Respiratory muscle strength is a proven predictor of long-term outcome of neuromuscular disease (NMD), including amyotrophic lateral sclerosis, Duchenne muscular dystrophy, and spinal muscular atrophy. Maximal inspiratory pressure (MIP), a sensitive measure of respiratory muscle strength, one of several useful tests of respiratory muscle strength, is gaining interest as a therapeutic clinical trial endpoint for NMD. In this comprehensive review we investigate the use of MIP as a measure of respiratory muscle strength in clinical trials of therapeutics targeting respiratory muscle, examine the correlation of MIP with survival, quality of life, and other measures of pulmonary function, and outline the role of MIP as a clinically significantly meaningful outcome measure. Our analysis supports the utility of MIP for the early evaluation of respiratory muscle strength, especially of the diaphragm, in patients with NMD and as a surrogate endpoint in clinical trials of therapies for NMD.

Aims: To estimate the effect of prophylactic angiotensin-converting enzyme inhibitors (ACEi) on survival in Duchenne muscular dystrophy (DMD). Methods and results: We analysed the data from the French multicentre DMD Heart Registry (ClinicalTrials.gov: NCT03443115). We estimated the association between the prophylactic prescription of ACEi and event-free survival in 668 patients aged 8 to 13 years, with normal left ventricular function, using (i) a Cox model with intervention as a time-dependent covariate, (ii) a propensity-based analysis comparing ACEi treatment vs. no treatment, and (iii) a set of sensitivity analyses. The study outcomes were overall survival and hospitalizations for heart failure (HF) or acute respiratory failure. Among the 668 patients included in the DMD Heart Registry, 576 (mean age 6.1 ± 2.8 years) were eligible for this study, of whom 390 were treated with ACEi prophylactically. Death occurred in 53 patients (13.5%) who were and 60 patients (32.3%) who were not treated prophylactically with ACEi, respectively. In a Cox model with intervention as a time-dependent variable, the hazard ratio (HR) associated with ACEi treatment was 0.49 [95% confidence interval (CI) 0.34–0.72] and 0.47 (95% CI 0.31–0.17) for overall mortality after adjustment for baseline variables. In the propensity-based analysis, 278 patients were included in the treatment group and 834 in the control group, with 18.5% and 30.4% 12-year estimated probability of death, respectively. ACEi were associated with a lower risk of death (HR 0.39; 95% CI 0.17–0.92) and hospitalization for HF (HR 0.16; 95% CI 0.04–0.62). All other sensitivity analyses yielded similar results. Conclusion: Prophylactic ACEi treatment in DMD was associated with a significantly higher overall survival and lower rates of hospitalization for HF.

About 30% of patients with Guillain-Barré syndrome become ventilator dependent, of whom roughly 75% develop pneumonia. This trial aimed at assessing the impact of early mechanical ventilation (EMV) on pneumonia occurrence in GBS patients. We hypothesize that EMV will reduce the incidence of pneumonia. This was a single centre, open-label, randomized controlled trial performed on two parallel groups. 50 intensive care unit adults admitted for Guillain-Barré syndrome and at risk for acute respiratory failure. Patients were randomized to early mechanical ventilation via face-mask or endotracheal intubation owing to the presence or absence of impaired swallowing (experimental arm), or to conventional care (control arm). The primary outcome was the incidence of pneumonia up to intensive care unit discharge (or 90 days, pending of which occurred first). Twenty-five patients were randomized in each group. There was no significant difference between groups for the incidence of pneumonia (10/25 (40%) vs 9/25 (36%), P = 1). There was no significant difference between groups for the time to onset of pneumonia (P = 0.50, Gray test). During follow-up, there were 16/25 (64%) mechanically ventilated patients in the control group, and 25/25 (100%) in the experimental arm (P < 000·1). The time on ventilator was non-significantly shorter in the experimental arm (14 [7; 29] versus 21.5 [17.3; 35.5], P = 0.10). There were no significant differences between groups for length of hospital stay, neurological scores, the proportion of patients who needed tracheostomy, in-hospital death, or any serious adverse events. In the present study including adults with Guillain-Barré syndrome at high risk of respiratory failure, we did not observe a prevention of pneumonia with early mechanical ventilation. Trial registration: ClinicalTrials.gov under the number NCT00167622. Registered 9 September 2005, https://clinicaltrials.gov/ct2/show/NCT00167622?cond=Guillain-Barre+Syndrome&cntry=FR&draw=2&rank=1

Identifying patients at high risk of post-extubation acute respiratory failure requiring respiratory or mechanical cough assistance remains challenging. Here, our primary aim was to evaluate the accuracy of easily collected parameters obtained before or just after extubation in predicting the risk of post-extubation acute respiratory failure requiring, at best, noninvasive mechanical ventilation (NIV) and/or mechanical cough assistance and, at worst, reintubation after extubation. We conducted a multicenter prospective, open-label, observational study from April 2012 through April 2015. Patients who passed a weaning test after at least 72 h of endotracheal mechanical ventilation (MV) were included. Just before extubation, spirometry and maximal pressures were measured by a technician. The results were not disclosed to the bedside physicians. Patients were followed until discharge or death. Among 3458 patients admitted to the ICU, 730 received endotracheal MV for longer than 72 h and were then extubated; among these, 130 were included. At inclusion, the 130 patients had mean ICU stay and endotracheal MV durations both equal to 11 ± 4.2 days. After extubation, 36 patients required curative NIV, 7 both curative NIV and mechanical cough assistance, and 8 only mechanical cough assistance; 6 patients, all of whom first received NIV, required reintubation within 48 h. The group that required NIV after extubation had a significantly higher proportion of patients with chronic respiratory disease (P = 0.015), longer endotracheal MV duration at inclusion, and lower Medical Research Council (MRC) score (P = 0.02, P = 0.01, and P = 0.004, respectively). By multivariate analysis, forced vital capacity (FVC) and peak cough expiratory flow (PCEF) were independently associated with (NIV) and/or mechanical cough assistance and/or reintubation after extubation. Areas under the ROC curves for pre-extubation PCEF and FVC were 0.71 and 0.76, respectively. In conclusion, FVC measured before extubation correlates closely with FVC after extubation and may serve as an objective predictor of post-extubation respiratory failure requiring NIV and/or mechanical cough assistance and/or reintubation in heterogeneous populations of medical ICU patients. ClinicalTrials.gov as #NCT01564745

In cardiac surgery, patients are at risk of phrenic nerve injury, which leads to diaphragm dysfunction and acute respiratory failure. Diaphragm dysfunction (DD) is relatively frequent in cardiac surgery and particularly affects patients after coronary artery bypass graft. The onset of DD affects patients’ prognosis in term of weaning from mechanical ventilation and hospital length of stay. The authors present a narrative review about diaphragm physiology, techniques used to assess diaphragm function, and the clinical application of diaphragm ultrasound in patients undergoing cardiac surgery.