparing two modes of neonatal ventilation in infants born less than 29 weeks of gestational age (GA)), and an observational study examining the impact of viral lower respiratory tract infections in infancy in those born less than 36 weeks of GA (virus study). The UKOS participants, but not those in the virus study, had regularly been contacted throughout the follow-up period. UKOS subjects were followed up at 11 to 14 years of age and subjects in the virus study at 5-7 years of age. At follow up in both studies, pulmonary function and respiratory morbidity were assessed. Retention rates to follow-up in the two studies and baseline characteristics of those who were and were not retained were assessed. RESULTS: Retention was significantly higher in UKOS than the virus study (61% versus 35%, p < 0.0001). Subjects lost to UKOS follow up had greater deprivation scores (p < 0.001), a greater likelihood of intrauterine tobacco exposure (p = 0.001) and were more likely to be of non-white ethnicity (p < 0.001). In the virus study, those lost to follow-up had higher birth weights (p = 0.036) and were less likely to be oxygen dependent at hospital discharge (p = 0.003) or be part of a multiple birth (p = 0.048). CONCLUSIONS: Higher retention was demonstrated when there was regular contact in the follow-up period. Both social factors and initial illness severity affected the retention into follow-up studies of prematurely born infants, though these factors were not consistent across the two studies.

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. PATIENTS: Parent(s) of infants receiving care on the neonatal unit. INTERVENTIONS: Structured interviews conducted at the cot side. MAIN OUTCOME MEASURES: Parents were asked if they knew when ward rounds occurred, whether they had attended ward rounds and if they had not what were the factors inhibiting them from doing so, their experience of attending ward rounds and whether they were concerned about issues of confidentiality. RESULTS: 23 of 24 consecutive parents agreed to be interviewed. The median age of their infants was 14 (range 3 - 123) days when they were interviewed. Eighty-five per cent were able to identify when a nursing handover or doctor's ward round occurred. Seventy-five per cent of parents had attended at least one ward round and the median score in terms of usefulness was 5 out of 5. Reasons for not attending included time and cost to travel to the unit, their partners were working and having other children. Parents volunteered that the nurses proactively updated them as soon as they arrived, hence making regular attendance less important. Regarding confidentiality, 85% were not concerned if other people overheard information about their baby, unless the news was bad. CONCLUSIONS: Parents recognised the value of attending ward rounds and generally found it a positive experience, but emphasised limitations on their ability to attend.

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. Healthy adult participants underwent measurement of EMGpara and respiratory flow and volume during exposure to four conditions: no stimulus, music, and tense and calm videos. Respiratory rate (RR), raw neural respiratory drive index (rawNRDI, the product of EMGpara in microvolts and RR) and minute ventilation (VE) differed significantly across conditions: RR and VE were significantly higher in the tense condition than all other conditions (all P<0·05); rawNRDI was higher in the tense compared to the calm video condition (P = 0·03). There was also a significant relationship between EMGpara and subjective tension ratings (measured via visual analogue scale) in the tense condition (Spearman's rho = 0·508, P = 0·016), with multivariate modelling indicating significant interactions between rawNRDI and subjective ratings of both tension and calmness. This suggests that anxiety could contribute to elevated respiratory muscle activity and ventilation. Greater consideration should be given to the influence of anxiety when undertaking measurement of respiratory muscle activity to ensure data accurately represent underlying respiratory load.

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. APPROACH: Fifty-one healthy adult participants underwent measurement of EMGpara, respiratory flow and volume in the seated, reclined at 45°, and supine positions. Resting peak EMGpara activity per breath was determined and expressed both as the raw signal and normalised to that obtained during a maximum inspiratory effort (EMGpara%max). Neural respiratory drive index (NRDI, the product of EMGpara%max and respiratory rate) and neuroventilatory efficiency (NVE, tidal volume divided by EMGpara) were also calculated. MAIN RESULTS: No significant differences were observed in raw EMGpara, EMGpara%max, NRDI, NVE or tidal volume from the seated to reclined or supine positions. Respiratory rate and minute ventilation were significantly lower in the supine position compared to seated (p  = 0.0043 and 0.0266 respectively). Poor agreement was observed between raw EMGpara and EMGpara%max, likely due to submaximal efforts or cross-talk from adjacent musculature during the maximal manoeuvres. Agreement was notably poorer in the supine posture. SIGNIFICANCE: Posture does not have a significant effect on EMGpara activity, suggesting that measurements can be made in the reclined or supine position if required or requested by the participant. Normalising the EMGpara signal to a maximal respiratory effort may give unreliable estimates of respiratory load.

