Antoine Cuvelier

Introduction: Myotonic dystrophy type 1 (DM1) is characterized by a lifelong progressive muscular weakness associated with life-threatening events such as chronic respiratory failure (CRF). Early identification of patients at risk remains challenging. Objective: To identify clinical and biological markers predictive of CRF onset and survival in a large DM1 cohort. Methods: We conducted a retrospective cohort study of 126 DM1 adult patients followed from 2000 to 2024 at Rouen University Hospital. The primary outcome was the first forced vital capacity (FVC) ≤ 70% of predicted value. Prognostic factors were analyzed using Cox proportional hazards models with the start of follow-up at the time of diagnosis of DM1 and were followed until the outcome occurred, or death (censorship according to Kalbfleisch & Prentice approach to competing risks). Results: During a median follow-up of 12.5 years, 45 patients developed FVC ≤ 70%. Muscular impairment rating scale (MIRS) (HR: 1.85, 95%CI:1.30–2.63) and conduction/rhythm disorders (HR: 3.13, 95%CI: 1.37–7.31) at diagnosis were independent predictors of FVC ≤ 70% adjusted on age, female sex (HR: 1.54, 95%CI: 0.82–2.91) and cataract at diagnosis (HR: 0.50, 95%CI: 0.22–1.16). CTG repeats ≥400 was associated with a doubled risk of respiratory decline but did not reach statistical significance. The 20-year mortality rate was 32%. MIRS (HR: 2.34, 95%CI:1.22- 4.51), male sex and older age at diagnosis significantly predicted death. Conclusions: Muscular impairment and cardiac rhythm/conduction disorders at diagnosis were strong predictors of respiratory complications. MIRS, male sex and older age at diagnosis were predictors of mortality in DM1. These prognostic markers should inform clinical management strategies to improve survival in DM1 patients.

Rationale: The benefit of noninvasive ventilation (NIV) in hypoxaemic acute respiratory failure is controversial and has never been studied in acute exacerbation of interstitial lung disease (AE-ILD). The potential protective effects of high-flow nasal cannula oxygen therapy (HFNC) also deserve to be evaluated in AE-ILD. Methods: We aimed to describe the respiratory management and compare outcome of adult patients with AE-ILD according to the initial oxygenation strategies, i.e. within 48 h of admission: HFNC alone or NIV±HFNC. Results: A multicentre retrospective study has been conducted in intensive care units of four French tertiary hospitals between 1 January 2010 and 31 December 2021 with in-hospital mortality as primary outcome. Among 3962 screened patients, 163 were included: 118 with HFNC and 45 with NIV±HFNC. Analysis of changes in oxygenation strategy applied over the past decade have shown an increase in the use of HFNC, from 33.3% in 2010 to 79.2% in 2020. The adjusted in-hospital mortality rate was 55.2% (95% CI 36.0–74.4%) in the NIV±HFNC group versus 45.9% (95% CI 36.5–55.4%) in the HFNC group (p=0.39). The adjusted intubation rates were 25.9% and 36.9% in the HFNC and NIV±HFNC groups, respectively (p=0.26). Conclusion: The management of AE-ILD has progressively include the HFNC use during the past decade, despite the lack of evidence in the literature. Our study did not find any superiority of HFNC compared with NIV±HFNC in AE-ILD outcome but deserve further prospective trials with a larger population.

Rare variants play an important role in α₁-antitrypsin deficiency (AATD) [1]. The Mediterranean area has a high variability for rare pathogenic variants, more frequently reported in Morocco, Portugal, Italy, Cyprus and Greece [1–4.] Among them, bi-allelic SERPINA1 Q0 variants are exceedingly rare [1, 4]. Q0 variants are not easily diagnosed. In heterozygosity they are invisible to isoelectric focusing and are observed indirectly through their effects on circulating α₁-antitrypsin (AAT) levels; therefore, molecular testing, such as SERPINA1 gene sequencing, is mandatory for correct classification and diagnosis [5].