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. The baseline characteristics of the infants were used to classify them into hierarchical agglomerative clusters. Rates of viral lower respiratory tract infections (LRTIs) were recorded for 151 infants in the first year after birth. RESULTS: Infants could be classified according to birth weight and duration of neonatal invasive mechanical ventilation (MV) into three clusters. Cluster one (MV ≤5 days) had few LRTIs. Clusters two and three (both MV ≥6 days, but BW ≥or <882 g respectively), had significantly higher LRTI rates. Cluster two had a higher proportion of infants experiencing respiratory syncytial virus LRTIs (P = 0.01) and cluster three a higher proportion of rhinovirus LRTIs (P < 0.001) CONCLUSIONS: Readily available clinical data allowed classification of prematurely born infants into one of three distinct groups with differing subsequent respiratory morbidity in infancy.

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. SUBJECT SELECTION: A cohort of prematurely born children who had symptomatic LRTIs during infancy documented, was recalled. METHODS: Pulmonary function was assessed at 5 to 7 years of age and health related costs of care from aged one to follow-up determined. RESULTS: Fifty-one children, median gestational age 33+6 weeks, were assessed at a median (IQR) age 7.03 (6.37-7.26) years. Twenty-one children had no LRTI, 14 RV LRTI, 10 RSV LRTI, and 6 another viral LRTI (other LRTI). Compared to the no LRTI group, the RV group had a lower FEV1 (P = 0.033) and the other LRTI group a lower FVC (P = 0.006). Non-respiratory medication costs were higher in the RV (P = 0.018) and RSV (P = 0.013) groups. Overall respiratory healthcare costs in the RV (£153/year) and RSV (£27/year) groups did not differ significantly from the no LRTI group (£56/year); the other LRTI group (£431/year) had higher respiratory healthcare costs (P = 0.042). CONCLUSIONS: In moderately prematurely born children, RV and RSV LRTIs in infancy were not associated with higher respiratory healthcare costs after infancy. Children who experienced LRTIs caused by other respiratory viruses (including RV) had higher respiratory healthcare costs and greater pulmonary function impairment.

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. Among these, 10 who were measured at ICU admission demonstrated muscle weakness. Despite significant reductions in tibialis anterior (Δ = -88.5 ± 78.8 mm2 , P = 0.002) and rectus femoris (Δ = -126.1 ± 129.1 mm2 , P = 0.006) cross-sectional areas between occasions, ADMF did not change (100-HZ ankle dorsiflexor force 9.8 [IQR, 8.0-14.4] kg vs. 8.6 (IQR, 6.7-19.2) kg, P = 0.9). DISCUSSION: Muscle weakness was evident at ICU admission. No additional decrements were observed 7 days later despite significant reductions in muscle size. These data suggest that not all ICU weakness is truly "acquired" and questions our understanding of muscle function during critical illness. Muscle Nerve 57: 964-972, 2018.

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. The apparatus required for gas collection, however, creates dead space within the system, which may result in sample dilution and hence inaccuracy. Our objective was to investigate the effect such dilution might have on the accuracy of offline FeNO by comparing the results to online results. APPROACH: Thirty-five adult subjects without respiratory disease underwent online measurement of FeNO and, thereafter, undertook offline FeNO measurements via exhalation into a collection reservoir using one, five or ten inhalation-exhalation cycles. Fifteen of the subjects also exhaled using the five-breath technique via apparatus with additional dead space. An equation incorporating dead space volume and the number of breaths was used to predict the degree of dilution; the predicted results were compared to the measured results. MAIN RESULTS: The median (IQR) FeNO from a one-breath technique (22 (15-28) ppb was not significantly different to online values (19 (12-27) ppb, p = 1.00), but the results from the five-breath technique (11 (4-19) ppb, p < 0.0001), the ten-breath technique (6 (4-15) ppb, p < 0.0001) and the additional dead space experiment (6 (3-8) ppb, p = 0.0006) were significantly lower than online FeNO. Measured values were consistently significantly different to those predicted by the dilution equation, even when incorporating the exact exhaled volume of gas. SIGNIFICANCE: Offline FeNO results may be inaccurate when subjects are unable to fill the collection reservoir with a single exhalation, thus the technique may not be suitable for preschool children.

Parasternal intercostal muscle activity during methacholine-induced bronchoconstriction.

NEW FINDINGS: 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. A strong inverse relationship was observed between EMGpara and airway obstruction, with no influence of inspiratory capacity. These data suggest that EMGpara is more strongly influenced by airway calibre than by changes in end-expiratory lung volume during airway challenge testing. Neural respiratory drive, measured via the parasternal intercostal electromyogram (EMGpara), provides a non-invasive index of the load-capacity balance of the respiratory muscle pump. Previous studies in patients with obstructive lung disease have shown strong relationships between EMGpara and the extent of both airflow obstruction and hyperinflation. The relative influence of the two factors has not, however, been described. Airflow obstruction was induced via methacholine challenge testing in 25 adult humans. Forced expiratory volume in 1 s (FEV1 ) and surface EMGpara during tidal breathing were measured after each dose, with 20 of the participants also undergoing measurements of inspiratory capacity (IC) at each stage. Linear mixed model analysis was used to assess dose-wise changes in FEV1 and EMGpara, and thereafter to determine the influence of changes in FEV1 and IC on change in EMGpara. Median (interquartile range) FEV1 decreased significantly [from 96.00 (80.00-122.30) to 67.80 (37.98-92.27)% predicted, P < 0.0001] and EMGpara increased significantly [from 5.37 (2.25-8.92) to 6.27 (3.37-19.60) µV, P < 0.0001] from baseline to end of test. Linear mixed model analysis showed a significant interaction between methacholine dose and induced change in EMGpara, with an increase in EMGpara of 0.24 (95% confidence interval 0.11-0.37) µV per methacholine dose2 . Change in FEV1 further influenced this relationship [increase in slope of 0.002 (0.004-0.001) µV dose-2 per % predicted fall in FEV1 , P = 0.011], but not with change in IC. These data suggest that bronchoconstriction exerts a more potent influence on levels of EMGpara than changes in end-expiratory lung volume during methacholine challenge.

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 electromyogram was used as an objective marker of respiratory load; this was expressed relative to tidal volume and reported as a ratio of the baseline value (neuroventilatory activity ratio (NVEAR)). Significant increases in perception scores (p<0.0001), and decreases in NVEAR (p<0.0001) were observed from lowest to highest resistive load. Higher BMI increased overall perception scores, with no influence of asthma or BMI-for-age percentile on the resistance-perception relationships. These data, indicating elevated overall respiratory effort in overweight asthmatic children but comparable responses to dynamic changes in load, suggest that the greater disease burden in overweight asthmatic children may be due to altered respiratory mechanics associated with increased body mass.

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

BACKGROUND AND OBJECTIVE: Peak aerobic capacity (VO2 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. The aim of the study was to investigate the relationship between exercise capacity, EMGpara and established measures of pulmonary function in clinically stable adult CF patients. METHODS: Twenty CF patients (12 males, median (range) age: 22.3 (17.0-43.1) years) performed the 10-m incremental shuttle walk test (ISWT) maximally with contemporaneous measures of aerobic metabolism. EMGpara was recorded from second intercostal space at rest and normalized using peak electromyogram activity obtained during maximum respiratory manoeuvres and expressed as EMGpara%max (EMGpara expressed as a percentage of maximum). RESULTS: VO2 peak was strongly correlated with ISWT distance (r = 0.864, P < 0.0001). Lung gas transfer (TL CO) % predicted was best correlated with VO2 peak (r = 0.842, P < 0.0001) and ISWT distance (r = 0.788, P < 0.0001). EMGpara%max also correlated with VO2 peak (-0.757, P < 0.0001), while the relationships between exercise outcome measures and forced expiratory volume in 1 s (FEV1 ) % predicted and forced vital capacity (FVC) % predicted were less strong. A TL CO% predicted of <70.5% was the strongest predictor of VO2 peak <32 mL/min/kg (area under the curve (AUC): 0.96, 100% sensitivity, 83.3% specificity). ISWT distance and EMGpara%max also performed well, with other pulmonary function variables demonstrating poorer predictive ability. CONCLUSION: TL CO% predicted and EMGpara%max relate strongly to exercise performance markers in CF and may provide alternative predictors of lung disease progression.