Background: The increasing number of patients requiring home noninvasive ventilation (HNIV) is a challenge for our healthcare system. Telemonitoring may be used to facilitate the management of HNIV patients. We aimed to assess the ability of telemonitoring algorithms to identify patients not adequately ventilated. Our secondary aim was to assess the consequences related to these algorithms, including costs.Methods: Eleven HNIV experts each provided an algorithm to identify patients with suboptimal ventilation. Each algorithm was tested using real-life data from a cohort of patients over a 90-day period.Inadequate HNIV was defined as the presence of at least one criterion amongst the following: uncontrolled hypoventilation, daily adherence 10/h.Results: One hundred patients were included in the cohort. According to our criteria, HNIV was considered as inadequate in 66 (66%) patients, without difference between underlying respiratory disease. Telemonitoring algorithms correctly classified patients in 65 [52–66] % of cases. They had a global sensitivity of 78 [37–95] %, a specificity of 40 [19–78] %, a positive predictive value of 72 [65–77] % and a negative predictive value of 45 [37–51] %.Applying telemonitoring algorithms resulted in 127 [84–238] alerts across the study population with a median cost increase of €2064 [952–6262].Conclusion: Telemonitoring algorithms have poor diagnostic performances in identifying inadequately ventilated patient. They increase workload for healthcare workers and costs.

Background: In patients with chronic respiratory failure, home non-invasive ventilation (NIV) is delivered through oronasal or nasal masks. Masks are a cornerstone for NIV success but can be associated with side-effects. However, the type, frequency and consequences of these side-effects are unknown. Here, we aimed to study the prevalence, nature and impact of mask-related adverse events in a cohort of stable patients. We then investigated differences between oronasal and nasal masks both in our cohort and in a bench study.Methods: This was a prospective observational cohort including patients established on long-term NIV admitted for their elective review. Data regarding mask-related side-effects were assessed using a structured questionnaire. Our bench study was performed using a three-dimensional printed head connected to an artificial lung.Results: 800 patients were included, of whom 84% had an oronasal mask. Moderate to very severe mask-related side-effects occurred in 47% of patients and severe to very severe side-effects occurred in 18% of patients. Side-effects were associated with poorer daytime arterial partial pressure of carbon dioxide (p=0.005), poorer subjective sleep quality (p=0.003) and poorer quality of life (p<0.001). Mask-related side-effects were more frequently reported with the use of oronasal masks compared to nasal masks (p=0.023). Our bench study showed that nasal masks were more stable than oronasal masks (p<0.001).Conclusions: Mask-related side-effects are frequent and associated with poorer outcomes. Our data suggest that nasal masks may have a better tolerance profile and should be used as a first-line interface.

Nasal high flow (NHF) has been proposed to sustain high intensity exercise in people with COPD, but we have a poor understanding of its physiological effects in this clinical setting. What is the effect of NHF during exercise on dynamic respiratory muscle function and activation, cardiorespiratory parameters, endurance capacity, dyspnoea and leg fatigue as compared to control intervention. Randomized single-blind crossover trial including COPD patients. Two constant workload exercise testing were performed at 75% of peak power with NHF (30L/min, 34°C) or with control intervention. Pressure time product of the transdiaphragmatic pressure (PTPdi/min) and other physiological measurements were continuously monitored. Dyspnoea and lower limb fatigue were assessed using the 10-Borg scale. 14 patients with severe obstruction (median FEV1: 40 (IQR 28 to 52) %) were included. Their median age was 70 (IQR 57 to 72) years. At isotime, NHF had little to no effect on PTPdi/min (MD -15cmH2O.s/min, 95% CI -62 to 33) but increased tidal volume (MD 77mL, 95% CI 21 to 133). NHF also improved endurance capacity (MD 20s, 95% CI 2 to 40) and dyspnoea at isotime (MD -1.1, 95% CI -2.1 to -0.1). NHF had no or uncertain effect on other outcomes. NHF has little to no effect on dynamic respiratory muscle function and activation but improves Vt. It leads to a trivially small increase in endurance capacity but a worthwhile improvement in dyspnoea. NHF may be beneficial for individuals experiencing critical inspiratory constraints and significant dyspnoea.

Introduction: A wide range of recent ventilators, dedicated or not, is available for non-invasive ventilation (NIV) in respiratory or intensive care units (ICU). We conducted a bench study to compare their technical performances. Methods: Ventilators, including five ICU ventilators with NIV mode on, two dedicated NIV ventilators and one transport ventilator, were evaluated on a test bench for NIV, consisting of a 3D manikin head connected to an ASL 5000 lung model via a non-vented mask. Ventilators were tested according to three simulated lung profiles (normal, obstructive, restrictive), three levels of simulated air leakage (0, 15, 30 L/min), two levels of pressure support (8, 14 cmH₂O) and two respiratory rates (15, 25 cycles/min). Results: The global median Asynchrony Index (AI) was higher with ICU ventilators than with dedicated NIV ventilators (4% (0; 76) vs 0% (0; 15), respectively; p<0.05) and different between all ventilators (p<0.001). The AI was higher with ICU ventilators for the normal and restrictive profiles (p<0.01) and not different between ventilators for the obstructive profile. Auto-triggering represented 43% of all patient-ventilator asynchrony. Triggering delay, cycling delay, inspiratory pressure-time product, pressure rise time and pressure at mask were different between all ventilators (p<0.01). Dedicated NIV ventilators induced a lower pressure-time product than ICU and transport ventilators (p<0.01). There was no difference between ventilators for minute ventilation and peak flow. Conclusion: Despite the integration of NIV algorithms, most recent ICU ventilators appear to be less efficient than dedicated NIV ventilators. Technical performances could change, however, according to the underlying respiratory disease and the level of air leakage.

Background In patients with chronic respiratory failure, home non-invasive ventilation (NIV) is delivered through nasal or oronasal masks. Masks are a cornerstone for NIV success but can be associated with side effects. However, the type, the frequency and the consequences of these side effects are unknown. Here, we aimed to study the prevalence, nature, and impact of mask-related adverse events in a cohort of stable patients. We then investigated differences between oronasal and nasal masks both in our cohort and in a bench study. Methods Prospective observational cohort including patients established on long-term non-invasive ventilation admitted for their elective review. Data regarding mask-related side effects were assessed using a structured questionnaire. Our bench study was performed using a 3-D printed head connected to an artificial lung. Results Eight hundred patients were included of whom, 84% had a oronasal mask. Moderate to very severe mask-related side effects occurred in 47% of patients and severe to very severe side effects occurred in 18%. Side effects were associated to a poorer daytime PaCO₂ (p=0.005), poorer subjective sleep quality (p=0.003), poorer quality of life (p<0.001). Mask-related side effects were more frequently reported with the use of oronasal masks as compared to nasal masks (p=0.023). Our bench study showed that nasal masks were more stable than oronasal masks (p<0.001). Conclusion Mask-related side effects are frequent and associated with poorer outcome. Our data suggest that nasal masks may have a better tolerance profile and should be used as a first-line interface.

The implementation of Enhanced Recovery After Surgery (ERAS) is a challenge for healthcare systems, especially in case of patients undergoing major surgery. Despite a proven significant reduction in postoperative complications and hospital lengths of stay, ERAS protocols are inconsistently used in real-world practice, and barriers have been poorly described in a cohort comprising medical and paramedical professionals. This study aims to assess the proportion of French healthcare providers who practiced ERAS and to identify barriers to its implementation amongst those surveyed. We conducted a prospective cross-sectional study to survey healthcare providers about their practice of ERAS using an online questionnaire. Healthcare providers were contacted through hospital requests, private hospital group requests, professional corporation requests, social networks, and personal contacts. The questionnaire was also designed to explore barriers to ERAS implementation. Identified barriers were allocated by two independent assessors to one of the fourteen domains of the Theoretical Domains Framework (TDF), which is an integrative framework based on behavior change theories that can be used to identify issues relating to evidence on the implementation of best practice in healthcare settings. One hundred and fifty-three French healthcare providers answered the online questionnaire (76% female, median age 35 years (IQR: 29 to 48)). Physiotherapists, nurses, and dieticians were the most represented professions (31.4%, 24.2%, and, 14.4%, respectively). Amongst those surveyed, thirty-one practiced ERAS (20.3%, 95%CI: 13.9 to 26.63). Major barriers to ERAS practice were related to the “Environmental context and resources” domain (57.6%, 95%CI: 49.5–65.4), e.g., lack of professionals, funding, and coordination, and the “Knowledge” domain (52.8%, 95%CI: 44.7–60.8), e.g., ERAS unawareness. ERAS in major surgery is seldom practiced in France due to the unfavorable environment (i.e., logistics issues, and lack of professionals and funding) and a low rate of procedure awareness. Future studies should focus on devising and assessing strategies (e.g., education and training, collaboration, institutional support, the development of healthcare networks, and leveraging telehealth and technology) to overcome these barriers, thereby promoting the wider implementation of ERAS.