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. RESULTS: EMGpara was related to age, height, and weight in the healthy group (r = -0.623, -0.625, -0.641 respectively, all P < 0.0001). An age-based equation for predicted EMGpara was developed and patient data expressed as z-scores. EMGpara was higher in wheezy children prebronchodilator than healthy controls (median interquartile range (IQR) z-score 0.53 (0.07-1.94), P = 0.0073), falling to levels not different to healthy children postbronchodilator (-0.08 (-0.50-1.00)). In the critically ill children, EMGpara was higher (P < 0.0001) than in healthy subjects during both mechanical ventilation (median (IQR) z-score 1.14 (0.33-1.93)) and continuous positive airways pressure (1.88 (0.91-3.03)). CONCLUSION: EMGpara is feasible in children and infants both healthy and diseased, is raised in those with elevated respiratory load, and is responsive to clinical interventions. EMGpara represents a potential method to assess respiratory status in patients conventionally challenging to assess.

Ultrasound for the assessment of peripheral skeletal muscle architecture in critical illness: a systematic review.

OBJECTIVES: To critically evaluate and summarize identified evidence for the use of ultrasound to measure peripheral skeletal muscle architecture during critical illness. DATA SOURCES: Seven electronic databases (Medline, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Physiotherapy Evidence Database, Scopus, Excerpta Medica Database, and Web of Science [including Science Citations and Conference Proceedings]) and personal libraries were searched for relevant articles. Cross-referencing further identified references. STUDY SELECTION: Quantitative study designs excluding abstracts, published in English, including adult critically ill patients in the ICU, evaluating peripheral skeletal muscle architecture during critical illness with ultrasound were included. Studies using ultrasonographic muscle data as outcome measures in interventional trials were excluded. DATA EXTRACTION: Performed by one reviewer using a standardized data extraction form and cross-checked by a second reviewer. Quality appraisal was undertaken by two independent reviewers-studies were classified, graded, and appraised according to standardized algorithms and checklists. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were adhered to. DATA SYNTHESIS: Seven studies with independent patient cohorts totaling 300 participants were included. One study adopted a case-control design, and the remainder were case series. Ultrasound data demonstrated deficits in a variety of peripheral skeletal muscle architecture variables across a range of muscle groups associated with critical illness. Ultrasound offered more accurate data compared to limb circumference measurement and has excellent reported reliability, but underestimated data acquired via more invasive muscle biopsy. CONCLUSION: Ultrasound provides clinical utility for assessing the trajectory of change in peripheral skeletal muscle architecture during critical illness, supplementing more detailed characterization, albeit rarely used, from muscle biopsy analysis. Adoption of standardized operating protocols for measurement will facilitate future meta-analysis of data.

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. Twenty healthy volunteers (mean (SD) age 45 (16) years) coughed through a pneumotachograph connected in series with each portable device in turn, and the differences in PCF readings were analysed. In addition, mechanically generated flow waves of constant peak flow were delivered through each device both independently and when connected in series with the pneumotachograph. Agreement between PCF readings obtained with the pneumotachograph and the portable devices was poor. Peak flow readings were on average lower by approximately 50 L min(-1) when measured using the portable devices; 95% limits of agreement spanned approximately 150 L min(-1). The findings highlight the potential for inaccuracy when using portable devices for the measurement of PCF. Depending on the measurement instrument used, absolute values of PCF reported in the literature may not be directly comparable.

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%. The diaphragmatic electromyogram (EMGdi) was measured using a multipair oesophageal catheter, and the parasternal intercostal muscle EMG (sEMGpara) was recorded from bipolar surface electrodes positioned in the second intercostal space. The EMGdi and sEMGpara were analysed over the last minute of each increment of both protocols, normalized using the peak EMG recorded during maximal respiratory manoeuvres and expressed as EMG%max. The EMGdi%max and sEMGpara%max increased in parallel during the two loading methods, although EMGdi%max was consistently greater than sEMGpara%max in both conditions, inspiratory threshold loading [bias (SD) 9 (3)%, 95% limits of agreement 4-15%] and hypercapnia [bias (SD) 6 (3)%, 95% limits of agreement -0.05 to 12%]. Inspiratory threshold loading resulted in more pronounced increases in mean (SD) EMGdi%max [10 (7)-45 (28)%] and sEMGpara%max [5.3 (3.1)-40 (28)%] from baseline compared with EMGdi%max [7 (4)-21 (8)%] and sEMGpara%max [4.7 (2.3)-10 (4)%] during hypercapnia, despite comparable levels of ventilation. These data support the use of sEMGpara%max, as a non-invasive alternative to EMGdi%max recorded with an invasive oesophageal electrode catheter, for the quantification of neural respiratory drive. This technique should make evaluation of respiratory muscle function easier to undertake and therefore more readily acceptable in patients with respiratory disease, in whom transduction of neural respiratory drive to pressure generation can be compromised.